6533b854fe1ef96bd12afc8c

RESEARCH PRODUCT

The nucleophilic addition of nitrones to carbonyl compounds: insights on the nature of the mechanism of the l-proline induced asymmetric reaction from a DFT analysis

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Abstract The mechanism of the l -proline induced asymmetric nitrone–aldol reaction of N -methyl- C -ethylnitrone with dimethyl ketomalonate has been studied by using density functional theory at B3LYP/6-31G** level. The reaction was initialized by the addition of l -proline to the nitrone to form an aminal, which by elimination of the hydroxylamine gave a chiral enamine. The nucleophilic addition of this chiral enamine to dimethyl ketomalonate corresponds to stereoselective C–C bond-formation step. Further nucleophilic addition of hydroxylamine to the zwitterionic intermediate formed in the enamine addition gave a second aminal, which by l -proline elimination afforded the corresponding β-hydroxynitrone. The B3LYP/6-31G** results are in acceptable agreement with previous experiments, allowing us to explain the stereoselectivity on the C–C bond-formation step.