Zirconocene-induced cocyclisation/elimination reactions of 2-heterosubstituted 1,6-dienes and 1,6-enynes

Article abstract of DOI:10.1055/s-2005-870029

Zirconocene-mediated cocyclisation of 2-heterosubstituted-1,6-dienes and -enynes gave zirconacycles bearing an endocyclic β-leaving group which eliminated under the reaction conditions to provide exocyclic alkylidene groups. The scope of this cyclisation/

Full text of DOI:10.1055/s-2005-870029

SPECIAL TOPIC
2061
Zirconocene-Induced Cocyclisation/Elimination Reactions of 2-Heterosubsti-
tuted 1,6-Dienes and 1,6-Enynes
Z
irconocene-Induc
a
ed Cocycli
v
sation/Elimin
i
ation R
d
eactions R. Owen, Richard J. Whitby*
School of Chemistry, University of Southampton, Southampton, Hants, SO17 1BJ, UK
Fax +44(23)80593781; E-mail: rjw1@soton.ac.uk
Received 15 February 2005
R4
R4
ZrCp2
R1
Abstract: Zirconocene-mediated cocyclisation of 2-heterosubsti-
R3O
R2
OR3
R4
ZrCp2
β-elimination
tuted-1,6-dienes and -enynes gave zirconacycles bearing an en-
docyclic b-leaving group which eliminated under the reaction
conditions to provide exocyclic alkylidene groups. The scope of this
cyclisation/elimination has been investigated along with further
elaboration of the monosubstituted zirconocene intermediates by in-
sertion of alkenyl carbenoids.
R1
+
hydrolysis
R2
R2
R1
Scheme 2
Key words: zirconium, cyclisation, elimination, alkylidene, car-
benoid insertion
O
(PrOi)2Ti
O
β-elimination
Ti(OiPr)2
hydrolysis
OH
The formation of zirconacycles by cocyclisation of 1,n-
dienes, -enynes, and- diynes, followed by various elabora-
tions has been developed into a powerful means to con-
struct organic molecules.1 To extend this chemistry we
have investigated the cocyclisation of substrates bearing
heteroatom substituents which undergo an endocyclic
elimination reaction (Scheme 1), and report our results
herein. Our substrates fall into three categories: cyclic
enol ethers (dihydrofurans and dihydropyrans), acyclic
enol ethers and alkenyl chlorides.
Scheme 3
We first examined the use of dihydrofuran and dihydropy-
ran containing substrates. Alkylation of lithiated 3,4-dihy-
dro-2H-pyran or 2,3-dihydrofuran with appropriate alkyl
iodides9 gave the cyclisation precursors 1a–f (Table 1).
Treatment with the Negishi ‘zirconocene equivalent’,10,11
zirconocene (1-butene), generated in situ by butane elim-
ination from dibutylzirconocene, gave the products 2–6
shown in Table 1. The products 2a and 2b derived by cy-
clisation onto dihydrofuran to give a 5-membered ring,
followed by elimination, were formed in good yield. It is
notable that cyclisation of the ‘all carbon’ analogue of 1a
is reported to fail,12 possibly indicating the importance of
the irreversible alkoxide elimination in the formation of
2a to displace an unfavourable equilibrium between the
intermediate zirconacyclopentane and the starting diene.
The compound 2a was formed as a 7:1 mixture of Z- and
E-isomers corresponding to predominant anti-elimination
of the intermediate zirconium alkoxide 7a or 7b, possibly
to give the zirconacycles 8 (Scheme 4).
R
Et
R
R
X
X
Cp2Zr
X
ZrCp2
ZrCp2
Scheme 1
Examples of the reaction described in Scheme 1 where
X = Br and Cl have been reported by Waymouth2a and Ta-
kahashi.2b The reaction of zirconocene-alkyne complexes
and zirconocene-alkene complexes with alkenyl ethers
has been reported by Takahashi3 and Barluenga4 respec-
tively and follows a closely related pathway (Scheme 2).
Barluenga has also reported the related addition of zir-
conocene h2-imine complexes to alkenyl ethers.5 Marek
has reported a reaction of zirconocene alkene complexes
with enol ethers which follows a different pathway to af-
ford alkenylzirconium species by overall replacement of
the alkoxide.6 Cyclisation/elimination of alkenyl ethers
where the oxygen is part of the linking chain, for example
as shown in Scheme 3, induced by low valent titanium is
also known.7 The elimination of exocyclic b-alkoxy
groups is well known for zirconacycles.8
O
O
H
H
"Cp2Zr"
and /
or
1a,b
ZrCp2
ZrCp2
R
R
H
H
H
H
7a
7b
H+
O
H
+
O
2a,b
ZrCp2
R
Zr
H
R
Cp2
H
H
H
8a (Major)
8b (Minor)
SYNTHESIS 2005, No. 12, pp 2061–2074
Advanced online publication: 14.07.2005
x
x.
x
x
.
2
0
0
5
Scheme 4
DOI: 10.1055/s-2005-870029; Art ID: C03705SS
© Georg Thieme Verlag Stuttgart · New York

2062
D. R. Owen, R. J. Whitby
SPECIAL TOPIC
Table 1 Cyclisation/Elimination Products from Dihydrofurans and
Dihydropyrans
constant. Indeed the methylidene analogue 19a described
later has an 11 Hz coupling between the corresponding
protons.
Entry Diene/Enyne
Product
Yield (%)
(Isomers)
H
O
ZrCp2
1
78 (Z:E = 7:1)
ZrCp2
O
O
H
OH
Me
R
R
R
10
9
R
2a R = H
Scheme 5
1a R = H
2
3
1b R = Ph
2b R = Ph
69 (>95% de)
O
H
O
13 (2c)
25 (3)
ZrCp2
O
+
O
ZrCp2
ZrCp2
H
OH
Pr
Pr
Pr
12a
61:31
Pr
Pr
12b
2c
Pr
11
1c
Scheme 6
O
3
With a longer chain connecting the alkene and dihydrofu-
ran moieties in cyclisation precursor 1c none of the ex-
pected adduct was formed. Instead a low yield of the
alkylidene cyclopentane 2c was formed by alkene isomer-
isation, cyclisation, and anti-elimination (Scheme 7). The
bulk of the isolated material was the allyl ether 3 resulting
from multi-positional isomerisation16 of the initially ter-
minal alkene to form the zirconium diene complex 13
which selectively protonates at the more substituted posi-
tions (Scheme 7).17 In a similar way the only product iso-
lated from the dihydropyran precursors 1d and 1e were
the allyl ethers 4 and 5, respectively, resulting from the
same multipositional isomerisation to afford zirconium
diene complexes as described for the formation of 13
(Scheme 7).16 Work-up of the reaction from 1e with deu-
terium oxide gave the bis-deuterated ether 5b.
4
31
X
( )n
O
( )n
O
X
1d n = 1
4, n = 1, X = H
5
6
1e n = 2
5a n = 2, X = H
5b n = 2, X = D
37 (5a)
30 (5b)
45 (2f)
24 (6)
O
OH
Pr
Pr
2f
1f
6
Pr
H
H
ZrCp2
ZrCp2
The alkene stereochemistry assigned to 2a is most clearly
indicated by the 13C chemical shift of the methine carbon
(d = 34.88 in the major and 39.27 in the minor isomer)
compared with (Z)- and (E)-1-ethylidene-2-methylcyclo-
pentane (d = 34.4 and 39.5 respectively).13 Although for
both 7a and 7b the lowest energy structures14 have a 90°
Zr–C–C–O dihedral angle, there are conformers only ~3
kJ/mol higher in energy for which the dihedral angles are
140–150°, better suited to anti-elimination. In similar
eliminations of monocyclic systems Barluenga obtains
exclusively the Z-isomers 10 (Scheme 5) corresponding
to an anti-elimination,4 and Takahashi observed a 61:39
Z:E ratio of products 12 corresponding to predominant
anti-elimination from 11 (Scheme 6).3 Compound 2b was
formed as a single isomer. The Z-alkene stereochemistry
is clear from comparison of the 13C NMR with 2a. The
shown cis-arrangement of the phenyl and methyl groups
is unexpected15 but follows from a 6.8 Hz coupling be-
tween the CHMe and CHPh protons. All reasonable con-
formers of the analogous trans isomer have 170–180°
HCCH dihedral angles corresponding to a larger coupling
O
O
O
further
isomerisation
ZrCp2
H2O
ZrCp2
O
13
cyclise
H
O
H2O
2c
3
ZrCp2
Scheme 7
Finally cyclisation of an alkyne to a dihydrofuran to form
a 5 member ring product 2f was successful (Table 1, entry
6), but to our surprise the product 6 where a second elim-
ination has occurred was also formed. The E,Z stereo-
chemistry of 2f follows from the substantial difference
between the 13C shifts of the alkene CH carbons (d = 126.7
Synthesis 2005, No. 12, 2061–2074 © Thieme Stuttgart · New York

SPECIAL TOPIC
Zirconocene-Induced Cocyclisation/Elimination Reactions
2063
and 117.9), and the allylic cyclopentane ring carbons (d = butyldimethylsilyl protected precursor 18cii cyclised with
36.65 and 32.87). The difference between the latter two is much poorer diastereocontrol, though to give the same
due to the g-gauche effect which shifts the ring methylene major isomer of 19c. Modest 1,3-diastereocontrol from a
adjacent to the E-alkylidene upfield.18 The alkene stereo- hydroxyl group was observed in the cyclisation of 18d to
chemistry of 6 follows from the 13C shifts of the allylic cy- afford 19d (entry 5). The analogous diene lacking the
clopentane ring carbons at d = 30.47 and 31.00, both being ethoxy group cyclises with 3:1 diastereocontrol, but with
shifted upfield by the g-gauche effect. Data on (E,E)- and the opposite 1,3-selectivity (hydroxyl and newly formed
(E,Z)-1,2-diethylidenecyclopentane supports the stereo- ring methyl group are cis).21 The relative stereochemis-
chemical assignments of 2f and 6.19 It is tempting to spec- tries of 19c and 19d were determined by both analysis of
ulate that the product 16 of syn-elimination of the coupling constants, and observation of substantial GOE-
intermediate 14 undergoes further elimination, whereas SY enhancements between the hydrogens adjacent to the
15 from the anti-elimination does not (Scheme 8). The hydroxyl group, and the methyl doublet. Six membered
minimum energy conformation of 16 is calculated by ring formation was facilitated by the ‘preorganising’ ac-
DFT14 to be 30kJ/mol less stable than that of 15 providing tion of the aromatic backbone in 18e to afford 19e
some rational for the difference in behaviour. The much (Table 2, entry 6) – the only successful cyclisation to give
stronger tendency towards syn-elimination of the interme- a carbocyclic 6 member ring we observed in this work.
diate zirconacycle 14 (cf. 7) may be due to the absence of There was very little diastereocontrol in the formation of
low lying conformers with other than around 90° ZrCCO 19e, but the diastereoisomers were chromatographically
dihedral angles.
separable. The lack of stereocontrol is in accord to that re-
cently observed in cyclisation of a similar diene lacking
the ethoxy group.22 Five membered ring formation when
fused to an aromatic ring (Table 2, entry 7) was poor
yielding, but provided 19f as a single diastereoisomer, al-
though we have not yet proven which.
O
2f
Zr
anti
syn
Cp2
O
H
Pr
15
16
H
ZrCp2
1f
In the case of enyne cocyclisation (Table 2, entries 8–10),
the five membered rings (19g,h) formed successfully,
whereas the 1,7-enyne (18i) underwent dimerisation23
showing that cyclisation from the initially formed zir-
conocene h2-alkyne complex is much slower than its in-
termolecular addition to another alkyne.
Pr
O
14
6
H
ZrCp2
Pr
Scheme 8
The overall success of the cocyclisations to ethyl vinyl
ether adducts in generating methylene cyclopentanes pro-
vides a viable alternative to the cocyclisation of terminal
alkynes, which is not possible using the standard Negishi
conditions [Cp2Zr(1-butene)]. Although the problem can
be overcome by the use of zirconocene(ethylene),24,25
Cp2ZrCl2/Mg/Hg,26 (i-PrO)2Ti(propene)27 or the alkenyl-
lithium/Cp2ZrClMe method of Barluenga,28 our route is
practically more straightforward, and equally successful.
As the above results demonstrate, the trisubstituted nature
of the enol ether in substrates 1 prevents cyclisation in all
but the most favoured cases, so we then examined less
hindered ethyl vinyl ether adducts 18. Lithiation of ethyl
vinyl ether with tert-butyllithium to produce 1-ethoxyvi-
nyllithium, and subsequent alkylation20 with aldehydes or
alkyl iodides 17a–i provide a rapid method for the synthe-
sis of the dienes and enynes 18a–i shown in Table 2.
Cyclisation/elimination using zirconocene(1-butene) oc-
curred as hoped for to provide a wide variety of meth-
ylidene carbocycles 19a–h (Table 2). For alcohol-con-
taining substrates, two equivalents of zirconocene(1-
butene) were used. In many cases the cyclisations were
highly diastereoselective, for example excellent diaste-
reocontrol was observed when a phenyl group was adja-
cent to the newly generated chiral centre (Table 2, entries
1 and 2). In the case of the cyclisation of 18b the hydroxyl
group appeared to have no significant influence on the
newly created chiral centre. For both 19a and 19b the
trans stereochemistry of the phenyl and methyl groups
followed from an 11 Hz coupling in the proton NMR be-
tween the adjacent vicinal hydrogens. Alcohol 18ci (entry
3) was formed with complete ‘Cram’ selectivity and on
cyclisation using an extra equivalent of zirconocene(1-
butene) for in situ protection of the alcohol group gave
19c with good control of the new stereocentre. The tert-
For reasons outlined below we needed to produce addi-
tion/elimination products carrying a chloro rather than
alkoxy substituent on the zirconium. One example of the
cocyclisation of an alkenyl chloride and an alkenyl bro-
mide has been reported by Takahashi2b and Waymouth2a
respectively. We prepared the alkenyl chlorides 20a–c by
reaction of the appropriate secondary amines with 1,2-
dichloro-2-propene and carried out the cyclisation/elimi-
nation reaction with zirconocene(1-butene) to give the
products 21a–c in good yield (Table 3). In the case of cy-
clisation of 20b oxidative addition of zirconocene into the
carbon–chlorine bond29 giving 22 on hydrolysis
(Scheme 9) competed with the desired cyclisation. The
rather unstable diene 21c was characterised as its Diels–
Alder adduct 23 (Scheme 10). The stereochemistry of 23
could not be unambiguously determined from NMR cou-
pling constants, and that shown is suggested by compari-
son to a similar Diels–Alder adduct obtained by Kemp et
al.30
Synthesis 2005, No. 12, 2061–2074 © Thieme Stuttgart · New York

