A Stille cyclisation approach to (-)-periplanone-B: Studies in alkene-selective ring-closing metathesis and an improved chromium(II)-mediated synthesis of (E)-alkenylstannanes from aldehydes

Article abstract of DOI:10.1039/a905560f

A synthesis of the dienone 7 via an efficient intramolecular Stille cross-coupling reaction, an improved chromium(II)-mediated synthesis of (E)-alkenylstannanes from aldehydes using Bu₃SnCHI₂ in DMF, and a synthesis of the substituted (-)-dienone 25 via ring-closing alkene metathesis to give dihydropyran 22 are described. The synthesis of (-)-dienone 25 constitutes a formal synthesis of (-)-periplanone-B. The Royal Society of Chemistry 1999.

Full text of DOI:10.1039/a905560f

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A Stille cyclisation approach to (؊)-periplanone-B: studies
in alkene-selective ring-closing metathesis and an improved
chromium(II)-mediated synthesis of (E)-alkenylstannanes from
aldehydes
ab
a
b
c
David M. Hodgson,* † Anne M. Foley, Lee T. Boulton, Peter J. Lovell and
Graham N. Maw
d
a
Dyson Perrins Laboratory, Department of Chemistry, University of Oxford,
South Parks Road, Oxford, UK OX1 3QY
Department of Chemistry, University of Reading, Whiteknights, Reading, UK RG6 2AD
SmithKline Beecham Pharmaceuticals, New Frontiers Science Park, Third Avenue, Harlow,
b
c
Essex, UK CM19 5AW
Pfizer Central Research, Ramsgate Road, Sandwich, Kent, UK CT13 9NJ
d
Received (in Cambridge, UK) 9th July 1999, Accepted 26th August 1999
A synthesis of the dienone 7 via an efficient intramolecular Stille cross-coupling reaction, an improved chromium()-
mediated synthesis of (E)-alkenylstannanes from aldehydes using Bu SnCHI in DMF, and a synthesis of the
3
2
substituted (Ϫ)-dienone 25 via ring-closing alkene metathesis to give dihydropyran 22 are described. The synthesis
of (Ϫ)-dienone 25 constitutes a formal synthesis of (Ϫ)-periplanone-B.
Introduction
sequent aim of applying the methodology in a natural product
synthesis by preparing the substituted (Ϫ)-dienone 1 (R = Pr ).
i
5
Intramolecular Pd-catalysed cross-coupling between alkenyl-
stannane and alkenyl halide (or triflate) functionality is now
firmly established as important methodology for the construc-
An elegant related free-radical based cyclisation approach to
the germacranes has been described by Parsons and co-
6
i
workers. The substituted dienone 1 (R = Pr ), as the racemate,
has been used by Schreiber and co-workers in syntheses of
the potent sex attractant pheromone of the American cock-
1
tion of unsaturated heterocycles and carbocycles. However,
there are only a limited number of efficient ways of introducing
both stannane and halide (or triflate) groups into the same sub-
strate. Structural and functional group constraints are particu-
larly apparent for all-carbon backbone cases. We considered
that our recently developed chromium()-based chemistry for
7
8
roach (±)-periplanone-B (first prepared by Still) and (±)-
9
germacrene-D. Schreiber constructed the dienone
1 via
anionic oxy-Cope rearrangement of a 1,2-divinylcyclohexanol.
Mori and co-workers have prepared natural (Ϫ)-periplanone-B
2
preparing (E)-alkenylstannanes from aldehydes could poten-
i
10
from substituted (Ϫ)-dienone 1 (R = Pr ). In this latter
synthesis, (ϩ)-limonene was elaborated via ozonolytic ring
cleavage to an acyclic substituted α-phenylthioacrylate which
underwent intramolecular alkylation to provide the ten-
membered carbocycle.
tially provide, in certain cases, an attractive solution to the
above problem. This process is highly chemoselective, comple-
menting the Stille reaction, and any pre-existing alkenyl halide
(
or triflate) functionality should be unaffected by CrCl , in the
2
3
absence of Ni or Pd salts. To illustrate this approach we
initially decided to examine a medium ring cyclisation strategy
4
for generating the dienone 1 (Scheme 1, R = H), with the sub-
Results and discussion
To examine the viability of our strategy in the unsubstituted
i
(
nor-Pr ) system, the ketoaldehyde 5 was prepared according to
11
Scheme 2. Thus, 2,5-diiodopent-1-ene 3 was conveniently
Scheme 1
Scheme 2 Reagents and conditions: i, NaI, butan-2-one, reflux, 15 h;
†
Address for correspondence: Dyson Perrins Laboratory, Department
ii, TMSCl, NaI, H O, MeCN, 25 ЊC, 1 h; iii, dihydropyran (4.6 equiv.),
2
t
of Chemistry, University of Oxford, South Parks Road, Oxford, UK
OX1 3QY.
Bu Li (4.5 equiv.), THF, Ϫ78 ЊC to 0 ЊC, then added to 3, THF, 0 ЊC,
0.5 h; iv, 1 M HCl, THF, 25 ЊC, 1 h; v, PCC, SiO , CH Cl , 25 ЊC, 1 h.
2
2
2
J. Chem. Soc., Perkin Trans. 1, 1999, 2911–2922
This journal is © The Royal Society of Chemistry 1999
2911

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prepared from commercially available 5-chloropent-1-yne 2
12
via chlorine–iodine exchange (77%) followed by addition of
13
HI (85%). It was important to limit the reaction time with
HI to 1 h in order to minimize acid-catalysed isomerisation of
2
,5-diiodopent-1-ene 3 to 2,5-diiodopent-2-ene. Addition of
14
lithiated dihydropyran to 2,5-diiodopent-1-ene 3 gave the
substituted dihydropyran 4 (46%). The modest yield for the
alkylation in this case stems from the basicity of lithiated
dihydropyran which resulted in competing formation of the
corresponding coupled material containing a triple bond
instead of the alkenyl iodide unit present in 4. Variation in
either the quantity of lithiated dihydropyran used, the order of
addition, the use of additives (HMPA or TMEDA) or reduced
temperatures did not result in improved yields for this step. The
substituted dihydropyran 4 was subjected to hydrolysis and
Scheme 4
(
Ϫ)-periplanone-B. We considered that an attractive alternative
would be to examine Grubbs’ ring-closing metathesis (RCM)
methodology for the synthesis of substituted dihydropyrans.
RCM involving an enol ether to generate dihydropyrans
i
usually requires PhCMe CH᎐Mo᎐N(2,6-Pr C H )[OCMe-
2
2
6
3
21
(
CF ) ] (Mo-F ) as the metathesis catalyst. Our strategy
would require selective RCM in the presence of an alkenyl
halide moiety (10→9).
Initial metathesis in a multiply unsaturated substrate usually
occurs at the less substituted alkene, suggesting that inter-
3 2 2 6
15
then immediate oxidation using PCC in the presence of SiO2
to give ketoaldehyde 5 (58%). PDC and Swern oxidations were
also examined, but were found to give considerably lower yields
of ketoaldehyde 5.
21
molecular alkylidene exchange should occur first at the ter-
minal (monoalkyl-substituted) alkene in 10, followed by RCM
onto the proximal enol ether. Tolerance of alkenyl halide func-
tionality during metathesis was unknown at the start of our
work. During the course of our studies Kirkland and Grubbs
reported that attempted RCM of a 2-bromohepta-1,6-diene
using Mo-F or (PCy ) Cl Ru᎐CHPh gave no cyclic product,
Chemoselective conversion of ketoaldehyde 5 to stannane 6
Scheme 3) proceeded smoothly (60%) using our original condi-
(
6
3
2
2
only starting diene and alkylidene decomposition products
22
were detected. Also, Nicolaou and co-workers recently demon-
strated that a 2,2-dialkyl-1-iodoalkene survived RCM using
23
(
PCy ) Cl Ru᎐CHPh. We first investigated RCM selectivity
3 2 2
Scheme 3 Reagents and conditions: i, Bu SnCHBr , LiI, CrCl , THF,
3
2
2
with trienes 14 (Scheme 5).
DMF, 40 h; ii, cat. Pd dba , AsPh , NMP, 70 ЊC, 12 h.
2
3
3
2
tions, although simple methylenation of the aldehyde (20%)
and the stannane with the ketone methylenated (9%) were also
observed (see Experimental section). Although we had previ-
ously found that bromostannane 6 (I = Br) was not a viable
16
precursor to the dienone 7, we were pleased to observe that
1,17
cyclisation of stannane 6 under Pd catalysis
reproducibly
gave the dienone 7 in excellent yields which ranged from
8
0
2% for 0.04 M 6 in N-methylpyrrolidone (NMP) to 96% at
.009 M.
The efficiency of the intramolecular Stille reaction may be
partly due to the presence of the ketone and diene groups,
which result in no serious transannular non-bonded inter-
actions arising during formation of the ten-membered ring.
This is evident from a conformational analysis of the dienone 7
Scheme 5 Reagents and conditions: i, B-I-9-BBN, hexane–CH Cl ,
2
2
0
ЊC, 18 h, then AcOH, 1 h; ii, pentenyl- or hexenylMgBr, Et O–
18
2
using molecular models, and a crystal structure and NOE
benzene, 25 ЊC, 22 h, then 2 M HCl; iii, CH Br , Zn, cat. PbCl . TiCl ,
2
2
2
4
19
i
studies of 1 (R = Pr ). In addition, models indicate that the Pd
centre in the intermediate resulting from initial oxidative addi-
tion of Pd(0) into the C–I bond of the stannane 6 may be able to
THF, 25 ЊC, 18 h; iv, Mo-F (12 mol%), pentane, 25 ЊC, 5 h.
6
Trienes 14 were prepared in three steps from commercially
17
24
form a π-complex with the ketone and then also with the
stannyl-substituted alkene thus creating a favourable arrange-
ment from which transmetallation could occur (Fig. 1).
available hex-5-ynenitrile 11 via iodoboration (74%), reaction
of the resultant alkenyl iodide 12 with either pent-4-enyl- or
hex-5-enylmagnesium bromide (61% and 58%, respectively) and
finally methylenation of the resulting ketones 13 under condi-
25
tions described by Takai and co-workers (88% and 92%).
Reaction of triene 14b with (PCy ) Cl Ru᎐CHPh under pre-
3
2
2
᎐
22
ferred conditions for RCM resulted only in dimerisation [44%
E:Z = 73:27), 61% based on recovered triene 14b, see Experi-
(
mental section] arising from metathesis at the terminal (mono-
Fig. 1
alkyl-substituted) alkene. Very recently, Grubbs has reported an
imidazolinylidene-Ru catalyst which may be more effective.
26
The above results encouraged us to pursue an enantio-
However, using commercially available Mo-F we were pleased
6
selective formal synthesis of natural (Ϫ)-periplanone-B by
to observe smooth RCM of trienes 14 to give cycloalkenes 15
(83%). Following the recent demonstration by Grigg and co-
workers of RCM–intramolecular Heck reactions using aryl
halides, our results suggest that tandem RCM–intramolecular
Heck reactions using tethered alkenyl halide functionality may
also be possible.
i
preparing the substituted (Ϫ)-dienone 1 (R = Pr ). A strategy
i
analogous to that carried out in the nor-Pr series would
27
require an asymmetric synthesis of substituted lithiated
i
dihydropyran 8 (R = Pr , Scheme 4). Although this appeared
20
feasible, the number of steps for its preparation together with
the problems anticipated on the basis of our above study in its
In order to examine the synthesis of the substituted
i
i
alkylation with 2,5-diiodopent-1-ene 3 to give 9 (R = Pr ) com-
(Ϫ)-dienone 1 (R = Pr ) using the RCM step outlined in Scheme
bined to make this a potentially unattractive strategy towards
4, the alcohol 18 was first prepared as a single enantiomer (by
2
912
J. Chem. Soc., Perkin Trans. 1, 1999, 2911–2922

