Enantioselective functionalizations of unbiased methylene C(sp )-H bonds of linear systems by metal insertion are intrinsically challenging and remain a largely unsolved problem. Herein, we report a palladium(II)-catalyzed enantioselective arylation of unbiased methylene β-C(sp )-H bonds enabled by the combination of a strongly coordinating bidentate PIP auxiliary with a monodentate chiral phosphoric acid (CPA). The synergistic effect between the PIP auxiliary and the non-C -symmetric CPA is crucial for effective stereocontrol. A broad range of aliphatic carboxylic acids and aryl bromides can be used, providing β-arylated aliphatic carboxylic acid derivatives in high yields (up to 96 %) with good enantioselectivities (up to 95:5 e.r.). Notably, this reaction also represents the first palladium(II)-catalyzed enantioselective C-H activation with less reactive and cost-effective aryl bromides as the arylating reagents. Mechanistic studies suggest that a single CPA is involved in the stereodetermining C-H palladation step.

A general and practical PdII‐catalyzed intermolecular silylation of primary and secondary C−H bonds of α‐amino acids and simple aliphatic acids is reported. This method provides divergent and stereoselective access to a variety of optical pure β‐silyl‐α‐amino acids, which are useful for genetic technologies and proteomics. It can also be readily performed on a gram scale and the auxiliary can be easily removed with retention of configuration. The synthetic importance of this method is further demonstrated by the late‐stage functionalization of biological small molecules, such as (−)‐santonin and β‐cholic acid. Moreover, several key palladacycles were successfully isolated and characterized to elucidate the mechanism of this β−C(sp3)‐H silylation process.

The first Pd(II)-catalyzed enantioselective alkynylation of unbiased methylene β-C(sp 3 )−H bonds is reported. The readily accessible and tunable BINOL derivatives are used as chiral ligands in C−H activation for the first time. 3,3′-Fluorinated-BINOL proved crucial in determining both the reactivity and enantioselectivity. A wide range of carboxylic acid derivatives are well tolerated with high enantioselectivities (up to 96% ee). Mechanistic studies suggest that multiple ligands may participate in the stereodetermining C−H palladation step, and a chiral amplification effect is observed.

The first nickel-catalyzed thiolation of unactivated C(sp(3))-H bonds with disulfides was described. This transformation uses (dppp)NiCl2 as a catalyst and BINOL as a ligand, which are efficient for the thiolation of β-methyl C(sp(3))-H bonds of a broad range of aliphatic carboxamides. The reaction provides an efficient synthetic pathway to access diverse thioethers.

A mild Co(III)-catalyzed oxidative annulation of N-arylureas and internal alkynes has been developed. The use of less electrophilic ureas other than acetamides as directing groups is crucial for the reaction. A broad range of synthetically useful functional groups are compatible with this reaction, thus providing a new opportunity for the synthesis of diverse indoles.