Accurate determinations of the extent to which the SE2′ reactions of allyl-, allenyl- and propargylsilanes are stereospecifically anti

View Article Online / Journal Homepage / Table of Contents for this issue

Accurate determinations of the extent to which the S_E2Ј reactions

of allyl-, allenyl- and propargylsilanes are stereospeciﬁcally anti

Michael J. C. Buckle, Ian Fleming,* Salvador Gil and Kah Ling Christine Pang

Department of Chemistry, Lensﬁeld Road, Cambridge, UK CB2 1EW.

E-mail: if10000@cam.ac.uk; Fax: ϩ44 (0)1223 336362; Tel: ϩ44 (0)1223 336372

Received 27th October 2003, Accepted 22nd December 2003

First published as an Advance Article on the web 9th February 2004

The allylsilanes, (R)-E- and (R)-Z-4-trimethylsilylpent-2-ene 16, were prepared in essentially an enantiomerically

and geometrically pure state (er >99.95 : 0.05, E : Z and Z : E >99.95 : 0.05) by, successively, conjugate addition of

lithium dimethylcuprate to N-[(E)-3Ј-trimethylsilylpropenoyl]-(7S)-10,10-dimethyl-4-aza-5-thiatricyclo[5.2.1.0^3,7]-

decane 5,5-dioxide, to give N-[(E)-(3ЈR)-3Ј-trimethylsilylbutanoyl]-(7S)-10,10-dimethyl-4-aza-5-thiatricyclo-

[5.2.1.0^3,7]decane 5,5-dioxide 13, removal of the chiral auxiliary with bromomagnesium benzyloxide, aldol reaction

with acetaldehyde, and decarboxylative elimination, to give either the Z- or E-isomer. Both the E- and Z-allylsilanes

16 reacted with the adamantyl cation to give mixtures of E- and Z-4-adamantylpent-2-enes 17. The E-allylsilane

gave the E- and Z-products in a ratio of 40 : 60, and the Z-allylsilane gave the E- and Z-products in a ratio of

99.8 : 0.02. The enantiomer ratio was >99 : 1 for the reaction of the E-allylsilane giving the Z-product, 90 : 10 for the

E-allylsilane giving the E-product, and 95 : 5 for the Z-allylsilane giving the E-product, showing that the reactions

were stereospeciﬁc to a high degree, but not always quite completely so. The allenylsilane, 2-trimethylsilylpenta-2,3-

diene 29, was prepared enantiomerically highly enriched (er 99 : 1) by copper-catalysed reaction of methylmagnesium

chloride with (S)-4-trimethylsilylbut-3-yn-2-yl camphor-10-sulfonate 28. The allenylsilane 29 reacted with the

adamantyl cation to give (S)-4-adamantylpent-2-yne (S)-30 with the same level of enantiomeric purity, showing

that the reaction was, as accurately as can be measured, completely stereospeciﬁc. The allenylsilane 29 also reacted

with isobutanal in the presence of titanium tetrachloride to give 2,4-dimethylhept-5-yn-3-ol as a mixture of

diastereoisomers, syn 31 and anti 32, in a ratio of 95 : 5, with the major diastereoisomer present as a mixture of

enantiomers (4R,5R) : (4S,5S) in a ratio of 99 : 1, showing that the reaction was, as accurately as can be measured,

completely stereospeciﬁc in the anti sense. The corresponding propargylsilane, 4-trimethylsilylpent-2-yne 37,

reacted with the adamantyl cation to give dienes assigned the structures 2,3-diadamantyl-1,3-pentadiene 42 and

2,4-diadamantyl-1,3-pentadiene 43, and reacted with isobutanal in the presence of titanium tetrachloride to give

2-(1-hydroxy-2-methylpropyl)-3-trimethylsilylpenta-1,3-dienes 45 and 2,4-dimethyl-5-trimethylsilylhept-5-en-3-one

46. The enantiomerically enriched propargylsilane (R)-1,3-bis(trimethylsilyl)but-1-yne 62 (er >99.7 : 0.3) was

prepared from the sultam 13, by removal of the chiral auxiliary with lithium ethoxide, reduction of the ethyl ester

to give (R)-3-trimethylsilylbutanal 60, enol triﬂate formation, β-elimination and C-silylation. The propargylsilane 62

reacted with 2,4-dinitrobenzaldehyde in the presence of titanium tetrachloride to give the allenes, 1-(2,4-dinitrophenyl)-

2-trimethylsilylpenta-2,3-dienols 63–66, as two diastereoisomers in a ratio of 2 : 1, each of which was a pair of

enantiomers in a ratio of approximately 3 : 1, showing that there was considerable loss of stereospeciﬁcity, but

that what there was was in the anti sense. A similar reaction with isobutanal gave a similar set of four allenes,

2-methyl-4-trimethylsilylhepta-4,5-dien-3-ol 73–76, but with a negligible degree of stereospeciﬁcity.

because the relatively weaker inherent preference for axial or

equatorial attack provided a less demanding constraint to set

Introduction

We reported our results measuring accurately the degree of

stereospeciﬁcity of the S_E2Ј reactions of allyl-, allenyl- and

propargylsilanes in three preliminary communications.¹This is

the full paper on that work, which is the culmination of an

extensive investigation on the diastereoselectivity of electro-

philic attack on a double bond adjacent to a stereogenic centre

carrying a silyl group.^2,3

When we started our investigation of the S_E2Ј reactions of

allylsilanes the sense and degree of the stereospeciﬁcity was

unknown. Our earliest work was conﬁned to the diastereo-

selectivity of the reactions of the chiral but racemic allylsilanes

1, 2, 3 and 4, each of which had more than one stereochemical

feature in the molecule, landing us with the problems of double

stereo-diﬀerentiation. The stereochemical constraints in the

allylsilane 1 were matched, with the preference for attack anti

to the ester groups the same as the preference for attack anti to

the silyl group,⁴whereas the stereochemical constraints in the

allylsilane 2 were mismatched, with the exo attack on the

bicyclic system forcing most, but not all, reactions to be syn to

the silyl group.⁵The allylsilanes 3 and 4 were more telling,

against the eﬀectiveness with which the allylsilane unit encour-

aged stereospeciﬁcally anti reactions. The allylsilane 3 was

matched for those electrophiles that preferred to attack axially,

and the allylsilane 4 was matched for those electrophiles that

preferred to attack equatorially. In both cases the matched

reactions were stereochemically clean, and in the mismatched

cases the allylsilane stereochemistry overpowered, but did not

remove, the eﬀect of the inherent axial or equatorial prefer-

ence.⁶Thus we were able to deduce that the S_E2Ј reactions of

allylsilanes are powerfully and predictably, but not overwhelm-

ingly, eﬀective for the transfer of stereochemical information

from C-1 to C-3.

At this stage, Kumada and his co-workers developed a

method for the synthesis of the enantiomerically enriched

allylsilane 5, and others like it, in which the only stereogenic

centre was that carrying the silyl group.⁷This enabled them to

measure the extent to which allylsilanes reacted in the anti sense

5

7, unconstrained by the inﬂuence of any other stereochemical

feature. The major product in these reactions had the trans

double bond and the absolute conﬁguration 7, with electro-

T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 4

O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 7 4 9 – 7 6 9

749

View Article Online

Since the work on allenylsilanes described in our prelimin-

ary communication, others have seen high levels of stereo-

speciﬁcally anti S_E2Ј reactions.²²Sometimes a hydrogen atom is

transferred in an ene reaction, instead of the loss of the silyl

group, but these reactions also take place with electrophilic

attack anti to the silyl group.²³Another variant is the stereo-

speciﬁcally syn reaction with aldehydes when the silyl group is a

trichlorosilyl group.²⁴

More recent work on the preparation and stereospeciﬁc

reactions of propargylsilanes has also been for syn reactions

when the silyl group is a trichlorosilyl group.²⁵

philic attack having taken place anti to the silyl group in the

most populated conformation 6. They reported their work in a

magisterial series of papers,^7,8which showed that the S_E2Ј reac-

tions were not only stereospeciﬁcally anti, but also that they

took place with a wide variety of electrophiles with essentially

complete stereospeciﬁcity, as accurately as they could measure.

This work was supplemented by reports from Eschenmoser,⁹

from Nakai¹⁰and from Kitching,¹¹who also found high, but

not always complete, levels of anti stereospeciﬁcity in the reac-

tions of other allylsilanes. Wetter found an exception to the anti

rule in an acylative desilylation,¹²in which there might have

been a cyclic transition structure,¹³but he found later that pro-

todesilylation of the same allyldisilane was a stereospeciﬁcally

anti reaction.¹⁴

Results and discussion

Synthesis of the allylsilanes 16 with high enantiomeric purity

The key to the synthesis of an allylsilane having a high level of

enantiomeric purity was to establish the stereogenic centre in a

stable intermediate 13 (Scheme 1). This allowed us to raise the

enantiomeric purity to a high level, before completing the syn-

thesis by introducing the double bond. Our method for setting

up the stereogenic centre carrying the silyl group took advan-

tage of earlier work²⁶and the work of Oppolzer.²⁷We obtained

the highest level of stereochemical purity (99 : 1) at the silicon-

bearing carbon by the conjugate addition of lithium dimethyl-

cuprate to the silicon-containing E-substrate 10 based on

Oppolzer’s sultam derived from (ϩ)-camphor. Unfortunately,

the major product 11 was the more soluble diastereoisomer, and

recrystallisation was not an eﬃcient method for removing even

the 1% of diastereoisomer 12. We resorted therefore to a simple

device that was guaranteed to work—we removed the chiral

auxiliary and replaced it with its enantiomer derived from

(Ϫ)-camphor, which was enantiomerically pure as judged by

Oppolzer’s test.²⁸The major product 13 was now the less

soluble diastereoisomer, and three recrystallisations served to

remove all of the minor component 14. This elaborate pro-

cedure would be unnecessary in synthesis, but it served us well

here, because diastereoisomer purity was our primary concern,

and not the overall yield. We could not detect, by careful GC

analysis, any of the diastereoisomer 14. A conservative estimate

of the amount of diastereoisomer present was <0.05%, using

expanded GC traces, and basing our estimate on comparisons

of peak areas with those from various (and unknown but surely

harmless) impurities present to the easily measurable extent of

0.6–2%.

Very little was known about the stereochemistry of S_E2Ј reac-

tions of allenyl- and propargylsilanes—a pair of allenylsilanes

analogous to the allylsilanes 3 and 4 showed high but not com-

plete stereospeciﬁcity in the anti sense for protodesilylation,⁶

and Hayashi found that the propargylsilane 8, of low enantio-

meric purity, reacted with the tert-butyl cation to give the allene

9 with an even lower level of enantiomeric purity, and hence a

low level (58 : 42) of anti stereospeciﬁcity.¹⁵

We developed two syntheses of enantiomerically enriched

allylsilanes, the ﬁrst of which was fairly good, but not good

enough for the purpose in hand.¹⁶The second, adapted from a

general method for the synthesis of unsymmetrical allyl-

silanes,¹⁷allowed us to make a pair of allylsilanes E- and Z-16

that were, within experimental error, enantiomerically pure, and

this in turn allowed us to measure the degree of stereospeciﬁcity

in the S_E2Ј reaction with greater accuracy than anyone had

before. We knew from Eschenmoser’s and Kumada’s work that

it would be high, hence the need for high levels of enantiomeric

purity in order to measure it accurately, but we did not know

just how high it would be. Subsequently, in order to complete

the picture, we found good methods for the synthesis in high

enantiomeric purity of an allenylsilane 29 and of a propargyl-

silane 62, and we studied their reactions as well, all of it

reported in detail here.

Electrophilic attack on allylsilanes anti to the silyl group has

also been observed in a variety of cycloadditions, and in other

reactions in which the silyl group remains in the molecule, at

least in the ﬁrst-formed product.^18,3Stereospeciﬁcally anti S_E2Ј

reactions of allylsilanes are now well established,¹⁹and they

have been applied to the total synthesis of several natural

products,²⁰conspicuously in the work of Panek.²¹

Scheme 1 Reagents and conditions: i, Me₂CuLi, EtAlCl₂, Et₂O,

Ϫ78 ЊC, 2 h; ii, LiOH, H₂O₂; iii, (COCl)₂; iv, NaH, Oppolzer’s (–)-

sultam.

O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 7 4 9 – 7 6 9

750

View Article Online

We removed the chiral auxiliary with bromomagnesium

benzyloxide (Scheme 2), and used the benzyl ester in our

allylsilane synthesis, 13

15

E-16 or Z-16, based on the

diastereoselective aldol reactions of β-silyl enolates, and stereo-

speciﬁc decarboxylative eliminations.¹⁷Since the E-allylsilane

E-16 and its Z isomer Z-16 will give opposite enantiomers on

electrophilic substitution, it was necessary to be as thorough

in removing each from the other as we had been in setting up

the silicon-bearing stereogenic centre in the ﬁrst place. We

achieved this using repeated column chromatography on silica

gel heavily impregnated with silver nitrate. After this procedure,

the allylsilanes E-16 and Z-16 were both geometrically pure,

with <0.05% of the other present in each, as determined by the

same careful GC analysis.

Scheme 3 Reagents and conditions: i, AdCl, TiCl₄(0.1 eq.), CH₂Cl₂,

Ϫ78 ЊC, 30 min; ii, separate E and Z; iii, O₃, CH₂Cl₂, MeOH Ϫ78 ЊC;

2 min; iv, NaBH₄, 0 ЊC, 1 h; v, (–)-Mosher’s acid, DCC, DMAP,

CH₂Cl₂, rt, 3 h.

those of Kitching, that, when other stereochemical constraints

are present, the extent to which the S_E2Ј reactions of allylsilanes

are anti can be eroded.

We oﬀer two simpliﬁed explanations for why the Z product

should be formed with higher enantiomeric purity. Attack on

the allylsilane E-16 in a conformation close to 21 may take

place on the lower surface more selectively than attack takes

place on the upper surface of the alternative conformation 20,

because the lower surface of 21 is occupied by a hydrogen atom,

whereas the upper surface of 20 is occupied by a methyl group.

This argument assumes that all of the E product is formed by

attack taking place in conformation 20, and that all of the

Z product is formed by attack taking place in conformation 21;

in other words, there is no rotation about the C2–C3 bond in

the intermediate cations before the silyl group is plucked oﬀ

by a nucleophile, presumably chloride ion. Alternatively, the

intermediate cation 22, produced by attack on the lower sur-

face of the conformation 21, may change its conformation, by

Scheme 2 Reagents and conditions: i, BnOMgBr, THF, rt, 20 h;

ii, LDA; iii, MeCHO; iv, H₂, Pd/C; v, (MeO)₂CHNMe₂, CHCl₃, reﬂux,

2 h; vi, PhSO₂Cl, Py; vii collidine, reﬂux, 5 h.

Electrophilic substitution reactions of the allylsilanes 16

We carried out the reaction E-16

17 twice, using adamantyl

chloride as a representative simple electrophile²⁹and a catalytic

amount of titanium tetrachloride at Ϫ78 ЊC, with the same

result each time (Scheme 3). We separated the Z and E products

17, which were present in a ratio of 60 : 40, using the same silver

nitrate-impregnated column, obtaining each free of the other

(<0.05%), as determined yet again by careful GC analysis. We

measured the enantiomeric purity of both alkenes by ozon-

olysis, followed by reduction with sodium borohydride, and

derivatisation with Mosher’s acid.³⁰We were unable to use GC

rotation about the C2–C3 bond 22

23 before the silyl group

is lost, to a greater extent than the intermediate 24, produced by

attack on the upper surface of conformation 20, changes its

conformation, because the lowering of energy is greater in the

former case.

1

analysis at this stage, but the ¹⁹F-NMR and H-NMR spectra

allowed us to measure the diastereoisomeric ratio of the ﬁnal

products 18 and 19 to within 0.5%. We found that the major

product Z-17 was enantiomerically pure (>99.5 : 0.5%). We

assume that the reaction is stereospeciﬁcally anti, not syn, there

being little doubt at this stage about the stereochemical sense of

this type of reaction. This result helpfully conﬁrmed that the

sample of Mosher’s acid was enantiomerically pure, and that

there was no loss of conﬁgurational purity during the synthesis

and degradation, including, most worryingly, the possibility of

some racemisation of the aldehyde and during the chromato-

graphic separations of the alkenes, where silver-coordination

might, but was not expected to, constitute a danger. Clearly, for

this product, the degree of stereospeciﬁcity was very high, at

least 99%.

However, the minor product E-17 was present as a 90 : 10

mixture of enantiomers. For this product, the degree of stereo-

speciﬁcity was still high, but it was also measurably incomplete,

in agreement with our earlier observations described above, and

We carried out one rather inconclusive experiment to try to

ﬁnd out which of these explanations is the more plausible. We

repeated the S_E2Ј reaction three times using the Z-allylsilane

O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 7 4 9 – 7 6 9

751

View Article Online

Z-16 in place of the E-allylsilane E-16 (Scheme 4). In each of

these reactions, we obtained largely the E-product. The Z

product was just detectable as 0.2% of the mixture, too little to

measure its enantiomeric purity. The major product proved on

conversion to the Mosher’s esters 18 and 19 to be 97 : 3, 95 : 5

and 93 : 7 mixtures of enantiomers in the three runs, averaging

as a 95 : 5 mixture.

Scheme 5 Reagents and conditions: i, (–)-camphorsulfonyl chloride,

DMAP, Et₃N, CH₂Cl₂, 0 ЊC, 1 h; ii, MeMgCl, LiBr, CuBr, THF,

Ϫ78 ЊC, 40 min, rt, 10 min.

treating it with the methyl Grignard reagent and copper()

bromide in place of lithium dimethylcuprate. The latter

reagent is known to racemise allenes,³⁶and did indeed give us

allene with considerable, and variable, loss of enantiomeric

purity. The enantiomeric purity of the allene 29 was measured

for us by Professor König using gas chromatography with a

chiral column,³⁷which gave full base-line resolution. We sub-

mitted three samples from three runs, which proved to have

ratios of enantiomers of 98.7 : 1.3, 99 : 1, and 99.25 : 0.75.

There must have been some minor losses of stereospeciﬁcity in

Scheme 4 Reagents and conditions: i, AdCl, TiCl₄(0.1 eq.), CH₂Cl₂,

Ϫ78 ЊC, 30 min; ii, separate E and Z; iii, O₃, CH₂Cl₂, MeOH Ϫ78 ЊC;

2 min; iv, NaBH₄, 0 ЊC, 1 h; v, (–)-Mosher’s acid, DCC, DMAP,

CH₂Cl₂, rt, 3 h.

the last step 28

29, since we would certainly have detected

This result might mean that 95% of the electrophilic attack

took place in conformation 25 and 5% in the high-energy con-

formation 26, with 100% selectivity for attack anti to the silyl

group in both cases. If the intermediate cation derived from the

minor conformer, not implausibly, changed its conformation

completely by rotation about the C2—C3 bond before the loss

of the silyl group, it would give the 5% of the product (R)-E-17.

It equally might mean that electrophilic attack took place only

in conformation 25, with 95% of attack from above and 5%

from below. Because the 95 : 5 ratio in these experiments and

the 90 : 10 ratio in the experiments on the E-isomer are so

similar, we are unable to distinguish between these explan-

ations, and must rest at this stage on the possibility that a

combination of the two is more than likely.

the presence of 1% of the diastereoisomer of the camphor-

sulfonate 28.

Because there was no intermediate in this synthesis in which

the conﬁguration could be securely preserved, we were unable

to prepare the allenylsilane 29 with quite such a high level of

enantiomeric purity as we had for the allylsilane 16. We have,

nevertheless, a synthesis of an allenylsilane of high enantio-

meric purity, which we needed for our work on the synthesis of

ebelactone A,^33,38as well as for the work reported in this paper.

Electrophilic substitution reactions of the allenylsilane 29

We carried out a reaction with adamantyl chloride and

titanium tetrachloride, and obtained the propargyladam-

antanes 30 in rather low yield (Scheme 6). We measured the

proportion of the enantiomers by semi-hydrogenation of the

acetylenic bonds to give the mixture of Z-alkenes, and meas-

ured the ratio by the method described above, using the ¹⁹F and

¹H NMR spectra of the Mosher’s esters 19 and 18. We estimate

from our NMR measurements, which agree with each other,

that the amount of the minor diastereoisomer present is 1%,

and certainly less than 2%. Since the starting material was a

mixture of enantiomers in a ratio of 99 : 1, the reaction must

have been close to 100% stereospeciﬁc.

Synthesis of the allenylsilane 29 of high enantiomeric purity

For the synthesis of the enantiomerically enriched allenylsilane

29, we introduced the chirality by reduction of 4-trimethyl-

silylbut-3-yn-2-one with Brown’s³¹and Midland’s³²“alpine”

borane, giving the propargyl alcohol 27 as a 94 : 6 ratio of

enantiomers (Scheme 5). More recently,³³we have been able to

make the same compound with higher enantiomeric purity

using Noyori’s catalytic asymmetric hydrogenation.³⁴To raise

the level of enantiomeric purity, we recrystallised the cam-

phorsulfonate 28 until it was, as well as we could measure, a

single diastereoisomer (>99.5 : 0.5), having ﬁrst determined that

the camphorsulfonate, derived from (Ϫ)-camphor, was higher

melting than the diastereoisomeric camphorsulfonate derived

from (ϩ)-camphor.

We also carried out reactions between the allenylsilane 29

and isobutyraldehyde in the presence of titanium tetrachloride,

and obtained a good yield of the homopropargyl alcohols 31

and 32 in three runs (Scheme 7). This reaction, which sometimes

gave us an unstable by-product in up to 20% yield,³⁹is a model

for a key step in our synthesis of ebelactone A, for which we

want the enantiomer modelled by (3R,4R)-31. The diastereo-

isomers, syn and anti with respect to the relative conﬁguration

between C-3 and C-4, were present in a ratio 31 : 32 of 95 : 5,

rather higher than that (80 : 20) for the known reaction of the

corresponding allenylsilane lacking a methyl group on C-1 with

cyclohexanecarboxaldehyde.⁴⁰

As a result, there was not enough of the anti alcohols 32 with

which to measure accurately the ratio of enantiomers, but the

syn pair 31, separated from the anti isomers by chromato-

graphy, gave the camphorsulfonates 33 and 34 (Scheme 7). The

The conversion of the camphorsulfonate into the allenyl-

silane was based on our earlier synthesis of the corresponding

racemic allenylsilane.³⁵We improved the earlier procedure by

O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 7 4 9 – 7 6 9

752

View Article Online

We converted the same mixture of the syn alcohols 31 into

the Mosher’s esters 35 and 36, which were also present in a

ratio of 99 : 1 (Scheme 7). All of the possible stereoisomers of

these Mosher’s esters were already known to us, with assigned

relative and absolute conﬁgurations,⁴¹conﬁrming that the S_E2Ј

reaction of the allenylsilane is indeed stereospeciﬁcally anti, as

well as being to a very high degree. This work conﬁrmed that

the major product 35 was the isomer with the syn relationship

between C-2 and C-3, and hence that the reaction with the

allenylsilane had given the homopropargylic alcohol (3R,4R)-

31 with the syn relationship between C-3 and C-4.

A search for a stereochemically deﬁned electrophilic substitution

reaction with a chiral propargylsilane

This left propargylsilanes to be investigated, an especially inter-

esting case, because Hayashi and Kumada had already found

that, although the one reaction they looked at 8

9 was

stereospeciﬁcally anti, the degree of stereospeciﬁcity appeared

to be low.¹⁵They found that the propargylsilane 8, prepared as a

mixture of enantiomers in a ratio of 59 : 41 (18% ee), reacted

with the tert-butyl cation to give the allene 9 in 23% yield as a

mixture of enantiomers in a ratio estimated on the basis of

semi-empirical rules⁴²to be 51.5 : 48.5 (3% ee). This indicated

that the reaction had been stereospeciﬁc in Zimmerman’s

sense,⁴³but the ratio of anti : syn attack was only about 58 : 42.

Although there was no reason to doubt their conclusions, the

proof of the absolute conﬁguration of the product, and, less

reliably, the measurements of the ratios of enantiomers were

all based upon rules, and estimates, rather than upon direct

physical measurements.

Scheme 6 Reagents and conditions: i, AdCl, TiCl₄(0.1 eq.), CH₂Cl₂,

Ϫ78 ЊC, 30 min; ii, H₂, Lindlar; iii, O₃; iv, NaBH₄; v, (–)-Mosher’s acid,

DCC, DMAP, CH₂Cl₂, rt, 3 h.

