In search of open-chain 1,3-stereocontrol

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Asun Barbero, David C. Blakemore, Ian Fleming* and Robert N. Wesley

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

M ethylation of methyl 4-phenylpentanoate 25 gives the diastereoisomers methyl (2RS,4SR)-2-methyl-

4-phenylpentanoate 26 and methyl (2RS,4RS)- 2-methyl-4-phenylpentanoate 27 in a ratio of 44 :56.

The aldehydes 3-dimethyl(phenyl)silylbutanal 28, 3-dimethyl(phenyl)silyl-3-phenylpropanal 32 and

3-dimethyl(phenyl)silyl-4-methylpentanal 36, each of which has a stereogenic centre on C-3 carrying a silyl

group and successively also a methyl, a phenyl and an isopropyl group, react with a range of methyl,

phenyl and isopropyl nucleophiles to give pairs of diastereoisomeric secondary alcohols 40–42, 47–49 and

54–56 having 1,3 related stereocentres. The same alcohols 43–45, 50–52 and 57–59 are also prepared by

reduction of the corresponding ketones 29–31, 33–35 and 37–39 with a range of hydride reagents, and three

of the ketones, 31, 35 and 39, react with phenyllithium to give mixtures of the tertiary alcohols 46, 53 and

60. The (E)- and (Z )-á,â-unsaturated methyl esters, 61, 62, 64, 65, 67 and 68, prepared from the same three

aldehydes with methoxycarbonylmethyltriphenylphosphorane, react with the phenyldimethylsilyl-cuprate

and -zincate reagents to give diastereoisomeric pairs of 1,3-disilylated esters. Likewise, the á,â-unsaturated

dimethyl diesters, 63, 66 and 69, prepared from the same three aldehydes with dimethyl malonate, react

with phenyldimethylsilyllithium and the corresponding cuprate and zincate reagents to give diastereo-

isomeric pairs of 1,3-disilylated diesters, and with various methyl and phenyl nucleophiles to give the

corresponding pairs of diastereoisomeric diesters with stereogenic centres at C-3 and C-5. The relative

stereochemistry of all but two of the products having 1,3-related stereocentres has been proved by silyl-to-

hydroxy conversion using mercuric acetate and peracetic acid to give the corresponding alcohols or their

derived lactones.

An attempt to identify a purely steric rule by which it might be possible to predict which diastereoisomer

would be the major product in each of these reactions was based on arguments about, and molecular

mechanics calculations of, the lowest-energy conformations of the starting materials. The only rule

that emerges is that ketones are regularly attacked in sense B, deﬁned in the drawings 21 and 23, in a

conformation that minimises the interaction between the group M on the stereogenic centre and the group

R ¹on the other side of the ketone, but even within this group of reactions, phenyl groups in either or both

locations sometimes lead to anomalies.

K rapcho reactions take place more rapidly and in higher yield using four equivalents of lithium chloride

in place of the usual sodium chloride, and adding two equivalents of water to the D M SO.

whole point of that synthesis had been to demonstrate how

Introduction

our stereochemically complementary allylsilane syntheses,¹¹

coupled to the predictably anti stereospeciﬁc protodesilylation

of an allylsilane, allowed us to converge on the correct stereo-

chemistry for C-6 from both diastereoisomers.

Cram’s rule¹for nucleophilic attack on a carbonyl group

adjacent to a stereogenic centre is well known, and the explan-

ation, successively advanced by Karabatsos,²Felkin,²and Anh

and Eisenstein,²is well accepted. We have pointed out ³that

Nevertheless, it would be much easier if one were not obliged

to use multi-step sequences to achieve such control. Explora-

tory work in this area includes that of Tiffenau ¹²and Brokaw

and Brode,¹³but the ﬁrst quantitative studies were by Leitereg

and Cram ¹⁴and by Jacques¹⁵in 1968. Cram obtained a good

level (83:17) of 1,3-control from the reaction of the phenyl

Grignard reagent on the ketone 1 at low temperature, and com-

plementary but lower selectivity (41:59) from the reaction of

the methyl Grignard reagent on the ketone 2. The correspond-

ing lithium reagents were less selective. He explained the stereo-

chemical sense of these reactions by attack of the nucleophile

from the less-hindered, rear side in the conformation 5, giving

the alcohol 3 (R = Ph) as the major product from the ketone 1,

and the alcohol 4 (R = Ph) as the major product from the

ketone 2. However, Jacques found only low levels of selectivity

(41:59) in the reduction of the ketone 1 by lithium aluminium

hydride,¹⁵and his reaction took place in the opposite sense

to Cram’s, giving the alcohol 4 (R = H) as the major product.

All these results are pretty typical—occasional high levels of

stereoselectivity, more often than not low levels, and the sense

somewhat unpredictable.

the corresponding rule for electrophilic attack on a C᎐C

᎐

double bond, developed successively by Zimmerman and

Chang,⁴Barton et al.⁴and Houk et al.,⁴is in one sense the

opposite of Cram’s rule, and we have done a lot of work apply-

ing the selectivity of this kind of reaction in synthesis, using a

stereogenic centre carrying a silyl group.⁵

The homologue of these reactions, in which the reaction site

and the stereogenic centre are separated by a methylene group,

is much less well understood. For good 1,3-control, a cyclic

substrate or transition structure is usually needed, as in the

methods for controlling the relative stereochemistry of 1,3-diols

by reduction of β-hydroxy ketones,⁶by the delivery of chelated

carbon nucleophiles to carbonyl groups,⁷and by the intra-

molecular delivery of electrophiles to a C᎐C double bond.⁸

᎐

There are now scores of other reactions having a cyclic com-

ponent to control the relative stereochemistry of other types of

1,3-related centres,⁹but, in the absence of a ring, it is much

more usual to get low levels of diastereocontrol. Thus we

found, in our synthesis of the Prelog–Djerassi lactone, that lith-

ium phenylacetylide reacted with a ketone having a stereogenic

centre at C-3 to give both possible alcohols in equal amounts.¹⁰

As it happens, that result was not a disappointment, since the

More recently, Evans has looked at this problem, extending

Jacques’ work on the reduction of ketones using the ketones 6,

J. Chem. Soc., Perkin Trans. 1, 1997

1329

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O

PhMe₂Si

O

PhMe₂Si

OH

PhMe₂Si

OH

Nu^–

NaBH₄

+

Ph

OH

1

2

R

+

13

14

75:25

Ph

R

3

4

OH

PhMe₂Si

1. 9-BBN

Ph

MeMgBr

+

3:4

83:17

R = Ph 76:24 100%

0 °C R = Ph 67:33

98%

35 °C R = H 41:59 100%

2. H₂O₂,

NaOH

Nu = PhMgBr on 1

PhMgBr on 1

LiAlH₄on 1

R = Ph

–110 °C

–78 °C

36%

75:25

H

MeMgBr on 2

R = Ph

41:59

??%

PhMe₂Si

O

H

–

H

BBN-9

H

BH₃

^–Nu

Ph

O

H H

15

16

5

matching some hydroboration results of Evans et al.,¹⁹where he

had a large alkyl group and we had a silyl group. We explained

our results with the models 15 and 16, which are similar in

concept to Evans’s but drawn differently. Stimulated by these

observations, we embarked upon a more systematic study of

this problem, aiming to ﬁnd a rule, or to support and ﬂesh out

Evans’, that predicts the sense of 1,3-control in open-chain

systems inﬂuenced only by steric effects. With such a rule, we

might be able to pin down more exactly the features that will

lead to high levels of 1,3-stereocontrol, and, if such control is

predictable, we can hope to save steps in syntheses. We report

our results here, with preliminary reports only in the form of

two published lectures.²⁰

Since it is not at ﬁrst sight obvious how a stereogenic centre

insulated from the reaction site is able to pass stereochemical

information along a chain, it is perhaps important to explain

the ideas embedded in the three families of models 5, 9–12, and

15 and 16, and to explain the basis of our thinking as we carried

out the reactions described here. We may be forgiven for using

our version 15 and 16, which we think gives a somewhat clearer

three-dimensional reading of the problem than the other two,

although our picture is essentially the same as Evans’, which is,

in its turn, based on Jacques’. Cram’s conformation 5, with the

carbon chain eclipsing the CO᎐Me bond, is unlikely to be

signiﬁcantly populated, except perhaps with aldehydes, and

neither Jacques nor Evans used this idea, and nor have we.

Using the drawings 17–24, we argue that the ﬁrst consider-

R¹

OH

R²

R¹

O

LiBu^s₃BH

R²

7

8

R¹

R²

6

+

7:8

92:8

3:97

R¹= Me, R²= vinyl

R¹= OSiMe₂Bu^t, R²= Me

Nu^–

^–Nu

H

O

H

O

F₃BO

Me

H

OR

H

OR

9

10

11

12

and ﬁnds that a hindered reducing agent can sometimes give

strikingly high levels of stereoselectivity, with the sense chan-

ging dramatically (from 92:8 in favour of the alcohol 7 to 3:97

in favour of the alcohol 8) when the medium-sized substituent

R¹on the stereogenic centre was changed from a methyl group

to a silyloxy substituent.¹⁶He explains his results with a model 9

for the steric case and a model 10 or possibly 11 for the case

with an oxygen substituent, each of which has a stabilising

dipolar contribution from the C᎐O dipole facing away from the

carbonyl dipole. Other models that he considers have steric

clashes or destabilising electrostatic interactions.

A attack:

Nu^–

Nu or E

H

X

H

R¹

M

H

1

R¹

L

R¹

L

X

H

X

H

2

H

M

L

3

H

M

H

M

L

Evans has also studied aldol reactions on aldehydes, using

metal enolates or silyl enol ethers as the nucleophiles, and

explained his results with a model similar to 10. The steric-only

cases gave low levels of stereoinduction, and not always in the

same sense, but the Mukaiyama aldol reactions on aldehydes

with β-oxygen functions, using boron triﬂuoride as the Lewis

acid, were often highly selective (≤92:8) in the sense 12 in

favour of the anti 1,3-diol derivative. This selectivity could be

extended to similar reactions with an α-stereogenic centre,

which gave very high levels of Cram control (≥97:3) when the

β-stereogenic centre was matched so as to give anti 1,3 diol

derivatives.¹⁷

17

18

19

20

B attack:

H

R¹

H

X

M

H

M

3

L

M

R¹

L

M

R¹

X

H

R¹

1

L

X

2

H

Nu^–

L

Nu or E

21

22

23

24

ation is that the large substituent L on the stereogenic centre

can be expected to position itself between the two hydrogen

atoms of the C-2 methylene group. The nucleophile or electro-

phile attacking the double bond can then be expected to attack

In the course of other work, we also came across examples of

moderately high 1,3-selectivity, both in the reduction of the

ketone 13 and in the hydroboration of the alkene 14,¹⁸the latter

1330

J. Chem. Soc., Perkin Trans. 1, 1997

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on the opposite side of the double bond from the C-2 to C-3

bond. The two surfaces of the double bond are therefore made

different by the direction in which the C-2 to C-3 bond is

rotated out of the plane of the double bond, and that in turn is

determined by the conﬁguration at the stereogenic centre C-3.

Although all our work has been carried out with racemic com-

pounds, we have drawn, throughout this paper, the same abso-

lute conﬁguration at the stereogenic centre C-3, both for our

own compounds and for those quoted from Cram’s, Jacques’

and Evans’ work. We can see that if the bond to C-3 is rotated

down, as in 17, the medium-sized group will be positioned in

the segment between the group R¹attached at C-1 and the ‘out-

side’ hydrogen atom, as shown more clearly in the Newman

projection 18; if it is rotated up, as in 21, the medium-sized

group will be positioned between the double bond and the

‘inside’ hydrogen, as seen in the Newman projection 22. In the

former case, the upper surface is more exposed, in the latter it is

the lower. The uncertainty lies in which conformation 17 or 21

is the lower in energy. Our feeling was that conformation

21 = 22 would be lower in energy when the group R¹was large,

but the alternative 17 = 18 might be lower in energy when the

group R¹was small. Thus Cram’s reactions on the ketones 1

and 2, Evans’ reaction on the ketone 6 (R¹= Me), and our

reactions on the ketone 13 and the alkene 14, all correspond to

attack on the lower surface of the conformation 21, and all have

a group, phenyl, methyl or isopropyl, attached as R¹to the

double bond. Jacques’ reaction, which takes place in the oppos-

ite sense, has the smallest of these groups as R¹. We label attack

on the upper surface as being in the A sense, as expected for the

conformations variously expressed as 17–20. Similarly, we label

attack on the lower surface as being in the B sense, as expected

for the conformations variously expressed as 21–24. The label A

or B is needed to identify the sense of attack, but is not neces-

sarily associated with any particular explanation. Throughout

this paper, all ratios are illustrated and expressed in the order

A:B, and products of attack in the sense A are labelled with an

A, and those from attack in the sense B are labelled with a B.

One detail should perhaps be clariﬁed. The drawings we are

using here are expected to be close to the low energy conform-

ations of the starting material. Following Felkin’s argument, we

can expect that, at the time of reaction, the C-2 to C-3 bond will

be more nearly perpendicular to the plane of the double bond,

as in Evans’ drawings 9–12. We ﬁnd that our drawings 17 and

21 are easier to visualise, easier to relate to the results of our

modelling work, which is entirely concerned with the ground

state, and they do not change the argument signiﬁcantly, involv-

ing as they do only a rotation of 30Њ or so before reaction. Who

knows what the exact angles are at the time of reaction? But if

we want to be more reﬁned, we can expect that the transition

structures will have the substituents more nearly staggered

throughout, as in the drawings 19 and 23, in which all the atoms

more or less occupy the positions of the carbon atoms in a

diamond lattice, as illustrated in the versions 20 and 24. One

feature of these pictures, and the rationalisations that go with

them, is that we can expect electrophilic attack to take place in

the same stereochemical sense as nucleophilic attack, in con-

trast to Cram’s and Houk’s rule for 1,2-control. We had already

seen in the pair of results 15 and 16, which are otherwise similar

examples of nucleophilic and electrophilic attack, respectively,

that this might well prove to be the case.

i, ii

+

Ph

CO₂Me

Ph

CO₂Me Ph

CO₂Me

25

26

44:56

27

Scheme 1 Reagents: i, LDA; ii, MeI

give the major product from reaction in the same sense, with the

methyl iodide attacking from behind, just as the nucleophile

attacks from behind in Cram’s picture 5. In our terminology the

sense is B. Thus, so far at least, the sense of 1,3-control is the

same both for electrophilic and nucleophilic reactions, as we

argued above they would be. However, in our later work,

described below, it became clear that a double bond with the

substitution pattern possessed by the enolate double bond in

this reaction is unlikely to demonstrate a reliable level of stereo-

chemical predictability. The fact that it reacts, just, in the same

stereochemical sense as the corresponding nucleophilic attack

on a carbonyl group can only be regarded as fortuitous.

With the exception of this one result, we have narrowed our

study so far to nucleophilic attack, and have uniformly used the

phenyldimethylsilyl group as the large group L. This choice is

based on our perception that, unlike a hydroxy or protected

hydroxy group, it would unambiguously be a larger group than

any carbon-based group that we planned to attach to the

stereogenic centre. Furthermore, it was unlikely to indulge in

coordination to set up a cyclic transition structure, nor would it

make a polar contribution, since there is no signiﬁcant dipole

moment associated with a silyl group having four tetrahedrally

disposed carbon substituents. Finally, it had the advantage that

it could be converted with retention of conﬁguration into a

hydroxy group,²¹the ideal group from which to establish the

relative stereochemistry in the pairs of products. With an inﬁn-

ite number of other variables to choose among, we then chose

to look systematically at the stereochemistry of nucleophilic

attack, with a range of hydride and organometallic carbon

nucleophiles, on the twelve aldehydes and ketones 28–39, giving

mixtures of the alcohols 40A–60A and 40B–60B, with all com-

binations of R¹as hydrogen, methyl, phenyl and isopropyl, and

the medium-sized group M as methyl, phenyl and isopropyl

(Scheme 2). We further studied nucleophilic attack, with a

range of organometallic silyl and carbon nucleophiles, on the

nine α,β-unsaturated esters 61–69, giving the esters 70A–81A

and 70B–81B, with the medium-sized group M as successively

methyl, phenyl and isopropyl. The results of our work with

aldehydes and ketones are presented in Table 1, and with the

α,β-unsaturated esters in Table 2. In all, we have carried out 92

reactions, some of them several times, and have identiﬁed the

relative stereochemistry of the major product in 24 pairs of

diastereoisomers.

If we start from the idea that the interaction between the

medium-sized substituent M and the group R¹determines

which conformation 17 or 21 is populated, we can suggest that

the ketones (R¹≠ H) will react in the sense B, because the inter-

action between M and the substituent R¹will disfavour con-

formation 17 and make conformation 21 the more populated.

In contrast, the aldehydes (R¹= H) and all the α,β-unsaturated

esters 61–69 could reasonably react in either sense, but we can

try the idea that the conformation 17 might be favoured, since

the interaction between the medium-sized group M and the

hydrogen atom will be small. Nucleophilic attack on this group

of compounds can then be expected to take place in the sense

A. The data in the Tables, discounting the two pairs of com-

pounds we were unable to assign stereochemistry to, support

this idea to some extent—the ratio of correctly to incorrectly

predicted results for reactions predicted to take place in sense A

is 43:19, and the ratio of correctly to incorrectly predicted

results for reactions predicted to take place in sense B is 20:6.

The overall ratio of success to failure is therefore a moderately

encouraging but hardly compelling 63:25. Furthermore, an

Results and discussion

1,3-Stereocontrol

Since we had provided the ﬁrst example³of electrophilic attack

complementing Cram’s work on nucleophilic attack,¹we looked

at one example of electrophilic attack to compare with his

results 1 → 3 ϩ 4. We chose the enolate methylation

25 → 26 ϩ 27, where we found very low selectivity 44:56 in

favour of the isomer 27 (Scheme 1). This result does happen to

J. Chem. Soc., Perkin Trans. 1, 1997

1331

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ivity is only rarely high enough to be useful in organic synthesis.

PhMe₂Si

M

R¹

PhMe₂Si

M

PhMe₂Si

M

Nu R¹

OH

Nu R¹

OH

Nu^–

One reason for the lack of correlation can be seen in the large

variation in the results depending upon the reagent used, as

already mentioned in connection with the anomalous results

with lithium reagents. Since we have been considering only the

conformation of the substrate, all reagents are treated as attack-

ing in the same sense and to more or less the same degree. This

is rather plainly not the case in practice, and as seen speciﬁcally

in the reactions of methyl- and phenyl-lithium with the alde-

hyde 28, which take place in the opposite sense to each other,

methyllithium in the sense B to give more of the alcohol 40B

and phenyllithium in the sense A to give more of the alcohol

41A (Scheme 3). In contrast, the corresponding Grignard

+

O

28 M = Me, R¹= H

29 M = Me, R¹= Me

30 M = Me, R¹= Ph

31 M = Me, R¹= Prⁱ

32 M = Ph, R¹= H

33 M = Ph, R¹= Me

34 M = Ph, R¹= Ph

35 M = Ph, R¹= Prⁱ

36 M = Prⁱ, R¹= H

37 M = Prⁱ, R¹= Me

38 M = Prⁱ, R¹= Ph

39 M = Prⁱ, R¹= Prⁱ

A

B

40 M = Me, R¹= H Nu = Me

41 M = Me, R¹= H Nu = Ph

42 M = Me, R¹= H Nu = Prⁱ

43 M = Me, R¹= Me Nu = H

44 M = Me, R¹= Ph Nu = H

45 M = Me, R¹= PrⁱNu = H

46 M = Me, R¹= PrⁱNu = Ph

47 M = Ph, R¹= H Nu = Me

48 M = Ph, R¹= H Nu = Ph

49 M = Ph, R¹= H Nu = Prⁱ

50 M = Ph, R¹= Me Nu = H

51 M = Ph, R¹= Ph Nu = H

52 M = Ph, R¹= PrⁱNu = H

53 M = Ph, R¹= PrⁱNu = Ph

54 M = Prⁱ, R¹= H Nu = Me

55 M = Prⁱ, R¹= H Nu = Ph

56 M = Prⁱ, R¹= H Nu = Prⁱ

PhMe₂Si

OH

PhMe₂Si

OH

R-metal

CHO

+

R

40A (R = Me)

41A (R = Ph)

40B (R = Me)

41B (R = Ph)

28

M = Prⁱ, R¹= Me Nu = H

M = Prⁱ, R¹= Ph Nu = H

M = Prⁱ, R¹= PrⁱNu = H

R-metal

MeLi

PhLi

MeMgI

PhMgBr

A:B

57

58

59

33:67

67:33

60:40

60 M = Prⁱ, R¹= PrⁱNu = Ph

PhMe₂Si

M

PhMe₂Si

R²

R-metal

CO₂Me

R³

61 M = Me, R²= CO₂Me, R³= H

CO₂Me

PhMe₂Si

62 M = Me, R²= H,

R³= CO₂Me

63

63 M = Me, R²= CO₂Me, R³= CO₂Me

64 M = Ph, R²= CO₂Me, R³= H

R

PhMe₂Si

R

CO₂Me

65 M = Ph, R²= H,

R³= CO₂Me

+

66 M = Ph, R²= CO₂Me, R³= CO₂Me

67 M = Prⁱ, R²= CO₂Me, R³= H

CO₂Me

72B R = Me

73B R = Ph

68 M = Prⁱ, R²= H,

69 M = Prⁱ, R²= CO₂Me, R³= CO₂Me

R³= CO₂Me

72A R = Me

73A R = Ph

R-metal

MeLi

PhLi

Me₂CuCN Li₂

Me₃Zn Li

Ph₂CuCN Li₂

PhZnMe₂Li

A:B

Nu^–

43:57

29:71

85:15

87:13

50:50

71:29

PhMe₂Si

M

Nu

PhMe₂Si

M

Nu

R²

+

CO₂Me

Scheme 3

A

B

reagents both react in the sense A to give the same diastereo-

isomeric relationship in the major products 40A and 41A. Also

in contrast, both methyl- and phenyl-lithium react with the

unsaturated diester 63, to give as the major products the esters

72B and 73B, respectively, corresponding to attack in the sense

B, whereas the corresponding cuprates and zincates mostly give

the opposite result, with the esters 72A and 73A as the major

products. Clearly, consideration only of the ground state can-

not deal with all these variations that depend upon the reagent.

We turned next to molecular modelling, which so far we have

used only on the aldehydes and ketones. Alas, modelling the

wide range of transition structures was impractical, so we were

still obliged to look only at the starting materials, in the hope of

ﬁnding a better correlation between the sense of the selectivity

and which of the diastereotopic surfaces appears to be the more

exposed in the model. We ﬁrst calculated the low-energy con-

formations within 20 kJ mol^Ϫ1of the global minimum. Most of

these conformations could be assigned as A-predictors or B-

predictors from the dihedral angle of the bond from C-2 to C-3

and the plane of the carbonyl group. With the few conform-

ations where this angle was close to 0 or 180Њ inspection of a

three-dimensional rendering of the structure usually allowed us

to make a similar but more tentative assignment. It is perhaps

worth noting at this stage that many of the low-energy con-

formations included in this assessment diverge quite substan-

tially from the paradigms 17–24, indicating that the conform-

ational preferences are not strong. We then calculated the

70 M = Me, R²= H,

Nu = SiMe₂Ph

71 M = Me, R²= CO₂Me, Nu = SiMe₂Ph

M = Me, R²= CO₂Me, Nu = Me

72

73

74

75

76

M = Me, R²= CO₂Me, Nu = Ph

M = Ph, R²= H,

M = Ph, R²= CO₂Me, Nu = SiMe₂Ph

M = Ph, R²= CO₂Me, Nu = Me

Nu = SiMe₂Ph

77 M = Ph, R²= CO₂Me, Nu = Ph

78 M = Prⁱ, R²= H,

Nu = SiMe₂Ph

79 M = Prⁱ, R²= CO₂Me, Nu = SiMe₂Ph

80 M = Prⁱ, R²= CO₂Me, Nu = Me

81 M = Prⁱ, R²= CO₂Me, Nu = Ph

Scheme 2

anomalously large number of the reactions unexpectedly taking

place in sense B with the aldehydes (i.e. R¹= H) and the diesters

63, 66 and 69 (i.e. R²= R³= CO₂Me) are reactions of methyl-

and phenyl-lithium reagents—if these results with lithium

reagents are discounted, the ratio of successful to unsuccessful

predictions of reaction in the sense A changes from 43:19 to a

somewhat more respectable 41:9. Clearly a simple rule along

these lines is not going to be completely reliable, but there is a

trend: when R¹= H, reaction usually takes place in sense A,

except with lithium reagents, but when R¹≠ H, reaction usually

takes place in sense B. In this discussion, we have paid no atten-

tion to the degree of selectivity, but there is no trend for the

incorrect predictions also to be reactions with low selectivity.

Typically, with many of the ratios very low, the degree of select-

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J. Chem. Soc., Perkin Trans. 1, 1997

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Table 1 Diastereoisomer ratios for the reactions of the aldehydes and ketones 28–39 with nucleophiles

M

R¹

H

Nu^Ϫ

Solvent

T/ЊC

Ϫ78

Yield (%)

A :B

Calc.

28

Me

MeLi

THF

Et₂O

THF

Et₂O

MeOH

Et₂O

EtOH

Et₂O

EtOH

THF

Et₂O

EtOH

Et₂O

EtOH

Et₂O

EtOH

THF

Et₂O

EtOH

Et₂O

EtOH

Et₂O

EtOH

THF

72

36

64

73

67

60

86

97

86

90

79

78

77

53

71

60

63

60

70

60

81

85

96

66

81

70

65

64

74

60

68

78

58

70

51

76

73

71

60

33:67

55:45

60:40

67:33

60:40

61:39

30:70

25:75

79:21

71:29

22:78

28:72

23:77

21:79

25:75

48:52

53:47

22:78

28:72

45:55

47:53

54:46

33:67

60:40

49:51

47:53

67:33

55:45^b

40:60

53:47

73:27

72:28

53:47

33:67

51:49

12:88

23:77

30:70

23:77

24:76

23:77

62:38

59:41

62:38

59:41

34:66

41:59

74:26

58:42

23:77

37:63^a

37:63

23:77

37:63^a

75:25

69:31

75:25

69:31

75:25

64:36

62:38

54:46

60:40

56:44^a

60:40

54:46

52:48

54:46

52:48

31:69

39:61^a

91:9

MeMgBr

MeMgI

PhLi

Ϫ78

0

Ϫ78

0

Ϫ78

0

Ϫ78

rt

Ϫ78

rt

0

Ϫ78

rt

Ϫ78

0

Ϫ78

0

Ϫ55

0

Ϫ55

0

Ϫ78

rt

PhMgBr

PrⁱMgCl

LiAlH₄

NaBH₄

LiAlH₄

NaBH₄

LiAlH₄

NaBH₄

Li(Bu^tO)₃AlH

N-Selectride

PhLi

29

30

31

Me

Ph

Prⁱ

PhMgBr

MeLi

MeMgBr

PhLi

32

Ph

H

PhMgBr

PrⁱMgCl

LiAlH₄

NaBH₄

LiAlH₄

NaBH₄

LiAlH₄

NaBH₄

Li(Bu^tO)₃AlH

PhLi

33

34

35

Me

Ph

Prⁱ

rt

Ϫ78

0

Ϫ78

0

Ϫ78

rt

Ϫ78

rt

Ϫ78

rt

Ϫ78

36

Prⁱ

H

MeLi

MeMgBr

PhLi

PhMgBr

PrⁱMgCl

LiAlH₄

NaBH₄

LiAlH₄

NaBH₄

LiAlH₄

NaBH₄

Li(Bu^tO)₃AlH

PhLi

37

38

39

Me

Ph

71:29^a

24:76

32:68^a

24:76

Prⁱ

a

Calc. for 0 ЊC. ^bOr the other way round. rt = room temp.

Boltzmann distribution for the low-energy conformations at

each of the temperatures at which reactions had been carried

out, and hence the proportion of conformations occupied by A-

and B-predictors. These numbers appear as the right hand

column in Table 1. All three aldehydes are predicted to react

in sense A, and of the nine ketones ﬁve are predicted to react in

sense A and four in sense B. Making the crude assumption that

conformations predicting attack in the A sense would react only

in the A sense, and that conformations predicting attack in the

B sense would react only in the B sense, these numbers could be

plotted directly against the corresponding experimental data in

a form that ought to place all the points in the upper-right and

lower-left quadrants, and more or less in a straight line. The

result, shown in Fig. 1, was distinctly disappointing.

