1,5-Stereocontrol in tin(IV) halide promoted reactions of 2-alkoxy-1-(2-tributylstannylethylidene)cyclohexanes with aldehydes

Article abstract of DOI:10.1016/j.tet.2007.03.070

2-Methoxy- and 2-(p-methoxybenzyloxy)-1-(2-tributylstannylethylidene)cyclohexanes 22 and 23 were prepared from 2-methoxy- and 2-(p-methoxybenzyloxy)cyclohexanones 12 and 13. The allylstannane 22 was transmetallated stereoselectively with tin(IV) chloride

Full text of DOI:10.1016/j.tet.2007.03.070

Tetrahedron 63 (2007) 6287–6295
1,5-Stereocontrol in tin(IV) halide promoted reactions of 2-alkoxy-
1-(2-tributylstannylethylidene)cyclohexanes with aldehydes
*
Poonam Kumar, Eric J. Thomas and Daniel Tray
The School of Chemistry, The University of Manchester, Oxford Road, Manchester M13 9PL, UK
Received 15 January 2007; revised 7 March 2007; accepted 12 March 2007
Available online 16 March 2007
Abstract—2-Methoxy- and 2-(p-methoxybenzyloxy)-1-(2-tributylstannylethylidene)cyclohexanes 22 and 23 were prepared from 2-
methoxy- and 2-(p-methoxybenzyloxy)cyclohexanones 12 and 13. The allylstannane 22 was transmetallated stereoselectively with tin(IV)
chloride at ꢀ78 ꢁC to generate an allyltin trihalide, which reacted with aldehydes to give (Z)-(3-hydroxyalkylidene)-2-methoxycyclohexanes
24 with excellent 1,5-syn-stereocontrol. Similar reactions with aldehydes were observed for the 2-(p-methoxybenzyloxy) substituted allyl-
stannane 23. The structure of the product 24f prepared from p-nitrobenzaldehyde was confirmed by an X-ray structure determination of
its p-nitrobenzoate ester 27.
Ó 2007 Elsevier Ltd. All rights reserved.
Me
SnCl4
Me
OBn
1. Introduction
Bu3Sn
-78 °C
5 min
Cl3Sn OBn
2
Alk-2-enylstannanes with heteroatom containing substituents
at the 4-, 5- or 6-positions undergo stereoselective transmetal-
lation on treatment with tin(IV) halides to generate allyltin
trihalides, which react with aldehydes and imines with useful
levels of 1,5-, 1,6- and 1,7-stereocontrol.1 For example, trans-
metallationof4-benzyloxypent-2-enylstannane1with tin(IV)
chloride kinetically2 generates allyltin trichloride 2, with the
methyl and ethenyl groups trans-disposed with respect to the
four-membered ring, which reacts with aldehydes to give
the (Z)-1,5-syn-products 3 with excellent stereoselectivity
for formation of the (Z)-alkene and the 1,5-syn-stereoisomer.3
This chemistry has been applied to complete syntheses of
complex, biologically active, natural products.4–6 Allyl-
germanes have been developed as alternatives to the alk-2-
enylstannanes for these reactions7 and allylic organobismuth
reagents have been shown to react with aldehydes with com-
plementary stereocontrol in favour of (E)-alk-3-enols.8
1
-78 °C
1 h
RCHO
OH
Me
OBn
R
3
2
SnCl4
OH
SiMe3
Me
Bu3Sn
Me
OBn
-78 °C, 5 min
then RCHO
1 h
R
Me3Si
OBn
4
5
However, the compatibility of this chemistry with an addi-
tional substituent at the 3-position of the alk-2-enylstannane
is difficult to predict. This would generate a tertiary allyltin
trichloride, for example, 7 from the alkenylstannane 6, and
the kinetic preference for the methyl substituent to be cis or
trans with respect to the vinyl group may be small. Moreover,
these intermediates may be very unstable and an elimination
reaction may compete with the formation of homoallylic
alcohols with aldehydes, cf. the formation of 8 or 9 from 7.
To delineate the scope of these reactions, it was necessary to
establish whether this chemistry is compatible with addi-
tional substituents at the 2- and 3-positions of the alk-2-enyl-
stannanes. It has been found that the stereoselectivity is not
significantly affected by the presence of a substituent at the
2-position, if anything, it is slightly enhanced. For example,
2-trimethylsilylpent-2-enylstannane 4, even as a mixture of
(E)- and (Z)-isomers, is transmetallated stereoselectively to
generate an allyltin trichloride, which reacts with aldehydes
with excellent overall stereoselectivity in favour of the 1,5-
syn-(Z)-stereoisomers 5.9
To probe the effects of a substituent at the 3-position of
an alk-2-enylstannane on the stereoselectivity of its trans-
metallation with tin(IV) halides and the reactivity of the al-
lyltin trihalides so formed, it was decided first to study the
reactions with aldehydes of allyltin trihalides generated by
transmetallation of 2-alkoxy-1-(2-tributylstannylethylide-
ne)cyclohexanes using tin(IV) chloride. The results of this
study are described herein.10
* Corresponding author. Tel.: +44 161 275 4614; fax: +44 161 275 4939;
e-mail: e.j.thomas@manchester.ac.uk
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.03.070

6288
P. Kumar et al. / Tetrahedron 63 (2007) 6287–6295
R
R
3
and mixtures of products were obtained in tetrahydrofuran.
However, better yields were obtained by adding the alcohol
to a suspension of sodium hydride in toluene and then heat-
ing the mixture under reflux for 30 min before the addition of
carbon disulfide. On heating under reflux in toluene, the xan-
thate 18 isomerised into the dithiocarbonate 20, which was
isolated as an 87:13 mixture of diastereoisomers, this ratio
being independent of the (E)/(Z)-ratio of the xanthate, al-
though the configurations of the dithiocarbonates were not
established. Reaction of the mixture of dithiocarbonate
epimers with tri-n-butyltin hydride under free-radical con-
ditions12 then gave the allylstannane 22, as an 85:15 mixture
of (E)- and (Z)-isomers, the double-bond configuration
being assigned by 1H NMR on the basis of significant
NOE effects between H(2) and the vinylic proton for
the major, but not for the minor, diastereoisomer. 2-(p-
Methoxybenzyloxy)cyclohexanone 1313 was also prepared
from cyclohexane-cis-1,2-diol 10 by reduction of 4-methoxy-
benzylidene acetal of the diol using diisobutylaluminium
hydride (DIBAL-H) followed by oxidation of the alcohol
11 under Swern conditions, and taken through to the 2-p-
methoxybenzyloxy substituted allylstannane 23 using the
chemistry outlined for preparation of the 2-methoxy ana-
logue 22, see Scheme 1.
Me
SnCl4
-78 °C
Me
OBn
Bu3Sn
OBn
Cl3Sn
6
7
?
RCHO
-78 °C
OH
R
or
Me
Me
R
R
OBn
8
9
2. Results and discussion
The racemic 2-methoxy- and 2-(p-methoxybenzyloxy)-1-(2-
tributylstannylethylidene)cyclohexanes 22 and 23 were
prepared as mixtures of (E)- and (Z)-isomers as outlined
in Scheme 1. Racemic 2-methoxycyclohexanone 12 was
converted into the unsaturated ester 14 using triethyl phos-
phonoacetate and via a Peterson reaction using ethyl tri-
methylsilylacetate. As reported in the literature,11 these
reactions gave very different stereoselectivities, with the
phosphonate reagent giving more of the (E)-alkene (E)-14,
(E)/(Z)¼60:40, whereas the Peterson reaction gave more
of the (Z)-isomer (Z)-14, (E)/(Z)¼20:80. The configurations
Reactions of the stannanes 22 and 23 with aldehydes were
carried out at ꢀ78 ꢁC by adding a cooled solution of tin(IV)
chloride in dichloromethane to the stannane in dichlorome-
thane, stirring for 5 min, and then adding a solution of the al-
dehyde. In all cases the reactions were highly stereoselective
with only one product, identified as the (Z)-1,5-syn-isomer
24, being detected by 1H NMR (>98:2), see Table 1.
