One-pot synthesis of conformationally restricted spirooxindoles |
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Authors: | Martha S. Morales-Rí os,Daphne E. Gonzá lez-Juá rez,Oscar  R. Suá rez-Castillo |
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Affiliation: | a Departamento de Química y Sección Externa de Farmacología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Apartado 14-740, Mexico, D. F., 07000 Mexico b Centro de Investigaciones Químicas, Universidad Autónoma del Estado de Hidalgo, Apartado 1-328, Pachuca, 42001 Hidalgo, Mexico |
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Abstract: | Diastereomeric three-, five- and six-membered spirocycloalkyloxindoles were successfully synthesized in a rapid and convenient manner from readily accessible starting materials in moderate to high yields using 1-methyl-3-acetonitriloxindole after a one-pot base-mediated double-alkylation strategy. It was found that the diastereoselection is dependent on the reaction conditions and the spirocycloalkyl ring size, with the 3R∗,8R∗ diastereomers being thermodynamically favored under the basic reaction conditions for three- and five-membered rings, and the 3R∗,8S∗ diastereomer in the case of six-membered rings, as predicted by DFT calculations. The relative stereochemistry was supported by 2D NMR spectra and X-ray crystal structural analysis. The conformational rigidity of the spirocycloalkyloxindoles in solution was established based on NMR experimental and theoretical DFT approaches. |
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Keywords: | Spirooxindoles Sequential metalations Diastereoselectivity DFT calculations |
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