Cross-metathesis of vinyl aromatic heterocycles: comparison of Grubbs catalyst and Schrock catalyst

Metathesis of 2-vinyl aromatic heterocycles such as furan and thiophene has been investigated in the presence of a ruthenium-based Grubbs catalyst from a synthetic standpoint. The self-metathesis of 2-vinyl aromatic heterocycles was not successful. However, the cross-metathesis of these aromatic heterocycles with 1-octene occurred efficiently, but the selectivity of cross-metathesis product was very low, below 50%. The origin of the low selectivity of heterodimer formation was elucidated through metallacyclobutane intermediate mechanism, observations of carbenes by in situ ¹H NMR, and the reaction products. The effect of oxygen on the reaction behavior was also examined. Furthermore, the data obtained on the Grubbs catalyst were compared with those on a molybdenum-based Schrock catalyst.     

Synthesis of Orthogonally Protected S,S-2,6-Diaminopimelic Acid via Olefin Cross-Metathesis

A short synthesis of orthogonally protected S,S-diaminopimelic acid, DAP, via a selective cross-metathesis between S-allyl glycine and S-vinyl glycine followed by hydrogenation is reported. By analogy, the S,S-diaminosuberic acid, DAS, is produced by self-metathesis of S-allyl glycine, and the self-metathesis of S-vinyl glycine is described.     

Radical dearomatization of arenes and heteroarenes

The stannane-mediated benzeneselenol-catalyzed addition of aryl iodides to a range of arenes and aromatic hetereocycles has been studied. With furan, thiophene, and several carbocyclic arenes, the addition takes place with quenching of the adduct radical by the catalytic selenol leading to moderate yields of aryl-dihydroarenes. With nitrogen heterocycles, on the other hand, it was not possible to suppress aromatization of the adduct radical and fully aromatized products were isolated. Aryl iodides bearing hydrogen bond donating groups in the ortho-position add to nitrogen heterocycles with high selectivity ortho- to the nitrogen, affording a simple one-step synthesis of potential chelating ligands. While 2-iodophenol is an excellent aryl radical source in these reactions, the homologous 1-iodo-2-naphthol fails owing to its reaction with diphenyl diselenide, which gives 1-phenylseleno-2-naphthol in high yield.     

Effect of acceptor heteroatoms on π-hydrogen bonding interactions: A study of indole⋅⋅⋅thiophene heterodimer in a supersonic jet

Resonant two photon ionization (R2PI), IR-UV, and UV-UV double resonance spectroscopic techniques combined with quantum chemistry calculations have been used to determine the structure of indole???thiophene dimer observed in a supersonic jet. With the help of combined experimental and theoretical IR spectra it has been found that the observed dimer has a N-H???π hydrogen bonded slanted T-shaped structure. The present study demonstrates the effect of heteroatoms present in the acceptors on the strength of the π-hydrogen bonding interactions. It was concluded by Sherrill and co-workers from their theoretical study of benzene???pyridine dimer that aromatic rings containing heteroatoms are poorest π-hydrogen bond acceptors [E. G. Hohenstein and C. D. Sherrill, J. Phys. Chem. A 113, 878 (2009)]. But the current spectroscopic investigation exhibits that five membered aromatic heterocycles are favorable π-hydrogen bond acceptors. In this study, it has also been shown that thiophene is a better π-hydrogen bond acceptor than furan. The present work has immense biological significance as indole is the chromophore of tryptophan residue in the proteins and thiophene derivatives have potential therapeutic applications. Thus, understanding the binding motif between indole and thiophene in the heterodimer studied in this work may help in designing efficient drugs.     

Ethynylation of 2-(furan-2-yl)- and 2-(thiophen-2-yl)pyrroles with acylbromoacetylenes in the Al2O3 medium: relative reactivity of heterocycles

2-(Furan-2-yl)- and 2-(thiophen-2-yl)pyrroles are readily ethynylated with acylbromoacetylenes in the solid Al₂O₃ medium (no solvent, room temperature, 1 h) to afford 5-(furan-2-yl)- and 5-(thiophen-2-yl)-2-acylethynylpyrroles in 39–74% yields. In the case of 2-(furan-2-yl)pyrroles, an alternative ethynylation of the furan ring takes place, the ratio of the furan and pyrrole ring ethynylation products being 1:5–7. No ethynylation of the thiophene ring as well as ethynylation of both heterocycles in a one molecule has been detected. Thus the reactivity of the heterocycles towards the ethynylation system (acylbromoacetylenes/Al₂O₃) falls in the order: pyrrole>furan>thiophene.     

