36266-40-7

-

The enantioselective hydroboration of vinylarenes catalyzed by a chiral, nonracemic nickel catalyst is presented as a facile method for generating chiral benzylic boronate esters. Various vinylarenes react with bis(pinacolato)diboron (B2pin2) in the presence of MeOH as a hydride source to form chiral boronate esters in up to 92% yield with up to 94% ee. The use of anhydrous Me4NF to activate B2pin2 is crucial for ensuring fast transmetalation to achieve high enantioselectivities.

In this study, we have assessed directed carbon-hydrogen activation (CHA) for alkylation of monomeric, dimeric, and polymeric lignin models using Murai's catalyst [RuH2(CO)(PPh3)3]. Based on related work from our laboratory showing that isolated organosolv lignin bears benzylic directing groups ideal for CHA reactions, this approach could offer new methodology for the valorization of biorefinery lignin. Monomeric and dimeric models bearing a keto group at the benzylic position undergo Ru-catalyzed alkylation in good to excellent yield. Similarly, models bearing a benzylic OH group also undergo alkylation via a tandem oxidation/alkylation process enabled by the Ru catalyst. Polymeric models show low levels of functionalization as a result of the poor solubility of the starting polymer. With unsymmetrical models, functionalization occurs first at the least sterically hindered ortho-site, but a subsequent alkylation, leading to disubstituted products can occur at the more sterically hindered site, leading to hexasubstituted arenes. The reaction shows sensitivity to free phenolic OH groups, which appears to reduce the yield in some reactions, and is also a contributing factor to the low yields observed with polymeric lignin models. Combining CHA methodology with lignin isolation technology able to introduce appropriate directing groups for catalytic functionalization will form the basis for improved conversion of lignin to high value chemical products.

The Meerwein-Ponndorf-Verley (MPV) reaction is an attractive approach to selectively reduce carbonyl groups, and the design of advanced catalysts is the key for these kinds of interesting reactions. Herein, we fabricated a novel zirconium organoborate using 1,4-benzenediboronic acid (BDB) as the precursor for MPV reduction. The prepared Zr-BDB had excellent catalytic performance for the MPV reduction of various biomass-derived carbonyl compounds (i.e., levulinate esters, aldehydes and ketones). More importantly, the number of borate groups on the ligands significantly affected the catalytic activity of the Zr-organic ligand hybrids, owing to the activation role of borate groups on hydroxyl groups in the hydrogen source. Detailed investigations revealed that the excellent performance of Zr-BDB was contributed by the synergetic effect of Zr4+and borate. Notably, this is the first work to enhance the activity of Zr-based catalysts in MPV reactions using borate groups.

Amines are among the most fundamental motifs in chemical synthesis, and the introduction of amine building blocks via selective C—C bond cleavage allows the construction of nitrogen compounds from simple hydrocarbons through direct skeleton modification. Herein, we report a novel method for the preparation of anilines from alkylarenes via Schmidt-type rearrangement using redox-active amination reagents, which are easily prepared from hydroxylamine. Primary amines and secondary amines were prepared from corresponding alkylarenes or benzyl alcohols under mild conditions. Good compatibility and valuable applications of the transformation were also displayed.

A simple, efficient, cost-effective, recyclable and green approach has been developed for the synthesis of new dihydropyrimidinone analogs via the Biginelli reaction. The methodology involves a multicomponent reaction catalyzed by "HPA-Montmorillonite-KSF"as a reusable and heterogeneous catalyst. This method gives an efficient and much improved modification of the original Biginelli reaction, in terms of yield and short reaction times under solvent free conditions. All the derivatives were subjected to cytotoxicity screening against a panel of four different human cancer cell lines viz. colon (Colo-205), prostate (PC-3), leukemia (THP-1) and lung (A549) to check their effect on percentage growth. MTT [3-(4,5-dimethylthiazol-yl)-diphenyl tetrazoliumbromide] cytotoxicity assay was employed to check IC50 values. Of the synthesized analogs, 16a showed the best activity with IC50 of 7.1 ± 0.8, 13.1 ± 1.4, 13.8 ± 0.9 and 14.7 ± 1.1 μM against lung (A549), leukemia (THP-1), prostate (PC-3) and colon (Colo-205) cancer lines, respectively. The 16a analog was further checked for its effect on cancer cell properties through clonogenic (colony formation) and scratch motility (wound healing) assays and thereby was found that it reduced both the colony formation and migratory properties of the lung cancer cell line (A549). Further, molecular docking studies were performed with 16a to show its binding mode. This journal is

