Abstract

The proline-catalyzed aldol reaction is the seminal example of asymmetric organocatalysis. Previous theoretical and experimental studies aimed at identifying its mechanism in order to rationalize the outcome of this reaction. Here, we focus on key steps with modern first principle methods, i.e. the M06-2X hybrid exchange–correlation functional combined to the solvation density model to account for environmental effects. In particular, different pathways leading to the formation of neutral and negatively charged enamine intermediates are investigated, and their reactivity towards two electrophiles, i.e. an aldehyde and a benzhydrylium cation, are compared. Regarding the self-aldol reaction, our calculations confirm that the neutral enamine intermediate is more reactive than the negatively charged one. For the reaction with benzhydrylium cations however, the negatively charged enamine intermediate is more reactive.
Original languageEnglish
Pages (from-to)30 - 36
Number of pages7
JournalChemical physics
Volume434
DOIs
Publication statusPublished - 15 Apr 2014

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Cations
Solvation
Proline
Aldehydes
Environmental impact
cations
aldehydes
solvation
reactivity
3-hydroxybutanal

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title = "Quantum Mechanical Investigations on the Role of Neutral and Negatively Charged Enamine Intermediates in Organocatalyzed Reactions",
abstract = "The proline-catalyzed aldol reaction is the seminal example of asymmetric organocatalysis. Previous theoretical and experimental studies aimed at identifying its mechanism in order to rationalize the outcome of this reaction. Here, we focus on key steps with modern first principle methods, i.e. the M06-2X hybrid exchange–correlation functional combined to the solvation density model to account for environmental effects. In particular, different pathways leading to the formation of neutral and negatively charged enamine intermediates are investigated, and their reactivity towards two electrophiles, i.e. an aldehyde and a benzhydrylium cation, are compared. Regarding the self-aldol reaction, our calculations confirm that the neutral enamine intermediate is more reactive than the negatively charged one. For the reaction with benzhydrylium cations however, the negatively charged enamine intermediate is more reactive.",
author = "Pierre Hubin and Denis Jacquemin and Laurence Leherte and Vercauteren, {Daniel P.}",
year = "2014",
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language = "English",
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T1 - Quantum Mechanical Investigations on the Role of Neutral and Negatively Charged Enamine Intermediates in Organocatalyzed Reactions

AU - Hubin, Pierre

AU - Jacquemin, Denis

AU - Leherte, Laurence

AU - Vercauteren, Daniel P.

PY - 2014/4/15

Y1 - 2014/4/15

N2 - The proline-catalyzed aldol reaction is the seminal example of asymmetric organocatalysis. Previous theoretical and experimental studies aimed at identifying its mechanism in order to rationalize the outcome of this reaction. Here, we focus on key steps with modern first principle methods, i.e. the M06-2X hybrid exchange–correlation functional combined to the solvation density model to account for environmental effects. In particular, different pathways leading to the formation of neutral and negatively charged enamine intermediates are investigated, and their reactivity towards two electrophiles, i.e. an aldehyde and a benzhydrylium cation, are compared. Regarding the self-aldol reaction, our calculations confirm that the neutral enamine intermediate is more reactive than the negatively charged one. For the reaction with benzhydrylium cations however, the negatively charged enamine intermediate is more reactive.

AB - The proline-catalyzed aldol reaction is the seminal example of asymmetric organocatalysis. Previous theoretical and experimental studies aimed at identifying its mechanism in order to rationalize the outcome of this reaction. Here, we focus on key steps with modern first principle methods, i.e. the M06-2X hybrid exchange–correlation functional combined to the solvation density model to account for environmental effects. In particular, different pathways leading to the formation of neutral and negatively charged enamine intermediates are investigated, and their reactivity towards two electrophiles, i.e. an aldehyde and a benzhydrylium cation, are compared. Regarding the self-aldol reaction, our calculations confirm that the neutral enamine intermediate is more reactive than the negatively charged one. For the reaction with benzhydrylium cations however, the negatively charged enamine intermediate is more reactive.

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DO - 10.1016/j.chemphys.2014.02.012

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SN - 0301-0104

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