2064
D. R. Owen, R. J. Whitby
SPECIAL TOPIC
Table 2 Formation and Cyclisation of Ethyl Vinyl Ether Adducts
R'
OEt
R'
OEt
EtO
Cp2Zr
I
O
R'
eliminate
hydrolyse
Li
or
ZrCp2
R
R
R
R
R
17
18 R' = H, OH
Alkylated Producta
EtO
19 R' = H, OH
Entry
1
Alkylating Agent
17
a
18
a
Yield (%)
81
Cyclised Productb,c
19
Yield (%)d (de)
72 (88)
a
b
c
Ph
I
Me
Ph
Ph
2
3
b
c
b
72
70
55 (>95)
44 (75)
HO
EtO
HO
Ph
Ph
O
Me
Ph
Ph
ci
O
HO
Ph
Me
4
5
c
R = SiMe2t-Bu
cii
d
57e
75
c
47f (11)
74 (60)
d
d
O
OEt
HO
HO
Me
OH
6
7
e
f
e
f
70
86
e
f
61 (7)
OH
O
OEt
Me
OH
26 (>95)
OH
OEt
O
Me
8
g
g
64
g
33
O
HO
HO
OEt
Ph
Ph
Ph
9
h
i
h
i
89
71
h
i
68
I
EtO
Pr
Pr
Pr
Pr
Pr
10
52g
O
Pr
Pr
EtO
I
+ isomers
O
a Alkylation conditions: H2C=CHOEt, 1. t-BuLi, –70 °C, 30 min; 2. RI or RCHO, –70 to 0 °C, 3 h; 3. aq NH4Cl.
b Cocyclisation conditions: 1. Cp2ZrCl2 + 2 n-BuLi, –78 to 20 °C, 3 h; 2. MeOH/aq NaHCO3, 20 °C, 16 h. Two equiv of Cp2ZrCl2 and four
equiv of n-BuLi were used in the cyclisation of substrates bearing free alcohol groups.
c Major diastereoisomer shown.
d Diastereoisomeric excess determined by GC.
e 57% yield for TBS protection of alcohol 18ci.
f Yield after deprotection using TFA–H2O–MeOH (1:1:1).
g Yield after hydrolysis of enol ether groups during silica gel chromatography.
Synthesis 2005, No. 12, 2061–2074 © Thieme Stuttgart · New York

SPECIAL TOPIC
Zirconocene-Induced Cocyclisation/Elimination Reactions
2065
Table 3 Cyclisation/Elimination of Alkenyl Chlorides
Cl
Li
Entry
1
Alkenyl Chloride
Product(s)
Yield (%)
i.
25a
19a +
71
ii. H2O
Ph
Ph
BnN
ZrCp2OEt
BnN
24
26 10%
Cl
20a
Scheme 11
21a
2
53 (21b),
36 (22)a
BnN
BnN
from the carbenoid into an empty orbital on the ‘16 elec-
tron’ zirconium complex to provide an ‘ate’ complex. The
lone pair on the ethoxy substituent will compete for this
empty orbital thus inhibiting attack of the carbenoid. To
combine the cocyclisation/elimination and carbenoid in-
sertion methodologies, we turned to the product 27 de-
rived from the cocyclisation/elimination reaction of
alkenyl chloride 20a and were delighted to find that car-
benoid 25a inserted efficiently to provide a good yield of
28a on aqueous work-up (Table 4, entry 1). In the same
way carbenoids 25b–d inserted successfully into orga-
nozirconium 27 to afford the products 28b–d (Table 4, en-
tries 2–4).
Cl
21b
20b
+
BnN
22
3
89
Cl
BnN
BnN
Pr
Pr
21c
20c
Table 4 Alkenyl Carbenoid Insertion into 27
a Contaminated with ~25% of a further reduced product, N-allyl-N-
butylbenzylamine.
Li
R1
R2
i.
BnN
BnN
R2
Cl
ZrCp2Cl
25a–d
R1
Cp2Zr
ii. H2O
BnN
28 a–d
BnN
27
20b
Cl
Et
Et
H2O
Entry R1
R2
25
28
Yield
(%)a
22
ClCp2Zr
–
ZrCp2Cl
Scheme 9
1
2
3
4
CH=CH2
H
a
b
c
a
b
c
75
62
40
65
(E)-CH=CH(CH2)3CH3
C≡C(CH2)5CH3
Me
H
Ph
O
NPh
N
O
O
H
BnN
21c
Me
d
d
a Based on diene 20a.
O
Pr
23, 87%
In conclusion, we have shown that zirconium mediated
cocyclisation/elimination of 2-alkoxy and 2-chloro-1,6-
dienes and -enynes is a useful entry to alkylidene cyclo-
pentanes but that 1,7-dienes successfully cyclised in only
two special cases. Cyclisation of substrates derived from
ethyl vinyl ether is a useful alternative to the cocyclisation
of terminal acetylenes in the production of methylene cy-
clopentanes. We have also shown an alkoxy group on zir-
conium to have a deactivating effect with respect to
carbenoid insertion, but the corresponding alkyl zir-
conocene chlorides insert alkenyl carbenoids in good
yield.
Scheme 10
The cyclisation/elimination reactions described above ul-
timately provide a monosubstituted zirconocene, rather
than the zirconacycle produced from standard enynes and
diynes. We wished to exploit this opportunity for selective
carbon–zirconium bond functionalisation using the car-
benoid insertion chemistry we have previously developed
for both zirconacycles31 and acyclic organozir-
conocenes.32 To this end, the organozirconium species 24
generated from diene 18a was reacted with 1-chloro-1-
lithio-1,3-butadiene32 (25a). The main product was 19a,
but a 10% yield of the desired inserted compound 26 was
isolated (Scheme 11).
NMR spectra were recorded at 300 MHz (proton) and 75 MHz (car-
bon) on Bruker AM300 or AC300 spectrometers in CDCl3 unless
otherwise stated. 400 MHz (1H)/100 MHz (13C) spectra were ac-
quired on a Bruker DPX400 spectrometer. The chemical shifts are
reported as values in ppm relative to internal tetramethylsilane stan-
dard, or residual solvent. The following abbreviations are used to
denote multiplicity and shape of signal and may be compounded:
s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet,
As carbenoid 25a has been shown to insert efficiently into
both zirconacycles31b and alkyl chlorozirconocenes,32 we
suggest the poor yield to be a consequence of the ethoxy
group on the zirconium in 24. The first stage of the car-
benoid insertion is thought to be donation of a lone pair
Synthesis 2005, No. 12, 2061–2074 © Thieme Stuttgart · New York