1
of these alkenes were assigned on the basis of H NMR
chemical shifts, for example, H(2) was considerably more
deshielded for the (Z)-isomer, cf. d 5.26 for the (Z)-isomer
with d 3.59 for the (E)-isomer, and were confirmed by
NOE data, for example, significant NOE effects between
H(2) and the vinylic proton for the (E)-isomer. The mixtures
of the (E)- and (Z)-esters 14 were reduced to the alcohol 16,
which was converted into the xanthate 18, still a mixture
of (E)- and (Z)-isomers, by reaction with sodium hydride,
carbon disulfide and methyl iodide. Initially, only low con-
versions, attributed to the low solubility of the initially
formed sodium alkoxide of the alcohol 16, were obtained
for this reaction in hydrocarbon solvents such as toluene,
The products appeared to be single diastereoisomers, but to
be sure of this it had to be demonstrated that the epimeric
alcohols could be distinguished by H NMR. Inversion of
1
configuration of the products 24a and 24c prepared from
benzaldehyde and butanal, respectively, was achieved using
a Mitsunobu reaction followed by saponification to give the
CO2Et
OH
O
OH
iii or iv
i
ii
OR
12 R = Me
OPMB
OR
OH
11
10
14 R = Me
13 R = p-MeOC6H4CH2
15 R = p-MeOC6H4CH2
v, vi
OR2
O
SnBu3
SMe
S
viii
vii
OR1
OR
OR
20 R = Me
21 R = p-MeOC6H4CH2
16 R1 = Me, R2 = H
22 R = Me
23 R = p-MeOC6H4CH2
17 R1 = p-MeOC6H4CH2, R2 = H
18 R1 = Me, R2 = CS2Me
19 R1 = p-MeOC6H4CH2, R2 = CS2Me
Scheme 1. Reagents and conditions: (i) p-MeOC6H4CH(OMe)2, p-TsOH (cat.), toluene, reflux, 1 h, then DIBAL-H in hexane, 0 ꢁC, 2 h (95%); (ii) (COCl)2,
DMSO, CH2Cl2, Et3N, ꢀ78 ꢁC to rt (96%); (iii) (EtO)2P(O)CH2CO2Et, NaH, THF, 0 ꢁC to rt [14, 87%, (E)/(Z)¼60:40]; (iv) Me3SiCH2CO2Et, LDA, THF,
ꢀ78 ꢁC, 30 min [14, 47%, (E)/(Z)¼20:80; 15, 79%]; (v) DIBAL-H, THF, ꢀ78 ꢁC to rt (16, 96%; 17, 97%); (vi) NaH, toluene, reflux, 30 min, then CS2,
0 ꢁC to rt, 1 h followed by MeI, rt, 30 min (18, 88%); (vii) toluene, reflux (20, 100%, an 87:13 mixture of diastereoisomers; 21, 72% from 17); (viii) Bu3SnH,
AIBN (trace), benzene [22, 81%, (E)/(Z)¼85:15; 23, 78%].

P. Kumar et al. / Tetrahedron 63 (2007) 6287–6295
Table 1. Tin(IV) chloride promoted reactions of 2-alkoxy-(2-tributylstan-
nylethylidene)cyclohexanes with aldehydes
6289
SnBu3
OH
SnCl4,
-78 °C, 5 min
R2
then R2CHO,
-78 °C, 45 min
OR1
OR1
24
22 R = Me
23 R = p-MeOC6H4CH2
R1
R2
Product
Yielda (%)
Me
Me
Me
Me
Me
Me
Me
PMB
C6H5
i-Pr
n-Pr
CH3CH]CH
2-Naphthyl
4-O2NC6H4
4-BrC6H4
C6H5
24a
24b
24c
24d
24e
24f
77
45
70
50
62
63
61
32
Figure 1. Projection of the structure of ester 27 as established by X-ray
diffraction.
the hydroxyl bearing stereogenic centre and the geometry of
the exocyclic double bond as depicted in structure 24f. The
structures of the other products were assigned by analogy.
24g
24h
NO2
a
In all cases, no more than 2% of any other product was detected by
1H NMR.
(Z)-1,5-anti-alcohols 26a and 26c, see Scheme 2. In both
cases, although they were inseparable by TLC, the epimeric
alcohols were clearly distinguishable by 1H NMR; for exam-
ple, H(2) was observed at d 4.08 and d 4.20 in 1H NMR spec-
tra of 24a and its epimer 26a, respectively. Examination of
the product mixtures from tin(IV) chloride promoted reac-
tions between the stannane 22 and benzaldehyde and buta-
nal, and confirmed that less than 2% of the anti-epimers
26a and 26c had been formed. Examination of the 1H
NMR spectra of the products from the tin(IV) halide pro-
moted reactions between stannanes 22 and 23 and other
aldehydes indicated that these had also been highly stereo-
O
O
OMe
NO2
27
The formation of the (Z)-1,5-syn-products 24 in the tin(IV)
chloride promoted reactions of the allylstannane 22 with al-
dehydes is consistent with stereoselective transmetallation
of the allylstannane to give the intermediate allyltin trichloride
28, which reacts with aldehydes via a six-membered chair-
like transition structure 29.1 Whether there is any residual
bonding between the oxygen of the methoxy group and the
electrophilic tin in this transition structure is not clear.14
However, transition structure 29 shows the methoxy
substituted carbon of the cyclohexane in the axial position
so minimising steric and dipolar interactions with the apical
chloride on the tin so setting up the observed (Z)-double
bond geometry.15 The preference of the R group of the alde-
hyde to adopt the equatorial position, then establishes the
configuration at the hydroxyl bearing stereogenic centre.
Similar processes are involved in the reactions of p-methoxy-
benzyloxy substituted allylstannane 23.
1
selective, ꢂ98:2 in all cases. The H NMR data also indi-
cated that 2-alkoxy substituents appeared to be axial in all
compounds prepared during this work, perhaps to avoid
steric interaction with the exocyclic alkylidene groups.
The geometry of the double bonds in the products 24 was es-
tablished by NOE studies. For example, significant enhance-
ment of the 20-methylene group, but no enhancement of
H(10), was observed on irradiation of H(2) for 24a and 24g.
Finally, the structure of the product 24f from the reaction of
allylstannane 22 with 4-nitrobenzaldehyde was confirmed by
an X-ray crystal structure of its p-nitrobenzoate ester 27.
Figure 1 shows a projection of the ester 27 as determined
by the X-ray structure, which confirms the configuration at
SnCl4
SnCl3
OMe
OH
OR1
22
2'
R2
R2
H
i, ii
28
OR1
OMe
RCHO
25a R1 = p-O2NC6H4CO, R2 = Ph
24
Cl
25c R1 = p-O2NC6H4CO, R2 = n-Pr
26a R1 = H, R2 = Ph
26c R1 = H, R2 = n-Pr
H
Cl
Cl
Sn
H2O
R
O
24
MeO
Scheme 2. Reagents and conditions: (i) Ph3P, EtO2CN]NCO2Et, p-
O2NC6H4CO2H, toluene, rt (25a, 51%; 25c, 73%); (ii) NaOH, MeOH, rt
(26a, 93%; 26c, 77%).
H
29

6290
P. Kumar et al. / Tetrahedron 63 (2007) 6287–6295
3. Summary and conclusions
77.8, 69.8, 68.6, 55.2, 30.4, 26.5, 22.1 and 21.1; m/z (CI)
254 (M++18, 25%) and 121 (100).
This work has shown that the 1,5-stereocontrol observed for
open-chain allylstannanes 1 and 4 during tin(IV) halide pro-
moted reactions with aldehydes is also observed for the anal-
ogous reactions of the allylstannanes 22 and 23, which have
two substituents at the 3-position of the allylstannane. In
particular the second substituent at the 3-position does not
disrupt the transmetallation using tin(IV) chloride of the
4-alkoxyalk-2-enylstannanes 22 and 23 and the allyltin
trichloride so formed can react with aldehydes with excel-
lent stereocontrol without elimination to form a diene being
an evident problem. Further work may investigate the use
of these products for the synthesis of fragments of natural
products.
