Pd-catalyzed arylation/aza-Michael addition cascade to C2-spiroindolines and azabicyclo[3.2.2]nonanones

Abstract

A palladium-catalyzed arylation/aza-Michael addition cascade reaction of β-substituted cyclic enones and 2-haloanilines has been reported. Using 1 mol% Pd(PPh₃)₄ as a catalyst, C2-spiroindolines are accessed via an intermolecular vinylogous arylation of β-alkyl cyclic enones and 2-haloanilines followed by an intramolecular aza-Michael addition. The functional group tolerance of this transformation is examined by 18 examples in up to 93% yield. In the second part, we developed an α′-arylation/aza-Michael addition cascade strategy to construct azabicyclo[3.2.2]nonanones catalyzed by Pd(MeCN)₂Cl₂·PPh₃. This study provides a quick route to complex and useful spiro- and bridged-heterocycles from readily available starting materials in good yields with high regioselectivity.