Triflic Acid-Promoted 1,2-Amino Migration Reactions in α-Arylaminoacrylamides: Access to Substituted ß-Aminoamides.

A straightforward synthesis of substituted ß-aminoamides from α-arylamino-ß-hydroxyacrylamides, α-arylamino-ß-oxoamides, or their tautomeric mixture has been described. The (E)-enol triflate intermediates are readily generated in situ from these substrates in the presence of triflic anhydride (Tf2O) and triethylamine (Et3N) in a chemoselective manner and undergo triflic acid (TfOH)-promoted cyclization and ring-opening reactions with alcohols to deliver the desired products. The one-pot two-step synthetic protocol features the use of readily available starting materials, mild reaction conditions, high chemoselectivity, operational simplicity, and a wide range of synthetic potential of the products.

Novel glycosyl prodrug of RXP03 as MMP-11 prodrug: design, synthesis and virtual screening.

Like most phosphinic acids, the potent and selective RXP03 inhibitor of different MMPs exhibited moderate absorption and low bioavailability, which impaired its use. In an unprecedented attempt, we present an interesting synthetic approach to a new class of phosphinate prodrug, glycosyl ester of RXP03, to provide a potentially improved blood-brain barrier (BBB) behavior compared to the former lead compound RXP03. To validate this speculation, a predictive study for permeability enhancer of glycosyl ester of RXP03 showed encouraging insights to improve drug delivery across biological barriers.

Highly Chemoselective Synthesis of Indole Derivatives.

A facile and efficient synthesis of polysubstituted indoles from α-arylamino-ß-hydroxy-2-enamides, α-arylamino-ß-oxo-amides, or their tautomeric mixture via electrophilic activation strategy is described. The salient feature of this methodology is the use of either combined Hendrickson reagent and triflic anhydride (Tf2 O) or triflic acid (TfOH) to control the chemoselectivity in the intramolecular cyclodehydration to provide a predictable approach to these valuable indoles with flexible substituent patterns. Moreover, the mild reaction conditions, simple execution, high chemoselectivity, excellent yields, and wide range of synthetic potential of products make this protocol much attractive for academic research and practical applications.

Design, Synthesis, and Study of a Novel RXPA380-Proline Hybrid (RXPA380-P) as an Antihypertensive Agent.

In drug discovery, molecular modification over the lead molecule is often crucial for the development of a drug. Herein, we report the molecular hybridization design of a novel RXPA380-proline hybrid via linking the parent compound, phosphinic peptide RXPA380, with a proline analogue. The presented synthetic route is straightforward and produces the desired product RXPA380-P in moderate yield. The C- and N-domain constructs of the angiotensin-converting enzyme of RXPA380-P appeared to be poor inhibitors of ACE as compared to the parent compound RXPA380.

Ultrastrong and Hydrophobic Sandwich-Structured MXene-Based Composite Films for High-Efficiency Electromagnetic Interference Shielding.

Electromagnetic interference (EMI) shielding materials are highly necessary to solve the problem of electromagnetic radiation. Transition-metal carbide/nitride (MXene) materials offer great potential for the construction of high-performance EMI shields because of their high electrical conductivity and versatile surface chemistry. However, MXene generally suffers from poor mechanical and oxidation-resistant properties, which hinders its practical applications. Herein, flexible, strong, and hydrophobic sandwich-structured composite films (H-S-MXene), consisting of a conductive MXene layer and supporting aramid nanofiber layer, were fabricated using step-by-step vacuum-assisted filtration and dip coating. Given the unique sandwich structure, hydrogen bonding interactions, and covalent cross-linking of the MXene sheets, the H-S-MXene composite films demonstrated simultaneously excellent EMI shielding and mechanical properties. The EMI shielding effectiveness of the H-S-MXene composite film with 20 wt % MXene content reached 46.1 dB at thickness of 23.2 ± 0.5 µm, and the tensile strength of the film reached 302.1 MPa, which outperformed other reported EMI shielding materials. The excellent mechanical flexibility and hydrophobicity of the H-S-MXene composite films ensured a stable EMI shielding performance, which could withstand cycled bending, torsion, and exposure to aqueous environments. These impressive features made the H-S-MXene composite films promising candidates for electronic devices and aerospace. This study provides important guidance for the rational design of stable MXene-based composites with advanced properties.

PIFA-Mediated Tandem Hofmann-Type Rearrangement and Cyclization Reaction of α-Acyl-ß-aminoacrylamides: Access to Polysubstituted Oxazol-2(3H)-ones.

An efficient and straightforward synthesis of polysubstituted oxazol-2(3H)-ones has been developed via a tandem Hofmann-type rearrangement and cyclization reaction of various α-acyl-ß-aminoacrylamides mediated by phenyl iodine(III) bis(trifluoroacetate) (PIFA) in the presence of trifloroacetic acid (TFA). This novel protocol features readily available starting materials, mild reaction conditions, simple execution, high chemoselectivity, good functional group tolerance, and a metal-free oxidation process.

