A Facile Pathway to Enantiomerically Enriched 3-Hydroxy-2-Oxindoles: Asymmetric Intramolecular Arylation of α-Keto Amides Catalyzed by a Palladium-DifluorPhos Complex

摘要

Organic group-transfer reactions from halides and triflates to carbonyl compounds are a useful C-C bond-forming transformation. An example is the chromium-mediated Nozaki-Hiyama-Kishi (NHK) reaction whose utility has been demonstrated by numerous applications to total syntheses of complex natural products and biologically active compounds. The requirement for stoichiometric amounts of toxic chromium salts—a major drawback of this reaction— has been overcome by the use of a catalytic redox system developed by Furstner and Shi. This fundamental achievement allowed for extension to a catalytic enantioselective variant of the NHK reaction. Despite the great advantages of the catalytic system compared to the original stoichiometric system, the requirements for stoichiometric amounts of Mn~0 and TMSCl still conflicts with principles of modern, environmentally benign synthetic organic chemistry. A catalytic asymmetric NHK-type (or Grignard/Barbier-type) reaction without the use of stoichiometric amounts of metals is therefore in high demand.