Chiral beta-Amino Sulfenates: Synthetic Access and Diastereoselective Alkylation

Research into a new family of chiral sulfenates containing a β-substituted, N-protected β- amino functionality, derived from amino acids, has been extended in this investigation for its diastereoselective alkylation reactions of sulfenates. Two L-phenylalanine derived precursors to the in-situ generation of a β-amino sulfenate were prepared by multiple convergent pathways, and each sulfenate liberation method was evaluated by alkylation with BnBr for both its diastereoselection, and overall sulfoxide yield. It was demonstrated that sulfenate liberation from the β-sulfinyl ester proved to be a superior method when employed with the base LiHMDS. Evaluation of this method by variation of temperature, showed no significant variance in dr’s, but affected yields depending on the electrophile utilized. Other β-amino sulfenates derived from N- Boc protected D-phenylalanine, L-valine, L-alanine, as well as Cbz protected L-phenylalanine were also evaluated by alkylation with BnBr and showed mixed yields ranging from 58-90% and yields generally around 20:80.