Evaluating polymer-supported isothiourea catalysis in industrially-preferable solvents for the acylative kinetic resolution of secondary and tertiary heterocyclic alcohols in batch and flow

Nitul Guha; Rifahath Mon Neyya Ppadath; Mark Greenhalgh; Ross Chisholm; Samuel Smith; Megan McEvoy; Carles Rodríguez-Escrich; Claire M. Young; Miquel A. Pericas; Georg Hähner; Andrew D. Smith

doi:10.1039/C8GC02020E

Evaluating polymer-supported isothiourea catalysis in industrially-preferable solvents for the acylative kinetic resolution of secondary and tertiary heterocyclic alcohols in batch and flow

Nitul Guha, Rifahath Mon Neyya Ppadath, Mark Greenhalgh, Ross Chisholm, Samuel Smith, Megan McEvoy, Carles Rodríguez-Escrich, Claire M. Young, Miquel A. Pericas, Georg Hähner, Andrew D. Smith

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28 Citations (Scopus)

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Abstract

Polymer-supported Lewis base catalysts, based on the homogeneous isothioureas HyperBTM and BTM, have been synthesised and applied for the acylative kinetic resolution of secondary and tertiary heterocyclic alcohols. In batch, the use of industrially-preferable solvents was investigated, with dimethyl carbonate proving to be most generally-applicable. Significantly, the HyperBTM-derived immobilised catalysts were readily recycled, with no loss in either activity or selectivity. In addition to the kinetic resolution of secondary benzylic, propargylic, allylic and cycloalkanol derivatives, a range of 21 tertiary heterocyclic alcohols, based on privileged 3-hydroxyoxindole and 3-hydroxypyrrolidinone substructures, were resolved with up to excellent selectivity (s = 7–190). Finally, the immobilised isothiourea catalysts were applied in a packed bed reactor to demonstrate the first example of the kinetic resolution of tertiary heterocyclic alcohols in a continuous flow process. High selectivities were obtained for the resolution of 3-hydroxyoxindole derivatives in ethyl acetate (s up to 70); and for 3-hydroxypyrrolidinones derivatives in toluene (s up to 42).

Original language	English
Journal	Green Chemistry
Volume	In press
Early online date	24 Aug 2018
DOIs	https://doi.org/10.1039/C8GC02020E
Publication status	E-pub ahead of print - 24 Aug 2018

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10.1039/C8GC02020E

Smith_2018_GC_EvaluatingPolyIsoth_AAM
© 2018 the Authors. This work has been made available online in accordance with the publisher’s policies. This is the author created accepted version manuscript following peer review and as such may differ slightly from the final published version. The final published version of this work is available at https://doi.org/ 10.1039/C8GC02020E
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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
CRITICAT CDT: Critical Resource Catalysis - CRITICAT
Smith, A. D. (PI), Nolan, S. P. (CoI) & Westwood, N. J. (CoI)
EPSRC
1/05/14 → 31/10/22
Project: Standard
Modification of silicon substrates: Modification of Silicon Oxide Substrates with Functional Ultrthin Organic Films
Haehner, G. (PI) & Smith, A. D. (CoI)
EPSRC
31/03/13 → 30/04/16
Project: Standard

Isothiourea-mediated acylative kinetic resolution of heterocyclic and acyclic tertiary alcohols (thesis data)
Smith, S. (Creator) & Smith, A. D. (Supervisor), University of St Andrews, 6 Nov 2023
DOI: 10.17630/e1e170df-9006-4348-bc1e-1c57a3c032be, http://hdl.handle.net/10023/16470
Dataset: Thesis dataset

File
data underpinning "Evaluating polymer-supported isothiourea catalysis in industrially-preferable solvents for the acylative kinetic resolution of secondary and tertiary heterocyclic alcohols in batch and flow"
Smith, A. D. (Creator), Greenhalgh, M. D. (Contributor), Guha, N. R. (Creator) & Neyya Ppadath, R. M. (Creator), University of St Andrews, 30 Aug 2018
DOI: 10.17630/131807b4-8473-434e-a77d-ee950ac25464
Dataset

File

Cite this

Guha, N., Neyya Ppadath, R. M., Greenhalgh, M., Chisholm, R., Smith, S., McEvoy, M., Rodríguez-Escrich, C., Young, C. M., Pericas, M. A., Hähner, G., & Smith, A. D. (2018). Evaluating polymer-supported isothiourea catalysis in industrially-preferable solvents for the acylative kinetic resolution of secondary and tertiary heterocyclic alcohols in batch and flow. Green Chemistry, In press. Advance online publication. https://doi.org/10.1039/C8GC02020E