The lower-right quadrant was very nearly empty, but the

upper left quadrant had a similar number of points to each of

the other two, making the 2:1 statistical preference in favour of

the predicted sense of attack worse than before. However, by

classifying the points, some order is restored—one group, the

ketones without a phenyl group, fall in the lower-left quadrant

with only one point just outside it, and with most showing

healthy, if not dramatic, levels of selectivity. It appears that

phenyl groups, perhaps because of the many different con-

formations that they can fall into, make prediction difﬁcult,

but, leaving them out, the other ketones show substantial select-

ivity in the sense B. The uniformity of behaviour of this group

Fig. 1

J. Chem. Soc., Perkin Trans. 1, 1997

1333

View Article Online

Table 2 Diastereoisomer ratios for the reactions of the α.β-unsaturated esters 61–69 with nucleophiles

M

R²

R³

Nu^Ϫ

T/ЊC

Ϫ78

Yield (%)

A :B

61

62

63

Me

CO₂Me

H

(PhMe₂Si)₂Cu Li

PhMe₂SiZnMe₂Li

(PhMe₂Si)₂Cu Li

PhMe₂SiZnMe₂Li

PhMe₂SiLi

(PhMe₂Si)₂Cu Li

PhMe₂SiZnMe₂Li

MeLi

MeMgBr

Me₃ZN Li

Me₂CuCN Li₂

PhLi

PhZnMe₂Li

Ph₂CuCN Li₂

(PhMe₂Si)₂Cu Li

PhMe₂SiZnMe₂Li

(PhMe₂Si)₂Cu Li

PhMe₂SiZnMe₂Li

(PhMe₂Si)₂Cu Li

PhMe₂SiZnMe₂Li

PhMe₂SiLi

MeLi

MeMgBr

Me₃Zn Li

Me₂CuCN Li₂

PhLi

84

—

76

42

75

81

25

23

70

62

61

65

62

59

83

73

76

81

65

87

67

58

66

63

89

68

77

96

71

74

63

68

66

82

74

68

61

28

57

76

88

50

83

85

89

62

80

71:29

77:23

variable^a

94:6

Ϫ78

0

Ϫ78

0

CO₂Me

55:45

57:43

78:22

43:57

67:33

86:14

85:15

29:71

71:29

50:50

95:5

64

65

66

Ph

CO₂Me

H

86:14

48:52

95:5

CO₂Me

66:34

78:22

82:18

48:52

56:44

60:40

88:12

24:76

35:65

64:36

36:64

83:17

72:28

61:39

53:47

78:22

72:28

45:55^b

53:47^b

43:57^b

45:55^b

46:54

53:47

51:49

64:36

52:48

37:63

57:43

46:54

49:51

37:63

Ϫ78

0

PhZnMe₂Li

PhMgBr

Ph₂CuCN Li₂

(PhMe₂Si)₂Cu Li

PhMe₂SiZnMe₂Li

PhMe₂SiAlMe₂Li

(PhMe₂Si)₂Cu Li

PhMe₂SiZnMe₂Li

PhMe₂SiAlMe₂Li

(PhMe₂Si)₂Cu Li

PhMe₂SiZnMe₂

PhMe₂SiAlMe₃Li

PhMe₂SiLi

MeLi

MeMgBr

Me₃Zn Li

Me₂CuCN Li₂

Me₄Al Li

Ϫ78

0

Ϫ78

0

Ϫ78

67

68

69

Prⁱ

CO₂Me

H

CO₂Me

PhLi

PhMgBr

PhZnMe₂Li

Ph₂CuCn Li₂

PhAlMe₃Li

a

With A:B always >1. ^bOr other way round.

of ketones conﬁrmed that we had not made a rather doubtful

assumption in claiming that the phenyldimethylsilyl group

would unambiguously be a larger group than any carbon-

based group. It is of course larger than any of the carbon-

based groups that we have used, but, because of the long Si᎐C

bond, a silyl group is not always as sterically hindering as its

actual size might suggest. That the results with M = Me and

M = Prⁱare so similar implies that in our work here, the silyl

group is the ‘large’ group. Thus we have a limited rule for purely

steric cases: when R¹≠ H ≠ Ph, and when M ≠ Ph, reaction takes

place in sense B. This was where we started—tentatively predict-

ing that M and R¹would avoid a 1,3-diaxial-like interaction by

adopting the conformation 21, and the modelling supports this

idea.

This appears to be about as far as we can go at present. It is

consistent with some results of Kobayashi and Ohno ²²on

nucleophilic attack on acylsilanes, which inherently have a large

group R¹, but aldehydes and α,β-unsaturated esters, both of

which have R¹= H, are still rather unpredictable, with merely a

2:1 bias in favour of reaction in the sense A, improved to 4:1 if

lithium reagents are taken to be anomalous. Most of Evans’

results were with enolates reacting with aldehydes, but with the

saving grace of a polar contribution from the dipole-inducing

oxygen function on the stereogenic centre. Our results, with

large numbers of low ratios, and only steric effects in operation,

support his suggestion that a dipole is an important contribu-

tion to getting high levels of diastereocontrol.

One of our results deserves highlighting. The conjugate add-

ition of silyl nucleophiles to the (Z)-α,β-unsaturated esters 62

and 65 could be made to give, with a careful choice of reagent, a

high level of 1,3-control in the sense A (Scheme 4). The silyl-

PhMe₂Si

M

PhMe₂Si

M

SiMe₂Ph

CO₂Me

i

CO₂Me

A:B

70A M = Me

74A M = Ph

78A M = Prⁱ

94:6

95:5

78:22 68%

76%

62 M = Me

65 M = Ph

68 M = Prⁱ

Scheme 4 Reagents: i, PhMe₂SiZnMe₂Li, THF, Ϫ78 ЊC

zincate (but not the silylcuprate) gave excellent stereoselectivity

in setting up the anti related 1,3-disilyl esters 70A and 74A. This

result gives us an approach to a starting material for a second

synthesis of tetrahydrolipstatin,²³and also gives us a compound

1334

J. Chem. Soc., Perkin Trans. 1, 1997

View Article Online

having two silyl groups with correlated stereochemistry. Previ-

ously we had found a method for setting up such a compound

with 1,2-related silicon-bearing stereocentres;²⁴now we have

a method for setting up 1,3-related centres. The high level

of selectivity, however, fell off with the ester 68 having an iso-

propyl group on the stereogenic centre, which gave the esters

78A and 78B in a ratio of 78:22.

PhMe₂Si

M

PhMe₂Si

M

CO₂Me

+

CO₂Me

i

52%

47%

48%

31%

46%

39%

61 M = Me

64 M = Ph

67 M = Prⁱ

62 M = Me

65 M = Ph

68 M = Prⁱ

PhMe₂Si

M

CHO

Synthesis of substrates

We prepared the aldehydes 28, 32 and 36 by DIBAL-H reduc-

tion of the corresponding ethyl esters 85–87, themselves pre-

pared by silylzincation ²⁵of ethyl crotonate 82 and ethyl

cinnamate 83 or by silylalumination, which appears to work

comparably well, of the ester 84. The reactions of these alde-

hydes with lithium and Grignard reagents gave the correspond-

ing secondary alcohols, as recorded in Table 1, and the mixtures

of diastereoisomeric secondary alcohols were oxidised to give

the corresponding ketones (Scheme 5), ready for the hydride

28 M = Me

32 M = Ph

36 M = Prⁱ

PhMe₂Si

CO₂Me

ii

M

CO₂Me

70%

85%

77%

63 M = Me

66 M = Ph

69 M = Prⁱ

PhMe₂Si

i

Scheme 6 Reagents: i, Ph₃P᎐CHCO₂Me, MeOH, 0 ЊC; ii, CH₂-

᎐

(CO₂Me)₂, (CH₂)₅NH, AcOH, room temp.

CO₂Et

M

in higher yield than the other, we could easily mis-assign

stereochemistry, unless the overall yield were high enough to

make the changeover impossible. Unfortunately, we were

unable to perform this reaction in the high yield necessary in a

case like this, where the diastereoisomers were produced in

nearly equal amounts. Instead, we assigned stereochemistry

by synthesising an authentic sample of the major isomer 27,

using Heathcock’s aldol reaction giving the alcohol 90, as the

major product,³⁰and a Barton–McCombie dehydroxylation

(Scheme 7).³¹

82 M = Me

83 M = Ph

84 M = Prⁱ

85 M = Me 96%

86 M = Ph 98%

87 M = Prⁱ80%

ii

PhMe₂Si

O

iii, iv

PhMe₂Si

CHO

M

R¹

29 M = Me R¹= Me

30 M = Me R¹= Ph

31 M = Me R¹= Prⁱ

35 M = Ph R¹= Prⁱ

37 M = PrⁱR¹= Me

38 M = PrⁱR¹= Ph

39 M = PrⁱR¹= Prⁱ

28 M = Me

32 M = Ph

36 M = Prⁱ

50%

55%

47%

39%

47%

59%

53%

83%

82%

80%

i

ii, iii, iv, v

Ph

CHO

Ph

CO₂Ar

Ph

CO₂Me

OH

90

27

57%

35%

Scheme

7

Reagents: i, EtCO₂C₆H₃-2,6-Me₂ϩ LDA, THF; ii,

NaOMe, THF; iii, NaH, CS₂; iv, MeI; v, Bu₃SnH, toluene, reﬂux

PhMe₂Si

O

i

We had already assigned stereochemistry to the pair of alco-

hols 40.¹⁸In order to assign relative stereochemistry to the other

pairs of alcohols obtained by the reaction of Grignard and

organolithium reagents on the aldehydes 28, 32 and 36, we

simply converted the silyl groups to hydroxy groups to give the

known 1,3-diols 91–97 (Scheme 8). The ¹H NMR spectra were

usually deﬁnitive, and we did not need to separate the diastereo-

isomers either before or after the silyl-to-hydroxy conversion,

although we actually did so with the alcohols 44 and 51. Fortu-

nately, there is some redundancy in the assignments of stereo-

chemistry: the products from the reactions of Grignard or

organolithium reagents on the aldehydes are, of course, the

same as the products from the reductions of the corresponding

ketones. Thus, to take just one example, the alcohol 41A is the

same as the alcohol 44B. Once we had assigned a conﬁguration

to any one pair, we did not need to repeat the degradation, since

each pair had at least one pair of signals in either the ¹H NMR

or the ¹³C NMR spectrum, or both, that could be integrated to

give us the ratio of diastereoisomers. Furthermore, the diols 92

and 94, derived from the alcohols 45 and 52 are the same as the

diols 95 and 96, derived from the alcohols 57 and 58, respect-

ively. In this and all our subsequent work, for every pair of

compounds and at every stage, we were careful to ensure that

the yields were high enough not to have led us to mis-assign

stereochemistry because of the selectively higher yielding con-

version of a minor diastereoisomer, however unlikely that

selectivity might be.

M

R¹

Ph

R¹

R¹= Me

R¹= Ph

92%

83%

88

89

33 M = Ph R¹= Me

34 M = Ph R¹= Ph

Scheme 5 Reagents: i, PhMe₂SiZnMe₂Li, THF, Ϫ78 ЊC or PhMe₂-

SiAlMe₃Li, THF, Ϫ78 ЊC; ii, DIBAL-H, toulene, Ϫ78 ЊC; iii, R¹Li or

R¹MgCl, details; iv, PCC, Al₂O₃, light petroleum or CrO₃, Me₂CO

reductions and attack by lithium and Grignard reagents, also

recorded in Table 1. We prepared the other two ketones 33 and

34 directly by conjugate addition of the silylzincate to the

unsaturated ketones 88 and 89. We prepared the α,β-

unsaturated esters 61, 62, 64, 65, 67 and 68 by Wittig reaction

on the same aldehydes 28, 32 and 36, using methanol as a sol-

vent, because it was known to lead to mixtures of the E and Z

isomers (Scheme 6).²⁶Since we wanted both, it was easier to

separate a mixture than to prepare each individually by stereo-

selective methods, even though selective methods are avail-

able.²⁷We prepared the α,β-unsaturated diesters 63, 66 and 69

by Knoevenagel reaction on the same aldehydes (Scheme 6).²⁸

Proof of relative conﬁguration

To assign stereochemistry to the products 26 and 27, we

planned initially to oxidise the phenyl groups in the insepar-

able mixture of diastereoisomers to the corresponding carb-

oxylic acids,²⁹and to esterify them to make the RR, SS and RS

isomers of the dicarboxylic esters. The signals of the methyl-

1

ene groups in the H NMR spectrum would then have been

deﬁnitive. However, if one diastereoisomer were to be oxidised

We proved the relative conﬁguration of the tertiary alcohols

46 and 60 by displacing the phenyl group from the silyl

J. Chem. Soc., Perkin Trans. 1, 1997

1335

View Article Online

PhMe₂Si

M

OH

PhMe₂Si

M

OH

53B, but with a ratio of only 55:45, this was hardly a critical

result.

To assign conﬁgurations to the products 70, 74 and 78 from

+

R¹

the conjugate additions of the silyl nucleophiles to the α,β-

unsaturated esters, we carried out silyl-to-hydroxy conversions,

and isolated directly the known lactones 101–103 (Scheme 10).

A:B

44A M = Me R¹= Ph

44B M = Me R¹= Ph

-

45

M = Me R¹= Prⁱ

22:78

-

67:33

33:67

22:78

23:77

51A M = Ph R¹= Ph

51B M = Ph R¹= Ph

PhMe₂Si

M

SiMe₂Ph

CO₂Me

PhMe₂Si

M

SiMe₂Ph

CO₂Me

52

57

58

59

M = Ph R¹= Prⁱ

M = PrⁱR¹= Me

M = PrⁱR¹= Ph

M = PrⁱR¹= Prⁱ

+

70A M = Me

74A M = Ph

78A M = Prⁱ

86:14

95:5

83:17

70B M = Me

74B M = Ph

78B M = Prⁱ

i

OH

+

M

R¹

M

R¹

M

O

M

O

A:B

R¹= Ph

101A M = Me

102A M = Ph

103A M = Prⁱ

85:15 63%

100:0 35%

83:17 64%

101B M = Me

102B M = Ph

103B M = Prⁱ

54%

55%

88%

59%

74%

53%

57%

61%

91A M = Me

91B M = Me

-

R¹= Ph

R¹= Prⁱ

R¹= Ph

R¹= Prⁱ

R¹= Me

R¹= Ph

R¹= Prⁱ

92

M = Me

22:78

-

67:33

33:67

24:76

23:77

93A M = Ph

93B M = Ph

PhMe₂Si

SiMe₂Ph

CO₂Me

PhMe₂Si

SiMe₂Ph

94

95

96

97

M = Ph

M = Prⁱ

+

CO₂Me

M

CO₂Me

Scheme 8 Reagents: i, Hg(OAc)₂, AcOOH, AcOH, room temp.

71A M = Me

75A M = Ph

78:22

90:10

71B M = Me

75B M = Ph

group using the alkoxide derived from the alcohol in a well

precedented reaction.³²The mixture of alcohols 46 gave the

mixture of silyl ethers 98, and the separated alcohol 60B gave

the silyl ether 99 (Scheme 9). The relative stereochemistry of

ii

70A M = Me

74A M = Ph

78:22 69%

91:9

70B M = Me

74B M = Ph

57%

PhMe₂Si

HO Ph

Ph OH

Scheme 10 Reagents: i, Hg(OAc)₂, AcOOH, AcOH, room temp.; ii,

NaCl, H₂O, DMSO, reﬂux

+

Krapcho reaction ³³on the products 71 and 75 from the conju-

gate additions of silyl nucleophiles to the α,β-unsaturated

diesters gave the mono esters 70 and 74, to which we had

already assigned relative conﬁgurations (Scheme 10).

Unfortunately, when carried out on the diesters 79, this reac-

tion did not take place in high enough yield for us to be con-

ﬁdent that the major isomer in the starting mixture was still

the major isomer in the product mixture. This was made

difﬁcult in this case because the ratio of isomers was close

to 50:50 (45:55, 53:47, 43:57 and 45:55) with all the silyl

nucleophiles. The diesters 79 remain unassigned, both for this

reason and because there seemed little point in going to great

lengths for such an unselective and inconsistent set of

reactions.

46A

25:75

i

46B

Me₂Si

O

Me₂Si

O

Ph

+

Ph

98A

25:75 88%

98B

PhMe₂Si

Me₂Si

O

Ph OH

i

Ph

60B

99

99%

Krapcho reaction on the products 72, 73, 76, 77, 80 and 81

from the conjugate additions of methyl and phenyl nucleophiles

to the diesters, followed by silyl-to-hydroxy conversion, gave

successively the esters 104–109 and the lactones 110–115

(Scheme 11). In this case the low yield we experienced in the

formation of the mixture of diastereoisomers 108 would have

made the assignment ambiguous, so we carried out the conver-

sion on two mixtures with different proportions of diastereo-

isomers. The products were present in the same proportions in

each case, showing that there had not been a selectively more

efﬁcient reaction on the minor diastereoisomer. With two of

these Krapcho reactions, namely those on the diesters 80 and

81, we found that using four equivalents of lithium chloride in

place of the usual sodium chloride, and adding two equivalents

of water, led to signiﬁcantly shorter reaction times, typically

30 min instead of several hours, for the complete con-

sumption of the starting material, and to cleaner reaction

mixtures.

PhMe₂Si

Ph

HO Ph

i

PhMe₂SiO Ph

Ph

53A

PhMe₂Si

Ph

Ph OH

100

53B

Scheme 9 Reagents: i, NaH, THF, room temp.

these cyclic materials followed from a NOESY experiment.

This device did not work for the benzylsilanes 53, which instead

of losing the phenyl group in a 5-exo-tet reaction, suffered ben-

zylic cleavage in a 5-endo-tet reaction giving the silyl ether 100

from each of the diastereoisomers. Thus, we were not able easily

to determine the sense of attack in the formation of 53A and

1336

J. Chem. Soc., Perkin Trans. 1, 1997

View Article Online

cooled to Ϫ78 ЊC. The ester 25 (0.4 g, 2.08 mmol) in THF (20

PhMe₂Si

M

R¹

PhMe₂Si

M

R¹

cm³) was added dropwise with stirring over 15 min and the

mixture kept for a further 1.5 h at this temperature. Methyl

iodide (0.39 cm³, 6.24 mmol) was added to the solution and

after 10 min the mixture was allowed to warm to room temper-

ature. Saturated aqueous ammonium chloride (15 cm³) was

added to the mixture followed by dilute hydrochloric acid (30

cm³). The THF was evaporated under reduced pressure and the

residue was extracted with dichloromethane (3 × 50 cm³). The

combined organic extracts were washed with water (100 cm³),

and then brine (100 cm³), dried (MgSO₄) and evaporated under

reduced pressure to give the esters 26 and 27 in a ratio of 44:56.

The residue was chromatographed (SiO₂, Et₂O–light petroleum,

15:85) to give a mixture of diastereoisomers of the methylated

ester (0.34 g, 80%); ν_max(ﬁlm)/cm^Ϫ11737 (C᎐O); 26: δ (250

+

CO₂Me

72A M = Me R¹= Me

73A M = Me R¹= Ph

76A M = Ph R¹= Me

77A M = Ph R¹= Ph

80A M = PrⁱR¹= Me

81A M = PrⁱR¹= Ph

85:15 72B M = Me R¹= Me

29:71 73B M = Me R¹= Ph

81:19 76B M = Ph R¹= Me

100:0 77B M = Ph R¹= Ph

64:36 80B M = PrⁱR¹= Me

52:48 80B M = PrⁱR¹= Me

37:63 81B M = PrⁱR¹= Ph

i

PhMe₂Si

M

R¹

PhMe₂Si

M

R¹

᎐

H

MHz; CDCl₃) 7.33–7.09 (5 H, m, Ph), 3.57 (3 H, s, OMe), 2.71

(1 H, m, MeCHPh), 2.41–2.22 (1 H, m, MeO₂CCHMe), 2.05 (1

H, ddd, J 13.7, 8.9 and 6.8, CH_AH_B), 1.68–1.54 (1 H, m,

CH_AH_B), 1.26 (3 H, d, J 6.8, MeCHPh) and 1.14 (3 H, d, J 6.9,

MeO₂CCHMe); 27: δ_H(250 MHz; CDCl₃) 7.33–7.09 (5 H, m,

Ph), 3.66 (3 H, s, OMe), 2.71 (1 H, m, MeCHPh), 2.29 (1 H, m,

MeO₂CCHMe), 1.98 (1 H, ddd, J 13.7, 9.2 and 5.6, CH_AH_B),

1.61 (1 H, ddd, J 13.7, 9.5 and 5.2, CH_AH_B), 1.23 (3 H, d, J 6.9,

MeCHPh) and 1.09 (3 H, d, J 7.0, MeO₂CCHMe); m/z (EI) 206

(15%, M^ϩ), 175 (17, M Ϫ OMe), 88 (100, M Ϫ CH₂CMePh)

(Found: M^ϩ, 206.1307. C₁₃H₁₈O₂requires M, 206.1307). The

ratio of diastereoisomers was determined by integration of the

OMe signals in the ¹H NMR spectrum. The above experiment

was repeated but the mixture was left for 2 h at Ϫ78 ЊC after

addition of methyl iodide and then quenched at this temper-

ature with saturated aqueous ammonium chloride giving the

diastereoisomers in the same ratio.

+

CO₂Me

104A M = Me R¹= Me 85:15 81%

105A M = Me R¹= Ph

29:71 52%

106A M = Ph R¹= Me 84:16 71%

104B M = Me R¹= Me

105B M = Me R¹= Ph

106B M = Ph R¹= Me

107B M = Ph R¹= Ph

108B M = PrⁱR¹= Me

109B M = PrⁱR¹= Ph

107A M = Ph R¹= Ph

100:0 71%

108A M = PrⁱR¹= Me 64:36 68%

108A M = PrⁱR¹= Me 52:48 60%

109A M = PrⁱR¹= Ph

37:63 ??%

ii

R¹

+

M

O

M

O

110A M = Me R¹= Me 85:15 59%

111A M = Me R¹= Ph

29:71 57%

112A M = Ph R¹= Me 78:22 67%

113A M = Ph R¹= Ph

0:100 41%

114A M = PrⁱR¹= Me 64:36 65%

115A M = PrⁱR¹= Ph

40:60 83%

110B M = Me R¹= Me

111B M = Me R¹= Ph

112B M = Ph R¹= Me

113B M = Ph R¹= Ph

114B M = PrⁱR¹= Me

115B M = PrⁱR¹= Ph

Reaction of methyllithium with aldehydes

Typically, the aldehyde (2.18 mmol) in THF (5 cm³) was added

dropwise to methyllithium (1.4 mol dm^Ϫ3solution in Et₂O; 2

cm³, 2.8 mmol) in THF (12 cm³) at Ϫ78 ЊC under argon. After

1 h, saturated aqueous ammonium chloride (10 cm³) was

added and the mixture allowed to warm to room temperature.

Dilute hydrochloric acid (15 cm³) was added to the mixture

and the THF was evaporated under reduced pressure. The

residue was extracted with dichloromethane (3 × 25 cm³) and

the combined organic fractions were washed with brine, dried

(MgSO₄) and evaporated under reduced pressure to give the

mixture of alcohols. The following compounds were prepared

by this method.

Scheme 11 Reagents: i, NaCl or LiCl, H₂O, DMSO, reﬂux; ii,

Hg(OAc)₂, AcOOH, AcOH, room temp.

Conclusions

A reliable rule predicting the sense of 1,3-stereocontrol is still

not within our grasp. It is possible to make some generalisations

that are more often true than not, but a relatively ﬁrm predic-

tion is limited only to a small subset of all the reactions that we

have investigated: when R¹≠ H ≠ Ph, and when M ≠ Ph, nucleo-

philic attack takes place on ketone carbonyl groups in the

sense B, and simple modelling supports this picture. More gen-

erally, it is possible to suggest that more often than not, alde-

hydes and α,β-unsaturated esters with R¹= H react in the sense

A, and ketones react in the sense B. Notable exceptions to this

rule are (i) those reactions in which a lithium reagent is used, for

which some but not all the reactions show the opposite sense of

stereoselectivity, and (ii) those substrates in which a phenyl

group is present either on the stereogenic centre or attached as

R¹to the carbonyl group, which also give inconsistent results

not matched to the modelling results.

(2RS,4SR)-4-Dimethyl(phenyl)silylpentan-2-ol¹⁸40A and

(2RS,4RS)-4-dimethyl(phenyl)silylpentan-2-ol 40B. (72%) Sep-

arated by chromatography (SiO₂, Et₂O–CH₂Cl₂, 10:90); 40A:

R_F(Et₂O–CH₂Cl₂, 10:90) 0.42; ν_max(ﬁlm)/cm^Ϫ13356 (OH), 1248

(SiMe) and 1112 (SiPh); δ_H(250 MHz; CDCl₃) 7.51 (2 H, m, o-

Ph), 7.39–7.31 (3 H, m, m- and p-Ph), 3.89 (1 H, m, CHOH),

1.48 (1 H, m, CH_AH_B), 1.22–1.05 (2 H, m, CH_AH_Band SiCH),

1.16 (3 H, d, J 6.1, CHOHMe), 0.95 (3 H, d, J 6.6, SiCHMe)

and 0.27 (6 H, s, SiMe₂); 40B: R_F(Et₂O–CH₂Cl₂, 10:90) 0.38;

ν_max(ﬁlm)/cm^Ϫ13354 (OH), 1249 (SiMe) and 1112 (SiPh);

δ_H(250 MHz; CDCl₃) 7.52 (2 H, m, o-Ph), 7.41–7.34 (3 H, m, m-

and p-Ph) 3.86 (1 H, m, CHOH), 1.77 (1 H, br s, OH), 1.49–1.40

(2 H, m, CH₂), 1.12 (3 H, d, J 6.1, CHOHMe), 1.00 (1 H, m,

SiCH), 0.98 (3 H, d, J 1.8, SiCHMe), 0.29 (3 H, s, SiMe_AMe_B)

and 0.28 (3 H, s, SiMe_AMe_B). The ratio of the diastereoisomers

was determined by integration of the CHOHMe signals in the

¹H NMR spectrum. The stereochemistry of the alcohols 40

(= 43) had already been assigned.¹⁸

Experimental

Light petroleum refers to the fraction boiling between 40–60 ЊC

unless otherwise speciﬁed. Ether refers to diethyl ether. J Values

are given in Hz.

Methyl (2RS,4SR)-2-methyl-4-phenylpentanoate 26 and methyl

(2RS,4RS)-2-methyl-4-phenylpentanoate 27

(2RS,4RS)-4-Dimethyl(phenyl)silyl-4-phenylbutan-2-ol 47A

and (2RS,4SR)-4-dimethyl(phenyl)silyl-4-phenylbutan-2-ol 47B.

(63%) Separated by chromatography (SiO₂, Et₂O–CH₂Cl₂,

50:50); 47A: R_F(Et₂O–light petroleum, 50:50) 0.53; δ_H(200

MHz; CDCl₃) 7.44–6.94 (10 H, m, 2 × Ph), 3.62 (1 H, m,

CHOH), 2.62 (1 H, dd, J 12.7 and 3.3, CHSi), 1.89 (1 H, ddd,

Butyllithium (1.6 mol dm^Ϫ3solution in hexanes, 1.43 cm³, 2.29

mmol) was added dropwise with stirring to diisopropylamine

(0.32 cm³, 2.29 mmol) in THF (20 cm³) at 0 ЊC under argon.

The mixture was stirred at this temperature for 20 min and then

J. Chem. Soc., Perkin Trans. 1, 1997

1337

View Article Online

J 14.2, 12.7 and 2.9, CH_ACH_B), 1.68 (1 H, m, CH_ACH_B), 1.5 (1

H, br s, OH), 1.09 (3 H, d, J 6.2, CHMe), 0.28 (3 H, s, SiMe_A-

Me_B), 0.21 (3 H, s, SiMe_AMe_B); 47B; R_F(Et₂O–light petroleum,

50:50) 0.43; ν_max(ﬁlm)/cm^Ϫ13362 (OH) and 1598 (Ph); δ_H(200

MHz; CDCl₃) 7.44–6.94 (10 H, m, 2 × Ph), 3.62 (1 H, m,

CHOH), 2.29 (1 H, dd, J 12.5 and 2.9, CHSi), 2.13 (1 H, dt, J

12.5 and 4.9, CH_ACH_B), 1.68 (1 H, m, CH_ACH_B), 1.5 (1 H, br s,

OH), 1.07 (3 H, d, J 6.2, CHMe), 0.28 (3 H, s, SiMe_AMe_B), 0.19

(3 H, s, SiMe_AMe_B). The ratio of the diastereoisomers was

determined by integration of the CHSi signals in the ¹H NMR

spectrum.

(2RS,4RS)-4-Dimethyl(phenyl)silyl-5-methylhexan-2-ol 54A

and (2RS,4SR)-4-dimethyl(phenyl)silyl-5-methylhexan-2-ol 54B.

(65%) R_F(CH₂Cl₂) 0.25; ν_max(ﬁlm)/cm^Ϫ13404 (OH), 1250

(SiMe) and 1110 (SiPh); δ_H(250 MHz; CDCl₃) 54A: 7.52 (2 H,

m, o-Ph), 7.38–7.29 (3 H, m, m- and p-Ph), 3.65 (1 H, m,

CHOH), 1.94 (1 H, m, CHMe_AMe_B), 1.63–1.36 (2 H, m, CH₂),

1.10–0.97 (1 H, m, CHSi), 1.03 (3 H, d, J 6.0, CHMe), 0.95 (3

H, d, J 6.9, CHMe), 0.84 (3 H, d, J 6.9, CHMe), 0.32 (3 H, s,

SiMe_CMe_D) and 0.31 (3 H, s, SiMe_CMe_D); 54B: 7.52 (2 H, m, o-

Ph), 7.38–7.29 (3 H, m, m- and p-Ph) 3.65 (1 H, m, CHOH),

1.94 (1 H, m, CHMe_AMe_B), 1.63–1.36 (2 H, m, CH₂), 1.10–0.97

(1 H, m, CHSi), 1.09 (3 H, d, J 6.1, CHMe), 0.94 (3 H, d, J 6.9,

CHMe), 0.85 (3 H, d, J 6.9, CHMe), 0.33 (6 H, s, SiMe₂);

δ_C(CDCl₃) 54A: 139.9, 133.9, 128.8, 127.8, 67.5, 36.6, 29.1, 28.7,

23.8, 22.7, 21.4, Ϫ2.9 and Ϫ3.1; 54B: 140.0, 133.8, 128.8, 127.8,

67.6, 36.1, 29.4, 28.9, 23.4, 22.9, 20.9 and Ϫ2.1; m/z (EI) 235

(13%, M^ϩϪ Me), 233 (13, M Ϫ OH) and 135 (100, Me₂PhSi)

(Found: M^ϩϪ Me, 235.1516. C₁₅H₂₆OSi requires M Ϫ Me,

235.1518). The ratio of the diastereoisomers was determined by

integration of the CH₂signals in the ¹³C NMR spectrum (36.6

and 36.1 ppm).

(1RS,3RS)-3-Dimethyl(phenyl)silyl-1-phenylbutan-1-ol 41A

and (1RS,3SR)-3-dimethyl(phenyl)silyl-1-phenylbutan-1-ol 41B.

