Catalytic enantioselective synthesis of perfluoroalkyl-substituted β-lactones via a concerted asynchronous [2+2] cycloaddition: a synthetic and computational study

Diego-Javier Barrios Antunez; Mark D. Greenhalgh; Alexander C. Brueckner; Daniel M. Walden; Pilar Elías-Rodríguez; Patrick Roberts; Benjamin G. Young; Thomas H. West; Alexandra M. Z. Slawin; Paul Ha-Yeon Cheong; Andrew D. Smith

doi:10.1039/C9SC00390H

Catalytic enantioselective synthesis of perfluoroalkyl-substituted β-lactones via a concerted asynchronous [2+2] cycloaddition: a synthetic and computational study

Diego-Javier Barrios Antunez
, Mark D. Greenhalgh
, Alexander C. Brueckner
, Daniel M. Walden
, Pilar Elías-Rodríguez
, Patrick Roberts
, Benjamin G. Young
, Thomas H. West
, Alexandra M. Z. Slawin
, Paul Ha-Yeon Cheong
, Andrew D. Smith

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

Abstract

The enantioselective preparation of a range of perfluoroalkyl-substituted β-lactones through an isothiourea (HyperBTM) catalysed reaction using symmetric anhydrides as ammonium enolate precursors and perfluoroalkylketones (R_F = CF₃, C₂F₅, C₄F₉) is reported. Following optimisation, high diastereo- and enantioselectivty was observed for β-lactone formation using C₂F₅- and C₄F₉-substituted ketones at room temperature (26 examples, up to > 95:5 dr and > 99:1 er), whilst −78 ˚C was necessary for optimal dr and er with CF3-substituted ketones (11 examples, up to > 95:5 dr and > 99:1 er). Derivatisation of the β-lactones through ring-opening, as well as a two-step conversion to give perfluoroalkyl-substituted oxetanes, is demonstrated without loss of stereochemical integrity. Density functional theory computations, alongside ¹³C natural abundance KIE studies, have been used to probe the reaction mechanism with a concerted asynchronous [2 + 2]-cycloaddition pathway favoured over a stepwise aldol-lactonisation process.

Original language	English
Pages (from-to)	6162-6173
Number of pages	12
Journal	Chemical Science
Volume	10
Issue number	24
Early online date	29 Apr 2019
DOIs	https://doi.org/10.1039/C9SC00390H
Publication status	Published - 28 Jun 2019

Access to Document

10.1039/C9SC00390HLicence: CC BY

BarriosAntunez_2019_CS_Catalytic_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, 2.89 MBLicence: CC BY

Handle.net

Persistent link to portal record

RS Wolfson Merit Award: Developing Catalysis Research: New Reaction Discoveries and Practical Applications
Smith, A. (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. (PI)
Joint Research Centre European Commission
1/10/11 → 30/06/17
Project: Standard

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

Data underpinning "Catalytic enantioselective synthesis of perfluoroalkyl-substituted β-lactones via a concerted asynchronous [2+2] cycloaddition"
Smith, A. D. (Creator) & Greenhalgh, M. D. (Creator), University of St Andrews, 14 Jun 2013
DOI: 10.17630/07f4bb41-b486-4be0-87de-517ae9eb8d4d
Dataset

File
Catalytic enantioselective synthesis of perfluoroalkyl-substituted β-lactones via a concerted asynchronous [2+2] cycloaddition: a synthetic and computational study (crystallography data)
Barrios Antunez, D. J. (Creator), Greenhalgh, M. D. (Creator), Brueckner, A. C. (Creator), Walden, D. M. (Creator), Elías-Rodríguez, P. (Creator), Roberts, P. (Creator), Young, B. G. (Creator), West, T. H. (Creator), Slawin, A. M. Z. (Creator), Cheong, P.H.-Y. (Creator) & Smith, A. D. (Creator), Cambridge Crystallographic Data Centre, 30 Aug 2019
https://dx.doi.org/10.5517/ccdc.csd.cc219p9c and 2 more links, http://dx.doi.org/10.5517/ccdc.csd.cc219pbd, http://dx.doi.org/10.5517/ccdc.csd.cc219pcf (show fewer)
Dataset

