Lewis Acidic Ionic-Liquid-Catalyzed Radical-Cascade Alkylation/Cyclization of -Alkyl--methacryloyl Benzamides with Alkanes via Visible-Light-Induced Ligand-to-Metal Charge Transfer: Access to Alkylated Isoquinoline-1,3(2,4)-diones.

With the flourishing progress of ligand-to-metal charge transfer (LMCT) photocatalysis, various metals were developed as catalysts to activate abundant alkane feedstocks for the synthesis of functionalized organic compounds. However, to the best of our knowledge, most of the LMCT catalysts are difficult to recover and reuse for the next cycles. Herein, we report a reusable Lewis acidic ionic liquid (LAIL)-catalyzed radical-cascade alkylation/cyclization of -alkyl--methacryloyl benzamides with unactivated alkanes for the synthesis of alkylated isoquinoline-1,3-(2,4)-diketones.

Asymmetric α-Allylation of Amino Acid Esters with Alkynes Enabled by Chiral Aldehyde/Palladium Combined Catalysis.

A highly efficient, atom-economical α-allylation reaction of NH-unprotected amino acid esters and alkynes is achieved by chiral aldehyde/palladium combined catalysis. A diverse range of α,α-disubstituted nonproteinogenic α-amino acid esters are produced in 31-92% yields and 84-97% ee values. The allylation products are utilized for the synthesis of drug molecule BMS561392 and other chiral molecules possessing complex structures.

Visible-Light-Promoted and Electron Donor-Acceptor Complex-Driven Double Csp-H Bond Functionalization of 2-Arylindoles: A Strategy for the Synthesis of Benzo[]carbazoles.

A green and efficient protocol for the preparation of benzo[]carbazoles via visible-light-promoted and electron donor-acceptor (EDA) complex-driven intermolecular cyclization of 2-arylindoles with -α-bromocinnamaldehydes in the absence of external photocatalysts, transition metals, and oxidants was reported. This new approach demonstrates an intermolecular cyclization model using indole derivatives as electron donors under visible light. Mechanistic investigations have showed that 2-arylindoles with -α-bromocinnamaldehydes form EDA complexes, which undergo sequential single-electron transfer, radical coupling, 6π-electrocyclization, and dehydroaromatization to generate benzo[]carbazoles under visible light irradiation.

Photo-Driven Regiodivergent Arylation/Cyclization and Arylation/Hydroxylation of -Aryl Methacrylamides with Aryltriazenes: Access to Functionalized 3,3-Disubstituted Oxindoles and α-Hydroxylamides.

A metal-free, light-induced regiodivergent functionalization of α,β-unsaturated amides with aryltriazenes under ambient conditions was developed. The visible light and B(CF) cocatalyzed radical cascade arylation/cyclization of -alkyl--arylmethacrylamides can obtain functionalized 3,3-disubstituted oxindoles with the assistance of photocatalyst eosin Y-Na. In the absence of any catalyst, with purple light irradiation and electron-donor-acceptor (EDA) complex initiation, the radical cascade arylation/hydroxylation of -arylmethacrylamides affords α-hydroxylamides.

Photoredox-Catalyzed Amino-Radical-Transfer-Mediated Three-Component Alkylarylation of Alkenes.

We herein reported a novel photoredox-catalyzed three-component alkylarylation of vinyl arenes with alkylboronic pinacol esters (APEs) and cyanoarenes via radical addition/cross-coupling to construct 1,1-diarylalkanes. In this transformation, alkyl radicals were easily available by visible-light-induced oxidative N-H cleavage of morpholine, which used APEs as a radical precursor. Furthermore, this protocol exhibited a broad substrate scope, enabling various styrenes, APEs, and cyanoarenes, as well as bioactive molecule derivatives.

Electrochemical Oxidative 1,2-Dithiocyanation: Access to Functionalized Alkenes and Alkynes.

Reported herein is the 1,2-dithiocyanation of alkenes and alkynes an efficient and facile electrochemical method. This approach not only showed a broad substrate scope and good functional-group compatibility but also avoided stoichiometric oxidants. Different from previous reports, various internal alkynes could be tolerated to provide -substituted alkenes.

Photoinduced Catalyst-Free Deuterodefunctionalization of Aryltriazenes with CDCl.

A photoinduced deuterodetriazenation of aryltriazenes with CDCl under catalyst-free conditions is reported. The reactions featured simple operation, ecofriendly conditions, readily available reagents, inexpensive D sources, precise site selectivity, and a wide range of substrates. Since aryltriazenes could be readily synthesized from arylamine, this protocol can be used as a general method for easily and accurately incorporating deuterium into aromatic systems by using CDCl as a D source.

Visible-Light-Driven Bifunctional Photocatalytic Radical-Cascade Selenocyanation/Cyclization of Acrylamides with KSeCN.

