Ligand-Enabled β-Methylene C(sp3)−H Arylation of Masked Aliphatic Alcohols
Dr. Guoqin Xia
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037 USA
Search for more papers by this authorZhe Zhuang
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037 USA
Search for more papers by this authorLuo-Yan Liu
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037 USA
Search for more papers by this authorProf. Dr. Stuart L. Schreiber
Chemical Biology and Therapeutics Science Program, Broad Institute, Cambridge, MA, 02142 USA
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, 02138 USA
Search for more papers by this authorCorresponding Author
Dr. Bruno Melillo
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037 USA
Chemical Biology and Therapeutics Science Program, Broad Institute, Cambridge, MA, 02142 USA
Search for more papers by this authorCorresponding Author
Prof. Dr. Jin-Quan Yu
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037 USA
Search for more papers by this authorDr. Guoqin Xia
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037 USA
Search for more papers by this authorZhe Zhuang
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037 USA
Search for more papers by this authorLuo-Yan Liu
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037 USA
Search for more papers by this authorProf. Dr. Stuart L. Schreiber
Chemical Biology and Therapeutics Science Program, Broad Institute, Cambridge, MA, 02142 USA
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, 02138 USA
Search for more papers by this authorCorresponding Author
Dr. Bruno Melillo
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037 USA
Chemical Biology and Therapeutics Science Program, Broad Institute, Cambridge, MA, 02142 USA
Search for more papers by this authorCorresponding Author
Prof. Dr. Jin-Quan Yu
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037 USA
Search for more papers by this authorAbstract
Despite recent advances, reactivity and site-selectivity remain significant obstacles for the practical application of C(sp3)−H bond functionalization methods. Here, we describe a system that combines a salicylic-aldehyde-derived L,X-type directing group with an electron-deficient 2-pyridone ligand to enable the β-methylene C(sp3)−H arylation of aliphatic alcohols, which has not been possible previously. Notably, this protocol is compatible with heterocycles embedded in both alcohol substrates and aryl coupling partners. A site- and stereo-specific annulation of dihydrocholesterol and the synthesis of a key intermediate of englitazone illustrate the practicality of this method.
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