Chiral Brønsted acid-controlled intermolecular asymmetric [2 + 2] photocycloadditions

Abstract

Control over the stereochemistry of excited-state photoreactions remains a significant challenge in organic synthesis. Recently, it has become recognized that the photophysical properties of simple organic substrates can be altered upon coordination to Lewis acid catalysts, and that these changes can be exploited in the design of highly enantioselective catalytic photoreactions. Chromophore activation strategies, wherein simple organic substrates are activated towards photoexcitation upon binding to a Lewis acid catalyst, rank among the most successful asymmetric photoreactions. Herein, we show that chiral Brønsted acids can also catalyze asymmetric excited-state photoreactions by chromophore activation. This principle is demonstrated in the context of a highly enantio- and diastereoselective [2+2] photocycloaddition catalyzed by a chiral phosphoramide organocatalyst. Notably, the cyclobutane products arising from this method feature a trans-cis stereochemistry that is complementary to other enantioselective catalytic [2+2] photocycloadditions reported to date.

Lewis acids have recently been shown to enable stereocontrol in photochemical cycloadditions, a difficult task due to the reactivity of excited-state compounds. Here the authors show that chiral Brønsted acids are competent chromophore activators in [2+2] cycloadditions, forming diastereomers disfavored in similar Lewis acid catalyzed photochemical reactions.