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

2.1.1 Synthesis of SHydroxy-a-Amino Acids: General Routes
Many of the general methods described in chapter one are capable of synthesizing
P-hydroxy-a-amino acids and other recent methods include Sharpless AE,'." Sharpless
AD,I6 electrophilic amination" and hydro~ylation.~~ stereoseiective hydrolysis of
azindine carboxylate esters,I9 aldol condensationsm from oxazolidinone intermediates2'
and numerous other metho&.= A bnef overview of the synthesis of f3-hydroxy-a-amino
acids complementing that in chapter one will be described.
2.1.2 Synthesis of Racernic PHydroxy- a-Amino Acids
Racernic f!-hydroxy-a-amino acids have traàitionally been synthesized by the
addition of glycine enolates to aldehydes and ketones. Numerous examples of this
methodology exists and are typified by the report of Ozaki et al? in which a-
isocyanoacetamide 2.12 is reacted with aldehydes in the presence of KOH. forming the
truns-oxazoline4-~arboxafnides 2.13 (Scheme 2.1). Recrystallization followed by acid
h ydrol y sis gave pure threo- ph ydrox y amino acids in excellent yields.
Shanzer et al. have reported a route to synthesize both threo and erythro isomers
from glycine? Reaction of the N&-bis(aimethylsily1)glycine trimethylsilyl ester 2.14
with aldehydes or ketones gave pure eryrhro diastereomer, attributable to induction by
the bulky disilylated arnino group (Scheme 2.2) The threo isomers were obtained from