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28
Mosher’s ester analysis) starting with allylation of the known
29
N-isovaleryloxazolidinone 16, which gave a single alkene
diastereomer 17 (88%) (Scheme 6).
Scheme 7 Reagents and conditions: i, Bu SnCHI , CrCl , DMF, 25 ЊC,
3
2
2
3
h.
in THF or THF with DMF as an additive were less effective.
Bu SnCHI was prepared in quantitative yield from Bu Sn-
3
2
3
2
CHBr2 using NaI in acetone and was used directly without
further purification and within one week of its preparation.
3
4
It is important to minimize exposure of this reagent to light.
2
Compared with our previous results, the use of Bu SnCHI
3
2
in DMF also resulted in shorter reaction times and gave signifi-
cantly improved yields of (E)-alkenylstannanes for cyclo-
hexanecarbaldehyde (80% vs. 62%) and methyl 6-oxohexanoate
(
82% vs. 61%). However, the yield of stannnane from hex-5-
ynal (59%) was essentially unchanged compared with that
2
reported under the original conditions (60%); the lack of
improvement in yield in this case may suggest competing
chromium()-mediated reduction of the triple bond in DMF
(
CrCl2 3 is a stronger reducing agent in DMF compared to
THF). We had also found that hex-5-ynal gave a noticeably
lower yield (38%) than most other aldehydes examined (64–94%
yields) in our chromium()-mediated synthesis of 1,1-bis-
35
(
trimethylsilyl)alkenes in DMF. Although aliphatic aldehydes
gave only (E)-alkenylstannanes under the modified conditions,
the erosion in stereoselectivity seen with benzaldehyde on mov-
ing from THF to DMF (E:Z = 76:24, with CrCl –Bu SnCHI
Scheme 6 Reagents and conditions: i, LDA, allyl iodide, THF, Ϫ78 ЊC
to 25 ЊC, 3 h; ii, H O , LiOH, THF, H O, 0 ЊC to 25 ЊC, 5 h, then
2
3
2
2
2
2
in DMF) was also paralleled with 3-methylbut-2-enal. Whilst
,2-addition is observed with α,β-unsaturated aldehydes in
Na SO ; then LiAlH , Et O, 0 ЊC, 2 h; iii, hex-5-ynoic acid, DCC, cat.
2
3
4
2
1
DMAP, CH Cl , 25 ЊC, 4 h: iv, B-I-9-BBN, pentane, Ϫ25 ЊC, 2 h, then
2
2
chromium()-mediated olefinations, the stereoselectivity for the
E-isomer is usually slightly lower than that seen with aliphatic
AcOH, 1 h; v, CH Br , Zn, cat. PbCl , TiCl , TMEDA, THF, 25 ЊC, 3.5
2
2
2
4
h; vi, Mo-F (12 mol%), pentane, 25 ЊC, 5 h; vii, 2 M HCl, THF, 25 ЊC,
6
3,36,37
2
h, then PCC, SiO , CH Cl , 25 ЊC, 3 h; viii, see text.
(and aromatic) aldehydes.
We reported 3-methylbut-2-enal
2
2
2
gave 1-(tributylstannyl)-3-methylpenta-1,3-diene (58%) as a
Alkene 17 was converted to the alcohol 18 by reaction with
mixture of geometrical isomers (E:Z = 83:17) under the
original conditions; using the modified conditions 77% yield
30
2
LiOOH–Na SO3 to give the intermediate crude acid (96%)
2
[
with concomitant recovery (88%) of the chiral auxiliary]
of stannyldiene was obtained (E:Z = 58:42). Under the new
conditions improved aldehyde selectivity was also apparent, as
cyclododecanone was recovered unchanged after 5 h (96%),
whereas we had previously found that it was partially methyl-
followed by reduction with LiAlH (50%). Esterification of
the alcohol 18 with commercially available hex-5-ynoic acid to
give alkyne 19 (89%), was followed by chemoselective iodo-
boration to give on protonolysis, the alkenyl iodide 20 (90%).
Ester methylenation of iodide 20 gave the desired substrate
for RCM, triene 21 (58%). Pleasingly, RCM of triene 21 (0.06
M in pentane) using Mo-F gave the desired dihydropyran 22
4
24
enated (45%, 73% based on recovered ketone) using Bu Sn-
3
25
2
CHBr in THF with LiI and DMF as additives.
2
Our present results together with our earlier studies indicate
2
that revision is necessary of our suggestion regarding the
6
(
44%). Due to its sensitive nature, the crude dihydropyran 22
origin of the methylenated material observed in THF with
DMF as an additive. Chromium()-mediated olefinations using
gem-dihalides are generally accepted as proceeding via gem-
was best converted directly into the aldehyde 23 (55% from
triene 21). Homologation of the aldehyde 23 using our original
stannylation conditions gave the stannane 24 (59%); terminal
2
3
dichromium species. The present observations in preparing
(
monoalkyl-substituted) alkene signals could also be clearly
stannanes together with our earlier studies are consistent with
the methylenated material observed (in THF with DMF as
an additive) as arising from competitive formation of CH2-
(CrHal ) [along with the desired Bu SnCH(CrHal ) ] during
1
observed in the crude H NMR spectrum and were assigned to
simple methylenation of the aldehyde (ca. 30%), as in the
nor-Pr system.
i
2
2
3
2 2
Although our original method for preparing (E)-alkenyl-
chromium()-mediated reduction of Bu SnCHHal . CH2-
3 2
stannanes in one step from aldehydes using Bu SnCHBr in
(CrHal ) would be anticipated to be a selective reagent for
2 2
3
2
2
THF with LiI and DMF as additives has found utility in other
aldehydes, but also able to react with ketones. For example,
reaction of dodecanal with CH I using CrCl in THF with
31
syntheses, it suffers from cogeneration of simple aldehyde
methylenated product, as observed with aldehydes 5 and 23
2
2
2
37
DMF as an additive is known to give tridec-1-ene (73%),
2
above. As stated previously, our initial studies with benzalde-
and we find that cyclododecanone is similarly methylenated
(59%, 85% based on recovered ketone). Although related
chromium()-mediated alkylidenations of cyclododecanone
hyde originally led to the adoption of CrCl –Bu SnCHBr in
2
3
2
THF with LiI and DMF as additives as the preferred method
for aldehyde homologation, since this led exclusively to the
37
have also been observed, reaction with Me SiCHBr under
3
2
(
E)-alkenylstannane, whereas CrCl –Bu SnCHBr in DMF was
conditions (CrCl , THF) which produce (E)-alkenylsilanes
2
3
2
2
1
less stereoselective (E:Z = 87:13, by H NMR); however,
styrene was only observed as a by-product in the former
reaction. On further investigation we found that reaction of
nonanal (as a representative aliphatic aldehyde) with CrCl2–
Bu SnCHBr in DMF (25 ЊC, 2.5 h) gives only (E)-alkenyl-
stannane (78% vs. 60% reported in our original study); addi-
tion of LiI did not lead to an improvement in yield (75%),
however further improvement (85 and 89%, two runs) was
from aldehydes [presumably via Me SiCH(CrHal ) ] is known
3
2 2
38
to result in quantitative recovery of cyclododecanone; the
evidence brought together in the present paper suggests that
Bu SnCH(CrHal ) is similarly aldehyde selective. Partial gen-
3
2 2
eration of CH (CrHal ) from Bu SnCHBr using CrCl would
3
2
2
2
2
3
2
2
32
2
then explain why cyclododecanone is methylenated using
Bu SnCHBr in THF with DMF as an additive to approxi-
3
2
mately the same level as an aldehyde but with no alkenyl-
33
observed using Bu SnCHI in DMF (Scheme 7); Bu SnCHI2
stannane observed; it is possible that some CH (CrHal ) is
3
2
3
2
2 2
J. Chem. Soc., Perkin Trans. 1, 1999, 2911–2922
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also formed from Bu SnCHHal in DMF but has too short a
Under the original stannylation conditions we had previously
3
2
3,37
lifetime in this solvent
to react with a carbonyl compound.
established that (R)-glyceraldehyde acetonide could be con-
2
Consistent with this last suggestion we find that attempted reac-
verted into the corresponding stannane in у95% ee. However,
tion of cyclododecanone with CH I using CrCl in DMF gives
quantitative recovery of the ketone.
Application of the new stannylation conditions to aldehyde
an α-alkyl-substituted aldehyde could potentially show reduced
tolerence. For example, Burke et al. have observed partial epi-
merisation of such centres in chromium()-mediated syntheses
2
2
2
42
2
3 gave the stannane 24 in improved yield (66%, Scheme 8);
of (E)-alkenylsilanes from aldehydes. We first established that
S)-α-methylbutyraldehyde 26 (prepared from the correspond-
(
43
ing commercially available alcohol by Swern oxidation) could
be converted without loss of enantiomeric purity to the corres-
ponding stannane 27 {80%, [α]D ϩ14.7 (c 1.0 in CHCl )} under
24
3
the new stannylation conditions (Scheme 9) {using the original
Scheme 8 Reagents and conditions: i, Bu SnCHI , CrCl , DMF, 25 ЊC,
3
2
2
Scheme 9 Reagents and conditions: i, Bu SnCHI , CrCl , DMF, 25 ЊC,
3
.5 h; ii, cat. Pd dba , AsPh . NMP, 70 ЊC, 6 h.
3
2
2
2
3
3
3
h; ii, MPTA-Cl, cat. Pd dba , P(2-furyl) , THF, 55 ЊC, 3 h.
2 3 3
1
24
no methylenated material was observed in the crude H NMR.
The yield of stannane 24 could be further improved to 74% by
doubling the quantities of reagents used.
stannylation conditions a similar specific rotation, [α]D ϩ14.0
(c 1.0 in CHCl ), was observed but the yield was lower (50%)}.
The enantiomeric purity was determined by Pd-catalysed cross-
3
Intramolecular cross-coupling of stannane 24 under the con-
coupling of the stannane 27 with (S)-Mosher’s acid chloride
and inspection of the H NMR alkenyl regions of the resulting
1
ditions used for the nor-isopropyl substrate gave the substituted
25
10
22
(
Ϫ)-dienone 25 {62%, [α]D Ϫ310 (c 1.22 in hexane), lit., [α]D
enone 28. Racemic stannane 27 gave a 1:1 diastereomeric mix-
ture of enones 28 indicating that during the reactions there was
no preference for the formation (or destruction) of a particular
diastereomer.
As a structurally closer example to aldehyde 23, ketoaldehyde
31 was also examined to see if the ketone group promoted
racemisation (Scheme 10).
Ϫ362 (c 1.22 in hexane)}, which constitutes a formal synthesis
of (Ϫ)-periplanone-B. The apparent optical purity (86%) of
substituted (Ϫ)-dienone 25 led us to attempt to determine its
enantiomeric purity with greater confidence using chiral
chromatography. For this study a sample of aldehyde 23 was
Ϫ3
deliberately partially racemised [AcOH (2 mol dm in H O),
2
25
THF, 25 ЊC, 18 h] and carried through to dienone 25 {[α]D Ϫ236
(
c 1.22 in hexane)}. Accurate determination of the enantio-
meric purity of germacrene-D (by derivatisation to an alcohol)
was recently reported by HPLC analysis using a Daicel Chiral-
39
cel OD column. However, we found that for dienone 25 no
resolution whatsoever could be observed using a variety of
chiral GC and HPLC columns and conditions. Resolution
(
(
close to baseline) was only achieved using a β-cyclodextrin
cyclobond I) HPLC column which gave the ee of the sub-
stituted (Ϫ)-dienone 25 to be 93% (the ee of the partially
racemised material was 71%). Success with the β-cyclodextrin
column may be due to the 6.0–8.0 Å internal diameter of
β-cyclodextrin, which would be a suitable size for complexing
40
the dienone 25.
As the dienone 25 was derived from the alcohol 18 which had
been determined to be enantiomerically pure (by Mosher’s ester
analysis), we considered that slight reduction in enantiomeric
purity of substituted (Ϫ)-dienone 25 compared with alcohol 18
could arise during preparation and/or Cr()-coupling of the
aldehyde 23. Oxidation of primary alcohols bearing an α-stereo-
genic centre with tetrapropylammonium perruthenate (TPAP)
is known to give aldehydes without loss of enantiomeric
Scheme 10 Reagents and conditions: i, O , MeOH, Ϫ65 ЊC, then Me S;
3
2
ii, Bu SnCHI , CrCl , DMF, 3 h; iii, MPTA-Cl, cat. Pd dba , P(2-furyl) ,
3
2
2
2
3
3
THF, 55 ЊC, 3 h.
The starting material for the syntheis of ketoaldehyde 31 was
commercially available (S)-(ϩ)-β-citronellene 29, whose ee was
determined to be 90% following a literature procedure (hydro-
boration to give β-citronellol and chiral GC analysis of the
41
purity. Using 5 mol% TPAP (with NMO, 4 Å powdered
molecular sieves in CH Cl –MeCN, 25 ЊC, 12 h) in the prepar-
44
corresponding trifluoroacetate). Ozonolysis of the known
2
2
45
ation of aldehyde 23, though lower yielding [67% from crude
ketoalkene 30, derived in two steps from citronellene 29, gave
46
(
ca. 50% pure) dihydropyran 22], resulted in a slight rise in
the ketoaldehyde 31 (94%), for which no loss of enantiomeric
purity was observed [using the above cross-coupling method
with racemic and (S)-Mosher’s acid chlorides] on stannyl-
ation (68%). We conclude that α-alkyl-substituted aldehydes
can be used in chromium()-mediated synthesis of (E)-alkenyl-
stannanes without compromising enantiomeric purity (at
25
26
specific rotation {from [α]D ϩ16.7 (c 1.0 in CHCl ) to [α]D ϩ18.2
3
(
c 0.5 in CHCl )}. However, given the uncertainty over drawing
3
conclusions from small changes in low optical rotation values,
we also focused on the possible reduction of enantiomeric
purity in the chromium()-mediated olefination step (23→24).
2
914
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least within the limits of the detection methods used here),
and that slight reduction in enantiomeric purity of substituted
9-Iodo-5-oxodec-9-enal 5
Ϫ3
Aq. HCl (1 mol dm , 15 drops) was added to a stirred solution
(
Ϫ)-dienone 25 compared with alcohol 18 arises during the
3
of dihydropyran 4 (4.849 g, 17.4 mmol) in wet THF (20 cm ).
After stirring for 1 h, NaHCO (0.5 g) and MgSO (2 g) were
added and the reaction mixture was filtered and evaporated
oxidation to aldehyde 23.
3
4
In summary, we have demonstrated the tolerance of
alkenyl halide functionality in RCM, developed a modified
chromium()-mediated method for (E)-alkenylstannylation of
aldehydes (which should be particularly useful with synthetic-
ally valuable aldehydes in complex molecule synthesis) and used
this chemoselectivity in a Stille cyclisation strategy resulting in a
formal synthesis of (Ϫ)-periplanone-B.
under reduced pressure. The residue was dissolved in CH Cl
2
2
3
(
10 cm ) and added slowly dropwise to a stirred slurry of PCC
3
(
7.517 g, 34.9 mmol) and SiO (7.5 g) in CH Cl (15 cm ). After
2
2
2
3
1
h, the reaction mixture was diluted with Et O (50 cm ), fil-
2

