Concerning the 1,5-stereocontrol in tin(iv) chloride promoted reactions of 4- and 5-alkoxyalk-2-enylstannanes: Trapping intermediate allyltin trichlorides using phenyllithium

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PAPER

Concerning the 1,5-stereocontrol in tin(IV) chloride promoted reactions of

4- and 5-alkoxyalk-2-enylstannanes: trapping intermediate allyltin

trichlorides using phenyllithium†

Lindsay A. Hobson and Eric J. Thomas*

Received 20th April 2012, Accepted 2nd July 2012

DOI: 10.1039/c2ob25765c

Transmetallation of the 5-benzyloxy-4-methylpent-2-en-1-yl(tributyl)- and -(triphenyl)stannanes 1 and 8

using tin(^IV) chloride generates an allyltin trichloride that reacts with aldehydes to give (Z)-1,5-anti-6-

benzyloxy-5-methylhex-3-en-1-ols 2. The allyltin trichloride believed to be the key intermediate in these

reactions has been trapped by phenyllithium to give anti-5-benzyloxy-4-methylpent-1-en-3-yl(triphenyl)

stannane 9. Transmetallation of this anti-5-benzyloxy-4-methylpent-1-en-3-yl(triphenyl)stannane 9

generated an allyltin trichloride that reacted with aldehydes to give the (Z)-1,5-syn-6-benzyloxy-5-

methylhex-3-en-1-ols 23 and was trapped by phenyllithium to give syn-5-benzyloxy-4-methylpent-1-en-

3-yl(triphenyl)stannane 24. Similar stereoselectivity was observed for tin(^IV) chloride promoted reactions

of this syn-5-benzyloxy-4-methylpent-1-en-3-yl(triphenyl)stannane 24 with aldehydes and with

phenyllithium. The allyltin trichlorides generated by transmetallation of 4-hydroxy- and 4-benzyloxy-

pent-2-enyl(triphenyl)stannanes 34 and 35 were similarly trapped by phenyllithium to give 4-hydroxy-

and 4-benzyloxy-pent-1-en-3-ylstannanes 36 and 37 whose conﬁgurations were established by correlation

with known compounds. This work conﬁrmed the conﬁgurations of the intermediate allyltin trichlorides

involved in tin(^IV) chloride promoted reactions of 4- and 5-alkoxypent-2-enylstannanes with aldehydes

and showed that the high levels of remote stereocontrol were due mainly to kinetically controlled

transmetallation. A fuller mechanistic scheme is proposed for the reactions in the 5-benzyloxy-4-

methylpent-2-enylstannane series together with relevant ¹¹⁹Sn NMR data.

Introduction

Tin(IV) halide promoted reactions of 4-, 5- and 6-alkoxy- and

-hydroxy-alk-2-enylstannnanes with aldehydes give (Z)-alk-3-

enols with useful levels of 1,5-, 1,6- and 1,7-stereocontrol.^1,2For

example, the (Z)-1,5-anti-alk-3-en-1-ols 2 were obtained from

reactions of the 5-benzyloxy-4-methylpent-2-enyl(tributyl)stan-

nane 1 and aldehydes^2aand the 4-benzyloxypent-2-enylstann-

nane

4 gave the (Z)-1,5-syn-products 5 with excellent

stereoselectivity.^2bN- and S-substituted pentenylstannanes show

similar stereoselectivity^2cand useful stereoselectivity, albeit in

favour of the (E)-alkenes 3 and 6, was observed for the

reactions of alkoxyalk-2-enylstannanes

1

and

4

with

1-alkoxycarbonylimines.³

The School of Chemistry, The University of Manchester, Oxford Road,

Manchester, M13 9PL, UK. E-mail: e.J.thomas@manchester.ac.uk;

Fax: +44 (0)161275 4939; Tel: +44 (0)161 275 4613

†Electronic supplementary information (ESI) available. CCDC 122890.

For ESI and crystallographic data in CIF or other electronic format see

DOI: 10.1039/c2ob25765c

These reactions are believed to involve allyltin trichlorides

formed stereoselectively from the alk-2-enylstannanes and tin(^IV)

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chloride before the addition of the aldehyde. The transmetalla-

tion step would appear to be complete in less than ﬁve minutes

at −78 °C since no branched (SE′) product was ever obtained.

To explain the high stereoselectivities, it was suggested that the

transmetallation step must be highly stereoselective possibly due

to delivery of the trichlorotin group to one face of the double-

bond of the alk-2-enylstannanes after coordination of the tin(^IV)

chloride to the alkoxy substituent.^1,2However, an alternative

mechanism involving rapid equilibration of isomeric allyltin tri-

chlorides with selective reaction of the more reactive isomer

couldn’t be ruled out. It was therefore decided to probe the

mechanisms of these reactions by trapping the allyltin trichloride

intermediates using reactions that retained the carbon–tin bond.

We now report full details of reactions of allyltin trichlorides

generated from 4- and 5-alkoxypent-2-enylstannanes with phe-

nyllithium⁴together with relevant ¹¹⁹Sn NMR data.

tributylstannanes to triphenylstannanes had not had any effect on

this chemistry. Attempts were now made to trap the allyltin tri-

chloride believed to be an intermediate in these reactions. In the

event, it was found that the addition of an excess of phenyl-

lithium ﬁve minutes after the addition of tin(^IV) chloride at

−78 °C to the stannane 8 gave a new pentenylstannane identiﬁed

as the anti-5-benzyloxy-4-methylpent-1-en-3-yl(triphenyl)stan-

nane 9 together with a second minor product subsequently identiﬁ-

ed as the epimeric syn-stannane 24, ratio 9 : 24 = 90 : 10. Since

unsymmetric allylstannanes with the tin substituent at the more

substituted end of the allyl fragment are prone to undergo 1,3-

migration of the tin,⁶the pent-1-en-3-ylstannane 9 was reduced

using diimide to give the anti-pent-3-yl(triphenyl)stannane 10

containing ca. 10% of its syn-epimer 25, see Scheme 1.

The structures assigned to the products 9 and 10 were consist-

ent with their spectroscopic data. Comparison with later spectra

showed that the anti-pent-1-en-3-ylstannane

9 contained

ca. 10% of its syn-epimer. It remained to establish the relative

conﬁguration of the stannanes 9 and 10 at their stereogenic

centres, but attempts to prepare crystalline derivatives were

thwarted as debenzylation of the benzyl ether 10 by hydrogeno-

lysis or by using trimethyltin iodide gave either unchanged start-

ing material or complex mixtures of products. The 5-tert-

butyldimethylsilyloxy- and 5-hydroxy-pent-2-enylstannanes 11

and 12 are known to react with aldehydes with similar stereo-

selectivity to that observed for the 5-benzyloxystannane 1,⁷and

so it was decided to study reactions of the 5-silyloxy- and 5-

hydroxy-pent-2-enyl(triphenyl)stannanes to access derivatives

suitable for X-ray crystallography.

Results and discussion

Trapping alkenyltin trichlorides in the 5-alkoxypent-2-

enylstannane series

Studies were initiated using triphenylstannanes rather than the

previously used tributylstannanes since preliminary studies using

tributylstannanes led to some difﬁculties in purifying intermedi-

ates.⁵Thus the (R)-5-benzyloxypent-2-enyl(triphenyl)stannane 8

was prepared as an 80 : 20 mixture of (E)- and (Z)-isomers

(¹H NMR) by reaction of the dithiocarbonate 7^2awith triphenyltin

hydride under free radical conditions, see Scheme 1. The tin(^IV)

chloride mediated reactions of the pent-2-enyl(triphenyl)stan-

nane 8 with benzaldehyde, 2-methylpropanal and propanal were

then carried out under the usual conditions and gave the

known^2a(Z)-1,5-anti-alkenols 2a–c with excellent stereoselectiv-

ity, ca. 95 : 5, in all cases, so showing that the change from

The ( )-5-tert-butyldimethylsilyloxy-4-methylpent-2-enylstan-

nane 14 was prepared by reaction of the dithiocarbonate 13^2c

with triphenyltin hydride under free radical conditions and desi-

lylation gave the 5-hydroxypent-2-enylstannane 15. The pent-2-

enylstannanes 14 and 15 were separately treated with tin(^IV)

chloride for 5 min at −78 °C before an excess of phenyllithium

was added to trap any intermediate allyltin trichloride. Pent-1-

en-3-yl(triphenyl)stannanes 16 and 17 (anti : syn = 85 : 15) were

obtained and were reduced using diimide to give the pent-3-

ylstannanes 18 and 19. The 5-hydroxypent-3-ylstannane 19 was

then esteriﬁed using 4-bromobenzoyl chloride to give the crystal-

line 4-bromobenzoate 20 whose structure was established by

X-ray diffraction, see Fig. 1.^4aThis conﬁrmed the anti-conﬁgur-

ation indicated for the 5-hydroxypentylstannane 19.

Scheme 1 Tin(IV) chloride mediated reactions of the 5-benzyloxy-4-

methylpentenyl(triphenyl)stannane 8. Reagents and conditions: (i)

Ph₃SnH, AIBN (cat.), benzene, heat under reﬂux, 3 h (86%); (ii) SnCl₄,

DCM, −78 °C, 5 min, RCHO, −78 °C, 1 h (2a, 73%; 2b, 72%; 2c,

47%); (iii) SnCl₄, −78 °C, 5 min, PhLi, cyclohexane–ether, −78 °C, 2 h

(64%; 9 : 24 = 90 : 10); (iv) NaOAc, H₂O, TsNHNH₂, DME, heat under

reﬂux 4 h (72%; 10 : 25 = 90 :10).

Fig. 1 The structure of the 4-bromobenzoate 20 as established by

X-ray diffraction.^4a

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Fig. 2 The generation and reactions of allyltin trichlorides from 5-sub-

stituted-4-methylpent-2-enylstannanes.

Scheme 2 Conﬁrmation of the conﬁgurations of allyltin trichlorides

generated by transmetallation of 5-substituted 4-methylpent-2-enyl(tri-

phenyl)stannanes 14 and 15 by tin(^IV) chloride. Reagents and con-

ditions; (i) Ph₃SnH, AIBN (cat.), benzene, heat under reﬂux, 3 h (61%);

(ii) TBAF, THF, 0 °C to r.t., 4 h (74%); (iii) SnCl₄, DCM, 5 min,

−78 °C, then PhLi, −78 °C, 2 h (16, 61%; 17, 42%; anti : syn = 85 : 15);

(iv) NaOAc, H₂O, TsNHNH₂, DME, heat under reﬂux 4 h (18, 64%; 19,

74%); (v) TBSCl, imid., DCM, r.t., 20 h (86%); (vi) KO^tBu, THF, r.t.,

15 min, BnBr, TBAI, r.t., 15 h (48%); (vii) Et₃N, DMAP (cat.),

4-BrC₆H₄COCl, r.t., 3 h (77%).

O-Benzylation of the hydroxypent-3-ylstannane 19 gave the

benzyl ether 10 shown to be identical to the product prepared

from the 5-benzyloxypentenylstannane 8. O-Silylation of the alcohol

19 gave the TBS ether 18 prepared from the TBS-stannane 14.

These correlations established the structures of the triphenylstan-

nanes 9, 16 and 17 prepared from the allyltin trichlorides gener-

ated from the pent-2-enylstannanes 8, 14 and 15, see Scheme 2.

The stereoselective formation of the pent-1-en-3-ylstannanes

9, 16 and 17 in these trapping experiments is consistent with

stereoselective transmetallation of the 5-substituted pent-2-enyl-

stannanes 8, 14 and 15 by tin(^IV) chloride to generate an allyltin

trichloride, generic structure 21, in which the vinyl and methyl

substituents are trans-disposed about the 5-membered ring

formed by coordination of the electron deﬁcient tin by the

alkoxy group, see Fig. 2. The allyltin trichloride 21 can then

react with an aldehyde, possibly via the chair-like transition

structure 22, to give (3Z)-1,5-anti-alkenols 2 or be trapped by

reaction with the phenyllithium, with retention of the pentenyl

carbon–tin bond, to give the internal triphenylallylstannanes 9,

16 and 17.

These studies support the participation of the (3RS,4SR)-allyl-

tin trichlorides 21 in the tin(^IV) chloride promoted reactions of

5-substituted 4-methylpent-2-enylstannanes with aldehydes but

at this stage it was not clear whether they were being formed

stereoselectively by a kinetically controlled transmetallation or

whether they were the more reactive components of mixtures of

rapidly equilibrating allyltin trichlorides. However, the trapped

products 9, 16 and 17 are themselves allylstannanes and so it

was decided to investigate transmetallation of the internal allyl-

stannane 9 and reactions of the resulting allyltin trichloride.

Scheme 3 Transmetallation of the (3RS,4SR)-5-benzyloxy-4-methyl-

pent-1-en-3-yl(triphenyl)stannane 9. Reagents and conditions: (i) SnCl₄,

−78 °C, 2 min, then RCHO, −78 °C, 1 h (23a/2a, 44%, 23a : 2a =

75 : 25; 23b/2b, 21%, 23b : 2b = 60 : 40; 23c/2c, 60%, 23c : 2c =

82 : 18); (ii) SnCl₄, −78 °C, 2 min, then PhLi, −78 °C, 2 h (54%, 24 : 9

= 80 : 20); (iii) NaOAc, H₂O, TsNHNH₂, DME, heat under reﬂux 4 h

(58%); (iv) DEAD, Ph₃P, 4-O₂NC₆H₄CO₂H, toluene, −60 °C to r.t.,

20 h (26, 41%; 27, 53%); (v) NaOH, MeOH, r.t., 3 h (23b, 64%; 23c,

63%).

The stereoselectivity of the reaction of pentenylstannane 9

with tin(^IV) chloride at −78 °C and benzaldehyde was found to

depend on the time allowed before addition of the aldehyde.

With a short transmetallation time of 2 or 5 min, the major

product was the (3Z)-1,5-syn-isomer 23a, ratio 23a : 2a =

80–70 : 20–30, see Scheme 3. If the reaction mixture was

allowed to stand for longer at −78 °C before addition of the ben-

zaldehyde, then the stereoselectivity was reversed, e.g. allowing

10 min at −78 °C before addition of the benzaldehyde led to

selectivity for the 1,5-anti-epimer 2a, ratio 23a : 2a = 20 : 80.

This preference for formation of a (3Z)-1,5-syn-isomer when

2 min was allowed for the transmetallation, was also observed

for reactions of the stannane 9 with 2-methylpropanal and propa-

nal, see Scheme 3.

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Structures were assigned to the major products 23b and 23c

by comparison with samples prepared from the known (3Z)-1,5-

anti-epimers 2b and 2c^2avia saponiﬁcation of the inverted

4-nitrobenzoates 26 and 27 prepared using Mitsunobu reactions;

the (3Z)-1,5-syn-epimer 23a was a known compound.^2a

phenyllithium were derived from the phenyllithium and not from

the anti-triphenylstannane 9, the analogous anti-(trimethyl)stan-

nane 30 was prepared from the 5-benzyloxypent-2-enylstannane

8 using methyllithium to intercept the allyltin trichloride. Only a

modest yield of the anti-epimer 30 was isolated, its conﬁguration

being assigned by analogy with the formation of 9. Transmetalla-

tion of the (trimethyl)stannane 30 using tin(^IV) chloride with

trapping using phenyllithium gave the syn-triphenylstannane 24

together with some of the anti-epimer 9, so conﬁrming that the

phenyl moieties in stannane 24 were derived from the phenyl-

lithium and not from the starting allylstannane, see Scheme 4.

