Unveiling the Twisted Aromatic Donor Effect on the Nonlinear Response of D-π-A Type Malononitrile-Derived Chromophores.

This study presents the design, synthesis, and comprehensive characterization of a novel series of D-π-A type malononitrile-derived chromophores, BTC-1-BTC-4. Combining various spectroscopic techniques, nonlinear Z-scan measurements, and quantum chemical calculations, we revealed the intricate relationship between nonlinear optical properties and the interplay of molecular structure, intramolecular charge transfer (ICT), and dipole moments (µ). Our experimental and computational findings corroborate that the polarization degree in the ground state, the charge separation in the excited state and twisted intramolecular charge transfer (TICT) collectively dictate the nonlinear optical properties of the compounds. Notably, BTC-1 exhibits an exceptional nonlinear absorption coefficient ß value (2×10-8 m W-1), attributed to its optimized charge transfer efficiency and pronounced degree of charge separation. Our findings provide actionable insights for the rational design of high-performance organic Nonlinear optics (NLO) materials with potential applications in advanced photonic devices.

The anti-breast cancer potential of indole/isatin hybrids.

Breast cancer (BC) is one of the most prevalent malignancies and the major contributor to cancer mortality in women globally, with a high degree of heterogeneity and a dismal prognosis. As drug resistance is responsible for most BC fatalities and advanced BC is currently considered incurable, finding innovative anti-BC chemotherapeutics is urgently required. Indole and its analog isatin (indole-1H-2,3-dione) are prominent pharmacophores in the development of novel medications, and their derivatives exhibit strong anticancer activities, also against BC. In particular, indole/isatin hybrids exhibit significant potency against BC including multidrug-resistant forms and excellent selectivity by influencing a variety of biological targets associated with the disease, supplying helpful building blocks for the identification of potential new BC treatment options. This review includes articles from 2020 to the present and provides insights into the in vitro and in vivo anti-BC potential, molecular mechanisms, and structure-activity relationships (SARs) of indole/isatin hybrids that may be helpful in the development of innovative anti-BC chemotherapeutics.

Electrochemical Sulfoxidation of Thiols and Alkyl Halides.

Sulfoxides are actively engaged as versatile synthetic building blocks, chiral ligands, bioactive molecules, and function materials. However, their oxidative syntheses from thioethers are inevitably impeded by overoxidation, excess oxidants, and the tedious preparation of thioethers. To address these shortcomings, we report herein a highly selective electrochemical sulfoxidation reaction featuring the use of simple starting materials, i.e., thiols and alkyl halides, in a single operation.

Electrochemical 5-exo-dig aza-cyclization of 2-alkynylbenzamides toward 3-hydroxyisoindolinone derivatives.

Preparation of biologically relevant 3-hydroxyisoindolinones from readily available 2-alkynylbenzamides is an appealing synthetic approach. However, such kinds of compounds preferably undergo O-attacked 5-exo-dig/6-endo-dig cyclizations. Herein, we report an electrochemically generated amidyl radical proceeding via a highly selective N-attacked 5-exo-dig radical cyclization to form 3-hydroxyisoindolinone derivatives. This reaction features simple operation, good selectivity, and broad substrate scope. Moreover, gram-scale preparation and synthetic elaborations imply the potential applicability of this protocol for the synthesis of diverse isoindolinone derivatives.

Electrochemical Migratory Cyclization of N-Acylsulfonamides.

Benzoxathiazine dioxide, as a bioisostere of the clinically widely used diazoxide, exhibits interesting biological activity. However, limited success has been achieved in terms of its concise and direct synthesis. We report herein a facile electrochemical migratory cyclization of N-acylsulfonamides to access a diverse array of benzoxathiazine dioxides. The inclusion of electrochemistry is crucial for realizing such a novel transformation, which is substantiated both by the experiments and density-functional-theory calculations.

Silver-Catalyzed Asymmetric Dearomatization of Electron-Deficient Heteroarenes via Interrupted Barton-Zard Reaction.

Herein we report a catalytic asymmetric dearomatization reaction of electron-deficient heteroarenes with α-substituted isocyanoacetates through an interrupted Barton-Zard reaction. A range of optically active pyrrolo[3,4-b]indole derivatives was obtained in good yields (up to 97 %) with high stereoselectivities (up to >20:1 dr and 97 % ee), using a catalytic system consisting of a cinchona-derived amino-phosphine and silver oxide. This reaction features wide substrate scope and mild conditions, and provides a new strategy for developing asymmetric dearomatization reactions.

Chiral-at-Metal Rh(III) Complex Catalyzed Cascade Reduction-Michael Addition Reaction.

An enantioselective three-component cascade reduction-Michael addition reaction catalyzed by chiral-at-metal Rh(III) complexes has been developed. With a Hantzsch ester as the hydride source, a number of malononitrile derivatives were prepared in good yields and excellent enantioselectivities. A model that accounts for the origin and influence factors of the stereoselectivity has been proposed based on experiments.