tered through a pad of Florisil and evaporated under reduced
pressure. Purification of the residue by column chromatography
(
50% Et O–light petroleum) gave a colourless oil, the ketoalde-
2
Experimental
General details
hyde 5 (3.137 g, 58%); R 0.23 (50% Et O–light petroleum);
f 2
Ϫ1
νmax(neat)/cm 2949s, 2895s, 1710s, 1615m, 1429m, 1409m,
374m, 1198m, 1105m and 898m; δ (300 MHz) 9.75 (1H, s,
1
H
All reactions requiring anhydrous conditions were conducted in
flame-dried apparatus under an atmosphere of argon. Syringes
and needles for the transfer of reagents were dried at 140 ЊC and
allowed to cool in a desiccator over P O before use. Ethers were
CHO), 6.02 (1H, d, J 1, CHH᎐CI), 5.72 (1H, s, CHH᎐CI), 2.46
᎐ ᎐
[4H, t, J 7, (CH ) CO], 2.42 (2H, t, J 7, CH CHO), 2.40 (2H,
2
2
2
t, J 7, ᎐CICH ), 1.90 (2H, quintet, J 7, CH ) and 1.80 (2H,
᎐
2
2
quintet, J 7, CH ); δ (75 MHz) 209.3 [(CH ) CO], 201.7 (CHO),
2
5
2
C
2 2
distilled from sodium benzophenone ketyl; (chlorinated) hydro-
carbons, and amines from CaH . DMF was dried (MgSO ) and
126.1 (CH ᎐), 111.2 (᎐CI), 44.1 (᎐CICH ), 42.8 (CH CO), 41.3
᎐ ᎐ ᎐
2 2 2
(CH CO), 40.5 (CH CO), 22.7 (CH ) and 15.9 (CH ); m/z
2
4
2
2
2
2
then distilled under reduced pressure. Internal reaction temper-
atures are reported unless stated otherwise. Reactions were
monitored by TLC using commercially available glass-backed
(thermospray) 312 (100%), 259 (35), 278 (10), 196 (5) and 167
ϩ
(10) (Found: M ϩ NH , 312.0461. C H INO requires M,
4
10 19
2
312.0461).
plates, pre-coated with either a 0.25 mm layer of SiO contain-
2
ing a fluorescent indicator (Merck), or a 0.2 mm layer of
octadecylsilane bonded silica containing a fluorescent indicator
(E)-11-(Tributylstannyl)-2-iodoundeca-1,10-dien-6-one 6
Dry, deoxygenated DMF (0.78 ml, 10 mmol) was added drop-
(
Whatman). Column chromatography was carried out either
wise to a well-stirred slurry of CrCl (Aldrich, 95% w/w pure;
2
on Kieselgel 60 (40–63 µm), or on Preparative C-18 (55-105
µm, Millipore). Light petroleum refers to the fraction with bp
3
1
.33 g, 10 mmol) in dry, deoxygenated THF (16 cm ) under
Ϫ1
2
Ϫ1
argon at room temperature. After 15 min a mixture of keto-
4
0–60 ЊC. [α] Values are given in 10 deg cm g . IR spectra
D
2
aldehyde 5 (0.294 g, 1.0 mmol) and Bu SnCHBr (926 mg,
2
3
2
were recorded as thin films unless stated otherwise. Peak
intensities are specified as strong (s), medium (m) or weak
3
mmol) in dry, deoxygenated THF (4 cm ) was added dropwise
1
13
to the reaction mixture. The flask was covered with aluminium
(
w). H and C NMR spectra were recorded in CDCl unless
3
Ϫ3
foil to exclude light and then anhydrous LiI (1 mol dm in dry,
stated otherwise with Varian Gemini 200, Bruker AC200,
Bruker WM250, Bruker WH300, JEOL EX400, Bruker
AM500 or Bruker AMX500 spectrometers. Chemical shifts
are reported relative to CHCl [δH 7.26, δ (central line of t)
3
deoxygenated THF; 4 cm , 4 mmol) was added dropwise. After
3
4
0 h at room temperature, water (30 cm ) was added and the
3
mixture was extracted with light petroleum (3 × 20 cm ). The
3
C
3
combined organic layers were washed with water (20 cm ), brine
7
7.0]. Coupling constants (J) are given in Hz. HPLC reten-
3
(
20 cm ), dried (MgSO ), and evaporated under reduced pres-
4
tion times for major (t mj) and minor (t mn) enantiomers
R
R
sure. The residue was purified by reversed-phase flash chrom-
atography (C-18, 5% CH Cl –MeCN). First to elute was a
are given in min.
2
2
colourless oil, the stannane 6 (0.351 g, 60%); R 0.20 (C-18
f
6
-(4-Iodopent-4-en-1-yl)-3,4-dihydro-2H-pyran 4
Ϫ1
reversed-phase, 5% CH Cl –MeCN); νmax(neat)/cm 2956s,
2
2
t
Ϫ3
3
Bu Li (1.7 mol dm in cyclohexane; 100 cm , 170 mmol] was
added dropwise to a well-stirred solution of 3,4-dihydropyran
2925s, 2871s, 2851s, 1716s, 1616m, 1599m, 1415m, 1375m and
1072w; δ (300 MHz) 6.06 (1H, s, CHH᎐CI), 5.93–5.92 (2H, m,
H
᎐
3
(
14.617 g, 174 mmol) in THF (25 cm ) at Ϫ78 ЊC. The reaction
CH᎐CHSn), 5.75 (1H, s, CHH᎐CI), 2.43 [6H, br, (CH ) C᎐O
᎐ ᎐
2 2
mixture was allowed to warm to room temperature for 10 min,
before being recooled to 0 ЊC. This solution was then added
dropwise by cannula to a stirred solution of 2,5-diiodopentene
and ᎐CICH ], 2.18–2.14 (2H, m, CH CH᎐CHSn), 1.82 (2H,
2 2
᎐ ᎐
quintet, J 7, CH ), 1.69 (2H, quintet, J 7, CH ), 1.58–1.42 [6H,
2
2
m, Sn(CH CH ) ], 1.41–1.26 [6H, m, Sn(CH CH CH ) ] and
2
2
3
2
2
2 3
1
1,47
3
3
(12.161 g, 38 mmol) in THF (20 cm ) at 0 ЊC over a period
1.05–0.71 [15H, m, Sn(CH CH CH Me) , incl. at 0.92 (9H, t,
2 2 2 3
3
of 30 min. Saturated aq. NH Cl (5 cm ) was then added cau-
J 7, 3 × Me)]; δ (75 MHz) 210.3 (C᎐O), 148.2 (CH᎐CHSn),
C
᎐ ᎐
4
tiously to the reaction. The solvents were removed by evapor-
128.5 (J119Sn-C 386, J117Sn-C 375, ᎐CHSn), 126.0 (CH ᎐), 111.3
᎐ ᎐
2
ation under reduced pressure and the resulting residue was
(᎐CI), 44.2 (CH ), 41.9 (CH ), 40.5 (CH ), 37.0 (CH ), 29.0
᎐
2 2 2 2
3
extracted with Et O (3 × 100 cm ). The combined organic layers
[JSn-C 19, Sn(CH CH ) ], 27.2 [J
52, Sn(CH CH CH ) ], 22.8
Sn-C 2 2 2 3
2
2
2
3
3
were washed with brine (50 cm ), dried (Na SO ) and evapor-
(CH ), 22.6 (CH ), 13.6 (3 × Me) and 9.4 [J
330, J117Sn-C
2
4
2
2
119Sn-C
ated under reduced pressure. Purification of the residue by
bulb-to-bulb distillation, first at 70 ЊC/0.5 mmHg and then at
316, Sn(CH ) ]; m/z (thermospray) 582 (10%), 350 (10), 323
2 3
ϩ
(40), 307 (45), 291 (100) and 287 (30) (Found: M ϩ H ,
120
1
20 ЊC/0.5 mmHg afforded a colourless oil, the dihydropyran 4
583.1460. C H IO Sn requires M, 583.1459].
23 44
Ϫ1
(
4.849 g, 46%): Rf 0.25 (light petroleum); νmax(neat)/cm
Second to elute was a colourless oil, (E)-10-(tributyl-
stannyl)-2-iodo-6-methyleneundeca-1,10-diene, (0.047 g, 8%); Rf
3
8
310m, 2927s, 2852s, 1717m, 1674s, 1616m, 1086m, 1064s and
Ϫ1
91m; δ (300 MHz) 6.01 (1H, s, CHH᎐CI), 5.70 (1H, s,
0.16 (C-18 reversed-phase, 5% CH Cl –MeCN); νmax(neat)/cm
H
2
2
CHH᎐CI), 4.48 (1H, br t, J 3, CHCO), 3.97 (2H, dd, J 5 and 5,
2955s, 2928s, 2871s, 2853s, 1642m, 1616m, 1598m, 1457m,
᎐
CH O), 2.41 (2H, t, J 7, ᎐CICH ), 2.02–1.98 (4H, m, CH CH O
987m and 891m; δ (250 MHz) 6.02 (1H, d, J 1, CHH᎐CI), 5.95
2
2
2
2
H
and CCH ) and 1.82–1.63 (4H, m, CCH CH and CH CHCO);
(1H, t, J 5, CH᎐CHSn), 5.92 (1H, s, J
78, J117Sn-H 75,
2
2
2
2
᎐
119Sn-H
δ (75 MHz) 153.4 (᎐CO), 125.4 (CH ᎐), 112.8 (᎐CI), 95.8
᎐CHSn), 5.71 (1H, s, CHH᎐CI), 4.75 [2H, d, J 3, (CH ) C᎐
C
2
᎐ ᎐
2 2
(
CH᎐), 66.0 (CH O), 44.5 (CH CI), 32.6 (OCCH ), 26.2 (CH ),
CH ], 2.40 (2H, t, J 7, ᎐CICH ), 2.15 (2H, td, J 7 and 5,
2 2
᎐
2
2
2
2
2
2.4 (CH ) and 20.2 (CH ); m/z (thermospray) 275 (100%), 211
CH CH᎐), 2.03 [4H, t, J 7, (CH ) C᎐CH ], 1.67 (2H, quintet,
J 7, CH ), 1.58–1.46 [8H, m, CH and Sn(CH CH ) ], 1.39–1.26
2 2 2 2 3
2
2
2
2
2
2
ϩ
(
5), 195 (5) 168 (5) and 151 (10) (Found: (M ϩ H , 279.0246.
C H IO requires M, 279.0246).
(6H, m, 3 × CH Me) and 0.93–0.85 [15H, m, Sn(CH CH -
1
0
16
2
2
2
J. Chem. Soc., Perkin Trans. 1, 1999, 2911–2922
2915

