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Asymmetric Fluorination of α-Branched Cyclohexanones Enabled by a Combination of Chiral Anion Phase-Transfer Catalysis and Enamine Catalysis using Protected Amino Acids

[Image: see text] We report a study involving the successful merger of two separate chiral catalytic cycles: a chiral anion phase-transfer catalysis cycle to activate Selectfluor and an enamine activation cycle, using a protected amino acid as organocatalyst. We have demonstrated the viability of th...

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Autores principales: Yang, Xiaoyu, Phipps, Robert J., Toste, F. Dean
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2014
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4119784/
https://www.ncbi.nlm.nih.gov/pubmed/24684209
http://dx.doi.org/10.1021/ja500882x
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author Yang, Xiaoyu
Phipps, Robert J.
Toste, F. Dean
author_facet Yang, Xiaoyu
Phipps, Robert J.
Toste, F. Dean
author_sort Yang, Xiaoyu
collection PubMed
description [Image: see text] We report a study involving the successful merger of two separate chiral catalytic cycles: a chiral anion phase-transfer catalysis cycle to activate Selectfluor and an enamine activation cycle, using a protected amino acid as organocatalyst. We have demonstrated the viability of this approach with the direct asymmetric fluorination of α-substituted cyclohexanones to generate quaternary fluorine-containing stereocenters. With these two chiral catalytic cycles operating together in a matched sense, high enantioselectivites can be achieved, and we envisage that this dual catalysis method has the potential to be more broadly applicable, given the breadth of enamine catalysis. It also represents a rare example of chiral enamine catalysis operating successfully on α-branched ketones, substrates commonly inert to this activation mode.
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spelling pubmed-41197842015-03-31 Asymmetric Fluorination of α-Branched Cyclohexanones Enabled by a Combination of Chiral Anion Phase-Transfer Catalysis and Enamine Catalysis using Protected Amino Acids Yang, Xiaoyu Phipps, Robert J. Toste, F. Dean J Am Chem Soc [Image: see text] We report a study involving the successful merger of two separate chiral catalytic cycles: a chiral anion phase-transfer catalysis cycle to activate Selectfluor and an enamine activation cycle, using a protected amino acid as organocatalyst. We have demonstrated the viability of this approach with the direct asymmetric fluorination of α-substituted cyclohexanones to generate quaternary fluorine-containing stereocenters. With these two chiral catalytic cycles operating together in a matched sense, high enantioselectivites can be achieved, and we envisage that this dual catalysis method has the potential to be more broadly applicable, given the breadth of enamine catalysis. It also represents a rare example of chiral enamine catalysis operating successfully on α-branched ketones, substrates commonly inert to this activation mode. American Chemical Society 2014-03-31 2014-04-09 /pmc/articles/PMC4119784/ /pubmed/24684209 http://dx.doi.org/10.1021/ja500882x Text en Copyright © 2014 American Chemical Society Terms of Use (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html)
spellingShingle Yang, Xiaoyu
Phipps, Robert J.
Toste, F. Dean
Asymmetric Fluorination of α-Branched Cyclohexanones Enabled by a Combination of Chiral Anion Phase-Transfer Catalysis and Enamine Catalysis using Protected Amino Acids
title Asymmetric Fluorination of α-Branched Cyclohexanones Enabled by a Combination of Chiral Anion Phase-Transfer Catalysis and Enamine Catalysis using Protected Amino Acids
title_full Asymmetric Fluorination of α-Branched Cyclohexanones Enabled by a Combination of Chiral Anion Phase-Transfer Catalysis and Enamine Catalysis using Protected Amino Acids
title_fullStr Asymmetric Fluorination of α-Branched Cyclohexanones Enabled by a Combination of Chiral Anion Phase-Transfer Catalysis and Enamine Catalysis using Protected Amino Acids
title_full_unstemmed Asymmetric Fluorination of α-Branched Cyclohexanones Enabled by a Combination of Chiral Anion Phase-Transfer Catalysis and Enamine Catalysis using Protected Amino Acids
title_short Asymmetric Fluorination of α-Branched Cyclohexanones Enabled by a Combination of Chiral Anion Phase-Transfer Catalysis and Enamine Catalysis using Protected Amino Acids
title_sort asymmetric fluorination of α-branched cyclohexanones enabled by a combination of chiral anion phase-transfer catalysis and enamine catalysis using protected amino acids
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4119784/
https://www.ncbi.nlm.nih.gov/pubmed/24684209
http://dx.doi.org/10.1021/ja500882x
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