Nucleophilic addition of bulk chemicals with imines using N-functionalized hydroxylamine reagents as precursors.

C-C and C-X bond forming reactions are essential tools in organic synthesis, constantly revolutionizing human life. Among the key methods for constructing new chemical bonds are nucleophilic addition reactions involving imines. However, the inherent challenges in synthesizing and storing imines have stimulated interest in designing stable precursors, which generates imines in situ during the reaction.

Visible-Light-Induced Markovnikov Hydroalkoxylation of α-Trifluoromethyl Alkenes with -Diketones.

We report, for the first time, a visible-light-promoted Markovnikov hydroalkoxylation of α-trifluoromethyl alkenes with 1,2-diketones. This transformation proceeded smoothly in the presence of a tertiary amine (EtN), providing a series of enol ethers containing the trifluoromethylated tetrasubstituted center in moderate to excellent yields. In this protocol, hydrogen atom transfer between this amine and 1,2-diketone substrate affords a ketyl radical and an α-aminoalkyl radical, which engages in the formation of a radical anion of the α-CF alkene via a single electron transfer.

Visible light-promoted C3-H alkoxycarbonylation of quinoxalin-2(1)-ones or coumarins with alkyloxalyl chlorides.

Herein, we describe a green and efficient photoredox catalytic C3-H alkoxycarbonylation between quinoxalin-2(1)-ones or coumarins and readily available alkyloxalyl chlorides under ambient conditions. A series of quinoxaline-3-carbonyl and coumarin-3-carbonyl compounds are prepared through the radical addition of -generated alkoxycarbonyl radicals. Notably, this protocol features mild conditions, operational simplicity, and excellent functional group tolerance.

Al(OTf)-Catalyzed Regioselective N-Arylation of Tetrazoles with Diazo Compounds.

Regioselective methods to access alkylated tetrazoles still remain a challenging goal. Herein, we describe a novel regioselective protocol for N-arylation of tetrazoles with diazo compounds using inexpensive Al(OTf). This reaction could be conducted under mild conditions to access a diverse array of alkylated tetrazoles with 2-substituted tetrazoles as the major products, demonstrating a comprehensive range of substrate compatibility and excellent functional group compatibility.

Synthesis of 2,4-Disubstituted Oxazoles and Thiazoles via Brønsted Acid-Catalyzed Cyclization of α-diazoketones with Amides.

A novel method is described for the synthesis of 2,4-disubstituted oxazole and thiazole derivates via the coupling of α-diazoketones with (thio)amides or thioureas using trifluoromethanesulfonic acid (TfOH) as a catalyst. This protocol is characterized by mild reaction conditions, metal-free, and simplicity and also features good functional group tolerance, good to excellent yields, and a broad substrate scope with more than 40 examples. Experimental studies suggest a mechanism involving 2-oxo-2-phenylethyl trifluoromethanesulfonate as the key intermediate.

Copper-Catalyzed Asymmetric Remote C(sp)-H Alkylation of -Fluorocarboxamides with Glycine Derivatives and Peptides.

Saturated hydrocarbon bonds are ubiquitous in organic molecules; to date, the selective functionalization of C(sp)-H bonds continues to pose a notorious difficulty, thereby garnering significant attention from the synthetic chemistry community. During the past several decades, a wide array of powerful new methodologies has been developed to enantioselectively modify C(sp)-H bonds that is successfully applied in asymmetric formation of diverse bonds, including C-C, C-N, and C-O bonds; nevertheless, the asymmetric C(sp)-H alkylation is elusive and, therefore, far less explored. In this work, we report a direct and robust strategy to construct highly valuable enantioenriched unnatural α-amino acid (α-AA) cognates and peptides by a copper-catalyzed enantioselective remote C(sp)-H alkylation of -fluorocarboxamides and readily accessible glycine esters under ambient conditions.

Visible-Light-Driven -Selective Heteroarylation of -Fluoroalkyl Hydroxylamine Reagents with Quinoxalin-2(1)-ones.

Herein, we disclose a direct and powerful strategy for the synthesis of highly valuable α-trifluoromethylamine and -trifluoroethylamine derivatives from a visible-light-promoted -selective heteroarylation of -trifluoroethyl hydroxylamine reagents with quinoxalin-2(1)-ones under ambient conditions. The chemoselectivity of the process (trifluoroalkylation or -trifluoroethylamination) can easily be dictated and modulated by a selection of -trifluoroethyl hydroxylamine substrates. The key to success is the protecting group on the N atom of hydroxylamine reagents, which can control the process of 1,2-H shift of the in situ-generated trifluoroethyl radical.