View Article Online
CH Me) , incl. at 0.90 (9H, t, J 7, 3 × Me)]; δ (100 MHz) 149.2
J 1, CHH᎐CI), 5.79 (1H, d, J 1.5, CHH᎐CI), 2.54 (2H, t, J 7,
᎐CICH ), 2.35 (2H, t, J 7, CH CN) and 1.87 (2H, quintet, J 7.0,
2
3
C
(
CH᎐CHSn), 148.8 [(CH ) C᎐CH ], 127.5 (J
398, J117Sn-C
᎐
2
2
2
119Sn-C
᎐
2
2
3
79, ᎐CHSn), 125.4 (CH ᎐CI), 112.3 (᎐CI), 109.4 [(CH ) C᎐
CH CH CN); δ (50 MHz) 127.9 (CH ᎐CI), 119.0 (CN), 108.8
᎐
2
᎐
᎐
2
2
᎐
2 2 C 2
᎐
CH ], 44.7 (CH ), 37.4 (CH ), 35.2 (CH ), 34.2 (CH ), 29.6
(CH ᎐CI), 43.3 (᎐CICH ), 24.4 (CH CN) and 15.4 (CH CH -
2 2 2 2 2
ϩ
2
2
2
2
2
(
CH ), 29.0 [J
21, Sn(CH CH ) ], 27.2 (J
53, 3 × CH2-
CH ); m/z (EI) 221 (M , 50%), 127 (15) and 94 (52) (Found:
2
Sn-C
2
2
3
Sn-C
2
ϩ
Me), 26.9 (CH ), 13.7 (3 × Me) and 9.3 [J
342, J117Sn-C 325,
M , 220.9702. C H IN requires M, 220.9702).
2
119-C
6
8
Sn(CH ) ]; m/z (EI) 483 (5%), 348 (20), 323 (60), 308 (70), 291
2
3
ϩ
120
(
100) and 165 (10) (Found: M Ϫ Bu , 523.0844. C H I Sn
20 36
2-Iodoundeca-1,10-dien-6-one 13a
requires M, 523.0884).
3
Alkenyl iodide 12 (1.00 g, 4.5 mmol) in Et O (3 cm ) was added
to a stirred solution of pent-4-enylmagnesium bromide [pre-
2
Fractions collected before elution of compound 6 were com-
bined and evaporated under reduced pressure to give a residue
which was purified by column chromatography (SiO , 15%
Et O–light petroleum) to give a colourless oil, 2-iodoundeca-
1
pared from Mg (0.440 g, 18.1 mmol) and 5-bromopentene (2.70
2
3
g, 18.1 mmol) in Et O (15 cm ), then diluted with C H (14
2
6
6
2
3
Ϫ3
cm )] at room temperature. After 22 h aq. HCl (2.0 mol dm ;
15 cm ) was added and after a further 2 h at room temperature
,10-dien-6-one (0.056 g, 19%); R 0.35 (15% Et O–light petrol-
f 2
Ϫ1
3
eum); νmax(neat)/cm 2929s, 2854m, 1712s, 1638m, 1616m,
433m, 1410m, 1371m, 911m and 897m; δ (250 MHz) 6.02
the organic layer was separated and the aqueous layer was
1
(
H
3
extracted with Et O (6 × 20 cm ). The combined organic layers
2
1H, t, J 1, CHH᎐CI), 5.80–5.73 (1H, m, CH᎐CH ), 5.72 (1H, s,
᎐ ᎐
2
3
were washed with H O (2 × 20 cm ), dried (MgSO ) and evap-
2
4
CHH᎐CI), 5.06 (1H, ddt, J 12, 1 and 1, CH᎐CHH), 4.99–4.96
᎐
᎐
orated under reduced pressure. Purification of the residue by
(
1H, m, CH᎐CHH), 2.42–2.38 [6H, m, (CH ) CO and
᎐
2 2
column chromatography (3% Et O–light petroleum) gave a col-
2
CH ᎐CICH ], 2.06 (2H, dt, J 7 and 7, CH CH᎐CH ), 1.80 (2H,
quintet, J 7, CH ) and 1.69 (2H, quintet, J 7, CH ); δ (75 MHz)
2
CH), 111.3 (᎐CI), 44.1 (᎐CICH ), 41.8 (CH CO), 40.5 (CH -
CO), 33.0 (CH CH᎐), 29.6 (CH ) and 22.8 (CH ); m/z
(
(
2
2
2
2
ourless oil, the ketone 13a (0.800 g, 61%); R 0.40 (10% Et O–
f
2
2
2
C
Ϫ1
light petroleum); νmax(neat)/cm 2932s, 2849w, 1714s, 1641m,
10.2 (C᎐O), 137.8 (CH ᎐CH), 126.1 (CH ᎐CI), 115.2 (CH ᎐
᎐
2
2
2
1
9
618m, 1432m, 1410m, 1372m, 1198w, 1167w, 1111w, 998w and
᎐
᎐
2
2
2
12m; δ (200 MHz) 6.03 (1H, d, J 1, CHH᎐CI), 5.77 (1H, ddt,
H
2
2
2
J 17, 10 and 7, CH᎐CHH), 5.72 (1H, d, J 1, CHH᎐CI), 5.07–
᎐
᎐
thermospray) 310 (100%), 292 (15), 279 (10), 182 (5) and 151
ϩ
4.96 (2H, m, CH᎐CH ), 2.41 (2H, t, J 8, ᎐CICH ), 2.40 [4H,
᎐ ᎐
2 2
10) (Found: M ϩ NH , 310.0668. C H INO requires M,
4
11 21
t, J 7, (CH )C᎐O], 2.06 (2H, q, J 7, CH CH᎐CH ) and 1.86–
2
2
2
3
10.0668).
1
.61 (4H, 2 × quintet, J 7, 2 × CH CH CH ); δ (50 MHz)
2 2 2 C
1
96.1 (C᎐O), 137.9 (CH᎐CH ), 126.1 (CH ᎐CI), 115.2 (CH᎐
᎐
᎐
2
2
(
E)-5-Methylenecyclodec-6-en-1-one 7
CH ), 112.0 (CI᎐CH ), 44.2 (CH CI᎐), 41.9 (CH C᎐O), 40.6
2
2
2
2
Pd dba (Aldrich, 7 mg, 0.01 mmol) was added to a stirred
solution of the stannane 6 (200 mg, 0.34 mmol) and AsPh (70
mg, 0.23 mmol) in degassed NMP (40 cm ) at 25 ЊC under N .
The reaction vessel was then wrapped in aluminium foil to
exclude light, and heated to 70 ЊC. After 12 h the reaction mix-
ture was cooled, diluted with water (50 cm ) and extracted with
Et O (3 × 30 cm ). The combined organic layers were washed
with aq. CuSO (1 mol dm ; 2 × 20 cm ), brine (20 cm ), dried
2
3
(CH C᎐O), 33.0 (CH CH᎐CH ), 22.8 (CH CH CH ) and 22.7
2 2 2 2 2 2
ϩ
3
(CH CH CH ); m/z (CI) 293 (M ϩ H , 5%), 279 (15), 252 (7),
2 2 2
3
2
235 (10), 220 (100), 217 (20), 179 (10), 167 (45), 165 (10), 149
ϩ
(
95), 122 (50), 113 (60) and 109 (10) (Found: M ϩ H ,
2
93.0402. C H OI requires M, 293.0402).
11 18
3
3
2
2
-Iodododeca-1,11-dien-6-one 13b
Ϫ3
3
3
4
Following the procedure for the preparation of ketone 13a, but
using alkenyl iodide 12 (0.988 g, 4.47 mmol) and 6-
bromohexene (2.80 g, 17.2 mmol) gave, after purification by
column chromatography (3% Et O–light petroleum), a colour-
less oil, the ketone 13b (0.792 g, 58%); R 0.50 (10% Et O–light
(
MgSO ) and evaporated under reduced pressure. The crude oil
4
3
48
3
was diluted with 10% Et O–pentane (0.5 cm ). DBN (0.1 cm )
was then added and the resultant mixture was purified by
column chromatography (10% Et O–pentane) to give a colour-
less oil, the dienone 7 (0.054g, 96%); R 0.27 (10% Et O–
pentane); δ (250 MHz) 6.10 (1H, d, J 16, CH᎐CHC), 5.36 (1H,
dt, J 16 and 7, CH᎐CHC), 4.88 (1H, s, CC᎐HH), 4.86 (1H, s,
CC᎐HH) and 2.51–1.95 (12H, m, 6 × CH ); δ (75 MHz) 212.8
2
2
2
f
2
f
2
Ϫ1
petroleum); νmax(neat)/cm
2932s, 2857m, 1714s, 1640m,
H
1
617m, 1431m, 1410m, 1372m, 1202w, 1109w, 993m and 909m;
᎐
᎐
δH(200 MHz) 6.03 (1H, d, J 1, CHH᎐CI), 5.79 (1H, ddt, J 17,
᎐
2
C
1
0 and 7, CH᎐CH ), 5.73 (1H, d, J 1, CHH᎐CI), 5.04–4.93 (2H,
᎐
2
(
(
(
C᎐O), 146.5 (C᎐CH ), 133.9 (CH᎐CH), 132.7 (CH᎐CH), 113.2
᎐
᎐
2
m, CH᎐CH ), 2.40 [6H, t, J 7, ᎐CICH and (CH )C᎐O], 2.06
C᎐CH ), 42.8 (CH CO), 42.2 (CH CO), 33.1 (CH ), 30.4
᎐
2
2
2
᎐
2
2
2
2
1
(
2H, q, J 7, CH CH᎐CH ), 1.79 (2H, quintet, J 7, CH CH -
CH ), 27.5 (CH ) and 23.9 (CH ). UV, IR, H NMR and MS
2
2
2
2
2
2
2
4
9
IC᎐), 1.59 (2H, quintet, J 7, CH CH CH᎐CH ) and 1.38 (2H,
quintet, J 7, CH CH CH CH᎐CH ); δ (50 MHz) 190.4 (C᎐O),
data were consistent with those previously reported.
᎐
2
2
2
2
2
2
2
C
1
38.4 (CH᎐CH ) 126.1 (CH ᎐CI), 114.7 (CH᎐CH ), 111.4
5
-Iodohex-5-enenitrile 12
᎐
2
2
2
(
CI᎐CH ), 44.2 (᎐CICH ), 42.6 (CH C᎐O), 40.5 (CH C᎐O),
᎐
2 2 2 2
3
Hex-5-ynenitrile 11 (2.57 cm , 24.5 mmol) was added dropwise
to a stirred solution of B-I-9-BBN [(Aldrich) 1 mol dm in
hexane; 54 cm , 54 mmol] in CH Cl (100 cm ) at 0 ЊC. The
reaction mixture was then allowed to reach room temperature
over 18 h, then cooled to 0 ЊC and glacial AcOH (30 cm ) added
slowly. After 1 h at 0 ЊC, NaOH (3 mol dm in H O; 150 cm )
and then H O (30% w/w in H O, 45 cm ) were carefully added
and the reaction stirred for 30 min at room temperature. The
organic layer was separated and the remaining aqueous layer
was extracted with light petroleum (6 × 100 cm ). The com-
bined organic extracts were washed successively with H O (50
cm ), saturated aq. NaHCO (40 cm ), saturated aq. Na SO (25
cm ), H O (40 cm ) and brine (25 cm ), dried (MgSO ) and
evaporated under reduced pressure. Purification of the residue
by bulb-to-bulb distillation (75ЊC/1 mmHg) gave a light yellow
oil, the alkenyl iodide 12 (3.99 g, 74%); R 0.56 (10% Et O–light
3
3.5 (CH CH᎐CH ), 28.4 (CH CH CH ), 23.3 (CH CH CH )
2 2 2 2 2 2 2 2
ϩ
Ϫ3
and 22.9 (CH CH CH᎐CH ); m/z (EI) 179 (M Ϫ I , 100%), 123
2
2
2
3
3
ϩ
2
2
(
10), 109 (7), 95 (15), 83 (20) and 67 (50) (Found: M Ϫ I ,
1
79.1436. C H O requires M, 179.1436).
12 19
3
Ϫ3
3
2
2
-Iodo-6-(pent-4-en-1-yl)hepta-1,6-diene 14a
3
2
2
2
3
CH Br (1.1 cm , 16 mmol) was added to a stirred suspension
of zinc dust (1.86 g, 28.4 mmol) and PbCl (0.40 g, 0.14 mmol)
in THF (28 cm ) at room temperature. After 30 min, TiCl (1
mol dm in CH Cl ; 3.2 cm , 3.2 mmol) was added slowly to
the reaction mixture at 0 ЊC and the resulting dark brown solu-
tion was stirred at room temperature. After 30 min a solution of
ketone 13a (0.900 g, 3.1 mmol) in THF (3 cm ) was added
dropwise to the reaction mixture. After 18 h the mixture was
2
2
2
3
3
4
Ϫ3
3
2
2 2
3
3
3
2
3
3
3
3
2
4
3
3
diluted with Et O (25 cm ) and the organic layers was washed
with aq. HCl (2 mol dm ; 15 cm ), then brine (15 cm ), dried
f
2
2
Ϫ1
Ϫ3
3
3
petroleum); vmax(neat)/cm 2936s, 2247s, 1728m, 1618s, 1453m,
1
428m, 1196s, 1185s, 1113s and 901s; δ (200 MHz) 6.16 (1H, d,
(MgSO ) and evaporated under reduced pressure. Purification
H
4
2
916
J. Chem. Soc., Perkin Trans. 1, 1999, 2911–2922

