The importance of 1,5-oxygen···chalcogen interactions in enantioselective isochalcogenourea catalysis

Claire Mary Young; Alex Elmi; Dominic J. Pascoe; Rylie K. Morris; Calum McLaughlin; Andrew Woods; Aileen Frost; Alix De La Houpliere; Kenneth B. Ling; Terry K Smith; Alexandra Martha Zoya Slawin; Patrick H. Willoughby; Scott L. Cockroft; Andrew David Smith

doi:10.1002/anie.201914421

The importance of 1,5-oxygen···chalcogen interactions in enantioselective isochalcogenourea catalysis

Claire Mary Young, Alex Elmi, Dominic J. Pascoe, Rylie K. Morris, Calum McLaughlin, Andrew Woods, Aileen Frost, Alix De La Houpliere, Kenneth B. Ling, Terry K Smith, Alexandra Martha Zoya Slawin, Patrick H. Willoughby, Scott L. Cockroft, Andrew David Smith

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

Abstract

The importance of 1,5-O···chalcogen (Ch) interactions in isochalcogenourea catalysis (Ch = O, S, Se) is investigated. Conformational analyses of N-acyl isochalcogenouronium species and comparison with kinetic data demonstrate the significance of 1,5-O···Ch interactions in enantioselective catalysis. Importantly, the selenium analogue demonstrates enhanced rate and selectivity profiles across a range of reaction processes including nitronate conjugate addition and formal [4+2] cycloadditions. A gram-scale synthesis of the most active selenium analogue was developed using a previously unreported seleno-Hugerschoff reaction, allowing the challenging kinetic resolutions of tertiary alcohols to be performed at 500 ppm catalyst loading. Density Functional Theory (DFT) and natural bond orbital (NBO) calculations support the role of orbital delocalization (occurring by intramolecular chalcogen bonding) in determining the conformation, equilibrium population, and reactivity of N-acylated intermediates.

Original language	English
Pages (from-to)	3705-3710
Journal	Angewandte Chemie International Edition
Volume	59
Issue number	9
Early online date	3 Feb 2020
DOIs	https://doi.org/10.1002/anie.201914421
Publication status	Published - 17 Feb 2020

Keywords

Organocatalysis
Chalcogen bonding
Isothioureas
Isoselenoureas
1,5-O···Ch
Asymmetric catalysis

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10.1002/anie.201914421

Young_2019_ACIE_1,5oxygen_AAM
Copyright © 2019 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim. This work has been made available online in accordance with publisher policies or with permission. Permission for further reuse of this content should be sought from the publisher or the rights holder. This is the author created accepted manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at https://doi.org/10.1002/anie.201914421
Accepted author manuscript, 1.26 MB

Andrew David Smith
- ads10st-andrews.acuk
- School of Chemistry - Professor, Director of Research
- Biomedical Sciences Research Complex
- EaSTCHEM
Person: Academic

Data underpinning "The Importance of 1,5-Oxygen---Chalcogen Interactions in Enantioselective Isochalcogenourea Catalysis"
Smith, A. D. (Creator), Young, C. M. (Owner) & Slawin, A. M. Z. (Owner), University of St Andrews, 5 Feb 2020
DOI: 10.17630/2a46952f-ed2c-4145-9dcd-ad1d2634e0a2
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Young, C. M., Elmi, A., Pascoe, D. J., Morris, R. K., McLaughlin, C., Woods, A., Frost, A., De La Houpliere, A., Ling, K. B., Smith, T. K., Slawin, A. M. Z., Willoughby, P. H., Cockroft, S. L., & Smith, A. D. (2020). The importance of 1,5-oxygen···chalcogen interactions in enantioselective isochalcogenourea catalysis. Angewandte Chemie International Edition, 59(9), 3705-3710. https://doi.org/10.1002/anie.201914421

@article{c415814af29e4891ae49ee57521f3775,

title = "The importance of 1,5-oxygen···chalcogen interactions in enantioselective isochalcogenourea catalysis",

abstract = "The importance of 1,5-O···chalcogen (Ch) interactions in isochalcogenourea catalysis (Ch = O, S, Se) is investigated. Conformational analyses of N-acyl isochalcogenouronium species and comparison with kinetic data demonstrate the significance of 1,5-O···Ch interactions in enantioselective catalysis. Importantly, the selenium analogue demonstrates enhanced rate and selectivity profiles across a range of reaction processes including nitronate conjugate addition and formal [4+2] cycloadditions. A gram-scale synthesis of the most active selenium analogue was developed using a previously unreported seleno-Hugerschoff reaction, allowing the challenging kinetic resolutions of tertiary alcohols to be performed at 500 ppm catalyst loading. Density Functional Theory (DFT) and natural bond orbital (NBO) calculations support the role of orbital delocalization (occurring by intramolecular chalcogen bonding) in determining the conformation, equilibrium population, and reactivity of N-acylated intermediates.",

