Total Synthesis of (−)-Lepadiformine A Utilizing Hg(OTf)2‑Catalyzed Cycloisomerization Reaction

A cytotoxic marine alkaloid (−)-lepadiformine A (1) possesses a unique structure characterized by the trans-1-azadecalin AB ring system fused with the AC spiro-cyclic ring. In this research, we found that a cycloisomerization reaction from amino ynone 2 to a 1-azaspiro[4.5]­decane skeleton 3, corresponding to the AC ring system of 1, is promoted by Hg­(OTf)2. Thus, we have accomplished the efficient total synthesis of (−)-lepadiformine A in 28% overall yield by featuring the novel Hg­(OTf)2-catalyzed cycloisomerization.