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A simple, convenient, transition metal-free one pot synthesis of 3,5-disubstituted-1,2,4-triazoles has been established. The innovation in this reaction is the use of easily available 1,1-diaminoazines as substrates. This method provides the products with wider substrate scope, at an expedited rate, and with relatively better yields in comparison to the reported methods. The reaction mechanism involves an initial intermolecular nucleophilic addition (facilitated by I2) followed by intramolecular nucleophilic cyclization.

The phytochemical study of the CH2Cl2- MeOH (1:1, v/v) extract of the stem bark of Carapa procera DC (Meliaceae) led to the isolation and characterisation of a new natural limonoid 7β-obacunol (6),...

A direct and operationally simple method for the regioselective synthesis of 2-aryl-substituted 2H-indazoles is reported. The Pd-catalyzed reaction between easily available 2-bromobenzyl bromides and arylhydrazines employing Cs2CO3 as the base and t-Bu3PHBF4 as the ligand in DMSO at 120 °C in a sealed tube delivers the 2-substituted-2H-indazoles in a single synthetic step with yields up to 79%. The new method is based on a regioselective intermolecular N-benzylation followed by intramolecular N-arylation and oxidation.

The tautomeric preference of guanylhydrazones towards the azine form induces an unprecedented intramolecular to intermolecular mechanistic switch during the I2-catalyzed oxidative transformation leading to 4,5-disubstituted-3-amino-1,2,4-triazoles in contrast to the reaction of semicarbazones and thiosemicarbazones to form 1,3,4-oxa/thiadiazoles. This intramolecular to intermolecular cyclization shift was established through control experiments and was attributed to the high energy demand (∼22 kcal mol−1) for the azine tautomer to adopt the s-cis conformation which is essential for the intramolecular reaction. An I2 induced protocol for an efficient and straightforward synthesis of 4,5-disubstituted-3-amino-1,2,4-triazoles has been developed via tandem oxidative transformation of guanylhydrazones (in its preferentially existing azine tautomeric form) with distinct advantages such as wide substrate scope, use of substoichiometric amounts of iodine, no requirement of external oxidizing agents, base free reaction conditions, short reaction time and moderate to good yields. The role of silver salt in improving the yield and shortening of reaction time was also highlighted.

The laccase-catalyzed iodination of p-hydroxyarylcarbonyl- and p-hydroxyarylcarboxylic acid derivatives using KI as iodine source and aerial oxygen as the oxidant delivers the corresponding iodophenols in a highly efficient and sustainable manner with yields up to 93% on a preparative scale under mild reaction conditions.

The Cu2O-catalyzed reaction between equimolar amounts of easily available 3-substituted-2-bromo-2-propen-1-ols and dicyclohexyl carbodiimide in DMSO at 100 °C using K3PO4 as the base and in the absence of any additive exclusively delivers substituted 2-iminooxazolidines with yields up to 80%. The highly selective transformation is assumed to start with an intermolecular 1,2-addition, which is followed by an intramolecular N-vinylation. The products can also be obtained in the absence of Cu2O, albeit in lower yields.

Treatment of 1,3-diaryl-propene-2-one with aminoguanidine under acidic conditions for a short reaction period (1 h) delivers - in accordance with a literature report - the corresponding guanylhydrazones. However, when the reaction time was increased to 12 h, formation of the ring annulated product 4,5-dihydro-1H-pyrazole-1-carboximidamide was observed. This is the first case of ring-chain isomerism in conjugated guanylhydrazones. The acyclic conjugated guanylhydrazone and the corresponding annulated product (4,5-dihydro-1H-pyrazole-1-carboximidamide) could be clearly distinguished by means of UV and NMR spectroscopy. The formation of the ring isomer was further confirmed by single crystal XRD analysis. The time-dependent 1H NMR study indicated the gradual transformation of the open-chain compound into the cyclic one. The mechanistic insights into the formation of these two products were explored using quantum chemical methods which revealed that the ring isomer is thermodynamically more stable than the open-chain isomer by 6–11 kcal/mol and the barrier for cyclization was found to be 31.37 kcal/mol.

Considering their growing attention in the field of medicinal chemistry and drug-discovery research, the facile and convenient approaches towards the preparation of 2-aryl benzoxazole derivatives have been described. The transformation is accomplished by using Fe(III)-catalyzed C–H activation of benzoxazoles with boronic acids to obtain a wide range of C2-arylated benzoxazoles in high yields. The developed method excludes the formation of self-coupling compounds as side products. On the other hand, the synthesis of the products is also achieved via a metal-free domino protocol by the reaction between 1-nitroso-2-naphthol and acetophenones using catalytic amounts of CBr4 in the presence of Cs2CO3 as base. The devised tandem method avoids the use of pre-activated α-haloketones as substrates. Due to their immense impact in marketed drugs and molecules under clinical trial, the described method can be a powerful tool for their synthesis which ­restricts the use of precious metals as catalyst.