View Article Online
of the residue by column chromatography (light petroleum)
diisopropylphenylimidoneophylidenemolybdenum
bis(hexa-
gave a colourless oil, the triene 14a (0.785 g, 88%); R 0.82 (10%
Et O–light petroleum); νmax(neat)/cm 3076m, 2978m, 2935s,
2
fluoro-tert-butoxide) (Strem, 0.210 g, 0.27 mmol) in dry,
degassed (freeze–pump–thawed) pentane (25 cm ) at room
f
Ϫ1
3
2
8
860m, 1642m, 1618m, 1440m, 1173w, 1108w, 991w, 911m and
temperature under a gentle flow of argon. The reaction flask
was then wrapped in foil to exclude light. After 5 h the reaction
mixture was exposed to air for 15 min and then evaporated
under reduced pressure. Purification of the residue by column
chromatography (light petroleum) gave a colourless oil, the
91s; δ (200 MHz) 6.04 (1H, d, J 1, CHH᎐CI), 5.84 (1H, ddt,
H
J 17, 10 and 7, CH᎐CH ), 5.72 (1H, s, CHH᎐CI), 5.08–4.95
᎐
2
(
2H, m, CH᎐CH ), 4.76 (2H, s, C᎐CH ), 2.39 (2H, t, J 7,
᎐
2
2
᎐
᎐
CICH ), 2.13–2.00 (6H, m, 2 × CH C᎐CH and CH CH᎐
2 2 2 2
CH ), 1.66 (2H, quintet, J 7, CH CH CH ) and 1.54 (2H, quin-
cycloalkene 15a (0.488 g, 83%); R 0.57 (light petroleum);
νmax(neat)/cm 2937s, 2842s, 1618m, 1428m, 1172m, 1105m,
2
2
2
2
f
Ϫ1
tet, J 7, CH CH CH ); δ (50 MHz) 148.7 (C᎐CH ), 138.7
2
2
2
C
2
(
CH᎐CH ), 125.5 (CH ᎐CI), 114.5 (CH᎐CH ), 112.3 (CH ᎐
1040w, 945w, 891s and 816w; δ (200 MHz) 6.03 (1H, d, J 1,
᎐
2
2
2
2
H
CI), 109.6 (C᎐CH ), 44.7 (᎐CICH ), 35.3 (CH C᎐CH ), 34.3
CHH᎐CI), 5.71 (1H, s, CHH᎐CI), 5.36 (1H, t, J 2, CH᎐C),
᎐ ᎐ ᎐
᎐
2
2
2
2
(
2
2
CH C᎐CH ), 33.4 (CH CH᎐CH ), 27.0 (᎐CICH CH ) and
2.50–2.21 (6H, m, 2 × CH C᎐ and ᎐CICH ), 2.08 (2H, t, J 7,
CH C᎐), 1.84–1.74 (2H, m, CH ) and 1.67 (2H, quintet, J 7,
2 2
2
2
2
2
2
2
2
2
ϩ
6.9 (CH CH C᎐CH ); m/z (CI) 308 (M ϩ NH , 5%), 291 (5),
2
2
2
4
18 (100), 173 (12), 163 (25), 149 (20) and 122 (35) (Found:
CH ); δ (50 MHz) 143.8 (CH C᎐CH), 125.4 (CI᎐CH ), 123.9
2 C 2 2
ϩ
M ϩ NH , 308.0875. C H IN requires M, 308.0875).
(᎐CH), 112.5 (CI᎐CH ), 44.9 (᎐CICH ), 35.0 (CH C᎐CH), 32.4
2 2 2
4
12 23
(
CH C᎐CH), 29.5 (CH CH᎐C), 27.1 (CICH CH CH ) and
2 2 2 2 2
2
1
3.4 (CH CH CH ); m/z (EI) 262 (10%), 261 (100), 259 (15),
2 2 2
2
-Iodo-6-(hex-5-en-1-yl)hepta-1,6-diene 14b
75 (15), 151 (25), 149 (25), 134 (15), 133 (65), 122 (30) and 109
Following the procedure for the preparation of triene 14a, but
using ketone 13b (2.93 g, 9.6 mmol) gave after purification by
column chromatography (light petroleum) a colourless oil, the
triene 14b (2.67 g, 92%); R 0.83 (10% Et O–light petroleum);
ϩ
(
55) (Found: M , 262.0219. C H I requires M, 262.0219).
10 16
1
-(4-Iodopent-4-en-1-yl)cyclohex-1-ene 15b
f
2
Ϫ1
Following the procedure for the preparation of cycloalkene 15a,
but using triene 14b (0.100 g, 0.33 mmol) gave, after purification
by column chromatography (light petroleum), a colourless oil,
the cycloalkene 15b (0.075 g, 83%); R 0.65 (light petroleum);
νmax(neat)/cm 2930s, 2856s, 2834s, 1617m, 1447m, 1437m,
νmax(neat)/cm 3076m, 2977m, 2931s, 2857m, 1641m and
618m, 1439w, 1173w, 1107w, 992w, 910m and 891s; δ (200
1
H
MHz) 6.03 (1H, d, J 1, CHH᎐CI), 5.82 (1H, ddt, J 17, 10 and 7,
CH᎐CH ), 5.71 (1H, s, CHH᎐CI), 5.07–4.92 (2H, m, CH᎐CH ),
4
᎐
᎐
2
2
f
Ϫ1
.74 (2H, s, C᎐CH ), 2.39 (2H, t, J 7, ᎐CICH ), 2.12–1.98
᎐
2
2
1
108m, 918w and 891s; δ (200 MHz) 6.02 (1H, d, J 1, CHH᎐
[6H, m, (CH ) C᎐CH and CH CH᎐CH ], 1.66 (2H, quintet,
H
2
2
2
2
2
CI), 5.70 (1H, d, J 1, CHH᎐CI), 5.41 (1H, s, CH᎐C), 2.37 (2H,
t, J 7, ᎐CICH ), 1.94 (6H, t, J 7, 3 × CH C᎐) and 1.72–1.50
J 7, CH CH CH᎐CH ) and 1.58–1.26 (4H, m, 2 × CH CH -
CH ); δ (50 MHz) 148.8 (C᎐CH ), 138.9 (CH᎐CH ), 125.5
᎐
᎐
2
2
2
2
2
᎐
2
2
2
C
2
2
(
6H, m, 3 × CH ); δ (50 MHz) 136.9 (CH C᎐CH), 125.3
(
CH ᎐CI), 114.3 (CH᎐CH ), 112.4 (CH ᎐CI), 109.4 (C᎐CH ),
2
C
2
2
2
2
2
(
CI᎐CH ), 121.5 (CH᎐), 112.7 (CI᎐CH ), 44.8 (᎐CICH ), 36.4
4
4.7 (᎐CICH ), 35.7 (CH C᎐CH ), 34.3 (CH C(᎐CH ), 33.6
᎐
2
2
2
᎐
2
2
2
2
2
(
(
CH C᎐CH), 28.2 (CH C᎐CH), 27.0 (CICH CH CH ), 25.2
2 2 2 2 2
ϩ
(
CH CH᎐CH ), 28.6 (CH CH CH᎐CH ), 27.2 (᎐CICH CH )
2
2
2
2
2
2
2
ϩ
CH CH᎐C), 23.0 (CH ) and 22.5 (CH ); m/z (EI) 149 (M Ϫ I ,
2 2 2
and 27.0 (CH CH CH ); m/z (CI) 305 (M ϩ H , 5%), 233 (15),
2
2
2
7
5%), 121 (5), 108 (35), 93 (57), 81 (100) and 67 (95) (Found:
2
1
32 (100), 177 (25), 173 (30), 149 (20), 124 (35), 122 (100) and
02 (10) (Found: M , 304.0688. C H I requires M, 304.0688).
ϩ
ϩ
M Ϫ I , 149.1330. C H requires M, 149.1330).
11 17
13
21
(
4S)-3-[(2S)-2-(1-Methylethyl)pent-4-enoyl]-4-(phenylmethyl)-
Dimerisation of 2-iodo-6-(hex-5-en-1-yl)hepta-1,6-diene 14b
oxazolidin-2-one 17
3
Triene 14b (0.071 g, 0.23 mmol) in CH Cl (5 cm ) was added to
2
2
n
Ϫ3
3
Bu Li (2.5 mol dm in hexanes; 142.0 cm , 354.8 mmol) was
added dropwise to a stirred solution of diisopropylamine (48.4
cm , 369.0 mmol) in THF (160 cm ) at 0 ЊC. After 15 min, the
solution was cooled to Ϫ78 ЊC and N-isovaleryloxazolidinone
a stirred solution of bis(tricyclohexylphosphine)benzylidene-
ruthenium dichloride (Strem, 0.010 g, 5 mol%) in CH Cl (15
2
2
3
3
3
cm ) at room temperature. After 22 h the reaction mixture was
exposed to air for 5 h and then evaporated under reduced pres-
sure and the residue purified by column chromatography (light
petroleum). First to elute was starting triene 14b (0.020 g).
29
3
1
6
(74.16 g, 283.8 mmol) in THF (100 cm ) was added drop-
3
wise. After 1 h at Ϫ78 ЊC, allyl iodide (39.0 cm , 426 mmol) in
3
THF (36 cm ) was added dropwise, the cooling bath was then
removed and the reaction mixture allowed to reach room
temperature. After 3 h saturated aq. NH Cl (30 cm ) was
added cautiously to the reaction mixture, which was then evap-
orated under reduced pressure. The resulting concentrate was
extracted with Et O (3 × 300 cm ) and the combined organic
layers were washed with H O (30 cm ), brine (30 cm ), dried
Second to elute was a colourless oil, the dimer (0.030 g, 44%,
1
6
1% based on recovered triene 14b) (E:Z = 2.7:1, by H NMR
3
4
analysis of the isomeric ᎐CHs in the δ 5.40–5.37 region); R 0.35
᎐
f
Ϫ1
(
light petroleum); νmax(neat)/cm 2929s, 2855m, 1644s, 1617m,
1
436m, 968m and 890s; m/z (CI) 598 (10%), 597 (15), 596 (30),
3
2
5
95 (60), 579 (25), 451 (60), 173 (70) and 149 (100) (Found:
3
3
ϩ
2
M ϩ NH , 598.1407. C H I N requires M, 598.1407); data
4
24 42 2
(
MgSO ) and evaporated under reduced pressure. Purification
4
for E-isomer: δ (400 MHz) 6.03 (1H, d, J 1, 2 × CHH᎐CI),
H
of the residue by column chromatography (30% Et O–light pet-
roleum) gave a light yellow oil, the alkene 17 (75.07 g, 88%); R
0
2
5
4
.71 (1H, s, 2 × CHH᎐CI), 5.40 (2H, dt, J 4 and 2, CH᎐CH),
᎐ ᎐
f
.75 (2H, d, J 6, C᎐CH ), 2.39 (2H, t, J 7, ᎐CICH ), 2.01 (6H, t,
᎐
2
2
24
.50 (35% Et O–light petroleum); [α] ϩ67.6 (c 1.0 in CHCl );
2 D 3
Ϫ1
J 7, 2 × CH C᎐CH and CH CH᎐CH), 1.65 (2H, quintet, J 8,
2
2
2
νmax(neat)/cm 3029m, 2963s, 1781s, 1695s, 1641w, 1454m,
386s, 1349s, 1291m, 1208s, 1100m, 1051m, 999m, 917m, 747m
and 703s; δ (500 MHz) 7.35–7.23 [5H, m, Ar, incl. at 7.33 (2H,
CH CH CH᎐CH) and 1.49–1.32 (4H, m, 2 × CH CH CH );
2
2
2
2
2
1
δ (125 MHz) 149.0 (C᎐CH ), 130.3 (CH᎐CH), 125.5 (CH ᎐CI),
C
2
2
H
1
12.4 (CH ᎐CI), 109.4 (C᎐CH ), 44.8 (᎐CICH ), 35.8 (CH C᎐
2 2 2 2
t, J 7, 2 × ArH)], 5.88–5.79 (1H, m, CH᎐CH ), 5.10 (1H, dd,
J 17 and 1, CH᎐CHH), 5.03 (1H, d, J 10, CH᎐CHH), 4.72–
4
d, J 9 and 3, NCHCHHO), 3.87 (1H, ddd, J 11, 7 and 4,
NC᎐OCH), 3.32 (1H, dd, J 13 and 3, CHHPh), 2.65 (1H, dd,
J 13 and 10, CHHPh), 2.52–2.38 (2H, m, CH CH᎐CH ), 2.00
᎐
2
CH ), 34.4 (CH C᎐CH ), 32.4 (CH CH᎐CH), 29.4 (CH CH -
2
2
2
2
2
2
᎐
᎐
CH᎐CH), 27.4 (᎐CICH CH ) and 27.1 (CH CH CH ); discern-
᎐
᎐
2
2
2
2
2
.68 (1H, m, NCH), 4.16 (1H, d, J 9, NCHCHHO), 4.14 (1H,
ible data for Z-isomer: δ (400 MHz) 5.37 (1H, t, J 5, CH᎐CH);
H
δ (125 MHz) 149.0 (C᎐CH ), 129.8 (CH᎐CH), 35.8 (CH C᎐
C
2
2
᎐
CH ), 29.3 (CH CH CH᎐CH) and 27.2 (᎐CICH CH ).
2
2
2
2
2
2
2
(
(
1H, app. sextet, J 7, CHMe ), 1.00 (3H, d, J 7, Me) and 0.98
2
1
-(4-Iodopent-4-en-1-yl)cyclopent-1-ene 15a
3H, d, J 7, Me); δ (125 MHz) 175.8 (OC᎐O), 153.2 (C᎐O),
C
Triene 14a (0.650 g, 2.24 mmol) in dry, degassed (freeze–pump–
thawed) pentane (20 cm ) was added to a stirred solution of 2,6-
135.6 (CH᎐CH ), 135.5 (Ar, quat.), 129.4 (2 × Ar), 128.9
(2 × Ar), 127.3 (Ar), 116.9 (᎐CH ), 65.9 (CH O), 55.6 (NCH),
᎐
2 2
᎐
2
3
J. Chem. Soc., Perkin Trans. 1, 1999, 2911–2922
2917

