Palladium-catalyzed functionalizations of acidic and non-acidic C(sp3)-H bonds - recent advances.

A tremendous upsurge has been seen in the recent decade for the proximal and remote functionalization of activated and unactivated substrates via palladium redox pathways. This feature article discusses some of the recent reports on direct as well as indirect C(sp3)-H functionalization via cross-coupling reactions under palladium catalysis. Activated substrates (possessing acidic C(sp3)-H) including enones, ketones, aldehydes, silylenol ethers, esters, silyl ketene acetals, amides, cyano, α-amino esters, and O-carbamates, capable of undergoing cross-coupling reactions at the α-, β-, γ-, δ- and ε-positions, will be discussed. To overcome the challenging task of achieving regioselectivity, a variety of innovative modifications have been reported. The reports of C-H activations based on directing group, and as native functionality have been illustrated at the β-, γ- and δ-positions. Substrates such as α-amino esters, carbonyls, carboxylic acids and their derivatives, afford site-selective C(sp3)-H functionalization via varied-sized reactive metallacycles and are a unique class of substrates whose C(sp3)-H functionalizations were earlier considered as very difficult.