Electroreductive Carbofunctionalization of Alkenes with Alkyl Bromides via a Radical-Polar Crossover Mechanism

Abstract

Electrochemistry grants direct access to reactive intermediates (radicals and ions) in a controlled fashion toward selective organic transformations. This feature has been demonstrated in a variety of alkene functionalization reactions, most of which proceed via an anodic oxidation pathway. In this report, we further expand the scope of electrochemistry to the reductive functionalization of alkenes. In particular, the strategic choice of reagents and reaction conditions enabled a radical-polar crossover pathway wherein two distinct electrophiles can be added across an alkene in a highly chemo- and regioselective fashion. Specifically, we used this strategy in the intermolecular carboformylation, anti-Markovnikov hydroalkylation, and carbocarboxylation of alkenesreactions with rare precedents in the literatureby means of the electroreductive generation of alkyl radical and carbanion intermediates. These reactions employ readily available starting materials (alkyl halides, alkenes, etc.) and simple, transition-metal-free conditions and display broad substrate scope and good tolerance of functional groups. A uniform protocol can be used to achieve all three transformations by simply altering the reaction medium. This development provides a new avenue for constructing Csp3–Csp3 bonds.

Spirocyclizative Remote Arylcarboxylation of Non-Activated Arenes with CO2 via Visible-Light-Induced Reductive Dearomatization

“…More recently, our group reported the reductive arylcarboxylation of styrenes with CO2 via a radical-polar crossover cascade (RPCC), which was initiated by highly reactive aryl radicals that were generated from the reduction of readily available aryl halides. 75 We wondered whether this RPCC process [75][76][77][78][79][80][81][82][83][84][85][86][87][88][89] could be applied for dearomative di-functionalization of non-activated arenes with CO2. Notably, during our investigation, the Yu group reported the 2,3-arylcarboxylation of indoles, a class of well-studied electron-rich heteroarene in dearomatization reactions, via 5-exo-trig cyclization (Scheme 1b).…”

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

“…4). 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). Besides this, drug analogues bearing a glutarimide group (25), adamatane (26) functionality or an extended conjugated system (27) are accepted, too. Functionalized amino acids (28) and more challenging short peptide chains (29) can be deuterated, likewise.…”

“…[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. 1a).…”

Spirocyclizative Remote Arylcarboxylation of Nonactivated Arenes with CO 2 via Visible-Light-Induced Reductive Dearomatization

“…More recently, our group reported the reductive arylcarboxylation of styrenes with CO 2 via a radical-polar crossover cascade (RPCC), which was initiated by highly reactive aryl radicals that were generated from the reduction of readily available aryl halides. 76 We wondered whether this RPCC process [76][77][78][79][80][81][82][83][84][85][86][87][88][89][90][91]…”