Diversity-Oriented Enantioselective Construction of Atropisomeric Heterobiaryls and N-Aryl Indoles via Vinylidene Ortho-Quinone Methides

Abstract

An atroposelectively diversity-oriented synthetic strategy was developed for the divergent synthesis of axially chiral heterocycles through organocatalytic asymmetric intramolecular annulation of alkyne via vinylidene ortho-quinone methides (VQMs). The methodology reported herein was characterized by rapid reactions (most completed in seconds), high stereocontrol (up to 98% ee), and broad substrate scope (60 examples of different skeletal types, stereogenicelements,andringsizes).Withthismethodology, a vast array of axially chiral heterobiaryls bearing silicon, oxygen, nitrogen, and boron heterocycles were successfully constructed with high efficiency and stereoselectivities. In addition, different stereogenic elements, including the C–C and C–N, were successfully formed atroposelectively. This method was applicable to the synthesis of axially chiral heterocycles with different ring sizes as well (five-, six-, and seven-membered rings). More importantly, the stereodivergent synthesis of the axially chiral aryl-indole framework bearing both stereogenic C–C and C–N axes was achieved with a single organocatalyst and simple starting materials.(Figure Presented)