Molybdenum(VI)-catalyzed domino reductive cyclization of nitroarenes has been devised for the syntheses of 1,4-benzoxazines and 1,4-benzothiazines in the presence of pinacol as deoxygenating agent. The scope of the described method was further extended to the syntheses of the rarely explored scaffolds, 1-hydroxyphenazines and quinoxalines. The present method avoids the use of hazardous deoxygenating agents and operates under solvent-free conditions.

The laccase-catalyzed reaction between unsubstituted catechol and 2-thioxopyrimidin-4(1H)-ones using aerial O2 as the oxidant delivers novel pyrimidobenzothiazoles with high yields in an aqueous solvent system under mild reaction conditions. With 4-substituted catechols, catechol thioethers are formed exclusively. The synthetic protocols developed provide a sustainable approach for these compound classes. In addition, the cytotoxicity of the products against HepG2 cell line is reported. Most compounds exhibit antiproliferative activities with IC50 values at the micromolar level. A structure–activity relationship study will facilitate the further development of these compounds as cytotoxic agents.

Substrates bearing both a β-ketoester moiety and a (het)aryl halide structure element were dimerized to 1-naphthols and related products in the presence of catalytic amounts of CuI in isopropanol. The reaction starts with an intermolecular C-arylation, which is followed by an intramolecular condensation. The final aromatization delivers the highly substituted products with yields up to 81%.

A transition metal-free, diastereospecific reaction between substituted (Z)-1,2-dibromo-3-phenyl-2-propenes and substituted catechols using Cs2CO3 as a base at 140 °C for 18 h delivers exclusively substituted (Z)-2-arylidene-2,3-dihydrobenzo[b][1,4]dioxines in yields up to 89%. Experiments as well as quantum chemical calculations support the assumption that the one pot transformation proceeds as an intermolecular O-allylation/intramolecular O-vinylation.

The copper-catalyzed double intramolecular Ullmann coupling of syn-1,2-bis(2-bromoaryl)ethane-1,2-diols with catalytic amounts of CuII oxinate as the copper source, K3PO4 as a base, and KI as a reductant in aqueous acetonitrile selectively delivers 4b,9b-dihydrobenzofuro[3,2-b]benzofurans in diastereomerically and enantiomerically pure form and yields of up to 90 %. The substrates can be obtained in both diastereomerically and enantiomerically pure form by catalytic dihydroxylation of the corresponding (E)-stilbenes.

Fucosylated oligosaccharides present a predominant group of free oligosaccharides found in human milk. Here, a microbial conversion of lactose, D-glucose and L-fucose to fucosylated lacto-N-tetraose by growing Escherichia coli cultures is presented. The recombinant expression of genes encoding for the β1,3-N-acetylglucosaminyltransferase (LgtA) and the β1,3-galactosyltransferase (WbgO) enables the whole-cell biotransformation of lactose to lacto-N-tetraose. By the additional expression of a recombinant GDP-L-fucose salvage pathway together with a bacterial fucosyltransferase, lacto-N-tetraose is further converted into the respective fucosylated compounds. The expression of a gene encoding the α1,2-fucosyltransferase (FutC) in the lacto-N-tetraose producing E. coli strain led to the formation of lacto-N-fucopentaose I, whereas the expression of a gene encoding the α1,4-fucosyltransferase (FucT14) mainly led to the conversion of lacto-N-tetraose to lacto-N-difucohexaose II.

The reaction of 5-substituted 2-nitrosophenols with bromomethyl aryl ketones and related compounds employing K2CO3 as a base in refluxing THF and DMF at 80 °C, respectively, delivers 2-aroylbenzoxazoles in a single step with yields up to 85%. The new method involves an intermolecular nucleophilic substitution followed by intramolecular 1,2-addition and elimination. It allows an efficient and practical access to 2-aroylbenzoxazoles under transition-metal-free conditions.

The use of 2-halobenzyl tosylates as substrates in copper-catalyzed domino intermolecular substitution/intramolecular arylation processes for the efficient and selective preparation of heterocycles is reported for the first time. Reaction of 2-halobenzyl tosylates with β-ketoesters delivers 4H-chromenes with yields ranging between 59 and 89%. Imidazobenzothiazines are formed with yields up to 82% upon reaction of 2-halobenzyl tosylates with 2-mercaptoimidazoles. When 2-halobenzyl tosylates are reacted with benzamidines the corresponding quinazolines are obtained.