View Article Online
2
2
4
8.2 (NC᎐OCH), 38.0 (CH Ar), 33.7 (CH CH᎐CH ), 30.3
R 0.64 (35% Et O–light petroleum); [α] ϩ9.1 (c 1.0 in CHCl );
f 2 D 3
Ϫ1
᎐
2
2
2
ϩ
(
CHMe ), 20.9 (Me) and 19.2 (Me); m/z (EI) 301 (M , 35%),
νmax(neat)/cm 3308m, 2961s, 2360w, 1735s, 1641w, 1467w,
2
2
59 (50), 178 (20), 170 (15), 125 (100), 117 (25), 97 (90) and 85
1388w, 1370w, 1313w, 1161s, 996w and 915m; δ (200 MHz)
H
ϩ
(
60) (Found: M , 301.1678. C H NO requires M, 301.1678).
5.77 (1H, ddt, J 17, 10 and 7, CH᎐CH ), 5.07–4.99 (2H, m,
18
23
3
2
CH᎐CH ), 4.05 (1H, d, J 6, CHHOC᎐O), 4.04 (1H, d, J 6,
᎐
2
(
2S)-2-(1-Methylethyl)pent-4-en-1-ol 18
CHHOC᎐O), 2.45 (2H, t, J 7, CH C᎐O), 2.27 (2H, td, J 6 and
᎐ ᎐
2
3
, C᎐CCH ), 2.21–2.10 (2H, m, CH CH᎐CH ), 1.98 (1H, t, J 3,
᎐
2 2 2
3
H O (35% w/w in H O, 66.4 cm , 684 mmol] was added drop-
wise to a stirred solution of alkene 17 (25.75 g, 85.4 mmol) in
THF (800 cm ) and H O (250 cm ) at 0 ЊC. LiOH (4.1 g, 170
mmol] in H O (167 cm ) was added portionwise to the reaction
mixture which was then allowed to warm to room temperature.
After 5 h the reaction mixture was recooled to 0 ЊC, and aq.
Na SO (1.5 mol dm ; 513 cm , 770 mmol) was added and the
reaction mixture was then evaporated under reduced pressure.
The resulting concentrate was adjusted to pH 12–13 using aq.
NaOH (1.5 mol dm ) and extracted with CH Cl (5 × 200
cm ). The combined organic extracts were washed with brine
(
sure to give an off-white solid, the chiral auxiliary, (4S)-4-
benzyloxazolidin-2-one (13.32 g, 88%). The combined aqueous
layers were acidified to pH 1 at 0 ЊC with aq. HCl (5 mol dm )
and extracted with EtOAc (5 × 200 cm ). The combined organic
2
2
2
C᎐CH), 1.94–1.65 (3H, m, CH CH C᎐O and CHMe ), 1.64–
᎐
2
2
2
1
.56 (1H, m, CHCHMe ), 0.92 (3H, d, J 7, Me) and 0.90 (3H, d,
3
3
2
2
3
J 7, Me); δ (50 MHz) 173.1 (C᎐O), 136.9 (CH᎐CH ), 116.2
C
2
2
(
CH᎐CH ), 83.2 (C᎐CH), 69.1 (C᎐CH), 64.9 (OCH ), 42.9
᎐ ᎐
2 2
(
CHCHMe ), 32.9 (CH C᎐O), 32.8 (CH CH᎐CH ), 28.0
2 2 2 2
(
CHMe ), 23.6 (᎐CCH ), 19.5 (Me), 19.4 (Me) and 17.8
Ϫ3
3
2
2
2
3
(
6
CH CH C᎐O); m/z (EI) 223 (10%), 111 (50), 95 (75), 81 (15),
9 (100), 55 (50) and 41 (65) (Found: M ϩ H , 223.1698.
2
2
ϩ
C H O requires M, 223.1698).
Ϫ3
14 23
2
2
2
3
(
2S)-2-(1-Methylethyl)pent-4-en-1-yl 5-iodohex-5-enoate 20
3
50 cm ), dried (MgSO ) and evaporated under reduced pres-
4
3
Alkyne 19 (7.40 g, 33.3 mmol) in pentane (25 cm ) was added
Ϫ3
slowly to a stirred solution of B-I-9-BBN [(Aldrich) 1 mol dm
Ϫ3
3
3
in hexanes; 73.2 cm , 73.2 mmol] in n-pentane (240 cm ) at
Ϫ25 ЊC. After 2 h glacial acetic acid (37 cm ) was added to the
3
3
3
layers were washed with brine (50 cm ), dried (MgSO ) and
concentrated under reduced pressure to give a light yellow oil,
(
was used in the next stage without further purification; R 0.20
(
reaction mixture which was then stirred at 0 ЊC. After 1 h aq.
4
Ϫ3
3
NaOH (3 mol dm ; 265 cm ) and H O (35% w/w in H O, 51
2 2 2
3
5
0
2S)-2-(1-methylethyl)pent-4-enoic acid (11.64 g, 96%) which
cm ) were cautiously added to the reaction mixture which was
then allowed to warm to room temperature. After 30 min the
f
2
4
35% Et O–light petroleum); [α] ϩ5.6 (c 1.0 in CHCl );
organic layer was separated and the aqueous layer further
2
D
3
Ϫ1
3
νmax(neat)/cm 3081m, 2965s, 1707s, 1643w, 1470w, 1440m,
285m, 1244m, 1212m, 995w and 917m; δ (500 MHz) 5.79
extracted with light petroleum (5 × 100 cm ) and Et O (1 × 100
2
3
1
(
cm ). The combined organic layers were washed with H O
H
2
3
3
1H, ddt, J 17, 10 and 7, CH᎐CH ), 5.09 (1H, dq, J 17 and 1,
(20 cm ), saturated aq. NaHCO (20 cm ), saturated aq. Na SO
3 2 3
3 3 3
᎐
2
cis-CHH᎐CHCH ), 5.03 (1H, dd, J 10 and 1, trans-CHH᎐
(20 cm ), H O (20 cm ), brine (20 cm ), dried (MgSO ) and
2 4
᎐
2
CHCH ), 2.39–2.24 (3H, m, CH CHC᎐O), 1.93 (1H, app.
evaporated under reduced pressure. Purification of the residue
2
2
sextet, J 7, CHMe ), 1.00 (3H, J 7, Me) and 0.99 (3H, J 7, Me);
by column chromatgraphy (5% Et O–light petroleum) gave a
2
2
δ (125 MHz) 180.5 (C᎐O), 135.6 (CH᎐CH ), 116.7 (᎐CH ),
light yellow oil, the alkenyl iodide 20 (10.48 g, 90%); R 0.65
C
2
2
f
24
5
2.1 (CH CH᎐CH ), 33.6 (CHC᎐O), 30.0 (CHMe ), 20.2 (Me)
(35% Et O–light petroleum); [α] ϩ5.7 (c 1.0 in CHCl );
2 D 3
Ϫ1
2
2
2
ϩ
and 20.1 (Me); m/z (EI) 143 (M ϩ H , 40%), 125 (35), 100 (75),
νmax(neat)/cm 2959s, 1735s, 1640w, 1617w, 1466w, 1388w,
9
9 (100), 97 (30), 55 (60), 43 (45), 41 (40) and 39 (30).
1369w, 1167s, 1110w, 995w and 912w; δ (400 MHz) 6.05 (1H,
H
LiAlH (2.76 g, 72.7 mmol) was added portionwise to a
q, J 1, CHH᎐CI), 5.76 (1H, ddt, J 17, 10 and 7, CH᎐CH ), 5.74
4
2
stirred solution of the above acid (10.36 g, 72.9 mmol) in Et O
(1H, d, J 1, CHH᎐CI), 5.07–5.01 (2H, m, CH᎐CH ), 4.07 (1H,
2
᎐ ᎐
2
3
3
(
520 cm ) at 0 ЊC. After 2 h H O (2.76 cm ), aq. NaOH (15%
dd, J 11 and 6, OCHH), 4.02 (1H, dd, J 11 and 6, OCHH), 2.44
(2H, t, J 7, CH C᎐O), 2.32 (2H, t, J 7, CH CI᎐), 2.21–2.13 (1H,
2
3
3
w/w, 2.76 cm ) and H O (8.28 cm ) were cautiously added suc-
2
2
2
cessively to the reaction mixture. The resulting very thick white
m, CHHCH᎐CH ), 2.07–1.99 (1H, m, CHHCH᎐CH ), 1.89–
᎐
2
2
precipitate was slowly filtered on a sinter funnel and washed
1.75 (3H, m, CH CH C᎐O and CHMe ), 1.63–1.59 (1H, m,
2 2 2
3
with Et O (250 cm ). The filtrate was evaporated under reduced
CHCHMe ), 0.93 (3H, d, J 7, Me) and 0.92 (3H, d, J 7, Me);
2
2
pressure to give a colourless oil, the alcohol 18 (4.70 g, 50%)
δ (100 MHz) 173.2 (C᎐O), 136.9 (CH᎐CH ), 126.3 (CH ᎐CI),
C
2
2
which was used in the next stage without further purification; R
116.3 (CH᎐CH ), 110.9 (CH ᎐CI), 65.0 (OCH ), 44.3
f
2
2
2
24
0
.29 (35% Et O–light petroleum); [α] ϩ10.1 (c 1.0 in CHCl );
(᎐CICH ), 43.0 (CHCHMe ), 32.8 (CH C᎐O), 32.5 (CH CH᎐
2 2 2 2
᎐ ᎐ ᎐
2
Ϫ1
D
3
νmax(neat)/cm 3340br, 2959s, 2874s, 1640w, 1467w, 1387w,
368w, 1043m, 994w and 910m; δ (200 MHz) 5.92–5.71 (1H,
CH ), 28.1 (CHMe ), 24.2 (CH CH C᎐O), 19.5 (Me) and 19.4
2 2 2 2
ϩ
1
(Me); m/z (EI) 351 (MϩH , 25%), 222 (15), 195 (10), 113 (80)
H
ϩ
m, CH᎐CH ), 5.09–4.96 (2H, m, CH᎐CH ), 3.62 (1H, d, J 6,
and 69 (100) (Found: M ϩ H , 351.0821. C H IO requires
14 24 2
᎐
2
2
CHHOH), 3.55 (1H, s, CHHOH), 2.22–1.94 (2H, m,
CH CH᎐CH ), 1.87–1.71 (1H, m, CHMe ), 1.49–1.34 (1H, m,
M, 351.0821).
2
2
2
CHCHMe ), 0.89 (3H, d, J 7, Me) and 0.88 (3H, d, J 7, Me);
(2S)-[2-(1-Methylethyl)pent-4-en-1-yloxy]-6-iodohepta-1,6-
2
δ (50 MHz) 138.2 (CH᎐CH ), 115.9 (CH᎐CH ), 63.4 (CH -
diene 21
C
2
2
2
OH), 46.3 (CHCHMe ), 32.7 (CH CH᎐CH ), 27.6 (CHMe ),
2
2
2
2
Ϫ3
3
TiCl (1 mol dm in CH Cl ; 3.9 cm , 3.9 mmol] and TMEDA
(
4
2
2
1
9.6 (Me) and 19.1 (Me); m/z (CI) 129 (10%), 111 (15), 57 (100)
3
1.17 cm , 7.8 mmol) were successively added slowly dropwise
3
ϩ
and 43 (15) (Found: M ϩ H , 129.1280. C H O requires M,
8
17
to THF (2.5 cm ) at 0 ЊC. After 20 min a mixture of zinc dust
0.572 g, 8.75 mmol) and PbCl [(Aldrich) 0.013 g, 0.047 mmol]
1
29.1279).
(
2
was added portionwise to the reaction mixture which was then
allowed to warm to room temperature. After 30 min a solution
of alkenyl iodide 20 (0.227 g, 0.65 mmol) and CH Br (0.150
(
2S)-2-(1-Methylethyl)pent-4-en-1-yl hex-5-ynoate 19
DMAP (0.98 g, 8.0 mmol) was added to a stirred solution of
alcohol 18 (9.33 g, 72.8 mmol), hex-5-ynoic acid (8.97 g, 80.0
mmol) and DCC (16.5 g, 80.0 mmol) in CH Cl (725 cm ) at
room temperature. After 4 h Et O (250 cm ) was added and the
reaction mixture was filtered through Celite and the precipitate
washed with further Et O (200 cm ). The combined organic
filtrates were evaporated under reduced pressure and the resi-
2
2
3
3
cm , 2.14 mmol) in THF (1.2 cm ) was added dropwise to the
3
reaction mixture over 10 min. After 3.5 h the reaction mixture
2
2
3
3
was cooled to 0 ЊC then Et N (1.0 cm ) and saturated aq.
2
3
3
K CO (1.3 cm ) were added. After 15 min the reaction mixture
2
3
3
was filtered through a pad of basic alumina (activity III, 40 g)
2
3
using 1% Et N–Et O (100 cm ) as eluent and then evaporated
3
2
due was purified by column chromatography (5% Et O–light
under reduced pressure. Purification of the residue by column
2
petroleum) to give a colourless oil, the alkyne 19 (14.42 g, 89%);
chromatography (10% Et O–light petroleum) gave a clear col-
2
2
918
J. Chem. Soc., Perkin Trans. 1, 1999, 2911–2922

View Article Online
Ϫ1
ourless oil, the triene 21 (0.131 g, 58%); R 0.78 (35% CH Cl –
νmax(neat)/cm 3429s, 2960s, 2931m, 1716s, 1618m, 1371w,
f
2
2
24
light petroleum with 1% Et N); [α] ϩ1.5 (c 1.0 in CHCl );
1166w and 896w; δ (500 MHz) 9.61 (1H, d, J 3, CHO), 6.04
(1H, d, J 1, CHH᎐CI), 5.73 (1H, d, J 1, CHH᎐CI), 2.51–2.27
[7H, m, ᎐CICH , (CH ) CO and CHCHO], 2.10–2.00 (1H, m,
᎐
2 2 2
CHMe ), 1.89–1.75 (4H, m, 2 × CH ), 1.01 (3H, d, J 7, Me) and
3
D
3
H
Ϫ1
νmax(neat)/cm 2957s, 2929s, 2873m, 1652s, 1617m, 1466w,
438w, 1282m, 1265m, 1174m, 1071m, 912w, 893w and 798m;
δH(500 MHz) 6.08 (1H, d, J 1, CHH᎐CI), 5.84 (1H, ddt, J 17,
0 and 7, CH᎐CH ), 5.76 (1H, d, J 1, CHH᎐CI), 5.10–5.04 (2H,
᎐ ᎐
1
2
2
1
0.98 (3H, d, J 7, Me); δ (125 MHz) 209.5 (CO), 205.3 (CHO),
᎐
2
C
m, CH᎐CH ), 3.88 (1H, d, J 9, C᎐CHH), 3.89 (1H, s, C᎐CHH),
126.2 (CH ᎐), 111.3 (᎐CI), 57.6 (CHCHO), 44.2 (᎐CICH ), 40.7
2 2
᎐
2
3
.67–3.60 (2H, m, COCH ), 2.45 [2H, t, J 7, CH C(᎐CH )],
(CH CO), 40.4 (CH CO), 28.4 (CHMe ), 22.8 (CH ), 20.3
2
2
2
2 2 2 2
2
.26–2.08 [4H, m, CH CH᎐CH and ᎐CICH , incl. at 2.15 (2H,
(Me), 19.5 (Me) and 19.4 (CH ); m/z (CI, NH ) 337 (5%), 319
2 3
2
2
2
t, J 7, ᎐CICH )], 1.93–1.87 (1H, m, CHMe ), 1.77 (2H, quintet,
(25), 301 (15), 223 (45), 209 (90), 191 (35), 173 (20), 151 (50) and
113 (100) (Found: M ϩ H , 337.0665. C H IO requires M,
13 22 2
᎐
2
2
ϩ
J 7, ᎐CICH CH ), 1.71–1.64 (1H, m, CHCHMe ) and 0.97 (6H,
᎐
2
2
2
t, J 6, 2 × Me); δ (125 MHz) 162.5 (C᎐CH ), 137.5 (CH᎐CH ),
337.0665).
C
2
2
1
25.6 (CH ᎐CI), 115.9 (CH᎐CH ), 112.2 (CH ᎐CI), 80.9
2
2
2
(
(
(
(
1
3
C᎐CH ), 67.3 (OCH ), 44.4 (᎐CICH ), 43.5 (OCH CH), 33.5
᎐
2 2 2 2
Tributyl(diiodomethyl)stannane
CH C᎐CH ), 33.0 (CH CH᎐CH ), 28.3 (CHMe ), 26.6
2
2
2
2
2
Dry NaI (0.78 g, 5.2 mmol) was added to a stirred solution of
᎐CICH CH ), 19.7 (Me), and 19.6 (Me); m/z (EI) 349
᎐
2
ϩ
2
2
3
Bu SnCHBr2 (0.600 g, 1.30 mmol) in acetone (7.7 cm ) at room
3
M ϩ H , 100%), 305 (15), 279 (35), 151 (10), 141 (30), 120 (30),
ϩ
temperature and the reaction flask was then wrapped in foil to
exclude light. After 18 h the reaction mixture was evaporated
11 (70), 99 (40), 81 (55) and 70 (45) (Found: M ϩ H ,
49.1028. C H IO requires M, 349.1028).
15
26
under reduced pressure. The residue was diluted with hexane
3
(
20 cm ), filtered, concentrated under reduced pressure, diluted
(
2
3S)-6-(4-Iodopent-4-en-1-yl)-3-(1-methylethyl)-3,4-dihydro-
H-pyran 22
3
with CHCl (20 cm ), filtered and further concentrated under
3
reduced pressure to afford a yellow oil, Bu SnCHI (0.720 g,
3
2
A solution of triene 21 (0.123 g, 0.35 mmol) in dry, degassed
pentane (3.5 cm ) was added dropwise to a stirred solution
of 2,6-diisopropylphenylimidoneophylidenemolybdenum bis-
quant.); R 0.5 (100% light petroleum) (Found: C, 28.4; H, 5.4.
f
3
Ϫ1
C H I Sn requires C, 28.0, H, 5.1%); νmax(neat)/cm 2956s,
13
28 2
2
4
926s, 2851m, 1463w, 1375w, 1071w and 875w; δ (400 MHz)
H
(
hexafluoro-tert-butoxide) [(Strem) 0.037 g, 0.05 mmol] in dry,
.27 (1H, s, CHI ), 1.71–1.55 [6H, m, Sn(CH CH ) ], 1.33 (6H,
2
2
2 3
3
degassed pentane (4 cm ) at 25 ЊC under a gentle flow of Ar.
The reaction vessel was wrapped in aluminium foil to exclude
light and after 5 h the reaction mixture was exposed to air. After
1
filtered through a pad of basic alumina (activity III, 10 g) and
evaporated under reduced pressure. Purification of the residue
by column chromatography (1% Et O–light petroleum with 1%
sextet, J 7, 3 × MeCH ), 1.16–1.08 [6H, m, Sn(CH ) ] and 0.94
2
2 3
(
(
9H, t, J 7, 3 × Me); δ (125 MHz) 28.4 [Sn(CH CH ) ], 27.3
C 2 2 3
JSn-C 60, 3 × MeCH ), 16.4 (CHI ), 13.7 (3 × Me) and 12.9
2
2
3
ϩ
5 min the reaction was diluted with 1% Et N–Et O (10 cm ),
3
2
[Sn(CH ) ]; m/z (CI) 557 (M , 20%), 536 (30), 291 (40), 289
2 3
(
30), 287 (15), 235 (30), 233 (25), 231 (15), 172.7 (100), 124 (30)
and 122 (95).
2
Et N) gave a light yellow oil, the dihydropyran 22 (0.050 g,
3
Typical procedure for the preparation of (E)-alkenylstannanes
4
4%); R 0.64 (5% Et O–light petroleum with 1% Et N);
f 2 3
23 Ϫ1
using Bu SnCHI
3
2
[α] Ϫ28.3 (c 1.0 in CHCl ); νmax(neat)/cm 2963s, 2928s, 2872s,
D
3
3
Dry, deoxygenated DMF (7 cm ) was added dropwise to well-
1
1
679m, 1618w, 1464w, 1386w, 1368w, 1314w, 1173m, 1056m,
stirred CrCl (0.527 g, Aldrich 99.9% w/w pure, 4.3 mmol) in a
032w, 923w, 882m and 754w; δ (500 MHz) 6.03 (1H, d,
2
H
flask under argon in an ice-bath. After allowing the flask to
warm to room temperature over 15 min it was surrounded by
aluminium foil to exclude light and then a mixture of nonanal
J 1, CHH᎐CI), 5.70 (1H, d, J 1, CHH᎐CI), 4.49 (1H, dd, J 5
᎐
᎐
and 2, CH᎐CO), 4.12 (1H, dq, J 10 and 2, CHHO), 3.54 (1H,
᎐
t, J 10, CHHO), 2.39 (2H, t, J 7, CH CI), 2.00 (2H, t, J 7,
2
(
0.061 g, 0.43 mmol) and Bu SnCHI (0.478 g, 0.86 mmol) in
3 2
3
CH᎐CCH ), 1.80–1.74 (1H, m, CHMe ), 1.72–1.65 (2H, m,
᎐
2
2
dry, deoxygenated DMF (2 cm ) was added dropwise to the
reaction mixture. After 2.5 h at 25 ЊC, H O (14 cm ) was added
and the mixture extracted with Et O (3 × 10 cm ). The com-
bined organic layers were washed with H O (10 cm ) and brine
CH CH᎐CO), 1.58–1.44 (3H, m, CH and CHCHMe ), 0.94
2
2
2
3
(
(
3H, d, J 7, Me) and 0.92 (3H, d, J 7, Me); δ (100 MHz) 153.3
2
C
3
᎐CO), 125.5 (᎐CH ), 112.2 (᎐CI), 95.5 (CH᎐), 69.2 (CH O),
2
᎐
᎐
2
2
3
4
4.6 (CH CI), 38.7 (CHCHMe ), 32.3 (CH C᎐CH), 29.6
2
2
2
2
3
(
10 cm ), dried (MgSO ) and evaporated under reduced pres-
4
51
(
(
2
CHMe ), 26.3 (CH CH᎐CO), 24.6 (CH ), 20.3 (Me) and 19.7
2
2
2
ϩ
sure. Purification by reversed-phase column chromatography
Me); m/z (CI) 339 (15%), 321 (M ϩ H , 100%), 211 (45),
07 (40), 193 (M Ϫ I, 30), 175 (20), 153 (80), 135 (15), 107 (15)
(
(
C-18, 30% CH Cl –MeCN) gave a colourless oil, (E)-tributyl-
2 2
2
ϩ
dec-1-enyl)stannane (0.157 g, 85%); spectral data as lit.
and 102 (20) (Found: M ϩ H , 321.0715. C H IO requires M,
13
22
3
21.0715).
(
9S,10E)-11-(Tributylstannyl)-2-iodo-9-(1-methylethyl)undec-1-
(
2S)-9-Iodo-2-(1-methylethyl)-5-oxodec-9-enal 23
Following the procedure for the preparation of dihydropyran
2, but using triene 21 (0.758 g, 2.18 mmol) and 2,6-diisopropyl-
phenylimidoneophylidenemolybdenum bis(hexafluoro-tert-
en-6-one 24
Following the typical procedure for the preparation of (E)-
alkenylstannanes, but using double the relative quantities of
reagents [CrCl (0.300 g, 2.4 mmol) and Bu SnCHI (0.265 mg,
2
2
3
2
butoxide) [(Strem) 0.200 g, 0.26 mmol] in dry, degassed pen-
0.48 mmol)] with aldehyde 23 (0.040 g, 0.119 mmol) in DMF
(3.7 cm ) gave, after purification by reversed-phase column
3
3
tane (220 cm ), gave crude dihydropyran which was immedi-
3
Ϫ3
ately dissolved in THF (12 cm ) and HCl (2 mol dm in H O,
chromatography (C-18, 5% CH Cl –MeCN), a colourless oil,
2
2
2
2
4 drops) added. After 2 h, NaHCO (2.3 g) was added and the
the stannane 24 (0.055 g, 74%); R 0.24 (10% CH Cl –MeCN);
f 2 2
24 Ϫ1
3
reaction mixture was filtered and evaporated under reduced
pressure. The residue was dissolved in CH Cl (12 cm ) and
PCC (2.10 g, 9.74 mmol) and SiO (2.10 g) added to the stirred
solution. After 3 h, the reaction mixture was diluted with Et O
[α] Ϫ11.4 (c 1.0 in CHCl ); νmax(neat)/cm 2956s, 2926s,
D 3
3
2871m, 1716m, 1617w, 1596w, 1464w, 1376w, 997w and 893w;
δH(500 MHz) 6.03 (1H, d, J 1, CHH᎐CI), 5.79 (1H, d, J 19,
J119Sn-H 81 and J117Sn-H 78, ᎐CHSn), 5.72 (1H, s, CHH᎐CI), 5.60
2
2
2
2
3

