Isothiourea-catalyzed functionalization of pyrrolyl- and indolylacetic acid: enantioselective synthesis of dihydropyridinones and one-pot synthesis of pyridinones

Shuyue Zhang; Lucas Bacheley; Claire Mary Young; Daniel Graham Stark; Timothy O'Riordan; Alexandra Martha Zoya Slawin; Andrew David Smith

doi:10.1002/ajoc.202000290

Isothiourea-catalyzed functionalization of pyrrolyl- and indolylacetic acid: enantioselective synthesis of dihydropyridinones and one-pot synthesis of pyridinones

Shuyue Zhang, Lucas Bacheley, Claire Mary Young, Daniel Graham Stark, Timothy O'Riordan, Alexandra Martha Zoya Slawin, Andrew David Smith

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

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Abstract

A protocol for the isothiourea‐catalyzed enantioselective functionalization of pyrrolyl‐ and indolylacetic acids has been developed. Stereodefined dihydropyridinones are accessed through formal [4+2] cycloaddition of an in situ generated isothiouronium enolate with α,β‐unsaturated ketimines. The dihydropyridinones are obtained in moderate to excellent yield (26–97%), excellent diastereocontrol (all >95 : 5 dr) and moderate to excellent enantiocontrol (75 : 25–99 : 1 er). An unusual elimination of pyrrole or indole from the dihydropyridinone to access achiral pyridinones was observed and could be selectively promoted. A further one‐pot synthesis using an acyl imidazole was developed to give pyridinones in good to excellent yields (67–91%).

Original language	English
Pages (from-to)	1562-1566
Number of pages	5
Journal	Asian Journal of Organic Chemistry
Volume	9
Issue number	10
Early online date	10 Jul 2020
DOIs	https://doi.org/10.1002/ajoc.202000290
Publication status	Published - Oct 2020

Keywords

Heterocycle synthesis
Organocatalysis
Pyrrole elimination
Indole elimination
Isothiourea

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10.1002/ajoc.202000290Licence: CC BY

Zhang-2020-Isothioruea-catalyzed-AJOC-1562-CCBY
Copyright © 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Final published version, 4.02 MBLicence: CC BY

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
ERC Starting Grant EnolCat: Emulating nature: Reaction diversity and understanding through asymmetric catalysis
Smith, A. D. (PI)
European Commission
1/10/11 → 30/06/17
Project: Standard

Isothiourea-catalyzed functionalization of pyrrolyl- and indolylacetic acid: enantioselective synthesis of dihydropyridinones and one-pot synthesis of pyridinones (dataset)
Smith, A. D. (Creator), Young, C. M. (Creator) & Zhang, S. (Creator), University of St Andrews, 14 Jul 2020
DOI: 10.17630/1b8cace6-ad7c-4452-b3ab-35f5d42ad409
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title = "Isothiourea-catalyzed functionalization of pyrrolyl- and indolylacetic acid: enantioselective synthesis of dihydropyridinones and one-pot synthesis of pyridinones",

abstract = "A protocol for the isothiourea‐catalyzed enantioselective functionalization of pyrrolyl‐ and indolylacetic acids has been developed. Stereodefined dihydropyridinones are accessed through formal [4+2] cycloaddition of an in situ generated isothiouronium enolate with α,β‐unsaturated ketimines. The dihydropyridinones are obtained in moderate to excellent yield (26–97%), excellent diastereocontrol (all >95 : 5 dr) and moderate to excellent enantiocontrol (75 : 25–99 : 1 er). An unusual elimination of pyrrole or indole from the dihydropyridinone to access achiral pyridinones was observed and could be selectively promoted. A further one‐pot synthesis using an acyl imidazole was developed to give pyridinones in good to excellent yields (67–91%).",

keywords = "Heterocycle synthesis, Organocatalysis, Pyrrole elimination, Indole elimination, Isothiourea",

author = "Shuyue Zhang and Lucas Bacheley and Young, {Claire Mary} and Stark, {Daniel Graham} and Timothy O'Riordan and Slawin, {Alexandra Martha Zoya} and Smith, {Andrew David}",

