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

The direct and selective C(sp(3))-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(sp(3))-H precursor, a SO2 surrogate and a common alpha,beta-unsaturated carbonyl compound proceeds smoothly under mild conditions, delivering a wide range of biologically interesting alpha-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. The direct and selective C(sp(3))-H functionalization of cycloalkanes and alkanes is useful in organic synthesis but its application to asymmetric catalysis has been less explored. Here, the authors demonstrate the incorporation of a dual asymmetric photocatalyst which leads to the development of asymmetric sulfonylation involving direct functionalization of cycloalkanes, alkanes, toluene derivatives or ethers.

Automated summary

The study demonstrates the use of a dual asymmetric photocatalyst leading to the development of asymmetric sulfonylation involving direct functionalization of cycloalkanes, alkanes, toluene derivatives or ethers.