Hydride-Abstraction-Initiated Catalytic Stereoselective Intermolecular Bond-Forming Processes.

ConspectusThe stereoselective intermolecular bond-forming reactions through the direct manipulation of ubiquitous yet inert C(sp 3 )-H bonds represent an important and long-standing goal in chemistry. In particular, developing such a stereoselective bimolecular transformation involving carbocation intermediates generated via site-selective hydride abstraction or formal hydride abstraction by organic oxidants would avoid the preinstallation of directing groups and is therefore attractive. Hydride-abstraction-initiated bimolecular transformations have received considerable attention, but existing examples lack stereoselective studies. Prevalent stereoselective studies typically suffer from the narrow substrate scope of specific and highly reactive N -aryl amines and diarylmethanes together with limited synthetic utility. This Account describes our recent advances in the development and synthetic application of hydride-abstraction-initiated stereoselective intermolecular C-C and C-H bond-forming processes with significantly expanded scopes involving structurally diverse N -acyl amines and ethers together with nitriles, esters, and perfluoroalkyl moieties.We first explored hydride-abstraction-initiated stereoselective intermolecular C-C bond-forming processes. Utilizing triarylmethyl cations or oxoammonium ions as hydride abstractors, we accomplished the diastereoselective oxidative C-H functionalization of structurally diverse N -acyl amines and ethers with a range of organoboranes and C-H components, efficiently installing a series of alkyl, alkenyl, aryl, and alkynyl species into the α-position of heteroatoms with good levels of diastereocontrol. Subsequently, we developed an "acetal pool" strategy as the toolbox to regulate the stability of cationic intermediates and the compatibility of organic oxidants with a delicate asymmetric catalysis system. Utilizing this strategy, we achieved the catalytic enantioselective oxidative C-H alkenylation, arylation, alkynylation, and alkylation of diverse N -acyl heterocycles with a range of boronates and C-H components. Simultaneously, we extended this strategy to the asymmetric oxidative C-H alkylation of ethers. Notably, the method allows solvents that are used daily, such as tetrahydrofuran, tetrahydropyran, and diethyl ether, to be facilely transformed to high-value-added optically pure bioactive molecules. We further expanded the scope of this challenging area from the C(sp 3 )-H bond adjacent to electron-donating heteroatoms to valuable electron-withdrawing functional groups including nitriles, esters, and perfluoroalkyl moieties for the stereoselective construction of single and vicinal quaternary carbon stereocenters, respectively.We studied hydride-abstraction-initiated catalytic asymmetric intermolecular C-H bond-forming processes, known as redox deracemization. Utilizing the acetal pool strategy, we reported the first redox deracemization of cyclic benzylic ethers. Later, we disclosed an aerobic one-pot deracemization of diverse α-amino acid derivatives with excellent functional group compatibility. We further achieved the deracemization of the tertiary stereogenic center adjacent to electron-withdrawing groups including perfluoroalkyl, cyano, and ester moieties, which are otherwise difficult to construct.