A mechanistic study of the Lewis acid-Brønsted base-Brønsted acid catalysed asymmetric Michael addition of diethyl malonate to cyclohexenone

Yuri Samoilichenko; Veronica Kondratenko; Mariam Ezernitskaya; Konstantin Lyssenko; Alexander Peregudov; Victor Khrustalev; Victor Maleev; Margarita Moskalenko; Michael North; Alan Tsaloev; Zalina T. Gugkaeva; Yuri Belokon

doi:10.1039/c6cy01697a

A mechanistic study of the Lewis acid-Brønsted base-Brønsted acid catalysed asymmetric Michael addition of diethyl malonate to cyclohexenone

Yuri Samoilichenko, Veronica Kondratenko, Mariam Ezernitskaya, Konstantin Lyssenko, Alexander Peregudov, Victor Khrustalev, Victor Maleev, Margarita Moskalenko, Michael North, Alan Tsaloev, Zalina T. Gugkaeva, Yuri Belokon^*

^*Corresponding author for this work

Chemistry

Research output: Contribution to journal › Article › peer-review

Abstract

The Michael addition of diethyl malonate (Michael Donor, MD) to cyclohexenone (Michael Acceptor, MA) catalysed by the mono-lithium salt of (S)- or (R)-BIMBOL in dichloromethane is shown to exhibit biomimetic behavior. A combination of kinetics, spectroscopic studies, synthesis of catalyst analogues, inhibition studies and DFT calculations are used to show that the catalyst activates both components of the reaction and uses a chain of proton transfers to facilitate the deprotonation of diethyl malonate. The initial reaction rate was first order relative to both MA and MD and 0.5 order relative to the catalyst, indicating that an equilibrium exists between monomeric and dimeric forms of the catalyst, with the dimer predominating, but only the monomeric form being catalytically active. This was supported by DOSY ¹H NMR experiments. The importance of the Lewis acidic lithium cation in the catalytic step was established by complete inhibition of the reaction by lithium complexing agents. The importance of the number of OH-groups and their relative intramolecular orientation and acidities in the polyol catalyst was shown by studying the relative catalytic activities of catalyst analogues. DFT calculations allowed the relative energies and structures of the likely intermediates on the reaction coordinate to be calculated and indicated that the ionisation of MD was facilitated due to the Lewis acidity of the lithium cation and hydrogen bond formation between deprotonated MD (MD^-1) and the OH groups of the BIMBOL moiety.

Original language	English
Pages (from-to)	90-101
Number of pages	12
Journal	Catalysis Science and Technology
Volume	7
Issue number	1
Early online date	14 Nov 2016
DOIs	https://doi.org/10.1039/c6cy01697a
Publication status	Published - 7 Jan 2017

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© The Royal Society of Chemistry 2017. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details

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Samoilichenko, Y., Kondratenko, V., Ezernitskaya, M., Lyssenko, K., Peregudov, A., Khrustalev, V., Maleev, V., Moskalenko, M., North, M., Tsaloev, A., Gugkaeva, Z. T., & Belokon, Y. (2017). A mechanistic study of the Lewis acid-Brønsted base-Brønsted acid catalysed asymmetric Michael addition of diethyl malonate to cyclohexenone. Catalysis Science and Technology, 7(1), 90-101. https://doi.org/10.1039/c6cy01697a

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title = "A mechanistic study of the Lewis acid-Br{\o}nsted base-Br{\o}nsted acid catalysed asymmetric Michael addition of diethyl malonate to cyclohexenone",

abstract = "The Michael addition of diethyl malonate (Michael Donor, MD) to cyclohexenone (Michael Acceptor, MA) catalysed by the mono-lithium salt of (S)- or (R)-BIMBOL in dichloromethane is shown to exhibit biomimetic behavior. A combination of kinetics, spectroscopic studies, synthesis of catalyst analogues, inhibition studies and DFT calculations are used to show that the catalyst activates both components of the reaction and uses a chain of proton transfers to facilitate the deprotonation of diethyl malonate. The initial reaction rate was first order relative to both MA and MD and 0.5 order relative to the catalyst, indicating that an equilibrium exists between monomeric and dimeric forms of the catalyst, with the dimer predominating, but only the monomeric form being catalytically active. This was supported by DOSY 1H NMR experiments. The importance of the Lewis acidic lithium cation in the catalytic step was established by complete inhibition of the reaction by lithium complexing agents. The importance of the number of OH-groups and their relative intramolecular orientation and acidities in the polyol catalyst was shown by studying the relative catalytic activities of catalyst analogues. DFT calculations allowed the relative energies and structures of the likely intermediates on the reaction coordinate to be calculated and indicated that the ionisation of MD was facilitated due to the Lewis acidity of the lithium cation and hydrogen bond formation between deprotonated MD (MD-1) and the OH groups of the BIMBOL moiety.",

author = "Yuri Samoilichenko and Veronica Kondratenko and Mariam Ezernitskaya and Konstantin Lyssenko and Alexander Peregudov and Victor Khrustalev and Victor Maleev and Margarita Moskalenko and Michael North and Alan Tsaloev and Gugkaeva, {Zalina T.} and Yuri Belokon",

