Pd-Catalyzed Cross-Coupling Reactions of Hydrazones: Regioselective Synthesis of Highly Branched Dienes

The regioselective formation of highly branched dienes is a challenging task. Design and exploration of alternative working models to achieve such a regioselectivity to accomplish highly branched dienes is considered to be a historical advancement of Heck reaction to construct branched dienes. On the basis of the utility of carbene transfer reactions, in the reaction of hydrazones with Pd(II) under oxidative conditions, we envisioned obtaining a Pd-bis-carbene complex with alpha-hydrogens, which can lead to branched dienes. Herein, we report a novel Pd-catalyzed selective coupling reaction of hydrazones in the presence of t-BuOLi and benzoquinone to form the corresponding branched dienes. The utility of the Pd catalyst for the cross-coupling reactions for synthesizing branched conjugated dienes is rare. The reaction is very versatile and compatible with a variety of functional groups and is useful in synthesizing heterocyclic molecules. We anticipate that this Pd-catalyzed cross-coupling reaction will open new avenues for synthesizing useful compounds.

Palladium Catalyzed Coupling of Tosylhydrazones with Aryl and Heteroaryl Halides in the Absence of External Ligands: Synthesis of Substituted Olefins

Palladium catalyzed cross-coupling reaction of hydrazones with aryl halides in the absence of external ligand is reported. The versatility of this coupling reaction is demonstrated in showcasing the selectivity of coupling reaction in the presence of hydroxyl and amine functional groups. This method allows synthesizing a variety of heterocyclic compounds, which are difficult to access from other traditional methods and are not synthesized by employing similar coupling reactions. Application of the present methodology is validated in tandem reaction of ketones to the corresponding substituted olefins in a single pot experiment.

Cyclometalated complexes derived from calix[4] arene bisphosphites and their catalytic applications in cross-coupling reactions

Palladium and platinum dichloride complexes of a series of symmetrically and unsymmetrically substituted 25,26;27,28-dibridged p-tert-butyl-calix[4]arene bisphosphites in which two proximal phenolic oxygen atoms of p-tert-butyl-or p-H-calix[4]arene are connected to a P(OR) ( R = substituted phenyl) moiety have been synthesized. The palladium dichloride complexes of calix[4]arene bisphosphites bearing sterically bulky aryl substituents undergo cyclometalation by C-C or C-H bond scission. An example of cycloplatinated complex is also reported. The complexes have been characterized by NMR spectroscopic and single crystal X-ray diffraction studies. During crystallization of the palladium dichloride complex of a symmetrically substituted calix[4]arene bisphosphite in dichloromethane, insertion of oxygen occurs into the Pd-P bond to give a P,O-coordinated palladium dichloride complex. The calix[4]arene framework in these bisphosphites and their metal complexes adopt distorted cone conformation; the cone conformation is more flattened in the metal complexes than in the free calix[4]arene bisphosphites. Some of these cyclometalated complexes proved to be active catalysts for Heck and Suzuki C-C cross-coupling reactions but, on an average, the yields are only modest. (C) 2011 Elsevier B.V. All rights reserved.

C-H functionalization of tertiary amines by cross dehydrogenative coupling reactions: solvent-free synthesis of alpha-aminonitriles and beta-nitroamines under aerobic condition

A solvent-free synthesis of alpha-aminonitriles and beta-nitroamines by oxidative cross-dehydrogenative coupling under aerobic condition is reported. A catalytic amount of molybdenum(VI) acetylacetonoate was found to catalyze cyanation of tertiary amines to form alpha-aminonitriles, whereas vanadium pentoxide was found to promote aza-Henry reaction to furnish beta-nitroamines. Both of these environmentally benign reactions are performed in the absence of solvents using molecular oxygen as an oxidant.