Although the original objectives of this work had been

achieved, there remained an explanation as to why transmetalla-

tion of the anti-pent-1-en-3-yl(triphenyl)stannane 9 gave rise

predominantly to the syn-pent-1-en-3-yltin trichloride 28, a reac-

tion that is the equivalent of an ipso replacement of the tin with

inversion of conﬁguration at the more hindered end of the allyl

moiety. It was therefore decided to study transmetallation of the

third available isomeric allylstannane, the syn-pent-1-en-3-yl(tri-

phenyl)stannane 24.

In the event, the syn-pent-1-en-3-ylstannane 24, after trans-

metallation using tin(^IV) chloride for 5 min, gave the 1,5-syn-

alkenol 23a as the major product with benzaldehyde, ratio

23a : 2a = 80 : 20. Trapping the allyltin trichloride with phenyl-

lithium in this case was a little capricious, but typically mixtures

of the syn- and anti-pent-1-en-3-yl(triphenyl)stannanes 24 and 9

were obtained with the syn-epimer predominating, see Scheme 5.

This suggests that the syn-allyltin trichloride 28 is the major

product of transmetallation of both the anti- and syn-stannanes 9

and 24. Both of these reactions correspond to an ipso substi-

tution of the triphenylstannyl group, one with inversion, one

with predominant retention.

The formation of the 1,5-syn-epimers 23 in these reactions of

the pentenylstannane 9 contrasts with the highly selective for-

mation of the 1,5-anti-epimers 2a–c from the terminal triphenyl-

stannanes 1 and 8 and suggests that a diastereoisomeric allyltin

trichloride is involved. This was investigated by treatment of the

internal allylstannane 9 with tin(^IV) chloride at −78 °C for 2 min

followed by addition of an excess of phenyllithium. The major

product from this reaction was the syn-3-(triphenylstannyl)pent-

1-ene 24 together with the anti-epimer 9 as a minor component,

ratio 24 : 9 = 80 : 20. These products could not be separated but

were identiﬁed from spectroscopic data and by comparison of a

sample of the anti-epimer 9 prepared earlier. Again to prevent

1,3-migration of the tin, the mixture of internal stannanes 24 and

9 was reduced using diimide to give the corresponding syn-pen-

tylstannane 25 containing ca. 20% of its anti-epimer 10, see

Scheme 3.

This work showed that the anti- and syn-epimers 9 and 24 can

be distinguished spectroscopically so conﬁrming that the anti-

epimer 9 had been obtained stereoselectively when the allyltin

trichloride generated by transmetallation of the terminal pent-

2-enylstannane 8 was trapped by phenyllithium. Moreover, the

formation of the (3Z)-1,5-syn-products 23a–c and the syn-triphe-

nylstannane 24 from tin(^IV) chloride mediated reactions of the

anti-pentenylstannane

9 is consistent with the epimeric

(3SR,4SR)-allyltin trichloride 28 being involved, the formation

of the 1,5-syn-products 23 from reactions with aldehydes being

compatible with participation of transition structure 29, see

Fig. 3. Since the epimeric allyltin trichlorides 21 and 28 give

rise to different products, these allyltin trichlorides cannot be

equilibrating substantially during their reactions with aldehydes

at −78 °C unless the transmetallation time is prolonged. The

high selectivity for formation of the (3Z)-1,5-anti-products 2 in

the tin(^IV) chloride mediated reactions of the 5-alkoxy-4-methyl-

pent-2-enylstannanes 1 and 8 must therefore be due to kinetic

control of the stereoselectivity of transmetallation.

Scheme 4 Trapping an allyltin trichloride using methyllithium.

Reagents and conditions: (i) SnCl₄, −78 °C, 5 min, then MeLi, −78 °C,

2 h (20%); (ii) SnCl₄, −78 °C, 2 min, PhLi, −78 °C, 2 h (54%; 24 : 9 =

60 : 40).

To check that the phenyl substituents of the internal syn-tri-

phenylstannane 24 prepared from the allyltin trichloride 28 and

Scheme 5 Tin(IV) chloride mediated reactions of the (3S,4S)-pent-1-

en-3-yl(triphenyl)stannane 24. Reagents and conditions: (i) SnCl₄,

DCM, −78 °C, 3 min, then PhCHO, −78 °C, 1 h (42%, 23a : 2a =

80 : 20); (ii) SnCl₄, −78 °C, 5 min, PhLi, −78 °C, 2 h (44%, 24 : 9 =

66 : 34).

Fig. 3 The generation and reactions of the allyltin trichloride 28

derived from the anti-5-benzyloxy-4-methylpent-1-en-3-yl(triphenyl)-

stannane 9.

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Trapping alkenyltin trichlorides in the 4-alkoxypent-

2-enylstannane series

(Z)-pent-2-ene using triphenylstannyllithium gave mixtures of

the regioisomeric hydroxypentylstannanes 41/42 and 45/38.

Their structures were assigned spectroscopically and their

conﬁgurations on the basis that analogous epoxide ring openings

are known to proceed with inversion of conﬁguration.⁹The

syn-2-hydroxypent-3-yl(triphenyl)stannane 38 obtained from

the (Z)-pent-2-ene oxide 44 was identical to that obtained from

the trapping of the allyltin trichloride generated from the

4-hydroxypent-3-enylstannane 34 after reduction using diimide.

Moreover, O-benzylation gave the benzyl ether 39 identical to

that obtained from the transmetallation and trapping using the

4-benzyloxypent-2-enylstannane 35. The 2-hydroxy- and 2-ben-

zyloxy-pent-3-enyl(triphenyl)stannanes 42 and 43 obtained from

the epoxide derived from the (E)-pent-2-ene oxide 40 were

signiﬁcantly different spectroscopically from their isomers 38

and 39 (¹H NMR), see Scheme 7.

The stereoselective formation of the internal triphenylstan-

nanes 36 and 37 from interception of the allyltin trichlorides

generated from the 4-hydroxy- and 4-benzyloxypent-2-enylstan-

nanes 34 and 35 on treatment with tin(^IV) chloride is consistent

with the allyltin trichlorides having the syn-conﬁguration as indi-

cated in structure 46, see Fig. 4. Trapping the allyltin trichlorides

46 by phenyllithium with retention of conﬁguration of the stereo-

genic tin-bearing centre would then give the observed syn-

The racemic hydroxy- and 4-benzyloxypent-2-enyl(triphenyl)-

stannanes 34 and 35 were prepared by reaction of the allylsul-

fones 32 and 33 with triphenyltin hydride under free radical

conditions. The allylic sulfone 32 was prepared as a mixture of

diastereoisomers by addition of lithiated propenyl phenyl sulfone

31 to ethanal. O-Benzylation gave the corresponding benzyl

ether 33. The tin(^IV) chloride mediated reaction of the 4-benzyl-

oxypentenylstannane 35 with benzaldehyde proceeded as

expected to give the known^2b(3Z)-1,5-syn-hex-3-enol 5a with

excellent stereoselectivity, 1,5-syn : 1,5-anti = 97 : 3 (¹H NMR),

see Scheme 6.

Trapping the allyltin trichlorides generated by treatment of

both the 4-hydroxy- and 4-benzyloxy-pent-2-enylstannanes 34

and 35 with phenyllithium was highly stereoselective and gave

the syn-pent-1-en-3-ylstannanes 36 and 37 containing less than

5% of any other isomer. Diimide reduction of these pentenyl-

stannanes gave the pent-3-ylstannanes 38 and 39, the 2-benzy-

loxypent-3-ylstannane 39 also being obtained by O-benzylation

of the hydroxystannane 38.

The structures of the products 36–39 were consistent with

spectroscopic data but it remained to conﬁrm their conﬁgur-

ations. Attempts to prepare crystalline derivatives by esteriﬁca-

tion of the 2-hydroxypent-3-ylstannane 38 were unsuccessful.

Recovered starting material was invariably obtained perhaps

because of steric hindrance to functionalization of the alcohol. It

was therefore decided to prepare authentic samples of the pro-

ducts 38 and 39 by a stereochemically deﬁned path. Ring-

opening of the epoxides 40 and 44⁸prepared from (E)- and

Scheme 7 Stereoselective synthesis of 2-hydroxy- and 2-benzyloxy-

pent-3-yl(triphenyl)stannanes. Reagents and conditions: (i) LiNⁱPr₂,

THF, hexanes, −78 °C, add Ph₃SnH, −78 °C, 1 h, add epoxide, −10 °C

to r.t., 4 h (41, 30%; 42, 19%; 45, 22%; 38, 23%); (ii) NaH, THF, BnBr,

TBAI, r.t., 15 h (43, 61%; 39, 72%).

Scheme 6 Synthesis and tin(IV) chloride mediated reactions of the

4-hydroxy and 4-benzyloxypent-2-enylstannanes 34 and 35. Reagents

and conditions: (i) BuLi, −78 °C, 15 min, ethanal, −78 °C, 1 h (91%); (ii)

BnOC(NH)CCl₃, TFA, r.t., 18 h (91%); (iii) Ph₃SnH, AIBN (cat.),

benzene, heat under reﬂux, 3 h (34, 56%; 35, 42%); (iv) SnCl₄, −78 °C,

5 min, then PhCHO, −78 °C, 1 h (66%; 1,5-syn : 1,5-anti = 97 : 3); (v)

SnCl₄, −78 °C, 5 min, PhLi, −78 °C, 1 h (36, 35%; 37, 54%); (vi)

NaOAc, H₂O, TsNHNH₂, DME, heat under reﬂux (38, 69%; 39, 68%);

(vii) NaH, THF, r.t., 1 h, then BnBr, TBAI, r.t., 15 h (63%).

Fig. 4 Outline mechanism for the generation and reactions of allyltin

trichlorides from 4-hydroxy- and 4-benzyloxypent-2-enyl(triphenyl)-

stannanes 34 and 35.

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triphenylstannanes 36 and 37, and reaction with an aldehyde,

possibly via the chair-like transition structure 47, would give rise

to the observed (3Z)-1,5-syn-products 5.

shifts of the allyltin trichlorides generated by transmetallation of

the alkoxypent-2-enylstannanes to see whether they were consist-

ent with co-ordination of the tin by the alkoxy groups.^12,13

Transmetallation of prop-2-enyl(tributyl)- and -(triphenyl)-stan-

nanes 56 and 59 gave prop-2-enyltin trichloride 57 and either tri-

butyltin chloride 58 or triphenyltin chloride 60 with ¹¹⁹Sn

chemical shifts similar to those in the literature,^12,14,15see Fig. 5.

The ¹¹⁹Sn chemical shifts observed for the 5-benzyloxy-4-

methylpent-2-enyl(tributyl)- and -(triphenyl)-stannanes 1 and 8

were similar to those of the prop-2-enylstannanes 56 and 59,

respectively, indicating that, as would be expected, no signiﬁcant

co-ordination of the benzyloxy group to the tin in these benzyl-

oxypentenylstannanes. The two peaks observed for the pentenyl-

stannanes 1 and 8 were attributed to the presence of both (E)-

and (Z)-isomers, (E) : (Z) ca. 70 : 30 and the shielding effect of

the phenyl groups over the butyl groups is consistent with that

observed for the simple prop-2-enyl(triphenyl)- and -(tributyl)-

stannanes 56 and 59. However, transmetallation of the 5-benzy-

loxypent-2-enyl(tributyl)- and (triphenyl)-stannanes 1 and 8

using tin(^IV) chloride gave rise to a new ¹¹⁹Sn peak at δ −197

that was assigned to the intermediate allyltin trichloride 21a. The

signiﬁcant shielding observed for this intermediate relative to

that of prop-2-enyltin trichloride 57, δ −36, was attributed to co-

ordination of the electron deﬁcient tin by the benzyloxy-substitu-

ent.¹¹Similarly transmetallation of the 4-benzyloxypent-2-enyl

(triphenyl)stannane 35 gave rise to an intermediate with a ¹¹⁹Sn

chemical shift of δ −149 attributed to the co-ordinated allyltin

trichloride 46a.

In the 4-alkoxypent-2-enylstannane series, reactions of the

4-tert-butyldimethylsilyloxypent-2-enylstannane 48 with benz-

aldehyde and imines differed from the analogous reactions of the

4-benzyloxypentenylstannane 4 in that the (3E)-1,5-anti-isomer

49 was the major product with benzaldehyde¹⁰and the (4E)-2,6-

syn-epimers 50 predominated with imines,³albeit in pretty non-

stereoselective reactions. It was therefore decided to attempt to

trap the allyltin trichlorides generated from a 4-silyloxypent-2-

enylstannane.

O-Silylation of the 4-hydroxypent-2-enyl(triphenyl)stannane

34 gave the tert-butyldimethylsilyl ether 51. Following transme-

tallation using tin(^IV) chloride and subsequent addition of phenyl-

lithium, an approximately 50 : 50 mixture of the two internal

pent-1-en-3-yl(triphenyl)stannanes 52 and 53 was obtained, see

Scheme 8. The structures of these products were conﬁrmed by

hydrogenation using diimide and desilylation of the resulting

pent-3-ylstannanes 54 and 55 which gave the known 2-hydroxy-

pent-3-ylstannanes 42 and 38. This shows that in the case of

4-(tert-butyldimethylsilyloxy)pent-2-enylstannanes the initial transme-

tallation is pretty non-stereoselective perhaps because the O-silyloxy

substituent is not involved directly in delivering the trichlorotin

substituent to the double-bond of the pent-2-enylstannane.

1

These H NMR studies are consistent with pentaco-ordinated

tin trichlorides being involved in the reactions of the benzyloxy-

pent-2-enylstannanes 1, 8 and 35.^11,16The tin in the proposed

four-membered ring intermediate 46a, δ −149, is deshielded

¹¹⁹Tin NMR studies

¹¹⁹Tin chemical shifts are very sensitive to the environment of

the tin.¹¹It was therefore of interest to study the ¹¹⁹tin chemical

Scheme 8 Trapping the allyltin trichlorides formed from the 4-(tert-

butyldimethylsilyloxy)pent-2-enyl(triphenyl)stannane 51. Reagents and

conditions: (i) SnCl₄, −78 °C, 5 min, PhLi, −78 °C, 1 h (80%; 52 : 53 =

50 : 50); (ii) NaOAc, H₂O, TsNHNH₂, DME, heat under reﬂux 4 h

(77%); (iii) TBAF, THF, r.t., 3 h (42, 12%; 38, 26%).

Fig. 5 ¹¹⁹Tin NMR studies (chemical shifts in parentheses).

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relative to that in the proposed ﬁve-membered ring intermediate

21a, δ −197, consistent with the effect of ring size on ¹¹⁹Sn

chemical shifts.¹¹

5-alkoxypent-2-enylstannanes 8 must be due primarily to kinetic

control, and the same is inferred for the stannane 35, see Fig. 6.

