Solution and Solid Phase Synthesis of Unusual a-Amino Acids From

4.1.4.4 anion Chernisîry (Including Pyroglutamic Acid)
Various groups have tried to utilize the chiraiity of glutamic acid in an attempt to
induce stereochemistry in addition reactions. The fmt report of the use of carôanion
chemistry to generate 4-substituted glutamic acids was in 1980 when Robert et al.
attempted to synthesize y-carboxyglutarnic acid in what they termed an effort to mimic
nature? Glutarnic acid, protected as the N-trityl dibenzyl ester 4.43, was treated with
lithium diisopropylamide (LDA) to generate the enolate. The buky trityl group was used
to decrease the acidity of the a-proton through stenc effects and hence reduce
racemization. The enolate was treated with benzyl chloroformate, then hydrogenated to
give y-carôoxyglutamic acid 4.10 in 50% yield frorn the hilly protected glutamate. The
authors reported no detectable racemization occurred at the a-carbon.
Scheme 4.12
Tanaka et al.' introduced the use of y-anion chemistry with pyroglutamate, using
the chiral template to synthesize y-carboxyglutamic acid in a rnanner identical to that
reported by Robert and CO-workers six years previously.
Baldwin et al., in the first of a series of papers. described enolate generation and
subsequent aldol chemistry on N-trityl-glutamic acid-ymethyl ester a-t-butyl ester 4.45
(P=Trt, R'=?BU, R~=M~)." Although no mention was made conceming any