Synthesis of Dihydromotuporamine C via 3‐Azonia‐Cope Rearrangement of 11‐Membered Cyclic α‐Vinylamine

Abstract

AbstractA new synthesis of dihydromotuporamine C (dhMotC), a synthetic analogue of cytotoxic marine alkaloid, has been achieved from inexpensive starting materials. The first stage was the preparation of cyclodecanone by sequential [2+2]‐cycloaddition of N‐(1‐cycloocten‐1‐yl)pyrrolidine with methyl propiolate and electrocyclic ring‐opening, followed by basic hydrolysis. Beckmann rearrangement of cyclodecanone oxime and several step manipulations afforded the pivotal intermediate of the N‐benzylated 11‐membered cyclic α‐vinylamine. The final synthesis of dihydromotuporamine C involved tandem nucleophilic addition with ethynyl p‐tolyl sulfone and 3‐azonia‐Cope rearrangement to form the 15‐membered aza‐macrocycle and reductive amination to install the appended spermidine‐like moiety.