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 journalArticlepeer-review

11 Scopus citations

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

Keywords

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

ASJC Scopus subject areas

  • General

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