The co-ordinated structures with trigonal bipyramidal tin indi-

cated in structures 21 and 46 are consistent with the ¹¹⁹Sn NMR

data.¹¹Although dimeric structures that would avoid the for-

mation of the four-membered ring shown in structure 21 can also

be envisaged, the phenyllithium trapping experiments establish

the conﬁguration of the tin-bearing carbon in the intermediate

allyltin trichlorides and it is the conﬁguration at this centre that

determines the stereoselectivity of reactions with aldehydes (and

imines).

The generation of the (3RS,4RS)-5-benzyloxy-4-methylpent-

1-enyltin trichloride 28 from both epimers 9 and 24 of 5-ben-

zyoxy-4-methylpent-1-enyl(triphenyl)stannane was unexpected

since these reactions involve ipso electrophilic substitutions, one

with inversion and one with retention, at the more hindered end

of an allylic system. It is possible that both of these reactions are

SE′ type processes that generate a terminal allyltin trichloride

that rapidly undergoes an allylic rearrangement to give the

internal (3RS,4RS)-pent-1-enyltin trichloride 28. With this in

mind an outline summarising all of the transmetallations in the

5-benzyloxypentenylstannane series is suggested in Fig. 7. The

initial transmetallation of the 5-benzyloxy-4-methylpent-2-enyl-

stannane 8 gives the (3RS,4SR)-pent-1-en-3-yltin trichloride 21a

with excellent stereoselectivity by a kinetically controlled

process. This then reacts with aldehydes to give the (3Z)-1,5-

anti-products 2 with good overall stereoselectivity possibly by

the transition structure 22 shown in Fig. 2. Trapping the tin tri-

chloride 21a using phenyllithium gives the anti-pent-1-en-3-yl-

(triphenyl)stannane 9. This may be transmetallated by tin(^IV)

chloride via an SE′ process to give the unstable 5-benzyloxy-

pent-2-enyltin trichloride 61 which rapidly rearranges, with

reasonable stereoselectivity, to give the (3RS,4RS)-pent-1-en-3-

yltin trichloride 28. In turn, this reacts with aldehydes to give the

(3Z)-1,5-syn-products 23, possibly via transition structure 29, see

Fig. 3, or is trapped by phenyllithium to give the syn-pent-1-en-

3-ylstannane 24. Transmetallation of this syn-pent-1-en-3-

Summary and conclusions

The reactions of the intermediate allyltin trichlorides prepared

from 5- and 4-benzyloxypent-2-enylstannanes 8 and 35 with

phenyllithium gave the pent-1-en-3-yl(triphenyl)stannanes 9 and

37 stereoselectively. Since the pentenyl carbon–tin bond in the

allyltin trichlorides is retained in these reactions, this work

conﬁrmed the conﬁgurations of the intermediate allyltin trichlo-

rides shown in structures 21a and 46a that had been postulated

on the basis of the stereoselectivities of their reactions with alde-

hydes. Moreover, since the pent-1-en-3-yltin trichloride 28, gen-

erated from the internal pent-1-en-3-ylstannanes 9 and 24 gave

different products with both aldehydes and phenyllithium from

those obtained from the pent-1-en-3-yltin trichloride 21a,

the stereoselectivity of the initial transmetallation of the

Fig. 6 Summary of trapping allyltin trihalides.

Fig. 7 Outline scheme for tin(IV) chloride promoted reactions in the 5-pentenyl(triphenyl)stannane series.

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ylstannane again delivers the unstable primary allyltin trichloride

61 which rearranges into the (3S,4S)-pent-1-en-3-yltin trichloride

28 hence providing moderately stereoselective access to the

(Z)-1,5-syn-products 23 on reaction with aldehydes and returning the

syn-pent-1-en-3-ylstannane 24 when trapped by phenyllithium.¹⁷

In Fig. 7 it is suggested that the primary allyltin trichloride 61

isomerises to the (3RS,4RS)-pent-1-en-3-yltin trichloride 28 rela-

tively rapidly but that equilibration of the (3RS,4SR)- and

(3RS,4RS)-pent-1-en-3-intermediates 21a and 28 is relatively

slow. The evidence for this is that no 5-benzyloxy-4-methylpent-

2-enyl(triphenyl)stannane 62 was isolated on trapping the inter-

mediates from the transmetallation of the internal triphenylstan-

nanes 9 and 24 and that the epimeric allyltin trichlorides 21a

and 28 give rise to substantially different products. However,

there would appear to be some leakage from the (3RS,4RS)-

epimer 28 to the (3RS,4SR)-epimer 21a on standing as indicated

by the reversal in stereoselectivity with aldehydes when the

transmetallation time for the reaction of the anti-pentenylstan-

nane 9 was increased. Indeed it looks as if an equilibrium

mixture is ca. 75 : 25 in favour of the (3RS,4SR)-epimer 21a, but

this is only an estimate.^17,18

Both antarafacial and suprafacial processes can be envisaged

for the transmetallation of allylstannanes with tin(^IV) chloride.

However, the selective formation of the (3RS,4SR)-epimer 21a

from the pent-2-enylstannane 8 is consistent with the preferred

reaction taking place via either the antarafacial transition struc-

ture 63, in which the 4-methyl substituent is in the less hindered

exo-position, or the suprafacial transition structure 64 with the

4-methyl in the preferred pseudo-equatorial position. For

the alternative transition structures 65 and 66 that would give the

(3RS,4RS)-allyltin trichloride 28, the 4-methyl group is in either

the more hindered endo or the pseudo-axial position, see

Fig. 8.^19,20

consistent with approach of the tin(^IV) chloride on the opposite

face of the 7-membered ring present in the co-ordinated allyltin

trichloride 61 to the allylic methyl substituent. A suprafacial

process via transition structure 67 for this is outlined in Fig. 9.²²

The effect of an OTBS substituent on the stereoselectivity of

transmetallation appears to vary according to its position in the

pent-2-enylstannane. In the 5-position, there is a small attenu-

ation on the 1,5-anti-stereocontrol,⁷whereas in the 4-position, an

OTBS group delivers low stereoselectivity that if anything is

reversed from that observed for 4-O-alkoxypent-2-enylstan-

nanes.¹⁰It would appear that the bulky OTBS group is less

effective at co-ordinating to the electron deﬁcient tin in the allyl-

tin trichloride intermediates and that this is more pronounced in

the more compact 4-alkoxy series.

The mechanism of the reactions of allyltin trichlorides with

aldehydes has not been studied. However, the high preference

for cis-alkenol formation observed for tin(^IV) halide mediated

reactions of 4-, 5- and 6-substituted alk-2-enylstannnanes with

aldehydes shows that the length of the tether connecting the

alkoxy group does not appear to be critical in establishing cis-

alkenol formation.¹Thermal reactions of 1-substituted but-2-

enylstannanes with aldehydes are known to give (Z)-alk-3-enols,

and six-membered chair-like transition structures in which the

group next to tin is axial have been postulated to rationalise this

stereoselectivity.²³For this reason, transition structures with

penta-co-ordinated tin have been postulated for the reactions of

the allyltin trichlorides 21, 28 and 46 with aldehydes, see

Fig. 2–4. However, the formation of cis-hex-3-enols from

4-alkoxypent-2-enylstannanes is also consistent with partici-

pation of a transition structure with octahedral tin^24,25so this

question remains to be resolved.

Experimental

The selective isomerisation of the terminal allyltin trichloride

61 into the (3RS,4RS)-pent-1-en-3-yltin trichloride 28 is

General experimental procedures

¹H NMR and ¹³C NMR spectra were recorded on Bruker

AC-300, Varian Inova or Varian Gemini 200 spectrometers.

Coupling constants are given in Hz. ¹¹⁹Sn NMR spectra

(112 MHz) were recorded at −80 °C in a 5 mm NMR tube using

0.15 mmol of substrate in 0.7 mL CD₂Cl₂. Chemical shifts are

relative to TMS.

IR spectra were recorded on an ATI Mattson Genesis Series

FTIR spectrometer as a thin ﬁlm produced by evaporation of a

chloroform solution on a sodium chloride plate. Low resolution

chemical ionisation (C.I.) and electron impact (E.I.) mass spectra

were recorded on a Fisons TRIO 2000 quadrupole mass spec-

trometer. High resolution mass spectra were recorded on a

Kratos Concept-1S mass spectrometer coupled to a Mach 3 data

system. Compounds containing tin showed characteristic clusters

of peaks in their mass spectra, only those corresponding to ¹²⁰Sn

are quoted.

Fig. 8 Possible transition structures for transmetallation of the 5-ben-

zyloxypent-2-enylstannane 8.

All optical rotations were recorded at ambient temperature on

an Optical Activity AA-100 polarimeter at 589 nm, using chloro-

form as the solvent.

Capillary gas chromatography was carried out on a Perkin-

Elmer 8320 using a 25 m × 0.32 mm (ID) of CP-Sil-cB (OV-1),

carrier gas He, split injection technique at 700 : 1 split ratio and

FID detection. Chromatography refers to ﬂash chromatography

Fig. 9 Stereoselective isomerisation of the primary tin trichloride 61

into the secondary tin trichloride 28.

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and was performed using Merck silica gel 60H (40–63 m,

230–300 mesh) as the stationary phase. Thin layer chromato-

graphy was performed using Machery Nagel DC-Fertigplatten

SIL G-25 UV₂₅₄silica gel glass plates. Visualisation was by

ultraviolet absorption at 254 nm and by treatment with 10% w/v

methanolic dodecamolybdophosphoric acid followed by heating.

Light petroleum refers to the fraction of petroleum ether

which boils between 40 °C and 60 °C and was redistilled prior

to use. Tetrahydrofuran was dried over sodium–benzophenone

and distilled under an atmosphere of nitrogen. DCM was dried

over calcium hydride and distilled under an atmosphere of nitro-

gen. Ether refers to diethyl ether and was dried over sodium

wire. Benzene and toluene were dried over sodium wire. Tri-

ethylamine and diisopropylamine were dried over potassium

hydroxide pellets. All other commercially available reagents

were puriﬁed following standard procedures.

(1%) as eluent gave the title compound 8 (4.52 g, 86%) as a col-

ourless oil, (E) : (Z) = 85 : 15 (¹H NMR) [α]_D+3.8 (c 0.73,

CHCl₃) (Found: M⁺, 540.1479. C₃₁H₃₂O¹²⁰Sn requires M,

540.1475); ν_max/cm⁻¹2924, 1480, 1453, 1428, 1094, 1075, 727

and 697; δ_H(300 MHz, CDCl₃) (E)-isomer 1.05 (3 H, d, J 7, 4-

CH₃), 2.54 (3 H, m, 1-H₂and 4-H), 3.24 (1 H, dd, J 7, 10, 5-H),

3.35 (1 H, dd, J 7, 10, 5-H), 4.54 and 4.60 (each 1 H, d, J 11,

HCHPh), 5.46 (1 H, dd, J 7, 15, 3-H), 5.86 (1 H, dt, J 15, 8, 2-

H) and 7.35–7.72 (20 H, m, ArH); (Z)-isomer 0.93 (3 H, d, J 7,

4-CH₃), 2.88 (1 H, m, 4-H), 4.46 and 4.50 (each 1 H, d, J 11,

HCHPh) and 5.15 (1 H, t, J 10.5, 3-H); δ_C(75 MHz, CDCl₃)

(E)-isomer 16.3, 17.5, 37.0, 72.9, 75.7, 127.2, 128.5, 128.6,

129.1, 131.0, 137.2, and 138.8; m/z (E.I.) 540 (30%), 463 (50),

351 (90) and 49 (100).

General procedure for trapping the intermediate allyltin

trichlorides: (3R,4S)-5-benzyloxy-4-methylpent-1-en-3-yl-

(triphenyl)stannane 9

General procedure for the tin(IV) halide promoted reactions of

allylstannanes with aldehydes: (1S,5R,3Z)-6-benzyloxy-5-methyl-

l-phenylhex-3-en-l-ol 2a^2a

Tin(IV) chloride (1.85 mL, 1.0 M in DCM, 1.85 mmol) was

added to the stannane 8 (1.0 g, 1.85 mmol) in DCM (10 mL) at

−78 °C. After 5 min, phenyllithium (6.16 mL, 1.8 M in

cyc1ohexane : ether, 11.1 mmol) was added and the solution

stirred at −78 °C for 2 h. Saturated ammonium chloride was

added at −78 °C and the mixture allowed to warm to room temp-

erature. After extraction with ether, the extracts were dried

(MgSO₄) and concentrated under reduced pressure. Chromato-

graphy of the residue using hexane : ether (50 : 1) and triethyl-

amine (1%) as eluent afforded the title compound 9 (0.64 g,

64%), as a colourless oil, containing ca. 10% of its syn-epimer

24 (¹H NMR) [α]_D−3.7 (c 1.17, CHCl₃) (Found: M⁺, 540.1473.

C₃₁H₃₂O¹²⁰Sn requires M, 540.1475); ν_max/cm⁻¹2922, 1480,

1453, 1428, 1092, 1074, 997, 841, 728 and 692; δ_H(300 MHz,

CDCl₃) major anti-epimer 9 1.12 (3 H, d, J 7, 4-CH₃), 2.46

(1 H, septet, J 7, 4-H), 3.15 (1 H, dd, J 6, 11, 3-H), 3.40 (2 H, d,

J 6, 5-H₂), 4.25 and 4.32 (each 1 H, d, J 11, HCHPh), 4.96 (2 H,

m, 1-H₂), 6.14 (1 H, dt, J 10, 16, 2-H) and 7.21–7.66 (20 H, m,

ArH); minor syn-epimer 24 3.03 (1 H, m, 3-H) and 4.30 (2 H, s,

CH₂Ph); δ_C(75 MHz, CDCl₃) 17.6, 35.5, 40.0, 72.8, 75.0,

112.8, 127.5, 127.7, 128.3, 128.4, 128.7, 137.3, and 139.6; m/z

(E.I.) 540 (20%), 351 (60) and 91 (100).

Tin(IV) chloride (0.185 mL, 1.0 M in DCM, 0.185 mmol) cooled

to −78 °C was added to the stannane 8 (0.10 g, 0.185 mmol) in

DCM (2 mL) at −78 °C. After 5 min, benzaldehyde (0.20 mL,

1.0 M in DCM, 0.20 mmol) cooled to −78 °C was added and

the mixture stirred at −78 °C for 1 h. Saturated aqueous sodium

hydrogen carbonate (2 mL) was added and the mixture allowed

to warm to room temperature then partitioned between DCM

(25 mL) and water (25 mL). The organic phase was washed with

water (15 mL) and brine (15 mL) then dried (MgSO₄). After

concentration under reduced pressure, chromatography of the

residue using hexane : ether, (3 : 1) as eluent gave the title com-

pound 2a^2a(40 mg, 73%) as a colourless oil (Found: M⁺,

296.1781. C₂₀H₂₄O₂requires M, 296.1776).

(3R,7S,5Z)-8-Benzyloxy-2,7-dimethyloct-5-en-3-ol 2b.^2aFol-

lowing the general procedure, stannane 8 (0.10 g, 0.185 mmol),

tin(^IV) chloride (0.185 mL, 0.185 mmol) and 2-methylpropanal

(0.20 mL, 0.20 mmol), after chromatography using hexane :

ether (3 : 1) as eluent gave the title compound 2b^2a(35 mg,

72%), as a colourless oil (Found: M⁺, 263.2007. C₁₇H₂₆O₂

requires M, 263.2011).

