Nickel-Catalyzed Reductive Cross-Coupling of Aryl Bromides with Alkyl Bromides: Et₃N as the Terminal Reductant

Abstract

Reductive cross-coupling has emerged as a direct method for the construction of carbon-carbon bonds. Most cobalt-, nickel-, and palladium-catalyzed reductive cross-coupling reactions to date are limited to stoichiometric Mn(0) or Zn(0) as the reductant. One nickel-catalyzed cross-coupling paradigm using Et3N as the terminal reductant is reported. By using this photoredox catalysis and nickel catalysis approach, a direct Csp(2)-Csp(3) reductive cross-coupling of aryl bromides with alkyl bromides is achieved under mild conditions without stoichiometric metal reductants.

Visible‐Light Photocatalysis as an Enabling Tool for the Functionalization of Unactivated C(sp3)‐Substrates

“…Cross-coupling of alkyl bromides with aryl bromides under visible-light conditions by the Ir/Ni dual-catalysis approach has been reported (Scheme 14). [49,50] Similarly to the mechanism depicted in Scheme 7D, the reaction was suggested to proceed through formation of an alkyl radical followed by addition to an Ni II complex and finally reductive elimination to give the cross-coupled product. However, reaction by the alternative Ni 0 addition pathway cannot be ruled out.…”

“…Under slightly different reaction conditions, and without a silyl radical source, Lei and co-workers were also able to couple primary and secondary alkyl bromides with aryl bromides (Scheme 14B). [50] In this case, reductive activation of the alkyl bromide substrates by the excited-state Ir III * catalyst led to the formation of the key radical intermediates.…”

The Persistent Radical Effect in Organic Synthesis

“…In contrast to the other examples discussed thus far, where a nucleophilic aryl donor is reacted with an alkyl halide radical precursor, these processes involve the unusual coupling of two electrophilic partners by using a stoichiometric external reductant such as Zn 0 or Mn 0 . By combining this strategy with photoredox catalysis, triethylamine can be used as the stoichiometric reductant replacing zinc or manganese . Furthermore, it is also possible to use tris(trimethylsilyl)silane (TMSSH) as the reducing reagent, where the corresponding silyl radical is generating the alkyl radical by halogen atom abstraction .…”

A Retrosynthetic Approach for Photocatalysis

“…The reaction is compatible with functional groups including unprotected amines, esters, nitriles, 3‐ and 4‐membered rings and more. Different conditions for the same type of transformation were developed by Lei et al They succeeded in coupling primary and secondary alkyl bromides with the strongly reducing Ir(dtbby)(ppy) 2 PF 6 complex and the addition of MgCl 2 …”