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Modular, stereocontrolled C(β)–H/C(α)–C activation of alkyl carboxylic acids

The union of two powerful transformations, directed C–H activation and decarboxylative cross-coupling, for the enantioselective synthesis of vicinally functionalized alkyl, carbocyclic, and heterocyclic compounds is described. Starting from simple carboxylic acid building blocks, this modular sequen...

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Autores principales: Shang, Ming, Feu, Karla S., Vantourout, Julien C., Barton, Lisa M., Osswald, Heather L., Kato, Nobutaka, Gagaring, Kerstin, McNamara, Case W., Chen, Gang, Hu, Liang, Ni, Shengyang, Fernández-Canelas, Paula, Chen, Miao, Merchant, Rohan R., Qin, Tian, Schreiber, Stuart L., Melillo, Bruno, Yu, Jin-Quan, Baran, Phil S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6500144/
https://www.ncbi.nlm.nih.gov/pubmed/30996125
http://dx.doi.org/10.1073/pnas.1903048116
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author Shang, Ming
Feu, Karla S.
Vantourout, Julien C.
Barton, Lisa M.
Osswald, Heather L.
Kato, Nobutaka
Gagaring, Kerstin
McNamara, Case W.
Chen, Gang
Hu, Liang
Ni, Shengyang
Fernández-Canelas, Paula
Chen, Miao
Merchant, Rohan R.
Qin, Tian
Schreiber, Stuart L.
Melillo, Bruno
Yu, Jin-Quan
Baran, Phil S.
author_facet Shang, Ming
Feu, Karla S.
Vantourout, Julien C.
Barton, Lisa M.
Osswald, Heather L.
Kato, Nobutaka
Gagaring, Kerstin
McNamara, Case W.
Chen, Gang
Hu, Liang
Ni, Shengyang
Fernández-Canelas, Paula
Chen, Miao
Merchant, Rohan R.
Qin, Tian
Schreiber, Stuart L.
Melillo, Bruno
Yu, Jin-Quan
Baran, Phil S.
author_sort Shang, Ming
collection PubMed
description The union of two powerful transformations, directed C–H activation and decarboxylative cross-coupling, for the enantioselective synthesis of vicinally functionalized alkyl, carbocyclic, and heterocyclic compounds is described. Starting from simple carboxylic acid building blocks, this modular sequence exploits the residual directing group to access more than 50 scaffolds that would be otherwise extremely difficult to prepare. The tactical use of these two transformations accomplishes a formal vicinal difunctionalization of carbon centers in a way that is modular and thus, amenable to rapid diversity incorporation. A simplification of routes to known preclinical drug candidates is presented along with the rapid diversification of an antimalarial compound series.
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spelling pubmed-65001442019-05-20 Modular, stereocontrolled C(β)–H/C(α)–C activation of alkyl carboxylic acids Shang, Ming Feu, Karla S. Vantourout, Julien C. Barton, Lisa M. Osswald, Heather L. Kato, Nobutaka Gagaring, Kerstin McNamara, Case W. Chen, Gang Hu, Liang Ni, Shengyang Fernández-Canelas, Paula Chen, Miao Merchant, Rohan R. Qin, Tian Schreiber, Stuart L. Melillo, Bruno Yu, Jin-Quan Baran, Phil S. Proc Natl Acad Sci U S A PNAS Plus The union of two powerful transformations, directed C–H activation and decarboxylative cross-coupling, for the enantioselective synthesis of vicinally functionalized alkyl, carbocyclic, and heterocyclic compounds is described. Starting from simple carboxylic acid building blocks, this modular sequence exploits the residual directing group to access more than 50 scaffolds that would be otherwise extremely difficult to prepare. The tactical use of these two transformations accomplishes a formal vicinal difunctionalization of carbon centers in a way that is modular and thus, amenable to rapid diversity incorporation. A simplification of routes to known preclinical drug candidates is presented along with the rapid diversification of an antimalarial compound series. National Academy of Sciences 2019-04-30 2019-04-17 /pmc/articles/PMC6500144/ /pubmed/30996125 http://dx.doi.org/10.1073/pnas.1903048116 Text en Copyright © 2019 the Author(s). Published by PNAS. http://creativecommons.org/licenses/by/4.0/ This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) .
spellingShingle PNAS Plus
Shang, Ming
Feu, Karla S.
Vantourout, Julien C.
Barton, Lisa M.
Osswald, Heather L.
Kato, Nobutaka
Gagaring, Kerstin
McNamara, Case W.
Chen, Gang
Hu, Liang
Ni, Shengyang
Fernández-Canelas, Paula
Chen, Miao
Merchant, Rohan R.
Qin, Tian
Schreiber, Stuart L.
Melillo, Bruno
Yu, Jin-Quan
Baran, Phil S.
Modular, stereocontrolled C(β)–H/C(α)–C activation of alkyl carboxylic acids
title Modular, stereocontrolled C(β)–H/C(α)–C activation of alkyl carboxylic acids
title_full Modular, stereocontrolled C(β)–H/C(α)–C activation of alkyl carboxylic acids
title_fullStr Modular, stereocontrolled C(β)–H/C(α)–C activation of alkyl carboxylic acids
title_full_unstemmed Modular, stereocontrolled C(β)–H/C(α)–C activation of alkyl carboxylic acids
title_short Modular, stereocontrolled C(β)–H/C(α)–C activation of alkyl carboxylic acids
title_sort modular, stereocontrolled c(β)–h/c(α)–c activation of alkyl carboxylic acids
topic PNAS Plus
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6500144/
https://www.ncbi.nlm.nih.gov/pubmed/30996125
http://dx.doi.org/10.1073/pnas.1903048116
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