Cite this

Barrios Antunez, D.-J., Greenhalgh, M. D., Brueckner, A. C., Walden, D. M., Elías-Rodríguez, P., Roberts, P., Young, B. G., West, T. H., Slawin, A. M. Z., Cheong, P. H.-Y., & Smith, A. D. (2019). Catalytic enantioselective synthesis of perfluoroalkyl-substituted β-lactones via a concerted asynchronous [2+2] cycloaddition: a synthetic and computational study. Chemical Science, 10(24), 6162-6173. https://doi.org/10.1039/C9SC00390H

@article{5b5a8da5cade4ce18a40644f1b92fe6e,

title = "Catalytic enantioselective synthesis of perfluoroalkyl-substituted β-lactones via a concerted asynchronous [2+2] cycloaddition: a synthetic and computational study",

abstract = "The enantioselective preparation of a range of perfluoroalkyl-substituted β-lactones through an isothiourea (HyperBTM) catalysed reaction using symmetric anhydrides as ammonium enolate precursors and perfluoroalkylketones (RF = CF3, C2F5, C4F9) is reported. Following optimisation, high diastereo- and enantioselectivty was observed for β-lactone formation using C2F5- and C4F9-substituted ketones at room temperature (26 examples, up to > 95:5 dr and > 99:1 er), whilst −78 ˚C was necessary for optimal dr and er with CF3-substituted ketones (11 examples, up to > 95:5 dr and > 99:1 er). Derivatisation of the β-lactones through ring-opening, as well as a two-step conversion to give perfluoroalkyl-substituted oxetanes, is demonstrated without loss of stereochemical integrity. Density functional theory computations, alongside 13C natural abundance KIE studies, have been used to probe the reaction mechanism with a concerted asynchronous [2 + 2]-cycloaddition pathway favoured over a stepwise aldol-lactonisation process.",

author = "\{Barrios Antunez\}, Diego-Javier and Greenhalgh, \{Mark D.\} and Brueckner, \{Alexander C.\} and Walden, \{Daniel M.\} and Pilar El{\'i}as-Rodr{\'i}guez and Patrick Roberts and Young, \{Benjamin G.\} and West, \{Thomas H.\} and Slawin, \{Alexandra M. Z.\} and Cheong, \{Paul Ha-Yeon\} and Smith, \{Andrew D.\}",

note = "The research leading to these results (D.-J.B.A., T.H.W., A.D.S.) has received funding from the ERC under the European Union{\textquoteright}s Seventh Framework Programme (FP7/2007-2013)/E.R.C. Grant Agreement No. 279850. A.D.S. thanks the Royal Society for a Wolfson Research Merit Award. We also thank the EPSRC UK National Mass Spectrometry Facility at Swansea University. P.H.Y.C. is the Bert and Emelyn Christensen professor of OSU, and gratefully acknowledges financial support from the Vicki \& Patrick F. Stone family. P.H.Y.C., A.C.B., D.M.W. and B.G.Y. gratefully acknowledge support from the National Science Foundation (NSF CHE-1352663) and the computing infrastructure in part provided by the NSF Phase-2 CCI, Center for Sustainable Materials Chemistry (NSF CHE-1102637).",

year = "2019",

month = jun,

day = "28",

doi = "10.1039/C9SC00390H",

language = "English",

volume = "10",

pages = "6162--6173",

journal = "Chemical Science",

issn = "2041-6520",

publisher = "Royal Society of Chemistry",

number = "24",

}

Barrios Antunez, D-J, Greenhalgh, MD, Brueckner, AC, Walden, DM, Elías-Rodríguez, P, Roberts, P, Young, BG, West, TH, Slawin, AMZ, Cheong, PH-Y & Smith, AD 2019, 'Catalytic enantioselective synthesis of perfluoroalkyl-substituted β-lactones via a concerted asynchronous [2+2] cycloaddition: a synthetic and computational study', Chemical Science, vol. 10, no. 24, pp. 6162-6173. https://doi.org/10.1039/C9SC00390H

Catalytic enantioselective synthesis of perfluoroalkyl-substituted β-lactones via a concerted asynchronous [2+2] cycloaddition: a synthetic and computational study. / Barrios Antunez, Diego-Javier; Greenhalgh, Mark D.; Brueckner, Alexander C. et al.
In: Chemical Science, Vol. 10, No. 24, 28.06.2019, p. 6162-6173.

