Stereoselective Domino Semipinacol-Schmidt Reaction: Diastereoselective Synthesis of 7 a-epi-(+)-Lepadiformine C and Formal Synthesis of 7 a-epi-(-)-Lepadiformine A

A concise approach has been developed for the diastereoselective synthesis of the azatricyclic core of (-)-7 a-epi-lepadiformine A (8 a) and (-)-7 a-epi-lepadiformine C (8 b) using stereoselective domino semipinacol-Schmidt reaction as a key step. In presence of TiCl4, the oxaspiropentane-azide derivatives underwent stereoselective domino cyclization to furnish the corresponding angularly fused azatricyclic cores in very good yields. Moreover, azatricyclic core of (-)-7 a-epi-lepadiformine A has also been realized, in a stepwise manner, through the intramolecular Schmidt reaction of azido-spirocyclobutanone intermediate. The synthetic utility of domino semipinacol-Schmidt reaction is further shown in the diastereoselective synthesis of (+)-7 a-epi-lepadiformine C (7).