Tandem [4 + 2]/[3 + 2] Cycloadditions of Nitroalkenes. 9. Synthesis of (−)-Rosmarinecine

Abstract

(−)-Rosmarinecine (2) is the necine base portion of the pyrrolizidine alkaloid (−)-rosmarinine. (−)-Rosmarinecine is a representative of the group of pyrrolizidines that show a cis relationship between adjacent stereocenters C(1), C(7), and C(7a), in addition to a highly oxygenated skeleton. (−)-Rosmarinecine (2) has been synthesized in eight steps and 14.8% overall yield, as an illustration of a general approach for the construction of pyrrolizidines having this stereochemical feature. The key step in the asymmetric synthesis is a Lewis acid-promoted, tandem inter-[4 + 2]/intra-[3 + 2] cycloaddition between a fumaroyloxy nitroalkene and a chiral vinyl ether.