(2RS,6SR,5Z)-8-Benzyloxy-7-methyloct-5-en-3-ol

2c.^2aFol-

General procedure for reduction of pent-1-en-3-ylstannanes:

(2S,3R)-1-benzyloxy-2-methylpent-3-yl(triphenyl)stannane 10

lowing the general procedure, stannane 8 (0.416 g, 0.77 mmol),

tin(^IV) chloride (0.77 mL, 0.77 mmol) and propanal (0.92 mL,

0.92 mmol), after chromatography using hexane : ether (3 : 1) as

eluent gave the title compound 2c^2a(90 mg, 47%), as a colour-

less oil (Found: M⁺+ NH₄, 266.2119. C₁₆H₂₈NO₂requires M,

266.2119).

Sodium acetate (1.73 g, 20.60 mmol) in water (12 mL) was

added to the pent-1-enylstannane 9 (0.56 g, 1.03 mmol) and

toluene 4-sulfonylhydrazide (2.30 g, 12.36 mmol) in DME

(40 mL) under reﬂux over a period of 2 h. The solution was

heated under reﬂux for a further 2 h and then allowed to cool to

room temperature. The reaction mixture was extracted with ether,

dried (MgSO₄) and concentrated under reduced pressure. Chrom-

atography of the residue using light petroleum : ether (50 : 1) and

triethylamine (1%) as eluent yielded the title compound 10

(0.40 g, 72%), as a colourless oil, as a 90 : 10 mixture of 10 and

25 (¹H NMR) [α]_D−9.3 (c 0.56, CHCl₃) (Found: M⁺− Ph,

465.1245. C₂₅H₂₉O¹²⁰Sn requires M, 465.1240); ν_max/cm⁻¹

2924, 1480, 1453, 1427, 1073, 1022, 997, 728 and 698; δ_H

(4R,2E)-5-Benzyloxy-4-methylpent-2-enyl(triphenyl)stannane 8

Triphenyltin hydride (4.17 g, 11.88 mmol) and α-azo-bis-isobu-

tyronitrile (5 mg, cat.) were added to a thoroughly degassed solu-

tion of the dithiocarbonate 7^2a(2.9 g, 9.78 mmol) in benzene

(150 mL) and the solution heated under reﬂux for 3 h. After con-

centration under reduced pressure, chromatography of the

residue using light petroleum : ether (50 : 1) and triethylamine

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(300 MHz, CDCl₃) anti-epimer 10 1.09 (6 H, m, 5-H₃, 2-CH₃),

1.95 (2 H, m, 4-H₂), 2.28 (1 H, dd, J 7, 3, 3-H), 2.47 (1 H, m,

2-H), 3.44 (2 H, d, J 6, 1-H₂), 4.30 (2 H, s, CH₂Ph), and

7.20–7.73 (20 H, m, ArH); syn-epimer 25 3.31 (2 H, d, J 6,

1-H₂); δ_C(75 MHz, CDCl₃) 15.2, 17.9, 22.3, 35.3, 36.6, 72.7,

74.5, 127.5, 127.8, 128.3, 128.4, 137.5 and 141.0; m/z (C.I.) 465

(70%) and 78 (100).

phenyllithium (6.73 mL, 1.8 M, in cyclohexane–ether,

12.12 mmol), after chromatography using light petroleum : ether

(50 : 1) and triethylamine (1%) as eluent, gave the title com-

pound 16 (0.69 g, 61%) as a yellow oil (Found: M⁺− C₆H₅,

487.1476. C₂₄H₃₅OSi¹²⁰Sn requires M, 487.1478); ν_max/cm⁻¹

3063, 2955, 2928, 2856, 1481, 1428, 1255, 1093, 1075, 838,

728 and 699; δ_H(300 MHz, CDCl₃) 0.03 and 0.05 (each 3 H, s,

SiCH₃), 0.96 [9 H, s, SiC(CH₃)₃], 1.08 (3 H, d, J 7, 4-CH₃),

2.31 (1 H, m, 4-H), 3.38 (1 H, dd, J 5, 11, 3-H), 3.44 and 3.59

(each 1 H, dd, J 6, 8, 5-H), 4.99 (2 H, m, 1-H₂), 6.15 (1 H, dt, J

10, 16, 2-H) and 7.40–7.74 (15 H, m, ArH); δ_C(75 MHz,

CDCl₃) −5.3, −5.2, 16.6, 18.4, 26.0, 37.7, 39.1, 68.2, 112.9,

127.2, 128.4, 128.8, 137.3 and 139.1; m/z (C.I.) 487 (22%) and

318 (100).

5-tert-Butyldimethylsilyloxy-4-methylpent-2-enyl(triphenyl)-

stannane 14

Triphenyltin hydride (21.92 g, 62.4 mmol) and α-azo-bis-isobu-

tyronitrile (50 mg) were added to a thoroughly degassed solution

of the dithiocarbonate 13^2c(16.46 g, 51.4 mmol) in benzene

(250 cm³) and the solution heated under reﬂux for 3 h. After

concentration under reduced pressure, chromatography of the

residue using light petroleum : ether (50 : 1) and triethylamine

(1%) as eluent gave the title compound 14 (17.79 g, 61%) as a

colourless oil, (E) : (Z) = 85 : 15 (¹H NMR), (Found: M⁺− Ph,

487.1489. C₂₄H₃₅OSi¹²⁰Sn requires M, 487.1478); ν_max/cm^−l

2955, 2928, 2855, 1470, 1428, 1254, 1076, 837, 776, 727, 698;

δ_H(300 MHz, CDCl₃) (E)-isomer 0.10 (6 H, s, 2 × SiCH₃), 0.96

[12 H, m, Si(CH₃)₃and 4-CH₃], 2.28 (1 H, m, 4-H), 2.46 (2 H,

d, J 7, 1-H₂), 3.24 (1 H, dd, J 8, 9, 5-H), 3.45 (1 H, dd, J 5, 9,

5-H), 5.37 (1 H, dd, J 5, 7, 3-H), 5.78 (1 H dt, J 15, 7, 2-H) and

7.40–7.63 (15 H, m, ArH); (Z)-isomer 0.83 (3 H, d, J 7, 4-CH₃),

2.63 (1 H, m, 4-H), 3.39 (1 H, dd, J 5, 9, 5-H), 5.08 (1 H, t,

J 10, 3-H); δ_C(75 MHz, CDCl₃) (E)-isomer −5.2(2), 16.3, 17.0,

18.5, 26.1, 39.5, 68.4, 128.8, 129.0, 130.9, 137.1 and 138.6;

(Z)-isomer 12.7, 17.1, 34.6, 67.7; m/z (C.I.) 565 (2%), 487 (32)

and 368 (100).

[(3RS,4SR)-2-Methyl-1-hydroxypent-4-en-3-yl](triphenyl)-

stannane 17

The general procedure using stannane 15 (1.0 g, 2.22 mmol), tin

(^IV) chloride (2.22 mL, 1 M in DCM, 2.22 mmol), and phenyl-

lithium (7.41 mL, 1.8 M in cyclohexane–ether, 13.32 mmol),

after chromatography using light petroleum : ether (3 : 1) and tri-

ethylamine (1%), gave the title compound 17 (0.42 g, 42%) as a

yellow oil containing ca. 15% of its syn-epimer (¹H NMR)

(Found: M⁺− C₆H₅, 373.0617. C_l5H₂₁O¹²⁰Sn requires M,

373.0613); ν_max/cm⁻¹3386, 3063, 2959, 2833, 1480, 1428,

1073, 1024, 997, 895, 729 and 699; δ_H(300 MHz, CDCl₃)

major anti-epimer 17 0.91 (3 H, d, J 7, 2-CH₃), 2.27 (1 H, m,

2-H), 3.04 (1 H, dd, J 6, 11, 3-H), 3.57 (2 H, m, 1-H₂), 4.95

(2 H, m, 5-H₂), 6.13 (1 H, dt, J 11, 16, 4-H) and 7.36–7.64

(15 H, m, ArH); minor syn-epimer 3.16 (1 H, dd, J 6, 11, 3-H);

δ_C(75 MHz, CDCl₃) 11.5, 39.7, 46.2, 67.7, 112.7, 128.4, 128.7,

137.3 and 139.6; m/z (C.I.) 373 (100%).

5-Hydroxy-4-methylpent-2-enyl(triphenyl)stannane 15

TBAF (93.5 mL, 1 M in THF, 93.5 mmol) was added to the

stannane 14 (17.6 g, 31.19 mmol) in THF (150 mL) at 0 °C.

After 4 h at room temperature, water (200 mL) was added and

the mixture was extracted with ether, washed with water

(100 mL) and brine (100 mL) then dried (MgSO₄). After con-

centration under reduced pressure, chromatography of the

residue using light petroleum : ether (3 : 1) and triethylamine

(1%) as eluent gave the title compound 15 (10.33 g, 74%) as a

yellow oil (Found: M⁺− C₆H₅, 373.0612. C₁₅H₂₁O¹²⁰Sn

requires M, 373.0613); ν_max/cm⁻¹3370, 3063, 2957, 2870,

1480, 1428, 1075, 1024, 971, 965, 728 and 699; δ_H(300 MHz,

CDCl₃) (E)-isomer 0.94 (3 H, d, J 7, 4-CH₃), 2.29 (1 H, m,

4-H), 2.50 (2 H, d, J 8, 1-H₂), 3.25 (1 H, dd, J 8, 11, 5-H), 3.37

(1 H, dd, J 6, 11, 5-H), 5.27 (1 H, dd, J 8, 15, 3-H), 5.86 (1 H,

dt, J 16, 8, 2-H) and 7.42–7.67 (15 H, m, ArH); (Z)-isomer 0.80

(3 H, d, J 7, 4-CH₃) and 5.05 (1 H, t, J 10, 3-H); δ_C(75 MHz,

CDCl₃) 11.5, 16.3, 39.9, 46.2, 67.5, 128.7, 129.4, 130.6, 137.1

and 138.3; m/z (C.l.) 450 (M⁺, 1%) and 373 (100).

[(3RS,4SR)-1-tert-Butyldimethylsilyloxy-2-methylpent-3-yl]-

(triphenyl)stannane 18

The general procedure using pentenylstannane 16 (0.57 g,

1.01 mmol), toluene 4-sulfonylhydrazide (2.25 g, 12.12 mmol),

DME (50 mL) and sodium acetate (1.69 g, 20.2 mmol in water,

16 mL), after chromatography using light petroleum : ether,

(50 : 1) and triethylamine (1%) gave the title compound 18

(0.36 g, 64%) as a colourless oil (Found: M⁺− C₆H₅, 489.1639.

C₂₄H₃₇OSi¹²⁰Sn requires M, 489.1635); ν_max/cm⁻¹3063, 2955,

2856, 1428, 1255, 1097, 1074, 837, 776, 728 and 699; δ_H

(300 MHz, CDCl₃) 0.05 and 0.07 (each 3 H, s, SiCH₃), 0.97

[9 H, s, SiC(CH₃)₃], 1.09 (6 H, m, 2-CH₃and 5-H₃), 1.94 (2 H,

m, 4-H₂), 2.40 (2 H, m, 3-H and 2-H), 3.50 (1 H, dd, J 7, 10,

1-H), 3.74 (1 H, dd, J 6, 10, 1-H) and 7.40–7.76 (15 H, m,

ArH); δ_C(75 MHz, CDCl₃) −5.4, −5.3, 15.6, 16.6, 18.4, 21.7,

26.1, 36.2, 37.9, 68.1, 127.2, 128.4, 128.8, 137.3 and 140.2; m/z

(C.I.) 489 (100%).

[(3RS,4SR)-5-tert-Butyldimethylsilyloxy-4-methylpent-1-en-3-yl]-

[(3RS,4SR)-1-Hydroxy-2-methylpent-3-yl](triphenyl)stannane 19

(triphenyl)stannane 16

The general procedure using pentenylstannane 17 (0.22 g,

0.48 mmol), toluene 4-sulfonylhydrazide (1.09 g, 5.86 mmol),

DME (40 mL) and sodium acetate (0.82 g, 9.6 mmol in water,

The general procedure using stannane 14 (1.14 g, 2.02 mmol),

tin(^IV) chloride (2.02 mL, 1 M in DCM, 2.02 mmol) and

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10 mL), after chromatography using light petroleum : ether

(3 : 1) and triethylamine (l%) as eluent, gave the title compound

19 (0.16 g, 74%) as a yellow oil (Found: M⁺− C₆H₅, 375.0766.

C_l5H₂₃O¹²⁰Sn requires M, 375.0770); ν_max/cm⁻¹3569, 3393,

3063, 2955, 2870, 1480, 1428, 1073, 1022, 997, 728 and 699;

δ_H(300 MHz, CDCl₃) 0.91 (3 H, t, J 6, 5-H₃), 1.06 (3 H, d, J 6,

2-CH₃), 1.92 (2 H, m, 4-H₂), 2.14 (1 H, q, J 6, 3-H), 2.29 (1 H,

m, 2-H), 3.63 (2 H, m, 1-H₂) and 7.35–7.67 (15 H, m, ArH); δ_C

(75 MHz, CDCl₃) 15.1, 17.6, 22.7, 36.1, 37.2, 66.8, 128.3,

137.2 and 141.1; m/z (C.I.) 375 (100%).

69.9, 128.7, 128.8, 131.1, 131.7, 137.2, 139.4 and 165.8; m/z

(C.I.) 557 (68%) and 479 (100).