The cleavage of representative lignin systems has been achieved in a metal-free two-step sequence first employing nitrogen monoxide for oxidation followed by hydrazine for reductive C?O bond scission. In combining nitrogen monoxide and lignin, the newly developed valorization strategy shows the particular feature of starting from two waste materials, and it further exploits the attractive conditions of a Wolff-Kishner reduction for C?O bond cleavage for the first time. (Figure presented.).

An experimental protocol to achieve the Meerwein-Ponndorf-Verley (MPV) reduction of ketones under mildly basic conditions is reported. The transformation is tolerant of a range of ketone substrates, including O- and S-containing heterocycles, is scalable, and shows potential to be used as a platform to access enantioenriched products. These studies provide a general method for achieving the reduction of ketones under mildly basic conditions and offer an alternative protocol to more well-known Al-based MPV reduction conditions.

An efficient method for the reduction of ketones with 1-hydrosilatrane is described. In the presence of a Lewis base activator, the resulting secondary alcohols are rapidly formed in good to excellent yields (20 examples, 71–99 % yields). The relative bulkiness of 1-hydrosilatrane also enables the diastereoselective reduction of (–)-menthone to (+)-neomenthol, and the use of a chiral alkoxide activator can lead to the enantioselective reduction of prochiral ketones.

Half-sandwich ruthenium(ii) complexes 1-6 bearing imidazolylidene and pyridyl-imidazolylidene ligands have been synthesised in good yields and were characterised on the basis of spectral and analytical evidence. In addition, the structures of the complexes 1-4 were unambiguously established through single crystal X-ray analysis. Transmetalation of the ligands followed by complexation with ruthenium precursors yielded the air and moisture stable complexes. The crystal structures of these complexes exhibited piano-stool geometries with η6-coordination of the p-cymene or hexamethylbenzene moieties. These complexes exhibited catalytic activity in the transfer hydrogenation of carbonyls in an alkaline medium using 2-propanol as the hydrogen source. The effect of variations in the catalyst structure on the transfer hydrogenation and stability was investigated in detail, and theoretical calculations were employed to understand the mechanism of the catalytic activity. The neutral ruthenium-NHC complexes 1 and 2 showed the efficiency of ca. 100% at a catalyst loading of ca. 2 mol% within 2 h of the reaction in 2-propanol, whereas quantitative yields were obtained in the presence of cationic ruthenium-NHC complexes 3-6 within 1 h at a low catalyst loading of ca. 0.5 mol%, thereby demonstrating their robustness for the transfer hydrogenation of the aromatic ketones.

A method of producing an alcohol, comprises reducing an aldehyde or a ketone with a hydridosilatrane. The reducing is carried out with an activator.

New 1,3-dialkyltetrahydropyrimidinium salts as NHC precursors have been synthesized and characterized. The in situ prepared three-component 1,3-dialkyltetrahydropyrimidinium salts/[RuCl2(p-cymene)]2 and KOH catalyzes quantitatively t

An immobilised iridium hydrogen transfer catalyst has been developed for use in flow based processing by incorporation of a ligand into a porous polymeric monolithic flow reactor. The monolithic construct has been used for several redox reductions demonstrating excellent recyclability, good turnover numbers and high chemical stability giving negligible metal leaching over extended periods of use.

A direct process for the trifluoromethylthiolation of allylic and benzylic alcohols under mild conditions has been developed. A wide range of free alcohols underwent nucleophilic substitution in the presence of stable CuSCF3 and BF3·Et2O to give the corresponding products in good to excellent yields.

