Oximes succumb to asymmetric hydrogenation

Asymmetric hydrogenation, wherein a double bond is reduced using molecular hydrogen, is a popular way to add a stereocenter to a molecule. But asymmetric hydrogenation tends to break oximes’ N–O bonds. It is possible to use chiral oxazaborolidine borane adducts to enantioselectively reduce oximes to hydroxylamines, but that reaction can generate unwanted by-products. And cost and waste build-up make that method difficult to use on a large scale. Now, Nicolai Cramer and Josep Mas-Roselló of the Swiss Federal Institute of Technology, Lausanne (EPFL), and Tomas Smejkal of Syngenta report they can use an iridium catalyst with a chiral cyclopentadienyl ligand to asymmetrically reduce oximes under acidic conditions (Science 2020, DOI: 10.1126/science.abb2559).The reaction works on oxime ethers, as well as on free oximes, without breaking the weak N–O bond. The chemists note that the reaction can produce a desired enantiomer with a selectivity of up to 98%. To demonstrate scalability, they hydrogenated 25 g of an oxime using a scant 0.05 mol % of the catalyst (reaction shown). The reaction gave the desired methoxyamine quantitatively, indicating the catalyst facilitated about 4,000 reactions before becoming inactive. The researchers say their findings could be a blueprint for hydrogenation of challenging substrates and also highlight the potential of cyclometalated chiral cyclopentadienyl metal complexes in catalysis.