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

TY - JOUR

T1 - Catalytic enantioselective synthesis of perfluoroalkyl-substituted β-lactones via a concerted asynchronous [2+2] cycloaddition

T2 - a synthetic and computational study

AU - Barrios Antunez, Diego-Javier

AU - Greenhalgh, Mark D.

AU - Brueckner, Alexander C.

AU - Walden, Daniel M.

AU - Elías-Rodríguez, Pilar

AU - Roberts, Patrick

AU - Young, Benjamin G.

AU - West, Thomas H.

AU - Slawin, Alexandra M. Z.

AU - Cheong, Paul Ha-Yeon

AU - Smith, Andrew D.

N1 - The research leading to these results (D.-J.B.A., T.H.W., A.D.S.) has received funding from the ERC under the European Union’s Seventh Framework Programme (FP7/2007-2013)/E.R.C. Grant Agreement No. 279850. A.D.S. thanks the Royal Society for a Wolfson Research Merit Award. We also thank the EPSRC UK National Mass Spectrometry Facility at Swansea University. P.H.Y.C. is the Bert and Emelyn Christensen professor of OSU, and gratefully acknowledges financial support from the Vicki & Patrick F. Stone family. P.H.Y.C., A.C.B., D.M.W. and B.G.Y. gratefully acknowledge support from the National Science Foundation (NSF CHE-1352663) and the computing infrastructure in part provided by the NSF Phase-2 CCI, Center for Sustainable Materials Chemistry (NSF CHE-1102637).

PY - 2019/6/28

Y1 - 2019/6/28

N2 - The enantioselective preparation of a range of perfluoroalkyl-substituted β-lactones through an isothiourea (HyperBTM) catalysed reaction using symmetric anhydrides as ammonium enolate precursors and perfluoroalkylketones (RF = CF3, C2F5, C4F9) is reported. Following optimisation, high diastereo- and enantioselectivty was observed for β-lactone formation using C2F5- and C4F9-substituted ketones at room temperature (26 examples, up to > 95:5 dr and > 99:1 er), whilst −78 ˚C was necessary for optimal dr and er with CF3-substituted ketones (11 examples, up to > 95:5 dr and > 99:1 er). Derivatisation of the β-lactones through ring-opening, as well as a two-step conversion to give perfluoroalkyl-substituted oxetanes, is demonstrated without loss of stereochemical integrity. Density functional theory computations, alongside 13C natural abundance KIE studies, have been used to probe the reaction mechanism with a concerted asynchronous [2 + 2]-cycloaddition pathway favoured over a stepwise aldol-lactonisation process.

AB - The enantioselective preparation of a range of perfluoroalkyl-substituted β-lactones through an isothiourea (HyperBTM) catalysed reaction using symmetric anhydrides as ammonium enolate precursors and perfluoroalkylketones (RF = CF3, C2F5, C4F9) is reported. Following optimisation, high diastereo- and enantioselectivty was observed for β-lactone formation using C2F5- and C4F9-substituted ketones at room temperature (26 examples, up to > 95:5 dr and > 99:1 er), whilst −78 ˚C was necessary for optimal dr and er with CF3-substituted ketones (11 examples, up to > 95:5 dr and > 99:1 er). Derivatisation of the β-lactones through ring-opening, as well as a two-step conversion to give perfluoroalkyl-substituted oxetanes, is demonstrated without loss of stereochemical integrity. Density functional theory computations, alongside 13C natural abundance KIE studies, have been used to probe the reaction mechanism with a concerted asynchronous [2 + 2]-cycloaddition pathway favoured over a stepwise aldol-lactonisation process.

U2 - 10.1039/C9SC00390H

DO - 10.1039/C9SC00390H

M3 - Article

SN - 2041-6520

VL - 10

SP - 6162

EP - 6173

JO - Chemical Science

JF - Chemical Science

IS - 24

ER -

Catalytic enantioselective synthesis of perfluoroalkyl-substituted β-lactones via a concerted asynchronous [2+2] cycloaddition: a synthetic and computational study

Abstract

Access to Document

Handle.net

Fingerprint

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

Profiles

Andrew Smith

Datasets

Data underpinning "Catalytic enantioselective synthesis of perfluoroalkyl-substituted β-lactones via a concerted asynchronous [2+2] cycloaddition"

Catalytic enantioselective synthesis of perfluoroalkyl-substituted β-lactones via a concerted asynchronous [2+2] cycloaddition: a synthetic and computational study (crystallography data)

Cite this