Guosheng Liu

Asymmetric catalytic hydroamination of alkenes represents one of the most efficient strategies for constructing chiral N-heterocycles. Herein, we realize the asymmetric intramolecular remote hydroamination of internal cis-alkenes via palladium catalysis. The reaction proceeds through sequential alkene aminopalladation, palladium migration, and reduction of terminal alkyl-palladium intermediates. The corresponding nitrogen-containing heterocycles are furnished in good yields with high enantioselectivity, offering a straightforward and robust route to the synthesis of piperidone, pyrrolidone, and oxazolidin-2-one scaffolds. Detailed mechanistic studies disclose that the stereochemical outcome and reversibility of aminopalladation are strongly solvent-dependent. Furthermore, the reduction of the alkyl–Pd(II) bond is highly susceptible to steric hindrance, which enables the achievement of remote asymmetric hydroamination.

The first copper-catalyzed enantioselective allylic C-H cyanation of electron-deficient alkenes was established herein. With a sequential catalytic hydrogenation in a one-pot fashion, the current method provides easy access to structurally diverse γ-cyanated carbonyls in good yields with excellent enantioselectivity, which are difficult to synthesize by the previously reported methods. Additional mechanistic investigations of the controlling experiments, kinetic study, isotopic effect, and DFT calculations revealed a new reaction pathway. We found that the previously reported Cu(II)-bound N-centered radical (NCR) undergoes dissociation in polar solvents to generate a free NCR species. This free sulfonamidyl radical, derived from the NF reagent, has a greater hydrogen-atom abstraction (HAA) ability, which is crucial for the successful allylic C-H abstraction of electron-deficient alkenes. Although the off-cycle existed to quench free NCR species by the extra Cu(I) catalyst, this side reaction can be effectively suppressed by reducing the catalyst concentration. Therefore, highly selective and efficient allylic C-H cyanation of electron-deficient alkenes could be achieved by using a low catalyst loading (0.25 mol %). These findings highlight the method to adjust the interaction between the copper(II) intermediate and free NCRs, which opens a window to carry out asymmetric C-H bond functionalization reactions across a range of substrate types.

Carboxylic acids are important chemical feedstocks, and direct decarboxylative asymmetric transformation holds significant synthetic value. Herein, we report a copper‐catalyzed direct enantioselective decarboxylative cyanation of benzyl carboxylic acids under electrophotocatalytic conditions. Benzylic radicals are efficiently generated via ligand–to–metal charge transfer of copper(II) carboxylate species under irradiation of blue LEDs. Concurrently, the generation of copper(II) cyanide occurred simultaneously at the anode via electro‐oxidation, avoiding the use of the stoichiometric amount of chemical oxidants. Then the coupling of benzylic radical and chiral Cu(II) cyanide leads to enantioselective decarboxylative cyanation. This reaction features a broad substrate scope and excellent functional group tolerance, enabling the direct conversion of carboxylic acids into diverse chiral benzyl nitriles.

Herein, we established a copper-catalyzed asymmetric alkynylation of the sp² C-H bond of silylallenes, which was presented as an efficient method for the synthesis of enantioenriched skipped diynes with excellent enantioselectivity. The reaction was initiated by hydrogen atom abstraction of sp² allenic C-H bonds, in which the resonance forms of allenic and propargylic radicals were chemo- and enantioselectively trapped by chiral alkynyl-Cu(II) species to deliver a variety of skipped diynes. The method features a broad substrate scope and robust functional group tolerance, accommodating both alkynyl silanes and boronic esters. Moreover, the resulting skipped diynes serve as versatile key synthons for incorporating enantiomerically enriched enynes, alkynes, alkanes, and their derivatives, which could be applied in the concise synthesis of several bioactive molecules.

Asymmetric allylic C(sp³)-H oxidation of terminal alkenes provides a streamlined process for accessing allylic alcohols and their derivatives; however, it represents a long-standing challenge in the field for several decades. Herein, we disclosed a copper-catalyzed approach for the enantioselective allylic C(sp³)-H oxidation of terminal alkenes, facilitated by introducing a sterically bulky B₂Im(C₆F₅)₆ anion. Notably, a wide range of aryl-substituted terminal alkenes were used as limiting reagents, delivering various products with excellent enantioselectivity and regioselectivity (up to 99% ee, >20:1 b/l). Mechanistically, the bulky counteranion was found to be essential for achieving excellent enantioselective control and high catalytic efficiency.

Selective transformation of C–H bonds represents a frontier research area in synthetic chemistry. While the high reactivity of radicals provides an alternative and efficient pathway for C–H bond functionalization, controlling their selectivity─particularly in processes such as site-selective hydrogen atom abstraction (HAA)─remains a long-standing and unresolved challenge in radical chemistry, largely due to the lack of effective regulation strategies. This review deliberately avoids a comprehensive discussion of the field’s current state or landmark discoveries in C–H functionalization. Instead, by focusing on recent advances in metal-catalyzed, highly site-selective C–H bond transformations, this Perspective elucidates how metal-bound radicals enable precise hydrogen abstraction for targeted functionalization. This emerging paradigm offers innovative strategies for regulating radical behavior, potentially unlocking novel radical-mediated selective transformations─including but not limited to the precise functionalization of C–H bonds.