(73%) Separated by chromatography (SiO₂, CH₂Cl₂); 41A:

R_F(CH₂Cl₂) 0.30; ν_max(ﬁlm)/cm^Ϫ13380 (OH), 1248 (SiMe) and

1111 (SiPh); δ_H(250 MHz; CDCl₃) 7.43–7.19 (10 H, m, Ph), 4.69

(1 H, dd, J 8.5 and 6.0, PhCHOH), 1.86 (1 H, ddd, J 13.5, 8.5

and 3.8, CH_AH_B), 1.67 (1 H, ddd, J 13.5, 10.3 and 6.0, CH_AH_B),

1.02 (3 H, d, J 7.3, MeCHSi), 0.71 (1 H, m, MeCHSi), 0.23 (3

H, s, SiMe_AMe_B) and 0.21 (3 H, s, SiMe_AMe_B); δ_C(CDCl₃)

144.2, 138.2, 134.0, 129.0, 128.5, 127.8, 127.3, 126.6, 73.9, 40.7,

15.7, 14.6, Ϫ4.6 and Ϫ5.4; m/z (EI) 269 (3%, M^ϩϪ Me) and

135 (44, Me₂PhSi) (Found: M^ϩϪ Me, 269.1363. C₁₈H₂₄OSi

requires M Ϫ Me, 269.1362); 41B: R_F(CH₂Cl₂) 0.37; ν_max(ﬁlm)/

cm^Ϫ13414 (OH), 1248 (SiMe) and 1112 (SiPh); δ_H(250 MHz;

CDCl₃) 7.53–7.47 (2 H, m, Ph), 7.38–7.21 (8 H, m, Ph), 4.77 (1

H, dd, J 10.0 and 2.8, PhCHOH), 1.85 (1 H, ddd, J 13.5, 10.0

and 2.2, CH_AH_B), 1.41 (1 H, ddd, J 13.5, 11.6 and 2.8, CH_AH_B),

1.29 (1 H, m, MeCHSi), 1.03 (3 H, d, J 6.9, MeCHSi), 0.27 (3

H, s, SiMe_AMe_B) and 0.26 (3 H, s, SiMe_AMe_B); δ_C(CDCl₃)

145.7, 138.1, 134.0, 128.9, 128.5, 127.8, 127.3, 125.9, 71.6, 41.4,

14.6, 13.6 and Ϫ5.0 ; m/z (EI) 269 (5%, M^ϩϪ Me), 177 (56,

PhCHOH) and 135 (100, Me₂PhSi) (Found:

M

^ϩϪ Me,

269.1346. C₁₈H₂₄OSi requires M Ϫ Me, 269.1362). The ratio of

the diastereoisomers was determined by integration of the

PhCHOH signals in the ¹H NMR spectrum.

(1RS,3SR)-3-Dimethyl(phenyl)silyl-1,3-diphenylpropan-1-ol

48A and (1RS,3RS)-3-dimethyl(phenyl)silyl-1,3-diphenylpropan-

1-ol 48B. (70%) Separated by chromatography (SiO₂, CH₂Cl₂–

light petroleum, 80:20); 48A: R_F(CH₂Cl₂–light petroleum,

80:20) 0.33; ν_max(ﬁlm)/cm^Ϫ13600 (OH) and 1600 (Ph); δ_H(400

MHz; CDCl₃) 7.4–7.0 (15 H, m, 3 × Ph), 4.47 (1 H, dd, J 10 and

2.5, CHOH), 2.8 (1 H, dd, J 12.7 and 3.3, CHSi), 2.12 (1 H,

ddd, J 14.5, 12.7 and 2.5, CH_ACH_B), 2.03 (1 H, ddd, J 14.5, 10

and 3.3, CH_ACH_B), 1.8 (1 H, br s, OH), 0.3 (3 H, s, SiMe_AMe_B)

and 0.2 (3 H, s, SiMe_AMe_B); δ_C(400 MHz; CDCl₃) 145.5, 142.1,

137.2, 134.2, 129.1, 128.4, 128.3, 127.7, 127.3, 125.5, 124.9,

71.7, 39.3, 32.7, Ϫ4.0 and Ϫ5.1 (Found: M^ϩ, 346.1747; C, 79.6;

H, 7.5%. C₂₃H₂₆OSi requires M, 346.1753; C, 79.7; H, 7.6%);

48B: R_F(CH₂Cl₂–light petroleum, 80:20) 0.21; ν_max(ﬁlm)/cm^Ϫ1

3600 (OH) and 1600 (Ph); δ_H(400 MHz; CDCl₃) 7.35–6.9 (15 H,

m, 3 × Ph), 4.42 (1 H, dd, J 9.5 and 4.9, CHOH), 2.4 (1 H, ddd,

J 13.5, 12.6 and 4.9, CH_ACH_B), 2.06 (1 H, ddd, J 13.5, 9.5 and

3, CH_ACH_B), 1.91 (1 H, dd, J 12.6 and 3, CHSi), 1.73 (1 H, br s,

OH), 0.2 (3 H, s, SiMe_AMe_B) and 0.08 (3 H, s, SiMe_AMe_B);

δ_C(CDCl₃) 143.6, 142.2, 137.03, 134.1, 129.1, 128.4, 128.3,

128.02, 127.8, 127.6, 126.6, 124.8, 74.2, 38.2, 32.8, Ϫ4.0 and

Ϫ5.6 (Found: C, 79.6; H, 7.7. C₂₃H₂₆OSi requires C, 79.7; H,

7.6%).

Reaction of methylmagnesium bromide with aldehydes

Typically, the aldehyde (1.9 mmol) in THF (5 cm³) was added

dropwise to a stirred solution of methylmagnesium bromide (3

mol dm^Ϫ3solution in Et₂O, 0.95 cm³, 2.85 mmol) in THF (12

cm³) at 0 ЊC under argon. After 2 h, the mixture was quenched

with saturated aqueous ammonium chloride (10 cm³) and

allowed to warm to room temperature. Dilute hydrochloric acid

(15 cm³) was added, and the THF was evaporated under

reduced pressure. The residue was extracted with dichlo-

romethane (3 × 25 cm³) and the combined organic fractions

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

reduced pressure to give the alcohols. The alcohols 40 (36%), 47

(60%) and 54 (64%), identical with the earlier samples, were

prepared by this method.

Reaction of methylmagnesium iodide with the aldehyde 28

The aldehyde 28 (0.39 g, 1.89 mmol) in ether (12 cm³) was

added to methylmagnesium iodide (2.83 mmol) freshly pre-

pared in ether (40 cm³) over 10 min at 0 ЊC, and the mixture

kept for 1 h. An aqueous work-up, as for the reaction with the

bromide, and chromatography gave each of the diastereo-

isomers of the alcohols 40 (0.27 g, 64%).

(1RS,3SR)-3-Dimethyl(phenyl)silyl-4-methyl-1-phenylpentan-

1-ol 55A and (1RS,3RS)-3-dimethyl(phenyl)silyl-4-methyl-1-

phenylpentan-1-ol 55B. (74%) Separated by chromatography

(SiO₂, CH₂Cl₂–light petroleum, 80:20); R_F(CH₂Cl₂–light pet-

roleum, 80:20) 0.33; ν_max(ﬁlm)/cm^Ϫ13422 (OH) and 1492 (Ph);

55A: δ_H(400 MHz; CDCl₃) 7.57–7.14 (10 H, m, 2 × Ph), 4.55 (1

H, t, J 6.9, CHOH), 2.00 (1 H, dseptet, J 3.0 and 6.9, CHMe₂),

1.80 (2 H, t, J 6.6, CH_ACH_B), 1.61 (1 H, br s, OH), 1.11 (1 H, dt,

J 3.0 and 6.3, CHSi), 0.89 (3 H, d, J 6.9, CHMe_AMe_B), 0.87 (3

H, d, J 6.9, CHMe_AMe_B), 0.38 (3 H, s, SiMe_AMe_B) and 0.36 (3

H, s, SiMe_AMe_B); 55B: δ_H(400 MHz; CDCl₃) 7.57–7.14 (10 H,

m, 2 × Ph), 4.50 (1 H, dd, J 8.0 and 6.0, CHOH), 2.04 (1 H, m,

CHMe₂), 1.92–1.7 (3 H, m, CH_AH_Band CHSi), 1.61 (1 H, br s,

OH), 1.02 (6 H, d, J 6.8, CHMe_AMe_B), 0.33 (3 H, s, SiMe_AMe_B)

and 0.31 (3 H, s, SiMe_AMe_B); δ_C(CDCl₃) 145.1, 139.9, 134.0,

128.9, 128.4, 127.8, 126.0, 73.9, 36.5, 28.8, 22.5, 21.3, Ϫ2.1 and

Reaction of phenyllithium with aldehydes and ketones

Typically, the aldehyde (1.89 mmol) in THF (5 cm³) was added

dropwise to a stirred solution of phenyllithium (1.8 mol dm^Ϫ3

solution in cyclohexane–Et₂O, 70:30; 1.4 cm³, 2.52 mmol) in

THF (12 cm³) at Ϫ78 ЊC under argon. After 1 h (aldehydes) or

3–10 h (ketones), the reaction was quenched with saturated

aqueous ammonium chloride (10 cm³) and allowed to warm to

room temperature. Dilute hydrochloric acid (15 cm³) was added

to the mixture and the THF was evaporated under reduced

pressure. The residue was extracted with dichloromethane

(3 × 25 cm³) and the combined organic fractions were washed

with brine, dried (MgSO₄) and evaporated under reduced pres-

sure to give a mixture of alcohols. The following compounds

were prepared by this method.

Ϫ2.9 (Found:

M Ϫ Me, 297.1675).

(3RS,5SR)-5-Dimethyl(phenyl)silyl-2-methyl-3-phenylhexan-

3-ol 46A and (3RS,5RS)-5-dimethyl(phenyl)silyl-2-methyl-3-

phenylhexan-3-ol 46B. (71%) Separated by chromatography

(SiO₂, Et₂O–light petroleum, 10:90); R_F(Et₂O–light petroleum,

M

^ϩϪ Me, 297.1668. C₂₀H₂₈OSi requires

1338

J. Chem. Soc., Perkin Trans. 1, 1997

View Article Online

10:90) 0.30; ν_max(ﬁlm)/cm^Ϫ13591 (OH), 1248 (SiMe) and 1111

(SiPh); 46A: δ_H(400 MHz; CDCl₃) 7.52–7.45 (2 H, m, Ph), 7.39–

7.23 (6 H, m, Ph), 7.22–7.12 (2 H, m, Ph), 2.02–1.86 (2 H, m,

CH_AH_Band CHMe_AMe_B), 1.66 (1 H, dd, J 14.6 and 10.9,

CH_AH_B), 1.02 (1 H, m, CHSi), 1.00 (3 H, d, J 7.3, CHMe), 0.94

(3 H, d, J 7.6, CHMe), 0.58 (3 H, d, J 6.8, CHMe), 0.20 (3 H, s,

SiMe_CMe_D) and 0.17 (3 H, s, SiMe_CMe_D); δ_C(400 MHz; CDCl₃)

145.5, 138.2, 128.8, 127.9, 127.7, 126.0, 125.8, 81.6, 40.8, 39.0,

17.6, 16.5, 15.6, 15.0, Ϫ4.8 and Ϫ5.6; 46B: δ_H(400 MHz;

CDCl₃) 7.52–7.45 (2 H, m, Ph), 7.39–7.23 (6 H, m, Ph), 7.22–

7.12 (2 H, m, Ph), 2.11 (1 H, dd, J 14.6 and 3.2, CH_AH_B), 1.95 (1

H, m, CHMe_AMe_B), 1.60 (1 H, dd, J 14.6 and 7.8, CH_AH_B),

0.95 (1 H, m, CHSi), 0.81 (3 H, d, J 6.7, CHMe), 0.58 (3 H, d, J

6.8, CHMe), 0.53 (3 H, d, J 7.3, CHMe), 0.25 (3 H, s, SiMe_A-

Me_B) and 0.23 (3 H, s, SiMe_AMe_B); δ_C(CDCl₃) 145.6, 138.5,

134.0, 129.0, 127.7, 127.5, 125.9, 78.9, 41.3, 38.0, 17.6, 16.6,

16.2, 13.5, Ϫ4.5 and Ϫ5.6; m/z (EI) 283 (7%, M^ϩϪ Prⁱ), 135

Me₂PhSi) (Found: M^ϩϪ Prⁱ, 311.1814. C₂₃H₃₄SiO requires

M Ϫ Prⁱ, 311.1831). The ratio of the diastereoisomers was

determined by integration of the CH₂signals (37.5 to 36.3 ppm)

in the ¹³C NMR spectrum.

Reaction of phenylmagnesium bromide with aldehydes and

ketones

Typically, the aldehyde (1.89 mmol) in THF (5 cm³) was added

dropwise with stirring to a solution of phenylmagnesium brom-

ide (3 mol dm^Ϫ3solution in Et₂O; 0.82 cm³, 2.46 mmol) in THF

(12 cm³) at 0 ЊC under argon. After 1 h at 0 ЊC, the reaction was

quenched with saturated aqueous ammonium chloride (10 cm³)

and allowed to warm to room temperature. Dilute hydrochloric

acid (15 cm³) was added to the mixture and the THF was evap-

orated under reduced pressure. The residue was extracted with

dichloromethane (3 × 25 cm³) and the combined organic frac-

tions were washed with brine, dried (MgSO₄) and evaporated

under reduced pressure to give a mixture of alcohols. The alco-

hols 41 (67%), 46 (60%), 48 (70%) and 55 (60%), identical with

the earlier samples, were prepared by this method.

(100, Me₂PhSi) (Found:

M

^ϩϪ Prⁱ, 283.1524. C₂₁H₃₀OSi

requires M Ϫ Prⁱ, 283.1518). The ratio of the diastereoisomers

was determined by integration of the CH₂signals (41.3 and 40.8

ppm) in the ¹³C NMR spectrum.

(1RS,3RS)-1-Dimethyl(phenyl)silyl-1,3-diphenyl-4-methyl-

pentan-3-ol 53A and (1RS,3SR)-1-dimethyl(phenyl)silyl-1,3-

diphenyl-4-methylpentan-3-ol 53B. (65%) chromatography

(SiO₂, Et₂O–light petroleum, 10:90) gave complete separation

of the alcohols; minor isomer: R_F(Et₂O–light petroleum, 10:90)

0.40; ν_max(ﬁlm)/cm^Ϫ13576 (OH), 1249 (SiMe) and 1113 (SiPh);

δ_H(400 MHz; CDCl₃) 7.47–6.80 (15 H, m, Ph), 2.47 (1 H, dd, J

14.7 and 12.2), 2.17 (1 H, dd, J 14.7 and 1.0), 1.93 (1 H, dd, J

12.3 and 1.0), 1.80 (1 H, septet, J 6.7, CHMe_AMe_B), 0.90 (3 H,

d, J 6.7, CHMe_AMe_B), 0.53 (3 H, d, J 6.8, CHMe_AMe_B), 0.22 (3

H, s, SiMe_CMe_D) and Ϫ0.01 (3 H, s, SiMe_CMe_D); δ_C(CDCl₃)

145.6, 142.8, 137.1, 134.2, 129.2, 128.8, 128.1, 127.7, 126.1,

126.0, 125.3, 82.0, 38.8, 38.5, 31.9, 17.5, 16.7, Ϫ4.1 and Ϫ6.0;

m/z (EI) 371 (23%, M^ϩϪ OH), 345 (45, M Ϫ Prⁱ) and 135 (100,

Me₂PhSi) (Found: M^ϩϪ OH, 371.2190. C₂₆H₃₂SiO requires

M Ϫ OH, 371.2195); major isomer: ν_max(ﬁlm)/cm^Ϫ13581 (OH),

1263 (SiMe) and 1113 (SiPh); δ_H(400 MHz; CDCl₃) 7.44–6.67

(15 H, m, Ph), 2.42–2.24 (3 H, m, PhCHSi, CH_AH_Band

CH_AH_B), 1.93 (1 H, septet, J 6.8, CHMe_AMe_B), 0.73 (3 H, d, J

6.7, CHMe_AMe_B), 0.53 (3 H, d, J 6.9, CHMe_AMe_B), 0.23 (3 H,

s, SiMe_CMe_D) and 0.07 (3 H, s, SiMe_CMe_D); δ_C(CDCl₃) 144.5,

144.1, 137.6, 134.2, 129.2, 128.8, 128.0, 127.9, 127.2, 126.1,

126.0, 124.1, 79.8, 40.1, 31.2, 17.6, 16.6, Ϫ3.9 and Ϫ5.7; m/z

(EI) 371 (35%, M^ϩϪ OH), 345 (28, M Ϫ Prⁱ) and 135 (100,

Me₂PhSi) (Found: M^ϩϪ OH, 371.2167. C₂₆H₃₂SiO requires

M Ϫ OH, 371.2195). The ratio of the diastereoisomers was

determined by integration of the CH₂signals (40.1 to 38.5 ppm)

in the ¹³C NMR spectrum.

(3RS,5RS)-5-Dimethyl(phenyl)silyl-2,6-dimethyl-3-phenyl-

heptan-3-ol 60A and (3RS,5SR)-5-dimethyl(phenyl)silyl-2,6-

dimethyl-3-phenylheptan-3-ol 60B. (60%) Chromatography

(SiO₂, Et₂O–light petroleum, 5:95) gave the major alcohol 60B;

R_F(Et₂O–light petroleum, 5:95) 0.32; ν_max(ﬁlm)/cm^Ϫ13584

(OH), 1248 (SiMe) and 1108 (SiPh); 60A: δ_H(400 MHz; CDCl₃)

(some signals) 7.51–7.09 (10 H, m, Ph), 2.22 (1 H, m,

CHMe_AMe_B), 0.95 (3 H, d, J 6.7, CHMe), 0.94 (3 H, d, J 7.0,

CHMe), 0.71 (3 H, d, J 7.1, CHMe), 0.55 (3 H, d, J 6.9,

CHMe), 0.20 (3 H, s, SiMe_CMe_D) and 0.19 (3 H, s, SiMe_CMe_D);

δ_C(CDCl₃) (some signals) 81.0, 38.6, 37.5, 29.1, 29.0, 23.3, 20.9,

16.4, 1.0 and Ϫ0.88; 60B: δ_H(400 MHz; CDCl₃) 7.51–7.09 (10

H, m, Ph), 2.05 (1 H, dd, J 14.6 and 6.9, CH_AH_B), 1.95 (1 H,

septet, J 6.8, CPhOHCHMe_AMe_B), 1.75 (1 H, dd, J 14.6 and

4.0, CH_AH_B), 1.45 (1 H, dseptet, J 2.3 and 6.9, CHMe_CMe_D-

CHSi), 0.83–0.77 (1 H, m, CHSi), 0.80 (3 H, d, J 4.0, CHMe),

0.67 (3 H, d, J 6.9, CHMe), 0.66 (3 H, d, J 7.0, CHMe), 0.50 (3

H, d, J 6.8, CHMe), 0.38 (3 H, s, SiMe_EMe_F) and 0.29 (3 H, s,

SiMe_EMe_F); δ_C(CDCl₃) 145.4, 140.3, 134.2, 128.9, 128.0, 127.4,

125.9, 79.0, 41.4, 38.3, 36.3, 30.0, 26.5, 21.8, 21.2, 17.7, 16.5,

Ϫ0.78 and Ϫ2.78; m/z (EI) 311 (8%, M^ϩϪ Prⁱ), 135 (100,

Reaction of isopropylmagnesium chloride with aldehydes

Typically, the aldehyde (30.6 mmol) in THF (20 cm³) was added

dropwise with stirring to a solution of isopropylmagnesium

chloride (2.0 mol dm^Ϫ3solution in Et₂O; 23.0 cm³, 46.0 mmol)

in THF (60 cm³) at 0 ЊC under argon. After 2 h at 0 ЊC, the

mixture was quenched by addition of saturated aqueous

ammonium chloride (20 cm³) and allowed to warm to room

temperature. Dilute hydrochloric acid (50 cm³) was added and

the THF was evaporated under reduced pressure. The residue

was extracted with dichloromethane (3 × 50 cm³) and the com-

bined organic fractions were washed with brine (100 cm³), dried

(MgSO₄) and evaporated under reduced pressure to give a mix-

ture of the alcohols. The following compounds were prepared

by this method.

(3RS,5RS)-5-Dimethyl(phenyl)silyl-2-methylhexan-3-ol 42A

and (3RS,5SR)-5-dimethyl(phenyl)silyl-2-methylhexan-3-ol 42B.

(60%) Chromatography (SiO₂, Et₂O–light petroleum, 30:70)

gave the alcohols as a mixture; R_F(Et₂O–light petroleum, 30:70)

0.32; ν_max(ﬁlm)/cm^Ϫ13398 (OH), 1249 (SiMe) and 1112 (SiPh);

42A: δ_H(400 MHz; CDCl₃) 7.51 (2 H, m, o-Ph), 7.38–7.31 (3 H,

m, m- and p-Ph), 3.43 (1 H, m, CHOH), 1.57 (1 H, m), 1.46 (1

H, m), 1.30–1.10 (2 H, m), 0.98 (3 H, d, J 6.9, MeCH), 0.89 (3

H, d, J 6.8, MeCH), 0.87 (3 H, d, J 6.9, MeCH), 0.28 (3 H, s,

SiMe_AMe_B) and 0.27 (3 H, s, SiMe_AMe_B); δ_C(CDCl₃) 138.3,

134.0, 128.9, 127.7, 73.5, 35.6, 34.2, 18.9, 17.6, 14.6, 13.4, Ϫ5.0

and Ϫ5.1; 42B: δ_H(400 MHz; CDCl₃) 7.51 (2 H, m, o-Ph), 7.38–

7.31 (3 H, m, m- and p-Ph), 3.43 (1 H, m, CHOH), 1.68–1.60 (1

H, m), 1.30–1.10 (2 H, m), 1.02–0.85 (7 H, m, 2 × MeCH and

CHSi), 0.75 (3 H, d, J 6.8, MeCH) and 0.29–0.27 (6 H, s,

SiMe₂); δ_C(CDCl₃) 138.5, 133.9, 128.9, 127.7, 75.7, 36.9, 31.9,

19.4, 16.5, 15.5, 15.3, Ϫ4.6 and Ϫ4.7; m/z (EI) 235 (27%,

M

^ϩϪ Me) and 135 (100, Me₂PhSi) (Found: ^ϩϪ Me,

M

235.1517. C₁₅H₂₆SiO requires M Ϫ Me, 235.1518). The ratio of

the diastereoisomers was found by integration of the CH₂sig-

nals (36.9 and 35.6 ppm) in the ¹³C NMR spectrum.

(3RS,5SR)-5-Dimethyl(phenyl)silyl-2-methyl-5-phenylpentan-

3-ol 49A and (3RS,5RS)-5-dimethyl(phenyl)silyl-2-methyl-5-

phenylpentan-3-ol 49B. (60%) Chromatography (SiO₂, Et₂O–

light petroleum, 30:70) gave the alcohols as a mixture;

R_F(Et₂O–light petroleum, 30:70) 0.27; ν_max(ﬁlm)/cm^Ϫ13422

(OH), 1249 (SiMe) and 1113 (SiPh); 49A: δ_H(400 MHz; CDCl₃)

7.42–6.88 (10 H, m, Ph), 3.09 (1 H, m, CHOH), 2.61 (1 H, dd, J

13.1 and 3.0, PhCHSi), 1.98–1.83 and 1.67–1.46 (3 H, m), 0.81

(3 H, d, J 6.7, CHMe_AMe_B), 0.80 (3 H, d, J 6.6, CHMe_AMe_B),

0.24 (3 H, s, SiMe_CMe_D) and 0.18 (3 H, s, SiMe_CMe_D);

δ_C(CDCl₃) 142.3, 137.4, 134.2, 129.2, 128.3, 128.1, 127.7, 124.6,

74.0, 34.0, 33.3, 32.1, 18.7, 17.7, Ϫ4.0 and Ϫ5.2; 49B: δ_H(400

MHz; CDCl₃) 7.42–6.88 (10 H, m, Ph), 3.30 (1 H, m, CHOH),

2.27 (1 H, dd, J 10.5 and 4.7, PhCHSi), 1.98–1.83 (2 H, m),

J. Chem. Soc., Perkin Trans. 1, 1997

1339

View Article Online

1.67–1.46 (1 H, m), 0.78 (3 H, d, J 6.8, CHMe_AMe_B), 0.73 (3 H,

d, J 6.8, CHMe_AMe_B), 0.25 (3 H, s, SiMe_CMe_D) and 0.16 (3 H,

s, SiMe_CMe_D); δ_C(CDCl₃) 142.9, 137.3, 134.1, 129.0, 128.2,

127.9, 127.6, 124.8, 76.6, 34.5, 34.0, 31.5, 19.3, 15.4, Ϫ3.9 and

Ϫ5.6; m/z (EI) 269 (52%, M^ϩϪ Prⁱ) and 135 (92, Me₂PhSi)

(Found: M^ϩϪ Prⁱ, 269.1357. C₂₀H₂₈SiO requires M Ϫ Prⁱ,

269.1362). The ratio of the diastereoisomers was found by inte-

gration of the CHOH signals in the ¹H NMR spectrum.

mixture was quenched with dilute hydrochloric acid (10 cm³).

The resulting turbid solution was shaken vigorously with satur-

ated aqueous potassium sodium tartrate (50 cm³), and the

aqueous layer was extracted with ether (3 × 50 cm³). The com-

bined organic fractions were washed with brine (100 cm³), dried

(MgSO₄) and evaporated under reduced pressure to give a

mixture of the alcohols. The pairs of alcohols 45 (=42) (77%),

52 (=49) (70%) and 59 (=56) (71%), identical with the earlier

samples, were prepared by this method.

(3RS,5SR)-5-Dimethyl(phenyl)silyl-2,6-dimethylheptan-3-ol

56A and (3RS,5RS)-5-dimethyl(phenyl)silyl-2,6-dimethylheptan-

3-ol 56B. (68%) Chromatography (SiO₂, Et₂O–light petroleum,

20:80) gave the alcohols as a mixture; R_F(Et₂O–light petroleum,

20:80) 0.27; ν_max(ﬁlm)/cm^Ϫ13440 (OH), 1248 (SiMe) and 1109

(SiPh); 56A: δ_H(400 MHz; CDCl₃) 7.52 (2 H, m, o-Ph), 7.36–

7.29 (3 H, m, m- and p-Ph), 3.31 (1 H, m, CHOH), 2.02–1.89 (1

H, m, CHMe_AMe_B), 1.60–1.47 (2 H, m), 1.32 (1 H, ddd, J 14.5,

9.4 and 4.1), 1.11 (1 H, ddd, J 8.8, 4.0 and 3.2), 0.93 (3 H, d, J

6.9, CHMe), 0.87 (3 H, d, J 7.0, CHMe), 0.83 (3 H, d, J 7.3,

CHMe), 0.81 (3 H, d, J 7.1, CHMe) and 0.32 (6 H, s, SiMe₂);

δ_C(CDCl₃) 139.9, 133.9, 128.8, 127.8, 75.8, 33.7, 31.4, 28.9,

28.8, 21.8, 18.9, 16.9, Ϫ2.0 and Ϫ3.0; 56B: δ_H(400 MHz;

CDCl₃) 7.52 (2 H, m, o-Ph), 7.36–7.29 (3 H, m, m- and p-Ph),

3.15 (1 H, m, CHOH), 2.02–1.89 (1 H, m, CHMe_AMe_B), 1.60–

1.49 (2 H, m), 1.47–1.38 (1 H, m), 1.09–1.04 (1 H, m), 0.95 (3 H,

d, J 6.9, CHMe), 0.86–0.78 (6 H, m, 2 × CHMe), 0.73 (3 H, d, J

6.8, CHMe) and 0.34–0.30 (6 H, m, SiMe₂); δ_C(CDCl₃) 139.9,

133.8, 128.8, 127.8, 75.7, 33.4, 30.5, 28.9, 22.9, 20.7, 19.0, 16.6,

Ϫ2.0 and Ϫ3.0 (Found: C 73.4; H 10.8. C₁₇H₃₀SiO requires C,

73.3; H 10.9%). The ratio of the diastereoisomers was found by

integration of the CHOH signals in the ¹H NMR spectrum.

Reduction of the ketone 31 with sodium Selectride

The ketone 31 (0.108 g, 0.435 mmol) in THF (10 cm³) was

added with stirring to a solution of N-Selectride (1.0 mol dm^Ϫ3

solution in THF; 0.60 cm³, 0.60 mmol) in THF (20 cm³) at 0 ЊC

under argon. The mixture was stirred for 8 h and then quenched

with methanol (10 cm³). The mixture was allowed to warm to

room temperature and the solvent was removed under reduced

pressure. Light petroleum (40 cm³) was added to the residue and

the mixture was cooled to 0 ЊC. Aqueous sodium hydroxide (1

mol dm^Ϫ3; 0.6 cm³) was added to the stirred mixture, followed

by hydrogen peroxide (30% in water; 2 cm³). After 30 min the

mixture was allowed to warm to room temperature and stirred

for a further hour. Water (50 cm³) was added to the mixture and

the organic layer was separated off. The aqueous layer was

extracted with ether (3 × 50 cm³) and the combined organic

fractions were washed with brine (100 cm³), dried (MgSO₄) and

the solvent was evaporated under reduced pressure to give a

mixture of the alcohols 45A and 45B (0.058 g, 53%) after chro-

matography (SiO₂, Et₂O–light petroleum, 30:70).

Reaction of lithium bis[dimethyl(phenyl)silyl]cuprate with á,â-

unsaturated esters and diesters

Reduction of ketones with lithium aluminium hydride

Typically, the ketone (0.682 mmol) in dry ether (15 cm³) was

added with stirring to a suspension of lithium aluminium

hydride (0.026 g, 0.682 mmol) in dry ether (40 cm³) at Ϫ78 or

Ϫ55 ЊC under argon. After 1 h, the reaction was quenched with

methanol (10 cm³) and the mixture allowed to warm to room

temperature. The resulting turbid solution was shaken vigor-

ously with saturated aqueous potassium sodium tartrate (25

cm³), and the aqueous layer was extracted with ether (3 × 25

cm³). The combined organic fractions were washed with brine

(100 cm³), dried (MgSO₄) and evaporated under reduced pres-

sure to give the alcohols. The pairs of alcohols 43 (=40) (86%),

44 (=41) (86%), 45 (=42) (79%), 50 (=47) (81%), 51 (=48) (96%),

52 (=49) (66%), 57 (=54) (78%), 58 (=55) (70%) and 59 (=56)

(76%), identical with the earlier samples, were prepared by this

method.

Typically, dimethyl(phenyl)silyllithium (1.0 mol dm^Ϫ3solution

in THF; 3.9 cm³, 3.9 mmol) was added to a stirred suspension

of copper() cyanide (0.18 g, 2.0 mmol) in THF (15 cm³) at 0 ЊC

under argon. The mixture was stirred at this temperature for 45

min and then cooled to Ϫ78 ЊC. A solution of the α,β-

unsaturated ester or diester (1.54 mmol) in THF (5 cm³) was

added dropwise over 5 min. After stirring for 1 h, the reaction

was quenched with saturated aqueous basic ammonium chlor-

ide (10 cm³) and allowed to warm to room temperature. The

residue was extracted with ether (3 × 25 cm³). The combined

organic fractions were washed with basic ammonium chloride

solution until the washings were no longer blue, then washed

with brine, dried (MgSO₄) and evaporated under reduced pres-

sure. The residue was chromatographed (SiO₂, Et₂O–light

petroleum, 10:90) to give the mixtures of β-silyl esters. The

following compounds were prepared by this method.