The first electron-rich N-heterocyclic silylene (NHSi)-iron(0) complexes are reported. The synthesis of the starting complex is accomplished by reaction of the electron-rich Fe0 precursor [(dmpe)2Fe(PMe 3)] 1 (dmpe =1,2-bis(dimethylphosphino)ethane) with the N-heterocyclic chlorosilylene LSiCl (L = PhC(NtBu)2) 2 to give, via Me3P elimination, the corresponding iron complex [(dmpe)2Fe(←:Si(Cl)L)] 3. Reaction of in situ generated 3 with MeLi afforded [(dmpe)2Fe(←:Si(Me)L)] 4 under salt metathesis reaction, while its reaction with Li[BHEt3] yielded [(dmpe) 2Fe(←:Si(H)L)] 5, a rare example of an isolable SiII hydride complex and the first such example for iron. All complexes were fully characterized by spectroscopic means and by single-crystal X-ray diffraction analyses. DFT calculations further characterizing the bonding situation between the SiII and Fe0 centers were also carried out, whereby multiple bonding character is detected in all cases (Wiberg Bond Index >1). For the first time, the catalytic activity of a SiII hydride complex was investigated. Complex 5 was used as a precatalyst for the hydrosilylation of a variety of ketones in the presence of (EtO)3SiH as a hydridosilane source. In most cases excellent conversions to the corresponding alcohols were obtained after workup. The reaction pathway presumably involves a ketone-assisted 1,2-hydride transfer from the SiII to Fe0 center, as a key elementary step, resulting in a betaine-like silyliumylidene intermediate. The appearance of the latter intermediate is supported by DFT calculations, and a mechanistic proposal for the catalytic process is presented.

The reaction of [RuCl2(p-cymene]2 with Ag-N-heterocyclic carbene (NHC) complexes yields a series of [(p-cymene)Ru(NHC)] complexes (2a-f). All synthesised compounds were characterized by elemental analysis, NMR spectroscopy and the mo

Aryl alkyl-, heteroaryl alkyl- and dialkyl ketones were readily reduced to their corresponding secondary alcohols in high yields, using the commercially available and inexpensive polymeric silane polymethylhydrosiloxane (PMHS), as reducing agent. The reaction is catalyzed by an in situ-generated iron complex, conveniently generated from iron(II) acetate and the commercially available N-heterocyclic carbene (NHC) precursor IPr·HCl.

Hydrogen-transfer reduction processes are attracting increasing interest from synthetic chemists in view of their operational simplicity. In the present study novel ruthenium carbene complexes were generated in situ and tested for their transfer hydrogena

In the present study the abilities of catalysts modified by formamidine ligands have been examined in the zinc-catalyzed hydrosilylation of ketones and the iron-catalyzed epoxidation of stilbene, In case of hydrosilylation diethylzinc combined with easily accessible formamidine ligands allow for the efficient reduction of various aryl and alkyl ketones. By using a convenient in situ catalyst system high turnover frequencies up to more than 1.000 h -1 and a broad functional group tolerance were achieved. Moreover, the formamidine ligands were successfully applied, in the iron-catalyzed epoxidation of stilbene with hydrogen peroxide in good yield and chemoselectivity.

A series of benzimidazolium ligand precursors were metalated with [RuCl2(p-cymene)]2 to give ruthenium(II) N-heterocyclic carbene complexes. All compounds were fully characterized by elemental analyses, 1H NMR, 13/su

In the present study, the zinc-catalyzed hydrosilylation of various ketones to give their corresponding alcohols has been examined in detail. Diethyl zinc that can be modified by easily accessible phenol ligands allows the efficient reduction of various aryl and alkyl ketones. By using a practical in situ catalyst, excellent turnover frequencies up to 1000 h-1 and a broad functional group tolerance were achieved.

Structural redesign of selected non-steroidal estrogen receptor binding compounds has previously been successful in the discovery of new inhibitors of tubulin assembly. Accordingly, tetra-substituted alkene analogues (21-30) were designed based in part on combinations of the structural and electronic components of tamoxifen and combretastatin A-4 (CA4). The McMurry coupling reaction was used as the key synthetic step in the preparation of these tri- and tetra-arylethylene analogues. The structural assignment of E, Z isomers was determined on the basis of 2D-NOESY experiments. The ability of these compounds to inhibit tubulin polymerization and cell growth in selected human cancer cell lines was evaluated. Although the compounds were found to be less potent than CA4, these analogues significantly advance the known structure-activity relationship associated with the colchicine binding site on β-tubulin.

