Organocatalytic C-H Functionalization of Simple Alkanes

The direct functionalization of inert C(sp3)-H bonds to form carbon-carbon and carbon-heteroatom bonds offers vast potential for chemical synthesis and therefore receives increasing attention. At present, most successes come from strategies using metal catalysts/reagents or photo/electrochemical processes. The use of organocatalysis for this purpose remains scarce, especially when dealing with challenging C-H bonds such as those from simple alkanes. Here we disclose the first organocatalytic direct functionalization/acylation of inert C(sp3)-H bonds of completely unfunctionalized alkanes. Our approach involves N-heterocyclic carbene catalyst-mediated carbonyl radical intermediate generation and coupling with simple alkanes (through the corresponding alkyl radical intermediates generated via a hydrogen atom transfer process). Unreactive C-H bonds are widely present in fossil fuel feedstocks, commercially important organic polymers, and complex molecules such as natural products. Our present study shall inspire a new avenue for quick functionalization of these molecules under the light- and metal-free catalytic conditions. An organocatalytic direct functionalization/acylation of strong aliphatic C(sp3)-H bonds is disclosed via an N-heterocyclic carbene (NHC)-catalyzed dehydrogenative coupling of aldehydes with simple alkanes. The inert aliphatic C-H bonds are efficiently cleaved through intermolecular hydrogen atom transfer, providing an alternative organocatalytic approach for alkane C-H functionalization under transition metal- and light free conditions.+image

Automated summary

This study discloses the first organocatalytic direct functionalization/acylation of inert C(sp3)-H bonds of completely unfunctionalized alkanes. The approach involves N-heterocyclic carbene catalyst-mediated carbonyl radical intermediate generation and coupling with simple alkanes through the corresponding alkyl radical intermediates generated via a hydrogen atom transfer process. This method provides a new avenue for functionalization of challenging C-H bonds.