Transition-Metal and Photocatalyst-Free, Redox-Neutral Heteroarylation of C(sp³)-H Bonds

Developing a transition-metal-free system for functionalizing the C(sp³)-H bond has posed a long-standing challenge in synthetic organic chemistry and is of significance in drug discovery. In this context, we present a straightforward protocol for the heteroarylation of benzylic and alpha-amino C-H bonds, achieved without transition metals or photocatalysts. A pivotal aspect of redox-neutral hydroarylation is the utilization of commercially available triisopropylsilanethiol (ⁱPr₃SiSH) as an organocatalyst. This organocatalyst serves a dual function in forming an electron donor-acceptor complex (EDA) and acting as a hydrogen atom transfer catalyst, generating alkyl/benzylic radicals from the corresponding C-H bonds. Applying this mild methodology, various benzylic and amino C-H bonds were functionalized to give a C(sp³)-H and C(sp²)-heteroaryl C-C cross-coupled product. To demonstrate the practical utility of this protocol, pyridine was incorporated into a drug molecule via late-stage modification. Additionally, a gram-scale reaction was also performed to show the advantages of this protocol.