The Role of LiBr and ZnBr2 on the Cross-Coupling of Aryl Bromides with Bu2 Zn or BuZnBr.

The impact of LiBr and ZnBr2 salts on the Negishi coupling of alkylZnBr and dialkylzinc nucleophiles with both electron-rich and -poor aryl electrophiles has been examined. Focusing only on the more difficult coupling of deactivated (electron-rich) oxidative addition partners, LiBr promotes coupling with BuZnBr, but does not have such an effect with Bu2 Zn. The presence of exogenous ZnBr2 shuts down the coupling of both BuZnBr and Bu2 Zn, which has been shown before with alkyl electrophiles. Strikingly, the addition of LiBr to Bu2 Zn reactions containing exogenous ZnBr2 now fully restores coupling to levels seen without any salt present. This suggests that there is a very important interaction between LiBr and ZnBr2 . It is proposed that Lewis acid adducts are forming between ZnBr2 and the electron-rich Pd0 centre and the bromide from LiBr forms inorganic zincates that prevent the catalyst from binding to ZnBr2 . This idea has been supported by catalyst design as chlorinating the backbone of the NHC ring of Pd-PEPPSI-IPent to produce Pd-PEPPSI-IPentCl catalyst now gives quantitative conversion, up from a ceiling of only 50 % with the former catalyst.