Three-Component Reaction between 3-Acetylcoumarins, Amines, and Elemental Sulfur: A Designed Approach to 3-Amino-4H-thieno[3,2-c]coumarins.

In this work, a series of novel 3-amino-4H-thieno[3,2-c]coumarins were designed and synthesized by a one-pot, catalyst-free, and three-component reaction of 3-acetylcoumarins with amines and elemental sulfur. Readily available starting materials, simple heating conditions, facile installation of a sulfur atom into the molecule using S8 as a sulfur source, acceptable functional group tolerance, and synthetically useful yields are some highlighted benefits of this process.

In Situ Conversion of Ligand to a Coordination Polymer via a Core@Shell Crystal: A Multi-Step Phase-Dependent Structural Transformation.

Two pseudopolymorphic 1D coordination polymers of the formulas [Cd(3,3'-pytz)(CH3OH)2(ClO4)2]n (1) and [Cd(3,3'-pytz)(CH3CN)2(ClO4)2]n (2) have been prepared using the electron-deficient 3,6-bis(pyridin-3-yl)-1,2,4,5-tetrazine (3,3'-pytz) ligand and cadmium perchlorate in the chloroform/methanol and chloroform/acetonitrile solvent system, respectively. It was observed that compounds 1 and 2 experienced one-step (CPreagent → CPproduct) single-crystal-to-powder structural transformation to the pure water-coordinated compound [Cd(3,3'-pytz)(H2O)2(ClO4)2]n (3) by absorbing water vapor from air (solid-gas phase transformation). Interestingly, compounds 1, 2, and 3 undergo a different transformation path and show an in situ unique three-step (CPreagent → CPproduct → Ligandintermediate → CPproduct) single-crystal-to-single-crystal (SCSC) structural transformation process through soaking in deionized water (solid-liquid phase transformation). In this fascinating transformation, we report for the first time the direct conversion of a ligand into a coordination polymer by a rare core-shell pathway in a solid-liquid phase transformation. In this process, we obtained compound {[Cd(3,3'-pytz)(H2O)4](3,3'-pytz)2(ClO4)2(H2O)6}n (4) (single-crystal = S, crystal = C, or microcrystal = P) as mixed compounds of core-shell L@4C and 4S or core-shell L@4P and 4P for compounds (1 and 2) and 3, respectively.

Substrate-Controlled Diastereo- and Enantiodivergent Synthesis of Bis-Spirocyclopropyloxindoles from Available Isatin as a Single Starting Material.

The first diastereo- and enantiodivergent asymmetric synthesis of new bis-spirocyclopropyloxindole scaffolds has been accomplished from the readily available isatin as a single starting material. Four rel-(1R,2R,3R), rel-(1S,2S,3R), rel-(1R,2R,3S), and rel-(1S,2S,3S) configurations of desired products were constructed in excellent enantiopurity via a simple switch in substrates using the chiral auxiliary-controlled method. The absolute configuration of cycloadducts with three contiguous quaternary/tertiary stereogenic centers was confirmed through X-ray diffraction analysis. A facile synthesis of versatile precursor 3-chlorooxindoles was also introduced.

Using Triazolobenzodiazepine as the Cyclic Imine in Various Types of Joullié-Ugi Reactions.

The triazolobenzodiazepine as a cyclic imine was employed in a variety of Joullié-Ugi reactions, and three new families of unique triazolobenzodiazepine connected to carboxamide and tetrazole products were synthesized via a three-component reaction of the cyclic imine and isocyanides with each species of a carboxylic acid/water/TMSN3 under mild conditions in high yields. Furthermore, triazolobenzodiazepine imine was used in an interesting strategy based on the modified Ugi reaction (pseudo-Joullié-Ugi reaction) of cyclic imines with an isocyanide and acetylenedicarboxylates under catalyst-free conditions for the synthesis of triazolobenzodiazepine-fused pyrroles. Mechanistic investigation reveals that triazolobenzodiazepine-fused pyrroles have been generated via a surprising route. Significantly, the use of triazolobenzodiazepine in the Joullié-Ugi, azido-Joullié-Ugi, and pseudo-Joullié-Ugi reactions of a broad scope of biological scaffolds occurred under mild, simple conditions without any catalyst.

The new synthesis of pyrrole-fused dibenzo[b,f][1,4]oxazepine/thiazepines by the pseudo-Joullié-Ugi reaction via an unexpected route with high chemoselectivity.

