Coupling of Secondary Alkylzinc Halides with Aryl Bromides and Chlorides

Negishi coupling - alkylzinc halides - aryl halides - palladium

Significance

Direct cross-coupling of secondary acyclic organometallic species is a rather challenging task. This reaction is often plagued by β-hydride elimination or metal migration. The fine tuning of the ligand for the Negishi coupling allowed the development of a high-yielding, simple procedure for this coupling reaction, suitable for a broad substrate range with excellent functional group tolerance.

Comment

One of the main side products of the sp^²-sp^³ coupling of i-PrZnHal and similar species is the n-propyl adduct. Mechanistic studies of the authors showed that the ratio of i-Pr to n-Pr products depends on the rate of reductive elimination from the ligated ArPd(i-Pr) species, which competes with the β-hydride elimination-reinsertion process. Interestingly, free alcohols are tolerated in this coupling.