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Organocatalytic Asymmetric Addition of Aldehyde to Nitroolefin by H-d-Pro-Pro-Glu-NH(2): A Mechanistic Study
[Image: see text] The mechanism of the asymmetric addition of aldehyde (butanal) to nitroolefin (β-nitrostyrene) catalyzed by H-d-Pro-Pro-Glu-NH(2) (dPPE-NH(2); 1) was explored using density functional theory methods in chloroform. By conformational search, it was confirmed that catalyst 1 and its e...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2019
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6648279/ https://www.ncbi.nlm.nih.gov/pubmed/31459974 http://dx.doi.org/10.1021/acsomega.9b00465 |
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author | Maillard, Ludovic T. Park, Hae Sook Kang, Young Kee |
author_facet | Maillard, Ludovic T. Park, Hae Sook Kang, Young Kee |
author_sort | Maillard, Ludovic T. |
collection | PubMed |
description | [Image: see text] The mechanism of the asymmetric addition of aldehyde (butanal) to nitroolefin (β-nitrostyrene) catalyzed by H-d-Pro-Pro-Glu-NH(2) (dPPE-NH(2); 1) was explored using density functional theory methods in chloroform. By conformational search, it was confirmed that catalyst 1 and its enamine intermediate adopted a dominant conformation with a βI structure stabilized by a C(10) H-bond between the C=O of d-Pro1 and C-terminal NH(2) proton and by an additional H-bond between the side chain and the backbone of Glu3. This βI turn structure was conserved all along the catalytic cycle. Consistently with the kinetic studies, the C–C bond formation between the enamine and electrophile was also confirmed as the rate-determining step. The stereoselectivity results from a re → re prochiral approach of enamine and β-nitrostyrene with a gauche(–) orientation of the double bonds. Although it was suggested as the possible formation of dihydrooxazine oxide species, this process was confirmed to be kinetically less accessible than the formation of acyclic nitronate. In particular, our calculated results supported that the carboxylic acid group of Glu3 in 1 played a central role by acting as general acid/base all along the catalytic cycle and orienting the asymmetric C–C bond formation. |
format | Online Article Text |
id | pubmed-6648279 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-66482792019-08-27 Organocatalytic Asymmetric Addition of Aldehyde to Nitroolefin by H-d-Pro-Pro-Glu-NH(2): A Mechanistic Study Maillard, Ludovic T. Park, Hae Sook Kang, Young Kee ACS Omega [Image: see text] The mechanism of the asymmetric addition of aldehyde (butanal) to nitroolefin (β-nitrostyrene) catalyzed by H-d-Pro-Pro-Glu-NH(2) (dPPE-NH(2); 1) was explored using density functional theory methods in chloroform. By conformational search, it was confirmed that catalyst 1 and its enamine intermediate adopted a dominant conformation with a βI structure stabilized by a C(10) H-bond between the C=O of d-Pro1 and C-terminal NH(2) proton and by an additional H-bond between the side chain and the backbone of Glu3. This βI turn structure was conserved all along the catalytic cycle. Consistently with the kinetic studies, the C–C bond formation between the enamine and electrophile was also confirmed as the rate-determining step. The stereoselectivity results from a re → re prochiral approach of enamine and β-nitrostyrene with a gauche(–) orientation of the double bonds. Although it was suggested as the possible formation of dihydrooxazine oxide species, this process was confirmed to be kinetically less accessible than the formation of acyclic nitronate. In particular, our calculated results supported that the carboxylic acid group of Glu3 in 1 played a central role by acting as general acid/base all along the catalytic cycle and orienting the asymmetric C–C bond formation. American Chemical Society 2019-05-22 /pmc/articles/PMC6648279/ /pubmed/31459974 http://dx.doi.org/10.1021/acsomega.9b00465 Text en Copyright © 2019 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 | Maillard, Ludovic T. Park, Hae Sook Kang, Young Kee Organocatalytic Asymmetric Addition of Aldehyde to Nitroolefin by H-d-Pro-Pro-Glu-NH(2): A Mechanistic Study |
title | Organocatalytic Asymmetric Addition of Aldehyde to
Nitroolefin by H-d-Pro-Pro-Glu-NH(2): A Mechanistic Study |
title_full | Organocatalytic Asymmetric Addition of Aldehyde to
Nitroolefin by H-d-Pro-Pro-Glu-NH(2): A Mechanistic Study |
title_fullStr | Organocatalytic Asymmetric Addition of Aldehyde to
Nitroolefin by H-d-Pro-Pro-Glu-NH(2): A Mechanistic Study |
title_full_unstemmed | Organocatalytic Asymmetric Addition of Aldehyde to
Nitroolefin by H-d-Pro-Pro-Glu-NH(2): A Mechanistic Study |
title_short | Organocatalytic Asymmetric Addition of Aldehyde to
Nitroolefin by H-d-Pro-Pro-Glu-NH(2): A Mechanistic Study |
title_sort | organocatalytic asymmetric addition of aldehyde to
nitroolefin by h-d-pro-pro-glu-nh(2): a mechanistic study |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6648279/ https://www.ncbi.nlm.nih.gov/pubmed/31459974 http://dx.doi.org/10.1021/acsomega.9b00465 |
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