Isothiourea-catalyzed enantioselective Michael addition of malonates to α,β-unsaturated aryl esters

Jiufeng Wu; Claire Mary Young; Amy A. Watts; Alexandra Martha Zoya Slawin; Greg Boyce; Michael Buehl; Andrew David Smith

doi:10.1021/acs.orglett.2c01486

Isothiourea-catalyzed enantioselective Michael addition of malonates to α,β-unsaturated aryl esters

Jiufeng Wu, Claire Mary Young, Amy A. Watts, Alexandra Martha Zoya Slawin, Greg Boyce^*, Michael Buehl^*, Andrew David Smith^*

^*Corresponding author for this work

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

Abstract

An enantioselective Michael addition of malonates to α,β-unsaturated para-nitrophenyl esters was achieved using the Lewis basic isothiourea HyperBTM, giving excellent levels of product enantioselectivity (up to >99:1 enantiomeric ratio) in good yields and with complete regioselectivity (>20:1 regioselectivity ratio) in the presence of alternative (phenyl ketone and ethyl ester) Michael acceptors. Density functional theory calculations indicate that N-acylation is rate-limiting. This constitutes a rare example of a highly enantioselective addition of simple, readily available malonates to α,β-unsaturated esters.

Original language	English
Pages (from-to)	4040-4045
Number of pages	6
Journal	Organic Letters
Volume	24
Issue number	22
Early online date	2 Jun 2022
DOIs	https://doi.org/10.1021/acs.orglett.2c01486
Publication status	Published - 10 Jun 2022

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data underpinning "Isothiourea-catalyzed enantioselective Michael addition of ma-lonates to α,β-unsaturated aryl esters"
Smith, A. D. (Creator), Young, C. M. (Creator), Boyce, G. (Creator) & Buehl, M. (Creator), University of St Andrews, May 2022
DOI: 10.17630/807cc4de-3e6c-43d6-a091-54f073849543
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title = "Isothiourea-catalyzed enantioselective Michael addition of malonates to α,β-unsaturated aryl esters",

abstract = "An enantioselective Michael addition of malonates to α,β-unsaturated para-nitrophenyl esters was achieved using the Lewis basic isothiourea HyperBTM, giving excellent levels of product enantioselectivity (up to >99:1 enantiomeric ratio) in good yields and with complete regioselectivity (>20:1 regioselectivity ratio) in the presence of alternative (phenyl ketone and ethyl ester) Michael acceptors. Density functional theory calculations indicate that N-acylation is rate-limiting. This constitutes a rare example of a highly enantioselective addition of simple, readily available malonates to α,β-unsaturated esters.",

author = "Jiufeng Wu and Young, {Claire Mary} and Watts, {Amy A.} and Slawin, {Alexandra Martha Zoya} and Greg Boyce and Michael Buehl and Smith, {Andrew David}",

note = "MB thanks EaStCHEM and the School of Chemistry for support.",

year = "2022",

month = jun,

day = "10",

doi = "10.1021/acs.orglett.2c01486",

language = "English",

volume = "24",

pages = "4040--4045",

journal = "Organic Letters",

issn = "1523-7060",

publisher = "American Chemical Society (ACS)",

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TY - JOUR

T1 - Isothiourea-catalyzed enantioselective Michael addition of malonates to α,β-unsaturated aryl esters

AU - Wu, Jiufeng

AU - Young, Claire Mary

AU - Watts, Amy A.

AU - Slawin, Alexandra Martha Zoya

AU - Boyce, Greg

AU - Buehl, Michael

AU - Smith, Andrew David

N1 - MB thanks EaStCHEM and the School of Chemistry for support.

PY - 2022/6/10

Y1 - 2022/6/10

N2 - An enantioselective Michael addition of malonates to α,β-unsaturated para-nitrophenyl esters was achieved using the Lewis basic isothiourea HyperBTM, giving excellent levels of product enantioselectivity (up to >99:1 enantiomeric ratio) in good yields and with complete regioselectivity (>20:1 regioselectivity ratio) in the presence of alternative (phenyl ketone and ethyl ester) Michael acceptors. Density functional theory calculations indicate that N-acylation is rate-limiting. This constitutes a rare example of a highly enantioselective addition of simple, readily available malonates to α,β-unsaturated esters.

AB - An enantioselective Michael addition of malonates to α,β-unsaturated para-nitrophenyl esters was achieved using the Lewis basic isothiourea HyperBTM, giving excellent levels of product enantioselectivity (up to >99:1 enantiomeric ratio) in good yields and with complete regioselectivity (>20:1 regioselectivity ratio) in the presence of alternative (phenyl ketone and ethyl ester) Michael acceptors. Density functional theory calculations indicate that N-acylation is rate-limiting. This constitutes a rare example of a highly enantioselective addition of simple, readily available malonates to α,β-unsaturated esters.

U2 - 10.1021/acs.orglett.2c01486

DO - 10.1021/acs.orglett.2c01486

M3 - Article

SN - 1523-7060

VL - 24

SP - 4040

EP - 4045

JO - Organic Letters

JF - Organic Letters

IS - 22

ER -

Isothiourea-catalyzed enantioselective Michael addition of malonates to α,β-unsaturated aryl esters

Abstract

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data underpinning "Isothiourea-catalyzed enantioselective Michael addition of ma-lonates to α,β-unsaturated aryl esters"

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