Bifunctional thiourea-catalyzed enantioselective double Michael reaction of γ,δ-unsaturated β-ketoester to nitroalkene:: asymmetric synthesis of (-)-epibatidine

The asymmetric synthesis of 4-nitrocyclohexanone derivatives has been accomplished by enantio selective double Michael additions of gamma,delta-unsaturated beta-ketoesters to nitroalkenes using a catalytic amount of bifunctional thiourea and TMG. The three contiguous stereogenic centers of the obtained products were constructed with good to high diastereoselectivity and up to 92% ee. The biologically active natural product, (-)-epibatidine, has been synthesized from the intermediate 11a in seven steps in 30% overall yield. (C) 2004 Elsevier Ltd. All rights reserved.