Stereoselective Synthesis of Methylene Oxindoles via Palladium(II)-Catalyzed Intramolecular Cross-Coupling of Carbamoyl Chlorides.

doi:10.1021/JACS.6B08925

Paper

Stereoselective Synthesis of Methylene Oxindoles via Palladium(II)-Catalyzed Intramolecular Cross-Coupling of Carbamoyl Chlorides.

Published Oct 20, 2016 · C. Le, T. Sperger, Rui Fu

Journal of the American Chemical Society

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Abstract

We report a highly robust, general and stereoselective method for the synthesis of 3-(chloromethylene)oxindoles from alkyne-tethered carbamoyl chlorides using PdCl2(PhCN)2 as the catalyst. The transformation involves a stereo- and regioselective chloropalladation of an internal alkyne to generate a nucleophilic vinyl PdII species, which then undergoes an intramolecular cross-coupling with a carbamoyl chloride. The reaction proceeds under mild conditions, is insensitive to the presence of moisture and air, and is readily scalable. The products obtained from this reaction are formed with >95:5 Z:E selectivity in nearly all cases and can be used to access biologically relevant oxindole cores. Through combined experimental and computational studies, we provide insight into stereo- and regioselectivity of the chloropalladation step, as well as the mechanism for the C-C bond forming process. Calculations provide support for a mechanism involving oxidative addition into the carbamoyl chloride bond to generate a high valent PdIV species, which then undergoes facile C-C reductive elimination to form the final product. Overall, the transformation constitutes a formal PdII-catalyzed intramolecular alkyne chlorocarbamoylation reaction.

Study Snapshot

This study presents a robust, stereoselective method for the synthesis of 3-(chloromethylene)oxindoles from alkyne-tethered carbamoyl chlorides using PdCl2(PhCN)2, offering potential for biologically relevant oxindole

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Stereoselective Synthesis of Methylene Oxindoles via Palladium(II)-Catalyzed Intramolecular Cross-Coupling of Carbamoyl Chlorides.

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