2066
D. R. Owen, R. J. Whitby
SPECIAL TOPIC
br = broad. 13C NMR spectra were proton decoupled, referenced to
solvent and reported with the number of attached protons (0, 1, 2,
3), this being determined by DEPT experiments. 2D (H-H and C-H
COSY) and GOESY experiments were performed on the DPX400
machine to assign otherwise ambiguous signals where necessary. IR
spectra were recorded on Perkin-Elmer 1600 series FTIR, Nicolet
Impact 400 or Bio-Rad FTIR Spectrometers. Only absorptions char-
acteristic of functional groups are given. Low-resolution mass spec-
tra were recorded on a Micromass Platform quadrupole mass
analyser using positive (ES+) or negative (ES–) ion electrospray, or
atmospheric pressure chemical ionisation (APCI) from solutions in
acetonitrile, or on a VG Analytical 70-250-SE double focusing
mass spectrometer by chemical ionisation (CI, NH3 reagent gas) or
electron impact ionisation (EI, 70 eV). When % abundances are not
given the reported peak was the only significant one. High-resolu-
tion mass spectra were obtained on the 70-250-SE using EI unless
otherwise stated. Gas chromatography experiments were performed
using a Hewlett Packard HP 6890 series chromatograph, using an
HP-Wax column for alcohols, or a HP-5 column otherwise. The
conditions were the same for both columns and all samples, and are
as follows: 5 min at 60 °C, then increase at 15 °C per min to 250 °C,
then 2 min at 250 °C.
1H NMR (C6D6): d = 5.70 (1 H, ddt, J = 17.0, 10.0, 6.6 Hz), 4.98 (1
H, dd, J = 17.0, 1.1 Hz), 4.94 (1 H, dd, J = 10.0, 1.1 Hz), 4.47 (1 H,
t, J = 2.0 Hz), 4.07 (2 H, t, J = 9.4 Hz), 2.31 (2 H, td, J = 9.4, 2.0
Hz), 2.10 (2 H, t, J = 7.2 Hz), 1.96 (2 H, br q, J = 7.2 Hz), 1.58 (2
H, quintet, J = 7.2 Hz).
13C NMR (C6D6): d = 159.37 (0), 138.73 (1), 115.05 (2), 93.82 (1),
69.84 (2), 33.69 (2), 30.44 (2), 27.81 (2), 26.45 (2).
LRMS (CI): m/z (%) = 139 (M + H+, 100), 121 (12), 97 (52).
HRMS (CI): m/z calcd for C9H15O (M + H)+: 139.1123; found:
139.1121.
5-(3-Phenyl-4-pentenyl)-2,3-dihydrofuran (1b)
Alkylation of 5-lithio-2,3-dihydrofuran with 1-iodo-3-phenyl-4-
pentene with purification by Kugelrohr distillation (100 °C/0.8
mbar) gave 1b as a viscous clear, colourless oil (83%).
IR (film): 1666 (s), 1636 (m), 1600 (m) cm–1.
1H NMR (C6D6): d = 7.3–7.0 (5 H, m), 5.899 (1 H, ddd, J = 17.3,
10.2, 7.4 Hz), 5.036 (1 H, d, J = 17.2 Hz), 5.005 (1 H, d, J = 10.0
Hz), 4.517 (1 H, tt, J = 2.2, 1.3 Hz), 4.129 (2 H, t, J = 9.3 Hz), 3.256
(1 H, q, J = 7.4 Hz), 2.362 (2 H, tq, J = 9.4, 2.0 Hz), 2.17 (2 H, m),
2.03 (2 H, m).
Melting points were recorded on a Gallenkamp melting point appa-
ratus, and are uncorrected. All cocyclisation reactions and experi-
ments involving organometallics were carried out using standard
Schlenk and syringe techniques. THF and ether were freshly dis-
tilled from purple solutions over sodium and benzophenone. n-BuLi
was titrated against diphenylacetic acid. t-BuLi was titrated against
borneol using fluorene as indicator. Ethyl vinyl ether was distilled
from sodium before use. Petroleum ether used had bp 40–60 °C.
Zirconocene dichloride was obtained from Aldrich co. and was not
purified further, but was stored in a desiccator. Specific purifica-
tions of commercial compounds were carried out according to stan-
dard methods.33 Microanalytical measurements were performed by
the Microanalytical Department, University College London or by
Medac Ltd.
13C NMR (C6D6): d = 159.20 (0), 144.28 (0), 142.34 (1), 128.78 (1),
127.94 (1), 126.53 (1), 114.30 (2), 93.80 (1), 69.76 (2), 49.63 (1),
32.74 (2), 30.36 (2), 26.42 (2).
LRMS (APCI): m/z (%) = 215 (M + H+, 100), 214 (M+, 50) 199
(27), 197 (54), 171 (43), 169 (52), 155 (30), 123 (56).
HRMS: m/z calcd for C15H18O (M+): 214.1358; found: 214.1362.
2-(4-Pentenyl)-5,6-dihydro-4H-pyran (1d)
Alkylation of 6-lithio-3,4-dihydro-2H-pyran with 1-iodo-4-pentene
with purification by Kugelrohr distillation (75 °C/0.4 mbar) gave 1d
as a clear, colourless oil (91%).
IR (film): 1674 (s), 1640 (m) cm–1.
1H NMR (C6D6): d = 5.83 (1 H, ddt, J = 16.9, 9.9, 6.6 Hz), 5.09 (1
H, dd, J = 16.9, 1.5 Hz), 5.03 (1 H, m), 4.52 (1 H, t, J = 3.7 Hz), 3.82
(2 H, t, J = 5.1 Hz), 2.1 (4 H, m), 1.88 (2 H, m), 1.71 (2 H, quintet,
J = 7.4 Hz), 1.54 (2 H, quintet, J = 5.8 Hz).
13C NMR (C6D6): d = 154.59 (0), 138.83 (1), 114.66 (2), 95.20 (1),
65.87 (2), 34.14 (2), 33.42 (2), 26.60 (2), 22.67 (2), 20.51 (2).
The following compounds were prepared by literature methods, and
had spectral data consistent with that previously reported: 1-iodo-3-
phenyl-4-pentene (17a),34 3-phenyl-4-pentenal (17b),35 2-phenyl-4-
pentenal (17c),36 2-allylbenzaldehyde (17e),37 2-vinylbenzaldehyde
(17f),38 5-phenyl-4-pentynal (17g),39 1-iodo-4-octyne (17h),40 2-(5-
hexenyl)-4,5-dihydrofuran (1c).6
LRMS (EI): m/z (%) = 152 (M+, 29), 137 (6), 113 (19), 98 (77), 83
(18), 57 (100).
HRMS: m/z calcd for C10H16O (M+): 152.1201; found: 152.1201.
Lithiation of 2,3-Dihydrofuran or 3,4-Dihydro-2H-pyran and
Subsequent Alkylation with an Alkyl Iodide; General
Procedure9
To a solution of 2,3-dihydrofuran (1.06 mL, 0.981 mg, 14 mmol) or
3,4-dihydro-2H-pyran (1.28 mL, 1.18 g, 14 mmol) in THF (8 mL)
at –40 °C under argon, was added dropwise t-BuLi (6.1 mL of a 1.3
M solution in pentanes, 8 mmol). The solution was allowed to warm
to 0 °C and stirred for 30 min before cooling to –20 °C and a solu-
tion of the alkyl iodide (6 mmol) in THF (2 mL) added. The yellow
reaction mixture was allowed to warm to r.t. then refluxed for 1 h.
After cooling to r.t., the solution was poured into aq sat. NaHCO3
solution (10 mL) and pentane (20 mL). The aqueous layer was sep-
arated and extracted with pentane (3 × 50 mL), and the combined
organic phases were dried (Na2SO4), filtered and concentrated. The
crude products were purified by column chromatography or Kugel-
rohr distillation.
2-(5-Hexenyl)-5,6-dihydro-4H-pyran (1e)
Alkylation of 6-lithio-3,4-dihydro-2H-pyran with 1-iodo-5-hexene
with purification by Kugelrohr distillation (100 °C/0.8 mbar) gave
1e as a clear, colourless oil (83%).
IR (film): 1674 (s), 1640 (m) cm–1.
1H NMR (C6D6): d = 5.75 (1 H, ddt, J = 16.9, 10.3, 6.6 Hz), 5.00 (1
H, d + fs, J = 16.9 Hz), 4.96 (1 H, d, J = 10.3 Hz), 4.45 (1 H, t,
J = 3.5 Hz), 3.77 (2 H, t, J = 5.1 Hz), 2.06 (2 H, t, J = 7.4 Hz), 1.97
(2 H, m), 1.82 (2 H, q, J = 5.4 Hz), 1.55 (2 H, quintet, J = 7.5 Hz),
1.48 (2 H, quintet, J = 6.1 Hz), 1.35 (2 H, m).
13C NMR (C6D6): d = 155.21 (0), 139.40 (1), 114.82 (2), 95.37 (1),
66.28 (2), 35.02 (2), 34.32 (2), 29.09 (2), 27.24 (2), 23.10 (2), 20.94
(2).
LRMS (EI): m/z (%) = 166 (M+, 28), 111 (100), 98 (91), 57 (88).
HRMS: m/z calcd for C11H18O (M+): 166.1358; found: 166.1350.
2-(4-Pentenyl)-4,5-dihydrofuran (1a)
Alkylation of 5-lithio-2,3-dihydrofuran with 1-iodo-4-pentene with
purification by chromatography (alumina, petroleum ether) gave 1a
as a clear, colourless oil (68%).
IR (film): 1666 (s), 1640 (m) cm–1.
Synthesis 2005, No. 12, 2061–2074 © Thieme Stuttgart · New York

SPECIAL TOPIC
Zirconocene-Induced Cocyclisation/Elimination Reactions
2067
2-(4-Octynyl)-4,5-dihydrofuran (1f)
dtd, J = 12.3, 7.0, 3.3 Hz), 1.623 (1 H, dddd, J = 12.0, 10.5, 9.5, 7.0
Hz), 1.436 (1 H, s), 1.076 (3 H, d, J = 6.8 Hz).
13C NMR: d = 150.62 (0), 145.62 (0), 128.50 (1), 127.48 (1), 126.23
(1), 116.68 (1), 62.82 (2), 54.99 (1), 43.61 (1), 34.28 (2), 34.06 (2),
32.43 (2), 20.38 (3).
Alkylation of 5-lithio-2,3-dihydrofuran with 1-iodo-4-octyne with
purification by Kugelrohr distillation (120 °C/0.7 mbar) gave 1f as
a clear, colourless oil (88%).
IR (film): 1667 (s) cm–1.
1H NMR (C6D6): d = 4.590 (1 H, m), 4.152 (2 H, t, J = 9.2 Hz),
2.42–2.32 (4 H), 2.252 (2 H, tt, J = 7.2, 2.4 Hz), 2.133 (2 H, tt,
J = 7.0, 2.4 Hz), 1.842 (2 H, quintet, J = 7.3 Hz), 1.505 (2 H, app.
sextet, J = 7.2 Hz), 0.998 (3 H, t, J = 7.4 Hz).
LRMS (ES–): m/z = 198 (M – H2O).
Anal. Calcd for C15H20O: C, 83.28; H, 9.32. Found: C, 83.48; H,
9.09.
13C NMR (C6D6): d = 158.91 (0), 94.08 (1), 80.85 (0), 80.20 (0),
69.83 (2), 30.42 (2), 27.52 (2), 26.90 (2), 22.98 (2), 21.22 (2), 18.83
(2), 13.71 (3).
LRMS (APCI): m/z (%) = 179 (M + H+, 70), 178 (M+, 100).
HRMS: m/z calcd for C12H18O (M+): 178.1358; found: 178.1353.
3-[2-(Z)-Ethylcyclopentylidene]-1-propanol (2c) and 2-[1-(E)-
Hexenyl]tetrahydrofuran (3)
Prepared from 1c by Method A. After separation and purification by
column chromatography (silica gel, 10% Et2O in petroleum ether–
30% Et2O in petroleum ether) 2c was obtained as a clear, colourless
oil (20 mg, 13%) and 3 as a clear, colourless oil (39 mg, 25%).
Cocyclisation of Dienes and Enynes Using Zirconocene(1-
butene); General Procedure
2c
IR (film): 3343 (br s) cm–1.
Method A: To a solution of ZrCp2Cl2 (321 mg, 1.1 mmol) in THF (5
mL) at –80 °C under argon was added dropwise n-BuLi (0.88 mL
of a 2.5 M solution in hexanes, 2.2 mmol). In the case of substrates
containing a free hydroxyl group, 2.2 equiv of ZrCp2Cl2 (642 mg)
and 4.4 equiv of n-BuLi (1.76 mL) were used. After the addition of
n-BuLi, a solution of the diene or enyne (1 mmol) in THF (2 mL)
was added dropwise and the solution allowed to warm to r.t. After
3–16 h at r.t., MeOH (3 mL) and aq sat. NaHCO3 solution (7 mL)
were added and the cloudy white or pale yellow reaction mixture
was stirred for 2–16 h. After dilution of the mixture with Et2O (20
mL) and H2O (20 mL), the aqueous phase was separated and ex-
tracted with Et2O (3 × 50 mL). The combined organic phases were
combined and washed with brine, dried (MgSO4), filtered and con-
centrated.
1H NMR: d = 5.200 (1 H, tq, J = 6.6, 1.8 Hz), 3.648 (2 H, m), 2.505
(1 H, m), 2.315 (4 H, m), 1.8–1.74 (1 H, m), 1.73–1.65 (1 H, m),
1.63–1.44 (4 H, m), 1.25 (1 H, m), 0.897 (3 H, t, J = 7.4 Hz).
13C NMR: d = 151.10 (0), 116.07 (2), 62.88 (2), 42.12 (1), 33.71
(2), 32.93 (2), 31.48 (2), 27.89 (2), 24.11 (2), 12.34 (3).
LRMS (APCI): m/z = 196 (M + H+ + MeCN).
HRMS: m/z calcd for C10H18O (M+): 154.1358; found: 154.1359.
3
IR (film): 1665 (w) cm–1.
1H NMR: d = 5.67 (1 H, dtd, J = 15.4, 6.6, 0.75 Hz), 5.44 (1 H, ddt,
J = 15.1, 7.0, 1.5 Hz), 4.21 (1 H, q, J = 7.0 Hz), 3.89 (1 H, dt,
J = 8.5, 7.0 Hz), 3.75 (1 H, td, J = 7.9, 6.2 Hz), 2.02 (2 H, q, J = 6.4
Hz), 1.90 (2 H, m), 1.57 (1 H, dq, J = 11.8, 8.1 Hz), 1.34 (5 H, m),
0.88 (3 H, t, J = 7.2 Hz).
13C NMR: d = 133.01 (1), 130.71 (1), 80.15 (1), 67.98 (2), 32.38
(2), 32.04 (2), 31.40 (2), 26.09 (2), 22.35 (2), 14.06 (3).
3-[2-(Z)-Methylcyclopentylidene]-1-propanol (2a)
Prepared by cocyclisation of 1a (Method A, 2.4 mmol scale). Col-
umn chromatography (silica gel, 25% Et2O in petroleum ether) pro-
vided a clear, colourless oil (263 mg, 78%) which contained 13% of
the E-isomer. An analytically pure sample was obtained by Kugel-
rohr distillation (70 °C/1 mbar).
LRMS (EI): m/z (%) = 154 (M+, 3), 111 (26), 97 (100).
HRMS: m/z calcd for C10H18O (M+): 154.1358; found: 154.1371.
IR (film): 3330 (br s), 1650 (w) cm–1.
1H NMR: d = 5.18 (1 H, tq, J = 7.4, 1.8 Hz), 3.64 (2 H, br s), 2.71
(1 H, m), 2.32 (4 H, m), 1.84 (1 H, dq, J = 12.5, 7.7 Hz), 1.69 (1 H,
m), 1.6 (1 H, m), 1.5 [1 H, m (obscured)], 1.40 (1 H, m), 1.02 (3 H,
d, J = 7.4 Hz).
13C NMR: d = 152.02 (0), 115.79 (1), 62.84 (2), 35.07 (2), 34.88
(1), 33.51 (2), 32.81 (2), 24.14 (2), 20.92 (3). Minor E-isomer: d =
114.63 (1), 62.57 (2), 39.27 (1), 35.59 (2), 33.15 (2), 29.44 (2),
24.04 (2), 19.17 (3), tertiary carbon at ~152 not observed.
(E)-2-(1-Pentenyl)tetrahydro-2H-pyran (4)
Prepared from 1d by Method A (2 mmol scale). Purification by col-
umn chromatography (5% Et2O in petroleum ether) provided a
clear, colourless oil (95 mg, 31%).
IR (film): 1664 (w) cm–1.
1H NMR: d = 5.67 (1 H, dtd, J = 15.5, 6.6, 0.75 Hz), 5.47 (1 H, ddt,
J = 15.5, 6.3, 1.3 Hz), 4.01 (1 H, d + fs, J = 11 Hz), 3.75 (1 H, br dd,
J = 10, 7 Hz), 3.48 (1 H, t, J = 11 Hz), 2.00 (2 H, q, J = 7.1 Hz), 1.85
(1 H, m), 1.65–1.45 (5 H, m), 1.39 (2 H, app. sextet, J = 7.4 Hz),
0.89 (3 H, t, J = 7.4 Hz).
LRMS (EI): m/z (%) = 140 (M+, 100), 122 (19), 109 (66), 107 (84),
93 (54), 81 (81), 67 (72).
Anal. Calcd for C9H16O: C, 77.09; H, 11.50. Found: C, 69.98; H,
11.53.
13C NMR: d = 131.83 (1), 131.50 (1), 78.45 (1), 68.49 (2), 34.58
(2), 32.37 (2), 26.03 (2), 23.58 (2), 22.39 (2), 13.86 (3).
LRMS (APCI): m/z (%) = 196 (M + H+ + CH3CN, 52), 153 (M +
(Z)-3-[(2S*,3S*)-2-Methyl-3-phenylcyclopentylidene]propan-1-
ol (2b)
H+ – H2, 100), 137 (53).
Prepared by cocyclisation of 1b (Method A). Column chromatogra-
phy (silica gel, 20% Et2O in hexane) provided a viscous, clear co-
lourless oil (150 mg, 69%). An analytically pure sample was
obtained by Kugelrohr distillation (100 °C/1 mbar).
HRMS: m/z calcd for C10H17O (M+· – H): 153.1279; found:
153.1274.
(E)-2-(1-Hexenyl)tetrahydro-2H-pyran (5a)
IR (film): 3344 (br s), 1675 (w), 1600 (m), 1580 (w) cm–1.
Prepared from 1e by Method A (2 mmol scale). Purification by col-
umn chromatography (5% Et2O in petroleum ether) provided a
clear, colourless oil (124 mg, 37%) with data in accordance with lit-
erature values.41
1H NMR (400 MHz): d = 7.25–7.1 (5 H, m), 5.213 (1 H, tq, J = 7.4,
1.9 Hz), 3.585 (2 H, td, J = 6.5, 1.5 Hz), 2.656 (1 H, dt, J = 9.6, 6.6
Hz), 2.580 (1 H, quintet, J = 7.0 Hz), 2.2–2.4 (4 H, m), 2.014 (1 H,
Synthesis 2005, No. 12, 2061–2074 © Thieme Stuttgart · New York

