Stereoselective Installation of Five Contiguous Stereogenic Centers in a Double Aldol-Tishchenko Cascade and Evaluation of the Key Transition State through DFT Calculation
Stereoselective Installation of Five Contiguous Stereogenic Centers in a Double Aldol-Tishchenko Cascade and Evaluation of the Key Transition State through DFT Calculation
The stereoselective formation of 5 contiguous chiral centers in a single pot reaction is demonstrated using an aldol, aldol-Tishchenko reaction of N-tert-butyl sulfinimines. One diastereoisomer (from 32 possibilities) predominates, and a series of cyclic and acyclic 3-amino-1,5-diol derivatives are synthesized in good yields (up to 80%) and excellent diastereoselectivities (up to >98:2 dr). Investigations support two reversible aldol steps, and multiple intermediates which are funnelled through a remarkably selective, irreversible, Tishchenko reduction, in a Curtin-Hammett phenomenon. DFT calculations using a disolvated (THF) model reveal the factors controlling stereoselectivity in the final irreversible Tishchenko step.
6372-6376
MacKey, Pamela
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Turlik, Aneta
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Ando, Kaori
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Light, Mark E.
cf57314e-6856-491b-a8d2-2dffc452e161
Houk, K. N.
038f0df8-ab7f-4bcc-87ce-53342be57e23
McGlacken, Gerard P.
7232768a-94ff-4794-81b3-1467726505e0
20 August 2021
MacKey, Pamela
8817de93-dc6b-4d93-bfa5-8409929bf955
Turlik, Aneta
cb9c3da1-2729-47ce-9c13-883d033843c5
Ando, Kaori
91358af5-39e6-4045-bc9d-32741a444574
Light, Mark E.
cf57314e-6856-491b-a8d2-2dffc452e161
Houk, K. N.
038f0df8-ab7f-4bcc-87ce-53342be57e23
McGlacken, Gerard P.
7232768a-94ff-4794-81b3-1467726505e0
MacKey, Pamela, Turlik, Aneta, Ando, Kaori, Light, Mark E., Houk, K. N. and McGlacken, Gerard P.
(2021)
Stereoselective Installation of Five Contiguous Stereogenic Centers in a Double Aldol-Tishchenko Cascade and Evaluation of the Key Transition State through DFT Calculation.
Organic Letters, 23 (16), .
(doi:10.1021/acs.orglett.1c02179).
Abstract
The stereoselective formation of 5 contiguous chiral centers in a single pot reaction is demonstrated using an aldol, aldol-Tishchenko reaction of N-tert-butyl sulfinimines. One diastereoisomer (from 32 possibilities) predominates, and a series of cyclic and acyclic 3-amino-1,5-diol derivatives are synthesized in good yields (up to 80%) and excellent diastereoselectivities (up to >98:2 dr). Investigations support two reversible aldol steps, and multiple intermediates which are funnelled through a remarkably selective, irreversible, Tishchenko reduction, in a Curtin-Hammett phenomenon. DFT calculations using a disolvated (THF) model reveal the factors controlling stereoselectivity in the final irreversible Tishchenko step.
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Accepted/In Press date: 10 August 2021
Published date: 20 August 2021
Additional Information:
Funding Information:
We thank the Irish Research Council for funding (IRC GOIPG/2014/343). 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 for editing and proof-reading.
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Copyright 2021 Elsevier B.V., All rights reserved.
Identifiers
Local EPrints ID: 453807
URI: http://eprints.soton.ac.uk/id/eprint/453807
ISSN: 1523-7060
PURE UUID: ac4ce7b4-92c1-4966-b0b2-15ccb817d11f
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Date deposited: 24 Jan 2022 17:53
Last modified: 18 Mar 2024 02:50
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Author:
Pamela MacKey
Author:
Aneta Turlik
Author:
Kaori Ando
Author:
K. N. Houk
Author:
Gerard P. McGlacken
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