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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
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202000632
Subject(s) - chemistry , methylene , ligand (biochemistry) , aldehyde , reactivity (psychology) , annulation , alcohol , combinatorial chemistry , aryl , selectivity , medicinal chemistry , chemoselectivity , stereochemistry , organic chemistry , catalysis , alternative medicine , pathology , medicine , biochemistry , alkyl , receptor
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.