Enantioselective synthesis of ?-amino acids. Part 11: Diastereoselective alkylation of chiral derivatives of ?-aminopropionic acid containing the ?-phenethyl group

Several novel, chiral derivatives of ?-aminopropionic acid were studied as potentially useful precursors of enantiopure ?-substituted-?-amino acids. In particular, the diastereoselectivity of alkylation of (R,R)-2-Li enolate showed substantial stereoinduction by the bis[?-phenylethyl]amide auxiliary, leading to 80% ds in the methylation reaction. No appreciable effect upon diastereoselectivity was observed by the presence of additives (LiCl, HMPA, DMPU) in the reaction. On the other hand, stereoinduction by the ?-phenylethylamino group in the methylation of ester enolate (S)-3-Li was lower (65% ds) under standard conditions (THF, ?78C) but improved to 81% ds in the presence of 3 equiv. of HMPA as cosolvent. Matched and mismatched derivatives, (R,R,S)-11 and (R,R,R)-11, respectively, were methylated via their corresponding lithium enolates. Observed diastereoselectivities generally followed the anticipated tendencies based on double stereoinduction. Thus diastereoselectivity reached 89% ds in the methylation of the matched isomer, (R,R,S)-11-Li.