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
Citations Over TimeTop 10% of 2009 papers
Abstract
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.
Related Papers
- → 1,3-Butadienylzinc Trimer Formed via Transmetalation from 1,4-Dilithio-1,3-butadienes: Synthesis, Structural Characterization, and Application in Negishi Cross-Coupling(2012)16 cited
- → Online and In Situ Monitoring of the Exchange, Transmetalation, and Cross-Coupling of a Negishi Reaction(2022)11 cited
- → Atroposelective NiII‐Catalyzed Cross‐Coupling Reactions Enable a Deeper Understanding of Negishi Couplings: Isolation and Application of Solid Aryl Higher‐Order Zincates(2023)6 cited
- → Arylzinc species by microwave assisted Grignard formation–transmetallation sequence: application in the Negishi coupling(2005)43 cited
- → Experiences with Negishi Couplings on Technical Scale in Early Development(2003)10 cited