The CuI-catalyzed domino reaction between 1-(2-bromophenyl)methanamines and amidines using K3PO4 as the base, pivalic acid as the additive, and aerial oxygen as the oxidant gives access to substituted quinazolines in a single step with yields in the range between 43 and 90%. It is assumed that the reaction proceeds as a Cu(I)-catalyzed intermolecular N-arylation followed by an intramolecular nucleophilic substitution and a Cu(II)-catalyzed oxidation. The amidines can be replaced with imidates and the reaction can also be run with 1-(2-iodophenyl)methanamine.

Two methods for the synthesis of 3,5-diaryl-1,2,4-triazoles, both domino reactions, are reported. The first procedure, the Cu(OTf)2-catalyzed reaction between two amidines using NaHCO3 as a base, 1,10-phenanthroline as an additive and K3[Fe(CN)6]/atmospheric oxygen as the oxidant, delivers 3,5-diaryl-1,2,4-triazoles with yields up to 68%. The second procedure for the synthesis of 3,5-diaryl-1,2,4-triazoles with yields up to 64% rests on the Cu(OTf)2-catalyzed reaction between two imidates and ammonium carbonate. This method features the formation of three bonds in a single synthetic step.

The laccase-catalyzed reaction between catechols and thiols using aerial oxygen as the oxidant delivers the corresponding catechol thioethers with yields up to 96% under mild reaction conditions.

The three-component reaction of aniline, benzaldehyde, and dienophiles such as 2,3-dihydrofuran, ethyl vinyl ether, 2,3-dihydropyran, and cyclopentadiene can be promoted by ionic liquids like imidazolium salts and guanidinium salts under thermal as well as microwave conditions. The chemical yield as well as the diastereoselectivity of the Povarov reaction strongly depend on the ionic liquid employed. The guanidinium salts can be recycled and reused several times without loss of reactivity.

The reductive cyclization of o -nitrobenzylidene amines under microwave conditions employing MoO 2 Cl 2 (dmf) 2 as catalyst and Ph 3 P as reducing agent delivers 2-aryl-2 H -indazoles with yields ranging from 61–92%.

The laccase-catalyzed reaction of 3-tert-butyl-1H-pyrazol-5(4H)-one with a number of catechols and aerial oxygen as an oxidant selectively affords 4-substituted 3-tert-butyl-1H-pyrazol-5-ol derivatives with yields ranging from 77 to 99%.

The reaction of 2-(bromomethyl)benzaldehydes with arylhydrazines employing K(2)CO(3) as a base and FeCl(3) as a catalyst in CH(3)CN at 100 °C delivers 2-aryl-1,2-dihydrophthalazines with yields ranging from 60 to 91%. The transformation is considered to proceed as an intermolecular condensation/intramolecular nucleophilic substitution.

Although catalytic reductions, cross-couplings, metathesis, and oxidation of CC double bonds are well established, the corresponding catalytic hydroxylations of CH bonds in alkanes, arenes, or benzylic (allylic) positions, particularly with O2, the cheapest, “greenest”, and most abundant oxidant, are severely lacking. Certainly, some promising examples in homogenous and heterogenous catalysis exist, as well as enzymes that can perform catalytic aerobic oxidations on various substrates, but these have never achieved an industrial-scale, owing to a low space-time-yield and poor stability. This review illustrates recent advances in aerobic oxidation catalysis by discussing selected examples, and aims to stimulate further exciting work in this area. Theoretical work on catalyst precursors, resting states, and elementary steps, as well as model reactions complemented by spectroscopic studies provide detailed insight into the molecular mechanisms of oxidation catalyses and pave the way for preparative applications. However, O2 also poses a safety hazard, especially when used for large scale reactions, therefore sophisticated methodologies have been developed to minimize these risks and to allow convenient transfer onto industrial scale.

The Cu(I)-catalyzed reaction of 1-bromo-2-iodobenzenes and other 1,2-dihalobenzenes with 1,3-cyclohexanediones in DMF at 130 °C using Cs(2)CO(3) as a base and pivalic acid as an additive selectively delivers 3,4-dihydrodibenzo[b,d]furan-1(2H)-ones with yields ranging from 47 to 83%. The highly regioselective domino process is based on an intermolecular Ullmann-type C-arylation followed by an intramolecular Ullmann-type O-arylation. Substituted products are accessible by employing substituted 1-bromo-2-iodobenzenes and substituted 1,3-cyclohexanediones as substrates. Reaction with an acyclic 1,3-diketone yields the corresponding benzo[b]furan.

