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

preprint
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.

Funding

NIH (GM-118176)

History

Email Address of Submitting Author

pbaran@scripps.edu

Institution

Scripps research

Country

USA

ORCID For Submitting Author

0000-0001-9193-9053

Declaration of Conflict of Interest

no conflict

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in Proceedings of the National Academy of Sciences

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