Catalytic, asymmetric indolizidinone aza-quaternary stereocenter synthesis: expedient synthesis of the cylindricine alkaloid core

Abstract

The Rh(I)•CKphos catalyzed [2 + 2 + 2] cycloaddition of 1,1-disubstituted alkenyl isocyanates and alkyl alkynes selectively forms previously inaccessible vinylogous amide indolizidinone cycloadducts, establishing an aza-quaternery stereocenter with excellent enantioselectivities (up to 98% ee). This advance enables a seven step catalytic, asymmetric synthesis of the tricyclic core of the cylindricine alkaloids with excellent control of product selectivity as well as regio- and enantioselectivity.