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DFT study of the dual catalytic role of L-proline in the aldol reaction and the effect of water on it

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Abstract

The aldol reaction in the presence of L-proline acting as an organocatalyst is a well-known example of asymmetric synthesis. Many theoretical and experimental studies have been carried out to probe the mechanism of this reaction. In this work, two levels of density functional theory in the gas phase and DMSO were used to elucidate the best pathways for this reaction, with the enamine and enol considered intermediates and L-proline considered either a reactant or a facilitator. The calculations indicated that both intermediates are formed simultaneously in the reaction medium. Interestingly, the formation of the enamine intermediate predominates in DMSO at room temperature, whereas the enol becomes the predominant intermediate upon the addition of water.

The dual role of L-proline leads to single stereoisomeric aldol product via two completely different pathways.

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Acknowledgments

We gratefully acknowledge the Department of Chemistry of the University of Zanjan for its support of this work.

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Authors and Affiliations

  1. Department of Chemistry, Faculty of Sciences, University of Zanjan, Zanjan, Iran

    Yasaman Nobakht & Nematollah Arshadi

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  1. Yasaman Nobakht
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Correspondence to Nematollah Arshadi.

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Nobakht, Y., Arshadi, N. DFT study of the dual catalytic role of L-proline in the aldol reaction and the effect of water on it. J Mol Model 24, 334 (2018). https://doi.org/10.1007/s00894-018-3851-0

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