Ferrocene-Alkynyl Conjugated Molecular Wires: Synthesis, Characterization, and Conductance Properties.

A novel series of 1,2,3-substituted ferrocene-based wires a1-a2 and b4-b5 have been synthesized by using an iterative Pd-mediated Sonogashira cross-coupling methodology. The molecular structures of a2 and b3 were determined by single-crystal X-ray analysis. Electrochemical data showed that there was a strong electronic communication among the ferrocenyl moieties in b1-b5. The UV absorption spectra indicated that replacing the 1,1'-substituted ferrocene unit with a 1,2,3-substituted ferrocene moiety causes delocalization of electrons in the extended π orbitals. The self-assembled monolayers of wire a1 and a2 on Au surfaces have been comprehensively characterized by electrochemistry and scanning tunneling microscopy break junction. The data demonstrated that 1,2,3-substituted ferrocene-based wires reduced the intermolecular π-π stacking, and furthermore solved the rotation problem in the 1,1'-substituted ferrocene-based wires.

Pd-Catalyzed Arylperfluoroalkylation of Unactivated Olefins for the Synthesis of Heterocycles.

An efficient and highly practical palladium-catalyzed arylperfluoroalkylation of unactivated olefins is presented here. A variety of perfluoroalkylated heterocyclic derivatives can be obtained in high regioselectivity. The reaction proceeds mildly without the electronic activation of the aryl group and features high generality, low-cost fluoroalkylated sources and good functional-group compatibility.

Radical Desulfur-Fragmentation and Reconstruction of Enol Triflates: Facile Access to α-Trifluoromethyl Ketones.

We report an efficient oxidative radical desulfur-fragmentation and reconstruction of enol triflates for the synthesis of α-CF3 ketones. Preliminary mechanistic studies disclosed that oxidative fragmentation to release a CF3 radical from the triflyl group of enol triflate and subsequent addition of the CF3 radical to another enol triflate form the desired α-CF3 ketones. This method provides a new approach to α-CF3 ketones, featuring the utilization of catalytic amount of oxidants, broad substrate scope, and potential to control the regioselectivity.

Dynamic Aminal-Based TPA Ligands.

The use of dynamic covalent reactions (DCRs) is gaining popularity for the construction of self-assembling architectures. We have recently introduced DCRs that exchange alcohols and aldehydes to create hemiaminal ethers within tri(2-picolyl)amine (TPA) ligands, all of which are templated by Zn(II). To expand the scope of this assembly, aromatic imines derived from pyridine-2-carboxyaldehyde were explored as dynamic covalent receptors for di(2-picolyl)amine in the presence of Zn(II) to create TPA ligands that contain aminal linkages. This represents another metal-templated in situ multicomponent assembly. The stability of the assembly was successfully modulated through substituent effects, and the equilibrium constants from imines to aminals were correlated by a linear free energy relationship (LFER) with σ(+) values. Dynamic component exchange was investigated as a means of probing multiple equilibriums quantitatively in the system. Further, the mechanism was analyzed with a qualitative kinetics study. NMR spectra reveal the different extents of two competing pathways for assembly depending upon whether the aromatic amine has electron-withdrawing or electron-donating groups on the ring. Finally, mass spectral evidence supports the presence and differing extents of dominance of the two pathways as a function of the substituents.

Synthesis of Cu(I) trifluoromethylselenates for trifluoromethylselenolation of aryl and alkyl halides.

The development of new strategies for synthesis of trifluoromethylthiolate compounds is of considerable importance in pharmaceuticals, agrochemicals, and advanced materials. Accordingly, currently much attention is being devoted to the development of effective methods and reagents for their synthesis. In contrast, considerably less effort has been afforded to the development of preparing CSeCF3 bonds. Herein we report a concise route to synthesize a family of copper(I) trifluoromethylselenolate reagents by the reaction of CuI with the Ruppert's reagent (Me3 SiCF3 ), KF, and elemental selenium in the presence of dinitrogen ligands in CH3 CN at room temperature. The reagent [Cu(bpy)(SeCF3 )]2 was proven to be air-stable and highly efficient for nucleophilic trifluoromethylthselenolation of a broad range of (hetero)aryl halides and alkyl halides. This method represents a powerful protocol for the construction trifluoromethylselenolate compounds.

Efficient C(sp3alkyl)-SCF3 bond formations via copper-mediated trifluoromethylthiolation of alkyl halides.

A general and convenient copper-mediated trifluoromethylthiolation of primary and secondary alkyl halides was described. Variation of the solvent, additives and time allowed optimization of the reaction. A wide range of alkyl halides were explored to give a set of alkyl trifluoromethyl thioethers in moderate to excellent yields. A variety of functional groups, including ethers, thioether, esters, nitriles, amides, and ketal groups, were well tolerated in the electrophilic partner.