A novel and unexpected route for synthesizing pyrrole-fused dibenzoxazepines/thiazepines has been designed based on a modified Ugi reaction of cyclic imines with isocyanides and acetylenedicarboxylates under catalyst-free conditions. Mechanism investigation indicates that this process is carried out through the production of zwitterion species (Huisgen's 1,4-dipole), which is a key intermediate in the chemoselectivity of products. This Huisgen's 1,4-dipole is trapped in situ with isocyanides and a variety of pyrrole-fused dibenzoxazepines/thiazepines are synthesized in a simple one-pot operation with high yields and chemoselectivity. This strategy opens a new route in Ugi reactions (pseudo-Joullié-Ugi reaction) for the synthesis of pyrrole-fused heterocycles as special pharmaceutical scaffolds.

Regioselective synthesis of enantiopure 1,2- and 1,3-dispirooxindoles along with a DFT study.

In the present study, a library of important enantiopure dispirooxindole [indolizidine, pyrrolizidine, and pyrrolidine] derivatives with three or four contiguous and two quaternary stereogenic centers using different amino acids (pipecolic acid, sarcosine, proline and hydroxyproline) were synthesized in high yields (up to 96%) through a regio- and diastereoselective (up to 99 : 1) multicomponent 1,3-dipolar cycloaddition strategy. Based on the results, the alteration of amino acids led to a change in the regioselectivity and unusual regioisomers (pyrrolizidine versus indolizidine/pyrrolidine) were obtained to construct a novel enantiopure 1,3-dispirooxindole skeleton. The stereochemical outcome of the cycloaddition was determined by single crystal X-ray diffraction analysis and the self-disproportionation of enantiomers (SDE) test confirmed the enantiomeric purity of the desired products. The mechanism and differences in the regioselectivity of the 1,3-dipolar cycloaddition reactions between the stable azomethane ylides obtained from ninhydrin, pipecolinic acid, and proline with (E)-2-oxoindolin-3-ylideneacetyl sultam were theoretically studied through DFT calculations at the M06-2X/6-31G(d,p) level in methanol.

Biocatalytic stereoselective synthesis of pyrrolidine-2,3-diones containing all-carbon quaternary stereocenters.

Highly functionalized pyrrolidine-2,3-diones can be synthesized efficiently and stereoselectively under mild conditions using a biocatalytic approach. The reaction led to the formation of new all-carbon quaternary stereocenters from Myceliophthora thermophila laccase (Novozym 51003) catalyzed oxidation of catechols to ortho-quinones and subsequent 1,4-addition with 3-hydroxy-1,5-dihydro-2H-pyrrol-2-ones. The reaction was conducted with various substituents on both reactants, resulting in 13 products in moderate to good yields (42-91%). The same 15 reactions were also tested with K3Fe(CN)6 as a catalyst, but here only one reaction resulted in a product (60% yield).

Iodide-Catalyzed Selenium-Assisted Sequential Multicomponent Synthesis of a Luminescence Benzo-Oxazino-Isoindole Framework.

We have described an unexpected pathway using the R-NC/Se system for the synthesis of the unreported benzo-oxazino-isoindole framework by the iodide-catalyzed selenium-assisted sequential multicomponent reaction of the Knoevenagel adduct of ninhydrin and malononitrile, isocyanide, amine, and elemental selenium under mild reaction conditions. The photophysical properties of the products were investigated by absorption and emission spectroscopy, revealing that the new heterocyclic system has good fluorescence properties.

Humidity-Induced Structural Transformation in Pseudopolymorph Coordination Polymers.

Three cadmium coordination polymers, namely, {[CdL(OAc)2](C2H5OH)}n (1), {[CdL(OAc)2](CH3CN)}n (2), and [CdL(OAc)2(H2O)]n (3), were synthesized by an exoditopic 1,4-bis(4-pyridyl)-2,3-diaza-1,3-butadiene Schiff base ligand (L) and cadmium acetate in the presence of different solvent systems. Single-crystal X-ray diffraction, powder X-ray diffraction, and thermogravimetric analysis showed that 1D ladder pseudopolymorphic compounds (1 and 2) transformed to the solvent-free 1D linear compound 3 through a rare case of water absorption from air at room temperature. Interestingly, compound 3 was transformed to compound 1 through a dissolution-recrystallization structural transformation process. The results illustrated that solvents and humidity have an important role in the formation of pseudopolymorphs with the same or different structural motifs.

Chemoselective synthesis of fully substituted pyrroles via a one-pot four-component isocyanide-based reaction.

