A tandem radical macrocyclisation-transannular cyclisation approach towards the taxanes

Article abstract of DOI:10.1039/a805268i

Separate treatment of the iodotrienedione 19 and the iododienynedione 38 with Bu₃SnH-AIBN produces the corresponding taxane ring systems 25 (25-30%) and 56 (50-60%) respectively by way of tandem radical macrocyclisation-radical transannular cyc

Full text of DOI:10.1039/a805268i

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A tandem radical macrocyclisation-transannular cyclisation
approach towards the taxanes
Stephen A. Hitchcock, Stephen J. Houldsworth, Gerald Pattenden,* David C. Pryde,
Nicholas M. Thomson and Alexander J. Blake
School of Chemistry, Nottingham University, Nottingham, UK NG7 2RD
Received (in Cambridge) 7th July 1998, Accepted 24th July 1998
Separate treatment of the iodotrienedione 19 and the iododienynedione 38 with Bu3SnH–AIBN produces the
corresponding taxane ring systems 25 (25–30%) and 56 (50–60%) respectively by way of tandem radical
macrocyclisation-radical transannular cyclisations. By contrast the analogous iodopolyenones 61, 63, 65a, 66a,
86a and 87a, together with the corresponding iodoenynones 39a and 59 failed to undergo similar tandem radical
reactions, and instead gave products resulting from direct reduction of the carbon–iodine bonds in these substrates.
The structures of the taxane analogues 25 and 56 followed from analysis of their NMR spectroscopic data and
comparison with similar NMR data for related taxoids described in the literature. The stereochemistry of 56 was
secured from an X-ray crystal structure determination of the 1,5-diol 57 produced from reduction of 56 with DIBAL.
TaxolTM 1 together with its congeners and analogues have now
been a preoccupation of medicinal and synthetic chemists for
2
•
over a decade, ever since the profound anti-cancer properties of
•
several of their members were disclosed.1 The ‘taxoids’ as they
have become known have as their core the novel and unusual
3
4
tricyclo[9.3.1.03,8]pentadecane framework 2, which has proven
O
AcO
OH
Bz
Ph
NH
O
Br
O
H
OBz
O
OAc
OH
5
OH
1
3.7 The outcome of this idea, and the development of the
proposal are now laid down in this paper.8
Thus, the first precursor system we examined was the
iodotrienedione 19, which incorporates two conjugated enone
electrophores built into the system to facilitate the sequential
12-endo-trig radical macrocyclisation and 8-endo-trig radical
transannulation reactions from the appropriate alkyl radical
precursors in the desired regioselective senses. The iodotriene-
dione 19 was synthesised from the cyclohexene aldehyde
product 13 resulting from the Diels–Alder reaction between
the diene 12 and acrolein, as illustrated in Scheme 3. Thus the
known acetoxy diene 124b was first prepared starting from the
dibromocyclopropane 69 or from the ethyl acetoacetate deriv-
ative 9 as shown in Scheme 2. A Diels–Alder reaction between
the diene 12 and acrolein in the presence of boron trifluoride–
diethyl ether at Ϫ78 ЊC then produced the cyclohexene 13 in
79% yield. Treatment of this aldehyde with two equivalents of
vinylmagnesium bromide next led to the alcohol 14a which on
selective oxidation with TPAP–NMO10 was then converted into
the unstable hydroxy aldehyde 15a in 51% yield. When the alde-
hyde 15a was next treated with the vinyllithium reagent derived
by tin–lithium exchange from the vinylstannane 16,11 it was
converted into the labile bis-allylic alcohol 17a. Oxidation of
17a to the trienedione 18 was readily accomplished using
barium manganate,12 and treatment of the bromide 18 with
sodium iodide in refluxing butan-2-one finally produced the
radical precursor compound 19. The intermediate alcohol 17a
in this sequence was found to be extremely unstable and under-
went rapid and quantitative cyclisation on storage overnight
H
H
2
to be a significant challenge to the synthetic chemist.2 As a
consequence, a bewildering array of ingenious synthetic designs
towards the taxane carbon framework have been forthcoming,3
with four of them culminating in the total synthesis of TaxolTM
1 itself.4 For several years our own research group has had an
interest in developing the scope for an approach to polycyclic
frameworks based on the principle of a cascade radical-
mediated macrocyclisation-transannular cyclisation strategy
from an appropriate polyene precursor.5 The overall principle is
illustrated in Scheme 1 and several examples of the scope for
•
•
Scheme 1
this strategy have now been communicated in the contemporary
literature.6 An early example of this design towards polycycles
was revealed in our approach to the taxane carbon framework 2
where we planned to effect a radical cascade sequence from the
substituted A-ring precursor 5 via the key intermediates 4 and
J. Chem. Soc., Perkin Trans. 1, 1998, 3181–3206
3181

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leading to the bridged bicyclic ether 20. In order to circumvent
this problem a modification to the earlier route from 13 to 19
was developed involving protection of the secondary hydroxy
group in 14a as its MOM ether 14b and proceeding via the
intermediates 15b, 17b, 21 and 22 (Scheme 3).
When a solution of the iodotrienedione 19 in dry, degassed
benzene was heated under reflux in the presence of 1.1 equiv-
alents of tributyltin hydride (Bu3SnH) and catalytic azoiso-
butyronitrile (AIBN) for 6 h, work-up and chromatography
separated: (i) the product 23 (28%) resulting from straight-
forward reduction of the carbon–iodine bond in 19; (ii) the
bicyclo[9.3.1]pentadecadienedione 24 (~30%), the product of
12-endo-trig macrocyclisation of 19 and in situ hydrogen atom
quench, and (iii) a 3:1 mixture of C-1 epimers of the tri-
cyclo[9.3.1.0]pentadecenedione, 25 and 26, respectively (~25%)
produced via the aforementioned tandem radical 12-endo-
trig macrocyclisation-6-exo-trig transannulation (Scheme 4).
O
Br
Br
HO2C
CO2H
Br
O
O
i
ii
Bu3SnH
AlBN
19
+
6
7
8
iii,iv
O
H
23
24
O
OH
EtO2C
O
O
EtO2C
v
iv,vi HO
H
H
H
7
6
5
8
15
1
3
9
11
vii
10
4
H
O
O
H
H
26
25
AcO
H
H
0.76
12
50.8
62.8
Scheme 2 Reagents, conditions and yields: i, nBuLi, CO2, THF, Ϫ78 ЊC,
82%; ii, AgOAc, AcOH, 120 ЊC, 76%; iii, CH3I, K2CO3, CH3COCH3,
room temp., 73%; iv, DIBAL-H, C6H5CH3, Ϫ60 ЊC, 92%; v, CH3MgBr,
THF, room temp., 98%; vi, PTSA, C6H6, 65 ЊC, 93%; vii, AcCl, DMAP,
Et3N, CH2Cl2, room temp., 95%.
1.04
H
O
H
O
H
O
2.96
H
H
H
27
28
29
Scheme 4
O
O
OR
OR
AcO
HO
iii
ii
i
12
13
15
14
a R = H
b R = MOM
a R = H
b R = MOM
O
O
O
O
OH
OR
iv
vi
vii
Bu3Sn
Br
16
I
Br
Br
19
17
a R = H b R = MOM
18
xv
xiii
v
O
OMOM
O
OH
xiv
O
Br
Br
Br
20
21
22
xi
xii
viii,ix,x
13
14b
15b
17b
Scheme 3 Reagents, conditions and yields: i, H2C᎐CHCHO, BF3ؒOEt2, C6H5CH3, Ϫ50 ЊC, 79%; ii, H2C᎐CHMgBr, THF, room temp., 84%; iii,
᎐
᎐
TPAP, NMO, CH2Cl2, room temp., 51%; iv, nBuLi, 16, THF, Ϫ78 ЊC, 58%; v, CDCl3, Ϫ5 ЊC, quantitative; vi, BaMnO4, CH2Cl2, room temp., 90%; vii,
NaI, butan-2-one, 80 ЊC, 99%; viii, H2C᎐CHMgBr, THF, room temp., 72%; ix, ClCH2OCH3, Hunig’s base, CH2Cl2, 0 ЊC, 91%; x, K2CO3, MeOH,
᎐
room temp., 98%; xi, TPAP, NMO, CH2Cl2, room temp., 99%; xii, MeLiؒLiBr, 16, THF, Ϫ78 ЊC, 76%; xiii, TPAP, NMO, CH2Cl2, room temp., 84%;
xiv, HCl, H2O, THF, 50 ЊC, 90%; xv, TPAP, NMO, CH2Cl2, room temp., 89%.
3182
J. Chem. Soc., Perkin Trans. 1, 1998, 3181–3206

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O
Extensive investigations were carried out in order to optimise
the yield of 25/26 at the expense of 23 and 24, e.g. using high
dilution techniques, the use of (Me3Si)3SiH in place of Bu3SnH,
and atom transfer methods, but only in one instance, where
AIBN was added slowly portionwise to a mixture of 19 and
Bu3SnH, were we able to secure a higher yield, i.e. 35% of the
tricycle 25/26.13 Chromatography of the mixture of tricyclo-
[9.3.1.0]pentadecenediones 25 and 26 produced a pure sample
of the C-1 β-epimer 25. The structures and stereochemistries of
the bicyclic 24, and tricyclic products, 25 and 26, followed
unambiguously from analysis of their NMR spectroscopic data
and, in the case of the C-1 epimeric tricyclic products 25 and
26, by comparison with similar NMR data reported earlier for
related taxoids by Swindell et al.14 and Jenkins et al.15 Thus, in
O
H
•
R′
•
R′
R
R
H
30
Z -radical
31
E -radical
O
R′
R
R′
R
O
32
s-cis
33
s- trans
O
1
O
the H NMR spectrum of the C-1 β-epimer of the tricyclic
1
19
dione 25, the C-15 β-methyl and C-15 α-methyl signals occur at
δ 0.79 and 1.10 ppm respectively (cf. δ 0.76 and 1.04 ppm in 27)
and the C-3 α-H occurs as a double triplet [J 6 and 7 Hz at
δ 2.85 ppm (cf. δ 2.96 ppm in 27]. Methine signals characteristic
of the taxane ring system were observed at δ 58.7 (C-1), 53.3 (C-
3) and 37.1 (C-8) ppm in the 13C NMR spectrum of 25 and at
δ 67.7, 55.4 and 37.2 ppm respectively for the minor α-1 epimer
26. Comparison of these 13C NMR spectroscopic data with
corresponding data for the C-3 epimeric tricyclic ketones 27
and 28 reported by Swindell et al.,14 established that the mole-
cules were not epimeric at C-3, i.e. the BC ring junction. This
evidence, supported by further correlation with the 13C NMR
data reported for the taxoid 29 by Jenkins et al.,15 finally led us
to assign the relative configurations shown in 25 and 26 for the
epimeric tricyclic (taxane) products produced when 19 was
treated with Bu3SnH–AIBN.
•
O
O
•
34
35
O
H
O
•
O
O
•
H
37
36
Explanations which rationalise the stereochemical outcome
of the tandem radical cyclisation leading to the taxane ring
system 25/26 from the precursor 19 are manifold. Furthermore
the situation is not helped by the limited knowledge of the
structures of the reacting α-keto radicals [i.e. (Z)-30 or (E)-31]
and their facial selectivities in reactions with s-cis and s-trans
enone electrophores (i.e. 32 and 33). Nevertheless, simply on the
grounds of accessibility of reaction centres, the initial 12-endo-
trig macrocyclisation of 19 to 35 will take place most favourably
when the enone electrophore at C-1 assumes an axial orient-
ation, viz. 34. The bicyclic intermediate 35 can then adopt any
number of conformations depending on whether the α-keto
radical unit orientates itself (Z)- or (E)-, and whether the (E)-
enone electrophore has an s-trans or s-cis conformation. These
features will then determine the stereochemical outcomes of the
resulting 6-exo-trig transannulations. Thus, it seems most likely
that an alignment of centres presented by the conformation 36
will lead to the major C-1 β-taxane 25, whereas the conform-
ation reflected in structure 37 will produce the corresponding
C-1 α-taxane 26 (Scheme 5).16
With the establishment of a new and novel radical-mediated
macrocyclisation-transannulation strategy towards the taxanes,
we next decided to examine a variety of alternative precursors,
analogous to 19, in order to develop and explore the limits of
the method. We surmised that replacement of either of the
enone electrophores in 19 by alkynones, viz. 38 and 39a, would
have a beneficial effect on the efficacy of the cascade macro-
cyclisation-transannulation process and, in addition, lead to
more unsaturated taxane products thereby providing further
opportunities for synthetic transformations in the tricyclic
products. Thus, the iododienynedione positional isomers 38
and 39a were both synthesised starting from the substituted
ring-A precursor 13 using synthetic transformations similar to
those used to convert 13 into 19 (Schemes 6 and 7).
•
O
H
O
H
O
•
H
O
H
26
25
Scheme 5
when the ‘terminal’ alkynone 38 was treated with Bu3SnH–
AIBN it underwent a facile cascade 12-endo-dig macrocyclis-
ation (to 55) followed by a 6-exo-trig transannulation pro-
ducing the tricyclo[9.3.1.03,8]pentadecadienedione 56 in 45–60%
yield, as a 6:1 mixture of C-1 epimers (Scheme 8). The struc-
ture of 56 followed from analysis of its NMR spectroscopic
data and comparison with corresponding data recorded for the
analogues 25, 27, 28 and 29. Finally, the stereochemistry of 56
was secured from an X-ray crystal structure determination of
the 1,5-diol 57 produced from reduction of the dione 56 with
DIBAL; a view of the structure is shown in Fig. 1.
The differing outcomes of the attempted cascade cyclisations
of 19, 38 and 39a are surely intriguing, but attempts to rational-
ise the results using computer modelling and energy minimis-
ation data on little-known processes involving ill-defined
reactive intermediates were unrewarding.13 Although not
unknown, at the outset of our studies with 38 and 39a, alkynes
had been used less frequently than alkenes as electrophores
in radical macrocyclisations.17 The success we enjoyed in con-
verting 38 into 56 was not matched when we attempted an
ambitious double cyclisation from the enediynedione 59 in the
presence of Bu3SnH–AIBN when only the product 60 of
carbon–iodine bond reduction (~21%) was identified amongst
the products (cf. 39a → 39b).
When the ‘internal’ alkynone 39a was treated with Bu3SnH–
AIBN under the same conditions that were used to convert 19
into 25 it failed to undergo any intramolecular cyclisation at all,
and instead gave only the product of direct reduction of the
carbon–iodine bond, i.e. 39b (21%). To our satisfaction however,
The availability of a facile radical-based cascade process
allowing easy access to the functionalised taxane ring system 56
from the substituted A-ring precursor 38 encouraged us to
J. Chem. Soc., Perkin Trans. 1, 1998, 3181–3206
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O
O
O
O
I
38
39 a R = I
b R = H
R
OH
O
O
O
O
O
O
i
O
iv
iii
RO
13
Br
41
42
40
a R = Ac
b R = H
ii
O
O
O
O
OH
O
O
v
vii
vi
viii,ix
38
Br
Br
Br
45
xiv
44
43
OH
O
OH
OH
OH
OH
HO
AcO
xi
xiii
xii
x
13
Br
47
48
46
49
Scheme 6 Reagents, conditions and yields: i, (CH2OH)2, CSA, C6H6, room temp., 87%; ii, K2CO3, MeOH, room temp., 94%; iii, TPAP, NMO,
CH2Cl2, room temp., 88%; iv, nBuLi, 16, THF, Ϫ84 ЊC, 81%; v, TPAP, NMO, CH2Cl2, room temp., 81%; vi, CSA, THF, H2O, reflux, 89%; vii,
HCCMgBr, THF, room temp., 81%; viii, BaMnO4, CH2Cl2, room temp, 59%; ix, NaI, butan-2-one, reflux, 99%; x, HCCMgBr, THF, room temp.,
93%; xi, K2CO3, MeOH, room temp., 91%; xii, (ClCO)2, DMSO, Et3N, Ϫ60 ЊC, 58%; xiii, nBuLi, 16, THF, Ϫ84 ЊC, 75%; xiv, BaMnO4, CH2Cl2, room
temp., 51%.
O
O
OH
O
O
O
O
O
ii
iii
i
41
Cl
Cl
Cl
50
51
52
O
O
OH
O
iv
v
vi
39a
Cl
Cl
53
54
Scheme 7 Reagents, conditions and yields: i, Cl(CH2)3CCH, nBuLi, THF, Ϫ78 ЊC, 96%; ii, TPAP, NMO, CH2Cl2, room temp., 98%; iii, CSA, THF,
H2O, reflux, 98%; iv, H2C᎐CHMgCl, THF, room temp., 98%; v, TPAP, NMO, CH2Cl2, room temp., 89%; vi, NaI, butan-2-one, reflux, 94%.
᎐
examine some chemistry of 56 with a view to introducing the
C-8 angular methyl group and additional oxygenation in ring C
in the molecule. In the event, it rapidly became apparent that
we were going to have considerable problems introducing the
C-8-methyl into the taxane 56.18 This situation made us re-think
our overall strategy and we elected to overcome the problem by
examining the cascade cyclisations of the vinyl methyl substi-
tuted analogues 61 and 63 of 19, together with the exo-
methylene-containing substrates 65a and 66a. The syntheses we
employed to elaborate these substrates are summarised in
Schemes 9 and 10, and they used closely similar methods and
procedures to those we had developed earlier to prepare the
molecules 19 and 38; indeed the syntheses used some common
intermediates. Much to our chagrin however each of the sub-
strates led only to the products of direct reduction of their
carbon–iodine bonds, i.e. 62, 64, 65b and 66b on treatment with
Bu3SnH–AIBN. Whilst this outcome, in retrospect, was per-
haps not too surprising in view of the possibilities for facile
1,5-hydrogen abstraction processes by the precursor radical
centres in these substrates,19 there are clearly many additional
subtle stereoelectronic/energy features associated with the ease
or otherwise of cascade radical-mediated macrocyclisation-
3184
J. Chem. Soc., Perkin Trans. 1, 1998, 3181–3206

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O
OH
O
O
i
ii
53
Cl
Cl
67
68
iii
61
O
OH
O
O
iv,v
vi
52
Cl
Cl
69
70
vii
Fig. 1 X-Ray structure of compound 57.
63
O
H
H
Scheme 9 Reagents, conditions and yields: i, MeLiؒLiI, CuI, THF,
91%; ii, TPAP, NMO, CH2Cl2, room temp., 75%; iii, NaI, butan-2-one,
reflux, 93%; iv, HCCMgBr, THF, room temp., 94%; v, MeLiؒLiBr, CuI,
THF, 94%; vi, BaMnO4, CH2Cl2, room temp., 75%; vii, NaI, butan-2-
one, reflux, 98%.
Bu3SnH
AIBN
38
O
•
H
O
O
H
O
H
55
56
91 into 93 via 92 which was then oxidised to the aldehyde 94.
Addition of vinylmagnesium bromide to 94, followed by oxid-
ation of the resulting alcohol 95 using Dess–Martin periodin-
ane21 next produced the corresponding bromoenone 96 which
by bromine–iodine exchange then led to the target molecule 86a
(Scheme 12). The analogous (E)-alkene 87a was synthesised
from the cyclohexene ring A precursor 89 using the methods
and procedures collected in Scheme 13. Unfortunately, when
either of the iodotrienones 86a and 87a were treated separately
with Bu3SnH–AIBN the only products isolated were those of
direct reduction of the carbon–iodine bonds in the substrates,
i.e. 86b and 87b in 92 and 63% yield respectively.
Scheme 8
HO
O
H
OH
H
R
57
59 R = I
60 R = H
O
O
O
O
Experimental
General details
R
R
63 R = I
64 R = H
61 R = I
62 R = H
All melting points were determined on a Kofler hot-stage
apparatus and are uncorrected. Ultraviolet spectra were
recorded on a Philips PU 8700 spectrophotometer as solutions
in spectroscopic grade ethanol. Infrared spectra were obtained
using a Perkin-Elmer 1600 series FT-IR instrument either as
liquid films or as dilute solutions in spectroscopic grade chloro-
form. Proton NMR spectra were recorded on either a Bruker
WM 250 (250 MHz), a Bruker AM 400 (400 MHz) or a JEOL
EX-270 (270 MHz) spectrometer as dilute solutions in
deuteriochloroform. The chemical shifts are recorded relative to
trimethylsilane as internal standard and the multiplicity of a
signal is designated by one of the following abbreviations: s,
singlet; d, doublet; t, triplet; q, quartet; quin, quintet; br, broad;
m, multiplet; app., apparent; obsc., obscured. All coupling con-
stants, J, are reported in hertz. Carbon-13 NMR spectra were
recorded on either a Bruker AM 400 (at 100.6 MHz) or a JEOL
EX-270 (at 68 MHz) instrument. The spectra were recorded as
dilute solutions in deuteriochloroform with chemical shifts
reported relative to internal chloroform standard in a broad
band decoupled mode, and the multiplicities obtained using a
MeO
O
MeO
O
R
R
65a R = I
b R = H
66a R = I
b R = H
transannulation processes from the precursors 19, 38, 39a, 59,
61, 63, 65a and 66a, leading to the corresponding taxane ring
systems, which seem beyond our comprehension at this time.
At the outset of our studies on the radical cascade macro-
cyclisation-transannulation to taxanes shown by the sequences
5 → 4 → 3 → 2 we were aware that the same B/C ring
juncture in 2 could be disconnected by alternative radical-
mediated retro macrocyclisation-transannulation strategies
including the one shown in Scheme 11. In contemporaneous
studies we therefore examined the scope for this alternative
strategy, and decided to synthesise specific geometrical isomers
of the model compounds 86a and 87a. The molecules were
prepared starting from the same substituted cyclohexene 89
produced by way of a Diels–Alder reaction between the diene
88 and acrolein. Thus, a Wittig reaction between 89 and the
phosphonium salt 9020 using sodium hexamethyldisilylazide as
base in THF at 0 ЊC first led to the (Z)-alkene 91. A series of
functional group manipulations next allowed the conversion of
1
DEPT sequence. Where required, assignments for H and 13C
NMR spectra were confirmed by two dimensional homo-
nuclear (1H–13C) correlation spectroscopy. Matrix dimensions
for two dimensional spectra were either 1024 points × 256
columns (homonuclear 1H) or 2048 points × 128 columns
(heteronuclear 1H–13C), and were recorded on a JEOL EX-270
instrument or a Bruker AM 400 (400 MHz). Mass spectra were
J. Chem. Soc., Perkin Trans. 1, 1998, 3181–3206
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ii
i
OTBDPS
OTBDPS
OTBDPS
Br
R
71
72
73
a R = CHO
b R = CH2OH
c R = CH2Br
iii
iv
O
viii
v
vi
AcO
OH
RO
OTBDMS
OTBDMS
13
76
74
75
a R = Ac
b R = H
vii
MeO
HO
OR
OTBDMS
ix
x
73c
OTBDPS
OTBDPS
77
78
a R = TBDMS
b R = H
xi
MeO
MeO
MeO
O
O
OH
xiv
xii
xiii
xvii
65a
OTBDPS
OR
OTBDPS
81
79
80
a R = TBDPS
b R = H
c R = Ts
xv
xvi
xvii
MeO
MeO
OH
O
xxi
xix
66a
OTBDPS
OR
xx
82
83
a R = TBDMS
b R = H
t
Scheme 10 Reagents, conditions and yields: i, 9-BrBBN, CH2Cl2, 0 ЊC; H2O2, 0 ЊC; 95%; ii, BuLi, DMF, Et2O, Ϫ110 ЊC, 82%; iii, NaBH4,
CeCl3ؒ7H2O, MeOH, 0 ЊC, 99%; iv, NBS, PPh3, CH2Cl2, room temp., 99%; v, NaBH4, MeOH, Et2O, 0 ЊC, 98%; vi, TBDMSCl, DMAP, Et3N, CH2Cl2,
room temp., 94%; vii, K2CO3, MeOH, room temp., 95%; viii, TPAP, NMO, CH2Cl2, room temp., 97%; ix, SnCl2, NaI, 73c, DMF, room temp., 82%; x,
KHMDS, (MeO)2SO2, Ϫ78 ЊC to room temp., 97%; xi, PPTS, MeOH, room temp., 88%; xii, Dess–Martin, CH2Cl2, room temp., 94%; xiii,
H2C᎐CHMgCl, THF, room temp., 94%; xiv, Dess–Martin, CH2Cl2, room temp., 86%; xv, TBAF, PTSA, THF, room temp., 97%; xvi, TsCl, Et3N,
᎐
CH2Cl2, room temp., 79%; xvii, NaI, butan-2-one, reflux, 93%; xviii, HCCMgCl, THF, room temp., 97%; xix, Dess–Martin, CH2Cl2, room temp.,
93%; xx, TBAF, PTSA, THF, room temp., 93%; xxi, I2, PPh3, imidazole, room temp., 56%.
recorded on AE1 MS-902 or MM-701CF spectrometers using
electron ionisation (EI) techniques. Microanalytical data were
obtained on a Perkin-Elmer 240B elemental analyser.
removed on a Buchi rotary evaporator. Where necessary, reac-
tions requiring anhydrous conditions were performed in a
flame- or oven-dried apparatus under a nitrogen or argon
atmosphere. A Buchi GKR-50 Kugelrohr apparatus was used
for bulb-to-bulb distillations.
Flash chromatography was performed on Merck silica gel 60
as the stationary phase and the solvents employed were either
of analytical grade or were distilled before use. All reactions
were monitored by TLC using Merck silica gel 60 F254 pre-
coated aluminium backed plates which were visualised with
ultraviolet light and then with either acidic alcoholic vanillin
solution, basic potassium permanganate solution, or phos-
phomolybdic acid. Ether refers to diethyl ether and light petrol-
eum to the fraction of bp 40–60 ЊC.
Routinely, dry organic solvents were stored under nitrogen
and/or over sodium wire. Other organic solvents were dried by
distillation from the following: THF (sodium benzophenone
ketyl), dichloromethane (calcium hydride) and methanol (mag-
nesium methoxide). Other organic solvents and reagents were
purified by the accepted literature procedures. Solvent was
Tetra(n-propyl)ammonium perruthenate/4-methylmorpholine
N-oxide oxidations. General procedure
Tetra(n-propyl)ammonium perruthenate (0.05 equiv.) was
added portionwise over 5 min to a stirred suspension of the
alcohol (1 equiv.), 4-methylmorpholine N-oxide (1.2 equiv.) and
dried powdered 4 Å molecular sieves (0.5 g per mmol) in dry
dichloromethane (0.5 M) at 0 ЊC under nitrogen. The suspen-
sion was allowed to warm to room temperature where it was
stirred for 1 h and then purified directly by chromatography on
silica, eluting with 20% ether in light petroleum (bp 40–60 ЊC),
to give the oxidation product (51–99%) as a colourless oil.
3186
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Preparation of alkyl iodides by Finkelstein exchange. General
procedure
temperature for 8 h over 20% aqueous potassium fluoride (5 ml).
The organic layer was separated and then dried and evaporated
in vacuo to a yellow oil which was purified by chromatography
on silica, eluting with 20% ether in light petroleum (bp 40–
60 ЊC), to give the reduced products.
A stirred suspension of the bromide (1 equiv.), sodium iodide (3
equiv.) and butan-2-one (0.1 M) was heated at reflux for 90 min
and then cooled. Water (20 ml) and ether (20 ml) were added
and the organic layer was then separated, dried and evaporated
in vacuo to leave the iodide (89–99%) as a pale yellow oil.
1-Bromo-2,2,3,3-tetramethylcyclopropane-1-carboxylic acid
7. A solution of n-butyllithium (127 ml) in hexanes (1.6 M, 0.20
mol) was added dropwise over 25 min to a stirred solution of
the dibromide 69 (52.0 g, 0.20 mol) in THF (750 ml) at Ϫ78 ЊC
under nitrogen and the mixture was then stirred at Ϫ78 ЊC for
10 min. Carbon dioxide gas was bubbled through the mixture
for 3 h and the mixture was then allowed to return to room
temperature. The mixture was quenched with water (15 ml) and
then concentrated in vacuo to ~50 ml. Ether (150 ml) was added
and the organic layer was separated, washed with aqueous
hydrochloric acid (2 M, 50 ml) and extracted with saturated
aqueous sodium hydrogen carbonate (2 × 150 ml). The com-
bined basic extracts were acidified to pH 1 with hydrochloric
acid (2 M) and extracted with dichloromethane (2 × 150 ml).
The dried organic extracts were concentrated in vacuo to leave
the acid (38.6 g, 82%) as a white solid, mp 162–164 ЊC (from
pentane); νmax(CHCl3)/cmϪ1 3180, 1716 and 957; δH(250 MHz)
1.19 (s, 6H, Me), 1.18 (s, 6H, Me); δC(67.8 MHz) 173.8 (s), 49.5
(s), 28.1 (s), 21.5 (q), 19.1 (q) (Found: Mϩ Ϫ Me, 204.9858.
C7H10BrO2 requires M, 204.9864) (Found: C, 43.5; H, 5.9.
C8H13BrO2 requires C, 43.7; H, 6.1%).
Reductive radical reactions of alkyl iodides. General procedure
A solution of tri-n-butyltin hydride (1.1 equiv.), and azoiso-
butyronitrile (0.05 equiv.) in dry benzene (5 ml) was added
dropwise over 4 h to a stirred, refluxing solution of the iodide (1
equiv.) and azoisobutyronitrile (0.02 equiv.) in dry, degassed
benzene (3 mM), under argon. The mixture was held at reflux
for a further 4 h and then cooled and concentrated in vacuo. The
residue was taken up in ether (10 ml) and then stirred at room
•
C
B
H
O
H
84
3-Carboxy-2,4-dimethylpenta-2,4-diene 8. A stirred mixture
of the cyclopropanecarboxylic acid 7 (14.0 g, 63.3 mmol) and
silver acetate (15.9 g, 95.0 mmol) in glacial acetic acid (150 ml)
was heated to 120 ЊC for 45 min. The cooled mixture was
diluted with ether (200 ml) and then filtered through kieselguhr.
The filtrate was concentrated in vacuo and the residue was redis-
solved in ether (50 ml) and extracted with saturated aqueous
sodium hydrogen carbonate (2 × 50 ml). The combined basic
extracts were acidified to pH l with aqueous hydrochloric acid
(2 M) and extracted with dichloromethane (3 × 50 ml). The
combined organic extracts were dried and concentrated in
vacuo to leave the acid (6.7 g, 76%) as white crystals, mp 54–
55 ЊC (from pentane); λmax(EtOH)/nm 222 (ε/dm3 molϪ1 cmϪ1
6 600); νmax(CHCl3)/cmϪ1 3176, 1688, 1671, 1309 and 905;
R
•
86
a R = I
b R = H
85
O
R
OAc
87
a R = I
b R = H
δ (250 MHz) 5.13 (br s, 1H, ᎐CHH), 4.77 (br s, 1H, ᎐CHH),
᎐
᎐
H
2.13 (s, 3H, Me), 1.89 (s, 3H, Me), 1.88 (s, 3H, Me);
δC(67.8 MHz) 173.8 (s), 150.1 (s), 143.2 (s), 130.6 (s), 116.5 (t),
Scheme 11
O
RO
AcO
AcO
iii
ii
OTBDMS
I
– Ph3P+
OTBDMS
88
89
90
91
a R = H
b R = Ac
i
O
AcO
HO
vi
vii
iv
Br
R
Br
92
94
93
a R = OH
b R = Br
v
viii
ix
x
86a
OH
Br
O
Br
96
95
Scheme 12 Reagents, conditions and yields: i, AcCl, DMAP, Et3N, CH2Cl2, room temp., 78%; ii, H2C᎐CHCHO, BF3ؒOEt2, C6H5CH3, Ϫ50 ЊC, 74%;
᎐
iii, NaHMDS, 90, THF, 0 ЊC, 74%; iv, TBAF, THF, room temp., 91%; v, CBr4, PPh3, CH2Cl2, room temp., 74%; vi, DIBAL-H, THF, Ϫ20 ЊC, 74%;
vii, TPAP, NMO, CH2Cl2, room temp., 73%; viii, H2C᎐CHMgBr, THF, Ϫ78 ЊC, 47%; ix, Dess–Martin, CH2Cl2, room temp., 99%; x, NaI, butan-2-
᎐
one, reflux, 98%.
J. Chem. Soc., Perkin Trans. 1, 1998, 3181–3206
3187

