Controlling Ni redox states by dynamic ligand exchange for electroreductive Csp3–Csp2 coupling

Abstract

Cross-electrophile coupling (XEC) reactions of aryl and alkyl electrophiles are appealing but limited to specific substrate classes. Here, we report electroreductive XEC of previously incompatible electrophiles including tertiary alkyl bromides, aryl chlorides, and aryl/vinyl triflates. Reactions rely on the merger of an electrochemically active complex that selectively reacts with alkyl bromides through 1e – processes and an electrochemically inactive Ni 0 (phosphine) complex that selectively reacts with aryl electrophiles through 2e – processes. Accessing Ni 0 (phosphine) intermediates is critical to the strategy but is often challenging. We uncover a previously unknown pathway for electrochemically generating these key complexes at mild potentials through a choreographed series of ligand-exchange reactions. The mild methodology is applied to the alkylation of a range of substrates including natural products and pharmaceuticals.

Electrocatalytic synthesis: an environmentally benign alternative for radical-mediated aryl/alkenyl C(sp2)–C(sp3) cross-coupling reactions

“…Very recently, Sevov et al designed an unprecedented ligand-exchange strategy for achieving the electrochemical nickel-catalyzed C(sp 2 )–C(sp 3 ) cross-coupling of aryl halides with tertiary alkyl bromides using a zinc sacrificial anode (Scheme 47). 75 Gratifyingly, the previously reported incompatible electrophiles such as tertiary alkyl bromides, aryl chlorides, and aryl/alkenyl trifluorosulfonates all reacted smoothly in this electrocatalytic system. This ligand-exchange synthetic strategy featured mild catalytic conditions and good functional group tolerance, making it suitable for the late-stage modification of natural products and some synthetically and biologically valuable molecules.…”

Nickel-Catalyzed Electrochemical Reductive Cross-Electrophile Coupling of Alkylpyridinium Salts and Aryl Halides

“…For instance, electrochemical reductive C(sp 2 )-C(sp 3 ) couplings of aryl halides with alkyl electrophiles have been demonstrated using both divided and undivided cells. [52][53][54][55][56][57][58] In addition, couplings of redox-active esters and aryl halides under electrochemical conditions recently reported by Baran and co-workers suggest that electrochemistry provides superior generality versus several non-electrochemical methods with pharmaceutically relevant building blocks. 25…”

The Formal Cross-Coupling of Amines and Carboxylic Acids to Form sp3–sp2 Carbon–Carbon Bonds

“…Other primary alkyl pyridinium salts were successfully coupled to 1 in good yield (3)(4)(5)(6)(7)(8). Alternative acids with electron withdrawing groups could also be coupled (9)(10)(11)(12)(13)(14)(15)(16), and the reaction was found to be tolerant of a variety of functionalities, such as alkenes (7), phenols (10,11), ethers (8, 12), aryl chlorides (3, 9, 13, 15), aryl fluorides (11,12) and tert-butyl carbamates (14, 16, 17, 18). Quinoline derived glutarimides were also successfully coupled (15)(16)(17).…”