Mild ketyl radical generation and coupling with alkynes enabled by Cr catalysis: stereoselective access to E-exocyclic allyl alcohols

Abstract

The mild catalytic generation of ketyl radicals for organic transformations remains an unsolved issue, although it facilitates the discovery of metal-catalyzed reactions with the features of high functional group tolerance. Here, we report the generation of the ketyl radicals and coupling with alkynes that was enabled by cost-effective chromium catalysis, allowing for the formation of valuable E-exocyclic allyl alcohols with high stereo- and chemoselectivity. A broad range of synthetically useful functional groups that are sensitive to strong reductants are compatible with the catalytic system, providing access to diverse substituted E-exocyclic allyl alcohols under mild conditions. Appended hydroxyl groups in products are facilely late-stage functionalized in accessing numerous derivatives, as well as the enantio-enrichment of exocyclic allyl alcohol using chiral ligands. Mechanistic studies suggest that bipyridine-ligated Cr(II) complex serves as a reactive catalyst enabling the generation of the ketyl radical for coupling, giving vinyl radical, followed by the combination of Cr and transmetalation with Cp₂ZrCl moiety in affording oxazirconiumacycle. This reaction provides a new opportunity for the mild formation of transient ketyl radicals from widely accessible aliphatic aldehydes for coupling with Earth-abundant metal catalysis.