By means of DFT and AIM calculations, the steric and stereoelectronic effects that control the enantioselectivity in the cross-aldol addition of acetone to isatin catalysed by L-proline have been studied. This reaction results in a reversal of enantioselectivity when compared with the corresponding cross-aldol addition to 4,6-dibromoisatin and to aldehydes. DFT calculations of the cross-aldol transition states indicate that product formation follows different pathways for the substrates isatin and 4,6-dibromoisatin. In the case of isatin, the S-enantiomer is favoured as a consequence of a stereoelectronic effect that results in a lower energy transition state for the S-enantiomer relative to the R- enantiomer. In contrast, the cross-aldol addition of acetone to 4,6-dibromoisatin furnishes the expected R-enantiomer due to a steric effect of the 4-bromo substituent which inhibits formation of the S-enantiomer via the stereoelectronically favoured transition state.

A DFT and AIM study of the proline catalysed asymmetric cross-aldol addition of acetone to isatins: a rationalization for the reversal of chirality

ANGELICI, GAETANO;TOMASINI, CLAUDIA
2008

Abstract

By means of DFT and AIM calculations, the steric and stereoelectronic effects that control the enantioselectivity in the cross-aldol addition of acetone to isatin catalysed by L-proline have been studied. This reaction results in a reversal of enantioselectivity when compared with the corresponding cross-aldol addition to 4,6-dibromoisatin and to aldehydes. DFT calculations of the cross-aldol transition states indicate that product formation follows different pathways for the substrates isatin and 4,6-dibromoisatin. In the case of isatin, the S-enantiomer is favoured as a consequence of a stereoelectronic effect that results in a lower energy transition state for the S-enantiomer relative to the R- enantiomer. In contrast, the cross-aldol addition of acetone to 4,6-dibromoisatin furnishes the expected R-enantiomer due to a steric effect of the 4-bromo substituent which inhibits formation of the S-enantiomer via the stereoelectronically favoured transition state.
R. J. Corrêa; S. J. Garden; G. Angelici; C. Tomasini
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/57595
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