Design of a cyclopropyl quinone methide reductive alkylating agent. 2

A cyclopropyl quinone methide is formed by elimination of a leaving group from an appropriately functionalized hydroquinone. The presence of a carbon spacer results in the formation of a fused ring rather than the classic methide species. Discussed herein is cyclopropyl quinone methide formation from a pyrido1,2-a]indole ring system. Both nucleophilic and electrophilic attack on the fused cyclopropane ring results in pyrido1,2-a]indole and azepino1,2-a]indole products. The stereoelectronic effect plays less a role in the relatively flexible pyrido1,2-a]indole system compared to its role in the pyrrolo1,2-a]-indole system. A 13C label on the fused cyclopropane ring permitted the rapid identification of complex rearrangement products observed in this study.