A visible-light-induced radical-cascade selenocyanation/cyclization of -alkyl--methacryloyl benzamides, 2-aryl--acryloyl indoles, and -methacryloyl-2-phenylbenzimidazoles with potassium isoselenocyanate (KSeCN) was developed. The reactions were carried out with inexpensive KSeCN as a selenocyanation reagent, potassium persulfate as an oxidant, 2,4,6-triphenylpyrylium tetrafluoroborate as a bifunctional catalyst for phase-transfer catalysis, and photocatalysis. A library of selenocyanate-containing isoquinoline-1,3(2,4)-diones, indolo[2,1-]isoquinoline-6(5)-ones, and benzimidazo[2,1-]isoquinolin-6(5)-ones were achieved in moderate to excellent yields at room temperature under visible-light and ambient conditions.

Visible-Light-Promoted and EDA Complex-Driven [4 + 2] Annulation for the Construction of Naphtho[1',2':4,5]imidazo[1,2-]pyridines.

A green visible-light-promoted and electron donor-acceptor (EDA) complex-driven synthetic strategy for the construction of value-added naphtho[1',2':4,5]imidazo[1,2-]pyridines from 2-arylimidazo[1,2-]pyridines with -α-bromocinnamaldehydes has been accomplished under photocatalyst- and transition-metal-free conditions. This efficient annulation approach provides a new and straightforward pathway for the annulative π-extension of imidazo[1,2-]pyridine-based aromatics. Moreover, the sustainable methodology exhibits simple operation, a wide range of substrates, benign conditions, and good functional group compatibility.

Pd-Catalyzed Direct C7 Trifluoromethylation of Indolines with Umemoto's Reagent.

An efficient palladium-catalyzed region-selective C7-trifluoromethylation of indolines using commercially available Umemoto's reagent was reported. The reaction utilizing Umemoto's reagent as CF radical precursor, pyrimidine as a removable directing group, Pd(II) as a catalyst, and Cu(II) as an oxidant furnished the required products with excellent regioselectivities and good yields. The present strategy has good region-selectivity, broad substrate scope, and scale-up application.

Electrochemical Synthesis of α-Thiocyanated/Methoxylated Ketones Using Enol Acetates.

We have developed the synthesis of α-substituted ketone compounds with enol acetates in an electrochemical way. By using cheap NHSCN and MeOH as the radical sources, a series of valuable α-thiocyanates/methoxy ketones were synthesized under mild electrolysis conditions in acceptable yields with diverse functional group compatibility. Additionally, the scale-up experiment and synthetic transformations reveal potential applications in organic synthesis.

Electrooxidative Hofmann Rearrangement of Phthalimides to Access Anthranilate Derivatives.

A simple and efficient electrooxidative Hofmann rearrangement reaction of phthalimides was developed. Anthranilate derivatives were synthesized in moderate to good yields under green and mild conditions using phthalimides as a rearrangement precursor. This approach not only provides a strategy for synthesizing anthranilates and deuterated anthranilate derivatives with high deuteration efficiency but also realizes efficient conversion at the gram scale.

Pd-Catalyzed C-7 Arylation of Indolines with Aryltriazenes under Mild Conditions.

A palladium-catalyzed direct C-H arylation of indolines at C-7 position has been achieved at near-ambient temperature. The reaction was carried out with aryltriazene as a stable aryl source and electron shuttle to sustainably release aryl radical under the action of promoter, and pyrimidine as a detachable directing group for the synthesis of 7-arylindolines under oxidant- and ligand-free conditions. Notably, this catalytic system can also be applied to the direct and site-selective arylation of tetrahydroquinolines (C-8) and carbazoles (C-1).

Molecular Dynamics-Based Design and Biophysical Evaluation of Thermostable Single-Chain Fv Antibody Mutants Derived from Pharmaceutical Antibodies.

Antibody drugs are denatured under physical stress, e.g., friction, heat, and freezing, which triggers formation of aggregates and resultant allergic reactions.

Palladium-catalyzed intramolecular Heck dearomative -difluorovinylation of indoles.

A palladium-catalyzed dearomative reaction of indoles has been developed through a domino Heck/-difluorovinylation sequence. By taking advantage of a difluorocarbene precursor (ClCFCOONa), the palladium difluorocarbene ([Pd][double bond, length as m-dash]CF) species was formed smoothly. Then, a migratory insertion/β-H elimination process enabled access to polycyclic indolines containing 1,1-difluoroethylene units in acceptable yields with a broad substrate scope, which also showed dearomative -difluorovinylation for the first time.

Visible-Light-Promoted [3 + 2] Cyclization of Chalcones with 2-Mercaptobenzimidazoles: A Protocol for the Synthesis of Imidazo[2,1-]thiazoles.