Small-ring heterocycles comprising pyrrole and pyrazole are well known for their rich biological properties. In this article, an efficient green sonochemical approach was designed for the synthesis of novel, fully substituted pyrroles connected to pyrazole scaffolds via a one-pot, four-component isocyanide-based sequential reaction. This reaction was carried out using various 5-amino-pyrazoles, aldehydes, dialkyl acetylenedicarboxylates and isocyanides for the synthesis of fully functionalized pyrroles with high chemoselectivity in the presence of a catalytic amount of PTSA·H2O, in good to excellent yields under ultrasound irradiation. This waste-free (-H2O) reaction exhibited a high atom economy and step economy via creating four new bonds, including two C-N and two C-C bonds, and the formation of two five-member heterocycles which are connected in a single operation. The mechanism of this four-component domino process involved sequential imination-dipolar cyclization-[1,5]-H shift reactions. The synthesized compounds possess interesting fluorescence features, and the bioactive scaffolds might attract great interest in the fields of clinical diagnostics and biomedical research in the future.

Organocatalytic synthesis of enantiopure spiro acenaphthyl-pyrrolizidine/pyrrolidines: justifying the regioselectivity based on a distortion/interaction model.

An efficient organocatalytic [3 + 2] reaction with Schreiner's thiourea organocatalyst for the synthesis of a small library of novel enantiopure stable spiroacenaphthyl-pyrrolidines/pyrrolizidines with high regio- and diastereoselectivity (up to 99%) is described for the first time. These chiral compounds were synthesized by a three-component 1,3-dipolar cycloaddition of (E)-1-(2-oxoacenaphthylen-1(2H)-ylidene) pyrrolidin-1-ium-2-ide as a dipolar and (S)-cinnamoyl/crotonoyl oxazolidinone as a dipolarophile. The absolute configuration of cycloadducts was confirmed by X-ray diffraction analysis. The origin of catalyst reactivity and regio- and stereoselectivity was investigated through DFT calculations. DFT calculations showed that the regioselectivity was controlled by the distortion (deformation) of reactants and Schreiner's thiourea acts as a LUMO-lowering catalyst.

Influence of the Diphosphine Coordination Mode on the Structural and Optical Properties of Cyclometalated Platinum(II) Complexes: An Experimental and Theoretical Study on Intramolecular Pt···Pt and π···π Interactions.

The reaction of [Pt(C^N)(CF3CO2)(SMe2)] (1), in which C^N is either benzo[ h]quinolinate (bhq), 1a, or 2-phenylpyridinate (ppy), 1b, with 1 equiv of bis(diphenylphosphino)methane (dppm) gave the bischelate complexes [Pt(C^N)dppm]CF3CO2 (2). The binuclear complexes [Pt2(C^N)2(CF3CO2)2(µ-dppm)] (3) were prepared, using an unusual reaction pathway, by the addition of equimolar amount of complexes 1 and 2, through the ring opening of the chelating dppm ligand and coordination of the CF3CO2 anion to the platinum center. The proposed reaction pathway and effect of the solvent polarity were investigated by density functional theory (DFT) calculations. The crystal structure of 3a shows considerable intramolecular Pt···Pt and π···π interactions. The crystal structure and formation pathway toward 3 were compared with the similar analogue [Pt2(bhq)2(Cl)2(µ-dppm)] (5). All complexes were fully characterized using multinuclear NMR spectroscopy and elemental analysis. Furthermore, the crystal structures of some complexes including 1b, 2a, 2b, 3a, and 5 were confirmed by X-ray crystallography. The effect of dimerization via a change in the coordination mode of dppm, from a chelate mode in complex 2 to a bridge mode in complexes 3 and 5, upon the excited states of the studied compounds was investigated in their distinguished absorption and emission profiles. The appearance of a remarkably low energy band in the absorption spectra of 3, which was assigned to a metal-metal to ligand charge transfer [MMLCT; dσ*(Pt2) → π*(C^N)] transition showing negative solvatochromism, is important evidence for the Pt···Pt intramolecular interaction. The vibronically resolved and long-lifetime emission of 2a in poly(methyl methacrylate) media and powder states at 77 and 300 K, along with time-dependent DFT calculations, suggested that the triplet ligand-centered (3LC) emission was mixed with some 3MLCT character. Unstructured and short-lifetime emission in 3 refers to the phosphorescence 3MMLCT [dσ*(Pt2) → π*(C^N)] transition. Although complex 5 is a binuclear compound, the long distance of the Pt···Pt interaction caused the occurrence of the 3MMLCT transition to fade and act as a mononuclear unit, and the emission originated mostly from the 3MLCT transition. As a result, more metal participation leads to more red-shifted absorption and emission spectra of the studied complexes upon going from LC to MLCT to MMLCT transitions (λabs and λem: 3a > 3b > 5 > 2a > 2b).

