Resurgence and advancement of photochemical hydrogen atom transfer processes in selective alkane functionalizations

Abstract

The selective functionalization of alkanes has long been recognized as a prominent challenge and an arduous task in organic synthesis. Hydrogen atom transfer (HAT) processes enable the direct generation of reactive alkyl radicals from feedstock alkanes and have been successfully employed in industrial applications such as the methane chlorination process, etc. Nevertheless, challenges in the regulation of radical generation and reaction pathways have created substantial obstacles in the development of diversified alkane functionalizations. In recent years, the application of photoredox catalysis has provided exciting opportunities for alkane C-H functionalization under extremely mild conditions to trigger HAT processes and achieve radical-mediated functionalizations in a more selective manner. Considerable efforts have been devoted to building more efficient and cost-effective photocatalytic systems for sustainable transformations. In this perspective, we highlight the recent development of photocatalytic systems and provide our views on current challenges and future opportunities in this field.

Scheme 1. Functionalization of C(sp³)–H bonds via HAT.

Scheme 2. Factors that govern HAT from alkanes.

Scheme 3. Photochemical and photocatalytic transformations mediated by halogen radicals.

Scheme 4. Nickel-catalyzed C(sp³)–H cross coupling enabled by catalytic generation of a chlorine radical.

Scheme 5. Site-selective alkane functionalization enabled by a chlorine radical complex.

Scheme 6. Transformations mediated by nitrogen-centered radicals.

Scheme 7. Transformations enabled by the generation of oxygen-centered radicals from a stoichiometric amount of precursors.

Scheme 8. Transformations enabled by the catalytic generation of oxygen-centered radicals or a PCET event from oxides.

Scheme 9. Transformation enabled by the catalytic LMCT strategy for the generation of alkoxy radicals from free alcohols.

Scheme 10. Photocatalytic HAT enabled by excited species.

Scheme 11. Various trapping reagents for decatungstate-catalyzed transformations.

Scheme 12. C–H arylation via nickel/decatungstate dual catalysis.

Scheme 13. Dual catalysis for alkane functionalization enabled by triplet ketone.

Scheme 14. HAT enabled alkane functionalizations under continuous-flow conditions. (A) Picture of the set-up. Adapted with permission from ref. copyright 2018, The American Association for the Advancement of Science; (B) picture of the reactor (left) and set-up (right). Reprinted with permission from ref. Copyright 2020, The American Association for the Advancement of Science.