Isothiourea-catalysed enantioselective Michael addition of N-heterocyclic pronucleophiles to α,β-unsaturated aryl esters

Chang Shu; Honglei Liu; Alexandra Slawin; Cameron L. Carpenter-Warren; Andrew David Smith

doi:10.1039/C9SC04303A

Isothiourea-catalysed enantioselective Michael addition of N-heterocyclic pronucleophiles to α,β-unsaturated aryl esters

Chang Shu, Honglei Liu, Alexandra Slawin, Cameron L. Carpenter-Warren, Andrew David Smith

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

Abstract

The isothiourea-catalysed enantioselective Michael addition of 3-aryloxindole and 4-substituted-dihydropyrazol-3-one pronucleophiles to α,β-unsaturated p-nitrophenyl esters is reported. This process generates products containing two contiguous stereocentres, one quaternary, in good yields and excellent enantioselectivities (>30 examples, up to > 95 : 5 dr and 99 : 1 er). This protocol harnesses the multifunctional ability of p-nitrophenoxide to promote effective catalysis. In contrast to previous methodologies using tertiary amine Lewis bases, in which the pronucleophile was used as the solvent, this work allows bespoke pronucleophiles to be used in stoichiometric quantities.

Original language	English
Number of pages	7
Journal	Chemical Science
Volume	Advance Article
Early online date	23 Oct 2019
DOIs	https://doi.org/10.1039/C9SC04303A
Publication status	E-pub ahead of print - 23 Oct 2019

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10.1039/C9SC04303ALicence: CC BY

Shu_2019_CS_Michael_CC
Copyright © 2019 The Author(s). Open Access Article. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.
Final published version, 1.11 MBLicence: CC BY

Honglei Liu - Newton Fellowship: Dynamic Kinetic Resolution/Desynnetrisation of Atropisomeric Biaryl Diols Using Isothioureas
Smith, A. D. (PI)
The Royal Society
1/02/18 → 31/01/20
Project: Fellowship
RS Wolfson Merit Award: Developing Catalysis Research: New Reaction Discoveries and Practical Applications
Smith, A. D. (PI)
The Royal Society
1/01/15 → 31/12/19
Project: Fellowship

Data underpinning "Isothiourea-catalysed enantioselective Michael addition of N-heterocyclic pronucleophiles to α,β-unsaturated aryl esters"
Smith, A. D. (Creator) & Liu, H. (Owner), University of St Andrews, 2019
DOI: 10.17630/aa042eff-5b55-4096-991f-e92cf4f51375
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title = "Isothiourea-catalysed enantioselective Michael addition of N-heterocyclic pronucleophiles to α,β-unsaturated aryl esters",

abstract = "The isothiourea-catalysed enantioselective Michael addition of 3-aryloxindole and 4-substituted-dihydropyrazol-3-one pronucleophiles to α,β-unsaturated p-nitrophenyl esters is reported. This process generates products containing two contiguous stereocentres, one quaternary, in good yields and excellent enantioselectivities (>30 examples, up to > 95 : 5 dr and 99 : 1 er). This protocol harnesses the multifunctional ability of p-nitrophenoxide to promote effective catalysis. In contrast to previous methodologies using tertiary amine Lewis bases, in which the pronucleophile was used as the solvent, this work allows bespoke pronucleophiles to be used in stoichiometric quantities.",

author = "Chang Shu and Honglei Liu and Alexandra Slawin and Carpenter-Warren, {Cameron L.} and Smith, {Andrew David}",

note = "The research leading to these results (C. S., H. L.) has received funding from the Royal Society Newton Fellowship Programme. A.D.S. thanks the Royal Society for a Wolfson Research Merit Award. ",

year = "2019",

month = oct,

day = "23",

doi = "10.1039/C9SC04303A",

language = "English",

volume = "Advance Article",

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TY - JOUR

T1 - Isothiourea-catalysed enantioselective Michael addition of N-heterocyclic pronucleophiles to α,β-unsaturated aryl esters

AU - Shu, Chang

AU - Liu, Honglei

AU - Slawin, Alexandra

AU - Carpenter-Warren, Cameron L.

AU - Smith, Andrew David

N1 - The research leading to these results (C. S., H. L.) has received funding from the Royal Society Newton Fellowship Programme. A.D.S. thanks the Royal Society for a Wolfson Research Merit Award.

PY - 2019/10/23

Y1 - 2019/10/23

N2 - The isothiourea-catalysed enantioselective Michael addition of 3-aryloxindole and 4-substituted-dihydropyrazol-3-one pronucleophiles to α,β-unsaturated p-nitrophenyl esters is reported. This process generates products containing two contiguous stereocentres, one quaternary, in good yields and excellent enantioselectivities (>30 examples, up to > 95 : 5 dr and 99 : 1 er). This protocol harnesses the multifunctional ability of p-nitrophenoxide to promote effective catalysis. In contrast to previous methodologies using tertiary amine Lewis bases, in which the pronucleophile was used as the solvent, this work allows bespoke pronucleophiles to be used in stoichiometric quantities.

AB - The isothiourea-catalysed enantioselective Michael addition of 3-aryloxindole and 4-substituted-dihydropyrazol-3-one pronucleophiles to α,β-unsaturated p-nitrophenyl esters is reported. This process generates products containing two contiguous stereocentres, one quaternary, in good yields and excellent enantioselectivities (>30 examples, up to > 95 : 5 dr and 99 : 1 er). This protocol harnesses the multifunctional ability of p-nitrophenoxide to promote effective catalysis. In contrast to previous methodologies using tertiary amine Lewis bases, in which the pronucleophile was used as the solvent, this work allows bespoke pronucleophiles to be used in stoichiometric quantities.

U2 - 10.1039/C9SC04303A

DO - 10.1039/C9SC04303A

M3 - Article

SN - 2041-6520

VL - Advance Article

JO - Chemical Science

JF - Chemical Science

ER -

Isothiourea-catalysed enantioselective Michael addition of N-heterocyclic pronucleophiles to α,β-unsaturated aryl esters

Abstract

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Projects

Honglei Liu - Newton Fellowship: Dynamic Kinetic Resolution/Desynnetrisation of Atropisomeric Biaryl Diols Using Isothioureas

RS Wolfson Merit Award: Developing Catalysis Research: New Reaction Discoveries and Practical Applications

Datasets

Data underpinning "Isothiourea-catalysed enantioselective Michael addition of N-heterocyclic pronucleophiles to α,β-unsaturated aryl esters"

Cite this