2068
D. R. Owen, R. J. Whitby
SPECIAL TOPIC
(E)-2-(1-Hexenyl)-2,3-dideuterotetrahydro-2H-pyran (5b)
Prepared from 1e by Method A, but with quench of the organozir-
conium intermediate by D2O and MeOD. Purification by column
chromatography (5% Et2O in petroleum ether) provided a clear, co-
lourless oil (51 mg, 30%).
2-Ethoxy-5-phenyl-1,6-heptadiene (18a)
Purified by Kugelrohr distillation (100 °C/0.6 mbar) to give a clear,
colourless oil (81%).
IR (film): 1652 (s), 1630 (m), 1600 (m) cm–1.
1H NMR (C6D6): d = 7.3–7.0 (5 H, m), 5.923 (1 H, ddd, J = 17.4,
9.9, 7.7 Hz), 5.1–4.9 (2 H, m), 3.977 (1 H, s), 3.915 (1 H, s), 3.523
(2 H, q, J = 7.0 Hz), 3.278 (1 H, q, J = 7.3 Hz), 2.21 (2 H, m), 2.09
(2 H, m), 1.122 (3 H, t, J = 6.9 Hz).
13C NMR (C6D6): d = 163.36 (0), 144.45 (0), 142.50 (1), 128.73 (1),
128.09 (1), 126.46 (1), 114.20 (2), 81.04 (2), 62.67 (2), 49.63 (1),
33.63 (2), 33.51 (2), 14.52 (3).
IR (film): 2176 (w), 2079 (w), 1665 (w) cm–1.
1H NMR: d = 5.66 (1 H, dt, J = 15.5, 6.6 Hz), 5.45 (1 H, d, J = 15.4
Hz), 4.00 (1 H, ddt, J = 11.0, 4.1, 1.8 Hz), 3.47 (1 H, td, J = 11.4,
2.9 Hz), 2.02 (2 H, q, J = 6.6 Hz), 1.83 (1 H, m), 1.52 (3 H, m), 1.34
(5 H, m), 0.88 (3 H, t, J = 7.2 Hz).
13C NMR: d = 132.08 (1), 131.24 (1), [78.29 (0), triplet, J = 15.3
Hz], 68.44 (2), 32.16 (2), [31.73 (1), triplet, J = 19.4 Hz], 31.40 (2),
25.98 (2), 23.45 (2), 22.37 (2), 14.07 (3).
LRMS (APCI): m/z (%) = 217 (M + H+, 30), 215 (M + H+ – H2, 20),
187 (100), 171 (55).
HRMS: m/z calcd for C15H20O (M+): 216.1514; found: 216.1530.
LRMS (APCI): m/z (%) = 212 (M + MeCN + H+, 40), 168 (M + H+
– HD, 100), 153 (M + H+ – H2O, 40), 152 (M + H+ – HDO, 20).
HRMS: m/z calcd for C11H18OD2 (M+):170.1640; found: 170.1650.
2-Ethoxy-3-hydroxy-5-phenylhepta-1,6-diene (18b)
Purified by Kugelrohr distillation (130 °C/0.8 mbar) to give a clear,
colourless oil (72%) as a 1:1 mixture of diastereoisomers.
IR (film): 3383 (br m), 1660 (m), 1646 (m), 1630 (m) cm–1.
1H NMR (C6D6): d = 7.4–7.1 (5 H, m), 6.046 (1 H, m), 5.3–5.0 (2
H, m), 4.3–3.7 (4 H, m), 3.495 (2 H, m), 2.4–2.2 (2 H, m), 1.846 (1
H, m), 1.123 and 1.083 (3 H, each t, J = 7.2 Hz).
(Z)-3-[(E)-2-Butylidenecyclopentylidene]propan-1-ol (2f) and
(1E,2E)-1-Allylidene-2-butylidenecyclopentane (6)
Prepared from enyne 1f by Method A. After separation and purifi-
cation by column chromatography (silica gel, 0 to 20 to 40% Et2O
in petroleum ether) 2f was obtained as a clear, colourless oil (80 mg,
45%), and 6 as a clear, colourless oil (39 mg, 24%).
13C NMR (C6D6): d = 164.77 (0), 164.68 (0), 144.84 (0), 143.78 (0),
142.97 (1), 141.90 (1), 128.80 (1), 128.47 (1), 126.59 (1), 126.46
(1), 80.86 (2), 80.72 (2), 70.92 (1), 70.75 (1), 62.90 (2), 62.83 (2),
46.49 (1), 46.35 (1), 41.85 (2), 41.44 (2), 14.35 (3), 14.29 (3).
LRMS (APCI): m/z (%) = 232 (M+, 10), 215 (100), 187 (60), 169
(70).
2f
IR (film): 3330 (br m) cm–1.
1H NMR: d = 5.729 (1 H, t, J = 7.3 Hz), 5.363 (1 H, t, J = 7.1 Hz),
3.319 (2 H, m), 2.563 (2 H, q, J = 7.0 Hz), 2.42–2.33 (4 H, m), 2.077
(2 H, q, J = 7.4 Hz), 1.648 (2 H, quintet, J = 7.3 Hz), 1.5 (1 H, br,
s), 1.447 (2 H, app. sextet, J = 7.2 Hz), 0.938 (3 H, t, J = 7.4 Hz).
13C NMR: d = 143.16 (0), 140.00 (0), 126.75 (1), 117.89 (1), 63.08
(2), 36.65 (2), 32.87 (2), 32.43 (2), 31.24 (2), 23.89 (2), 22.89 (2),
14.14 (3).
HRMS: m/z calcd for C15H20O2 (M+): 232.1463; found: 232.1457.
2-Ethoxy-3-hydroxy-4-phenyl-1,6-heptadiene (18ci)
Purified by Kugelrohr distillation (100 °C/1 mbar) to give a clear,
colourless oil (70%).
IR (film): 3440 (br m), 1650 (m), 1639 (m), 1630 (m) cm–1.
LRMS (APCI): m/z = 181 (M + H+).
HRMS: m/z calcd for C12H20O (M+): 180.1514; found: 180.1510.
1H NMR (C6D6): d = 7.3–7.1 (5 H, m), 5.844 (1 H, ddt, J = 17.1,
10.2, 6.9 Hz), 5.154 (1 H, ddt, J = 17.1, 2.2, 1.5 Hz), 5.014 (1 H, ddt,
J = 10.2, 2.2, 1.3 Hz), 4.214 (1 H, br t, J = 6.2 Hz), 4.154 (1 H, d,
J = 2.0 Hz), 3.863 (1 H, d, J = 2.0 Hz), 3.376 (2 H, m), 3.228 (1 H,
ddd, J = 10.9, 6.7, 4.0 Hz), 2.956 (1 H, dddt, J = 14.4, 7.0, 3.0, 1.5
Hz), 2.611 (1 H, dddt, J = 14.4, 10.9, 7.0, 1.5 Hz), 1.974 (1 H, d,
J = 6.2 Hz), 1.068 (3 H, t, J = 6.9 Hz).
13C NMR (C6D6): d = 162.26 (0), 142.31 (0), 137.59 (1), 129.12 (1),
128.31 (1), 126.60 (1), 115.99 (2), 82.83 (2), 77.17 (1), 62.69 (2),
50.66 (1), 35.21 (2), 14.28 (3).
6
1H NMR (400 MHz): d = 6.465 (1 H, ddd, J = 16.9, 11.0. 10.1 Hz),
6.294 (1 H, dt, J = 11.2, 2.4 Hz), 5.802 (1 H, tt, J = 7.5 Hz, 2.6 Hz),
5.100 (1 H, dd, J = 16.7, 1.5 Hz), 4.956 (1 H, dd, J = 10.2, 1.0 Hz),
2.434 (2 H, td, J = 7.3, 2.4 Hz), 2.296 (2 H, tdt, J = 7.4, 2.4, 1.4 Hz),
2.015 (2 H, q, J = 7.3 Hz), 1.640 (2 H, pentet, J = 7.4 Hz), 0.853 (3
H, t, J = 7.2 Hz).
13C NMR: d = 144.20 (0), 141.09 (0), 134.99 (1), 120.53 (1), 117.73
(1), 115.35 (2), 31.90 (2), 31.00 (2), 30.47 (2), 23.98 (2), 23.01 (2),
14.17 (3).
LRMS (APCI): m/z (%) = 232 (M+, 30), 215 (100), 187 (60), 169
(65).
Compound 6 decomposed before other data could be obtained.
HRMS: m/z calcd for C15H20O2 (M+): 232.1463; found: 232.1468.
Deprotonation of Ethyl Vinyl Ether and Subsequent Alkylation
with an Alkyl Iodide or Aldehyde;20 General Procedure
tert-Butyl{[1-(1-ethoxyvinyl)-2-phenyl-4-pentenyl]oxy}dimeth-
ylsilane (18cii)
To a solution of ethyl vinyl ether (0.95 mL, 721 mg, 10 mmol) in
THF (8 mL) at –70 °C under argon was added dropwise t-BuLi (4.7
mL of a 1.7 M solution in pentanes, 8 mmol), resulting in a bright
yellow suspension. The reaction was allowed to warm, resulting in
dissolution of the yellow precipitate, and disappearance of the yel-
low colour at around 0 °C. The resultant solution of ethoxyvinyllith-
ium was re-cooled to –70 °C and a solution of the electrophile (5
mmol) in THF (2 mL) was added. After warming to 0 °C and stir-
ring for 1–5 h, aq sat. NH4Cl solution (10 mL) was added. After di-
lution with Et2O (20 mL), the aqueous phase was separated and
extracted with Et2O (3 × 50 mL), and the combined organic phases
were washed with brine, dried (Na2SO4), filtered and concentrated.
The crude product was purified by Kugelrohr distillation (Table 2).
tert-Butyldimethylsilyl chloride (155 mg, 1.03 mmol) and imida-
zole (64 mg, 0.94 mmol) were added to a solution of 18ci (203 mg,
0.94 mmol) in DMF (1.5 mL). The mixture was stirred 16 h, and
poured into aq sat. NH4Cl solution and Et2O. The layers were sepa-
rated and the aqueous phase was extracted with Et2O. The combined
organic phases were washed with brine, dried (Na2SO4), filtered and
concentrated. The crude product was purified by column chroma-
tography (Al2O3, petroleum ether) to give the desired silyl ether
(186 mg, 57%).
IR (film): 1660 (w), 1640 (w), 1620 (w) cm–1.
Synthesis 2005, No. 12, 2061–2074 © Thieme Stuttgart · New York

