Bifunctional chiral auxiliaries 4: Alkylation of enolates derived from 1,3-diacyl-trans-4,5-tetramethyleneimidazolidin-2-ones

Tetrahedron Letters. Vol. 33. No. 8. pp. 1117-1120.1992 Printed in Great Britain

0040439/92 $3.00 + .oO Pergamon Press plc

Bifunctional C hiral Auxiliaries 4: Alkylation Enolates Derived from 1,3-Diacyl-trans-4,5tetramethyleneimidazolidin-2-ones’ Stephen

G. Davies*

The Dyson Pert-ins Laboratory,

Abstract:

Addition of alkyl halides

tetramethyleneimidazolidin-2-ones

and Andrew

to sodium

and potassium

allows diastereoselective

prepared in this way with a 93% enantiomeric

The diastereoselective in natural

synthesis 2. Typically

of the newly-formed

introduced3.

Evans has reported alkylation reactions

stereogenic

such asymmetric

alkylations

and consequently,

centre is determined

three diastereoisomers

stereoregular,

starting from an acetyl group, the undergo

are

highly

with the more reactive alkyl halides (methyl iodide, benzyl bromide, ally1 aldol reactions

elaboration

in which dibutylboron

enolates

derived from 1,3-

N-acyl oxazolidone

of both acyl sidechains 1.5, In this communication

alkylation of these bifunctional diastereoisomers

are highly

of N-acyl oxazolidones

of the dialkylated

(l-3) of this dialkylated

enolates so as we report the

chiral auxiliaries viu their sodium and potassium enolates.

As alkylation of both acyl sidechains may generate two new stereogenic four possible

was

by the order in which the substituents

reproduce the transition states of the corresponding

to allow the stereoselective stereoselective

alkylation of both acyl sidechains with the S-(-)-3-Phenyl-Z-methylpropan-l-016

that lithium and sodium enolates

etc.)4. We have already reported

diacylimidazolidin-2-ones

of 1,3-diacyl-trans-4,5-

alkylation of chiral enolates is a powerful synthetic method which has been widely

product

configuration stereoselective

enolates

excess.

occurring via a specific enolate geometry and conformation

bromide,

A. Mortlock

South Parks Road, Oxford, OX1 3QY, U.K.

latter enolates showing generally higher stereoselectivities.

employed

of

centres, it might be expected that

product could, in theory, be formed. In fact, there are only material, two of which (1 and 3) have a C2 symmetry

and one (2) which does not.

1117

element

1118

This phenomenon

has been reperted in a related system by Seebach during a synthesis of (+)-I 1 ,l l’-di-O-

methylelaiophylidene, diastereoisomer

in which the low stereoselectivity

of the reaction ensured

Simple acyl derivatives of truns-4,5-tetramethyleneimidazolidin-2-one and homochiral

form7. Thus, treatment

imidazolidin-2-one

4a at -78°C with sodium bis(trimethylsilyl)amide

using potassium

bis(trimethylsilyl)amide

which

are readily prepared in both racemic

of 1,3-dipropionyl-trans-4,5tetramethylene-

of a THF solution

(3eq) followed by addition of methyl iodide

and further stirring at -78°C for 3 h, gave 5 in 69%, after work-up repeated,

that the non-C2 symmetric

was formed as the major product (as expected from a statistical product distribution)6.

and chromatography.

The reaction

gave 5 in 87% yield under identical

was

reaction

conditions

i) MN(SiMe& * ii) Mel M= Na 69% K 87%

Whilst

methylation

of the butanoyl

tetramethyleneimidazolidine-2-one

occurred

(4b)

and hydrocinnamoyl

cleanly at -78“C, repetition

(4~) derivatives of these conditions

of tram-4,5would not allow

alkylation with either ally1 bromide or benzyl bromide. However, by allowing the reaction to warm to -30°C after addition of the alkyl halide, clean dialkylation could be achieved in good chemical yield. In those diastereoisomers

cases

where

suggested

assumed that the selectivity

all three diastereoisomers that both alkylation

could

steps proceeded

be detected,

the distribution

of these three

with the same diastereoselectivity.

Thus, x may be calculated from the ratio of I :2 as this ratio is equivalent to x/2.

T’ 0

0

ii) RZX

+I---

R’

2E

i) NaN(SiMe& or KN(SiMe&

N

2:

-

CI:

0

N

H

R’

0 + R’=CH3

If it is

of one of these alkylation steps is x: 1, the expected ratio of 1:2:3 should be x2:2x: 1.

4a

R’=

CHS CH3

CH,CH3 CH,CH:, CH,Ph CH3

CH,Ph

i=+ R2 = C3H5 CH2Ph CH,Ph 1 3 ::: CH:CHs CH,CH,,

; c d ; g

1119

Table 1: Alkylation

Reactions

of Sodium Enolates

* Values in parantheses are calculated assuming the same stereoselectivity # Calculated from the ratio of 1 to 2 The stereoregularity methylanon

of these reactions

assignment

should also be noted; thus, the third diastereoisomer

of 4b is the major product in the ethylation

of product stereochemistry

of 4a. Because of this stereoregularity,

was made by analogy with the alkylation

of this stereochemistry

synthesis of ($6

This may result from the higher temperatures

lower temperature silyl)amide.

and consequently

the series of reactions

It was found that both allylation

enhanced diastereoselectivities.