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O
O
O
O
RO
O
O
O
iv
iii
i
89
OR
99
98
97
a R = Ac
b R = H
ii
OR
O
I
v, vi
vii
viii
TIPSO
TIPSO
TIPSO
PMBO
100
101
102
a R = H
b R = Ac
ix
OAc
OAc
OAc
R
xii
x
xiv
xiii
87a
O
OH
TIPSO
Br
Br
103
104
105
a R = OH
b R = Br
xi
Scheme 13 Reagents, conditions and yields: i, (CH2OH)2, CSA, C6H6, reflux, 93%; ii, DIBAL-H, THF, Ϫ20 ЊC, 73%; iii, TPAP, NMO, CH2Cl2, room
temp., 94%; iv, CeCl3, H2C᎐CHMgBr, THF, Ϫ78 ЊC, 74%; v, CSA, THF, H2O, 60 ЊC; vi, TIPSCl, 2,6-lutidine, CH2Cl2, Ϫ20 ЊC, 91%; vii, CHI3,
᎐
chromous chloride, THF, room temp., 64%; viii, PMBO(CH2)2CHO; DMSO, chromous chloride, NiCl2, THF, 31%; ix, Ac2O, DMAP, Et3N, CH2Cl2,
0 ЊC, 92%; x, DDQ, H2O, CH2Cl2, room temp., 85%; xi, CBr4, PPh3, CH2Cl2, 0 ЊC, 96%; xii, HF, CH3CN, room temp., 79%; xiii, Dess–Martin,
CH2Cl2, room temp., 81%; xiv, NaI, butan-2-one, reflux, 89%.
24.6 (q), 23.6 (q), 23.0 (q) (Found: Mϩ, 140.0825. C8H12O2
requires M, 140.0837) (Found: C, 68.6; H, 8.6. C8H12O2
requires C, 68.5; H, 8.9%).
g, 22.9 mmol), 4-dimethylaminopyridine (20 mg, 0.16 mmol)
and the diene alcohol 11 (1.92 g, 15.2 mmol) in dry dichloro-
methane (100 ml) was stirred at room temperature for 18 h. The
mixture was quenched with water (25 ml), and the organic layer
was then separated and washed with saturated aqueous sodium
hydrogen carbonate (25 ml) and brine (25 ml). The dried
organic extracts were then concentrated in vacuo to leave the
acetate (2.4 g, 95%) as a colourless oil; λmax(EtOH)/nm 224
(ε/dm3 molϪ1 cmϪ1 3 500); νmax(film)/cmϪ1 1741, 1633 and 898;
2,4-Dimethyl-3-(hydroxymethyl)penta-2,4-diene 11.4b A mix-
ture of the diene acid 8 (10.1 g, 72 mmol), potassium carbonate
(25 g, 170 mmol) and methyl iodide (102 g, 720 mmol) in dry
acetone (200 ml) was stirred at room temperature for 24 h. The
mixture was filtered and the filtrate was evaporated in vacuo and
the residue redissolved in dichloromethane (100 ml). The mix-
ture was refiltered and the filtrate was concentrated in vacuo to
leave an oil which was distilled under vacuum to give 3-methoxy-
carbonyl-2,4-dimethylpenta-2,4-diene (8.0 g, 73%) as a colour-
less oil, bp 69–71 ЊC/12mm Hg; λmax(EtOH)/nm 222 (ε/dm3
molϪ1 cmϪ1 6 500); νmax(film)/cmϪ1 1718, 1627 and 901; δH(250
δ (250 MHz) 5.01 (br s, 1H ᎐CHH), 4.68 (br s, 3H, CH OAc
᎐
H
2
and ᎐CHH), 2.06 (s, 3H, COMe), 1.81 (s, 3H, Me), 1.80 (s, 3H,
᎐
Me), 1.78 (s, 3H, Me); δC(67.8 MHz) 171.1 (s), 144.8 (s), 133.2
(s), 131.4 (s), 114.4 (t), 63.0 (t), 22.6 (q), 22.0 (q), 21.0 (q), 19.8
(q) (Found: Mϩ Ϫ AcOH, 108.0941. C8H12 requires M,
108.0939) (Found C, 71.4; H, 10.0. Calc. for C10H16O2: C, 71.4;
H, 9.6%); which was used without further purification. The
diene acetate was also prepared according to the procedure
published by Nicolaou et al.4b
Ethyl 3-methyl-2-(1-oxoethyl)but-2-enoate 9. The title enone
was prepared from ethyl acetoacetate according to the pro-
cedure described by Alkonyi et al.22 and showed: νmax(film)/cmϪ1
1723, 1699 and 1632; δH(250 MHz) 4.20 (q, 2H, J 7 Hz,
MHz) 5.08 (br s, 1H, CHH), 4.74 (br s, 1H, ᎐CHH), 3.68 (s,
᎐
3H, OMe), 1.98 (s, 3H, Me), 1.80 (s, 6H, Me); δC(67.8 MHz)
159.3 (s), 137.3 (s), 136.1 (s), 125.1 (s), 112.2 (t), 53.9 (q), 28.6
(q), 28.6 (q), 27.6 (q) (Found: Mϩ, 154.1003. C9H14O2 requires
M, 154.0994).
A solution of diisobutylaluminium hydride (91.0 ml) in tolu-
ene (1 M, 91.0 mmol) was added dropwise over 20 min to a
stirred solution of the diene ester from above (7.0 g, 45.5 mmol)
in dry toluene (250 ml) at Ϫ60 ЊC under nitrogen. The mixture
was stirred for 2 h and then allowed to warm to 0 ЊC where it
was quenched with water (25 ml) and aqueous hydrochloric
acid (2 M, 50 ml). The organic layer was separated, dried and
concentrated in vacuo to leave a yellow oil. Purification by
chromatography on silica, eluting with 30% ether in pentane,
gave the alcohol 11 (5.2 g, 92%) as a colourless oil; λmax(EtOH)/
nm 225 (ε/dm3 molϪ1 cmϪ1 3 400); νmax(film)/cmϪ1 3349, 1632
and 894; δ (250 MHz) 5.07 (br s, 1H, ᎐CHH), 4.70 (br s, 1H,
CH CH O), 2.25 (s, 3H, CH C᎐), 2.09 (s, 3H, CH C᎐), 1.95 (s,
᎐
᎐
3
3
2
3
3H, CH3CO), 1.25 (t, 3H, J 7 Hz, CH3CH2O); δC(67.8 MHz)
200.4 (s), 165.8 (s), 153.2 (s), 132.1 (s), 60.7 (t), 30.6 (q), 23.3 (q),
22.9 (q), 14.0 (q) (Found: Mϩ, 170.0931. C9H14O3 requires M,
170.0943) (Found: C, 63.3; H, 8.5. Calc. for C9H14O3: C, 63.5;
H, 8.3%).
Ethyl 2-(1-hydroxy-1-methylethyl)-3-methylbut-2-enoate 10.
The title alcohol was prepared from 9 according to the pro-
cedure published by Nicolaou et al.4b and showed: λmax(EtOH)/
nm 231 (ε/dm3 molϪ1 cmϪ1 2 100); νmax(film)/cmϪ1 3480, 1719
and 1648; δH(250 MHz) 4.14 (q, J 7 Hz, 2H, CH3CH2O), 2.59
(br, 1H, OH), 1.85 (s, 3H, Me), 1.61 (s, 3H, Me), 1.38 (s, 6H,
2 × Me), 1.23 (t, J 7 Hz, 3H, CH3CH2O); δC(67.8 MHz) 171.1
(s), 137.7 (s), 133.3 (s), 71.4 (s), 60.5 (t), 30.1 (q), 24.0 (q), 20.8
(q), 14.3 (q) (Found: Mϩ Ϫ H2O, 168.1204. C10H16O2 requires
M, 168.1150) (Found: C, 64.1; H, 9.7; Calc. for C10H18O3: C,
64.5; H, 9.7%).
᎐
H
᎐CHH), 4.05 (s, 2H, CH OH), 1.82 (s, 3H, Me), 1.76 (s, 3H,
᎐
2
Me), 1.72 (s, 3H, Me); δC(67.8 MHz) 144.8 (s), 135.9 (s), 129.5
(s), 114.25 (t), 60.1 (t), 22.4 (q), 21.6 (q), 19.1 (q) (Found: Mϩ,
126.1043. C8H14O requires M, 126.1044). The diene alcohol was
also prepared by the modified procedure published by Nicolaou
et al.4b
2,4-Dimethyl-3-(acetoxymethyl)penta-2,4-diene 12.4b A solu-
tion of acetyl chloride (1.79 g, 22.9 mmol), triethylamine (1.54
3188
J. Chem. Soc., Perkin Trans. 1, 1998, 3181–3206

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1-Acetoxymethyl-2,6,6-trimethylcyclohex-1-ene-5-carbox-
aldehyde 13. Acrolein (2.0 g, 35 mmol) was added in one por-
tion to a stirred solution of boron trifluoride–diethyl ether (5.4
g, 35 mmol) in dry toluene (150 ml) at Ϫ78 ЊC under nitrogen.
After 5 min, a solution of the diene 12 (4.0 g, 24 mmol) in
toluene (10 ml) was added dropwise over 15 min and the mix-
ture was then stirred at Ϫ78 ЊC for 10 h. The mixture was
quenched at Ϫ78 ЊC with water (50 ml) and pentane (100 ml),
and was then allowed to return to room temperature. The
organic layer was separated, dried and evaporated in vacuo to
leave a yellow oil. Purification by chromatography on silica elut-
ing with 20% ether in pentane gave the aldehyde (4.2 g, 79%) as
a colourless liquid; νmax(film)/cmϪ1 1736, 1658 and 954; δH(250
MHz) 9.86 (d, J 3 Hz, 1H, CHO), 4.62 (s, 2H, CH2OAc), 2.23
(app. dt, J 10, 3 Hz, 1H, CHCHO), 2.12 (app. t, J 6 Hz, 2H,
᎐CHCH ), 6.12–5.70 (m, 1H, SnCH᎐), 3.65 (t, J 7 Hz,
᎐ ᎐
2
CH2OH), 2.34–2.15 (m, 2H), 2.04–1.90 (m, 2H), 1.68–1.20 (m,
12H), 0.98–0.85 (m, 15H); δC(67.8 MHz) 147.0 (d), 129.8 (d),
36.0 (t), 33.0 (t), 32.8 (t), 31.8 (t), 29.2 (t), 29.1 (t), 29.0 (t), 28.9
(t), 27.3 (t), 27.2 (t), 13.7 (q) 10.2 (t) (Found: Mϩ Ϫ C4H8,
321.1166. C13H28OSn requires M, 320.1162).
A solution of triphenylphosphine (5.25 g, 13.3 mmol) in dry
dichloromethane (10 ml) was added dropwise over 15 min to an
ice-cold, stirred solution of carbon tetrabromide (6.63 g, 20.0
mmol) and the alcohol from above (5.00 g, 13.3 mmol) in dry
dichloromethane (25 ml) under nitrogen. The mixture was
stirred for a further 5 min and then concentrated in vacuo to
leave a residue which was triturated with pentane. The resulting
suspension was filtered and the filtrate was evaporated in vacuo
to leave a residue which was distilled at reduced pressure to give
a 6:1 mixture of (E)- and (Z)-isomers of the bromide (4.8 g,
82%) as a colourless oil, bp 103–105 ЊC/0.1mm Hg. Data for
(E)-isomer only: νmax(film)/cmϪ1 1599 and 747; δH(250 MHz)
6.53 (dt, J 12, 7 Hz, ᎐CHCH ), 6.12–5.70 (m, 1H, SnCH᎐), 3.42
᎐CCH ), 2.06 (s, 3H, COMe), 1.95 (m, 2H, CH ), 1.71 (s, 3H,
᎐
2
2
Me), 1.22 (s, 3H, Me), 1.07 (s, 3H, Me); δC(67.8 MHz) 205.7 (d),
171.3 (s), 136.5 (s), 131.5 (s), 60.2 (t), 56.8 (d), 36.3 (t), 30.8 (q),
27.2 (s), 23.5 (q), 21.0 (q), 19.7 (q), 19.6 (t) (Found: Mϩ Ϫ
AcOH, 164.1202. C11H16O requires M, 164.1201) (Found: C,
69.2; H, 9.4. C13H20O3 requires C, 69.6; H, 9.0%).
᎐
᎐
2
(t, J 7 Hz, 2H, CH2Br), 2.34–2.15 (m, 2H), 2.04–1.90 (m, 2H),
1.68–1.20 (m, 12H), 0.98–0.85 (m, 15H); δC(67.8 MHz) 148.6
(d), 148.2 (d), 128.6 (d), 128.0 (d), 62.3 (t), 34.0 (t), 33.3 (t), 32.7
(t), 31.7 (t), 29.2 (t), 29.1 (t), 29.0 (t), 28.8 (t), 27.6 (t), 27.3 (t),
27.2 (t), 26.7 (t), 13.6 (q), 10.1 (t) and 9.3 (t) (Found:
Mϩ Ϫ C4H8, 381.0348. C13H27BrSn requires M, 381.0348).
1-[(E)-6-Bromo-1-hydroxyhex-2-enyl]-2,6,6-trimethyl-5-(1-
hydroxyprop-2-enyl)cyclohex-1-ene 17a. A solution of n-butyl-
lithium (1.68 ml) in hexanes (1.6 M, 2.69 mmol) was added
dropwise over 15 min to a stirred solution of the vinylstannane
16 (1.26 g, 2.88 mmol) in dry THF (10 ml) at Ϫ78 ЊC under
nitrogen. The mixture was stirred at Ϫ78 ЊC for 1 h and then a
solution of the freshly purified aldehyde 15a (0.18 g, 0.85 mmol)
in dry THF (2 ml) was added dropwise over 5 min. The mixture
was stirred at Ϫ78 ЊC for a further 30 min and then quenched
with water (10 ml) and ether (20 ml) and allowed to warm to
room temperature. The organic layer was separated and washed
with brine (25 ml). Evaporation of the dried organic extracts in
vacuo left a yellow oil which was purified by chromatography on
silica eluting with 50% ether in pentane to give a mixture of
diastereoisomers of the diol (0.18 g, 58%) as a colourless oil.
Data for one diastereoisomer: νmax(film)/cmϪ1 3431, 1709 and
1-Hydroxymethyl-5-(1-hydroxyprop-2-enyl)-2,6,6-trimethyl-
cyclohex-1-ene 14a. A solution of vinylmagnesium bromide
(70.8 ml) in THF (1 M, 70.8 mmol) was added dropwise over 15
min to a stirred solution of the aldehyde 13 (4.0 g, 17.7 mmol)
in dry THF (250 ml) at Ϫ78 ЊC under nitrogen. The mixture
was allowed to return to room temperature over 5 h where it
was stirred for a further 2 h. The mixture was cooled to 0 ЊC
and then quenched with saturated aqueous ammonium chlor-
ide (50 ml) and ether (200 ml). The organic layer was separated
and the aqueous layer was re-extracted with ether (2 × 50 ml).
The combined organic extracts were washed with brine (200
ml), dried and concentrated in vacuo to leave a yellow oil. Puri-
fication by chromatography on silica eluting with 25% pentane
in ether gave the diol (3.1 g, 84%) as a colourless oil which
crystallised on standing, mp 78–80 ЊC (from pentane);
νmax(film)/cmϪ1 3392, 3084, 1642, 1367, 1092 and 986; δH(250
MHz) 5.90 (ddd, J 16, 11, 5 Hz, 1H, CH᎐CH ), 5.26 (d, J 16 Hz,
᎐
2
1H, ᎐CHH), 5.14 (d, J 11 Hz, 1H, ᎐CHH), 4.48–4.45 (m, 1H,
᎐
᎐
CHCHOH), 4.18 (d, J 14 Hz, 1H, CH2OH), 4.10 (d, J 14 Hz,
1H, CH OH), 2.12 (br s, OH), 2.06 (app. t, J 6 Hz, 2H, ᎐CCH ),
᎐
2
2
1.77 (s, 3H, Me), 1.68–1.20 (m, 3H), 1.14 (s, 3H, Me), 1.08 (s,
3H, Me); δC(67.8 MHz) 142.1 (d), 137.9 (s), 133.9 (s), 113.4 (t),
71.1 (d), 58.7 (t), 49.5 (d), 37.6 (s), 32.5 (t), 27.1 (q), 23.1 (q),
19.8 (q), 17.5 (t) (Found: Mϩ Ϫ H2O, 192.1515. C13H20O
969; δ (250 MHz) 5.90 (ddd, J 16, 11, 5 Hz, 1H, CH᎐CH ), 5.78
᎐
H 2
(dd, J 16, 7 Hz, 1H, CH CH᎐CH), 5.58 (dt, J 16, 7 Hz, 1H,
᎐
2
CH CH᎐CH), 5.24 (d, J 16 Hz, 1H, ᎐CHH), 5.12 (d, J 11 Hz,
᎐
᎐
2
1H, ᎐CHH), 4.80 (d, J 7 Hz, 1H, CHOH), 4.46 (br d, J 5 Hz,
᎐
requires M, 192.1514) (Found: C, 74.2; H, 11.0; C13H22O2
requires C, 74.2; H, 10.5%).
1H, CHOH), 3.38 (t, J 7 Hz, 2H, CH2Br), 2.20 (app. q, J 7 Hz,
2H, CH CH᎐), 2.02–1.86 (m, 2H, ᎐CCH ), 1.78 (s, 3H, Me),
᎐
᎐
2
2
1-Formyl-5-(1-hydroxyprop-2-enyl)-2,6,6-trimethylcyclohex-
1-ene 15a. Treatment of a solution of the diol 14a (1.08 g, 5.1
mmol) in dry dichloromethane with tetra(n-propyl)ammonium
perruthenate and 4-methylmorpholine N-oxide, according to
the general procedure, gave the title aldehyde (0.55 g, 51%) as a
colourless oil; νmax(film)/cmϪ1 3467, 1670, 1610 and 735; δH(250
MHz) 10.11 (s, 1H, CHO), 5.92 (ddd, J 17, 11, 5 Hz, 1H,
1.75–1.26 (m, 5H), 1.22 (s, 3H, Me), 1.02 (s, 3H, Me); δC(67.8
MHz) 141.8 (d), 139.4 (s), 134.3 (d), 133.5 (s), 128.1 (d), 113.5
(t), 71.4 (d), 70.6 (d), 49.8 (d), 38.4 (s), 33.5 (t), 33.2 (t), 32.0 (t),
30.5 (t), 27.2 (q), 22.7 (q), 21.3 (q), 17.5 (t) (Found: Mϩ Ϫ H2O,
340.1266. C18H27BrO requires M, 340.1262).
6-(6-Bromo-hex-2-enylidene)-3-ethenyl-2-oxa-1,5,5-trimethyl-
bicyclo[2.2.2]octane 20. A solution of the diol 17a in deuterated
chloroform was evaporated, and the residue was kept at Ϫ5 ЊC
for 12 h to afford the bicyclic ether as a colourless oil; δH(250
CH᎐CH ), 5.29 (d, J 17 Hz, 1H, ᎐CHH), 5.16 (d, J 11 Hz, 1H,
᎐
᎐
2
᎐CHH), 4.58 (br d, J 5 Hz, 1H, CHOH), 2.30–2.25 (m, 2H,
᎐
᎐CCH ), 2.22 (s, 3H, Me), 1.78–1.48 (m, 3H), 1.33 (s, 3H, Me),
MHz) 7.36 (dd, J 16, 11 Hz, 1H, CH᎐CHCH), 6.70 (ddd, J 16,
᎐
᎐
2
1.32 (s, 3H, Me); δC(67.8 MHz) 192.1 (d), 156.3 (s), 141.7 (s),
140.6 (d), 113.6 (t), 70.2 (d), 50.3 (d), 36.6 (s), 35.7 (t), 26.5 (q),
21.8 (q), 19.5 (q), 16.8 (t) (Found: Mϩ, 208.1451. C13H20O2
requires M, 208.1463); which was used immediately.
11, 6 Hz, 1H, CH᎐CH ), 6.64 (d, J 11 Hz, 1H, CH᎐C), 6.56 (dt,
᎐ ᎐
2
J 16, 7 Hz, 1H, CH CH᎐CH), 6.16 (d, J 16 Hz, 1H, ᎐CHH),
᎐
᎐
2
5.94 (d, J 11 Hz, 1H, ᎐CHH), 4.60 (br s, 1H, CHOR), 3.44 (t,
᎐
J 7 Hz, 2H, CH Br), 2.30 (q, J 7 Hz, 2H, CH CH᎐), 2.00–1.50
᎐
2
2
(E)-1-Tributylstannyl-5-bromopent-1-ene 16. A stirred mix-
ture of pent-4-yn-1-ol (3.0 g, 36 mmol), tributyltin hydride
(13.5 g, 46.4 mmol) and azoisobutyronitrile (20 mg) was heated
to 80 ЊC for 2 h under nitrogen. The cooled mixture was puri-
fied by dry column chromatography eluting with 25% ether in
pentane to give a mixture of (E)- and (Z)-isomers (6:1 ratio) of
the (E)-1-tributylstannylpent-1-en-5-ol (11.8 g, 88%) as a col-
ourless liquid.11 Data for (E)-isomer only: νmax(film)/cmϪ1 3328,
1600 and 1070; δH(250 MHz) 6.53 (dt, J 12, 7 Hz, 1H,
(m, 5H), 1.47 (s, 3H, Me), 1.40 (s, 3H, Me), 1.26 (s, 3H, Me);
δC(67.8 MHz) 149.6 (s), 140.1 (d), 132.6 (d), 128.7 (d), 120.6 (d),
114.4 (t), 73.9 (d), 73.2 (s), 44.9 (d), 37.3 (s), 33.2 (t), 33.0 (t),
32.0 (t), 31.2 (t), 28.4 (q), 27.6 (q), 24.3 (q) and 15.7 (t) (Found:
Mϩ, 338.1266. C18H27BrO requires M, 340.1262).
1-[(E)-6-Bromo-1-oxohex-2-enyl]-2,6,6-trimethyl-5-(1-oxo-
prop-2-enyl)cyclohex-1-ene 18. A mixture of the diol 17a (38
mg, 0.11 mmol) and barium manganate (0.27 g, 1.1 mmol) in
dry dichloromethane (10 ml) was stirred at room temperature
J. Chem. Soc., Perkin Trans. 1, 1998, 3181–3206
3189

View Article Online
for 24 h. The mixture was filtered through kieselguhr and the
filtrate was evaporated in vacuo to leave the enone (34 mg, 90%)
as a colourless oil; λmax(EtOH)/nm 235 (ε/dm3 molϪ1 cmϪ1
13 000); νmax(film)/cmϪ1 1675, 1645 and 985; δH(250 MHz) 6.96
dichloromethane (50 ml) and then washed with water (100 ml).
The aqueous layer was extracted with dichloromethane (2 × 50
ml) and then the combined organic layers were washed with
saturated aqueous ammonium chloride (100 ml) and water (100
ml), dried (MgSO4), and evaporated to dryness in vacuo to leave
a yellow oil. Purification by chromatography on silica eluting
with 25% ether in light petroleum (bp 40–60 ЊC) gave two
diastereoisomers of the corresponding MOM ether (6.5 g, 91%)
as a pale yellow oil; (data for one diastereoisomer): νmax(film)/
cmϪ1 1736, 953, 920 and 733; δH(250 MHz) 5.81 (ddd, J 17, 10,
(dt, J 16, 7 Hz, 1H, CH CH᎐CH), 6.42 (dd, J 16, 11 Hz, 1H,
᎐
2
CH᎐CH ), 6.22 (d, J 16 Hz, 1H, ᎐CHH), 6.35 (d, J 16 Hz, 1H,
᎐
᎐
2
CH᎐CHCO), 5.74 (d, J 11 Hz, 1H, ᎐CHH), 3.41 (t, J 7 Hz, 2H,
᎐
᎐
CH2Br), 2.86 (app. t, J 7 Hz, 1H, CHCO), 2.43 (app. q, J 7 Hz,
2H, CH CH᎐), 2.22–1.80 (m, 6H), 1.52 (s, 3H, Me), 1.14 (s, 3H,
᎐
2
Me), 1.02 (s, 3H, Me); δC(67.8 MHz) 200.5 (s), 199.5 (s), 147.8
(d), 137.0 (s), 134.9 (d), 132.0 (d), 128.0 (s), 125.7 (t), 51.7 (d),
33.7 (s), 30.5 (t), 28.8 (t), 28.7 (t), 27.2 (q), 26.9 (t), 22.0 (q), 19.2
(t), and 19.2 (q) (Found: Mϩ, 352.0912. C18H25BrO2 requires M,
352.0924).
7 Hz, 1H, CHOMOMCH᎐CH ), 5.20–5.14 (m, 2H, CH᎐CH ),
᎐
᎐
2
2
4.67 (d, J 7 Hz, 1H, OCHHOCH3), 4.58 (s, 2H, AcOCH2), 4.50
(d, J 7 Hz, 1H, OCHHOCH3), 4.24 (d, J 7 Hz, 1H, CHO-
MOM), 3.37 (s, 3H, OCH3), 2.12–1.97 (m, 2H), 2.05 (obsc. s,
The title ketone was also prepared from the alcohol 22 by
treatment of the alcohol in dry dichloromethane with tetra-
(n-propyl)ammonium perruthenate and 4-methylmorpholine
N-oxide, according to the general procedure (89%).
1-[(E)-6-Iodo-1-oxohex-2-enyl]-2,6,6-trimethyl-5-(1-oxoprop-
2-enyl)cyclohex-1-ene 19. Treatment of a solution of the brom-
ide 18 (35 mg, 0.10 mmol) in butan-2-one with sodium iodide,
according to the general procedure, gave the title iodide (39 mg,
99%) as a colourless oil; λmax(EtOH)/nm 235 (ε/dm3 molϪ1 cmϪ1
13 000); νmax(film)/cmϪ1 1675, 1645 and 986; δH(250 MHz)
3H, CH CO), 1.79–1.38 (m, 3H), 1.66 (obsc. s, 3H, ᎐CCH ),
᎐
3 3
1.06 (s, 3H, Me), 1.01 (s, 3H, Me); δC(67.8 MHz) 171.4 (s), 138.9
(d), 136.3 (s), 132.6 (s), 115.8 (t), 94.6 (t), 77.5 (d), 61.2 (t), 56.4
(q), 50.0 (d), 37.7 (s), 33.0 (t), 26.4 (q), 22.4 (q), 21.1 (q), 19.8
(q), 18.6 (t) (Found: Mϩ Ϫ AcOH Ϫ MOMOH, 174.1414.
C13H18 requires M, 174.1404).
Potassium carbonate (6.8 g, 49.2 mmol) was added in one
portion to a stirred solution of the above MOM ether acetate
(4.9 g, 16.4 mmol) in methanol (100 ml) at room temperature.
The solution was stirred at room temperature for 14 h and then
concentrated in vacuo. The residue was dissolved in ether (100
ml) and water (100 ml). The organic layer was separated and the
aqueous layer was re-extracted with ether (2 × 50 ml). The
combined organic extracts were washed with saturated aqueous
ammonium chloride (100 ml) and brine (100 ml) and then dried
and concentrated in vacuo to leave a colourless oil. Purification
by chromatography on silica eluting with 50% ether in light
petroleum (bp 40–60 ЊC) gave two diastereoisomers of the
MOM ether (4.1 g, 98%) as a pale yellow oil. Data for one
diastereoisomer: νmax(film)/cmϪ1 3424, 1716, 919 and 734;
6.96 (dt, J 16, 7 Hz, 1H, CH CH᎐CH), 6.42 (dd, J 16, 11 Hz,
᎐
2
1H, CH᎐CH ), 6.22 (d, J 16 Hz, 1H, ᎐CHH), 6.35 (d, J 16 Hz,
᎐
᎐
2
1H, CH᎐CHCO), 5.74 (d, J 11 Hz, 1H, ᎐CHH), 3.22 (t, J 7 Hz,
᎐
᎐
2H, CH2I), 2.86 (app. t, J 7 Hz, 1H, CHCO), 2.43 (app. q, J 7
Hz, 2H, CH CH᎐), 2.22–1.80 (m, 6H), 1.52 (s, 3H, Me), 1.14 (s,
᎐
2
3H, Me), 1.02 (s, 3H, Me); δC(67.8 MHz) 202.3 (s), 201.6 (s),
149.3 (d), 139.1 (s), 137.0 (d), 134.0 (d), 130.0 (s), 127.8 (t), 53.9
(d), 35.8 (t), 33.2 (t), 31.5 (q), 29.3 (q), 29.0 (t), 24.1 (q), 21.3 (q),
21.3 (t), 5.4 (t) (Found: Mϩ 400.0892. C18H25IO2 requires M,
400.0899).
1-Hydroxymethyl-5-[1-(methoxymethoxy)prop-2-enyl]-2,6,6-
trimethylcyclohex-1-ene 14b. A solution of vinylmagnesium
bromide (6.69 ml) in THF (1 M, 6.69 mmol) was added drop-
wise over 10 min to a stirred solution of the aldehyde 13 (1.5 g,
6.69 mmol) in dry THF (50 ml) at Ϫ78 ЊC under an atmosphere
of nitrogen. The solution was stirred at Ϫ78 ЊC for 1 h and then
allowed to warm to room temperature where it was stirred for a
further 1 h. The solution was cooled to 0 ЊC and then quenched
with water (10 ml), saturated aqueous ammonium chloride (25
ml) and ether (50 ml). The organic layer was separated and the
aqueous layer was then extracted with ether (2 × 50 ml). The
combined organic extracts were washed with saturated aqueous
sodium hydrogen carbonate (50 ml) and brine (50 ml), and then
dried and evaporated to dryness in vacuo to leave a viscous
yellow oil. Purification by chromatography on silica eluting
with 35% ether in light petroleum (bp 40–60 ЊC) gave firstly
recovered starting material (0.15 g, 10%). Further elution then
gave two diastereoisomers of 1-acetoxymethyl-5-(1-hydroxy-
prop-2-enyl)-2,6,6-trimethylcyclohex-1-ene (1.2 g, 72%) as a
colourless oil; (data for one diastereoisomer): νmax(film)/cmϪ1
3499, 1733, 991, 953 and 918; δH(250 MHz) 5.89 (ddd, J 17, 10,
δ (250 MHz) 5.82 (ddd, J 17, 10, 7 Hz, 1H, CH᎐CH ), 5.17–
᎐
H 2
5.12 (m, 2H, CH᎐CH ), 4.68 (d, J 7 Hz, 1H, OCHHOCH ),
᎐
2
3
4.51 (d, J 7 Hz, 1H, OCHHOCH3), 4.24 (d, J 7 Hz, 1H, CHO-
MOM), 4.19 (d, J 11 Hz, 1H, HOCHH), 4.10 (d, J 11 Hz, 1H,
HOCHH), 3.38 (s, 3H, OCH ), 2.05–2.00 (m, 2H, ᎐CCH ), 1.76
᎐
3
2
(obsc. s, 3H, ᎐CCH ), 1.78–1.52 (m, 2H, ᎐CCH CH ), 1.41–
᎐
᎐
3
2
2
1.37 (dt, J 2, 12 Hz, 1H, CHCHOMOM), 1.06 (s, 3H, Me), 1.01
(s, 3H, Me); δC(67.8 MHz) 138.9 (d), 138.3 (s), 133.7 (s), 115.9
(t), 94.6 (t), 77.1 (d), 59.0 (t), 56.4 (q), 50.2 (d), 37.7 (s), 32.9 (t),
28.9 (q), 22.5 (q), 19.7 (q), 18.7 (t) (Found: Mϩ Ϫ H2O Ϫ
MOMO, 175.1441. C13H19 requires M, 175.1487).
1-Formyl-5-[1-(methoxymethoxy)prop-2-enyl]-2,6,6-tri-
methylcyclohex-1-ene 15b. Treatment of a solution of the alco-
hol 14b (0.25 g, 0.98 mmol) in dry dichloromethane with tetra-
(n-propyl)ammonium perruthenate and 4-methylmorpholine
N-oxide, according to the general procedure, gave the title
aldehyde (0.24 g, 99%) as a colourless oil; λmax(EtOH)/nm 247
(ε/dm3 molϪ1 cmϪ1 15 100); νmax(film)/cmϪ1 1672, 1613 and 920;
δH(250 MHz) 10.10 (s, 1H, CHO), 5.81 (ddd, J 17, 10, 7 Hz, 1H,
CH᎐CH ), 5.22–5.14 (m, 2H, CH᎐CH ), 4.67 (d, J 7 Hz, 1H,
᎐
᎐
2
2
OCHHOCH3), 4.50 (d, J 7 Hz, 1H, OCHHOCH3), 4.29 (d, J 7
Hz, 1H, CHOMOM), 3.36 (s, 3H, OCH3), 2.27–2.20 (m, 2H,
5 Hz, 1H, CHCH᎐CH ), 5.25 (app. dt, J 17, 2 Hz, 1H, CHCH᎐
᎐
᎐
2
CHH), 5.13 (app. dt, J 10, 2 Hz, 1H, CHCH᎐CHH), 4.59 (s,
᎐CCH ), 2.09 (s, 3H, ᎐CCH ), 1.84–1.51 (m, 2H, ᎐CCH CH ),
᎐ ᎐ ᎐
2 3 2 2
᎐
2H, AcOCH ), 4.50–4.45 (m, 1H, HOCHCH᎐), 2.10–2.04 (m,
1.35 (dt, J 12, 2 Hz, 1H, CHCHOMOM), 1.30 (s, 3H, CH3),
1.25 (s, 3H, CH3); δC(67.8 MHz) 192.5 (d), 155.9 (s), 140.8 (s),
138.7 (d), 116.0 (t), 94.6 (t), 76.3 (d), 56.4 (q), 50.8 (d), 36.7 (s),
35.9 (t), 26.7 (q), 21.5 (q), 19.4 (q), 18.0 (t).
᎐
2
2H, ᎐CCH CH ), 2.04 (obsc. s, 3H, CH CO), 1.67 (s, 3H,
᎐
2
2
3
᎐CCH ), 1.63–1.38 (m, 3H), 1.06 (s, 3H, Me), 1.05 (s, 3H, Me);
᎐
3
δC(67.8 MHz) 171.9 (s), 142.2 (d), 137.1 (s), 132.8 (s), 113.8 (t),
71.5 (d), 61.5 (t), 49.6 (d), 37.9 (s), 33.0 (t), 27.1 (q), 23.4 (q),
21.5 (q), 20.2 (q), 17.7 (t) (Found: Mϩ Ϫ AcOH, 192.1511.
C13H20O requires M, 192.1514).
Chloromethyl methyl ether (3.6 ml, 47.8 mmol) was added
dropwise over 5 min to a stirred solution of the above alcohol
(6.0 g, 23.9 mmol) and Hunig’s base (8.3 ml, 47.8 mmol) in dry
dichloromethane (100 ml) at 0 ЊC under an atmosphere of
nitrogen. The solution was allowed to warm to room temper-
ature where it was stirred for 14 h. The mixture was diluted with
1-[(E)-6-Bromo-1-hydroxyhex-2-enyl]-5-[1-(methoxy-
methoxy)prop-2-enyl]-2,6,6-trimethylcyclohex-1-ene 17b.
A
solution of methyllithium–lithium bromide complex (4.43 ml)
in ether (1.5 M, 6.64 mmol) was added dropwise over 5 min to a
stirred solution of the stannane 16 (2.9 g) in dry THF (35 ml) at
Ϫ78 ЊC under an atmosphere of nitrogen. The mixture was
allowed to warm to 0 ЊC for 30 min and then recooled to
Ϫ78 ЊC. A solution of the aldehyde 15b (0.42 g, 1.66 mmol) in
dry THF (15 ml) was added portionwise over 5 min and the
3190
J. Chem. Soc., Perkin Trans. 1, 1998, 3181–3206