SPECIAL TOPIC
Zirconocene-Induced Cocyclisation/Elimination Reactions
2069
1H NMR: d = 7.3–7.1 (5 H, m), 5.817 (1 H, ddt, J = 17.1, 10.1, 6.8
Hz), 5.116 (1 H, d + fs, J = 17.4 Hz), 4.955 (1 H, d + fs, J = 10.1
Hz), 4.298 (1 H, d, J = 1.7 Hz), 4.270 (1 H, d, J = 5.5 Hz), 3.932 (1
H, d, J = 1.7 Hz), 3.390 (2 H, m), 3.317 (1 H, ddd, J = 11.2, 5.5, 3.7
Hz), 2.955 (1 H, ddd, J = 14.4, 6.8, 3.7 Hz), 2.750 (1 H, ddd,
J = 14.4, 11.2, 6.8 Hz), 1.077 (9 H, s), 1.072 (3 H, t, J = 7.1 Hz),
0.078 (3 H, s), –0.147 (3 H, s).
13C NMR: d = 163.37 (0), 142.26 (0), 137.78 (1), 129.56 (1), 128.19
(1), 126.54 (1), 115.88 (2), 82.88 (2), 78.30 (1), 62.72 (2), 50.73 (1),
33.75 (2), 26.22 (3), 18.48 (0), 14.40 (3), –4.56 (3), –5.41 (3).
HRMS: m/z calcd for C13H16O2 (M+): 204.1150; found: 204.1145.
2-Ethoxy-3-hydroxy-7-phenylhepta-1-ene-6-yne (18g)
Purified by Kugelrohr distillation (150 °C/0.8 mbar) to give a clear,
colourless oil (64%).
IR (film): 3417 (br m), 2240 (w), 1659 (m), 1626 (m), 1606 (w)
cm–1.
1H NMR (C6D6): d = 7.506 (2 H, m), 7.038 (3 H, m), 4.258 (1 H, d,
J = 2.3 Hz), 4.232 (1 H, m), 3.895 (1 H, d, J = 2.0 Hz), 3.420 (2 H,
q, J = 7.0 Hz), 2.569 (1 H, dd, J = 7.7, 3.2 Hz), 2.546 (1 H, dd,
J = 7.7, 1.7 Hz), 2.15–1.85 (2 H, m), 1.780 (1 H, d, J = 5.0 Hz),
1.035 (3 H, t, J = 7.1 Hz).
LRMS (APCI): m/z (%) = 301 (M + H+ – EtOH, 10), 215 (M + H+
– HOSiMe2Bu-i, 25), 156 (65), 124 (100).
HRMS: m/z calcd for C21H34O2Si (M+): 346.2328; found: 346.2328.
13C NMR (C6D6): d = 164.03 (0), 131.98 (1), 128.51 (1), 127.73 (1),
124.79 (0), 90.39 (0), 81.64 (0), 80.95 (2), 71.83 (1), 62.92 (2),
34.97 (2), 16.11 (2), 14.31 (3).
4,4-Dimethyl-2-ethoxy-3-hydroxy-1,6-heptadiene (18d)
Purified by Kugelrohr distillation (110 °C/1.0 mbar) to give a clear,
colourless oil (75%).
IR (film): 3466 (br m), 1657 (m), 1637 (m), 1625 (m) cm–1.
LRMS (APCI): m/z (%) = 231 (30), 185 (50).
HRMS: m/z calcd for C15H18O2 (M+): 230.1307; found: 230.1314.
1H NMR (C6D6): d = 6.031 (1 H, ddt, J = 17.9, 10.4, 7.7 Hz), 5.20–
5.10 (2 H, m), 4.163 (1 H, d, J = 1.0 Hz), 3.990 (1 H, d, J = 1.0 Hz),
3.908 (1 H, d, J = 6.2 Hz), 3.428 (2 H, m), 2.432 (1 H, dd, J = 13.4,
7.7 Hz), 2.233 (1 H, dd, J = 13.4, 7.2 Hz), 1.990 (1 H, d, J = 6.2 Hz),
1.133 (3 H, s), 1.089 (3 H, s), 1.068 (3 H, t, J = 7.0 Hz).
13C NMR (C6D6): d = 163.21 (0), 136.56 (1), 117.72 (2), 83.81 (2),
79.82 (1), 63.09 (2), 44.58 (2), 38.58 (0), 24.04 (3), 23.72 (3), 14.79
(3).
2-Ethoxydec-1-ene-6-yne (18h)
Purified by Kugelrohr distillation (100 °C/1 mbar) to give a clear,
colourless oil (89%).
IR (film): 1653 (s) cm–1.
1H NMR (C6D6): d = 4.046 (1 H, d, J = 1.5 Hz), 3.939 (1 H, d,
J = 1.5 Hz), 3.546 (2 H, q, J = 7.0 Hz), 2.375 (2 H, t, J = 7.4 Hz),
2.261 (2 H, tt, J = 7.2, 2.4 Hz), 2.133 (2 H, tt, J = 7.0, 2.4 Hz), 1.877
(2 H, quintet, J = 7.2 Hz), 1.506 (2 H, sextet, J = 7.1 Hz), 1.156 (3
H, t, J = 7.0 Hz), 0.998 (3 H, t, J = 7.4 Hz).
13C NMR (C6D6): d = 163.06 (0), 81.25 (2), 80.65 (0), 80.35 (0),
62.72 (2), 34.80 (2), 27.59 (2), 22.98 (2), 21.21 (2), 18.70 (2), 14.57
(3), 13.65 (3).
LRMS (APCI): m/z (%) = 184 (M+, 20), 183 (15), 167 (100).
HRMS: m/z calcd for C11H20O2 (M+): 184.1463; found: 184.1457.
1-(2-Allylphenyl)-2-ethoxy-2-propen-1-ol (18e)
Purified by Kugelrohr distillation (110 °C/1 mbar) to give a clear,
colourless oil (70%).
IR (film): 3422 (br m), 1636 (m) cm–1.
1H NMR (C6D6): d = 7.636 (1 H, d, J = 6.9 Hz), 7.1–7.0 (3 H, m),
5.875 (1 H, ddt, J = 15.9, 9.4, 6.3 Hz), 5.325 (1 H, s), 5.0–4.9 (2 H,
m), 4.298 (1 H, d, J = 2.2 Hz), 3.918 (1 H, d, J = 2.3 Hz), 3.2–3.4 (4
H, m), 2.065 (1 H, s), 0.853 (3 H, t, J = 7.1 Hz).
13C NMR (C6D6): d = 164.13 (0), 140.24 (0), 138.23 (0), 137.86 (1),
129.94 (1), 128.04 (1), 127.50 (1), 126.73 (1), 115.81 (2), 82.08 (2),
71.25 (1), 63.09 (2), 37.11 (2), 14.26 (3).
LRMS (EI): m/z (%) = 180 (M+, 7), 165 (14), 152 (59), 137 (48),
119 (31), 86 (50), 58 (100).
HRMS: m/z calcd for C12H20O (M+): 180.1514; found: 180.1521.
1-Iodo-5-nonyne (17i)
Prepared in 68% yield by alkylation of 1-pentynyllithium with 1-
chloro-4-iodobutane followed by conversion of chloride to iodide
with NaI in acetone.
IR (film): no characteristic absorptions.
1H NMR: d = 3.218 (2 H, t, J = 7.0 Hz), 2.199 (2 H, tt, J = 7.0, 2.4
Hz), 2.123 (2 H, tt, J = 7.2, 2.4 Hz), 1.943 (2 H, m), 1.593 (2 H, m),
1.503 (2 H, app. sextet, J = 7.4 Hz), 0.970 (3 H, t, J = 7.4 Hz).
LRMS (APCI): m/z (%) = 218 (M+, 10), 201 (100), 189 (15), 173
(50).
HRMS: m/z calcd for C14H18O2 (M+): 218.1307; found: 218.1306.
13C NMR: d = 81.00 (0), 79.41 (0), 32.62 (2), 29.89 (2), 22.63 (2),
20.88 (2), 17.88 (2), 13.66 (3), 6.62 (2).
1-(2-Vinylphenyl)-2-ethoxy-2-propen-1-ol (18f)
Purified by Kugelrohr distillation (110 °C/0.8 mbar) to give a clear,
colourless oil (86%).
IR (film): 3412 (br s), 1660 (m), 1626 (s) cm–1.
1H NMR (C6D6): d = 7.732 (1 H, dd, J = 7.7, 1.7 Hz), 7.456 (1 H,
dd, J = 7.7, 1.5 Hz), 7.249 (1 H, dd, J = 17.4, 10.9 Hz), 7.203 (1 H,
td, J = 7.7, 1.5 Hz), 7.126 (1 H, td, J = 7.7, 1.5 Hz), 5.587 (1 H, dd,
J = 17.4, 1.5 Hz), 5.472 (1 H, br s), 5.214 (1 H, dd, J = 10.9, 1.5 Hz),
4.361 (1 H, dd, J = 2.3, 0.7 Hz), 4.016 (1 H, d, J = 2.2 Hz), 3.398 (2
H, m), 2.187 (1 H, br s), 0.961 (3 H, t, J = 7.1 Hz).
13C NMR (C6D6): d = 163.75 (0), 139.29 (0), 137.34 (0), 135.27 (1),
128.33 (1), 128.00 (1), 127.35 (1), 126.25 (1), 116.02 (2), 82.47 (2),
71.49 (1), 63.11 (2), 14.24 (3).
HRMS: m/z calcd for C9H15I (M+): 250.0212; found: 250.0219.
2-Ethoxyundec-1-ene-7-yne (18i)
Purified by Kugelrohr distillation (130 °C/0.8 mbar) to give a clear,
colourless oil (71%).
IR (film): 1652 (s) cm–1.
1H NMR (C6D6): d = 3.976 (1 H, d, J = 1.5 Hz), 3.898 (1 H, d,
J = 1.5 Hz), 3.524 (2 H, q, J = 7.0 Hz), 2.20–2.14 (4 H, m), 2.100 (2
H, tt, J = 7.0, 2.4 Hz), 1.744 (2 H, m), 1.63–1.41 (4 H, m), 1.136 (3
H, t, J = 7.2 Hz), 0.962 (3 H, t, J = 7.4 Hz).
13C NMR (C6D6): d = 163.31 (0), 80.72 (2), 80.31 (0), 80.22 (0),
62.48 (2), 34.98 (2), 28.86 (2), 26.86 (2), 22.77 (2), 21.01 (2), 18.87
(2), 14.42 (3), 13.47 (3).
LRMS (APCI): m/z (%) = 200 (M + H+ + MeCN – H2O, 34), 187
LRMS (APCI): m/z (%) = 195 (M + H+, 100), 194 (M+, 30).
HRMS: m/z calcd for C13H22O (M+): 194.1670; found: 194.1670.
(M + H+ – H2O, 100), 175 (20), 159 (85).
Synthesis 2005, No. 12, 2061–2074 © Thieme Stuttgart · New York