Visible-Light-Induced Defluorinative α-C(sp)-H Alkylation for the Synthesis of -Difluoroallylated α-Trifluoromethylamines.

Herein, we describe a novel and efficient photoredox catalytic C radical addition/defluoroalkylation coupling reaction between α-trifluoromethyl alkenes and -trifluoroethyl hydroxylamine. A series of -difluoroallylated α-trifluoromethylamines were synthesized by the C radical addition enabled by a 1,2-H shift of the in situ-generated trifluoroethyl radical. Notably, this protocol is distinguished by its mild conditions, easy operation, and excellent functional group tolerability.

Chemodivergent Synthesis of Sulfonamide and Sulfones from -Tosylhydrazones by Switching Catalyst and Temperature.

A catalyst- and temperature-controlled selective synthesis of sulfonamide and sulfones from -tosylhydrazones and MBH carbonates has been developed. The use of palladium catalysts exclusively leads to sulfonamide products at room temperature, whereas the selective synthesis of sulfones is dominant for a temperature-controlled coupling reaction without palladium catalysis. Importantly, the catalyst- or temperature-controlled reaction exhibits high nucleophilicity rather than carbene reactivity in these transformations.

TfOH-Catalyzed Regioselective S-H Insertion of Cyclic Thioamide Derivatives with Diazo Compounds at Room Temperature.

We have developed a method for highly regioselective S-H bond insertion reactions of various diazo compounds and cyclic thioamide derivatives at room temperature. These reactions provide straightforward access to alkylated benzimidazoles, benzothiazoles, and benzoxazoles. This mild method uses readily available TfOH as a catalyst and features a broad substrate scope, good functional group tolerance, good to excellent yields, and high regioselectivities.

Correction: Regioselective -alkylation of 2-pyridones by TfOH-catalyzed carbenoid insertion.

Correction for 'Regioselective -alkylation of 2-pyridones by TfOH-catalyzed carbenoid insertion' by Zhewei Yan , , 2023, , 106-109, https://doi.org/10.1039/d2cc05676c.

Regioselective -alkylation of 2-pyridones by TfOH-catalyzed carbenoid insertion.

Selective alkylation of 2-pyridone could solve a challenge in chemistry and streamline the synthesis of important molecules. Here we report the regioselective -alkylation of 2-pyridones by TfOH-catalyzed carbenoid insertion. In the catalytic system, alkylation of 2-pyridone was achieved with unprecedented regioselectiviy (>99 : 1).

Visible-Light-Promoted Xanthate-Transfer Cyclization Reactions of Unactivated Olefins under Photocatalyst- and Additive-Free Conditions.

A general visible-light-induced photocatalyst-/additive-free strategy was developed for the construction of various nitrogen-heterocycles (42 examples, up to 97% yield) such as γ-lactams, δ-lactams, pyrrolidines, indolones, quinolinones, and fused polycyclic structures at room temperature. The prominent features of this protocol are mild and environmentally friendly conditions, broad substrate scope, and good functional group tolerance. Importantly, the reaction can be performed under natural sunlight, the most sustainable energy source imaginable.

TfOH-catalyzed regioselective -alkylation of indazoles with diazo compounds.

Selective alkylation of indazoles is still a highly challenging topic in chemistry and the synthesis of important molecules. Herein, a novel highly selective -alkylation of indazoles with diazo compounds is described in the presence of TfOH. Unlike the traditional metal- and base-catalysed version, this protocol highlights the regioselectivity of alkylation of indazoles and a metal-free catalysis system, affording -alkylated products in good to excellent yields with high regioselectivity (/ up to 100/0) and excellent functional group tolerance.

Painful Terminal Neuroma Prevention by Capping PRGD/PDLLA Conduit in Rat Sciatic Nerves.

Neuroma formation after amputation as a long-term deficiency leads to spontaneous neuropathic pain that reduces quality of life of patients. To prevent neuroma formation, capping techniques are implemented as effective treatments. However, an ideal, biocompatible material covering the nerves is an unmet clinical need.

Construction and in vitro evaluation of enzyme nanoreactors based on carboxymethyl chitosan for arginine deprivation in cancer therapy.

In this study, a pH-induced morphological transition from micelles to vesicles for an amphiphilic photo cross-linkable biocopolymer (Az-NaCMCS), synthesized by mixing azidobenzaldehyde (Az) and an aqueous solution of carboxymethyl chitosan sodium salt (NaCMCS), was used for encapsulation of l-arginine deiminase (ADI). The aqueous solution of enzyme-loaded vesicles obtained was followed by UV-irradiation to result in shell cross-linked enzyme nanoreactors. The nanoreactors were characterized by TEM and DLS.

