Three-Component Assembly of Dihydropyrrolo[3,4-e][1,3]thiazines from Elemental Sulfur, Maleimides, and 1,3,5-Triazinanes.

A three-component reaction for the synthesis of dihydropyrrolo[3,4-e][1,3]thiazines has been developed. Elemental sulfur, maleimides, and 1,3,5-triazinanes are assembled together through sulfuration/nucleophilic attack in N-methylpyrrolidin-2-one (NMP) under mild conditions. A small amount of NaHCO3 is important for the activation of the reaction. In this method, sulfur plays a dual role in thiazine ring formation, while triazinanes are utilized as three-atom synthons in the annulation reaction.

Anderson-type polyoxometalate-based metal-organic framework as an efficient heterogeneous catalyst for selective oxidation of benzylic C-H bonds.

Oxidative transformation of benzylic C-H bonds into functional carbonyl groups under mild conditions represents an efficient method for the synthesis of aromatic carboxylic acids and ketones. Here we report a high-efficiency catalyst system constructed from an Anderson-type polyoxometalate-based metal-Organic framework (POMOF-1) and N-hydroxyphthalimide (NHPI) for selective oxidation of methylarenes and alkylarenes under 1 atm O2 atmosphere. POMOF-1 exerted a synergistic effect originating from the well-aligned Anderson {CrMo6} clusters and Cu centers within the framework, and this entailed good cooperation with NHPI to catalyze the selective oxidation. Accordingly, the reactions exhibit good tolerance and chemical selectivity for a wide range of substrates bearing diverse substituent groups, and the corresponding carboxylic acids and ketones were harvested in good yields under mild conditions. Mechanism study reveals that POMOF-1 worked synergistically with NPHI to activate the benzylic C-H bonds of substrates, which are sequentially oxidized by oxygen and HOO˙ to give rise to the products. This work may pave a way to design high-efficiency catalysts by integration of polyoxometalate-based materials with NPHI for challenging C-H activation.

A porous Anderson-type polyoxometalate-based metal-organic framework as a multifunctional platform for selective oxidative coupling with amines.

Incorporating catalytic units into a crystalline porous matrix represents a facile way to build high-efficiency heterogeneous catalysts, and by rational design of the porous skeleton with appropriate building blocks the catalytic performance can be significantly enhanced for a series of organic transformations owing to the synergistic effect from the multicomponent and confined porous microenvironment around catalytically active sites. Herein, we demonstrate that the design and synthesis of a porous polyoxometalate-based metal-organic framework YL2(H2O)2[CrMo6O18(PET)2]·4H2O (POMOF-1) constructed from Anderson-type [CrMo6O18(PET)2] (PET = pentaerythritol), which can be employed as a multifunctional platform for synthesis of N-containing compounds via selective oxidative coupling with amines. POMOF-1 features microporous 1D channels defined by Y3+ and L, with [CrMo6O18(PET)2] arranged orderly between adjacent Lvia electrostatic interactions. Upon using POMOF-1 as a catalyst and H2O2 as an oxidant, a variety of amines could be effectively converted to value-added amides, imines and azobenzenes via the oxidative cross-coupling with alcohols or homo-coupling. In particular, POMOF-1 showed dramatically improved activity for the N-formylation reaction owing to the synergistic and confinement effect, with the yield of amides up to 95% and 4 times higher than that of homogeneous [CrMo6O18(PET)2]. Meanwhile, the oxidative homo-coupling of arylmethylamines and arylamines can be facilely tuned by adjustment of the amount of oxidant, solvent and additive, affording imines and azobenzenes in high selectivity and yield, respectively. POMOF-1 is robust and can be reused for 5 cycles with little loss of catalytic activity and structural integrity. The work demonstrates that the combination of catalytically active POMs with crystalline porous MOFs holds great potential to build robust and recyclable heterogeneous systems with enhanced activity and selectivity for multifunctional catalysis.