A Borane Platinum Complex Undergoing Reversible Hydride Migration in Solution.

Reaction of [Pt(κ2-C,N-ppy)(dmso)Cl], 1 (Hppy = 2-phenylpyridine), with Na[H2B(mb)2] (Hmb = 2-mercapto-benzimidazole) smoothly afforded the complex {[(κ3-S,B,S-HB(mb)2]Pt(κ2-C,N-ppy)H}, 2, featuring a strong reverse-dative Pt → B σ interaction in the solid state. When dissolved in thf (or acetone) solution, 2 undergoes a reversible Pt-H bond activation, establishing an equilibrium between the hexacoordinated 2 and the tetracoordinate complex {[(κ2-S,S-H2B(mb)2]Pt(κ2-C,N-ppy)}, 3, as ascertained by multinuclear NMR. Hydrolysis of the B-N bond in 2/3 resulted ultimately in the formation of a dimeric half-lantern platinum(II,II) complex [{Pt(κ2-C,N-ppy)(µ2-κ2-N,S-mb)}2], 4. The SC-XRD structures of 2 and 4 are reported.

A facile and regioselective one-pot synthesis of novel pyrazolo[1[Formula: see text],5[Formula: see text]:1,2]pyrrolo[3,4-b]quinoline-2,3-dicarboxylate hybrids via intramolecular Wittig reaction.

The regioselective syntheses of novel pyrazolo[1[Formula: see text],5[Formula: see text]:1,2]pyrrolo[3,4-b]quinoline-2,3-dicarboxylates (6a-l) from pyrrolo([3,4-b]quinolin-2(3H)-yl)benzamides through an intramolecular Wittig reaction are described. This protocol takes advantages of mild conditions, simple workup and high yield which make this method attractive for the synthesis of these hybrid of pyrazolo[1[Formula: see text],5[Formula: see text]:1,2]pyrrolo[3,4-b]quinolines.

Palladium-catalyzed tandem reaction of 2-chloroquinoline-3-carbaldehydes and isocyanides.

A facile domino reaction of 2-chloroquinoline-3-carbaldehydes in one and two equivalents of isocyanide has been investigated. Three-component reactions of 2-chloroquinoline-3-carbaldehydes, isocyanides and amines are also described. In this Pd-catalyzed reaction under controlled conditions, three novel types of quinoline derivatives were formed via amidation, lactamization or carbamate formation along with the formation of C-C, C-N, and C-O bonds in a one-pot procedure.

Structure-bioactivity relationship study on anticancer Pd and Pt complexes with aliphatic glycine derivative ligands.

To investigate the structure and bioactivity relationship, six Pd(II)/Pt(II) complexes with N-isobutylglycine (L1) and cyclohexylglycine (L2) as N^O amino acid bidentate ligands, 1,10'-phenanthroline (phen) and 2,2'-bipyridine (bipy) as N^N donor ligands, and [Pd(L1)(bipy)]NO3 (1), [Pd(L2)(bipy)]NO3 (2), [Pd(L1)(phen)]NO3 (3), [Pd(L2)(phen)]NO3·2H2O (4), [Pt(L1)(phen)]NO3 (5), along with [Pt(L2)(phen)]NO3 (6) were prepared and then characterized. The geometry of each compound was validated by doing a DFT calculation. Furthermore, tests were conducted on the complexes' water solubilities and lipophilicity. All bipy complexes had superior aqueous solubility and less lipophilicity in comparison with phen complexes, as well as complexes containing cyclohexyl-glycine compared to isobutyl-glycine complexes, probably because of the steric effects and polarity of cyclohexylglycine. The in-vitro anticancer activities of these compounds were examined against HCT116, A549, and MCF7 cancerous cell lines. Data revealed that all Pd/Pt complexes demonstrate higher anticancer activity than carboplatin, and complexes 3 and 4 are more cytotoxic than cisplatin against the HCT116 cell line, particularly against MCF7 cancerous cells. In addition, among all compounds, complex 4 has more anticancer ability than oxaliplatin. Due to different solubility and lipophilicity behavior, the accumulation of Pt complexes and clinical Pt drugs in each cancerous cell was investigated. The binding capabilities of these complexes to DNA, as the main target in chemotherapy, occur through minor grooves and intercalate into DNA, which was done using absorption, fluorescence, and circular dichroism spectroscopy. Finally, the docking simulation study showed the mode of DNA bindings is in good agreement with the spectral binding data.

