Remote C-H functionalization using radical translocating arylating groups.

Abstract

Site selective chemical functionalization at unactivated C(sp³)-H bonds is highly challenging and recent successful studies mostly focus on the use of transition metal catalysis in combination with directing groups. Radical chemistry offers a complementary approach with the Barton and the Hofmann-Löffler-Freytag reactions being landmark contributions in the area of remote C-H functionalization at unactivated aliphatic sites. Herein we introduce the concept of radical translocation arylation at unactivated secondary and tertiary C(sp³)-H bonds in various alcohols. The straightforward two-step sequence comprises an ionic alcohol sulfonylation with especially designed ortho-iodoaryl sulfonyl chlorides followed by a radical cascade reaction including aryl radical generation, remote radical translocation, aryl migration, reduction, and SO₂ extrusion to give the corresponding γ-arylated alcohols. Moderate to good yields are obtained, remote C-H arylation occurs with excellent regioselectivity and for secondary C(sp³)-H bonds good to excellent stereoselectivity is achieved.