Hydrogen-bond-directed highly stereoselective synthesis of Z-enamides via Pd-catalyzed oxidative amidation of conjugated olefins

An efficient procedure for the preparation of Z-enamides has been developed, involving the reaction of primary amides with conjugated olefins using a Pd/Cu cocatalyst system. It was found that certain additives, such as phosphine oxides and phosphonates, increase the efficiency of the reaction in nonpolar solvents under an oxygen atmosphere, thus producing a variety of Z-enamides in high yields with excellent stereoselectivity under Wacker-type conditions. The oxidative amidation reaction has a broad substrate scope, allowing alkyl, aryl, and vinyl amides to react with olefins conjugated with ester, amide, phosphonate, and ketone groups. The notable preference for the formation of Z-enamides is presumably due to the presence of an intramolecular hydrogen bond between the amido proton and the carbonyl oxygen. The energy difference between two plausible sigma-alkylamidopalladium intermediates, leading to Z- and E-isomeric enamide products, respectively, was calculated to be 4.18 kcal/mol. The beta-hydride elimination step is assumed to be a stereochemistry-determining step in the overall oxidative amidation process, with the energy level for the transition state leading to the Z- enamide being 5.35 kcal/mol lower than that leading to the E-isomer. The efficiency of photoisomerization between Z- and E-enamides was observed to be largely dependent on the substrates' substituents, and certain E-enamides could be obtained in synthetically useful yields by photoirradiation of Z- isomers. Synthetic application of the present method was successfully demonstrated by a direct formal synthesis of cis-CJ-15,801.
Publisher
AMER CHEMICAL SOC
Issue Date
2006-10
Language
ENG
Keywords

CROSS-COUPLING REACTIONS; DIELS-ALDER REACTIONS; BETA-HYDRIDE ELIMINATION; ASYMMETRIC CATALYSIS; ENANTIOSELECTIVE HYDROGENATION; AEROBIC OXIDATION; MOLECULAR-OXYGEN; PALLADIUM(II)-CATALYZED CYCLIZATION; BIOLOGICAL-PROPERTIES; VINYLIC SUBSTITUTION

Citation

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, v.128, no.39, pp.12954 - 12962

ISSN
0002-7863
DOI
10.1021/ja0639315
URI
http://hdl.handle.net/10203/10826
Appears in Collection
CH-Journal Papers(저널논문)
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