Transition-Metal and Photocatalyst-Free, Redox-Neutral Heteroarylation of C(sp<sup>3</sup>)–H Bonds
Kamila Almagambetova, Kathiravan Murugesan, Magnus Rueping
Abstract
Developing a transition-metal-free system for functionalizing the C(sp 3 )–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 ( i Pr 3 SiSH) 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(sp 3 )–H and C(sp 2 )–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.