Borrowing Hydrogen ß-Phosphinomethylation of Alcohols Using Methanol as C1 Source by Pincer Manganese Complex.

Herein, we report a manganese-catalyzed three-component coupling of ß-H containing alcohols, methanol, and phosphines for the synthesis of γ-hydroxy phosphines via a borrowing hydrogen strategy. In this development, methanol serves as a sustainable C1 source. A variety of aromatic and aliphatic substituted alcohols and phosphines could undergo the dehydrogenative cross-coupling process efficiently and deliver the corresponding ß-phosphinomethylated alcohol products in moderate to good yields. Mechanistic studies suggest that this transformation proceeds in a sequential manner including catalytic dehydrogenation, aldol condensation, Michael addition, and catalytic hydrogenation.

Access to 3-Aminomethylated Maleimides via a Phosphine-Catalyzed Aza-Morita-Baylis-Hillman Type Coupling.

A designed method for the preparation of 3-aminomethylated maleimides via Morita-Baylis-Hillman (MBH) reaction was developed. This phosphine-catalyzed coupling adopted maleimides and 1,3,5-triazinanes as the substrate, giving a series of 3-aminomethylated maleimide derivatives with a double bond retained on the maleimide ring in 41-90% yield. Acylation, isomerization, and Michael addition of the obtained products demonstrated the synthetic application of the present protocol. The results of control experiments indicated that phosphorus ylide formation and elimination take place during the reaction pathway.

Manganese-Catalyzed Chemoselective Coupling of Secondary Alcohols, Primary Alcohols and Methanol.

Herein, we report a manganese-catalyzed three-component coupling of secondary alcohols, primary alcohols and methanol for the synthesis of ß,ß-methylated/alkylated secondary alcohols. Using our method, a series of 1-arylethanol, benzyl alcohol derivatives, and methanol undergo sequential coupling efficiently to construct assembled alcohols with high chemoselectivity in moderate to good yields. Mechanistic studies suggest that the reaction proceeds via methylation of a benzylated secondary alcohol intermediate to generate the final product.

Copper(I)-Catalyzed Three-Component Selenosulfonation of Maleimides with Sulfonyl Hydrazides and Diselenides via Radical Relay.

By employing Cu(CH3CN)4PF6 as the catalyst and tert-butyl hydroperoxide as the oxidant, we realized a three-component radical selenosulfonation of substituted maleimides, sulfonyl hydrazides, and diphenyl diselenides, providing a series of 3,4-selenosulfonylated succinimides in moderate to good yields. This reaction features broad substrate scopes, high functional-group tolerability, and feasibility of gram-scale synthesis, enabling one-step construction of C-SO2 and C-Se bonds under mild reaction conditions. Preliminary mechanistic studies support the free-radical-induced pathway.

Transition-Metal-Free Radical-Triggered Hydrosulfonylation and Disulfonylation Reaction of Substituted Maleimides with Sulfonyl Hydrazides.

A convenient and practical hydrosulfonylation and disulfonylation of substituted maleimides was realized using sulfonyl hydrazides as the sulfur reagent and tert-butyl hydroperoxide as the oxidant. The advantages of the reactions include mild and transition-metal-free reaction conditions, good functional group tolerance, and readily available starting materials. The radical species-induced pathway is also demonstrated by mechanistic studies.

Copper(I)-Catalyzed Direct Oxidative Annulation of 1,3-Dicarbonyl Compounds with Maleimides: Access to Polysubstituted Dihydrofuran Derivatives.

An efficient annulation method for the synthesis of polysubstituted dihydrofurans from 1,3-dicarbonyl compounds and maleimides is described. The reactions can afford furo[2,3-c]pyrrole derivatives with satisfactory yields. The developed strategy realizes the direct oxidative double C(sp3)-H functionalization in the presence of copper(I) salts and 2-(tert-butylperoxy)-2-methylpropane. Meanwhile, this protocol features a mild reaction condition and simple catalytic system. A reaction mechanism involving a single electron oxidation is also proposed.