2070
D. R. Owen, R. J. Whitby
SPECIAL TOPIC
(1R*,2S*)-1-(2-Methyl-3-methylenecyclopentyl)benzene (19a)
Prepared by cocyclisation of diene 18a (Method A). Purification by
column chromatography (silica gel, hexane) provided a clear, co-
lourless oil (123 mg, 72%). The product was a 17:1 mixture of dia-
stereoisomers, as determined by GC, tR 13.85 min (major), 14.06
min (minor).
13C NMR: d = 159.37 (0), 139.61 (0), 128.86 (1), 128.66 (1), 126.90
(1), 109.45 (2), 77.63 (1), 48.58 (1), 35.89 (2), 34.93 (1), 22.34 (3).
LRMS (APCI): m/z = 171 (M + H+ – H2O).
HRMS: m/z calcd for C13H16O (M+): 188.1201; found: 188.1196.
The title compound was also prepared by cocyclisation of the silyl
protected diene 18cii (Method A, 0.78 mmol scale) and subsequent
deprotection using TFA–H2O–MeOH (1:1:1) by stirring for 20 h to
afford 19c (47%) as a 5:4 mixture of diastereoisomers (GC). NMR
data for the minor (1S*,3R*,5R*)-diastereoisomer could be distin-
guished:
1H NMR: d = 7.4–7.2 (5 H, m), 5.319 (1 H, d, J = 2.0 Hz), 5.121 (1
H, s), 4.556 (1 H, d, J = 5.2 Hz), 3.168 (1 H, dt, J = 11.9, 5.7 Hz),
2.7–2.55 (1 H, m), 2.189 (1 H, dt, J = 11.9, 6.7 Hz), 1.912 (1 H, q,
J = 11.8 Hz), 1.290 (3 H, d, J = 6.7 Hz).
IR (film): 1654 (m), 1602 (m) cm–1.
1H NMR (400 MHz): d (major diastereoisomer) = 7.3–7.1 (5 H, m),
4.844 (1 H, q, J = 2.3 Hz), 4.759 (1 H, q, J = 2.5 Hz), 2.525 (1 H,
ddq, J = 15.7, 8.9, 2.0 Hz), 2.411 (1 H, td, J = 11.1, 6.3 Hz), 2.4–2.3
(2 H, m), 1.983 (1 H, dddd, J = 12.3, 8.1, 6.3, 1.9 Hz), 1.689 (1 H,
dtd, J = 12.4, 10.9, 8.9 Hz), 0.929 (3 H, d, J = 6.2 Hz). Methyl
group of minor diastereoisomer, d = 0.629 (3 H, d, J = 7.0 Hz).
13C NMR (100 MHz): d (major isomer) = 157.35 (0), 144.29 (0),
128.82 (1), 127.92 (1), 126.68 (1), 104.86 (2), 54.80 (1), 46.94 (1),
33.60 (2), 32.21 (2), 16.63 (3); d (Minor diastereoisomer (quaterna-
ries not seen) = 128.66 (1), 128.42 (1), 126.28 (1), 105.43 (2), 49.66
(1), 43.76 (1), 31.84 (2), 28.85 (2), 16.22 (3).
13C NMR: d = 158.95 (0), 139.31 (0), 128.66 (1), 128.51 (1), 126.75
(1), 109.33 (2), 76.74 (1), 49.57 (1), 36.81 (2), 36.47 (1), 19.35 (3).
(1S*,4S*)-2,2,4-Trimethyl-5-methylene-1-cyclopentanol (19d)
Prepared by cocyclisation of diene 18d (Method A). Purification by
column chromatography (silica gel, 20% Et2O in petroleum ether)
provided a viscous, colourless oil (103 mg, 74%). The product was
a 4:1 mixture of diastereoisomers as determined by GC; tR 8.64 min
(minor), 8.77 min (major).
LRMS (APCI): m/z = 172 (M+, 10), 157 (100).
HRMS: m/z calcd for C13H16 (M+): 172.1252; found: 172.1251.
Anal. Calcd for C13H16: C, 90.64; H, 9.36. Found: C, 90.42; H, 9.39.
(1S*,3S*,4R*)- and (1R*, 3S*, 4R*)-3-Methyl-2-methylene-4-
phenyl-1-cyclopentanol (19b)
IR (film): 3386 (br m), 1650 (m) cm–1.
Prepared by cocyclisation of diene 18b (Method A). Purification by
column chromatography (10% Et2O in hexanes) provided a viscous,
colourless oil (103 mg, 55%). The product was a 1:1 mixture of
diastereoisomers, as determined by GC, corresponding to a 100%
de; tR 16.95 and 19.05 min.
1H NMR (400 MHz): d (major diastereoisomer) = 5.113 (1 H, t,
J = 2.6 Hz), 4.989 (1 H, td, J = 2.5, 0.6 Hz), 4.001 (1 H, q, J = 2.5
Hz), 2.57 (1 H, m), 1.743 (1 H, dd, J = 12.7, 8.2 Hz), 1.582 (1 H, br
s), 1.098 (3 H, d, J = 6.9 Hz), 1.081 (3 H, s), 1.050 (1 H, ddq,
J = 12.7, 10.2, 0.7 Hz), 0.791 (3 H, s); d [minor diastereoisomer
(where seen)] = 5.157 (1 H, m), 4.966 (1 H, td, J = 2.2, 0.6 Hz),
3.923 (1 H, t, J = 1.6 Hz), 1.145 (3 H, d, J = 7.0 Hz), 0.988 (3 H, s),
0.906 (3 H, s).
13C NMR: d (major diastereoisomer) = 159.98 (0), 106.52 (2),
82.46 (1), 45.15 (1), 41.06 (0), 33.52 (2), 26.64 (3), 21.45 (3), 19.61
(3); d [minor diastereoisomer (where seen)] = 106.74 (2), 83.00 (1),
33.08 (2), 26.79 (3), 22.19 (3), 20.88 (3).
IR (film): 3352 (br s), 1648 (w), 1601 (w) cm–1.
1H NMR: d = 7.4–7.2 (5 H, m), 5.320 (0.5 H, dd, J = 2.9, 1.5 Hz),
5.248 (0.5 H, dd, J = 2.9, 2.2 Hz), 5.090 (0.5 H, dd, J = 2.2, 1.5 Hz),
5.051 (0.5 H, t, J = 2.6 Hz), 4.690 (0.5 H, m), 4.628 (0.5 H, tt,
J = 6.8, 2.2 Hz), 2.914 (0.5 H, td, J = 11.4, 7.0 Hz), 2.669 (0.5 H,
m), 2.489 (1 H, m), 2.135 (0.5 H, ddd, J = 13.6, 6.6, 1.8 Hz), 2.006
(0.5 H, ddd, J = 13.6, 11.8, 5.9 Hz), 1.796 (1 H, m), 1.449 (0.5 H,
s), 1.292 (0.5 H, s), 1.105 (1.5 H, d, J = 6.6 Hz), 1.054 (1.5 H, d,
J = 6.6 Hz).
13C NMR: d = 160.68 (0), 159.43 (0), 143.45 (0), 143.04 (0), 128.65
(1), 128.63 (1), 127.65 (1), 127.62 (1), 126.67 (1), 126.58 (1),
108.55 (2), 107.41 (2), 74.42 (1), 73.83 (1), 50.93 (1), 50.10 (1),
45.73 (1), 45.00 (1), 43.13 (2), 42.89 (2), 17.11 (3), 16.79 (3).
LRMS (APCI): m/z = 123 (M + H+ – H2O).
HRMS: m/z calcd for C9H16O (M+): 140.1201; found: 140.1205.
3-Methyl-2-methylene-1,2,3,4-tetrahydro-1-naphthalenol (19e)
Prepared by cocyclisation of diene 18e (Method A, 2 mmol scale).
Chromatographic separation (silica gel, 5% Et2O in hexanes) of the
diastereoisomers and purification provided a less polar isomer as a
white wax (85 mg, 24%) and a more polar diastereoisomer as a
white powder (130 mg, 37%), which was further purified by precip-
itation from MeOH–pentane. GC analysis of the crude product
showed an 8:7 mixture of diastereoisomers; tR 18.35 min (major)
and 18.92 min (minor).
LRMS (APCI): m/z = 171 (M + H+ – H2O).
HRMS: m/z calcd for C13H16O (M+): 188.1201; found: 188.1208.
(1S*,3S*,5R*)-3-Methyl-2-methylene-5-phenyl-1-cyclopen-
tanol (19c)
Prepared by cocyclisation of diene 18ci (Method A). Purification by
column chromatography (5% Et2O in hexanes) provided a viscous,
colourless oil (82 mg, 44%). The product was a 7:1 mixture of dia-
stereoisomers, as determined by GC; tR 14.51 min (major), 14.20
min (minor). The major diastereoisomer has the relative stereo-
chemistry (1S,3S,5R), as determined by GOESY experiments (cor-
relation between proton adjacent to phenyl group, and methyl
group). NMR data provided is for the major diastereoisomer:
Less Polar Diastereoisomer
Mp 39–41°C.
IR (film): 3271(w), 1657 (m) cm–1.
1H NMR: d = 7.604 (1 H, d, J = 7.0 Hz), 7.271 (1 H, td, J = 7.2, 1.2
Hz), 7.222 (1 H, td, J = 7.2, 1.7 Hz), 7.097 (1 H, dd, J = 7.0, 1.7 Hz),
5.283 (1 H, br s), 5.228 (1 H, br d, J = 3.7 Hz), 5.029 (1 H, dt,
J = 2.2, 1.1 Hz), 2.959 (1 H, apparent q, J = 10.3 Hz), 2.4 (2 H, m),
2.162 (1 H, br d, J = 7.4 Hz), 1.278 (3 H, d, J = 6.2 Hz).
13C NMR: d = 153.34 (0), 139.48 (0), 136.69 (0), 128.16 (1), 127.54
(1), 127.23 (1), 126.67 (1), 105.02 (2), 72.35 (1), 39.89 (2), 33.97
(1), 18.91 (3).
IR (film): 3415 (br m), 1660 (w), 1600 (m) cm–1.
1H NMR (400 MHz): d = 7.4–7.2 (5 H, m), 5.249 (1 H, ddd, J = 2.4,
1.3, 0.6 Hz), 5.094 (1 H, ddd, J = 2.2, 1.5, 0.7 Hz), 4.603 (1 H, d,
J = 5.0 Hz), 3.364 (1 H, td, J = 7.8, 5.5 Hz), 3.0–2.9 (1 H, m), 2.461
(1 H, dtd, J = 12.9, 8.8, 0.3 Hz), 1.710 (1 H, dddt, J = 12.3, 7.2, 4.5,
0.5 Hz), 1.564 (1 H, br s), 1.200 (3 H, d, J = 7.1 Hz).
LRMS (APCI): m/z = 157 (M + H+ – H2O).
Synthesis 2005, No. 12, 2061–2074 © Thieme Stuttgart · New York