Reduction of ketones with sodium borohydride

Methyl (3RS,5RS)-3,5-bis[dimethyl(phenyl)silyl]hexanoate

70A and methyl (3RS,5SR)-3,5-bis[dimethyl(phenyl)silyl]-

hexanoate 70B. (71:29, 84% from 61) (A mixture varying from

71:29 to 86:14 from 62); R_F(Et₂O–light petroleum, 10:90)

0.34; ν_max(ﬁlm)/cm^Ϫ11737 (C᎐O) and 1589 (Ph); 70A: δ (400

MHz; CDCl₃) 7.47–7.30 (10 H, m, 2Ph), 3.49 (3 H, s, OMe),

2.23 (1 H, dd, J 15.4 and 7.1, CH_ACH_BCO₂Me), 2.18 (1 H, dd, J

15.4 and 6.1, CH_ACH_BCO₂Me), 1.54 (1 H, dddd, J 11.3, 7.1, 6.1

and 2.8, CH₂CHSiCH₂), 1.37 (1 H, ddd, J 14.0, 11.3 and 2.6,

CSiCH_ACH_BCSi), 1.24 (1 H, ddd, J 14.0, 11.0 and 2.8, CSiCH_A-

CH_BCSi), 0.87 (1 H, m, MeCHSi), 0.83 (3 H, d, J 5.7, MeCH-

Typically, the ketone (0.397 mmol) in ethanol (10 cm³) was

added with stirring to a suspension of sodium borohydride

(0.105 g, 2.78 mmol) in ethanol (20 cm³) at 0 ЊC or room tem-

perature. After 2 h, the reaction was quenched with dilute

hydrochloric acid (15 cm³). The solvent was evaporated under

reduced pressure, the residue taken up into water (50 cm³) and

extracted with ether (3 × 50 cm³). The combined organic frac-

tions were washed with brine (100 cm³), dried (MgSO₄) and

evaporated under reduced pressure to give the alcohols. The

pairs of alcohols 43 (=40) (97%),¹⁸44 (=41) (90%), 45 (=42)

(78%), 50 (=47) (85%), 51 (=48) (96%), 52 (=49) (81%), 57 (=54)

(58%), 58 (=55) (51%) and 59 (=56) (73%), identical with the

earlier samples, were prepared by this method.

᎐

H

Si), 0.25 (3 H, s, SiMe_AMe_B), 0.24 [3 H, s, SiMe_A_{(or D )}Me_B(or

]

C)

and 0.21 (6 H, s, SiMe_{C ϩ D}or SiMe_AMe_Bϩ SiMe_CMe_D);

δ_C(CDCl₃) 174.7, 138.3, 137.8, 134.0 (2 C), 133.9 (2 C), 129.0,

128.8, 127.7 (2 C), 127.6 (2 C), 51.3, 33.9, 31.3, 18.6, 16.2, 13.0,

Ϫ4.5, Ϫ4.6, Ϫ5.1 and Ϫ5.2; 70B: δ_H(400 MHz; CDCl₃) 3.56 (3

H, s, OMe), 2.34 (1 H, dd, J 15.4 and 9.2, CH_ACH_BCO₂Me),

2.11 (1 H, dd, J 15.4 and 5.3, CH_ACH_BCO₂Me), 1.66 (1 H,

m, CH₂CHSiCH₂), 0.22 (3 H, s, SiMe_AMe_B), 0.21 [3 H, s,

Reduction of ketones with lithium tri-tert-butoxyaluminium

hydride

Typically, the ketone (0.605 mmol) in THF (10 cm³) was added

with stirring to a solution of lithium tri-tert-butoxyaluminium

hydride (1.0 mol dm^Ϫ3solution in THF; 0.85 cm³, 0.85 mmol)

in THF (20 cm³) at 0 ЊC under argon. After 1 h, the reaction

was allowed to warm to room temperature, and after 24 h, the

SiMe_A_{(or D )}Me_{B(or C)}], 0.18 [3 H, s, SiMe_C(or

_{D )}Me_{D (or}

]

B

or

A

or C)

and 0.17 [3 H, s, SiMe_C_{(or A)}Me_{D (or B)}]; δ_C(CDCl₃) 174.4, 138.4,

138.1, 129.0, 127.8, 36.3, 32.9, 20.7, 18.5, 14.3, Ϫ4.0 and Ϫ4.1

1340

J. Chem. Soc., Perkin Trans. 1, 1997

View Article Online

(Found: C, 69.4; H, 8.6. C₂₃H₃₄O₂Si₂requires C, 69.3; H, 8.6%).

The ratio of the diastereoisomers was determined by integra-

tion of the OMe signals in the ¹H NMR spectrum.

CH_AH_BCO₂Me), 1.84–1.81 (2 H, m, CSiCH_AH_BCSi), 1.35 (1 H,

m, CH₂CHSiCH₂), 0.18 (3 H, s, SiMe_AMe_B), 0.14 (3 H, s,

SiMe_CMe_D) and 0.03 (3 H, s, SiMe_CMe_D); δ_C(CDCl₃) 174.0,

142.2, 138.2, 137.4, 134.1, 134.0, 128.1, 127.9, 127.8, 127.7,

127.6, 127.5, 124.4, 51.2, 36.3, 36.0, 29.9, 21.5, Ϫ3.7, Ϫ4.3,

Ϫ4.6 and Ϫ5.8 (Found: M^ϩ, 460.2244. C₂₈H₃₆O₂Si₂requires M,

460.2254). The ratio of the diastereoisomers was determined by

integration of the OMe signals in the ¹H NMR spectrum.

Methyl (3RS,5RS)-3,5-bis[dimethyl(phenyl)silyl]-2-methoxy-

carbonyl-5-phenylpentanoate 75A and methyl (3RS,5SR)-3,5-

bis[dimethyl(phenyl)silyl]-2-methoxycarbonyl-5-phenyl-

Ethyl (3RS,5RS)-3,5-bis[dimethyl(phenyl)silyl]hexanoate and

ethyl (3RS,5SR)-3,5-bis[dimethyl(phenyl)silyl]hexanoate. (86:

14, 46%); R_F(Et₂O–light petroleum, 10:90) 0.34; ν_max(ﬁlm)/

cm^Ϫ11733 (C᎐O) and 1589 (Ph); major isomer (3RS,5RS):

᎐

δ_H(400 MHz; CDCl₃) 7.48–7.30 (10 H, m, 2 × Ph), 3.98 (1 H, dq,

J 14.4 and 7.2, OCH_AH_BCH₃), 3.95 (1 H, dq, J 14.4 and 7.2,

OCH_AH_BCH₃), 2.23 (1 H, dd, J 15.6 and 7.0, CH_ACH_BCO),

2.16 (1 H, dd, J 15.6 and 6.1, CH_ACH_BCO), 1.55 (1 H, m,

CH₂CHSiCH₂), 1.38 (1 H, ddd, J 13.9, 11.5 and 2.6, CSiCH_A-

CH_BCSi), 1.24 (1 H, ddd, J 13.9, 11.1 and 2.8, CSiCH_ACH_B-

CSi), 1.18 (3 H, t, J 7.2, OCH₂CH₃), 0.90 (1 H, m, CH₃CHSi),

0.83 (3 H, d, J 6.4, H₃CCHSi), 0.252 (3 H, s, SiMe_AMe_B),

0.250 [3 H, s, SiMe_A_{(or D )}Me_{B(or C)}] and 0.22 (6 H, s, SiMe_CϩDor

SiMe_AMe_Bϩ SiMe_CMe_D); δ_C(CDCl₃) 174.3, 138.3, 137.9, 134.0

(2 C), 133.9 (2 C), 128.9, 128.8, 127.7 (2 C), 127.6 (2 C), 60.2,

34.2, 31.4, 18.5, 16.2, 14.2, 13.0, Ϫ4.5, Ϫ4.5, Ϫ5.0 and Ϫ5.2;

minor isomer (3RS,5SR): δ_H(400 MHz; CDCl₃) 4.02 (2 H, q, J

7.1, OCH₂CH₃), 2.34 (1 H, dd, J 15.3 and 4.7, CH_ACH_BCO),

2.09 (1 H, dd, J 15.3 and 9.4, CH_ACH_BCO), 1.19 (3 H, t, J 7.1,

OCH₂CH₃), 0.23 (3 H, s, SiMe_AMe_B), 0.22 [3 H, s, SiMe_{A(or D )}

pentanoate 75B. (81%); R_F(Et₂O–light petroleum, 10:90) 0.21;

ν_max(ﬁlm)/cm^Ϫ11735 (C᎐O), 1598 (Ph); 75A: δ (400 MHz;

᎐

H

CDCl₃) 7.42–6.5 (15 H, m, 3 × Ph), 3.57 [1 H, d, J 2.8,

CH(CO₂Me)₂], 3.53 (3 H, s, OMe), 3.49 (3 H, s, OMe), 2.33 (1

H, dd, J 12.6 and 2.3, PhCHSi), 2.00–1.90 (1 H, m, CH_AH_B),

1.60–1.55 [2 H, m, CH_AH_Band SiCHCH(CO₂Me)₂], 0.26 (3 H,

s, SiMe_AMe_B), 0.21 (3 H, s, SiMe_AMe_B), 0.14 (3 H, s, SiMe_C-

Me_D) and 0.11 (3 H, s, SiMe_CMe_D); δ_C(CDCl₃) 170.4, 170.1,

140.7, 138.7, 137.2, 134.2, 134.1, 129.0, 128.8, 128.0, 127.8,

127.5, 124.6, 52.1, 51.9, 50.5, 33.2, 27.1, 23.6, Ϫ2.8, Ϫ4.1, Ϫ4.7

and Ϫ5.5; 75B: δ_H(400 MHz; CDCl₃) 7.42–6.50 (15 H, m,

3 × Ph), 3.57 (3 H, s, OMe), 3.55 (3 H, s, OMe), 3.4 [1 H, d, J

4.5, CH(CO₂Me)₂], 2.14 (1 H, ddd, J 10.7, 5.9 and 2.2, CH_AH_B),

2.11 (1 H, dd, J 12.7 and 2.2, PhCHSi), 2.00–1.90 (1 H, m,

CH_AH_B), 1.60–1.55 [1 H, m, SiCHCH(CO₂Me)₂], 0.20 (3 H, s,

SiMe_AMe_B), 0.17 (3 H, s, SiMe_AMe_B), 0.15 (3 H, s, SiMe_CMe_D)

and 0.04 (3 H, s, SiMe_CMe_D) (Found: M^ϩ, 518.2308.

C₃₀H₃₈O₄Si₂requires M, 518.2308). The ratio of the diastereo-

isomers was determined by integration of the OMe signals in

the ¹H NMR spectrum.

Me_{B(or C)}], 0.17 [3 H, s, SiMe_C(or

_{D )}Me_{D (or}

_C)] and 0.16 [3

B

or

A

or

H, s, SiMe_C_{(or A)}Me_{D (or B)}]; δ_C(CDCl₃) 127.7, 36.5, 32.8, 20.6,

18.6 and Ϫ4.0 (Found: M^ϩ, 412.2255. C₂₄H₃₆O₂Si₂requires M,

412.2231). The ratio of the diastereoisomers was determined by

integration of the SiMe signals in the ¹H NMR spectrum.

Methyl (3RS,5RS)-3,5-bis[dimethyl(phenyl)silyl]-2-methoxy-

carbonylhexanoate

bis[dimethyl(phenyl)silyl]-2-methoxycarbonylhexanoate

(75%); R_F(Et₂O–light petroleum, 20:80) 0.38; ν_max(ﬁlm)/cm^Ϫ1

1735 (C᎐O) and 1589 (Ph); 71A: δ (400 MHz; CDCl ) 7.53–

71A

and

methyl

(3RS,5SR)-3,5-

71B.

Methyl (3RS,5SR)-3,5-bis[dimethyl(phenyl)silyl]-6-methyl-

heptanoate 78A and methyl (3RS,5RS)-3,5-bis[dimethyl-

(phenyl)silyl]-6-methylheptanoate 78B. (71% from 67, 68% from

68); R_F(Et₂O–light petroleum, 5:95) 0.28; ν_max(ﬁlm)/cm^Ϫ11736

᎐

H

3

7.29 (10 H, m, 2Ph), 3.55 (3 H, s, OMe), 3.55 [1 H, d, J 5,

CH(CO₂Me)₂], 3.54 (3 H, s, OMe), 1.88 (1 H, m, CH₂CHSiCH),

1.45 (1 H, ddd, J 14.5, 11.6 and 2.7, CSiCH_ACH_BCSi), 1.23

(1 H, ddd, J 14.5, 11.6 and 3.0, CSiCH_ACH_BCSi), 0.86 (1 H,

m, MeCHSi), 0.74 (3 H, d, J 7.1, MeCHSi), 0.28 (3 H, s,

SiMe_AMe_B), 0.27 [3 H, s, SiMe_A_{(or D )}Me_{B(or C)}], 0.195 [3 H, s,

(C᎐O), 1249 (SiMe) and 1111 (SiPh); 78A: δ (250 MHz;

᎐

H

CDCl₃) 7.42 (2 H, m, o-Ph), 7.37–7.27 (3 H, m, m- and p-Ph),

3.48 (3 H, s, OMe), 2.11 (1 H, dd, J 15.7 and 6.8, CH_AH_B-

CO₂Me), 2.02 (1 H, dd, J 15.6 and 5.9, CH_AH_BCO₂Me), 1.88 (1

H, dseptet, J 2.6 and 6.7, Me_AMe_BCHCHSi), 1.54–1.12 (3 H,

m), 0.94–0.83 (1 H, m), 0.80 (3 H, d, J 6.5, Me_AMe_BCHCHSi),

0.77 (3 H, d, J 6.6, Me_AMe_BCHCHSi), 0.27 (3 H, s, SiMe), 0.25

(3 H, s, SiMe) and 0.23 (6 H, s, 2 × SiMe); δ_C(CDCl₃) 174.6,

140.0, 137.8, 134.0, 133.9, 129.0, 128.6, 127.7, 127.6, 51.4, 34.1,

30.4, 28.1, 27.8, 22.9, 21.1, 20.1, Ϫ1.8, Ϫ2.7, Ϫ4.5 and Ϫ4.6;

78B: δ_H(250 MHz; CDCl₃) 7.42 (2 H, m, o-Ph), 7.37–7.27 (3 H,

m, m- and p-Ph), 3.51 (3 H, s, OMe), 2.25 (1 H, dd, J 15.6 and

6.3, CH_AH_BCO₂Me), 2.14 (1 H, dd, J 15.7 and 6.9, CH_AH_B-

CO₂Me), 1.88 (1 H, m, Me_AMe_BCHCHSi), 1.54–1.12 and 0.94–

0.83 (4 H, m), 0.84 (3 H, d, J 6.9, Me_AMe_BCHCHSi), 0.68 (3 H,

d, J 6.8, Me_AMe_BCHCHSi), 0.23 (3 H, s, SiMe), 0.22 (3 H, s,

SiMe), 0.16 (3 H, s, SiMe) and 0.15 (3 H, s, SiMe); δ_C(CDCl₃)

174.5, 140.0, 137.8, 134.0, 133.9, 129.0, 128.6, 127.7, 127.6,

51.4, 35.1, 31.2, 28.3, 26.9, 21.7, 21.4, 20.9, Ϫ1.8, Ϫ2.7, Ϫ4.4

and Ϫ4.6; m/z (EI) 426 (8%, M^ϩ), 411 (35, M Ϫ Me) and 135

(100, Me₂PhSi) (Found: M^ϩ, 426.2426. C₂₅H₃₈O₂Si requires M,

426.2410). The ratio of diastereoisomers was determined by

integration of the OMe signals in the ¹H NMR spectrum.

Methyl (3RS,5RS)-3,5-bis[dimethyl(phenyl)silyl]-2-methoxy-

carbonyl-6-methylheptanoate 79A and methyl (3RS,5SR)-3,5-

bis[dimethyl(phenyl)silyl]-2-methoxycarbonyl-6-methylheptan-

oate 79B. (82%); R_F(Et₂O–light petroleum, 15:85) 0.28;

ν_max(ﬁlm)/cm^Ϫ11752 (C᎐O), 1736 (C᎐O), 1248 (SiMe) and 1110

SiMe_C(or

_{D )}Me_{D (or}

_C)] and 0.190 [3 H, s, SiMe_C(or

-

B

or

A

or

A)

Me_{D (or}_B)]; δ_C(CDCl₃) 170.4, 170.3, 138.8, 138.1, 134.2 (2 C),

133.9 (2 C), 128.8 (2 C), 127.6 (2 C), 127.5 (2 C), 52.2, 52.0,

51.1, 29.6, 23.1, 16.0, 12.8, Ϫ2.9, Ϫ4.2, Ϫ5.21 and Ϫ5.24; 71B:

δ_H(400 MHz; CDCl₃) 3.61 (3 H, s, OMe), 3.56 (3 H, s, OMe),

3.47 [1 H, d, J 5.1, CH(CO₂Me)₂], 1.82 (1 H, m, CH₂CHSiCH₂),

1.09 (1 H, ddd, J 13.3, 10 and 3.6, CSiCH_ACH_BCSi), 0.78

(3 H, d, J 6.4, MeCHSi), 0.26 (3 H, s, SiMe_AMe_B), 0.22 [3 H, s,

SiMe_A_{(or D )}Me_{B(or C)}], 0.15 [3 H, s, SiMe_C(or

_{D )}Me_{D (or}

]

B

or

A

or C)

and 0.14 [3 H, s, SiMe_C_{(or A)}Me_{D (or B)}]; δ_C(CDCl₃) 170.0, 138.2,

134.1, 128.9, 127.7, 53.6, 30.6, 18.1, 13.7, Ϫ3.5, Ϫ5.1 and Ϫ5.3

(Found: M^ϩ, 456.2149. C₂₅H₃₆O₄Si₂requires M, 456.2152). The

ratio of the diastereoisomers was determined by integration of

the OMe signals in the ¹H NMR spectrum.

Methyl

(3RS,5SR)-3,5-bis[dimethyl(phenyl)silyl]-5-phenyl-

pentanoate 74A and methyl (3RS,5RS)-3,5-bis[dimethyl-

(phenyl)silyl]-5-phenylpentanoate 74B. (59% from 64, 73% from

65);R_F(Et₂O–light petroleum, 8:92) 0.28; ν_max(ﬁlm)/cm^Ϫ11736

(C᎐O) and 1599 (Ph); 74A: δ (400 MHz; CDCl ) 7.40–6.60 (15

᎐

H

3

H, m, 3 × Ph), 3.4 (3 H, s, OMe), 2.38 (1 H, dd, J 12.8 and 3,

PhCHSi), 2.28 (1 H, dd, J 15.0 and 6.4, CH_AH_BCO₂Me), 2.14 (1

H, dd, J 15 and 5.8, CH_AH_BCO₂Me), 1.95 (1 H, ddd, J 14.6,

12.8 and 2.4, CSiCH_AH_BCSi), 1.6 (1 H, ddd, J 14.6, 11.6 and 3,

CSiCH_AH_BCSi), 1.18 (1 H, m, CH₂CHSiCH₂), 0.21 (3 H, s,

SiMe_AMe_B), 0.20 (3 H, s, SiMe_AMe_B), 0.16 (3 H, s, SiMe_CMe_D)

and 0.13 (3 H, s, SiMe_CMe_D); δ_C(CDCl₃) 174.2, 141.6, 137.8,

137.3, 134.1, 134.0, 128.9, 128.2, 127.9, 127.8, 127.6, 127.5,

124.5, 51.1, 33.7, 33.3, 28.5, 19.8, Ϫ4.1, Ϫ4.4, Ϫ5.0 and Ϫ5.4;

74B: δ_H(400 MHz; CDCl₃) 7.4–6.6 (15 H, m, 3 × Ph), 3.52 (3 H,

s, OMe), 2.28 (1 H, dd, J 9.9 and 4.7, PhCHSi), 2.07 (1 H, dd, J

15.2 and 7.5, CH_AH_BCO₂Me), 2.04 (1 H, dd, J 15.2 and 9.8,

᎐

(SiPh); δ_H(250 MHz; CDCl₃) major isomer: 7.54–7.27 (10 H, m,

Ph), 3.66 (3 H, s, OMe), 3.53 (3 H, s, OMe), 3.50 [1 H, m,

CH(CO₂Me)₂], 1.92–1.06 (4 H, m), 0.91 (1 H, m), 0.86–0.57 (6

H, m, Me_AMe_BCH and Me_AMe_BCH), 0.28 (3 H, s, SiMe), 0.25

(3 H, s, SiMe), 0.23 (3 H, s, SiMe) and 0.18 (3 H, s, SiMe);

δ_C(CDCl₃) 52.3 (OMe), 52.1 (OMe) and 24.9 (CH₂); minor iso-

mer: δ_H(250 MHz; CDCl₃) 7.54–7.27 (10 H, m, Ph), 3.55 (3 H, s,

J. Chem. Soc., Perkin Trans. 1, 1997

1341

View Article Online

OMe), 3.50 [1 H, m, CH(CO₂Me)₂], 3.48 (3 H, s, OMe), 1.92–

1.06 (4 H, m), 0.91 (1 H, m), 0.86–0.57 (6 H, m, Me_AMe_BCH

and Me_AMe_BCH), 0.31 (3 H, s, SiMe), 0.27 (3 H, s, SiMe), 0.26

(3 H, s, SiMe) and 0.23 (3 H, s, SiMe); δ_C(CDCl₃) 52.1 (OMe),

50.8 (OMe) and 26.2 (CH₂); m/z (EI) 484 (4%, M^ϩ), 469 (20,

M Ϫ Me), 425 (18, M Ϫ CO₂Me) and 135 (100, Me₂PhSi)

(Found: M^ϩ, 484.2445. C₂₇H₄₀O₄Si₂requires M, 484.2465). The

ratio of diastereoisomers was determined by integration of the

OMe signals in the ¹H NMR spectrum or the CH₂signals in the

¹³C NMR spectrum.

(0.63 mmol) in THF (20 cm³) was added dropwise over 5 min,

and the mixture kept for 1 h. The reaction was quenched with

saturated aqueous ammonium chloride (10 cm³) and allowed to

warm to room temperature. Dilute hydrochloric acid (50 cm³)

was added and the THF was evaporated under reduced pres-

sure. The residue was extracted with dichloromethane (3 × 50

cm³), washed with brine (50 cm³), dried (MgSO₄), evaporated

under reduced pressure and chromatographed (SiO₂, Et₂O–

light petroleum, 5:95) to give a mixture of the esters. The pairs

of esters 78 (63% from 67, 66% from 68) and 79 (68%), identical

with the earlier samples, were prepared by this method. Simi-

larly, the following ester was prepared by this method.

Reaction of lithium dimethyl[dimethyl(phenyl)silyl]zincate with

á,â-unsaturated esters and diesters

Ethyl 3-dimethyl(phenyl)silyl-4-methylpentanoate 87. (80% on

Typically, dimethyl(phenyl)silyllithium (1.05 mol dm^Ϫ3solution

in THF; 2.5 cm³, 2.6 mmol) was added to a stirred solution of

dimethylzinc (2.0 mol dm^Ϫ3solution in toluene; 1.3 cm³, 2.6

mmol) in THF (15 cm³) at 0 ЊC under argon. The mixture was

stirred at this temperature for 10 min and then cooled to

Ϫ78 ЊC. A solution of the α,β-unsaturated ester or diester (2.1

mmol) in THF (5 cm³) was added dropwise over 5 min. After

stirring for 1 h, the reaction was quenched carefully by dropwise

addition of saturated aqueous ammonium chloride (10 cm³)

and allowed to warm to room temperature. Dilute hydrochloric

acid (20 cm³) was added to dissolve the precipitated zinc salts,

and the THF was evaporated under reduced pressure. The resi-

due was extracted with dichloromethane (3 × 25 cm³), the com-

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

and evaporated under reduced pressure. The residue was chro-

matographed (SiO₂, Et₂O–light petroleum 10:90) to give a mix-

ture of the disilyl esters. The pairs of esters 70 (84% from 61,

variable yield from 62), the corresponding ethyl esters (75:25,

60% from the E starting material), 71 (81%), 74 (83% from 64,

76% from 65), 75 (65%), 78 (74% from 67, 68% from 68) and 79

(74%), identical with the earlier samples, were prepared by this

method. Similarly, the following esters and ketones were pre-

pared by this method.

28 mmol scale); R_F(Et₂O–light petroleum, 5:95) 0.25; ν_max-

(ﬁlm)/cm^Ϫ11735 (C᎐O), 1250 (SiPh) and 1111 (SiMe); δ (250

᎐

H

MHz; CDCl₃) 7.52 (2 H, m, o-Ph), 7.38–7.30 (3 H, m, m- and p-

Ph), 4.01 (2 H, q, J 7.1, OCH₂Me), 2.37 (1 H, dd, J 15.9 and 7.7,

CH_ACH_B), 2.28 (1 H, dd, J 15.9 and 6.2, CH_ACH_B), 1.91 (1 H,

m, CHMe_AMe_B), 1.51 (1 H, ddd, J 7.6, 6.2 and 3.9,

CHSiCH_AH_B), 1.20 (3 H, t, J 7.1, MeCH₂O), 0.91 (3 H, d, J 6.8,

CHMe_AMe_B), 0.83 (3 H, d, J 6.9, CHMe_AMe_B), 0.33 (3 H, s,

SiMe_CMe_D) and 0.32 (3 H, s, SiMe_CMe_D); δ_C(CDCl₃) 174.7,

138.8, 133.9, 128.9, 127.7, 60.3, 31.9, 29.2, 28.8, 22.8, 20.9, 14.2,

Ϫ2.6 and Ϫ3.0; m/z (EI) 278 (M^ϩ, 4%), 263 (M Ϫ Me, 69) and

135 (Me₂PhSi, 100) (Found: M^ϩ, 278.1706. C₁₆H₂₆O₂Si requires

M, 278.1702).

Reaction of dimethyl(phenyl)silyllithium with á,â-unsaturated

diesters

Typically, dimethyl(phenyl)silyllithium (0.94 mol dm³solution

in THF; 0.67 cm³, 0.633 mmol) in THF (30 cm³) was added

dropwise over 5 min with stirring to a solution of diester (0.575

mmol) in THF (20 cm³) under argon at Ϫ78 ЊC, and the mixture

kept for 1 h. The reaction was quenched with saturated aqueous

ammonium chloride (15 cm³) and allowed to warm to room

temperature. Dilute hydrochloric acid (50 cm³) was added and

the THF was evaporated under reduced pressure. The residue

was extracted with dichloromethane (3 × 50 cm³), washed with

brine (50 cm³), dried (MgSO₄) and evaporated under reduced

pressure, and chromatographed (SiO₂, Et₂O–light petroleum,

15:85) to give the mixtures of β-silyl diesters. The pairs of

esters 71 (42%), 75 (87%) and 79 (61%), identical with the

earlier samples, were prepared by this method.

Ethyl 3-dimethyl(phenyl)silylbutanoate³⁴85. (96% on a 32

mmol scale); R_F(Et₂O–light petroleum, 10:90) 0.35; ν_max(ﬁlm)/

cm^Ϫ11734 (C᎐O), 1251 (SiMe) and 1112 (SiPh); δ (250 MHz;

᎐

H

CDCl₃) 7.49 (2 H, m, o-Ph), 7.38–7.31 (3 H, m, m- and p-Ph),

4.08 (2 H, q, J 7.1, OCH₂Me), 2.39 (1 H, dd, J 15.2 and 4.1,

CH_ACH_B), 2.05 (1 H, dd, J 15.2 and 11.2, CH_ACH_B), 1.46 (1 H,

m, CHSiCH_AH_B), 1.23 (3 H, t, J 7.1, OCH₂Me), 0.98 (3 H, d, J

7.3, MeCHSi) and 0.29 (6 H, s, SiMe₂).

Ethyl 3-dimethyl(phenyl)silyl-3-phenylpropanoate³⁵86. (98%

on a 31 mmol scale); R_F(Et₂O–light petroleum, 10:90) 0.37;

ν_max(ﬁlm)/cm^Ϫ11740 (C᎐O) and 1599 (Ph); δ (200 MHz;

Reaction of methyllithium with á,â-unsaturated diesters

Typically, the diester (1.56 mmol) in THF (15 cm³) was added

dropwise with stirring to a solution of methyllithium (1.4 mol

dm^Ϫ3solution in ether; 1.45 cm³, 2.03 mmol) in THF (60 cm³) at

Ϫ78 ЊC under argon, and the mixture kept for 1 h. The reaction

was quenched with saturated aqueous ammonium chloride (10

cm³) and allowed to warm to room temperature. Dilute hydro-

chloric acid (15 cm³) was added to the mixture and the THF

was evaporated under reduced pressure. The residue was

extracted with dichloromethane (3 × 25 cm³) and the combined

organic fractions were washed with brine (50 cm³), dried

(MgSO₄), evaporated under reduced pressure and chromato-

graphed (SiO₂, Et₂O–light petroleum, 25:75) to give the mix-

tures of diesters. The following compounds were prepared by

this method.

᎐

H

CDCl₃) 7.48–6.99 (10 H, m, 2 × Ph), 3.50 (3 H, s, OMe), 2.96–

2.64 (3 H, m, SiCH and CH₂CO), 0.30 (3 H, s, SiMe_AMe_B) and

0.26 (3 H, s, SiMe_AMe_B).

4-Dimethyl(phenyl)silyl-4-phenylbutan-2-one³⁶33. (92%);

R_F(CH₂Cl₂–light petroleum, 80:20) 0.39; ν_max(ﬁlm)/cm^Ϫ11718

(C᎐O) and 1599 (Ph); δ (200 MHz; CDCl ) 7.45–6.93 (10 H, m,

᎐

H

3

2 × Ph), 3.00–2.60 (3 H, m, SiCH and CH₂CO), 1.96 (3 H, s,

MeCO), 0.27 (3 H, s, SiMe_AMe_B) and 0.23 (3 H, s, SiMe_AMe_B).

3-Dimethyl(phenyl)silyl-1,3-diphenylpropan-1-one³⁶34. (83%)

Mp 67–69 ЊC; R_F(Et₂O–light petroleum, 15:85) 0.3; ν_max(ﬁlm)/

cm^Ϫ11687 (C᎐O) and 1597 (Ph); δ (200 MHz; CDCl ) 7.83–

᎐

H

3

6.98 (15 H, m, 3 × Ph), 3.51 (1 H, dd, J 17.0 and 10.0, SiCH),

3.28–3.1 (2 H, m, CH₂CO), 0.32 (3 H, s, SiMe_AMe_B) and 0.26 (3

H, s, SiMe_AMe_B).

