Vinylogous Mannich reactions. The asymmetric total synthesis of (+)-croomine

We have recently investigated the vinylogous Mannich reaction as a key construction for the synthesis of alkaloid natural products. The general plan is illustrated by the nucleophilic addition of 2-trialkylsilyloxy furan to the cyclic iminium ion to provide a mixture of the isomeric adducts threo-5 and erythro-5 in which the threo-5 product typically dominates. Since the stereochemistry at the newly created stereogenic centers in the threo-5 adduct corresponds to the pairwise relationships at C(9)-C(9a) and C(3)-C(14) of croomine (1), it occurred to us that vinylogous Mannich reactions might be applied to the design of a highly convergent strategy for the synthesis of 1 and related alkaloids. We report the successful implementation of this strategy in an extraordinarily concise, asymmetric synthesis of (+)-croomine (1).