@article{7d05db4f6b53459ba84991ad1f9da461,

title = "Evaluating polymer-supported isothiourea catalysis in industrially-preferable solvents for the acylative kinetic resolution of secondary and tertiary heterocyclic alcohols in batch and flow",

abstract = "Polymer-supported Lewis base catalysts, based on the homogeneous isothioureas HyperBTM and BTM, have been synthesised and applied for the acylative kinetic resolution of secondary and tertiary heterocyclic alcohols. In batch, the use of industrially-preferable solvents was investigated, with dimethyl carbonate proving to be most generally-applicable. Significantly, the HyperBTM-derived immobilised catalysts were readily recycled, with no loss in either activity or selectivity. In addition to the kinetic resolution of secondary benzylic, propargylic, allylic and cycloalkanol derivatives, a range of 21 tertiary heterocyclic alcohols, based on privileged 3-hydroxyoxindole and 3-hydroxypyrrolidinone substructures, were resolved with up to excellent selectivity (s = 7–190). Finally, the immobilised isothiourea catalysts were applied in a packed bed reactor to demonstrate the first example of the kinetic resolution of tertiary heterocyclic alcohols in a continuous flow process. High selectivities were obtained for the resolution of 3-hydroxyoxindole derivatives in ethyl acetate (s up to 70); and for 3-hydroxypyrrolidinones derivatives in toluene (s up to 42).",

author = "Nitul Guha and {Neyya Ppadath}, {Rifahath Mon} and Mark Greenhalgh and Ross Chisholm and Samuel Smith and Megan McEvoy and Carles Rodr{\'i}guez-Escrich and Young, {Claire M.} and Pericas, {Miquel A.} and Georg H{\"a}hner and Smith, {Andrew D.}",

note = "The authors thank the Royal Society and the Science and Engineering Board of India (SERB) for the award of a Royal Society-SERB Newton International Fellowship (N.R.G.). The authors also thank the EPSRC Centre for Doctoral Training in Critical Resource Catalysis (CRITICAT, grant code EP/L016419/1, R.M.N.P.) for funding. Financial support from the EPSRC (EP/K000411/1) is gratefully acknowledged (R.C.). The authors thank the European Research Council under the European Union's Seventh Framework Programme (FP7/2007-2013) ERC grant agreement no. 279850 (A.D.S). A.D.S. thanks the Royal Society for a Wolfson Research Merit Award. C.R.-E. and M.A.P. acknowledge the financial support from CERCA Programme/Generalitat de Catalunya, MINECO (CTQ2015-69136-R, AEI/MINECO/FEDER, UE and Severo Ochoa Excellence Accreditation 2014–2018, SEV-2013-0319) and DEC Generalitat de Catalunya (Grant 2014SGR827).",

year = "2018",

month = aug,

day = "24",

doi = "10.1039/C8GC02020E",

language = "English",

volume = "In press",

journal = "Green Chemistry",

issn = "1463-9262",

publisher = "Royal Society of Chemistry",

}

Guha, N, Neyya Ppadath, RM, Greenhalgh, M, Chisholm, R, Smith, S, McEvoy, M, Rodríguez-Escrich, C, Young, CM, Pericas, MA, Hähner, G & Smith, AD 2018, 'Evaluating polymer-supported isothiourea catalysis in industrially-preferable solvents for the acylative kinetic resolution of secondary and tertiary heterocyclic alcohols in batch and flow', Green Chemistry, vol. In press. https://doi.org/10.1039/C8GC02020E

Evaluating polymer-supported isothiourea catalysis in industrially-preferable solvents for the acylative kinetic resolution of secondary and tertiary heterocyclic alcohols in batch and flow. / Guha, Nitul; Neyya Ppadath, Rifahath Mon; Greenhalgh, Mark et al.
In: Green Chemistry, Vol. In press, 24.08.2018.

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

TY - JOUR

T1 - Evaluating polymer-supported isothiourea catalysis in industrially-preferable solvents for the acylative kinetic resolution of secondary and tertiary heterocyclic alcohols in batch and flow

AU - Guha, Nitul

AU - Neyya Ppadath, Rifahath Mon

AU - Greenhalgh, Mark

AU - Chisholm, Ross

AU - Smith, Samuel

AU - McEvoy, Megan

AU - Rodríguez-Escrich, Carles

AU - Young, Claire M.

