Nickel-catalysed Negishi cross-coupling reactions: scope and mechanisms

Abstract

The Negishi cross-coupling of organozinc reagents is a valuable tool for the formation of C-C bonds in the presence of functional groups. Although this reaction is catalysed by Ni or Pd complexes, the latter have been much more developed. Nevertheless, Ni derivatives have become important in recent years, especially for their activity in the formation of alkyl-alkyl bonds. The mechanisms involved in Ni-catalysed reactions are different from the usual catalytic cycle involving oxidative addition-transmetalation-reductive elimination that is generally accepted for Pd-catalysed reactions. This tutorial review presents the more recent advances in Ni-catalysed Negishi cross-couplings for the formation of different kinds of C-C bonds and discusses their proposed reaction mechanisms.

Total Synthesis of Carolacton, a Highly Potent Biofilm Inhibitor

“…[14] However, this crucial reaction step succeeded only after optimization, [15] because initially we obtained regioisomer 13 as a mixture of diastereomers. We found that the added sodium chloride must be ground first in order to generate the cross-coupling product 12 in good yield and high diastereomeric ratio (d.r.…”

Carbon–Carbon Bond Forming Reactions Mediated by Organozinc Reagents

“…As in the case of palladium, the fundamentals of these reactions were disclosed more than 30 years ago [196]. Developments over the past decade in nickel catalysis for the Negishi coupling of aryl and heteroaryl and to a minor extent alkenylzinc reagents have been directed toward achieving enhanced reaction scope.…”

“…However, often disregarded and considered less practical than palladium catalysis, it is not until recently that the use of nickel catalysis to couple C(sp 3 )-organozincs has regained interest, and that its distinctive features had led to the introduction of powerful variants to palladium catalysis. This is especially true in the challenging field of C(sp 3 )-C(sp 3 )-bond-forming reactions [124,126,196,276].…”

“…This, in addition to the fact that the reaction between organozincs and isolated alkye-Ni(II) halides only affords low yields of coupling products [299b], causes reaction mechanisms involving a Ni(0)/Ni(II) redox cycle to appear rather unlikely. Ni-catalyzed cross-couplings can proceed along several different pathways that vary according to the ligands on the metal, the electrophile (aryl halide vs alkyl halide), and also the nucleophile (aryl-vs alkylzincs) [124,126,196]. Of late, researchers have evinced keen interest to probe the mechanism of Nicatalyzed couplings involving bi-and tridentate nitrogen ligands.…”

Carbon–Carbon‐Bond‐Forming Reactions Mediated by Organomagnesium Reagents

“…Thus, these findings suggest that the transmetallation step occurs before the activation of the aryl halide and that Scheme 5. 44 Proposed mechanism for the carbon-carbon bond formation from (aryl)(alkyl)nickel(II) species in the presence of phosphine ligands [123,124].…”