Unraveling the Origin of Solvent Induced Enantioselectivity in the Henry Reaction with Cinchona Thiourea as Catalyst

Mojgan Heshmat*

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review


In this work, we report an energy decomposition and electronic structure analysis using DFT calculations for the C-C coupling step in the Henry reaction with cinchona thiourea as catalyst and DMF solvent to unravel the origin of enantioselectivity. We found that the conformation of flexible thiourea moiety is affected by the solvent, and in the preferred conformation of thiourea in strong Lewis basic DMF solvent, the N-H sites are in the opposite direction, i.e., in trans conformation. Hence, the thiourea moiety acts via single hydrogen bonding with substrates. The conformation of the substrates with respect to the forming C-C bond plays critical role to increase orbital interaction between two substrates and enhances hydrogen bond strength between substrates and catalyst, which in turn stabilizes the positive charge developing on the catalyst at the transition state for one of the enantiomers (S). Thus, the enantioselectivity has electronic structure origin. The stronger H-bond formation in the S enantiomer has been confirmed by the calculated IR spectra and is in agreement with thus far experimental and computational results.

Original languageEnglish
Pages (from-to)7974-7982
Number of pages9
JournalJournal of Physical Chemistry A
Issue number40
Early online date19 Sept 2018
Publication statusPublished - 11 Oct 2018


A grant of computing time by The Netherlands Scientific Research Council (NWO) is gratefully acknowledged. The author deeply thanks Prof. Evert Jan Baerends for numerous fruitful discussions and invaluable help which took place during this work.

FundersFunder number
Netherlands Scientific Research Council
Nederlandse Organisatie voor Wetenschappelijk Onderzoek


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