title: An enantioselective Claisen rearrangement catalyzed by N-heterocyclic carbenes.
abstract: In the presence of a chiral azolium salt (10 mol %), enols and ynals undergo a highly enantioselective annulation reaction to form enantiomerically enriched dihydropyranones via an N-heterocyclic carbene catalyzed variant of the Claisen rearrangement. Unlike other azolium-catalyzed reactions, this process requires no added base to generate the putative NHC-catalyst, and our investigations demonstrate that the counterion of the azolium salt plays a key role in the formation of the catalytically active species. Detailed kinetic studies eliminate a potential 1,4-addition as the mechanistic pathway; the observed rate law and activation parameters are consistent with a Claisen rearrangement as the rate-limiting step. This catalytic system was applied to the synthesis of enantioenriched kojic acid derivatives, a reaction of demonstrated synthetic utility for which other methods for catalytic enantioselective Claisen rearrangements have not provided a satisfactory solution.
authors.affiliation: Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6323, USA.
authors.forename: Juthanat
authors.initials: J
authors.lastname: Kaeobamrung
authors.forename: Jessada
authors.initials: J
authors.lastname: Mahatthananchai
authors.forename: Pinguan
authors.initials: P
authors.lastname: Zheng
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Bode
mesh_terms: D001393:Azoles / Q000737:chemistry*; D002384:Catalysis; D008697:Methane / Q000031:analogs & derivatives* / Q000737:chemistry; D009584:Nitrogen / Q000737:chemistry*; D013237:Stereoisomerism; D013379:Substrate Specificity
chemical_list: D001393:Azoles; C030011:carbene; D009584:Nitrogen; D008697:Methane