In Situ Fabrication of Nerve Growth Factor Encapsulated Chitosan Nanoparticles in Oxidized Bacterial Nanocellulose for Rat Sciatic Nerve Regeneration.

Autograft is currently the gold standard in the clinical treatment of peripheral nerve injury (PNI), which, however, is limited by the availability of a donor nerve and secondary injuries. Nerve guidance conduits (NGC) provide a suitable microenvironment to promote the regeneration of injured nerves, which could be the substitutes for autografts. In this study, nerve growth factor (NGF) encapsulated chitosan nanoparticles (CSNPs) were first constructed in situ in an oxidized bacterial cellulose (OBC) conduit using the ion gel method after the introduction of a CS/NGF solution under pressure to enable a sustainable release of NGF. A novel NGF@CSNPs/OBC nanocomposite with antibacterial activity, biodegradability, and porous microstructure was successfully developed. In vitro experiments showed that the nanocomposite promoted the adhesion and proliferation of Schwann cells. When the nanocomposite was applied as NGC to repair the sciatic nerve defect of rats, a successful repair of the 10 mm nerve defect was observed after 4 weeks. At week 9, the diameter, morphology, histology, and functional recovery of the regenerated nerve was comparable to the autografts, indicating that the NGC effectively promoted the regeneration and function recovery of the nerve. In summary, the NGF@CSNPs/OBC as a novel NGC provides great potential in the treatment of PNI.

Iodine-Catalyzed Regioselective Oxidative Cyclization of Aldehyde Hydrazones with Electron-Deficient Olefins for the Synthesis of Mefenpyr-Diethyl.

A regioselective synthesis of polysubstituted dihydropyrazoles and pyrazoles through an iodine-catalyzed oxidative cyclization strategy of aldehyde hydrazones with electron-deficient olefins is described. The protocol adopts very mild reaction conditions and provides desirable yields. The reaction is supposed to proceed via a cascade C-H functionalization, C-N bond formation, and oxidation sequential processes. The overall simplicity and regioselectivity of the catalytic system make this approach a valuable and step-economical tool to construct a C-C bond for the synthesis of Mefenpyr-Diethyl.

Cascade Functionalization of C(sp3)-Br/C(sp2)-H Bonds: Access to Fused Benzo[e]isoindole-1,3,5-trione via Visible-Light-Induced Reductive Radical Relay Strategy.

A reductive radical relay strategy for the construction of fused benzo[e]isoindole-1,3,5-trione through a reaction of α-bromo ketones with maleimides in the presence of Ir(ppy)3 under visible-light irradiation is described. The protocol employs very mild reaction conditions and offers satisfactory yields. Moreover, the reaction proceeds through a cascade C(sp3)-Br/C(sp2)-H functionalization, double C-C bond formation, and oxidative aromatization sequence.

Pyrrolo[3,4- c]pyrazole Synthesis via Copper(Ι) Chloride-Catalyzed Oxidative Coupling of Hydrazones to Maleimides.

A variety of pyrrolo[3,4- c]pyrazole derivatives from readily available aldehyde hydrazones and maleimides via direct oxidative coupling under radical cascade reaction have been reported. This method offers satisfactory chemical yields and good functional group compatibility. Moreover, this practical approach is catalyzed by CuCl utilizing air as the oxidant and some control experiments were performed to elaborate the mechanism.

Copper-Catalyzed Oxidative Cyclization of Maleimides with Amines and Alkyne Esters: Direct Access to Fully Substituted Dihydropyrroles and Pyrrole Derivatives.

An efficient and practical Cu(I)-catalyzed oxidative cyclization cascade reaction of diverse amines, alkyne esters and maleimides has been developed. The reactions can afford 4,6-dioxopyrrolo[3,4-b]pyrrole-2,3-dicarboxylates and related derivatives with satisfactory yields by altering the reaction conditions slightly. The substrate scope highlights the flexibility of the catalyst, and a reaction mechanism is also proposed.