Furthermore,

was repeated

and benzylation

occurred

Unambiguous

(vide infra).

in these reactions is lower than is observed

It was felt that a more reactive enolate might show higher stereoselectivity

formed in the the assignment

of N-acyl oxazolidones.

was later achieved with the asymmetric

It is clear that the level of diastereoselection reactions of N-acyl oxazolidones:

for each alkylation step

in the analogous

required for reaction. due to the reaction occurring at using potassium

readily

bis(trimethyl-

at -78°C with dramatically

alkylation with ethyl iodide was now possible although it required

the reaction to be warmed to -30°C before being quenched and worked-up in the normal manner.

Table 2: Alkylation

Reactions

of Potassium

Enolates

* Values in parantheses are calculated assuming the same stereoselectivity # Calculated from the ratio of 1 to 2 To confirm the assignment

of stereochemistry

derived from (R,R)-4a was quenched mixture

of the diastereoisomers

of the products

for each alkylation step

of these reactions,

the potassium

with benzyl bromide in the manner already described

la, 2a and 3a, consistent

with a facial selectivity

enolate

to give a 94:5:(l)

of 97:3. This mixture of

dialkylated products was treated with lithium aluminum hydride at -20°C to give 3-phenyl-2-methylpropan-l-01 6 as a colourless

oil, after work-up and chromatography.

The specific rotation of this material was found to be

[a]$0

-10.2 (c 1.1, benzene) corresponding

to an enantiomeric

[a]$0

+11.0 (c 1.1, benzene) for the homochiral R enantiomefl, g. Thus, reductive cleavage proceeds without

excess of 93% based on the literature value of

1120

detectable epimerisation, excess

as the 94:5:(l) mixture of diastereoisomers

of Y4%, and confirms

obtained

with N-acyl

oxazolidones

should give a product with an enantiomeric

of la. This is as expected

the configuration

and allows assignment

dialkylated products by virtue of the stereoregularity

after consideration

of the results

stereochemistries

within all the

of the relative

of the alkylation process. 0

Ph

Y+

i) Et,B / HOAc ii) LiAlH, _

HO&Ph

iii) H202 (25)-6

35% Ph

(R,R)-4a

la - 88% d.e.

It is proposed

that the transition

state models

between

the enolate

trajectories reaction

with the reaction occurring counterion

’

for these alkylation

described for the analogous reactions of N-acyl oxazolidone is consistent

which an electrophile

reactions

parallel

those previously

enolates 4. Thus, the sense of asymmetric

via a syn enolate which is conformationally

and the imidazolidin-2-one

occurs predominantly

93% e.e.

carbonyl

restrained

group. Of the two possible

may adopt, one is sterically hindered by the cyclohexyl

methylene

on the face of the enolate exo to this group, The reduced

The greater stereoselectivities by chelation.

For the corresponding

requires higher temperatures

which makes

sodium enolates,

by the greater reactivity of

where the enolate is more conformationally

which are somewhat

less reactive,

alkylation

and reaction may occur via both the chelated syn and open anti enolates, causing a

marked reduction in the stereoselectivity

Acknowledgements.

group and

shielding of the two faces of the enolate. shown by potassium enolates may be rationalised

these species which allows alkylation to occur at lower temperature, restricted

approach

diastereoselection

observed with methyl and ethyl iodide may then be ascribed to the small size of these electrophiles them less sensitive to this differential

induction

by chelation

of alkylation.

We thank BP International,

Sunbury

for a Research

Studentship

(to AAM) and a

Venture Research Award.

References 1. For Part 3 see: Davies, S.G.;

2. Evans, D.A.

‘Asymmetric

3. Baird, G.J,;

Bandy, J.A.;

4. Evans, D.A.;

Mortlock,

Synthesis’,

A.A. Tetrahedron: Morrison,

Davies, S.G.;

Ennis, M.D.;

Prout, K. J. Chem. Sot.,

6. Seebach, D.; Chow, H-F.; Jackson, R.F.W.; 1986,107,

Sutter, M.A.; Thraisrivongs 4791-4794.

S.; Yamada, S-I. Chem. Pharm. Bull. 1968, 16, 1953-1971.

(Received in UK 9 December

1991)

1001-1004. 1983, 1202-1203.

1737-1739.

4787-4790.

1281-1308.

7. Davies, S.G.; Mortlock, A.A. Tetrahedron Lett. 1991,32, 8. Terashima,

1991,2,

Chem. Commun.

Mathre, D.J. J. Am. Chem. Sot. 1982,104,

5. Davies, S.G.; Mortlock, A.A. Tetrahedron Lett. 1991,32, Ann. Chem.

Asymmetry.

J.D. Ed.; VoE3, 1983, 1.

S.; Zimmermann,

J. Liebigs