The reaction site of aryl diazonium salt was restricted in the position of diazonium moiety, due to the intrinsic electrophilicity of diazonium moiety. Herein, we described an unprecedented chemoselective alkylation of Csp2-H of aryl diazonium salts with 1-iodo-3-pentafluorosulfanylbicyclo[1,1,1]pentane (SF5-BCP-I). This novel alkylation of aryl diazonium salts provided an efficient access to various SF5-BCP substituted aromatics that might have great potential application in the drug discovery. Mechanistic experiments and theoretical studies revealed that the intrinsic electrophilic SF5-BCP radical resulted in the thermodynamic favorable radical addition on Csp2-H site rather than diazonium moiety of aryl diazonium salt.

Rationale: Stable isotope-labeled organic compounds, containing D, N-15, or C-13, have widespread applications in chemistry, biology, environmental science, and agriculture. However, the isotopic purity calculations for these labeled organic compounds are usually complicated, especially in mixed isotopes-labeled scenarios. Herein, the electrospray ionization-high-resolution mass spectrometry (ESI-HRMS) was applied to determine the isotopic purity for stable isotope-labeled organic compounds, containing D, N-15, or C-13. Methods: The representative isotopolog ion with its specific molecular formula was proposed to represent various labeled states. The isotopic purity was calculated using the corrected intensities of representative isotopolog ions by removing the natural isotopic contributions from preceding peaks. A unified equation has been proposed for the calculation of isotopic purity for various labeled situations including D, N-15, or C-13. Results: Several case studies were presented and our calculated isotopic purities were all consistent with the isotopic purities provided in the certificate. In-source CID method was applied for the labeled compound (molecular weight > 400 u), when the maximum resolution setting was insufficient to differentiate isobaric isotopolog ions. Conclusion: Finally, a workflow with a Python calculation program was summarized for determinations of the isotopic purity for mono isotope-labeled or mixed isotopes-labeled organic compounds, involving D, N-15, or C-13, by using ESI-HRMS to assign the representative isotopolog ions with accurate mass and excluding the isobar interference.

Selectivity control of the reactions of propargylic and/or allenylic radicals remains particularly elusive. Here, a visible light-mediated Cu-catalyzed protocol for the highly selective syntheses of tri- and tetra-substituted allenols from alkynol derivatives has been developed. The synthetic potential of the products has been demonstrated. The control experiments, Stern-Volmer quenching, and cyclic voltammetry studies support a reaction pathway involving the generation of allenyl radicals via photo-mediated N-O bond scission, an intramolecular 1,5-HAT process, the resonance to propargylic radicals, and coupling. A non-common intramolecular 1,6-HAT process has also been observed.

A class of sulfonium ylide-based reagents for electrophilic deuteriodifluoromethylation is reported. Thus, a wide array of ubiquitous O-nucleophiles such as sulfonic acid, alcohol, carboxyl acid, and phosphoric acid are deuteriodifluoromethylated, providing a straightforward approach to access the OCF2D-functionalizazed scaffolds that are otherwise challenging to synthesize using conventional methods. This base-free protocol also displays broad functional group compatibility and is amenable to effective late-stage modification of bioactive molecules.