(1RS,5RS,3Z)-6-Benzyloxy-5-methyl-1-phenylhex-3-en-1-ol 23a

The general procedure with transmetallation using tin(IV) chlor-

ide (0.389 mL, 1.0 M in DCM, 0.389 mmol) and penten-3-

ylstannane 9 (0.21 g, 0.389 mmol) in DCM (5 mL) for 2 min at

−78 °C followed by addition of benzaldehyde (0.467 mL, 1.0 M

in DCM, 0.467 mmol) after chromatography using hexane :

ether, (3 : 1) as eluent gave a mixture of the 1,5-syn-hexenol 23a

(51 mg, 44%) containing ca. 25% of its 1,5-anti-epimer 2a (¹H

NMR) as a colourless oil. HPLC gave the title compound 23a

The hydroxypentylstannane 19 (134 mg, 0297 mmol) in THF

(1 mL) was added to potassium tert-butoxide (38 mg,

0.342 mmol) in THF (1 mL) at ambient temperature. After

15 min, benzyl bromide (0.042 mL, 0.357 mmol) and TBAI

(5 mg) in THF (1 mL) were added and the suspension stirred at

room temperature for 15 h. Water (3 mL) was added and the

mixture extracted with ether, washed with brine, dried (MgSO₄)

and concentrated under reduced pressure. Chromatography of the

residue using light petroleum : ether (30 : 1) and triethylamine

(1%) gave the benzyl ether 10 (77 mg, 48%) as a colourless oil

(Found: M⁺

+ NH₄, 314.2125. C₂₀H₂₈NO₂requires M,

314.2120); ν_max/cm⁻¹3432, 2925, 2872, 1453, 1090, 1073 and

738; δ_H(300 MHz, CDCl₃) 0.98 (3 H, d, J 7, 5-CH₃), 2.58 and

2.72 (each 1 H, m, 2-H), 2.90 (1 H, m, 5-H), 2.99 (1 H, br d,

J 4, OH), 3.21 (1 H, t, J 8, 6-H), 3.35 (1 H, dd, J 6, 8, 6-H),

4.55 (2 H, s, CH₂Ph), 4.85 (1 H, m, 1-H), 5.36 (2 H, m, 3-H and

4-H) and 7.28–7.41 (10 H, m, ArH); δ_C(75 MHz, CDCl₃) 17.5,

32.5, 36.9, 73.1, 74.9, 124.6, 125.7, 127.1, 127.7, 127.8, 128.2,

128.4, 136.8, 138.2 and 144.2; m/z (C.I.) 296 (10%), 279 (80)

and 85 (100). The 1,5-anti-epimer 2a (Found: M⁺+ NH₄,

314.2131. C₂₀H₂₈NO₂requires M, 314.2120) had spectroscopic

data identical to those of samples prepared using the stannane 1.

(Found: M⁺

−

C₆H₅, 465.1234. C₂₅H₂₉O¹²⁰Sn requires

M, 465.1239); spectroscopic data were identical to those of a

sample prepared by hydrogenation of pentenylstannane 9.

The hydroxypentylstannane 19 (0.195 g, 0.432 mmol) in

DCM (l mL) was added to tert-butyldimethylsilyl chloride

(0.072 g, 0.476 mmol) and imidazole (0.195 g, 0.865 mmol) in

DCM (2 mL). After stirring at room temperature for 20 h, water

(5 mL) was added and the mixture extracted with DCM and

dried (MgSO₄). After concentration under reduced pressure

chromatography of the residue using light petroleum : ether

(5 : 1) and triethylamine (1%) as eluent gave the silyl ether 18

(0.21 g, 86%) as a colourless oil (Found: M⁺− C₆H₅, 489.1640.

C₂₄H₃₇OSi¹²⁰Sn requires M, 489.1635); spectroscopic data were

identical to those of a sample prepared by hydrogenation of

pentenylstannane 16.

(3RS,7RS,5Z)-8-Benzyloxy-2,7-dimethyloct-5-en-3-ol 23b

The general procedure with 2 min for transmetallation using

stannane 9 (0.108 g, 0.20 mmol), tin(^IV) chloride (0.20 mL,

0.20 mmol) and 2-methylpropanal (0.22 mL, 0.22 mmol), after

chromatography using hexane : ether (3 : 1) as eluent gave the

title compound 23b (11 mg, 21%) as a colourless oil (Found:

M⁺+ NH₄, 280.2272. C₁₇H₃₀NO₂requires M, 280.2276); ν_max/cm⁻¹

3442, 2958, 2871, 1454, 1366, 1096, 1029 737 and 698; δ_H

(300 MHz, CDCl₃) 0.96, 0.97 and 1.01 (each 3 H, d, J 7, CH₃),

1.68 (1 H, m, 2-H), 2.04 (1 H, d, J 5, OH), 2.33 (2 H, m, 4-H₂),

2.90 (1 H, m, 7-H), 3.35 (3 H, m, 3-H, 8-H₂), 4.52 (2 H, s,

CH₂Ph), 5.47 (2 H, m, 5-H and 6-H) and 7.36 (5 H, s, ArH); δ_C

(75 MHz, CDCl₃) 17.6, 18.1, 19.0, 32.3, 32.5, 33.0, 73.0, 75.1,

76.3, 125.8, 127.6, 127.6, 128.4, 136.4 and 138.4; m/z (C.I.)

280 (40%) and 263 (100). The minor product was the 1,5-anti-

epimer 2b (7 mg, 13%) (Found: M⁺+ NH₄, 280.2277.

C₁₇H₃₀NO₂requires M, 280.2276) with spectroscopic data iden-

tical to those of an authentic sample prepared using stannane 1.

[(3RS,4SR)-1-(4-Bromobenzoyloxy)-2-methylpent-3-yl]

(triphenyl)stannane 20

Triethylamine (0.16 mL, 1.15 mmol) was added to the hydroxy-

pentylstannane 19 (0.13 g, 0.287 mmol) and DMAP (cat.) in

DCM (2.8 mL) at 0 °C. After 5 min, 4-bromobenzoyl chloride

(0.126 g, 0.575 mmol) was added and the solution stirred for 3 h

at room temperature. Saturated aqueous sodium carbonate

(10 mL) was added and the mixture extracted with DCM, dried

(MgSO₄) and concentrated under reduced pressure. Chromato-

graphy of the residue using light petroleum : ether (5 : 1) and tri-

ethylamine (l%) as eluent gave the title compound 20 (0.139 g,

77%) as a white solid which was recrystallised from hexane, mp

92–94 °C (Found: M⁺− C₆H₅, 557.0134. C₂₅H₂₆⁷⁹BrO₂¹²⁰Sn

requires M, 557.0138); ν_max/cm⁻¹3425, 3063, 2959, 1720,

1590, 1428, 1397, 1269, 1173, 1102, 1072, 1012, 847, 757, 728

and 699; δ_H(300 MHz, CDCl₃) 1.04 (3 H, t, J 7, 5-H₃), 1.14

(3 H, d, J 7, 2-CH₃), 1.95 (2 H, m, 4-H₂), 2.35 (1 H, m, 3-H),

2.61 (1 H, m, 2-H), 4.20 (1 H, dd, J 7, 11, 1-H), 4.42 (1 H, dd,

J 6, 10, 1-H), 7.36–7.70 (17 H, m, ArH) and 7.88 (2 H, d, J 8,

ArH); δ_C(75 MHz, CDCl₃) 15.6, 17.0, 21.7, 34.9, 36.5, 65.9,

(3RS,7SR,5Z)-8-Benzyloxy-7-methyloct-5-en-3-ol 23c

The general procedure with 2 min for transmetallation using,

stannane 9 (0.11 g, 0.205 mmol), tin(^IV) chloride (0.205 mL,

0.205 mmol) and propanal (0.247 mL, 0.247 mmol), after

chromatography using hexane : ether (3 : 1) as eluent gave the

title compound 23c (30 mg, 60%) as a colourless oil containing

its 1,5-anti-epimer 2c, ratio 23c : 2c = 82 : 18 (¹H NMR) (Found:

M⁺+ NH₄, 266.2119. C₁₆H₂₈NO₂requires M, 266.2120); ν_max

/

cm⁻¹3419, 2960, 2927, 2858, 1454, 1095, 737 and 697; δ_H

(300 MHz, CDCl₃) 0.95 (3 H, t, J 7, 1-H₃), 1.00 (3 H, d, J 7,

7-CH₃), 1.51 (2 H, m, 2-H₂), 2.24 (2 H, m, OH and 4-H), 2.39

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(1 H, m, 4-H), 2.90 (1 H, m, 7-H), 3.32 (2 H, m, 8-H₂), 3.57

(1 H, m, 3-H), 4.54 (2 H, s, CH₂Ph), 5.47 (2 H, m, 5-H and

6-H) and 7.36 (5 H, s, ArH); δ_C(75 MHz, CDCl₃) 10.2, 17.6,

29.4, 32.5, 34.6, 72.6, 73.0, 75.0, 125.3, 127.6, 127.7, 127.6,

128.3, 136.5 and 138.4; m/z (C.I.) 266 (100%) and 249 (70).

allowed to warm to room temperature. After 20 h, water (5 mL)

was added and the mixture was extracted with ether. The extracts

were washed with brine, dried (MgSO₄) and concentrated under

reduced pressure. Chromatography of the residue using light

petroleum : ether (3 : 1) as eluent gave the title compound 26

(38 mg, 41%) as a yellow oil (Found: M⁺+ NH₄, 429.2383.

C₂₄H₃₃N₂O₅requires M, 429.2389); ν_max/cm⁻¹2963, 2873,

1723, 1529, 1347, 1274, 1101 and 720; δ_H(300 MHz, CDCl₃)

0.83, 0.94 and 0.96 (each 3 H, d, J 6, CH₃), 1.98 (l H, m, 2-H),

2.40 and 2.50 (each 1 H, m, 4-H), 2.75 (1 H, m, 7-H), 3.21 (2 H,

m, 8-H₂), 4.25 and 4.35 (each 1 H, d, J 11, HCHPh), 5.02 (1 H,

dt, J 8, 5, 3-H), 5.23 (1 H, t, J 10, 6-H), 5.35 (l H, dt, J 10, 7,

5-H), 7.26 (5 H, m, ArH) and 8.14 and 8.23 (each 2 H, d, J 9,

ArH); δ_C(75 MHz, CDCl₃) 17.4, 17.5, 18.6, 29.5, 31.1, 32.4,

72.6, 74.8, 79.7, 123.1, 124.4, 127.0, 127.9, 130.2, 135.0,

137.8, 138.3 and 163.9; m/z (C.I.) 429 (35%), 412 (10) and 382

(100).

Sodium hydroxide (10 mg, 0.25 mmol) was added to the ester

26 (25 mg, 0.06 mmol) in methanol (3 mL) and the solution

stirred at room temperature for 3 h. Water (10 mL) was added

and the reaction mixture extracted with ether. The ethereal

extracts were washed with brine, dried (MgSO₄) and concen-

trated under reduced pressure. Chromatography of the residue

using light petroleum : ether, (3 : 1) as eluent gave the 3,7-syn-

alkenol 23b (10 mg, 64%) as a colourless oil (Found: M⁺+ H,

263.2008. C₁₇H₂₇O₂requires M, 263.2010); spectroscopic data

were identical to those of the alkenol 23b prepared from the stan-

nane 9.

[(3RS,4RS)-5-Benzyloxy-4-methylpent-l-en-3-yl](triphenyl)-

stannane 24

Tin(IV) chloride (0.33 mL, 1.0 M in DCM, 0.33 mmol) was

added to the pentenylstannane 9 (0.178 g, 0.33 mmol) in DCM

(5 mL) at −78 °C. After 2 min, phenyllithium (1.10 mL, 1.8 M

in cyclohexane : ether, 1.98 mmol) was added and the solution

stirred at −78 °C for 2 h. Saturated ammonium chloride was

added at −78 °C and the mixture allowed to warm to room temp-

erature then extracted with ether. The ethereal extracts were dried

(MgSO₄) and concentrated under reduced pressure. Chromato-

graphy of the residue using hexane : ether (50 : 1) and triethyl-

amine (1%) as eluent afforded a mixture of the title compound

24 and its epimer 9 (96 mg, 54%) as a yellow oil, 24 : 9 =

80 : 20 (¹H NMR) (Found: M⁺

−

C₆H₅, 463.1083.

C₂₅H₂₇O¹²⁰Sn requires M, 463.1083); ν_max/cm⁻¹3063, 3046,

1428, 1074, 728 and 699; δ_H(300 MHz, CDCl₃) major epimer

24 1.05 (3 H, d, J 7, 4-CH₃), 2.46 (1 H, m, 4-H), 2.99 (1 H, dd,

J 5, 11, 3-H), 3.36 (2 H, m, 5-H₂), 4.29 (2 H, s, CH₂Ph), 4.94

(2 H, m, 1-H₂), 6.12 (1 H, m, 2-H) and 7.30–7.75 (20 H, m,

ArH); minor epimer 9 1.10 (3 H, d, J 7, 4-CH₃), 3.13 (1 H, dd,

J 6, 11, 3-H), 4.25 and 4.32 (each 1 H, J 11, HCHPh); δ_C

(75 MHz, CDCl₃) major epimer 24 19.0, 35.4, 40.5, 72.9, 73.5,

112.6, 128.2, 128.5, 128.6, 137.2 and 140.1; m/z (C.I.) 541 (15),

463 (20) and 208 (l00).

(3RS,7SR,5Z)-8-Benzyloxy-7-methyl-3-(4-nitrobenzoyloxy)oct-5-

ene 27

DEAD (0.053 mL, 0.342 mmol) was added to the alcohol 2c

(0.056 g, 0.228 mmol), triphenylphosphine (0.0898 g,

0.342 mmol) and 4-nitrobenzoic acid (0.0573 g, 0.342 mmol) in

toluene (3 mL) at −60 °C and the mixture allowed to warm to

room temperature. After 20 h, water (5 mL) was added and the

mixture was extracted with ether. The ethereal extracts were

washed with brine, dried (MgSO₄) and concentrated under

reduced pressure. Chromatography of the residue using light

petroleum : ether (3 : l) as eluent yielded the title compound 27

(48 mg, 53%) as a yellow oil (Found: M⁺+ NH₄, 415.2227.

C₂₃H₃₁N₂O₅requires M, 415.2233); ν_max/cm⁻¹2967, 1722,

1529, 1349, 1275, 1102 and 720; δ_H(300 MHz, CDCl₃) 0.78

(3 H, d, J 7, 7-CH₃), 0.82 (3 H, t, J 7, 1-H₃), 1.70 (2 H, m,

2-H₂), 2.48 (2 H, m, 4-H₂), 2.77 (1 H, m, 7-H), 3.24 (2 H,

m, 8-H₂), 4.45 (2 H, s, CH₂Ph), 5.08 (1 H, m, 3-H), 5.33 (2 H,

m, 5-H and 6-H), 7.25 (5 H, m, ArH) and 8.15 and 8.25 (each 2 H,

d, J 8, ArH); δ_C(75 MHz, CDCl₃) 9.6, 17.6, 26.5, 31.7, 32.4,

72.8, 74.9, 76.9, 123.2, 124.1, 127.1(2), 128.0, 130.3, 135.4,

135.7, 138.2 and 163.9; m/z (C.I.) 415 (88%), 398 (22) and

368 (100).

[(2RS,3RS)-1-Benzyloxy-2-methylpent-3-yl](triphenyl)stannane

25

The general procedure using pentenylstannane 24 (64 mg,

0.118 mmol), toluene 4-sulfonylhydrazide (0.265 g,

1.424 mmol), DME (5 mL) and sodium acetate (0.199 g,

2.37 mmol in water 2 mL), after chromatography using light

petroleum : ether (50 : 1) and triethylamine (1%) as eluent, gave

the title compound 25 (37 mg, 58%) as a colourless oil (Found:

M⁺− C₆H₅, 465.1242. C₂₅H₂₉O¹²⁰Sn requires M, 465.1239);

ν_max/cm⁻¹3062, 2955, 2857, 1428, 1073, 728 and 699; δ_H

(300 MHz, CDCl₃) major syn-epimer 25 1.08 (6 H, m, 2-CH₃,

5-H₃), 1.92 (2 H, m, 4-H₂), 2.37 (1 H, m, 3-H), 2.50 (1 H, m,

2-H), 3.31 (2 H, d, J 7, 1-H₂), 4.25 and 4.32 (each 1 H, d, J 12,

HCHPh) and 7.18–7.75 (20 H, m, ArH); minor anti-epimer 10

3.44 (2 H, d, J 7, 1-H₂); δ_C(75 MHz, CDCl₃) 15.4, 18.2, 23.0,

35.7, 37.8, 72.9, 74.5, 127.8, 128.3, 137.3 and 140.9; m/z (C.I.)