(
20 cm ), filtered through a pad of Florisil (Aldrich) and
(1H, dd, J 19 and 8, CH᎐CHSn), 2.48–2.29 [7H, m, ᎐CICH ,
᎐ ᎐
2
evaporated under reduced pressure. Purification of the residue
(CH ) CO and CHCH᎐], 1.81–1.69 (4H, m, 2 × CH ), 1.60–
2 2 2
by column chromatography (20% Et O–light petroleum) gave a
1.42 [7H, m, CHMe , and Sn(CH CH ) ] 1.37–1.26 (6H, m,
2
2 2 2 3
colourless oil, the aldehyde 23 (0.400 g, 55% from 21): R 0.15
3 × CH Me) and 0.94–0.82 [21H, m, Sn(CH CH CH Me) and
2 2 2 2 3
2 × Me, incl. at 0.87 (3H, d, J 8, Me) and 0.85 (3H, d, J 7, Me)];
f
25
(
20% Et O–light petroleum); [α] ϩ16.7 (c 1.0 in CHCl );
2
D
3
J. Chem. Soc., Perkin Trans. 1, 1999, 2911–2922 2919

View Article Online
4
8
δC(125 MHz) 210.7 (CO), 150.8 (CH᎐CHSn), 129.5 (JSn-C 432,
CHSn), 126.1 (᎐CI), 111.4 (CH ᎐), 54.5 (CHCH᎐), 44.3
residue was diluted with 5% Et O–pentane, DBN (1 drop) was
2
᎐
᎐
then added and the resultant mixture was purified by column
᎐
2
(
᎐CICH ), 41.2 (CH CO), 40.7 (CH CO), 31.8 (CHMe ), 29.2
chromatography (5% Et O–light petroleum) to give a light
᎐
2
2
2
2
2
[
(
3
(
Sn(CH CH ) ], 27.2 (J
52, 3 × CH Me), 25.6 (CH ), 22.9
yellow oil, the enone 28 [0.031 g, 63%, diastereomerically pure
(by H NMR comparison with a diastereomeric mixture of
2
2
3
Sn-C
2
2
1
CH ), 20.6 (Me), 19.2 (Me), 13.8 (3 × CH Me) and 9.5 [J
2
2
Sn-C
ϩ
25, Sn(CH ) ]; m/z (CI) 625 (M ϩ H , 35%), 567 (100), 441
similarly prepared enones in the δ 7.1–6.2 region)]; R 0.50
2
3
f
ϩ
24
D
55), 360 (65), 308 (80) and 123 (25) (Found: M ϩ H ,
(5% Et O–light petroleum); [α] Ϫ173.0 (c 0.15 in CHCl );
νmax(neat)/cm 3411br, 2968s, 1707s, 1626s, 1495w, 1452m,
2
3
120
Ϫ1
6
25.1948. C H IO Sn requires M, 625.1928).
26
50
1
9
354w, 1271s, 1226m, 1166s, 1107m, 1079m, 1005m, 948w,
14w, 857w, 762w and 705s; δ (500 MHz) 7.50–7.29 (5H, m,
(
4S,5E)-7–Methylene-4-(1-methylethyl)cyclodec-5-en-1-one 25
H
Ar), 7.01 (1H, dd, J 16 and 8, CH᎐CHCO), 6.21 (1H, dd, J 16
and 1, ᎐CHCO), 3.61 (3H, q, J 2, OMe), 2.15 (1H, quintet,
J 7, CHMe), 1.42–1.20 (2H, m, CH ), 0.97 (3H, d, J 7, CHMe)
and 0.81 (3H, t, J 7, CH Me); δ (125 MHz) 192.6 (C᎐O), 156.8
᎐
Following the procedure for the preparation of dienone 7, but
using stannane 24 (0.307 g, 0.49 mmol), Pd (dba) (0.027 g,
0
gave, after column chromatography (10% Et O–pentane), a
colourless oil, the substituted (Ϫ)-dienone 25 (0.063 g, 62%); R
᎐
H-F
2
3
2
3
.029 mmol) and AsPh (0.091 g, 0.30 mmol) in NMP (49 cm )
3
2
C
2
(
CH᎐CHCO), 133.2 (Ar, quat.), 129.9 (Ar), 128.9 (2 × Ar),
᎐
f
1
27.8 (2 × Ar), 123.4 (Q, JC-F 290, CF ), 121.5 (᎐CHCO), 86.0
3
25
10
0
.24 (10% Et O–pentane); [α] Ϫ310 (c 1.22 in hexane) [lit.,
2 D
22
(
CCF ), 56.3 (OMe), 39.0 (CHMe), 29.2 (CH ), 19.3 (CHMe)
3
2
[α] Ϫ362 (c 1.22 in hexane)]; δ (500 MHz; C D ; C H ) 5.89
D H 6 6 6 6
and 11.9 (CH Me); δ (235 MHz; ref. CFCl ) Ϫ70.17; m/z (CI)
3
2
F
3
(
1H, d, J 16, CH ᎐CCH᎐CH), 5.24 (1H, dd, J 16 and 10,
ϩ
2
23 (M ϩ Na, 80%), 301 (M ϩ H , 25), 273 (65), 269 (90), 251
CH᎐CHCH), 4.85 (1H, br s, C᎐CHH), 4.81 (1H, d, J 2,
C᎐CHH), 2.55 (1H, dt, J 13 and 5, CHHC᎐CH ), 2.32–2.23
(
᎐
᎐
(
100), 227 (35), 199 (25), 197 (25), 157 (25), 156 (70), 139 (30),
ϩ
᎐
᎐
2
1
24 (15) and 102 (15) (Found: M ϩ H , 301.1415. C H F O
16 20 3 2
2H, m, CH CO), 2.09 (1H, app. dq, J 12 and 3, CHHCH-
2
requires M, 301.1415).
CHMe ), 1.99 (1H, ddd, J 13, 7 and 2, CHHC᎐CH ), 1.89–1.79
2
2
(
3H, m, CH CO and CHHCH C᎐CH ), 1.59–1.53 (1H, m,
2
2
2
(
2S)-2,6-Dimethyl-5-oxoheptanal 31
CHHCHCHMe ), 1.47–1.38 (1H, m, CHCHMe ), 1.35–1.25
(
(
C H ) 210.6 (C᎐O), 146.9 (C᎐CH ), 136.9 (CH᎐CHC᎐CH ),
1
(
3
(
ously reported. The ee was determined to be 93% by chiral
HPLC [Cyclobond I (β-cyclodextrin) column (4.6 mm × 250
mm), 42:58 MeOH–H O, 1 cm min ], t mj, 36.2 min; t mn,
4
2
2
A mixture of O and O was bubbled through a stirred mixture
of (6S)-2,6-dimethyloct-7-en-3-one (0.757 g, 4.9 mmol) and
NaHCO (0.023 g) in MeOH (10.3 cm ) at Ϫ65 ЊC until the
appearance of O at the outlet (starch–iodide test). The reaction
mixture was then purged with argon until no more O expelled,
Me S (0.915 g, 14.7 mmol) was added and the reaction was
allowed to warm to room temperature. After 16 h the reaction
mixture was filtered and concentrated under reduced pressure.
H O (10 cm ) was added to the residue which was then
extracted with Et O (3 × 20 cm ). The combined organic layers
were dried (MgSO ) and concentrated under reduced pressure.
Purification of the residue by column chromatography (20%
1H, m, CHMe ), 1.22–1.11 (1H, m, CHHCH C᎐CH ), 0.79
2
3
2
2
2
4
5
3H, d, J 7, Me) and 0.77 (3H, m, J 7, Me); δ (125 MHz; C D ;
C
6
6
3
3
6
6
2
2
32.6 (CH᎐CHCH), 113.4 (C᎐CH ), 52.8 (CHCH᎐), 42.4
3
᎐
᎐
2
CH C᎐O), 42.0 (CH C᎐O), 31.9 (CHMe ), 31.7 (CH C᎐CH ),
3
2
᎐
2
᎐
2
2
᎐
2
0.2 (CH CHCH), 24.5 (CH CH CH ), 20.9 (Me) and 20.8
2
2
2
2
2
1
Me). UV, IR, H NMR data were consistent with those previ-
10
3
2
3
3
Ϫ1
2
2
R
R
0.9 min.
4
Et O–light petroleum) gave a colourless oil, the ketoaldehyde 31
2
(
3S,1E)-Tributyl(3-methylpent-1-enyl)stannane 27
Following the typical procedure for the preparation of
E)-alkenylstannanes using Bu SnCHI with (S)-α-methyl-
23
(
(
0.720 g, 94%); R 0.15 (15% Et O–light petroleum); [α] ϩ18.0
f
2
Ϫ1
D
c 0.3 in CHCl ); νmax(neat)/cm 2973s, 2937m, 1709s, 1467m,
3
(
3
2
1411w, 1384w, 1213w, 1099w and 928w; δ (200 MHz); 9.51
H
43
butyraldehyde 26 (0.066 g, 0.77 mmol) gave, after purification
by reversed-phase column chromatography (C-18, 10%
CH Cl –MeCN), a colourless oil, stannane 27 (0.230 g, 80%);
R 0.22 (10% CH Cl –MeCN); [α] ϩ14.7 (c 1.0 in CHCl );
(
1H, d, J 2, CHO), 2.58–2.23 [4H, m, CH C᎐O and CH CHMe,
2 2
incl. at 2.43 (2H, t, J 7, CH C᎐O)], 1.87 (1H, septet, J 7,
2
2
2
CHMe ), 1.56 (1H, sextet, J 7, CHMe), 1.02 (3H, d, J 7,
2
2
4
f
2
2
D
3
Me) and 0.99 (6H, d, J 7, 2 × Me); δ (50 MHz) 204.5 (C᎐O),
C
Ϫ1
νmax(neat)/cm 2958s, 2925s, 2872m, 2854m, 1597w, 1463m,
376w, 1071w, 990w and 874w; δ (400 MHz) 5.80 (1H, s,
192.9 (CHO), 45.5 (CHMe), 40.7 (CHMe ), 37.0 (CH C᎐O),
2
2
1
H
24.0 (CH CHMe), 18.1 (2 × Me) and 13.3 (Me); m/z (CI)
2
ϩ
CH᎐CHSn) 5.80 (1H, d, J 2, J
2
and MeCH ] and 0.99–0.78 [21H, m, CHMe, CH Me and
Sn(CH CH CH Me) , incl. at 0.98 (3H, d, J 7, CHMe) and
75, J117Sn-H 72, ᎐CHSn),
᎐
119Sn-H
157 (M ϩ H , 10%), 155 (11), 141 (100), 139 (30), 123 (5) and
ϩ
.04 (1H, m, CHMe), 1.56–1.26 [14H, m, Sn(CH CH CH )
2 2 2 3
111 (10) (Found: M ϩ H , 157.1229. C H O requires M,
9
17
2
2
2
157.1229).
2
2
2
3
0
1
.89 (9H, t, J 7, 3 × Me)]; δ (125 MHz) 155.3 (CH᎐CHSn),
C
(6S,7E)-8-Tributylstannyl-2,6-dimethyloct-7-en-3-one 32
24.6 (᎐CHSn), 43.2 (CHMe), 29.3 (MeCH ), 29.1 [J 20,
Sn-C
᎐
2
Following the typical procedure for the preparation of (E)-
alkenylstannanes using Bu SnCHI with ketoaldehyde 31 (0.078
Sn(CH CH ) ], 27.2 (J
52, 3 × CH Me), 19.8 (CHMe), 13.7
2
2
3
Sn-C
2
3
2
(
3 × Me), 11.7 (MeCH ) and 9.4 [J
330, Sn(CH ) ]; m/z (EI)
2
Sn-C 2 3
ϩ
g, 0.50 mmol) gave, after purification by column chroma-
3
1
3
17 (M Ϫ Bu , 80%), 291 (100), 269 (80), 235 (40), 205 (40) and
ϩ 120
tography (2% Et O–light petroleum), a colourless oil, stannane
2
77 (50) (Found: M Ϫ Bu , 317.1291. C H
29
Sn requires M,
14
23
3
2 (0.150 g, 68%); R 0.25 (15% Et O–light petroleum); [α]
f 2 D
Ϫ1
17.1291).
ϩ14.5 (c 1.0 in CHCl ); νmax(neat)/cm 2958s, 2926s, 2872m,
3
1
5
2
715m, 1597w, 1464m, 1376w, 992w and 874w; δ (500 MHz)
H
(
2R,6S,4E)-1,1,1-Trifluoro-2-methoxy-6-methyl-2-phenyloct-4-
.83 (1H, d, J 19, CHSn), 5.72 (1H, dd, J 19 and 7, CH᎐CHSn),
᎐
en-3-one 28
.58 (1H, septet, J 7, CHMe ), 2.43 (2H, t, J 8, CH C᎐O), 2.11
2
2
Ϫ3
Pd dba (1.5 mg, 1.6 × 10 mmol) and tri(2-furyl)phosphine
(1H, sextet, J 7, CHMe), 1.66–1.58 (2H, m, CH CHMe), 1.55–
1.43 [6H, quintet, J 8, Sn(CH CH ) ], 1.36–1.26 (6H, m,
3 × CH Me), 1.08 (6H, d, J 7, CHMe ), 1.01 (3H, d, J 7,
2
3
2
Ϫ3
(
(
1.5 mg, 6.5 × 10 mmol) were added to a stirred solution of
2
2 3
3
S)-MPTA-Cl (34 µl, 0.18 mmol) in THF (1.5 cm ). After 10
2
2
min a solution of (S)-stannane 27 (0.061 g, 0.16 mmol) in THF
CHMe) and 0.93–0.82 [15H, m, Sn(CH CH CH Me) , incl. at
2 2 2 3
3
(
0.5 cm ) was added, the reaction vessel was wrapped in foil to
0.89 (9H, t, J 7, 3 × Me)]; δ (125 MHz) 215.1 (C᎐O), 154.3
C
exclude light and then heated at 55 ЊC. After 3 h the reaction
(CH᎐CHSn), 126.1 (CH᎐CHSn), 41.4 (CHMe), 40.9 (CHMe ),
᎐ ᎐
2
3
mixture was cooled to room temperature, then Et O (15 cm )
38.2 (CH C᎐O), 30.0 (CH CHMe), 29.1 (Sn(CH CH ), 27.2
2
2 2 2 2

