A highly effective protocol for the synthesis of C-3-substituted prolines has been developed. Pd-catalyzed C(sp³)–H activation is used for the straightforward functionalization of prolines. The use of an 8-aminoquinolinecarboxamide directing group allows direct arylation, alkenylation, and alkylation at the C-3 position of prolines in moderate to high yields with diverse iodo- or bromo precursors. The resulting 3-substituted proline derivatives are important units in many biologically active compounds and are useful promoters for a variety of functional group transformations.

An efficient Rh^III-catalyzed ortho-C–H bond activation for the synthesis of substituted isoquinolines and heterocycle-fused pyridines in aqueous medium has been developed. This method involves the in situ generation of ketimines from ketones and ammonium acetate and subsequent oxidative C–H bond activation/annulation of ketimines with alkynes to form the C–C/C–N bonds spontaneously. Various aryl ketones and internal alkynes were smoothly transformed into the desired heterocycles in moderate to excellent yields. The reaction exploits molecular oxygen as the sole oxidant by producing water as the only byproduct. Moreover, easily available NH₄OAc was utilized as the nitrogen source, which makes this protocol practical and environmentally friendly.

An effective copper-mediated synthesis of 1,5-dialkyl-4-aryl-1,2,3-triazoles and 1,4-dialkyl-5-aryl-1,2,3-triazoles has been achieved by the use of different N-tosylhydrazones and alkyl amines. The scope of the substrates could be extended from anilines to aliphatic amines when 30 mol % amino acid is added into the reaction mixture. This methodology exhibits many notable features, such as broad substrates scope, high efficiency, and good regioselectivity. Preliminary mechanistic studies indicated that the reaction probably proceeded through a 1-tosyl-2-vinyldiazene intermediate and subsequent aza-Michael addition and NN bond formation process.

A novel synthetic approach toward 1,4-disubstituted 1,2,3-triazoles by CN- and NN-bond formation has been established under transition-metal-free conditions. Complete control of the regioselectivity was successfully achieved. Commercially available anilines, ketones, and N-tosylhydrazine were treated with molecular iodine in one pot to allow the regioselective generation of 1,4-disubstituted 1,2,3-triazoles in high yields without the use of azides.

An efficient palladium-catalyzed decarboxylative ortho-acylation of 2-aryloxypyridines with α-oxocarboxylic acids is described. In this new transformation, the aromatic C(sp²)H bond was successfully acylated to give diverse aromatic ketones regioselectively in moderate to good yields. The pyridine group can be removed easily after the acylation to give the corresponding 2-hydroxy aromatic ketones.

Palladium(II)-catalyzed arylation of arenes with aryl boronic acids and a free amine as directing group in aqueous medium has been developed. High reactivity and chemoselectivity for the formation of carbon–carbon bonds were achieved by the use of soluble silver salts. The addition of water is crucial to improve the arylation yield.

A series of unusual six-ring-fused heterocycles containing indole and quinoline skeletons was successfully synthesized by a copper-catalyzed reaction from 2-arylated indoles. Two new bonds were regioselectively formed from CH and CH coupling. ¹⁸O-Labelled experiments revealed that the dioxygen is not only the oxidant but also the reactant.

Thioethers have proven to be efficient directing groups for the arylation of arenes under palladium catalysis. The thioether group can be readily removed or converted to other functional groups. Kinetic isotopic effect studies reveal that the CH cleavage of arenes might be the turnover-limiting step.

A new protocol for the palladium-catalyzed free-amine-directed alkenylation of C(sp²)H bonds and cycloamination is described. Substituted biaryl-2-amines react with various alkenes, including electron-deficient alkenes, aryl alkenes and alkyl alkenes, to give the corresponding phenanthridines with exclusive regioselectivity. The use of α-branched styrenes leads to the formation of tricyclic compounds with a seven-membered amine ring. The method operates through a free-amine-directed alkenylation and a subsequent hydroamination cyclization reaction.

Palladium-catalyzed direct mono- and diarylations involving C(sp³)H cleavage at the γ-position of acrylamides are described. The monoarylation products can be obtained with ortho-substituted aryl halides. Single crystal X-ray diffraction has shown that the double bond has shifted towards the introduced aryl group to afford the γ-arylated β,γ-unsaturated amide products. A second arylation occurs when less sterically hindered aryl halides are employed. This chemistry offers a novel disconnection for the synthesis of γ-arylated compounds.