4.3. 2-(p-Methoxybenzyloxy)cyclohexanone 1213
Dimethyl sulfoxide (2.7 cm3, 36.3 mmol) and dichloro-
methane (1 cm3) were added to oxalyl chloride (1.6 cm3,
18.5 mmol) in dichloromethane (2 cm3) at ꢀ78 ꢁC under
argon. After 5 min, the alcohol 11 (3.99 g, 16.9 mmol) in
dichloromethane (2 cm3) was added and the solution stirred
for 90 min at ꢀ78 ꢁC. Triethylamine (11.7 cm3, 84.5 mmol)
was added and, after 5 min, the solution was warmed to
room temperature. After 20 min, water (5 cm3) was added
and the mixture extracted with dichloromethane. The or-
ganic extracts were washed with brine and dried (MgSO4),
then concentrated under reduced pressure to give the title
compound 12 (3.8 g, 96%) as a colourless oil (found: M+,
234.1258. C14H18O3 requires M, 234.1256); nmax 1721,
1513, 1247, 1110 and 1035 cmꢀ1; dH (300 MHz; CDCl3)
7.3 and 6.9 (each 2H, br d, J 8.5, ArH), 4.70 and 4.48
(each 1H, d, J 11, HCHAr), 3.91 (1H, dd, J 10, 6, 2-H),
3.82 (3H, s, OCH3) and 2.64–1.6 (8H, m); dC (75 MHz;
CDCl3) 210.3, 159.2, 129.9, 129.4, 113.7, 81.3, 71.2, 55.2,
40.6, 34.5, 27.6 and 23.0; m/z (CI) 252 (M++18, 100%).
4. Experimental
4.1. General
1H and 13C NMR spectra were recorded on Bruker AC300
and Varian XL300 spectrometers in chloroform-d1. Cou-
pling constants are given in Hertz. Mass spectra were re-
corded on Kratos Concept and Fisons VG Trio 2000 mass
spectrometers using electron impact (EI) or chemical ionisa-
tion (CI) mode. IR spectra were recorded on an ATI Matte-
son genesis FTIR spectrometer as evaporated films on
sodium chloride plates unless otherwise stated. Flash col-
umn chromatography was carried out using Merck silica
gel 60H (40–60 m, 230–300 mesh) as the stationary phase.
Melting points were recorded on a Kofler heated stage appa-
ratus. Light petroleum refers to the fraction with bp 40–
60 ꢁC and was redistilled before use. Ether refers to diethyl
ether. All solvents were distilled and purified by standard
procedures. All products were obtained as colourless oils
after chromatography unless otherwise stated.
4.4. 1-(Ethoxycarbonylmethylidene)-2-methoxycyclo-
hexane 14
4.4.1. Using a Horner–Wadsworth–Emmons olefination.
Triethyl phosphonoacetate (17.5 g, 78.0 mmol) in tetrahy-
drofuran (50 cm3) was added dropwise to a suspension of
sodium hydride (60% dispersion in mineral oil, 3.12 g,
78.0 mmol) in tetrahydrofuran (100 cm3) at 0 ꢁC. The mix-
ture was allowed to warm to ambient temperature and stirred
for 30 min. After cooling to 0 ꢁC, 2-methoxycyclohexanone
12 (10.0 g, 78.0 mmol) in tetrahydrofuran (50 cm3) was
added. The mixture was allowed to warm to ambient temper-
ature and left to stir for 1 h before being poured into water
(200 cm3) and extracted with ether (3ꢃ100 cm3). The or-
ganic extracts were dried (MgSO4), filtered and concentrated
under reduced pressure. Chromatography of the residue
using ether–light petroleum (1:10) as an eluent, afforded
the title compound 14 [13.38 g, 87%, (E)/(Z)¼60:40] as a
colourless oil with partial separation of the stereoisomers.
(E)-14: Rf [ether–light petroleum (1:10)] 0.28 (found: M+,
198.1254. C11H18O3 requires M, 198.1256); nmax (neat)
1714, 1655, 1447, 1382, 1294, 1270, 1218, 1197, 1162,
1099, 1036, 942 and 875 cmꢀ1; dH (300 MHz; CDCl3)
5.85 (1H, s, 10-H), 4.19 (2H, q, J 7, OCH2CH3), 3.59 (1H,
dd, J 7.5, 3, 2-H), 3.33 (3H, s, OCH3), 3.09 (1H, m, 6-H),
2.61 (1H, m, 6-H0), 2.00–1.43 (6H, m, 3-H2, 4-H2 and 5-H2)
and 1.31 (3H, t, J 7.1, OCH2CH3); dC (75 MHz; CDCl3)
166.6, 160.9, 112.7, 82.4, 59.6, 56.5, 34.6, 27.7, 27.1, 22.6
and 14.2; m/z (CI) 216 (M++18, 88%) and 199 (M++1,
100). (Z)-14: Rf [ether–light petroleum (1:10)] 0.29 (found:
M+, 198.1253. C11H18O3 requires M, 198.1256); nmax (neat)
1715, 1650, 1446, 1436, 1380, 1334, 1264, 1223, 1161,
1094, 1037, 946, 863 and 805 cmꢀ1; dH (300 MHz; CDCl3)
5.79 (1H, d, J 1, 10-H), 5.26 (1H, m, 2-H), 4.16 (2H, q, J 7,
OCH2CH3), 3.27 (3H, s, OCH3), 2.53 (1H, m, 6-H), 2.14–
1.96 (2H, m, 3-H and 6-H0), 1.96–1.70 (2H, m, 4-H and
5-H), 1.57–1.33 (3H, m, 3-H0, 4-H0 and 5-H0) and 1.29
(3H, t, J 7, OCH2CH3); dC (75 MHz; CDCl3) 166.0, 160.8,
4.2. cis-2-(p-Methoxybenzyloxy)cyclohexanol 11
p-Methoxybenzaldehyde dimethylacetal (1.0 cm3, 5.98 mmol)
and toluene p-sulfonic acid (34 mg) were added to a solution
of cis-cyclohexane-1,2-diol (233 mg, 2 mmol) in toluene
(10 cm3) at room temperature under argon. The mixture
was heated under reflux for 1 h, then cooled to room tem-
perature and anhydrous potassium carbonate added. After
stirring for a few minutes, the mixture was filtered and
cooled to 0 ꢁC. Diisobutylaluminium hydride (10 cm3,
1.0 M in hexane) was added and the mixture stirred at
0 ꢁC for 2 h. Methanol (2 cm3) and saturated aqueous
ammonium chloride were added, and the mixture filtered
through Celite and extracted with ether. The combined or-
ganic layers were washed with water and brine, and then
dried (MgSO4). After concentration under reduced pressure,
chromatography of the residue using light petroleum–ether
(80:20) as an eluent gave the title compound 11 (450 mg,
95%) as a colourless oil (found: M+, 236.1413. C14H20O3 re-
quires M, 236.1412); nmax 3438, 1612, 1513, 1247, 1175,
1079 and 1034 cmꢀ1; dH (300 MHz; CDCl3) 7.38 and 6.92
(each 2H, br d, J 8.5, ArH), 4.58 and 4.50 (each 1H, d, J
11, HCHAr), 3.9 (1H, m, 1-H), 3.85 (3H, s, OCH3), 3.52
(1H, m, 2-H), 2.34 (1H, d, J 7, OH) and 1.9–1.2 (8H, m,
4ꢃH2); dC (75 MHz; CDCl3) 159.1, 130.6, 129.0, 113.8,

P. Kumar et al. / Tetrahedron 63 (2007) 6287–6295
6291
116.4, 72.4, 59.7, 55.6, 32.8, 32.7, 28.4, 20.0 and 14.1; m/z
(CI) 199 (M++1, 100%).