A visible-light-promoted [3 + 2] cyclization between chalcones and 2-mercaptobenzoimidazoles for the construction of diverse imidazo[2,1-]thiazoles via an electron-donor-acceptor (EDA) complex has been developed. This novel aminothiolation can be realized under only visible light irradiation without the aid of external photocatalysts, transition metals, and oxidants. Mechanistic investigations have revealed that the thiol anions and chalcones form EDA complexes, providing a novel strategy for the synthesis of imidazo[2,1-]thiazoles.

Electrochemical Enabled Cascade Phosphorylation of N-H/O-H/S-H Bonds with P-H Compounds: An Efficient Access to P(O)-X Bonds.

An electrochemical three component cascade phosphorylation reaction of various heteroatoms-containing nucleophiles including carbazoles, indoles, phenols, alcohols, and thiols with Ph PH has been established. Electricity is used as the "traceless" oxidant and water and air are utilized as the "green" oxygen source. All kinds of structurally diverse organophosphorus compounds with P(O)-N/P(O)-O/P(O)-S bonds are assembled in moderate to excellent yields (three categories of phosphorylation products, 50 examples, up to 97 % yield).

Molecular recognition of a single-chain Fv antibody specific for GA-pyridine, an advanced glycation end-product (AGE), elucidated using biophysical techniques and synthetic antigen analogues.

Advanced glycation end-products (AGEs) are a heterogeneous group of compounds formed by non-enzymatic reaction between reducing-sugar and Arg/Lys in proteins and are involved in various diabetic complications. GA-pyridine is derived from glycolaldehyde and is one of the most cytotoxic AGEs. Here, we established a single-chain Fv (scFv) antibody against GA-pyridine, 73MuL9-scFv, and examined the details of its specificity and antigen recognition by using various techniques involving biophysics, chemical biology and structural biology.

Aminothiolation of α-Bromocinnamaldehydes to Access Imidazo[2,1-]thiazoles by Incorporation of Two Distinct Photoinduced Processes.

A visible-light-promoted metal-free catalytic system was developed to achieve the aminothiolation of α-bromocinnamaldehydes. This mechanistically novel approach allows the synthesis of diverse imidazo[2,1-]thiazole derivatives in satisfactory yields at room temperature under visible-light irradiation by incorporation of two distinct photoinduced processes. The reaction features readily accessible feedstocks, easy operation, mild reaction conditions, and wide reaction scope.

Convenient method of producing cyclic single-chain Fv antibodies by split-intein-mediated protein ligation and chaperone co-expression.

Single-chain Fv (scFv) is a recombinant antibody in which the variable regions of the heavy chain (VH) and light chain (VL) are connected by a short flexible polypeptide linker. Compared with monoclonal antibodies, scFvs have the advantages of low-cost production using Escherichia coli and easy genetic manipulation. ScFvs are, therefore, regarded as useful modules for producing next-generation medical antibodies.

Electrochemical Oxidative Dehydrogenative Phosphorylation of -Heterocycles with P(O)-H Compounds in Imidazolium-Based Ionic Liquid.

We report a direct and green electrochemical oxidative cross-dehydrogenative coupling reaction of -heterocycles with hydrogen phosphoryl compounds under external oxidant-free conditions. Various phosphorylation products of substituted carbazoles and indoles are assembled in modest to excellent yields. A hydrogen release process is preliminarily demonstrated and H is the sole byproduct.

Preparation of single-chain Fv antibodies in the cytoplasm of Escherichia coli by simplified and systematic chaperone optimization.

A single-chain variable fragment (scFv) antibody is a recombinant protein in which a peptide linker connects the variable regions of the heavy chain and light chain. Due to its smaller molecular size, an scFv can be expressed using Escherichia coli. The presence of two disulphide bonds in the molecule often prevents expression of correctly folded scFv in the E.

Switchable Synthesis of Aryl Sulfones and Sulfoxides through Solvent-Promoted Oxidation of Sulfides with O/Air.

A practical and switchable method for the synthesis of aryl sulfones and sulfoxides via sulfide oxidation was developed. The chemoselectivities of products were simply controlled by reaction temperature using O/air as the terminal oxidant and oxygen source. The broad substrate scope, easy realization of gram-scale production, and the simplification of a sulfide oxidation system render the strategy attractive and valuable.

Trash to Treasure: Eco-Friendly and Practical Synthesis of Amides by Nitriles Hydrolysis in WEPPA.

The hydration of nitriles to amides in a water extract of pomelo peel ash (WEPPA) was realized with moderate to excellent yields without using external transition metals, bases or organic solvents. This reaction features a broad substrate scope, wide functional group tolerance, prominent chemoselectivity, and good reusability. Notably, a magnification experiment in this bio-based solvent at 100 mmol further demonstrated its practicability.