was added, the mixture filtered through a pad of Florisil
(3 × CH Me), 20.5 (CHMe), 18.3 (CHMe ), 13.7 (3 × Me) and
2 2
ϩ ϩ
(
Aldrich, 10 g) and concentrated under reduced pressure. The
9.4 (Sn(CH ) ); m/z (EI) 443 (M Ϫ H , 20%), 387 (M Ϫ Bu ,
2 3
2
920 J. Chem. Soc., Perkin Trans. 1, 1999, 2911–2922

View Article Online
1
00), 331 (10), 175 (15), 121 (10), 71 (15), 43 (40) and 29
8 W. C. Still, J. Am. Chem. Soc., 1979, 101, 2493. For a recent review
ϩ
120
on the synthesis of germacrane sesquiterpenes and related
compounds see: A. J. Minnaard, J. P. B. A. Wijnberg and A. de
Groot, Tetrahedron, 1999, 55, 2115.
(
20) (Found: M Ϫ Bu , 387.1710. C H O Sn requires M,
18 35
3
87.1710).
9
S. L. Schreiber and R. C. Hawley, Tetrahedron Lett., 1985, 26, 5971.
(
2R,6S,4E)-1,1,1-Trifluoro-2-methoxy-6,10-dimethyl-2-phenyl-
1
0 T. Kitahara, M. Mori and K. Mori, Tetrahedron, 1987, 43, 2689.
11 T. L. Gilchrist, L. Thomas, P. D. Kemmitt and A. L. Germain,
undec-4-ene-3,9-dione 33
Tetrahedron, 1997, 53, 4447.
2 P. M. Jackson, C. J. Moody and P. Shah, J. Chem. Soc., Perkin Trans.
1, 1990, 2909.
Following the procedure for the preparation of enone 28, but
using stannane 32 (0.019 g, 0.04 mmol), Pd (dba) (0.4 mg,
1
2
3
Ϫ4
Ϫ3
4
.4 × 10 mmol), tri(2-furyl)phosphine (0.4 mg, 1.7 × 10
13 N. Kamiya, Y. Chikami and Y. Ishii, Synlett, 1990, 675.
14 R. K. Boeckman, Jr. and K. J. Bruza, Tetrahedron, 1981, 37, 3997.
15 L. L. Adams and F. A. Luzzio, J. Org. Chem., 1989, 54, 5387.
mmol) and (S)-MPTA-Cl (8.9 µl, 0.048 mmol) in THF (0.3
cm ) gave, after column chromatography (5% Et O–pentane), a
light, yellow oil, the enone 33 [0.013 g, 81%, diastereomerically
pure (by H NMR comparison with a diastereomeric mixture
3
2
1
1
1
6 L. T. Boulton, PhD Thesis, University of Reading, 1994.
7 V. Farina and B. Krishnan, J. Am. Chem. Soc., 1991, 113, 9585.
8 R. C. Hawley and S. L. Schreiber, Synth. Commun., 1990, 20, 1159.
1
of similarly prepared enones in the δ 7.0–6.2 region)]; R 0.10
19 M. Mori, K. Okada, K. Shimazaki, T. Chuman, S. Kuwahara,
f
2
3
(
5% Et O–light petroleum); [α] ϩ54.0 (c 0.1 in CHCl );
T. Kitahara and K. Mori, J. Chem. Soc., Perkin Trans. 1, 1990, 1769.
2
D
3
Ϫ1
νmax(neat)/cm 2970m, 2360m, 1708s, 1626m, 1272m, 1166s,
005w and 708m; δ (500 MHz) 7.78–7.32 (5H, m, Ar), 6.95
2
2
0 C. Barber, K. Jarowicki and P. Kocienski, Synlett, 1991, 197;
M. T. Crimmins and R. O’Mahony, J. Org. Chem., 1989, 54, 1157.
1 O. Fujimura, G. C. Fu and R. H. Grubbs, J. Org. Chem., 1994, 59,
1
H
(
1H, dd, J 16 and 9, CH᎐CHCO), 6.19 (1H, dd, J 16 and 1,
᎐
4
029. Reviews: R. R. Schrock, Tetrahedron, 1999, 55, 8141; R. R.
CH᎐CHCO), 3.61 (3H, q, J 1.5, OMe), 2.35 (1H, septet, J 8,
CHMe ), 2.22 (2H, t, J 7, CH C᎐O), 1.56–1.43 (2H, m,
CH CHMe), 1.39–1.26 (1H, m, CHMe), 1.02 (3H, d, J 7,
CHMe) and 1.00–0.93 (6H, m, CHMe ); δ (125 MHz) 213.9
᎐
H-F
Schrock, Top. Organomet. Chem., 1998, 1, 1; A. Fürstner, Top.
Organomet. Chem., 1998, 1, 37; R. H. Grubbs and S. Chang,
Tetrahedron, 1998, 54, 4413; S. K. Armstrong, J. Chem. Soc.,
Perkin Trans. 1, 1998, 371; A. Fürstner, Top. Catal., 1997, 4, 285;
M. Schuster and S. Blechert, Angew. Chem., Int. Ed. Engl., 1997,
2
2
2
2
C
(
CH CO), 192.4 (CHCO), 155.2 (CH᎐CHCO), 132.5 (Ar,
2
3
6, 2036. Certain unsubstituted enol ethers have recently been
quat.), 129.4 (Ar), 128.4 (2 × Ar), 127.2 (2 × Ar), 123.4
shown to undergo RCM using (PCy ) Cl Ru᎐CHPh: C. F. Sturino
3
2
2
(
᎐CHCO), 122.1 (CF ), 86.0 (CCF ), 55.8 (OMe), 40.8
᎐
3
3
and J. C. Y. Wong, Tetrahedron Lett., 1998, 39, 9623.
(
CHMe ), 37.4 (CH CO), 36.4 (CHMe), 29.3 (CH CHMe),
22 T. A. Kirkland and R. H. Grubbs, J. Org. Chem., 1997, 62, 7310.
23 K. C. Nicolaou, Y. He, F. Roschangar, N. P. King, D. Vourloumis
and T. Li, Angew. Chem., Int. Ed., 1998, 37, 84. K. C. Nicolaou,
N. P. King, M. R. V. Finlay, Y. He, F. Roschangar, D. Vourloumis,
H. Vallberg, F. Sarabia, S. Ninkovic and D. Hepworth, Bioorg. Med.
Chem., 1999, 7, 665. See also footnote 18 in: S.-H. Kim, W. J.
Zuercher, N. B. Bowden and R. H. Grubbs, J. Org. Chem., 1996, 61,
2
2
2
1
9.6 (CHMe), 18.2 (Me) and 18.1 (Me); δ (235 MHz; ref.
F
ϩ
CFCl ) Ϫ70.07; m/z (CI) 393 (M ϩ Na, 20%), 371 (M ϩ H ,
8
and 122 (45) (Found: M ϩ H , 371.1834. C H F O requires
M, 371.1834).
3
0%), 339 (100), 319 (60), 253 (50), 235 (10), 149 (10), 124 (15)
ϩ
20
26
3
3
1
073.
4 S. Hara, H. Dojo, S. Takinami and A. Suzuki, Tetrahedron Lett.,
983, 24, 731.
5 K. Takai, T. Kakiuchi, Y. Kataoka and K. Utimoto, J. Org. Chem.,
994, 59, 2668; K. Takai, Y. Kataoka, J. Miyai, T. Okazoe,
2
2
Acknowledgements
1
We thank the EPSRC and Pfizer Central Research for a CASE
award (to L. T. B.), SmithKline Beecham Pharmaceuticals
and the EPSRC for an Industrial CASE award (to A. M. F.),
Zeneca (Strategic Research Fund) and Pfizer for additional
financial support, Professor V. C. Gibson for initial assistance
with RCM of triene 21, Dr J. Zukowski (SmithKline Beecham
Pharmaceuticals) for expert HPLC analysis and the EPSRC
National Mass Spectrometry Service Centre for mass spectra.
1
K. Oshima and K. Utimoto, Org. Synth., 1995, 73, 73.
6 M. Scholl, T. M. Trnka, J. P. Morgan and R. H. Grubbs, Tetrahedron
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2
27 R. Grigg, V. Sridharan and M. York, Tetrahedron Lett., 1998, 39,
4139.
2
2
3
8 J. A. Dale, D. L. Dull and H. S. Mosher, J. Org. Chem., 1969, 34,
2
543.
9 D. A. Evans, T. C. Britton, R. L. Dorow and J. F. Dellaria, Jr.,
Tetrahedron, 1988, 44, 5525.
0 D. A. Evans, T. C. Britton and J. A. Ellman, Tetrahedron Lett., 1987,
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Paper 9/05560F
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J. Chem. Soc., Perkin Trans. 1, 1999, 2911–2922