Methyl

(3RS,5SR)-5-dimethyl(phenyl)silyl-2-methoxycar-

bonyl-3-methylhexanoate 72A and methyl (3RS,5RS)-5-

dimethyl(phenyl)silyl-2-methoxycarbonyl-3-methylhexanoate

72B. (25%); R_F(Et₂O–light petroleum, 25:75) 0.33;

Reaction of lithium trimethyl[dimethyl(phenyl)silyl]aluminate

with á,â-unsaturated esters and the diester 69

ν_max(CH₂Cl₂)/cm^Ϫ11737 (C᎐O), 1249 (SiMe) and 1112 (SiPh);

᎐

Typically, dimethyl(phenyl)silyllithium (1.2 mol dm^Ϫ3solution

in THF; 1.15 cm³, 1.38 mmol) was added with stirring to a

solution of trimethylaluminium (2.0 mol dm^Ϫ3solution in hex-

anes; 0.35 cm³, 0.70 mmol) in THF (30 cm³) at 0 ЊC under

argon. The mixture was stirred at this temperature for 15 min

and then cooled to Ϫ78 ЊC. The α,β-unsaturated ester or diester

72A: δ_H(400 MHz; CDCl₃) 7.48 (2 H, m, o-Ph), 7.40–7.28 (3 H,

m, m- and p-Ph), 3.69 (3 H, s, OMe), 3.62 (3 H, s, OMe), 3.38 [1

H, d, J 5.8, CH(CO₂Me)₂], 2.34 (1 H, m), 1.51 (1 H, m), 1.08 (1

H, m), 0.98 [3 H, d, J 6.8, MeCHCH(CO₂Me)₂], 0.92 (3 H, d, J

1.8, MeCHSi), 0.91 (1 H, m), 0.26 (3 H, s, SiMe_AMe_B) and 0.25

(3 H, s, SiMe_AMe_B); δ_C(CDCl₃) 169.8, 169.0, 138.2, 134.0,

1342

J. Chem. Soc., Perkin Trans. 1, 1997

View Article Online

128.9, 127.7, 54.8, 52.3, 51.9, 36.9, 31.9, 17.9, 16.7, 14.5 and

Ϫ5.0; 72B: δ_H(400 MHz; CDCl₃) 7.48 (2 H, m, o-Ph), 7.40–7.28

(3 H, m, m- and p-Ph), 3.69 (3 H, s, OMe), 3.67 (3 H, s, OMe),

3.16 [1 H, d, J 8.6, CH(CO₂Me)₂], 2.34 (1 H, m), 1.30–1.16 (2 H,

m), 0.92 (3 H, d, J 1.8, MeCHSi), 0.88 [3 H, d, J 5.6, MeCH-

CH(CO₂Me)₂], 0.81 (1 H, m), 0.26 (3 H, s, SiMe_AMe_B) and 0.24

(3 H, s, SiMe_AMe_B); δ_C(CDCl₃) 169.8, 169.2, 138.2, 133.9,

128.9, 127.7, 58.4, 52.3, 52.0, 35.9, 31.1, 17.9, 16.0, 13.0 and

Ϫ5.3; m/z (EI) 336 (9%, M^ϩ), 321 (27, M Ϫ Me) and 135 (100,

Me₂PhSi) (Found: M^ϩ, 336.1756. C₁₈H₂₈O₄Si requires M,

336.1757). The ratio of diastereoisomers was determined by

57.7, 52.2, 52.1, 32.6, 32.0, 30.0, 28.4, 22.2, 21.9, 16.5, Ϫ1.9 and

Ϫ3.0; m/z (EI) 364 (12%, M^ϩ), 349 (52, M Ϫ Me) and 135 (100,

Me₂PhSi) (Found: M^ϩ, 364.2069. C₂₀H₃₂O₄Si requires M,

364.2070). The ratio of diastereoisomers was determined by

integration of the CH(CO₂Me)₂signals in the ¹H NMR

spectrum.

Reaction of methylmagnesium bromide with á,â-unsaturated

diesters

Typically, the diester (1.56 mmol) in THF (10 cm³) was added

dropwise with stirring to a solution of methylmagnesium brom-

ide (3 mol dm^Ϫ3in Et₂O; 0.7 cm³, 2.03 mmol) in THF (60 cm³)

at 0 ЊC under argon and the mixture kept for 2 h. The reaction

was quenched with saturated aqueous ammonium chloride (10

cm³) and allowed to warm to room temperature. Dilute hydro-

chloric acid (15 cm³) was added to the mixture and the THF

was evaporated under reduced pressure. The residue was

extracted with dichloromethane (3 × 25 cm³) and the combined

organic fractions were washed with brine (50 cm³), dried

(MgSO₄), evaporated under reduced pressure and chromato-

graphed (SiO₂, Et₂O–light petroleum, 25:75) to give mixed

diesters. The pairs of esters 72 (23%), 76 (58%) and 80 (57%),

identical with the earlier samples, were prepared by this

method. A by-product in the reaction with the ester 63 was the

deconjugated starting material methyl 5-dimethyl(phenyl)silyl-

2-methoxycarbonylhex-3-enoate (47%); R_F(Et₂O–light petrol-

eum, 15:85) 0.20; ν_max(CH₂Cl₂)/cm^Ϫ11738 (C᎐O), 1652 (C᎐C),

1

integration of the CH(CO₂Me)₂signals in the H NMR spec-

trum. In addition to the esters 72 produced from 1,4-addition

of methyllithium to 63, 1,2-addition also occurred to give the

tertiary alcohol 1,1-dimethyl-5-dimethyl(phenyl)silyl-2-methoxy-

carbonylhex-2-en-1-ol (18%); R_F(Et₂O–light petroleum, 25:75)

0.12; ν_max(ﬁlm)/cm^Ϫ13448 (OH), 1719 (C᎐O), 1648 (C᎐C), 1249

᎐

(SiMe) and 1112 (SiPh); δ_H(250 MHz; CDCl₃) 7.49 (2 H, m, o-

Ph), 7.39–7.31 (3 H, m, m- and p-Ph), 5.93 (1 H, dd, J 7.7 and

7.3, CHCCO₂Me), 3.67 (3 H, s, OMe), 2.32 (1 H, ddd, J 14.9,

7.3 and 4.4, CH_AH_B), 2.04 (1 H, ddd, J 14.9, 8.8 and 7.7,

CH_AH_B), 1.34 (6 H, s, CMe₂OH), 0.98 (1 H, m, MeCHSi), 0.95

(3 H, d, J 5.1, MeCHSi), 0.27 (3 H, s, SiMe_AMe_B) and 0.26 (3 H,

s, SiMe_AMe_B); δ_C(CDCl₃) 169.8, 139.6, 138.2, 135.0, 134.0,

129.0, 127.9, 71.7, 51.3, 31.5, 29.3, 29.2, 20.2, 14.3, Ϫ4.6 and

Ϫ5.3; m/z (EI) 305 (29%, M^ϩϪ Me), 302 (56, M Ϫ H₂O), 135

(100, Me₂PhSi) (Found: M^ϩϪ H₂O, 302.1688. C₁₈H₂₈O₃Si

requires M Ϫ H₂O, 302.1702).

᎐

1250 (SiMe) and 1112 (SiPh); δ_H(250 MHz; CDCl₃) 7.47 (2 H,

m, o-Ph), 7.39–7.30 (3 H, m, m- and p-Ph), 5.70 (1 H, dd, J 15.5

and 7.6, CHSiCH), 5.44 [1 H, ddd, J 15.5, 8.9 and 1.3,

CHCH(CO₂Me)₂], 4.00 [1 H, d, J 8.9, CH(CO₂Me)₂], 3.74 (3 H,

s, OMe), 3.73 (3 H, s, OMe), 1.88 (1 H, ddq, J 7.6, 1.3 and 7.1,

MeCHSi), 1.06 (3 H, d, J 7.1, MeCHSi), 0.26 (3 H, s, SiMe_A-

Me_B) and 0.25 (3 H, s, SiMe_AMe_B); δ_C(CDCl₃) 169.0, 139.8,

137.3, 134.0, 129.1, 127.8, 117.5, 55.6, 52.6, 26.3, 13.3, Ϫ5.1

and Ϫ5.3; m/z (EI) 320 (28%, M^ϩ), 261 (92, M Ϫ CO₂Me), 135

(97, Me₂PhSi) (Found: M^ϩ, 320.1446. C₁₇H₂₄SiO₄requires M,

320.1444). This compound could also be made deliberately

(85%) by treating the diester 63 (4.7 mmol) with DABCO

(4.7 mmol) in dichloromethane (50 cm³) at room temperature

for 24 h.

Methyl

(3RS,5RS)-5-dimethyl(phenyl)silyl-2-methoxycar-

bonyl-3-methyl-5-phenylpentanoate 76A and methyl (3RS,5SR)-

5-dimethyl(phenyl)silyl-2-methoxycarbonyl-3-methyl-5-phenyl-

pentanoate 76B. (67%); R_F(Et₂O–light petroleum, 10:90) 0.20;

ν_max(ﬁlm)/cm^Ϫ11735 (C᎐O), 1598 (Ph); from which 76A could

᎐

be separated after a second chromatography stage as cubes, mp

72–74 ЊC (from light petroleum); δ_H(400 MHz; CDCl₃) 7.40–

6.90 (10 H, m, 2 × Ph), 3.59 (3 H, s, OMe), 3.58 (3 H, s, OMe),

3.36 [1 H, d, J 5.9, CH(CO₂Me)₂], 2.30 (1 H, dd, J 11.6 and 3.6,

CHSi), 2.15 (1 H, m, CHMe), 1.84 (1 H, ddd, J 14.5, 11.6 and

5.4, CH_AH_B), 1.74 (1 H, ddd, J 14.5, 8.3 and 3.6, CH_AH_B), 0.87

(3 H, d, J 6.8, MeCH), 0.23 (3 H, s, SiMe_AMe_B) and 0.15 (3 H, s,

SiMe_AMe_B); δ_C(CDCl₃) 169.4, 169.0, 142.3, 137.2, 134.1, 129.0,

128.2, 127.8, 127.6, 124.7, 54.3, 52.1, 51.9, 34.2, 34.1, 32.8, 17.7,

Ϫ4.1 and Ϫ5.5; 76B: 7.4–6.9 (10 H, m, 2 × Ph), 3.70 (3 H, s,

OMe), 3.6 (3 H, s, OMe), 3.16 [1 H, d, J 8.0, CH(CO₂Me)₂],

2.37 (1 H, dd, J 13.2 and 3.2, CHSi), 2.09 (1 H, m, CHMe), 1.99

(1 H, dt, J 2.9 and 13.5, CH_AH_B), 1.42 (1 H, ddd, J 13.9, 11.0

and 3.2, CH_AH_B), 0.82 (3 H, d, J 6.7, CHMe) and 0.21 (6 H, s,

SiMe_AMe_B) (Found: M^ϩ, 398.1912. C₂₃H₃₀O₄Si requires M,

398.1913). The ratio of the diastereoisomers was determined

Reaction of lithium trimethylzincate with á,â-unsaturated

diesters

Typically, methyllithium (1.4 mol dm^Ϫ3solution in Et₂O; 1.0

cm³, 1.40 mmol) was added with stirring to a solution of

dimethylzinc (2.0 mol dm^Ϫ3solution in toluene; 0.35 cm³, 0.70

mmol) in THF (30 cm³) at 0 ЊC under argon. The mixture was

stirred at this temperature for 15 min and then cooled to

Ϫ78 ЊC. A solution of the diester (0.625 mmol) in THF (20 cm³)

was added dropwise over 5 min, and the mixture kept for 1 h.

The reaction was quenched with saturated aqueous ammonium

chloride (10 cm³) and allowed to warm to room temperature.

Dilute hydrochloric acid (30 cm³) was added and the THF was

evaporated under reduced pressure. The residue was extracted

with dichloromethane (3 × 50 cm³), washed with brine (50 cm³),

dried (MgSO₄), the solvent evaporated under reduced pressure

and the residue chromatographed (SiO₂, Et₂O–light petroleum,

25:75) to give the mixtures of diesters. The pairs of esters

72 (70%), 76 (66%) and 80 (76%), identical with the earlier

samples, were prepared by this method.

1

by integration of the CH(CO₂Me)₂signals in the H NMR

spectrum.

Methyl

(3RS,5RS)-3,6-dimethyl-5-dimethyl(phenyl)silyl-2-

methoxycarbonylheptanoate 80A and methyl (3RS,5SR)-3,6-

dimethyl-5-dimethyl(phenyl)silyl-2-methoxycarbonylheptanoate

80B. (28%); R_F(Et₂O–light petroleum, 15:85) 0.23;

ν_max(CH₂Cl₂)/cm^Ϫ11750 (C᎐O), 1736 (C᎐O), 1249 (SiMe) and

᎐

1110 (SiPh); 80A: δ_H(250 MHz; CDCl₃) 7.51 (2 H, m, o-Ph),

7.37–7.29 (3 H, m, m- and p-Ph), 3.71 (3 H, s, OMe), 3.65 (3 H,

s, OMe), 3.22 [1 H, d, J 6.9, CH(CO₂Me)₂], 2.19 (1 H, m), 1.93

(1 H, m), 1.46 (1 H, m, CH_AH_B), 1.28 (1 H, m, CH_AH_B), 1.11 (1

H, m, CHSi), 0.94–0.73 (9 H, m, 3 × CHMe), 0.34 (3 H, s,

SiMe_AMe_B) and 0.32 (3 H, s, SiMe_AMe_B); δ_C(CDCl₃) 169.5,

169.0, 139.3, 133.9, 128.7, 127.7, 57.0, 52.3, 52.2, 32.7, 30.9,

30.0, 28.6, 22.5, 20.6, 16.8, Ϫ2.5 and Ϫ2.6; 80B: δ_H(250 MHz;

CDCl₃) 7.51 (2 H, m, o-Ph), 7.37–7.29 (3 H, m, m- and p-Ph),

3.69 (3 H, s, OMe), 3.68 (3 H, s, OMe), 3.15 [1 H, d, J 8.0,

CH(CO₂Me)₂], 2.19 (1 H, m), 1.93 (1 H, m), 1.46 (1 H, m,

CH_AH_B), 1.28 (1 H, m, CH_AH_B), 0.96 (1 H, m, CHSi), 0.94–0.73

(9 H, m, 3 ×CHMe), 0.31 (3 H, s, SiMe_AMe_B) and 0.29 (3 H, s,

SiMe_AMe_B); δ_C(CDCl₃) 169.3, 169.1, 139.2, 133.9, 128.7, 127.7,

Reaction of dilithium cyanodimethylcuprate with á,â-unsaturated

diesters

Typically, methyllithium (1.4 mol dm^Ϫ3solution in Et₂O; 1.2

cm³, 1.68 mmol) was added to a stirred suspension of pre-dried

copper() cyanide (0.073 g, 0.813 mmol) in THF (30 cm³) at 0 ЊC

under argon. The mixture was stirred at this temperature for 45

min and then cooled to Ϫ78 ЊC. The diester (0.625 mmol) in

THF (20 cm³) was added dropwise over 5 min and the mixture

J. Chem. Soc., Perkin Trans. 1, 1997

1343

View Article Online

kept for 1 h. The reaction was quenched with saturated basic

aqueous ammonium chloride (50 cm³) and allowed to warm to

room temperature. The mixture was extracted with ether

(3 × 50 cm³), the combined organic fractions were washed with

basic aqueous ammonium chloride until the washings were no

longer blue (3 × 50 cm³), washed with brine (50 cm³), dried

(MgSO₄), and the solvent evaporated off under reduced pres-

sure. The residue was chromatographed (SiO₂, Et₂O–light

petroleum, 25:75) to give the mixture of diesters. The pairs

of esters 72 (62%), 76 (63%) and 80 (88%), identical with the

earlier samples, were prepared by this method.

Methyl

(3RS,5RS)-5-dimethyl(phenyl)silyl-3,5-diphenyl-2-

methoxycarbonylpentanoate 77A and methyl (3RS,5SR)-5-

dimethyl(phenyl)silyl-3,5-diphenyl-2-methoxycarbonylpentan-

oate 77B. (89%) The major isomer 77B could be separated by

crystallisation as prisms, mp 98–100 ЊC (from light petroleum);

R_F(Et₂O–light petroleum, 10:90) 0.17; ν_max(ﬁlm)/cm^Ϫ11737

(C᎐O), 1598 (Ph) and 1494 (Ph); 77A: δ (400 MHz; CDCl )

᎐

H

3

7.36–6.70 (15 H, m, 3 × Ph), 3.66 (3 H, s, OMe), 3.57 [1 H, d, J

10.8, CH(CO₂Me)₂], 3.36 (3 H, s, OMe), 3.36 [1 H, m, CHPh-

CH(CO₂Me)₂], 2.27 (1 H, m, CH_AH_B), 2.18–2.10 (2 H, m,

CH_AH_Band CHSi), 0.26 (3 H, s, SiMe_AMe_B) and 0.10 (3 H, s,

SiMe_AMe_B); 77B: δ_H(400 MHz; CDCl₃) 7.36–6.70 (15 H, m,

3 × Ph), 3.72 (3 H, s, OMe), 3.55 [1 H, d, J 10.8, CH(CO₂Me)₂],

3.3 (3 H, s, OMe), 3.2 [1 H, dt, J 10.8 and 2.6, CHPhCH-

(CO₂Me)₂], 2.15 (1 H, m, CH_AH_B), 1.89–1.82 (2 H, m, CH_AH_Bϩ

CHSi), 0.18 (3 H, s, SiMe_AMe_B) and 0.01 (3 H, s, SiMe_AMe_B);

δ_C(CDCl₃) 168.6, 168.1, 141.1, 139.8, 137.2, 134.0, 129.0, 128.5,

128.2, 128.1, 127.8, 127.6, 126.9, 124.8, 58.6, 52.4, 52.0, 43.7,

33.0, 32.7, Ϫ3.8 and Ϫ5.95 (Found: M^ϩ, 460.2070. C₂₈H₃₂O₄Si

requires M, 460.2070). The ratio of the diastereoisomers was

determined by integration of the SiMe signals in the ¹H NMR

spectrum.

Reaction of lithium tetramethylaluminate with the á,â-

unsaturated diester 69

Methyllithium (1.4 mol dm^Ϫ3solution in Et₂O; 1.1 cm³, 1.54

mmol) was added with stirring to trimethylaluminium (2.0 mol

dm^Ϫ3solution in hexanes; 0.38 cm³, 0.76 mmol) in THF (30

cm³) at 0 ЊC under argon. The mixture was stirred at this tem-

perature for 20 min and then cooled to Ϫ78 ЊC. A solution of

diester 69 (0.2 g, 0.575 mmol) in THF (20 cm³) was added

dropwise over 5 min. After 1 h, the reaction was quenched with

saturated aqueous ammonium chloride (15 cm³) and allowed to

warm to room temperature. Dilute hydrochloric acid (50 cm³)

was added and the THF was evaporated under reduced pres-

sure. The residue was extracted with dichloromethane (3 × 50

cm³), the extracts were washed with brine (50 cm³), dried

(MgSO₄), evaporated under reduced pressure and the residue

chromatographed (SiO₂, Et₂O–light petroleum, 15:85) to give

the mixture of esters 80 (0.105 g, 50%), identical with the earlier

samples.

Methyl

(3RS,5RS)-5-dimethyl(phenyl)silyl-2-methoxycar-

bonyl-6-methyl-3-phenylheptanoate 81A and methyl (3RS,5SR)-

5-dimethyl(phenyl)silyl-2-methoxycarbonyl-6-methyl-3-phenyl-

heptanoate 81B. (83%); R_F(Et₂O–light petroleum, 20:80) 0.39;

ν_max(ﬁlm)/cm^Ϫ11758 (C᎐O), 1739 (C᎐O), 1494 (Ph) and 1454

᎐

(Ph); 81A: δ_H(400 MHz; CDCl₃) 7.52–6.73 (10 H, m, 2 × Ph),

3.77 (3 H, s, OMe), 3.51 [1 H, d, J 10.9, CH(CO₂Me)₂], 3.33 (3

H, s, OMe), 3.24 (1 H, dt, J 10.9 and 4.4, CHPh), 1.8–1.56 [3

H, m, CH_AH_Band CH(Me)₂], 0.71 (1 H, d, J 6.9, Me_AMe_B-

CH), 0.64 (3 H, d, J 6.8, Me_AMe_BCH), 0.56 (1 H, dt, J 2.7

and 9.9, CHSi), 0.45 (3 H, s, SiMe_AMe_B) and 0.29 (3 H, s,

SiMe_AMe_B); 81B: δ_H(400 MHz; CDCl₃) 7.52–6.73 (10 H, m,

2 × Ph), 3.74 (3 H, s, OMe), 3.56–3.49 [2 H, m, CH(CO₂Me)₂

and CHPh], 3.35 (3 H, s, OMe), 2.06 [1 H, dseptet, J 2.4 and

7.0, CH(CH₃)₂], 1.80–1.56 (2 H, m, CH_AH_B), 0.98 (3 H, d,

J 6.9, Me_AMe_BCH), 0.84 (3 H, d, J 7.1, Me_AMe_BCH), 0.62

(1 H, m, CHSi), 0.19 (3 H, s, SiMe_AMe_B) and 0.18 (3 H, s,

SiMe_AMe_B); δ_C(CDCl₃) 168.6, 139.7, 139.4, 133.8, 128.6, 128.5,

128.2, 127.9, 127.7, 127.5, 126.7, 59.0, 52.6, 44.5, 31.6, 29.3,

27.9, 23.0, 21.7, Ϫ1.4 and Ϫ3.2 (Found: M^ϩ, 426.2234.

C₂₅H₃₄O₄Si requires M, 426.2226). The ratio of the diastereo-

isomers was determined by integration of the SiMe signals in

the ¹H NMR spectrum.

Reaction of phenyllithium with á,â-unsaturated diesters

Typically, the diester (0.50 mmol) in THF (5 cm³) was added

dropwise with stirring to a solution of phenyllithium (1.8 mol

dm^Ϫ3solution in cyclohexane–Et₂O; 0.36 cm³, 0.65 mmol) in

THF (12 cm³) at Ϫ78 ЊC under argon, and the mixture kept for

1 h. The reaction was quenched with saturated aqueous ammo-

nium chloride (5 cm³) and allowed to warm to room temperature.

Dilute hydrochloric acid (15 cm³) was added to the mixture and

the THF was evaporated under reduced pressure. The residue

was extracted with dichloromethane (3 × 25 cm³) and the com-

bined organic fractions were washed with dilute aqueous sodium

hydroxide (50 cm³), brine (50 cm³), dried (MgSO₄), evaporated

under reduced pressure and the residue chromatographed (SiO₂,

Et₂O–light petroleum, 25:75) to give a mixture of the diesters.

The following compounds were prepared by this method.

Methyl

(3RS,5SR)-5-dimethyl(phenyl)silyl-2-methoxycar-

Reaction of phenylmagnesium bromide with á,â-unsaturated

diesters

bonyl-3-phenylhexanoate 73A and methyl (3RS,5RS)-5-

dimethyl(phenyl)silyl-2-methoxycarbonyl-3-phenylhexanoate

73B. (61%); R_F(Et₂O–light petroleum, 25:75) 0.27;

Typically, a stirred solution of the diester (0.606 mmol) in dry

THF (50 cm³) was added to phenylmagnesium bromide (3 mol

dm^Ϫ3solution in Et₂O; 0.3 cm³, 0.9 mmol) at 0 ЊC under argon

and the mixture kept for 1.5 h at 0 ЊC. The reaction was

quenched with saturated aqueous ammonium chloride (15 cm³)

and allowed to warm to room temperature. The mixture was

extracted with ether (3 × 15 cm³). The organic layers were com-

bined, washed with brine, dried (MgSO₄), evaporated under

reduced pressure and chromatographed (SiO₂, Et₂O–light pet-

roleum, 20:80) to give a mixture of the diesters. The pairs of

esters 77 (77%) and 81 (85%), identical with the earlier samples,

were prepared by this method.

ν_max(CH₂Cl₂)/cm^Ϫ11740 (C᎐O), 1250 (SiMe) and 1113 (SiPh);

᎐

73A: δ_H(400 MHz; CDCl₃) 7.50 (1 H, m, Ph), 7.40–7.16 (7 H, m,

Ph), 7.10–7.01 (2 H, m, Ph), 3.70 (3 H, s, OMe), 3.53 [1 H, d, J

10.2, CH(CO₂Me)₂], 3.38 (3 H, s, OMe), 3.37 (1 H, m, CHPh),

1.73 (1 H, m, CH_AH_B), 1.60–1.47 (1 H, m, CH_AH_B), 0.76 (1 H,

m, MeCHSi), 0.75 (3 H, s, MeCHSi), 0.31 (3 H, s, SiMe_AMe_B)

and 0.28 (3 H, s, SiMe_AMe_B); δ_C(CDCl₃) 168.3, 168.1, 141.3,

138.5, 134.1, 128.9, 128.5, 128.4, 128.3, 126.9, 59.1, 52.5, 52.1,

45.6, 37.3, 17.7, 16.5, Ϫ4.5 and Ϫ4.9; 73B: δ_H(400 MHz;

CDCl₃) 7.50 (1 H, m, Ph), 7.40–7.16 (7 H, m, Ph), 7.10–7.01 (2

H, m, Ph), 3.73 (3 H, s, OMe), 3.60–3.47 [2 H, m, CH(CO₂Me)₂

and CHPh], 3.38 (3 H, s, OMe), 1.76 (1 H, m, CH_AH_B), 1.35 (1

H, m, CH_AH_B), 0.97 (3 H, d, J 7.3, MeCHSi), 0.55 (1 H, m,

MeCHSi), 0.18 (3 H, s, SiMe_AMe_B) and 0.14 (3 H, s, SiMe_A-

Me_B); δ_C(CDCl₃) 168.8, 168.3, 140.0, 137.9, 134.1, 128.9, 128.5,

128.3, 128.2, 126.9, 59.1, 52.5, 52.2, 43.4, 35.0, 15.4, 12.8, Ϫ4.7

and Ϫ5.8; m/z (EI) 398 (4%, M^ϩ), 383 (36, M Ϫ Me) and 135

(100, Me₂PhSi) (Found: M^ϩ, 398.1898. C₂₃H₃₀O₄Si requires M,

398.1913). The ratio of diastereoisomers was determined by

integration of the SiMe_AMe_Bsignals in the ¹H NMR spectrum.

Reaction of lithium dimethyl(phenyl)zincate with á,â-unsaturated

diesters

Typically, phenyllithium (1.8 mol dm^Ϫ3solution in cyclo-

hexane–Et₂O; 0.76 cm³, 1.37 mmol) was added to a stirring

solution of dimethylzinc (2.0 mol dm^Ϫ3solution in toluene;

0.35 cm³, 0.70 mmol) in THF (30 cm³) at 0 ЊC under argon. The

mixture was stirred at this temperature for 15 min and then

cooled to Ϫ78 ЊC. A solution of diester (0.625 mmol) in THF

(20 cm³) was added dropwise over 5 min, and the mixture kept

1344

J. Chem. Soc., Perkin Trans. 1, 1997

View Article Online

for 1 h. The reaction was quenched with saturated aqueous

ammonium chloride (10 cm³) and allowed to warm to room

temperature. Dilute hydrochloric acid (30 cm³) was added and

the THF was evaporated under reduced pressure. The residue

was extracted with dichloromethane (3 × 50 cm³), washed with

dilute sodium hydroxide (50 cm³), brine (50 cm³), dried

(MgSO₄), evaporated under reduced pressure and chromato-

graphed (SiO₂, Et₂O–light petroleum, 25:75) to give a mixture

of diesters. The pairs of esters 73 (65%), 77 (68%) and 81 (89%),

identical with the earlier samples, were prepared by this

method.

and 3.2, CH_ACH_BCHO), 1.50 (1 H, m, HCSi), 0.98 (3 H, d, J

7.3, MeCHSi) and 0.30 (6 H, s, SiMe₂); δ_C(CDCl₃) 203.2, 137.1,

133.9, 129.3, 127.9, 46.0, 14.6, 13.9, Ϫ4.9 and Ϫ5.3 (Found:

M^ϩ, 206.1117. C₁₂H₁₈OSi requires M, 206.1127).

3-Dimethyl(phenyl)silyl-3-phenylpropanal ³⁴

32.

(82%);

R_F(Et₂O–light petroleum, 20:80) 0.42; δ_H(200 MHz; CDCl₃)

9.6 (1 H, s, CHO), 7.45–6.97 (10 H, m, 2 × Ph), 2.94–2.62 (3 H,

m SiCH and CH₂CO), 0.30 (3 H, s, SiMe_AMe_B) and 0.28 (3 H, s,

SiMe_AMe_B).

3-Dimethyl(phenyl)silyl-4-methylpentanal

R_F(Et₂O–light petroleum, 10:90) 0.35; ν_max(ﬁlm)/cm^Ϫ11723

(C᎐O), 1250 (SiMe) and 1111 (SiPh); δ (250 MHz; CDCl ) 9.62

36.

(80%);

᎐

H

3

Reaction of dilithium cyanodiphenylcuprate with á,â-unsaturated

diesters

(1 H, dd, J 2.5 and 1.8, CHO), 7.50 (2 H, m, o-Ph), 7.39–7.30 (3

H, m, m- and p-Ph), 2.46 (1 H, ddd, J 17.2, 7.7 and 2.5,

CH_ACH_BCHO), 2.34 (1 H, ddd, J 17.2, 5.4 and 1.8, CH_ACH_B-

CHO), 1.92 (1 H, m, CHMe_AMe_B), 1.54 (1 H, ddd, J 7.7, 5.4

and 3.9, CHSiCH_AH_B), 0.90 (3 H, d, J 6.8, CHMe_AMe_B), 0.83

(3 H, d, J 6.9, CHMe_AMe_B), 0.35 (3 H, s, SiMe_CMe_D) and 0.33

(3 H, s, SiMe_CMe_D); δ_C(CDCl₃) 203.6, 138.4, 133.9, 129.1,

127.9, 41.5, 28.7, 27.0, 23.3, 20.9, Ϫ2.5 and Ϫ3.2; m/z (EI) 234

(M^ϩ, 3%), 219 (M Ϫ Me, 77) and 135 (Me₂PhSi, 100) (Found:

M^ϩ, 234.1440. C₁₄H₂₂OSi requires M, 234.1440).