keywords = "Organocatalysis, Chalcogen bonding, Isothioureas, Isoselenoureas, 1,5-O···Ch, Asymmetric catalysis",

author = "Young, {Claire Mary} and Alex Elmi and Pascoe, {Dominic J.} and Morris, {Rylie K.} and Calum McLaughlin and Andrew Woods and Aileen Frost and {De La Houpliere}, Alix and Ling, {Kenneth B.} and Smith, {Terry K} and Slawin, {Alexandra Martha Zoya} and Willoughby, {Patrick H.} and Cockroft, {Scott L.} and Smith, {Andrew David}",

note = "Syngenta (Case Award to DJP) and a Philip Leverhulme Prize for funding (SLC, AE). RKM and PHW are grateful to the American Chemical Society Petroleum Research Fund and National Science Foundation (NSF-MRI: CHE-1429616).",

year = "2020",

month = feb,

day = "17",

doi = "10.1002/anie.201914421",

language = "English",

volume = "59",

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Young, CM, Elmi, A, Pascoe, DJ, Morris, RK, McLaughlin, C, Woods, A, Frost, A, De La Houpliere, A, Ling, KB, Smith, TK , Slawin, AMZ, Willoughby, PH, Cockroft, SL & Smith, AD 2020, 'The importance of 1,5-oxygen···chalcogen interactions in enantioselective isochalcogenourea catalysis', Angewandte Chemie International Edition, vol. 59, no. 9, pp. 3705-3710. https://doi.org/10.1002/anie.201914421

TY - JOUR

T1 - The importance of 1,5-oxygen···chalcogen interactions in enantioselective isochalcogenourea catalysis

AU - Young, Claire Mary

AU - Elmi, Alex

AU - Pascoe, Dominic J.

AU - Morris, Rylie K.

AU - McLaughlin, Calum

AU - Woods, Andrew

AU - Frost, Aileen

AU - De La Houpliere, Alix

AU - Ling, Kenneth B.

AU - Smith, Terry K

AU - Slawin, Alexandra Martha Zoya

AU - Willoughby, Patrick H.

AU - Cockroft, Scott L.

AU - Smith, Andrew David

N1 - Syngenta (Case Award to DJP) and a Philip Leverhulme Prize for funding (SLC, AE). RKM and PHW are grateful to the American Chemical Society Petroleum Research Fund and National Science Foundation (NSF-MRI: CHE-1429616).

PY - 2020/2/17

Y1 - 2020/2/17

N2 - The importance of 1,5-O···chalcogen (Ch) interactions in isochalcogenourea catalysis (Ch = O, S, Se) is investigated. Conformational analyses of N-acyl isochalcogenouronium species and comparison with kinetic data demonstrate the significance of 1,5-O···Ch interactions in enantioselective catalysis. Importantly, the selenium analogue demonstrates enhanced rate and selectivity profiles across a range of reaction processes including nitronate conjugate addition and formal [4+2] cycloadditions. A gram-scale synthesis of the most active selenium analogue was developed using a previously unreported seleno-Hugerschoff reaction, allowing the challenging kinetic resolutions of tertiary alcohols to be performed at 500 ppm catalyst loading. Density Functional Theory (DFT) and natural bond orbital (NBO) calculations support the role of orbital delocalization (occurring by intramolecular chalcogen bonding) in determining the conformation, equilibrium population, and reactivity of N-acylated intermediates.

AB - The importance of 1,5-O···chalcogen (Ch) interactions in isochalcogenourea catalysis (Ch = O, S, Se) is investigated. Conformational analyses of N-acyl isochalcogenouronium species and comparison with kinetic data demonstrate the significance of 1,5-O···Ch interactions in enantioselective catalysis. Importantly, the selenium analogue demonstrates enhanced rate and selectivity profiles across a range of reaction processes including nitronate conjugate addition and formal [4+2] cycloadditions. A gram-scale synthesis of the most active selenium analogue was developed using a previously unreported seleno-Hugerschoff reaction, allowing the challenging kinetic resolutions of tertiary alcohols to be performed at 500 ppm catalyst loading. Density Functional Theory (DFT) and natural bond orbital (NBO) calculations support the role of orbital delocalization (occurring by intramolecular chalcogen bonding) in determining the conformation, equilibrium population, and reactivity of N-acylated intermediates.

KW - Organocatalysis

KW - Chalcogen bonding

KW - Isothioureas

KW - Isoselenoureas

KW - 1,5-O···Ch

KW - Asymmetric catalysis

U2 - 10.1002/anie.201914421

DO - 10.1002/anie.201914421

M3 - Article

SN - 1433-7851

VL - 59

SP - 3705

EP - 3710

JO - Angewandte Chemie International Edition

JF - Angewandte Chemie International Edition

IS - 9

ER -

The importance of 1,5-oxygen···chalcogen interactions in enantioselective isochalcogenourea catalysis

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Data underpinning "The Importance of 1,5-Oxygen---Chalcogen Interactions in Enantioselective Isochalcogenourea Catalysis"

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