Recombinant adeno-associated viral vectors (rAAVs) can effectively deliver transgene to the nervous system. The selection of AAV serotype and promoter significantly influences the dynamics of the transgene expression, including its strength and cell-specificity. Previous studies demonstrated that in neonatal mice, the intramuscular (IM) injection of the rAAV2-retro vector could efficiently deliver transgene to lower motor neurons (LMNs) of the brainstem and spinal cord. However, the best promoter for the expression of transgene in the central neural system (CNS) using rAAV2-retro remains undetermined. This study compared five commonly used promoters, including mouse phosphoglycerate cytomegalovirus (hCMV), chicken (3-actin (CBA), and human synapsin (hSyn) promoters. The IM (unilateral gastrocnemius muscle) injection of rAAV2-retro vectors packaged with the reporter constructs containing each promoter was performed in the newborn C57BL/6J mice. The levels of gene expression and the types of cells were examined using the light-sheet illumination imaging technique and confocal microscopy. Our findings revealed that rAAV2-retro primarily targeted the brainstem and spinal cord within the CNS. Among the five promoters tested, CAG and hCMV showed the highest gene expression. Almost all the transduced cells were identified as LMNs. Additionally, gene expression driven by hCMV was found to be dependent of the inclusion of WPRE and (3-globin intron elements. Importantly, none of the promoters induced hepatotoxicity, ensuring the safety of rAAV2-retro-mediated expression. This study provided valuable insights for optimizing the rAAV2-retro-mediated gene delivery system to LMNs in the brainstem and spinal cord, which might have potential implications for research on motor neuron-related diseases.

Catalytic stereoconvergent coupling of racemic heterobiaryl triflates and aldehydes promoted by a readily available chiral cobalt complex is presented. Such processes represent an unprecedented reaction pathway for cobalt catalysis that enable simultaneous construction of axial and central stereogenicity through diastereo- and enantioselective dynamic kinetic transformations and introduction of a chiral fragment onto the heterobiaryl cores without the requirement of preforming stoichiometric amounts of organometallic reagents, affording densely functionalized secondary alcohols in up to 96 % yield, >98 : 2 dr and >99.5:0.5 er. Preliminary investigations on the application of the products demonstrate their potential for serving as a new class of chiral catalysts and ligands. Mechanistic studies suggest that a dynamic kinetic stereoselective process induced by chiral cobalt catalysis is involved.

The installation of polyfluoroaryl group in functional molecules is of interest due to the presence of polyfluoroarenes in pharmaceuticals, agrochemicals, and advanced materials. Herein, we report the direct coupling of polyfluoroarenes with acylsilanes for synthesis of fluorinated benzylic alcohols in the presence of a catalytic base. This reaction could tolerate a wide range of polyfluoroarenes and polyfluoroheteroarenes, providing an efficient entry to fluoroarylated compounds. Deuteration experiments showed that the hydrogen source in the product was mainly from the polyfluoroarenes. The utility of this method was demonstrated by the derivatization of the product and the synthesis of a fluorinated analogue with antituberculous activity.

The combination of CuI and 4-(dimethylamino)picolinamide offers an effective catalytic system for the successful coupling of (hetero)aryl halides (I and Br) with sulfinamides for the first time. A large number of functional groups and heterocycles were tolerated under the coupling conditions, providing a powerful approach for diverse synthesis of pharmaceutically important (hetero)aryl sulfoximines. The efficiency of the coupling reaction was highly dependent upon the electronic nature of (hetero)aryl halides and the substituents at the amide part of sulfinamides. By using enantioenriched sulfinamides as the coupling partners, the reaction proceeds in a highly stereospecific manner to afford (hetero)aryl sulfoximines with excellent enantioselectivity.

This study explores the application of machine learning to predict the bond dissociation energies (BDEs) of metal-trifluoromethyl compounds. We constructed a dataset comprising 2219 metal-trifluoromethyl BDEs using density functional theory (DFT). Through a comparative analysis of various machine learning algorithms and molecular fingerprints, we determined that the XGBoost algorithm, when combined with MACCS and Morgan fingerprints, exhibited superior performance. To further enhance predictive accuracy, we integrated chemical descriptors alongside multiple fingerprints, achieving an R2 value of 0.951 on the test set. The model demonstrated excellent generalization capabilities when applied to synthesized metal-trifluoromethyl compounds, highlighting the critical role of chemical descriptors in improving predictive performance. This research not only establishes a robust predictive model for metal-trifluoromethyl BDEs but also underscores the value of incorporating chemical insights into machine learning workflows to enhance the prediction of chemical properties.