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

4.1.4.3 Catalytic HydrogeMrion
The fmt use of catalytic hydrogenation to synthesize y-substituted glutamic acids
was reported in 1990 by Hon et al." TBDMS protected pyrollidinone 4.23 derived from
L-pyroglutamic acid 4.29 was alkylated and then selenenylated/deselenylated to give
both endo 4.25 and exo 4.26 a$-unsaturateci lactams. Catalytic hydrogenation gave the
(2S,4S) diastereomer 4.27 as the sole product through steric approach control induced by
the TBDMS protecting group. Deprotection evennially gave the desired y-
benzylglutarnate 4.28 in 13% overall yield (Scheme 4.7).
hoc
Scheme 4.7
OTBS 2) PTSA, MeOH
4) Jones oxidaüori
5) TF& CH& H
In 1992, Young et al., while preparing isotopically labeled valines, used 2S-
pyroglutamatic acid as the starting point of their synthesis since it "not only had the
desired stereochemistry at C2, but the 1.3 relationship of C2 and C4 in the ring offered
the possibility of inducing chirality at C4.''38 The t-butyl ester of pyroglutarnate 4.29 was
converted to the enaminone 4.31 in 91% yield using Bredereck's reagent 4-30," and the
intermediate then reduced by catalytic hydrogenation using 10% Pd-C to give the
stereochemically pure cis4methyl derivative 4.32 (Scheme 4.8).