Palladium-Catalyzed Tandem Regioselective Oxidative Coupling from Indoles and Maleimides: One-Pot Synthesis of Indolopyrrolocarbazoles and Related Indolylmaleimides.

An efficient Pd(II)-catalyzed approach for the direct synthesis of indolo[3,2-a]pyrrolo[3,4-c]carbazole-6,8-diones has been developed from both free and protected (NH) indoles and maleimides via a regioselective tandem oxidative coupling reaction. The yields are moderate to excellent. In addition, 2-substituted indoles are suitable substrates in this protocol, leading to the formation of indolylmaleimides. The present methodology provides a concise route to highly functionalized indolopyrrolocarbazole derivatives.

Unconventional origin and hybrid system for construction of pyrrolopyrrole moiety in kosinostatin biosynthesis.

Kosinostatin (KST), an antitumor antibiotic, features a pyrrolopyrrole moiety spirally jointed to a five-membered ring of an anthraquinone framework glycosylated with a γ-branched octose. By a combination of in silico analysis, genetic characterization, biochemical assay, and precursor feeding experiments, a biosynthetic pathway for KST was proposed, which revealed (1) the pyrrolopyrrole moiety originates from nicotinic acid and ribose, (2) the bicyclic amidine is constructed by a process similar to the tryptophan biosynthetic pathway, and (3) a discrete adenylation enzyme and a peptidyl carrier protein (PCP) are responsible for producing a PCP-tethered building block parallel to type II polyketide synthase (PKS) rather than for the PKS priming step by providing the starter unit. These findings provide an opportunity to further explore the inexplicable enzymatic logic that governs the formation of pyrrolopyrrole moiety and the spirocyclic skeleton.

Cytotoxic alkoxylated xanthones from the resin of Garcinia hanburyi.

Three new xanthones, garcinolic acid (1), 10α-ethoxy-9,10-dihydromorellic acid (2), and 10α-ethoxy-9,10-dihydrogambogenic acid (3), along with six known compounds were isolated from the resin of Garcinia hanburyi. These compounds were tested for their cytotoxicities against A549, HCT116, SK-BR-3 and HepG2, and showed high inhibitory effects on the cell lines.

Ethyl (E)-3-hy-droxy-2-{N-[2-(thio-phen-2-yl)ethen-yl]carbamo-yl}but-2-enoate.

In the title compound, C(13)H(15)NO(4)S, there are two independent but conformationally similar mol-ecules in the asymmetric unit, both having an E conformation of the side-chain C=C group. Intra-molecular N-H⋯O and O-H⋯O hydrogen-bonding inter-actions are present in both molecules. In the crystal, one of the mol-ecule types is linked through inter-molecular hy-droxy-ketone O-H⋯O inter-actions, forming one-dimensional chains extending along [010], whereas the other mol-ecule type shows no associations.

Ethyl (E)-3-hy-droxy-2-[(4-meth-oxy-styr-yl)-carbamo-yl]but-2-enoate.

The title compound, C(16)H(19)NO(5), which was synthesized from p-meth-oxy-cinnamic acid, has intra-molecular O-H⋯O and N-H⋯O hydrogen-bonding inter-actions. In the crystal, mol-ecules are linked by weak C-H⋯O hydrogen bonds and aromatic π-π stacking inter-actions [minimum ring centroid-centroid separation = 3.790 (1) Å].

1-(2-Hy-droxy-eth-yl)-3-[(2-hy-droxy-eth-yl)amino]-4-(1H-indol-3-yl)-1H-pyrrole-2,5-dione.

There are four molecules in the asymmetric unit of the title compound, C(16)H(17)N(3)O(4), in which the dihedral angles between the indole ring system and maleimide ring are 4.5 (3), 8.3 (3), 8.4 (2) and 10.4 (2)°. In the crystal, mol-ecules are linked by numerous N-H⋯O and O-H⋯O hydrogen bonds, generating a three-dimensional network.