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

This methodology was fùrther expanded to include other yralkyl groups (R=Et,
nPr, Bn)" in an elegant 1 &addition of Grignard reagents to the vinyl amide 4.33 to give
the alky lidene derivative 4.34 (Scherne 4.9)." Hydrogenation gave one stereoisomer.
4.34
R = Et, nPr, Bn
Scheme 4.8
Scheme 4.9
4.32
R = Et, Wr, Bn
A similar approach has been described to synthesize 4-substituted glutamic acids
by using aldol reactions to introduce various substituents." The hydroxylated products
4.35 were dehydrated to the Calkylidene pyroglutarnates 4.36 and then hydrogenated to
give exclusively the 2S,4S stereoisomer 4.37 (Scheme 4.10). A variety of esters have
been used as protecting groups in both this synthesis and by other groups indicating a
bulky group is not necessary to achieve stereoselectivity in this step?