Rare‐Earth‐Catalyzed C−H Silylation of Aromatic Heterocycles with Hydrosilanes

The catalytic C?H silylation of a variety of aromatic heterocycles such as furan, pyrrole and thiophene derivatives with secondary hydrosilanes has been achieved by using an yttrium metallocene complex. This protocol provides an efficient and straightforward way for the synthesis of a series of silylated heteroaromatic compounds containing tertiary silane moieties without the need for an additive or H₂ acceptor.     

A theoretical study on the aromaticity of thiadiazoles and related compounds

Three different approaches have been considered to determinate the aromatic character of isomeric thiadiazoles. Several indices have been obtained from calculations made in the context of nonlocal (B3LYP) density functional calculations. The results were compared with the existing experimental evidence for analog heterocycles. It is concluded that the thiadiazoles are aromatic compounds, with a larger aromatic character than pyrrole, thiophene and furan. The monoxide and dioxide derivatives are shown to be non-aromatic or antiaromatic molecules.     

Quantum-chemical investigation of the 1,2-proton shift in protonated five-membered aromatic heterocycles

Calculations of the energetics of the 1,2-proton shift in protonated five-membered aromatic heterocycles — pyrrole, furan, and thiophene — have been carried out by the SCF MO LCAO method in the MINDO/3 approximation and nonempirically on the OST-3GF (OST-3GF*) basis. The general features of this process, and also the influence of solvation and of taking into account the vacant d-AOs of the sulfur atom in the protonated form of thiophene on the results of the calculation are considered. The results obtained have been used for a discussion of the activity and selectivity of the heterocycles considered in aromatic electrophilic substitution reactions.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1186–1190, September, 1984.     

Tandem arylation-reduction of acyl heterocycles. Convenient synthesis of benzyl heterocycles

Tandem arylation-reduction of a series of acyl heterocycles using phenyl-, 4-methylphenyl-, and 4-methoxy-phenyllithium reagents followed by lithium-ammonia-ammonium chloride reduction afforded the corresponding benzyl heterocycles. The acyl heterocycles surveyed in this study contained furan, 2,3-dihydro-4H-1-benzopyran, 4H-1-benzopyran, thiophene, 4,5,6,7-tetrahydrobenzo[b]thiophene, 2,3-dihydro-4H-1-benzothiopyran, and pyridine nuclei. All acyl heterocycles yielded the corresponding benzyl heterocycles except 2,3-dihydro-4H-1-benzothiopyran-4-one, which selectively cleaved during reduction to give the corresponding 2-(1-arylpropyl)benzenethiols.     

Reactions that generate aromatic molecules: is aromatic stabilization less or more advanced than bond changes at the transition state? Kinetic and thermodynamic acidities of rhenium carbene complexes

A kinetic study of the reversible deprotonation of the rhenium carbene complexes 1H(+)(O), 1H(+)(S) and 2H(+)(O) by carboxylate ions, primary aliphatic and secondary alicyclic amines, water and OH(-) in 50% MeCN-50% water (v/v) at 25 degrees C is reported. These carbene complexes are of special interest because in their deprotonated form they represent derivatives of the aromatic heterocycles furan, thiophene and benzofuran. Intrinsic rate constants (k(o) for Delta G degrees = 0) determined from appropriate Br?nsted plots for these rhenium carbene complexes and for the corresponding selenophene (1H(+)(Se)) and benzothiophene (2H(+)(S)) derivatives investigated earlier follow the orders furan < selenophene < thiophene and benzofuran less, similar benzothiophene. These orders indicate that an increase in aromaticity leads to an increase in the intrinsic rate constant or a decrease in the intrinsic barrier. This is an unexpected result; it implies that, in contrast to common resonance effects, the development of aromaticity at the transition state is ahead of proton transfer, i.e., the percentage development of the aromatic stabilization energy at the transition state is higher than the percentage of proton transfer.     

Furan and Thiophene Oximes: Synthesis, Reactions, and Biological Activity. (Review)

Data on methods for the production of furan and thiophene aldoximes, ketoximes, and amidoximes and their reactions are reviewed. The synthesis of new heterocycles from furan and thiophene oximes and the biological activity of derivatives of the oximes are discussed individually.     

Highly selective ruthenium metathesis catalysts for ethenolysis

N-Aryl,N-alkyl N-heterocyclic carbene (NHC) ruthenium metathesis catalysts are highly selective toward the ethenolysis of methyl oleate, giving selectivity as high as 95% for the kinetic ethenolysis products over the thermodynamic self-metathesis products. The examples described herein represent some of the most selective NHC-based ruthenium catalysts for ethenolysis reactions to date. Furthermore, many of these catalysts show unusual preference and stability toward propagation as a methylidene species and provide good yields and turnover numbers at relatively low catalyst loading (<500 ppm). A catalyst comparison showed that ruthenium complexes bearing sterically hindered NHC substituents afforded greater selectivity and stability and exhibited longer catalyst lifetime during reactions. Comparative analysis of the catalyst preference for kinetic versus thermodynamic product formation was achieved via evaluation of their steady-state conversion in the cross-metathesis reaction of terminal olefins. These results coincided with the observed ethenolysis selectivities, in which the more selective catalysts reach a steady state characterized by lower conversion to cross-metathesis products compared to less selective catalysts, which show higher conversion to cross-metathesis products.     