Sulfur- and DABCO-Promoted Reaction between Alkylidene Rhodanines and Isothiocyanates: Access to Aminoalkylidene Rhodanines.

In this work, an efficient sulfur- and DABCO-promoted reaction for the synthesis of aminoalkylidene rhodanines from available alkylidene rhodanines and isothiocyanates is reported. A tandem process including sulfurative annulation/ring-opening by liberation of a CS2 molecule/olefination allows the synthesis of aminoalkylidene rhodanines with acceptable functional group tolerance. Chemo- and stereoselectivity, operational simplicity, and synthetically useful yields are some highlighted advantages of these transformations.

Efficient synthesis of novel thiadiazolo[2,3-b]quinazolin-6-ones catalyzed by diphenhydramine hydrochloride-CoCl⋠6H2O deep eutectic solvent.

In this research, a new Lewis acid-based deep eutectic solvent (LA-DES) was synthesized using diphenhydramine hydrochloride and CoCl2·6H2O, (2[HDPH]:CoCl42-), and identified by FT-IR and 1HNMR techniques. The physicochemical properties of this LA-DES, such as thermal behavior, thermal stability, and solubility in common solvents were also investigated. The catalytic ability of 2[HDPH]:CoCl42- was ascertained in the efficient synthesis of a novel array of thiadiazolo[2,3-b]quinazolin-6-one scaffolds via a one-pot three-component reaction of dimedone/1,3-cyclohexanedione, aldehydes, and 5-aryl-1,3,4-thiadiazol-2-amines/3-(5-amino-1,3,4-thiadiazol-2-yl)-2H-chromen-2-one under solvent-free conditions. This catalyst was also successfully utilized for the synthesis of mono- and bis-thiadiazolo[2,3-b]quinazolin-6-ones from dialdehydes or bis-1,3,4-thiadiazol-2-amine. The simplicity of enforcement, short reaction time, avoidance of toxic organic solvents, scalability of the synthesis procedure, excellent atom economy, high reaction mass efficiency, and low E-factor are other outstanding advantages of this newly developed method. Furthermore, due to the convenient recovery and reuse of LA-DES, this protocol is economically justified and environmentally friendly.

catena-Poly[[di-µ2-aqua-hexaaquabis(µ3-4-oxidopyridine-2,6-dicarboxylato)trimanganese(II)] trihydrate]: a new one-dimensional coordination polymer based on a trinuclear Mn(II) complex of chelidamic acid.

4-Hydroxypyridine-2,6-dicarboxylic acid (chelidamic acid, hypydc[H]H2) reacts with MnCl2·2H2O in the presence of piperazine in water to afford the title complex, {[Mn3(C7H2NO5)2(H2O)8]·3H2O}n or {[Mn3(hypydc)2(H2O)8]·3H2O}n. This compound is a one-dimensional coordination polymer, with the twofold symmetric repeat unit containing three metal centres. Two different coordination geometries are observed for the two independent Mn(II) metal centres, viz. a distorted pentagonal bipyramid and a distorted octahedron. The 4-oxidopyridine-2,6-dicarboxylate anions and two of the water molecules act as bridging ligands. The zigzag-like geometry of the coordination polymer is stabilized by hydrogen bonds. O-H···O and C-H···O hydrogen bonds and water clusters consolidate the three-dimensional network structure.

Dichloridodi-µ(2)-hydroxido-di-µ(3)-oxido-octa-phenyl-tetra-tin(IV) dimethyl sulfoxide disolvate.

In the centrosymmetric tetra-nuclear title mol-ecule, [Sn(4)(C(6)H(5))(8)Cl(2)O(2)(OH)(2)]·2C(2)H(6)OS, the two independent tin(IV) atoms show distorted trigonal-bipyramidal SnC(2)O(3) and SnC(2)O(2)Cl coordination geometries. The four tin(IV) atoms are bridged by the hydroxo and oxo ligands, forming a ladder-like array of three edge-connected Sn(2)O(2) squares. The solvent mol-ecules are linked to the tetra-nuclear mol-ecule via O-H⋯O hydrogen bonds.