Photocatalytic three-component asymmetric sulfonylation via direct C(sp3)-H functionalization

Shi Cao,Ziqi Ye,Wei Hong,Lei Gong

doi:10.1038/s41467-021-22690-3

Abstract

The direct and selective C(sp3)-H functionalization of cycloalkanes and alkanes is a highly useful process in organic synthesis owing to the low-cost starting materials, the high step and atom economy. Its application to asymmetric catalysis, however, has been scarcely explored. Herein, we disclose our effort toward this goal by incorporation of dual asymmetric photocatalysis by a chiral nickel catalyst and a commercially available organophotocatalyst with a radical relay strategy through sulfur dioxide insertion. Such design leads to the development of three-component asymmetric sulfonylation involving direct functionalization of cycloalkanes, alkanes, toluene derivatives or ethers. The photochemical reaction of a C(sp3)-H precursor, a SO2 surrogate and a common α,β-unsaturated carbonyl compound proceeds smoothly under mild conditions, delivering a wide range of biologically interesting α-C chiral sulfones with high regio- and enantioselectivity (>50 examples, up to >50:1 rr and 95% ee). This method is applicable to late-stage functionalization of bioactive molecules, and provides an appealing access to enantioenriched compounds starting from the abundant hydrocarbon compounds.

Highlights

The direct and selective C(sp3)-H functionalization of cycloalkanes and alkanes is a highly useful process in organic synthesis owing to the low-cost starting materials, the high step and atom economy
We found a photocatalytic enantioselective alkylation reaction of N-sulfonylimines with benzylic or alkyl C(sp3)-H precursors enabled by copper-based asymmetric catalysis and organophotocatalysis
We questioned whether incorporation of sulfur dioxide insertion with appropriate dual asymmetric photocatalysis[48,49,50,51] would allow us to find an effective approach for stereoselective transformations starting from most abundant hydrocarbon compounds

Summary

Introduction

The direct and selective C(sp3)-H functionalization of cycloalkanes and alkanes is a highly useful process in organic synthesis owing to the low-cost starting materials, the high step and atom economy. On the basis of these considerations, a photocatalytic asymmetric threecomponent sulfonylation reaction of a cycloalkane (an alkane, a toluene derivative, or an ether), an SO2 surrogate, and a common Michael acceptor was developed, whose stereochemistry was governed by a nickel catalyst of a well-tailored chiral bisoxazoline ligand.

Results

Conclusion