A versatile access to vicinal diamine motifs by highly anti-selective asymmetric vinylogous Mannich reactions: an efficient total synthesis of (+)-absouline

Abstract

We report the asymmetric vinylogous Mannich reactions (VMRs) of N-Boc-2-tert-(butyldimethylsilyloxy)pyrrole (TBSOP) with N-tert-butanesulfinylimines. The reaction is highly anti-diastereoselective and shows good generality for the direct construction of a variety of vicinal anti-diamine motifs that are found in a number of biologically active alkaloids and medicinal agents. A VMR adduct was elaborated in six steps into the 1-aminopyrrolizidine alkaloid (+)-absouline, which constitutes the second and also the most efficient total synthesis of the natural enantiomer of the title alkaloid.