Formal Synthesis of Gracilamine Using Rh(I)-Catalyzed [3+2+1] Cycloaddition of 1-Yne-Vinylcyclopropanes and CO

Reported here is a formal synthesis of gracilamine using Rh(I)-catalyzed [3 + 2 + 1] reaction of yne-VCP (+/-)-4 and CO. The key reaction gave the cycloadduct (+/-)-trans-3 with the A-B-C core structure of gracilamine. This advanced intermediate was further transformed to Gao's intermediate (+/-)-2 via regular transformations to realize the formal synthesis of gracilamine. The present strategy was used to accomplish the asymmetric formal synthesis of gracilamine using chiral substrate (+)-4.