Photocatalytic enantioselective \u03b1-aminoalkylation of acyclic imine derivatives by a chiral copper catalyst

Bowen Han,Yanjun Li,Lei Gong,Ying Yu

doi:10.1038/s41467-019-11688-7

Abstract

Copper-based asymmetric photocatalysis has great potential in the development of green synthetic approaches to chiral molecules. However, there are several formidable challenges associated with such a conception. These include the relatively weak visible light absorption, short excited-state lifetimes, incompatibility of different catalytic cycles, and the difficulty of the stereocontrol. We report here an effective strategy by means of single-electron-transfer (SET) initiated formation of radicals and photoactive intermediates to address the long-standing problems. Through elaborate selection of well-matched reaction partners, the chiral bisoxazoline copper catalyst is engaged in the SET process, photoredox catalysis, Lewis acid activation and asymmetric induction. Accordingly, a highly enantioselective photocatalytic α-aminoalkylation of acyclic imine derivatives has been accessed. This strategy sheds light on how to make use of diverse functions of a single transition metal catalyst in one reaction, and offers an economic and simplified approach to construction of highly valuable chiral vicinal diamines.

Highlights

Copper-based asymmetric photocatalysis has great potential in the development of green synthetic approaches to chiral molecules
The unique features and reactivities of copper complexes in visible light photocatalysis have been well investigated by the group of Reiser and the others[10,11,12,13,14,15,16,17]
These include (i) the relatively weaker visible-light absorption and shorter excited-state lifetimes compared to those of conventional heavy metal photosentisizers[6,7], (ii) the incompatibility of different catalytic cycles[21,22,23,24,25], (iii) the difficulty of controlling the stereochemistry of the transformations of highly active intermediates such as radicals[26,27,28,29,30,31,32,33], (iv) the possible diminishing of enantioselectivity raised by fast ligand exchange under photochemical conditions[34,35,36]

Summary

Introduction

Copper-based asymmetric photocatalysis has great potential in the development of green synthetic approaches to chiral molecules. We report a highly enantioselective photocatalytic αaminoalkylation of acyclic imine derivatives by a chiral bisoxazoline copper catalyst This catalyst has been found to play diverse roles in the photochemical reaction, including initiation of the single electron transfer to generate an α-aminoalkyl radical and visible-light active copper(I) species, Lewis acid activation towards the imine substrate, asymmetric induction in the radical addition process, and anticipation of the photoredox process through copper(I) intermediates to close the catalytic cycles (Fig. 1). This method treats with difficult synthetic problems, i.e., enantioselective radical addition to acyclic imines to prepare optically active vicinal diamines. This method treats with difficult synthetic problems, i.e., enantioselective radical addition to acyclic imines to prepare optically active vicinal diamines39,40. and demonstrates how to make use of diverse functions of a single transition metal catalyst in one reaction

Methods

Results

Conclusion