CDCl3) (E)-isomer: 5.55 (1H, t, J 7, 10-H), 4.21 (2H, m,
20-H2), 3.57 (1H, m, 2-H), 3.26 (3H, s, OCH3) and 2.23–
1.25 (9H, m); (Z)-isomer: 5.59 (1H, td, J 7, 1.5, 10-H),
4.21 (2H, m, 20-H2), 4.16 (1H, m, 2-H), 3.22 (3H, s, OCH3),
2.31 (1H, m, 6-H) and 2.23–1.25 (8H, m); dC (75 MHz;
CDCl3; (E)/(Z)-mixture) 141.50, 141.45, 124.9, 122.9,
82.4, 74.1, 58.2, 57.7, 55.7, 55.2, 33.5, 32.6, 32.4, 27.8,
27.3, 25.4, 21.8 and 20.8; m/z (CI) 174 (M++18, 53%), 156
(M+, 53), 142 (49), 139 (M+ꢀ17, 100), 125 (M+ꢀ31, 25),
124 (19) and 107 (29).
4.4.2. Using Peterson olefination. n-Butyllithium (4.6 cm3,
1.68 M in hexanes, 7.8 mmol) was added to diisopropyl-
amine (790 mg, 7.8 mmol) in tetrahydrofuran (10 cm3) at
0 ꢁC, the mixture stirred for 15 min, then cooled to
ꢀ78 ꢁC and ethyl trimethylsilylacetate (1.25 g, 7.8 mmol)
in tetrahydrofuran (5 cm3) added. After 30 min, 2-methoxy-
cyclohexanone (1.0 g, 7.8 mmol) in tetrahydrofuran (5 cm3)
was added and the mixture stirred for 2 h at ꢀ78 ꢁC. After
allowing the mixture to warm to room temperature, saturated
aqueous ammonium chloride (20 cm3) was added and the
mixture was poured into water (50 cm3) and extracted with
ether (3ꢃ50 cm3). The organic extracts were dried
(MgSO4), filtered and concentrated under reduced pressure.
Chromatography of the residue using ether–light petroleum
(1:10) as an eluent, afforded the title compound 14 [0.73 g,
47%, (E)/(Z)¼20:80)] as a colourless oil.
4.7. 1-(2-Hydroxyethylidene)-2-p-methoxybenzyloxy-
cyclohexane 17
Following the procedure outlined for the synthesis of the al-
cohol 16, the ester 15 (3.65 g, 12 mmol) in dichloromethane
(50 cm3) gave the title compound 17 (3.05 g, 97%) as a mix-
ture of diastereoisomers (found: M++NH4, 280.1905.
C16H26NO3 requires M, 280.1912); nmax 3408, 1612, 1513,
1247, 1067, 1034 and 819 cmꢀ1; dH (300 MHz; CDCl3) 7.12
and 6.88 (each 2H, d, J 8, ArH), 5.55 (1H, m, l0-H), 4.5–4.0
(5H, m), 3.78 (3H, s, OCH3), 3.74 (1H, m, 2-H) and 2.44–
1.18 (8H, m); dC (75 MHz; CDCl3) 159.0, 142.2, 130.9,
129.0, 128.9, 124.6, 122.6, 113.7, 113.6, 99.9, 79.7, 71.4,
69.3, 68.8, 58.4, 57.9, 55.2, 33.9, 33.0, 32.7, 28.0, 27.5, 25.7,
22.0 and 20.9; m/z (CI) 280 (M++18, 30%), 263 (M++1, 10),
245 (30) and 121 (100).
4.5. 1-(Ethoxycarbonylmethylidene)-2-p-methoxy-
benzyloxycyclohexane 15
Following the procedure outlined for the synthesis of the
unsaturated ester 14 using the Peterson reaction, 2-p-
methoxybenzyloxycyclohexanone 13 (4 g, 17 mmol) gave,
after chromatography using light petroleum–ethyl acetate
(10:1) as an eluent, the title compound 15 (4.09 g, 79%) as
a mixture of diastereoisomers (E)/(Z)¼20:80. (Found:
M++H, 305.1746. C18H25O4 requires M, 305.1753); nmax
1713, 1513, 1247, 1224, 1164 and 1035 cmꢀ1; dH
(300 MHz; CDCl3) major (Z)-isomer: 7.12 and 6.72 (each
2H, d, J 8, ArH), 5.68 (1H, s, l0-H), 5.31 (1H, m, 2-H),
4.22 (2H, s, OCH2Ar), 4.02 (2H, q, J 7, CH2CH3), 3.64
(3H, s, OCH3), 2.50 (1H, m, 6-H), 1.96 (2H, m), 1.75 (2H,
m), 1.5–1.2 (3H, m) and 1.18 (3H, t, J 7, CH2CH3); distinc-
tive peaks for the minor (E)-isomer: 5.76 (1H, s, 1-H), 4.38
and 4.22 (each 1H, d, J 11, HCHAr), 3.62 (3H, s, OCH3) and
3.63 (1H, m, 2-H); dC (75 MHz; CDCl3) major (Z)-isomer:
166.1, 161.2, 158.9, 131.1, 129.0, 116.2, 113.6, 70.9, 69.6,
59.8, 55.2, 33.1, 28.5, 20.2 and 14.2; m/z (CI) 322
(M++18, 100%) and 305 (45).
4.8. 2-Methoxy-(2-methyldithiocarbonyloxyethylidene)-
cyclohexane 18
The allylic alcohol 16 (6.5 g, 41.67 mmol) in toluene
(40 cm3) was added to a suspension of sodium hydride
(60% dispersion in mineral oil, 2.5 g dispersion,
62.50 mmol) in toluene (40 cm3) at ambient temperature.
The mixture was heated under reflux for 30 min, allowed
to cool to ambient temperature and further cooled to 0 ꢁC.
Carbon disulfide (5.0 cm3, 83.33 mmol) in toluene (40 cm3)
was added and the mixture stirred for 1 h at ambient temper-
ature. Iodomethane (5.2 cm3, 83.33 mmol) in tetrahydro-
furan (40 cm3) was added and the mixture stirred for 30 min
before the cautious addition of water (20 cm3), then poured
into water (300 cm3) and extracted with ether (3ꢃ100 cm3).
The organic extracts were dried (MgSO4), filtered and con-
centrated under reduced pressure. Chromatography of the
residue using ether–light petroleum (1:20) as an eluent
gave the title compound 18 [9.0 g, 88%, (E)/(Z)¼60:40) as
a pale yellow oil with partial separation of the geometrical
isomers. (E)-18: Rf [ether–light petroleum (1:20)] 0.3
(found: M+, 246.0748. C11H18O2S2 requires M, 246.0748);
nmax (neat) 1669, 1639, 1446, 1216, 1140, 1093, 1063,
1051, 966, 908 and 852 cmꢀ1; dH (300 MHz; CDCl3) 5.65
(1H, t, J 7, 10-H), 5.21 (2H, d, J 7, 20-H2), 3.62 (1H, m,
2-H), 3.29 (3H, s, OCH3), 2.59 (3H, s, SCH3), 2.25 (2H,
m, 6-H2) and 1.90–1.40 (6H, m); dC (75 MHz; CDCl3)
215.5, 146.1, 115.9, 82.1, 69.5, 55.9, 33.6, 27.3, 26.1, 21.9
and 19.0; m/z (CI) 264 (M++18, 5%), 247 (M++1, 13), 215
(M+ꢀ31, 21), 156 (18), 155 (32) and 139 (100). (Z)-18: Rf
[ether–light petroleum (1:20)] 0.4 (found: M+, 246.0750.
C11H18O2S2 requires M, 246.0748); nmax (neat) 1665,
1638, 1446, 1434, 1263, 1215, 1087, 1063, 1052, 963,
946, 910 and 853 cmꢀ1; dH (300 MHz; CDCl3) 5.69 (1H,
td, J 7.5, 1.5, 10-H), 5.22 (2H, d, J 7.5, 20-H2), 4.21 (1H,
4.6. 1-(2-Hydroxyethylidene)-2-methoxycyclohexane 16
Diisobutylaluminium hydride (163 cm3, 1.0 M in hexanes,
163 mmol) was added to the a,b-unsaturated ester 14
(12.9 g, 65 mmol) in tetrahydrofuran (130 cm3) at ꢀ78 ꢁC.
