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

Scheme 2.10
Schollkopf et al. have synthesized the protected denvatives of Dfhreo-p-
phenylserine with 86% ee and 4% de and D-threo-p-benzylserine with 89% ee and 66%
de from the lithium enolate of the bis-lactim ether 133. The titanium enolates generally
gave much better diastereoselectivities upon condensation with a number of aromatic
aldehydes to give the desired adducts in 65-8396 yield (Scheme 2.1 l)." Deprotection by
acid hydrolysis gave the methyl esters in 4666% yields, significantly lower than yields
obtained for the aliphatic B-hydroxy-a-amino acids indicating the relative instability of
the aromatic compounds. The bis-lactim ether 1.33 enolate has also been reacted with
acetone to give the P-duwthyl-P-hydroxy adduct in 98% yield and after deprotection
obtained in 48% overall yield with >95% ee.*'
Scheme 2.11
OMe
L-Val-OMe
Me Me
HO
R
1.33
R H2 '"'co~H
R = H, -Me. CCN, 4-Br, 4-NO2, 2-OCH2Ph
Seebach's oxazolidinone enolate 1.42 has ken reacted with aromatic aldehydes
to give the threo adduct with concomitant transfer of the N-benzoyl protecting group to
the hydroxyl in 77-85% yield and 88-96% diastereoselectivity (Scheme 2.12):' Only