Asymmetric synthesis of alpha-substituted beta-amino sulfones by aza-Michael addition to alkenyl sulfones and subsequent alpha-alkylation

The aza-Michael addition of enantiopure 1-aminopyrrolidines to (E)-alkenyl sulfones in the presence of a catalytic amount of ytterbium trifluoromethan esulfonate [Yb(OTf)(3)] yields beta-hydrazino sulfones in moderate to good yields and with diastereoselectivities of up to 98%, The latter undergo red uctive N-N bond cleavage with BH3 THF and, after N-protection with Boc(2)O or benzyl bromide, afford N-protected beta-amino sulfones with moderate to high enantiomeric excesses (ee = 42 to greater than or equal to 96%) withou t racemization. Subsequent alpha-alkylation of the N,N-dibenzyl protected b eta-amino sulfones with various electrophiles yields alpha-alkyl-beta-amino sulfones in excellent yields (88-97%) with high diastereomeric (de greater than or equal to 96 to greater than or equal to 98%) and enantiomeric puri ty (ee = 94 to greater than or equal to 96%). The absolute configuration of the new stereogenic centre was determined by X-ray structural analysis and confirmed by NMR spectroscopy (NOE experiments). Possible reaction mechani sms for the conjugate addition and alpha-alkylation are presented.