View Article Online
mixture was then stirred at Ϫ78 ЊC for 1 h. The mixture was
then allowed to warm to room temperature where it was
quenched with water (50 ml) and ether (50 ml). The organic
layer was separated and the aqueous layer was extracted with
ether (2 × 50 ml). The combined organic extracts were washed
with saturated aqueous ammonium chloride (75 ml) and brine
(75 ml), and then dried and concentrated in vacuo to leave a
yellow oil. Purification by chromatography on silica eluting
with 35% ether in light petroleum (bp 40–60 ЊC) gave a mixture
of diastereoisomers of the alcohol (0.51 g, 76%) as a pale yellow
oil. Data for one diastereoisomer: νmax(film)/cmϪ1 3456, 1641,
969 and 921; δH(270 MHz) 5.65–5.35 (m, 3H), 5.12–5.00 (m,
mmol) in benzene with tri-n-butyltin hydride and azoisobutyro-
nitrile according to the general procedure gave (i) the reduced
product 23 (19 mg, 28%) (eluted first) as a colourless oil;
λmax(EtOH)/nm 237 (ε/dm3 molϪ1 cmϪ1 13 000); νmax(film)/cmϪ1
2930, 1677, 1645, 1404, 1279 and 980; δH(250 MHz) 6.94 (dt,
J 16, 7 Hz, 1H, COCH᎐CH), 6.44 (dd, J 16, 12 Hz, 1H,
᎐
CH᎐CH ), 6.23 (dd, J 16, 1 Hz, 1H, COCH᎐CH), 6.12 (dd,
᎐
᎐
2
J 16, 1 Hz, 1H, ᎐CHH), 5.74 (dd, J 12, 1 Hz, 1H, ᎐CHH), 2.86
᎐
᎐
(dd, J 7, 4 Hz, 1H, CHCO), 2.24 (app. dq. J 7, 1 Hz, 2H,
CH CH᎐), 2.15–1.15 (m, 6H), 1.50 (s, 3H, Me), 1.12 (s, 3H,
᎐
2
Me), 1.04 (s, 3H, Me), 0.94 (t, J 7 Hz, 3H, Me); δC(67.8 MHz)
202.4 (s), 201.9 (s), 152.2 (d), 139.2 (s), 133.2 (d), 129.9 (d),
128.4 (s), 127.7 (t), 53.9 (d), 35.9 (t), 34.6 (t), 29.7 (q), 29.2 (q),
29.1 (t), 24.0 (q), 21.3 (t), 21.2 (q), 13.7 (q) (Found: Mϩ,
274.1901. C18H26O2 requires M, 274.1933); and (ii) an insepar-
able mixture of the bicyclic diketone 24 (~30%) and a 3:1 mix-
ture of β- and α-epimers of the title tricyclic diketone (19 mg,
25%) (eluted second) as a colourless oil; λmax(EtOH)/nm 237;
νmax(film)/cmϪ1 2928, 1691, 1666, 1619, 1415 and 1240; δH(400
2H, CH᎐CH ), 4.60 (s, 1H, ᎐CCHOHCH᎐), 4.49 (d, J 7 Hz, 1H,
᎐
᎐
᎐
2
OCHHOCH3), 4.32 (d, J 7 Hz, 1H, OCHHOCH3), 4.05 (d, J 7
Hz, 1H, CHOMOM), 3.22 (t, J 7 Hz, 2H, CH2Br), 3.19 (s, 3H,
OCH OCH ), 2.02 (app. q, J 7 Hz, 2H, CH᎐CHCH ), 1.81–
᎐
2
3
2
1.70 (m, 4H), 1.58 (s, 3H, ᎐CCH ), 1.52–1.17 (m, 3H), 1.03 (s,
᎐
3
3H, Me), 0.80 (s, 3H, Me); δC(67.8 MHz) 139.3 (s), 138.7 (d),
134.4 (d), 133.1 (s), 127.6 (d), 115.8 (t), 94.4 (t), 77.1 (d), 70.4
(d), 56.3 (q), 50.5 (d), 38.4 (s), 33.8 (t), 33.1 (t), 32.1 (t), 30.5 (t),
26.8 (q), 22.0 (q), 21.2 (q), 18.7 (t) (Found: Mϩ Ϫ MOMOH,
338.1241. C18H27OBr requires 338.1245).
1-[(E)-6-Bromo-1-oxohex-2-enyl]-5-[1-(methoxymethoxy)-
prop-2-enyl]-2,6,6-trimethylcyclohex-1-ene 21. Treatment of a
solution of the alcohol 17b (0.34 g, 0.84 mmol) in dry dichloro-
methane with tetra(n-propyl)ammonium perruthenate and 4-
methylmorpholine N-oxide, according to the general procedure,
gave the ketone (0.28 g, 84%) as a colourless oil; λmax(EtOH)/nm
227 (ε/dm3 molϪ1 cmϪ1 14 000); νmax(film)/cmϪ1 1675, 1644, 1616
MHz) 6.57 (ddd, J 16, 8, 6 Hz, 1H, COCH᎐CH), 5.92 (d, J 16
᎐
Hz, 1H, COCH᎐CH), 2.85 (app. dt, J 6, 6 Hz, 1H, CHCO),
᎐
2.62–1.28 (m), 1.51 (s, 3H, Me), 1.49 (s, 3H, Me), 1.19 (s, 3H,
Me) 1.13 (s, 3H, Me), 1.10 (s, 3H, Me), 1.06 (s, 3H, Me), 0.81 (s,
3H, Me), 0.79 (s, 3H, Me); 13C signals assigned to 24; δC(67.8
MHz) 212.9 (s), 201.9 (s), 154.2 (d), 136.2 (s), 131.3 (d), 129.7
(s), 56.2 (t), 39.6 (t), 32.0 (q), 30.8 (t), 26.1 (t), 25.9 (q), 25.8 (t),
23.3 (t), 22.6 (t), 20.1 (q) and 19.3 (t); 13C signals assigned to 26
(minor isomer); δC(67.8 MHz) 219.5 (s), 211.9 (s), 146.8 (s), 67.7
(d), 55.4 (d), 46.1 (t), 37.2 (d), 35.3 (t), 30.1 (q), 28.1 (t), 26.3 (t),
24.7 (q), 24.6 (t), 20.4 (t), 19.9 (q), 18.2 (t); a pure sample of the
C-1 β-epimer 25 was separated by reversed-phase HPLC and
showed: δC(67.8 MHz) 213.12 (s), 206.0 (s), 141.7 (s), 137.5 (s),
58.7 (d), 54.3 (t), 53.3 (d), 37.1 (d), 35.4 (t), 30.2 (t), 29.3 (q),
27.6 (t), 27.5 (q), 24.3 (t), 23.9 (t), 19.7 (q) and 19.6 (t) (Found:
Mϩ, 274.1874. C18H26O2 requires M, 274.1933).
and 920; δ (400 MHz) 6.65 (dt, J 16, 7 Hz, 1H, CH᎐CHCH ),
᎐
H
2
6.14 (d, J 16 Hz, 1H, CH᎐CHCH ), 5.84–5.75 (m, 1H,
᎐
2
CH᎐CH ), 5.17–5.13 (m, 2H, CH᎐CH ), 4.64 (d, J 7 Hz, 1H,
᎐
᎐
2
2
OCHHOCH3), 4.48 (d, J 7 Hz, 1H, OCHHOCH3), 4.21 (d, J 6
Hz, 1H, CHOMOM), 3.38 (t, J 7 Hz, 2H, CH2Br), 3.34 (s, 3H,
OCH OCH ), 2.38 (app. q, J 7 Hz, 2H, ᎐CHCH ), 2.04–1.97
᎐
2
3
2
(m, 4H, CH᎐CCH , CH CH Br), 1.83–1.68 (m, 2H, ᎐CCH -
1-Acetoxymethyl-5-(1,3-dioxolan-2-yl)-2,6,6-trimethylcyclo-
hex-1-ene 40a. A mixture of the aldehyde 13 (5.0 g, 20.0 mmol),
ethylene glycol (25 ml), ( )-camphor-10-sulfonic acid (0.36 g,
1.4 mmol) and dry benzene (170 ml) was stirred vigorously at
room temperature for 14 h under nitrogen. The mixture was
then diluted with ether (200 ml) and the organic solution was
extracted with saturated brine (2 × 200 ml). The organic frac-
tion was then dried and evaporated in vacuo to a yellow oil
which was purified by chromatography on silica, eluting with
30% ether in light petroleum (bp 40–60 ЊC) to give the acetal
(5.2 g, 87%) as a colourless oil; νmax(film)/cmϪ1 1734 and 949;
δH(250 MHz) 4.94 (d, J 3 Hz, 1H, OCHO), 4.60 (s, 2H,
CH2OAc), 3.97–3.94 (m, 2H, OCH2CH2O), 3.87–3.82 (m, 2H,
᎐
᎐
2
2
2
2
CH ), 1.48 (s, 3H, ᎐CCH ), 1.44–1.41 (m, 1H, CHCHOMOM),
᎐
2
3
1.12 (s, 3H, Me), 1.01 (s, 3H, Me); δC(67.8 MHz) 202.0 (s), 147.9
(d), 141.0 (s), 138.9 (d), 134.3 (d), 130.7 (s), 116.4 (t), 94.7 (t),
76.7 (d), 56.7 (q), 49.6 (d), 37.1 (s), 32.8 (t), 31.8 (t), 31.1 (t),
30.9 (t), 28.0 (q), 23.4 (q), 21.5 (q), 18.7 (t) (Found: Mϩ,
398.1445. C20H31BrO3 requires M, 398.1457).
1-[(E)-6-Bromo-1-oxohex-2-enyl]-5-(1-hydroxyprop-2-enyl)-
2,6,6-trimethylcyclohex-1-ene 22. A mixture of the MOM ether
21 (0.11 g, 0.266 mmol) and hydrochloric acid (6 M, 4.5 ml) in
THF (2 ml) and water (2 ml) was heated at 50–60 ЊC for 2 h and
then allowed to cool to room temperature. The mixture was
diluted with ether (10 ml) and brine (10 ml) and the organic
layer was separated. The aqueous layer was extracted with ether
(2 × 10 ml) and the combined organic extracts were washed
successively with saturated aqueous sodium hydrogen carbon-
ate (10 ml), water (10 ml), and brine (10 ml), then dried and
concentrated in vacuo to leave an orange oil. Purification by
chromatography on silica eluting with 40% ether in light petrol-
eum (bp 40–60 ЊC) gave the alcohol (85 mg, 90%) as a colourless
oil; λmax(EtOH)/nm 227 (ε/dm3 molϪ1 cmϪ1 11 200); νmax(film)/
cmϪ1 3453, 1643, 1616, 918, 732 and 647; δH(270 MHz) 6.73 (dt,
OCH CH O), 2.13–2.04 [obsc. m, 2H, ᎐C(Me)CH ], 2.06 (s,
᎐
2
2
2
3H, Me), 1.78–1.49 (obsc. m, 3H, CHCH2), 1.68 (s, 3H, Me),
1.12 (s, 3H, Me), 0.99 (s, 3H, Me); δC(67.8 MHz) 171.1 (s), 136.3
(s), 132.1 (s), 104.3 (d), 64.8 (t), 64.2 (t), 60.6 (t), 47.9 (d), 36.2
(s), 32.0 (t), 26.4 (q), 23.3 (q), 22.5 (q), 20.8 (q), 18.4 (t) (Found:
Mϩ, 268.1626. C15H24O4 requires M, 268.1675) (Found: C, 67.3;
H, 9.4. C15H24O4 requires C, 67.1; H, 9.0%).
5-(1,3-Dioxolan-2-yl)-1-hydroxymethyl-2,6,6-trimethylcyclo-
hex-1-ene 40b. A suspension of the acetate 40a (2.0 g, 7.5
mmol), potassium carbonate (3.3 g, 22.5 mmol) and methanol
(75 ml) was stirred vigorously at room temperature for 24 h
under nitrogen. The suspension was diluted with ether (120 ml)
and water (100 ml) and the organic layer was separated. The
aqueous layer was re-extracted with ether (2 × 100 ml) and the
combined organic fractions were dried and evaporated in vacuo
to a colourless oil, which was purified by chromatography on
silica, eluting with 50% ether in light petroleum (bp 40–60 ЊC)
to give the hydroxy acetal (1.6 g, 94%) as a colourless oil;
νmax(film)/cmϪ1 3404 and 979; δH(250 MHz) 4.94 (d, J 3 Hz, 1H,
OCHO), 4.21 (app. dd, J 10, 4 Hz, 1H, CHHOH), 4.11 (app.
dd, J 10, 4 Hz, 1H, CHHOH), 3.98–3.94 (m, 2H, OCH2CH2O),
J 16, 7 Hz, 1H, CH᎐CHCH ), 6.20 (dt, J 16, 1 Hz, 1H, CH᎐
᎐
᎐
2
CHCH ), 5.94 (ddd, J 17, 11, 5 Hz, 1H, CH᎐CH ), 5.29 (app.
᎐
2
2
dt, J 17, 2 Hz, 1H, CH᎐CHH), 5.17 (app. dt, J 11, 2 Hz, 1H,
᎐
CH᎐CHH), 4.52 (br s, 1H, CHOH), 3.38 (t, J 7 Hz, 2H,
᎐
CH Br), 2.44 (app. q, J 7 Hz, 2H, CH᎐CHCH ), 2.11–2.00 (m,
᎐
2
2
4H), 1.91 (d, 1H, J 5 Hz, OH), 1.75–1.66 (m, 2H), 1.54 (s, 3H,
᎐CCH ), 1.46–1.41 (m, 1H), 1.19 (s, 3H, Me), 1.08 (s, 3H, Me);
᎐
3
δC(67.8 MHz) 201.7 (s), 147.9 (d), 141.6 (d), 140.3 (s), 133.8 (d),
130.5 (s), 113.5 (t), 70.5 (d), 48.5 (d), 36.5 (s), 32.4 (t), 31.1 (t),
30.64 (t), 30.57 (t), 27.8 (q), 23.6 (q), 21.1 (q), 17.1 (t) (Found:
Mϩ Ϫ C3H5O Ϫ HBr, 215.1395. C15H19O requires 215.1436).
2,10-Dioxo-12,15,15-trimethyltricyclo[9.3.1.03,8]pentadec-11-
ene 25. Treatment of a solution of the iodide 19 (100 mg, 0.25
3.87–3.82 (m, 2H, OCH CH O), 2.10–1.99 [m, 2H, ᎐C(Me)-
᎐
2
2
J. Chem. Soc., Perkin Trans. 1, 1998, 3181–3206
3191

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CH2], 1.78 (s, 3H, Me), 1.77–1.42 (m, 3H, CHCH2), 1.20 (s, 3H,
Me), 1.01 (s, 3H, Me); δC(67.8 MHz) 137.5 (s), 133.4 (s), 104.3
(d), 64.8 (t), 64.2 (t), 58.2 (t), 48.0 (d), 36.0 (s), 31.8 (t), 26.7 (q),
22.6 (q), 19.5 (q), 18.5 (t) (Found: Mϩ, 226.1532. C13H22O3
requires M, 226.1569) (Found: C, 68.7; H, 10.2. C13H22O3
requires C, 68.9; H, 9.8%).
was purified by chromatography on silica, eluting with 30%
ether in light petroleum (bp 40–60 ЊC) to afford the aldehyde
(0.57 g, 89%) as a colourless oil; λmax(EtOH)/nm 228 (ε/dm3
molϪ1 cmϪ 12 300); νmax(film)/cmϪ1 1716, 1643 and 1237; δH 9.87
(d, J 3 Hz, 1H, CHO), 6.73 (dt, J 16, 7 Hz, 1H, ᎐CHCH ), 6.20
᎐
2
(dt, J 16, 1 Hz, 1H, ᎐CHCO), 3.42 (t, 2H, J 7 Hz, 2H, CH Br),
᎐
2
1-Formyl-5-(1,3-dioxolan-2-yl)-2,6,6-trimethylcyclohex-1-ene
41. Treatment of a solution of the alcohol 40b (3.90 g, 17.2
mmol) in dry dichloromethane with tetra(n-propyl)ammonium
perruthenate and 4-methylmorpholine N-oxide, according to
the general procedure, gave the title aldehyde (3.4 g, 88%) as an
unstable colourless oil; λmax/nm 247 (ε/dm3 molϪ1 cmϪ1 12 600);
νmax(film)/cmϪ1 1677 and 944; δH(250 MHz) 10.11 (s, 1H, CHO),
4.98 (d, J 2 Hz, 1H, OCHO), 3.97–3.93 (m, 2H, OCH2CH2O),
3.88–3.82 (m, 2H, OCH2CH2O), 2.27–2.23 [m, 2H,
2.44 (app. q, J 7 Hz, 2H, ᎐CHCH ), 2.29 (ddd, J 7, 7, 1 Hz, 1H,
᎐
2
CHCHO), 2.14–1.87 [m, 6H, ᎐C(Me)CH CH , CH CH Br],
᎐
2
2
2
2
1.56 (s, 3H, Me), 1.22 (s, 3H, Me), 1.16 (s, 3H, Me); δC(67.8
MHz) 204.5 (d), 200.3 (s), 148,3 (d), 138.9 (s), 133.5 (d), 130.7
(s), 56.0 (d), 35.2 (s), 32.3 (t), 30.5 (t), 29.1 (t), 28.9 (t), 28.1 (q),
23.8 (q), 20.9 (q), 18.8 (t) (Found: Mϩ, 326.0909. C16H23BrO2
requires M, 326.0881).
1-(6-Bromo-1-oxohex-2-enyl)-5-(1-hydroxyprop-2-ynyl)-
2,6,6-trimethylcyclohex-1-ene 45. A solution of ethynylmag-
nesium bromide (4.1 ml) in THF (0.5 M, 2.0 mmol) was added
dropwise over 10 min to a stirred solution of the aldehyde 44
(0.56 g, 1.70 mmol) in dry THF (20 ml) at Ϫ78 ЊC under nitro-
gen. The yellow solution was allowed to warm to room tem-
perature over a period of 12 h and was then quenched with
water (40 ml) and ether (40 ml). The organic layer was separated
and the aqueous layer was re-extracted with ether (3 × 40 ml).
The combined organic fractions were dried and evaporated in
vacuo to a yellow oil which was purified by chromatography on
silica, eluting with 50% ether in light petroleum (bp 40–60 ЊC)
to give two diastereoisomers (1:1 ratio) of the propargylic alco-
hol (0.49 g, 81%) as a colourless oil; (data for one diastereo-
isomer): λmax/nm 228 (ε/dm3 molϪ1 cmϪ1 17 800); νmax(film)/cmϪ1
3301, 2210, 1639 and 756; δH(250 MHz) 6.70 (dt, J 16, 7 Hz,
᎐C(Me)CH ], 2.11 (s, 3H, Me), 1.78–1.49 (m, 3H, CHCH ),
᎐
2
2
1.35 (s, 3H, Me), 1.22 (s, 3H, Me); δC(67.8 MHz) 192.3 (d),
156.2 (s), 140.9 (s), 103.8 (d), 65.2 (t), 64.4 (t), 48.9 (d), 35.4 (s),
35.2 (t), 26.7 (q), 21.8 (q), 19.5 (q), 17.8 (t), which was used
immediately.
5-(1,3-Dioxolan-2-yl)-1-(6-bromo-1-hydroxyhex-2-enyl)-
2,6,6-trimethylcyclohex-1-ene 42. A solution of n-butyllithium
(4.88 ml) in hexanes (1.6 M, 7.80 mmol) was added dropwise
over 10 min to a stirred solution of the stannane 16 (3.64 g, 8.32
mmol) in dry THF (80 ml) at Ϫ84 ЊC under nitrogen, and the
yellow solution then stirred at Ϫ84 ЊC for 1 h. The aldehyde 41
(0.57 g, 2.60 mmol) was taken up in dry THF (10 ml) and then
added dropwise over 10 min, and the resulting mixture allowed
to warm to room temperature over 2 h. Water (100 ml) and
ether (100 ml) were added and the organic layer was separated.
The aqueous layer was re-extracted with ether (2 × 100 ml) and
the combined organic fractions were dried and evaporated in
vacuo to a yellow oil which was purified by chromatography on
silica, eluting with 30% ether in light petroleum (bp 40–60 ЊC)
to give two diastereoisomers (5:1 ratio) of the hydroxy acetal
(0.90 mg, 81%) as a colourless oil; (data for major diastereo-
isomer): νmax(film)/cmϪ1 3455, 1652 and 970; δH(250 MHz) 5.78
(dd, J 15, 5 Hz, 1H, ᎐CHCHOH), 5.62–5.54 (m, 1H, ᎐CHCH ),
᎐CHCH ), 6.18 (dt, J 16, 1 Hz, 1H, ᎐CHCO), 4.73 (m, 1H,
᎐
᎐
2
CHOH), 3.41 (t, J 7 Hz, 2H, CH2Br), 2.48 (d, J 2 Hz, 1H,
alkyne-H), 2.40 (app. q, J 7 Hz, 2H, ᎐CHCH ), 2.14 [dd, J 8, 5
᎐
2
Hz, 2H, ᎐C(Me)CH ], 2.08–1.87 (m, 4H, CHCH , CH CH Br),
᎐
2
2
2
2
1.69–1.63 (m, 1H, CHCHOH), 1.52 (s, 3H, Me), 1.13 (s, 3H,
Me), 1.09 (s, 3H, Me); δC(67.8 MHz) 201.7 (s), 148.2 (d), 139.9
(s), 133.9 (d), 130.7 (s), 85.6 (d), 72.6 (s), 61.8 (d), 50.0 (d), 36.4
(s), 32.5 (t), 30.8 (t), 30.7 (t), 30.7 (t), 28.2 (q), 23.8 (q), 21.2
(q), 18.5 (t) (Found: Mϩ, 352.1027. C18H25BrO2 requires M,
352.1038).
5-(1-Oxoprop-2-ynyl)-1-(6-iodo-1-oxohex-2-enyl)-2,6,6-
trimethylcyclohex-1-ene 38. (a) A suspension of the alcohol 45
(0.24 g, 0.67 mmol), barium manganate (0.92 g, 3.35 mmol) and
dry dichloromethane (7 ml) was agitated, on a Decon FS100
ultrasonic bath, at room temperature for 7 h under nitrogen.
The suspension was filtered through a plug of celite and the
residue was then washed with dichloromethane (100 ml). The
combined filtrate was evaporated in vacuo to a yellow oil which
was purified by chromatography on silica, eluting with 30%
ether in light petroleum (bp 40–60 ЊC) to give 1-(6-bromo-1-oxo-
hex-2-enyl)-5-(1-oxoprop-2-ynyl)-2,6,6-trimethylcyclohex-1-
ene (0.14 g, 59%) as a colourless oil; λmax(EtOH)/nm 224 (ε/dm3
molϪ1 cmϪ1 15 900); νmax(film)/cmϪ1 3246, 2088, 1667, 1643 and
᎐
᎐
2
4.92 (d, J 3 Hz, 1H, OCHO), 4.80 (br d, J 5 Hz, 1H, CHOH),
3.98–3.93 (m, 2H, OCH2CH2O), 3.87–3.83 (m, 2H, OCH2-
CH2O), 3.40 (t, J 7 Hz, 2H, CH2Br), 2.20 (app. q, J 7 Hz, 2H,
᎐CHCH ), 2.04–1.88 [m, 4H, ᎐C(Me)CH CH ], 1.78 (s, 3H,
᎐
᎐
2
2
2
Me), 1.72–1.30 (m, 3H, CH2CH2Br, CHCH2), 1.27 (s, 3H, Me),
0.94 (s, 3H, Me); δC(67.8 MHz) 138.8 (s), 134.2 (d), 133.0 (s),
127.5 (d), 104.4 (d), 69.9 (d), 64.8 (t), 64.2 (t), 48.4 (d), 36.7
(s), 33.0 (t), 32.7 (t), 32.0 (t), 30.3 (t), 26.8 (q), 22.2 (q), 21.1 (q),
18.6 (t) (Found: Mϩ Ϫ H2O, 354.1210. C18H27O2Br requires M,
354.1194).
1-(6-Bromo-1-oxohex-2-enyl)-5-(1,3-dioxolan-2-yl)-2,6,6-
trimethylcyclohex-1-ene 43. Treatment of a solution of the
alcohol 42 (0.90 g, 0.24 mmol) in dry dichloromethane with
tetra(n-propyl)ammonium perruthenate and 4-methylmorpho-
line N-oxide, according to the general procedure, gave the title
ketone (0.73 g, 81%) as a colourless oil; λmax(EtOH)/nm 227
(ε/dm3 molϪ1 cmϪ1 10 700); νmax(film)/cmϪ1 1643 and 1060;
1041; δ (400 MHz) 6.86 (dt, J 16, 7 Hz, 1H, ᎐CHCH ), 6.16 (dt,
᎐
H
2
J 16, 1 Hz, 1H, ᎐CHCO), 3.41 (t, J 7 Hz, 2H, CH Br), 3.29 (s,
᎐
2
1H, alkyne-H), 2.73–2.68 (m, 1H, CHCO), 2.42 (app. q, J 7 Hz,
δ (250 MHz) 6.68 (dt, J 16, 7 Hz, 1H, ᎐CHCH ), 6.17 (dt, J 16,
2H, ᎐CHCH ), 2.08–2.01 [m, 6H, ᎐C(Me)CH CH , CH CH -
᎐ ᎐
2 2 2 2 2
᎐
H
2
1 Hz, 1H, ᎐CHCO), 4.92 (d, J 3 Hz, 1H, OCHO), 3.97–3.90 (m,
2H, OCH2CH2O), 3.85–3.81 (m, 2H, OCH2CH2O), 3.40, (t, J 7
Br], 1.52 (s, 3H, Me), 1.18 (s, 3H, Me), 1.11 (s, 3H, Me); δC
201.1 (s), 189.4 (s), 149.4 (d), 139.2 (s), 133.9 (d), 130.1 (s), 82.4
(s), 78.9 (d), 58.7 (d), 36.1 (s), 32.5 (t), 30.9 (t), 30.8 (t), 29.0 (t),
28.8 (q), 23.9 (q), 21.2 (q), 21.0 (t) (Found: Mϩ, 350.0884.
C18H23BrO2 requires M, 350.0881). The same bromide was also
produced when a suspension of the diol 49 (129 mg, 0.36
mmol), barium manganate (922 mg, 3.60 mmol) and dry
dichloromethane (5 ml) was agitated, on a Decon FS100
ultrasonic bath, at room temperature for 4 h under nitrogen,
followed by work-up and chromatography (66 mg, 51%).
᎐
Hz, 2H, CH Br), 2.40 (app. q, J 7 Hz, 2H, ᎐CHCH ), 2.09–2.00
᎐
2
2
[m, 4H, ᎐C(Me)CH , CH CH Br], 1.81–1.68 (m, 3H, CHCH ),
᎐
2
2
2
2
1.51 (s, 3H, Me), 1.09 (s, 6H, 2 × Me) (Found: Mϩ, 370.1181.
C18H27BrO3 requires M, 370.1144).
1-(6-Bromo-1-oxohex-2-enyl)-5-formyl-2,6,6-trimethylcyclo-
hex-1-ene 44. A solution of the acetal 43 (0.72 g, 1.95 mmol),
( )-camphor-10-sulfonic acid (0.23 g, 0.98 mmol) in water (20
ml) and THF (20 ml) was held at reflux for 14 h. The cooled
solution was diluted with water (20 ml) and ether (50 ml) and
the organic layer was separated. The aqueous layer was re-
extracted with ether (2 × 50 ml) and the combined organic frac-
tions were dried and evaporated in vacuo to a yellow oil which
(b) Treatment of a solution of the bromide from above (95 g,
0.27 mmol) in butan-2-one with sodium iodide, according
to the general procedure, gave the title iodide (106 mg, 99%)
as a pale yellow oil; δH(270 MHz) 6.70 (dt, J 16, 7 Hz, 1H,
3192
J. Chem. Soc., Perkin Trans. 1, 1998, 3181–3206