Although many S_E2Ј reactions of propargylsilanes have been

reported, a high proportion of them have no other substituent

on C-1 than the silyl group. These include the reactions of

propargyltrimethylsilane itself,⁴⁴and both intermolecular⁴⁵and

intramolecular reactions⁴⁶of propargylsilanes having a substit-

uent at the acetylenic terminus C-3, all of which produce a

terminal allene. In several cases, even with these simple propar-

gylsilanes, alternative reactions took place, including nucleo-

philic capture of the intermediate cation, with^47,48or without⁴⁹

migration of the silyl group and without the loss of the silyl

group, and ene reactions in which the silyl group is also

retained.⁵⁰In other cases, the allene is formed, but subsequent

reactions took place, including nucleophilic attack⁵¹and

rearrangements.⁵²Only a few reactions have been reported in

which the α carbon had a second substituent in addition to the

silyl group, an essential feature if we are to produce a chiral

allene. Furthermore, relatively few of the latter actually gave

allenes,^53,54with subsequent reaction of one kind or another

taking place, apparently more easily as a consequence of the

presence of the extra substituent.^55,56

Thus we needed to ﬁnd a clean reaction of this type, and

ideally one using the propargylsilane 37, in order that our

results could be compared with those from the corresponding

allyl- and allenylsilanes 16 and 29. We were not successful. The

chiral (but racemic) propargylsilane 37 did not give an allene

with adamantyl bromide and titanium tetrachloride (Scheme 8).

The products were conjugated dienes, C₂₅H₃₆, which have two

adamantyl units for each C₅unit derived from the propargyl-

silane. We suggest the structures 42 and 43 for these dienes.

They were probably the result of electrophilic attack by a

second adamantyl cation on the ﬁrst-formed allene 38, and we

were unable to stop the reaction at this stage. This was perhaps

no surprise, since it has been reported that even the usually

well-behaved propargyltrimethylsilane does not give allenyl-

adamantane under these conditions,²⁹but Hayashi’s result

Scheme 7 Reagents and conditions: i, Me₂CHCHO, TiCl₄, CH₂Cl₂,

Ϫ78 ЊC, 1.5 h; ii, separate 31 from 32; iii, (ϩ)-camphorsulfonyl chloride,

DMAP, Et₃N, CH₂Cl₂, reﬂux, 18 h; iv, H₂, Lindlar; v, NaH, DMSO,

Me₂SO₄; vi, O₃; vii, NaBH₄; viii, (–)-Mosher’s acid, DCC, DMAP.

ﬁrst and second runs used the allenylsilane with a ratio of

enantiomers of 98.7 : 1.3. The products 33 and 34 were present

1

in ratios of 99.1 : 0.9 and 98.8 : 1.2, as measured by H NMR

spectroscopy. The third run used the allenylsilane with a ratio

of enantiomers of 99.25 : 0.75, and the products were present in

a ratio of 99.3 : 0.7, averaging to a ratio of 99 : 1, essentially the

same for all three runs. As in the reaction with adamantyl chlor-

ide, the products and the starting material had the same degree

of enantiomeric purity, indicating that the transfer of chirality

had been close to 100%.

8

9 had encouraged us to try this reaction.

In any case, we preferred a reaction in which the product was

not only a chiral allene, but one in which the product had a

substituent to which a chiral auxiliary could be attached, in

O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 7 4 9 – 7 6 9

753

View Article Online

Scheme 10 Reagents and conditions: i, Me₂CHCHO, TiCl₄, CH₂Cl₂; ii,

2,4-(O₂N)₂C₆H₃CHO, TiCl₄, CH₂Cl₂.

Scheme 8 Reagents and conditions: i, adamant-1-yl bromide, TiCl₄,

CH₂Cl₂, Ϫ78 ЊC, 1 h.

order to measure the sense of electrophilic attack and the

degree of enantiomeric purity without having to rely upon the

rotation of polarised light. With this requirement, adamantyl

bromide was of no use, because derivatisation of any allene

products, even if they had been formed, would lose the chiral

information. Schemes 9–11 illustrate some of the unhelpful

reactions that we observed between various propargylsilanes

and aldehydes or acetals.

Scheme 11 Reagents and conditions: i, Me₂CHCH(OCH₂CH₂Cl)₂,

BF₃ؒOEt₂, CH₂Cl₂, Ϫ78 ЊC, 1 h; ii, Me₂CHCHO, various Lewis acids,

CH₂Cl₂.

49, which gave the dihydrofurans 48, 50a and 50b (Scheme 10).

The phenyl groups no doubt were even better at stabilising the

cation produced by silyl migration, but again Hayashi’s result

8

9 had encouraged us to try this reaction. The formation of

dihydrofurans as a result of the rearranged cation being

trapped by the oxygen atom is well precedented.⁴⁷We saw other

unfruitful outcomes with the propargylsilane 53, including

nucleophilic capture in the formation of the allylic chlorides 51,

54 and 55, as well as the formation of the dihydrofuran 52

(Scheme 11).

The alkyl or aryl groups on C-1 in the propargylsilanes 37,

47, 49 and 52, which were necessary adjuncts in order to make

the product allenes chiral, had fatally encouraged unwelcome

reactions. We reasoned that a silyl group at the acetylenic ter-

minus would electronically stabilise, and sterically hinder, the

intermediate cation, perhaps enough to prevent silyl migration,

and allow the formation of an allene product. There was some

evidence in the literature that this would work.⁵⁴Happily, the

racemic propargylsilane 56 with 2,4-dinitrobenzaldehyde in the

presence of titanium tetrachloride gave a pair of diastereo-

isomeric allenyl carbinols 57 in good yield and in a ratio of

2.2 : 1 (Scheme 12). These could be oxidised to a single ketone

58. We now had a reaction that we could use.

Scheme 9 Reagents and conditions: i, TiCl₄, CH₂Cl₂, Ϫ78 ЊC, 1 h.

Isobutyraldehyde gave the dienes 45 (E : Z 66 : 34 or 34 : 66)

and the ketones 46 (E : Z 50 : 50) (Scheme 9), both of which are

the result of a migration of the silyl group in the intermediate

cation 44, followed by proton loss, instead of the loss of

the silyl group, and the presence of the methyl group on C-4 in

the propargylsilane 37 only made the migration easier. Silyl

migration was also a problem with the propargylsilanes 47 and

In order to set up an analytical system, we also prepared

Mosher’s esters of the carbinols. There were four products 59,

with well resolved singlets in the ¹⁹F-NMR spectrum, which

O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 7 4 9 – 7 6 9

754

View Article Online

the mixture of four allenyl carbinols 63–66, from which we

prepared the Mosher’s esters 67–70 (Scheme 14). The four

isomers A, B, C and D were present in ratios of 6.3 : 1.7 : 1 : 3,

respectively. We assigned relative stereochemistry at the

1

carbinol carbon using the H-NMR method of Kakisawa and

his co-workers,⁵⁸in which the Mosher’s derivatives with the

R- and the S-acid are compared. Finally, we assigned the abso-

lute stereochemistry by synthesising authentic samples of the

allenylcarbinols 63 and 65 by the method of Marshall and

Adams.²⁵The propargyl camphorsulfonate 71 (the enantiomer

of the camphorsulfonate 28), prepared from (ϩ)-camphor-

sulfonyl chloride and the R-alcohol, and recrystallised to give a

>99 : 1 ratio of diastereoisomers, reacted with 2,4-dinitro-

benzaldehyde and trichlorosilane to give a mixture of the alco-

hols 63 and 65 (58%), together with a little of the corresponding

homopropargylic alcohols 72 (13%) (Scheme 15). The relative

and absolute conﬁgurations assigned to the major and minor

Scheme 12 Reagents and conditions: i, 2,4-(O₂N)₂C₆H₃CHO, TiCl₄,

CH₂Cl₂, Ϫ78 ЊC, 15 min; ii, Dess–Martin periodinane, CH₂Cl₂, rt, 20

min; iii, (ϩ)-Mosher’s acid chloride, Et₃N, DMAP, CH₂Cl₂, rt, 1 h.

appeared at δ Ϫ70.81, Ϫ70.88, Ϫ71.03 and Ϫ70.96, to which we

gave labels A, B, C and D, respectively. They were present in

ratios of 2 : 2 : 1 : 1, which established that A and B were

derived from one diastereoisomer, and C and D from the other.

Synthesis of the propargylsilane 62 of high enantiomeric purity

In anticipation of the work described above, we had already

developed a general synthesis of chiral propargylsilanes.⁵⁷Using

this route, we prepared the enantiomerically enriched propargyl-

silane 62 (Scheme 13), starting with the sultam 13, obtained

this time as a mixture of diastereoisomers in a ratio better than

99.7 : 0.3. We removed the chiral auxiliary using ethoxide ion,

reduced the ethyl ester to the aldehyde 60, formed the enol triﬂate

61, and carried out the elimination and silylation in one pot to

give the propargylsilane 62, which was a mixture of enantiomers

presumably in a ratio of at least 99.7 : 0.3.

i

Scheme 13 Reagents and conditions: i, LiOEt; ii, Bu₂AlH; iii, Tf₂O,

2,6-^tBu₂Py; iv LDA; v, Me₃SiCl.

Electrophilic substitution reactions using the enantiomerically

enriched propargylsilane 62

Scheme 14 Reagents and conditions: i, 2,4-(O₂N)₂C₆H₃CHO, TiCl₄,

CH₂Cl₂, Ϫ78 ЊC, 15 min; ii, (ϩ)-Mosher’s acid chloride, Et₃N, DMAP,

CH₂Cl₂, rt, 1 h.

We repeated the reaction with 2,4-dinitrobenzaldehyde using

the enantiomerically enriched propargylsilane 62, and obtained

O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 7 4 9 – 7 6 9

755

View Article Online

Ϫ71.68, Ϫ71.86 and Ϫ71.75. From the racemic propargylsilane,

the product mixture showed the two signals at δ Ϫ71.42 and

Ϫ71.68 and the two signals at δ Ϫ71.86 and Ϫ71.75 of equal

intensity within the pair, with the ﬁrst pair twice as intense as

1

the second. Comparison of the H-NMR spectra of the deriv-

atives of the alcohol 73 with Mosher’s R-acid and S-acid iden-

tiﬁed that this diastereoisomer was R at the carbinol carbon.

Finally, the synthesis using Marshall’s method gave only the

pair 73 and 75 in low yield (9%), but the Mosher’s derivatives

showed that they were present in a ratio of 98 : 2. The results of

two runs were not completely consistent, the major pair, 75 and

76, indicated that the reaction had been selectively anti (anti : syn

67 : 33 and 55 : 45), while the minor pair, 73 and 74, indicated that

it had been selectively syn (anti : syn 43 : 57 and 48 : 52). Com-

bined, and averaged over the two runs, this S_E2Ј reaction

appeared to be anti : syn in a ratio of 53 : 47, which, within

experimental error, is as close to 50 : 50 as makes no matter.

We have too little information to explain why isobutyralde-

hyde should be even less selective than 2,4-dinitrobenzaldehyde.

The reactive species will be the aldehyde coordinated to the

Lewis acid. 2,4-Dinitrobenzaldehyde may be more reactive than

isobutyraldehyde, but its coordinated form will probably be

present in lower concentration. As a result it is not possible to

say whether its greater selectivity is a violation of the reactivity–

selectivity principle. Since we do not know whether the erosion

of stereospeciﬁcity is caused by rotation in the intermediate

cation or by the initial attack not being anti to the silyl group,

we can only speculate. One possibility is that the intermediate

cation in the isobutyraldehyde reaction might be a little more

stable than that in the 2,4-dinitrobenzaldehyde reaction, and

might therefore have lived long enough to lose more of its

stereochemical information. Our anti : syn ratios are close to

those of Hayashi’s and Kumada’s, conﬁrming the erosion of

stereospeciﬁcity that they also saw. We are inclined to agree

with their tentative explanation: that the intermediate cation is

able to undergo rotation about the σ-bond before the loss of the

silyl group. In our series, with a second silyl group stabilising

the intermediate cation, we may have unwittingly exacerbated

this problem. There is also the possibility that the direction of

attack on a triple bond, with nearly cylindrical symmetry in the

π-orbitals, is less constrained than it is on a double bond, where

attack is only proﬁtable if it is more or less directly above or

below the plane of the π-bond.

Scheme 15 Reagents and conditions: i, 2,4-(O₂N)₂C₆H₃CHO, Cl₃SiH,

CuCl, ⁱPr₂NEt, DMF, Et₃N.

allenes 63 and 65 are based on the stereochemistry Marshall has

proved for closely similar reactions, and like his they ﬁt the

Lowe–Brewster rules. The Mosher’s derivatives of these allenyl

carbinols corresponded to the diastereoisomers A and D, and

they were present in a ratio of 93 : 7, similar to the diastereo-

isomer ratios found by Marshall for other aldehydes. We were

now able to assign structures to the isomers A, B, C and D

as 67, 68, 70 and 69, respectively, from which we calculated

the ratios of diastereoisomers (67 : 33) and the ratios of the

anti : syn reaction (79 : 21 and 76 : 24) shown in Scheme 14. Our

proof of the relative and absolute stereochemistry is not quite

as complete as we would like (none of our products crystal-

lised), but, coupled with Marshall’s extensive work with several

interrelated conversions, it ﬁts an internally consistent pattern

that is compelling. Evidently, the S_E2Ј reaction 62

63–66

takes place predominantly in the anti sense, but, in contrast to

the reactions of allyl- and allenylsilanes, the anti : syn ratio is

only about 3 : 1.

In addition, we carried out the same series of reactions with

isobutyraldehyde (Scheme 16). We assigned structures to the

products 73–76 in the same way as for the products with 2,4-

dinitrobenzaldehyde. The Mosher’s derivatives from the R-acid

showed four singlets in the ¹⁹F-NMR spectrum at δ Ϫ71.42,

Conclusions

We have developed syntheses capable of making allylsilanes,

allenylsilanes and propargylsilanes in a state of high enantio-

meric purity. Using these compounds, we have conﬁrmed, with

accurate measurements, that the stereochemistry of the S_E2Ј

reactions of the allylsilanes 16 and the allenylsilane 29 are

highly selective in the anti sense, especially the latter, which

is uncomplicated by the formation of mixtures of Z- and

E-alkenes. In contrast, the S_E2Ј reaction of the propargylsilane

62 with 2,4-dinitrobenzaldehyde is stereospeciﬁcally anti to a

lower degree (75 : 25). Furthermore, the selectivity in the latter

reaction depends upon the electrophile, being negligible with

isobutyraldehyde.

Experimental

General

Melting points were taken on a Gallenkamp melting point

apparatus and are uncorrected. Infrared spectra were recorded

on a Perkin-Elmer 297 infra-red grating and a Perkin-Elmer

FT-IR 1600 spectrophotometer and wavenumbers were meas-

ured relative to polystyrene (1603 cm^Ϫ1). ¹H-NMR spectra were

recorded on a Varian EM 390 and Bruker WM 250, AM 400,

DPX250, DPX 400, DRX 400 and DRX 500 spectrometers

Scheme 16 Reagents and conditions: i, Me₂CHCHO, TiCl₄, CH₂Cl₂,

Ϫ78 ЊC, 30 min.

O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 7 4 9 – 7 6 9

756

View Article Online

with chemical shifts measured relative to TMS (δ 0.0 ppm) or

CHCl₃(δ 7.25 ppm) as an internal standard. The coupling con-

stant J is expressed in Hertz. ¹³C-NMR spectra were also

recorded on the Bruker WM 250, AM 400, DPX 250, DPX 400,

DRX 400 and DRX 500 spectrometers. ¹⁹F-NMR spectra

were recorded on the Bruker WM 250 and DPX 400 spectro-

meters with chemical shifts measured relative to CCl₃F. In ¹³C

attached-proton test (APT) spectra, ϩ denotes signals in the

same direction as the NMR solvent. Mass spectra were

recorded on AE1 MS 9 and MS 30 and on Kratos Concept (EI)

and Micromass Q-TOF (ESI) spectrometers. Column chrom-

atography was carried out using Merck Kieselgel 60 (230–

400 mesh ASTM). Silver nitrate-impregnated silica was pre-

pared by suspending Merck Kieselgel 60 in a solution of silver

nitrate in acetonitrile and evaporating oﬀ the solvent.⁵⁹Thin

layer chromatography (TLC) was performed on plates coated to

a thickness of 0.5 or 1.0 mm with Kieselgel 60 PF₂₅₄. Gas-liquid

chromatography (GLC) was carried out on a Carlo Erba 4130

instrument, using a 24 m, BP5, 5% phenylmethylsiloxane capil-

lary column (5 µm ﬁlm thickness) and helium as the carrier gas

(∼0.3 m s^Ϫ1), with nitrogen “make-up” leading to a hydrogen/

oxygen ﬂame ionisation detector. The temperature programmes

used accompany the data. Optical rotations were recorded on a

Perkin-Elmer 241 digital polarimeter using a sodium lamp (589

nm) as the light source. Concentrations are given in units of

10^Ϫ2g cm^Ϫ3. The length of the optical rotation cell used was 10

cm. Tetrahydrofuran (THF) and diethyl ether (ether) were

freshly distilled from lithium aluminium hydride under argon.

All other solvents were distilled before use. Dichloromethane

and toluene were freshly distilled from calcium hydride under

argon. Light petroleum, unless otherwise stated, refers to the

fraction boiling in the range 40–60 ЊC. Organolithium reagents

were titrated using the method of Gilman.⁶⁰

slowly added to a stirred mixture of copper() iodide (44.1 g,

230 mmol) and tributylphosphine (73 cm³) in ether (430 cm³)

under argon at Ϫ20 ЊC until a clear solution was obtained.

After 20 min the solution was cooled to Ϫ78 ЊC and ethyl-

aluminium dichloride (230 cm³of a 1 mol dm^Ϫ3solution in

hexane, 230 mmol) was slowly added. After 20 min a solution

of the sultam (8.0 g, 23 mmol) in dry ether (330 cm³) was slowly

added, and the mixture stirred for 2 h. Saturated ammonium

chloride solution (250 cm³) was added, the layers were separ-

ated, and the aqueous phase extracted with ether ( 3 × 150 cm³).

The combined organic layers were washed with ammonia

solution (pH 8), dried (MgSO₄) and evaporated under reduced

pressure to give a mixture of the sultams 11 and 12 (7.8 g, 93%)

1

in a ratio of 99 : 1 (GLC, H-NMR); [GLC retention times:

100 ЊC–20 ЊC/min–200 ЊC)/min 32.6 (12) and 33.8 (11)];

ν_max(CH₂Cl₂)/cm^Ϫ11695 (C᎐O), 1335 and 1140 (SO N) 1225

᎐

2

and 835 (SiMe₃); δ_H(250 MHz; CDCl₃) 3.85 (1 H, t, J 6.3,

CHN), 3.45 (1 H, d, J 13.8, CH_AH_BSO₂), 3.42 (1 H, d, J 13.8,

CH_AH_BSO₂), 2.60 (1 H, dd, J 13.6 and 2.6, CH_AH_BCO), 2.55

(1 H, dd, J 13.6 and 6.8, CH_AH_BCO), 2.08 (2 H, d, J 6.3,

CH₂CHN), 1.9–1.8 (3 H, m, CHCH₂CHN and CH₂CCHN),

1.45–1.2 (3 H, m, CH₂CH₂CCHN and CHSi), 1.14 and 0.94

(3 H each, s, CMe₂), 0.92 (3 H, d, J 7.7, MeCHSi) and Ϫ0.04

(9 H, s, Me₃Si); δ_C(CDCl₃) 172.7, 65.4, 53.0, 48.3, 47.7, 44.6,

38.6, 37.4, 32.8, 28.4, 20.8, 19.9, 16.7, 14.2 and Ϫ3.5; m/z

(EI) 342 (30%, M Ϫ Me), 293 (20, M Ϫ SO₂) and 278 (30,

M Ϫ MeSO₂)(Found: M^ϩϪ Me, 342.1542. C₁₇H₃₁NO₃SiS

requires M Ϫ Me, 342.1559).

(3R)-3-Trimethylsilylbutanoic acid

Using reaction conditions developed by Evans,⁶³hydrogen

peroxide (54 cm³of a 30% solution in water, 480 mmol) and

lithium hydroxide (9.9 g of the monohydrate, 240 mmol) and

the sultam 11 (21.1 g, 59 mmol) in THF (440 cm³) and water

(150 cm³) were stirred at room temperature for 2 h. The mix-

ture was cooled to 0 ЊC and sodium sulﬁte solution (150 cm³,

1.5 mol dm^Ϫ3) was added. The THF was evaporated under

reduced pressure and the pH of the aqueous residue was

adjusted to 9–10 by the addition of saturated sodium hydro-

gencarbonate solution, extracted with dichloromethane (4 ×

N-[(E )-3Ј-Trimethylsilylpropenoyl]-(7S )-2,10-camphorsultam

10

Using reaction conditions developed by Vandewalle and

Oppolzer,²⁸oxalyl chloride (4.5 cm³) and (E)-3-trimethylsilyl-

propenoic acid¹⁷(7.4 g, 51 mmol) were kept in dry dichloro-

methane (24 cm³) under argon at room temperature for 2 h. The

solvent and excess of reagent were evaporated oﬀ under

reduced pressure, and the residue dissolved in dry toluene (120

cm³). Meanwhile sodium hydride (2.5 g of a 60% dispersion in

oil) in dry hexane (20 cm³) was stirred under argon at room

temperature for 5 min. The hexane was then syringed out and a

solution of (7S)(Ϫ)-camphorsultam⁶¹(9.2 g, 43 mmol, with its

enantiomeric purity, which cannot be relied upon absolutely,⁶²

conﬁrmed by the method of Vandewalle and Oppolzer²⁸) in dry

toluene (230 cm³) was slowly added, and the mixture stirred for

1 h. The acid chloride was slowly added, and the resulting mix-

ture stirred for a further 2 h. Water (20 cm³) was added drop-

wise, the mixture diluted with more water, and extracted with

toluene. The organic layer was dried (MgSO₄), and evaporated

under reduced pressure to give the sultam 10 (12.2 g, 84%), mp

150 cm³), acidiﬁed with hydrochloric acid solution (3 mol dm^Ϫ3

)

and extracted with ethyl acetate (3 × 300 cm³). The dichloro-

methane and ethyl acetate extracts were separately washed with

brine, dried (MgSO₄) and evaporated under reduced pressure to

give, respectively, Oppolzer’s sultam (10.8 g, 85%) as a solid,

1

identical (TLC, H-NMR) to the original compound, and the

acid (7.0 g, 74%) as an oil; R_f(hexane–Et₂O) 0.3; ν_max(CHCl₃)/

cm^Ϫ13500–2500 (COOH), 1705 (C᎐O) and 835 (SiMe ); δ (250

᎐

3

H

MHz; CDCl₃) 11.0 (1 H, br s, COOH), 2.43 (1 H, dd, J 15.2 and

4.0, CH_AH_BCOOH), 2.08 (1 H, dd, J 15.2 and 10.9, CH_AH_B-

COOH), 1.17 (1 H, m, CHSi), 0.98 (3 H, d, J 7.1, MeCHSi) and

Ϫ0.02 (9 H, s, SiMe₃); m/z (EI) 160 (6%, M^ϩ), 145 (60, M – Me)

and 73 (100, SiMe₃) (Found: M^ϩ, 160.0908. C₇H₁₆O₂Si requires

M, 160.0915).

148–150 ЊC (from EtOH); ν_max(CH₂Cl₂)/cm^Ϫ11665 (C᎐O), 1595

᎐

(C᎐C), 1330 and 1130 (SO N) 1220 and 850 (SiMe ) and 990

N-[(E )-(3ЈR)-3Ј-Trimethylsilylbutanoyl]-(7R)-2,10-camphor-

᎐

2

3

(E C᎐C); δ (250 MHz; CDCl ) 7.36 (1 H, d, J 18.2, SiCH᎐CH),

sultam 13

᎐

H

3

6.91 (1 H, d, J 18.2, SiCH᎐CH ), 3.91 (1 H, t, J 6.3, CHN), 3.48

᎐

This was prepared in the same way as the sultam 10 above from

(3R)-3-trimethylsilylbutanoic acid (7.2 g, 45 mmol) and the

(7R)(ϩ)-sultam⁶¹(7.6 g, 35 mmol) to give a solid, which was

recrystallised three times to give the pure sultam 13 (10.2 g,

63%), mp 132.5–133.5 ЊC (from hexane), with dr >99.95 : 0.05

(GLC); ν_max(CH₂Cl₂)/cm^Ϫ11685 (C᎐O), 1335 and 1135 (SO N)

1215 and 845 (SiMe₃); δ_H(250 MHz; CDCl₃) 3.87 (1 H, t, J 6.3,

CHN), 3.45 (1 H, d, J 13.8, CH_AH_BSO₂), 3.42 (1 H, d, J 13.8,

CH_AH_BSO₂), 2.81 (1 H, dd, J 15.7 and 4.3, CH_AH_BCO), 2.39

(1 H, dd, J 15.7 and 10.4, CH_AH_BCO), 2.07 (2 H, d, J 6.3,

CH₂CHN), 1.9–1.8 (3 H, m, CHCH₂CHN and CH₂CCHN),

1.45–1.2 (3 H, m, CH₂CH₂CCHN and CHSi), 1.13 and 0.95

(1 H, d, J 13.8, CH_AH_BSO₂), 3.44 (1 H, d, J 13.8, CH_AH_BSO₂),

2.09 (2 H, d, J 6.3, CH₂CHN), 1.9–1.8 (3 H, m, CHCH₂CHN

and CH₂CCHN), 1.45–1.2 (3 H, m, CH₂CH₂CCHN and

CHSi), 1.16 and 0.96 (3 H each, s, Me) and 0.13 (9 H, s, SiMe₃);

[α]_DϪ89 (c. 1.1 in CHCl₃) (Found: C, 56.3; H, 8.1; N, 3.9.

