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

Abstract

Several novel, chiral derivatives of β-aminopropionic acid were studied as potentially useful precursors of enantiopure α-substituted-β-amino acids. In particular, the diastereoselectivity of alkylation of ( R, R)- 2-Li enolate showed substantial stereoinduction by the bis[α-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 α-phenylethylamino group in the methylation of ester enolate ( S)- 3-Li was lower (65% ds) under standard conditions (THF, −78°C) 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.