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᎐CHCH ), 6.18 (dt, J 16, 1 Hz, 1H, ᎐CHCO), 4.73 (dd, J 2,
silica, eluting with 50% ether in light petroleum (bp 40–60 ЊC)
᎐
᎐
2
2 Hz, 1H, CHOH), 3.16 (t, J 7 Hz, 2H, CH2I), 2.46 (d, J 2 Hz,
1H, alkyne-H), 2.35 (app. q, J 7 Hz, 2H, ᎐CHCH ), 2.11 [app.
to give the hydroxy aldehyde (57 mg, 58%) as a colourless solid,
mp 85–87 ЊC (from pentane); λmax(EtOH)/nm 247 (ε/dm3 molϪ1
cmϪ1 11 900); νmax(film)/cmϪ1 3420, 3305, 1668 and 1121; δH(250
MHz) 9.39 (s, 1H, CHO), 4.77 (br s, 1H, CHOH), 2.46 (d, J 2
᎐
2
t, J 6 Hz, 2H, ᎐C(Me)CH ], 1.98–1.74 (m, 4H, CH CH I,
᎐
2
2
2
CHCH2), 1.65 (dt, J 10, 3 Hz, 1H, CHCHOH), 1.50 (s, 3H,
Me), 1.11 (s, 3H, Me), 1.07 (s, 3H, Me); δC(67.8 MHz) 201.7 (s),
148.0 (d), 139.9 (s), 133.9 (d), 130.7 (s), 85.6 (d), 72.6 (s), 61.7
(d), 50.0 (d), 36.4 (s), 32.9 (t), 31.3 (t), 30.8 (t), 28.2 (q), 23.8 (q),
21.2 (q), 18.5 (t), 5.3 (t); which was used without further
purification.
Hz, 1H, alkyne-H), 2.37–2.32 [m, 2H, ᎐C(Me)CH ], 2.12 (s, 3H,
᎐
2
Me), 2.02–1.92 (m, 1H, CHCH2), 1.81–1.55 (m, 2H, CHCH2),
1.34 (s, 3H, Me), 1.25 (s, 3H, Me); δC(67.8 MHz) 192.3 (d),
156.3 (s), 140.2 (s), 85.8 (d), 72.4 (s), 61.3 (d), 51.8 (d), 36.4 (s),
35.3 (t), 26.7 (q), 21.9 (q), 19.4 (q), 18.1 (t) (Found: Mϩ,
206.1316. C13H18O2 requires M, 206.1307).
1-Acetoxymethyl-5-(1-hydroxyprop-2-ynyl)-2,6,6-trimethyl-
cyclohex-1-ene 46. A solution of ethynylmagnesium bromide
(50.0 ml) in THF (0.5 M, 24.9 mmol) was added dropwise over
30 min to a stirred solution of the aldehyde 13 (3.50 g, 15.6
mmol) in dry THF (60 ml) at Ϫ78 ЊC under nitrogen. The yel-
low solution was stirred at Ϫ78 ЊC for 40 min and then allowed
to warm to room temperature over 3 h. The reaction was
quenched by the addition of water (100 ml) and ether (100 ml)
and the organic layer was separated. The aqueous layer was re-
extracted with ether (2 × 100 ml) and the combined organic
fractions were dried and evaporated in vacuo to a yellow oil.
Purification by chromatography on silica eluting with 40% ether
in light petroleum (bp 40–60 ЊC) gave the acetoxy alcohol (3.6 g,
93%) as a colourless oil; νmax(film)/cmϪ1 3435, 3242, 2109, 1709
and 951; δH(250 MHz) 4.75–4.71 (m, 1H, CHOH), 4.60 (s, 2H,
CH2OAc), 2.46 (d, J 2 Hz, 1H, alkyne-H), 2.16–2.14 [m, 2H,
1-(6-Bromo-1-hydroxyhex-2-enyl)-5-(1-hydroxyprop-2-ynyl)-
2,6,6-trimethylcyclohex-1-ene 49. A solution of n-butyllithium
(1.2 ml) in hexanes (1.6 M, 1.92 mmol) was added dropwise
over 5 min to a stirred solution of the stannane 16 (0.88 g, 2.02
mmol) in dry THF (20 ml) at Ϫ84 ЊC under nitrogen and the
yellow solution then stirred at Ϫ84 ЊC for 1 h. The aldehyde 48
(100 mg, 0.48 mmol) was taken up in dry THF (2 ml) and then
added dropwise over 5 min, and the resulting pale yellow solu-
tion allowed to warm to room temperature over 2 h. Water
(20 ml) and ether (20 ml) were then added and the organic layer
was separated. The aqueous layer was re-extracted with ether
(2 × 20 ml) and the combined organic fractions were dried and
evaporated in vacuo to a yellow oil which was purified by chrom-
atography on silica, eluting with 20% ether in light petroleum
(bp 40–60 ЊC) to give two diastereoisomers (5:1 ratio) of the
diol (130 mg, 75%) as a colourless oil; (data for major diastereo-
isomer): νmax(film)/cmϪ1 3416, 3303 and 909; δH(250 MHz) 5.77
᎐C(Me)CH ], 2.06 (s, 3H, COCH3), 1.94–1.92 (m, 1H,
᎐
2
CH2CH), 1.70 (s, 3H, Me), 1.74–1.60 (m, 2H, CHCH2), 1.10 (s,
3H, Me), 1.03 (s, 3H, Me); δC(67.8 MHz) 172.0 (s), 136.7 (s),
132.1 (s), 85.8 (d), 72.5 (s), 62.2 (d), 60.9 (t), 50.8 (d), 37.3 (s),
32.3 (t), 26.9 (q), 23.0 (q), 21.1 (q), 19.8 (q), 18.6 (t) (Found:
Mϩ Ϫ AcOH, 190.1366. C13H18O requires M, 190.1315)
(Found: C, 72.0; H, 9.1. C15H22O3 requires C, 72.0; H, 8.9%).
1-Hydroxymethyl-5-(1-hydroxyprop-2-ynyl)-2,6,6-trimethyl-
cyclohex-1-ene 47. A suspension of the acetate 46 (3.43 g, 13.7
mmol), potassium carbonate (8.00 g, 54.8 mmol) and methanol
(100 ml) was stirred vigorously at room temperature for 2 h.
The suspension was diluted with ether (150 ml) and water (100
ml) and the organic layer was separated. The aqueous layer was
re-extracted with ether (2 × 100 ml) and the combined organic
fractions were dried and evaporated in vacuo to a colourless oil
which was purified by chromatography on silica eluting with
50% ether in light petroleum (bp 40–60 ЊC) to give the diol (2.6
g, 91%) as a colourless solid, mp 119–20 ЊC (from pentane);
νmax(film)/cmϪ1 3306, 2110 and 987; δH(250 MHz) 4.73–4.71 (m,
1H, CHOH), 4.18 (d, J 11.6 Hz, 1H, CHHOH), 4.10 (d, J 12
Hz, 1H, CHHOH), 2.46 (d, J 2 Hz, 1H, alkyne-H), 2.16–2.06
(dd, J 15, 5 Hz, 1H, ᎐CHCHOH), 5.65–5.51 (m, 1H, ᎐CHCH ),
᎐
᎐
2
4.80 (br s, 1H, CHOH), 4.69 (br s, 1H, CHOH), 3.41 (t, J 7 Hz,
2H, CH2Br), 2.47 (d, J 2 Hz, 1H, alkyne-H), 2.21 (app. q, J 7
Hz, 2H, ᎐CHCH ), 2.10–2.06 (m, 1H, CHCHOH), 2.00–1.82
᎐
2
[m, 2H, ᎐C(Me)CH ], 1.80 (s, 3H, Me), 1.72–1.54 (m, 4H,
᎐
2
CHCH2, CH2CH2Br), 1.25 (s, 3H, Me), 0.99 (s, 3H, Me);
δC(67.8 MHz) 139.0 (s), 134.1 (d), 132.5 (s), 128.2 (d), 85.9 (s),
72.4 (d), 70.5 (d), 62.4 (d), 51.5 (d), 38.1 (s), 33.3 (t), 33.2 (t),
32.1 (t), 30.5 (t), 27.4 (q), 22.7 (q), 21.2 (q), 18.9 (t) (Found:
Mϩ Ϫ H2O, 336.1099. C18H25BrO requires M, 336.1089).
12,15,15-Trimethyltricyclo[9.3.1.03,8]pentadeca-3,11-diene-
2,10-dione 56. Treatment of a solution of the iodide 38 (169
mg, 0.42 mmol) in benzene with tri-n-butyltin hydride and
azoisobutyronitrile according to the general procedure gave (i)
1-(1-oxohex-2-enyl)-5-(1-oxoprop-2-ynyl)-2,6,6-trimethylcyclo-
hex-1-ene (19 mg, 17%) (eluted first) as a colourless oil;
λmax(EtOH)/nm 223 (ε/dm3 molϪ1 cmϪ1 9 500); νmax(film)/cmϪ1
3241, 2087, 1669, 1641 and 1095; δH(250 MHz) 6.86 (dt, J 16, 7
Hz, 1H, ᎐CHCH ), 6.11 (d, J 16 Hz, 1H, ᎐CHCO), 3.29 (s, 1H,
᎐
᎐
2
(m, 2H, ᎐C(Me)CH ), 1.99–1.89 (m, 1H, CHCH ), 1.77 (s, 3H,
alkyne-H), 2.72–2.49 (m, 1H, CHCO), 2.23 (app. q, J 7 Hz, 2H,
᎐CHCH ), 2.10–1.89 (m, 4H, ᎐C(Me)CH CH ), 1.69–1.50 (m,
᎐
2
2
Me), 1.75–1.58 (m, 2H, CHCH2), 1.18 (s, 3H, Me), 1.06 (s, 3H,
Me); δC(67.8 MHz) 137.3 (s), 134.0 (s), 85.9 (d), 72.4 (s), 62.3
(d), 58.8 (t), 51.0 (d), 37.3 (s), 32.2 (t), 27.3 (q), 23.1 (q), 19.7 (q),
18.7 (t) (Found: Mϩ Ϫ H2O, 190.1359. C13H18O requires M,
190.1358) (Found: C, 75.0; H, 9.8. C13H20O2 requires C, 75.0;
H, 9.9%).
᎐
᎐
2
2
2
2H, CH2CH3), 1.52 (s, 3H, Me), 1.17 (s, 3H, Me), 1.13 (s, 3H,
Me), 0.93 (t, J 7 Hz, 3H, CH2CH3); δC(67.8 MHz) 201.4 (s),
189.6 (s), 152.1 (d), 139.0 (s), 133.1 (d), 129.9 (s), 82.4 (s), 79.1
(d), 58.7 (d), 36.2 (s), 34.5 (t), 29.1 (t), 28.4 (q), 23.9 (q), 21.3 (q),
21.2 (t), 21.1 (t), 13.6 (q) (Found Mϩ, 272.1756. C18H24O2
requires M, 272.1776); and (ii) the title compound as a 6:1
mixture of C-1 epimers (50.2 mg, 43%) (eluted second) as a
colourless oil; (data for major diastereoisomer): λmax(EtOH)/
nm 228 (ε/dm3 molϪ1 cmϪ1 4 500); νmax(film)/cmϪ1 1731, 1681 and
703; δH(250 MHz) 5.61 (t, J 4 Hz, 1H, H-4), 2.79 (dd, J 19,
13 Hz, 1H, 1 × H-9), 2.48–2.29 (m, 4H, H-1, H-8, 1 × H-9,
1 × H-13), 2.13–1.92 (m, 5H, 2 × H-5, 2 × H-6, 1 × H-13),
1.72–1.50 (m, 3H, 1 × H-7, 2 × H-14), 1.38–1.14 (m, 1H, 1 ×
H-7), 1.47 (s, 3H, Me), 1.40 (s, 3H, Me), 1.07 (s, 3H, Me);
δC(67.8 MHz) 210.3 (s), 210.2 (s), 146.7 (s), 143.4 (s), 134.3 (s),
128.2 (d), 57.9 (d), 51.4 (t), 33.7 (s), 33.1 (d), 30.3 (q), 30.1 (t),
27.4 (q), 26.9 (t), 24.7 (t), 22.0 (t), 21.3 (q), 16.8 (t) (Found: Mϩ,
272.1753. C18H24O2 requires M, 272.1776), which crystallised
on standing at 0 ЊC.
1-Formyl-5-(1-hydroxyprop-2-ynyl)-2,6,6-trimethylcyclohex-
1-ene 48. A solution of dimethyl sulfoxide (68 µl, 0.96 mmol) in
dry dichloromethane (0.2 ml) was added dropwise over 2 min to
a solution of oxalyl chloride (50 µl, 0.57 mmol) in dry dichloro-
methane (1.5 ml) at Ϫ60 ЊC under nitrogen. The solution was
stirred at Ϫ60 ЊC for 2 min and then a solution of the diol 47
(100 mg, 0.48 mmol) in dry dichloromethane (0.5 ml) was
added dropwise over 2 min. The solution was stirred at Ϫ60 ЊC
for a further 15 min and then triethylamine (333 µl, 2.4 mmol)
was added dropwise over 2 min and the resulting cloudy
suspension was allowed to warm to room temperature. The
suspension was diluted with dichloromethane (3 ml) and
water (5 ml) and the organic layer was separated. The aqueous
layer was re-extracted with dichloromethane (2 × 5 ml) and the
combined organic fractions were dried and evaporated in vacuo
to a colourless solid which was purified by chromatography on
2â,10á-Dihydroxy-12,15,15-trimethyltricyclo[9.3.1.03,8]-
pentadeca-3,11-diene 57. A solution of diisobutylaluminium
J. Chem. Soc., Perkin Trans. 1, 1998, 3181–3206
3193

View Article Online
hydride (42 µl) in toluene (1.5 M, 0.065 mmol) was added
dropwise over 2 min to a stirred solution of the dione 56 (4.0
mg, 0.026 mmol) in dry dichloromethane (260 µl) at Ϫ78 ЊC
under nitrogen. The mixture was stirred at Ϫ78 ЊC for 30 min
and then quenched with dichloromethane (0.5 ml) and water
(0.5 ml). The mixture was then allowed to warm to room tem-
perature and the organic layer was separated. The aqueous
layer was re-extracted with dichloromethane (2 × 0.5 ml) and
the combined organic fractions were dried and evaporated in
vacuo to a yellow oil. Purification by chromatography on silica
eluting with 30% ether in light petroleum (40–60 ЊC) gave (i) the
anti-diol diastereoisomer 57 (2.4 mg, 60%) (eluted first) as a
white crystals, mp 86–88 ЊC (from pentane); νmax(CHCl3)/cmϪ1
3372, 1652 and 1456; δH(500 MHz) 5.83 (t, J 4 Hz, 1H, H-4),
4.69 (dd, J 5, 5 Hz, 1H, H-10), 3.59 (d, J 7 Hz, 1H, H-2),
2.42–2.28 (m, 3H, H-8, 1 × H-13, 1 × H-9), 2.16–2.11 (m, 1H,
1 × H-5), 2.10–2.00 (obs. m, 4H, 1 × H-5, 1 × H-7, 1 × H-9,
1 × H-13), 2.00 (obs. s, 3H, Me), 1.99–1.94 (m, 1H, 1 × H-7),
1.73–1.56 (m, 4H, 2 × H-6, 2 × H-14), 1.49–1.44 (m, 1H, H-1),
1.22 (s, 3H, Me), 1.01 (s, 3H, Me); δC(125.8 MHz) 147.5 (s),
139.7 (s), 130.0 (s), 124.3 (d), 78.9 (d), 69.0 (d), 55.6 (d), 44.5 (t),
36.5 (s), 36.2 (d), 32.2 (t), 30.2 (t), 30.0 (q), 27.9 (q), 24.5 (t),
23.5 (t), 21.4 (q), 19.0 (t) (Found: Mϩ, 276.2087. C18H28O2
requires M, 276.2089); and (ii) a minor diastereoisomer (0.4
mg, 10%) (eluted second) as a colourless oil; δH (500 MHz) 5.88
(t, J 4 Hz, 1H, H-4), 4.77 (dd, J 3, 1 Hz, 1H, H-10), 4.41 (dd,
J 1, 1 Hz, 1H, H-2), 2.30–2.17 (m, 3H, H-8, 1 × H-13, 1 × H-9),
1.89 (obs. s, 3H, Me), 2.05–1.38 (obs. m, 11H, H-1, 2 × H-6,
2 × H-14, 2 × H-7, 2 × H-5, 1 × H-9, 1 × H-13), 1.31 (s, 3H,
Me), 1.10 (s, 3H, Me).
refined parameters. The highest peak of 1.09 e ÅϪ3 in the final
∆F synthesis was located 1.4 Å from both C(9) and C(10). The
Figure was produced using SHELXTL/PC.25
1-(6-Chloro-1-hydroxyhex-2-ynyl)-5-(1,3-dioxolan-2-yl)-
2,6,6-trimethylcyclohex-1-ene 50. A solution of n-butyllithium
(1.6 ml) in hexane (2.5 M, 3.99 mmol) was added dropwise over
5 min to a stirred solution of 5-chloropent-1-yne (0.41 g, 3.99
mmol) in dry THF (40 ml) at 0 ЊC under an atmosphere of
nitrogen. The solution was stirred at 0 ЊC for 15 min and then
cooled to Ϫ78 ЊC. A solution of the aldehyde 41 (0.51 g, 2.28
mmol) in dry THF (25 ml) was added dropwise over 5 min to
the stirred solution at Ϫ78 ЊC. The solution was stirred at
Ϫ78 ЊC for a further 30 min and then allowed to warm to 0 ЊC
where it was quenched with water (100 ml) and ether (50 ml).
The organic layer was separated and the aqueous layer was
extracted with ether (3 × 50 ml). The combined organic extracts
were washed with saturated aqueous ammonium chloride (50
ml) and brine (2 × 50 ml), then dried and concentrated in vacuo
to leave a yellow oil. Purification by chromatography on silica,
eluting with 60% ether in light petroleum (bp 40–60 ЊC), gave
the alcohol (0.72 g, 96%) as a colourless oil; νmax(film)/cmϪ1
3442 and 979; δH(270 MHz) 5.03 (m, 1H, CHOH), 4.91 (d, J 3
Hz, 1H, OCHO), 4.00–3.80 (m, 4H, OCH2CH2O), 3.62 (t, J 7
Hz, 2H, CH2Cl), 2.40 (dt, J 7, 2 Hz, 2H, alkyne-CH2), 2.11–1.98
(m, 4H), 1.97 (obsc. s, 3H, ᎐CCH ), 1.76 (d, J 4 Hz, OH), 1.72–
᎐
3
1.40 (m, 3H), 1.23 (s, 3H, Me), 0.99 (s, 3H, Me); δC(67.8 MHz)
138.2 (s), 134.5 (s), 104.5 (d), 82.7 (s), 82.4 (s), 64.9 (t), 64.4 (t),
59.5 (d), 48.3 (d), 43.6 (t), 36.8 (s), 32.6 (t), 31.3 (t), 26.5 (q),
22.6 (q), 21.1 (q), 18.7 (t), 16.2 (t) (Found: Mϩ, 326.1653.
C18H27ClO3 requires M, 326.1649).
1-(6-Chloro-1-oxohex-2-ynyl)-5-(1,3-dioxolan-2-yl)-2,6,6-tri-
methylcyclohex-1-ene 51. Treatment of a solution of the alcohol
50 (0.59 g, 1.81 mmol) in dry dichloromethane with tetra-
(n-propyl)ammonium perruthenate and 4-methylmorpholine
N-oxide, according to the general procedure, gave the title
aldehyde (0.58 g, 98%) as a colourless oil; λmax(EtOH)/nm
226 (ε/dm3 molϪ1 cmϪ1 7 600), 231 (7 600); νmax(film)/cmϪ1
2207, 1648 and 888; δH(250 MHz) 4.86 (d, J 3 Hz, 1H, OCHO),
3.92–3.75 (m, 4H, OCH2CH2O), 3.59 (t, J 6 Hz, 2H, CH2Cl),
2.56 (t, J 7 Hz, 2H, alkyne-CH2), 2.05–1.94 (m, 4H), 1.74–
X-ray crystal structure determination of diol 57†
A colourless cuboid was mounted on a glass fibre and trans-
ferred to the diffractometer.
Crystal data. C18H28O2ؒ¹CH2Cl2, M = 318.86. Tetragonal,
¯
²
a = 20.095(4), c = 8.598(4) Å, V = 3472(2) Å3 [from 2θ values of
32 reflections measured at ω (22 р 2θ р 31Њ, λ = 0.710 73 Å,
T = 260 K)], space group P4/n (No. 85), Z = 8, Dx = 1.216 g
cmϪ3
µ(Mo-Kα) = 0.224 mmϪ1
, colourless cuboidal crystal 0.77 × 0.62 × 0.50 mm,
.
1.57 (m, 3H), 1.67 (obsc. s, 3H, ᎐CCH ), 1.18 (s, 3H, Me),
᎐
3
Data collection and processing. Stoe Stadi-4 four-circle dif-
fractometer, ω/θ scans with ω scan width (1.1 ϩ 0.35tanθ)Њ,
graphite-monochromated Mo-Kα X-radiation; 3366 reflections
measured (5 р 2θ р 50Њ, h, k, l), 3042 unique [merging
R = 0.011], giving 1969 with F у 4σ(F) and 3019 which were
retained in all calculations. No crystal decay was observed and
no corrections were applied for absorption.
1.15 (s, 3H, Me); δC(67.8 MHz) 186.7 (s), 142.2 (s), 133.3 (s),
103.8 (d), 93.1 (s), 83.7 (s), 64.8 (t), 64.4 (t), 47.4 (d), 43.1
(t), 35.9 (s), 31.1 (t), 30.3 (t), 27.4 (q), 23.2 (q), 20.5 (q), 18.3
(t), 16.5 (t) (Found: Mϩ, 324.1468. C18H25ClO3 requires M,
324.1492).
5-Formyl-1-(6-chloro-1-oxohex-2-ynyl)-2,6,6-trimethylcyclo-
hex-1-ene 52. A stirred mixture of the acetal 51 (0.11 g, 0.344
mmol), ( )-camphor-10-sulfonic acid (0.04 g, 0.172 mmol) and
water (1.7 ml) in THF (1.7 ml) was heated to reflux for 14 h and
then cooled to room temperature. The mixture was diluted with
ether (5 ml) and saturated aqueous sodium hydrogen carbonate
(5 ml) and the organic layer was separated. The aqueous layer
was extracted with ether (3 × 5 ml) and the combined organic
extracts were washed with brine (5 ml) and then dried and con-
centrated in vacuo to leave a yellow oil. Purification by chrom-
atography on silica, eluting with 25% ether in light petroleum
(bp 40–60 ЊC), gave the aldehyde (95 mg, 98%) as a colourless
oil; λmax(EtOH)/nm 224 (ε/dm3 molϪ1 cmϪ1 9 600), 230 (9 300),
νmax(film)/cmϪ1 2207, 1717, 1841 and 668; δH(400 MHz) 9.83 (d,
J 3 Hz, 1H, HCO), 3.61 (t, J 6 Hz, 2H, CH2Cl), 2.58 (t, J 7 Hz,
2H, alkyne-CH2), 2.21 (ddd, J 10, 3, 3 Hz, 1H, CHCHO), 2.10
Structure solution and refinement. Automatic direct
methods23 (all non-H atoms). Full-matrix least squares refine-
ment24 with all ordered non-H atoms anisotropic; H atoms
were located from a ∆F synthesis (OH) or introduced at geo-
metrically calculated positions (all others) and thereafter re-
fined as rigid rotating groups or riding on their parent C atoms,
respectively, with Uiso(H) = xUeq(C) [x = 1.5 for OH and 1.2
for others]. Disorder was identified in the C(3)–C(8) ring and
was modelled by allowing equal occupations of alternative
positions for C(5), C(6) and their H atoms. However, the dis-
order appears to be more extensive and could not be modelled
further, contributing to the rather high residuals. The weighting
2
2
scheme wϪ1 = [σ2(Fo ) ϩ (0.178P)2 ϩ 5.73P], P = ¹[MAX(Fo ,0)
¯
³
ϩ 2Fc2], gave satisfactory agreement analyses. Final R1 [F у
4σ(F)] = 0.101, wR2 [all data] = 0.340, S[F2] = 1.11 for 208
(dd, J 8, 6 Hz, 2H, ᎐CCH ), 2.02 (app. quintet., J 7 Hz, 2H,
᎐
2
alkyne-CH CH ), 1.91–1.77 (m, 2H, ᎐CCH CH ), 1.72 (s, 3H,
᎐
2
2
2
2
† Full crystallographic details, excluding structure factor tables, have
been deposited at the Cambridge Crystallographic Data Centre
(CCDC). For details of the deposition scheme, see ‘Instructions for
authors’, J. Chem. Soc., Perkin Trans. 1, available via the RSC Web page
(http://www.rsc.org/authors). Any request to the CCDC for this
material should quote the full literature citation and the reference
number 207/249.
᎐CCH ), 1.30 (s, 3H, Me), 1.22 (s, 3H, Me); δ (67.8 MHz) 204.8
᎐
3
C
(d), 185.4 (s), 141.1 (s), 134.3 (s), 93.8 (s), 83.6 (s), 56.3 (d), 43.2
(t), 35.8 (s), 30.3 (t), 29.9 (t), 27.7 (q), 23.9 (q), 20.6 (q), 19.0 (t),
16.6 (t).
1-(6-Chloro-1-oxohex-2-ynyl)-5-(1-hydroxyprop-2-enyl)-2,6,6-
trimethylcyclohex-1-ene 53. A solution of vinylmagnesium
3194
J. Chem. Soc., Perkin Trans. 1, 1998, 3181–3206

View Article Online
chloride (0.24 ml) in THF (1.7 M, 0.40 mmol) was added drop-
wise over 10 min to a stirred solution of the aldehyde 52 (0.113
g, 0.40 mmol) in dry THF (4 ml) at Ϫ78 ЊC under an atmos-
phere of nitrogen. The solution was stirred at Ϫ78 ЊC for 2 h
and then quenched with water (2 ml), saturated aqueous
ammonium chloride (2 ml) and ether (5 ml). The mixture was
allowed to warm to room temperature and the organic layer was
separated. The aqueous layer was extracted with ether (2 × 5
ml) and the combined organic extracts were washed with satur-
ated aqueous ammonium chloride (5 ml) and brine (5 ml), and
then dried and concentrated in vacuo to leave a slightly yellow
oil. Purification by chromatography on silica, eluting with 40%
ether in light petroleum (bp 40–60 ЊC) gave the alcohol (0.12 g,
98%) as a colourless oil; λmax(EtOH)/nm 224 (ε/dm3 molϪ1 cmϪ1
8 000), 229 (7 800); νmax(film)/cmϪ1 3478, 2208, 1940 and 660;
20.5 (q), 13.4 (q) (Found: Mϩ, 272.1784. C18H24O2 requires M,
272.1776).
1-(E,Z-6-Chloro-3-methyl-1-oxohex-2-enyl)-5-(1-hydroxy-
prop-2-enyl)-2,6,6-trimethylcyclohex-1-ene 67. A solution of
methyllithium–lithium iodide complex (1.74 ml) in ether (1 M,
1.7 mmol) was added dropwise over 5 min to a stirred suspen-
sion of copper() iodide (0.16 g, 0.87 mmol) in dry THF (8 ml)
at 0 ЊC under an atmosphere of nitrogen. The solution was
stirred at 0 ЊC for 10 min until the solution became colourless
and all solids were dissolved. The stirred solution was cooled to
Ϫ78 ЊC and a solution of the enone 53 (0.122 g, 0.40 mmol) in
dry THF (4 ml) was added portionwise over 5 min. The solu-
tion was stirred at Ϫ78 ЊC for 30 min and then allowed to
warm to 0 ЊC, where it was quenched with saturated aqueous
ammonium chloride (10 ml) and ether (15 ml). The organic
layer was separated and the aqueous layer was extracted with
ether (2 × 15 ml). The combined ether extracts were washed
with saturated aqueous ammonium chloride (20 ml), water (20
ml) and brine (20 ml), and then dried and evaporated in vacuo
to leave a yellow oil. Purification by chromatography on silica
eluting with 15% ether in light petroluem (bp 40–60 ЊC) gave a
mixture of (E)- and (Z)-isomers (1:1 ratio) of the alcohol (0.12
g, 91%) as a colourless oil; [data for (E)-isomer]: λmax(EtOH)/
nm 244 (ε/dm3 molϪ1 cmϪ1 6 300); νmax(film)/cmϪ1 3442, 1665,
δ (250 MHz) 5.91 (ddd, J 17, 10, 5 Hz, 1H, CH᎐CH ), 5.28
᎐
H
2
(app. dt, J 17, 2 Hz, 2H, CH᎐CHH), 5.16 (app. dt, J 10, 2 Hz,
᎐
1H, CH᎐CHH), 4.52 (m, 1H, CHOH), 3.65 (t, J 6 Hz, 2H,
᎐
CH2Cl), 2.61 (t, J 7 Hz, 2H, alkyne-CH2), 2.10–1.96 (m, 4H),
1.79–1.36 (m, 3H), 1.72 (obsc. s, 3H, =CCH3), 1.28 (s, 3H, Me),
1.19 (s, 3H, Me); δC(67.8 MHz) 186.7 (s), 142.3 (s), 141.5 (d),
133.4 (s), 113.5 (t), 93.2 (s), 83.6 (s), 70.3 (d), 48.5 (d), 43.1 (t),
36.9 (s), 31.6 (t), 30.2 (t), 27.1 (q), 23.4 (q), 20.5 (q), 16.9 (t),
16.4 (t) (Found: Mϩ, 308.1554. C18H25ClO2 requires M,
308.1543).
1601 and 919; δ (400 MHz) 6.10 [d, J 1 Hz, 1H, CH᎐C(CH )],
᎐
H
3
1-(6-Chloro-1-oxohex-2-ynyl)-5-(1-oxoprop-2-enyl)-2,6,6-
trimethylcyclohex-1-ene 54. Treatment of a solution of the
alcohol 53 (0.18 g, 0.58 mmol) in dry dichloromethane with
tetra(n-propyl)ammonium perruthenate and 4-methylmorpho-
line N-oxide, according to the general procedure, gave the title
ketone (0.16 g, 89%) as a colourless oil; νmax(film)/cmϪ1 2209,
1690, 1642, 1609, 764 and 658; δH(400 MHz) 6.46 (dd, J 17, 11
5.87 (ddd, J 17, 10, 5 Hz, 1H, CH᎐CH ), 5.23 (app. dt, J 17, 2
᎐
2
Hz, 1H, CH᎐CHH), 5.11 (app. dt, J 10, 2 Hz, 1H, CH᎐CHH),
᎐
᎐
4.46 (s, 1H, CHOH), 3.58 (t, J 7 Hz, 2H, CH2Cl), 2.70 [t, J 7
Hz, 2H, CH᎐C(CH )CH ], 2.00–1.92 (m, 4H), 1.88 (d, J 1.2 Hz,
᎐
3
2
3H, CH᎐CCH ), 1.63–1.57 (m, 2H), 1.52 (s, 3H, C᎐CCH ),
᎐
᎐
3
3
1.36–1.32 (m, 1H), 1.16 (s, 3H, Me), 1.06 (s, 3H, Me); δC(67.8
MHz) 200.6 (s), 156.7 (s), 144.0 (s), 141.6 (d), 128.8 (s), 127.7
(d), 113.5 (t), 70.6 (d), 48.7 (d), 44.9 (t), 36.9 (s), 31.4 (t), 31.2
(t), 31.1 (t), 27.4 (q), 25.6 (q), 23.4 (q), 20.3 (q), 17.2 (t).
Hz, 1H, CH᎐CH ), 6.25 (d, J 17 Hz, 1H, CH᎐CHH), 5.74 (d,
᎐
᎐
2
J 11 Hz, 1H, CH᎐CHH), 3.66 (t, J 6 Hz, 2H, CH Cl), 2.84 (dd,
᎐
2
J 11, 3 Hz, 1H, CHCOCH᎐), 2.62 (t, J 7 Hz, 2H, alkyne-CH ),
1-(E,Z-6-Chloro-3-methyl-1-oxohex-2-enyl)-5-(1-oxoprop-2-
enyl)-2,6,6-trimethylcyclohex-1-ene 68. Treatment of a solution
of the alcohol 67 (0.59 g, 1.81 mmol) in dry dichloromethane
with tetra(n-propyl)ammonium perruthenate and 4-methyl-
morpholine N-oxide, according to the general procedure, gave
a mixture of (E)- and (Z)-isomers (1:1 ratio) of the title
ketone (0.44 g, 75%) as a colourless oil; (data for (E)-isomer):
λmax(EtOH)/nm 243 (ε/dm3 molϪ1 cmϪ1 14 300); νmax(film)/cmϪ1
1666, 1604 and 966; δH(250 MHz) 6.45 (dd, J 17, 10 Hz, 1H,
᎐
2
2.13–1.72 (m, 6H), 1.75 (obsc. s, 3H, ᎐CCH ), 1.22 (s, 3H, Me),
᎐
3
1.20 (s, 3H, Me); δC(67.8 MHz) 202.3 (s), 185.6 (s), 141.6 (s),
137.1 (d), 133.3 (s), 127.7 (t), 93.6 (s), 83.5 (d), 53.6 (d), 43.2 (t),
36.5 (s), 30.5 (t), 30.2 (t), 27.8 (q), 23.5 (q), 21.2 (t), 20.4 (q),
16.5 (t).
1-(6-Iodo-1-oxohex-2-ynyl)-5-(1-oxoprop-2-enyl)-2,6,6-tri-
methylcyclohex-1-ene 39a. A stirred mixture of the chloride 54
(50 mg, 0.16 mmol) and sodium iodide (37 mg, 0.24 mmol) in
butan-2-one (2 ml) was heated under reflux for 18 hr. The cooled
mixture was diluted with ether (5 ml) and water (2 ml) and the
organic layer was separated. The aqueous layer was extracted
with ether (2 × 5 ml) and the combined organic extracts were
washed with 10% aqueous sodium thiosulfate (5 ml) and brine
(5 ml), and then dried and concentrated in vacuo to give the
iodide (61 mg, 94%) as a colourless oil; δH(250 MHz) 6.46 (dd,
CH᎐CH ), 6.23 (dd, J 17, 1 Hz, 1H, CH᎐CHH), 6.18 (d, J 1 Hz,
᎐
᎐
2
1H, CH᎐CCH ), 5.72 (dd, J 10, 1 Hz, 1H, CH᎐CHH), 3.60 (t,
᎐
᎐
3
J 7 Hz, 2H, CH Cl), 2.82 (dd, J 10, 3 Hz, 2H, CHCOCH᎐), 2.73
᎐
2
[d, J 8 Hz, 1H, CH᎐C(CH )CHH], 2.70 [d, J 8 Hz, 1H, CH᎐
᎐
᎐
3
C(CH3)CHH], 2.02–1.61 (m, 6H), 1.92 (obsc. d, J 1 Hz, 3H,
CH᎐CCH ), 1.56 (s, 3H, ᎐CCH ), 1.10 [s, 6H, C(CH ) ]; δ (67.8
᎐
᎐
3
3
3
2
C
MHz) 202.7 (s), 200.0 (s), 157.3 (s), 143.1 (s), 137.1 (d), 128.2
(s), 127.6 (t), 127.5 (d), 54.1 (d), 44.9 (t), 36.4 (s), 31.5 (t), 31.1
(t), 29.8 (t), 28.3 (q), 25.6 (q), 23.6 (q), 21.4 (t), 20.3 (q).
J 17, 10 Hz, 1H, CH᎐CH ), 6.24 (d, J 17 Hz, 1H, CH᎐CHH),
᎐
᎐
2
5.74 (d, J 10 Hz, 1H, CH᎐CHH), 3.29 (t, J 7 Hz, 2H, CH I),
᎐
2
2.84 (dd, J 11, 3 Hz, 1H, CHCOCH᎐), 2.57 (t, J 7 Hz, 2H,
1-(E,Z-6-Iodo-3-methyl-1-oxohex-2-enyl)-5-(1-oxoprop-2-
enyl)-2,6,6-trimethylcyclohex-1-ene 61. A stirred mixture of the
chloride 68 (67 mg, 0.21 mmol) and sodium iodide (93 mg, 0.63
mmol) in butan-2-one (2 ml) was heated to reflux for 18 h. The
mixture was allowed to cool to room temperature and then
diluted with ether (5 ml) and water (2 ml). The organic layer
was separated and the aqueous layer was extracted with ether
(2 × 5 ml). The combined ether extracts were washed with 10%
aqueous sodium thiosulfate (5 ml) and brine (5 ml) and then
dried and evaporated in vacuo to give a mixture of (E)- and (Z)-
isomers of the the iodide (80 mg, 93%) as a colourless oil; (data
for both isomers): δH(250 MHz) 6.46 (dd, J 17, 10 Hz, 1H,
᎐
alkyne-CH ), 2.09–1.54 (m, 6H), 1.73 (obsc. s, 3H, ᎐CCH ),
᎐
2
3
1.21 (s, 3H, Me), 1.18 (s, 3H, Me); which was used directly
without any further purification.
1-(1-Oxohex-2-ynyl)-5-(1-oxoprop-2-enyl)-2,6,6-trimethyl-
cyclohex-1-ene 39b. Treatment of a solution of the alkyl iodide
39a (50 mg, 0.12 mmol) in benzene with tri-n-butyltin hydride
and azoisobutyronitrile, according to the general procedure,
gave the title cyclohexene (15 mg, 43%) as a colourless oil;
λmax(EtOH)/nm 225 (ε/dm3 molϪ1 cmϪ1 6 500); νmax(film)/cmϪ1
2203, 1704, 1643, 914, 733 and 648; δH(270 MHz) 6.39 (dd, J 17,
10 Hz, 1H, CH᎐CH ), 6.17 (dd, J 17, 1 Hz, 1H, CH᎐CHH),
᎐
᎐
2
5.67 (dd, J 10, 1 Hz, 1H, CH᎐CHH), 2.78 (dd, J 11, 3 Hz, 1H,
CH᎐CH ), 6.45 (dd, J 17, 10 Hz, 1H, CH᎐CH ), 6.27–6.18 (m,
᎐ ᎐
2 2
᎐
CHCO), 2.31 (t, J 7 Hz, 2H, alkyne-CH2), 2.03–1.51 (m, 6H),
4H, CH᎐CHH, CH᎐CCH ), 5.73 (d, J 10 Hz, 1H, CHCHH),
᎐ ᎐
3
1.67 (obsc. s, 3H, ᎐CCH ), 1.15 (s, 3H, Me), 1.12 (s, 3H, Me),
5.72 (d, J 10 Hz, 1H, CH᎐CHH), 3.26 (t, J 7 Hz, 2H, CH I),
᎐
᎐
3
2
0.95 (t, J 7 Hz, 3H, CH2CH3); δC(67.8 MHz) 202.6 (s), 185.9 (s),
141.6 (s), 137.2 (d), 133.3 (s), 127.8 (t), 96.3 (s), 83.3 (d), 53.8
(d), 36.6 (s), 30.6 (t), 27.8 (q), 23.6 (q), 21.3 (t), 21.2 (t), 21.1 (t),
3.17 (t, J 7 Hz, 2H, CH2I), 2.86–2.81 (m, 2H, CHCO), 2.69 [dd,
J 8, 7 Hz, 2H, CH᎐C(CH )CH ], 2.27 [dd, J 8, 7 Hz, 2H,
᎐
3
2
CH᎐C(CH )CH ], 2.17 (d, J 1 Hz, 3H, CH᎐CCH ), 2.10–1.90
᎐
᎐
3
2
3
J. Chem. Soc., Perkin Trans. 1, 1998, 3181–3206
3195