C₁₆H₂₇NO₃SiS requires C, 56.3; H, 8.0; N, 4.1%).

᎐

2

N-[(E )-(3ЈR)-3Ј-Trimethylsilylbutanoyl]-(7S )-2,10-camphor-

sultam 11

Using reaction conditions developed by Oppolzer,²⁷methyl-

lithium (1.6 mol dm^Ϫ3solution in Et₂O, 300 cm³, 4.8 mmol) was

O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 7 4 9 – 7 6 9

757

View Article Online

(3 H each, s, CMe₂), 0.94 (3 H, d, J 7.7, MeCHSi) and Ϫ0.02

(9 H, s, Me₃Si); δ_C(CDCl₃) 172.5, 65.2, 53.0, 48.3, 47.7, 44.6,

38.6, 38.3, 32.8, 26.5, 20.8, 19.9, 16.3, 14.2 and Ϫ3.5; [α]_Dϩ83

(c. 1.2 in CHCl₃) (Found: C, 57.1; H, 8.8; N, 3.8. C₁₇H₃₁NO₃SiS

requires C, 57.1; H, 8.7; N, 3.9%).

(E )-(4R)-4-Adamantylpent-2-ene (E )-17 and (Z )-(4S )-4-

adamantylpent-2-ene (Z )-17

Using reaction conditions developed by Sasaki,²⁹the allylsilane

(E)-16 (142 mg, 1.0 mmol) in dry dichloromethane (1 cm³)

was added to the yellow solution of titanium tetrachloride

(0.070 cm³of a 1.0 mol dm^Ϫ3solution in CH₂Cl₂, 0.07 mmol)

and 1-chloroadamantane (171 mg, 1.0 mmol) in dry dichloro-

methane (3 cm³) under argon at Ϫ78 ЊC, and kept at Ϫ78 ЊC for

30 min. Sodium hydrogencarbonate solution (5 cm³) and THF

(1 cm³) was added, and the mixture extracted with hexane (3 ×

5 cm³). The combined organic extracts were washed with water,

dried (MgSO₄) and evaporated under reduced pressure. The

residue was ﬂash chromatographed (SiO₂, hexane) to give a

mixture of the E- and Z-alkenes (103 mg, 51%) in a ratio of

40 : 60 (GLC). The mixture was separated by repeated ﬂash

chromatography (SiO₂–AgNO₃, 4 : 1; hexane)⁵⁹optimising for

geometrical purity to give a sample of the pure E-alkene (E)-17

(17 mg); R_f(SiO₂–AgNO₃, 4 : 1; hexane) 0.2; (GLC retention

Benzyl (3R)-3-trimethylsilylbutanoate 15

Using reaction conditions developed by Evans,⁶⁴methyl-

magnesium bromide (29 cm³of a 3.0 mol dm^Ϫ3solution in

ether, 87 mmol) was slowly added to a stirred solution of benzyl

alcohol (12 cm³, 116 mmol) in dry THF (50 cm³) under argon at

0 ЊC. After 10 min a solution of the sultam 13 (10.4 g, 29 mmol)

in dry THF (100 ml) was added at 0 ЊC and the solution was

stirred at room temperature for 20 h. Light petroleum (bp 40–

60 ЊC) (20 cm³) was added, followed by saturated ammonium

chloride solution (20 cm³). The layers were separated and the

aqueous phase was extracted with light petroleum (bp 40–

60 ЊC) (3 × 20 cm³). The combined organic layers were dried

(MgSO₄) and evaporated under reduced pressure. The residue

was ﬂash chromatographed (SiO₂, hexane–Et₂O, 9 : 1–1 : 1) to

give Oppolzer’s sultam (5.6 g, 89%), identical (TLC, ¹H-NMR)

to the original compound, and the ester (7.0 g, 96%) as an oil,

identical (TLC, ¹H-NMR) to the racemic ester;¹⁷[α]_Dϩ9.2

(c. 1.2 in CHCl₃); R_f(hexane–Et₂O, 9 : 1) 0.5; (Found: C, 67.0;

H, 8.8. C₁₄H₂₂O₂Si requires C, 67.2; H, 8.9%).

time; 150 ЊC/min, 8.3); ν_max(CHCl₃)/cm^Ϫ11630 (C᎐C) and 980

᎐

(E C᎐C); δ (250 MHz; CDCl ) 5.4–5.3 (2 H, m, CH᎐CH), 2.0–

᎐

H

3

1.9 (4 H, m, MeCH and adamantyl CHs), 1.75–1.5 (12 H, m,

adamantyl CH s), 1.65 (3 H, d, J 4.7 Hz, MeCH᎐), and 0.86

᎐

2

(3 H, d, J 7.0, MeCHCH᎐); δ (CDCl ) 133.9, 124.2, 47.8, 39.8,

᎐

C

3

37.5, 34.5, 28.8, 18.0 and 14.1; m/z (EI) 204 (11%, M^ϩ), and 135

(100, C₁₀H₁₅) (Found: M^ϩ, 204.1875. C₁₅H₂₄requires M,

204.1878); and the pure Z-alkene (Z)-17 (36 mg); R_f(SiO₂–

AgNO₃, 4 : 1; hexane) 0.1; (GLC retention time; 150 ЊC/min

8.9); δ_H(250 MHz; CDCl₃) 5.43 (1 H, dq, J 11.0 and 6.5,

Benzyl (2S,3R,1ЈR)-3-hydroxy-2-(1Ј-trimethylsilylethyl)-

butanoate 15

MeCH᎐), 5.28 (1 H, dd, J 11.0 and 10.2, CHCH᎐), 2.07 (1 H,

᎐

This was prepared in the same way as the racemic ester¹⁷using

the enantiomerically enriched ester (6.9 g, 28 mmol) to give the

dq, J 10.2 and 6.9, CHCH᎐), 2.0–1.9 (3 H, m, adamantyl CHs),

᎐

1.7–1.5 (12 H, m, adamantyl CH s), 1.58 (3 H, d, J 6.5, MeCH᎐),

᎐

2

1

ester (6.4 g, 79%), identical (TLC, H NMR) to the racemic

and 0.82 (3 H, d, J 6.9, MeCH); δ_C(CDCl₃) 133.7, 122.7, 41.3,

39.6, 37.4, 35.1, 28.8, 13.9 and 13.1; m/z (EI) 204 (25%, M^ϩ),

and 135 (100, C₁₀H₁₅) (Found: M^ϩ, 204.1865. C₁₅H₂₄requires

M, 204.1878). Similarly, the Z-allylsilane Z-16 (17 mg, 0.12

mmol) gave a mixture of the E- and Z-alkenes (20 mg, 82%) in a

ratio of 99.7 : 0.3 (GLC). The mixture was separated by ﬂash

chromatography (SiO₂–AgNO₃, 4 : 1; hexane) to give the pure

material; R_f(hexane–Et₂O, 3 : 1) 0.14.

(2S,3R,1ЈR)-3-hydroxy-2-(1Ј-trimethylsilylethyl)butanoic acid

This was prepared in the same way as the racemic acid¹⁷using

the ester 15 (6.0 g, 20 mmol) to give the acid (3.7 g, 89%) as

prisms, mp 79–84 ЊC (from hexane), identical (TLC, ¹H NMR)

to the racemic material.

1

E-alkene, identical (GLC, H-NMR) to the material described

above; [α]_DϪ17 (c. 0.47 in CHCl₃). The structures of these

compounds were conﬁrmed by independent synthesis of

racemic samples described below.

(E )-(4R)-4-Trimethylsilylpent-2-ene (E )-16

This was prepared in the same way as the racemic allylsilane¹⁷

using N,N-dimethylformamide dimethylacetal and the enan-

tiomerically enriched acid (1.50 g, 7.3 mmol) to give a mixture

of E- and Z-allylsilanes in a ratio of 94 : 6 (GLC). The mixture

was separated by ﬂash chromatography (SiO₂–AgNO₃, 4 : 1;

pentane)⁵⁹to give the pure E-allylsilane (0.61 g, 58%), identical

(GLC, ¹H NMR) to the racemic material; R_f(SiO₂–AgNO₃,

4 : 1; hexane–Et₂O, 19 : 1) 0.5; [α]_Dϩ29 (c. 1.2 in CHCl₃).

(2RS )-2-Adamantylpropanoic acid

Using reaction conditions developed by Reetz,⁶⁵1,1-bis(tri-

methylsilyloxy)prop-1-ene⁶⁶(10.0 g, 46 mmol) was added drop-

wise with stirring to dry zinc chloride (1.88 g, 14 mmol) in dry

dichloromethane (50 cm³) under argon at room temperature.

After 5 min, 1-bromoadamantane (9.86 g, 46 mmol) in dry di-

chloromethane (25 cm³) was added dropwise, and the mixture

kept for 5 h. The mixture was poured into cooled hydrochloric

acid solution (175 cm³, 6 mol dm^Ϫ3) and extracted with di-

chloromethane (3 × 125 cm³). The combined organic extracts

were washed with sodium hydroxide solution (3 × 125 cm³,

10%). The combined aqueous layers were cooled, acidiﬁed with

hydrochloric acid solution (3 mol dm^Ϫ3) and extracted with di-

chloromethane (3 × 200 cm³). The combined organic extracts

were dried (MgSO₄) and evaporated under reduced pressure to

give the acid (3.0 g, 31%) as prisms, mp 155–159 ЊC (from

hexane) (lit.,⁶⁷158–159 ЊC); ν_max(CHCl₃)/cm^Ϫ13500–2500

(2S,3R,1ЈR)-3-Methyl-2-(1Ј-trimethylsilylethyl)propan-3-olide

This was prepared in the same way as the as the racemic

lactone¹⁷using benzenesulfonyl chloride and the enantio-

merically enriched acid (1.44 g, 7.0 mmol) to give the β-lactone

(0.62 g, 47%) as an oil, identical (TLC, ¹H NMR) to the racemic

material, and, and like it, contaminated with 12% (¹H NMR) of

another diastereoisomer.

(Z )-(4R)-4-Trimethylsilylpent-2-ene (Z )-16

(COOH) and 1700 (C᎐O); δ (250 MHz; CDCl ) 10.2 (1 H, br s,

᎐

H

3

This was prepared in the same way as the as the racemic

allylsilane¹⁷using the enantiomerically enriched β-lactone

(0.62 g, 3.3 mmol) to give a mixture of Z- and E-allylsilanes in a

ratio of 85 : 15 (GLC). The mixture was separated by ﬂash

chromatography (SiO₂–AgNO₃, 4 : 1; pentane–Et₂O, 19 : 1)⁵⁹to

COOH), 2.13 (1 H, q, J 7.1, MeCH ), 2.05–1.95 (3 H, m, adam-

antyl CHs), 1.8–1.4 (12 H, m, adamantyl CH₂s) and 1.09 (3 H,

d, J 7.1, MeCH).

(2RS )-2-Adamantylpropanal

1

give the pure Z-allylsilane (0.25 g, 53%), identical (GLC, H

NMR) to the racemic material; [α]_DϪ79 (c. 1.5 in CHCl₃);

R_f(SiO₂–AgNO₃, 4 : 1; hexane–Et₂O, 19 : 1) 0.35.

Using reaction conditions developed by Peters and van

Bekkum,⁶⁸oxalyl chloride (0.84 cm³) was added dropwise to a

O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 7 4 9 – 7 6 9

758

View Article Online

stirred mixture of the acid (1.63 g, 7.8 mmol) in dry dichloro-

methane (11 cm³) under argon at 0 ЊC. After 2 h the solvent and

excess reagent were evaporated oﬀ under reduced pressure. The

residue was dissolved in dry ethyl acetate (25 cm³) and added to

palladium on charcoal (0.39 g, 10%), ethyl acetate (25 cm³) and

ethyldiisopropylamine (2.2 cm³) under hydrogen at room tem-

perature. After 3 h the catalyst was ﬁltered oﬀ, and the ﬁltrate

washed with hydrochloric acid solution (2 × 100 cm³, 3 mol

dm^Ϫ3), sodium hydroxide solution (2 × 100 cm³, 10%), brine,

dried (MgSO₄) and evaporated under reduced pressure to give

the aldehyde (1.34 g, 89%); ν_max(ﬁlm)/cm^Ϫ11720 (C᎐O); δ (250

MHz; CDCl₃) 9.85 (1 H, d, J 4.0, CHO), 2.2–1.9 (4 H, m,

MeCH and adamantyl CHs), 1.8–1.4 (12 H, m, adamantyl

CH₂s), and 1.09 (3 H, d, J 7.0, MeCH); m/z (EI) 192 (1.5%,

M^ϩ), 163 (45, M Ϫ CHO) and 135 (100, C₁₀H₁₅) (Found: M^ϩ,

192.1504. C₁₃H₂₀O requires M, 192.1514).

[27 mg, 0.14 mmol, derived from the (Z)-alkene derived from

the reaction with the (E)-allylsilane], dimethylaminopyridine

(3.2 mg, 0.03 mmol) and (Ϫ)-Mosher’s acid (45 mg, 0.19 mmol)

in dry dichloromethane (0.2 cm³) under argon at room temper-

ature. After 3 h the mixture was ﬁltered through silica gel

eluting with dichloromethane. The solvent was removed under

reduced pressure and the residue chromatographed (prepar-

ative TLC, hexane–Et₂O, 9 : 1) to give the Mosher’s ester 18

(45 mg, 79%) free (>95.5 : 0.5, ¹⁹F-NMR) of the isomer 19;

δ_H(250 MHz; CDCl₃) 7.5–7.3 (5 H, m, Ph), 4.46 (1 H, dd,

J 10.7 and 3.8, CH_AH_BO), 4.07 (1 H, dd, J 10.7 and 8.5,

CH_AH_BO), 3.54 (3 H, q, J 1.1, OMe), 2.0–1.9 (4 H, m, MeCH

and adamantyl CHs), 1.7–1.4 (12 H, m, adamantyl CH₂s)

and 0.85 (3 H, d, J 6.9, MeCH); δ_F(CDCl₃; relative to CCl₃F)

Ϫ72.02. Similarly, the alcohol [13 mg, 0.07 mmol, derived

from the (E)-alkene derived from the reaction with the

(E)-allylsilane] gave a mixture of the Mosher’s esters 18 and 19

(20 mg, 73%) rich (90 : 10, ¹⁹F-NMR) in the isomer 19; δ_H(250

MHz; CDCl₃) 7.5–7.3 (5 H, m, Ph), 4.54 (1 H, dd, J 10.7 and

3.9, CH_AH_BO), 4.00 (1 H, dd, J 10.7 and 8.7, CH_AH_BO), 3.54

(3 H, q, J 1.1, OMe), 2.0–1.9 (4 H, m, MeCH and adam-

antyl CHs), 1.7–1.4 (12 H, m, adamantyl CH₂s) and 0.84 (3 H,

d, J 6.9, MeCH); δ_F(CDCl₃; relative to CCl₃F) Ϫ71.95.

Similarly, the alcohol [11 mg, 0.06 mmol, derived from the

(E)-alkene derived from the reaction with the (Z)-allyl-

silane] gave a mixture of the Mosher’s esters 18 and 19 (19 mg,

82%) in a ratio of 95 : 5 (¹H-NMR, ¹⁹F-NMR). A 50 : 50

mixture of the (2ЈR)- and (2ЈS)-esters, prepared from racemic

alcohol, showed that there was no chiral recognition in the

making of the Mosher’s esters, and gave additional data:

᎐

H

(E )-(4RS )-4-Adamantylpent-2-ene and (Z )-(4RS )-4-adamantyl-

pent-2-ene

Using reaction conditions developed by Meyers and Colling-

ton,⁶⁹n-butyllithium (5.4 cm³of a 1.6 mol dm^Ϫ3solution in

hexane) was added dropwise to a stirred mixture of ethyl-

triphenylphosphonium bromide (2.56 g, 8.7 mmol) in dry THF

(45 cm³) under argon at room temperature. The resulting red

solution was stirred for 20 min and a solution of the aldehyde

(1.33 g, 6.9 mmol) in dry THF (25 cm³) was added dropwise.

The orange suspension was stirred for 30 min, poured over

water (120 cm³), extracted with ether (3 × 120 cm³), dried

(MgSO₄), evaporated under reduced pressure, and the residue

ﬂash chromatographed (SiO₂, hexane) to give a mixture of the

E- and Z-alkenes (0.31 g 22%) in a ratio of 17 : 83 (GLC);

R_f(hexane) 0.6; the mixture was separated by ﬂash chromato-

graphy (SiO₂–AgNO₃, 4 : 1; hexane)⁵⁹to give the pure E-alkene

and Z-alkenes, identical (TLC, GLC, ¹H-NMR) with the enan-

tiomerically enriched samples E- and Z-17 described above.

R_f(hexane–Et₂O, 9 : 1) 0.35; ν_max(CHCl₃)/cm^Ϫ11740 (C᎐O)

᎐

and 1500 (Ph); δ_C(CDCl₃) 166.8, 132.4, 129.5, 128.4, 127.3,

68.7, 55.4, 42.4, 39.6, 37.1, 34.1, 28.6 and 11.1; m/z (EI)

410 (13%, M^ϩ), 189 (25, C₉H₈F₃O), 177 (28, C₁₃H₂₁) and 135

(100, C₁₀H₁₅) (Found: M^ϩ, 410.2032. C₂₃H₂₉F₃O₃requires M,

410.2069).

(2S )-2-Adamantylpropanol and (2R)-2-adamantylpropanol

(2S )-4-Trimethylsilylbut-3-yn-2-ol 27

Ozone was bubbled through the pure E-alkene [rich in the

R-isomer (R)-E-17, derived from the reaction with the (E)-

allylsilane] (17 mg, 0.08 mmol) in a mixture of dry dichloro-

methane (1 cm³) and methanol (1 cm³) at Ϫ78 ЊC for 2 min. The

solution was then purged with nitrogen and allowed to warm to

0 ЊC. Sodium borohydride (10 mg, 0.26 mmol) was added and

the solution stirred for 1 h. The solvent was then evaporated

oﬀ under reduced pressure and the residue dissolved in ether

(10 cm³), washed with water (10 cm³), dried (MgSO₄) and evap-

orated under reduced pressure to give largely the (2S)-alcohol

(13 mg, 80%). Similarly, the pure Z-alkene [rich in the S-isomer

(S)-Z-17, derived from the reaction with the (E)-allylsilane]

(36 mg, 0.18 mmol) gave largely the (2R)-alcohol (27 mg, 79%).

Similarly, the pure E-alkene [rich in the S-isomer (S)-Z-17,

derived from the reaction with the (Z)-allylsilane] (13 mg, 0.06

mmol) gave largely the (2R)-alcohol (11 mg, 89%). Physical data

(TLC, ¹H-NMR) for all three samples were identical with those

determined on a racemic sample: R_f(hexane–Et₂O, 1 : 1) 0.3;

ν_max(ﬁlm)/cm^Ϫ13500–3100 (OH); δ_H(250 MHz; CDCl₃) 3.84

(1 H, dd, J 10.4 and 3.9, CH_AH_BO), 3.35 (1 H, dd, J 10.4 and

8.4, CH_AH_BO), 2.5 (1 H, br s, OH), 2.2–1.9 (4 H, m, MeCH and

adamantyl CHs), 1.7–1.4 (12 H, m, adamantyl CH₂s) and 0.91

(3 H, d, J 6.9, MeCH); m/z (EI) 194 (15%, M^ϩ), 177 (16,

M Ϫ OH), 163 (37, M Ϫ CH₂OH) and 135 (100, C₁₀H₁₅)

(Found: M^ϩ, 194.1660. C₁₃H₂₂O requires M, 194.1671).

Following Brown,³¹9-BBN dimer (11.2 g, 92 mmol) and

(Ϫ)-α-pinene (14.6 cm³, 91 mmol) were stirred together and

heated at 65 ЊC under argon for 5 h. The mixture was cooled to

room temperature and 4-trimethylsilylbut-3-yn-2-one⁷⁰(6.4 g,

46 mmol) was added. The orange mixture was stirred at room

temperature for 18 h, then cooled to 0 ЊC. Acetaldehyde (8 cm³,

141 mmol) was added and the mixture stirred for 15 min. The

liberated α-pinene was removed by evaporation under reduced

pressure with gentle heating. The mixture was then cooled back

to 0 ЊC and ether (60 cm³) and distilled ethanolamine (5.3 cm³,

130 mmol) were added. A white precipitate appeared and the

mixture was stirred for 15 min. The mixture was then ﬁltered

and the residue washed with cold ether (120 cm³). The com-

bined organic layers were washed with brine, dried (MgSO₄),

concentrated by evaporation under reduced pressure and distil-

led to give the alcohol (4.0 g, 62%) as an oil, bp 71–72 ЊC/20

mmHg (lit.,³⁵83–85 ЊC/13 mmHg); ν_max(CHCl₃)/cm^Ϫ13580

᎐

(OH), 2160 (C᎐C) and 1250 (SiMe ); δ (250 MHz; CDCl ) 4.50

᎐

3

H

3

(1 H, q, J 6.6, CHMe), 1.43 (3 H, d, J 6.6, CHMe) and 0.16

(9 H, s, SiMe₃).

(2S )-4-Trimethylsilylbut-3-yn-2-yl (1R)-camphorsulfonate 28

(Ϫ)-Camphorsulfonyl chloride⁷¹(8.4 g, 33 mmol) in dry di-

chloromethane (30 cm³) was added to a stirred mixture of the

alcohol 27 (4.0 g, 28 mmol), 4-dimethylaminopyridine (0.68 g,

6 mmol) and triethylamine (4.7 cm³, 33 mmol) in dry dichloro-

methane (18 cm³) under argon at Ϫ5 ЊC. A white precipitate

appeared and the mixture was stirred at 0 ЊC for 1 h, then

poured onto a mixture of ice and water and extracted with

dichloromethane (3 × 150 cm³). The combined organic layers

(2ЈR)-2Ј-Adamantylpropyl (2S )-2-methoxy-2-phenyl-3,3,3-

triﬂuoropropanoate 18 and (2ЈS )-2Ј-adamantylpropyl (2S )-2-

methoxy-2-phenyl-3,3,3-triﬂuoropropanoate 19

Dicyclohexylcarbodiimide (41 mg, 0.2 mmol) in dry dichloro-

methane (0.1 cm³) was added to a stirred solution of the alcohol

O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 7 4 9 – 7 6 9

759

View Article Online

were washed with hydrochloric acid solution (2 × 150 cm³,

3 mol dm^Ϫ3) and sodium hydrogencarbonate solution (2 ×

150 cm³), dried (MgSO₄), evaporated under reduced pressure,

and the residue ﬂash chromatographed (SiO₂, hexane–Et₂O,

4 : 1) to give a mixture of the sulfonate esters (9.0 g, 90%) in a

ratio of 94 : 6 (¹H-NMR); R_f(hexane–Et₂O, 4 : 1) 0.2. The mix-

ture was recrystallised three times from hexane to give the pure

sulfonate ester (4.6 g, 51%) as plates, diastereomerically pure

(Z )-(4R)-4-Adamantylpent-2-ene (R)-(Z )-17

The alkyne 30 (30 mg, 0.15 mmol), Lindlar catalyst (10 mg) and

quinoline (20 mg) in hexane (3 cm³) were stirred under hydro-

gen at room temperature for 5 h. The mixture was ﬁltered

through Celite, the solvent evaporated under reduced pressure

and the residue ﬂash chromatographed (SiO₂, hexane) to give

the Z-alkene Z-17 (8 mg, 26%), identical (TLC, ¹H-NMR) with

the earlier sample.

(>99.5 : 0.5, ¹H-NMR), mp 67–68.5 ЊC; ν_max(CHCl₃)/cm^Ϫ12150

᎐

(C᎐C), 1745 (C᎐O), 1350 and 1165 (SO ) and 835 (SiMe );

᎐

2

3

(2S )-2-Adamantylpropanol

δ_H(250 MHz; CDCl₃) 5.31 (1 H, q, J 6.7, CHMe), 3.82 (1 H, d,

J 15.0, CH_AH_BSO₂), 3.09 (1 H, d, J 15.0, CH_AH_BSO₂), 2.6–1.4

(7 H), 1.61 (3 H, d, J 6.7, CHMe) 1.14 (3 H, s, CMe_AMe_B) and

0.88 (3 H, s, CMe_AMe_B) and 0.16 (9 H, s, SiMe₃); [α]_DϪ69

(c. 1.1 in CHCl₃)(Found: C, 57.4; H, 8.0. C₁₇H₂₈O₄SiS requires

C, 57.3; H, 7.9%). The RR diastereoisomer gave recognisable

signals in the ¹H-NMR spectrum at: δ_H(250 MHz; CDCl₃) 5.28

(1 H, q, J 6.7, CHMe), 3.70 (1 H, d, J 15.2, CH_AH_BSO₂), 3.23

(1 H, d, J 15.2, CH_AH_BSO₂), 2.6–1.4 (7 H), 1.61 (3 H, d, J 6.7,

CHMe), 1.15 (3 H, s, CMe_AMe_B) and 0.90 (3 H, s, CMe_AMe_B)

and 0.17 (9 H, s, SiMe₃).

