Photocatalytic Single-Electron Reduction of Electron-Deficient π-Systems for Regioselective Carbon-Carbon Bond Formation

Identifier:  TDX:4481

Handle: https://hdl.handle.net/20.500.11797/TDX4481

Authors:  Dmitriev, Igor

Abstract:
In this thesis, the synthetic potential of photocatalytic strategies has been utilized to selectively forge new C(sp2)-C(sp3) and C(sp3)-C(sp3) bonds. Specifically, single-electron reduction of electron-deficient π-systems was exploited as a means of achieving unconventional reactivity. Chapter II described a new strategy for the regioselective radical functionalization of pyridines and related heteroarenes, enriching the radical-based chemistry of pyridines. This strategy is enabled by the formation of previously neglected pyridinyl radicals, obtained in a catalytic manner via single electron transfer (SET) reduction of pyridinium ions. This reduction was facilitated by the lowering of the lowest unoccupied molecular orbital (LUMO) of the pyridine, achieved by protonation. The pyridinyl radical intermediates underwent effective and regioselective radical coupling with allylic radicals formed via hydrogen atom transfer (HAT) from allylic C-H bonds of readily available olefins. Key to the design of this protocol was the use of the dithiophosphoric acid catalyst, which served three distinct roles during the reaction, sequentially acting as a Brønsted acid for pyridine protonation, an SET reductant of pyridinium ions upon light excitation, and a HAT acceptor for the allylic C-H bonds upon formation of the thiyl radical. In chapter III, a new light-driven strategy for the reductive olefin cross-coupling has been detailed, providing sp3-rich products with a distinct connectivity starting from broadly available olefin substrates. Central to this strategy was the exploitation of the electronic differences between the two olefin partners, enabling selective radical generation via photoredox-mediated SET reduction of the electron-deficient olefins. Overall, the electron-poor substrates were readily coupled with various styrenes and other electron-neutral olefins, finally undergoing reduction via HAT process mediated by a thiol catalyst. A notable feature of this method is its high functional group tolerance, which was leveraged for the late-stage modification of biorelevant compounds.