Phosphine-mediated azine C-H couplings with water and ammonia.

The unique reactivity of transition metals has advanced C-H functionalization chemistry, enabling practitioners to directly modify drug and agrochemical compounds during structure-activity relationship (SAR) studies. These metals are particularly adept at transforming the C-H bonds of arenes and aromatic heterocycles, generating new reactions that form C-C and C-heteroatom bonds. However, among the many potential coupling partners, (hetero)arene C-H coupling reactions with water and ammonia are rare1-5. Despite being two of the most abundant chemicals on Earth, their reactivity can be at odds with transition metal complexes and the elementary steps associated with C-O/C-N bond formation6. We suspected that elements outside of the transition metal block might instead facilitate these reactions. Here we show that simple triarylphosphines enable selective azine C-H coupling with water and ammonia. The reactions proceed by a distinct mechanism, in which pendant aldehyde and imine functional groups interconvert to acetal- and aminal-type forms, studied here both experimentally and computationally. This unusual example of neighbouring group participation effectively delivers water and ammonia molecules into a phosphorus(V) coordination environment, promoting C-O and C-N bond formation through ligand-coupling reactions7. A broad range of pyridines are compatible, as well as quinolines and diazines, and the chemistry functions as a late-stage tactic for hydroxylation and amination of complex pharmaceuticals and agrochemicals.