An enantioselective Claisen rearrangement catalyzed by N-heterocyclic carbenes.
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.
Kaeobamrung
Juthanat
J
Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6323, USA.
Mahatthananchai
Jessada
J
Zheng
Pinguan
P
Bode
Jeffrey W
JW
D001393:Azoles / Q000737:chemistry*; D002384:Catalysis; D008697:Methane / Q000031:analogs & derivatives* / Q000737:chemistry; D009584:Nitrogen / Q000737:chemistry*; D013237:Stereoisomerism; D013379:Substrate Specificity
D001393:Azoles; C030011:carbene; D009584:Nitrogen; D008697:Methane