Computational tools for mechanistic discrimination in the reductive and metathesis coupling reactions mediated by titanium(IV) isopropoxide

A theoretical study has been carried out at the B3LYP/LANL2DZ level to compare the reactivity of phenyl isocyanate and phenyl isothiocyanate towards titanium(IV) alkoxides. Isocyanates are shown to favour both mono insertion and double insertion reactions. Double insertion in a head-to-tail fashion is shown to be more exothermic than double insertion in a head-to-head fashion. The head-to-head double insertion leads to the metathesis product, a carbodiimide, after the extrusion of carbon dioxide. In the case of phenyl isothiocyanate, calculations favour the formation of only mono insertion products. Formation of a double insertion product is highly unfavourable. Further, these studies indicate that the reverse reaction involving the metathesis of N,N-'-diphenyl carbodiimide with carbon dioxide is likely to proceed more efficiently than the metathesis reaction with carbon disulphide. This is in excellent agreement with experimental results as metathesis with carbon disulphide fails to occur. In a second study, multilayer MM/QM calculations are carried out on intermediates generated from reduction of titanium(IV) alkoxides to investigate the effect of alkoxy bridging on the reactivity of multinuclear Ti species. Bimolecular coupling of imines initiated by Ti(III) species leads to a mixture of diastereomers and not diastereoselective coupling of the imine. However if the reaction is carried out by a trimeric biradical species, diastereoselective coupling of the imine is predicted. The presence of alkoxy bridges greatly favours the formation of the d,l (+/-) isomer, whereas the intermediate without alkoxy bridges favours the more stable meso isomer. As a bridged trimeric species, stabilized by bridging alkoxy groups, correctly explains the diastereoselective reaction, it is the most likely intermediate in the reaction.

Highly regioselective C2-alkenylation of indoles using the N-benzoyl directing group: an efficient Ru-catalyzed coupling reaction

A highly regioselective alkenylation of indole at the C2-position has been achieved using the Ru(II) catalyst by employing a directing group strategy. This strategy offers rare selectivity for the alkenylation N-benzoylindole at the C-2 position in the presence of the more active C3- and C7-position of indole and the ortho-positions of the benzoyl protecting group. A simple deprotection of the benzoyl group has also been exemplified, and the resulting product serves as a useful synthon for natural product syntheses.

An easily prepared palladium-hydrogel nanocomposite catalyst for C-C coupling reactions

Supported metallic nanoparticles are important composite materials owing to their enormous potential for applications in various fields. In this work, palladium nanoparticles were prepared in situ in a calcium-cholate (Ca-Ch) hydrogel by reduction with sodium cyanoborohydride. The hydrogel matrix appeared to assist the controlled growth as well as stabilization of palladium nanoparticles. The palladium nanoparticle/Ca-Ch hydrogel hybrid was characterized by scanning and transmission electron microscopy, atomic force microscopy, X-ray diffraction, and energy-dispersive X-ray spectroscopy. Furthermore, the PdNP/Ca-Ch hybrid xerogel was shown to act as an active catalyst for the Suzuki reaction under aqueous aerobic conditions. The PdNP/Ca-Ch xerogel retains its catalytic activities on storage for several months.

A chemoselective alpha-aminoxylation of aryl ketones: a cross dehydrogenative coupling reaction catalysed by Bu4NI

Tetrabutyl ammonium iodide (TBAI) catalyzed alpha-aminoxylation of ketones using aq. TBHP as an oxidant has been accomplished. We have shown that the CDC (cross dehydrogenative coupling) reactions of ketones with N-hydroxyimidates such as N-hydroxysuccinimide (NHSI), N-hydroxyphthalimide (NHPI), N-hydroxybenzotriazole (HOBt) and 1-hydroxy-7-azabenzotriazole (HOAt) lead to the corresponding oxygenated products in good to moderate yields. The application of this method has been demonstrated by transforming a few coupled products into synthetically useful intermediates and products.

Increased Efficacies of an Individual Catalytic Site in Clustered Multivalent Dendritic Catalysts

In the studies reported so far on dendrimer-mediated catalysis, the efficacies of the catalytic units were studied and compared primarily across the generations. In order to identify the efficacy of an individual catalytic unit with respect to the number of such units present within a given generation, a series of catalysts were prepared within a generation. Dendrimers incorporated with phosphinemetal complexes were chosen for the study and as many as 11 catalysts within three generations were synthesized. The C-C bond-forming reactions, namely, the Heck and the Suzuki coupling reactions, were then selected to study the catalytic efficiencies of the series of partially and fully phosphine-metal complex functionalized dendrimers. The efficacies of the formation of cinnamate and biphenyl. catalyzed by the dendritic catalysts, were compared. The comparative analyses show that an individual catalytic site is far more effective in its catalytic activity when presented in multiple numbers, i.e., in a multivalent dendritic system, than as a single unit within the same generation, i.e., in a monovalent dendritic system. The study identifies the beneficial effects of the multivalent presentation of the catalytic moieties, both within and across the dendrimer generations.