The mixture was stirred for 2 h, then allowed to warm to
0 ꢁC, stirred for 30 min, and then water (30 cm3) added
cautiously. Saturated aqueous potassium sodium tartrate
(150 cm3) followed by ether (150 cm3) were added. The
mixture was agitated rapidly at 0 ꢁC until a gel had formed,
then allowed to warm to ambient temperature and stirred
rapidly until the gel had completely dispersed (ca. 2 h).
The aqueous layer was extracted with ether (2ꢃ100 cm3)
and the combined organic extracts dried (MgSO4), filtered
and concentrated under reduced pressure. Chromatography
of the residue using ether–light petroleum (50:50) as an elu-
ent gave the title compound 16 [9.77 g, 96%, (E)/(Z)¼60:40]
as a colourless oil (found: M+, 156.1151. C9H16O2 requires
M, 156.1150); nmax (neat) 3368, 1670, 1445, 1320, 1195,
1139, 1094, 997, 943, 872 and 804 cmꢀ1; dH (300 MHz;

6292
P. Kumar et al. / Tetrahedron 63 (2007) 6287–6295
m, 2-H), 3.25 (3H, s, OCH3), 2.60 (3H, s, SCH3), 2.39 (1H,
m, 6-H), 2.06 (2H, m, 6-H0 and 3-H), 1.80 (2H, m, 4-H and 5-
H) and 1.60–1.30 (3H, m, 3-H0, 4-H0 and 5-H0); dC (75 MHz;
CDCl3) 215.5, 146.2, 118.3, 74.0, 68.9, 55.4, 32.8, 32.4,
27.9, 20.6 and 19.0; m/z (CI) 247 (M++1, 14%), 215
(M+ꢀ31, 19), 156 (17), 155 (33) and 139 (100).
with dichloromethane. The extracts were washed with brine,
dried (MgSO4) and concentrated under reduced pressure to
give the xanthate 19, which was used without further purifi-
cation. Small samples of the two diastereoisomers were sep-
arated by chromatography using ether–light petroleum as an
eluent: data for the minor, less polar (E)-isomer (E)-19:
(found: M+, 352.1164. C18H24O3S2 requires M, 352.1167);
dH (300 MHz; CDCl3) 7.31 and 6.92 (each 2H, br d, J 8,
ArH), 5.71 (1H, t, J 7.5, 10-H), 5.23 (2H, d, J 7.5, 20-H2),
4.47 and 4.35 (each 1H, d, J 11, HCHPh), 3.86 (3H, s,
OCH3), 3.8 (1H, m, 2-H), 2.61 (3H, s, SCH3) and 2.40–
1.20 (8H, m); m/z (CI) 370 (M++18, 2%), 353 (M++1, 1),
293 (9), 215 (10) and 121 (100): data for the more polar, ma-
jor (Z)-isomer (Z)-19: (found: M+, 352.1166. C18H24O3S2
requires M, 352.1167); dH (300 MHz; CDCl3) 7.28 and
6.92 (each 2H, br d, J 9, ArH), 5.68 (1H, t, J 8, 10-H), 5.12
(2H, d, J 7.5, 20-H2), 4.49 (1H, d, J 11, HCHAr), 4.38 (1H,
m, 2-H), 4.34 (1H, d, J 11, HCHPh), 3.86 (3H, s, OCH3),
2.61 (3H, s, SCH3) and 2.54–1.28 (8H, m); m/z (CI) 370
(M++18, 10%), 353 (M++1, 1), 293 (16), 215 (25) and 121
(100).
4.9. 1-Ethenyl-2-methoxy-l-thiomethylcarbonylthio-
cyclohexane 20
A solution of the allylic xanthate 18 (8.5 g, 34.55 mmol) in
toluene (50 cm3) was heated under reflux for 4 h. After being
allowed to cool to ambient temperature, concentration under
reduced pressure gave the title compound 20 (8.5 g, 100%),
a mixture of diastereoisomers, in the ratio of 87:13, as a pale
yellow oil and used without further purification, Rf [ether–
light petroleum (1:20)] 0.4 (found: M+, 246.0753.
C11H18O2S2 requires M, 246.0748); nmax (neat) 1715, 1638,
1449, 1411, 1365, 1310, 1196, 1159, 1145, 1101, 964,
921, 851 and 813 cmꢀ1; dH (300 MHz; CDCl3) major dia-
stereoisomer: 6.17 (1H, dd, J 17.5, 11, 10-H), 5.40 (1H, d,
J 17.5, 20-H), 5.34 (1H, d, J 11, 20-H0), 3.70 (1H, dd, J 9,
3.5, 2-H), 3.41 (3H, s, OCH3), 2.60–1.26 (8H, m) and 2.37
(3H, s, SCH3); dC (75 MHz; CDCl3) major diastereoisomer:
188.8, 136.1, 117.2, 81.5, 62.7, 57.6, 32.9, 26.7, 22.8, 22.2
and 12.8; m/z (CI) 247 (M++1, 100%), 215 (M+ꢀ31, 12),
155 (22) and 139 (74).
A solution of this xanthate in toluene (20 cm3) was heated
under reflux overnight and then concentrated under reduced
pressure. Chromatography of the residue using light petro-
leum–ethyl acetate (10:1) gave the dithiocarbonate 21
(2.87 g, 72%) (found: M+, 352.1171. C18H24O3S2 requires
M, 352.1167); nmax 1637, 1513, 1247, 1036 and 853 cmꢀ1
;
4.10. 2-Methoxy-l-(2-tributylstannylethylidene)-
cyclohexane 22
dH (300 MHz; CDCl3) major isomer: 7.28 and 6.92 (each
2H, d, J 8, ArH), 6.22 (1H, dd, J 17, 10, 10-H), 5.4 (2H, m,
20-H2), 4.58 and 4.53 (each 1H, d, J 11, HCHAr), 4.0 (1H,
dd, J 9, 3, 2-H), 3.82 (3H, s, OCH3), 2.37 (3H, s, SCH3)
and 2.6–1.3 (8H, m); m/z (CI) 353 (M++1, 1%), 310 (7)
and 293 (15).
The dithiocarbonate 18 (8.3 g, 33.74 mmol), tri-n-butyltin
hydride (13.6 cm3, 50.61 mmol) and azobisisobutyronitrile
(554 mg, 3.37 mmol) were combined together in benzene
(80 cm3) and the resulting mixture degassed for 15 min us-
ing argon. The mixture was then heated under reflux for
1 h before being allowed to cool to ambient temperature.
The mixture was concentrated under reduced pressure. Flash
column chromatography of the residue, eluting with ether–
light petroleum–triethylamine (1:50:0.5), afforded the title
compound 22 [11.76 g, 81%, (E)/(Z)¼85:15] as a colourless
oil, Rf [ether–light petroleum (1:50)] 0.3; nmax (neat) 1654,
1462, 1417, 1376, 1346, 1319, 1194, 1141, 1095, 1040,
1025, 941, 868 and 718 cmꢀ1; dH (300 MHz; C6D6) (E)-iso-
mer: 5.62 (1H, t, J 9, 10-H), 3.58 (1H, m, 2-H), 3.25 (3H, s,
OCH3) and 2.44–0.86 (37H, m, 20-H2, 3-H2, 4-H2, 5-H2,
6-H2 and SnBu3); dC (75 MHz; C6D6) (E)-isomer: 133.5,
124.8, 84.2, 55.9, 35.1, 30.3, 28.5, 28.3, 25.4, 22.8, 14.6,
10.8 and 10.3; m/z (ES+) 350 (10%), 332 (100), 291 (70),
276 (17) and 235 (7).
