Chiral Br\xf8nsted acid-controlled intermolecular asymmetric [2\u2009+\u20092] photocycloadditions

Evan M Sherbrook,Tehshik P Yoon,Bohyun Park,Ilia A Guzei,Mu-Hyun Baik,Matthew J Genzink

doi:10.1038/s41467-021-25878-9

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.

Highlights

Control over the stereochemistry of excited-state photoreactions remains a significant challenge in organic synthesis
The difficulty of conducting asymmetric photochemical reactions has often been attributed to the very short lifetimes and high reactivities associated with electronically excited compounds; these features challenge the ability of catalysts to intercept and modulate the behavior of organic excited states
The insight that the same privileged classes of chiral Lewis acid structures that have been so enabling in ground-state asymmetric synthesis can be applied to enantioselective photochemistry has increased the pace of discovery in this area

Summary

Introduction

Control over the stereochemistry of excited-state photoreactions remains a significant challenge in organic synthesis. There are two general mechanisms by which chiral Lewis acids can influence the enantioselectivity of excited-state photoreactions. Bach pioneered the chromophore activation strategy in which chiral Lewis acids are used to attenuate the singlet excited-state energy of α,β-unsaturated carbonyl compounds (Fig. 1a)[9,10].

Results

Conclusion