Pd-Catalyzed Intramolecular α‑Allylic Alkylation of Ketones with Alkynes: Rapid and Stereodivergent Construction of [3.2.1] Bicycles

Here we describe a palladium-catalyzed intramolecular α-allylic alkylation of unactivated ketones with alkynes. The reaction proceeds in the absence of any amine cocatalyst; both endo and exo-bridged cyclohexanone bicycles can be obtained diastereoselectively. The stereodivergency is controlled by the ligand and acid additive used. Specifically, the monodentate DTBMPP ligand favors forming the endo isomer, while the bidentate DIOP ligand prefers to give the exo isomer. A broad range of functional groups are tolerated, which provides a chemoselective approach to access [3.2.1] bicyclic skeletons. Further deuterium labeling studies support a pathway involving an alkyne/allene isomerization and Pd-π-allyl complex formation.