A simple and inexpensive procedure for the pinacol formation of aromatic aldehydes and reduction of aromatic ketones to the corresponding alcohols with magnesium in dry methanol at ambient temperature is reported. The pinacol formation and reduction are proposed to be proceeding by SET from magnesium.

Inhibitors of drug metabolism have important implications in pharmaco- toxicology and agriculture. We have reported earlier that piperine, a major alkaloid of black and long peppers inhibits both constitutive and inducible cytochrome P450 (CYP)-dependent drug metabolising enzymes. In the present study, an attempt has been made to prepare several novel synthetic analogues so as to relate various modifications in the parent molecule to the inhibition of CYP activities. Two types of mono-oxygenase reactions arylhydrocarbon hydroxylase (AHH) and 7-methoxycoumarin-O-demethylase (MOCD) have been studied. Inhibition studies were investigated in rat microsomal fraction prepared from untreated, 3MC- and PB- treated rat liver in vitro. Modifications were introduced into the piperine molecule: (i) in the phenyl nucleus, (ii) in the side chain and (iii) in the basic moiety. Thus, 38 compounds have been subjected to such studies, and simultaneously an attempt has also been made to arrive at the structure-activity relationship of synthetic analogues. In general, most of the inhibitory potential of the parent molecule is lost with modification in either of the three components of piperine. Saturation of the side chain resulted in significantly enhanced inhibition of CYP while modifications in the phenyl and basic moieties in few analogues offered maximal selectivity in inhibiting either constitutive or inducible CYP activities. Thus few novel analogues as CYP inactivators have been synthesized which may have important consequences in pharmacokinetics and bioavailability of drugs. (C) 2000 Elsevier Science Ltd.

A range of carboxylic esters and acids have been converted efficiently to the corresponding alcohols with polymethylhydrosiloxane in the presence of catalytic tetrabutylammonium fluoride. The reduction of ketones and aldehydes with PMHS and other alkoxysilanes in the presence of TBAF or benzyltrimethylammonium hydroxide is also described.

The discrimination between enantiomers that have a chiral centre directly attached to the electron rich aromatic ring by interactions with optically pure electron deficient aromatic compounds was studied by 1H NMR and molecular mechanics calculations.The enantiomeric spectroscopic discrimination is due to formation of non-bonding interactions which lead to the formation of diastereoisomeric complexes.The calculated HOMO energy values for electron rich racemic compounds and LUMO values for electron poor resolving agents are in good agreement with the observed chemicalshift differences between enantiomers by 1H NMR.Exceptions to these observations are seen for compounds which possess groups that are in a position to sterically push apart the complexation components and thus decrease the binding energy and diminish the enantiomeric discrimination.The discrimination strongly depends on concentration of the components in the solution, their ratio, temperature and the polarity of the media.Polar racemic compounds show the smallest enantiomeric discrimination by increasing the polarity of the media.For good enantiomeric discrimination both chiral centres must be rigidly bound to the aromatic rings.If the chiral centre is separated from the aromatic ring by flexible bonds the enantiomeric recognition fails despite the formation of strong non-bonding interactions.The binding energies calculated by AMBER and MM + force fields are relatively weak (ca. 2 kcal mol-1) suggesting that only a small portion of the molecules in solution are incorporated into the complexes.Our attempt to provide evidence for selective binding of only one enantiomer to the template molecule was unsuccessful.Neverthelessour results support the formation of inter-exchangeable diastereomeric complexes.Although it might be argued that two sets of signals should also be obtained for the template molecule, all our 1H NMR spectra show only one set of signals for the optically pure template and two sets of signals for the racemic component in their chloroform solutions.Despite low binding energies enantiomeric discrimination with strong electron accepting resolving agents can be achieved in as low as 0.01 mol dm-3 chloroform solution.

A series of 6-benzyl-1,3-benzodioxoles have been synthesized and evaluated against the in vivo ip P388 murine lymphocytic leukemia. Selected actives against this system were tested against the additional in vivo systems L1210, B16, M5076, and MX1. The mos