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

O
Scheme 1.11
O
R1,qH2
m OH
RI= H, ~ 0, NHR'
Bn, NH2
a-Hydroxy-carboxylates are also readily available chiral compounds and lend
themselves to N-nucleophilic substitution (Scheme 1.12). The reactions are generally
clean although racemization difficulties have been encountered. Direct substitution by N-
nucleophiles has ken achieved with sodium azide," amines:2 phthalimidef3 and imides3)
under Mitsunobu conditions. Conversion of the alcohol to the triflate and subsequent
direct displacement with di-N-Boc-imide has proven to be especially effective3' and has
advantages over the Mitsunobu method, which requires harsh conditions for the
unmasking of the nitrogen functionality.
Scheme 1.12
One of the best methods for the generation of a-amino acids by nucleophilic
amination has been developed by Evans et al? The use of N-acyloxazolidinones 18M to
generate a-bromides followed by SN2 displacement to the azide gives the desired
precursor in high diastereoselectivity (usuaily 90% de) (Scheme 1.13). Altering the
stereochemistry of the N-acyloxazolidinones 18m cm generate both enantiomers of 1.6.
Furthemore, P-substituted-a-amino acids have been synthesized by first incorporating