The Aldol-Tishchenko Reaction of Butanone, Cyclobutanone and a 3-Pentanone Derived Sulfinylimine and DFT Calculations of the Stereo-determining Step
The Aldol-Tishchenko Reaction of Butanone, Cyclobutanone and a 3-Pentanone Derived Sulfinylimine and DFT Calculations of the Stereo-determining Step
Herein, we present a highly diastereoselective method to furnish acyclic 3-amino-1,5-diol derivatives using a tandem double-aldol-Tishchenko protocol (dr up to >99 : 1) using a butanone derived sulfinylimine. In most cases only 1 diastereomer predominates, from a possible 16. The reaction is also regioselective. In addition, the highly challenging cyclobutanone and 3-pentanone derivatives are also amenable to a double-aldol-Tishchenko reaction, although the dr values are modest. Despite that, clean single diastereomers can be isolated, which should prove very useful in medicinal chemistry and other areas. Detailed DFT calculations support the observed stereoselectivities in all cases, providing a rationale for the excellent dr values in the butanone series and the moderate values for the 3-pentanone class.
1,3-amino alcohol, DFT, diastereoselective, stereochemistry
Alcock, Emma
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Mackey, Pamela
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Turlik, Aneta
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Bhatt, Khushi
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Light, Mark E.
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Houk, Kendall N.
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McGlacken, Gerard P.
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18 April 2023
Alcock, Emma
b60352b8-fda7-4bd5-89a2-ca407d176b9e
Mackey, Pamela
8817de93-dc6b-4d93-bfa5-8409929bf955
Turlik, Aneta
cb9c3da1-2729-47ce-9c13-883d033843c5
Bhatt, Khushi
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Light, Mark E.
cf57314e-6856-491b-a8d2-2dffc452e161
Houk, Kendall N.
038f0df8-ab7f-4bcc-87ce-53342be57e23
McGlacken, Gerard P.
7232768a-94ff-4794-81b3-1467726505e0
Alcock, Emma, Mackey, Pamela, Turlik, Aneta, Bhatt, Khushi, Light, Mark E., Houk, Kendall N. and McGlacken, Gerard P.
(2023)
The Aldol-Tishchenko Reaction of Butanone, Cyclobutanone and a 3-Pentanone Derived Sulfinylimine and DFT Calculations of the Stereo-determining Step.
Chemistry - A European Journal, 29 (22), [e202203029].
(doi:10.1002/chem.202203029).
Abstract
Herein, we present a highly diastereoselective method to furnish acyclic 3-amino-1,5-diol derivatives using a tandem double-aldol-Tishchenko protocol (dr up to >99 : 1) using a butanone derived sulfinylimine. In most cases only 1 diastereomer predominates, from a possible 16. The reaction is also regioselective. In addition, the highly challenging cyclobutanone and 3-pentanone derivatives are also amenable to a double-aldol-Tishchenko reaction, although the dr values are modest. Despite that, clean single diastereomers can be isolated, which should prove very useful in medicinal chemistry and other areas. Detailed DFT calculations support the observed stereoselectivities in all cases, providing a rationale for the excellent dr values in the butanone series and the moderate values for the 3-pentanone class.
Text
Chemistry A European J - 2023 - Alcock - The Aldol‐Tishchenko Reaction of Butanone Cyclobutanone and a 3‐Pentanone Derived
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Accepted/In Press date: 8 January 2023
Published date: 18 April 2023
Additional Information:
Funding Information:
We thank the Irish Research Council for funding (IRCGOIPG/2017/7). The authors are grateful to the National Science Foundation (Grant CHE‐1764328) for financial support. Calculations were performed on the Hoffman2 cluster at the University of California, Los Angeles, and the Extreme Science and Engineering Discovery Environment (XSEDE), which is supported by the National Science Foundation (Grant OCI‐1053575). G.P.M would like to thank Dr Katrina Mackey and Mark Power for proof‐reading and editing. Open Access funding provided by IReL.
Publisher Copyright:
© 2023 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.
Keywords:
1,3-amino alcohol, DFT, diastereoselective, stereochemistry
Identifiers
Local EPrints ID: 476678
URI: http://eprints.soton.ac.uk/id/eprint/476678
ISSN: 0947-6539
PURE UUID: 2542e57b-1199-49e6-b589-df68f2c112b8
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Date deposited: 11 May 2023 16:35
Last modified: 18 Mar 2024 02:50
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Contributors
Author:
Emma Alcock
Author:
Pamela Mackey
Author:
Aneta Turlik
Author:
Khushi Bhatt
Author:
Kendall N. Houk
Author:
Gerard P. McGlacken
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