This was prepared in the same way as the alcohol above using

the alkene (10 mg, 0.05 mmol) to give the alcohol (5 mg, 53%),

identical (TLC, ¹H-NMR) with the earlier sample.

(2ЈS )-2Ј-Adamantylpropyl (2S )-2-methoxy-2-phenyl-3,3,3-

triﬂuoropropanoate 19

This was prepared in the same way as the mixture of esters

above using the alcohol (5 mg, 0.03 mmol) to give a mixture of

the Mosher’s esters 18 and 19 (10.5 mg, 100%) in a ratio of

1 : 99 (¹H-NMR, ¹⁹F-NMR), identical (TLC, ¹H NMR) to the

earlier samples.

(S )-2-Trimethylsilylpenta-2,3-diene 29

Using reaction conditions developed by Danheiser,⁷²methyl-

magnesium chloride (1.0 cm³of a 3.0 mol dm^Ϫ3solution in

THF, 3 mmol) was added to a stirred solution of dry copper()

bromide⁷³(0.45 g, 3.15 mmol) and dry lithium bromide (0.27 g,

3.15 mmol) in dry THF (4.8 cm³) under argon at 0 ЊC. The

resulting yellow paste was stirred for 20 min, and then cooled to

Ϫ78 ЊC. A solution of the sulfonate ester (1.07 g, 3 mmol) in

dry THF (4.8 cm³) was slowly added, and the resulting yellow-

green mixture was stirred at Ϫ78 ЊC for 40 min, warmed to

room temperature and stirred for a further 10 min. The mixture

was then poured into a mixture of pentane (45 cm³), water

(12 cm³) and saturated ammonium chloride solution (12 cm³).

The organic layer was separated, washed with saturated ammo-

nium chloride solution (2 × 15 cm³), water (10 × 30 cm³) and

brine, dried (MgSO₄), and the solvent removed by fractional

distillation. The residue was ﬂash chromatographed (SiO₂,

pentane) and the solvent removed by fractional distillation,

followed by careful evaporation under reduced pressure (water

pump) at Ϫ20 ЊC to give the allene³⁵(0.35 g, 83%) as an oil with

enantiomer ratios measured as 98.7 : 1.3, 99 : 1 and 99.25 : 0.75

in three runs [chiral GLC using heptakis(6-O-methyl-2,3-di-O-

n-pentyl)-β-cyclodextrin, with retention times of 14.9 (S) and

(3R,4R)-2,4-Dimethylhept-5-yn-3-ol (3R,4R)-31 and

2,4-Dimethylhept-5-yn-3-ol 32

Using reaction conditions developed by Danheiser,⁴⁰iso-

butyraldehyde (0.023 cm³, 0.25 mmol) was added to titanium

tetrachloride (0.28 cm³of a 1 mol dm^Ϫ3solution in dichloro-

methane, 0.28 mmol) under argon at Ϫ78 ЊC and the mixture

stirred for 5 min. The allene (28 mg, 0.20 mmol) in dry di-

chloromethane (0.2 cm³) was added dropwise and the resulting

brown mixture was stirred at Ϫ78 ЊC for 1.5 h. Sodium hydro-

gencarbonate solution (2.5 cm³) was added and the aqueous

phase was extracted with dichloromethane (3 × 5 cm³). The

combined organic layers were washed with sodium hydro-

gencarbonate solution, dried (MgSO₄) and concentrated by

evaporation under reduced pressure (with ice-bath cooling) to

give a mixture of the alcohols 31 and 32 (24 mg, 89%) in a ratio

of 95 : 5 (¹H-NMR) as an oil. The mixture was separated by

ﬂash chromatography (SiO₂, pentane–Et₂O, 19 : 1) to give the

syn alcohol 31; R_f(hexane–Et₂O, 4 : 1) 0.25; ν_max(CHCl₃)/cm^Ϫ1

3600–3400 (OH); δ_H(250 MHz; CDCl₃) 3.25 (1 H, t, J 5.9,

᎐

CHOH), 2.55 (1 H, m, CHC᎐), 1.91 (1 H, octet, J 6.8, CHMe ),

᎐

2

᎐

1.78 (3 H, d, J 2.4, MeC᎐), 1.70 (1 H, br s, OH), 1.13 (3 H, d,

16.0 (R) ];³⁷R_f(hexane) 0.65; ν_max(CHCl₃)/cm^Ϫ11935 (C᎐C᎐C),

᎐

᎐ ᎐

᎐

J 6.9, MeCHC᎐), 0.94 and 0.89 (3 H each, d, J 6.7, CHMe );

᎐

2

1240 and 840 (SiMe₃); δ_H(250 MHz; CDCl₃) 4.68 (1 H, qq, J 6.9

m/z (EI) 140 (3%, M^ϩ), 123 (23, M – OH), 73 (27, C₄H₉O) and

68 (100, C₅H₈)(Found: M^ϩ, 140.1266. C₉H₁₆O requires M,

140.1197), and the anti alcohol 32; R_f(hexane–Et₂O, 4 : 1) 0.20;

and 2.8, MeCH᎐), 1.65 (3 H, d, J 2.8, MeSiC᎐), 1.43 (3 H, d,

᎐

J 6.9, MeCH᎐) and 0.06 (9 H, s, SiMe ); [α] ϩ79 (c. 1.4 in

᎐

3

D

CHCl₃).

δ_H(250 MHz; CDCl₃) 2.97 (1 H, m, CHOH), 2.65 (1 H, m,

᎐

CHC᎐), 1.9–1.6 (2 H, m, CHMe and OH), 1.80 (3 H, d, J 2.4,

᎐

2

(4R)-4-Adamantylpent-2-yne (S )-30

᎐

MeC᎐), 1.18 (3 H, d, J 7.0, MeCHC᎐), (3 H, d, J 6.9,

᎐

A solution of titanium tetrachloride in dichloromethane

(0.11 cm³of a 1.0 mol dm^Ϫ3solution, 0.11 mmol) was added to

a stirred solution of 1-chloroadamantane (122 mg, 0.70 mmol)

in dry dichloromethane (2 cm³) under argon at Ϫ78 ЊC. After

10 min, the allene (100 mg, 0.70 mmol) in dry dichloromethane

(1 cm³) was added, and the mixture stirred under argon at

Ϫ78 ЊC for 30 min. Cold sodium hydrogencarbonate solution

(5 cm³) was added, and the mixture extracted with hexane (3 ×

5 cm³). The combined organic extracts were washed with water,

dried (MgSO₄), evaporated under reduced pressure and ﬂash

chromatographed (SiO₂, hexane) to give the alkyne (∼40 mg,

30%) as an oil, contaminated with 1-chloroadamantane;

R_f(hexane) 0.4; δ_H(250 MHz; CDCl₃) 2.0–1.95 (4 H, m,

CHMe_AMe_B) and 0.92 (3 H, d, J 6.7, CHMe_AMe_B).

(3R,4R)-2,4-Dimethylhept-5-yn-3-yl (1S )-camphorsulfonate 33

and (3S,4S )-2,4-Dimethylhept-5-yn-3-yl (1S )-camphorsulfonate

34

(ϩ)-Camphorsulfonyl chloride (42 mg, 0.17 mmol) in dry di-

chloromethane (0.2 cm³) was added to a stirred mixture rich in

the (3R,4R)-alcohol 31 (10 mg, 0.07 mmol), 4-dimethylamino-

pyridine (3.4 mg, 0.03 mmol) and triethylamine (0.025 cm³,

0.17 mmol) in dry dichloromethane (0.4 cm³) under argon at

room temperature. The mixture was reﬂuxed for 16 h, then

cooled to 0 ЊC. Ice-cold water was added and the mixture

extracted with dichloromethane (3 × 5 cm³). The combined

organic layers were washed with hydrochloric acid solution

(2 × 5 cm³, 3 mol dm^Ϫ3) and sodium hydrogencarbonate solu-

tion (2 × 5 cm³), dried (MgSO₄), evaporated under reduced

᎐

R CH), 1.80 (3 H, d, J 2.5, MeC᎐), 1.7–1.5 (12 H, m, R CH )

᎐

3

2

and 1.02 (3 H, d, J 7.1, MeCH); m/z (EI) 202 (32%, M^ϩ) and

135 (100, C₁₀H₁₅) (Found: M^ϩ, 202.1724. C₁₅H₂₂requires M,

202.1716).

O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 7 4 9 – 7 6 9

760

View Article Online

pressure, and the residue ﬂash chromatographed (SiO₂, hexane–

Et₂O, 9 : 1) to give a mixture of the sulfonate esters (13.5 mg,

53%) in a ratio of 99 : 1 (¹H-NMR) rich in the R,R,S-isomer 33;

δ_H(250 MHz; CDCl₃) 4.54 (1 H, dd, J 6.5 and 5.1, CHOSO₂),

dq, J 10.9 and 6.7, MeCH᎐), 5.23 (1 H, m, CHMeCH᎐), 3.45

᎐ ᎐

(3 H, s, OMe), 2.65 (2 H, m, CHMeCHOMe), 1.74 (1 H, m,

CHMe ), 1.61 (3 H, dd, J 6.7 and 1.5, MeCH᎐), 0.98 (3 H, d,

᎐

2

J 6.3, CHMeCH᎐), 0.94 (3 H, d, J 6.9, CHMe Me ) and 0.86

᎐

A

B

3.82 (1 H, d, J 15.0, CH_AH_BSO₂), 3.09 (0.5 H, d, J 15.0, CH_A-

(3 H, d, J 6.7, CHMe_AMe_B).

᎐

H SO ), 2.77 (1 H, m, CHC᎐), 2.6–1.9 (5 H), 1.78 (3 H, d, J 2.4,

᎐

B

2

᎐

MeC᎐), 1.7–1.3 (2 H), 1.24 (3 H, d, J 6.9, MeCHC᎐), 1.14 (3 H,

᎐

(2R,3R)-3-Methoxy-2,4-dimethylpentanol

s, CMe_AMe_B), 0.89 (3 H, s, CMe_AMe_B) and 1.00 (3 H, d, J 6.8,

CHMe₂). A similar preparation from racemic alcohol (9 mg,

0.06 mmol) gave a 50 : 50 mixture of the camphorsulfonates 33

and 34 (19 mg, 84%); R_f(hexane–Et₂O, 4 : 1) 0.20; ν_max(CHCl₃)/

Ozone was bubbled through a solution of the methyl ether

(22 mg, 0.14 mmol) in methanol (3 cm³) at Ϫ78 ЊC for 1 min.

The solution was then purged with nitrogen and allowed to

warm to 0 ЊC. Sodium borohydride (21 mg, 0.28 mmol) was

then added and the solution, and the mixture stirred for 1 h.

The solvent was evaporated under reduced pressure and the

residue dissolved in ether (5 cm³), washed with water (2 ×

5 cm³), dried (MgSO₄), evaporated under reduced pressure

(water pump) with ice-bath cooling and ﬂash chromatographed

(SiO₂, pentane–Et₂O, 1 : 1) to give the alcohol (22 mg, 100%);

R_f(hexane–Et₂O, 1 : 1) 0.2; δ_H(250 MHz; CDCl₃) 3.64 (1 H, dd,

J 10.4 and 6.8, CH_AH_BOH), 3.60 (1 H, dd, J 10.4 and 5.6,

CH_AH_BOH), 3.45 (3 H, s, OMe), 2.94 (1 H, dd, J 7.8 and 3.2,

CHOMe), 2.0–1.7 (2 H, m, CHMe and CHMe₂), 1.67 (1 H, br s,

OH), 0.99 (3 H, d, J 6.6, CHMe_AMe_B), 0.89 (3 H, d, J 7.0,

CHMe) and 0.87 (3 H, d, J 6.8, CHMe_AMe_B). A similar prepar-

ation from racemic alkene (33 mg, 0.21 mmol) gave racemic

alcohol (10 mg, 32%), identical (¹H-NMR) to the enantio-

merically enriched product; ν_max(CHCl₃)/cm^Ϫ13610 (OH); m/z

(EI) 103 (63%, M^ϩϪ CHMe₂) and 87 (100, M Ϫ CHMe-

CH₂OH) (Found: M^ϩϪ CHMe₂, 103.0760. C₈H₁₈O₂Ϫ CHMe₂

requires M, 103.0759).

cm^Ϫ12230 (C᎐C), 1730 (C᎐O), 1330 and 1150 (OSO ); δ (250

᎐

2

H

MHz; CDCl₃) as above for the isomer 33 together with the

following diﬀerent signals from the S,S,S-isomer: 4.53 (1 H, dd,

J 6.8 and 4.7, CHOSO₂), 3.69 (1 H, d, J 15.0, CH_AH_BSO₂), 3.17

᎐

(1 H, d, J 15.0, CH H SO ), 1.77 (3 H, d, J 2.7, MeC᎐), 1.02

᎐

A

B

2

(3 H, d, J 5.2, CHMe_AMe_B) and 0.99 (3 H, d, J 5.0, CHMe_A-

Me_B); δ_C(CDCl₃) 214.5, 90.7, 80.0, 78.4, 58.1, 48.5, 47.7, 42.8,

42.5, 30.3, 29.0, 26.8, 25.0, 20.0, 19.9, 19.7, 17.2, 17.1 and 3.5

(R,R,S dias.), 214.6, 90.6, 79.9, 78.3, 58.2, 48.6, 47.6, 42.9, 42.5,

30.3, 29.1, 26.8, 25.0, 20.0, 19.9, 19.7, 17.2, 17.1 and 3.5 (S,S,S

dias.); m/z (EI) 287 (34%, M^ϩϪ C₅H₇) and 215 (100, C₁₀H₁₅-

O₃S) (Found: M^ϩϪ C₅H₇, 287.1330. C₁₉H₃₀O₄S Ϫ C₅H₇

requires M, 287.1317).

(3S,4R)-2,4-Dimethylhept-5-yn-3-yl (1S )-camphorsulfonate

This was prepared in the same way as the sulfonate esters 33

and 34 using the alcohol 32 (1 mg, 0.01 mmol) to give the

sulfonate ester (1.5 mg, 60%) with a ratio of diastereoisomers

>95 : 5 (¹H-NMR), presumably in favour of the 3S,4R-isomer;

δ_H(250 MHz; CDCl₃) 4.43 (1 H, t, J 5.6, CHOSO₂), 3.73 (1 H, d,

J 15.1, CH_AH_BSO₂), 3.20 (1 H, d, J 15.1, CH_AH_BSO₂), 2.81

(2ЈR,3ЈR)-3Ј-Methoxy-2Ј,4Ј-dimethylpentyl (2S )-2-methoxy-2-

phenyl-3,3,3-triﬂuoropropanoate 35 and (2ЈS,3ЈS )-3Ј-Methoxy-

2Ј,4Ј-dimethylpentyl (2S )-2-methoxy-2-phenyl-3,3,3-

triﬂuoropropanoate 36

᎐

(1 H, m, CHC᎐), 2.65–1.9 (5 H), 1.78 (3 H, d, J 2.4, MeC᎐),

᎐

1.7–1.3 (2 H), 1.23 (3 H, d, J 7.0, MeCHC᎐), 1.17 (3 H, s,

᎐

CMe_AMe_B), 1.03 (3 H, d, J 7.1, CHMe_AMe_B), 1.00 (3 H, d,

J 7.1, CHMe_AMe_B) and 0.90 (3 H, s, CMe_AMe_B).

Dicyclohexylcarbodiimide (20 mg, 0.10 mmol) in dry di-

chloromethane (0.2 cm³) was added to a stirred solution of

the alcohol (10 mg, 0.07 mmol), (Ϫ)-Mosher’s acid (22 mg,

0.09 mmol) and 4-dimethylaminopyridine (1.5 mg, 0.01 mmol)

in dry dichloromethane (0.2 cm³) under argon at room temper-

ature. After 3 h the solution was ﬁltered through silica gel, elut-

ing with dichloromethane. The ﬁltrate was evaporated under

reduced pressure and the residue ﬂash chromatographed (SiO₂,

hexane–Et₂O, 9 : 1) to give a mixture of the known Mosher’s

esters⁴¹35 and 36 (14 mg, 56%) in a ratio of 99 : 1 (¹H-NMR) as

an oil; δ_H(250 MHz; CDCl₃) 7.53–7.50 (2 H, m, o-ArH), 7.43–

7.35 (3 H, m, m- and p-ArH), 4.25 (1 H, dd, J 10.6 and 7.6,

CH_AH_BO), 4.21 (1 H, dd, J 10.6 and 6.4, CH_AH_BO), 3.54 (3 H,

s, PhCOMe), 3.33 (3 H, s, CHOMe), 2.70 (1 H, dd, J 8.0 and

3.2, CHOMe), 2.01 (1 H, dsextet, J 3.3 and 7.0, CHMe), 1.75

(1 H, octet, J 6.7, CHMe₂), 0.93 (3 H, d, J 6.6, CHMe_AMe_B),

0.88 (3 H, d, J 6.9, CHMe) and 0.80 (3 H, d, J 6.8, CHMe_A-

Me_B). A similar preparation from racemic alcohol (10 mg, 0.07

mmol) gave a 50 : 50 mixture of the Mosher’s esters 35 and 36

(18 mg, 73%); δ_H(250 MHz; CDCl₃) as above for the isomer 35

together with the following diﬀerent signals: δ_H(250 MHz;

CDCl₃) 4.33 (1 H, dd, J 10.6 and 6.1, CH_AH_BO), 4.14 (1 H, dd,

J 10.6 and 7.8, CH_AH_BO), 3.34 (3 H, s, CHOMe), 2.65 (1 H, dd,

J 8.0 and 3.4, CHOMe), 0.92 (3 H, d, J 6.6, CHMe_AMe_B), 0.87

(3 H, d, J 6.9, CHMe) and 0.78 (3 H, d, J 6.7, CHMe_AMe_B);

(Z )-(3R,4R)-2,4-Dimethylhept-5-en-3-ol

The syn alcohol 31 (60 mg, 0.43 mmol), Lindlar catalyst (21 mg)

and quinoline (43 mg) in hexane (3 cm³) were stirred under

hydrogen at room temperature for 5 h. The mixture was then

ﬁltered through Celite, the solvent evaporated under reduced

pressure (water pump) with ice-bath cooling and the residue

ﬂash chromatographed (SiO₂, pentane–Et₂O, 9 : 1) to give the

alcohol (42 mg, 69%); R_f(hexane–Et₂O, 4 : 1) 0.25; ν_max(CHCl₃)/

cm^Ϫ13630 (OH) and 1600 (C᎐C); δ (250 MHz; CDCl )

᎐

H

3

5.42 (1 H, ddq, J 10.9, 0.8 and 6.7, MeCH᎐), 5.22 (1 H,

᎐

ddq, J 10.9, 9.6 and 1.6, CHMeCH᎐), 3.14 (1 H, dd, J 7.1

᎐

and 4.4, CHOH), 2.60 (1 H, dquintet, J 9.6 and 7.0, CH-

MeCH᎐), 1.76 (1 H, m, CHMe ), 1.62 (3 H, dd, J 6.7 and 1.6,

᎐

2

MeCH᎐), 1.33 (1 H, br s, OH), 0.99 (3 H, d, J 6.7, CHMeCH᎐),

᎐

0.93 (3 H, d, J 6.9, CHMe_AMe_B) and 0.85 (3 H, d, J 6.7,

CHMe_AMe_B).

(Z )-(4R,5R)-5-Methoxy-4,6-dimethylhept-2-ene

Using reaction conditions developed by Sjöberg,⁷⁴sodium

methylsulﬁnylmethanide⁷⁵was added to the alcohol (42 mg,

0.30 mmol) and a trace of triphenylmethane in dry DMSO

(0.3 cm³) until a deep red colour was produced. Distilled di-

methyl sulfate (0.15 cm³, 1.58 mmol) was then added and the

solution stirred at room temperature for 1 h. Pentane (2 cm³)

and water (2 cm³) were added and the aqueous layer was

extracted with pentane (3 × 5 cm³). The combined organic

layers were washed with water, dried (MgSO₄), evaporated

under reduced pressure (water pump) with ice-bath cooling and

ﬂash chromatographed (SiO₂, pentane–Et₂O, 19 : 1) to give the

methyl ether (22 mg, 48%) as an oil; R_f(hexane–Et₂O, 9 : 1) 0.5;

R_f(hexane–Et₂O, 9 : 1) 0.2; ν_max(CHCl₃)/cm^Ϫ11745 (C᎐O); m/z

᎐

(EI) 331 (19%, M^ϩϪ OMe), 319 (41, M Ϫ CHMe₂), 189 (50,

PhCCF₃OMe), 87 (97, CHOMeCHMe₂) and 85 (100, CH₂-

CHMeCHOMe) (Found: M^ϩϪ OMe, 331.1515. C₁₈H₂₅O₄F₃Ϫ

OMe requires M, 331.1521).

Ethyl (3RS )-3-trimethylsilylbutanoate

n-Butyllithium (1.1 mol dm^Ϫ3in hexanes, 172 cm³, 189.0 mmol)

was added dropwise to a stirred solution of absolute ethanol

ν_max(CHCl₃)/cm^Ϫ11600 (C᎐C); δ (250 MHz; CDCl ) 5.38 (1 H,

᎐

H

3

O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 7 4 9 – 7 6 9

761

View Article Online

(17.6 g, 22.0 cm³, 382.0 mmol) in dry THF (144 cm³) under

argon at Ϫ10 ЊC. After 10 min, 1-(3-trimethylsilylbutanoyl)-2-

pyrrolidone¹⁷(13.1 g, 57.6 mmol) in dry THF (140 cm³) was

added. The mixture was stirred at Ϫ10 ЊC for 2 h and allowed to

warm to room temperature. The mixture was then stirred at

room temperature overnight. Water (300 cm³) was added and

the mixture was extracted with light petroleum (3 × 100 cm³).

The combined organic extracts were washed with brine

(50 cm³), dried (MgSO₄) and evaporated under reduced pres-

sure to give the ester⁷⁶(10.8 g, 100%) as an oil; R_f(light petrol-

(4RS )-4-Trimethylsilylpent-2-yne 37

A solution of LDA (72.1 mmol) was added dropwise to the

racemic enol triﬂates (8.30 g, 30.0 mmol) in dry THF (200 cm³)

and the mixture was allowed to stir at 0 ЊC for 2 h. Methyl

iodide (75.9 g, 33.3 cm³, 534 mmol) was added and the mixture

was stirred at room temperature for 1 h. The mixture was

washed with dilute aqueous hydrochloric acid (3 mol dm^Ϫ3

,

330 cm³), water (2 × 330 cm³), brine (500 cm³), dried (MgSO₄)

and the solvent evaporated under reduced pressure. Distillation

give the alkyne⁷⁹(2.19 g, 52%), bp 55 ЊC at 130 mmHg; R_f(light

eum–Et₂O, 9 : 1) 0.43; ν_max(ﬁlm)/cm^Ϫ11738 (C᎐O), 1250 (SiMe)

᎐

petroleum) 0.37; ν_max(ﬁlm)/cm^Ϫ12360 (C᎐C) and 1249 (SiMe);

᎐

and 836 (SiMe); δ_H(400 MHz; CDCl₃) 4.15 (2 H, q, J 7.1,

OCH₂Me), 2.40 (1 H, dd, J 15.0 and 4.3, COCH_AH_B), 2.07

(1 H, dd, J 15.0 and 11.0, COCH_AH_B), 1.28 (3 H, t, J 7.1,

OCH₂Me), 1.25–1.15 (1 H, m, MeCHSi), 0.98 (3 H, d, J 7.3,

MeCHSi) and 0.00 (9 H, s, SiMe₃); δ_C(400 MHz; CDCl₃)

174.1ϩ, 60.1ϩ, 36.9ϩ, 16.8Ϫ, 14.3Ϫ, 14.2Ϫ and Ϫ3.4Ϫ; m/z

(EI) 188 (23%, M^ϩ), 173 (15, M Ϫ Me) and 143 (12, M Ϫ OEt)

(Found: M^ϩ, 188.1237. C₉H₂₀O₂Si requires M, 188.1233).

δ (400 MHz; CDCl ) 1.79 (3 H, d, J 2.7, C᎐CMe), 1.62–1.53

᎐

H

3

(1 H, m, MeCHSi), 1.11 (3 H, d, J 7.3, MeCHSi) and 0.04 (9 H,

s, SiMe₃); δ_C(400 MHz; CDCl₃) 82.4ϩ, 74.5ϩ, 15.0Ϫ, 13.0Ϫ,

3.6Ϫ and Ϫ3.6Ϫ; m/z (EI) 140 (80%, M^ϩ), 125 (10, M Ϫ Me)

and 97 (100, M Ϫ C₃H₇)(Found: M^ϩ, 140.1018. C₈H₁₆Si

requires M, 140.1021).

