Stereoselective nucleophilic addition of chiral lithium enolates to (N-tosyl)imines: enantioselective synthesis of -aryl- -amino acid derivatives

Nucleophilic addition of the chiral lithium enolates of (S)-(−)-4-benzyl-2-oxazolidinone acetamide with N-tosyl arylaldehyde imines gives -aryl-amino acid derivatives in good yields and excellent diastereoselectivity. © 2002 Elsevier Science Ltd. All rights reserved. -Amino acids and their derivatives have attracted considerable attention in recent years due to their occurrence in biologically active natural products. -Amino acids also serve as precursors in the synthesis of -lactams, piperidines, indolizidines, and therapeutically enhanced peptides. Moreover, peptides consisting of -amino acids, the so-called -peptides, have been extensively studied recently. Given their importance in various fields, considerable efforts have been directed to the stereoselective preparation of -amino acids and their derivatives. Among the various methodologies, the reactions of imines with ester enolates or ketenes are powerful approaches for the synthesis of -amino acids and -lactams, and they have been extensively explored in the past decades. N-Sulfonylimines have attracted considerable attention in recent years, since these highly electrophilic species are capable of undergoing some unique transformations, including nucleophilic additions and cycloadditions. They are also readily available. Evans’ chiral oxazolidinones have been widely employed in asymmetric synthesis, in particular, the aldol reactions of aldehydes with lithium or boron enolates have been found to give high diastereoselectivities in the presence of oxazolidinone as the chiral auxiliary. The analogous reaction of N-sulfonylimines with chiral lithium enolates would be expected to give -amino acid derivatives with high diastereocontrol (Scheme 1). Despite the apparent advantages of this approach, there is no report in the literature of the investigation of this reaction so far. In this communication, we report our study on the reactions of N-tosyl arylaldehyde imines with chiral lithium enolates derived from (S)-4-benzyl-2-oxazolidinone amides. The results indicate that the reaction is highly efficient and stereoselective, thus constituting a practical procedure for the synthesis of enantiomerically pure -aryl amino acids. Thus, the (S)-4-benzyl-2-oxazolidinone acetamide 1a was deprotonated with 1.1 equivalents of lithium diiso-