Typically, phenyllithium (1.8 mol dm^Ϫ3solution in

cyclohexane–Et₂O; 0.9 cm³, 1.63 mmol) was added to a stirred

suspension of pre-dried copper() cyanide (0.073 g, 0.813

mmol) in THF (30 cm³) at 0 ЊC under argon. The mixture was

stirred at this temperature for 45 min and then cooled to

Ϫ78 ЊC. A solution of the diester (0.625 mmol) in THF (20 cm³)

was added dropwise over 5 min, and the mixture kept for 1 h.

The reaction was quenched with saturated basic aqueous

ammonium chloride (10 cm³) and the mixture allowed to warm

to room temperature. The mixture was extracted with ether

(3 × 50 cm³). The combined organic fractions were washed with

basic aqueous ammonium chloride until the washings were no

longer blue (3 × 50 cm³), washed with dilute sodium hydroxide

(50 cm³) and brine (50 cm³), dried (MgSO₄), evaporated under

reduced pressure and the residue chromatographed (SiO₂,

Et₂O–light petroleum, 25:75) to give a mixture of diesters. The

pairs of esters 73 (62%), 77 (96%) and 81 (62%), identical with

the earlier samples, were prepared by this method.

Preparation of the ketones 29 and 30 by PCC oxidation

Typically, PCC on alumina³⁷(5.0 g, 5 mmol) was stirred with

the diastereoisomeric mixture of alcohols (2.43 mmol) in light

petroleum (15 cm³) at room temperature for 8 h, after which

complete consumption of the starting alcohols had occurred

(TLC). The mixture was ﬁltered through Celite and the residue

was washed with light petroleum. The solvent was evaporated

under reduced pressure and the residue was chromatographed

(SiO₂, CH₂Cl₂) to give the ketone. The following known ketones

were prepared by this method.

Reaction of lithium trimethyl(phenyl)aluminate with the á,â-

unsaturated diester 69

4-Dimethyl(phenyl)silylpentan-2-one³⁴29. (60%); R_F(CH₂Cl₂)

0.48; ν_max(ﬁlm)/cm^Ϫ11717 (C᎐O), 1247 (SiMe) and 1112 (SiPh);

᎐

Phenyllithium (0.63 cm³; 1.8 mol dm³solution in cyclohexane–

ether) was added with stirring to a solution of trimethylalu-

minium (2.0 mol dm³solution in toluene; 0.28 cm³, 0.57 mmol)

in THF (30 cm³) at 0 ЊC under argon. The mixture was stirred at

this temperature for 15 min and then cooled to Ϫ78 ЊC. A solu-

tion of the diester 69 (0.099 g, 0.284 mmol) in THF (20 cm³)

was added dropwise over 5 min, and the mixture kept for 1 h.

The reaction was quenched with saturated aqueous ammonium

chloride (25 cm³) and allowed to warm to room temperature.

Dilute hydrochloric acid (15 cm³) was added to dissolve the

aluminium salts, and the residue was extracted with ether

(3 × 25 cm³). The combined organic fractions were washed with

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

chromatographed (SiO₂, Et₂O–light petroleum, 20:80) to give a

mixture of the two esters 81 (0.097 g, 80%).

δ_H(250 MHz; CDCl₃) 7.48 (2 H, m, o-Ph), 7.39–7.32 (3 H, m, m-

and p-Ph), 2.41 (1 H, dd, J 16.3 and 3.5, CH_AH_B), 2.17 (1 H, dd,

J 16.3 and 10.9, CH_AH_B), 1.49 (1 H, ddq, J 10.9, 3.5 and 7.3,

MeCHSi), 0.92 (3 H, d, J 7.3, MeCHSi) and 0.27 (6 H, s,

SiMe₂).

3-Dimethyl(phenyl)silyl-1-phenylbutan-1-one³⁸30. As needles,

mp 84 ЊC (from light petroleum) (60%); R_F(CH₂Cl₂) 0.60;

ν_max(CH₂Cl₂)/cm^Ϫ11682 (C᎐O), 1265 (SiMe) and 1112 (SiPh);

᎐

δ_H(250 MHz; CDCl₃) 7.82 (2 H, m, Ph), 7.58–7.47 (3 H, m, Ph),

7.45–7.34 (5 H, m, Ph), 3.00 (1 H, dd, J 15.8 and 3.3, CH_AH_B),

2.65 (1 H, dd, J 15.8 and 10.9, CH_AH_B), 1.61 (1 H, ddq, J 10.9,

3.3 and 7.3, MeCHSi), 0.98 (3 H, d, J 7.3, MeCHSi), 0.54 (3 H,

s, SiMe_AMe_B) and 0.53 (3 H, s, SiMe_AMe_B).

Preparation of the ketones 31, 35 and 37–39 by chromium(VI)

oxidation

Preparation of the aldehydes 28, 32 and 36

Typically, chromium() oxide (26.7 g) was added to concen-

trated sulfuric acid (23 cm³), and the mixture was diluted care-

fully to 100 cm³with water at 0 ЊC. The reagent was then added

dropwise with stirring to a mixture of the diastereoisomeric

alcohols (9.9 mmol) in acetone (30 cm³) at 0 ЊC. When a per-

manent orange–brown colour was obtained the addition was

stopped. Water (100 cm³) was added, and the solution was

extracted with ether (3 × 100 cm³). The combined organic

layers were washed with brine (100 cm³), dried (MgSO₄) and

evaporated under reduced pressure. The residue was chromato-

graphed (SiO₂, Et₂O–light petroleum, 10:90) to give the ketone.

The following new ketones were prepared by this method.

2-Methyl-5-dimethyl(phenyl)silylhexan-3-one 31. (77%);

R_F(Et₂O–light petroleum, 10:90) 0.40; ν_max(ﬁlm)/cm^Ϫ11711

Typically, diisobutylaluminium hydride (1.0 mol dm^Ϫ3solution

in hexanes; 43.7 cm³, 43.7 mmol) in toluene (15 cm³) was added

dropwise over 30 min to a stirred solution of the ester 85, 86 or

87 (33.6 mmol) in toluene (80 cm³) at Ϫ78 ЊC under argon. The

mixture was stirred for a further 1 h, quenched with methanol

(20 cm³) and allowed to warm to room temperature. The result-

ing turbid solution was shaken vigorously with saturated aque-

ous potassium sodium tartrate (100 cm³). The aqueous layer

was further extracted with light petroleum (3 × 50 cm³) and the

combined organic fractions were washed with brine (100 cm³),

dried (MgSO₄) and evaporated under reduced pressure. The

residue was chromatographed (SiO₂, CH₂Cl₂) to give the alde-

hyde. The following aldehydes were prepared by this method.

3-Dimethyl(phenyl)silylbutanal 28. (83%); R_F(CH₂Cl₂) 0.65;

(C᎐O), 1249 (SiMe) and 1112 (SiPh); δ (250 MHz; CDCl )

᎐

H

3

ν_max(ﬁlm)/cm^Ϫ11724 (C᎐O), 1250 (SiMe) and 1111 (SiPh);

7.49 (2 H, m, o-Ph), 7.39–7.30 (3 H, m, m- and p-Ph), 2.53 (1 H,

septet, J 6.9, CHMe_AMe_BCO), 2.41 (1 H, dd, J 16.7 and 3.7,

CH_AH_B), 2.23 (1 H, dd, J 16.7 and 10.4, CH_AH_B), 1.53 (1 H, m,

CHMeCH_AH_B), 1.02 (3 H, d, J 6.9, CHMe_AMe_B), 1.01 (3 H, d,

᎐

δ_H(250 MHz; CDCl₃) 9.67 (1 H, dd, J 3.2 and 1.1, CHO), 7.49

(2 H, m, o-Ph), 7.41–7.31 (3 H, m, m- and p-Ph), 2.43 (1 H, ddd,

J 16.3, 3.5 and 1.1, CH_ACH_BCHO), 2.15 (1 H, ddd, J 16.3, 10.9

J. Chem. Soc., Perkin Trans. 1, 1997

1345

View Article Online

J 6.9, CHMe_AMe_B), 0.89 (3 H, d, J 7.3, CHMeCH_AH_B) and

0.27 (6 H, s, SiMe₂); δ_C(CDCl₃) 214.9, 137.7, 133.9, 129.1,

127.8, 42.7, 40.7, 18.3, 18.0, 14.7, Ϫ4.7 and Ϫ5.2; m/z (EI) 248

(24%, M^ϩ), 233 (31, M Ϫ Me), 205 (23, M Ϫ Prⁱ) and 135 (100,

Me₂PhSi) (Found: M^ϩ, 248.1601. C₁₅H₂₄OSi requires M,

248.1601).

3.71 (3 H, s, OMe), 2.35 (1 H, dddd, J 14.3, 6.4, 3.5 and 1.0,

CH CH CH᎐CHCO Me), 1.93 (1 H, ddt, J 14.3, 1.0 and 8.3,

᎐

A

B

2

CH CH CH᎐CHCO Me), 1.03 (1 H, m, HCSi), 0.94 (3 H, d, J

᎐

A

B

2

6.3, MeCSi) and 0.28 (6 H, s, SiMe₂); δ_C(CDCl₃) 167.0, 149.9,

137.7, 133.9 (2 C), 129.1, 127.8 (2 C), 121.4, 51.3, 34.7, 19.0,

14.0, Ϫ4.8 and Ϫ5.1 (Found: C, 68.6; H, 8.45. C₁₅H₂₂O₂Si

requires C, 68.7; H, 8.45%).

1-Dimethyl(phenyl)silyl-4-methyl-1-phenylpentan–3-one 35.

As needles, mp 45 ЊC (from propan-2-ol) (65%); R_F(Et₂O–light

Methyl (Z)-5-dimethyl(phenyl)silylhex-2-enoate 62. (31%);

petroleum, 10:90) 0.30; ν_max(ﬁlm)/cm^Ϫ11713 (C᎐O), 1249

R_F(Et₂O–light petroleum, 5:95) 0.35; ν_max(ﬁlm)/cm^Ϫ11723

᎐

(SiMe) and 1113 (SiPh); δ_H(250 MHz; C₆D₆) 7.42–6.93 (10 H,

m, 2 × Ph), 3.18 (1 H, dd, J 9.5 and 4.9), 2.80 (1 H, dd, J 17.3

and 9.5), 2.56 (1 H, dd, J 17.2 and 4.9), 2.09 (1 H, septet, J 6.9,

CHMe_AMe_B), 0.80 (3 H, d, J 6.9, CHMe_AMe_B), 0.74 (3 H, d, J

CHMe_AMe_B) and 0.18 (6 H, s, SiMe₂); δ_C(CDCl₃) 213.5, 142.6,

136.9, 134.2, 129.3, 128.1, 127.7, 124.8, 41.1, 40.6, 30.7, 18.1,

18.0, Ϫ3.9 and Ϫ5.1 (Found: C, 77.5; H, 8.55. C₂₀H₂₆OSi

requires C, 77.4; H, 8.45%). The ¹H NMR spectrum in CDCl₃

was not ﬁrst order.

(C᎐O) and 1641 (C᎐C); δ (250 MHz; CDCl ) 7.50 (2 H, m, Ph),

᎐ ᎐

H 3

7.39–7.32 (3 H, m, Ph), 6.19 (1 H, dt, J 11.5 and 7.5, HC᎐

᎐

CHCO Me), 5.76 (1 H, dt, J 11.5 and 1.7, HC᎐CHCO Me),

᎐

2

3.67 (3 H, s, OMe), 2.65 (2 H, dt, J 7.0 and 1.7, CH CH᎐CH-

᎐

2

CO₂Me), 0.99 (1 H, m, HCSi), 0.94 (3 H, d, J 4.2, MeCSi) and

0.30 (6 H, s, SiMe₂); δ_C(CDCl₃) 167.0, 149.9, 137.7, 133.9 (2 C),

129.1, 127.8 (2 C), 121.4, 51.3, 34.7, 19.0, 14.0, Ϫ4.8 and Ϫ5.1

(Found: M^ϩ, 262.1394. C₁₅H₂₂O₂Si requires M, 262.1389).

Methyl (E)-5-dimethyl(phenyl)silyl-5-phenylpent-2-enoate 64.

(48%); R_F(Et₂O–light petroleum, 8:92) 0.19; ν_max(ﬁlm)/cm^Ϫ1

1723 (C᎐O), 1654 (C᎐C) and 1599 (Ph); δ (400 MHz; CDCl )

4-Dimethyl(phenyl)silyl-5-methylhexan-2-one 37. (73%);

R_F(Et₂O–light petroleum, 15:85) 0.33; ν_max(ﬁlm)/cm^Ϫ11717

᎐

H

3

(C᎐O), 1249 (SiMe) and 1110 (SiPh); δ (250 MHz; CDCl ) 7.49

7.39–6.90 (10 H, m, 2 × Ph), 6.76 (1 H, dt, J 15.6 and 6.9,

᎐

H

3

(2 H, m, o-Ph), 7.37–7.29 (3 H, m, m- and p-Ph), 2.45 (1 H, dd,

J 17.6 and 7.0, CH_AH_BCHO) 2.34 (1 H, dd, J 17.6 and 5.6,

CH_AH_BCHO), 1.99 (3 H, s, COMe), 1.86 (1 H, m, Me_AMe_B-

CH), 1.59 (1 H, m, CHSi), 0.87 (3 H, d, J 6.8, Me_AMe_BCH),

0.81 (3 H, d, J 6.9, Me_AMe_BCH), 0.32 (3 H, s, SiMe_CMe_D) and

0.29 (3 H, s, SiMe_CMe_D); δ_C(CDCl₃) 209.3, 138.9, 134.0, 128.9,

127.8, 41.4, 29.7, 28.8, 27.5, 23.0, 21.3, Ϫ2.3 and Ϫ3.0; m/z (EI)

248 (17%, M^ϩ), 233 (65, M Ϫ Me) and 135 (100, Me₂PhSi)

(Found: M^ϩ, 248.1595. C₁₅H₂₄OSi requires M, 248.1596).

3-Dimethyl(phenyl)silyl-4-methyl-1-phenylpentan-1-one 38.

(80%); R_F(Et₂O–light petroleum, 20:80) 0.58; ν_max(ﬁlm)/cm^Ϫ1

HC᎐CHCO Me), 5.66 (1 H, dt, 15.6 and 1.4,

J

᎐

2

HC᎐CHCO Me), 3.60 (3 H, s, OMe), 2.65–2.51 (2 H, m,

᎐

2

CH_AH_B), 2.39 (1 H, dd, J 11.8 and 3.9, CHSi), 0.25 (3 H, s,

SiMe_AMe_B) and 0.22 (3 H, s, SiMe_AMe_B); δ_C(CDCl₃) 166.8,

149.1, 141.3, 136.8, 134.1, 130.4, 129.3, 128.2, 127.8, 127.7,

124.9, 121.3, 51.2, 35.7, 32.2, Ϫ3.9 and Ϫ5.5 (Found: M^ϩ,

324.1548; C, 74.0; H, 7.4. C₂₀H₂₄O₂Si requires M, 324.1545;

C, 74.0; H, 7.45%).

Methyl (Z)-5-dimethyl(phenyl)silyl-5-phenylpent-2-enoate 65.

(45%); R_F(Et₂O–light petroleum, 8:92) 0.33; ν_max(ﬁlm)/cm^Ϫ1

1722 (C᎐O), 1642 (C᎐C) and 1599 (Ph); δ (400 MHz; CDCl )

᎐

H

3

1686 (C᎐O) and 1597 (Ph); δ (250 MHz; CDCl ) 7.85–7.25 (10

7.41–6.9 (10 H, m, 2 × Ph), 6.03 (1 H, dt, J 11.4 and 7.1,

᎐

H

3

H, m, 2 × Ph), 3.04 (1 H, dd, J 17.1 and 7.3, CH_AH_B), 2.95 (1 H,

dd, J 17.1 and 5.5, CH_AH_B), 1.98 (1 H, dseptet, J 4.1 and 6.8,

CHMe₂), 1.84 (1 H, ddd, J 7.3, 5.5 and 4.1, CHSi), 0.96 (3 H, d,

J 6.8, CHMe_AMe_B), 0.92 (3 H, d, J 6.9, CHMe_AMe_B), 0.41 (3 H,

s, SiMe_AMe_B) and 0.39 (3 H, s, SiMe_AMe_B); δ_C(CDCl₃) 201.1,

139.1, 137.2, 134.0, 132.7, 128.7, 128.5, 128.4, 128.1, 36.2, 28.9,

28.2, 23.0, 21.5, Ϫ2.1 and Ϫ2.5 (Found: M^ϩ, 310.1753.

C₂₀H₂₆OSi requires M, 310.1753).

HC᎐CHCO Me), 5.61 (1 H, dt, 11.4 and 1.6,

J

᎐

2

HC᎐CHCO Me), 3.67 (3 H, s, OMe), 3.22–3.06 (2 H, m,

᎐

2

CH_AH_B), 2.38 (1 H, dd, J 12.1 and 4.4, CHSi), 0.29 (3 H, s,

SiMe_AMe_B) and 0.26 (3 H, s, SiMe_AMe_B); δ_C(400 MHz; CDCl₃)

166.9, 151.1, 141.8, 137.03, 134.2, 129.2, 128.1, 128.0, 127.6,

124.8, 119.3, 51.0, 36.7, 28.5, Ϫ4.2 and Ϫ5.3 (Found: M^ϩ,

324.1546; C, 73.9; H, 7.5. C₂₀H₂₄O₂Si requires M, 324.1545;

C, 74.0; H, 7.45%).

5-Dimethyl(phenyl)silyl-2,6-dimethylheptan-3-one 39. (78%);

Methyl (E)-5-dimethyl(phenyl)silyl-6-methylhept-2-enoate 67.

R_F(Et₂O–light petroleum, 5:95) 0.35; ν_max(ﬁlm)/cm^Ϫ11713

(48%); R_F(Et₂O–light petroleum, 10:90) 0.30; ν_max(ﬁlm)/cm^Ϫ1

(C᎐O), 1249 (SiMe) and 1110 (SiPh); δ (400 MHz; CDCl ) 7.49

1725 (C᎐O), 1268 (SiMe) and 1110 (SiPh); δ (250 MHz;

᎐

H

3

H

(2 H, m, o-Ph), 7.36–7.28 (3 H, m, m- and p-Ph), 2.54–2.34 (3 H,

m), 1.85 (1 H, m, CHMe_AMe_BCHSi), 1.61 (1 H, m), 0.99 (3 H,

d, J 6.9, CHMe), 0.96 (3 H, d, J 6.9, CHMe), 0.86 (3 H, d, J 6.8,

CHMe), 0.81 (3 H, d, J 6.9, CHMe), 0.32 (3 H, s, SiMe_CMe_D)

and 0.29 (3 H, s, SiMe_CMe_D); δ_C(CDCl₃) 214.7, 139.1, 134.0,

128.8, 127.7, 40.6, 38.2, 28.8, 26.8, 26.5, 22.9, 21.4, 18.6, 18.4,

Ϫ2.4 and Ϫ2.9; m/z (EI) 276 (12%, M^ϩ), 233 (27, M Ϫ Prⁱ) and

135 (100, Me₂PhSi) (Found: M^ϩ, 276.1906. C₁₇H₂₈OSi requires

M, 276.1909).

CDCl₃) 7.49 (2 H, m, o-Ph), 7.38–7.29 (3 H, m, m- and p-Ph),

6.86 (1 H, dt, J 15.6 and 7.6, CHCHCO₂Me), 5.71 (1 H, dt, J

15.5 and 1.4, CHCHCO₂Me), 3.69 (3 H, s, OMe), 2.28 (2 H, td,

J 7.1 and 1.5, CHSiCH₂), 1.92 (1 H, dseptet, J 3.6 and 6.8,

Me_AMe_BCHCHSi), 1.04 (1 H, td, J 6.8 and 3.6, CHSiCH₂),

0.92 (3 H, d, J 6.8, Me_AMe_BCHCHSi), 0.86 (3 H, d, J 6.8,

Me_AMe_BCHCHSi), 0.32 (3 H, s, SiMe_CMe_D) and 0.31 (3 H, s,

SiMe_CMe_D); δ_C(CDCl₃) 167.0, 151.4, 139.1, 133.9, 128.9, 127.8,

120.8, 51.4, 33.0, 30.0, 28.6, 22.7, 21.3, Ϫ2.1 and Ϫ2.7; m/z (EI)

290 (29%, M^ϩ), 275 (30, M Ϫ Me) and 135 (100, Me₂PhSi)

(Found: M^ϩ, 290.1702. C₁₇H₂₆O₂Si requires M, 290.1702).

Methyl (Z)-5-dimethyl(phenyl)silyl-6-methylhept-2-enoate 68.

(39%); R_F(Et₂O–light petroleum, 10:90) 0.38; ν_max(ﬁlm)/cm^Ϫ1

Preparation of the á,â-unsaturated esters 61, 62, 64, 65, 67 and 68

Typically, the aldehyde (17.9 mmol) in methanol (20 cm³)

was stirred with a suspension of methoxycarbonylmethyl(tri-

phenyl)phosphorane (10.30 g, 30.8 mmol) in methanol (80

cm³) under argon at 0 ЊC for 3 h when TLC showed no starting

material remained. The methanol was removed under reduced

pressure, and the residue was dissolved in light petroleum (30

cm³), ﬁltered and evaporated under reduced pressure. The resi-

due was chromatographed (SiO₂, Et₂O–light petroleum, 5:95)

to give the trans- and the cis-α,β-unsaturated esters. The follow-

ing compounds were prepared by this method.

1723 (C᎐O), 1250 (SiMe) and 1110 (SiPh); δ (250 MHz;

᎐

H

CDCl₃) 7.50 (2 H, m, o-Ph), 7.36–7.18 (3 H, m, m- and p-Ph),

6.11 (1 H, ddd, J 11.6, 7.8 and 7.0, CHCHCO₂Me), 5.67 (1 H,

dt, J 11.5 and 1.8, CHCHCO₂Me), 3.68 (3 H, s, OMe), 2.91 (1

H, ddt, J 16.2, 1.8 and 8.0, CHSiCH_AH_B), 2.78 (1 H, m,

CHSiCH_AH_B), 1.91 (1 H, dseptet, J 3.4 and 6.9, Me_AMe_BCH-

CHSi), 1.01 (1 H, ddd, J 8.0, 5.9 and 3.4, CHSiCH_AH_B), 0.93

(3 H, d, J 6.8, Me_AMe_BCHCHSi), 0.85 (3 H, d, J 6.9, Me_A-

Me_BCHCHSi), 0.33 (3 H, s, SiMe_CMe_D) and 0.32 (3 H, s,

SiMe_CMe_D); δ_C(CDCl₃) 167.0, 153.1, 139.5, 133.9, 128.8, 127.7,

118.7, 51.0, 34.0, 28.8, 26.4, 22.9, 21.3, Ϫ2.3 and Ϫ2.7; m/z

(EI) 290 (9%, M^ϩ), 275 (12, M Ϫ Me) and 135 (100, Me₂PhSi)

(Found: M^ϩ, 290.1705. C₁₇H₂₆O₂Si requires M, 290.1702).

Methyl (E)-5-dimethyl(phenyl)silylhex-2-enoate 61. (52%);

R_F(Et₂O–light petroleum, 10:90) 0.25; ν_max(ﬁlm)/cm^Ϫ11725

(C᎐O), 1654 (C᎐C) and 1589 (Ph); δ (250 MHz; CDCl ) 7.55–

᎐

H

3

7.35 (5 H, m, Ph), 6.90 (1 H, ddd, J 15.5, 8.3, 6.4,

HC᎐CHCO Me), 5.75 (1 H, dt, J 15.5 and 1, HC᎐CHCO Me),

᎐

2

1346

J. Chem. Soc., Perkin Trans. 1, 1997

View Article Online

Horner–Wadsworth–Emmons reactions

Methyl

5-dimethyl(phenyl)silyl-2-methoxycarbonylhex-2–

Using the reaction procedure of Marmor,³⁹sodium hydride

(60% dispersion in mineral oil; 1.28 g, 32 mmol) was washed

with light petroleum (2 × 10 cm³) and residual solvent was

removed under reduced pressure. Ether (60 cm³) was added and

the stirred suspension cooled to 0 ЊC. Diethyl ethoxycarbonyl-

methylphosphonate⁴⁰(6.36 g, 28 mmol) in ether (10 cm³) was

added dropwise over 10 min and the mixture was reﬂuxed for 20

min. After cooling the mixture to 0 ЊC, a solution of the alde-

hyde (28 mmol) in ether (10 cm³) was added dropwise over 10

min. The mixture was stirred at 0 ЊC for 10 min and reﬂuxed for

30 min. The mixture was cooled to room temperature, the clear

ether layer was decanted off, and water ( 50 cm³) was added to

the residue, which dissolved on warming. The aqueous layer

was extracted with ether (3 × 25 cm³) and the combined ether

fractions were washed with aqueous sodium hydrogen carbon-

ate (50 cm³), dried (MgSO₄) and evaporated under reduced

pressure. The residue was chromatographed (SiO₂, Et₂O–light

petroleum, 10:90) to give the ester. The following esters were

prepared by this method.

enoate 63. (61%); R_F(Et₂O–light petroleum, 15:85) 0.20;

ν_max(ﬁlm)/cm^Ϫ11732 (C᎐O), 1642 (C᎐C), 1264 (SiMe) and 1113

᎐

(SiPh); δ_H(250 MHz; CDCl₃) 7.47 (2 H, m, o-Ph), 7.39–7.30

(3 H, m, m- and p-Ph), 7.02 [1 H, dd, J 8.5 and 7.3, CHC-

(CO₂Me)₂], 3.75 (3 H, s, OMe), 3.72 (3 H, s, OMe), 2.38 (1 H,

ddd, J 14.7, 7.3 and 3.8, CH_AH_B), 2.08 (1 H, ddd, J 14.7, 10.0

and 8.6, CH_AH_B), 1.06 (1 H, m, CHSiCH_AH_B), 0.96 (3 H, d, J

6.5, MeCHSi) and 0.28 (6 H, s, SiMe₂); δ_C(CDCl₃) 165.9, 164.3,

151.1, 137.4, 133.9, 129.1, 128.0, 127.8, 52.3, 52.1, 32.0, 19.7,

14.1, Ϫ4.9 and Ϫ5.4 (Found: C, 63.8; H, 7.6. C₁₇H₂₄O₄Si

requires C, 63.7; H, 7.55%).

Methyl 5-dimethyl(phenyl)silyl-2-methoxycarbonyl-5-phenyl-

pent-2-enoate 66. (85%) as an oil; R_F(Et₂O–light petroleum,

15:85) 0.2; ν_max(ﬁlm)/cm^Ϫ11728 (C᎐O), 1641 (C᎐C) and 1599

᎐

(Ph); δ_H(400 MHz; CDCl₃) 7.40–6.80 (10 H, m, 2 × Ph), 6.83 [1

H, dd, J 8.4 and 6.9, HC᎐C(CO Me) ], 3.68 (3 H, s, OMe), 3.65

᎐

2

(3 H, s, OMe), 2.74 (1 H, ddd, J 15.4, 12.0 and 6.9, CH_AH_B),

2.65 (1 H, ddd, J 15.4, 8.4 and 4.1, CH_AH_B), 2.38 (1 H, dd, J

12.0 and 4.1, CHSi), 0.24 (3 H, s, SiMe_AMe_B) and 0.19 (3 H, s,

SiMe_AMe_B); δ_C(CDCl₃) 165.8, 164.2, 150.6, 140.9, 136.6, 134.1,

129.3, 128.3, 127.8, 127.6, 125.2, 52.2, 52.06, 36.05, 29.7, Ϫ4.1

and Ϫ5.7 (Found: M^ϩ, 382.1609. C₂₂H₂₆O₄Si requires M,

382.1600).

Ethyl

(E)-5-dimethyl(phenyl)silylhex-2-enoate.

(81%);

R_F(Et₂O–light petroleum, 10:90) 0.28; ν_max(ﬁlm)/cm^Ϫ11718

(C᎐O), 1651 (C᎐C) and 1589 (Ph); δ (250 MHz; CDCl ) 7.55–

᎐

H

3

7.35 (5 H, m, Ph), 6.90 (1 H, ddd, J 15.5, 8.3 and 6.4, CH=CH-

CO Et), 5.75 (1 H, dt, J 15.5 and 1.2, CH᎐CHCO Et), 4.16 (2

Methyl 5-dimethyl(phenyl)silyl-2-methoxycarbonyl-6-methyl-

hept-2-enoate 69. (77%); R_F(Et₂O–light petroleum, 30:70) 0.45;

᎐

2

H, q, J 7.1, OCH₂CH₃), 2.35 (1 H, dddd, J 14.3, 6.4, 3.5 and 1.2,

CH CH CH᎐CH), 1.93 (1 H, dddd, J 14.3, 10.3, 8.3 and 1.2,

ν_max(ﬁlm)/cm^Ϫ11724 (C᎐O), 1263 (SiMe) and 1111 (SiPh);

᎐

A

B

CH CH CH᎐CH), 1.27 (3 H, t, J 7.1, OCH CH ), 1.02 (1 H,

δ_H(250 MHz; CDCl₃) 7.49 (2 H, m, o-Ph), 7.38–7.29 (3 H, m, m-

and p-Ph), 6.94 [1 H, t, J 7.7, CHC(CO₂Me)₂], 3.77 (3 H, s,

OMe), 3.62 (3 H, s, OMe), 2.50–2.38 (2 H, m, CHSiCH_AH_B),

1.93 (1 H, m, Me_AMe_BCHCHSi), 1.09 (1 H, ddd, J 7.8, 6.2 and

3.2, Me_AMe_BCHCHSi), 0.92 (3 H, d, J 6.8, Me_AMe_BCHCHSi),

0.86 (3 H, d, J 6.9, Me_AMe_BCHCHSi) and 0.33 (6 H, s, SiMe₂);

δ_C(CDCl₃) 166.0, 164.3, 152.8, 138.8, 133.9, 128.9, 127.8, 127.1,

52.8, 52.2, 33.8, 28.7, 27.3, 22.7, 21.1, Ϫ2.3 and Ϫ3.0; m/z (EI)

348 (19%, M^ϩ), 333 (49, M Ϫ Me), 317 (54, M Ϫ OMe) and 135

(100, Me₂PhSi) (Found: M^ϩ, 348.1744. C₁₉H₂₈O₄Si requires M,

348.1757).

