Ligand‐Enabled β‐Methylene C(sp <sup>3</sup> )−H Arylation of Masked Aliphatic Alcohols
Guoqin Xia, Zhe Zhuang, Luo‐Yan Liu, Stuart L. Schreiber, Bruno Melillo, Jin‐Quan Yu
Abstract
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.