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

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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Zhang-2020-Isothioruea-catalyzed-AJOC-1562-CCBY
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Cite this

@article{a113b3cf7b5847789a72cfe240fcf546,

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

UR - https://www.scopus.com/pages/publications/85087709766

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

Abstract

Keywords

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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