᎐

A

B

2

3

m, HCSi), 0.94 (3 H, d, J 6.3, MeCSi) and 0.29 (6 H, s, SiMe₂);

δ_C(CDCl₃) 166.6, 149.5, 137.7, 133.9 (2 C), 129.1, 127.8 (2 C),

121.8, 60.1, 34.7, 19.0, 14.3, 14.0, Ϫ5.1 and Ϫ5.3 (Found: C,

69.6; H, 8.65. C₁₆H₂₄O₂Si requires C, 69.5; H, 8.75%).

Methyl (E)-4-phenylpent-2-enoate. ⁴¹(74%); R_F(Et₂O–light

petroleum) 0.40; ν_max(ﬁlm)/cm^Ϫ11724 (C᎐O) and 1653 (C᎐C);

᎐

δ_H(250 MHz; CDCl₃) 7.36–7.15 (5 H, m, Ph), 7.12 (1 H, dd, J

15.8 and 6.7, CHCHCO₂Me), 5.81 (1 H, dd, J 15.8 and 1.6,

CHCHCO₂Me), 3.72 (3 H, s, OMe), 3.62 (1 H, m, MeCHPh)

and 1.42 (3 H, d, J 7.0, MeCHPh); δ_C(CDCl₃) 167.2, 152.9,

143.3, 128.7, 127.3, 126.8, 119.7, 51.5, 42.6 and 20.2; m/z (EI)

190 (24%, M^ϩ), 159 (16, M Ϫ OMe) and 131 (65, M Ϫ CO₂Me)

(Found: M^ϩ, 190.0991. C₁₂H₁₄O₂requires M, 190.0994); (Z)-

isomer: R_F(Et₂O–light petroleum) 0.50; ν_max(ﬁlm)/cm^Ϫ11722

(C᎐O) and 1650 (C᎐C); δ (250 MHz; CDCl ) 7.32–7.17 (5 H,

Methyl 4-phenylpentanoate 25

Methyl (E)-4-phenylpent-2-enoate (1.0 g, 5.26 mmol) in metha-

nol (5 cm³) was stirred with a suspension of palladium on car-

bon (0.2 g) in methanol (10 cm³) at room temperature under

hydrogen for 48 h, when TLC indicated that complete con-

sumption of the starting trans-ester had occurred. The hydro-

gen atmosphere was removed and the system was ﬂushed twice

with argon. The catalyst was removed by ﬁltration through

Celite. The methanol was removed by evaporation under

reduced pressure and the residue was passed through a short

column of silica using ether as eluent to give the ester⁴²(0.85 g,

᎐

H

3

m, Ph), 6.28 (1 H, dd, J 11.3 and 10.4, CHCHCO₂Me), 5.74 (1

H, dd, J 11.4 and 0.9, CHCHCO₂Me), 4.91 (1 H, m, MeCHPh),

3.74 (3 H, s, OMe) and 1.40 (3 H, d, J 7.0, MeCHPh);

δ_C(CDCl₃) 166.7, 154.1, 144.5, 128.0, 127.1, 126.5, 117.4, 51.2,

37.7 and 20.9; m/z (EI) 190 (3%, M^ϩ) (Found: M^ϩ, 190.0995.

C₁₂H₁₄O₂requires M, 190.0994).

Preparation of the á,â-unsaturated diesters 63, 66 and 69

Typically, glacial acetic acid (0.16 cm³, 2.8 mmol) and piperi-

dine (0.28 cm³, 2.8 mmol) were added with stirring to a solution

of the aldehyde (27.9 mmol) and dimethyl malonate (4.06 g,

30.7 mmol) in dichloromethane (130 cm³) at 0 ЊC and the mix-

ture stirred for 45 min at room temperature. Additional glacial

acetic acid (0.16 cm³, 2.8 mmol) and piperidine (0.28 cm³, 2.8

mmol) were added and the mixture was stirred for a further 30

min. Molecular sieves (4 Å) were added and the mixture kept

for a further 4 h. The sieves were removed by ﬁltration and the

solvent was evaporated under reduced pressure. The residue

was taken up into ether (100 cm³), washed with saturated aque-

ous sodium hydrogen carbonate (50 cm³) and brine (50 cm³) and

dried (MgSO₄). The ether was evaporated under reduced pres-

sure and the residue was chromatographed (SiO₂, Et₂O–light

petroleum, 15:85) to give the diesters. Use of more than 0.2

equiv. of acetic acid and piperidine reduced the yield of the

diesters and promoted the formation of their deconjugated

isomers. The following compounds were prepared by this

method.

85%); ν_max(ﬁlm)/cm^Ϫ11733 (C᎐O); δ (250 MHz; CDCl ) 7.33–

᎐

H

3

7.12 (5 H, m, Ph), 3.61 (3 H, s, OMe), 2.70 (1 H, sextet, J 6.9,

MeCHPh), 2.24–2.14 (2 H, m, CH₂CO₂Me), 1.98–1.84 (2 H, m,

MeCHPhCH₂) and 1.27 (3 H, d, J 7.0, MeCHPh).

(2SR,3SR,4RS)-2Ј,6Ј-Dimethylphenyl 3-hydroxy-2-methyl-4-

phenylpentanoate 90

Butyllithium (1.6 mol dm^Ϫ3solution in hexanes; 11.6 cm³, 18.5

mmol) was added dropwise with stirring to a solution of diiso-

propylamine (2.43 cm³, 18.5 mmol) in THF (60 cm³) at 0 ЊC

under argon. After 20 min, the mixture was cooled to Ϫ78 ЊC

and 2,6-dimethylphenyl propanoate in THF (20 cm³) was

added slowly. The mixture was stirred for 1.5 h at this temper-

ature and then 2-phenylpropanal (2.24 cm³, 16.9 mmol) was

added. After stirring for a further 5 min the mixture was

quenched with saturated aqueous ammonium chloride (15 cm³)

and allowed to warm to room temperature. Dilute hydrochloric

acid (50 cm³) was added to the mixture and the THF was evap-

orated under reduced pressure. The residue was extracted with

dichloromethane (3 × 50 cm³), washed with brine (100 cm³),

J. Chem. Soc., Perkin Trans. 1, 1997

1347

View Article Online

dried (MgSO₄) and evaporated under reduced pressure. The

residue was chromatographed (SiO₂, Et₂O–light petroleum,

25:75) to give the ester³⁰(3.0 g, 57%) as cubes, mp 89–90 ЊC

(from light petroleum); R_F(Et₂O–light petroleum) 0.30;

ν_max(CH₂Cl₂)/cm^Ϫ13478 (OH) and 1746 (C᎐O); δ (250 MHz;

Methyl (2RS,4RS)-2-methyl-4-phenylpentanoate 27

Following the procedure of Barton and McCombie,³¹the

dithiocarbonate from above (0.09 g, 0.288 mmol) in toluene (15

cm³) was added dropwise over 15 min to a reﬂuxing solution of

tributyltin hydride (0.085 cm³) in toluene (15 cm³) under argon

and the mixture was reﬂuxed for 16 h. The solvent was evapor-

ated under reduced pressure and the residue was chromato-

graphed (SiO₂, Et₂O–light petroleum, 10:90) to give the ester 27

(0.033 g, 56%), identical (¹H NMR) with the signals assigned to

this isomer in the mixture from the methylation experiment;

δ_C(CDCl₃) 177.4, 146.7, 128.4, 127.1, 126.2, 51.5, 42.5, 38.0,

37.6, 22.6 and 18.0.

᎐

H

CDCl₃) 7.39–7.21 (5 H, m, Ph), 7.05 (3 H, s, Ph), 3.82 (1 H, m,

CHOH), 3.05 (1 H, quintet, J 6.9, MeCH), 2.84 (1 H, quintet,

J 7.2, MeCH), 2.58 (1 H, d, J 7.6, CHOH), 2.17 (6 H, s,

2 × MePh), 1.48 (3 H, d, J 7.3, MeCH) and 1.40 (3 H, d, J 7.0,

MeCH). Heathcock reported that a 4:1 ratio of diastereo-

isomers of the ester was obtained in this reaction. Although the

¹H NMR spectrum of the crude product suggested that a very

small amount of the second diastereoisomer, presumably the

anti,anti-Cram product, might have been obtained this was

inconclusive. Following chromatography, two minor products

were obtained: 2,6-dimethylphenol (0.38 g) and an unidentiﬁed

product (0.58 g) of R_F(Et₂O–light petroleum, 25:75) 0.15,

which had no OH frequency present in the IR spectrum and

may have been the elimination product from the minor

diastereoisomer.

Silyl-to-hydroxy conversions

Typically, mercuric acetate (0.23 g, 0.72 mmol) was added to a

stirring solution of the silane (0.48 mmol) in peracetic acid (35–

40% solution in dilute acetic acid; 3 cm³) and the mixture was

stirred for 3 h at room temperature. Toluene (10 cm³) was added

and the mixture of solvents was evaporated under reduced

pressure. The residue was taken up in ether, ﬁltered and evapor-

ated under reduced pressure. The residue was chromatographed

to give the alcohol. The following compounds were prepared by

this method, except that a larger excess of mercuric acetate

(typically 1.23 mmol) relative to the amount of the ester (typic-

ally 0.493 mol) was used for the doubly silylated esters 70, 74

and 78.

(1RS,3SR)-1-Phenylbutane-1,3-diol 91A. As needles, mp

77 ЊC (from Et₂O–light petroleum) (lit.,¹⁸78 ЊC) (54%);

R_F(Et₂O) 0.37; ν_max(CH₂Cl₂)/cm^Ϫ13422 (OH); δ_H(250 MHz;

CDCl₃) 7.38–7.22 (5 H, m, Ph), 4.89 (1 H, dd, J 9.8 and 3.4,

PhCHOH), 4.11 (1 H, ddq, J 9.3, 2.9 and 6.2, CHOHMe), 3.67

(2 H, br s, 2 × OH), 1.90–1.67 (2 H, m, CH₂) and 1.19 (3 H, d, J

6.2, CHOHMe).

Methyl (2SR,3SR,4RS)-3-hydroxy-2-methyl-4-phenyl-

pentanoate

Sodium (0.048 g, 2.1 mmol, pre-washed with light petroleum)

was added to methanol (20 cm³) at 0 ЊC. After the sodium had

been completely converted to sodium methoxide, THF (20 cm³)

was added and the solution allowed to warm to room temper-

ature. The ester 90 (0.592 g, 1.90 mmol) was added and the

mixture was stirred for 24 h when TLC indicated complete

consumption of the starting material. Ether (150 cm³) was

added and the mixture was washed with water (100 cm³). The

water layer was extracted with ether (3 × 50 cm³). The com-

bined organic fractions were washed with saturated aqueous

sodium hydrogen carbonate (100 cm³) and brine (100 cm³), dried

(MgSO₄) and evaporated under reduced pressure. The residue

was chromatographed (SiO₂, Et₂O–light petroleum, 50:50) to

give the methyl ester⁴³(0.34 g, 80%); R_F(Et₂O–light petroleum,

50:50) 0.28; ν_max(ﬁlm)/cm^Ϫ13504 (OH) and 1736 (C᎐O); δ (250

(1RS,3RS)-1-Phenylbutane-1,3-diol 91B. As prisms, mp 62–

63 ЊC (from Et₂O–light petroleum) (lit.,¹⁸62–63 ЊC) (55%);

R_F(Et₂O) 0.32; ν_max(CH₂Cl₂)/cm^Ϫ13386 (OH); δ_H(250 MHz;

CDCl₃) 7.33–7.21 (5 H, m, Ph), 5.01 (1 H, dd, J 7.3 and 4.2,

PhCHOH), 4.04 (1 H, m, CHOHMe), 3.54 (1 H, br s, OH), 2.94

(1 H, br s, OH), 1.94–1.73 (2 H, m, CH₂) and 1.21 (3 H, d, J 6.3,

CHOHMe).

᎐

H

MHz; CDCl₃) 7.35–7.13 (5 H, m, Ph), 3.69 (3 H, s, OMe), 3.63

(1 H, m, CHOH), 2.86 (1 H, quintet, J 7.0, CHMe), 2.74 (1 H,

d, J 8.1, CHOH), 2.47 (1 H, dq, J 5.0 and 7.3, CHMe), 1.35 (3

H, d, J 7.0, CHMe) and 1.22 (3 H, d, J 7.3, CHMe); δ_C(CDCl₃)

176.9, 144.3, 128.5, 127.7, 126.6, 78.5, 51.7, 43.9, 41.8, 16.3 and

15.4.

(2RS,4SR)-5-Methylhexane-2,4-diol⁴⁴92A (=95A) and

(2RS,4RS)-5-methylhexane-2,4-diol⁴⁴92B (=95B). (53%,

33:67 from a 33:67 mixture of 57A and 57B; 55%, 22:78 from

a 22:78 mixture of 42B and 42A); R_F(Et₂O) 0.33 and 0.23;

ν_max(CDCl₃)/cm^Ϫ13372 (OH); 92A: δ_H(250 MHz; CDCl₃) 4.12

(1 H, m, MeCHOH), 3.67–3.54 (1 H, m, CHCHOH), 1.71–1.34

(3 H, m, CH_AH_B, CH_AH_Band Me_AMe_BCH), 1.22 (3 H, d, J 6.4,

MeCH) and 0.95–0.81 (6 H, m, 2 × MeCH); 92B: δ_H(250 MHz;

CDCl₃) 4.00 (1 H, m, MeCHOH), 3.67–3.54 (1 H, m,

CHCHOH), 1.71–1.34 (3 H, m, CH_AH_B, CH_AH_Band Me_A-

Me_BCH), 1.18 (3 H, d, J 6.2, MeCH) and 0.95–0.81 (6 H, m,

2 × MeCH). The ratio of the diastereoisomers was determined

by integration of the MeCHOH signals in the ¹H NMR

spectrum.

Methyl (2SR,3SR,4RS)-3-[(methylthio)thiocarbonyloxy]-2-

methyl-4-phenylpentanoate

Following the method of Barton and McCombie,³¹the methyl

ester from above in THF (5 cm³), sodium hydride (0.036 g, 0.90

mmol) and imidazole (0.01 g) in THF (10 cm³) were stirred for

2 h under argon and then carbon disulﬁde (0.08 cm³, 1.35

mmol) was added, and the mixture stirred for 30 min. Methyl

iodide (0.085 cm³, 1.35 mmol) was added and the mixture was

stirred for an additional 1 h. Water (50 cm³) was added and the

mixture was extracted with ether (3 × 50 cm³). The combined

organic fractions were washed with dilute hydrochloric acid

(100 cm³), saturated aqueous sodium hydrogen carbonate (100

cm³) and brine (100 cm³), dried (MgSO₄) and evaporated under

reduced pressure. The residue was chromatographed (SiO₂,

Et₂O–light petroleum, 20:80) to give the dithiocarbonate (0.11

g, 78%); R_F(Et₂O–light petroleum, 20:80) 0.33; ν_max(ﬁlm)/cm^Ϫ1

(1RS,3RS)-1,3-Diphenylpropane-1,3-diol⁴⁵93A. As prisms

mp 135–139 ЊC (from CH₂Cl₂–light petroleum) (88%);

R_F(EtO₂–light petroleum, 50:50) 0.24; ν_max(ﬁlm)/cm^Ϫ13391

(OH) and 1492 (Ph); δ_H(250 MHz; CDCl₃): 7.42–7.22 (10 H, m,

2 × Ph), 4.97 (2 H, t, J 5.8, 2 × CHOH), 2.89 (2 H, br s,

2 × OH) and 2.17 (2 H, dd J 6.2 and 5.4, CH_AH_B).

(1RS,3SR)-1,3-Diphenylpropane-1,3-diol⁴⁵93B. As prisms

mp 107–112 ЊC (59%); R_F(EtO₂–light petroleum, 50:50) 0.24;

ν_max(ﬁlm)/cm^Ϫ13351 (OH) and 1602 (Ph); δ_H(250 MHz; CDCl₃)

7.67–6.82 (10 H, m, 2 × Ph), 5.03 (2 H, dd, J 10.1 and 2.8,

2 × CHOH), 3.31 (2 H, br s, 2 × OH), 2.15 (1 H, dt, J 14.7

and 10.1, CH_AH_B), 1.96 (1 H, dt, J 14.7 and 2.8, CH_AH_B).

(1RS,3RS)-4-Methyl-1-phenylpentane-1,3-diol⁴⁶94A and

(1RS,3SR)-4-methyl-1-phenylpentane-1,3-diol⁴⁶94B. (74%,

67:33 from a 67:33 mixture of 52A and 52B; 57%, 24:76 from

a 22:78 mixture of 55B and 55A); ν_max(ﬁlm)/cm^Ϫ13364 (OH);

1741 (C᎐O); δ (250 MHz; CDCl ) 7.35–7.19 (5 H, m, Ph), 6.27

᎐

H

3

(1 H, dd, J 9.4 and 4.0, CHOCS₂Me), 3.56 (3 H, s, OMe), 3.36

(1 H, dq, J 9.4 and 7.0, CHMe), 2.77 (1 H, dq, J 4.0 and 7.2,

CHMe), 2.58 (3 H, s, CS₂Me), 1.29 (3 H, d, J 7.0, CHMe) and

1.15 (3 H, d, J 7.2, CHMe); δ_C(CDCl₃) 216.3, 172.7, 142.2,

128.4, 128.3, 127.8, 87.3, 51.7, 42.2, 41.7, 18.7, 18.4 and 13.5;

m/z (EI) 281 (3%, M^ϩϪ OMe) and 253 (43, M Ϫ CO₂Me)

(Found: M^ϩϪ OMe, 281.0659. C₁₅H₂₀O₃S₂requires M Ϫ OMe,

281.0670).

1348

J. Chem. Soc., Perkin Trans. 1, 1997

View Article Online

94A: R_f(EtO₂–light petroleum, 50:50) 0.20; δ_H(250 MHz;

CDCl₃) 7.39–7.20 (5 H, m, Ph), 5.03 (1 H, t, J 5.6, PhCHOH),

3.59 (1 H, q, J 5.9, CHCHOH), 1.88–1.60 (3 H, m, CH_AH_Band

CHMe_AMe_B), 0.89 (3 H, d, J 6.7, CHMe_AMe_B) and 0.86 (3 H,

d, J 6.7, CHMe_AMe_B); δ_C(CDCl₃) 144.6, 128.4, 127.2, 125.5,

73.8, 71.8, 41.6, 33.7, 18.5 and 17.7; 94B: R_F(EtO₂–light petrol-

eum, 50:50) 0.28; δ_H(250 MHz; CDCl₃) 7.39–7.20 (5 H, m, Ph),

4.90 (1 H, dd, J 9.0 and 3.9, PhCHOH), 3.72 (1 H, m,

CHCHOH), 1.88–1.60 (3 H, m, CH_AH_Band CHMe_AMe_B), 0.90

(3 H, d, J 6.9, CHMe_AMe_B) and 0.89 (3 H, d, J 6.6,

CHMe_AMe_B); δ_C(CDCl₃) 144.6, 128.5, 127.6, 125.7, 77.6, 75.6,

42.0, 34.2, 18.2 and 17.4. The ratio of diastereoisomers was

J 11.6, 5.7 and 3.1, C₆-H_ax), 4.41 (1 H, m, CHOH), 2.71 (1 H,

dd, J 17.6 and 4.8, C₃-H_ax), 2.61 (1 H, ddd, J 17.7, 3.7 and 1.6,

C₃-H_eq), 1.98–1.83 (2 H, m, Me_AMe_BCH and C₅-H_eq), 1.74

(1 H, ddd, J 14.7, 11.7 and 3.4, C₅-H_ax), 1.00 (3 H, d, J 6.0,

Me_AMe_BCH) and 0.97 (3 H, d, J 5.9, Me_AMe_BCH). The ratio

of diastereoisomers was determined by integration of the

CHOH signals in the ¹H NMR spectrum.

(4RS,6SR)-4,6-Dimethyltetrahydro-2H-pyran-2-one⁵⁰110A

and (4RS,6RS)-4,6-dimethyltetrahydro-2H-pyran-2-one⁵⁰110B.

(59%, 85:15 from an 85:15 mixture of 104A and 104B);

R_F(Et₂O–CH₂Cl₂, 5:95) 0.37; ν_max(CH₂Cl₂)/cm^Ϫ11732 (C᎐O);

᎐

110A: δ_H(250 MHz; CDCl₃) 4.40 (1 H, ddq, J 17.9, 6.3 and 2.9,

C₆-H_ax), 2.64 (1 H, m), 2.19–1.82 (3 H, m), 1.35 (3 H, d, J 6.3,

C₆-Me), 1.22 (1 H, m) and 1.02 (3 H, d, J 6.2, C₄-Me); 110B:

δ_H(250 MHz; CDCl₃) (recognisable signals) 4.54 (1 H, ddq,

J 8.6, 4.3 and 6.3, C₆-H_ax), 1.35 (3 H, d, J 6.3, C₆-Me) and 1.07

(3 H, d, J 6.6, C₄-Me).

1

determined by integration of the PhCHOH signals in the H

NMR spectrum.

(3RS,5RS)-2,6-Dimethylheptane-3,5-diol⁴⁷97A and (3RS,

5SR)-2,6-dimethylheptane-3,5-diol 97B. (61%, 23:77 from a

23:77 mixture of 59A and 59B); R_F(Et₂O–light petroleum,

80:20) 0.37 and 0.28; ν_max(ﬁlm)/cm^Ϫ13388 (OH); 97A: δ_H(400

MHz; CDCl₃) 3.67–3.58 (2 H, m, 2 × CHOH), 1.73–1.60 (2 H,

m), 1.44–1.33 (2 H, m) and 0.97–0.91 (12 H, m, 4 × CHMe);

δ_C(CDCl₃) 74.2, 36.5, 33.7, 18.7 and 18.1; 97B: δ_H(400 MHz;

CDCl₃) 3.67–3.58 (2 H, m, 2 × CHOH), 1.73–1.60 (2 H, m),

1.58–1.52 (2 H, m) and 0.97–0.91 (12 H, m, 4 × CHMe);

δ_C(CDCl₃) 78.2, 35.8, 34.1, 18.4 and 17.8. The ratio of diastereo-

isomers was determined by integration of the CH₂signals (36.5

and 35.8 ppm) in the ¹³C NMR spectrum.

(4RS,6SR)-6-Methyl-4-phenyltetrahydro-2H-pyran-2-one

111A and (4RS,6RS)- 6-methyl-4-phenyltetrahydro-2H-pyran-2-

one 111B. (57%, 29:71 from a 29:71 mixture of 105A and

105B); R_F(CH₂Cl₂) 0.22; ν_max(CH₂Cl₂)/cm^Ϫ11731 (C᎐O); 111A:

᎐

δ_H(400 MHz; CDCl₃) 7.39–7.15 (5 H, m, Ph), 4.56 (1 H, m, C₆-

H_eq), 3.19 (1 H, m, C₄-H_ax), 2.90 (1 H, ddd, J 17.8, 6.0 and 1.9,

C₃-H_eq), 2.52 (1 H, dd, J 17.9 and 11.5, C₃-H_ax), 2.16 (1 H, m,

C₅-H), 1.73 (1 H, m, C₅-H) and 1.44 (3 H, d, J 6.3, C₆-Me);

δ_C(CDCl₃) 170.9, 142.9, 129.0, 127.2, 126.4, 73.9, 38.1, 37.7,

37.3 and 21.9; 111B: δ_H(400 MHz; CDCl₃) 7.39–7.15 (5 H, m,

Ph), 4.56 (1 H, m, C₆-H_eq), 3.37 (1 H, m, C₄-H_ax), 2.80 (1 H, dd,

J 17.1 and 6.2, C₃-H_eq), 2.72 (1 H, dd, J 17.1 and 8.5, C₃-H_ax),

2.12–1.97 (2 H, m, C₅-H_axand C₅-H_eq) and 1.40 (3 H, d, J 6.3,

C₆-Me); δ_C(CDCl₃) 171.7, 143.1, 129.0, 127.1, 126.7, 73.9, 36.8,

35.9, 34.7 and 21.3; m/z (EI) 190 (29, M^ϩ) (Found: M^ϩ,

190.0992. C₁₂H₁₄O₂requires M, 190.0994). Irradiation of the

proton signal at 4.56 ppm resulted in the enhancement of

the signal at 3.19 ppm (but not the signal at 3.37 ppm).

(4RS,6SR)-4-Hydroxy-6-methyltetrahydro-2H-pyran-2-one⁴⁸

101A and (4RS,6RS)-4-hydroxy-6-methyltetrahydro-2H-pyran-

2-one⁴⁹101B. (63%, 85:15 from an 86:14 mixture of 70A and

70B); R_F(EtOAc) 0.31; 101A: ν_max(ﬁlm)/cm^Ϫ13414 (OH) and

1726 (C᎐O); δ (400 MHz; CDCl ) 4.33 (1 H, ddq, J 11.7, 3.0

᎐

H

3

and 6.3, C₆-H_ax), 4.23 (1 H, m, C₄-H_ax), 2.86 (1 H, ddd, J 17.1,

5.9 and 1.4, C₃-H_eq), 2.73 (1 H, br s, OH), 2.43 (1 H, dd, J 17.1

and 7.7, C₃-H_ax), 2.25 (1 H, dddd, J 13.8, 5.5, 3.0 and 1.4, C₅-

H_ax), 1.56 (1 H, ddd, J 13.8, 11.7 and 9.2, C₅-H_ax) and 1.39 (3 H,

d, J 6.3, Me); δ_C(CDCl₃) 171.1, 73.8, 63.8, 39.5, 39.9 and 21.4;

101B: δ_H(400 MHz; CDCl₃) 4.83 (1 H, ddq, J 12.8, 3.0 and 6.4,

C₆-H_ax), 2.68 (1 H, dd, J 17.7 and 4.8, C₃-H_eq), 2.59 (1 H, ddd,

J 17.7, 3.6 and 1.7, C₃-H_ax), 1.97 (1 H, dddd, J 14.4, 3.8, 3.3 and

1.8, C₅-H_eq), 1.69 (1 H, ddd, J 14.4, 11.3 and 3.2, C₅-H_ax)

and 1.37 (3 H, d, J 7.0, Me); δ_C(CDCl₃) 170.9, 72.5, 62.7, 38.4

and 37.5.

(4RS,6RS)-4-Methyl-6-phenyltetrahydro-2H-pyran-2-one⁵¹

112A and (4RS,6SR)-4-methyl-6-phenyltetrahydro-2H-pyran-2-

one⁵¹112B. (67%, 78:22 from an 84:16 mixture of 106A and

106B); the major isomer 112A could be separated as needles,

mp 89–92 ЊC (from light petroleum); R_F(Et₂O–light petroleum,

30:70) 0.12; ν_max(ﬁlm)/cm^Ϫ11729 (C᎐O) and 1493 (Ph); δ (400

᎐

H

MHz; CDCl₃) 112A: 7.39–7.29 (5 H, m, Ph), 5.30 (1 H, dd,

J 12.0 and 3.0, C₆-H_ax), 2.80 (1 H, ddd, J 16.8, 5 and 2, C₃-H_eq),

2.27–2.13 (3 H, m, C₃-H_ax, C₄-H_axand C₅-H_eq), 1.52 (1 H, dt,

J 13.9 and 11.5, C₅-H_ax) and 1.08 (3 H, d, J 6.2, MeCH); 112B:

7.39–7.29 (5 H, m, Ph), 5.52 (1 H, dd, J 7.6 and 4.7, C₆-H_ax),

2.70 (1 H, ddd, J 16.9, 5.8 and 1.0, C₃-H_eq), 2.27–2.13 (3 H, m,

C₃-H_ax, C₄-H_eqand C₅-H_eq), 1.88 (1 H, m, C₅-H_ax) and 1.11 (3

H, d, J 6.6, MeCH).

(4RS,6RS)-4-Hydroxy-6-phenyltetrahydro-2H-pyran-2-one

102A and (4RS,6SR)-4-hydroxy-6-phenyltetrahydro-2H-pyran-

2-one 102B. (35%, 95:5 from a 95:5 mixture of 74A and 74B);

R_F(Et₂O–EtOAc, 65:35) 0.30; ν_max(ﬁlm)/cm^Ϫ13607 (OH), 1737

(C᎐O) and 1602 (Ph); 102A: δ (400 MHz; CDCl ) 7.40–7.25 (5

᎐

H

3

H, m, Ph), 5.21 (1 H, dd, J 12.1 and 3.1, C₆-H_ax), 4.40 (1 H, m,

C₄-H_ax), 3.45 (1 H, ddd, J 17.1, 6 and 1.3, C₃-H_eq), 2.6 (1 H, dd,

J 17.1 and 8, C₃-H_ax), 2.51 (1 H, dddd, J 13.9, 6.8, 3.1 and 1.3,

C₅-H_eq), 1.92 (1 H, ddd, J 13.9, 12.1 and 9.4, C₅-H_ax); δ_C(CDCl₃)

170.2, 138.6, 128.8, 128.7, 125.9, 78.5, 64.1, 40.4, 39.6; 102B:

δ_H(400 MHz; CDCl₃) 5.74 (1 H, dd, J 11.2 and 3.1, C₆-H_ax),

4.40 (1 H, m, C₄-H_eq), 2.85 (1 H, dd, J 17.9 and 5, C₃-H_ax), 2.70

(1 H, ddd, J 17.9, 3.7 and 1.5, C₃-H_eq), 2.20 (1 H, dtd, J 14.4, 3.7

and 1.5, C₅-H_eq), 2.05 (1 H, ddd, J 14.4 11.2 and 3.1, C₅-H_ax);

δ_C(CDCl₃) 170.2, 139.2, 128.7, 128.4, 125.9, 78.5, 62.8, 38.7 and

38.4 (Found: M^ϩ, 192.0778. C₁₁H₁₂O₃requires M, 192.0786).