2,3-Diadamantyl-1,3-pentadiene 42 and 2,4-diadamantyl-1,3-

pentadiene 43

(3RS )-3-Trimethylsilylbutanal

Titanium tetrachloride (1.0 mol dm^Ϫ3in CH₂Cl₂, 1.44 cm³,

1.44 mmol) was added to a stirred solution of 1-bromoadam-

antane (0.308 g, 1.44 mmol) in dry dichloromethane (4 cm³)

under argon at Ϫ78 ЊC. After 10 min, (4RS)-trimethylsilylpent-

2-yne 37 (0.20 g, 1.44 mmol) in dry dichloromethane (4 cm³)

was added to the yellow solution, and the mixture stirred under

argon at Ϫ78 ЊC for 1 h. Saturated aqueous sodium hydro-

gencarbonate (20 cm³) was added and the mixture extracted

with hexane (3 × 20 cm³). The combined organic extracts were

washed with water (2 × 10 cm³), brine (50 cm³), dried (MgSO₄)

and evaporated under reduced pressure. The residue was chrom-

atographed (SiO₂, light petroleum) to give the dienes 42 and

Using conditions reported by Zakharkin,⁷⁷diisobutyl-

aluminium hydride (1.0 mol dm^Ϫ3in hexanes, 65.0 cm³,

65.0 mmol) in hexane (94 cm³) was added dropwise over 10 min

to a stirred solution of racemic ethyl 3-trimethylsilylbutanoate

(10.9 g, 57.6 mmol) in hexane (160 cm³) at Ϫ78 ЊC under argon.

The mixture was stirred for 2 h, quenched with methanol

(117 cm³) and allowed to warm to room temperature. The mix-

ture was washed with saturated aqueous potassium sodium

tartrate (60 cm³). The aqueous layer was further extracted with

ether (3 × 60 cm³) and the combined organic fractions were

washed with brine (120 cm³), dried (MgSO₄) and evaporated

under reduced pressure to give the aldehyde⁷⁸(8.31 g, 100%) as

an oil; R_f(light petroleum–Et₂O, 9 : 1) 0.36; ν_max(ﬁlm)/cm^Ϫ11725

1

43 (27 mg, 6%) (major : minor: 1.5 : 1, H NMR); R_f(light

petroleum) 0.70; δ_H(500 MHz; CDCl₃) major isomer 42: 5.45

(C᎐O), 1250 (SiMe) and 837 (SiMe); δ (400 MHz; CDCl ) 9.73

᎐

H

3

(1 H, q, J 6.8, MeCH᎐C), 5.16 (1 H, d, J 1.8, C᎐CH H ), 4.65

᎐

A

B

(1 H, dd, J 3.3 and 1.4, CHO), 2.43 (1 H, ddd, J 16.1, 3.8 and

1.4, COCH_AH_B), 2.15 (1 H, ddd, J 16.1, 10.7 and 3.3,

COCH_AH_B), 1.27–1.17 (1 H, m, MeCHSi), 0.96 (3 H, d, J 7.3,

MeCHSi) and 0.00 (9 H, s, SiMe₃); δ_C(400 MHz; CDCl₃)

203.5ϩ, 46.0ϩ, 14.4Ϫ, 14.1Ϫ and Ϫ3.5Ϫ; m/z (EI) 144 (100%,

M^ϩ), 129 (57, M Ϫ Me) and 115 (26, M Ϫ CHO) (Found: M^ϩ,

144.0968. C₇H₁₆OSi requires M, 144.0970).

(1 H, d, J 1.8, C᎐CH H ), 2.01–1.63 (30 H, m, 2 × adamantyl)

᎐

A

B

and 1.55 (3 H, d, J 6.8, MeCH᎐C); minor isomer 43: 5.79 (1 H,

᎐

br s, CH᎐C), 4.92 (1 H, d, J 2.1, C᎐CH H ), 4.58 (1 H, dd, J 2.1

᎐

A

B

and 1.8, C᎐CH H ) and 2.01–1.63 (33 H, m, 2 × adamantyl,

᎐

A

B

MeC᎐C); m/z (EI) 336 (70%, M^ϩ), 201 (55, M Ϫ Ad) and 135

᎐

(100, Ad) (Found: M^ϩ, 336.2816. C₂₅H₃₆requires M, 336.2817).

(3RS )-3-Trimethylsilylbut-1-enyl triﬂuoromethanesulfonate

2-(1-Hydroxy-2-methylpropyl)-3-trimethylsilylpenta-1,3-dienes

45 and 2,4-dimethyl-5-trimethylsilylhept-5-en-3-ones 46

Using conditions developed by Mwaniki,⁵⁷the aldehyde (8.31 g,

57.6 mmol) in dichloromethane (195 cm³) was added over

20 min by syringe with the tip immersed in the solution

to a reﬂuxing solution of 2,6-di-tert-butylpyridine (14.87 g,

77.7 mmol, 17.5 cm³) and triﬂuoromethanesulfonic anhydride

(20.0 g, 70.9 mmol, 14.9 cm³) in dichloromethane (195 cm³)

under argon, and the solution reﬂuxed for 19 h. The mixture

was concentrated under reduced pressure. The combined

organic extracts were washed with light petroleum (3 × 380 cm³)

to precipitate the pyridinium salts. The combined organic

extracts were washed with dilute aqueous hydrochloric acid

(3 mol dm^Ϫ3, 4 × 400 cm³), brine (500 cm³) and dried (MgSO₄).

The solvent was evaporated under reduced pressure and the

residue chromatographed (SiO₂, light petroleum–Et₂O, 95 : 5)

to give the enol triﬂates (8.70 g, 55% over 3 steps) (Z : E, 6.6 : 1);

R_f(light petroleum–Et₂O, 8 : 2) 0.65; ν_max(ﬁlm)/cm^Ϫ11656

Titanium tetrachloride (1.0 mol dm^Ϫ3in CH₂Cl₂, 0.36 cm³,

0.36 mmol) was stirred at Ϫ78 ЊC under argon for 10 min before

addition of isobutyraldehyde (51 mg, 0.71 mmol) in dichloro-

methane (1 cm³). The mixture was stirred at Ϫ78 ЊC for 1 h. A

solution of propargylsilane 37 (100 mg, 0.71 mmol) in di-

chloromethane was added by cannula, and the mixture stirred

at Ϫ78 ЊC for 1.5 h. The mixture was quenched with saturated

aqueous ammonium chloride solution (5 cm³) and allowed to

stir at room temperature for 30 min. The aqueous layer was

extracted with dichloromethane (3 × 10 cm³). The combined

organic extracts were washed with dilute aqueous hydrochloric

acid (3 mol dm^Ϫ3, 10 cm³), water (2 × 10 cm³), brine (20 cm³),

dried (MgSO₄) and evaporated under reduced pressure. The

residue was chromatographed (SiO₂, light petroleum–Et₂O,

95 : 5) to give the diene 45 (30 mg, 20%) as a mixture of geo-

1

(C᎐C), 1250 (SiMe), 1210 (OTf ) and 840 (SiMe); δ (400 MHz;

metrical isomers (1.9 : 1, H NMR); R_f(light petroleum–Et₂O,

᎐

H

CDCl₃) Z isomer: 6.50 (1 H, d, J 5.6, CHOTf ), 5.06 (1 H, dd,

9 : 1) 0.23; ν_max(ﬁlm)/cm^Ϫ13400 (OH), 2998 (C᎐CH), 1243

᎐

J 11.6 and 5.6, CH᎐CHOTf ), 2.07 (1 H, dqd, J 11.6, 7.2 and

(SiMe) and 841 (SiMe); δ_H(500 MHz; CDCl₃) major isomer:

᎐

0.8, CHSi), 1.08 (3 H, d, J 7.2, MeCHSi), 0.01 (9 H, s, SiMe₃); E

isomer: 6.30 (1 H, dd, J 11.6 and 1.2, CHOTf ), 5.85 (1 H, dd,

6.07 (1 H, q, J 7.0, MeCH᎐C), 4.91 (1 H, s, C᎐CH H ), 4.70

᎐ ᎐

A B

(1 H, d, J 0.7, C᎐CH H ), 3.92 (1 H, s, CHOH), 1.85–1.75 (1 H,

᎐

A

B

J 11.6 and 8.6, CH᎐CHOTf ), 2.30–2.21 (1 H, m, CHSi), 1.09

m, CHMe ), 1.80 (3 H, d, J 7.0, MeCH᎐C), 0.99 (3 H, d, J 6.8,

᎐

2

(3 H, d, J 7.1, MeCHSi), 0.01 (9 H, s, SiMe₃); δ_C(400 MHz;

CDCl₃) 133.3Ϫ, 132.5Ϫ, 127.4Ϫ, 124.3Ϫ, 120.2ϩ. 117.0ϩ,

21.7Ϫ, 19.9Ϫ, 14.3Ϫ, 13.2Ϫ, Ϫ3.4Ϫ and Ϫ3.7Ϫ.

CHMe_AMe_B), 0.81 (3 H, d, J 6.8, CHMe_AMe_B) and 0.17 (9 H, s,

SiMe ); minor isomer: 5.96 (1 H, q, J 6.6, MeCH᎐C), 5.15 (1 H,

᎐

3

s, C᎐CH H ), 4.68 (1 H, s, C᎐CH H ), 3.97 (1 H, s, CHOH),

᎐

A

B

A

B

O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 7 4 9 – 7 6 9

762

View Article Online

1.85–1.75 (1 H, m, CHMe ), 1.73 (3 H, d, J 6.6, MeCH᎐C), 1.02

the solvent evaporated under reduced pressure. The crude

᎐

2

(3 H, d, J 6.9, CHMe_AMe_B), 0.87 (3 H, d, J 6.9, CHMe_AMe_B)

and 0.08 (9 H, s, SiMe₃); δ_C(500 MHz; CDCl₃) 151.7ϩ, 139.6ϩ,

138.9Ϫ, 136.6Ϫ, 109.1ϩ, 77.7Ϫ, 49.4Ϫ, 39.2Ϫ, 20.6Ϫ, 19.6Ϫ,

18.4Ϫ, 17.8Ϫ, 16.1Ϫ, 14.8Ϫ, Ϫ0.4Ϫ and Ϫ0.6Ϫ. m/z (EI) 212

(10%, M^ϩ), 197 (40, M Ϫ Me) and 73 (100, SiMe) (Found: M^ϩ,

212.1601. C₁₂H₂₄OSi requires M, 212.1596), and the ketone 46

product was chromatographed (SiO₂, light petroleum–CH₂Cl₂,

95 : 5) to give the alkyne (318 mg, 19%); R_f(light petroleum–

CH₂Cl₂, 9 : 1) 0.16; ν_max(ﬁlm)/cm^Ϫ12153 (C᎐C), 1597 (Ph), 1248

᎐

(SiMe) and 1115 (SiPh); δ_H(250 MHz; CDCl₃) 7.70–7.02 (10 H,

m, 2 × Ph), 3.28 (1 H, q, J 2.6, CHSi), 1.90 (3 H, d, J 2.6,

᎐

C᎐CMe), 0.39 (3 H, s, SiMe Me ) and 0.29 (3 H, s, SiMe Me );

᎐

A

B

A

B

1

(20 mg, 13%) as a mixture of geometrical isomers (1 : 1, H

δ_C(500 MHz; CDCl₃) 142.1ϩ, 139.4ϩ, 135.0Ϫ, 134.3Ϫ,

133.7Ϫ, 127.9Ϫ, 127.4Ϫ, 127.2Ϫ, 85.7ϩ, 78.5ϩ, 29.1Ϫ, 22.0Ϫ,

Ϫ4.9Ϫ and Ϫ5.0Ϫ; m/z (EI) 264 (12%, M^ϩ), 249 (32, M – Me)

and 135 (83, SiMe₂Ph) (Found: M^ϩ, 264.1328. C₁₈H₂₀Si requires

M, 264.1334), together with (4RS)-4-dimethyl(phenyl)silyl-4-

phenylpent-2-yne (398 mg, 22%); R_f(light petroleum–CH₂Cl₂,

NMR); R_f(light petroleum–Et₂O, 95 : 5) 0.56; ν_max(ﬁlm)/cm^Ϫ1

1703 (C᎐O), 1603 (C᎐C), 1250 (SiMe) and 839 (SiMe); δ (500

᎐

H

MHz; CDCl ) isomer A: 5.97 (1 H, q, J 6.8, MeCH᎐C), 3.34

᎐

3

(1 H, q, J 6.8, MeCH᎐CCH ), 2.73 (1 H, sep, J 6.8, CHMe ),

᎐

2

1.67 (3 H, d, J 6.8, MeCH᎐C), 1.06 (3 H, d, J 6.8, C᎐CCHMe),

᎐

9 : 1) 0.28; ν_max(ﬁlm)/cm^Ϫ12193 (C᎐C), 1597 (Ph), 1248 (SiMe)

᎐

1.00 (6 H, d, J 6.8, CHMe₂) and 0.08 (9 H, s, SiMe₃); isomer B:

5.93 (1 H, q, J 7.0, MeCH᎐C), 3.57 (1 H, q, J 6.9, MeCH᎐

᎐

and 1112 (SiPh); δ_H(250 MHz; CDCl₃) 7.68–7.04 (10 H, m,

᎐

CCH ), 2.61 (1 H, sep, J 6.9, CHMe₂), 1.75 (3 H, d, J 7.0,

MeCH᎐C), 1.14 (3 H, d, J 6.9, C᎐CCHMe), 1.00 (6 H, d, J 6.9,

2 × Ph), 1.96 (3 H, s, C᎐CMe), 1.58 (3 H, s, SiCMe), 0.37 (3 H,

᎐

s, SiMe_AMe_B) and 0.28 (3 H, s, SiMe_AMe_B); δ_C(500 MHz;

CDCl₃) 143.4ϩ, 135.7ϩ, 135.0Ϫ, 129.2Ϫ, 127.5Ϫ, 127.2Ϫ,

126.6Ϫ, 124.9Ϫ, 83.7ϩ, 79.2ϩ, 29.9ϩ, 22.4Ϫ, 3.8Ϫ, Ϫ5.5Ϫ

and Ϫ5.8Ϫ; m/z (EI) 278 (20%, M^ϩ), 263 (10, M Ϫ Me) and 135

(70, SiMe₂Ph) (Found: M^ϩ, 278.1481. C₁₉H₂₂Si requires M,

278.1491), and 4-dimethyl(phenyl)silyl-4-phenylbuta-2,3-diene

᎐

CHMe₂) and 0.06 (9 H, s, SiMe₃); δ_C(500 MHz; CDCl₃) 216.3ϩ,

215.4ϩ, 141.6ϩ, 139.6ϩ, 138.9Ϫ, 137.4Ϫ, 49.4Ϫ, 46.2Ϫ,

39.2Ϫ, 38.1Ϫ, 20.0Ϫ, 19.6Ϫ, 18.1Ϫ, 17.8Ϫ, 15.3Ϫ, 14.0Ϫ,

Ϫ0.3Ϫ and Ϫ0.6Ϫ; m/z (EI) 212 (5%, M^ϩ), 197 (22, M Ϫ Me)

and 73 (100, SiMe) (Found: M^ϩ, 212.1602).

(144 mg, 8.4%); R_f(light petroleum–CH₂Cl₂, 9 : 1) 0.38; ν_max

᎐ ᎐

(SiPh); δ_H(250 MHz; CDCl₃) 7.65–7.17 (10 H, m, 2 × Ph), 5.22

-

5-(2-Methylpropyl)-2-phenyl-3-dimethyl(phenyl)silyl-2,5-

dihydrofuran 48

(ﬁlm)/cm^Ϫ11926 (C᎐C᎐C), 1596 (Ph), 1249 (SiMe) and 1112

(1 H, q, J 7.0, C᎐C᎐CHMe), 1.78 (3 H, d, J 7.0, C᎐C᎐CHMe)

᎐ ᎐ ᎐ ᎐

Titanium tetrachloride (1.0 mol dm^Ϫ3in CH₂Cl₂, 0.14 cm³,

0.14 mmol) was added to a solution of isobutyraldehyde

(20 mg, 0.025 cm³, 0.28 mmol) in dry dichloromethane (1 cm³)

at Ϫ78 ЊC under argon. The mixture was stirred at Ϫ78 ЊC for

5 min and a solution of the propargylsilane⁵⁷47 (70 mg,

0.28 mmol) in dry dichloromethane (0.75 cm³) was added, and

the mixture stirred at Ϫ78 ЊC for 15 min, warmed to 0 ЊC and

stirred for 1.5 h, warmed to room temperature and stirred over-

night. The mixture was quenched with saturated aqueous

sodium hydrogencarbonate (5 cm³), and the aqueous layer was

extracted with dichloromethane (3 × 5 cm³). The combined

organic extracts were washed with brine (20 cm³), dried

(MgSO₄) and evaporated under reduced pressure. The crude

product was chromatographed (SiO₂, light petroleum–CH₂Cl₂,

8 : 2) to give the dihydrofuran 47 (23 mg, 26%) as a mixture of

and 0.49 (6 H, s, SiMe₂); δ_C(500 MHz; CDCl₃) 210.7ϩ, 138.7ϩ,

137.6ϩ, 133.9Ϫ, 133.0Ϫ, 129.1Ϫ, 128.3Ϫ, 127.9Ϫ, 126.0Ϫ,

97.9ϩ, 82.2Ϫ, 13.5Ϫ, Ϫ1.6Ϫ and Ϫ1.8Ϫ; m/z (EI) 264 (25%,

M^ϩ) and 135 (64, SiMe₂Ph) (Found: M^ϩ, 264.1337. C₁₈H₂₀Si

requires M, 264.1334).

4-Methyl-2-phenyl-5-(2-methylethyl)-3-dimethyl(phenyl)silyl-

2,5-dihydrofuran 50a

Titanium tetrachloride (1.0 mol dm^Ϫ3in CH₂Cl₂, 0.19 cm³,

0.19 mmol) was added to isobutyraldehyde (27 mg, 0.03 cm³,

0.38 mmol) in dry dichloromethane (1.5 cm³) at Ϫ78 ЊC under

argon. The mixture was stirred at Ϫ78 ЊC for 5 min and a solu-

tion of the propargylsilane 49 (100 mg, 0.38 mmol) in dry di-

chloromethane (1 cm³) was added. The mixture was stirred at

Ϫ78 ЊC for 1 h, warmed to 0 ЊC and stirred for 2 h, and warmed

to room temperature and stirred for 30 min. The reaction was

quenched with saturated aqueous sodium hydrogencarbonate

(5 cm³) and the aqueous layer was extracted with dichloro-

methane (3 × 5 cm³). The combined organic extracts were

washed with brine (20 cm³), dried (MgSO₄) and evaporated

under reduced pressure. The crude product was chromato-

graphed (SiO₂, light petroleum–Et₂O, 9 : 1) to give the dihydro-

furan (14 mg, 11%) as an oil; R_f(light petroleum–Et₂O, 8 : 2)

1

diastereoisomers (1.8 : 1, H NMR); R_f(light petroleum–Et₂O,

9 : 1) 0.38; ν_max(ﬁlm)/cm^Ϫ11646 (C᎐C), 1252 (SiMe), 1111

᎐

(SiPh) and 1088 (C-O); δ_H(500 MHz; CDCl₃) major isomer:

7.35–7.10 (10 H, m, 2 × Ph), 6.16 (1 H, dd, J 2.3 and 1.3,

C᎐CH), 5.64 (1 H, dd, J 4.8 and 2.3, PhCHO), 4.54–4.52 (1 H,

᎐

m, OCHCH), 1.88–1.75 (1 H, m, CHMe₂), 1.02–0.92 (6 H, m,

CHMe₂), 0.12 (3 H, s, SiMe_AMe_B) and Ϫ0.02 (3 H, s, SiMe_A-

Me_B); Minor isomer: 7.35–7.10 (10 H, m, 2 × Ph), 6.10 (1 H, dd,

J 2.1 and 1.4, C᎐CH), 5.72 (1 H, dd, J 5.8 and 2.1, PhCHO),

᎐

4.93–4.90 (1 H, m, OCHCH), 1.88–1.75 (1 H, m, CHMe₂),

1.02–0.92 (6 H, m, CHMe₂), 0.14 (3 H, s, SiMe_AMe_B) and

Ϫ0.01 (3 H, s, SiMe_AMe_B); δ_C(500 MHz; CDCl₃) 143.3ϩ,

143.2ϩ, 142.2ϩ, 141.8ϩ, 140.7Ϫ, 139.7Ϫ, 137.2ϩ, 137.1ϩ,

133.8Ϫ, 133.7Ϫ, 129.1Ϫ, 129.0Ϫ, 128.3Ϫ, 128.2Ϫ, 128.1Ϫ,

127.9Ϫ, 127.8Ϫ, 127.7Ϫ, 127.3Ϫ, 92.9Ϫ, 92.8Ϫ, 92.7Ϫ, 92.2Ϫ,

33.8Ϫ, 33.6Ϫ, 19.3Ϫ, 19.2Ϫ, 18.9Ϫ, 18.8Ϫ, Ϫ2.6Ϫ, Ϫ2.7Ϫ,

Ϫ3.1Ϫ and Ϫ3.2Ϫ; m/z (EI) 322 (36%, M^ϩ), 307 (15, M Ϫ Me),

279 (77, M Ϫ C₃H₇) and 135 (100, SiMe₂Ph) (Found: M^ϩ,

322.1752. C₂₁H₂₆OSi requires M, 322.1753).

0.47; ν_max(ﬁlm)/cm^Ϫ11623 (C᎐C), 1258 (SiMe), 1109 (SiPh) and

᎐

1090 (C-O); δ_H(400 MHz; CDCl₃) 7.39 (10 H, m, 2 Ph), 5.65

(1 H, dq, J 4.8 and 2.1, PhCHO), 4.85–4.57 (1 H, m, OCHCH),

1.95 (1 H, sepd, J 6.9 and 2.4, CHMe₂), 1.68–1.67 (3 H, m,

C᎐CMe), 1.02 (3 H, d, J 6.9, CHMe Me ), 0.86 (3 H, d, J 6.9,

᎐

A

B

CHMe_AMe_B), 0.16 (3 H, s, SiMe_AMe_B) and 0.02 (3 H, s, SiMe_A-

Me_B); δ_C(500 MHz; CDCl₃) 151.0ϩ, 142.0ϩ, 138.4ϩ, 133.7Ϫ,

132.6ϩ, 129.0Ϫ, 128.8Ϫ, 128.0Ϫ, 127.9Ϫ, 127.7Ϫ, 93.6Ϫ,

92.1Ϫ, 30.2Ϫ, 20.1Ϫ, 15.9Ϫ, 13.5Ϫ, Ϫ1.7Ϫ and Ϫ1.8Ϫ; m/z

(ESI) 359 (68%, MNa^ϩ) and 316 (100, MNa Ϫ C₃H₇) (Found:

M ϩ Na^ϩ, 359.1797. C₂₂H₂₈OSi requires M ϩ Na, 359.1807).

(1RS )-1-Dimethyl(phenyl)silyl-1-phenylbut-2-yne 49

4-Methyl-2-phenyl-5-(2,4-dinitrophenyl)-3-dimethyl(phenyl)silyl-

2,5-dihydrofuran 50b

A solution of LDA (15.6 mmol) was added dropwise to

(3RS)-3-dimethyl(phenyl)silyl-3-phenylprop-1-enyl triﬂuoro-

methanesulfonate⁵⁷(2.60 g, 6.49 mmol) in dry THF (65 cm³)

and the mixture was allowed to stir at 0 ЊC for 2 h. Methyl

iodide (18.5 g, 8.1 cm³, 0.13 mol) was added and the mixture

was stirred at room temperature for 30 min. The mixture was

Similarly, 2,4-dinitrobenzaldehyde (74 mg, 0.38 mmol) and the

propargylsilane 49 (60 mg, 0.23 mmol) gave the dihydrofuran

1

(19 mg, 18%) as a mixture of diastereoisomers (9.3 : 1, H

NMR); R_f(light petroleum–Et₂O, 8 : 2) 0.37; ν_max(CDCl₃)/cm^Ϫ1

1606 (Ph), 1538 and 1348 (ArNO₂), 1259 (SiMe) and 1112

(SiPh); δ_H(500 MHz; CDCl₃) major isomer: 8.76 (1 H, d, J 2.0,

washed with dilute aqueous hydrochloric acid (3 mol dm^Ϫ3

,

80 cm³), water (2 × 80 cm³), brine (110 cm³), dried (MgSO₄) and

O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 7 4 9 – 7 6 9

763

View Article Online

ArH), 8.37 (1 H, dd, J 8.7 and 2.0, ArH), 7.90 (1 H, d, J 8.7,

ArH), 7.37–7.18 (10 H, m, 2 × Ph), 6.42 (1 H, d, J 4.0, PhCHO),

0.27 mmol) was added and the mixture was stirred at Ϫ78 ЊC

for 5 min. A solution of propargylsilane⁵⁷53 (100 mg,

0.53 mmol) in dry dichloromethane (0.5 cm³) was added. The

mixture was stirred at Ϫ78 ЊC for 2 h, warmed to Ϫ20 ЊC and

stirred at Ϫ20 ЊC for 18 h. Saturated aqueous sodium hydrogen

carbonate (5 cm³) was added and the mixture was stirred at

room temperature for 30 min. The aqueous phase was extracted

with ether (3 × 5 cm³) and the combined organic extracts

were dried (MgSO₄) and evaporated under reduced pressure.

