Asymmetric synthesis of alpha-substituted beta-amino sulfones by aza-Michael addition alpha-alkylation

The aza-Michael addition of (S)-1-amino-2-methoxymethyl-pyrrolidine (SAMP) to alkenyl sulfones (E)-1, followed by reductive N-N bond cleavage with BH3 . THF and N-benzylation yields N-benzyl-protected beta-amino sulfones (R)-3 with high enantiomeric excesses (ee greater than or equal to 96 %). Subseq uent alpha-alkylation of (R)-3 with various electrophiles leads to alpha-al kyl-beta-amino sulfones (R,R)-4a-e in excellent yields (88-97 %) and finall y high diastereomeric (de = 96 - greater than or equal to 98 %) and enantio meric purity (ee greater than or equal to 96 %). The absolute configuration was determined by X-ray structural analysis and confirmed by NMR spectrosc opy (NOE-experiments).