Enantioselective tandem Michael reaction to nitroalkene catalyzed by bifunctional thiourea: total synthesis of (-)-epibatidine

Successive treatment of gamma,delta-unsaturated beta-ketoesters and nitroalkenes with a bifunctional thiourea and TMG promoted the tandem Michael addition, giving rise to highly functionalized cyclohexanones in good yields. The three contiguous stereogenic centers of the obtained products were constructed with high diastereo- and enantioselectivity (up to > 99% de and 92% ee). The reaction was successfully applied to the asymmetric synthesis of (-)-epibatidine, which was synthesized from the cyclohexanone derivative in seven steps in 30% overall yield. (c) 2005 Elsevier Ltd. All rights reserved.