Revealing a second transmetalation step in the Negishi coupling and its competition with reductive elimination: Improvement in the interpretation of the mechanism of biaryl syntheses

Article abstract of DOI:10.1021/ja903277d

This paper presents an experimental and theoretical investigation of the Pd-catalyzed Negishi coupling reaction and reveals a novel second transmetalation reaction between an Ar¹-Pd-Ar² species and the organozinc reagent Ar²-ZnX. Understanding of this second step reveals how homocoupling and dehalogenation products are formed. Thus, the second transmetalation generates Ar²PdAr² and Ar ¹ZnCl, which upon reductive elimination and hydrolysis, respectively, give the homocoupling product Ar²-Ar² and the dehalogenation product Ar¹H. The ratio of the cross-coupling product Ar¹-Ar² and the homocoupling product Ar ²-Ar² is determined by competition between the second transmetalation and reductive elimination steps. This mechanism is further supported by density functional theoretical calculations. Calculations on a series of reactions suggest a strategy in controlling the selectivity of cross-coupling and homocoupling pathways, which we have experimentally verified.