@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.}",
note = "Funding Information: ACKNOWLEDGMENTS. We thank Dr. Dee-Hua Huang and Dr. Laura Pasternack (Scripps Research) for assistance with NMR spectroscopy; Dr. Jason Chen and Brittany Sanchez (Scripps Automated Synthesis Facility) for assistance with HPLC, high-resolution mass spectrometry, and liquid chromatography mass spectrometry; and Dr. Arnold Rheingold, Dr. Curtis Moore, and Dr. Milan Gembicky (University of California, San Diego) for assistance with X-ray crystallographic analysis. We also thank Cindy Hon (Broad Institute) for logistical support, Dr. Florence Wagner and Ryan Babcock (Broad Institute) for assistance obtaining analytical samples, Dr. Eamon Comer (Broad Institute) for helpful discussions regarding compound synthesis, and Dr. Guoqin Xia (Scripps Research) for sharing valuable reagents. Financial support for this work was provided by NIH Grant GM-118176, Bill & Melinda Gates Foundation Grant OPP11823830, Vividion, Zhejiang Yuanhong Medicine Technology Co. Ltd. (M.S.), S{\~a}o Paulo Research Foundation Grant 2017/08128-7 (to K.S.F.), NSF Graduate Research Fellowship Program (L.M.B.), the China Scholarship Council (L.H. and S.N.), and Spanish Ministerio de Econom{\'i}a, Industria y Competitividad Formacion de Personal Investigador Predoctoral Fellowships BES-2014-069879 (to P.F.-C.) and EEBB-I-2018-12962 (to P.F.-C.). Publisher Copyright: {\textcopyright} 2019 National Academy of Sciences. All rights reserved.",
year = "2019",
month = apr,
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",
publisher = "National Academy of Sciences",
number = "18",
}