Inhibition of peroxidase-catalyzed protein tyrosine nitration by antithyroid drugs and their analogues

In this paper, we describe the effect of some commonly used thiourea-based antithyroid drugs and their analogues on the peroxidase-catalyzed nitration reactions. The nitration of bovine serum albumin (BSA) and cytochrome c was studied using the antibody against 3-nitro-L-tyrosine. This study reveals that the thione-based antithyroid drugs effectively inhibit lactoperoxidase (LPO)-catalyzed nitration of BSA. These compounds show very weak inhibition towards the nitration of cytochrome c. Some of these compounds also inhibit myeloperoxidase (MPO)-catalyzed nitration of L-tyrosine. A structure-activity correlation study on the peroxidase-catalyzed nitration of L-tyrosine reveals that the presence of thione/selone moiety is important for the inhibition. Although the presence of a free N-H group adjacent to C=S moiety is necessary for most of the thiones to inhibit the LPO-catalyzed nitration, the corresponding selones do not require the presence of any free N-H group for their activity. Furthermore, experiments with different concentrations of H2O2 suggest that the antithyroid drugs and related thiones inhibit the nitration reaction mainly by coordinating to the Fe(III)-center of the enzyme active site as previously proposed for the inhibition of peroxidase-catalyzed iodination. On the other hand, the selenium compounds inhibit the nitration by scavenging H2O2 without interacting with the enzyme active site. This assumption is based on the observations that catalase effectively inhibits tyrosine nitration by scavenging H2O2, which is one of the substrates for the nitration. In contrast, superoxide dismutase (SOD) does not alter the nitration reactions, indicating the absence of superoxide radical anion (O-2 center dot(-)) during the peroxidase-catalyzed nitration reactions. (C) 2010 Elsevier B.V. All rights reserved.

Inhibition of Lactoperoxidase-Catalyzed Oxidation by Imidazole-Based Thiones and Selones: A Mechanistic Study

Herein, we describe the synthesis and biomimetic activity of a series of N,N-disubstituted thiones and selones that contain an imidazole pharmacophore. The N,N-disubstituted thiones do not show any inhibitory activity towards LPO-catalyzed oxidation reactions, but their corresponding N,N-disubstituted selones exhibit inhibitory activity towards LPO-catalyzed oxidation reactions. Substituents on the N atom of the imidazole ring appear to have a significant effect on the inhibition of LPO-catalyzed oxidation and iodination reactions. Selones 16, 17, and 19, which contain methyl, ethyl, and benzyl substituents, exhibit similar inhibition activities towards LPO-catalyzed oxidation reactions with IC50 values of 24.4, 22.5, and 22.5M, respectively. However, their activities are almost three-fold lower than that of the commonly used anti-thyroid drug methimazole (MMI). In contrast, selone 21, which contains a NCH2CH2OH substituent, exhibits high inhibitory activity, with an IC50 value of 7.2M, which is similar to that of MMI. The inhibitory activity of these selones towards LPO-catalyzed oxidation/iodination reactions is due to their ability to decrease the concentrations of the co-substrates (H2O2 and I2), either by catalytically reducing H2O2 (anti-oxidant activity) or by forming stable charge-transfer complexes with oxidized iodide species. The inhibition of LPO-catalyzed oxidation/iodination reactions by N,N-disubstituted selones can be reversed by increasing the concentration of H2O2. Interestingly, all of the N,N-disubstituted selones exhibit high anti-oxidant activities and their glutathione peroxidase (GPx)-like activity is 4-12-fold higher than that of the well-known GPx-mimic ebselen. These experimental and theoretical studies suggest that the selones exist as zwitterions, in which the imidazole ring contains a positive charge and the selenium atom carries a large negative charge. Therefore, the selenium moieties of these selones possess highly nucleophilic character. The 77SeNMR chemical shifts for the selones show large upfield shift, thus confirming the zwitterionic structure in solution.