Column chromatography (SiO₂, light petroleum–Et₂O, 9 : 1)

gave the dihydrofuran 52 (12 mg, 9%) as a mixture of

diastereoisomers (1.3 : 1) the major one of which was identical

(¹H NMR) with the earlier sample, and the minor gave the

following data: δ_H(500 MHz; CDCl₃) 7.52–7.48 (4 H, m, 2 ×

5.88 (1 H, br s, ArCHO), 1.61 (3 H, br s, C᎐CMe), 0.25 (3 H, s,

᎐

SiMe_AMe_B) and 0.14 (3 H, s, SiMe_AMe_B); minor isomer: 8.73

(1 H, d, J 2.0, ArH), 8.47 (1 H, dd, J 8.7 and 2.0, ArH), 7.84

(1 H, d, J 8.7, ArH), 7.37–7.18 (10 H, m, 2 × Ph), 6.52 (1 H, d,

J 5.0, PhCHO), 6.06 (1 H, br s, ArCHO), 1.65 (3 H, br s,

C᎐CMe), 0.32 (3 H, s, SiMe Me ) and 0.17 (3 H, s, SiMe Me );

᎐

A

B

A

B

δ_C(500 MHz; CDCl₃) 149.3ϩ, 148.5ϩ, 147.0ϩ, 143.0ϩ,

140.5ϩ, 136.9ϩ, 134.7ϩ, 133.7Ϫ, 131.7Ϫ, 129.3Ϫ, 128.8Ϫ,

128.7Ϫ, 127.9Ϫ, 127.3Ϫ, 119.8Ϫ, 95.7Ϫ, 93.9Ϫ, 86.2Ϫ, 85.4Ϫ,

13.9Ϫ, 13.4Ϫ, Ϫ1.9Ϫ, Ϫ2.1Ϫ, Ϫ2.2Ϫ and Ϫ2.3Ϫ; m/z (ESI)

483 (100%, MNa^ϩ) (Found: M ϩ Na^ϩ, 483.1351. C₂₅H₂₄N₂O₅Si

requires M ϩ Na, 483.1352).

Ph), 7.37–7.32 (6 H, m, 2 × Ph), 5.97–5.95 (2 H, m, 2 × SiC᎐

᎐

2-Chloro-5-(2-Chloroethoxy)-6-methyl-3-dimethyl(phenyl)-

silylhept-3-ene 51 and 2-methyl-3-dimethyl(phenyl)silyl-5-

(2-methylpropyl)-2,5-dihydrofuran 52

CH), 5.00–4.95 (1 H, m, MeCHO), 4.67 (1 H, td, J 5.3 and 1.4,

OCHCH), 1.78–1.69 (2 H, m, 2 × CHMe₂), 1.15 (3 H, d, J 6.4,

MeCHO), 0.88 (6 H, d, J 6.8, CHMe₂), 0.40 (6 H, s, 2 × SiMe_A-

Me_B) and 0.39 (6 H, s, 2 × SiMe_AMe_B), the alcohol 55 (28 mg,

18%) as a single diastereoisomer; R_f(light petroleum–Et₂O,

9 : 1) 0.13; ν_max(CDCl₃)/cm^Ϫ13604 (OH), 1602 (Ph), 1252

(SiMe), 1111 (SiPh) and 836 (SiMe); δ_H(500 MHz; CDCl₃)

7.55–7.51 (2 H, m, Ph), 7.36–7.33 (3 H, m, Ph), 5.78 (1 H, dd,

Boron triﬂuoride-diethyletherate (0.01 cm³, 0.13 mmol) was

added to isobutyraldehyde di-(2-chloroethyl) acetal⁸⁰(54 mg,

0.25 mmol) in dry dichloromethane (1 cm³) at Ϫ78 ЊC under

argon. The mixture was stirred at Ϫ78 ЊC for 5 min and a

solution of (3RS)-3-dimethyl(phenyl)silylbutyne⁵⁷53 (47 mg,

0.25 mmol) in dichloromethane (0.5 cm³) was added. The mix-

ture was stirred at Ϫ78 ЊC for 10 min, warmed to 0 ЊC and

stirred for 1 h. Saturated aqueous sodium hydrogencarbonate

(3 cm³) was added and the mixture was stirred at room temper-

ature for 30 min. The aqueous layer was extracted with di-

chloromethane (3 × 3 cm³) and the combined organic extracts

were washed with brine (10 cm³), dried (MgSO₄) and evapor-

ated under reduced pressure. Chromatography (SiO₂, light

petroleum–Et₂O, 99 : 1) gave the dihydrofuran 52 (11 mg, 17%)

as a single diastereoisomer; R_f(light petroleum–Et₂O, 9 : 1) 0.44;

ν_max(CDCl₃)/cm^Ϫ11600 (Ph), 1252 (SiMe), 1112 (SiPh) and 833

(SiMe); δ_H(400 MHz; CDCl₃) 7.53–7.50 (2 H, m, Ph), 7.39–7.33

J 8.9 and 0.5, SiC᎐CH), 5.16 (1 H, q, J 6.9, MeCHCl), 4.31

᎐

(1 H, dd, J 8.9 and 6.8, CHOH), 1.67 (1 H, oct, J 6.8, CHMe₂),

1.51 (3 H, d, J 6.9, MeCHCl), 0.95 (3 H, d, J 6.8, CHMe_AMe_B),

0.85 (3 H, d, J 6.8, CHMe_AMe_B), 0.54 (3 H, s, SiMe_AMe_B) and

0.49 (3 H, s, SiMe_AMe_B); δ_C(500 MHz; CDCl₃) 145.2Ϫ, 143.7ϩ,

138.5ϩ, 134.0Ϫ, 129.0Ϫ, 127.8Ϫ, 72.2Ϫ, 56.6Ϫ, 34.0Ϫ, 25.8Ϫ,

18.4Ϫ, 17.9Ϫ, Ϫ0.8Ϫ and Ϫ0.9Ϫ; m/z (EI) 296 (5%, M^ϩ)

and 135 (100, SiMe₂Ph) (Found: M^ϩ, 296.1360. C₁₆H₂₅ClOSi

requires M, 296.1363), and the alcohol 54 (22 mg, 14%) as a

single diastereoisomer; R_f(light petroleum–Et₂O, 9 : 1) 0.30;

ν_max(CDCl₃)/cm^Ϫ13582 (OH), 1601 (Ph), 1260 (SiMe), 1110

(SiPh) and 835 (SiMe); δ_H(500 MHz; CDCl₃) 7.55–7.51 (2 H, m,

Ph), 7.36–7.32 (3 H, m, Ph), 6.10 (1 H, qd, J 6.9 and 0.6,

(3 H, m, Ph), 5.97 (1 H, br s, SiC᎐CH), 4.94 (1 H, qdd, J 6.4, 4.1

᎐

MeHC᎐C), 5.07 (1 H, dd, J 8.7 and 0.6, CHCl), 3.53 (1 H, dt,

᎐

and 2.2, MeCHO), 4.55 (1 H, ddd, J 5.4, 4.1 and 1.4, OCHCH),

1.73 (1 H, sepd, J 6.8 and 5.4, CHMe₂), 1.17 (3 H, d, J 6.4,

MeCHO), 0.92 (3 H, d, J 6.8, CHMe_AMe_B), 0.90 (3 H, d, J 6.8,

CHMe_AMe_B), 0.41 (3 H, s, SiMe_AMe_B) and 0.39 (3 H, s, SiMe_A-

Me_B); δ_C(500 MHz; CDCl₃) 143.5ϩ, 139.9Ϫ, 137.5ϩ, 133.8Ϫ,

129.2Ϫ, 127.8Ϫ, 91.9Ϫ, 86.0Ϫ, 33.1Ϫ, 23.0Ϫ, 18.4Ϫ, 18.3Ϫ,

Ϫ2.2Ϫ and Ϫ2.7Ϫ, and the ether 51 (18 mg, 20%) as a mixture

J 8.7 and 3.1, CHOH), 2.19 (1 H, dd, J 3.5 and 0.9, OH), 1.82

(3 H, d, J 6.8, MeHC᎐C), 1.60–1.53 (1 H, m, CHMe ), 0.78

᎐

2

(3 H, d, J 6.8, CHMe_AMe_B), 0.77 (3 H, d, J 6.9, CHMe_AMe_B),

0.48 (3 H, s, SiMe_AMe_B) and 0.45 (3 H, s, SiMe_AMe_B); δ_C(500

MHz; CDCl₃) 142.1Ϫ, 138.8ϩ, 138.5ϩ, 134.1Ϫ, 129.0Ϫ,

127.7Ϫ, 77.2Ϫ, 67.6Ϫ, 29.9Ϫ, 20.5Ϫ, 15.3Ϫ, 14.8Ϫ, Ϫ0.3Ϫ

and Ϫ0.4Ϫ; m/z (EI) 253 (10%, M Ϫ C₃H₇), 135 (45, SiMe₂Ph)

and 118 (32, M Ϫ C₁₁H₁₈Si) (Found: (M Ϫ C₃H₇)^ϩ, 253.0800.

C₁₃H₁₈ClOSi requires M Ϫ C₃H₇, 253.0815). Other Lewis acids

gave similar mixtures of one or more of these three products

with titanium tetrachloride giving largely (43%) the dihydro-

furan 52, as a mixture of diastereoisomers (1.2 : 1) having iden-

tical signals (¹H NMR) with the earlier samples (Found: M^ϩ,

260.1607. C₁₆H₂₄OSi requires M, 260.1596).

1

of diastereoisomers (1.8 : 1, H NMR); R_f(light petroleum–

Et₂O, 98 : 2) 0.21; ν_max(ﬁlm)/cm^Ϫ11603 (Ph), 1251 (SiMe) and

1111 (SiPh); δ_H(500 MHz; CDCl₃) 7.58–7.48 (4 H, m, Ph), 7.35–

7.34 (6 H, m, Ph), 5.64 (2 H, d, J 9.0, 2 × SiC᎐CH), 5.16–5.10

᎐

(2 H, m, 2 × MeCHCl), 3.92 (1 H, dd, J 9.0 and 6.9, CHOR

major), 3.92–3.87 (1 H, m, CHOR), 3.70–3.48 (8 H, m, 2 ×

OCH₂CH₂Cl), 1.78–1.62 (2 H, m, 2 × CHMe₂), 1.53 (3 H, d,

J 6.9, MeCHCl major), 1.51 (3 H, d, J 6.9, MeCHCl minor),

0.96 (3 H, d, J 6.7, CHMe_AMe_Bmajor), 0.95 (3 H, d, J 6.6,

CHMe_AMe_Bminor), 0.86 (3 H, d, J 6.9, CHMe_AMe_Bmajor),

0.80 (3 H, d, J 6.9, CHMe_AMe_Bminor), 0.55 (3 H, s, SiMe_AMe_B

minor), 0.54 (3 H, s, SiMe_AMe_Bmajor) and 0.49 (6 H, s, 2 ×

SiMe_AMe_B); δ_C(500 MHz; CDCl₃) 145.6ϩ, 145.5ϩ, 143.8Ϫ,

143.6Ϫ, 138.7ϩ, 138.6ϩ, 134.0Ϫ, 133.9Ϫ, 129.1Ϫ, 127.8Ϫ,

80.7Ϫ, 80.3Ϫ, 69.0ϩ, 68.9ϩ, 56.6Ϫ, 56.5Ϫ, 43.2ϩ, 43.0ϩ,

32.9Ϫ, 32.8Ϫ, 26.0Ϫ, 25.5Ϫ, 18.6Ϫ, 18.5Ϫ, 18.4Ϫ, 18.3Ϫ,

Ϫ0.4Ϫ, Ϫ0.5Ϫ, Ϫ0.6Ϫ and Ϫ0.7Ϫ; m/z (ESI) 385 (5%, MNa^ϩ),

383 (9, MNa^ϩ), 381 (10, MNa^ϩ), 345 (100, M – Cl) and 316 (26,

M – C₂H₄Cl) (Found: M ϩ Na^ϩ, 381.1177. C₁₈H₂₈Cl₂OSi

requires M ϩ Na, 381.1184).

1-(2,4-dinitrophenyl)-2-trimethylsilylpenta-2,3-dienol 57

2,4-Dinitrobenzaldehyde (0.50 g, 2.52 mmol) in dry dichloro-

methane (9 cm³) under argon was cooled to Ϫ78 ЊC. Titanium

tetrachloride (1.0 mol dm^Ϫ3in CH₂Cl₂, 1.25 cm³, 1.25 mmol)

was added and the mixture was stirred at Ϫ78 ЊC for 5 min. A

solution of racemic 1,3-bis(trimethylsilyl)butyne⁸¹56 (0.50 g,

2.52 mmol) in dry dichloromethane (5 cm³) was added. The

mixture was stirred at Ϫ78 ЊC for 15 min and saturated aqueous

sodium hydrogencarbonate (25 cm³) was added. The mixture

was stirred at room temperature for 30 min. The aqueous phase

was extracted with ether (3 × 15 cm³) and the combined organic

extracts were dried (MgSO₄) and concentrated under reduced

pressure. Flash column chromatography (SiO₂, light petrol-

eum–Et₂O, 8 : 2) gave the allene (0.61 g, 76%) as a mixture of

4-Chloro-6-methyl-3-dimethyl(phenyl)silylhept-2-en-5-ol 54 and

2-chloro-6-methyl-3-dimethyl(phenyl)silylhept-3-en-5-ol 55

Isobutyraldehyde (38 mg, 0.05 cm³, 0.53 mmol) in dry di-

chloromethane (1.25 cm³) under argon was cooled to Ϫ78 ЊC.

Titanium tetrachloride (1.0 mol dm^Ϫ3in CH₂Cl₂, 0.27 cm³,

1

diastereoisomers (2.2 : 1, H NMR); R_f(light petroleum–Et₂O,

᎐ ᎐

9 : 1) 0.05; ν_max(ﬁlm)/cm^Ϫ13422 (OH), 1938 (C᎐C᎐C), 1535 and

1346 (Ar–NO₂), 1248 (SiMe) and 841 (SiMe); δ_H(500 MHz;

O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 7 4 9 – 7 6 9

764

View Article Online

CDCl₃) major isomer: 8.75 (1 H, d, J 2.3, ArH), 8.44 (1 H, dd,

J 8.8 and 2.3, ArH), 8.05 (1 H, d, J 8.8, ArH), 6.11 (1 H, br s,

J 2.3, ArH isomer C), 8.25 (1 H, dd, J 8.7 and 2.3, ArH isomer

A), 8.24 (1 H, dd, J 8.7 and 2.3, ArH isomer C), 7.48–7.36

(12 H, m, ArH and Ph), 7.12 (1 H, d, J 1.8, CHO isomer A),

CHOH), 4.70 (1 H, qd, J 7.1 and 2.0, MeHC᎐C᎐C), 2.29 (1 H,

᎐ ᎐

br s, CHOH ), 1.34 (3 H, d, J 7.1, MeHC᎐C᎐C) and 0.17 (9 H, s,

7.08 (1 H, d, J 1.8, CHO isomer C), 4.83–4.78 (1 H, m, MeHC᎐

᎐ ᎐

᎐

SiMe₃); minor isomer: 8.72 (1 H, d, J 2.3, ArH), 8.42 (1 H, dd,

J 8.7 and 2.3, ArH), 8.03 (1 H, d, J 8.7, ArH), 6.01 (1 H, br s,

C᎐C isomer C), 4.81 (1 H, qd, J 7.1 and 1.8, MeHC᎐C᎐C iso-

᎐ ᎐

mer A), 3.52 (3 H, s, OMe), 3.51 (3 H, s, OMe), 1.47 (3 H, d,

᎐

CHOH), 4.77 (1 H, qd, J 7.1 and 2.2, MeHC᎐C᎐C), 2.39 (1 H,

J 7.1, MeHC᎐C᎐C isomer C), 1.29 (3 H, d, J 7.1, MeHC᎐C᎐C

᎐ ᎐

᎐ ᎐ ᎐ ᎐

br s, CHOH ), 1.43 (3 H, d, J 7.1, MeHC᎐C᎐C) and 0.14 (9 H, s,

isomer A), 0.12 (9 H, s, SiMe₃isomer A) and 0.06 (9 H, s, SiMe₃

isomer C); B ϩ D: 8.83 (2 H, d, J 2.3, ArH), 8.34 (2 H, dd, J 8.7

and 2.3, ArH), 7.61 (1 H, d, J 8.7, ArH isomer D), 7.60 (1 H, d,

J 8.7, ArH isomer B), 7.48–7.36 (10 H, m, 2 × Ph), 7.10 (1 H, d,

J 1.8, CHO isomer B), 7.06 (1 H, d, J 1.8, CHO isomer D),

᎐ ᎐

SiMe₃); δ_C(500 MHz; CDCl₃) 207.2ϩ, 207.1ϩ, 147.7ϩ, 147.4ϩ,

146.9ϩ, 146.7ϩ, 146.3ϩ, 145.8ϩ, 130.0Ϫ, 129.9Ϫ, 126.9Ϫ,

126.7Ϫ, 119.9Ϫ, 119.7Ϫ, 101.0ϩ, 100.9ϩ, 84.1Ϫ, 84.0Ϫ,

70.0Ϫ, 69.7Ϫ, 13.0Ϫ, 12.7Ϫ, Ϫ0.8Ϫ and Ϫ0.9Ϫ; m/z (ESI) 345

(89%, M ϩ Na^ϩ) (Found: M ϩ Na^ϩ, 345.0894. C₁₄H₁₈N₂O₅Si

requires M ϩ Na, 345.0883).

4.80–4.75 (1 H, m, MeHC᎐C᎐C isomer D), 4.77 (1 H, qd, J 7.1

᎐ ᎐

and 1.8, MeHC᎐C᎐C isomer B), 3.50 (6 H, s, 2 × OMe), 1.45

᎐ ᎐

(3 H, d, J 7.1, MeHC᎐C᎐C isomer D), 1.30 (3 H, d, J 7.1,

᎐ ᎐

1-(2,4-Dinitrophenyl)-2-trimethylsilylpenta-2,3-dienone 58

MeHC᎐C᎐C isomer B), 0.10 (9 H, s, SiMe isomer D) and 0.07

(9 H, s, SiMe₃isomer B).

᎐ ᎐

3

Following the precedent of Marshall,⁸²1,1,1-triacetoxy-1,1-di-

hydro-1,2-benziodoxol-3(1H )-one (Dess–Martin periodinane)

(53 mg, 0.126 mmol) was added to the allenyl alcohols 57

(27 mg, 0.08 mmol) in dry dichloromethane (0.5 cm³) at room

temperature under argon. After 20 min, the mixture was ﬁltered

through a pad of silica gel and eluted with dichloromethane

(10 cm³). The organic solvents were evaporated under reduced

pressure and the crude product was chromatographed (SiO₂,

light petroleum) to give the ketone (22 mg, 85%) as an

oil; R_f(light petroleum–Et₂O, 9 : 1) 0.18; ν_max(ﬁlm)/cm^Ϫ11928

Ethyl (3R)-3-trimethylsilylbutanoate

This was prepared in the same way as the racemic ester using

the sultam 13 (5.70 g, 15.9 mmol) to give the enantiomerically

enriched ester, which was used in the next reaction without

puriﬁcation; [α]_Dϩ5.5 (c. 1.47 in CHCl₃).

(3R)-3-Trimethylsilylbutanal (R)-60

This was prepared in the same way as the racemic aldehyde

using the enantiomerically enriched ester (derived from 5.70 g

of sultam 13, 15.9 mmol) to give the enantiomerically enriched

aldehyde (R)-60, which was used in the next step without

puriﬁcation; [α]_DϪ34 (c. 1.28 in CHCl₃).

(C᎐C᎐C), 1665 (C᎐O), 1535 and 1347 (ArNO ), 1248 (SiMe)

᎐ ᎐

᎐

2

and 846 (SiMe); δ_H(500 MHz; CDCl₃) 8.90 (1 H, d, J 2.2, ArH),

8.50 (1 H, dd, J 8.4 and 2.2, ArH), 7.56 (1 H, d, J 8.4, ArH),

5.01 (1 H, q, J 7.4, MeHC᎐C᎐C), 1.48 (3 H, d, J 7.4, MeHC᎐C᎐

᎐ ᎐ ᎐ ᎐

C) and 0.27 (9 H, s, SiMe₃); δ_C(500 MHz; CDCl₃) 218.3ϩ,

193.3ϩ, 147.8ϩ, 146.3ϩ, 142.6ϩ, 129.7Ϫ, 128.0Ϫ, 119.3Ϫ,

104.4ϩ, 84.9Ϫ, 12.2Ϫ and Ϫ1.5Ϫ; m/z (EI) 320 (92%, M^ϩ), 305

(33, M Ϫ Me) and 73 (100, SiMe₃) (Found: M^ϩ, 320.0819.

C₁₄H₁₆N₂O₅Si requires M, 320.0828).

(3R)-3-Trimethylsilylbut-1-enyl triﬂuoromethanesulfonates

(R)-61

This was prepared in the same way as the racemic enol triﬂates

using the enantiomerically enriched aldehyde (R)-60 to give

the enantiomerically enriched enol triﬂates (1.90 g, 43% over

3 steps) (Z : E, 5.5 : 1); [α]_DϪ65 (c. 1.15 in CHCl₃).

1Ј-(2,4-Dinitrophenyl)-2Ј-trimethylsilylpenta-2Ј,3Ј-dienyl

(2R)-2-methoxy-2-phenyl-3,3,3-triﬂuoropropanoate 59

Following a recipe of Ward’s,⁸³oxalyl chloride (206 mg,

0.14 cm³, 1.62 mmol) was added to (R)-(ϩ)-Mosher’s acid

(80 mg, 0.34 mmol) and N,N-dimethylformamide (DMF)

(25 mg, 0.03 cm³, 0.34 mmol) in hexane (14 cm³) at room tem-

perature. After 1 h, the mixture was ﬁltered and concentrated.

The alcohol 57 (64 mg, 0.22 mmol), triethylamine (103 mg,

0.14 cm³, 1.02 mmol) and 4-dimethylaminopyridine (42 mg,

0.34 mmol) in dry dichloromethane (2 cm³) were added, and

after 1 h the mixture was ﬁltered through a silica pad, eluting

with dichloromethane. The solvent was removed under

reduced pressure, and the residue ﬂash column chromato-

graphed (SiO₂, light petroleum–Et₂O, 8 : 2) to give the mixture

of four esters 59 (99 mg, 84%) in a ratio A : B : C : D of 2 : 2 : 1 :

1; R_f(light petroleum–Et₂O, 8 : 2) 0.45; ν_max(CDCl₃)/cm^Ϫ11940

(3R)-1,3-Bis(trimethylsilyl)butyne (R)-62

This was prepared in the same way as the racemic propargyl-

silane 56 from the enol triﬂates (R)-60 (1.20 g, 4.34 mmol)

giving the alkyne (R)-62 (0.34 g, 40%), identical (TLC, IR, H

NMR) to the racemic sample; [α]_DϪ6.2 (c. 1.06 in CHCl₃).

1

1-(2,4-Dinitrophenyl)-2-trimethylsilylpenta-2,3-dienols 63–66

These were prepared in the same way as the allenyl alcohol 57

using the enantiomerically enriched propargylsilane (R)-62

(0.20 g, 1.00 mmol) and 2,4-dinitrobenzaldehyde (198 mg,

1.00 mmol) to give the allenyl alcohols (0.25 g, 74%) as a mix-

ture of diastereoisomers (2 : 1), identical (TLC, IR, H NMR)

to the earlier sample; [α]_DϪ89.3 (c. 1.1 in CHCl₃).

1

(C᎐C᎐C), 1750 (C᎐O), 1606 (Ar), 1540 and 1347 (ArNO ), 1262

᎐ ᎐

᎐

2

(SiMe) and 844 (SiMe); δ_C(500 MHz; CDCl₃) 211.0ϩ, 210.7ϩ,

165.7ϩ, 165.6ϩ, 165.5ϩ, 147.3ϩ, 147.1ϩ, 147.0ϩ, 146.9ϩ,

141.8ϩ, 141.7ϩ, 131.2ϩ, 131.1ϩ, 129.9Ϫ, 129.8Ϫ, 129.7ϩ,

129.5Ϫ, 128.6Ϫ, 128.5Ϫ, 127.5Ϫ, 127.4Ϫ, 126.9Ϫ, 126.8Ϫ,

126.7Ϫ, 120.0Ϫ, 119.9Ϫ, 97.3ϩ, 97.2ϩ, 97.0ϩ, 84.6Ϫ, 84.4Ϫ,

72.7Ϫ, 72.5Ϫ, 55.5Ϫ, 55.4Ϫ, 12.6Ϫ, 12.5Ϫ, 12.3Ϫ, Ϫ1.1Ϫ,

Ϫ1.2Ϫ, Ϫ1.3Ϫ and Ϫ1.4Ϫ; δ_F(400 MHz; CDCl₃) A Ϫ70.81,

B Ϫ70.88, C Ϫ70.96 and D Ϫ71.03; m/z (EI) 538 (10%, M^ϩ),

321 (10, M Ϫ C₁₀H₈F₃O₂) and 73 (89, SiMe₃)(Found: M^ϩ,

538.1383. C₂₄H₂₅F₃N₂O₇Si requires M, 538.1383); chromato-

graphy allowed the separation of a mixture rich in isomers A

and C (2 : 1), which we guessed had the same relative conﬁgur-

ation between the carbinol carbon and the stereogenic centre in

the Mosher’s acid fragment, as later proved to be true, and

another rich in the isomers B and D (2 : 1); δ_H(500 MHz;

CDCl₃) A ϩ C: 8.83 (1 H, d, J 2.3, ArH isomer A), 8.82 (1 H, d,

1Ј-(2,4-Dinitrophenyl)-2Ј-trimethylsilylpenta-2Ј,3Ј-dienyl

(2R)-2-methoxy-2-phenyl-3,3,3-triﬂuoropropanoate 67–70

These were prepared in the same way as the esters 59 using the

mixture of allenyl alcohols 63–65 to give the esters 66–70 as a

mixture of diastereoisomers A : B : C : D in the ratios 6.3 : 1.7 :

1 : 3, identical (TLC, IR) to the earlier sample, and with

appropriate signals in the ¹H NMR spectrum.

