Science of Synthesis

Gandeepan, P.; Cheng, C.-H., Science of Synthesis: Catalytic Transformations via C—H Activation, (2015) 1, 70.

Palladium-catalyzed biaryl formation by C—H activation has recently become more attractive than traditional cross-coupling reactions because no prefunctionalization of the starting materials is required. However, the direct functionalization of C—H bonds is difficult owing to their inert nature. Another great challenge in directing C—H activation and functionalization is the ubiquitous nature of C—H bonds, which makes controlled site-selective C—H functionalization within a molecule difficult. In most cases, a directing group (DG) is employed to control the position of the C—H bond to be functionalized.[‌16‌–‌18‌] Various heteroatom-containing functional groups such as amides, amines, alcohols, carboxylic acids, imines, ketones, aldehydes, and nitrogen-containing heterocycles are often employed as directing groups. The functional group coordinates to the metal complex and assists interaction of the metal complex with the nearby C—H bond to form a chelated metal intermediate (metallacycle). On the basis of this scenario, numerous site-selective palladium-catalyzed C—H arylation reactions have been achieved. In these reactions, a variety of aryl sources including aryl halides, aryl pseudohalides, and organometallic reagents have been used as the arylation agents. In particular, directing-group-assisted arylation of aromatic C—H bonds by using a palladium(II)/palladium(IV) catalyst system has been successful with various arylating agents such as diaryliodonium salts, aryl halides, and arenes.

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