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A Twist on Facial Selectivity of Hydride Reductions of Cyclic Ketones: Twist-Boat Conformers in Cyclohexanone, Piperidone, and Tropinone Reactions

[Image: see text] The role of twist-boat conformers of cyclohexanones in hydride reductions was explored. The hydride reductions of a cis-2,6-disubstituted N-acylpiperidone, an N-acyltropinone, and tert-butylcyclohexanone by lithium aluminum hydride and by a bulky borohydride reagent were investigat...

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Autores principales: Neufeldt, Sharon R., Jiménez-Osés, Gonzalo, Comins, Daniel L., Houk, K. N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2014
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260662/
https://www.ncbi.nlm.nih.gov/pubmed/25372509
http://dx.doi.org/10.1021/jo5022635
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author Neufeldt, Sharon R.
Jiménez-Osés, Gonzalo
Comins, Daniel L.
Houk, K. N.
author_facet Neufeldt, Sharon R.
Jiménez-Osés, Gonzalo
Comins, Daniel L.
Houk, K. N.
author_sort Neufeldt, Sharon R.
collection PubMed
description [Image: see text] The role of twist-boat conformers of cyclohexanones in hydride reductions was explored. The hydride reductions of a cis-2,6-disubstituted N-acylpiperidone, an N-acyltropinone, and tert-butylcyclohexanone by lithium aluminum hydride and by a bulky borohydride reagent were investigated computationally and compared to experiment. Our results indicate that in certain cases, factors such as substrate conformation, nucleophile bulkiness, and remote steric features can affect stereoselectivity in ways that are difficult to predict by the general Felkin–Anh model. In particular, we have calculated that a twist-boat conformation is relevant to the reactivity and facial selectivity of hydride reduction of cis-2,6-disubstituted N-acylpiperidones with a small hydride reagent (LiAlH(4)) but not with a bulky hydride (lithium triisopropylborohydride).
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spelling pubmed-42606622015-11-05 A Twist on Facial Selectivity of Hydride Reductions of Cyclic Ketones: Twist-Boat Conformers in Cyclohexanone, Piperidone, and Tropinone Reactions Neufeldt, Sharon R. Jiménez-Osés, Gonzalo Comins, Daniel L. Houk, K. N. J Org Chem [Image: see text] The role of twist-boat conformers of cyclohexanones in hydride reductions was explored. The hydride reductions of a cis-2,6-disubstituted N-acylpiperidone, an N-acyltropinone, and tert-butylcyclohexanone by lithium aluminum hydride and by a bulky borohydride reagent were investigated computationally and compared to experiment. Our results indicate that in certain cases, factors such as substrate conformation, nucleophile bulkiness, and remote steric features can affect stereoselectivity in ways that are difficult to predict by the general Felkin–Anh model. In particular, we have calculated that a twist-boat conformation is relevant to the reactivity and facial selectivity of hydride reduction of cis-2,6-disubstituted N-acylpiperidones with a small hydride reagent (LiAlH(4)) but not with a bulky hydride (lithium triisopropylborohydride). American Chemical Society 2014-11-05 2014-12-05 /pmc/articles/PMC4260662/ /pubmed/25372509 http://dx.doi.org/10.1021/jo5022635 Text en Copyright © 2014 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Neufeldt, Sharon R.
Jiménez-Osés, Gonzalo
Comins, Daniel L.
Houk, K. N.
A Twist on Facial Selectivity of Hydride Reductions of Cyclic Ketones: Twist-Boat Conformers in Cyclohexanone, Piperidone, and Tropinone Reactions
title A Twist on Facial Selectivity of Hydride Reductions of Cyclic Ketones: Twist-Boat Conformers in Cyclohexanone, Piperidone, and Tropinone Reactions
title_full A Twist on Facial Selectivity of Hydride Reductions of Cyclic Ketones: Twist-Boat Conformers in Cyclohexanone, Piperidone, and Tropinone Reactions
title_fullStr A Twist on Facial Selectivity of Hydride Reductions of Cyclic Ketones: Twist-Boat Conformers in Cyclohexanone, Piperidone, and Tropinone Reactions
title_full_unstemmed A Twist on Facial Selectivity of Hydride Reductions of Cyclic Ketones: Twist-Boat Conformers in Cyclohexanone, Piperidone, and Tropinone Reactions
title_short A Twist on Facial Selectivity of Hydride Reductions of Cyclic Ketones: Twist-Boat Conformers in Cyclohexanone, Piperidone, and Tropinone Reactions
title_sort twist on facial selectivity of hydride reductions of cyclic ketones: twist-boat conformers in cyclohexanone, piperidone, and tropinone reactions
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260662/
https://www.ncbi.nlm.nih.gov/pubmed/25372509
http://dx.doi.org/10.1021/jo5022635
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