Cargando…
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...
Autores principales: | , , , |
---|---|
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 |
_version_ | 1782348202735828992 |
---|---|
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). |
format | Online Article Text |
id | pubmed-4260662 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | American Chemical
Society |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT neufeldtsharonr atwistonfacialselectivityofhydridereductionsofcyclicketonestwistboatconformersincyclohexanonepiperidoneandtropinonereactions AT jimenezosesgonzalo atwistonfacialselectivityofhydridereductionsofcyclicketonestwistboatconformersincyclohexanonepiperidoneandtropinonereactions AT cominsdaniell atwistonfacialselectivityofhydridereductionsofcyclicketonestwistboatconformersincyclohexanonepiperidoneandtropinonereactions AT houkkn atwistonfacialselectivityofhydridereductionsofcyclicketonestwistboatconformersincyclohexanonepiperidoneandtropinonereactions AT neufeldtsharonr twistonfacialselectivityofhydridereductionsofcyclicketonestwistboatconformersincyclohexanonepiperidoneandtropinonereactions AT jimenezosesgonzalo twistonfacialselectivityofhydridereductionsofcyclicketonestwistboatconformersincyclohexanonepiperidoneandtropinonereactions AT cominsdaniell twistonfacialselectivityofhydridereductionsofcyclicketonestwistboatconformersincyclohexanonepiperidoneandtropinonereactions AT houkkn twistonfacialselectivityofhydridereductionsofcyclicketonestwistboatconformersincyclohexanonepiperidoneandtropinonereactions |