Chiral sulfilimines, the aza-analogues of sulfoxides, represent versatile synthetic intermediates and privileged structural motifs found in various bioactive molecules. Nevertheless, the catalytic enantioselective synthesis of sulfilimines remains a formidable challenge. While asymmetric S-functionalization of sulfenamides offers an attractive alternative, previous methodologies have predominantly relied on polar mechanisms with preactivated coupling partners. Herein, we report a direct and robust strategy for the asymmetric construction of chiral sulfilimines via copper-catalyzed enantioselective remote benzylic C-H sulfilimination of N-fluorocarboxamides using readily accessible sulfenamides as both sulfur and nitrogen sources. The success of this approach relies on the formation of a Cu-sulfinimidoyl intermediate through S(II)/S(IV) tautomerization, which facilitates single-electron reduction of the N-fluoro-carboxamide followed by an enantio-determining C-S bond formation. Furthermore, cyclobutanone oxime esters are also compatible substrates under this newly developed protocol, enabling enantioselective remote sulfilimination via iminyl radical-induced beta-C-C bond cleavage. This methodology constitutes the first example of enantioselective C-H or C-C sulfilimination via a radical pathway, offering a complementary and orthogonal alternative to conventional polar mechanisms, thereby establishing a new paradigm in asymmetric sulfilimination chemistry.
The self-assembly reaction of 2-benzylaminoethanol (Hbae) with CuCl2 or Cu(NO3)2 leads to the formation of binuclear [Cu2(bae)2(Cl)2] (1) and [Cu2(Hbae)2(bae)2](NO3)2 (2) complexes, while the trinuclear [Cu3(Hbae)2(bae)2(dmba)2](NO3)2 (3) compound was obtained using the auxiliar bulky substituted 2,2-dimethylbutyric acid (Hdmba). Crystallographic studies reveal the molecular structures of 1 and 2 based on the similar {Cu2(μ-O)2} core, while the structure of 3 features the {Cu3(μ-O)2} core with consecutive arranement of the metal centres, supported by the additional carboxylate bridges. The strong intermolecular hydrogen bonds join the molecular structures into 1D (for 1 and 3) or 2D (for 2) architectures. All three compounds act as catalysts for the aerobic oxidation of 2-aminophenol to the phenoxazinone chromophore (phenoxazinone synthase-like activity) with the maximum reaction rates up to 2.3×10-8 M s-1. The substrate scope involves methyl-, nitro- and chloro-substituted 2-aminophenols, disclosing the negligible activity of nitro-derivatives, while the 6-amino-m-cresol substrate shows the highest activity with the initial reaction rate of 5.8×10-8 M s-1. The mechanism of the rate-limiting reaction step (copper-catalysed formation of 2-aminophenoxyl radicals) was investigated at the DFT level. The combined DFT and CASSCF studies of the copper superoxo CuII-OO⋅ radical species as possible unconventional reaction intermediates resulted in a rational mechanism of H-atom abstraction, where the activation energies follow the experimental reactivity of substituted 2-aminophenols. The TDDFT and STEOM-DLPNO-CCSD theoretical calculations of the absorption spectra of substrates, phenoxazinone chromophores and putative polynuclear species containing 2-aminophenoxo ligand are reported.
Amide-amide, acid-amide, and acid-pyridine synthons are among the most effective hydrogen-bonded building blocks in multicomponent drug systems. In this work, a conformationally flexible compound with prolific polymorphism was chosen as a carboxylic acid model drug, combined with three pyridinecarboxamide positional isomers as co-formers-picolinamide, nicotinamide, and isonicotinamide. Quench-cooling molten mixtures with different molar ratios produced binary coamorphous systems. Their thermal stability was dependent on the heating rate, relaxing to equimolar cocrystals with picolinamide and isonicotinamide, also obtained by mechanochemistry. Contrarily, both methods could only produce physical mixtures with nicotinamide. Thermal analysis and X-ray diffraction were used to characterize the crystalline phases. Furthermore, the molecular dynamics of the pure compounds and binary phases were studied by dielectric spectroscopy, while the main intermolecular interactions were investigated by FTIR-ATR and computational methods based on DFT calculations-molecular electrostatic potential, NBO, and IGM-delta g analyses. The acid hydroxyl group was the strongest hydrogen bond donor, and the amide carbonyl group was the best acceptor. However, the synthon competition outcome was found to depend on the pyridinecarboxamide isomer, with picolinamide having a more different behavior because of electronic and steric effects. Experimental and computational results suggest an acid-amide synthon in the nateglinide-picolinamide cocrystal, which was fully confirmed by single-crystal X-ray diffraction.
Two major factors governing the spin crossover (SCO) behavior are the electronic and steric aspects of the ligand. The electronic effects directly alter the energy gap between the frontier molecular (t2g and eg) orbitals, whereas the steric effects can lead to a distorted structure, which then can change the electronic properties of the complex, leading to a change in the spin state. Here, we investigated how the steric modulation of the ligand by its peripheral modification affects the spin states of the corresponding Fe(III) complexes. We chose three different amines, N-ethylethylenediamine, N-phenylethylenediamine, and N-benzylethylenediamine, and condensed them with salicylaldehyde and 3-methoxysalicylaldehyde to afford the corresponding Schiff base ligands, HL1, HL3, and HL2, respectively. Interaction of these ligands with Fe(III) salts afforded [Fe(L1)2]NCS (1), [Fe(L2)2NCS]H2O (2H 2 O), and [Fe(L3)2]NCS (3), respectively. 3-Methoxysalicylaldehyde with N-phenylethylenediamine afforded ligand HL2 and complex 2H 2 O. 1 and 3 exhibit SCO behavior, while complex 2H 2 O remains in the high spin state. These results were rationalized by a combination of experimental and theoretical studies.
Global dependence on fossil fuels raises environmental and energy concerns, encouraging the search for renewable sources, such as biodiesel. However, their limited oxidative stability compromises their commercial viability. This study investigates two pyrazoline analogues (CNF and CNO) as potential antioxidant additives for biodiesel using a combined molecular modeling and machine learning approach. Supramolecular analysis revealed that C-H···O and C-H···π interactions influence molecular stability. Chemical reactivity descriptors indicated that the methoxy group (-OCH3) in CNO enhances the electron-withdrawing effect, making it more susceptible to oxidation. Kinetic evaluation predicted that both compounds have intermediate oxidation rates when exposed to hydroxyl radicals, with a performance comparable to widely used commercial antioxidants. These results suggest that pyrazoline analogues are promising candidates to mitigate the oxidative degradation of biodiesel, contributing to the greater efficiency and sustainability of biofuels.
