Electrochemically Enabled, Nickel-Catalyzed Dehydroxylative Cross-Coupling of Alcohols with Aryl Halides

Abstract

As alcohols are ubiquitous throughout chemical science, this functional group represents a highly attractive starting material for forging new C−C bonds. Here, we demonstrate that the combination of anodic preparation of the alkoxy triphenylphosphonium ion and nickel-catalyzed cathodic reductive crosscoupling provides an efficient method to construct C(sp 2 )−C(sp 3 ) bonds, in which free alcohols and aryl bromidesboth readily available chemicalscan be directly used as coupling partners. This nickel-catalyzed paired electrolysis reaction features a broad substrate scope bearing a wide gamut of functionalities, which was illustrated by the late-stage arylation of several structurally complex natural products and pharmaceuticals.

Transition metal-catalyzed organic reactions in undivided electrochemical cells

“…7 ). 43 The use of stoichiometric hazardous CBr 4 or Br 2 in the thermochemical Appel reaction and the use of stoichiometric Zn or Mn in traditional reductive cross-couplings are avoided using this procedure (LiBr serves as the source of bromine atoms). Cyclic voltammetry has shown that the bromide ion has lower oxidative potential than both PPh 3 and alcohols in NMP (oxidative potential: 1.1, 1.7, and >2.0 V, respectively, for LiBr, PPh 3 , and alcohol vs. Ag/AgCl).…”

Nickel-Catalyzed Paired Electrochemical Cross-Coupling of Aryl Halides with Nucleophiles

“…In 2021, our group reported an electrochemically enabled, nickel catalyzed direct dehydroxylative cross-coupling of alcohols with aryl halides. 34 It is known that alcohols are seldom directly employed as alkylating agents in cross-couplings reactions on account of the strong bond dissociation energy of the C−O bond and poor leaving ability of the OH group. [35][36][37] We employed a direct C−O bond activation strategy via electrochemical generation of the key intermediate of the Mitsunobu reaction.…”

Synthetic Applications of Nickel‐Catalyzed Cross‐Coupling and Cyclisation Reactions

“…Arylsulfonates appear to be good candidates in these kinds of homocoupling reactions, as they have been extensively used with palladium catalysis, [25] and also with Ni(cod) 2 [26] . In addition, alcohols have recently been used as in situ halide precursors in an electrochemical process [27] . So that, we have developed a handy way of generating Ni(0) in situ in the presence of organic compounds, by simple reduction of a catalytic amount of Ni(II) complex (10 % NiBr 2 bipy) by manganese metal, allowing homocoupling reaction of aryl sulfonates [28] .…”

“…[26] In addition, alcohols have recently been used as in situ halide precursors in an electrochemical process. [27] So that, we have developed a handy way of generating Ni(0) in situ in the presence of organic compounds, by simple reduction of a catalytic amount of Ni(II) complex (10 % NiBr 2 bipy) by manganese metal, allowing homocoupling reaction of aryl sulfonates. [28] Biaryls were thus obtained with very good to excellent yields (70-100 %), at room temperature, from aryltosylates, which are easily prepared from the corresponding phenols (Scheme 4).…”