Tf2O-Mediated Cyclization of α-Acyl-ß-(2-aminopyridinyl)acrylamides: Access to N-Substituted 4H-Pyrido[1,2-a]pyrimidin-4-imines.

A facile and efficient direct synthesis of N-substituted 4H-pyrido[1,2-a]pyrimidin-4-imines is developed from α-acyl-ß-(2-aminopyridinyl)acrylamides mediated by triflic anhydride (Tf2O) in the presence of 2-chloropyridine. This amide activation protocol features mild reaction conditions, simple execution, excellent yields, and high chemoselectivity, and is also applied to the synthesis of substituted 4H-pyrido[1,2-a]pyrimidin-4-ones via a practical one-pot procedure.

Oxidative Cyclization of ß-Aminoacrylamides Mediated by PhIO: Chemoselective Synthesis of Isoxazoles and 2 H-Azirines.

Cyclization of a variety of ß-aminoacrylamides in the presence of iodosobenzene (PhIO) is described. This process features mild reaction conditions, simple execution, and high chemoselectivity and thereby provides an efficient protocol for the divergent synthesis of substituted isoxazoles and 2 H-azirines via switchable N-O and N-C bond formation controlled by simply varying the ß-substituent R3 of the readily available substrates.

Iodosobenzene-Mediated α-Acyloxylation of 1,3-Dicarbonyl Compounds with Carboxylic Acids and Insight into the Reaction Mechanism.

A highly efficient direct α-acyloxylation of 1,3-dicarbonyl compounds with carboxylic acids mediated by hypervalent iodine reagent is presented. Treatment of a variety of 1,3-dicarbonyl compounds with carboxylic acids in the presence of iodosobenzene provides the corresponding α-acyloxylated products in good to excellent yields. The mechanistic investigation by means of NMR spectroscopy reveals that the in situ-generated phenyliodine biscarboxylate proves to be the key intermediate for the α-acyloxylation, and the loading sequence of reactants and oxidant is crucial for the generation of the active species. The mild reaction conditions, wide substrate scope, short reaction time, good yields, high chemoselectivity, excellent functional group tolerance, and metal catalyst-free conversion make this acyloxylation a significant synthetic protocol.

Lewis Pair-Mediated Surface-Initiated Polymerization.

We present the first example of surface-initiated polymerization mediated by Lewis pairs for the synthesis of polymer brushes on planar substrates. The method enables the rapid grafting polymerization from the self-assembled monolayer or surface-attached macroinitiators, furnishing linear polymer brushes and bottle-brush brushes. Both homopolyester and block copolyester brushes can be synthesized via this versatile approach. This work not only opens up new opportunities for the application of Lewis pair-mediated polymerization but also enriches the surface-initiated polymerization on different surfaces.

Controlled Growth of Metal-Organic Frameworks on Polymer Brushes.

Polymer brushes are for the first time used to induce the synthesis of metal-organic frameworks (MOFs). The semi-fixed polymer chains provide a confined environment, which allows a mild growth of MOFs in between polymer chains to give surface-attached spherical MOF nanoparticles, in contrast to the larger MOF cubes/plates formed simultaneously in solution. Polymer brushes bearing carboxylate acid functionalities are indispensable for the formation of surface bound MOFs, while no MOF nanoparticles are observed on neutral polymer brushes. Characterization of the resultant MOF/polymer brushes hybrid film indicates the formation of crystalline MOF structure. The dimension of surface-attached MOFs can be fine-tuned from 20 nm to 1.4 µm simply by varying the structural parameter of polymer brushes and the nucleation duration. The method is not only applicable to the synthesis of MOF-5 and MIL-125, but shows great potential for the preparation of other surface-attached MOFs.

Indocyanine green-functionalized bottle brushes of poly(2-oxazoline) on cellulose nanocrystals for photothermal cancer therapy.

Deriving from the most abundant and renewable material, cellulose nanocrystals (CNCs) have drawn increasing attention in nanomedicine as well as other biomedical fields due to their excellent physicochemical properties and unique rod-like geometry. In this work, we report an efficient procedure to create biocompatible poly(2-oxazoline)s with a defined bottle brush architecture on CNCs through UV-induced photopolymerization and subsequent living cationic ring-opening polymerization. Characterization of the poly(2-oxazoline) modified CNCs indicates an improved thermal stability with the crystalline structure as well as the rod-like contour intact. The side chain terminal piperidinium of the bottle brush was utilized to immobilize indocyanine green (ICG) via electrostatic interactions. The resulting nanorods exhibit low toxicity in the dark and an efficient photothermal therapeutic effect against HeLa cells under 808 nm near infrared laser irradiation after being internalized by cancer cells. Moreover, bottle brushes on CNCs with amphiphilic poly(2-n-propyl-2-oxazoline) side chains show a higher efficiency in stabilizing ICG in comparison to those with hydrophilic poly(2-methyl-2-oxazoline) side chains, thus a higher photostability and a greater therapeutic effect were revealed for amphiphilic polymer modified CNCs. This work indicates that poly(2-oxazoline) functionalized CNCs represent a novel and promising platform for the design of other CNC-based drug delivery systems.