note = "Funding: ERC under the European Union's Seventh Framework Programme (FP7/2007–2013) / ERC grant agreement no 279850. We thank Syngenta and EPSRC grant No. EP/K503162/1 (DGS), ADS thanks the Royal Society for a Wolfson Research Merit Award. ",

year = "2020",

month = oct,

doi = "10.1002/ajoc.202000290",

language = "English",

volume = "9",

pages = "1562--1566",

journal = "Asian Journal of Organic Chemistry",

issn = "2193-5815",

publisher = "Wiley-VCH, Weinheim",

number = "10",

}

Isothiourea-catalyzed functionalization of pyrrolyl- and indolylacetic acid: enantioselective synthesis of dihydropyridinones and one-pot synthesis of pyridinones. / Zhang, Shuyue; Bacheley, Lucas; Young, Claire Mary et al.
In: Asian Journal of Organic Chemistry, Vol. 9, No. 10, 10.2020, p. 1562-1566.

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

TY - JOUR

T1 - Isothiourea-catalyzed functionalization of pyrrolyl- and indolylacetic acid

T2 - enantioselective synthesis of dihydropyridinones and one-pot synthesis of pyridinones

AU - Zhang, Shuyue

AU - Bacheley, Lucas

AU - Young, Claire Mary

AU - Stark, Daniel Graham

AU - O'Riordan, Timothy

AU - Slawin, Alexandra Martha Zoya

AU - Smith, Andrew David

N1 - Funding: ERC under the European Union's Seventh Framework Programme (FP7/2007–2013) / ERC grant agreement no 279850. We thank Syngenta and EPSRC grant No. EP/K503162/1 (DGS), ADS thanks the Royal Society for a Wolfson Research Merit Award.

PY - 2020/10

Y1 - 2020/10

N2 - A protocol for the isothiourea‐catalyzed enantioselective functionalization of pyrrolyl‐ and indolylacetic acids has been developed. Stereodefined dihydropyridinones are accessed through formal [4+2] cycloaddition of an in situ generated isothiouronium enolate with α,β‐unsaturated ketimines. The dihydropyridinones are obtained in moderate to excellent yield (26–97%), excellent diastereocontrol (all >95 : 5 dr) and moderate to excellent enantiocontrol (75 : 25–99 : 1 er). An unusual elimination of pyrrole or indole from the dihydropyridinone to access achiral pyridinones was observed and could be selectively promoted. A further one‐pot synthesis using an acyl imidazole was developed to give pyridinones in good to excellent yields (67–91%).

AB - A protocol for the isothiourea‐catalyzed enantioselective functionalization of pyrrolyl‐ and indolylacetic acids has been developed. Stereodefined dihydropyridinones are accessed through formal [4+2] cycloaddition of an in situ generated isothiouronium enolate with α,β‐unsaturated ketimines. The dihydropyridinones are obtained in moderate to excellent yield (26–97%), excellent diastereocontrol (all >95 : 5 dr) and moderate to excellent enantiocontrol (75 : 25–99 : 1 er). An unusual elimination of pyrrole or indole from the dihydropyridinone to access achiral pyridinones was observed and could be selectively promoted. A further one‐pot synthesis using an acyl imidazole was developed to give pyridinones in good to excellent yields (67–91%).

KW - Heterocycle synthesis

KW - Organocatalysis

KW - Pyrrole elimination

KW - Indole elimination

KW - Isothiourea

U2 - 10.1002/ajoc.202000290

DO - 10.1002/ajoc.202000290

M3 - Article

SN - 2193-5815

VL - 9

SP - 1562

EP - 1566

JO - Asian Journal of Organic Chemistry

JF - Asian Journal of Organic Chemistry

IS - 10

ER -

Isothiourea-catalyzed functionalization of pyrrolyl- and indolylacetic acid: enantioselective synthesis of dihydropyridinones and one-pot synthesis of pyridinones

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Projects

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

ERC Starting Grant EnolCat: Emulating nature: Reaction diversity and understanding through asymmetric catalysis

Datasets

Isothiourea-catalyzed functionalization of pyrrolyl- and indolylacetic acid: enantioselective synthesis of dihydropyridinones and one-pot synthesis of pyridinones (dataset)

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