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Modular, Stereocontrolled Cβ–H/Cα–C Activation of Alkyl Carboxylic Acids

submitted on 29.01.2019, 17:21 and posted on 30.01.2019, 15:56 by 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 Schreiber, Bruno Melillo, jin-quan yu, Phil Baran

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.


NIH (GM-118176)


Email Address of Submitting Author


Scripps research



ORCID For Submitting Author


Declaration of Conflict of Interest

no conflict

Version Notes

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in Proceedings of the National Academy of Sciences