The laccase-catalyzed oxidative coupling of sesamol, a naturally occurring phenolic antioxidant, with O 2 as the oxidant proceeds with high selectivity and delivers a previously unknown trimer in 61% yield. Further experiments demonstrate that the outcome of the sesamol oxidation strongly depends on the catalyst and the oxidant employed.

The oxidative dimerization of 2-propenylsesamol to carpanone with O(2) as the oxidant, which probably proceeds as a domino phenol oxidation/anti-β,β-radical coupling/intramolecular hetero Diels-Alder reaction, can be efficiently catalyzed by laccases. Experiments with laccases and other catalysts like a Co(salen) type catalyst and PdCl(2) clearly demonstrate that the diastereoselectivity of the carpanone formation does not depend on the catalyst but on the double-bond geometry of the substrate. With (E)-2-propenylsesamol as the substrate, carpanone and a so far unknown carpanone diastereoisomer are formed in a 9:1 ratio. When (Z)-2-propenylsesamol is used as starting material, carpanone is accompanied by two carpanone diastereoisomers unknown so far in a 5:1:4 ratio. All three carpanone diastereoisomers have been separated by HPLC, and their structures have been elucidated unambiguously by NMR spectroscopy, DFT calculations, and spin work analysis. When the oxidation of 2-propenylsesamol with O(2) is performed in the absence of any catalyst two diastereoisomeric benzopyrans are formed, probably as the result of a domino oxidation/intermolecular hetero Diels-Alder reaction. Under these conditions, carpanone is formed in trace amounts only.

Highly substituted p-benzoquinones were obtained in yields ranging from 39% to 98% by laccase-catalyzed domino reactions between hydroquinones and cyclic 1,3-dicarbonyls using aerial oxygen as the oxidant. In almost all reactions bis-adducts with two adjacent 1,3-dicarbonyl substituents on the quinone moiety were formed selectively. The transformations can be regarded as domino oxidation/1,4-addition/oxidation/1,4-addition/oxidation processes. With unsubstituted hydroquinone as the substrate 2,3-disubstituted p-benzoquinones were isolated. Bis-adducts were also formed exclusively upon reaction with monosubstituted hydroquinones. In almost all cases the 2,3,5-trisubstituted p-benzoquinones were obtained. When 2,3-disubstituted hydroquinones were employed as starting materials the 2,3,5,6-tetrasubstituted p-benzoquinones were isolated. The unambiguous structure elucidation of all products has been achieved by NMR spectroscopic methods including spin pattern analysis of the long-range coupled C═O carbons and (13)C satellites analysis in (1)H NMR spectra.

The novel Pd-catalyzed C(sp(2))-H/C(sp(2))-H cross-coupling of unactivated xanthines with unactivated arenes utilizing a combination of Ag(I) and O(2) as oxidants exclusively yields C-8 arylated xanthines in a single synthetic operation.

The laccase-catalyzed domino reaction of o -phenylenediamine and benzaldehydes with aerial oxygen as the oxidant exclusively yields 2-aryl-1 H -benzimidazoles in good to very good yields. It is easy to perform under very mild reaction conditions.

Using the transformation of allyl 2-nitrophenyl thio-ethersto 3,4-dihydro-2 H-1,4-benzothiazinesas an example the reductive cyclization of ω-nitroalkenesto saturated N-heterocycles can be performed highly selective andwith high yields if a combination of MoO 2 Cl 2 (dmf) 2 asa catalyst and Ph 3 P as reducing agent are employed.

A new single-step transformation of readily available nitroarenes with trialkyl phosphites, which can be performed both under thermal and microwave conditions, delivers dialkyl N-arylphosphoramidates in good yields and short reaction times.

The laccase-catalyzed reaction between catechols and heterocyclic 1,3-dicarbonyls (pyridinones, quinolinones, thiocoumarins) using aerial oxygen as the oxidant delivers benzofuropyridinones, benzofuroquinolinones, and thiocoumestans in a simple fashion, highly regioselectively with yields ranging from 55 to 98%. With barbituric acid derivatives the exclusive formation of dispiropyrimidinone derivatives takes place. The unambiguous and complete structure elucidation of all reaction products has been achieved by means of NMR spectroscopic methods (HSQMBC and band-selective HMBC) as well as by X-ray crystal structure analysis.