View Article Online
(m, 8H), 1.92 (obsc. d, J 1 Hz, 3H, CH᎐CCH ), 1.88–1.65 (m,
fication by chromatography on silica, eluting with 15% ether
᎐
3
4H), 1.58 (s, 3H, ᎐CCH ), 1.57 (s, 3H, ᎐CCH ), 1.12 [s, 6H,
C(CH3)2], 1.11 [s, 6H, C(CH3)2], which was used directly with-
out any further purification.
5-(1-Oxoprop-2-enyl)-2,6,6-trimethyl-1-(E,Z-3-methyl-1-oxo-
hex-2-enyl)cyclohex-1-ene 62. Treatment of a solution of the
alkyl iodide 61 (0.25 g, 0.562 mmol) in benzene with tri-
n-butyltin hydride and azoisobutyronitrile, according to the
general procedure, gave a mixture of (E)- and (Z)-isomers (1:1
ratio) of the title cyclohexene (0.12 g, 67%) as a colourless oil;
(data for both isomers): νmax(film)/cmϪ1 1705, 1666 and 838;
in light petroleum (bp 40–60 ЊC), gave a mixture of (E)- and
(Z)-isomers (1:1 ratio) of the 1-(6-chloro-3-methyl-1-oxohex-
2-ynyl)-5-(1-hydroxyprop-2-ynyl)-2,6,6-trimethylcyclohex-1-
ene (0.12 g, 94%) as a colourless oil; [data for (E)-isomer]:
λmax(EtOH)/nm 244 (ε/dm3 molϪ1 cmϪ1 13 800); νmax(film)/
cmϪ1 3440, 3297, 1662, 1599 and 835; δH(400 MHz) 6.12 [s,
᎐
᎐
3
3
1H, CH᎐C(CH )], 4.71 (s, 1H, CHOH), 3.62 (t, J 7 Hz, 2H,
᎐
3
CH Cl), 2.74 [app. t, J 8 Hz, 2H, CH᎐C(CH )CH ], 2.47 (d,
᎐
2
3
2
J 2 Hz, 1H, alkyne-H), 2.11 (d, J 5 Hz, 1H, C᎐CCHH), 2.09 (d,
᎐
J 5 Hz, 1H, C᎐CCHH), 2.02–1.94 (m, 3H), 1.92 (d, J 1 Hz,
᎐
δ (250 MHz) 6.45 (dd, J 17, 10 Hz, 2H, CH᎐CH ), 6.23 (dd,
3H, CH᎐CCH ), 1.86–1.78 (m, 1H), 1.63 (dt, J 11, 3 Hz, 1H,
᎐
3
᎐
H
2
J 17 Hz, 2H, CH᎐CHH), 6.12 (s, 2H, CH᎐CCH ), 5.71 (d, J 10
CHCHOH), 1.57 (s, 3H, C᎐CCH ), 1.16 (s, 3H, Me), 1.13 (s,
᎐
᎐
᎐
3
3
Hz, 2H, CH᎐CHH), 2.82 (dd, J 11, 2 Hz, 2H, CHCO), 2.62 [t,
3H, Me); δC(67.8 MHz) 201.1 (s), 157.7 (s), 144.2 (s), 129.5 (s),
128.3 (d), 86.3 (s), 73.2 (d), 62.5 (d), 50.8 (d), 45.6 (t), 37.2 (s),
32.1 (t), 31.8 (t), 31.6 (t), 28.4 (q), 26.3 (q), 24.3 (q), 21.0 (q),
19.2 (t) (Found: Mϩ, 322.1696. C19H27ClO2 requires M,
322.1670).
᎐
J 8 Hz, 2H, (E)-CH᎐C(CH )CH ], 2.16 [s, 3H, (Z)-CH᎐CCH ],
᎐
᎐
3
2
3
2.12 [t, J 8 Hz, 2H, (Z)-CH᎐C(CH )CH ], 2.03–1.62 (m, 6H),
᎐
3
2
1.88 (obsc. s, 3H, (E)-CH᎐CCH ), 1.92 (obsc. d, J 1 Hz, 3H,
᎐
3
CH᎐CCH ), 1.58 (s, 6H, ᎐CCH ), 1.55–1.17 (m, 4H, CH CH ),
᎐
᎐
3
3
2
3
1.12 [s, 6H, C(CH3)2], 1.11 [s, 6H, C(CH3)2], 0.97 [t, J 7 Hz, 3H,
(E)-CH2CH3], 0.91 [t, J 7 Hz, 3H, (Z)-CH2CH3]; δC(67.8 MHz)
202.8 (s), 200.5 (s), 199.8 (s), 159.3 (s), 158.0 (s), 143.4 (s), 137.2
(d), 127.9 (t), 127.8 (s), 127.5 (t), 127.0 (d), 126.7 (d), 54.2 (d),
43.2 (t), 36.5 (s), 35.6 (t), 29.9 (t), 28.25 (q), 28.2 (q), 25.5
(q), 23.6 (q), 21.5 (t), 21.3 (t), 20.7 (t), 20.3 (q), 19.2 (q), 14.2
(q), 13.6 (q) (Found: Mϩ, 288.2079. C19H28O2 requires M,
288.2089).
1-(E,Z-6-Chloro-3-methyl-1-oxohex-2-enyl)-5-(1-oxoprop-2-
ynyl)-2,6,6-trimethylcyclohex-1-ene 70. Barium manganate
(0.16 g, 0.61 mmol) was added in one portion to a stirred solu-
tion of the propargylic alcohol 69 (39 mg, 0.12 mmol) in dry
dichloromethane (5 ml) at room temperature. The mixture was
stirred at room temperature for 30 min and then a further por-
tion of barium manganate (0.16 g, 0.12 mmol) was added. The
mixture was stirred at room temperature for a further 30 min
and then filtered through a short plug of Celite. The Celite plug
was washed exhaustively with dichloromethane (100 ml) and
then the combined filtrate was evaporated to dryness in vacuo to
leave a pale yellow oil. Purification by chromatography on silica
eluting with 20% ether in light petroleum (bp 40–60 ЊC) gave a
mixture of (E)- and (Z)-isomers (1:1 ratio) of the ketone (30
mg, 75%) as a colourless oil; [data for (E)-isomer]: λmax(EtOH)/
nm 245 (ε/dm3 molϪ1 cmϪ1 12 200); νmax(film)/cmϪ1 3249, 1665,
1-(E,Z-6-Chloro-3-methyl-1-oxohex-2-enyl)-5-(1-hydroxy-
prop-2-ynyl)-2,6,6-trimethylcyclohex-1-ene 69. A solution of
ethynylmagnesium bromide (1.94 ml) in THF (0.5 M, 0.97
mmol) was added dropwise over 10 min to a stirred solution of
the aldehyde 52 (0.25 g, 0.88 mmol) in dry THF (10 ml) at
Ϫ78 ЊC under nitrogen. The solution was stirred at Ϫ78 ЊC for
2 h and then quenched with water (5 ml), saturated aqueous
ammonium chloride (10 ml) and ether (10 ml). The mixture was
allowed to warm to room temperature and the organic layer
was separated. The aqueous layer was extracted with ether
(2 × 10 ml) and the combined organic extracts were washed
with saturated aqueous ammonium chloride (10 ml) and brine
(10 ml) and then dried and evaporated in vacuo to a yellow oil.
Purification by chromatography on silica, eluting with 40%
ether in light petroleum (bp 40–60 ЊC), gave 1-(6-chloro-1-
oxohex-2-ynyl)-5-(1-hydroxyprop-2-ynyl)-2,6,6-trimethylcyclo-
hex-1-ene (0.26 g, 94%) as a colourless oil; λmax(EtOH)/nm
230 (ε/dm3 molϪ1 cmϪ1 7 200); νmax(film)/cmϪ1 3452, 3297, 2208,
1640 and 733; δH(250 MHz) 4.72–4.70 (m, 1H, CHOH), 3.64 (t,
J 6 Hz, 2H, CH2Cl), 2.60 (t, J 7 Hz, 2H, alkyne-CH2), 2.47 (d,
1601 and 762; δ (250 MHz) 6.15 (d, J 1 Hz, 1H, CH᎐CCH ),
᎐
H
3
3.60 (t, J 7 Hz, 2H, CH2Cl), 3.31 (s, 1H, alkyne-H), 2.72 [m, 2H,
CH᎐C(CH )CH ], 2.62 (m, 1H, CHCO-alkyne), 2.05–1.89
᎐
3
2
(m, 6H), 1.92 (obsc. d, J 1 Hz, 3H, CH᎐CCH ), 1.56 (s, 3H,
᎐
3
᎐CCH ), 1.19 (s, 3H, Me), 1.18 (s, 3H, Me); δ (67.8 MHz) 199.5
᎐
3
C
(s), 189.9 (s), 157.5 (s), 142.7 (s), 128.3 (s), 127.4 (d), 82.5 (s),
79.4 (s), 58.6 (d), 44.9 (t), 36.7 (s), 31.5 (t), 31.1 (t), 29.7 (t), 27.7
(q), 25.7 (q), 23.6 (q), 21.2 (t), 20.3 (q).
1-(E,Z-6-Iodo-3-methyl-1-oxohex-2-enyl)-5-(1-oxoprop-2-
ynyl)-2,6,6-trimethylcyclohex-1-ene 63. A stirred mixture of the
chloride 70 (50 mg, 0.16 mmol) and sodium iodide (35 mg, 0.23
mmol) in butan-2-one (2 ml) was heated to reflux for 18 h and
then cooled. The mixture was diluted with ether (5 ml) and
water (2 ml) and the organic layer was separated. The aqueous
layer was extracted with ether (2 × 5 ml) and the combined
organic extracts were washed with 10% aqueous sodium thio-
sulfate (5 ml) and brine (5 ml), and then dried and concentrated
in vacuo to give a mixture of (E)- and (Z)-isomers (1:1 ratio) of
the iodide (63 mg, 98%) as a colourless oil; (data for both iso-
J 2 Hz, 1H, alkyne-H), 2.15 (dd, J 8, 5 Hz, 2H, ᎐CCH ), 2.04
᎐
2
(app. quintet, J 7 Hz, 2H, CH2CH2Cl), 2.00–1.76 (m, 3H), 1.72
(obsc. s, 3H, ᎐CCH ), 1.64 (dt, J 11, 3 Hz, 1H, CHCHOH), 1.23
᎐
3
(s, 3H, Me), 1.22 (s, 3H, Me); δC(67.8 MHz) 186.6 (s), 141.8 (s),
133.5 (s), 93.5 (s), 85.6 (s), 83.6 (s), 72.5 (d), 61.3 (d), 50.0 (d),
43.1 (t), 36.7 (s), 31.3 (t), 30.4 (t), 27.4 (q), 23.7 (q), 20.5 (q),
18.2 (t), 16.4 (t) (Found: Mϩ, 306.1386. C18H23ClO2 requires M,
306.1387).
mers): δ (250 MHz) 6.14 (br s, 2H, CH᎐CCH ), 3.30 (s, 2H,
᎐
H
3
A solution of methyllithium–lithium bromide complex (1.38
ml) in ether (1.5 M, 2.1 mmol) was added dropwise over 5
min to a stirred suspension of copper() iodide (0.20 g, 1.0
mmol) in dry THF (5 ml), at 0 ЊC under nitrogen. The solu-
tion was stirred at 0 ЊC for 10 min until the solution became
colourless and all solids had dissolved. The stirred solution
was cooled to Ϫ78 ЊC and a solution of the ynone from
above (0.127 g, 0.413 mmol) in dry THF (4 ml) was added
portionwise over 5 min. The solution was stirred at Ϫ78 ЊC
for 30 min and then allowed to warm to 0 ЊC where it was
quenched with saturated aqueous ammonium chloride (5 ml)
and ether (10 ml). The organic layer was separated and the
aqueous layer was extracted with ether (2 × 10 ml). The com-
bined organic extracts were washed with saturated aqueous
ammonium chloride (10 ml), water (10 ml) and brine (10 ml),
and then dried and evaporated in vacuo to a yellow oil. Puri-
alkyne-H), 3.26 (t, J 7 Hz, 2H, CH2I), 3.17 (t, J 7 Hz, 2H,
CH I), 2.72 [m, 2H, CH᎐C(CH )CH ], 2.65–2.60 (m, 2H,
᎐
2
3
2
CHCO), 2.30 [m, 2H, CH᎐C(CH )CH ], 2.16 (d, J 1 Hz, 3H,
᎐
3
2
CH᎐CCH ), 2.05–1.88 (m, 12H), 1.92 (obsc. d, J 1 Hz, 3H,
᎐
3
CH᎐CCH ), 1.56 (s, 6H, ᎐CCH ), 1.19 [s, 6H, C(CH ) ], 1.18
᎐
᎐
3
3
3 2
[s, 6H, C(CH3)2], which was used directly without any further
purification.
1-(E,Z-3-Methyl-1-oxohex-2-enyl)-5-(1-oxoprop-2-ynyl)-
2,6,6-trimethylcyclohex-1-ene 64. Treatment of a solution of the
iodide 63 (64 mg, 0.16 mmol) in benzene with tri-n-butyltin
hydride and azoisobutyronitrile, according to the general pro-
cedure, gave a mixture of (E)- and (Z)-isomers (1:1 ratio) of
the title cyclohexane (18 mg, 41%) as a colourless oil; (data for
both isomers): λmax(EtOH)/nm 225 (ε/dm3 molϪ1 cmϪ1 900), 246
(1 500); νmax(film)/cmϪ1 3244, 2088, 1720, 1666 and 764; δH(270
MHz) 6.03 (s, 2H, CH᎐CCH ), 3.24 (s, 2H, alkyne-H), 2.56–
᎐
3
3196
J. Chem. Soc., Perkin Trans. 1, 1998, 3181–3206

View Article Online
2.52 [m, 4H, CHCO, (E)-CH᎐C(CH )CH ], 2.09 [s, 3H, (Z)-
72 (13.7 g, 34.0 mmol) in dry ether (300 ml) at Ϫ110 ЊC under
᎐
3
2
CH᎐CCH ], 2.08–1.84 (m, 10H), 1.82 [s, 3H, (E)-CH᎐CCH ],
argon. The solution was stirred at Ϫ110 ЊC for 1 h and then
dimethylformamide (26.0 ml, 340 mmol) was added dropwise
over 20 min. The solution was allowed to warm to room tem-
perature over 1 h and was then diluted with ether (200 ml)
and water (300 ml). The organic layer was separated and the
aqueous layer was re-extracted with ether (2 × 200 ml). The
combined organic extracts were dried and concentrated in
vacuo to an orange oil which was purified by chromatography
on silica, eluting with 20% ether in light petroleum (bp 40–
60 ЊC), to give the aldehyde (9.8 g, 82%) as a colourless oil;
λmax(EtOH)/nm 264 (ε/dm3 molϪ1 cmϪ1 800); νmax(film)/cmϪ1
1695 and 702; δH(250 MHz) 9.54 (s, 1H, CHO), 7.70–7.67 (m,
᎐
᎐
3
3
1.53–1.39 (m, 4H, CH CH ), 1.51 (obsc. s, 6H, ᎐CCH ), 1.13 [s,
᎐
2
3
3
12H, C(CH3)2], 0.90 [t, J 7 Hz, 3H, (E)-CH2CH3], 0.84 [t, J 7
Hz, 3H, (Z)-CH2CH3]; δC(67.8 MHz) 200.2 (s), 199.5 (s), 190.1
(s), 159.6 (s), 158.5 (s), 143.0 (s), 142.9 (s), 128.0 (s), 127.9 (s),
126.9 (d), 126.6 (d), 82.5 (s), 79.4 (d), 58.7 (d), 43.2 (t), 36.7 (t),
35.7 (s), 29.7 (t), 27.6 (q), 27.5 (q), 25.6 (q), 23.6 (q), 21.3 (t),
21.2 (t), 20.7 (t), 20.3 (q), 19.2 (q), 14.2 (q), 13.6 (q) (Found:
Mϩ, 286.1955. C19H26O2 requires M, 286.1933).
1-(tert-Butyldiphenylsiloxy)-pent-4-yne 71. tert-Butyldi-
phenylsilyl chloride (7.4 ml, 28.8 mmol) was added dropwise
over 10 min to a stirred solution of pent-4-yn-1-ol (2.0 g, 24.0
mmol), 4-dimethylaminopyridine (0.29 g, 2.4 mmol) and tri-
ethylamine (4.0 ml, 28.8 mmol) in dry dichloromethane (80 ml)
at 0 ЊC under nitrogen. The mixture was stirred at 0 ЊC for 1 h
and then allowed to warm to room temperature where it was
stirred for a further 14 h. The mixture was diluted with dichloro-
methane (80 ml) and then washed with saturated aqueous
ammonium chloride (100 ml). The organic layer was separated
and the aqueous layer was re-extracted with dichloromethane
(2 × 80 ml). The combined organic extracts were washed with
brine (80 ml) and then dried and evaporated in vacuo to a col-
ourless oil, which was purified by chromatography on silica,
eluting with 10% ether in light petroleum (bp 40–60 ЊC), to give
the silyl ether (7.75 g, 99%) as a colourless oil; λmax(EtOH)/nm
254 (ε/dm3 molϪ1 cmϪ1 500), 260 (700), 264 (800), 270 (600);
νmax(film)/cmϪ1 3306, 2118, 1958, 1888, 1823 and 702; δH(250
MHz) 7.73–7.69 (m, 4H, Ar-H), 7.46–7.41 (m, 6H, Ar-H), 3.79
(t, J 6 Hz, 2H, CH2OTBDPS), 2.38 (dt, J 2, 7 Hz, 2H,
CH2CH2CH2OTBDPS), 1.95 (t, J 2 Hz, 1H, alkyne-H), 1.85–
1.75 (m, 2H, CH2CH2OTBDPS), 1.09 [s, 9H, C(CH3)3]; δC(67.8
MHz) 135.5 (d), 133.8 (s), 129.6 (d), 127.6 (d), 84.2 (s), 68.3 (d),
62.6 (t), 31.4 (t), 26.8 (q), 19.2 (s), 15.0 (t) (Found: Mϩ Ϫ tBu,
265.1036. C17H17OSi requires M, 265.1049).
4H, Ar-H), 7.45–7.37 (m, 6H, Ar-H), 6.22 (s, 1H, ᎐CHH), 5.98
᎐
(s, 1H, ᎐CHH), 3.68 (t, J 6 Hz, 2H, CH OTBDPS), 2.37 (t, J 8
᎐
2
Hz, 2H, CH2CH2CH2OTBDPS), 1.80–1.68 (m, 2H, CH2CH2-
OTBDPS), 1.07 [s, 9H, C(CH3)3]; δC(67.8 MHz) 194.6 (d), 149.9
(s), 135.6 (d), 134.1 (t), 133.9 (s), 129.6 (d), 127.7 (d), 63.1 (t),
30.5 (t), 26.9 (q), 24.3 (t), 19.3 (s) (Found: Mϩ Ϫ tBu, 297.1363.
C18H21O2Si requires M, 297.1311).
1-tert-Butyldiphenylsiloxy-4-hydroxymethylpent-4-ene 73b.
Sodium borohydride (1.17 g, 30.8 mmol) was added portion-
wise over 20 min to a stirred solution of the aldehyde 73a (9.83
g, 28.0 mmol) and cerium trichloride heptahydrate (11.48 g,
30.8 mmol) in methanol (70 ml) at 0 ЊC under nitrogen. The
solution was stirred at 0 ЊC for 20 min and then diluted with
water (1000 ml) and ether (100 ml). The organic layer was
separated and the aqueous layer was re-extracted with ether
(2 × 100 ml). The combined organic extracts were dried and
then concentrated in vacuo to a colourless oil which was purified
by chromatography on silica, eluting with 30% ether in light
petroleum (bp 40–60 ЊC), to give the alcohol (9.8 g, 99%) as a
colourless oil; λmax(EtOH)/nm 254 (600), 259 (700), 264 (700),
271 (600); νmax(film)/cmϪ1 3353, 1959, 1889 and 702; δH(250
MHz) 7.71–7.67 (m, 4H, Ar-H), 7.48–7.36 (m, 6H, Ar-H), 5.02
4-Bromo-1-(tert-butyldiphenylsiloxy)pent-4-ene 72. A solu-
tion of 9-bromoborabicyclo[3.3.1]nonane (56.0 ml) in dichloro-
methane (1.0 M, 56.0 mmol) was added dropwise over 10 min
to a stirred solution of the alkyne 71 in dry dichloromethane
(290 ml) at 0 ЊC under nitrogen. The solution was allowed to
warm to room temperature over 14 h and was then cooled to
0 ЊC. Dilute acetic acid (19.0 ml) was added dropwise over 5
min and the mixture was allowed to warm to room temperature
where it was stirred vigourously for 1hr. The mixture was
cooled to 0 ЊC and then aqueous sodium hydroxide (112 ml, 5
N) was added dropwise over 30 min. The mixture was stirred at
0 ЊC for 1 h and then a solution of hydrogen peroxide (30%) in
water (31.0 m) was added dropwise over 30 min. The mixture
was stirred at 0 ЊC for 2 h and then diluted with water (200 ml)
and dichloromethane (100 ml). The organic layer was separated
and the aqueous layer was re-extracted with dichloromethane
(2 × 200 ml). The combined organic extracts were washed with
saturated aqueous ammonium chloride (100 ml) and brine (100
ml) and then dried and evaporated in vacuo to a yellow oil,
which was purified by chromatography on silica, eluting with
10% ether in light petroleum (bp 40–60 ЊC), to give the bromide
(10.7 g, 95%) as a colourless oil; λmax(EtOH)/nm 254 (ε/dm3
molϪ1 cmϪ1 500), 260 (700), 264 (700), 270 (500); νmax(film)/cmϪ1
1958, 1888, 1822, 1770, 1628 and 701; δH(250 MHz) 7.68–
7.66 (m, 4H, Ar-H), 7.44–7.37 (m, 6H, Ar-H), 5.56 (d, J
2 Hz, 1H, ᎐CHH), 5.39 (d, J 2 Hz, 1H, ᎐CHH), 3.70 (t, J 6 Hz,
(s, 1H, ᎐CHH), 4.87 (s, 1H, ᎐CHH), 4.08–4.02 (m, 2H,
᎐ ᎐
CH2OH), 3.70 (t, J 6 Hz, 2H, CH2OTBDPS), 2.17 (t, J 8 Hz,
2H, CH2CH2CH2OTBDPS), 1.80–1.68 (m, 2H, CH2CH2OTB-
DPS), 1.07 [s, 9H, C(CH3)3]; δC(67.8 MHz) 148.7 (s), 135.6
(d), 134.0 (s), 129.6 (d), 127.7 (d), 109.3 (t), 65.9 (t), 63.5 (t),
30.7 (t), 29.2 (t), 26.9 (q), 19.3 (s) (Found: Mϩ Ϫ tBu, 297.1351.
C18H21O2Si requires M, 297.1311).
4-Bromomethyl-1-tert-butyldiphenylsiloxypent-4-ene 73c. N-
Bromosuccinimide (1.6 g, 9.1 mmol) was added in one portion
to a stirred solution of the alcohol 73b (2.2 g, 6.1 mmol) and
triphenylphosphine (2.4 g, 9.1 mmol) in dry dichloromethane
(60 ml) at 0 ЊC under nitrogen. The solution was allowed to
warm to room temperature over 20 min and then diluted with
ether (100 ml) and water (100 ml). The organic layer was separ-
ated and the aqueous layer was re-extracted with ether (2 × 100
ml). The combined organic fractions were washed with satur-
ated aqueous sodium hydrogen carbonate (100 ml) and satur-
ated brine (100 ml) and then dried and concentrated in vacuo to
a volume of ca. 10 ml. The resulting orange suspension was
poured into light petroleum (bp 40–60 ЊC) (100 ml) and the
white precipitate was removed by filtration. The filtrate was
evaporated in vacuo to a yellow oil which was purified by
chromatography on silica, eluting with 10% ether in light
petroleum (bp 40–60 ЊC) to give the bromide (2.3 g, 99%)
as a colourless oil; λmax(EtOH)/nm 254 (ε/dm3 molϪ1 cmϪ1
400), 260 (513), 264 (600), 270 (400); νmax(film)/cmϪ1 1959,
1889, 1822 and 701; δH(250 MHz) 7.71–7.68 (m, 4H, Ar-H),
᎐
᎐
2H, CH2OTBDPS), 2.58 (t, J 7 Hz, 2H, CH2CH2CH2-
OTBDPS), 1.85–1.75 (m, 2H, CH2CH2OTBDPS), 1.06 [s,
9H, C(CH3)3]; δC(67.8 MHz) 135.6 (d), 133.9 (s), 134.4 (s), 129.7
(d), 127.7 (d), 116.8 (t), 62.4 (t), 38.0 (t), 31.0 (t), 26.9 (q), 19.3
(s) (Found: Mϩ Ϫ tBu, 345.0285. C17H18OBrSi requires M,
345.0310).
1-tert-Butyldiphenylsiloxy-4-formylpent-4-ene 73a. A solu-
tion of t-butyllithium (50.0 ml) in THF (1.7 M, 85.0 mmol) was
added dropwise over 30 min to a stirred solution of the bromide
7.48–7.37 (m, 6H, Ar-H), 5.17 (s, 1H, ᎐CHH), 4.96 (s, 1H,
᎐
᎐CHH), 3.96 (s, 2H, CH Br), 3.71 (t, J 6 Hz, 2H, CH -
᎐
2
2
OTBDPS), 2.34 (t, J 8 Hz, 2H, CH2CH2CH2OTBDPS),
1.77–1.69 (m, 2H, CH2CH2OTBDPS), 1.08 [s, 9H, C(CH3)3];
δC(67.8 MHz) 145.1 (s), 135.5 (d), 133.8 (s), 129.5 (d), 127.6
(d), 114.9 (t), 63.1 (t), 36.6 (t), 30.3 (t), 29.6 (t), 26.8 (q), 19.2
(s) (Found: Mϩ Ϫ tBu, 349.0259. C17H18BrOSi requires M,
349.0310).
J. Chem. Soc., Perkin Trans. 1, 1998, 3181–3206
3197

