Enantioselective Synthesis of the Spirotropanyl Oxindole Scaffold through Bimetallic Relay Catalysis

Abstract

Spirotropanyl oxindole alkaloids like alstonisine and chitosenine show a wide range of bioactivites. We report the first enantioselective synthesis of the spirotropanyl oxindole scaffold by means of a bimetallic relay catalysis strategy. A new class of E-oximino α-diazo ketones was developed for the intramolecular generation of transient azomethine ylides catalyzed by an achiral Rh^II complex and a subsequent intermolecular 1,3-dipolar cycloaddition catalyzed by a chiral N,N'-dioxide Nd^III Lewis acid complex. The enantioselectively catalyzed transformation has broad scope and yields the desired spirotropanyl oxindole cycloadducts in high yields and with very high enantio- and diastereoselectivity.

Keywords: asymmetric synthesis; cycloaddition; oxindole alkaloids; relay catalysis; tropane.