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Samoilichenko, Y, Kondratenko, V, Ezernitskaya, M, Lyssenko, K, Peregudov, A, Khrustalev, V, Maleev, V, Moskalenko, M, North, M, Tsaloev, A, Gugkaeva, ZT & Belokon, Y 2017, 'A mechanistic study of the Lewis acid-Brønsted base-Brønsted acid catalysed asymmetric Michael addition of diethyl malonate to cyclohexenone', Catalysis Science and Technology, vol. 7, no. 1, pp. 90-101. https://doi.org/10.1039/c6cy01697a

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T1 - A mechanistic study of the Lewis acid-Brønsted base-Brønsted acid catalysed asymmetric Michael addition of diethyl malonate to cyclohexenone

AU - Samoilichenko, Yuri

AU - Kondratenko, Veronica

AU - Ezernitskaya, Mariam

AU - Lyssenko, Konstantin

AU - Peregudov, Alexander

AU - Khrustalev, Victor

AU - Maleev, Victor

AU - Moskalenko, Margarita

AU - North, Michael

AU - Tsaloev, Alan

AU - Gugkaeva, Zalina T.

AU - Belokon, Yuri

N1 - © The Royal Society of Chemistry 2017. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details

PY - 2017/1/7

Y1 - 2017/1/7

N2 - The Michael addition of diethyl malonate (Michael Donor, MD) to cyclohexenone (Michael Acceptor, MA) catalysed by the mono-lithium salt of (S)- or (R)-BIMBOL in dichloromethane is shown to exhibit biomimetic behavior. A combination of kinetics, spectroscopic studies, synthesis of catalyst analogues, inhibition studies and DFT calculations are used to show that the catalyst activates both components of the reaction and uses a chain of proton transfers to facilitate the deprotonation of diethyl malonate. The initial reaction rate was first order relative to both MA and MD and 0.5 order relative to the catalyst, indicating that an equilibrium exists between monomeric and dimeric forms of the catalyst, with the dimer predominating, but only the monomeric form being catalytically active. This was supported by DOSY 1H NMR experiments. The importance of the Lewis acidic lithium cation in the catalytic step was established by complete inhibition of the reaction by lithium complexing agents. The importance of the number of OH-groups and their relative intramolecular orientation and acidities in the polyol catalyst was shown by studying the relative catalytic activities of catalyst analogues. DFT calculations allowed the relative energies and structures of the likely intermediates on the reaction coordinate to be calculated and indicated that the ionisation of MD was facilitated due to the Lewis acidity of the lithium cation and hydrogen bond formation between deprotonated MD (MD-1) and the OH groups of the BIMBOL moiety.

AB - The Michael addition of diethyl malonate (Michael Donor, MD) to cyclohexenone (Michael Acceptor, MA) catalysed by the mono-lithium salt of (S)- or (R)-BIMBOL in dichloromethane is shown to exhibit biomimetic behavior. A combination of kinetics, spectroscopic studies, synthesis of catalyst analogues, inhibition studies and DFT calculations are used to show that the catalyst activates both components of the reaction and uses a chain of proton transfers to facilitate the deprotonation of diethyl malonate. The initial reaction rate was first order relative to both MA and MD and 0.5 order relative to the catalyst, indicating that an equilibrium exists between monomeric and dimeric forms of the catalyst, with the dimer predominating, but only the monomeric form being catalytically active. This was supported by DOSY 1H NMR experiments. The importance of the Lewis acidic lithium cation in the catalytic step was established by complete inhibition of the reaction by lithium complexing agents. The importance of the number of OH-groups and their relative intramolecular orientation and acidities in the polyol catalyst was shown by studying the relative catalytic activities of catalyst analogues. DFT calculations allowed the relative energies and structures of the likely intermediates on the reaction coordinate to be calculated and indicated that the ionisation of MD was facilitated due to the Lewis acidity of the lithium cation and hydrogen bond formation between deprotonated MD (MD-1) and the OH groups of the BIMBOL moiety.

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A mechanistic study of the Lewis acid-Brønsted base-Brønsted acid catalysed asymmetric Michael addition of diethyl malonate to cyclohexenone

Abstract

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