Negishi coupling mechanism

Negishi coupling Another named coupling that follows the mechanism of Figure 12.16 involves the use of vinyl zirconium and aluminum species with vinyl halides. This efficiently gives conjugated alkenes, and has been extensively used in the creation of oligomeric alkenes. 

As in all C-C cross-coupling reactions, the Negishi reaction mechanism consists in three steps (Fig.4.1) oxidative addition, transmetalation, and reductive elimination. The former and the latter are common to all the other cross-coupling reactions, whereas the transmetalation step is particular of this reaction. Unfortunately, this transmetalation has been less studied compared to the ones in the Stille [12-17] or Suzuki reactions, [18-21] in spite of the fact that the transmetalation between organozinc and palladium complexes is also involved in other relevant processes, such as the hydroalkylation of styrenes, [22] the asymmetric allylation of aryl aldehydes, [23] the coupling propargylic benzoates and aldehydes, [24] or the double-transmetalation oxidative cross-coupling reaction [25, 26]. 

Scheme 3.3 Possible mechanism for the 1,2-migration in the Negishi coupling. Reprinted (adapted) with permission from J. Org. Chem. 2009, 74, 135. Copyright 2009 American Chemical Society...

The reaction of alkynylzinc or zincates with azides has been reported to deliver metallotriazoles that can be further functionalized using a Negishi coupling reaction [142]. Although the mechanism has not been discussed, formation of a metalated heterocycle might be related to the one proposed by Krasinski (Scheme 57). 

Consequently, to narrow the definition a bit further, we will adhere to Negishi s suggestion and define cross-coupling reactions as those that follow some variation of the mechanism depicted in Scheme 1 (where Mt is a transition metal, L is an ancillary hgand see Ancillary Ligand), and n is the oxidation state of the reduced metal in the catalytic cycle). This mechanism is supported by stoichiometric studies on isolated metal complexes (mostly where Mt = Pd, n = 0, L = triphenylphosphine) thought to be the intermediates in this cycle. 

Negishi, E., Takahashi, T., Baba, S., Van Horn, D. E., Okukado, N. Nickel- or palladium-catalyzed cross coupling. 31. Palladium- or nickel-catalyzed reactions of alkenylmetals with unsaturated organic halides as a selective route to arylated alkenes and conjugated dienes scope, limitations, and mechanism. J. Am. Chem. Soc. 1987,109, 2393-2401. 

Negishi proposes a similar mechanism for the Pd-catalyzed Sonogashira coupling of aryl halides and alkynes when performed without Cu catalysts (Scheme 20). 

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