A Redox Auxiliary Strategy for Pyrrolidine Synthesis via Photocatalytic [3+2] Cycloaddition

Asian J Org Chem. 2019 Jul;8(7):978-985. doi: 10.1002/ajoc.201900113. Epub 2019 Mar 21.

Abstract

Cycloaddition reactions can be used to efficiently assemble pyrrolidine rings that are significant in a variety of chemical and biological applications. We have developed a method for the formal cycloaddition of cyclopropyl ketones with hydrazones that utlizes photoredox catalysis to enable the synthesis of a range of structurally diverse pyrrolidine rings. The key insight enabling the scope of photoredox [3+2] cycloadditions to be expanded to C=N electrophiles was the use of a redox auxiliary strategy that allowed for photoreductive activation of the cyclopropyl ketone without the need for an exogenous tertiary amine co-reductant. These conditions prevent the deleterious reductive ring-opening of the cyclopropyl substrates, enabling a range of less-reactive coupling partners to participate in this cycloaddition.

Keywords: cycloaddition; heterocycles; photocatalysis; radical ions; small ring systems.