Minimization of Back‐Electron Transfer Enables the Elusive sp³ C−H Functionalization of Secondary Anilines

Abstract

Anilines are some of the most used class of substrates for application in photoinduced electron transfer. N,N-Dialkylderivatives enable radical generation a to the N-atom by oxidation followed by deprotonation. This approach is however elusive to monosubstituted anilines owing to fast backelectron transfer (BET). Here we demonstrate that BET can be minimised by using photoredox catalysis in the presence of an exogenous alkylamine. This approach synergistically aids aniline SET oxidation and then accelerates the following deprotonation. In this way, the generation of a-anilinoalkyl radicals is now possible and these species can be used in a general sense to achieve divergent sp 3 CÀH functionalization.

Photoredox Catalyzed Site-Selective Generation of Carbanions from C(sp3)-H bonds in Amines

“…2b) starts with the oxidation of the amine (I) by the excited photocatalyst. Analogous to previously reported mechanisms, 22 the thus formed amino radical cation (II) triggers rapid α-amino deprotonation, yielding a carbon-centered α-amino radical (III). This radical should then be converted to the desired carbanion intermediate (IV) by the reduced photocatalyst species, facilitated by the presence of an electron-withdrawing group.…”

“…Remarkably, the targeted selectivity could be achieved in the presence of various other α-amine or α-hetero atom positions (17)(18)(19)(20)(21)(22)(23)(24)(25), e.g. present in the prominent morpholine (17), piperidine (18)(19), and piperazine (20)(21)(22) moieties, which would likely be affected in a photocatalytic hydrogen atom abstraction approach. Along the same line, sugar derivatives could be deuterated in good yield and remarkable selectivity as well (23)(24).…”

“…[3][4][5][6][7] Recently, photocatalysis has proven to be a valuable tool for C-H functionalization as well, offering novel approaches via single-electron transfer (SET) and hydrogen atom transfer mechanisms (HAT), in some cases including the aid of a metal catalyst. [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] While photocatalysis is most commonly known for radical reactivity, 18,19 carbanion or carbocation species can be generated via a radical-polar crossover as well. [24][25][26][27][28][29] In particular, the formation of carbanion 28,29 intermediates in a photocatalytic and redox neutral fashion offers several advantages compared to traditional methods, 30,31 such as full atom economy, no stoichiometric amount of metal waste (low valent Mg, Zn, or Li metals), and high functional group tolerance (limitation of classical methods; Fig.…”

A cross-dehydrogenative C(sp3)−H heteroarylation via photo-induced catalytic chlorine radical generation

“…The addition of the so-formed alkyl radical to another equivalent of heteroarene 1-H + followed by hydrogen atom removal would give the desired alkylated heteroarene 3-H + . Meanwhile, to efficiently quench the generated radical intermediate II, a readily accessible cobaloxime catalyst [Co(dmgH) 2 (py)]Cl was introduced to the system [51][52][53][54][55] not only to prevent the over-reduction of intermediate II but also to serve as a terminal oxidant for the rearomatisation of alkylated intermediate III though H 2 evolution.…”

Development of a Quinolinium/Cobaloxime Dual Photocatalytic System for Oxidative CC Cross-Couplings via H2 Release

“…Two generally accepted mechanisms were believed to be operative for the hydrogen evolution. 20 The key Co(III)-H species could be formed through radical recombination (2' and Co(II) to 3') followed by β-hydride elimination to give product 4' and Co(III)-H. Alternatively, single-electron transfer (SET) between 2' and Co(II) furnished the product 4' directly, with the simultaneous generation of Co(I), which could undergo the oxidation addition with proton (TFA) to give Co(III)-H. To be noticed, direct hydrogen atom abstraction from 2' to 4' by Co(II) not be excluded. It is known that the Co(III)-H could be quenched by a protic source and effect the hydrogen evolution.…”