Hui Gao

Selective hydrosilylation of 1,3‐conjugated dienes affords high‐value allylsilanes and homoallylsilanes with broad applications in organic synthesis, pharmaceuticals, and functional materials. Nevertheless, precise chemo‐, regio‐, and stereocontrol remains a fundamental challenge, and conventional noble‐metal catalysts are limited by scarcity and low sustainability. Earth‐abundant metals combined with ligand engineering represent a promising alternative. This review covers 2020–2025 advances in ligand‐controlled hydrosilylation over Fe, Co, Ni, and Cu systems, focusing on structure–selectivity relationships, regulatory mechanisms, remaining challenges and future outlooks.

Enantioselective meta-C─H functionalization of pyridines represents a long-standing challenge that, if resolved, would open transformative avenues in synthesis and drug discovery. Radical-based approaches are particularly attractive yet have remained elusive. We here report a radical enantioconvergent meta-C─H alkylation of pyridines enabled by temporary dearomatization. Our strategy comprises dearomative cycloaddition, nickel-catalyzed enantioselective dehydrogenative coupling of oxazino-pyridines with cyclic β-ketoamides, and acid-mediated rearomatization. Integrated experimental and computational studies support a mechanism based on enantio-determining cross-coupling of simultaneously generated oxazino-pyridine–derived allyl and nickel-bound α-carbonyl radicals. This protocol exhibits high regio- and enantioselectivity, remarkable functional group tolerance, scale-up potential and enables late-stage functionalization of pyridine-containing pharmaceuticals.

Reported is an electrochemical cobalt-catalyzed enantioselective C–H and C–F functionalization with gem -difluoromethylene allenes, providing access to diverse fluoroalkenyl N-heterocycles bearing P-centered, axial, planar, and inherent chirality.

A solvent-free Buchwald–Hartwig N -arylation of benzocyclic amines with (hetero)aryl chlorides was achieved at RT using hindered NHC–Pd catalyst C4 (0.05–4 mol%), giving N -aryl products (79–99%) in 2 h.

The regulation of CO₂ hydroboration selectivity by Lewis acid (LA) additives was investigated using density functional theory (DFT) calculations. This study elucidates the mechanism by which a [Ni]H catalyst mediates the reduction of CO₂ to methanol derivatives. The entire transformation involves three hydride (H^δ-) transfer steps, with the [Ni]H complex actively participating in each step. The catalyst promotes the transfer of H^δ- from pinacolborane (HBPin) to CO₂, formoxyborane (HCOOBPin), and formaldehyde (CH₂O). Direct reaction of HBPin with CO₂ was found to be highly unfavorable. In the absence of the LA, the reaction was reduced only to the level of formic acid; however, in the presence of the LA, the reaction progresses to the methanol. The LA additive facilitates the formation of methoxyborane, a six-electron reduction product. Compared to the unassisted transition state (TS), the LA-assisted transition state (TS-LA) benefits from donor-acceptor interaction between the electron-deficient boron center of Trimethylborate [B(OMe)₃] and the carbonyl oxygen atom. This interaction renders the carbonyl carbon more electron-deficient and thus more electrophilic, promoting H^δ- transfer from [Ni]. The computational results align well with the experimental observations. Overall, the inclusion of LA additives represents a promising strategy to modulate selectivity in CO₂ hydroboration. This approach may be extended to CO₂ hydroboration systems catalyzed by frustrated Lewis pairs or other transition metal catalysts, as well as to CO₂ hydrosilylation reactions.

Thiazolidinediones (TZDs) including rosiglitazone and pioglitazone function as peroxisome proliferator-activated receptor gamma (PPARγ) full agonists, which have been known as a class to be among the most effective drugs for the treatment of type 2 diabetes mellitus (T2DM). However, side effects of TZDs such as fluid retention and weight gain are associated with their full agonistic activities toward PPARγ induced by the AF-2 helix-involved “locked” mechanism. Thereby, this study aimed to obtain novel PPARγ partial agonists without direct interaction with the AF-2 helix. Through performing virtual screening of the Targetmol L6000 Natural Product Library and utilizing molecular dynamics (MD) simulation, as well as molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) analysis, four compounds including tubuloside b, podophyllotoxone, endomorphin 1 and paliperidone were identified as potential PPARγ partial agonists. An in vitro TR-FRET competitive binding assay showed podophyllotoxone displayed the optimal binding affinity toward PPARγ among the screened compounds, exhibiting IC₅₀ and ki values of 27.43 µM and 9.86 µM, respectively. Further cell-based transcription assays were conducted and demonstrated podophyllotoxone’s weak agonistic activity against PPARγ compared to that of the PPARγ full agonist rosiglitazone. These results collectively demonstrated that podophyllotoxone could serve as a PPARγ partial agonist and might provide a novel candidate for the treatment of various diseases such as T2DM.

Merging electrochemistry with asymmetric C−H activation has proven as an advantageous alternative to prepare valuable enantiopure molecules. However, established methods require a stoichiometric use of supporting electrolytes to promote electron transfer in solution and often additionally serve as a base to assist C−H bond cleavage, which are hazardous and would produce additional waste. Herein, we described an exogenous electrolyte- and base-free electrocatalytic atroposelective C–H annulation, providing facile and sustainable access to N–N axially chiral isoquinolinones in excellent enantioselectivities and good yields. This protocol is enabled by a combination of simple Co(OAc)2·4H2O and readily available chiral salicyloxazoline (Salox), proceeds well with 13 classes of alkynes, and tolerates a wealth of functional groups for streamlined transformations.