AU - Pericas, Miquel A.

AU - Hähner, Georg

AU - Smith, Andrew D.

N1 - The authors thank the Royal Society and the Science and Engineering Board of India (SERB) for the award of a Royal Society-SERB Newton International Fellowship (N.R.G.). The authors also thank the EPSRC Centre for Doctoral Training in Critical Resource Catalysis (CRITICAT, grant code EP/L016419/1, R.M.N.P.) for funding. Financial support from the EPSRC (EP/K000411/1) is gratefully acknowledged (R.C.). The authors thank the European Research Council under the European Union's Seventh Framework Programme (FP7/2007-2013) ERC grant agreement no. 279850 (A.D.S). A.D.S. thanks the Royal Society for a Wolfson Research Merit Award. C.R.-E. and M.A.P. acknowledge the financial support from CERCA Programme/Generalitat de Catalunya, MINECO (CTQ2015-69136-R, AEI/MINECO/FEDER, UE and Severo Ochoa Excellence Accreditation 2014–2018, SEV-2013-0319) and DEC Generalitat de Catalunya (Grant 2014SGR827).

PY - 2018/8/24

Y1 - 2018/8/24

N2 - Polymer-supported Lewis base catalysts, based on the homogeneous isothioureas HyperBTM and BTM, have been synthesised and applied for the acylative kinetic resolution of secondary and tertiary heterocyclic alcohols. In batch, the use of industrially-preferable solvents was investigated, with dimethyl carbonate proving to be most generally-applicable. Significantly, the HyperBTM-derived immobilised catalysts were readily recycled, with no loss in either activity or selectivity. In addition to the kinetic resolution of secondary benzylic, propargylic, allylic and cycloalkanol derivatives, a range of 21 tertiary heterocyclic alcohols, based on privileged 3-hydroxyoxindole and 3-hydroxypyrrolidinone substructures, were resolved with up to excellent selectivity (s = 7–190). Finally, the immobilised isothiourea catalysts were applied in a packed bed reactor to demonstrate the first example of the kinetic resolution of tertiary heterocyclic alcohols in a continuous flow process. High selectivities were obtained for the resolution of 3-hydroxyoxindole derivatives in ethyl acetate (s up to 70); and for 3-hydroxypyrrolidinones derivatives in toluene (s up to 42).

AB - Polymer-supported Lewis base catalysts, based on the homogeneous isothioureas HyperBTM and BTM, have been synthesised and applied for the acylative kinetic resolution of secondary and tertiary heterocyclic alcohols. In batch, the use of industrially-preferable solvents was investigated, with dimethyl carbonate proving to be most generally-applicable. Significantly, the HyperBTM-derived immobilised catalysts were readily recycled, with no loss in either activity or selectivity. In addition to the kinetic resolution of secondary benzylic, propargylic, allylic and cycloalkanol derivatives, a range of 21 tertiary heterocyclic alcohols, based on privileged 3-hydroxyoxindole and 3-hydroxypyrrolidinone substructures, were resolved with up to excellent selectivity (s = 7–190). Finally, the immobilised isothiourea catalysts were applied in a packed bed reactor to demonstrate the first example of the kinetic resolution of tertiary heterocyclic alcohols in a continuous flow process. High selectivities were obtained for the resolution of 3-hydroxyoxindole derivatives in ethyl acetate (s up to 70); and for 3-hydroxypyrrolidinones derivatives in toluene (s up to 42).

U2 - 10.1039/C8GC02020E

DO - 10.1039/C8GC02020E

M3 - Article

SN - 1463-9262

VL - In press

JO - Green Chemistry

JF - Green Chemistry

ER -

Evaluating polymer-supported isothiourea catalysis in industrially-preferable solvents for the acylative kinetic resolution of secondary and tertiary heterocyclic alcohols in batch and flow

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Projects

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

CRITICAT CDT: Critical Resource Catalysis - CRITICAT

Modification of silicon substrates: Modification of Silicon Oxide Substrates with Functional Ultrthin Organic Films

Datasets

Isothiourea-mediated acylative kinetic resolution of heterocyclic and acyclic tertiary alcohols (thesis data)

data underpinning "Evaluating polymer-supported isothiourea catalysis in industrially-preferable solvents for the acylative kinetic resolution of secondary and tertiary heterocyclic alcohols in batch and flow"

Cite this