(4RS,6RS)-4-Hydroxy-6-isopropyltetrahydro-2H-pyran-2-

one⁶103A and (4RS,6SR)-4-hydroxy-6-isopropyltetrahydro-2H-

pyran-2-one⁶103B. (64%, 83:17 from an 83:17 mixture of

78A and 78B; 50%, 53:47 from a 53:47 mixture of 78A and

78B); R_F(Et₂O–MeOH, 96:4) 0.30; ν_max(CDCl₃)/cm^Ϫ13422

(4RS,6RS)-4,6-Diphenyltetrahydro-2H-pyran-2-one 113A and

(4RS,6SR)-4,6-diphenyltetrahydro-2H-pyran-2-one 113B. (35%,

78:22 from an 84:16 mixture of 107A and 107B; 41%, 113B

pure from a pure sample of 107B); R_F(Et₂O–light petroleum,

30:70) 0.20; ν_max(ﬁlm)/cm^Ϫ11730 (C᎐O), 1599 (Ph); 113A:

᎐

δ_H(400 MHz; CDCl₃) 7.4–7.2 (10 H, m, 2 × Ph), 5.47 (1 H, dd,

J 11.9 and 3.0, C₆-H_ax), 3.38 (1 H, m, C₄-H_ax), 3.05 (1 H, ddd,

J 17.9, 5.9 and 2.0, C₃-H_eq), 2.68 (1 H, dd, J 17.9 and 11.5,

C₃-H_ax), 2.43–2.32 (1 H, m, C₅-H_eq) and 2.06 (1 H, dt, J 14.0

and 12.1, C₅-H_ax); 113B: needles, mp 63–65 ЊC (from light pet-

roleum); δ_H(400 MHz; CDCl₃) 7.40–7.20 (10 H, m, 2 × Ph), 5.55

(1 H, dd, J 7.0 and 5.1, C₆-H_ax), 3.3 (1 H, m, C₄-H_eq), 2.93 (1 H,

dd, J 17.3 and 6.2, C₃-H_eq), 2.84 (1 H, dd, J 17.3 and 9.0, C₃-H_ax)

and 2.43–2.32 (2 H, m, C₅-H_eqand C₅-H_ax); 113B: δ_C(CDCl₃)

171.2, 142.6, 139.8, 129.1, 128.7, 128.2, 127.3, 126.6, 125.5,

78.7, 37.3, 36.4 and 34.2 (Found: M^ϩ, 252.1147. C₁₇H₁₆O₂

requires M, 252.1150).

(OH) and 1717 (C᎐O); 103A: δ (250 MHz; CDCl ) 4.24 (1 H,

᎐

H

3

m, CHOH), 3.99 (1 H, ddd, J 12.0, 5.6 and 3.0, C₆-H_ax), 2.91

(1 H, ddd, J 17.2, 5.9 and 1.5, C₃-H_eq), 2.44 (1 H, dd, J 17.1 and

8.2, C₃-H_ax), 2.21 (1 H, dddd, J 13.5, 5.3, 2.9 and 1.5, C₅-H_eq),

1.92 (1 H, m, Me_AMe_BCH), 1.59 (1 H, ddd, J 13.5, 12.0 and

11.5, C₅-H_ax), 1.00 (3 H, d, J 5.9, Me_AMe_BCH) and 0.97 (3 H, d,

J 6.0, Me_AMe_BCH); 103B: δ_H(250 MHz; CDCl₃) 4.49 (1 H, ddd,

(4RS,6RS)-6-Isopropyl-4-methyltetrahydro-2H-pyran-2-

one^52,53114A and (4RS,6SR)-6-isopropyl-4-methyltetrahydro-

2H-pyran-2-one⁵²114B. (65%, 64:36 from a 64:36 mixture of

108A and 108B); R_F(Et₂O–CH₂Cl₂, 4:96) 0.37; ν_max(CDCl₃)/

J. Chem. Soc., Perkin Trans. 1, 1997

1349

View Article Online

cm^Ϫ11734 (C᎐O); 114A: δ (500 MHz; CDCl ) 4.07 (1 H, m,

CHMeCH_AH_B), 0.84 (3 H, d, J 6.6, CHMe_AMe_B), 0.77 (3 H, d,

᎐

H

3

C₆-H_ax), 2.66 (1 H, m, C₃-H), 2.07–1.95 (2 H, m, C₃-H and C₄-

H_ax), 1.92–1.78 (2 H, m, C₅-H and CHMe_AMe_B), 1.21 (1 H, m,

C₅-H), 1.04 (3 H, d, J 6.1, CHMe), 0.99 (3 H, d, J 6.8, CHMe)

and 0.96 (3 H, d, J 6.7, CHMe); δ_C(CDCl₃) 171.8, 85.3, 38.2,

33.5, 32.8, 26.7, 21.8, 17.8 and 17.6; 114B: δ_H(500 MHz; CDCl₃)

4.07 (1 H, m, C₆-H_ax), 2.54 (1 H, m, C₃-H), 2.22–2.15 (2 H, m,

C₃-H and C₄-H_ax), 1.92–1.78 (2 H, m, C₅-H and CHMe_AMe_B),

1.52 (1 H, m, C₅-H), 1.09 (3 H, d, J 6.4, CHMe), 1.01 (3 H, d, J

6.8, CHMe) and 0.95 (3 H, d, J 6.1, CHMe); δ_C(CDCl₃) 173.0,

81.7, 37.3, 32.5, 32.0, 23.9, 21.4, 18.1 and 18.0. The ratio of

diastereoisomers was determined by integration of the C₃-H

J 6.9, CHMe_AMe_B), 0.14 (3 H, s, SiMe_CMe_D) and 0.08 (3 H, s,

SiMe_CMe_D); δ_C(CDCl₃) 146.2, 127.6, 126.3, 126.1, 87.2, 42.7,

39.2, 17.9, 17.6, 13.3, 1.05, Ϫ0.63 and Ϫ2.94; m/z (EI) 248 (7%,

M^ϩ), 205 (73, M Ϫ Prⁱ) and 135 (100, Me₂PhSi) (Found: M^ϩ,

248.1584. C₁₅H₂₄SiO requires M, 248.1596). The ratio of the

diastereoisomers was determined by integration of the CHMe-

1

CH_AH_Bsignals in the H NMR spectrum. COSY couplings

were found for the major diastereoisomer 98B between the

following signals: (1) 2.46 to 1.76, 1.00, (0.90–0.81 ϩ 0.84), 0.77

ppm (weak); (2) 1.92 to (0.90–0.81 ϩ 0.84), 0.77 ppm; (3) 1.76

to 2.46, (0.90–0.81 ϩ 0.84) ppm; and (4) (0.90–0.81 ϩ 0.84)

to 2.46, 1.92, 1.76 (weak), 0.14, 0.08 ppm. NOESY enhance-

ments were found for the major diastereoisomer 98B between

the following signals: (1) 1.00 (CHMeCH_AH_B) to 1.76 ppm

(CHMeCH_AH_B); (2) 1.76 (CHMeCH_AH_B) to 1.92 ppm (CH-

Me_AMe_B); (3) 2.46 (CHMeCH_AH_B) to 7.39–7.18 ppm (Ph);

and (4) no enhancement between 1.76 (CHMeCH_AH_B) and

7.39–7.18 ppm (Ph).

1

signals in the H NMR spectrum (2.66 and 2.54 ppm). The

assignment was made on the basis of COSY couplings between

the following signals: (1) 4.07 to 1.92–1.78 ppm, 1.52 and 1.21

ppm; (2) 2.66 to 2.07–1.95 and 1.04 ppm; (3) 2.54 to 2.22–2.15

and 1.09 ppm; (4) 2.22–2.15 to 2.54, 1.52 and 1.09 ppm; (5)

2.07–1.95 to 2.66, 1.92–1.78, 1.21 and 1.04 ppm; (6) 1.92–1.78

to 4.07, 2.07–1.95, 1.52, 1.21, 1.01, 0.99, 0.96 and 0.95 ppm; (7)

1.52 to 2.22–2.15 and 1.92–1.78 ppm. The assignment of the

stereochemistry of this lactone made in the literature^52,53was

conﬁrmed by the presence of an NOE enhancement between

the signal at 2.07–1.95 ppm (C₄-H_ax) and the signal at 4.07 ppm

(C₆-H_ax) in 114A; no such NOE enhancement was present in

114B.

(3RS,5SR)-2,2-Dimethyl-3,5-diisopropyl-5-phenyl-1-oxa-2-

silacyclopentane 99. (99%); ν_max(ﬁlm)/cm^Ϫ11250 (SiMe); δ_H(500

MHz; CDCl₃) 7.40–7.35 (2 H, m, Ph), 7.32–7.25 (2 H, m, Ph),

7.20 (1 H, m, Ph), 2.49 (1 H, dd, J 12.9 and 7.0, CH_AH_B), 1.92 (1

H, septet, J 6.8, CHMe_AMe_BCPh), 1.76 (1 H, t, J 13.4,

CH_AH_B), 1.60 (1 H, m, CHMe_CMe_DCHSi), 0.92 (3 H, d, J 6.5,

CHMe_AMe_BCPh), 0.84 (6 H, d, J 6.7, CHMe_AMe_BCPh and

CHMe_CMe_DCHSi), 0.77 (3 H, d, J 6.9, CHMe_CMe_DCHSi),

0.55 (1 H, ddd, J 13.6, 10.8 and 7.0, CHMe_CMe_DCHSi), 0.19 (3

H, s, SiMe_EMe_F) and 0.18 (3 H, s, SiMe_EMe_F); δ_C(CDCl₃) 146.3,

127.4, 126.3, 126.0, 87.1, 39.3, 39.1, 33.7, 29.2, 24.2, 23.4, 17.8,

17.6, 0.84 and Ϫ2.4; m/z (EI) 276 (12%, M^ϩ), 261 (73, M Ϫ Me)

and 233 (100, M Ϫ Prⁱ) (Found: M^ϩ, 276. 1908. C₁₇H₂₈SiO

requires M, 276.1909). COSY couplings were found between the

following signals: (1) 2.49 to 2.45, 0.92, 0.84 ppm; (2) 1.92 to

0.84, 0.77 ppm; (3) 1.76 to 2.49, 0.55 ppm; and (4) 1.60 to 0.92,

0.84, 0.55 ppm. NOESY enhancements were found between

the following signals: (1) 0.57 to 2.45, 0.92, 0.84 ppm; (2) 2.45

to 7.40–7.18, 1.78 ppm; and (3) 1.78 to 2.45, 0.84, 0.77 ppm.

1,3-Diphenyl-3-dimethyl(phenyl)silyloxy-4-methylpentane

100. ν_max(ﬁlm)/cm^Ϫ11253 (SiMe) and 1117 (SiPh); δ_H(400 MHz;

CDCl₃) 7.73–7.67 (2 H, m, Ph), 7.44–7.09 (7 H, m, Ph), 6.96–

6.91 (2 H, m, Ph), 2.54 (1 H, m), 2.34–2.10 (3 H, m), 2.06 (1 H,

septet, J 6.8, CHMe_AMe_B), 0.79 (3 H, d, J 6.7, CHMe_AMe_B),

0.76 (3 H, d, J 6.9, CHMe_AMe_B), 0.53 (3 H, s, SiMe_CMe_D) and

0.52 (3 H, s, SiMe_CMe_D); δ_C(CDCl₃) 144.2, 142.7, 140.1, 133.5,

129.3, 128.8, 128.3, 128.2, 127.8, 127.5, 126.6, 126.2, 125.6,

84.7, 41.3, 39.5, 30.5, 29.7, 18.1, 17.7, 1.8 and 1.6; m/z (EI) 345

(100, M^ϩϪ Prⁱ) and 135 (100, Me₂PhSi) (Found: M^ϩϪ Prⁱ,

345.1676. C₂₆H₃₂OSi requires M Ϫ Prⁱ, 345.1675).

(4RS,6RS)-6-Isopropyl-4-phenyltetrahydro-2H-pyran-2-one

115A and (4RS,6SR)-6-isopropyl-4-phenyltetrahydro–2H-pyran-

2-one 115B. (83%, 40:60 from a 38:62 mixture of 109A and

109B); R_F(Et₂O–light petroleum, 30:70) 0.19; ν_max(ﬁlm)/cm^Ϫ1

1733 (C᎐O) and 1603 (Ph); 115A: δ (250 MHz; CDCl ) 7.40–

᎐

H

3

7.16 (5 H, m, Ph), 4.22 (1 H, ddd, J 11.8, 5.5 and 2.9, C₆-H_ax),

3.16 (1 H, tdd, J 11.9, 5.9 and 3.7, C₄-H_ax), 2.90 (1 H, ddd, J

17.8, 5.9 and 2.0, C₃-H_eq), 2.53 (1 H, dd, J 17.8 and 11.6, C₃-

H_ax), 2.18–1.94 (3 H, m, C₅-H_eq, C₅-H_axand CHMe₂), 1.02 (3 H,

d, J 7.0, CHMe_AMe_B) and 1.98 (3 H, d, J 7.1, CHMe_AMe_B);

δ_C(CDCl₃) 171.2, 143.1, 129.0, 127.2, 126.5, 85.2, 37.7, 37.6,

32.9, 32.5, 17.9 and 17.7; 115B: δ_H(250 MHz; CDCl₃) 7.4–7.16

(5 H, m, Ph), 4.10 (1 H, ddd, J 10.4, 6.5 and 4.3, C₆-H_ax), 3.33 (1

H, m, C₄-H_eq), 2.77 (2 H, d, J 7.3, C₃-H_eqand C₃-H_ax), 2.11

(1 H, m, C₅-H_eq), 1.91 (1 H, m, CHMe₂), 1.72 (1 H, dt, J 13.7

and 12.0, C₅-H_ax), 1.01 (3 H, d, J 6.7, CHMe_AMe_B) and 0.94 (3

H, d, J 6.8, CHMe_AMe_B); δ_C(CDCl₃) 172.3, 143.4, 129.0, 127.1,

126.6, 82.0, 35.9, 34.8, 33.1, 32.5, 18.1 and 18.0 (Found: M^ϩ,

218.1312. C₁₄H₁₈O₂requires M, 218.1307).

Preparation of the silyl ethers 98, 99 and 100

Typically, a mixture of the diastereoisomers of the alcohols 46,

or the single diastereoisomer 60B, or each of the separate dia-

stereoisomers 53A and 53B (0.28 mmol) in THF (5 cm³) was

stirred with a suspension of sodium hydride (60% dispersion in

oil pre-washed with light petroleum, 0.067 g, 1.65 mmol) in

THF (10 cm³) under argon at room temperature for 24 h. The

mixture was quenched with water (10 cm³) and extracted with

ether (3 × 25 cm³). The combined organic fractions were

washed with brine (50 cm³), dried (MgSO₄) and evaporated

under reduced pressure to give the silyl ethers. The following

compounds were prepared by this method.

(3RS,5RS)-5-Isopropyl-5-phenyl-2,2,3-trimethyl-1-oxa-2-

silacyclopentane 98A and (3RS,5SR)-5-isopropyl-5-phenyl-2,2,3-

trimethyl-1-oxa-2-silacyclopentane 98B. (88%, 25:75 from a

25:75 mixture of 46A and 46B); ν_max(ﬁlm)/cm^Ϫ11250 (SiMe);

98A: δ_H(500 MHz; CDCl₃) (recognisable signals) 7.39–7.37 (2

H, m, Ph), 7.30–7.26 (2 H, m, Ph), 7.21–7.18 (1 H, m, Ph), 2.59

(1 H, dd, J 13.5 and 8.4, CHMeCH_AH_B), 1.85 (1 H, dd, J 13.5

and 8.2, CHMeCH_AH_B); δ_C(CDCl₃) (recognisable signals) 86.9,

44.7, 39.0, 18.2, 15.6, Ϫ0.4 and Ϫ2.6; 98B: δ_H(500 MHz;

CDCl₃) 7.39–7.37 (2 H, m, Ph), 7.30–7.26 (2 H, m, Ph), 7.21–

7.18 (1 H, m, Ph), 2.46 (1 H, dd, J 13.0 and 7.1, CHMeCH_AH_B),

1.92 (1 H, m, CHMe_AMe_B), 1.76 (1 H, t, J 13.1, CHMe-

CH_AH_B), 1.00 (3 H, d, J 7.2, CHMeCH_AH_B), 0.90–0.81 (1 H, m,

Krapcho demethoxycarbonylations

Typically, following Krapcho,³³sodium chloride (0.04 g, 0.684

mmol) and water (0.012 g, 0.684 mmol) and a mixture of

diesters (0.342 mmol) were reﬂuxed in DMSO (40 cm³) for 24 h

when TLC showed complete consumption of the starting

diesters. Water (100 cm³) was added and the mixture extracted

with dichloromethane (3 × 50 cm³). The combined organic

fractions were washed with brine (100 cm³), dried (MgSO₄) and

evaporated under reduced pressure to give a mixture of

monoesters. The following compounds, except 108, were pre-

pared by this method. Later, we found that reaction could be

achieved in higher yield by using lithium chloride (4 equiv.),

water (2 equiv.) and fresh DMSO (typically 15 cm³for 1 mmol

of ester). These conditions not only provided better yields but

also achieved complete reaction typically in 30 min. The com-

pounds 108 and 109 was prepared by this method.

Methyl

(3RS,5RS)-5-dimethyl(phenyl)silyl-3-methylhexan-

oate 104A and methyl (3RS,5SR)-5-dimethyl(phenyl)silyl-3-

methylhexanoate 104B. (81%, 85:15 from an 85:15 mixture

of 72A and 72B); R_F(Et₂O–light petroleum, 10:90) 0.33;

1350

J. Chem. Soc., Perkin Trans. 1, 1997

View Article Online

ν_max(ﬁlm)/cm^Ϫ11740 (C᎐O), 1249 (SiMe) and 1112 (SiPh);

CHSi), 2.04 (1 H, ddd, J 13.8, 9.2 and 4.3, CH_AH_BCHSi),

᎐

104A: δ_H(400 MHz; CDCl₃) 7.48 (2 H, m, o-Ph), 7.39–7.30 (3 H,

m, m- and p-Ph), 3.63 (3 H, s, OMe), 2.35 (1 H, dd, J 14.2 and

4.2, CH_AH_BCO₂Me), 2.05 (1 H, m, MeCHCH_AH_BCO₂Me),

1.89 (1 H, dd, J 14.2 and 9.0, CH_AH_BCO₂Me), 1.28 (1 H, ddd, J

11.7, 4.4 and 2.0, CHSiCH_AH_B), 1.17 (1 H, m, CHSiCH_AH_B),

0.92 (3 H, d, J 2.4, MeCHSi), 0.90 (3 H, d, J 13.0, MeCH-

CH_AH_BCO₂Me), 0.87 (1 H, m, MeCHSi), 0.24 (3 H, s, SiMe_A-

Me_B) and 0.23 (3 H, s, SiMe_AMe_B); δ_C(CDCl₃) 173.9, 138.4,

133.9, 128.8, 127.7, 51.3, 40.1, 39.0, 28.3, 21.1, 16.4, 14.2, Ϫ5.0

and Ϫ5.1; m/z (EI) 278 (11%, M^ϩ), 263 (75, M Ϫ Me), 247 (67,

M Ϫ OMe) and 135 (100, Me₂PhSi); 104B: δ_H(400 MHz; CDCl₃)

(recognisable signals) 2.40 (1 H, dd, J 14.8 and 4.4, CH_AH_B-

CO₂Me) and 1.91 (1 H, dd, J 14.6 and 9.5, CH_AH_BCO₂Me)

(Found: M^ϩ, 278.1701. C₁₆H₂₆O₂Si requires M, 278.1702). The

ratio of diastereoisomers was obtained by integration of the

CH_AH_BCO₂Me signals in the ¹H NMR spectrum; it could also

be measured from the CH₂resonances in the ¹³C NMR spec-

trum (40.1 and 39.0 ppm in 104A and 40.2 and 38.4 ppm in

104B).

0.26(3 H, s, SiMe_AMe_B), 0.16 (3 H, s, SiMe_AMe_B); 107B: δ_H(400

MHz; CDCl₃) 7.30–6.80 (15 H, m, 3 × Ph), 3.50 (3 H, s, OMe),

2.90 (1 H, m, CHPhCH₂CO₂Me), 2.46 (2 H, d, J 7.6, CH_AH_B-

CO₂Me), 2.14 (1 H, dt, J 3.2 and 13.4, CH_AH_BCHSi), 1.91 (1 H,

dd, J 12.8 and 2.4, CHSi), 1.83 (1 H, ddd, J 13.8, 11.6 and 2.4,

CH_AH_BCHSi), 0.17 (3 H, s, SiMe_AMe_B), 0.01 (3 H, s, SiMe_A-

Me_B); δ_C(CDCl₃) 172.5, 142.9, 141.7, 137.2, 134.0, 128.9, 128.3,

128.2, 128.1, 127.8, 127.5, 126.4, 124.6, 51.3, 42.0, 40.3, 35.1,

33.3, Ϫ3.8 and Ϫ5.9 (Found: M^ϩ, 402.2006. C₂₆H₃₀O₂Si

requires M, 402.2015).

Methyl

(3RS,5SR)-3,6-dimethyl-5-dimethyl(phenyl)silyl-

heptanoate 108A and methyl (3RS,5RS)-3,6-dimethyl-5-di-

methyl(phenyl)silylheptanoate 108B. (68%, 64:36 from a 64:36

mixture of 80A and 80B; 60%, 52:48 from a 52:48 mixture of

80A and 80B); R_F(Et₂O–light petroleum, 10:90) 0.33;

ν_max(ﬁlm)/cm^Ϫ11739 (C᎐O), 1249 (SiMe) and 1110 (SiPh);

᎐

108A: δ_H(400 MHz; CDCl₃) 7.49 (2 H, m, o-Ph), 7.35–7.26 (3 H,

m, m- and p-Ph), 3.64 (3 H, s, OMe), 2.27–1.83 and 1.47–1.06 (7

H, m), 0.92–0.72 (9 H, m, 3 × CHMe) and 0.32 (6 H, s, SiMe₂);

δ_C(CDCl₃) 173.8, 140.0, 133.9, 128.7, 127.7, 51.4, 41.5, 33.7,

30.1, 29.8, 28.8, 22.5, 21.1, 20.1, Ϫ2.7 and Ϫ2.8; 108B: δ_H(400

MHz; CDCl₃) 7.49 (2 H, m, o-Ph), 7.35–7.26 (3 H, m, m- and p-

Ph), 3.63 (3 H, s, OMe), 2.27–1.83 and 1.47–1.06 (7 H, m),

0.92–0.72 (9 H, m, 3 × CHMe) and 0.30 (3 H, s, SiMe₂);

δ_C(CDCl₃) 173.7, 139.9, 133.8, 128.7, 127.7, 51.4, 42.0, 34.1,

30.0, 29.7, 28.7, 22.3, 21.9, 19.4, Ϫ2.0 and Ϫ2.2; m/z (EI) 306

(18%, M^ϩ), 291 (52, M Ϫ Me), 275 (44, M Ϫ OMe) and 135

(100, Me₂PhSi) (Found: M^ϩ, 306.2015. C₁₈H₃₀SiO₂requires M,

306.2015). The ratio of diastereoisomers was determined by

integration of the CH₂signals in the ¹³C NMR spectrum (42.0

to 41.5 and 34.1 to 33.7 ppm).

Methyl (3RS,5RS)-5-dimethyl(phenyl)silyl-3-phenylhexanoate

105A

and

methyl

(3RS,5SR)-5-dimethyl(phenyl)silyl-3-

phenylhexanoate 105B. (52%, 29:71 from a 29:71 mixture of

73A and 73B); R_F(Et₂O–light petroleum, 20:80) 0.42;

ν_max(ﬁlm)/cm^Ϫ11738 (C᎐O), 1248 (SiMe) and 1112 (SiPh);

᎐

105A: δ_H(400 MHz; CDCl₃) (recognisable signals) 7.56–7.02 (10

H, m, Ph), 3.53 (3 H, s, OMe), 3.16 (1 H, m, CHPh), 2.62 (1 H,

dd, J 15.1 and 5.9, CH_AH_BCO₂Me), 2.42 (1 H, dd, J 15.1 and

9.1, CH_AH_BCO₂Me), 0.28 (3 H, s, SiMe_AMe_B) and 0.26 (3 H, s,

SiMe_AMe_B); 105B: δ_H(400 MHz; CDCl₃) 7.56–7.02 (10 H,

m, 2 × Ph), 3.55 (3 H, s, OMe), 3.28 (1 H, m, CHPh), 2.51

(2 H, d, J 7.5, CH₂CO₂Me), 1.75 (1 H, ddd, J 13.7, 11.6 and

2.2, CHSiCH_AH_B), 1.37 (1 H, ddd, J 13.6, 11.9 and 3.6,

CHSiCH_AH_B), 0.96 (3 H, d, J 7.3, MeCHSi), 0.60 (1 H, m,

MeCHSi), 0.20 (3 H, s, SiMe_AMe_B) and 0.16 (3 H, s, SiMe_A-

Me_B); δ_C(CDCl₃) 172.8, 143.2, 138.1, 133.9, 128.9, 128.8, 128.5,

128.4, 127.8, 51.4, 42.6, 39.8, 37.2, 15.2, 13.2, Ϫ4.8 and Ϫ5.7;

m/z (EI) 325 (37%, M^ϩϪ Me), 309 (65, M Ϫ OMe) and 135

(100, Me₂PhSi) (Found: M^ϩϪ Me, 325.1624. C₂₁H₂₈SiO₂

requires M Ϫ Me, 325.1624).

Methyl

(3RS,5SR)-5-dimethyl(phenyl)silyl-6-methyl-3-

phenylheptanoate 109A and methyl (3RS,5RS)-5-dimethyl-

(phenyl)silyl-6–methyl-3-phenylheptanoate 109B. (70%, 37:63

from a 37:63 mixture of 81A and 81B); R_F(Et₂O–light petrol-

eum, 10:90) 0.37; ν_max(ﬁlm)/cm^Ϫ11735 (C᎐O) and 1602 (Ph);

᎐

109A: δ_H(250 MHz; CDCl₃) 7.5–6.85 (10 H, m, 2 × Ph), 3.56

(3 H, s, OMe), 2.94 (1 H, m, PhCHCH₂CO₂Me), 2.52 (1 H,

dd, J 15.1 and 7.2, CH_AH_BCO₂Me), 2.36 (1 H, dd, J 15.1

and 7.8, CH_AH_BCO₂Me), 1.84 (1 H, dseptet, J 2.6 and 6.9,

CHMe₂), 1.72–1.53 (3 H, m, CH₂CHSi and CHSi), 0.77 (3 H, d,

J 6.9, CHMe_AMe_B), 0.74 (3 H, d, J 6.8 CHMe_AMe_B), 0.38

(3 H, s, SiMe_AMe_B) and 0.31 (3 H, s, SiMe_AMe_B); 109B: δ_H(250

MHz; CDCl₃) 7.50–6.85 (10 H, m, 2 × Ph), 3.54 (3 H, s, OMe),

3.16 (1 H, m, PhCHCH₂CO₂Me), 2.50 (1 H, dd, J 7.3 and 4.9,

CH_AH_BCO₂Me), 2.47 (1 H, dd, J 14.6 and 7.3, CH_AH_BCO₂Me),

2.02 (1 H, dseptet, J 2.6 and 7.1, CHMe₂), 1.72–1.53 (2 H,

m, CH₂CHSi), 0.96 (3 H, d, J 6.9, CHMe_AMe_B), 0.82 (3 H, d,

J 7.0, CHMe_AMe_B), 0.68 (1 H, dt, J 2.6 and 9.9, CHSi), 0.22

(3 H, s, SiMe_AMe_B) and 0.21 (3 H, s, SiMe_AMe_B); δ_C(CDCl₃)

172.8, 143.3, 139.6, 133.9, 128.3, 128.2, 127.7, 127.6, 126.3,

51.4, 42.0, 41.0, 33.6, 29.6, 28.3, 22.5, 22.1, Ϫ1.6 and Ϫ3.1

(Found: M^ϩϪ Me, 353.1938. C₂₃H₃₂O₂Si requires M Ϫ Me,

353.1937).

Methyl(3RS,5SR)-5-dimethyl(phenyl)silyl-3-methyl-5-phenyl-

pentanoate 106A and methyl (3RS,5RS)-5-dimethyl(phenyl)silyl-

3-methyl-5-phenylpentanoate 106B. (71%, 84:16 from an 81:19

mixture of 76A and 76B); R_F(Et₂O–light petroleum, 10:90)

0.41; ν_max(ﬁlm)/cm^Ϫ11737 (C᎐O) and 1599 (Ph); 106A: δ (400

᎐

H

MHz; CDCl₃) 7.40–6.91 (10 H, m, 2 × Ph), 3.55 (3 H, s, OMe),

2.33 (1 H, dd, J 11.7 and 3.2, CHSi), 2.27 (1 H, dd, J 14.5 and

4.6, CH_AH_BCO₂Me), 1.97 (1 H, dd, J 14.5 and 8.1, CH_AH_B-

CO₂Me), 1.86–1.78 (2 H, m, CHMe and CH_AH_BCHSi), 1.58 (1

H, ddd, J 15.0, 10.1 and 3.2, CH_AH_BCHSi), 0.84 (3 H, d, J 6.5,

MeCH), 0.24 (3 H, s, SiMe_AMe_B) and 0.16 (3 H, s, SiMe_AMe_B);

δ_C(CDCl₃) 173.5, 142.5, 137.3, 134.1, 129.0, 128.0, 127.9, 127.6,

124.5, 51.2, 39.6, 36.1, 33.9, 29.04, 20.8, Ϫ4.0 and Ϫ5.5; 106B:

δ_H(400 MHz; CDCl₃) 7.40–6.91 (10 H, m, 2 × Ph), 3.59 (3 H, s,

OMe), 2.38 (1 H, dd, J 12.9 and 3.1, CHSi), 2.16 (1 H, dd, J

14.8 and 7.0, CH_AH_BCO₂Me), 2.08 (1 H, dd, J 14.8 and 7.4,

CH_AH_BCO₂Me), 1.95 (1 H, m, CH_AH_BCHSi), 1.80 (1 H, m,

CHMe), 1.36 (1 H, ddd, J 13.7, 10.3 and 3.1, CH_AH_BCHSi),

0.80 (3 H, d, J 6.6, MeCH), 0.24 (3 H, s, SiMe_AMe_B) and 0.15 (3

H, s, SiMe_AMe_B) (Found: M^ϩ, 340.1853. C₂₁H₂₈O₂Si requires

M, 340.1858).

Acknowledgements

We thank the EPSRC (D. C. B., R. N. W.) and the EU (A. B.)

for ﬁnancial support.

References

Methyl

(3RS,5SR)-5-dimethyl(phenyl)silyl-3,5-diphenyl-

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Paper 6/07545B

Received 5th November 1996

Accepted 2nd January 1997

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1352

J. Chem. Soc., Perkin Trans. 1, 1997

Article Doi

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