Synthesis of Azo Coupled Crown Ethers Containing Transition Metal and other Chromophoric Environments and Their Ion Complexation Properties

The crown ethers, 2,3-benzo-1,4,7,10,13-pentaoxa-cyclopentadeca-2-ene and 2,3, ll,12-dibenzo-l,4,7,10,13,16-hexaoxscyclooctadeca-2,11-diene are incorporated into H,N'-ethylenebis(acetylacetoneimino) nickel(II) and copper(II), phenol, and β-naphthol by diazo coupling reactions. The selective nature of the coupling reaction has-been demonstrated by the isolation of both asymmetric mono- and symmetric bis(glyoxalarylcrownhydrazoneimino) metal(II) complexes. An interesting binuclear complex containing two intramolecularly rearranged (glyoxal-hydrazonearylimino) metal(II) groups joined by 18-crown-6 result8 when bis(arenediazonium)-18-crown-6 is coupled with the metal(I1) Schiff bases. The substituted ethers form cationic salts with NaClO4, KCNS, NH4CNS, 14g(CNS)2 and Ca(CNS)2. All the synthesised ethers exhibit ion selectivity sequence as K+ > Na+ and Ca2+ > Mg2+.

Synthesis of Azo Coupled Crown Ethers Containing Transition Metal and other Chromophoric Environments and Their Ion Complexation Properties

The crown ethers, 2,3-benzo-1,4,7,10,13-pentaoxa-cyclopentadeca-2-ene and 2,3, ll,12-dibenzo-l,4,7,10,13,16-hexaoxscyclooctadeca-2,11-diene are incorporated into H,N'-ethylenebis(acetylacetoneimino) nickel(II) and copper(II), phenol, and β-naphthol by diazo coupling reactions. The selective nature of the coupling reaction has-been demonstrated by the isolation of both asymmetric mono- and symmetric bis(glyoxalarylcrownhydrazoneimino) metal(II) complexes. An interesting binuclear complex containing two intramolecularly rearranged (glyoxal-hydrazonearylimino) metal(II) groups joined by 18-crown-6 result8 when bis(arenediazonium)-18-crown-6 is coupled with the metal(I1) Schiff bases. The substituted ethers form cationic salts with NaClO4, KCNS, NH4CNS, 14g(CNS)2 and Ca(CNS)2. All the synthesised ethers exhibit ion selectivity sequence as K+ > Na+ and Ca2+ > Mg2+.

Preparation of lithium amalgam

Lithium amalgam is useful in effecting Wurtz type intramolecular and intermolecular coupling reactions.

Branching out at C-2 of septanosides. Synthesis of 2-deoxy-2-C-alkyl/aryl septanosides from a bromo-oxepine

This paper deals with the synthesis of 2-deoxy-2-C-alkyl/aryl septanosides. A range of such septanoside derivatives was synthesized by using a common bromo-oxepine intermediate, involving C-C bond forming organometallic reactions. Unsaturated, seven-membered septanoside vinyl bromides or bromo-oxepines, obtained through a ring expansion methodology of the cyclopropane derivatives of oxyglycals, displayed a good reactivity towards several acceptor moieties in C-C bond forming Heck, Suzuki and Sonogashira coupling reactions, thus affording 2-deoxy-2-C-alkyl/aryl septanosides. Whereas Heck and Sonogashira coupling reactions afforded 2-deoxy-2-C-alkenyl and -alkynyl derivatives, respectively, the Suzuki reaction afforded 2-deoxy-2-C-aryl septanosides. Deprotection and reduction of the 2-deoxy-2-alkenyl derivative afforded the corresponding 2-deoxy-2-C-alkyl septanoside free of protecting groups. The present study illustrates the reactivity of bromo-oxepine in the synthesis of hitherto unknown septanosides, branching out at C-2, through C-C bond formation with alkyl and aryl substituents.