View Article Online
1-Acetoxymethyl-5-hydroxymethyl-2,6,6-trimethylcyclohex-1-
ene 74. Methanol (7.61 ml, 188 mmol) was added dropwise over
10 min to a stirred solution of the aldehyde 13 (4.22 g, 18.8
mmol) and sodium borohydride (0.78 g, 20.7 mmol) in dry ether
(94 ml) at 0 ЊC under nitrogen. The solution was stirred at 0 ЊC
for 30 min and then warmed to room temperature over 20 min.
The solution was quenched with water (100 ml) and the organic
layer was separated. The aqueous layer was re-extracted with
ether (2 × 100 ml) and the combined organic extracts were dried
and evaporated in vacuo to a yellow oil, which was purified by
chromatography on silica, eluting with 50% ether in light
petroleum (bp 40–60 ЊC), to give the alcohol (4.21 g, 98%) as a
colourless oil; νmax(film)/cmϪ1 3429, 1735 and 733; δH(250 MHz)
4.55 (s, 2H, CH2OAc), 3.83 (dd, J 10, 3 Hz, 1H, CHHOH), 3.37
(dd, J 10, 9 Hz, 1H, CHHOH), 2.62 (br s, 1H, OH), 2.02 (s, 3H,
(Found: C, 68.4; H, 11.9. C17H34O2Si requires C, 68.5; H,
11.5%).
5-tert-Butyldimethylsilyloxymethyl-1-formyl-2,6,6-trimethyl-
cyclohex-1-ene 76. Treatment of a solution of the alcohol 75b
(1.12 g, 3.76 mmol) in dry dichloromethane with tetra(n-propyl)-
ammonium perruthenate and 4-methylmorpholine N-oxide,
according to the general procedure, gave the title aldehyde (1.1
g, 97%) as an unstable colourless oil; λmax(EtOH)/nm 247 (ε/dm3
molϪ1 cmϪ1 15 000); νmax(film)/cmϪ1 1674, 1613 and 775; δH(400
MHz) 10.11 (s, 1H, CHO), 3.82 (dd, J 10, 4 Hz, 1H, CHHO-
TBDMS), 3.37 (dd, J 10, 9 Hz, 1H, CHHOTBDMS), 2.24–2.21
[m, 2H, ᎐C(Me)CH ], 2.10 (s, 3H, Me), 1.91–1.88 (m, 1H,
᎐
2
CHCHH), 1.46–1.41 (m, 2H, CHCHH), 1.31 (s, 3H, Me), 1.08
(s, 3H, Me), 0.90 [s, 9H, SiC(CH3)3], 0.06 [s, 6H, Si(CH3)2];
δC(67.8 MHz) 192.2 (d), 156.1 (s), 140.4 (s), 62.9 (t), 47.7 (d),
35.3 (s), 34.5 (t), 26.7 (q), 25.6 (q), 21.4 (q), 20.6 (t), 19.4 (q),
18.2 (s), Ϫ5.4 (q); which was used immediately.
COCH ), 2.10–1.81 [m, 3H, CHCHH, ᎐C(Me)CH ], 1.65 (s,
᎐
3
2
3H, Me), 1.49–1.42 (m, 2H, CHCHH), 1.05 (s, 3H, Me), 0.82 (s,
3H, Me); δC(67.8 MHz) 171.5 (s), 136.5 (s), 131.9 (s), 63.4 (t),
60.9 (t), 47.0 (d), 36.2 (s), 31.5 (t), 26.6 (q), 22.2 (q), 21.4 (t),
21.0 (q), 19.8 (q) (Found: Mϩ Ϫ AcOH, 166.1312. C11H18O
requires M, 166.1358) (Found: C, 68.6; H, 9.9. C13H22O3
requires C, 69.0; H, 9.8%).
5-tert-Butyldimethylsilyloxymethyl-1-(6-tert-butyldiphenyl-
silyloxy-1-hydroxy-3-methylenehexyl)-2,6,6-trimethylcyclohex-
1-ene 77. Sodium iodide (0.66 g, 4.39 mmol) and tin() chloride
dihydrate (0.99 g, 4.39 mmol) were added in one portion to a
stirred solution of the aldehyde 76 (1.24 g, 4.18 mmol) and the
bromide 73c (2.10 g, 5.02 mmol) in dry dimethylformamide
(42 ml) at room temperature under nitrogen. The mixture was
stirred at room temperature for 4 h and then diluted with ether
(400 ml) and water (5 ml). The suspension was dried with mag-
nesium sulfate and then filtered through a short plug of Celite.
The filtrate was diluted with water (200 ml) and the organic
layer was separated. The aqueous layer was re-extracted with
ether (2 × 200 ml) and the combined organic extracts were dried
and evaporated in vacuo to an orange oil, which was purified by
chromatogaphy on silica, eluting with 5% ether in light petrol-
eum (bp 40–60 ЊC), to give two diastereoisomers (5:4 ratio) of
the alcohol (2.2 g, 82%) as a colourless oil; (data for major
diastereoisomer): λmax(EtOH)/nm 217 (ε/dm3 molϪ1 cmϪ1
16 800), 252 (800); νmax(film)/cmϪ1 1956, 1888, 1821, 1674, 1642
and 702; δH(400 MHz) 7.75–7.69 (m, 4H, Ar-H), 7.46–7.33 (m,
6H, Ar-H), 4.91 (s, 2H, C᎐CH ), 4.38 (br d, J 11 Hz, 1H,
1-Acetoxymethyl-5-tert-butyldimethylsilyloxymethyl-2,6,6-
trimethylcyclohex-1-ene 75a. Triethylamine (1.67 ml, 11.9
mmol) was added portionwise over 5 min to a stirred solution
of the alcohol 74 (2.24 g, 9.91 mmol), tert-butyldimethylsilyl
chloride (1.80 g, 11.9 mmol) and 4-dimethylaminopyridine (122
mg, 0.99 mmol) in dry dichloromethane (30 ml) at 0 ЊC under
nitrogen. The mixture was allowed to warm to room temper-
ature over a period of 12 h and then diluted with dichloro-
methane (30 ml) and saturated aqueous ammonium chloride
(100 ml). The organic layer was separated and the aqueous layer
was re-extracted with dichloromethane (2 × 60 ml). The com-
bined organic extracts were dried and evaporated in vacuo to
a yellow oil which was purified by chromatography on silica,
eluting with 30% ether in light petroleum (bp 40–60 ЊC), to
give the silyl ether (3.16 g, 94%) as a colourless oil; νmax(film)/
cmϪ1 1738, 1471 and 774; δH(400 MHz) 4.57 (s, 2H, CH2OAc),
3.83 (dd, J 10, 4 Hz, 1H, CHHOTBDMS), 3.37 (dd, J 10,
10 Hz, 1H, CHHOTBDMS), 2.04 (s, 3H, COCH3), 2.06–
᎐
2
CHOH), 3.81–3.76 (m, 1H, CHHOTBDMS), 3.71 (t, J 6 Hz,
2H, CH2OTBDPS), 3.41–3.31 (m, 1H, CHHOTBDMS), 2.71–
1.95 [obs. m, 2H, ᎐C(Me)CH ], 1.88–1.82 (m, 1H, CHCHH),
2.60 [m, 1H, CH(OH)CHH], 2.29–2.11 [m, 3H, ᎐C(Me)CH ,
᎐
᎐
2
2
1.67 (s, 3H, Me), 1.51–1.37 (m, 2H, CHCHH), 1.07 (s, 3H,
Me), 0.89 [s, 9H, SiC(CH3)3], 0.84 (s, 3H, Me), 0.05 [s, 6H,
Si(CH3)2]; δC(67.8 MHz) 171.4 (s), 136.5 (s), 132.2 (s), 63.2
(t), 61.0 (t), 46.9 (d), 36.4 (s), 31.2 (t), 26.6 (q), 26.0 (q), 22.3
(q), 21.3 (t), 21.1 (q), 19.9 (q), 18.3 (s), Ϫ5.3 (q)
(Found: Mϩ Ϫ AcOH, 280.2185. C17H32OSi requires M,
280.2222).
5-tert-Butyldimethylsilyloxymethyl-1-hydroxymethyl-2,6,6-
trimethylcyclohex-1-ene 75b. Potassium carbonate (3.99 g, 27.3
mmol) was added in one portion to a stirred solution of the
acetate 75a (3.16 g, 9.1 mmol) in methanol (91 ml) at room
temperature under nitrogen. The solution was stirred at room
temperature for 14 h and then diluted with ether (200 ml)
and water (200 ml). The organic layer was separated and the
aqueous layer was re-extracted with ether (2 × 100 ml). The
combined organic extracts were dried and evaporated in vacuo
to give a white solid which was purified by chromatography on
silica, eluting with 50% ether in light petroleum (bp 40–60 ЊC),
to give the alcohol (2.64 g, 95%) as a white crystalline solid, mp
50–51 ЊC (from pentane); νmax(film)/cmϪ1 3344, 1471 and 774;
δH(400 MHz) 4.12 (app. q, J 12 Hz, 2H, CH2OH), 3.78 (dd,
J 10, 4 Hz, 1H, CHHOTBDMS), 3.37 (dd, J 10, 10 Hz, 1H,
CH(OH)CHH], 2.01–1.97 (m, 2H, CH2CH2CH2OTBDPS),
1.90 (s, 3H, Me), 1.87–1.65 (m, 3H, CHCHH, CH2CH2OTB-
DPS), 1.52–1.39 (m, 2H, CHCHH), 1.23 (s, 3H, Me), 1.09 (obs.
s, 3H, Me), 1.08 [s, 9H, SiC(CH3)3], 0.93 [s, 9H, SiC(CH3)3], 0.08
[s, 6H, Si(CH3)2]; δC(67.8 MHz) 147.2 (s), 138.6 (s), 135.5 (d),
133.9 (s), 132.3 (s), 129.5 (d), 127.5 (d), 112.1 (t), 67.9 (d), 63.6
(t), 63.4 (t), 47.2 (d), 43.6 (t), 37.1 (s), 32.4 (t), 31.9 (t), 30.7 (t),
27.4 (q), 26.8 (q), 25.9 (q), 21.4 (t), 21.2 (q), 19.2 (s), 18.2 (s),
15.2 (q), Ϫ5.3 (q).
5-tert-Butyldimethylsilyloxymethyl-1-(6-tert-butyldiphenyl-
silyloxy-1-methoxy-3-methylenehexyl)-2,6,6-trimethylcyclohex-
1-ene 78a. Potassium hexamethyldisilazide (0.47 g, 2.36 mmol)
was added portionwise over 5 min to a stirred solution of the
alcohol 77 (0.75 g, 1.18 mmol) in dry THF (24 ml) at Ϫ78 ЊC
under nitrogen. The solution was stirred at Ϫ78 ЊC for 7 min
and then dimethyl sulfate (0.56 ml, 17.7 mmol) was added
dropwise over 5 min. The mixture was warmed to room tem-
perature over 30 min and then diluted with ether (50 ml) and
water (50 ml). The organic layer was separated and the aqueous
layer was re-extracted with ether (2 × 50 ml). The combined
organic extracts were dried and evaporated in vacuo to a colour-
less oil, which was purified by chromatography on silica, eluting
with 10% ether in light petroleum (bp 40–60 ЊC), to give two
diastereoisomers (5:4 ratio) of the methyl ether (0.75 g, 97%) as
a colourless oil; (data for major diastereoisomer): λmax/nm 248
(ε/dm3 molϪ1 cmϪ1 400), 254 (500), 260 (600), 264 (600), 271
(400); νmax(film)/cmϪ1 1956, 1888, 1821, 1462, 836 and 701;
δH(270 MHz) 7.75–7.69 (m, 4H, Ar-H), 7.46–7.33 (m, 6H,
Ar-H), 4.85 (s, 2H, C᎐CH ), 4.02–3.96 (m, 1H, CHOMe), 3.87–
CHHOTBDMS), 2.00–1.97 [m, 2H, ᎐C(Me)CH ], 1.84–1.79
᎐
2
(m, 1H, CHCHH), 1.76 (s, 3H, Me), 1.47–1.36 (m, 2H,
CHCHH), 1.14 (s, 3H, Me), 0.89 [s, 9H, SiC(CH3)3], 0.87 (s,
3H, Me), 0.05 [s, 6H, Si(CH3)2]; δC(67.8 MHz) 137.7 (s), 133.9
(s), 63.7 (t) 58.7 (t), 46.9 (d), 36.3 (s), 31.5 (t), 27.1 (q), 25.9
(q), 22.3 (q), 21.5 (t), 19.7 (q), 18.2 (s), Ϫ5.4 (q) (Found:
Mϩ Ϫ tBu Ϫ H2O, 223.1502. C13H23OSi requires M, 223.1518)
᎐
2
3198
J. Chem. Soc., Perkin Trans. 1, 1998, 3181–3206

View Article Online
3.79 (m, 1H, CHHOTBDMS), 3.74 (t, J 6 Hz, 2H, CH2OTB-
DPS), 3.47–3.39 (m, 1H, CHHOTBDMS), 3.23 (s, 3H, OCH3),
2.65–2.55 [m, 1H, CH(OMe)CHH], 2.29–2.20 [m, 3H,
(s), 135.0 (d), 134.5 (s), 133.4 (s), 130.9 (s), 129.0 (d), 127.0 (d),
110.0 (t), 77.5 (d), 63.1 (t), 57.5 (d), 55.6 (q), 42.3 (t), 35.4 (s),
31.6 (t), 30.5 (t), 30.3 (t), 28.2 (q), 26.3 (q), 23.9 (q), 19.8 (q),
19.7 (s), 18.8 (t) (Found: [M ϩ NH4]ϩ, 550.3720. C34H52NO3Si
requires M, 550.3716).
᎐C(Me)CH , CH(OMe)CHH], 2.04–1.97 (m, 2H, CH CH -
᎐
2
2
2
CH2OTBDPS), 1.85 (s, 3H, Me), 1.89–1.72 (m, 3H, CHCHH,
CH2CH2OTBDPS), 1.68–1.40 (m, 2H, CHCHH), 1.24 (s, 3H,
Me), 1.10 [s, 9H, SiC(CH3)3], 1.08 (s, 3H, Me), 0.94 [s,
9H, SiC(CH3)3], 0.10 [s, 6H, Si(CH3)2]; δC(67.8 MHz) 147.6
(s), 135.5 (s), 135.5 (d), 134.0 (s), 131.8 (s), 129.5 (d), 127.6
(d), 110.2 (t), 78.0 (d), 63.6 (t), 63.0 (t), 56.0 (q), 47.8 (d),
42.8 (t), 36.4 (s), 32.1 (t), 31.4 (t), 30.8 (t), 28.9 (q), 26.8
(q), 25.9 (q), 23.4 (q), 20.9 (t), 20.4 (q), 19.2 (s), 18.2 (s), Ϫ5.3
(q).
1-(6-tert-Butyldiphenylsilyloxy-1-methoxy-3-methylene-
hexyl)-5-(1-hydroxyprop-2-enyl)-2,6,6-trimethylcyclohex-1-ene
80. A solution of vinylmagnesium chloride (1.60 ml) in THF
(1.7 M, 2.68 mmol) was added dropwise over 10 min to a stirred
solution of the aldehyde 79 (0.71 g, 1.34 mmol) in dry THF (14
ml) at Ϫ78 ЊC under nitrogen. The solution was stirred at
Ϫ78 ЊC for 1 h and then warmed to room temperature over 1 h.
The mixture was then quenched with water (30 ml) and diluted
with ether (30 ml). The organic layer was separated and the
aqueous layer was re-extracted with ether (2 × 30 ml). The
combined organic extracts were dried and evaporated in vacuo
to a yellow oil which was purified by chromatography on silica,
eluting with a gradient of 30 to 50% ether in light petroleum (bp
40–60 ЊC), to give two diastereoisomers (5:4 ratio) of the alco-
hol (0.71 g, 95%) as a colourless oil; (data for major diastereo-
isomer): λmax(EtOH)/nm 254 (ε/dm3 molϪ1 cmϪ1 800), 259 (900),
264 (1000), 271 (800); νmax(film)/cmϪ1 3478, 1644 and 702;
δH(250 MHz) 7.70–7.66 (m, 4H, Ar-H), 7.44–7.35 (m, 6H,
1-(6-tert-Butyldiphenylsilyloxy-1-methoxy-3-methylene-
hexyl)-5-hydroxymethyl-2,6,6-trimethylcyclohex-1-ene
78b.
Pyridinium toluene-p-sulfonate (2.21 g, 8.80 mmol) was added
in one portion to a solution of the silyl ether 78a (1.14 g, 1.76
mmol) in methanol (18 ml) at room temperature under
nitrogen. The solution was stirred at room temperature for 4.5 h
and then diluted with ether (50 ml) and water (50 ml). The
organic layer was separated and the aqueous layer was re-
extracted with ether (2 × 50 ml). The combined organic extracts
were dried and evaporated in vacuo to a colourless oil which was
purified by chromatography on silica, eluting with a gradient of
5 to 70% ether in light petroleum (bp 40–60 ЊC), to give two
diastereoisomers (5:4 ratio) of the alcohol (0.83 g, 88%) as a
colourless oil; (data for major diastereoisomer): λmax(EtOH)/
nm 248 (ε/dm3 molϪ1 cmϪ1 700), 253 (800), 259 (800), 264 (700),
270 (500); νmax(film)/cmϪ1 3416, 1890, 1824, 1644, 1471 and 702;
δH(400 MHz) 7.70–7.66 (m, 4H, Ar-H), 7.44–7.36 (m, 6H,
Ar-H), 5.92 (ddd, J 17, 10 Hz, 5 Hz, 1H, CH᎐CH ), 5.32 (ddd,
᎐
2
J 17, 2, 2 Hz, 1H, CH᎐CHH), 5.17 (ddd, J 10, 2, 2 Hz, 1H,
᎐
CH᎐CHH), 4.86 (s, 2H, C᎐CH ), 4.56 (br s, 1H, CHOH), 4.11–
᎐
᎐
2
4.03 (m, 1H, CHOMe), 3.74 (t, J 6 Hz, 2H, CH2OTBDPS), 3.24
(s, 3H, OCH3), 2.61 [dd, J 15, 10 Hz, 1H, CH(OMe)CHH],
2.31–2.21 [m, 3H, ᎐C(Me)CH , CH(OMe)CHH], 2.09–2.02 (m,
᎐
2
2H, CH2CH2CH2OTBDPS), 1.87 (s, 3H, Me), 1.82–1.55 (m,
4H, CHCH2, CH2CH2OTBDPS), 1.46–1.39 (m, 1H, CHCH2),
1.25 (s, 3H, Me), 1.13 (s, 3H, Me), 1.10 [s, 9H, SiC(CH3)3];
δC(67.8 MHz) 147.4 (s), 141.3 (d), 136.6 (s), 135.5 (d), 133.9 (s),
132.7 (s), 129.4 (d), 127.5 (d), 113.3 (t), 110.4 (t), 78.2 (d), 71.9
(d), 63.6 (t), 56.0 (q), 49.4 (d), 42.8 (t), 37.4 (s), 33.1 (t), 32.1 (t),
30.7 (t), 28.7 (q), 26.8 (q), 23.5 (q), 20.4 (q), 19.2 (s), 17.9 (t)
(Found: [M ϩ NH4]ϩ, 578.4030. C36H56NO3Si requires M,
578.4029).
Ar-H), 4.81 (s, 2H, C᎐CH ), 4.00–3.91 (m, 1H, CHOMe), 3.91–
᎐
2
3.79 (m, 1H, CHHOH), 3.70 (t, J 6 Hz, 2H, CH2OTBDPS),
3.52–3.39 (m, 1H, CHHOH), 3.20 (s, 3H, OCH3), 2.67–2.51 [m,
1H, CH(OMe)CHH], 2.29–2.13 [m, 3H, ᎐C(Me)CH , CH-
᎐
2
(OMe)CHH], 2.08–1.98 (m, 2H, CH2CH2CH2OTBDPS), 1.82
(s, 3H, Me), 1.95–1.70 (m, 3H, CHCHH, CH2CH2OTBDPS),
1.62–1.41 (m, 2H, CHCHH), 1.21 (s, 3H, Me), 1.06 [s, 9H,
SiC(CH3)3], 0.89 (s, 3H, Me); δC(67.8 MHz) 147.4 (s), 135.5 (s),
135.1 (d), 133.9 (s), 131.7 (s), 129.4 (d), 127.5 (d), 110.3 (t), 78.0
(d), 63.6 (t), 63.0 (t), 56.0 (q), 48.2 (d), 42.8 (t), 36.4 (s), 32.1 (t),
31.3 (t), 30.8 (t), 28.8 (q), 26.8 (q), 23.4 (q), 20.9 (t), 20.4 (q),
19.2 (s).
1-(6-tert-Butyldiphenylsilyloxy-1-methoxy-3-methylene-
hexyl)-5-(1-oxoprop-2-enyl)-2,6,6-trimethylcyclohex-1-ene 81a.
Dess–Martin periodinane (1.07 g, 2.52 mmol) was added in one
portion to the alcohol 80 (0.71 g, 1.26 mmol) in dry dichloro-
methane (13 ml) at 0 ЊC under nitrogen. The mixture was
warmed to room temperature and the whole stirred for 3 h. The
mixture was then diluted with dichloromethane (13 ml) and
quenched with 5% aqueous sodium thiosulfate (8 ml). The mix-
ture was stirred vigorously at room temperature for 20 min and
then neutralised with potassium carbonate and diluted with
water (20 ml). The organic layer was separated and the aqueous
layer was re-extracted with dichloromethane (2 × 30 ml). The
combined organic extracts were washed with saturated brine
(30 ml) and then dried and concentrated in vacuo to a yellow oil.
Purification by chromatography on silica, eluting with 30%
ether in light petroleum (bp 40–60 ЊC) gave two diastereo-
isomers (5:4 ratio) of the ketone (0.61 g, 86%) as a colourless
oil; (data for major diastereoisomer): λmax(EtOH)/nm 254
(ε/dm3 molϪ1 cmϪ1 100), 260 (300), 265 (300), 270 (100);
νmax(film)/cmϪ1 1958, 1889, 1823, 1691, 1644, 1608 and 702;
δH(400 MHz) 7.70–7.66 (m, 4H, Ar-H), 7.44–7.35 (m, 6H,
Ar-H), 6.48 (dd, J 17, 10 Hz, 1H, CH᎐CH ), 6.26 (dd, J 17, 1
1-(6-tert-Butyldiphenylsilyloxy-1-methoxy-3-methylene-
hexyl)-5-formyl-2,6,6-trimethylcyclohex-1-ene 79. Dess–Martin
periodinane (1.59 g, 3.37 mmol) was added in one portion to
the alcohol 78b (1.00 g, 1.87 mmol) in dry dichloromethane (20
ml) at 0 ЊC under nitrogen. The mixture was warmed to room
temperature and the whole stirred for 3 h. The mixture was then
diluted with dichloromethane (20 ml) and quenched with 5%
aqueous sodium thiosulfate (10 ml). The mixture was stirred
vigorously at room temperature for 20 min and then neutralised
with potassium carbonate and diluted with water (20 ml). The
organic layer was separated and the aqueous layer was re-
extracted with dichloromethane (2 × 30 ml). The combined
organic extracts were washed with saturated brine (30 ml) and
then dried and concentrated in vacuo to a yellow oil. Purifi-
cation by chromatography on silica, eluting with 30% ether in
light petroleum (bp 40–60 ЊC), gave two diastereoisomers (5:4
ratio) of the aldehyde (0.93 g, 94%) as a colourless oil; (data for
major diastereoisomer): λmax(EtOH)/nm 254 (ε/dm3 molϪ1 cmϪ1
700), 260 (900), 265 (900), 270 (700); νmax(film)/cmϪ1 3070, 2929,
1959, 1889, 1823, 1719, 1644, 1471, 1428, 1109, 823, 703; δH(250
MHz) 9.85 (d, J 3 Hz, 1H, CHO), 7.70–7.66 (m, 4H, Ar-H),
᎐
2
Hz, 1H, CH᎐CHH), 5.72 (dd, J 10, 1 Hz, 1H, CH᎐CHH), 4.83
᎐
᎐
(s, 2H, C᎐CH ), 3.95 (br d, J 10 Hz, 1H, CHOMe), 3.71 (t, J 6
᎐
2
Hz, 2H, CH2OTBDPS), 3.19 (s, 3H, OCH3), 2.81 (dd, J 12, 3
Hz, 1H, CHCO), 2.60 [dd, J 16, 10 Hz, 1H, CH(OMe)CHH],
7.44–7.35 (m, 6H, Ar-H), 4.83 (s, 2H, C᎐CH ), 4.09–3.95 (m,
᎐
2
1H, CHOMe), 3.71 (t, J 6 Hz, 2H, CH2OTBDPS), 3.22 (s, 3H,
OCH3), 2.58 [d, J 10 Hz, 1H, CH(OMe)CHH], 2.29–2.14 [m,
2.28–2.17 [m, 3H, ᎐C(Me)CH , CH(OMe)CHH], 2.10–2.05
᎐
2
(m, 2H, CH2CH2CH2OTBDPS), 1.82 (obs s, 3H, Me), 1.98–
1.63 (m, 4H, CHCH2, CH2CH2OTBDPS), 1.14 (s, 3H, Me),
1.08 (s, 3H, Me), 1.07 [s, 9H, SiC(CH3)3]; δC(67.8 MHz) 203.4
(s), 147.5 (s), 137.3 (d), 135.4 (d), 135.4 (s), 133.9 (s), 130.7 (s),
129.4 (d), 127.5 (d), 127.1 (t), 110.2 (t), 77.9 (d), 63.5 (t), 55.9
4H, CHCHO, ᎐C(Me)CH , CH(OMe)CHH], 2.13–2.06 (m,
᎐
2
2H, CH2CH2CH2OTBDPS), 1.94–1.71 (m, 4H, CHCH2,
CH2CH2OTBDPS), 1.85 (s, 3H, Me), 1.30 (s, 3H, Me), 1.08 (s,
3H, Me), 1.07 [s, 9H, SiC(CH3)3]; δC(67.8 MHz) 205.8 (d), 146.8
J. Chem. Soc., Perkin Trans. 1, 1998, 3181–3206
3199

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(d), 55.6 (q), 42.7 (t), 37.4 (s), 32.1 (t), 31.5 (t), 30.7 (t), 29.1 (q),
26.8 (q), 23.8 (q), 21.7 (t), 20.1 (q), 19.1 (s).
CHOMe), 3.22 (s, 3H, OCH3), 3.20 (obs. t, J 6, 2H, CH2I),
2.81–2.76 (m, 1H, CHCO), 2.64–2.51 [m, 1H, CH(OMe)CHH],
2.28–2.14 [m, 3H, CH(OMe)CHH, CH2CH2CH2I], 2.06–1.81
1-(6-Hydroxy-1-methoxy-3-methylenehexyl)-5-(1-oxoprop-2-
enyl)-2,6,6-trimethylcyclohex-1-ene 81b. Tetrabutylammonium
fluoride (0.34 g, 1.08 mmol) was added in one portion to a
stirred solution of the silyl ether 81a (0.10 g, 0.18 mmol) and
toluene-p-sulfonic acid (0.07 g, 0.54 mmol) in THF (11 ml) at
0 ЊC under nitrogen. The solution was allowed to warm to room
temperature where it was stirred for 60 h. The mixture was then
diluted with ether (20 ml) and water (20 ml) and the organic
layer was separated. The aqueous layer was re-extracted with
ether (2 × 20 ml) and the combined organic extracts were dried
and evaporated in vacuo to a yellow oil which was purified by
chromatography on silica, eluting with 70% ether in light
petroleum (bp 40–60 ЊC), to give two diastereoisomers (5:4
ratio) of the alcohol (0.06 g, 97%) as a colourless oil; (data for
major diastereoisomer): νmax(film)/cmϪ1 3424, 1684, 1644, 1608
[m, 5H, ᎐C(Me)CH CHH, CH CH I], 1.80 (s, 3H, Me), 1.68–
᎐
2
2
2
1.56 (m, 1H, CHCHH), 1.23 (s, 3H, Me), 1.12 (s, 3H, Me);
δC(67.8 MHz) 203.6 (s), 145.9 (s), 137.3 (d), 135.3 (s), 130.7 (s),
127.3 (t), 111.4 (t), 78.0 (d), 55.8 (d), 55.6 (q), 42.3 (t), 37.4 (s),
36.5 (t), 31.4 (t), 31.3 (t), 29.2 (q), 23.9 (q), 21.7 (t), 20.1 (q),
6.8 (t); which was used without further purification.
1-(1-Methoxy-3-methylenehexyl)-5-(1-oxoprop-2-enyl)-2,6,6-
trimethylcyclohex-1-ene 65b. Treatment of a solution of the
iodide 65a (55 mg, 0.13 mmol) in benzene with tri-n-butyltin
hydride and azoisobutyronitrile, according to the general pro-
cedure, gave two diastereoisomers (5:4 ratio) of the title
cyclohexene (12 mg, 31%) as a colourless oil; (data for major
diastereoisomer): νmax(film)/cmϪ1 1689, 1644, 1609 and 891;
δ (250 MHz) 6.44 (dd, J 17, 10, 1H, CH᎐CH ), 6.21 (dd, J 17,
᎐
H
2
and 891; δ (270 MHz) 6.36 (dd, J 17, 10, 1H, CH᎐CH ), 6.16
1, 1H, CH᎐CHH), 5.68 (dd, J 10, 1, 1H, CH᎐CHH), 4.80 (s,
᎐
᎐ ᎐
H
2
(dd, J 17, 1, 1H, CH᎐CHH), 5.63 (dd, J 10, 1, 1H, CH᎐CHH),
2H, C᎐CH ), 4.03–3.93 (m, 1H, CHOMe), 3.21 (s, 3H, OCH ),
᎐
2 3
᎐
᎐
4.76 (s, 2H, C᎐CH ), 3.92 (br d, J 10, 1H, CHOMe), 3.56 (t, J 6,
2H, CH2OH), 3.14 (s, 3H, OCH3), 2.74–2.70 (m, 1H, CHCO),
2.57–2.47 [m, 1H, CH(OMe)CHH], 2.24–2.18 [m, 1H, CH-
2.82–2.74 (m, 1H, CHCO), 2.27–2.14 [m, 1H, CH(OMe)-
CHH], 2.14–2.01 [m, 1H, CH(OMe)CHH], 2.09–1.72 [m, 4H,
᎐
2
᎐C(Me)CH , CH CH CH ], 1.79 (obs. s, 3H, Me), 1.70–1.52 (m,
᎐
2
2
2
3
(OMe)CHH], 2.11–2.06 [m, 2H, ᎐C(Me)CH ], 1.72 (obs. s, 3H,
4H, CHCH2, CH2CH3), 1.24 (s, 3H, Me), 1.22 (s, 3H, Me), 0.89
(t, J 7, 3H, CH2CH3); δC(67.8 MHz) 204.0 (s), 147.7 (s), 137.4
(d), 135.7 (s), 130.8 (s), 127.5 (t), 110.1 (t), 77.8 (d), 55.8 (d),
55.8 (q), 42.4 (t), 38.2 (t), 37.5 (s), 31.6 (t), 29.2 (q), 23.8 (q),
21.8 (t), 20.9 (t), 20.2 (q), 13.9 (q) (Found: Mϩ, 304.2404.
C20H32O2 requires M, 304.2402).
᎐
2
Me), 2.00–1.60 (m, 6H, CHCH2, CH2CH2CH2OH), 1.16 (s, 3H,
Me), 1.05 (s, 3H, Me); δC(67.8 MHz) 203.7 (s), 147.2 (s), 137.1
(d), 135.1 (s), 130.5 (s), 127.4 (t), 110.3 (t), 78.0 (d), 62.1 (t), 55.8
(d), 55.5 (q), 42.2 (t), 37.2 (s), 32.1 (t), 31.3 (t), 30.4 (t), 29.0 (q),
23.7 (q), 21.5 (t), 20.0 (q) (Found: Mϩ Ϫ MeOH, 288.2088.
C19H28O2 requires M, 288.2089).
1-(6-tert-Butyldiphenylsilyloxy-1-methoxy-3-methylene-
1-(1-Methoxy-3-methylene-6-p-tolylsulfonylhexyl)-5-(1-oxo-
prop-2-enyl)-2,6,6-trimethylcyclohex-1-ene 81c. Toluene-p-
sulfonyl chloride (65 mg, 0.34 mmol) was added in one portion
to a stirred solution of the alcohol 81b (55 mg, 0.17 mmol) and
triethylamine (120 µl, 1.36 mmol) in dry dichloromethane (3.4
ml) at room temperature under nitrogen. The mixture was
stirred at room temperature for 24 h and then concentrated in
vacuo to a yellow oil which was purified by chromatography on
silica, eluting with 10% ether in light petroleum (bp 40–60 ЊC),
to give two diastereoisomers (5:4 ratio) of the tosylate (0.064 g,
79%) as a colourless oil; (data for major diastereoisomer):
λmax(EtOH)/nm 254 (ε/dm3 molϪ1 cmϪ1 800), 262 (800), 266
(800), 273 (700); νmax(film)/cmϪ1 1805, 1682, 1599 and 814;
δH(400 MHz) 7.80 (d, J 8, 2H, Ar-H), 7.35 (d, J 8, 2H, Ar-H),
6.47 (dd, J 17, 10, 1H, CH᎐CH ), 6.24 (dd, J 17, 1, 1H,
hexyl)-5-(1-hydroxyprop-2-ynyl)-2,6,6-trimethylcyclohex-1-ene
82. A solution of ethynylmagnesium chloride (4.0 ml) in THF
(0.5 M, 1.98 mmol) was added dropwise over 10 min to a stirred
solution of the aldehyde 79 (0.88 g, 1.65 mmol) in dry THF (16
ml) at Ϫ78 ЊC under nitrogen. The solution was stirred at
Ϫ78 ЊC for 1 h and then warmed to Ϫ30 ЊC over 1 h. The mix-
ture was then quenched with water (30 ml) and diluted with
ether (30 ml). The organic layer was separated and the aqueous
layer was re-extracted with ether (2 × 30 ml). The combined
organic extracts were dried and evaporated in vacuo to a yellow
oil which was purified by chromatography on silica, eluting
with 30% ether in light petroleum (bp 40–60 ЊC), to give two
diastereoisomers (5:4 ratio) of the alcohol (0.90 g, 97%) as a
colourless oil; (data for major diastereoisomer): λmax(EtOH)/
nm 254 (ε/dm3 molϪ1 cmϪ1 900), 259 (1100), 264 (1100), 27
(800); νmax(film)/cmϪ1 3428, 3306, 2089, 1956, 1890, 1823 and
702; δH(250 MHz) 7.70–7.63 (m, 4H, Ar-H), 7.45–7.38 (m, 6H,
᎐
2
CH᎐CHH), 5.73 (dd, J 10, 1, 1H, CH᎐CHH), 4.81 (s, 2H,
᎐
᎐
C᎐CH ), 4.05 (t, J 6, 2H, CH OTos), 3.90 (br d, J 10, 1H,
᎐
2
2
CHOMe), 3.19 (s, 3H, OCH3), 2.81–2.77 (m, 1H, CHCO),
2.59–2.48 [m, 1H, CH(OMe)CHH], 2.45 (s, 3H, ArCH3), 2.24–
Ar-H), 4.82 (s, 2H, C᎐CH ), 4.75–4.70 (m, 1H, CHOH), 4.03–
᎐
2
3.99 (m, 1H, CHOMe), 3.70 (t, J 6, 2H, CH2OTBDPS), 3.22 (s,
3H, OCH3), 2.57 [dd, J 15, 10, 1H, CH(OMe)CHH], 2.49 (d,
J 2, 1H, alkyne-H), 2.21–2.07 [m, 5H, CH2CH2CH2OTBDPS,
2.18 [m, 1H, CH(OMe)CHH], 2.16–2.10 [m, 2H, ᎐C(Me)CH ],
᎐
2
1.79 (obs. s, 3H, Me), 2.06–1.70 (m, 6H, CHCH2, CH2CH2-
CH2OTos), 1.21 (s, 3H, Me), 1.13 (s, 3H, Me); δC(67.8 MHz)
203.4 (s), 145.9 (s), 144.4 (s), 137.1 (d), 134.4 (s), 132.9 (s), 130.5
(s), 129.6 (d), 127.6 (d), 127.2 (t), 110.9 (t), 78.1 (d), 69.9 (t),
55.5 (d), 55.5 (q), 42.1 (t), 37.1 (s), 31.5 (t), 31.4 (t), 29.0 (q),
26.6 (t), 23.7 (q), 21.5 (t), 21.4 (q), 19.9 (q) (Found:
Mϩ Ϫ MeOH, 422.2180. C26H34O4S requires 422.2178).
᎐C(Me)CH , CH(OMe)CHH], 1.86 (obs. s, 3H, Me), 1.95–
᎐
2
1.69 (m, 4H, CHCH2, CH2CH2OTBDPS), 1.66–1.59 (m, 1H,
CHCHOH), 1.58 (s, 1H, OH), 1.23 (s, 3H, Me), 1.08 (obs. s, 3H,
Me), 1.08 [obs. s, 9H, SiC(CH3)3]; δC(67.8 MHz) 147.9 (s), 136.6
(s), 136.0 (d), 134.5 (s), 133.1 (s), 129.9 (d), 128.0 (d), 110.9 (t),
86.0 (s), 78.6 (d), 73.2 (d), 64.1 (t), 63.6 (d), 56.6 (q), 51.1 (d),
43.3 (t), 37.7 (s), 33.2 (t), 32.6 (t), 31.2 (t), 29.4 (q), 27.3 (q), 24.1
(q), 20.8 (q), 19.7 (t), 19.7 (s) (Found: Mϩ Ϫ tBu Ϫ MeOH,
469.2596. C31H37O2Si requires M, 469.2563).
1-(6-Iodo-1-methoxy-3-methylenehexyl)-5-(1-oxoprop-2-
enyl)-2,6,6-trimethylcyclohex-1-ene 65a. A stirred suspension of
sodium iodide (78 mg, 0.51 mmol), butan-2-one (9 ml) and the
tosylate 81c (83 mg, 0.18 mmol) was heated at reflux for 90 min
and then cooled. Water (15 ml) and ether (15 ml) were then
added and the organic layer was separated. The aqueous layer
was re-extracted with ether (2 × 10 ml) and the combined
organics were washed with 5% aqueous sodium thiosulfate
(15 ml) and then dried and evaporated in vacuo to give two
diastereoisomers (5:4 ratio) of the iodide (70 mg, 93%) as a
colourless oil; (data for major diastereoisomer): νmax(film)/cmϪ1
1689, 1644, 1608 and 892; δH(270 MHz) 6.44 (dd, J 17, 10, 1H,
1-(6-tert-Butyldiphenylsilyloxy-1-methoxy-3-methylene-
hexyl)-5-(1-oxoprop-2-ynyl)-2,6,6-trimethylcyclohex-1-ene 83a.
Dess–Martin periodinane (1.21 g, 2.86 mmol) was added in one
portion to the alcohol 82 (0.80 g, 1.43 mmol) in dry dichloro-
methane (14 ml) at 0 ЊC under nitrogen. The mixture was
warmed to room temperature and the whole stirred for 3 h. The
mixture was then diluted with dichloromethane (14 ml) and
quenched with 5% aqueous sodium thiosulfate (8 ml). The mix-
ture was stirred vigorously at room temperature for 20 min and
then neutralised with potassium carbonate and diluted with
water (20 ml). The organic layer was separated and the aqueous
CH᎐CH ), 6.24 (dd, J 17, 1 Hz, 1H, CH᎐CHH), 5.72 (dd, J 10,
᎐
᎐
2
1, 1H, CH᎐CHH), 4.84 (s, 2H, C᎐CH ), 4.01–3.88 (m, 1H,
᎐
᎐
2
3200
J. Chem. Soc., Perkin Trans. 1, 1998, 3181–3206

