Modular, stereocontrolled Cβ–H/Cα–C activation of alkyl carboxylic acids

Ming Shang, Karla S. Feu, Julien C. Vantourout, Lisa M. Barton, Heather L. Osswald, Nobutaka Kato, Kerstin Gagaring, Case W. McNamara, Gang Chen, Liang Hu, Shengyang Ni, Paula Fernández-Canelas, Miao Chen, Rohan R. Merchant, Tian Qin, Stuart L. Schreiber, Bruno Melillo, Jin Quan Yu, Phil S. Baran

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)8721-8727
Number of pages7
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number18
DOIs
StatePublished - Apr 30 2019
Externally publishedYes

Fingerprint

Heterocyclic Compounds
Antimalarials
Carboxylic Acids
Carbon
Pharmaceutical Preparations

Keywords

  • Carboxylic acids
  • C–H activation
  • Decarboxylative cross-coupling
  • Modular
  • Stereocontrolled

ASJC Scopus subject areas

  • General

Cite this

Shang, M., Feu, K. S., Vantourout, J. C., Barton, L. M., Osswald, H. L., Kato, N., ... Baran, P. S. (2019). Modular, stereocontrolled Cβ–H/Cα–C activation of alkyl carboxylic acids. Proceedings of the National Academy of Sciences of the United States of America, 116(18), 8721-8727. https://doi.org/10.1073/pnas.1903048116

Modular, stereocontrolled Cβ–H/Cα–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.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 116, No. 18, 30.04.2019, p. 8721-8727.

Research output: Contribution to journalArticle

Shang, M, Feu, KS, Vantourout, JC, Barton, LM, Osswald, HL, Kato, N, Gagaring, K, McNamara, CW, Chen, G, Hu, L, Ni, S, Fernández-Canelas, P, Chen, M, Merchant, RR, Qin, T, Schreiber, SL, Melillo, B, Yu, JQ & Baran, PS 2019, 'Modular, stereocontrolled Cβ–H/Cα–C activation of alkyl carboxylic acids', Proceedings of the National Academy of Sciences of the United States of America, vol. 116, no. 18, pp. 8721-8727. https://doi.org/10.1073/pnas.1903048116
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 Cβ–H/Cα–C activation of alkyl carboxylic acids. In: Proceedings of the National Academy of Sciences of the United States of America. 2019 ; Vol. 116, No. 18. pp. 8721-8727.
@article{a2ab9113331b4850a3e7eda61574fd7e,
title = "Modular, stereocontrolled Cβ–H/Cα–C activation of alkyl carboxylic acids",
abstract = "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.",
keywords = "Carboxylic acids, C–H activation, Decarboxylative cross-coupling, Modular, Stereocontrolled",
author = "Ming Shang and Feu, {Karla S.} and Vantourout, {Julien C.} and Barton, {Lisa M.} and Osswald, {Heather L.} and Nobutaka Kato and Kerstin Gagaring and McNamara, {Case W.} and Gang Chen and Liang Hu and Shengyang Ni and Paula Fern{\'a}ndez-Canelas and Miao Chen and Merchant, {Rohan R.} and Tian Qin and Schreiber, {Stuart L.} and Bruno Melillo and Yu, {Jin Quan} and Baran, {Phil S.}",
year = "2019",
month = "4",
day = "30",
doi = "10.1073/pnas.1903048116",
language = "English (US)",
volume = "116",
pages = "8721--8727",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "18",

}

TY - JOUR

T1 - Modular, stereocontrolled Cβ–H/Cα–C activation of alkyl carboxylic acids

AU - Shang, Ming

AU - Feu, Karla S.

AU - Vantourout, Julien C.

AU - Barton, Lisa M.

AU - Osswald, Heather L.

AU - Kato, Nobutaka

AU - Gagaring, Kerstin

AU - McNamara, Case W.

AU - Chen, Gang

AU - Hu, Liang

AU - Ni, Shengyang

AU - Fernández-Canelas, Paula

AU - Chen, Miao

AU - Merchant, Rohan R.

AU - Qin, Tian

AU - Schreiber, Stuart L.

AU - Melillo, Bruno

AU - Yu, Jin Quan

AU - Baran, Phil S.

PY - 2019/4/30

Y1 - 2019/4/30

N2 - 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.

AB - 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.

KW - Carboxylic acids

KW - C–H activation

KW - Decarboxylative cross-coupling

KW - Modular

KW - Stereocontrolled

UR - http://www.scopus.com/inward/record.url?scp=85065511025&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85065511025&partnerID=8YFLogxK

U2 - 10.1073/pnas.1903048116

DO - 10.1073/pnas.1903048116

M3 - Article

C2 - 30996125

AN - SCOPUS:85065511025

VL - 116

SP - 8721

EP - 8727

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 18

ER -