(2R)-4-Trimethylsilylbut-3-yn-2-ol

Following Marshall,⁸⁴(R)-Chirald® (16.7 g, 59.2 mmol) in

ether (130 cm³) was added dropwise to a suspension of lithium

aluminium hydride (1.01 g, 26.6 mmol) in ether (650 cm³) at

0 ЊC under argon. The mixture was cooled to Ϫ78 ЊC and a

solution of 4-trimethylsilylbut-3-en-2-one (3.13 g, 22.3 mmol)

O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 7 4 9 – 7 6 9

765

View Article Online

in ether (130 cm³) was added over 2 h. The mixture was stirred

at Ϫ78 ЊC for 5 h and quenched with dilute aqueous hydro-

chloric acid (3 mol dm^Ϫ3, 430 cm³). The aqueous layer was

extracted with ether (3 × 170 cm³) and the combined organic

extracts were washed with saturated aqueous sodium hydro-

gencarbonate (500 cm³), brine (500 cm³), dried (MgSO₄) and

evaporated under reduced pressure. Column chromatography

(SiO₂, light petroleum–Et₂O, 8 : 2) gave the (R)-alcohol (2.73 g,

identical signals (¹H NMR, ¹⁹F NMR) to the isomers hitherto

given the labels A and D, respectively.

(1ЈR,3ЈM)-1Ј-(2,4-Dinitrophenyl)-2Ј-trimethylsilylpenta-2Ј,3Ј-

dienyl (2S )-2-methoxy-2-phenyl-3,3,3-triﬂuoropropanoate

This was prepared in the same way as the ester above using the

allenyl alcohol 63 (50 mg, 0.16 mmol) and (S)-Mosher’s acid

chloride to give the ester (62 mg, 93%) as a mixture of

diastereoisomers (93 : 7), identical (TLC, IR) to the earlier mix-

ture of all four diastereoisomers, and with identical signals (¹H

NMR) to the isomers hitherto given the labels B and C,

respectively.

1

86%) as an oil identical (TLC, IR, H NMR) with the earlier

sample.

(2R)-4-Trimethylsilylbut-3-yn-2-yl (1S )-camphorsulfonate 71

This was prepared in the same way as its enantiomer 28 from

the (R)-alcohol (2.00 g, 14.1 mmol) giving the sulfonate

2-Methyl-4-trimethylsilylhepta-4,5-dien-3-ol

1

(2.61 g, 52%) diastereomerically pure (>99 : 1, H-NMR); mp

Isobutyraldehyde (0.98 g, 1.2 cm³, 13.6 mmol) in dry dichloro-

methane (34 cm³) under argon was cooled to Ϫ78 ЊC. Titanium

tetrachloride (1.0 mol dm^Ϫ3in CH₂Cl₂, 6.8 cm³, 6.80 mmol)

was added and the mixture was stirred at Ϫ78 ЊC for 5 min. A

solution of racemic propargylsilane 56 (2.70 g, 13.6 mmol) in

dry dichloromethane (13.6 cm³) was added. The mixture was

stirred at Ϫ78 ЊC for 30 min and saturated aqueous sodium

hydrogencarbonate (65 cm³) was added. The mixture was

stirred at room temperature for 30 min. The aqueous phase was

extracted with ether (3 × 15 cm³) and the combined organic

extracts were dried (MgSO₄) and concentrated under reduced

pressure. Flash column chromatography (SiO₂, light petrol-

eum–Et₂O, 94 : 6) gave the allenes (1.35 g, 50%) as a mixture

of diastereoisomers (2 : 1); R_f(light petroleum–Et₂O, 9 : 1)

67.5 ЊC; [α]_Dϩ98 (c. 1.06 in CHCl₃); ν_max(Nujol)/cm^Ϫ12178

᎐

(C᎐C), 1745 (C᎐O), 1364 (SO ), 1251 (SiMe ), 1176 (SO ) and

᎐

2

3

2

846 (SiMe₃); δ_H(250 MHz; CDCl₃) 5.32 (1 H, q, J 6.7, CHMe),

3.83 (1 H, d, J 15.0, CH_AH_BSO₂), 3.10 (1 H, d, J 15.0, CH_AH_B-

SO₂), 2.60–1.40 (7 H, m), 1.64 (3 H, d, J 6.7, MeCH), 1.16

(3 H, s, CMe_AMe_B), 0.90 (3 H, s, CMe_AMe_B) and 0.19 (9 H, s,

SiMe₃).

(1R,3M)-1-(2,4-Dinitrophenyl)-2-trimethylsilylpenta-2,3-dienol

63

Using the method developed by Marshall,²⁵copper() chloride

(20 mg, 0.20 mmol), trichlorosilane (0.12 cm³, 1.24 mmol) and

diisopropylethylamine (0.22 cm³, 1.24 mmol) were added suc-

cessively to the sulfonate ester (0.36 g, 1.00 mmol) in THF

(3 cm³) at room temperature, and the mixture stirred at room

temperature for 1 h. THF, DMF and acetonitrile (2 : 1 : 1,

40 cm³) were added, and the mixture cooled to 0 ЊC. 2,4-Di-

nitrobenzaldehyde (0.49 g, 2.50 mmol) in a mixture of THF,

DMF and acetonitrile (2 : 1 : 1, 6 cm³) was added. The mixture

was stirred at 0 ЊC for 5 h and kept at 10 ЊC overnight. The

mixture was quenched with cold water (40 cm³) and extracted

with ether (2 × 40 cm³). The combined organic extracts were

washed with brine (100 cm³), dried (MgSO₄) and concentrated

under reduced pressure. Flash column chromatography (SiO₂,

light petroleum–Et₂O, 8 : 2) gave the alkyne 72 (43 mg, 13%) as

a mixture of diastereoisomers (3.5 : 1); R_f(light petroleum–

0.28; ν_max(ﬁlm)/cm^Ϫ13469 (OH), 1935 (C᎐C᎐C), 1248 (SiMe)

᎐ ᎐

and 840 (SiMe); δ_H(500 MHz; CDCl₃) major isomer: 5.03

(1 H, qd, J 7.0 and 2.3, MeHC᎐C᎐C), 3.88–3.85 (1 H, m,

᎐ ᎐

CHOH), 1.80–1.70 (1 H, m, CHMe₂), 1.64 (3 H, d, J 7.0,

MeHC᎐C᎐C), 0.97 (3 H, d, J 6.9, CHMe Me ), 0.88 (3 H,

᎐ ᎐

A

B

d, J 6.7, CHMe_AMe_B) and 0.11 (9 H, s, SiMe₃); minor

isomer: 4.96 (1 H, qd, J 7.0 and 2.2, MeHC᎐C᎐C), 3.93–3.88

(1 H, m, CHOH), 1.80–1.70 (1 H, m, CHMe₂), 1.63 (3 H, d,

᎐ ᎐

J 7.0, MeHC᎐C᎐C), 0.96 (3 H, d, J 6.8, CHMe Me ), 0.87

᎐ ᎐

A

B

(3 H, d, J 6.8, CHMe_AMe_B) and 0.11 (9 H, s, SiMe₃); δ_C(500

MHz; CDCl₃) 205.0ϩ, 204.8ϩ, 101.4ϩ, 101.3ϩ, 83.6Ϫ, 83.2Ϫ,

75.8Ϫ, 75.1Ϫ, 33.5Ϫ, 33.4Ϫ, 20.1Ϫ, 19.6Ϫ, 15.9Ϫ, 15.7Ϫ,

13.6Ϫ, 13.5Ϫ, Ϫ0.7Ϫ and Ϫ0.9Ϫ; m/z (EI) 181 (80%,

M Ϫ OH) (Found: (M Ϫ OH)^ϩ, 181.1413. C₁₁H₂₁Si requires M

Ϫ OH, 181.1413).

Et₂O, 1 : 1) 0.40; ν_max(CDCl₃)/cm^Ϫ13604 (OH), 2164 (C᎐C),

᎐

1606 (Ar), 1537 and 1347 (ArNO₂), 1251 (SiMe) and 845

(SiMe); δ_H(500 MHz; CDCl₃) major isomer: 8.78 (1 H, d, J 2.3,

ArH), 8.46 (1 H, dd, J 8.7 and 2.3, ArH), 8.10 (1 H, d, J 8.7,

ArH), 5.53 (1 H, d, J 6.3, CHOH), 2.94 (1 H, qd, J 6.9 and 6.3,

MeCH ), 2.68 (1 H, br s, OH), 1.19 (3 H, d, J 6.9, MeCH)

and 0.08 (9 H, s, SiMe₃); minor isomer: 8.84 (1 H, d, J 2.3,

ArH), 8.46–8.43 (1 H, m, ArH), 8.08 (1 H, d, J 8.8, ArH),

5.34 (1 H, dd, J 6.3 and 3.0, CHOH), 3.02 (1 H, qd, J 7.1 and

3.0, MeCH ), 2.72 (1 H, d, J 6.3, OH), 1.42 (3 H, d, J 7.1,

MeCH) and 0.14 (9 H, s, SiMe₃); δ_C(500 MHz; CDCl₃) 148.2ϩ,

147.1ϩ, 143.5ϩ, 130.9Ϫ, 130.7Ϫ,126.9Ϫ, 126.8Ϫ, 120.0Ϫ,

119.7Ϫ, 105.8ϩ, 88.8ϩ, 71.2Ϫ, 35.7Ϫ, 34.6Ϫ, 18.5Ϫ, 16.1Ϫ,

Ϫ0.1Ϫ and Ϫ0.2Ϫ; m/z (EI) 307 (12%, M Ϫ Me), 197 (20,

M Ϫ C₇H₁₃Si), 126 (50, C₇H₁₄Si) and 73 (93, SiMe₃) (Found:

(M Ϫ Me)^ϩ, 307.0749. C₁₃H₁₅N₂O₅Si requires M Ϫ Me,

307.0750), and the allenyl alcohols 63 and 65 (187 mg, 58%) as a

mixture of diastereoisomers (93 : 7), identical (TLC, IR) to the

earlier mixture of all four diastereoisomers, and with identical

signals (¹H NMR) to the isomers hitherto given the labels major

and minor, respectively; [α]_DϪ203 (c. 1.13 in CHCl₃).

2Ј-Methyl-4Ј-trimethylsilylhepta-4Ј,5Ј-dien-3Ј-yl (2R)-2-

methoxy-2-phenyl-3,3,3-triﬂuoropropanoate

These were prepared by the same method as for the esters 59

using (R)-(ϩ)-Mosher’s acid (36 mg, 0.15 mmol) and the mix-

ture of alcohols (26 mg, 0.13 mmol), and chromatography

(SiO₂, light petroleum–Et₂O, 95 : 5) to give the esters (37 mg,

68%) as a mixture of diastereoisomers, labelled as A, B, C and

D, and correlated later as derived from the alcohols 73, 76, 74

and 75, respectively, in a ratio of 2 : 1 : 2 : 1; R_f(light petroleum–

Et₂O, 9 : 1) 0.58; ν_max(CDCl₃)/cm^Ϫ11937 (C᎐C᎐C), 1740 (C᎐O),

᎐ ᎐

᎐

1601 (Ph), 1250 (SiMe) and 842 (SiMe); δ_H(500 MHz; CDCl₃)

A: 7.60–7.34 (5 H, m, Ph), 5.11 (1 H, dd, J 6.3 and 1.4, CHO),

4.88 (1 H, qd, J 7.1 and 1.4, MeHC᎐C᎐C), 3.55 (3 H, s, OMe),

᎐ ᎐

1.91 (1 H, oct, J 6.6, CHMe ), 1.61 (3 H, d, J 7.1, MeHC᎐C᎐C),

᎐ ᎐

2

0.89 (3 H, d, J 6.9, CHMe_AMe_B), 0.86 (3 H, d, J 6.7,

CHMe_AMe_B) and 0.06 (9 H, s, SiMe₃); B: 7.60–7.34 (5 H, m,

Ph), 5.14 (1 H, dd, J 6.1 and 1.3, CHO), 4.94 (1 H, qd, J 7.1 and

1.3, MeHC᎐C᎐C), 3.57 (3 H, s, OMe), 1.97–1.85 (1 H, m,

᎐ ᎐

CHMe ), 1.54 (3 H, d, J 7.1, MeHC᎐C᎐C), 0.88 (3 H, d, J 6.7,

CHMe_AMe_B), 0.86 (3 H, d, J 6.7, CHMe_AMe_B) and 0.10 (9 H, s,

SiMe₃); C: 7.60–7.34 (5 H, m, Ph), 5.07 (1 H, dd, J 6.2 and 1.5,

᎐ ᎐

2

(1ЈR,3ЈM)-1Ј-(2,4-Dinitrophenyl)-2Ј-trimethylsilylpenta-2Ј,3Ј-

dienyl (2R)-2-methoxy-2-phenyl-3,3,3-triﬂuoropropanoate 67

This was prepared in the same way as before, using the allenyl

alcohol 63 to give the esters 67 and 69 (93 : 7), identical (TLC,

IR) to the earlier mixture of all four diastereoisomers, and with

CHO), 4.64 (1 H, qd, J 7.1 and 1.5, MeHC᎐C᎐C), 3.54 (3 H, s,

OMe), 1.92 (1 H, oct, J 6.5, CHMe₂), 1.54 (3 H, d, J 7.1,

᎐ ᎐

MeHC᎐C᎐C), 0.96 (3 H, d, J 6.9, CHMe Me ), 0.95 (3 H, d,

᎐ ᎐

A

B

O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 7 4 9 – 7 6 9

766

View Article Online

J 6.7, CHMe_AMe_B) and 0.11 (9 H, s, SiMe₃); and D: 7.60–7.34

(5 H, m, Ph), 5.13 (1 H, dd, J 6.3 and 1.2, CHO), 4.89 (1 H, qd,

References

1 M. J. C. Buckle, I. Fleming and S. Gil, Tetrahedron Lett., 1992, 33,

4479; M. J. C. Buckle and I. Fleming, Tetrahedron Lett., 1993, 34,

2383; I. Fleming and K. L. C. Pang, Tetrahedron Lett., 2002, 43,

5985.

2 R. A. N. C. Crump, I. Fleming, J. H. M. Hill, D. Parker, N. L. Reddy

and D. Waterson, J. Chem. Soc., Perkin Trans. 1, 1992, 3277;

I. Fleming and J. D. Kilburn, J. Chem. Soc., Perkin Trans. 1, 1992,

3295; I. Fleming, J. Chem. Soc., Perkin Trans. 1, 1992, 3363.

3 I. Fleming, N. J. Lawrence, A. K. Sarkar and A. P. Thomas, J. Chem.

Soc., Perkin Trans. 1, 1992, 3303; I. Fleming and N. J. Lawrence,

J. Chem. Soc., Perkin Trans. 1, 1992, 3309.

4 M. J. Carter, I. Fleming and A. Percival, J. Chem. Soc., Perkin Trans.

1, 1981, 2415.

5 I. Fleming and B.-W. Au-Yeung, Tetrahedron, Supplement No. 9,

1981, 37, Supplement No. 1, 13. See also: I. Fleming and R. V.

Williams, J. Chem. Soc., Perkin Trans. 1, 1981, 684.

J 7.1 and 1.2, MeHC᎐C᎐C), 3.52 (3 H, s, OMe), 1.97–1.85 (1 H,

᎐ ᎐

m, CHMe ), 1.44 (3 H, d, J 7.1, MeHC᎐C᎐C), 0.93 (6 H, d,

᎐ ᎐

2

J 6.6, CHMe₂) and 0.08 (9 H, s, SiMe₃); δ_C(500 MHz; CDCl₃)

208.5ϩ, 208.3ϩ, 165.8ϩ, 132.6ϩ, 132.4ϩ, 129.4Ϫ, 129.3Ϫ,

128.4Ϫ, 128.2Ϫ, 128.1Ϫ, 128.0Ϫ, 127.8Ϫ, 127.6Ϫ, 96.6ϩ,

96.3ϩ, 84.7ϩ, 84.5ϩ, 84.4ϩ, 84.2ϩ, 82.6Ϫ, 82.5Ϫ, 80.9Ϫ,

80.8Ϫ, 55.5Ϫ, 55.3Ϫ, 32.7Ϫ, 32.6Ϫ, 32.5Ϫ, 32.4Ϫ, 19.5Ϫ,

19.4Ϫ, 17.4Ϫ, 17.3Ϫ, 13.1Ϫ, 13.0Ϫ, 1.0Ϫ, Ϫ0.9Ϫ and Ϫ1.0Ϫ;

δ_F(400 MHz; CDCl₃) A Ϫ71.42, B Ϫ71.68, C Ϫ71.75, and D

Ϫ71.86; m/z (ESI) 437 (100%, MNa^ϩ), 393 (14, MNa Ϫ C₃H₈)

and 333 (22, MNa Ϫ C₄H₁₂OSi) (Found: MNa^ϩ, 437.1749.

C₂₁H₂₉F₃O₃SiNa requires MNa, 437.1736).

2-Methyl-4-trimethylsilylhepta-4,5-dien-3-ol 73–76

6 I. Fleming and N. K. Terrett, J. Organomet. Chem., 1984, 264, 99.

7 T. Hayashi, M. Konishi, H. Ito and M. Kumada, J. Am. Chem. Soc.,

1982, 104, 4962.

These were prepared in two runs in the same way as in the

preparation from the racemic propargylsilane, but using the

enantiomerically enriched propargylsilane (R)-62 (0.20 g,

1.00 mmol) and isobutyraldehyde (72 mg, 0.09 cm³, 1.00 mmol)

to give the allenyl alcohols (102 mg, 51%) as a mixture of

diastereoisomers (1.6 : 1), identical (TLC, IR, ¹H NMR) to the

earlier sample.

8 T. Hayashi, M. Konishi and M. Kumada, J. Am. Chem. Soc., 1982,

104, 4963; T. Hayashi, H. Ito and M. Kumada, Tetrahedron Lett.,

1982, 23, 4605; T. Hayashi, M. Konishi and M. Kumada, J. Chem.

Soc., Chem. Commun., 1983, 736; T. Hayashi, M. Konishi and

M. Kumada, J. Org. Chem., 1983, 48, 281; T. Hayashi, K. Kabeta,

T. Yamamoto, K. Tamao and M. Kumada, Tetrahedron Lett., 1983,

24, 5661; T. Hayashi, Y. Okamoto, K. Kabeta, T. Hagihara and

M. Kumada, J. Org. Chem., 1984, 49, 4224; T. Hayashi, M. Konishi,

Y. Okamoto, K. Kabeta and M. Kumada, J. Org. Chem., 1986, 51,

3772.

9 This work was carried out before that of Kumada, and was known

to us from personal communication. V. G. Matassa, P. R. Jenkins,

A. Kümin, L. Damm, J. Schreiber, D. Felix, E. Zass and

A. Eschenmoser, Isr. J. Chem., 1989, 29, 321.

10 K. Mikami, T. Maeda, N. Kishi and T. Nakai, Tetrahedron Lett.,

1984, 25, 5151.

11 G. Wickham and W. Kitching, Organometallics, 1983, 2, 541;

G. Wickham, D. Young and W. Kitching, Organometallics, 1988, 7,

1187; W. Kitching, K. G. Penman, B. Laycock and I. Maynard,

Tetrahedron, 1988, 44, 3819.

2Ј-Methyl-4Ј-trimethylsilylhepta-4Ј,5Ј-dien-3Ј-yl (2R)-2-

methoxy-2-phenyl-3,3,3-triﬂuoropropanoate

These were prepared in the same way as the esters derived

from the racemic propargylsilane, but using the mixture of

allenyl alcohols 73–76 to give the esters as a mixture of

diastereoisomers A : B : C : D, 1.2 : 1 : 1.6 : 2.8 from the ﬁrst run

and 1 : 1.9 : 1.1 : 2.3 from the second run, identical (TLC, IR)

with the earlier sample, and with matching signals (¹H NMR

and ¹⁹F NMR).

12 H. Wetter, P. Scherer and W. B. Schweizer, Helv. Chim. Acta, 1979,

62, 1985.

(3R,5M)-2-Methyl-4-trimethylsilylhepta-4,5-dien-3-ol 73

13 T. Hayashi, Y. Matsumoto and Y. Ito, Organometallics, 1987, 6, 884;

T. Hayashi, Y. Matsumoto, T. Kiyoi, Y. Ito, S. Kohra, Y. Tominaga

and A. Hosomi, Tetrahedron Lett., 1988, 29, 5667; K. Kitayama,

H. Tsuji, Y. Uozumi and T. Hayashi, Tetrahedron Lett., 1996, 37,

4169.

14 H. Wetter and P. Scherer, Helv. Chim. Acta, 1983, 66, 118.

15 T. Hayashi, Y. Okamoto and M. Kumada, Tetrahedron Lett., 1983,

24, 807.

This was prepared in the same way as the ester 63 from the

sulfonate ester 71 (0.36 g, 1.00 mmol) and isobutyraldehyde

(0.36 g, 0.45 cm³, 5.00 mmol) with chromatography (SiO₂, light

petroleum, 7 : 3) giving a mixture rich (98 : 2) in the allenyl

alcohol 73 (18 mg, 9%), identical (TLC, IR, H NMR) to the

major isomer in the racemic sample.

1

16 For an earlier, but stereochemically less eﬀective route, see:

I. Fleming, D. Higgins, N. J. Lawrence and A. P. Thomas, J. Chem.

Soc., Perkin Trans. 1, 1992, 3331.

17 I. Fleming, S. Gil, A. K. Sarkar and T. Schmidlin, J. Chem. Soc.,

Perkin Trans. 1, 1992, 3351.

(3ЈR,5ЈM)-2Ј-Methyl-4Ј-trimethylsilylhepta-4Ј,5Ј-dien-3Ј-yl

(2R)-2-methoxy-2-phenyl-3,3,3-triﬂuoropropanoate

This was prepared in the same way as the racemic esters using

the allenyl alcohol 73 to give the ester as a mixture of

18 E. Vedejs and C. K. McLure, J. Am. Chem. Soc., 1986, 108, 1094;

D. P. Curran and B. H. Kim, Synthesis, 1986, 312; D. P. Curran and

S. A. Gothe, Tetrahedron, 1988, 44, 3945; G. Procter, A. T. Russell,

P. J. Murphy, T. S. Tan and A. N. Mather, Tetrahedron, 1988, 44,

3953; S. R. Wilson and P. A. Zucker, J. Org. Chem., 1988, 53, 4682;

B. B. Lohray and D. Enders, Helv. Chim. Acta, 1989, 72, 980; P. J.

Murphy, A. T. Russell and G. Procter, Tetrahedron Lett., 1990, 31,

1055; P. J. Murphy and G. Procter, Tetrahedron Lett., 1990, 31, 1059;

B. B. Lohray and R. Zimbinski, Tetrahedron Lett., 1990, 31, 7273;

J. S. Panek and P. F. Cirillo, J. Am. Chem. Soc., 1990, 112, 4873;

R. A. Ward and G. Procter, Tetrahedron Lett., 1992, 33, 3363;

T. Harada, S. Imanaka, Y. Ohyama, Y. Matsuda and A. Oku,

Tetrahedron Lett., 1992, 33, 5807; J. S. Panek and J. Zhang, J. Org.

Chem., 1993, 58, 294; J. S. Panek and R. Beresis, J. Org. Chem., 1993,

58, 809; J. S. Panek, M. Yang and J. S. Solomon, J. Org. Chem., 1993,

58, 1003; J. S. Panek and N. F. Jain, J. Org. Chem., 1993, 58, 2345;

J. S. Panek, R. M. Garbaccio and N. F. Jain, Tetrahedron Lett., 1994,

35, 6453; D. L. J. Clive and C. Zhang, J. Org. Chem., 1995, 60, 1413;

B. A. Lorsbach, A. Prock and W. P. Giering, Organometallics, 1995,

14, 1694; M. A. Loreto, P. A. Tardella and D. Tofani, Tetrahedron

Lett., 1995, 36, 8295; Y. Landais and L. Parra-Rapado, Tetrahedron

Lett., 1996, 37, 1205; D. A. Singleton, S. C. Waller, Z. Zhang, D. E.

Frantz and S.-W. Leung, J. Am. Chem. Soc., 1996, 118, 9986;

R. Angelaud, Y. Landais and K. Schenk, Tetrahedron Lett., 1997,

38, 1407; O. Andrey, L. Ducry, Y. Landais, D. Planchenault and

V. Weber, Tetrahedron, 1997, 53, 4339; J. S. Panek and T. Hu, J. Org.

1

diastereoisomers, which matched (TLC, IR, H NMR and ¹⁹F

NMR) those labelled A and D (98 : 2).

