Asymmetric alkylations of a sultam-derived glycinate equivalent: practical preparation of enantiomerically pure α-amino acids

Tetrahedron Printed in

Letters,Vo1.30,No.44,pp Great Britain

6009-6010,1989

ASYMMETRIC ALKYLATIONS PRACTICAL

OF A SULTAM-DERIVED

PREPARATION

OF ENANTIOMERICALLY

Wolfgang Oppolzer’, Dgpartement

0040-4039/89 $3.00 Pergamon Press plc

de Chimie Organique,

+ .oo

GLYCINATE EQUIVALENT: PURE a-AMINO

ACIDS

Robert Moretti and Silvia Thomi

Universiti

de Geneve, CH- 1211 Geneve 4, Switzerland

Abstract: Deprotonation/alkylation of sultam-derived N-[bis(methyl)thiomethylene]glycinate equivalent 2 gave crystalline products 5 which on mild hydrolysis furnished a-amino acids 2 (-100% e.e.) in high overall yield. Chiral glycine equivalents pure o-amino

represent

acids ‘. Straightforward

an attractive pivotal source for asymmetric alkylations of glycine enolate derivatives

syntheses of enantiomerically

are, however, relatively scarce 2 and,

despite their elegance, leave plenty of room for more practical and general alternatives. We report here the advantageous

use of the readily available and widely applicable sultam auxiliary 1 3. Me3Al-

mediated acylation of 1 with methyl N-[bis(methylthio)methylene]glycinate “glycinate” 2 (89%) 4*5 which served as a common precursor

(a 4 furnished,

for various a-amino

after crystallization,

acids z (Scheme, Table).

I

nSuLi , THF, -7s”C

83 -100% W-l,aq.THF r.t

WNaOHISQNHSO,, Cl-&~

I H&J

, 0°C

NeSMe 0.5 N a&H’24 / THF r*

X’N 0

a b : ; t

5

of Enantiomerically R

1 2 3 4 5 6 7 8

HMPA

0

6 Table Preparation

R-Hal, x*+4

Me PhCH2 CHgCH-CH tBu02CCH2 J nC4H9 Me2CH-CH2 Me2CH PhCH,

Hal I I I Br I I I I

Pure a-Amino Deprotonation Conditions BuLi BuLi BuLi BuLi BuLi BuLi BuLi NaOH/PTC

Acids 7 by Alkylation/Hydrolysis

3 -+ 5 -+ 7 5

Yield [%I”) 5 from 3

d.e. [%I”) 5

M.p. [‘Cl 5

87bl 93 ( 96) 87 ( 94) 96 (100) 86 ( 89) 85 ( 87) 95’) - ( 90)

>99b) (96.4) >99 (94.7) .99 (96.8) >99 (98.4) >99 (95.6) ~99 (95.6) >99E) (97.7) - (99.6)

119-120 132-133 83 - 84 142-144 95 - 97 125:;)27

Yield [%] 7 from 5 >99 >99 >99 75d) >99 299 84

-

a) Values apply to chromatographed and recrystallized (crude) 5. b) Direct crystallization without FC. c) Alkylation in the presence of (nBu)4NI. d) Treatment of 5d with CF C02H/r.t./2 h prior to hydrolysis sequence to give free (S)-aspartic acid. e) Chromatographed non-crys ta&lme solid.

e.e. [%] 7 >99.8 >99.8 >99.8 >99.8 >99.8 99.5 >99.8