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Ligand‐Enabled β‐Methylene C(sp 3 )−H Arylation of Masked Aliphatic Alcohols
Author(s) -
Xia Guoqin,
Zhuang Zhe,
Liu LuoYan,
Schreiber Stuart L.,
Melillo Bruno,
Yu JinQuan
Publication year - 2020
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202000632
Subject(s) - methylene , ligand (biochemistry) , chemistry , aldehyde , reactivity (psychology) , annulation , alcohol , combinatorial chemistry , aryl , medicinal chemistry , surface modification , stereochemistry , selectivity , organic chemistry , catalysis , medicine , biochemistry , alkyl , receptor , alternative medicine , pathology
Abstract Despite recent advances, reactivity and site‐selectivity remain significant obstacles for the practical application of C(sp 3 )−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(sp 3 )−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.