Cu(I)-catalysed N-H insertion in water: a new tool for chemical biology

We demonstrate for the first time that Cu(I)-catalysis can deliver N-H insertion (NHI) with alpha-diazocarbonyl compounds in aqueous media. Despite being carried out in water only trace amounts of O-H insertion are seen, indicating the catalyst's overwhelming preference for NHI. Our optimized conditions for NHI converged with those used for the Cu-catalyzed azide-alkyne cycloaddition (CuAAC) for bioconjugation, spurring us to develop an auto-tandem catalytic process where both catalytic cycles operate simultaneously in one-pot. We explore the scope of the method with both small molecule and complex DNA and RNA substrates.