SPECIAL TOPIC
Zirconocene-Induced Cocyclisation/Elimination Reactions
2071
Anal. Calcd for C12H14O: C, 82.72; H, 8.10. Found: C, 82.42; H,
8.09.
1H NMR: d = 5.324 (2 H, qd, J = 7.4, 2.5 Hz), 2.135 (3 H, s), 2.125
(3 H, s), 0.905 (3 H, t, J = 7.4 Hz), 0.863 (3 H, t, J = 7.4 Hz).
13C NMR: d = 209.33 (0), 141.54 (0), 140.82 (0), 126.53 (1), 125.74
More Polar Diastereoisomer
Mp 74–75 °C.
IR (film): 3226 (br m), 1655 (w) cm–1.
(1), 29.99 (3), 14.25 (3), 14.08 (3).
LRMS (APCI): m/z (%) = 335 (M + H + 85), 317 (100).
1H NMR: d = 7.5–7.1 (4 H, m), 5.207 (1 H, d, J = 1.0 Hz), 5.121 (1
H, br s), 5.016 (1 H, t, J = 1.2 Hz), 3.023 (1 H, dd, J = 15.6, 5.3 Hz),
2.95–2.8 (1 H, m), 2.482 (1 H, dd, J = 15.6, 10.5 Hz), 1.992 (1 H,
br s), 1.253 (3 H, d, J = 6.7 Hz).
13C NMR: d = 152.62 (0), 138.06 (0), 137.05 (0), 128.85 (1), 128.49
(1), 127.95 (1), 126.66 (1), 109.31 (2), 72.89 (1), 39.67 (2), 30.99
(1), 18.22 (3).
N-Allyl-N-benzyl-N-(2-chloroallyl)amine (20a); Typical Proce-
dure
2,3-Dichloro-1-propene (3.33 g, 30 mmol) in MeCN (10 mL) was
added to a suspension of K2CO3 (6.9 g, 50 mmol) and N-allylben-
zylamine (2.94 g, 20 mmol) in MeCN (60 mL). The mixture was
subsequently refluxed for 19 h, before cooling and dilution with
H2O and Et2O. The aqueous phase was extracted with Et2O, and the
combined organic phases were washed with H2O and brine, dried
(MgSO4), filtered and concentrated. The crude material was puri-
fied by column chromatography (silica gel, petroleum ether), then
Kugelrohr distillation (120 °C/0.7 mbar) to provide a clear, colour-
less oil (3.282 g, 74%).
LRMS (APCI): m/z (%) = 173 (15), 157 (100).
Anal. Calcd for C12H14O: C, 82.72; H, 8.10. Found: C, 83.02; H,
8.12.
IR (film): 1634 (s) cm–1.
3-Methyl-2-methylene-1-indanol (19f)
Prepared by cocyclisation of diene 18f (Method A). Purification by
column chromatography (silica gel, 10% Et2O in petroleum ether),
then further chromatography (silica gel, 10% Et2O in hexanes) pro-
vided a single diastereoisomer of the title compound as a waxy
white solid (41 mg, 26%); mp 50–52 °C.
1H NMR: d = 7.4–7.2 (5 H, m), 5.904 (1 H, ddt, J = 16.9, 10.3, 6.2
Hz), 5.512 (1 H, s), 5.368 (1 H, s), 5.3–5.15 (2 H, m), 3.684 (2 H,
s), 3.259 (2 H, s), 3.164 (2 H, d, J = 5.9 Hz).
13C NMR: d = 140.35 (0), 139.16 (0), 135.48 (1), 128.85 (1), 128.43
(1), 127.16 (1), 117.90 (2), 113.99 (2), 59.69 (2), 57.57 (2), 56.29
(2).
LRMS (ES+): m/z = 224 and 222 (M + H+, 100%).
IR (CH2Cl2): 3350 (br s), 1664 (w), 1609 (w) cm–1.
1H NMR: d = 7.50–7.45 (1 H, m), 7.4–7.2 (3 H, m), 5.5 (2 H, m),
5.284 (1 H, d, J = 1.5 Hz), 3.884 (1 H, q, J = 7.1 Hz), 2.003 (1 H, br
s), 1.390 (3 H, d, J = 7.4 Hz).
HRMS: m/z calcd for C13H16NCl (M + H+): 224.1565; found:
224.1552.
13C NMR: d = 158.80 (0), 146.73 (0), 142.83 (0), 129.14 (1), 127.51
(1), 125.13 (1), 124.05 (1), 110.71 (2), 76.22 (1), 41.84 (1), 21.34
(3).
N-Benzyl-N-(3-butenyl)-N-(2-chloroallyl)amine (20b)
Prepared by alkylation of N-(3-butenyl)benzylamine (0.805g, 5
mmol) with 2,3-dichloro-1-propene. Purification by column chro-
matography (silica gel, 10% Et2O in petroleum ether) followed by
Kugelrohr distillation (115 °C/0.7 mbar) yielded 20b as a clear, co-
lourless oil (681 mg, 58%).
LRMS (APCI): m/z (%) = 160 (M+, 8), 143 (M + H+ – H2O, 100).
HRMS: m/z calcd for C11H12O (M+): 160.0888; found: 160.0887.
2-Methylene-3-[(E)-1-phenylmethylidene]-1-cyclopentanol
(19g)
Prepared by cyclisation of the enyne 18g (Method A). Purification
by column chromatography (silica gel, 20 to 35% Et2O in petroleum
ether) provided a viscous, colourless oil (62 mg, 33%).
IR (film): 1636 (s) cm–1.
1H NMR: d = 7.35–7.15 (5 H, m), 5.719 (1 H, ddt, J = 16.9, 9.9, 7.0
Hz), 5.400 (1 H, s), 5.246 (1 H, s), 5.0–4.9 (2 H, m), 3.591 (2 H, s),
3.158 (2 H, s), 2.520 (2 H, t, J = 7.4 Hz), 2.187 (2 H, q, J = 7.1 Hz).
13C NMR: d = 140.45 (0), 139.33 (0), 136.81 (1), 128.83 (1), 128.40
(1), 127.13 (1), 115.79 (2), 113.88 (2), 60.28 (2), 57.99 (2), 53.06
(2), 31.81 (2).
LRMS (ES+): m/z = 238 and 236 (M + H+).
HRMS: m/z calcd for C11H13N35Cl (M + H+ – C3H5): 194.0737;
IR (film): 1598 (w) cm–1.
1H NMR: d = 7.5–7.2 (5 H, m), 6.915 (1 H, t, J = 2.6 Hz), 5.603 (1
H, d, J = 1.7 Hz), 5.205 (1 H, d, J = 1.5 Hz), 4.618 (1 H, t, J = 6.2
Hz), 2.899 (1 H, dddd, J = 16.6, 8.2, 5.7, 2.5 Hz), 2.659 (1 H, dtd,
J = 16.8, 7.7, 2.7 Hz), 2.101 (1 H, ddt, J = 13.3, 7.9, 5.7 Hz), 2.05
(1 H, br s), 1.721 (1 H, m).
found: 194.0735.
13C NMR: d = 153.71 (0), 139.13 (0), 137.73 (0), 128.97 (1), 128.49
(1), 126.91 (1), 121.58 (1), 104.85 (2), 75.21 (1), 33.88 (2), 28.80
(2).
LRMS (EI): m/z (%) = 186 (M+, 13), 168 (M+ – H2O, 65), 142 (68).
HRMS: m/z calcd for C13H14O (M+): 186.1046; found: 186.1045.
N-Allyl-N-(2-chloro-2-propenyl)benzylamine
Prepared from benzylamine (10.7 g, 0.1 mol) and 2,3-dichloro-1-
propene. Purification by column chromatography (10% Et2O in pe-
troleum ether) and subsequent Kugelrohr distillation (100 °C/0.6
mbar) provided a clear, colourless oil (5.422 g, 30%).
IR (film): 1642 (s) cm–1.
1-[(E)-Butylidene]-2-methylenecyclopentane (19h)
Prepared by cocyclisation of enyne 18h (Method A). Purification by
column chromatography (silica gel, hexanes), then Kugelrohr distil-
lation (120 °C/10 mbar) provided a clear, colourless oil (92 mg,
68%) with data in accordance with literature values.42
1H NMR: d = 7.4–7.2 (5 H, m), 5.382 (2 H, s), 3.782 (2 H, s), 3.446
(2 H, s), 1.854 (1 H, s).
13C NMR: d = 141.02 (0), 139.85 (0), 128.63 (1), 128.44 (1), 127.29
(1), 113.75 (2), 54.91 (2), 51.88 (2).
Undec-7-ene-2-one Dimers 19i
LRMS (ES+): m/z = 184 and 182 (M + H+).
HRMS: m/z calcd for C10H12N35Cl (M+): 181.0658; found:
Prepared by treatment of the enyne 18i with zirconocene(1-butene)
(Method A). Column chromatography (silica gel, Et2O) provided a
mixture of dimeric products (87 mg, 52%). Selected signals from
the NMR spectra are listed below.
181.0651.
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2072
D. R. Owen, R. J. Whitby
SPECIAL TOPIC
(3aS*,4R*,8aR*)-6-Benzyl-2-phenyl-4-propyl-
1,2,3,3a,4,5,6,7,8,8a-decahydropyrrolo[3,4-f]isoindole-1,3-di-
one (23)
A solution of 13b (125 mg, 0.55 mmol) in anhyd Et2O (1 mL) was
added dropwise to a solution of N-phenylmaleimide (87 mg, 0.5
mmol) in anhyd Et2O (3 mL), and the resultant yellow solution was
stirred at r.t. for 7 h. The solvent was removed in vacuo and the res-
idue purified by column chromatography (silica gel, Et2O) to fur-
nish a sticky, colourless gum (173 mg, 87%).
N-Benzyl-N-(2-chloroallyl)-N-(2-hexynyl)amine (20c)
Prepared by alkylation N-allyl-N-(2-chloro-2-propenyl)benzyl-
amine (3.63 g, 20 mmol) with the mesylate of 2-hexyn-1-ol. Purifi-
cation by column chromatography (silica gel, 5% Et2O in petroleum
ether), then Kugelrohr distillation (110 °C/0.4 mbar) provided 20c
as a clear, colourless oil (3.236 g, 62%).
IR (film): 1642 (s) cm–1.
1H NMR: d = 7.5–7.2 (5 H, m), 5.526 (1 H, s), 5.384 (1 H, s), 3.708
(2 H, s), 3.370 (2 H, t, J = 2.2 Hz), 3.346 (2 H, s), 2.253 (2 H, tt,
J = 7.0, 2.2 Hz), 1.604 (2 H, app. sextet, J = 7.2 Hz), 1.062 (3 H, t,
J = 7.4 Hz).
13C NMR: d = 139.95 (0), 138.65 (0), 129.17 (1), 128.47 (1), 127.33
(1), 114.69 (2), 86.09 (0), 74.21 (0), 59.85 (2), 57.07 (2), 41.86 (2),
22.66 (2), 20.90 (2), 13.74 (3).
IR (film): 1716 (s) cm–1
1H NMR: d = 7.6–7.2 (10 H, m), 3.826 (2 H, s), 3.7–3.4 (4 H, m),
3.333 (1 H, td, J = 9.2, 4.4 Hz), 3.292 (1 H, dd, J = 8.8, 2.9 Hz),
2.764 (1 H, q, J = 6.5 Hz), 2.662 (1 H, d, J = 17.6 Hz), 2.475 (1 H,
d, J = 16.9, 8.1 Hz), 1.8–1.3 (4 H, m), 0.920 (3 H, t, J = 7.4 Hz).
13C NMR: d = 179.30 (0), 177.33 (0), 139.40 (0), 136.80 (0), 132.27
(0), 132.08 (0), 129.36 (1), 128.80 (1), 128.59 (1), 127.26 (1),
126.60 (1), 62.34 (2), 61.85 (2), 60.58 (2), 44.08 (1), 39.87 (1),
35.42 (1), 31.95 (2), 21.98 (2), 21.50 (2), 14.32 (3).
LRMS (ES+): m/z = 264 and 262 (M + H+).
Anal. Calcd for C16H20NCl: C, 73.4; H, 7.70; N, 5.35. Found: C,
73.35; H, 7.89; N, 5.37.
LRMS (ES+): m/z = 401 (M + H+).
HRMS: m/z calcd for C26H28N2O2 (M+): 400.2151; found:
1-Benzyl-3-methyl-4-methylenepyrrolidine (21a)
Prepared by cocyclisation of 20a (Method A). Purification by col-
umn chromatography (silica gel, 20% Et2O in petroleum ether) pro-
vided a clear, colourless oil (132 mg, 71%). This compound has
been synthesised previously by a different method,27 however, no
data was provided.
400.2146.
Insertion of Alkenyl Carbenoids into Organozirconium
Reagents; General Procedure
To a solution of the organozirconium species (~1 mmol) prepared
by the general cocyclisation procedure (Method A) cooled to
–90 °C was added the alkenyl chloride (1.3 equiv) in THF (1 mL),
followed by a solution of LiTMP [1.3 equiv, prepared by addition
of n-BuLi to a solution of 2,2,6,6-tetramethylpiperidine (1.3 equiv)
in THF (4 mL) under argon at 0 °C and stirring for 30 min]. In the
case of cis-1,4-dichloro-2-butene, 2.6 equiv of LiTMP are used. Af-
ter 30 min at –90 to –80 °C, MeOH (3 mL) and aq sat. NaHCO3 so-
lution (6 mL) were added and the reaction was allowed to warm to
r.t. and stirred for 16 h. The mixture was subsequently diluted with
H2O and Et2O. The aqueous phase was extracted with Et2O and the
combined organic phases were washed with brine, dried (MgSO4),
filtered and concentrated.
1H NMR: d = 7.4–7.2 (5 H, m), 4.905 (1 H, q, J = 2.2 Hz), 4.842 (1
H, q, J = 2.5 Hz), 3.676 (1 H, d, J = 13.2 Hz), 3.597 (1 H, d, J = 12.9
Hz), 3.466 (1 H, d, J = 13.2 Hz), 3.1–3.0 (2 H, m), 2.8–2.7 (1 H, m),
2.111 (1 H, t, J = 8.8 Hz), 1.132 (3 H, d, J = 6.6 Hz).
13C NMR: d = 154.08 (0), 138.96 (0), 129.01 (1), 128.42 (1), 127.17
(1), 104.06 (2), 62.44 (2), 60.83 (2), 59.63 (2), 37.67 (1), 17.82 (3).
LRMS (ES+): m/z = 188 (M + H+).
1-Benzyl-4-methyl-3-methylenepiperidine (21b) and N-Allyl-N-
benzyl-N-(3-butenyl)amine (22)
Prepared by cocyclisation of diene 20b (Method A). Separation and
purification by column chromatography (silica gel, 10% Et2O in pe-
troleum ether) and Kugelrohr distillation (110 °C/0.7 mbar) provid-
ed 21b as a clear, colourless oil (107 mg, 53%) with data consistent
with the literature.25 Also isolated was 2230 as a clear, colourless oil
(72 mg, 36%), contaminated with ~20% of the further reduced prod-
uct, N-allyl-N-butylbenzylamine.
(1R*,2S*)-1-{3-Methylene-2-[(2Z)-2,4-pentadienyl]cyclopen-
tyl}benzene (26)
Cocyclisation of diene 18a (1 mmol) (Method A) followed by inser-
tion of the carbenoid derived from (Z)-1,4-dichloro-2-butene, aque-
ous work-up and purification by column chromatography (silica
gel, petroleum ether) provided 26 as a clear, colourless oil (22 mg,
10%).
1-Benzyl-3-[(Z)-butylidene]-4-methylenepyrrolidine (21c)
Prepared by cocyclisation of enyne 20c (Method A, 3 mmol scale).
Purification by column chromatography (silica gel, 10% Et2O in pe-
troleum ether) followed by Kugelrohr distillation (110 °C/0.8 mbar)
provided a clear, colourless oil (605 mg, 89%).
IR (film): 1652 (w), 1602 (w) cm–1.
1H NMR: d = 7.4–7.1 (5 H, m), 6.527 (1 H, dddd, J = 16.9, 10.9,
9.9, 1.0 Hz), 6.018 (1 H, t, J = 11.0 Hz), 5.441 (1 H, q, J = 8.5 Hz),
5.177 (1 H, dd, J = 16.9, 1.7 Hz), 5.070 (1 H, d, J = 9.9 Hz), 5.006
(1 H, m), 4.928 (1 H, br q, J = 2.2 Hz), 2.786 (1 H, td, J = 10.5, 6.5
Hz), 2.69–2.52 (2 H, m), 2.50–2.33 (3 H, m), 2.081 (1 H, dddd,
J = 12.4, 7.6, 6.7, 2.3 Hz), 1.769 (1 H, dtd, J = 12.4, 10.9, 8.4 Hz).
13C NMR: d = 154.79 (0), 144.54 (0), 132.68 (1), 130.40 (1), 130.37
(1), 128.54 (1), 127.82 (1), 126.40 (1), 117.14 (2), 105.77 (2), 51.35
(1), 51.15 (1), 33.92 (2), 33.11 (2), 29.71 (2).
IR (film): 1676 (w), 1648 (m) cm–1
1H NMR: d = 7.4–7.2 (5 H, m), 5.867 (1 H, tt, J = 7.4, 2.2 Hz),
5.264 (1 H, t, J = 2.2 Hz), 4.796 (1 H, s), 3.694 (2 H, s), 3.337 (2 H,
d, J = 2.2 Hz), 3.316 (2 H, t, J = 2.2 Hz), 2.015 (2 H, q, J = 7.6 Hz),
1.434 (2 H, app. sextet, J = 7.4 Hz), 0.925 (3H, t, J = 7.4 Hz).
13C NMR: d = 145.27 (0), 138.80 (0), 136.44 (0), 129.03 (1), 128.46
(1), 127.24 (1), 120.70 (1), 100.70 (2), 60.91 (2), 60.28 (2), 57.10
(2), 31.84 (2), 22.64 (2), 14.07 (3).
LRMS (APCI): m/z (%) = 224 (M+, 6), 142 (100).
HRMS: m/z calcd for C17H20 (M+): 224.1565; found: 224.1552.
LRMS (ES+): m/z = 228 (M + H+).
HRMS: m/z calcd for C16H21N (M+): 227.1674; found: 227.1675.
1-Benzyl-3-methylene-4-[(2Z)-2,4-pentadienyl)pyrrolidine
(28a)
Prepared from 20a (1.5 mmol) by cocyclisation (Method A) and
subsequent insertion of the carbenoid produced by treatment of (Z)-
1,4-dichloro-2-butene with 2 equiv of LiTMP. Purification by col-
Synthesis 2005, No. 12, 2061–2074 © Thieme Stuttgart · New York

