Tandem Double-Michael-Addition/Cyclization/Acyl Migration of 1,4-Dien-3-ones and Ethyl Isocyanoacetate: Stereoselective Synthesis of Pyrrolidines

摘要

Pyrrolizidine alkaloids are widespread among various plants and insects and display important biological activities. The formation of the pyrrolizidine framework generally involves building a second five-membered ring onto a preformed pyrrolidine moiety. Therefore, the development of a new strategy for the efficient construction of the azabicyclic skeleton from simple acyclic starting materials in a single step is highly desirable. Herein, we report an organo-catalytic domino reaction of 1,4-dien-3-ones 1 with ethyl isocyanoacetate (2; Scheme 1). This new general approach allows, in a single reaction, the formation of three C—C and one C—N bonds in a regio- and diastereoselective manner, which provides efficient access to the azabicyclic compounds 3—the motif in pyrrolizidine alkaloids.