Brønsted Acid Catalyzed [3 + 2]-Cycloaddition of Cyclic Enamides with in Situ Generated 2-Methide-2H-indoles: Enantioselective Synthesis of Indolo[1,2-a]indoles.

Abstract

An efficient formal [3 + 2]-cycloaddition toward the highly diastereo- and enantioselective synthesis of indolo[1,2-a]indoles is disclosed. A chiral BINOL-derived phosphoric acid catalyzed the highly enantioselective conjugate addition of cyclic enamides to in situ generated 2-methide-2H-indoles and subsequent aminalization to give rise to acetamide-substituted indolo[1,2-a]indoles carrying three contiguous stereogenic centers. Importantly, these products were formed as single diastereomers and with excellent yields and enantioselectivities. Mild reaction conditions at ambient temperatures, the facile removal of the acetamido group, and the possibility of a scale-up highlight the practicality of this methodology.