A novel bioactive nerve conduit for the repair of peripheral nerve injury.

The use of a nerve conduit provides an opportunity to regulate cytokines, growth factors and neurotrophins in peripheral nerve regeneration and avoid autograft defects. We constructed a poly-D-L-lactide (PDLLA)-based nerve conduit that was modified using poly{(lactic acid)-co-[(glycolic acid)-alt-(L-lysine)]} and β-tricalcium phosphate. The effectiveness of this bioactive PDLLA-based nerve conduit was compared to that of PDLLA-only conduit in the nerve regeneration following a 10-mm sciatic nerve injury in rats.

Promotion of peripheral nerve regeneration and prevention of neuroma formation by PRGD/PDLLA/β-TCP conduit: report of two cases.

In the field of nerve repair, one major challenge is the formation of neuroma. However, reports on both the promotion of nerve regeneration and prevention of traumatic neuroma in the clinical settings are rare in the field of nerve repair. One of the reasons could be the insufficiency in the follow-up system.

PRGD/PDLLA conduit potentiates rat sciatic nerve regeneration and the underlying molecular mechanism.

Peripheral nerve injury requires optimal conditions in both macro-environment and micro-environment for reestablishment. Though various strategies have been carried out to improve the macro-environment, the underlying molecular mechanism of axon regeneration in the micro-environment provided by nerve conduit remains unclear. In this study, the rat sciatic nerve of 10 mm defect was made and bridged by PRGD/PDLLA nerve conduit.

PDLLA/PRGD/β-TCP conduits build the neurotrophin-rich microenvironment suppressing the oxidative stress and promoting the sciatic nerve regeneration.

A novel nerve guidance conduit comprising poly{(lactic acid)-co-[(glycolic acid)-alt-(l-lysine)]} (PRGD), poly (d,l-lactic acid) (PDLLA) and β-tricalcium phosphate (β-TCP) was constructed to facilitate the peripheral nerve regeneration. From the comparative study, PDLLA/PRGD/β-TCP conduit achieved the best recovery in regard of the ultrastructure observation and the SFI evaluation. At the first stage of the injury (7 days), the maximum expression augments in ZnSOD (6.

Dog tibial nerve regeneration across a 30-mm defect bridged by a PRGD/PDLLA/β-TCP/NGF sustained-release conduit.

Nerve conduits have emerged as alternatives to autologous nerve grafts, but their use in large-diameter, critical nerve repairs is limited. In the previous study, we prepared a PRGD/PDLLA/β-TCP/NGF sustained-release nerve conduit, which was made of RGD peptide modified poly{(lactic acid)-co-[(glycolic acid)-alt-(L-lysine)]} (PRGD), poly(d,l-lactic acid) (PDLLA), β-tricalcium phosphate (β-TCP) and nerve growth factor (NGF). Here we attempted to use the PRGD/PDLLA/β-TCP/NGF sustained-release nerve conduit to bridge a 30-mm dog tibial nerve defect in six beagles.

Use new PLGL-RGD-NGF nerve conduits for promoting peripheral nerve regeneration.

Background: Nerve conduits provide a promising strategy for peripheral nerve injury repair. However, the efficiency of nerve conduits to enhance nerve regeneration and functional recovery is often inferior to that of autografts. Nerve conduits require additional factors such as cell adhesion molecules and neurotrophic factors to provide a more conducive microenvironment for nerve regeneration.

Evaluation of PRGD/FK506/NGF conduits for peripheral nerve regeneration in rats.

Context: Both tacrolimus (FK506) and nerve growth factor (NGF) enhance peripheral nerve regeneration, and in vitro experimental results demonstrate that the combination of FK506 and NGF increased neurite outgrowth compared with either treatment alone.

Aim: To determine if the combination of FK506 and NGF benefits peripheral nerve regeneration compared with either treatment alone in vivo.

Settings And Design: Rat sciatic nerves were cut off to form a 10 mm defect and repaired with the nerve conduits.

Interaction of olfactory ensheathing cells with nerve repairing scaffolds.

Objective: To investigate a new way to yield plenty of high purity olfactory ensheathing cells (OECs) and its biocompatibility with appropriate scaffolds.

Methods: OECs were prepared from neonatal Wister rats and co-cultured with poly [LA-co-(Glc-alt-Lys)] (PLGL). Its contact angle, adherent rate, and activity rate were tested.