P,N Ligand Advances Ammonia Coupling

Palladium-catalyzed cross-coupling of aryl halides and amines, known as Buchwald-Hartwig amination, is a key tool for constructing arylamines in organic synthesis. In the latest twist on this reaction, Mark Stradiotto and coworkers at Dalhousie University, in Halifax, Nova Scotia, report a new ligand that enables chemists to selectively react ammonia—the simplest and most abundant N–H source—with a broad range of aryl halides and tosylates at room temperature (Angew. Chem. Int. Ed., DOI: 10.1002/anie.201000526). The chelating P,N ligand, which the team calls Mor-DalPhos, consists of an adamantyl-substituted phosphorus and a morpholine-substituted nitrogen bridged by phenylene. The team previously prepared a dimethyl version of the ligand, called Me-DalPhos, which is handy for traditional amine couplings (Chem. Eur. J. 2010, 16, 1983). Both Mor-DalPhos and Me-DalPhos are in demand by pharmaceutical companies, Stradiotto says. His group has made batches of the ligands that are already being sold by Strem Chemicals. The reactivity and selectivity of Mor-DalPhos with ammonia at room temperature “is remarkable,” says John F. Hartwig of the University of Illinois, Urbana-Champaign. Stradiotto’s group has found a ligand “sweet spot” for C–N coupling between tightly bound bidentate bisphosphines and labile hindered monodentate phosphines, Hartwig notes.