US EPA

6921759 

Journal Article 

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 

Liu, Q; Lan, Y; Liu, J; Li, G; Wu, YD; Lei, A; , 

2009 

Yes 

Journal of the American Chemical Society
ISSN: 0002-7863
EISSN: 1520-5126 

English 

19572717 

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 Ar(1)-Pd-Ar(2) species and the organozinc reagent Ar(2)-ZnX. Understanding of this second step reveals how homocoupling and dehalogenation products are formed. Thus, the second transmetalation generates Ar(2)PdAr(2) and Ar(1)ZnCl, which upon reductive elimination and hydrolysis, respectively, give the homocoupling product Ar(2)-Ar(2) and the dehalogenation product Ar(1)H. The ratio of the cross-coupling product Ar(1)-Ar(2) and the homocoupling product Ar(2)-Ar(2) 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.