Catalytic allylic oxidation of internal alkenes to a multifunctional chiral building block.

Abstract

The stereoselective oxidation of hydrocarbons represents one of the most significant advances in synthetic chemistry over the last fifty years1–3. Inspired by nature, chemists have developed enantioselective dihydroxylations, epoxidations, and other oxidations of unsaturated hydrocarbons. More recently, the catalytic enantioselective allylic C–H oxidation of alkenes has emerged as a powerful chemical strategy, streamlining the production of pharmaceuticals, natural products, fine chemicals and other functional materials4–7. Allylic functionalization provides a direct path to chiral synthons with a newly formed stereocenter from petrochemical feedstocks while preserving the olefin functionality as a handle for further elaboration. Various metal-based catalysts have been discovered for the enantioselective allylic C–H oxidation of simple alkenes with cyclic or terminal double bonds8–16. However, a general and selective allylic oxidation remains elusive with the more common internal alkenes. Here, we report the enantioselective, regioselective, and E/Z selective allylic oxidation of unactivated internal alkenes via a catalytic asymmetric hetero-ene reaction with a chalcogen-based oxidant. This method represents the first example of selectively converting unsymmetrical internal alkenes into allylic functionalized products with high stereoselectivity and regioselectivity. Stereospecific transformations of the multifunctional allylic oxidation products highlight the potential for rapidly converting internal alkenes into a broad range of enantioenriched structures that can be utilized in the synthesis of complex target molecules.