Acknowledgements

We thank Professor Albert Eschenmoser for several fruitful dis-

cussions before we began the work reported here. We thank the

Conselleria de Cultura Educació i Ciencia of the Generalitat

Valenciana for a grant (SG), the SERC for a maintenance

award (MJCB) and Nathalie Maugein for assistance with some

of the preparative work. We thank Professor König (Hamburg)

for his generous help in measuring the enantiomeric purity of

our allenylsilane, Jérôme Bazin for preliminary work on the

synthesis of the enantiomerically enriched allenylsilane, Profes-

sor Rick Danheiser for steering us towards the successful recipe

for that synthesis, and Ken Takaki, Anne Ware and Sarah

Archibald for exploratory work on the reaction between the

allenylsilane and isobutyraldehyde. We thank the Economic

Development Board of Singapore and GlaxoSmithKline for a

grant (KLCP) and Dr Valentin Martinez-Barrasa for some

exploratory work in the propargylsilane series.

O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 7 4 9 – 7 6 9

767

View Article Online

Chem., 1997, 62, 4914; K. Sakaguchi, H. Mano and Y. Ohfune,

Tetrahedron Lett., 1998, 39, 4311; C. Gibson, T. Buck, M. Walker

and R. Brückner, Synlett, 1998, 201; J.-M. Adam, L. Ghosez and

K. N. Houk, Angew. Chem., Int. Ed., 1999, 38, 2728; C. W. Roberson

and K. A. Woerpel, J. Org. Chem., 1999, 64, 1434; H.-J. Knölker,

N. Foitzik and O. Schmitt, Tetrahedron Lett., 1999, 40, 3557;

Y. Landais and E. Zekri, Tetrahedron Lett., 2001, 42, 6547;

A. Kamimura, Y. Kaneko, A. Ohta, K. Matsuura, Y. Fujimoto,

A. Kakehi and S. Kanemasa, Tetrahedron, 2002, 58, 9613; F. Allais,

R. Angelaud, B. Camuzat-Dedenis, K. Julienne and Y. Landais, Eur.

J. Org. Chem., 2003, 1069.

32 M. M. Midland, D. C. McDowell, R. L. Hatch and A. Tramontano,

J. Am. Chem. Soc., 1980, 102, 867.

33 D. J. Barden, Ph.D. Thesis, Cambridge, 2003; S. C. Archibald,

D. J. Barden, J. F. Y. Bazin, I. Fleming, C. F. Foster, A. K. Mandal,

D. Parker, K. Takaki, A. C. Ware, A. R. B. Williams and A. B.

Zwicky, Org. Biomol. Chem., 2004, 2, DOI: 10.1039/b316899a.

34 K. Matsumura, S. Hashiguchi, T. Ikariya and R. Noyori, J. Am.

Chem. Soc., 1997, 119, 8738.

35 I. Fleming, K. Takaki and A. P. Thomas, J. Chem. Soc.,

Perkin Trans. 1, 1987, 2269.

36 A. Claesson and L.-I. Olsson, J. Chem. Soc., Chem. Commun., 1979,

524.

19 S. E. Denmark, M. A. Wallace and C. B. Walker, Jr., J. Org. Chem.,

1990, 55, 5543; J. S. Panek and M. Yang, J. Am. Chem. Soc., 1991,

113, 6594; J. S. Panek and M. Yang, J. Org. Chem., 1991, 56, 5755;

J. S. Panek, M. Yang and I. Muler, J. Org. Chem., 1992, 57, 4063; J. S.

Panek, M. Yang and F. Xu, J. Org. Chem., 1992, 57, 5790;

G. Ladoucer and L. A. Paquette, Synthesis, 1992, 185; J. S. Panek

and P. F. Cirillo, J. Org. Chem., 1993, 58, 999; J. S. Panek and N. F.

Jain, J. Org. Chem., 1994, 59, 2674; Y. Hatanaka, K. Goda and

T. Hiyama, Tetrahedron Lett., 1994, 35, 1279; S. E. Denmark and

N. G. Almstead, J. Org. Chem., 1994, 59, 5130; C. Bismara, R. Di

Fabio, D. Donati, T. Rossi and R. J. Thomas, Tetrahedron Lett.,

1995, 36, 4283; R. T. Beresis, C. E. Masseo and J. S. Panek, J. Org.

Chem., 1995, 60, 7714; N. F. Jain, P. F. Cirillo, R. Pelletier and J. S.

Panek, Tetrahedron Lett., 1995, 36, 8727; N. F. Jain, N. Takenaka

and J. S. Panek, J. Am. Chem. Soc., 1996, 118, 12475; D. Enders,

D. Ward, J. Adam and G. Raabe, Angew. Chem., Int. Ed., 1996, 35,

981; J. S. Panek and B. Zhu, J. Am. Chem. Soc., 1997, 119, 12022;

J. S. Panek and J. V. Schaus, Tetrahedron, 1997, 53, 10971; J. S. Panek

and P. Liu, Tetrahedron Lett., 1997, 38, 5127; M. Suginome,

T. Iwanami and Y. Ito, J. Org. Chem., 1998, 63, 6096; H. Huang and

J. S. Panek, J. Am. Chem. Soc., 2000, 122, 9836; M. Sui and J. S.

Panek, Org. Lett., 2001, 3, 2439; M. Suginome, T. Iwanami,

A. Yamamoto and Y. Ito, Synlett, 2001, 1042; R. Yamaguchi,

M. Tanaka, T. Matsuda and K. Fujita, Chem. Commun., 1999, 2213;

M. Suginome, T. Iwanami and Y. Ito, Chem. Commun., 1999, 2537;

P. Liu, E. D. Binnun, J. V. Schaus, N. M. Valentino and J. S. Panek,

J. Org. Chem., 2002, 67, 1705.

20 R. K. Chaudhuri, T. Ikeda and C. R. Hutchinson, J. Am. Chem.

Soc., 1984, 106, 6004; G. Majetich, J. S. Song, C. Ringold and

G. A. Nemeth, Tetrahedron Lett., 1990, 31, 2239; C. Y. Hong,

N. Kado and L. E. Overman, J. Am. Chem. Soc., 1993, 115, 11028;

E. J. Corey, J. Lee and D. R. Liu, Tetrahedron Lett., 1994, 35,

9149; I. Fleming and N. K. Terrett, J. Chem. Soc., Perkin Trans. 1,

1998, 2645; H.-F. Chow and I. Fleming, J. Chem. Soc., Perkin Trans.

1, 1998, 2651; I. Fleming and N. J. Lawrence, J. Chem. Soc.,

Perkin Trans. 1, 1998, 2679; I. Fleming and S. K. Ghosh, J. Chem.

Soc., Perkin Trans. 1, 1998, 2733.

21 J. S. Panek, M. Yang and J. Solomon, Tetrahedron Lett., 1995, 36,

1003; J. S. Panek and F. Xu, J. Am. Chem. Soc., 1995, 117, 10587;

J. S. Panek, R. T. Beresis and C. A. Celatka, J. Org. Chem., 1996, 61,

6494; J. S. Panek and R. T. Beresis, J. Org. Chem., 1996, 61, 6496;

N. F. Jain and J. S. Panek, Tetrahedron Lett., 1997, 38, 1345 and

1349; J. S. Panek and C. E. Masse, J. Org. Chem., 1997, 62, 8290; J. S.

Panek, F. Xu and A. C. Rondón, J. Am. Chem. Soc., 1998, 120, 4113;

C. E. Masse, M. Yang, J. Solomon and J. S. Panek, J. Am. Chem.

Soc., 1998, 120, 4123; T. Hu, N. Takenaka and J. S. Panek, J. Am.

Chem. Soc., 1999, 121, 9229; J. S. Panek and C. E. Masse, Angew.

Chem., Int. Ed., 1999, 38, 1093; T. Hu and J. S. Panek, J. Org. Chem.,

1999, 64, 3000; J. S. Panek and P. Liu, J. Am. Chem. Soc., 2000, 122,

11090; B. Zhu and J. S. Panek, Org. Lett., 2000, 2, 2575; H. Huang

and J. S. Panek, Org. Lett., 2001, 3, 1693; A. Arefolov and J. S.

Panek, Org. Lett., 2002, 4, 2397; C. A. Celatka and J. S. Panek,

Tetrahedron Lett., 2002, 43, 7043.

37 J. Pietruszka, D. H. Hochmuth, B. Gehrcke, D. Icheln, T. Runge and

W. A. König, Tetrahedron: Asymmetry, 1992, 3, 661.

38 I. Fleming, Stereocontrol in Organic Synthesis Using Silicon

Compounds, Pure Appl. Chem., 1990, 62, 1879; I. Fleming and

A. K. Mandal, in Natural Products Chemistry at the Turn of the

Century, Proceedings of the 8th International Symposium on

Natural Product Chemistry, Karachi, 2000, ed. Atta-ur-Rahman,

A. I. Choudhary and K. M. Khan, privately published (ISBN

969.8113–06–1), Karachi, 2002, pp. 1–10.

39 S. C. Archibald and I. Fleming, Tetrahedron Lett., 1993, 34, 2387.

40 R. L. Danheiser, D. J. Carini and C. A. Kwasigroch, J. Org. Chem.,

1986, 51, 3870.

41 I. Fleming, G. R. Jones, N. D. Kindon, Y. Landais, C. P. Leslie, I. T.

Morgan, S. Peukert and A. K. Sarkar, J. Chem. Soc., Perkin Trans. 1,

1996, 1171.

42 W. Runge and G. Kresze, J. Am. Chem. Soc., 1977, 99, 5597.

43 H. E. Zimmerman, L. Singer and B. S. Thyagarajan, J. Am. Chem.

Soc., 1959, 81, 108, footnote 16. E. L. Eliel and S. H. Wilen,

Stereochemistry of Organic Compounds; Wiley: New York, 1994,

p. 1208.

44 T. Flood and P. E. Peterson, J. Org. Chem., 1980, 45, 5006; J. Pornet,

Tetrahedron Lett., 1981, 22, 455; S. A. Babirad, Y. Wang and

Y. Kishi, J. Org. Chem., 1987, 52, 1370; C. R. Bertozzi and M. D.

Bednarski, Tetrahedron Lett., 1992, 33, 3109; S.-C. Hung, C.-C. Lin

and C.-H. Wong, Tetrahedron Lett., 1997, 38, 5419; R. Zemribo and

K. T. Mead, Tetrahedron Lett., 1998, 39, 3891 and 3895;

O. Gaertzen, A. M. Misske, P. Wolbers and H. M. R. Hoﬀmann,

Synlett, 1999, 1041; I. Ungureanu, C. Bologa, S. Chayer and

A. Mann, Tetrahedron Lett., 1999, 40, 5315; C. Guo, S. Reich,

R. Showalter, E. Villafranca and L. Dong, Tetrahedron Lett., 2000,

41, 5307; G. Huang and M. Isobe, Tetrahedron, 2001, 57, 10241;

M. Billet, A. Schoenfelder, P. Klotz and A. Mann, Tetrahedron Lett.,

2002, 43, 1453.

45 J. Pornet, Tetrahedron Lett., 1980, 22, 2049; J. Pornet and N. Kolani,

Tetrahedron Lett., 1981, 3609; J. Pornet, B. Randrianoelina and

L. Miginiac, Tetrahedron Lett., 1984, 25, 651; J. Pornet, D. Damour

and L. Miginiac, Tetrahedron, 1986, 42, 2017; J. Pornet, D. Damour,

B. Randrianoelina and L. Miginiac, Tetrahedron, 1986, 42, 2501;

D. Damour, J. Pornet and L. Miginiac, J. Organomet. Chem., 1988,

349, 43; J. S. Prasad and L. S. Liebeskind, Tetrahedron Lett., 1988,

29, 4257; P. Magnus, J. Ródriguez-López, K. Mulholland and

I. Matthews, Tetrahedron, 1993, 49, 8059; E. Vedejs and

A. Cammers-Goodwin, J. Org. Chem., 1994, 59, 7541; P. Aubert,

B. Princet and J. Pornet, Synth. Commun., 1997, 27, 2615; W. F. J.

Karstens, D. Klomp, F. P. J. T. Rutjes and H. Hiemstra, Tetrahedron,

2001, 57, 5123; L. Niimi, K. Shiino, S. Hiraoka and T. Yokozawa,

Tetrahedron Lett., 2001, 42, 1721; H. Gardès-Gariglio and J. Pornet,

J. Organomet. Chem., 2001, 620, 94.

46 A. D. Despo, S. K. Chiu, T. Flood and P. E. Peterson, J. Am. Chem.

Soc., 1980, 102, 5121; R. Schmid, P. L. Huesmann and W. S.

Johnson, J. Am. Chem. Soc., 1980, 102, 5122; W. S. Johnson, J. D.

Elliott and G. J. Hanson, J. Am. Chem. Soc., 1984, 106, 1138;

H. Hiemstra, W. J. Klaver and W. N. Speckamp, Recl. Trav.

Chim. Pays-Bas, 1986, 105, 299; W. J. Klaver, M. J. Moolenaar,

H. Hiemstra and W. N. Speckamp, Tetrahedron, 1988, 44, 3805; W. J.

Klaver, H. Hiemstra and W. N. Speckamp, J. Am. Chem. Soc., 1989,

111, 2588; D. Guay, W. S. Johnson and U. Schubert, J. Org. Chem.,

1989, 54, 4731; S. Hatakeyama, H. Numata, K. Osanai and

S. Takano, J. Chem. Soc., Chem. Commun., 1989, 1893; H. H.

Wasserman, J. D. Cook and C. B. Vu, J. Org. Chem., 1990, 55, 1701;

D. Schinzer and M. Ruppelt, Chem. Ber., 1991, 124, 247;

D. Schinzer, J. Kabbara and K. Ringe, Tetrahedron Lett., 1992, 33,

8017; W. S. Johnson, V. R. Fletcher, B. Chenera, W. R. Bartlett,

F. S. Tham and R. K. Kullnig, J. Am. Chem. Soc., 1993, 115, 497;

W. S. Johnson, R. A. Buchanan, W. R. Bartlett, F. S. Tham and

R. K. Kullnig, J. Am. Chem. Soc., 1993, 115, 504; W. S. Johnson,

M. S. Plummer, S. P. Reddy and W. R. Bartlett, J. Am. Chem. Soc.,

1993, 115, 515; P. V. Fish and W. S. Johnson, J. Org. Chem., 1994, 59,

2324; P. V. Fish, W. S. Johnson, G. S. Jones, F. S. Tham and R. K.

Kullnig, J. Org. Chem., 1994, 59, 6150; P. V. Fish and W. S. Johnson,

22 M. Suginome, A. Matsumoto and Y. Ito, J. Org. Chem., 1996, 61,

4884; J. A. Marshall and K. Maxson, J. Org. Chem., 2000, 65, 630.

23 S. M. Weinreb, D. T. Smith and J. Jin, Synthesis, 1998, 509; K. M.

Brummond, A. D. Kerekes and H. Wan, J. Org. Chem., 2002, 67,

5156.

24 J. W. Han, N. Tokunaga and T. Hayashi, J. Am. Chem. Soc., 2001,

123, 12915.

25 J. A. Marshall and N. D. Adams, J. Org. Chem., 1997, 62, 8976.

26 I. Fleming and N. D. Kindon, J. Chem. Soc., Perkin Trans. 1, 1995,

303.

27 W. Oppolzer, R. J. Mills, W. Patchinger and T. Stevenson,

Helv. Chim. Acta, 1986, 69, 1542.

28 M. Vandewalle, J. Van der Eycken, W. Oppolzer and C. Vullioud,

Tetrahedron, 1986, 42, 4035.

29 T. Sasaki, A. Usuki and M. Ohno, J. Org. Chem., 1980, 45, 3559.

30 J. A. Dale, D. L. Dull and H. S. Mosher, J. Org. Chem., 1969, 34,

2543.

31 H. C. Brown and G. C. Pai, J. Org. Chem., 1982, 47, 1606.

O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 7 4 9 – 7 6 9

768

View Article Online

Tetrahedron Lett., 1994, 35, 1469; G. S. Jones, Tetrahedron Lett.,

1994, 35, 9685; D. Schinzer, K. Ringe, P. G. Jones and D. Döring,

Tetrahedron Lett., 1995, 36, 4051; E. M. Geertsema, C. W. Leung,

A. van Oeveren, A. Meetsma and B. L. Feringa, Tetrahedron Lett.,

1995, 36, 7315; S. E. Sen, Y. Zhang and S. L. Roach, J. Org. Chem.,

1996, 61, 9534; D. Schinzer and K. Ringe, Tetrahedron, 1996, 52,

7475; J. Bonjoch, D. Solé, S. García-Rubio and J. Bosch, J. Am.

Chem. Soc., 1997, 119, 7230; P. Aubert and J. Pornet, J. Organomet.

Chem., 1997, 538, 211; C. Agami, D. Bihan, L. Hamon, K. Kadouri-

Puchot and M. Lusinchi, Eur. J. Org. Chem., 1998, 2461; S. E. Sen,

Y. Zhang, S. M. Smith and J. C. Huﬀman, J. Org. Chem., 1998, 63,

4459; W. F. J. Karstens, M. J. Moolenaar, F. P. J. T. Rutjes,

U. Grabowska, W. N. Speckamp and H. Hiemstra, Tetrahedron

Lett., 1999, 40, 8629; Y.-H. Zhu and P. Vogel, Synlett, 2001, 79 and

82; M. Cordes, Synthesis, 2001, 2470.

58 I. Ohtani, T. Kusumi, Y. Kashman and H. Kakisawa, J. Am. Chem.

Soc., 1991, 113, 4092.

59 R. P. Evershed, E. D. Morgan and L. D. Thompson, J. Chromatogr.,

1982, 237, 350.

60 M. V. George, D. J. Peterson and H. Gilman, J. Am. Chem. Soc.,

1960, 82, 403.

61 M. C. Weismiller, J. C. Towson and F. A. Davis, Org. Synth., Coll.,

1993, Vol. 8, 104; J. C. Towson, M. C. Weismiller, G. S. Lal, A. C.

Sheppard and F. A. Davis, Org. Synth., Coll., 1993, Vol. 8, 110.

62 V. Rautenstrauch, M. Lindström, B. Bourdin, J. Currie and

E. Oliveros, Helv. Chim. Acta, 1993, 76, 607.

63 D. A. Evans, T. C. Britton and J. A. Ellman, Tetrahedron Lett., 1987,

28, 6141; W. Oppolzer and A. J. Kingma, Helv. Chim. Acta, 1989, 72,

1337.

64 D. A. Evans, M. D. Ennis and D. J. Mathre, J. Am. Chem. Soc., 1982,

104, 1737; W. Oppolzer, Pure Appl. Chem., 1988, 60, 39.

65 M. T. Reetz, K. Schwellnus, F. Hübner, W. Massa and R. E.

Schmidt, Chem. Ber., 1983, 116, 3708.

47 J. Pornet, D. Amour and L. Miginiac, J. Organomet. Chem., 1987,

319, 333; R. L. Danheiser, B. R. Dixon and R. W. Gleason, J. Org.

Chem., 1992, 57, 6094.

48 J. Pornet and B. Randrianoelina, Tetrahedron Lett., 1981, 22, 1327;

J. Pornet, J. Organomet. Chem., 1988, 340, 273; J. W. Herndon and

P. P. Patel, J. Org. Chem., 1996, 61, 4500.

66 C. Ainsworth, F. Chen and Y.-N. Kuo, J. Organomet. Chem., 1972,

46, 59.

67 J. A. Peters and H. van Bekkum, Recl. Trav. Chim. Pays-Bas, 1973,

92, 379.

68 J. A. Peters and H. van Bekkum, Recl. Trav. Chim. Pays-Bas, 1981,

100, 21.

69 A. I. Meyers and E. W. Collington, Tetrahedron, 1971, 27, 5979.

70 L. Birkofer, A. Ritter and H. Uhlenbrauck, Chem. Ber., 1963, 96,

3280.

71 P. D. Bartlett and L. H. Knox, Org. Synth., Coll., 1973, Vol. V, 196.

72 R. L. Danheiser, Y.-M. Tsai and D. M. Fink, Org. Synth., Coll.,

1993, Vol. 8, 471; R. L. Danheiser, E. J. Stoner, H. Koyama, D. S.

Yamashita and C. A. Klade, J. Am. Chem. Soc., 1989, 111, 4407.

73 R. N. Keller and H. D. Wycoﬀ, Inorg. Synth., 1946, 2, 1.

74 B. Sjöberg and K. Sjöberg, Acta Chem. Scand., 1972, 26, 275.

75 E. J. Corey and M. Chaykovsky, J. Am. Chem. Soc., 1962, 84, 866;

E. J. Corey and M. Chaykovsky, J. Am. Chem. Soc., 1965, 87, 1345;

K. Sjöberg, Tetrahedron Lett., 1966, 6383.

49 M. J. Fisher and L. E. Overman, J. Org. Chem., 1990, 55, 1447; P. M.

Esch, H. Hiemstra and W. N. Speckamp, Tetrahedron, 1992, 48,

3445; J. D. Spence, L. E. Lowrie and M. H. Nantz, Tetrahedron

Lett., 1995, 36, 5499; J. Pornet, B. Princet, L. M. Mévaa and

L. Miginiac, Synth. Commun., 1996, 26, 2099; B. Alcaide,

P. Almendros and C. Aragoncillo, Chem. Eur. J., 2002, 8, 1719.

50 D. L. J. Clive, X. He, M. H. D. Postema and M. J. Mashimbye,

J. Org. Chem., 1999, 64, 4397.

51 J. Pornet, Tetrahedron Lett., 1981, 22, 453.

52 M. Ochiai, T. Ito, Y. Takaoka and Y. Masaki, J. Am. Chem. Soc.,

1991, 113, 1319; M. Ochiai, T. Ito and Y. Masaki, J. Chem. Soc.,

Chem. Commun., 1992, 15; D. A. Gately, T. A. Luther, J. R. Norton,

M. M. Miller and O. P. Anderson, J. Org. Chem., 1992, 57, 6496;

M. Ochiai, T. Ito and M. Shiro, J. Chem. Soc., Chem. Commun.,

1993, 218; M. Ochiai and T. Ito, J. Org. Chem., 1995, 60, 2274;

M. Kida, T. Sueda, S. Goto, T. Okuyama and M. Ochiai, J. Chem.

Soc., Chem. Commun., 1996, 1933.

76 I. Fleming and T. W. Newton, J. Chem. Soc., Perkin Trans. 1, 1984,

1805.

53 D. Damour, J. Pornet, B. Randrianoelina and L. Miginiac,

J. Organomet. Chem., 1990, 396, 289; M. Taing and H. W. Moore,

J. Org. Chem., 1996, 61, 329.

54 B. Bennetau, J.-P. Pillot, J. Dunoguès and R. Calas, J. Chem.

Soc., Chem. Commun., 1981, 1094; J. Pornet, D. Mesnard and

L. Miginiac, Tetrahedron Lett., 1982, 23, 4083; A. Schnitt and H.-U.

Reissig, Eur. J. Org. Chem., 2000, 3893.

77 L. I. Zakharkin and I. M. Khorlina, Tetrahedron Lett., 1962, 619.

78 J.-P. Picard, A. Ekouya, J. Dunoguès, N. Duﬀaut and R. Calas,

J. Organomet. Chem., 1975, 93, 51.

79 S. Rajagopalan and G. Zweifel, Synthesis, 1984, 111.

80 S. G. Matsoyan, M. G. Avetyan, L. M. Akopyan, M. G. Voskanyan,

N. M. Morlyan and M. A. Eliazyan, Vysokomolekul. Soedin., 1961,

1010 (Chem. Abstr., 1962, 56, 13081b).

55 J.-P. Pillot, B. Bennetau, J. Dunoguès and R. Calas, Tetrahedron

Lett., 1981, 22, 3401.

56 J. D. Spencer, L. E. Lowrie and M. H. Nantz, Tetrahedron Lett.,

1995, 36, 5499.

81 I. Fleming, I. T. Morgan and A. K. Sarkar, J. Chem. Soc.,

Perkin Trans. 1, 1998, 2749.

82 J. A. Marshall, R. H. Yu and J. F. Perkins, J. Org. Chem., 1995, 60,

5550.

57 I. Fleming and J. M. Mwaniki, J. Chem. Soc., Perkin Trans. 1, 1998,

1237.

83 D. E. Ward and C. K. Rhee, Tetrahedron Lett., 1991, 32, 7165.

84 J. A. Marshall and X. Wang, J. Org. Chem., 1991, 56, 4913.

O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 7 4 9 – 7 6 9

769

Article Doi

Accurate determinations of the extent to which the SE2′ reactions of allyl-, allenyl- and propargylsilanes are stereospecifically anti

DOI: 10.1039/b313446f

Source and publish data:

Authors:

Article abstract of DOI:10.1039/b313446f

Full text of DOI:10.1039/b313446f

Products guided by the article

R&D Labs maybe for 705980-10-5

Relevant to this article

Hot Product