Asymmetric Synthesis of β-Amino-cyclohexyl Sulfonates via aza Michael Addition

Abstract

The Lewis acid catalyzed asymmetric synthesis of β-amino-cyclohexyl sulfonates via aza-Michael addition is reported. As key step the addition of (S)-1-amino-2-methoxymethyl-pyrrolidine (SAMP) or (R,R,R)-2-amino-3-methoxymethyl-2-azabicyclo[3.3.0]-octane (RAMBO) to alkenyl-cyclohexyl sulfonates is applied, to give β-hydrazino sulfonates in moderate to good yields and diastereomeric excesses (yield = 41-85%, de = 55-90%). The epimers are separated by preparative HPLC, followed by reductive N-N bond cleavage with BH 3 .THF and protection of the resulting amines with CbzCl to afford NCbz-protected-β-amino-cyclohexyl sulfonates in moderate to good yields (38-68%, 2 steps) and enantiomeric excesses (ee) of ≥96%.