465 (100%).

(3RS,7RS,5Z)-8-Benzyloxy-2,7-dimethyl-3-(4-nitrobenzoyloxy)-

Sodium hydroxide (10 mg, 0.25 mmol) was added to the ester

27 (38 mg, 0.095 mol) in methanol (3 mL) and the solution

stirred at room temperature for 3 h. Water (10 mL) was added

and the mixture extracted with ether. The ethereal extracts were

washed with brine, dried (MgSO₄) and concentrated under

reduced pressure. Chromatography of the residue using light

oct-5-ene 26

DEAD (0.053 mL, 0.338 mmol) was added to the 3,7-anti-7-

methyloctenol 2b (0.059 g, 0.225 mmol), triphenylphosphine

(0.088 g, 0.338 mmol) and 4-nitrobenzoic acid (0.057 g,

0.338 mmol) in toluene (3 mL) at −60 °C and the solution

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petroleum : ether, (3 : 1) as eluent afforded the 3,7-syn-alkenol

23c (15 mg, 63%) as a colourless oil (Found: M⁺+ H, 249.1854.

C₁₆H₂₅O₂requires M, 249.1854); spectroscopic data were identi-

cal to those of the alkenol 23c prepared from the stannane 9.

(33 mg, 42%) as a colourless oil, 23a : 2a = 80 : 20 (¹H NMR)

+ NH₄, 314.2126. C₂₀H₂₈NO₂requires M,

314.2119); spectroscopic data were identical to those of earlier

samples.

(Found: M⁺

Tin(^IV) chloride (0.370 mL, 1.0 M in DCM, 0.370 mmol) was

added to a cooled solution of stannane 24 (0.200 g, 0.370 mmol)

in DCM (2 mL) at −78 °C. After 5 min, phenyllithium

(1.23 mL, 1.8 M in cyclohexane : ether, 2.22 mmol) was added

and the suspension stirred at −78 °C for 2 h. Saturated

ammonium chloride (3 mL) was added at −78 °C and the

mixture allowed to warm to room temperature then extracted

with ether. The ethereal extracts were dried (MgSO₄) and con-

centrated under reduced pressure. Chromatography of the residue

using hexane : ether (50 : 1) and triethylamine (1%) as eluent

afforded a mixture of the stannanes 24 and 9 (87 mg, 44%) as a

yellow oil, 24 : 9 = 66 : 34 (¹H NMR) (Found: M⁺− C₆H₅,

463.1075. C₂₅H₂₇O¹²⁰Sn requires M, 463.1082); spectroscopic

data were identical to those of earlier samples.

(3RS,4SR)-5-Benzyloxy-4-methylpent-1-en-3-yl(trimethyl)-

stannane 30

Tin(IV) chloride (0.285 mL, 1.0 M in DCM, 0.285 mmol) was

added to the stannane 8 (0.154 g, 0.285 mmol) in DCM (2 mL)

at −78 °C. After 5 min, methyllithium (1.22 mL, 1.4 M in ether,

1.71 mmol) was added and the solution stirred at −78 °C for

2 h. Saturated aqueous ammonium chloride was added at

−78 °C and the mixture allowed to warm to room temperature

then extracted with ether. The ethereal extracts were dried

(MgSO₄) and concentrated under reduced pressure. Chromato-

graphy of the residue using hexane : ether (50 : 1) and triethyl-

amine (1%) as eluent afforded the title compound 30 (20 mg,

20%) as a colourless oil (Found: (M⁺− CH₃, 339.0775.

C_l5H₂₃O¹²⁰Sn requires M, 339.0770); ν_max/cm⁻¹2961, 2858,

1619, 1454, 1095, 886, 765 and 697; δ_H(300 MHz, CDCl₃)

0.10 (9 H, s, 3 × SnCH₃), 1.04 (3 H, d, J 6, 4-CH₃), 2.16 (1 H,

m, 4-H), 2.26 (1 H, dd J 6, 9, 3-H), 3.32 and 3.39 (each 1 H, dd

J 8, 6, 5-H), 4.52 (2 H, s, CH₂Ph), 4.80 (2 H, m, 1-H₂), 5.89

(1 H, dt, J 9, 17, 2-H) and 7.37 (5 H, s, ArH); δ_C(75 MHz,

CDCl₃) −9.6, 17.2, 35.5, 37.9, 65.9, 73.1, 109.7, 127.5, 127.7,

128.3, 138.6 and 139.5; m/z (C.I.) 339 (12%) and 182 (100).

Tin(^IV) chloride (0.338 mL, 1.0 M in DCM, 0.338 mmol) was

added to the stannane 30 (0.120 g, 0.338 mmol) in DCM (4 mL)

at −78 °C. After 2 min, phenyllithium (1.13 mL, 1.8 M in

cyclohexane : ether, 2.03 mmol) was added and the solution

stirred at −78 °C for 2 h. Saturated aqueous ammonium chloride

was added at −78 °C and the mixture allowed to warm to room

temperature then extracted with ether. The ethereal extracts were

dried (MgSO₄) and concentrated under reduced pressure. Chrom-

atography of the residue using hexane : ether (50 : 1) and triethyl-

amine (1%) as eluent afforded the syn- and anti-pent-1-en-3-yl

(triphenyl)stannanes 24 and 9, ratio 24 : 9 = 60 : 40 (¹H NMR)

(96 mg, 54%) as a yellow oil (Found: M⁺, 540.1470.

C₃₁H₃₂O¹²⁰Sn requires M, 540.1474); spectroscopic data were

identical to those of the stannanes 24 and 9 prepared earlier.

2-Hydroxypent-4-en-3-yl phenyl sulfone 32

ⁿButyllithium (31.7 mL, 1.6 M in hexanes, 50.72 mmol) was

added to phenyl (prop-2-en-1-yl) sulfone 31 (7.4 mL,

48.0 mmol) in THF (45 mL) at −78 °C. After 15 min, ethanal

(3.3 mL, 59.04 mmol) in THF (45 mL) was added and the sol-

ution stirred at −78 °C for 1 h. Water (50 mL) was added and

the mixture allowed to warm to room temperature then extracted

with ether. The organic extracts were washed with brine

(100 mL), dried (MgSO₄), and concentrated under reduced

pressure. Chromatography of the residue using light petroleum :

ether (1 : 1) as eluent gave the title compound 32 (9.93 g, 91%)

as a colourless oil, a 60 : 40 mixture of diastereoisomers (Found:

M⁺+ NH₄, 244.1011. C₁₁H₁₈NO₃S requires M, 244.1007); ν_max

/

cm⁻¹3513, 1447, 1305, 1288, 1146, 1082, 937, 756, 722 and

689; δ_H(500 MHz, CDCl₃) 1.16 (3 H, m, 1-H₃), 3.13 (0.6 H, s,

OH), 3.38 (0.6 H, d, J 10, 3-H), 3.52 (0.4 H, dd, J 8.5, 10, 3-H),

4.00 (0.4 H, s, OH), 4.42 (0.4 H, m, 2-H), 4.65 (0.6 H, m, 2-H),

4.92 (0.4 H, d, J 17.1, 5-H), 4.98 (0.6 H, d, J 17.3, 5-H), 5.21

(0.4 H, d, J 10.3, 5-H), 5.35 (0.6 H, d, J 10.3, 5-H), 5.46 (0.4 H,

dt, J 10.3, 17, 4-H), 5.97 (0.6 H, m, 4-H) and 7.48–7.82 (5 H,

m, ArH); δ_C(75 MHz, CDCl₃) 20.7, 21.0, 64.4, 65.3, 74.7,

76.6, 124.4, 125.5, 126.0, 127.6, 128.9, 129.0, 129.2, 134.0,

134.1, 137.0 and 137; m/z (C.I.) 244 (M⁺+ 18, 100%), 227 (M⁺

+ 1, 8) and 209 (10).

Transmetallation and trapping the tin(IV) chloride from the

[(3RS,4RS)-5-benzyloxy-4-methylpent-l-en-3-yl](triphenyl)-

stannane 24

2-Benzyloxypent-4-en-3-yl phenyl sulfone 33

A cooled solution of tin(IV) chloride (0.268 mL, 1.0 M in

dichloromethane, 0.268 mmol) was added to the stannane 24

(0.145 g, 0.268 mmol) in DCM (3 mL) at −78 °C. After 3 min,

benzaldehyde (0.322 mL, 1.0 M in DCM, 0.322 mmol) was

added and the mixture stirred at −78 °C for 1 h. Saturated

aqueous sodium hydrogen carbonate (2 mL) was added at

−78 °C and the mixture allowed to warm to room temperature

then partitioned between DCM (25 cm³) and water (25 cm³).

The organic phase was washed with water (15 mL) and brine

(15 mL) then dried (MgSO₄). After concentration under reduced

pressure, chromatography using hexane : ether (3 : 1) gave a

mixture of the 1,5-syn- and 1,5-anti-hex-3-enols 23a and 2a

Benzyl trichloroacetimidate (13.6 mL, 73.12 mmol) in cyclo-

hexane (20 mL) was added to the sulfone 32 (5.51 g,

24.37 mmol) in cyclohexane : DCM (120 mL, 5 : 1) at room

temperature. Triﬂuoromethanesulfonic acid (10 drops) was added

and the suspension stirred at room temperature for 16 h. Water

(100 mL) was added and the suspension stirred for a further 1 h.

The mixture was ﬁltered through Celite and the precipitate

washed with cyclohexane (2 × 50 mL). The ﬁltrate and washings

were washed with saturated aqueous sodium hydrogen carbonate

(100 mL) and brine (100 mL) then dried (MgSO₄). After con-

centration under reduced pressure, chromatography of the

7522 | Org. Biomol. Chem., 2012, 10, 7510–7526

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residue using light petroleum : ether (3 : 1) as eluent gave the

title compound 33 (8.32 g, 91%) as an orange oil, a

60 : 40 mixture of diastereoisomers (Found: M⁺+ NH₄,

334.1471. C₁₈H₂₄NO₃S requires M, 334.1477); ν_max/cm⁻¹3062,

3028, 2980, 2930, 1495, 1447, 1306, 1146, 1083, 1027, 998,

936, 723 and 691; δ_H(300 MHz, CDCl₃) 1.24 (1.8 H, d, J 6,

1-H₃), 1.40 (1.2 H, d, J 6, 1-H₃), 3.50 (0.6 H, d, J 10, 3-H), 3.86

(0.4 H, dd, J 10, 5, 3-H), 4.36 (0.4 H, m, 2-H), 4.49–4.74 (2.6

H, m, PhCH₂O and 2-H), 5.08 (0.4 H, d, J 17 5-H), 5.16 (0.6 H,

d, J 17, 5-H), 5.39 (0.4 H, d, J 10, 5-H), 5.44 (0.6 H, d, J 10,

5-H), 5.93 (1 H, m, 4-H) and 7.20–7.86 (10 H, m, ArH); m/z

(C.I.) 334 (M⁺+ 18, 100%) and 317 (M⁺+ 1, 5).

pressure, chromatography of the residue using hexane : ether

(3 : 1) as eluent gave the (Z)-1,5-syn-5-benzyloxy-1-phenylhex-

3-en-1-ol 5a (38 mg, 66%) as a colourless oil (Found: M⁺

+

NH₄, 300.1966. C₁₉H₂₆NO₂requires M, 300.1963); spectro-

scopic data were identical to those of an authentic sample.

(2RS,3RS)-2-Hydroxypent-4-en-3-yl(triphenyl)stannane 36

The general procedure with a 5 min transmetallation time using

stannane 34 (1.07 g, 2.45 mmol), tin(^IV) chloride (2.45 mL,

2.45 mmol) and phenyllithium (8.17 mL, 1.8 M in cyclohexane–

ether, 14.72 mmol), after chromatography using light petroleum :

ether (3 : 1) and triethylamine (1%) as eluent gave the title com-

pound 36 (0.37 g, 35%) as a colourless oil; ν_max/cm⁻¹3568,

3048, 2969, 1623, 1480, 1428, 1110, 1074, 908, 730 and 700;

δ_H(300 MHz, CDCl₃) 1.34 (3 H, d, J 6, 1-H₃), 1.89 (1 H, d, J 5,

OH), 3.09 (1 H, dd, J 6, 5, 3-H), 4.28 (1 H, m, 2-H), 4.91 (1 H,

d, J 10, 5-H), 4.97 (1 H, d, J 17, 5-H), 6.10 (1 H, dt, J 17, 10,

4-H) and 7.36–7.77 (15 H, m, ArH); δ_C(75 MHz, CDCl₃) 24.3,

48.3, 69.7, 112.5, 128.7, 128.9, 137.4, 137.9 and 139.6; m/z (C.

I.) 368 (99%), 152 (100), 135 (40) and 78 (53).

4-Hydroxypent-2-en-1-yl(triphenyl)stannane 34

Triphenyltin hydride (8.98 g, 25.5 mmol) and α-azo-bis-isobu-

tyronitrile (0.42 g, 10 mol%) were added to a degassed solution

of the sulfones 32 (5.26 g, 23.2 mmol) in benzene (100 mL) and

the solution heated under reﬂux for 3 h. After concentration

under reduced pressure, chromatography of the residue using

light petroleum : ether (1 : 1) and triethylamine (1%) as eluent

gave the title compound 34 (5.72 g, 56%) as a colourless oil, a

67 : 33 mixture of (E)- and (Z)-isomers, ν_max/cm⁻¹3420, 3063,

2970, 1652, 1480, 1447, 1428, 1318, 1306, 1147, 1075, 997,

965, 935, 867, 728 and 699; δ_H(300 MHz, CDCl₃) (E)-isomer

1.16 (3 H, d, J 6.3, 5-H₃), 2.44 (2 H, d, J 8.7, 1-H₂), 4.17 (1 H,

m, 4-H), 5.46 (1 H, dd, J 7.3, 15.1, 3-H), 5.88 (1 H, m, 2-H) and

7.32–7.72 (15 H, m, ArH); (Z)-isomer 1.04 (3 H, d, J 6.3, 5-H₃),

4.47 (1 H, m, 4-H) and 5.24 (1 H, t J 9, 3-H); m/z (C.I.) 418

(60%), 368 (100) and 78 (43).