The first phytochemical analysis of the aquatic macrophyte Stratiotes aloides afforded two new flavonoid glucuronides, luteolin 7-O-beta-D-glucopyranosiduronic acid-(1--2)-beta-D-glucopyranoside (1) and chrysoeriol 7-O-beta-D-glucopyranosiduronic acid-(1--2)-beta-D-glucopyranoside (2), as well as the new 2-(2-hydroxypentyl)-5-carboxy-7-methoxychromone (5) and chrysoeriol 7-O-beta-(6-O-malonyl)glucopyranoside (3), which has been assigned via NMR data for the first time. Additionally, free amino acids such as tryptophan, arginine, leucine, isoleucine, phenylalanine, and tyrosine along with choline, cis-aconitic acid, the phenolic glycoside alpha-arbutine, the chlorophyll derivative phaeophorbide a, and the flavonoid glycoside luteolin 7-O-beta-(6-O-malonyl)glucopyranoside (4) were isolated. Despite the low quantities obtained in some cases (between 50-300 microg), the structures of all compounds were unambiguously elucidated by extensive NMR and MS experiments. With a delay of 2 days compound 1 (10 and 50 microM test concentration) strongly inhibited the growth of human SH-SY5Y neuroblastoma cells in a dose-dependent manner, whereas only a moderate growth inhibition of human Patu 8902 carcinoma cells could be observed. Compounds 1 and 2 showed no activities against the bacteria Escherichia coli BW25113, Pseudomonas pudida KT2440, and Enterobacter cloacae subsp. dissolvens.

Pyrido[2',1':2,3]imidazo [4,5-c]isoquinolin-5(6H)-ones can be obtained by a microwave-assisted three-component reaction between 2-aminopyridines, isocyanides, and 2-carboxybenzaldehydes under acidic conditions.

The laccase genes lccalpha, lccbeta, lccgamma and lccdelta encoding four isoenzymes from Trametes versicolor have been cloned and expressed in Pichia pastoris. Biochemical characterization allowed classification of these laccases into two distinct groups: Lccalpha and Lccbeta possessed higher thermal stability, but lower catalytic activity towards 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) compared to Lccgamma and Lccdelta. Activities of the laccases were quite different as well. Laccase Lccdelta showed highest phenolic C-C coupling activity with sinapic acid, but lowest oxidizing activity towards polycyclic aromatic hydrocarbons (PAHs). Highest activity towards PAHs was observed with Lccbeta. After 72h, more than 80% of fluorene, anthracene, acenaphthene and acenaphthylene were oxidized by Lccbeta in the presence of ABTS. Investigation of the structural basis of the different activities of the laccases demonstrated the impact of positions 164 and 265 in the substrate binding site on oxidation of PAHs.

1-Arylbut-3-en-1-ols react with trimethyl orthoformate in the presence of Lewis acids like InCl 3 , BiCl 3 , TiCl 4 , or BF 3 ·OEt 2 providing homoallyl ethers or homoallyl chlorides in high yields.

New Pd-mediated reductive heteroannulations of N-allyl diphenylamines accessible through Pd-catalyzed N-arylation and of O-allylethers are reported.

The process of the cationic olefin cyclization of 3-sub-stituted 4-hydroxy-2 H-pyran-2-ones 3 that may produce both TRANS- and CIS-pyrano[4,3- B]chromen-1-ones ( 4) and TRANS- and CIS-pyrano[2,3- B]chromen-4-ones ( 5) can be efficiently controlled by properly choosing reagents and reaction conditions. The highly -selective formation of TRANS- 4 can be achieved with Et 2AlCl as a Lewis acid. Preferred formation of CIS- 4 is observed with PTSA -under microwave conditions at high temperatures. PTSA and low temperatures produce CIS- 5 in excess.

N-Allyl 2-nitrophenyl amines can be efficiently cyclized to yield alkenyl-1,2,3,4-tetrahydroquinoxalines in a single reaction step by means of a new microwave-assisted reductive domino -process.

Laccase initiated domino reactions of cyclohexane-1,3-diones with catechols using air as an oxidant afford 3,4-dihydro-7,8-dihydroxy-2 H -dibenzofuran-1-ones with yields ranging from 70% to 97%.

Lewis acids like BF 3 ·OEt 2 , TiCl 4 , ZnCl 2 ·OEt 2 , ZnI 2 , and InCl 3 in liquid SO 2 as a solvent at low temperatures have been found to be highly efficient in epoxyolefin cyclizations with pyrones as terminators.

Novel 24-nor-, 24-nor-2,3-seco, and 3,24-dinor-2,4-seco-ursane type triterpenes have been isolated along with one known compound from the stem bark of Diospyros decandra. The structures of these highly oxidized metabolites were established on the basis of extensive NMR and MS studies. They possibly represent intermediates in the biosynthetic transformation of ring A in an ursane triterpene. Some isolates showed mild anti-mycobacterial activity against Mycobacterium tuberculosis with MIC values ranging from 25 to 200 μg/mL.