Ni-Electrocatalytic C(sp3)–C(sp3) Doubly Decarboxylative Coupling

Abstract

This work presents a modern spin on one of the oldest known Csp3–Csp3 bond forming reactions in synthetic chemistry: the Kolbe electrolysis. This reaction holds incredible promise for synthesis, yet its use has been near non-existent in mainstream organic synthesis. In contrast to the strongly oxidative electrolytic protocol employed traditionally since the 19th century, the present method utilizes in situ generated redox-active esters (RAEs) which are combined with a mildly reductive Ni-electrocatalytic cycle. It can be used to heterocouple 1o, 2o, and even certain 3o RAEs with a protocol reminiscent of amide bond formation in terms of simplicity. Due to its mild nature the reaction tolerates a range of functional groups, is scalable, and was strategically enlisted for the synthesis of 25 known compounds to reduce overall step-counts by 74%.

Redox Inversion: A Radical Analog of Umpolung Reactivity for Base and Metal-Free Catalytic C(sp3)–C(sp3) Coupling

“…[1][2][3] Baran, MacMillan, and others have popularized transition-metal catalyzed C(sp 3 )-C(sp 3 ) coupling reactions using carboxylic acid derivatives paired with a traditional coupling partner such as alkyl Zn reagents and alkyl halides (Figure 1a). [6][7][8][9][10][11][12][13][14][15][16][17][18][19] In their work, carboxylic acids are commonly used as alkyl radical precursors via oxidative decarboxylation (acting as a single electron donor), and redox active Nhydroxyphthalimide (NHPI) esters typically utilized as alkyl precursors via reductive decarboxylation (acting as a single electron acceptor). 6,[20][21][22][23][24] However, to the best of our knowledge, the contrasting redox characteristics of these carboxylic acidderived substrates have not been exploited in conjunction for radical-radical coupling to form C(sp 3 )-C(sp 3 ) bonds.…”