Zinc Dianion Drives Cross-Coupling

In a surprise finding, Canadian chemists have discovered that an organozinc dianion is the active transmetalating reagent in the Nobel Prize-winning Negishi cross-coupling reaction, not a monoanion species as previously believed (Angew. Chem. Int. Ed., DOI: 10.1002/anie.201203547). The zinc species in a Negishi reaction, typically prepared from an organolithium reagent and a zinc halide, transfers its organo group to a palladium catalyst, which in turn mediates C–C coupling with an organo group contributed by an organohalide. Organic chemists had taken for granted that RZnX₂^– was the active transmetalator, where R is the organo group and X is a halide. But a team led by Michael G. Organ of York University, in Toronto, and Jason A. C. Clyburne of Saint Mary’s University, in Halifax, Nova Scotia, discovered otherwise. Through titration studies they observed that cross-coupling doesn’t occur when one equivalent of organolithium reagent is used—the organolithium goes to form RZnX₂^–. Only when additional lithium reagent is added and RZnX₃^2– forms does cross-coupling take place. The team proved the dianion’s pivotal role by synthesizing a (CH₃CH₂)ZnBr₃^2– salt and showing that cross-coupling proceeds when using it without adding any auxiliary reagents.