SPECIAL TOPIC
Zirconocene-Induced Cocyclisation/Elimination Reactions
2073
umn chromatography (silica gel, 10% Et2O in hexanes) provided a
clear, colourless oil (270 mg, 75%).
1-Benzyl-3-methylene-4-(3,3-dimethyl-2-propenyl)pyrrolidine
(28d)
Prepared from diene 20a (1 mmol) by cocyclisation (Method A) and
subsequent insertion of the carbenoid derived from 1-chloro-2-
methyl-1-propene. Purification by column chromatography (silica
gel, 10% Et2O in hexanes) provided a clear, colourless oil (156 mg,
65%).
IR (film): 1663 (m) cm–1.
1H NMR: d = 7.4–7.2 (5 H, m), 6.657 (1 H, dddd, J = 16.6, 11.2,
9.9, 1.0 Hz), 6.059 (1 H, t, J = 11.0 Hz), 5.470 (1 H, dt, J = 10.4, 7.7
Hz), 5.209 (1 H, d, J = 16.8 Hz), 5.120 (1 H, d, J = 10.1 Hz), 4.946
(1 H, q, J = 2.2 Hz), 4.910 (1 H, q, J = 2.2 Hz), 3.682 (1 H, d,
J = 12.9 Hz), 3.583 (1 H, d, J = 12.9 Hz), 3.369 (1 H, d, J = 13.4
Hz), 3.117 (1 H, d, J = 13.4 Hz), 2.925 (1 H, t, J = 7.9 Hz), 2.754 (1
H, m), 2.55–2.3 (2 H, m), 2.276 (1 H, t, J = 8.1 Hz).
13C NMR: d = 152.01 (0), 138.96 (0), 132.34 (1), 130.52 (2C, 1),
128.86 (1), 128.38 (1), 127.11 (1), 117.46 (2), 104.94 (2), 60.65 (2),
59.81 (2C, 2), 42.93 (1), 31.80 (2).
IR (film): 1665 (m) cm–1.
1H NMR: d = 7.4–7.2 (5 H, m), 5.144 (1 H, t + fs, J = 7.2 Hz), 4.920
(1 H, q, J = 2.2 Hz), 4.890 (1 H, q, J = 2.2 Hz), 3.673 (1 H, d,
J = 13.2 Hz), 3.575 (1 H, d, J = 13.2 Hz), 3.361 (1 H, d + fs, J = 13.6
Hz), 3.090 (1 H, dq, J = 13.6, 2.3 Hz), 2.922 (1 H, dd, J = 8.8, 7.0
Hz), 2.78 (1 H, m), 2.298 (1 H, dt, J = 14.5, 7.0 Hz), 2.223 (1 H, dd,
J = 8.8, 7.4 Hz), 2.125 (1 H, dt, J = 14.5, 8.1), 1.707 (3 H, d, J = 1.1
Hz), 1.624 (3 H, s).
LRMS (ES+): m/z = 240 (M + H+).
13C NMR: d = 152.66 (0), 139.18 (0), 132.71 (0), 128.92 (1), 128.38
(1), 127.08 (1), 122.81 (1), 104.51 (2), 60.82 (2), 60.15 (2), 60.01
(2), 43.34 (1), 32.32 (2), 25.95 (3), 18.05 (3).
LRMS (ES+): m/z = 242 (M + H+).
HRMS: m/z calcd for C17H23N (M+): 241.1831; found: 241.1827.
Anal. Calcd for C17H21N: C, 85.30; H, 8.84; N, 5.85. Found: C,
84.94; H, 8.94; N, 5.90.
1-Benzyl-3-methylene-4-[(2Z,4E)-2,4-nonadienyl)pyrrolidine
(28b)
Prepared by cocyclisation (Method A) of 20a (0.8 mmol), and sub-
sequent insertion of the carbenoid derived from (E,E)-1-chloro-1,3-
octadiene. Purification by column chromatography (silica gel, 10%
Et2O in hexanes) provided a clear, colourless oil (145 mg, 62%).
Acknowledgment
IR (film): 1671 (w) cm–1.
We thank the EPSRC for funding this work.
1H NMR: d = 7.4–7.2 (5 H, m), 6.331 (1 H, dd, J = 14.9, 11.0 Hz),
6.011 (1 H, t, J = 11.0 Hz), 5.698 (1 H, dt, J = 14.9, 7.4 Hz), 5.318
(1 H, dt, J = 11.0, 7.4 Hz), 4.940 (1 H, q, J = 2.2 Hz), 4.912 (1 H, q,
J = 2.2 Hz), 3.662 (1 H, d, J = 12.9 Hz), 3.584 (1 H, d, J = 12.9 Hz),
3.361 (1 H, d, J = 13.6 Hz), 3.094 (1 H, dq, J = 13.2, 2.2 Hz), 2.932
(1 H, dd, J = 8.8, 7.4 Hz), 2.75 (1 H, m), 2.468 (1 H, dt, J = 14.3,
6.0 Hz), 2.334 (1 H, dt, J = 14.3, 8.8 Hz), 2.264 (1 H, t, J = 8.1 Hz),
2.129 (2 H, q, J = 6.6 Hz), 1.5–1.3 (4 H, m), 0.926 (3 H, t, J = 7.0
Hz).
13C NMR: d = 152.12 (0), 138.94 (0), 135.33 (1), 129.89 (1), 128.74
(1), 128.23 (1), 127.39 (1), 126.94 (1), 125.53 (1), 104.65 (2), 60.61
(2), 59.84 (2), 59.74 (2), 42.92 (1), 32.60 (2), 31.60 (2), 31.54 (2),
22.30 (2), 13.98 (3).
References
(1) (a) Negishi, E. Zirconium-Promoted Bicyclization of
Enynes, In Comprehensive Organic Synthesis, Vol. 5; Trost,
B. M.; Fleming, I., Eds.; Pergamon: Oxford, 1991, 1163.
(b) Broene, R. D. Transition Metal Alkyl Complexes:
Reductive Dimerization of Alkenes and Alkynes, In
Comprehensive Organometallic Chemistry II: A Review of
the Literature 1982–1994, Vol. 12; Abel, E. W.; Stone, F. G.
A.; Wilkinson, G., Eds.; Pergamon: Oxford, 1995, 323–348.
(2) (a) Millward, D. B.; Waymouth, R. M. Organometallics
1997, 16, 1153. (b) Kotora, M.; Gao, G.; Li, Z.; Xi, Z.;
Takahashi, T. Tetrahedron Lett. 2000, 41, 7905.
(3) Takahashi, T.; Kondakov, D. Y.; Xi, Z.; Suzuki, N. J. Am.
Chem. Soc. 1995, 117, 5871.
LRMS (ES+): m/z = 296.
HRMS: m/z calcd for C21H29N (M+): 295.2300; found: 295.2287.
(4) Barluenga, J.; Alvarez-Rodrigo, L.; Rodriguez, F.; Fananas,
F. J. Angew. Chem. Int. Ed. 2004, 43, 3932.
(5) Barluenga, J.; Rodriguez, F.; Alvarez-Rodrigo, L.; Zapico, J.
M.; Fananas, F. J. Chem. Eur. J. 2004, 10, 109.
(6) Chinkov, N.; Chechik, H.; Majumdar, S.; Liard, A.; Marek,
I. Synthesis 2002, 2473.
(7) Nakajima, R.; Urabe, H.; Sato, F. Chem. Lett. 2002, 4.
(8) (a) Takahashi, T.; Kondakov, D. Y.; Suzuki, N.
Organometallics 1994, 13, 3411. (b) Campbell, A. D.;
Raynham, T. M.; Taylor, R. J. K. J. Chem. Soc., Perkin
Trans. 1 2000, 3194.
(9) Kocienski, P. J.; Pritchard, M.; Wadman, S. N.; Whitby, R.
J.; Yeates, C. L. J. Chem. Soc., Perkin Trans. 1 1992, 3419.
(10) Negishi, E.; Cederbaum, F. E.; Takahashi, T. Tetrahedron
Lett. 1986, 27, 2829.
(11) Negishi, E.; Holmes, S. J.; Tour, J. M.; Miller, J. A.;
Cederbaum, F. E.; Swanson, D. R.; Takahashi, T. J. Am.
Chem. Soc. 1989, 111, 3336.
(12) Maye, J. P.; Negishi, E. Tetrahedron Lett. 1993, 34, 3359.
(13) Wuvkulich, P. M.; Uskovic, M. R. J. Org. Chem. 1982, 47,
1600.
1-Benzyl-3-methylene-4-[(2Z)-undeca-2-en-4-ynyl)pyrrolidine
(28c)
Prepared from 20a (0.8 mmol) by cocyclisation (Method A) and
subsequent insertion of the carbenoid prepared from (E)-1-chloro-
dec-1-en-3-yne. Column chromatography (silica gel, 10% Et2O in
hexanes) provided a clear, colourless oil (102 mg, 40%).
IR (film): 2210 (w), 1665 (w) cm–1.
1H NMR: d = 7.4–7.2 (5 H, m), 5.850 (1 H, dt, J = 10.3, 7.4 Hz),
5.510 (1 H, d + fs, J = 11.0 Hz), 4.949 (1 H, q, J = 2.2 Hz), 4.917 (1
H, q, J = 2.2 Hz), 3.668 (1 H, d, J = 12.5 Hz), 3.587 (1 H, d, J = 12.5
Hz), 3.395 (1 H, d, J = 13.2 Hz), 3.053 (1 H, dq, J = 13.2, 2.2 Hz),
2.976 (1 H, dd, J = 8.8, 7.4 Hz), 2.85–2.4 (3 H, m), 2.362 (2 H, td,
J = 7.0, 2.2 Hz), 2.272 (1 H, t, J = 8.5 Hz), 1.6–1.25 (8 H, m), 0.915
(3 H, t, J = 7.0 Hz).
13C NMR: d = 151.96 (0), 140.05 (1), 139.11 (0), 128.89 (1), 128.40
(1), 127.11 (1), 110.87 (1), 104.87 (2), 95.22 (0), 77.46 (0), 60.77
(2), 60.02 (2), 59.83 (2), 42.53 (1), 33.74 (2), 31.54 (2), 29.00 (2),
28.75 (2), 22.76 (2), 19.71 (2), 14.26 (3).
LRMS (ES+): m/z = 322 (M + H+).
HRMS: m/z calcd for C23H31N (M+): 321.2457; found: 321.2449.
(14) Molecular modeling studies were performed with Spartan 04
(Wavefunction inc.). Conformational searches were carried
out using molecular mechanics (MMFF94 force field
extended to include transition metals, and cyclopentadiene
Synthesis 2005, No. 12, 2061–2074 © Thieme Stuttgart · New York

2074
D. R. Owen, R. J. Whitby
SPECIAL TOPIC
(29) Takahashi, T.; Kotora, M.; Fischer, R.; Nishihara, Y.;
Nakajima, K. J. Am. Chem. Soc. 1995, 117, 11039.
(30) Kemp, M. I.; Whitby, R. J.; Coote, S. J. Synthesis 1998, 557.
(31) (a) Gordon, G. J.; Luker, T.; Tuckett, M. W.; Whitby, R. J.
Tetrahedron 2000, 56, 2113. (b) Dixon, S.; Fillery, S. M.;
Kasatkin, A.; Norton, D.; Thomas, E.; Whitby, R. J.
Tetrahedron 2004, 60, 1401.
ligands). Final minimizations of likely global minima were
carried out using the hybrid DFT/HF B3LYP method using
the 6-31G* basis set, and core electron approximation for
zirconium.43
(15) The only example of a 1,6-diene cocyclisation on
zirconocene with control from a substituent adjacent to the
ring junction was reported by Taber and gives exclusive 1,2-
trans control: (a) Taber, D. F.; Louey, J. P. Tetrahedron
1995, 51, 4495. There are many examples of trans 1,2-
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