(2RS,3RS)-2-Benzyloxypent-4-en-3-yl(triphenyl)stannane 37

Tin(IV) chloride (0.95 mL, 1.0 M in DCM, 0.95 mmol) was

added to the stannane 35 (0.50 g, 0.950 mmol) in DCM (8 mL)

at −78 °C. After 5 min, phenyllithium (3.2 mL, 1.8 M in

cyclohexane : ether, 5.76 mmol) was added and the solution

stirred at −78 °C for 1 h. Saturated aqueous ammonium chloride

(10 mL) was added at −78 °C and the mixture allowed to warm

to room temperature. The mixture was extracted with ether (3 ×

10 mL) and the ethereal extracts dried (MgSO₄). After concen-

tration under reduced pressure, chromatography of the residue

using hexane : ether (50 : 1) and triethylamine (1%) as eluent

afforded the title compound 37 (0.27 g, 54%) as a colourless oil;

ν_max/cm⁻¹3062, 2969, 2863, 1623, 1480, 1428, 1073, 1024,

997, 894, 729 and 699; δ_H(300 MHz, CDCl₃) 1.31 (3 H, d, J 6,

1-H₃), 3.12 (1 H, dd, J 7, 10, 3-H), 3.98 (1 H, m, 2-H), 4.18 and

4.56 (each 1 H, d, J 11, PhHCH), 4.87 (1 H, d, J 10, 5-H), 4.95

(1 H, d, J 17, 5-H), 6.12 (1 H, dt, J 10, 17, 4-H) and 7.03–7.76

(20 H, m, ArH); δ_C(75 MHz, CDCl₃) 19.7, 47.0, 70.5, 76.7,

111.7, 128.2, 128.3, 128.4, 137.5 and 139.8; m/z (C.I.) 373

(5%), 368 (80) and 78 (100).

4-Benzyloxypent-2-en-1-yl(triphenyl)stannane 35

Triphenyltin hydride (10.99 g, 31.3 mmol) and α-azo-bis-isobu-

tyronitrile (0.51 g, 10 mol%) were added to a degassed solution

of sulfone 33 (8.25 g, 26.1 mmol) in benzene (150 mL) and the

solution was heated under reﬂux for 3 h. After concentration

under reduced pressure, chromatography of the residue using

light petroleum : ether (30 : 1) and triethylamine (1%) as eluent

gave the title compound 35 (5.74 g, 42%) as a colourless oil;

ν_max/cm⁻¹3063, 2973, 2860, 1480, 1453, 1428, 1073, 1023,

997, 965, 728 and 699; δ_H(300 MHz, CDCl₃) 1.21 (3 H, d,

J 6.3, 5-H₃), 2.51 (2 H, d, J 8.4, 1-H₂), 3.82 (1 H, m, 4-H), 4.17

and 4.39 (each 1 H, d, J 12, HCHPh), 5.41 (1 H, dd, J 8.3, 15.3,

3-H), 5.85 (1 H, dt, J 15, 7, 2-H) and 7.20–7.70 (20 H, m, ArH);

δ_C(75 MHz, CDCl₃) 15.9, 21.9, 69.2, 75.7, 127.1, 127.5, 128.1,

128.5, 129.0, 130.0, 130.3, 136.9, 138.1 and 138.9; m/z (C.I.)

368 (100%), 326 (28) and 292 (30).

(2RS,3RS)-2-Hydroxypent-3-yl(triphenyl)stannane 38

The general procedure using stannane 36 (0.45 g, 1.03 mmol),

toluene 4-sulfonylhydrazide (2.30 g, 12.35 mmol), DME

(40 mL) and sodium acetate (1.69 g, 20.61 mmol in water,

14 mL), after chromatography using light petroleum : ether

(3 : 1) and triethylamine (1%) as eluent, afforded the title com-

pound 38 (0.31 g, 69%) as a colourless oil; ν_max/cm⁻¹3400,

3063, 2959, 1428, 1073, 782 and 699; δ_H(300 MHz, CDCl₃)

1.11 (3 H, t, J 7, 5-H₃), 1.30 (3 H, d, J 7, 1-H₃), 1.94 (3 H, m,

4-H₂and OH), 2.24 (1 H, q, J 7, 3-H), 4.29 (1 H, quin, J 6, 2-H)

and 7.37–7.76 (15 H, m, ArH); δ_C(75 MHz, CDCl₃) 14.8, 23.8,

24.6, 44.8, 70.0, 128.0, 128.4, 128.5, 137.3 and 140.5; m/z (C.I.)

368 (86%), 152 (60), 94 (70) and 78 (100).

A cooled solution of tin(^IV) chloride (0.203 mL, 1.0 M in

DCM, 0.203 mmol) was added to the stannane 35 (0.107 g,

0.203 mmol) in DCM (2 mL) at −78 °C. After 5 min, a cooled

solution of benzaldehyde (0.244 mL, 1.0

M in DCM,

0.244 mmol) was added and the mixture stirred at −78 °C for

1 h. Saturated aqueous sodium hydrogen carbonate (2 mL) was

added. The mixture allowed to warm to room temperature then

partitioned between DCM (25 mL) and water (25 mL). The

organic phase was washed with water (15 mL) and brine

(15 mL) then dried (MgSO₄). After concentration under reduced

Org. Biomol. Chem., 2012, 10, 7510–7526 | 7523

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(2RS,3RS)-2-Benzyloxypent-3-yl(triphenyl)stannane 39

added. The mixture was extracted with ether (3 × 5 mL) and the

organic extracts were washed with brine (10 mL) then dried

(MgSO₄). After concentration under reduced pressure, chromato-

graphy of the residue using light petroleum : ether (5 : 1) and tri-

ethylamine (1%) as eluent gave the title compound 41 (0.20 g,

30%) as a colourless oil; ν_max/cm⁻¹3570, 3434, 3062, 2960,

2868, 1578, 1480, 1428, 1073, 971, 913, 728 and 700; δ_H

(300 MHz, CDCl₃) 0.98 (3 H, t, J 7, 5-H₃), 1.45 (3 H, d, J 7, 1-

H₃), 1.54–1.78 (2 H, m, 4-H₂), 1.81 (1 H, d, J 5, OH), 2.43

(1 H, dq, J 4, 7, 2-H), 3.98 (1 H, m, 3-H) and 7.38–7.80 (15 H,

m, ArH); δ_C(75 MHz, CDCl₃) 10.7, 11.9, 28.6, 30.1, 75.9,

128.3, 128.6, 137.2 and 139.3; m/z (C.I.) 368 (100%) and 78

(33%). The second fraction contained the title compound 42

(0.128 g, 19%) as a colourless oil; ν_max/cm⁻¹3569, 3432, 3062,

2959, 2869, 1480, 1428, 1073, 998, 728 and 699; δ_H(300 MHz,

CDCl₃) 0.91 (3 H, t, J 7, 5-H₃), 1.19 (3 H, d, J 6, 1-H₃), 1.53

(1 H, d, J 5, OH), 1.79 (2 H, m, 4-H₂), 2.23 (1 H, m, 3-H), 4.25

(1 H, m, 2-H) and 7.24–7.62 (15 H, m, ArH); δ_C(75 MHz,

CDCl₃) 15.3, 21.0, 23.2, 43.4, 69.6, 128.3, 128.5, 137.2 and

139.9; m/z (C.I.) 368 (100%), 94 (49) and 78 (88).

The general procedure using stannane 37 (0.107 g, 0.203 mmol),

toluene 4-sulfonylhydrazide (0.45 g, 2.436 mmol), DME

(10 mL) and sodium acetate (0.34 g, 0.414 mmol in water,

2 mL), after chromatography using light petroleum : ether

(50 : 1) and triethylamine (1%) as eluent, gave the title com-

pound 39 (0.073 g, 68%) as a colourless oil; ν_max/cm⁻¹3063,

2960, 2868, 1480, 1428, 1073, 728 and 699; δ_H(300 MHz,

CDCl₃) 1.02 (3 H, t, J 8, 5-H₃), 1.29 (3 H, d, J 6, 1-H₃), 1.96

(2 H, m, 4-H₂), 2.26 (1 H, m, 3-H), 4.01 (1 H, quint, J 6, 2-H),

4.32 and 4.64 (each 1 H, d, J 11, PhHCH) and 7.12–7.80 (20 H,

m, ArH); δ_C(75 MHz, CDCl₃) 15.0, 20.1, 24.2, 43.5, 70.6,

77.3, 127.8, 128.2, 128.4, 129.2, 136.8, 137.2 and 140.7; m/z

(C.I.) 444 (7%), 427 (17), 368 (100) and 78 (79).

The hydroxypentylstannane 38 (0.20 g, 0.456 mmol) in THF

(2 mL) was added to a stirred suspension of sodium hydride

(55 mg, 1.36 mmol, 60% dispersion) in THF (2 mL) at 0 °C.

After 1 h at room temperature, benzyl bromide (0.108 mL,

0.91 mmol) and TBAI (5 mg) were added and the mixture

stirred at room temperature overnight. Water (5 mL) was added

and the mixture was extracted with ether (3 × 5 mL). The ethe-

real extracts were washed with brine (10 mL), dried (MgSO₄)

and concentrated under reduced pressure. Chromatography of the

residue using light petroleum : ether (50 : 1) and triethylamine

(1%) as eluent gave the benzyloxypentylstannane 39 (151 mg,

63%) as a colourless oil with spectroscopic data identical to

those of the sample prepared by reduction of stannane 37.

(2RS,3SR)-2-Benzyloxypent-3-yl(triphenyl)stannane 43

The hydroxypentylstannane 42 (0.206 g, 0.470 mmol) in THF

(2 mL) was added to a suspension of sodium hydride (56 mg,

1.41 mmol, 60% dispersion) in THF (2 mL) at 0 °C. After 1 h at

room temperature, benzyl bromide (0.111 mL, 0.94 mmol) and

TBAI (5 mg) were added and the mixture was stirred at room

temperature overnight. Water (5 mL) was added and the reaction

mixture was extracted with ether (3 × 5 mL). The organic

extracts were washed with brine (10 mL), dried (MgSO₄) and

concentrated under reduced pressure. Chromatography of the

residue using light petroleum : ether (50 : 1) and triethylamine

(1%) as eluent gave the title compound 43 (151 mg, 61%) as a

colourless oil; ν_max/cm⁻¹3062, 2960, 2868, 1480, 1455, 1428,

1073, 728 and 698; δ_H(300 MHz, CDCl₃) 1.13 (3 H, t, J 7,

5-H₃), 1.35 (3 H, d, J 6, 1-H₃), 1.97 (2 H, m, 4-H₂), 2.49 (1 H,

dt, J 4, 7, 3-H), 4.09 (1 H, m, 2-H), 4.16 and 4.53 (each 1 H, d,

J 11, PhHCH) and 7.16–7.70 (20 H, m, ArH); δ_C(75 MHz,

CDCl₃) 15.4, 18.6, 21.3, 42.2, 70.2, 76.5, 127.1, 127.7, 128.0,

128.2, 128.4, 137.3, 138.7 and 140.1; m/z (C.I.) 368 (100%) and

94 (56).

(2RS,3RS)-2-Ethyl-3-methyloxirane 40⁸

N-Bromosuccinimide (15.81 g, 88.82 mmol) was added portion-

wise to (E)-pent-2-ene (9.6 mL, 88.82 mmol) in water (25 mL)

such that the temperature remained below 45 °C. The mixture

was stirred at room temperature for 18 h. Two layers formed and

the lower layer was separated. This layer was slowly added to a

solution of potassium hydroxide (13.45 g, 0.239 mol) in water

(30 mL). During the course of the addition (∼1 h) a lighter

yellow layer separated. The solution was saturated with sodium

chloride and the layers separated. The top layer was dried

(MgSO₄) and then fractionally distilled, bp 80 °C/760 mm (lit.⁸

bp 80.2 °C/750

15 mm) to afford the title compound 40

(2.27 g, 30%) as a colourless liquid; δ_H(300 MHz, CDCl₃) 1.20

(3 H, t, J 7.5, CH₃CH₂), 1.33 (3 H, d, J 5.21, CH₃CH), 1.59

(2 H, m, CH₂CH₃), 2.65 (1 H, dt, J 2, 5, 2-H) and 2.80 (1 H, dq,

J 2, 5, 3-H); δ_C(75 MHz, CDCl₃) 9.8, 17.6, 25.0, 54.2 and 60.8;

m/z (C.I.) 87 (M⁺+ 1, 70%), 86 (30), 69 (88) and 45 (100).

(2RS,3SR)-2-Ethyl-3-methyloxirane 44⁸

N-Bromosuccinimide (8.34 g, 46.83 mmol) was added portion-

wise to (Z)-2-pentene (5.0 mL, 46.83 mmol) in water (20 mL)

such that the temperature remained below 45 °C. The mixture

was stirred at room temperature for 18 h. During the reaction two

layers formed and the lower layer was separated and slowly

added to potassium hydroxide (7.09 g, 0.126 mol) in water

(15 mL). During the course of the addition (∼2 h) a lighter

yellow layer separated. The mixture was saturated with sodium

chloride and the layers separated. The top layer was dried

(MgSO₄) and fractionally distilled, bp 84–85 °C/760 mm (lit.⁸

(2RS,3SR)-3-Hydroxypent-2-yl(triphenyl)stannane 41 and

(2RS,3SR)-2-hydroxypent-3-yl(triphenyl)stannane 42

ⁿButyllithium (1.91 mL, 1.58 M in hexanes, 3.02 mmol) was

added to di-isopropylamine (0.425 mL, 3.02 mmol) in THF

(2 mL) at 0 °C. After 5 min, the solution was cooled to −78 °C

and triphenyltin hydride (1.06 g, 3.02 mmol) in THF (2 mL)

was added. The yellow suspension was stirred at −78 °C for 1 h,

warmed to −10 °C and epoxide 40 (0.130 g, 1.51 mmol) in THF

(1 mL) was added. The solution was stirred at room temperature

for 4 h then saturated aqueous ammonium chloride (3 mL) was

bp 85.4 °C/750

15 mm) to afford the title compound 44

(0.50 g, 13%) as a colourless liquid; δ_H(300 MHz, CDCl₃) 1.07

(3 H, t, J 7.5, CH₃CH₂), 1.31 (3 H, d, J 5.63, CH₃CH), 1.58

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(2 H, m, CH₂CH₃), 2.91 (1 H, dt, J 4, 6, 2-H) and 3.09 (1 H, m,

3-H); δ_C(75 MHz, CDCl₃) 10.3, 12.9, 20.8, 52.6 and 58.2; m/z

(C.I.) 87 (M⁺+ 1, 72%), 86 (25), 69 (80) and 45 (100).

d, J 6, 5-H₃), 2.48 (2 H, d, J 8, 1-H₂), 4.26 (1 H, quin, J 5.5,

4-H), 5.52 (1 H, dd, J 8, 15, 3-H), 5.90 (1 H, dt, J 15, 8, 2-H)

and 7.40–7.70 (15 H, m, ArH); δ_C(75 MHz, CDCl₃) −4.7,

−4.5, 15.8, 18.3, 24.8, 26.0, 69.3, 125.8, 128.9, 129.0, 133.1,

136.9 and 138.5; m/z (C.I.) 473 (M⁺− 77, 2%) and 368 (100).