Following the procedure outlined for the synthesis of the
stannane 22 but with heating under reflux overnight, the di-
thiocarbonate 19 (2.85 g, 8.09 mmol) gave the title com-
pound 23 (3.39 g, 78%) as a mixture of diastereoisomers;
nmax 1613, 1513, 1460, 1247, 1174, 1075 and 1040 cmꢀ1
;
dH (300 MHz; CDCl3) major (E)-diastereoisomer: 7.32 and
6.92 (each 2H, d, J 8, ArH), 5.52 (1H, t, J 8, 10-H), 4.44
and 4.22 (each 1H, d, J 11, HCHAr), 3.84 (3H, s, OCH3),
3.78 (1H, m, 2-H), 2.4–1.22 (28H, m), 0.98 (9H, t, J 7,
3ꢃCH3); m/z (CI) 308 (5%), 306 (4) and 304 (3).
4.12. General procedure for allylstannane–aldehyde
reactions
4.12.1. (Z)-(2SR,30RS)-1-(3-Hydroxy-3-phenylpropyl-
idene)-2-methoxycyclohexane 24a. A cooled solution of
tin(IV) chloride (4.7 cm3, 4.69 mmol) in dichloromethane
was added dropwise to a solution of the stannane 22
(1.08 g, 3.9 mmol) in dichloromethane under argon at
ꢀ78 ꢁC. After 5 min, a cooled solution of benzaldehyde
(0.6 cm3, 6 mmol) in dichloromethane (5 cm3) was added
and the mixture stirred at ꢀ78 ꢁC for 1 h. Saturated aqueous
sodium bicarbonate (2 cm3) was added and the mixture
allowed to warm to room temperature. Dichloromethane
and water were added and the organic extracts washed
with brine, dried (MgSO4) and concentrated under reduced
pressure. Chromatography of the residue using light petro-
leum–ether (3:1) as an eluent gave the title compound 24a
4.11. 2-p-Methoxybenzyloxy-l-(2-tributylstannylethyl-
idene)cyclohexane 23
The alcohol 17 (3 g, 11.45 mmol) in anhydrous benzene
(4 cm3) was added to a suspension of sodium hydride
(550 mg, 13.7 mmol) in benzene (10 cm3) at 0 ꢁC and the
mixture stirred at room temperature for 1 h. After cooling
to 0 ꢁC, carbon disulfide (2.8 cm3, 45.8 mmol) was added
and the mixture stirred at room temperature for 3 h, then
cooled to 0 ꢁC. Methyl iodide (2.8 cm3, 48.5 mmol) was
added and the mixture stirred for 16 h at room temperature.
The mixture was then filtered through Celite and extracted

P. Kumar et al. / Tetrahedron 63 (2007) 6287–6295
6293
(0.74 g, 77%) (found: M++NH4, 264.1969. C16H26NO2 re-
quires M, 264.1963); nmax 3400, 1602, 1493, 1447, 1197,
1143, 1088, 944, 762 and 700 cmꢀ1; dH (300 MHz;
CDCl3) 7.41–7.26 (5H, m, ArH), 5.41 (1H, td, J 7.5, 1.5,
l0-H), 4.71 (1H, t, J 7, 30-H), 4.08 (1H, m, 2-H), 3.23 (3H,
s, OCH3), 2.58 (3H, m, 20-H2 and OH) and 2.31 (1H, m,
6-H), 1.95 (2H, m, 6-H0 and 3-H), 1.70 (2H, m, 4-H and
5-H), 1.42 (1H, m, 4-H0), 1.23 (1H, m, 5-H0) and 1.07 (1H,
m 3-H0); dC (75 MHz; CDCl3) 144.0, 141.2, 128.3, 127.4,
125.9, 121.3, 74.1, 73.7, 55.0, 37.0, 32.6, 31.8 and 27.9,
20.6; m/z (CI) 264 (M++18, 6%), 247 (M++1, 5), 246 (M+,
8), 232 (100), 215 (27) and 197 (51).
85 mg, pale yellow oil (found: M+, 291.1467. C16H21NO4
requires M, 291.1471); nmax (neat) 3386, 1604, 1522,
1445, 1346, 1085, 1070, 942, 911, 853, 733 and 701 cmꢀ1
;
dH (300 MHz; CDCl3) 8.19 and 7.53 (each 2H, br d, J 8.5,
ArH), 5.33 (1H, td, J 7.5, 1.5, 10-H), 4.78 (1H, dd, J 7, 5.5,
30-H), 4.04 (1H, m, 2-H), 3.20 (3H, s, OCH3), 2.70 (1H, br
s, OH), 2.53 (2H, m, 20-H2), 2.29 (1H, m, 6-H) and 2.04–
1.05 (7H, m); dC (75 MHz; CDCl3) 151.4, 147.0, 142.5,
126.4, 123.4, 120.0, 73.8, 72.7, 55.0, 37.0, 32.7, 31.3, 27.6
and 20.5; m/z (EI) 277 (10%), 260 (M+ꢀ31, 15), 242 (21),
212 (13), 164 (9), 150 (9), 139 (29), 122 (26) and 108 (100).
4.12.7. (Z)-(2SR,30RS)-1-(3-p-Bromophenyl-3-hydroxy-
propylidene)-2-methoxycyclohexane 24g. Yield (61%)
93 mg, colourless oil (found: M++NH4, 342.1060.
C16H2579BrNO2 requires M, 342.1068); nmax (neat) 3399,
1592, 1486, 1444, 1403, 1196, 1143, 1070, 1010, 943 and
823 cmꢀ1; dH (300 MHz; CDCl3) 7.50 and 7.25 (each 2H,
br d, J 8.5, ArH), 5.36 (1H, br t, J 7.5, 10-H), 4.66 (1H, t,
J 7, 30-H), 4.06 (1H, m, 2-H), 3.22 (3H, s, OCH3), 2.53
(3H, m, 20-H2 and OH), 2.30 (1H, m, 6-H), 1.97 (2H, m,
6-H0 and 3-H) and 1.82–1.06 (5H, m, 3-H0, 4-H2 and
5-H2); dC (75 MHz; CDCl3) 143.1, 141.7, 131.3, 127.6,
121.1, 120.8, 73.8, 73.3, 55.1, 37.0, 32.7, 31.7, 27.9 and
20.6; m/z (CI) 344 (M++18, 12%), 342 (M++18, 15), 312
(96), 310 (96), 295 (17), 293 (23), 277 (37), 275 (40), 201
(44) and 199 (53).
4.12.2. (Z)-(2SR,30RS)-1-(3-Hydroxy-4-methylpentyl-
idene)-2-methoxycyclohexane 24b. Yield (45%) 79 mg
(found: M++NH4, 230.2107. C13H28NO2 requires M,
230.212); nmax 3435, 1465, 1446, 1197, 1142, 1096, 1085,
1000, 945 and 874 cmꢀ1; dH (300 MHz; CDCl3) 5.42 (1H,
t, J 8, 10-H), 4.22 (1H, m, 2-H), 3.41 (1H, m, 30-H), 3.24
(3H, s, OCH3), 2.62–1.4 (12H, m) and 0.98 and 0.96 (each
3H, d, J 7, CH3); dC (75 MHz; CDCl3) 141.0, 122.3, 76.5,
73.8, 55.1, 32.9, 32.7, 32.0, 31.7, 28.0, 20.7, 18.8 and
17.2; m/z (CI) 230 (M++18, 16%), 213 (M++1, 18), 198
(65), 181 (71) and 163 (100).
4.12.3. (Z)-(2RS,30RS)-1-(3-Hydroxyhexylidene)-2-
methoxycyclohexane 24c. Yield (70%) 275 mg (found:
M++NH4, 230.2119. C13H28NO2 requires M, 230.2120);
nmax 3409, 1446, 1379, 1197, 1141, 1085, 1025 and
945 cmꢀ1; dH (300 MHz; CDCl3) 5.42 (1H, t, J 7.5, 10-H),
4.2 (1H, m, 2-H), 3.48 (1H, m, 30-H), 3.28 (3H, s, OCH3)
and 2.42–0.98 (18H, m); dC (75 MHz; CDCl3) 141.0,
121.9, 73.7, 71.4, 55.1, 39.0, 34.9, 32.7, 32.1, 28.1, 20.7,
18.8 and 14.0; m/z (CI) 230 (M++18, 100%) and 213
(M++1, 88).
