Modern Trends of Organic Chemistry in Russian Universities

© 2018, Pleiades Publishing, Ltd. This review is devoted to the scientific achievements of the departments of organic chemistry in higher schools of Russia within the past decade

Pushing the boundaries of C–H bond functionalization chemistry using flow technology

\u3cp\u3eC–H functionalization chemistry is one of the most vibrant research areas within synthetic organic chemistry. While most researchers focus on the development of small-scale batch-type transformations, more recently such transformations have been carried out in flow reactors to explore new chemical space, to boost reactivity or to enable scalability of this important reaction class. Herein, an up-to-date overview of C–H bond functionalization reactions carried out in continuous-flow microreactors is presented. A comprehensive overview of reactions which establish the formal conversion of a C–H bond into carbon–carbon or carbon–heteroatom bonds is provided; this includes metal-assisted C–H bond cleavages, hydrogen atom transfer reactions and C–H bond functionalizations which involve an S\u3csub\u3eE\u3c/sub\u3e-type process to aromatic or olefinic systems. Particular focus is devoted to showcase the advantages of flow processing to enhance C–H bond functionalization chemistry. Consequently, it is our hope that this review will serve as a guide to inspire researchers to push the boundaries of C–H functionalization chemistry using flow technology.\u3c/p\u3

Mild and selective base-free C–H arylation of heteroarenes:experiment and computation

A mild and selective C–H arylation strategy for indoles, benzofurans and benzothiophenes is described. The arylation method engages aryldiazonium salts as arylating reagents in equimolar amounts. The protocol is operationally simple, base free, moisture tolerant and air tolerant. It utilizes low palladium loadings (0.5 to 2.0 mol% Pd), short reaction times, green solvents (EtOAc/2-MeTHF or MeOH) and is carried out at room temperature, providing a broad substrate scope (47 examples) and excellent selectivity (C-2 arylation for indoles and benzofurans, C-3 arylation for benzothiophenes). Mechanistic experiments and DFT calculations support a Heck–Matsuda type coupling mechanism

Decatungstate‐mediated C(sp3)‒H Heteroarylation via Radical‐Polar Crossover in Batch and Flow

Photocatalytic hydrogen atom transfer is a very powerful strategy for the regioselective C(sp(3))–H functionalization of organic molecules. Herein, we report on the unprecedented combination of decatungstate hydrogen atom transfer photocatalysis with the oxidative radical–polar crossover concept to access the direct net‐oxidative C(sp(3))–H heteroarylation. The present methodology demonstrates a high functional group tolerance (40 examples) and is scalable when using continuous‐flow reactor technology. The developed protocol is also amenable to the late‐stage functionalization of biologically relevant molecules such as stanozolol, (−)‐ambroxide, podophyllotoxin, and dideoxyribose

A First-in-Class β-Glucuronidase Responsive Conjugate for Selective Dual Targeted and Photodynamic Therapy of Bladder Cancer

In this report, we present a novel prodrug strategy that can significantly improve the efficiency and selectivity of combined therapy for bladder cancer. Our approach involved the synthesis of a conjugate based on a chlorin-e6 photosensitizer and a derivative of the tyrosine kinase inhibitor cabozantinib, linked by a β-glucuronidase-responsive linker. Upon activation by β-glucuronidase, which is overproduced in various tumors and localized in lysosomes, this conjugate released both therapeutic modules within targeted cells. This activation was accompanied by the recovery of its fluorescence and the generation of reactive oxygen species. Investigation of photodynamic and dark toxicity in vitro revealed that the novel conjugate had an excellent safety profile and was able to inhibit tumor cells proliferation at submicromolar concentrations. Additionally, combined therapy effects were also observed in 3D models of tumor growth, demonstrating synergistic suppression through the activation of both photodynamic and targeted therapy

The Cation Effect on the Free Volume and the Solubility of H₂S and CO₂ in Ionic Liquids Based on Bis(2-Ethylhexyl) Sulfosuccinate Anion

Herein, we report for the first time a study dedicated to acidic gases’ solubility in ionic liquids with sterically hindered bulky anion, namely bis(2-ethylhexyl) sulfosuccinate ([doc]), experimentally evaluated at low pressures. The effect of cation change (imidazolium, pyridinium, and pyrrolidinium) on the thermophysical properties and sorption capacities was also discussed. The densities and the activation energies of the tested ILs exhibited minor differences. Furthermore, the COSMO-RS model was used to predict the free volumes of ILs aiming to investigate its influence on gas solubilities. The conducted calculations have revealed an antibate correlation between the fractional free volume (FFV) and Henry’s law constant. In particular, the lowest FFV in 1-methylimidazolium [doc] corresponded to the minimal sorption and vice versa. In addition, it was shown that the presence of protic cation results in a significant reduction in CO2 and H2S solubilities. In general, the solubility measurement results of the synthesized ILs have shown their superiority compared to fluorinated ILs based on the physical absorption mechanism