(2RS,3RS)-3-Hydroxypent-2-yl(triphenyl)stannane 45 and

(2RS,3RS)-2-hydroxypent-3-yl(triphenyl)stannane 38

[(3RS,4SR)- and (3RS,4RS)-4-tert-Butyldimethylsilyloxypent-1-

en-3-yl](triphenyl)stannane 52 and 53

ⁿButyllithium (2.18 mL, 1.28 M in hexanes, 2.79 mmol) was

added to di-isopropylamine (0.39 mL, 2.79 mmol) in THF

(2 mL) at 0 °C. After 5 min, the solution was cooled to −78 °C

and a triphenyltin hydride (0.979 g, 2.79 mmol) in THF (2 mL)

was added. The yellow suspension was stirred at −78 °C for 1 h,

warmed to −10 °C and the epoxide 44 (0.12 g, 1.39 mmol) in

THF (1 mL) was added. The solution was stirred at room temp-

erature for 4 h and saturated aqueous ammonium chloride

(3 mL) was added. The mixture was extracted with ether (3 ×

5 mL) and the organic extracts washed with brine (10 mL), dried

(MgSO₄) and concentrated under reduced pressure. Chromato-

graphy of the residue using light petroleum : ether (5 : 1) and tri-

ethylamine (1%) gave the title compound 45 (0.132 g, 22%) as a

colourless oil; ν_max/cm⁻¹3578, 3062, 2961, 2931, 2860, 1480,

1428, 1073, 961, 728 and 699; δ_H(300 MHz, CDCl₃) 0.97 (3 H,

t, J 7, 5-H₃), 1.45 (3 H, d, J 7, 1-H₃), 1.72 (2 H, m, 4-H₂), 1.94

(1 H, d, J 4, OH), 2.29 (1 H, quint, J 7, 2-H), 3.77 (1 H, m, 3-H)

and 7.30–7.74 (15 H, m, ArH); δ_C(75 MHz, CDCl₃) 10.1, 16.5,

30.0, 33.2, 78.3, 128.2, 128.5, 137.4 and 140.0; m/z (C.I.) 368

(100%) and 78 (12). The second fraction was the title compound

38 (0.138 g, 23%), a colourless oil with spectroscopic data iden-

tical to those of a sample prepared by reduction of the penten-3-

ylstannane 36.

The general procedure using pentenylstannane 51 (0.74 g,

1.35 mmol), tin(^IV) chloride (1.35 mL, 1 M in DCM,

1.35 mmol) and phenyllithium (4.48 mL, 1.8 M in cyclohexane–

ether, 8.07 mmol) in DCM (13 mL), after chromatography using

light petroleum and triethylamine (1%) as eluent, gave the title

compounds 52 and 53 (0.60 g, 80%) as a yellow oil, 52 : 53 =

50 : 50; ν_max/cm⁻¹3063, 2956, 2981, 2855, 1428, 1255, 1074,

996, 834, 777, 728 and 699; δ_H(300 MHz, CDCl₃) 0.00, 0.03,

0.10 and 0.14 (each 1.5 H, s, SiCH₃), 0.90 [9 H, s, SiC(CH₃)₃],

1.31 (1.5 H, d, J 6.1, 5-H₃), 1.39 (1.5 H, d, J 8.0, 5-H₃), 3.18

(0.5 H, d, J 10.5, 3-H), 3.31 (0.5 H, dd, J 4.9, 11.1, 3-H), 4.47

(1 H, m, 4-H), 5.00 (2 H, m, 1-H₂), 6.19 and 6.36 (each 0.5 H,

dt, J 15, 10, 2-H) and 7.10–7.80 (15 H, m, ArH); δ_C(75 MHz,

CDCl₃) −4.3, 18.0, 24.5, 24.8, 26.0(2), 48.9, 49.1, 71.0, 71.5,

112.0, 113.0, 128.2, 128.4, 128.5, 137.5 and 139.7; m/z (C.I.)

425 (10%), 368 (45), 351 (52) and 78 (100).

[(2RS,3SR)- and (2RS,3RS)-2-tert-Butyldimethylsilyloxypent-3-

yl](triphenyl)stannane 54 and 55

The general procedure using a mixture of the stannanes 52 and

53 (0.48 g, 0.872 mmol), toluene 4-sulfonylhydrazide (1.94 g,

10.46 mmol), DME (35 mL) and sodium acetate (1.46 g in

17.80 mmol in water, 10 mL), after chromatography using light

petroleum and triethylamine (1%) afforded the title compounds

54 and 55 (0.37 g, 77%) as a colourless oil, 64 : 55 = 50 : 50

(Found: M⁺− C₆H₅, 475.1482. C₂₃H₃₅OSi¹²⁰Sn requires M,

475.1478); ν_max/cm⁻¹3063, 2956, 2928, 2856, 1428, 1255,

1073, 1043, 968, 833, 776, 728 and 699; δ_H(300 MHz, CDCl₃)

0.00, 0.03, 0.08 and 0.10 (each 1.5 H, s, CH₃Si), 0.86 and 0.89

[each 4.5 H, s, SiC(CH₃)₃], 1.01 (1.5 H, t, J 7.1, 5-H₃), 1.06 (1.5

H, t, J 7.2, 5-H₃), 1.23 (1.5 H, d, J 6.1, 1-H₃), 1.30 (1.5 H, d,

J 6.0, 1-H₃), 1.70–2.50 (3 H, m, 3-H and 4-H₂), 4.45 (1 H, m,

2-H) and 7.20–7.70 (15 H, m, ArH); δ_C(75 MHz, CDCl₃) −4.8,

−4.7, 14.9, 15.2, 18.2, 23.5, 23.9, 24.4, 25.3, 25.9, 26.0, 46.2,

46.4, 70.9, 71.0, 127.8, 128.1, 128.2, 136.9, 137.4 and 140.4;

m/z (C.I.) 475 (2%), 425 (11) and 368 (100).

Alcohol 38 (88 mg, 0.20 mmol) in THF (1 mL) was added to

a suspension of sodium hydride (24 mg, 0.602 mmol, 60% dis-

persion) in THF (1 mL) at 0 °C. After 1 h at room temperature,

benzyl bromide (47 μl, 0.402 mmol) and TBAI (5 mg) were

added and the mixture was stirred at room temperature overnight.

Water (3 mL) was added and the mixture was extracted with

ether (3 × 3 mL). The ether extracts were washed with brine

(5 mL), dried (MgSO₄) and concentrated under reduced pressure.

Chromatography of the residue using light petroleum : ether

(50 : 1) and triethylamine (1%) as eluent gave the 2-benzyloxy-

pent-3-ylstannane 39 (76 mg, 72%), a colourless oil with spec-

troscopic data identical to those of a sample prepared by

reduction of penten-3-ylstannane 37.

4-tert-Butyldimethylsilyloxypent-2-enyl(triphenyl)stannane 51

The 4-hydroxypent-2-enylstannane 34 (9.42 g, 21.6 mmol) in

DCM (150 mL) was added to a suspension of tert-butyldi-

methylsilyl chloride (3.58 g, 23.8 mmol) and imidazole (2.94 g,

43.2 mmol) in DCM (150 mL) and the mixture stirred at room

temperature for 24 h. Water (100 mL) was added and the organic

phase washed with brine (100 mL), dried (MgSO₄) and concen-

trated under reduced pressure. Chromatography of the residue

using light petroleum : ether (10 : 1) and triethylamine (1%) gave

TBAF (0.39 mL, 1.0 M in THF, 0.39 mmol) was added to a

mixture of the stannanes 54 and 55 (72 mg, 0.130 mmol) in

tetrahydrofuran (1 mL) at 0 °C. After 3 h at room temperature,

water (3 mL) was added and the mixture extracted with ether (3

× 5 mL). The organic extracts were washed with water (5 mL)

and brine (5 mL), dried (MgSO₄) and concentrated under

reduced pressure. Chromatography of the residue using light

petroleum : ether (3 : 1) and triethylamine (1%) as eluent gave

the (2RS,3RS)-2-hydroxypent-3-ylstannane 38 (15 mg, 26%) and

the (2RS,3SR)-2-hydroxypent-3-ylstannane 42 (7 mg, 12%) both

as colourless oils with spectroscopic data identical to those

obtained earlier.

the title compound 51 (6.86 g, 55%) as a colourless oil; ν_max

/

cm⁻¹3064, 2955, 2856, 1471, 1428, 1365, 1254, 1075, 996,

960, 834, 776, 727 and 699; δ_H(300 MHz, CDCl₃) 0.03 and

0.06 (each 3 H, s, SiCH₃), 0.93 [9 H, s, SiC(CH₃)₃], 1.17 (3 H,

Org. Biomol. Chem., 2012, 10, 7510–7526 | 7525

View Article Online

stereoselectivity of the transmetallation process would determine the pos-

ition of the deuterium in the allyltin trichloride ii and hence in the pent-1-

enylstannane iii. This investigation has not been carried out.

Acknowledgements

We thank GSK for support under the CASE scheme

(to L. A. H.) and R. Beddoes and J. Raftery with help with the

X-ray crystal structure.

Notes and references

1 (a) E. J. Thomas, Chem. Rec., 2007, 7, 115; (b) E. J. Thomas, Chem.

Commun., 1997, 411.

2 (a) J. S. Carey, S. MacCormick, S. J. Stanway, A. Teerawutgulrag and

E. J. Thomas, Org. Biomol. Chem., 2011, 9, 3896; (b) A. H. MacNeill

and E. J. Thomas, Synthesis, 1994, 322; (c) S. J. Stanway and

E. J. Thomas, Tetrahedron, 2012, 68, 5998.

3 D. J. Hallett, N. Tanikkul and E. J. Thomas, Org. Biomol. Chem., 2012,

10, 6130.

4 (a) R. Beddoes, L. A. Hobson and E. J. Thomas, Chem. Commun., 1997,

1929; (b) L. A. Hobson, M. Vincent, E. J. Thomas and I. H. Hillier,

Chem. Commun., 1998, 899.

5 It was of interest to vary the group on the tin and the triphenyltin chloride

was easier to remove from trapped products than tributyltin containing

residues.

6 V. J. Jephcote and E. J. Thomas, J. Chem. Soc., Perkin Trans. 1, 1991,

429.

7 J. C. Carey, T. S. Coulter and E. J. Thomas, Tetrahedron Lett., 1993, 34,

3933.

8 A. T. Bottini and R. L. VanEtten, J. Org. Chem., 1965, 30, 2994.

9 L. D. Hall, P. R. Steiner and D. G. Miller, Can. J. Chem., 1979, 57, 38.

10 G. W. Bradley, D. J. Hallett and E. J. Thomas, Tetrahedron: Asymmetry,

1995, 6, 2579.

11 G. A. Webb, Annu. Rep. NMR Spectrosc., 1985, 16, 85.

12 G. E. Keck, M. B. Andrus and S. Castellino, J. Am. Chem. Soc., 1989,

111, 8136.

13 S. E. Denmark, T. Wilson and T. M. Willson, J. Am. Chem. Soc., 1988,

110, 984.

14 M. Gielen, Bull. Soc. Chim. Belg., 1983, 92, 409.

15 A. G. Davies, P. G. Harrison, J. D. Kennedy, T. N. Mitchell,

R. J. Puddephatt and W. McFarlane, J. Chem. Soc. C, 1969, 1136.

16 M. T. Reetz, K. Harms and W. Reif, Tetrahedron Lett., 1988, 29, 5881.

17 Our results are qualitative rather than quantitative and the reaction

scheme shown in Fig. 7 is certainly an oversimpliﬁcation of the processes

that may be involved. The reactions postulated to proceed via the anti-

allyltin trichloride 21a are reliably stereoselective showing that the anti-

allyltin trichloride 21a has little tendency to epimerise into its syn-epimer

28. However although fast reactions postulated to involve the syn-allyltin

trichloride 28 proceed with stereoselectivity that is markedly different

from those that involve the anti-allyltin trichloride 21a, slower processes

proceed with reduced stereoselectivity showing that equilibration of 28

and 21a can occur. Indeed reactions of analogous allylsilanes require

transmetallation times of ca. 1.5 h and with aldehydes typically give mix-

tures of the 1,5-anti and 1,5-syn-products 2 and 23 with stereoselectivities

of 2 : 23 = 75 : 25. These reactions may well proceed via mixtures of 21a

and 28 that have effectively reached equilibrium (see ref. 18). The same

may be true of some of the slower reactions with imines, see ref. 3.

18 C. T. Brain and E. J. Thomas, Tetrahedron Lett., 1997, 38, 2387.

19 The suprafacial and antarafacial processes for transmetallation of allyl-

stannanes could be distinguished by using pent-2-enylstannane i that has

been labelled using deuterium stereospeciﬁcally at C(1). The

20 In this work using allylstannanes, mixtures of (E)- and (Z)-isomers of the

allylstannanes were usually used with (E) : (Z) ratios of typically 85 : 15.

It might be expected that (Z)-allylstannanes would undergo transmetalla-

tion with higher stereoselectivities that their (E)-isomers and so react, e.g.

with aldehydes, with higher overall stereoselectivity. This has not been

studied using allylstannanes but analogous reactions using allylgerma-

nesdo show better stereoselectivities for the (Z)-isomers – see ref. 21.

21 (a) P. Casteno, E. J. Thomas and A. Weston, Tetrahedron Lett., 2007, 48,

337; (b) E. J. Thomas and A. Weston, Tetrahedron Lett., 2007, 48, 341.

22 An analogous antarafacial process is also consistent with the stereo-

selective isomerisation of the terminal allylstannane 61 into the syn-

epimer 28.

23 (a) A. J. Pratt and E. J. Thomas, J. Chem. Soc., Perkin Trans. 1, 1989,

1521; (b) V. J. Jephcote, A. J. Pratt and E. J. Thomas, J. Chem. Soc.,

Perkin Trans. 1, 1989, 1529.

24 A transition structure with an octahedral tin must be involved if the

alkoxy group remains co-ordinated to the tin during the reaction with an

aldehyde. For allyltin trichlorides with four-membered oxastannane rings,

e.g. 46, such processes would be expected to give rise to (Z)-alkenes, see

ref. 25. However for reactions of allylstannanes with substituents in more

remote positions that are believed to involve reactions of allyltin trichlo-

rides with ﬁve- and six-membered oxastannane rings, the high selectivity

for (Z)-alkene formation is more difﬁcult to explain. If a trigonal bipyra-

midal tin is involved in the transition structure of the reaction with an

aldehyde as indicated in Fig. 2–4, the prefence for formation of

(Z)-alkenes is disconnected from the length of the tether and has analogy

in the thermal reactions discussed in ref. 23.

25 M. A. Vincent, I. H. Hillier, R. J. Hall and E. J. Thomas, J. Org. Chem.,

1999, 64, 4680.

7526 | Org. Biomol. Chem., 2012, 10, 7510–7526

Article Doi

Concerning the 1,5-stereocontrol in tin(iv) chloride promoted reactions of 4- and 5-alkoxyalk-2-enylstannanes: Trapping intermediate allyltin trichlorides using phenyllithium

DOI: 10.1039/c2ob25765c

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Article abstract of DOI:10.1039/c2ob25765c

Full text of DOI:10.1039/c2ob25765c

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