Remotely Chiral Amines

Amines with stereocenters three or four carbon atoms from the amine nitrogen atom, called γ- and δ-chiral amines, are important structural features in many drugs and natural products. So it would be nice if they were easy to make. But chemists have not been able to controllably add amines and other functional groups to positions more than one or two carbons from chiral centers without resorting to multistep procedures. Stephen L. Buchwald of Massachusetts Institute of Technology and coworkers have now devised a single-step reaction that creates γ-chiral amines from allylic alcohols, allylic esters, and allylic ethers and makes δ-chiral amines from allylic epoxides (Nat. Chem. 2016, DOI: 10.1038/nchem.2418). The reaction can also be used to sequentially aminate substrates with more than one allylic group. The copper hydride-catalyzed procedure, which the MIT researchers call reductive relay hydroamination, works by installing an amino group three or four carbon atoms from one of the allylic starting material’s double-bonded carbons, which is converted to a chiral center as part of the reaction.