Stereoselective cascade formal nucleophilic substitution and Mannich reaction of ethyl 2-aroyl-1-chlorocyclopropanecarboxylates.

A highly regio- and diastereoselective cascade formal nucleophilic substitution and Mannich reaction of ethyl 2-aroyl-1-chlorocyclopropanecarboxylates with salicylaldimines is described. Under basic conditions, ethyl 2-aroyl-1-chlorocyclopropanecarboxylate is easily converted into a cyclopropene intermediate via simple 1,2-elimination of hydrogen chloride. The highly reactive cyclopropene quickly combines with salicylaldimine through regioselective oxa-addition to the strained C═C bond and subsequent diastereoselective addition to C═N bond, constructing C-O and C-C bonds at one time. This provides a highly stereoselective novel methodology for synthesis of conformationally constrained cis-tetrahydrocyclopropa[b]chromene derivatives.