View Article Online
layer was re-extracted with dichloromethane (2 × 30 ml). The
combined organic extracts were washed with saturated brine
(30 ml) and then dried and concentrated in vacuo to a yellow oil.
Purification by chromatography on silica, eluting with 30%
ether in light petroleum (bp 40–60 ЊC), gave two diastereo-
isomers (5:4 ratio) of the ketone (0.74 g, 93%) as a colourless
oil; (data for the major diastereoisomer): λmax(EtOH)/nm 247
(ε/dm3 molϪ1 cmϪ1 800), 253 (900), 260 (1000), 264 (1000), 271
(800); νmax(film)/cmϪ1 3268, 2090, 1958, 1889, 1824 and 702;
δH(270 MHz) 7.70–7.63 (m, 4H, Ar-H), 7.45–7.38 (m, 6H,
(t), 31.4 (t), 31.3 (t), 28.6 (q), 23.8 (q), 21.6 (t), 20.1 (q),
6.8 (t).
1-(1-Methoxy-3-methylenehexyl)-5-(1-oxoprop-2-ynyl)-
2,6,6-trimethylcyclohex-1-ene 66b. Treatment of a solution
of the iodide 66a (180 mg, 0.42 mmol) in benzene with tri-
n-butyltin hydride and azoisobutyronitrile, according to the
general procedure, gave two diastereoisomers (5:4 ratio) of the
title cyclohexene (61 mg, 48%) as a colourless oil; (data for
major diastereoisomer): νmax(film)/cmϪ1 3252, 2089, 1668 and
892; δ (400 MHz) 4.82 (s, 2H, C᎐CH ), 3.93 (br d, J 10, 1H,
᎐
H
2
Ar-H), 4.83 (s, 2H, C᎐CH ), 4.03–3.98 (m, 1H, CHOMe), 3.71
CHOMe), 3.24 (s, 1H, alkyne-H), 3.19 (s, 3H, OCH3), 2.66–
2.54 [m, 2H, CH(OMe)CHH, CHCO], 2.26–2.17 [m, 1H,
᎐
2
(t, J 6, 2H, CH2OTBDPS), 3.25 (s, 1H, alkyne-H), 3.22 (s, 3H,
OCH3), 2.68–2.55 [m, 2H, CH(OMe)CHH, CHCO], 2.29–2.16
[m, 3H, CH2CH2CH2OTBDPS, CH(OMe)CHH], 2.07–2.01
CH(OMe)CHH], 2.14–2.04 [m, 4H, ᎐C(Me)CH , CH CH -
᎐
2
2
2
CH3], 2.03–1.96 (m, 2H, CHCH2), 1.81 (s, 3H, Me), 1.56–1.44
(m, 2H, CH2CH3), 1.20 (s, 3H, Me), 1.18 (s, 3H, Me), 0.92 (t,
J 7, 3H, CH2CH3); δC(67.8 MHz) 191.0 (s), 147.6 (s), 135.3 (s),
130.8 (s), 110.0 (t), 82.7 (s), 78.6 (d), 77.8 (d), 60.1 (d), 55.8 (q),
42.4 (t), 38.2 (t), 37.7 (s), 31.5 (t), 28.6 (q), 22.8 (q), 21.6 (t), 20.8
(t), 20.3 (q), 13.9 (q) (Found: Mϩ, 302.2233. C20H36O2 requires
M, 302.2246).
2,4-Dimethyl-3-(2-hydroxyethyl)penta-2,4-diene 88a. A solu-
tion of t-butyllithium (6.72 ml) in pentane (1.7 M, 11.4 mmol)
was added dropwise over 10 min to a stirred solution of 3-
bromo-2,4-dimethylpenta-2,4-diene26 (1.04 g, 5.7 mmol) in dry
THF (40 ml) at Ϫ78 ЊC under nitrogen. The mixture was stirred
for 30 min at Ϫ78 ЊC, and then excess ethylene oxide was bub-
bled through the yellow solution for 5 min. The mixture was
stirred at Ϫ78 ЊC for 30 min, and then warmed to Ϫ40 ЊC over
45 min. The solution was quenched with water (10 ml), and the
organic layer was then separated, dried and concentrated in
vacuo to leave a yellow residue. The residue was purified by
chromatography on silica eluting with 35% ether in hexane to
give the alcohol (0.56 g, 70%) as a colourless oil; νmax(film)/cmϪ1
[m, 2H, ᎐C(Me)CH ], 1.99–1.92 (m, 2H, CHCH ), 1.84 (s, 3H,
᎐
2
2
Me), 1.80–1.70 (m, 2H, CH2CH2OTBDPS), 1.31 (s, 3H, Me),
1.07 (obs. s, 3H, Me), 1.07 [obs. s, 9H, SiC(CH3)3]; δC(67.8 MHz)
190.2 (s), 147.5 (s), 135.5 (d), 134.9 (s), 134.0 (s), 131.3 (s), 129.5
(d), 127.6 (d), 110.4 (t), 82.5 (s), 78.6 (d), 78.0 (d), 63.6 (t), 60.2
(d), 56.2 (q), 42.6 (t), 37.1 (s), 32.1 (t), 31.5 (t), 30.8 (t), 28.5 (q),
26.8 (q), 23.8 (q), 21.6 (t), 20.2 (q), 19.2 (s).
1-(6-Hydroxy-1-methoxy-3-methylenehexyl)-5-(1-oxoprop-2-
ynyl)-2,6,6-trimethylcyclohex-1-ene 83b. Tetrabutylammonium
fluoride (1.53 g, 4.86 mmol) was added in one portion to a
stirred solution of the silyl ether 83a (0.45 g, 0.81 mmol) and
toluene-p-sulfonic acid (0.46 g, 2.43 mmol) in THF (48 ml) at
0 ЊC under nitrogen. The solution was allowed to warm to room
temperature where it was stirred for 72 h. The mixture was then
diluted with ether (100 ml) and water (100 ml) and the organic
layer was separated. The aqueous layer was re-extracted with
ether (2 × 100 ml) and the combined organic extracts were dried
and evaporated in vacuo to a yellow oil which was purified by
chromatography on silica, eluting with 70% ether in light
petroleum (bp 40–60 ЊC), to give two diastereoisomers (5:4
ratio) of the alcohol (0.24 g, 93%) as a colourless oil; (data for
major diastereoisomer): νmax(film)/cmϪ1 3406, 3252, 2088, 1666
3402, 1642 and 886; δ (250 MHz) 4.97 (s, 1H, ᎐CH ), 4.59 (s,
᎐
H
2
1H, ᎐CH ), 3.60 (t, J 7, 2H, CH OH), 2.42 (t, J 7, 2H,
᎐
2
2
CH2CH2OH), 1.78 (s, 3H, Me), 1.72 (s, 3H, Me), 1.69 (s, 3H,
Me); δC(67.8 MHz) 146.8 (s), 134.2 (s), 128.1 (s), 113.7 (t), 61.0
(t), 34.2 (t), 23.1 (q), 22.8 (q), 19.7 (q) (Found: Mϩ, 140.1204.
C9H16O requires M, 140.1201) (Found: C, 76.7; H, 11.3.
C9H16O requires C, 77.1; H, 11.5%).
and 892; δ (270 MHz) 5.03 (s, 2H, C᎐CH ), 3.91 (br d, J 9, 1H,
᎐
H
2
CHOMe), 3.65 (t, J 6, 2H, CH2OH), 3.32 (s, 1H, alkyne-H),
3.16 (s, 3H, OCH3), 2.64–2.53 [m, 2H, CH(OMe)CHH,
CHCO], 2.26–2.10 [m, 3H, CH(OMe)CHH, CH2CH2CH2OH],
2.07–1.96 [m, 2H, ᎐C(Me)CH ], 1.96–1.86 (m, 2H, CHCH ),
3-(2-Acetoxyethyl)-2,4-dimethylpenta-2,4-diene 88b. A solu-
tion of acetyl chloride (3.27 ml, 46.0 mmol), triethylamine (6.40
ml, 46.0 mmol), 4-dimethylaminopyridine (28 mg, 2.3 mmol)
and the diene alcohol 88a (4.30 g, 31.0 mmol) in dry dichloro-
methane (50 ml) was stirred at room temperature for 4 h. The
yellow mixture was quenched with water (40 ml) and the
organic layer was then separated and washed with saturated
aqueous sodium hydrogen bicarbonate (2 × 25 ml) and brine
(20 ml). Evaporation of the dried organic extracts left a yellow
oil which was purified by chromatography eluting with 15%
ether in hexane to give the acetate (4.4 g, 78%) as a colourless
oil; νmax(film)/cmϪ1 1742, 1666, 1632 and 1031; δH(250 MHz)
᎐
2
2
1.78 (s, 3H, Me), 1.77–1.68 (m, 2H, CH2CH2OH), 1.16 (s, 3H,
Me), 1.15 (s, 3H, Me); δC(67.8 MHz) 191.0 (s), 147.3 (s), 134.9
(s), 130.9 (s), 110.5 (t), 82.6 (s), 79.6 (d), 78.0 (d), 62.5 (t), 60.0
(d), 55.6 (q), 42.3 (t), 37.6 (s), 32.4 (t), 32.2 (t), 30.6 (t), 28.6 (q),
22.8 (q), 21.5 (t), 20.2 (q) (Found: Mϩ Ϫ MeOH, 286.1931.
C19H26O2 requires M, 286.1933).
1-(6-Iodo-1-methoxy-3-methylenehexyl)-5-(1-oxoprop-2-
ynyl)-2,6,6-trimethylcyclohex-1-ene 66a. Imidazole (0.05 g, 0.74
mmol) was added in one portion to a solution of triphenyl-
phosphine (0.20 g, 0.74 mmol) in dry dichloromethane (4.0 ml)
at 0 ЊC under nitrogen. The mixture was stirred at 0 ЊC for 10
min, until the imidazole had dissolved, and then iodine (0.19 g,
0.74 mmol) was added in one portion. The mixture was stirred
at 0 ЊC for 5 min and then a solution of the alcohol 83b (0.20 g,
0.62 mmol) in dry dichloromethane (2.2 ml) was added drop-
wise over 2 min. The mixture was warmed to room temperature,
stirred for 30 min, and then concentrated in vacuo to a yellow
oil. Purification by chromatography on silica, eluting with 5%
ether in light petroleum (bp 40–60 ЊC), gave two diastereo-
isomers (5:4 ratio) of the iodide (0.18 g, 68%) as a colourless
oil; (data for major diastereoisomer): νmax(film)/cmϪ1 3257,
4.93 (s, 1H, ᎐CH ), 4.58 (s, 1H, ᎐CH ), 4.03 (t, J 8, 2H,
᎐
᎐
2
2
CH2OAc), 2.42 (t, J 8, 2H, CH2CH2OAc), 2.06 (s, 3H,
OCOMe), 1.77 (s, 3H, Me), 1.69 (s, 3H, Me), 1.62 (s, 3H, Me);
δC(67.8 MHz) 171.4 (s), 146.1 (s), 132.8 (s), 128.8 (s), 114.2 (t),
63.3 (t), 30.4 (t), 23.4 (q), 22.8 (q), 21.6 (q), 19.8 (q) (Found:
Mϩ, 182.1317. C11H18O2 requires M, 182.1307) (Found: C, 72.8;
H, 10.1. C11H18O2 requires C, 72.4; H, 9.9%).
1-(2-Acetoxyethyl)-2,6,6-trimethylcyclohex-1-ene-5-carb-
oxaldehyde 89. Acrolein (4.40 ml, 67.0 mmol) was added in one
portion to a stirred solution of boron trifluoride–diethyl ether
(8.24 ml, 67.0 mmol) in dry toluene (180 ml) at Ϫ60 ЊC under
nitrogen. The mixture was stirred at Ϫ60 ЊC for 15 min and then
a solution of the diene 88b (8.09 g, 44.5 mmol) in toluene (20
ml) was added dropwise over 15 min. The yellow solution was
stirred at Ϫ60 ЊC for 10 h and then cooled to Ϫ78 ЊC and
quenched with water (150 ml) and pentane (150 ml). The mix-
ture was allowed to warm to room temperature overnight and
then the organic layer was separated, dried and evaporated
2089, 1666, 1574 and 733; δ (270 MHz) 4.86 (s, 2H, C᎐CH ),
᎐
H
2
3.91 (br d, J 10, 1H, CHOMe), 3.25 (s, 1H, alkyne-H), 3.21
(obs. t, J 6, 2H, CH2I), 3.20 (s, 3H, OCH3), 2.66–2.47 [m, 2H,
CH(OMe)CHH, CHCO], 2.26–2.14 [m, 3H, CH(OMe)CHH,
CH2CH2CH2I], 2.10–1.90 (m, 6H, CHCH2CH2, CH2CH2I),
1.79 (s, 3H, Me), 1.18 (s, 3H, Me), 1.16 (s, 3H, Me); δC(67.8
MHz) 190.9 (s), 145.8 (s), 135.0 (s), 130.9 (s), 111.4 (t), 82.4
(s), 78.6 (d), 78.0 (d), 60.1 (d), 55.8 (q), 42.3 (t), 37.6 (s), 36.5
J. Chem. Soc., Perkin Trans. 1, 1998, 3181–3206
3201

View Article Online
in vacuo to leave a yellow oil. Purification by chromatography
on silica gel eluting with 20% diethyl ether in hexane gave the
aldehyde (7.7 g, 74%) as a colourless oil, which crystallised on
standing at 0 ЊC to a white solid, mp 43–45 ЊC (from hexane);
νmax(film)/cmϪ1 1740, 1720 and 1031; δH(400 MHz) 9.84 (d, J 3,
1H, CHO), 4.01 (t, J 9, 2H, CH2OAc), 2.41 (br t, J 9, 2H,
CH2CH2OAc), 2.17 (app. dt, J 10, 3, 1H, CHCHO), 2.08 (s, 3H,
(t, J 8, 2H, CH2OAc), 3.39 (t, J 7, 2H, CH2Br), 2.38 (br t, J 8,
2H, CH2CH2OAc), 2.07 (s, 3H, OCOMe), 2.31–2.01 (m, 3H),
1.92 (app. t, J 7, 2H, ᎐CCH ), 1.71–1.63 (m, 2H), 1.68 (s, 3H,
᎐
2
Me), 1.55–1.49 (m, 2H), 1.01 (s, 3H, Me), 0.89 (s, 3H, Me);
δC(67.8 MHz) 170.8 (s), 133.5 (d), 132.0 (s), 129.6 (s), 128.2 (d),
63.6 (t), 43.0 (d), 37.6 (s), 33.0 (t), 32.3 (t), 31.0 (t), 27.6 (t), 27.0
(q), 25.6 (t), 25.3 (t), 27.3 (q), 20.7 (q), 19.7 (q) (Found: Mϩ,
356.1355. C18H29BrO2 requires M, 356.1351).
OCOMe), 2.04 (app. t, J 6, 2H, ᎐CCH ), 1.87–1.76 (m, 2H),
᎐
2
1.68 (s, 3H, Me), 1.24 (s, 3H, Me), 1.09 (s, 3H, Me); δC(67.8
MHz) 205.6 (d), 170.7 (s), 131.5 (s), 130.4 (s), 63.4 (t), 57.2 (d),
36.6 (s), 30.4 (t), 27.6 (q), 27.3 (t), 23.2 (q), 20.7 (q), 19.8 (q),
19.3 (t) (Found: Mϩ, 238.1572. C14H22O3 requires M, 238.1569)
(Found: C, 70.7; H, 9.3. C14H22O3 requires C, 70.6; H, 9.3%).
1-(2-Acetoxyethyl)-2,6,6-trimethyl-5-[(Z-5-tert-butyldimethyl-
siloxypent-1-enyl)]cyclohex-1-ene 91. A solution of sodium
hexamethyldisilazide (14.5 ml) in THF (1 M, 14.0 mmol) was
added dropwise over 5 min to a stirred solution of phosphon-
ium salt 90 (8.04 g, 14.0 mmol) in dry THF (75 ml) at 0 ЊC
under nitrogen. The deep orange solution was stirred at 0 ЊC for
15 min and then a solution of the aldehyde 89 (3.00 g, 13.0
mmol) in THF (7 ml) was added dropwise over 10 min. The
resulting yellow solution was allowed to warm slowly to room
temperature over 7 h. The solvent was evaporated in vacuo to
leave a pale yellow residue which was triturated with pentane
(6 × 10 ml). The pentane extracts were evaporated in vacuo to
leave a clear oil which was purified by column chromatography
on silica, eluting with 25% ether in hexane to give a mixture of
(E)- and (Z)-isomers (1:18 ratio) of the olefin (3.6 g, 74%) as
a colourless oil; [data for (Z)-isomer only]: νmax(film)/cmϪ1
1-(2-Hydroxyethyl)-2,6,6-trimethyl-5-[(Z)-5-bromopent-1-
enyl]cyclohex-1-ene 93. A solution of diisobutylaluminium
hydride (2.61 ml) in hexanes (1.0 M, 2.6 mmol) was added
dropwise to a stirred solution of the bromoacetate 92b (0.60 g,
1.7 mmol) in dry THF (10 ml) at Ϫ20 ЊC under nitrogen. The
mixture was stirred at Ϫ20 ЊC for 30 min and then quenched
with water (5 ml). The resulting emulsion was filtered through a
glass sinter and the organic layer was separated, washed with
brine (2 × 15 ml) and dried. The solvent was removed in vacuo
to leave the bromo alcohol (0.39 g, 74%), as a clear oil; λmax
-
(EtOH)/nm 223 (ε/dm3 molϪ1 cmϪ1 10 300); νmax(film)/cmϪ1
3490, 1719, 1686, 1631 and 981; δH(250 MHz) 5.50–5.34 (m,
2H, HC᎐CH), 3.73 (t, J 8, 2H, CH OH), 3.49 (t, J 7, 2H,
᎐
2
CH2Br), 2.43 (br t, J 8, 2H, CH2CH2OH), 2.36–2.19 (m, 2H),
2.11–1.97 (m, 3H), 1.61 (s, 3H, Me), 1.81–1.57 (m, 2H), 1.54–
1.30 (m, 2H), 1.09 (s, 3H, Me), 0.97 (s, 3H, Me); δC(67.8 MHz)
133.9 (d), 132.3 (s), 128.9 (s), 127.4 (d), 62.8 (t), 43.8 (t), 43.4
(d), 37.9 (s), 33.4 (t), 32.3 (t), 31.4 (t), 27.1 (q), 25.8 (t), 24.2 (t),
22.8 (q), 20.2 (q) (Found: C, 61.4; H, 8.1. Calc. for C16H27BrO:
C, 61.0; H, 8.6%) (Found: Mϩ, 314.1253. C16H27BrO requires
M, 314.1245); which was used without further purification.
1-Formylmethyl-2,6,6-trimethyl-5-[(Z)-5-bromopent-1-enyl]-
cyclohex-1-ene 94. Treatment of a solution of the alcohol
93 (0.90 g, 0.24 mmol) in dry dichloromethane with tetra(n-
propyl)ammonium perruthenate and 4-methylmorpholine N-
oxide, according to the general procedure, gave the title alde-
hyde (0.65 g, 73%) as a colourless oil; νmax(film)/cmϪ1 1721,
1673, 915 and 739; δH(250 MHz) 9.52 (t, J 2, 1H, CHO), 5.46–
1742 and 874; δ (400 MHz) 5.41–5.29 (m, 2H, HC᎐CH),
᎐
H
4.00 (t, J 9, 2H, CH2OAc), 3.58 (t, J 7, 2H, CH2OSi), 2.44–
2.29 (m, 2H, CH2CH2OAc), 2.07 (s, 3H, OCOMe), 2.19–2.01
(m, 2H), 1.97–1.79 (m, 3H), 1.58 (s, 3H, Me), 1.69–1.43 (m,
t
4H), 0.91 (s, 9H, Bu), 0.89 (s, 3H, Me), 0.86 (s, 3H, Me),
0.02 (s, 6H, Me2Si); δC(67.8 MHz) 171.1 (s), 133.4 (d), 132.1
(s), 129.6 (s), 128.3 (d), 64.1 (t), 62.9 (t), 43.0 (d), 37.8 (s),
32.3 (t), 31.0 (t), 28.1 (t), 27.0 (q), 25.8 (t), 25.6 (t), 22.9 (q),
22.4 (q), 20.8 (q), 19.7 (q), 14.3 (s) (Found: Mϩ, 408.3066.
C24H44O3Si requires M, 408.3060).
5.31 (m, 2H, C᎐CH), 3.41 (t, J 7, 2H, CH Br), 3.12 (br s, 2H,
᎐
2
CH CHO), 2.49–2.01 (m, 3H), 1.92 (app. q, J 7, 2H, ᎐CCH ),
᎐
2
2
1.72–1.59 (m, 2H), 1.51 (s, 3H, Me), 1.53–1.47 (m, 2H), 0.90 (s,
3H, Me), 0.82 (s, 3H, Me); δC(67.8 MHz) 201.0 (d), 133.4 (d),
132.2 (s), 128.6 (s), 127.7 (d), 43.7 (t), 43.0 (d), 37.6 (s), 33.3 (t),
32.4 (t), 31.5 (t), 27.4 (q), 26.6 (t), 25.7 (t), 22.5 (q), 20.1 (q)
(Found: Mϩ, 312.1087. C16H25BrO requires M, 312.1089)
(Found: C, 61.6; H, 7.7. C16H25BrO requires C, 61.3; H, 8.1%).
1-(2-Hydroxybut-3-enyl)-2,6,6-trimethyl-5-[(Z)-5-bromopent-
1-enyl]cyclohex-1-ene 95. A solution of vinylmagnesium brom-
ide (1.80 ml) in dry THF (1.0 M, 1.8 mmol) was added dropwise
over 5 min to a stirred solution of the aldehyde 94 (0.36 g, 1.2
mol) in dry THF (7 ml) at Ϫ78 ЊC under nitrogen. The mixture
was stirred at Ϫ78 ЊC for 30 min and then quenched with satur-
ated aqueous ammonium chloride (6 ml) and allowed to warm
to room temperature over 30 min. The organic layer was separ-
ated, washed with brine (15 ml) and then evaporated in vacuo to
leave a yellow oil which was purified by chromatography on
silica, eluting with 35% diethyl ether in hexane to give two
diastereoisomers of the alcohol (0.18 g, 47%) as a colourless
oil; (data for both diastereoisomers): νmax(film)/cmϪ1 3422,
1719, 1654 and 991; δH(400 MHz) 5.90 (ddd, J 17, 10, 6, 1H,
1-(2-Acetoxyethyl)-2,6,6-trimethyl-5-[(Z)-5-hydroxypent-1-
enyl]cyclohex-1-ene 92a. A solution of tetrabutylammonium
fluoride (3.95 ml) in THF (1.0 M, 3.95 mmol) was added in one
portion to a solution of the silyl ether 91 (1.50 g, 3.8 mmol) in
THF (12 ml) at room temperature. The pale yellow solution was
stirred at room temperature for 40 min and then quenched with
water (5 ml). The organic layer was separated, washed with
brine (2 × 10 ml) and then dried and evaporated in vacuo to
leave the alcohol as a clear oil (0.97 g, 91%); νmax(film)/cmϪ1
3426, 1741, 1654 and 738; δH(400 MHz) 5.46–5.34 (m, 2H,
HC᎐CH), 4.03 (t, J 8, 2H, CH OAc), 3.70–3.62 (br. m, 2H,
᎐
2
CH2OH), 2.43–2.32 (m, 2H, CH2CH2OAc), 2.18–2.10 (m, 1H),
2.06 (s, 3H, OCOMe), 2.01 (app. t, J 7, 2H, ᎐CCH ), 1.97–1.90
᎐
2
(m, 2H, ᎐CCH ), 1.67 (s, 3H, Me), 1.70–1.60 (m, 2H), 1.58–1.48
᎐
2
(m, 2H), 1.06 (s, 3H, Me), 0.89 (s, 3H, Me); δC(67.8 MHz)
170.7 (s), 132.6 (d), 132.2 (s), 129.7 (s), 128.7 (d), 63.8 (t), 62.4
(t), 43.0 (d), 37.7 (s), 32.5 (t), 31.2 (t), 27.6 (t), 27.1 (q), 25.3 (t),
24.2 (t), 22.6 (q), 22.3 (q), 19.6 (q) (Found: Mϩ, 294.2191.
C18H30O3 requires M, 294.2195), which was used without
further purification.
HC᎐CH ), 5.49–5.31 (m, 2H, HC᎐CH), 5.26 (dd, J 17, 2, 1H,
᎐
᎐
2
1-(2-Acetoxyethyl)-2,6,6-trimethyl-5-[(Z)-5-bromopent-1-
enyl]cyclohex-1-ene 92b. A solution of the alcohol 92a (1.60 g,
5.7 mmol) and carbon tetrabromide (2.83 g, 8.5 mmol) in dry
dichloromethane (15 ml) was stirred at 0 ЊC under nitrogen.
Triphenylphosphine (1.64 g, 6.3 mmol) was added in one por-
tion and the yellow solution was then stirred at room temper-
ature for 1 h. The solvent was evaporated in vacuo to leave a
pale yellow residue which was preadsorbed onto silica and
chromatographed, eluting with 15% ether in hexane to give the
bromide (1.5 g, 74%) as a clear oil; νmax(film)/cmϪ1 1736, 1654,
HC᎐CH ), 5.09 (dd, J 10, 2, 1H, HC᎐CH ), 4.28 (br m, 1H,
᎐ ᎐
2 2
CHOH), 3.41 (t, J 7, 2H, CH2Br), 2.42–1.97 (m, 3H), 1.92 (app.
q, J 7, 2H, ᎐CCH ), 1.74–1.63 (m, 4H), 1.61–1.56 (m, 2H), 1.56
᎐
2
(s, 3H, Me), 1.04 (s, 3H, Me), 0.94 (s, 3H, Me); δC(67.8 MHz)
140.9 (d), 133.5/133.6 (d), 132.7/132.8 (s), 131.0/131.1 (s), 127.3/
127.4 (d), 113.7/113.8 (t), 72.3 (t), 43.1/43.2 (d), 37.5/37.8 (s),
36.1/36.2 (t), 33.1/33.2 (t), 30.9/31.2 (t), 27.8/28.1 (d), 25.7/25.8
(t), 25.2/25.3 (t), 23.7 (q), 22.9 (q), 20.9 (q) (Found: Mϩ,
340.1405. C18H29BrO requires M, 340.1402).
1-(2-Oxobut-3-enyl)-2,6,6-trimethyl-5-[(Z)-5-bromopent-1-
1029 and 666; δ (400 MHz) 5.46–5.31 (m, 2H, HC᎐CH), 4.01
enyl]cyclohex-1-ene 96. A mixture of the alcohol 95 (36 mg, 0.1
᎐
H
3202
J. Chem. Soc., Perkin Trans. 1, 1998, 3181–3206