The synthesis and application of o-carborane-based macrocyclic arenes.

Two o-carborane-hybridized macrocyclic arenes have been synthesized via Friedel-Crafts alkylation of carborane diaryl derivatives. The single-crystal X-ray diffraction analysis clearly revealed their cavity structure and intermolecular interaction force. These novel macrocycles exhibited aggregation-induced luminescence and intramolecular charge transfer properties and also significant selectivity towards nitro explosive compounds. This work provided a method for the synthesis of hybridized macrocyclic arenes.

Electrochemical cascade migratory versus ortho-cyclization of 2-alkynylbenzenesulfonamides.

Efficient control over several possible reaction pathways of free radicals is the chemical basis of their highly selective transformations. Among various competing reaction pathways, sulfonimidyl radicals generated from the electrolysis of 2-alkynylbenzenesulfonamides undergo cascade migratory or ortho-cyclization cyclization selectively. It is found that the incorporation of an extra 2-methyl substituent biases the selective migration of the acyl- over vinyl-linker of the key spirocyclic cation intermediate and thus serves as an enabling handle to achieve the synthetically interesting yet under-investigated cascade migratory cyclization of spirocyclic cations.

Electrochemical synthesis of vicinal azidoacetamides.

Vicinal diamines are an important structural motif in bioactive natural products and pharmaceutical intermediates. Herein, an environmentally friendly and efficient electrochemical approach to azidoacetamides, as one variant of vicinal diamines, has been developed. This reaction features mild conditions and broad substrate scope, without the use of any chemical oxidant or transition-metal catalysts. The obtained vicinal azidoacetamides could be conveniently converted into various other vicinal diamine derivatives.

Two-carbon tethered artemisinin-isatin hybrids: design, synthesis, anti-breast cancer potential, and in silico study.

Eleven two-carbon tethered artemisinin-isatin hybrids (4a-k) were designed, synthesized, and evaluated for their antiproliferative activity against MCF-7, MDA-MB-231, and MDA-MB-231/ADR breast cancer cell lines, as well as cytotoxicity toward MCF-10A cells in this paper. Among them, the representative hybrid 4a (IC50: 2.49-12.6 µM) was superior to artemisinin (IC50: 72.4->100 µM), dihydroartemisinin (IC50: 69.6-89.8 µM), and Adriamycin (IC50: 4.46->100 µM) against the three tested breast cancer cell lines. The structure-activity relationship revealed that the length of the alkyl linker between artemisinin and isatin was critical for the activity, so further structural modification could focus on evaluation of the linker. The in silico studies were used to investigate the mechanism of the most promising hybrid 4a. Target prediction, bioinformatics, molecular docking, and molecular dynamics revealed that the most promising hybrid 4a may exert anti-breast cancer activity by acting on multiple targets such as EGFR, PIK3CA, and MAPK8 and thus participating in multiple tumor-related signaling pathways.

Electrochemical Dearomative Spirocyclization.

Electrochemical dearomative spirocyclization serves as a green and sustainable approach to convert the flat, two-dimension aromatic feedstock into the value-added three-dimension spirocyclic architectures. This review highlights the recent advances, emphasizes mechanistic discussions, and showcases synthetic applications of this emerging versatile and powerful transformation.

Conductance of o-carborane-based wires with different substitution patterns.

Here, we report the synthesis, structure, and single-molecule conductance of three o-carborane-based molecular wires (ortho-, meta- and para-CN) with multiple conduction channels. The effect of connectivity in target wires compared with the corresponding phenyl-centered wires was studied using the scanning tunneling microscope break junction (STM-BJ) technique and theoretical calculations. Interestingly, the three-dimensional structure in o-carborane-based wires can effectively promote the through-space transmission paths or the formation of stable molecular junctions compared to the corresponding phenyl-centered wires. Moreover, the significant conductance difference of o-carborane-based wires was due to the combination of multiple conduction channels and quantum interference. Understanding the effects of different bridging groups and anchor group substitution patterns provides guidelines for designing o-carborane-based multichannel molecular wires.

An electrochemical multicomponent reaction toward C-H tetrazolation of alkyl arenes and vicinal azidotetrazolation of alkenes.

The widespread use of tetrazoles in medicine, biology, and materials science continuously promotes the development of their efficient and selective syntheses. Despite the prosperous development of multicomponent reactions, the use of the most abundant and inexpensive chemical feedstocks, i.e., alkanes and alkenes, toward the preparation of diverse tetrazoles remains elusive. Herein, we developed an electrochemical multicomponent reaction (e-MCR) for highly efficient and selective C-H tetrazolation of alkyl arenes. When applied to alkenes, the corresponding vicinal azidotetrazoles were readily obtained, which were further demonstrated to be versatile building blocks and potential high-energy materials.