4.12.8. (Z)-(2SR,3RS)-1-(3-Hydroxy-3-phenylpropyl-
idene)-2-p-methoxybenzyloxycyclohexane 24h. Yield
(32%) 158 mg; nmax 3432, 1612, 1513, 1452, 1301, 1247,
1175, 1037 and 821 cmꢀ1; dH (300 MHz; CDCl3) 7.4 (7H,
m, ArH), 6.9 (2H, d, J 8, ArH), 5.42 (1H, t, J 6.5, l0-H),
4.64 (1H, t, J 6, 30-H), 4.42 (1H, d, J 11, HCHAr), 4.27
(2H, m, HCHAr and 2-H), 3.8 (3H, s, OCH3) and 2.6–1.0
(10H, overlapping m); dC (75 MHz; CDCl3) 158.9, 144.1,
141.3, 131.2, 129.1, 128.2, 127.4, 125.9, 121.4, 113.7,
74.1, 71.4, 68.6, 55.2, 37.0, 32.9, 32.2, 28.2 and 20.9; m/z
(CI) 370 (M++18, 1%), 352 (M+, 2) and 121 (100).
4.12.4. (Z)-(2SR,30RS,40E)-1-(3-Hydroxyhex-4-enyl-
idene)-2-methoxycyclohexane 24d. Yield (50%) 67 mg
(found: M++H, 211.1693. C13H23O2 requires M,
211.1697); dH (300 MHz; CDCl3) 5.6 (1H, dq, J 16, 7, 50-
H), 5.44 (1H, ddd, J 16, 8, 1, 40-H), 5.28 (1H, t, J 7, l0-H),
4.32 (1H, m, 2-H), 3.98 (1H, q, J 7, 30-H), 3.18 (3H, s,
OCH3), 2.22 and 1.92 (each 3H, m), 1.64 (3H, d, J 8, 60-H3)
and 1.27 (4H, m); dC (75 MHz; CDCl3) 140.6, 133.5, 126.8,
121.5, 73.7, 72.6, 55.0, 34.9, 32.6, 32.1, 28.1, 20.7 and 17.6;
m/z (CI) 211 (M++1, 8%) and 161 (100).
4.13. (Z)-(2SR,30SR)-2-Methoxy-l-(3-p-nitrobenzoyloxy-
3-phenylpropylidene)cyclohexane 25a
Diethyl azodicarboxylate (87 mg, 0.5 mmol) was added
dropwise to the alcohol 24a (114 mg, 0.46 mmol), p-nitro-
benzoic acid (92 mg, 0.55 mmol) and triphenylphosphine
(145 mg, 0.55 mmol) in toluene at room temperature under
an argon atmosphere. After 4 h, the solution was diluted
with ether and washed with water. The organic extracts
were washed with brine, dried (MgSO4) and concentrated
under reduced pressure. Chromatography of the residue
using light petroleum–ether (10:1) as an eluent gave the title
compound 25a (93 mg, 51%) (found: M++NH4, 413.2075.
C23H29N2O5 requires M, 413.2076); dH (300 MHz; CDCl3)
8.36 and 8.30 (each 2H, d, J 8, ArH), 7.4 (5H, m, ArH),
6.08 (1H, t, J 7, 30-H), 5.4 (1H, t, J 8, 10-H), 4.2 (1H, m,
2-H), 3.18 (3H, s, OCH3), 2.97 and 2.78 (each 1H, dt,
J 16, 8, 20-H), 2.29 (1H, m, 6-H), 1.97 and 1.72 (each
2H, m), 1.46 (1H, m) and 1.22 (2H, m); dC (75 MHz;
CDCl3) 163.8, 150.5, 141.5, 139.4, 135.7, 130.7, 128.6,
128.3, 126.4, 123.5, 119.9, 77.5, 73.6, 54.9, 34.0, 32.7,
32.5, 28.0 and 20.7; m/z (CI) 413 (M++18, 100%), 381
(10) and 364 (38).
4.12.5. (Z)-(2SR,30RS)-1-[3-(2-Naphthyl)propylidene]-2-
methoxycyclohexane 24e. Yield (62%) 85 mg, colourless
viscous oil (found: M+, 296.1767. C20H24O2 requires M,
296.1776); nmax (neat) 3399, 1632, 1601, 1508, 1444,
1318, 1197, 1143, 1086, 1071, 944, 856, 819 and 748 cmꢀ1
;
dH (300 MHz; CDCl3) 7.83 (4H, m, ArH), 7.48 (3H, m,
ArH), 5.40 (1H, td, J 7.5, 1.5, 10-H), 4.84 (1H, t, J 6.5, 30-
H), 4.09 (1H, m, 2-H), 3.21 (3H, s, OCH3), 2.63 (2H, m,
20-H2), 2.28 (1H, m, 6-H) and 2.01–0.94 (7H, m); dC
(75 MHz; CDCl3) 141.4, 141.3, 133.2, 132.9, 128.1, 127.8,
127.6, 126.0, 125.7, 124.6, 124.0, 121.3, 74.2, 73.8, 55.1,
36.9, 32.6, 31.8, 27.9 and 20.6; m/z (CI) 282 (13%), 279
(M+ꢀ17, 17), 247 (53), 171 (78), 125 (67) and 108 (100).
4.12.6. (Z)-(2SR,30RS)-1-(3-Hydroxy-3-p-nitrophenyl-
propylidene)-2-methoxycyclohexane 24f. Yield (63%)

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P. Kumar et al. / Tetrahedron 63 (2007) 6287–6295
4.14. (Z)-(2RS,3RS)-1-(3-Hydroxy-3-phenylpropyl-
idene)-2-methoxycyclohexane 26a
6.4%; M+, 440.1582. C23H24N2O7 requires C, 62.7; H, 5.5;
N, 6.4%; M, 440.1583); nmax (Nujol) 1721, 1608, 1529,
1460, 1350, 1269, 1116, 1098, 853 and 716 cmꢀ1; dH
(300 MHz; CDCl3) 8.41–8.14 (6H, m, ArH), 7.59 (2H, d,
J 8, ArH), 6.04 (1H, t, J 7, 30-H), 5.28 (1H, br t, J 7, 10-H),
4.01 (1H, m, 2-H), 3.17 (3H, s, OCH3), 2.86 (2H, m,
20-H2), 2.25 (1H, m, 6-H) and 1.97–0.81 (7H, m); dC
(75 MHz; CDCl3) 163.7, 150.7, 147.7, 146.4, 142.8, 135.0,
130.7, 127.4, 123.8, 123.6, 118.2, 76.4, 73.8, 55.1, 33.7,
32.7, 32.3, 28.0 and 20.5; m/z (CI) 458 (M++18, 6%), 409
(12), 379 (13), 242 (77), 212 (32), 155 (27) and 59 (100).
The ester 25a (0.187 mmol, 74 mg) in methanol (0.5 cm3)
was added dropwise to sodium hydroxide (8 mg,
0.20 mmol) in methanol (3 cm3) at room temperature. After
2 h, ether was added and the mixture washed with water. The
organic extracts were washed with brine, dried (MgSO4) and
concentrated under reduced pressure. Chromatography of
the residue using light petroleum–ether (70:1) as an eluent
gave the title compound 26a (43 mg, 93%) (found:
M++NH4, 264.1966. C16H26NO2 requires M, 264.1963);
dH (300 MHz; CDCl3) 7.3 (5H, m, ArH), 5.43 (1H, t, J 8,
l0-H), 4.76 (1H, m, 30-H), 4.20 (1H, m, 2-H), 3.17 (3H, s,
OCH3) 2.68 and 2.56 (each 1H, dt, J 14, 7, 20-H), 2.32
(1H, m, 6-H) and 2.2–1.2 (8H, m); m/z (CI) 264 (M++18,
20%), 247 (M++1, 22) and 232 (100).