View Article Online
mmol) and Dess–Martin periodinane (186 mg, 0.4 mmol) in dry
dichloromethane (2 ml) was stirred at room temperature for 2 h.
A 1:1 solution of hexane–diethyl ether (6 ml) was added, fol-
lowed immediately by 10% aqueous sodium metabisulfite (12
drops). The cloudy mixture was stirred at room temperature
for 45 min, during which time two layers separated out. The
biphasic solution was loaded directly onto a silica gel column
and chromatographed, eluting with 30% diethyl ether in hexane
to yield the desired enone (35 mg, 99%) as a colourless oil;
νmax(film)/cmϪ1 1687, 1464 and 981; δH(250 MHz) 6.45 (dd, J 18,
1-(2-Hydroxyethyl)-2,6,6-trimethyl-5-(1,3-dioxolan-2-yl)-
cyclohex-1-ene 97b. A solution of diisobutylaluminium hydride
(10.9 ml) in hexanes (1 M, 10.9 mmol) was added dropwise over
5 min to a stirred solution of the acetate 97a (2.56 g, 0.1 mmol)
in dry THF (26 ml) at Ϫ20 ЊC under argon. The mixture was
stirred at Ϫ20 ЊC for 30 min and then quenched with saturated
aqueous ammonium chloride (8 ml). The organic layer was sep-
arated, washed with brine (50 ml) and then dried and evapor-
ated in vacuo to leave a clear oil which was purified by column
chromatography on silica gel eluting with 30% diethyl ether in
hexane to give the hydroxy acetal (1.8 g, 73%) as a colourless oil;
νmax(film)/cmϪ1 3410, 1513 and 1061; δH(250 MHz) 4.90 [d, J 3,
1H, HC(O)2], 4.00–3.79 (m, 4H, 2 × CH2O), 3.61 (t, J 9, 2H,
CH2OH), 2.34 (br t, J 9, CH2CH2OH), 1.63 (s, 3H, Me), 2.10–
1.85 (m, 5H), 1.12 (s, 3H, Me), 0.97 (s, 3H, Me); δC(67.8 MHz)
132.8 (s), 129.8 (s), 104.7 (d), 65.0 (t), 64.4 (t), 62.5 (t), 48.4 (d),
37.0 (s), 32.1 (t), 32.0 (t), 27.3 (q), 22.6 (q), 20.3 (q), 18.7 (t)
(Found: Mϩ, 240.1726. C14H24O3 requires M, 240.1725)
(Found: C, 69.8; H, 10.4. C14H24O3 requires C, 70.0; H, 10.1%).
1-Formylmethyl-2,6,6-trimethyl-5-(1,3-dioxolan-2-yl)-
10, 1H, HC᎐CH ), 6.27 (dd, J 18, 2, 1H, HC᎐CH ), 5.75 (dd,
᎐
᎐
2
2
J 10, 2, 1H, HC᎐CH ), 5.48–5.29 (m, 2H, HC᎐CH), 3.40 (t, J 7,
᎐
᎐
2
2H, CH2Br), 3.32 (app. s, 2H, CH2CO), 2.41 (app. dt, J 10, 7,
1H, HCC᎐C), 2.32–2.01 (m, 4H), 1.93–1.86 (app. q, J 7, 2H,
᎐
᎐CCH ), 1.62–1.49 (m, 2H), 1.48 (s, 3H, Me), 0.91 (s, 3H,
᎐
2
Me), 0.86 (s, 3H, Me); δC(67.8 MHz) 198.6 (s), 135.8 (d), 133.8
(d), 131.0 (s), 130.7 (s), 127.7 (t), 127.0 (d), 43.2 (d), 40.7 (t),
37.7 (s), 36.2 (t), 33.6 (t), 31.7 (t), 28.3 (t), 27.2 (q), 26.3 (t), 22.5
(q), 20.6 (q) (Found: Mϩ, 338.1248. C18H27BrO requires M,
338.1245).
1-(2-Oxobut-3-enyl)-2,6,6-trimethyl-5-[(Z)-5-iodopent-1-
enyl]cyclohex-1-ene 86a. Treatment of a solution of the brom-
ide 96 (210 mg, 0.60 mmol) in butan-2-one with sodium iodide,
according to the general procedure, gave the title iodide (232
mg, 97%) as a pale yellow oil; νmax(film)/cmϪ1 1706, 1687, 1614,
cyclohex-1-ene 98. Treatment of a solution of the alcohol 97b
(1.10 g, 5.4 mmol) in dry dichloromethane with tetra(n-propyl)-
ammonium perruthenate and 4-methylmorpholine N-oxide,
according to the general procedure, gave the title aldehyde (1.0
g, 94%) as a colourless oil; νmax(film)/cmϪ1 1721 and 949; δH(250
MHz) 9.48 (app. s, 1H, CHO), 4.89 [d, J 3, 1H, HC(O)2], 3.94–
3.77 (m, 4H, CH2O), 3.07 (app. s, 2H, CH2CHO), 1.59 (s, 3H,
Me), 2.14–1.62 (m, 5H), 1.06 (s, 3H, Me), 0.93 (s, 3H, Me);
δC(67.8 MHz) 201.1 (d), 132.6 (s), 128.8 (s), 104.6 (d), 64.9 (t),
64.4 (t), 48.1 (d), 43.5 (t), 36.8 (s), 32.1 (t), 26.8 (q), 22.0 (q),
20.3 (q), 18.8 (t) (Found: Mϩ Ϫ CH2CHO, 195.1269. C12H19O2
requires M, 195.1385).
1-(2-Hydroxybut-3-enyl)-2,6,6-trimethyl-5-(1,3-dioxolan-2-
yl)cyclohex-1-ene 99. Cerium trichloride heptahydrate (1.21 g,
4.9 mmol) was dried by stirring at 140 ЊC and 0.1 Torr for 3 h.
The reaction vessel was vented to argon and dry THF (8 ml)
was then added, and the white slurry stirred at room temper-
ature overnight. The slurry was cooled to Ϫ78 ЊC and a solu-
tion of vinylmagnesium bromide (4.8 ml) in dry THF (1 M, 4.8
mmol) was then added dropwise over 5 min, and the resulting
dark tan suspension stirred at Ϫ78 ЊC for 1 h. To this suspen-
sion was then added the aldehyde 98 (0.96 g, 3.9 mmol) in dry
THF (4 ml), and the cream coloured mixture was stirred at
Ϫ78 ЊC for 1 h, then allowed to warm to room temperature over
2 h. The solution was quenched with saturated aqueous ammo-
nium chloride (3 ml) and the organic layer was separated. The
aqueous fraction was extracted with ether (3 × 10 ml) and then
washed with brine (5 ml). The combined organics were dried
and evaporated in vacuo to leave two diastereoisomers of the
alcohol (0.79 g, 74%) as a colourless oil; (data for both diastereo-
isomers): νmax(film)/cmϪ1 3447, 1642 and 920; δH(250 MHz)
984 and 746; δ (250 MHz) 6.45 (dd, J 18, 10, 1H, HC᎐CH ),
᎐
H
2
6.27 (dd, J 18, 2, 1H, HC᎐CH ), 5.75 (dd, J 10, 2, 1H, HC᎐
᎐
᎐
2
CH ), 5.46–5.29 (m, 2H, HC᎐CH), 3.34 (app. s, 2H, CH CO),
᎐
2
2
3.19 (t, J 7, 2H, CH I), 2.43 (app. dt, J 10, 7, 1H, HCC᎐C),
᎐
2
2.28–2.01 (m, 4H), 1.90–1.83 (app. q, J 7, 2H, ᎐CCH ), 1.62–
᎐
2
1.52 (m, 2H), 1.53 (s, 3H, Me), 0.89 (s, 3H, Me), 0.83 (s, 3H,
Me); δC(67.8 MHz) 198.6 (s), 135.8 (d), 133.8 (d), 131.0 (s),
130.7 (s), 127.5 (t), 127.4 (d), 43.2 (d), 40.7 (t), 37.7 (s), 33.6 (t),
31.3 (t), 28.3 (t), 27.1 (q), 25.7 (t), 22.5 (q), 20.6 (q), 6.6 (t)
(Found: Mϩ, 386.1113. C18H27IO requires M, 386.1107); which
was used without further purification.
1-(2-Oxobut-3-enyl)-2,6,6-trimethyl-5-[(Z)-pent-1-enyl)]-
cyclohex-1-ene 86b. Treatment of a solution of the iodide 86a
(110 mg, 0.3 mmol) in benzene with tri-n-butyltin hydride and
azoisobutyronitrile according to the general procedure gave the
title cyclohexene (68 mg, 92%) as a yellow oil; νmax(film)/cmϪ1
1706, 1686, 1614 and 986; δH(250 MHz) 6.45 (dd, J 18, 10, 1H,
HC᎐CH ), 6.27 (dd, J 18, 2, 1H, HC᎐CH ), 5.74 (dd, J 10, 2,
᎐
᎐
2
2
1H, HC᎐CH ), 5.46–5.29 (m, 2H, HC᎐CH), 3.34 (app. s, 2H,
᎐
᎐
2
CH CO), 2.42 (app. dt, J 10, 7, 1H, HCC᎐C), 2.17–1.93 (m,
᎐
2
4H), 1.63–1.52 (m, 2H), 1.52 (s, 3H, Me), 1.42–1.31 (m, 2H),
0.93–0.86 (m, 6H), 0.83 (s, 3H, Me); δC(67.8 MHz) 198.4 (s),
135.7 (d), 132.0 (d), 130.9 (s), 130.6 (s), 129.8 (d), 127.5 (t), 42.9
(d), 40.6 (t), 37.8 (s), 31.4 (t), 29.6 (t), 26.8 (q), 25.6 (t), 22.9 (t),
22.3 (q), 20.5 (q), 13.9 (q) (Found: Mϩ, 260.2143. C18H28O
requires M, 260.2140).
1-(2-Acetoxyethyl)-2,6,6-trimethyl-5-(1,3-dioxolan-2-yl)-
cyclohex-1-ene 97a. A stirred solution of the aldehyde 89 (0.87
g, 3.6 mmol), ( )-camphor-10-sulfonic acid (41 mg, 0.2 mmol),
ethylene glycol (2.03 ml, 36.4 mmol) and benzene (10 ml) was
heated to reflux for 30 min. The cooled solution was diluted
with water (4 ml) and ether (20 ml) and the organic layer was
separated, washed with brine (2 × 15 ml) and then dried and
evaporated in vacuo to leave the acetal (0.97 g, 93%) as a clear
oil, which crystallised on standing at Ϫ10 ЊC to give white
crystals, mp 54–56 ЊC (from pentane); νmax(film)/cmϪ1 1746,
1499 and 979; δH(250 MHz) 4.89 [d, J 3, 1H, HC(O)2], 4.07–
3.73 (m, 6H, 2 × CH2O and CH2OAc), 2.35 (br t, J 9, 2H,
CH2CH2OAc), 2.07 (s, 3H, OCOMe), 1.93–1.37 (m, 5H), 1.65
(s, 3H, Me), 1.12 (s, 3H, Me), 0.97 (s, 3H, Me); δC(67.8 MHz)
170.8 (s), 132.4 (s), 130.3 (s), 104.6 (d), 64.9 (t), 64.3 (t), 63.9 (t),
48.4 (d), 37.0 (s), 32.0 (t), 27.6 (t), 27.0 (q), 22.3 (q), 20.8 (q),
20.1 (q), 18.7 (t) (Found: Mϩ, 282.1834. C16H26O4 requires M,
282.1831) (Found: C, 67.8; H, 9.4. C16H26O4 requires C, 68.1;
H, 9.3%).
5.83 (ddd, J 17, 10, 6, 1H, HC᎐CH ), 5.14 (dd, J 17, 1, 1H,
᎐
2
HC᎐CH ), 4.96 (dd, J 10, 1, 1H, HC᎐CH ), 4.81 [d, J 2, 1H,
᎐
᎐
2
2
HC(O)2], 4.31–4.12 (br m, 1H, CHOH), 3.94–3.71 (m, 4H,
2 × CH2O), 2.40–2.11 (m, 3H), 1.99–1.86 (m, 2H), 1.78–1.46
(m, 2H), 1.49 (s, 3H, Me), 0.93 (s, 3H, Me), 0.82 (s, 3H, Me);
δC(67.8 MHz) 141.1 (d), 132.2/132.5 (s), 131.6/131.3 (s), 113.6/
113.5 (t), 104.8/104.4 (d), 72.4/72.3 (d), 64.8 (t), 64.7/64.3 (t),
48.2/47.9 (d), 36.9/36.7 (s), 36.0/35.8 (t), 31.9/31.7 (t), 28.6/27.9
(q), 23.8/23.3 (q), 21.3/21.2 (q), 18.6/18.5 (t) (Found: Mϩ,
266.1857. C16H26O3 requires M, 266.1882) (Found: C, 71.9; H,
10.0. C16H26O3 requires C, 72.1; H, 9.9%).
1-(2-Triisopropylsiloxybut-3-enyl)-2,6,6-trimethyl-5-formyl-
cyclohex-1-ene 100. A solution of the acetal 99 (0.79 g, 2.9
mmol) and ( )-camphor-10-sulfonic acid (0.32 g, 1.4 mmol) in
THF (6 ml) and water (6 ml) was heated to 60 ЊC for 3 h. The
cooled mixture was diluted with ether (8 ml) and the organic
layer was then separated. The aqueous layer was re-extracted
with ether (3 × 6 ml) and the combined organic extracts were
dried and evaporated in vacuo to a clear oil (0.70 g, 3.2 mmol)
J. Chem. Soc., Perkin Trans. 1, 1998, 3181–3206
3203

View Article Online
which was then taken up in dry dichloromethane (8 ml) and
cooled to Ϫ20 ЊC under argon. 2,6-Lutidine (670 µl, 5.7 mmol)
was then added dropwise, followed immediately by triisopro-
pylsilyl trifluoromethanesulfonate (1.02 ml, 3.8 mmol), and the
clear solution stirred at Ϫ20 ЊC for 20 min. The reaction was
quenched with water (2 ml), and the organic layer was separ-
ated and then dried. The solvent was evaporated in vacuo to
leave a pale yellow oil which was purified by chromatography
on silica gel, eluting with 20% ether in hexane to give two
diastereoisomers of the silyl ether (0.80 g, 91%) as a clear oil;
(data for both diastereoisomers): νmax(film)/cmϪ1 1721, 883 and
740; δH(250 MHz) 9.82 (d, J 1, 1H, CHO), 5.82 (ddd, J 17, 10, 6,
2H, Ar), 6.85 (d, J 9, 2H, Ar), 5.82 (ddd, J 18, 10, 6, 1H,
C᎐CH ), 5.71–5.59 (m, 1H, HC᎐CH), 5.43 (dd, J 15, 6, 1H,
᎐
᎐
2
HC᎐CH), 5.09 (dd, J 18, 1, 1H, HC᎐CHH), 4.97 (dd, J 10, 1,
᎐
᎐
1H, HC᎐CHH), 4.44 (s, 2H, OCH Ar), 4.42–4.39 (m, 1H,
᎐
2
CHOH), 4.37–4.23 (br m, 1H, CHOSi), 3.79 (s, 3H, OMe),
3.74–3.54 (m, 2H, CH2OPMB), 2.72–2.64 (m, 1H), 2.42 (dd,
J 14, 6, 1H, CHCHOSi), 2.34–2.14 (m, 1H), 2.06–1.90 (m, 2H),
1.89–1.74 (m, 2H), 1.72–1.53 (m, 2H), 1.60 (s, 3H, Me), 1.09–
0.92 (m, 24H, 2 × Me and 3 × Me2), 0.89 (m, 3H, 3 × CHMe2);
δC(67.8 MHz) 158.6/158.9 (s), 142.0/142.1 (d), 133.2/133.3 (d),
132.8/132.9 (d), 132.6/132.7 (s), 132.2/132.4 (s), 129.9/130.2 (s),
129.7/129.8 (d), 113.4/113.5 (d), 112.7 (t), 82.5 (d), 74.3/74.5 (d),
72.6/73.9 (t), 68.1/68.4 (t), 64.0/64.5 (t), 54.7 (q), 48.6/48.8 (d),
39.3/39.4 (t), 37.3/37.4 (t), 34.3 (s), 31.1/31.2 (t), 25.0/25.1 (q),
21.2/21.3 (q), 17.8/17.9 (q), 13.9/14.9 (q), 11.6/11.8 (d) (Found
(FAB-MS): Mϩ, 571. C35H58O4Si requires M, 571); and (ii) the
recovered vinyl iodide 101 (168 mg) (eluted second) as a colour-
less oil.
1H, HC᎐CH ), 5.07 (dd, J 17, 1, 1H, HC᎐CH ), 4.96 (dd, J 10,
᎐
᎐
2
2
1, 1H, HC᎐CH ), 4.47–4.37 (m, 1H, CHOSi), 2.48–2.39 (m,
᎐
2
1H), 2.36–2.12 (m, 2H), 2.06–1.99 (app. t, J 7, 2H, CH2), 1.91–
1.72 (m, 2H), 1.58 (s, 3H, Me), 1.17 (s, 3H, Me), 1.12 (s, 3H,
Me), 1.12–0.99 (m, 3H, 3 × CHMe2), 1.04 (d, J 7, 18H,
3 × Me2); δC(67.8 MHz) 206.5 (d), 141.8/141.7 (d), 132.5/132.6
(s), 130.2/130.1 (s), 113.4/113.3 (t), 74.9/74.7 (d), 57.8/57.6 (d),
37.6 (s), 37.4/37.1 (t), 30.6/30.5 (t), 28.6/28.3 (q), 24.5/24.3 (q),
21.6/21.5 (q), 19.8/19.9 (t), 17.7/18.0 (q), 11.9/12.2 (d) (Found:
Mϩ Ϫ iPr, 335.2448. C20H35O2Si requires M, 335.2406).
1-(2-Triisopropylsiloxybut-3-enyl)-2,6,6-trimethyl-5-[(E)-2-
iodoethenyl]cyclohex-1-ene 101. A solution of the aldehyde 100
(0.20 g, 0.5 mmol) and iodoform (314 mg, 0.6 mmol) in dry
THF was added dropwise to a stirred suspension of chromous
chloride (0.52 g, 3.0 mmol) in dry THF (3 ml) at room temper-
ature under nitrogen. The brown solution was stirred at room
temperature for 3 h and then quenched with water (6 ml) and
ether (6 ml). The organic layer was separated, washed with sat-
urated aqueous sodium metabisulfite (3 ml) and brine (6 ml),
then dried and evaporated in vacuo to leave a pale yellow oil.
Purification by chromatography on silica eluting with dichloro-
methane gave two diastereoisomers of the iodide (0.17 g, 64%)
as a colourless oil; (data for both diastereoisomers): νmax(film)/
cmϪ1 1658, 1646 and 883; δH(250 MHz) 6.52 (dd, J 14, 9, 1H,
1-(2-Triisopropylsiloxybut-3-enyl)-2,6,6-trimethyl-5-[(E)-3-
acetoxy-5-(4-methoxybenzyloxy)pent-1-enyl]cyclohex-1-ene
102b. Acetic anhydride (29 µl, 0.40 mmol) was added dropwise
over 5 min to a stirred solution of the alcohol 102a (0.15 g, 0.27
mmol), 4-dimethylaminopyridine (1.6 mg, 0.013 mmol) and tri-
ethylamine (56 µl, 0.40 mmol) in dry dichloromethane (2 ml) at
0 ЊC under nitrogen and the clear solution was then stirred at
0 ЊC for 2 h. The solution was diluted with water (2 ml) and the
organic layer was separated. The aqueous layer was extracted
with dichloromethane (3 × 10 ml) and the combined dichloro-
methane extracts were dried and concentrated in vacuo to leave
a pale yellow oil. Purification by column chromatography on
silica eluting with 20% ether in light petroleum gave two
diastereoisomers of the acetate (0.14 g, 92%) as a clear oil; (data
for both diastereoisomers): λmax(EtOH)/nm 217 (ε/dm3 molϪ1
cmϪ1 58 200); νmax(film)/cmϪ1 1738, 1614 and 821; δH(250 MHz)
7.21 (d, J 9, 2H, Ar), 6.84 (d, J 9, 2H, Ar), 5.82 (ddd, J 18, 10, 6,
1H, HC᎐CH ), 5.79–5.66 (m, 1H, HC᎐CH), 5.52–5.39 (m, 2H,
᎐
᎐
2
HC᎐CHI), 5.96 (d, J 14, 1H, IHC᎐CH), 5.81 (ddd, J 17, 10, 6,
CHOAc and HC᎐CH), 5.07 (dd, J 18, 1, 1H, HC᎐CH ), 4.96
᎐ ᎐
2
᎐
᎐
1H, HC᎐CH ), 5.07 (dd, J 17, 1, 1H, HC᎐CH ), 4.95 (dd, J 10,
(dd, J 10, 1, 1H, HC᎐CH ), 4.45 (s, 2H, OCH Ar), 4.41–4.30 (br
᎐
2 2
᎐
᎐
2
2
1, 1H, HC᎐CH ), 4.44–4.37 (m, 1H, CHOSi), 2.47–2.34 (m,
m, 1H, CHOSi), 3.80 (s, 3H, OMe), 3.69–3.50 (m, 2H, CH2-
OPMB), 2.67–2.60 (m, 1H), 2.37 (dd, J 14, 6, 1H, CHCHOSi),
2.29–2.12 (m, 3H), 2.04 (s, 3H, OCOMe), 1.82–1.43 (m, 4H),
1.56 (s, 3H, Me), 1.09–0.92 (m, 24H, 2 × Me and 3 × Me2), 0.92
(m, 3H, CHMe2); δC(67.8 MHz) 170.1/170.8 (s), 159.0 (s),
143.1/143.2 (d), 131.6/132.1 (d), 131.3/131.4 (d), 130.7/131.1 (s),
130.5/130.6 (s), 129.8/130.1 (s), 129.1/129.4 (d), 113.1/113.4 (d),
112.1 (t), 82.3/82.5 (d), 74.4/74.9 (d), 72.4/73.7 (t), 69.1/69.7 (t),
64.3/64.7 (t), 54.6 (q), 48.5/48.7 (d), 39.1/39.2 (t), 36.4/36.7 (t),
34.1 (s), 30.7/31.0 (t), 24.5/24.8 (q), 21.6 (q), 20.8/21.0 (q), 17.8/
17.9 (q), 13.3/13.6 (q), 11.7/11.8 (d) (Found: Mϩ Ϫ AcOH,
552.3983. C35H56O3Si requires M, 552.3999).
᎐
2
1H), 2.31–2.04 (m, 2H), 2.02–1.91 (app. t, J 7, 2H, CH2), 1.72–
1.42 (m, 2H), 1.60 (s, 3H, Me), 1.04 (d, J 7, 18H, 3 × Me2), 1.02
(s, 3H, Me), 0.94–0.89 (m, 3H, 3 × CHMe2), 0.89 (s, 3H, Me);
δC(67.8 MHz) 149.2/149.1 (d), 142.3/141.9 (d), 132.7 (s), 129.5/
129.3 (s), 113.2/113.1 (t), 74.7/74.6 (d), 74.5/74.2 (d), 53.5/53.2
(d), 37.9 (s), 37.8 (t), 31.0/30.9 (t), 28.5/28.2 (q), 24.5 (t), 24.3
(q), 21.5 (q), 17.8/17.7 (q), 12.4/12.2 (d) (Found: Mϩ Ϫ iPr,
459.1514. C21H36OISi requires M, 459.1580).
1-(2-Triisopropylsiloxybut-3-enyl)-2,6,6-trimethyl-5-[(E)-3-
hydroxy-5-(4-methoxybenzyloxy)pent-1-enyl]cyclohex-1-ene
102a. A solution of 3-(4-methoxybenzyloxy)propanal (0.13 g,
0.7 mmol) and the vinyl iodide 101 (0.45 g, 0.9 mmol) in toluene
(3 ml) was azeotroped for 2 h and then concentrated in vacuo
and dried under high vacuum for 1 h. The reaction vessel was
vented to argon and then dimethyl sulfoxide (5 ml) and THF (2
ml) were added and the resulting pale yellow solution was
stirred at room temperature for 5 min. Chromous chloride (0.58
g, 4.7 mmol), containing 0.1% nickel() chloride (0.6 mg, 0.07
mmol), was then added in one portion and the green suspension
was stirred at room temperature for 20 h. Saturated aqueous
ammonium chloride (4 ml) and ethyl acetate (4 ml) were added
and the mixture was then stirred at room temperature for 30
min. The organic layer was separated and the aqueous fraction
was extracted with ethyl acetate (3 × 10 ml). The combined
organic extracts were washed with brine (10 ml) and then dried
and evaporated in vacuo to a pale green oil, which was purified
by chromatography on silica gel eluting with 25% ether in hex-
ane to give (i) two diastereoisomers of the allylic alcohol (0.11 g,
31%) (eluted first) as a colourless oil; (data for both diastereo-
isomers): λmax(EtOH)/nm 226 (ε/dm3 molϪ1 cmϪ1 12 500);
νmax(film)/cmϪ1 3425, 1612 and 911; δH(250 MHz) 7.22 (d, J 9,
1-(2-Triisopropylsiloxybut-3-enyl)-2,6,6-trimethyl-5-[(E)-3-
acetoxy-5-hydroxypent-1-enyl]cyclohex-1-ene
103a.
2,3-
Dichloro-5,6-dicyano-1,4-benzoquinone (0.29 g, 1.26 mmol)
was added in one portion to a stirred solution of the p-
methoxybenzyl ether 102b (0.25 g, 0.42 mmol) and water (0.5
ml) in dichloromethane (8.8 ml) at room temperature. The
brown suspension was stirred at room temperature for 3 h and
then saturated aqueous sodium metabisulfite (3 ml) was added
dropwise over a period of 20 min. The mixture was diluted with
water (10 ml) and dichloromethane (12 ml) and the organic
layer was separated. The aqueous layer was re-extracted with
dichloromethane (× 2) and the combined organic extracts were
washed with saturated aqueous sodium hydrogen carbonate
(6 ml), then dried and evaporated in vacuo to leave a clear oil.
Purification by column chromatography on silica eluting
with 30% ether in light petroleum gave two diastereoisomers of
the alcohol (0.16 g, 85%) as a colourless oil; (data for both
diastereoisomers): νmax(film)/cmϪ1 3445, 1723 and 910; δH(250
MHz) 5.83 (ddd, J 18, 10, 6, 1H, HC᎐CH ), 5.79–5.66 (m, 1H,
᎐
2
HC᎐CH), 5.52–5.39 (m, 2H, CHOAc and HC᎐CH), 5.09 (dd,
᎐
᎐
3204
J. Chem. Soc., Perkin Trans. 1, 1998, 3181–3206

View Article Online
J 18, 1, 1H, HC᎐CH ), 4.95 (dd, J 10, 1, 1H, HC᎐CH ), 4.48–
purified directly by chromatography on silica, eluting with 30%
᎐
᎐
2
2
4.39 (m, 1H, CHOSi), 3.69–3.59 (m, 2H, CH2OH), 2.49–2.38
(m, 1H), 2.31–2.17 (m, 2H), 2.04 (s, 3H, OCOMe), 2.01–1.82
(m, 4H), 1.78–1.63 (m, 2H), 1.61 (s, 3H, Me), 1.09–1.01 (m,
24H, 2 × Me and 3 × Me2), 0.97 (m, 3H, CHMe2); δC(67.8
MHz) 171.0/172.4 (s), 141.9/142.4 (d), 136.8/136.9 (d), 132.9/
133.0 (s), 129.5 (s), 128.2/128.3 (d), 113.0 (t), 74.1/74.6 (d), 72.4
(d), 58.7 (t), 49.1/49.0 (d), 37.6/37.8 (t), 34.0 (s), 32.2 (t), 31.4/
32.1 (t), 25.1/25.8 (q), 23.8/24.0 (t), 21.5/21.6 (q), 20.9/21.3 (q),
18.0/18.1 (q), 17.9 (q), 11.9/12.4 (d) [Found (FAB-MS): Mϩ,
492. C29H52O4Si requires M, 492].
1-(2-Triisopropylsiloxybut-3-enyl)-2,6,6-trimethyl-5-[(E)-3-
acetoxy-5-bromopent-1-enyl]cyclohex-1-ene 103b. Triphenyl-
phosphine (0.11 g, 0.43 mmol) was added portionwise over 30
min to a stirred solution of the alcohol 103a (0.16 g, 0.36 mmol)
and carbon tetrabromide (0.24 g, 0.71 mmol) in dry dichloro-
methane (4 ml) at 0 ЊC under nitrogen and the mixture then
stirred at 0 ЊC for 3 h. The solution was warmed to room tem-
perature and then the solvent was evaporated in vacuo to afford
a pale yellow gum. Purification by column chromatography
eluting with 20% ether in light petroleum gave two diastereo-
isomers of the bromide (0.18 g, 96%) as a clear oil; (data for
both diastereoisomers): νmax(film)/cmϪ1 1734, 1464 and 741;
ether in light petroleum, to give two diastereoisomers of the
ketone (67 mg, 81%) as a clear oil; (data for both distereo-
isomers): νmax(film)/cmϪ1 1737, 1689, 1613, 912 and 734; δH(250
MHz) 6.39 (dd, J 18, 10, 1H, H C᎐CH), 6.20 (dd, J 18, 2, 1H,
᎐
2
H C᎐CH) , 5.81–5.68 (m, 1H, HC᎐CH), 5.71 (dd, J 10, 2, 1H,
᎐
᎐
2
H C᎐CH), 5.32–5.26 (m, 2H, HC᎐CH and CHOAc), 3.32 (app.
᎐
᎐
2
t, J 7, 2H, CH2Br), 3.25 (app. s, 2H, CH2CO), 2.18–1.99 (m,
3H), 2.08 (s, 3H, OCOMe), 1.53 (s, 3H, Me), 1.65–1.36 (m, 4H),
0.93 (s, 3H, Me), 0.89 (s, 3H, Me); δC(67.8 MHz) 198.5 (s), 170.1
(s), 141.6 (s), 137.7/137.9 (d), 135.7 (d), 130.9/131.0 (s), 128.0
(t), 127.7 (d), 73.4 (d), 48.4/48.6 (d), 40.5 (t), 37.4/37.5 (t), 33.2
(s), 31.2/31.3 (t), 29.7 (t), 26.6/26.7 (q), 24.9 (t), 22.5/22.6 (q),
20.5 (q), 20.4 (q) (Found: Mϩ Ϫ AcOH, 336.1094. C18H25BrO
requires M, 336.1089).
1-(2-Oxobut-3-enyl)-2,6,6-trimethyl-5-[(E)-3-acetoxy-5-iodo-
pent-1-enyl]cyclohex-1-ene 87a. Treatment of a solution of the
bromide 105 (65 mg, 0.16 mmol) in butan-2-one with sodium
iodide, according to the general procedure, gave the title iodide
(65 mg, 89%) as a pale yellow oil; (data for both diastereo-
isomers): νmax(film)/cmϪ1 1735, 1690, 1620 and 984; δH 6.44 (dd,
J 18, 10, 1H, H C᎐CH), 6.26 (dd, J 18, 2, 1H, H C᎐CH), 5.83–
᎐
᎐
2
2
5.76 (m, 1H, HC᎐CH), 5.76 (dd, J 10, 2, 1H, H C᎐CH), 5.40–
᎐
᎐
2
δ (250 MHz) 5.92–5.71 (m, 2H, HC᎐CH and HC᎐CH ), 5.46–
5.23 (m, 2H, HC᎐CH and CHOAc), 3.31 (app. s, 2H, CH CO),
᎐
᎐
᎐
H
2
2
5.31 (m, 2H, CHOAc and HC᎐CH), 5.09 (dd, J 18, 1, 1H,
3.10 (app. t, J 7, 2H, CH2I), 2.26–2.05 (m, 3H), 2.04 (s, 3H,
OCOMe), 1.59–1.51 (m, 4H), 1.56 (s, 3H, Me), 0.93 (s, 3H, Me),
0.89 (s, 3H, Me); δC(67.8 MHz) 198.7 (s), 170.4 (s), 140.9
(s), 137.7/137.9 (d), 135.1 (d), 130.7/130.9 (s), 127.8 (t), 127.4
(d), 73.7 (d), 48.2/48.6 (d), 40.9 (t), 31.6 (s), 31.0/31.3 (t),
28.7 (t), 26.4/26.7 (q), 23.8 (t), 22.5/22.6 (q), 20.5 (q), 20.0
(q), 8.6 (t) (Found: Mϩ Ϫ AcOH, 384.0943. C18H25IO requires
M, 384.0950); which was used immediately without further
purification.
1-(2-Oxobut-3-enyl)-2,6,6-trimethyl-5-[(E)-3-acetoxypent-1-
enyl]cyclohex-1-ene 87b. Treatment of a solution of the iodide
87a (65 mg, 0.15 mmol) in benzene with tri-n-butyltin hydride
and azoisobutyronitrile, according to the general procedure,
gave the title cyclohexene (29 mg, 63%) as a yellow oil; δH(250
᎐
HC᎐CH ), 4.95 (dd, J 10, 1, 1H, HC᎐CH ) , 4.50–4.39 (m, 1H,
᎐
᎐
2
2
CHOSi), 3.45–3.34 (m, 2H, CH2Br), 2.43–2.14 (m, 3H), 2.07 (s,
3H, OCOMe), 2.04–1.91 (m, 4H), 1.63–1.56 (m, 2H), 1.62 (s,
3H, Me), 1.09–1.01 (m, 24H, 2 × Me and 3 × Me2), 0.97 (m,
3H, 3 × CHMe2); δC(67.8 MHz) 169.7/170.9 (s), 140.6/141.1 (d),
136.7/136.8 (d), 130.9/131.7 (s), 129.6 (s), 127.5/128.1 (d), 112.6
(t), 74.0/74.4 (d), 70.9 (d), 57.8 (t), 48.7/48.9 (d), 37.4/37.9 (t),
34.0 (s), 33.0 (t), 31.9/32.3 (t), 25.0/25.6 (q), 23.4/24.0 (t), 21.4/
21.5 (q), 20.9/21.3 (q), 17.7/18.0 (q), 17.1 (q), 12.1/12.3 (d).
1-(2-Hydroxybut-3-enyl)-2,6,6-trimethyl-5-[(E)-3-acetoxy-5-
bromopent-1-enyl]cyclohex-1-ene 104. A solution of HF (3 M)
in dry acetonitrile (2 ml) was added dropwise over 5 min to a
stirred solution of the silyl ether 103b (35 mg, 0.067 mmol) in
acetonitrile (1 ml), in a teflon Eppendorf tube, at room tem-
perature and the resulting pale yellow solution was then stirred
at room temperature for 6 h. Saturated aqueous sodium hydro-
gen carbonate (3 ml) was added dropwise over 10 min, and the
mixture was then stirred at room temperature for a further 1 h.
The organic layer was separated and the aqueous fraction was
extracted with ether (3 × 8 ml). The combined organic layers
were dried and evaporated in vacuo to leave two diastereo-
isomers of the alcohol (16 mg, 79%) as a clear oil; (data for both
diastereoisomers): νmax(film)/cmϪ1 3456, 1737, 1644 and 738;
MHz) 6.38 (dd, J 17, 10, 1H, H C᎐CH), 6.24 (dd, J 17, 2, 1H,
᎐
2
H C᎐CH), 5.79–5.66 (m, 1H, HC᎐CH), 5.69 (dd, J 10, 2, 1H,
᎐
᎐
2
H C᎐CH), 5.33–5.24 (m, 2H, HC᎐CH and CHOAc), 3.29 (app.
᎐
᎐
2
s, 2H, CH2CO), 2.32–1.94 (m, 3H), 2.09 (s, 3H, OCOMe), 1.51
(s, 3H, Me), 1.61–1.31 (m, 4H), 0.91–0.93 (m, 3H, Me), 0.89 (s,
3H, Me), 0.87 (s, 3H, Me) (Found: Mϩ Ϫ AcOH, 257.1981.
C18H26O requires M, 258.1984).
Acknowledgements
δ (250 MHz) 5.82 (ddd, J 17, 10, 6, 1H, HC᎐CH ), 5.78–5.67
We thank the EPSRC (studentships to S. A. H., D. C. P. and
N. M. T.) and Astra Charnwood (studentship to S. J. H.) for
support of this work. We also thank Dr J. Bateson (SmithKline
Beecham), Drs M. F. Jones and P. J. Meyers (Glaxo Wellcome)
for their interest in this work, and Drs D. C. Harrowven and
A. D. Green for their contributions to our studies in this area.
᎐
H
2
(m, 1H, HC᎐CH), 5.37–5.21 (m, 2H, CHOAc and HC᎐CH),
᎐
᎐
5.17 (dd, J 17, 2, 1H, H C᎐CH), 5.03 (dd, J 10, 2, 1H,
᎐
2
H C᎐CH), 4.20–4.14 (br m, 1H, CHOH), 3.33–3.26 (m, 2H,
᎐
2
CH2Br), 2.42–1.99 (m, 5H), 1.98 (s, 3H, OCOMe), 1.76–1.43
(m, 4H), 1.61 (s, 3H, Me), 0.95 (s, 3H, Me), 0.83 (s, 3H, Me);
δC(67.8 MHz) 170.4 (s), 141.1 (d), 137.8/138.1 (d), 132.8 (s),
130.4/130.9 (s), 127.4/127.5 (d), 113.9/114.1 (t), 73.4 (d),
72.6/72.7 (d), 49.0/49.1 (d), 37.7 (s), 37.3/37.6 (t), 36.2/36.3 (t),
31.2/31.4 (t), 28.2/28.4 (t), 27.8/28.1 (q), 24.9/25.0 (t), 23.5 (q),
21.2 (q), 21.0 (q) (Found: Mϩ Ϫ AcOH Ϫ C3H4OH, 281.0893.
C15H22Br requires M, 281.0905); which was used without
further purification.
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Paper 8/05268I
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J. Chem. Soc., Perkin Trans. 1, 1998, 3181–3206