Formal [4 + 1] Annulation of α-Arylhydrazonoketones and Dimethylsulfoxonium Methylide: One-pot Synthesis of Substituted Pyrazoles and Dihydropyrazoles.

A formal [4 + 1] annulation of readily available α-arylhydrazonoketones and trimethylsulfoxonium iodide in the presence of cesium carbonate is described involving a sequential Corey-Chaykovsky reaction and intramolecular nucleophilic cyclization process. Substituted pyrazoles were obtained exclusively from the reactions of α-arylhydrazono-ß-oxo-amides and trimethylsulfoxonium iodide in moderate to good yields, whereas the reactions of α-arylhydrazono-ß-oxo-ketone/α-arylhydrazono- ß-oxo-ester afforded the corresponding dihydropyrazoles in good yields.

Phenyliodine(III) Diacetate Mediated Oxidative Cyclization of 1-Alkenoyl-1-carbamoyl Cycloalkanes: Access to Spiro-Fused Dihydrofuran-3(2H)-ones.

Facile and efficient synthesis of spiro-fused dihydrofuran-3(2H)-ones was developed via phenyliodine(III) diacetate (PIDA) mediated oxidative cyclization of 1-alkenoyl-1-carbamoyl cycloalkanes under very mild conditions.

POCl3-mediated reaction of 1-acyl-1-carbamoyl oximes: a new entry to cyanoformamides.

A facile and efficient one-pot synthesis of cyanoformamides was developed from readily available 1-acyl-1-carbamoyl oximes mediated by phosphoryltrichloride (POCl3) under mild conditions in good to high yields.

Formal [4+2] annulation of enaminones and cyanomethyl sulfur ylide: one-pot access to polysubstituted pyridin-2(1H)-ones.

A facile and efficient one-pot synthesis of polysubstituted pyridin-2(1H)-ones from readily available enaminones and the cyanomethyl sulfonium bromide salt in the presence of cesium carbonate is developed, and a mechanism involving sequential nucleophilic vinylic substitution (S(N)V), intramolecular nucleophilic cyclization and dealkylation reactions is proposed.

Divergent synthesis of 2,3-dihydro-1H-pyrroles, 3-alkyl-1H-pyrroles and 3-alkenyl-1H-pyrroles from 2,4-pentadienenitriles and isocyanides.

An efficient and divergent one-pot synthesis of 2,3-dihydro-1H-pyrroles, 3-alkyl-1H-pyrroles and 3-alkenyl-1H-pyrroles from readily accessible 2,4-pentadienenitriles with isocyanide based on reaction condition selection has been described. The reaction of 2,4-pentadienenitriles with ethyl isocyanoacetate undergoes a formal [2 + 3] annulation either to generate 2,3-dihydro-1H-pyrroles in the presence of DBU (0.3 equiv.) in EtOH at room temperature or to give 3-alkyl-1H-pyrroles in the presence of DBU (2.0 equiv.) in EtOH under reflux. Moreover, the 2,3-dihydro-1H-pyrroles could be converted to 3-alkenyl-1H-pyrroles with DDQ as an oxidant.

Polymer brushes on planar TiO2 substrates.

A facile and universal method is presented for the preparation of polymer brushes on amorphous TiO2 film. Homogeneous and stable poly(methyl methacrylate), polystyrene, poly(4-vinylpyridine), and poly(N-vinyl imidazole) (PNVI) brushes up to 550 nm are directly created onto TiO2 via UV-induced photopolymerization of corresponding monomers. Kinetic studies reveal a linear increase in thickness with the polymerization time. Characterization of the resulting polymer brushes by FTIR spectroscopy, X-ray photoelectron spectroscopy, contact angle, and atomic force microscopy (AFM) indicates an efficient UV-grafting reaction. Finally, we have demonstrated the possibility in converting the PNVI brushes to poly(vinyl imidazolium bromide), i.e., poly(ionic liquid) brushes by polymer-analogous reactions.

A copper-catalyzed formal O-H insertion reaction of α-diazo-1,3-dicarbonyl compounds to carboxylic acids with the assistance of isocyanide.

A novel copper-catalyzed formal O-H insertion of α-diazo-1,3-dicarbonyl compounds to carboxylic acids has been developed, providing a straightforward synthetic method for α-acyloxy-1,3-dicarbonyl compounds, in which the activation of carboxylic acids by isocyanide plays a crucial role.

Tandem halogenation/Michael-initiated ring-closing reaction of α,ß-unsaturated nitriles and activated methylene compounds: one-pot diastereoselective synthesis of functionalized cyclopropanes.

An efficient one-pot synthetic route to highly substituted cyclopropanes has been developed from readily available α,ß-unsaturated nitriles and doubly activated methylene compounds under very mild conditions in a highly diastereoselective manner, which involves halogenation, Michael addition and intramolecular ring-closing reaction sequences.