4.17. Crystallographic data for ester 27
˚
C23H24N2O7, M¼440.45, triclinic P-1, a¼8.869 A, b¼
20.469ꢁA, c¼6.201 A, a¼93.582ꢁ, b¼99.109ꢁ, g¼
˚
˚
3
˚
81.589 , V¼1098.7 A , Z¼2, T¼296 K, l¼1.5418. A tabu-
lar crystal, 0.35ꢃ0.25ꢃ0.17 mm3, was used to measure
4738 reflections on a Rigaku AFC5R (Rint¼0.02, 4445
unique). The structure was solved by direct methods and re-
fined anisotropically on F2. Hydrogen atoms were located
geometrically. The final agreement indices are: R¼0.054,
wR¼0.147 (I>2s(I), 3102 reflections), Rall¼0.083. The
structure is deposited at the Cambridge Crystallographic
Data Centre as CCDC no. 632903.
4.15. (Z)-(2SR,3RS)-1-(3-Hydroxyhexylidene)-2-
methoxycyclohexane 26c
Following the procedure outlined for the synthesis of p-
nitrobenzoate 25a, the alcohol 24c (127 mg, 0.59 mmol),
p-nitrobenzoic acid (120 mg, 0.71 mmol) and triphenyl-
phosphine (188 mg, 0.71 mmol) in toluene gave, after chro-
matography using light petroleum–ether (0.8:1) as an eluent,
the ester 25c (157 mg, 73%); dH (300 MHz; CDCl3) 8.33 and
8.27 (each 2H, d, J 8, ArH), 5.42 (1H, t, J 8, l0-H), 5.22 (1H,
q, J 6, 30-H), 4.22 (1H, m, 2-H), 3.22 (3H, s, OCH3), 2.60 and
2.49 (each 1H, dt, J 15, 7.5, 20-H), 2.29 (1H, m, 6-H), 2.10–
1.10 (11H, m) and 0.98 (3H, t, J 7, 60-H3); dC (75 MHz;
CDCl3) 164.2, 150.4, 140.9, 136.0, 130.5, 123.4, 120.4,
75.8, 73.6, 55.0, 35.8, 32.7, 32.5, 31.7, 28.1, 20.7, 18.6
and 13.8; m/z (CI) 379 (M++18, 4%), 330 (5), 300 (12)
and 163 (100).
Acknowledgements
We thank the EPSRC and Astra-Zeneca for a CASE student-
ship (to D.R.T.) and Dr. M. Helliwell and Dr. J. Raftery for
the X-ray study.
References and notes
Following the procedure outlined for the synthesis of
the alcohol 26a, the ester 25c (125 mg, 0.34 mmol) gave,
after chromatography using light petroleum–ether (10:1),
the title compound 26c (57 mg, 77%) (found: M++NH4,
230.2115. C13H28NO2 requires M, 230.2120); dH
(300 MHz; CDCl3) 5.44 (1H, t, J 8, l0-H), 4.24 (1H, m, 2-
H), 3.68 (1H, m, 30-H), 3.24 (3H, s, OCH3), 2.4–1.24
(14H, m) and 0.98 (3H, t, J 7, 60-H3); dC (75 MHz; CDCl3)
141.1, 121.9, 73.7, 71.1, 55.0, 38.9, 34.9, 32.6, 32.5, 28.2,
20.7, 18.9 and 14.0; m/z (CI) 230 (M++18, 100%) and 213
(M++1, 68).
1. (a) Thomas, E. J. Chem. Commun. 1997, 411; (b) Booth, C.;
Brain, M.; Castreno, P.; Donnelly, S.; Dorling, E. K.; Germay,
O.; Hobson, L. A.; Kumar, N.; Martin, N.; Moore, C.; Negi,
D.; Thomas, E. J.; Weston, A. Pure Appl. Chem. 2006, 78, 2015.
2. (a) Beddoes, R.; Hobson, L. A.; Thomas, E. J. Chem. Commun.
1997, 1929; (b) Hobson, L. A.; Vincent, M.; Thomas, E. J.;
Hillier, I. H. Chem. Commun. 1998, 899.
3. MacNeill, A. H.; Thomas, E. J. Synthesis 1994, 322.
4. (a) Dorling, E. K.; Thomas, E. J. Tetrahedron Lett. 1999, 40,
471; (b) Dorling, E. K.; Thomas, A. P.; Thomas, E. J. Tetra-
hedron Lett. 1999, 40, 475.
5. Martin, N.; Thomas, E. J. Tetrahedron Lett. 2001, 42, 8373.
6. Germay, O.; Kumar, N.; Thomas, E. J. Tetrahedron Lett. 2001,
42, 4969.
4.16. (Z)-(2SR,30RS)-2-Methoxy-1-(3-p-nitrophenyl-3-
p-nitrophenylcarbonyloxypropylidene)cyclohexane 27
7. (a) Castreno, P.; Thomas, E. J.; Weston, A. Tetrahedron Lett.
2007, 48, 337; (b) Thomas, E. J.; Weston, A. Tetrahedron
Lett. 2007, 48, 341.
8. (a) Donnelly, S.; Thomas, E. J.; Arnott, E. A. Chem. Commun.
2003, 1460; (b) Donnelly, S.; Fielding, M.; Thomas, E. J.
Tetrahedron Lett. 2004, 45, 6779.
9. (a) Taylor, N. H.; Thomas, E. J. Tetrahedron 1999, 55, 8757;
(b) Teerawutgulrag, A.; Thomas, E. J. J. Chem. Soc., Perkin
Trans. 1 1993, 2863.
10. Kumar, P.; Thomas, E. J.; Tray, D. R. J. Br. Chem. Soc. 2001,
12, 623.
p-Nitrobenzoyl chloride (124 mg, 0.668 mmol) was added
to the homoallylic alcohol 24f (65 mg, 0.223 mmol) and
triethylamine (155 ml, 1.112 mmol) in dichloromethane
(5 cm3) at ambient temperature. The resulting mixture was
stirred for 18 h then poured into water (10 cm3) and ex-
tracted with dichloromethane (2ꢃ10 cm3). The organic ex-
tracts were dried (MgSO4), filtered and concentrated under
reduced pressure. Flash column chromatography of the
residue, eluting with ether–light petroleum (1:2), afforded
the title compound 27 (72 mg, 73%) as a yellow solid. An an-
alytical sample was recrystallised from ether to give pale
yellow needles, mp 117–119 ꢁC (found: C, 62.3; H, 5.5; N,
11. Strekowski, L.; Visnick, M.; Battiste, M. A. Tetrahedron Lett.
1984, 25, 5603.

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6295
12. Ueno, Y.; Aoki, S.; Okawara, M. J. Am. Chem. Soc. 1979,
101, 5414.
(see Ref. 14). For allyltin trihalides with an additional group
coordinated to the tin, there is the possibility that the tin is oc-
tahedral in the transition structures in reactions with aldehydes.
However, with octahedral tin, it is difficult to rationalise the
very strong preference for (Z)-alkene formation in reactions,
which give 1,6- and 1,7-stereocontrol (see Ref. 1).
13. Bartoli, G.; Dalpozzo, R.; De Nino, A.; Maiuolo, L.; Nardi, M.;
Procopio, A.; Tagarelli, A. Eur. J. Org. Chem. 2004, 2176.
14. Reactions under thermal conditions between 1-substituted
allylstannanes and aldehydes lead to (Z)-homoallylic alcohols
and are believed to proceed via six-membered chair-like tran-
sition states analogous to that shown in 29 with the group
next to tin in the axial position and the tin trigonal bipyramidal
15. (a) Pratt, A. J.; Thomas, E. J. J. Chem. Soc., Perkin Trans. 1
1989, 1521; (b) Jephcote, V. J.; Pratt, A. J.; Thomas, E. J.
J. Chem. Soc., Perkin Trans. 1 1989, 1529.