Synthesis and characterization of benzo[c]thiophene analogs incorporating benzo[b]thiophene/1-hexylindole/benzo[b]furan

Synthesis of 1,3-disubstituted benzo[c]thiophene analogs incorporating heterocycles such as benzo[b]thiophene/1-hexylindole/benzo[b]furan and thiophene units is described. Optical and electrochemical studies of the benzo[c]thiophene analogs are also reported.     

THERMAL AND PHOTOCHEMICAL REACTIONS BETWEEN α, α′-DIBROMOKETONES AND FIVE-MEMBERED HETEROCYCLES IN THE PRESENCE OF IRON NONACARBONYL

Abstract

[3 + 4] Cycloaddition reactions of 2-oxyallilic cations to furan¹ to form seven-membered oxobicyclic compounds have been known for some time. The purpose of this paper has been to try to extend the reaction to five-membered heterocycles with more aromatic character than furan. An analogy has been found between the behavior of thiophene, selenophene and tellurophene in these reactions and in oxetane-forming reactions. The higher the aromaticity of the heterocycle, the more difficult it is to achieve the formation of the seven-membered ring. Contrary to what is observed in oxetane-forming reactions, where it is not possible to isolate a stable tellurium compound, the tellurabicyclic compound was isolated and identified by spectroscopic methods in the present investigation.     

Hydrosilylation Of (Hetero)aromatic Aldimines in the Presence of a Pd(I) Complex

The reaction of triethylsilane with heterocyclic and aromatic azomethines, catalyzed by the [Pd(allyl)Cl]₂ complex, was studied. It was found that the reaction is affected by the nature of the functional groups in the aza and methine parts of the aldimine molecules, which were produced by the condensation of furan, thiophene, and benzene aldehydes with aniline and its derivatives. The reactivity of a series of imines is compared with their electronic and structural characteristics, determined by quantum-chemical methods. The corresponding furan, thiophene, and aromatic amines and also certain silylamines were synthesized.     

Nuclear magnetic resonance studies of boron compounds : XVI. Carbon-13 studies of organoboranes: Phenylboranes and boron-substituted aromatic heterocycles

¹³C and ¹¹B NMR data of 29 phenylboranes and 9 boron-substituted aromatic heterocycles (thiophene, N-methylpyrrole and furan) are discussed. The observed ¹³C chemical shifts of the para-carbon atoms in phenylboranes and the corresponding carbon atoms in the aromatic heterocycles are consistent with mesomeric interactions of the boryl group with the aromatic system. The trend of δ(¹³C(para)) in phenylboranes corresponds to that observed for isoelectronic phenylcarbocations. Low temperature ¹³C NMR and/or ¹³C {¹¹B, ¹H} heterocuclear triple resonance experiments were employed to obtain the ¹³C chemical shifts of the boron-bonded carbon atoms.     

The induced current strengths and aromatic pathways of heteroporphyrins and their antiaromatic derivatives

The magnetically induced current strengths as well as nucleus independent chemical shifts of aromatic heteroporphyrins and antiaromatic 22,24‐dideazaheteroporphyrins have been studied using the density functional theory method. The induced current strengths and pathways are obtained by numerical integration of the induced current densities following the specific chemical bonds. The total induced current strengths of antiaromatic 22,24‐dideazaheteroporphyrins is about 6 nA/T weaker than the one for the heteroporphyrins in absolute value. The substitution of pyrrole NH groups by O and S atoms does not change the total induced current strengths. The induced currents around the molecular macroring split at the heterocycles (pyrrole, furan, and thiophene) into the inner and outer routes. The heteroatoms (N, O, and S) have high resistance and consequently lead to a weaker induced current strength than the one passing the outer route in aromatic heteroporphyrins. For antiaromatic 22,24‐dideazaheteroporphyrins, the heteroatoms enhance the current strength and change the main current pathway into the inner route. The induced current strength following the NH moiety is stronger than the one passing the oxygen moiety of furan ring and the sulfur moiety of the thiophene ring in both heteroporphyrins and 22,24‐dideazaheteroporphyrins. © 2015 Wiley Periodicals, Inc.     

Cyclopentadienes Annelated with Five-membered Heterocycles: Methods of Synthesis, Heteroorganic Derivatives, and Synthetic Precursors. (Review)

The review is devoted to cyclopentadienes annelated with five-membered heterocycles (furan, pyrrole, thiophene, and their benzo analogs) (hetarenocyclopentadienes), their heteroorganic derivatives, and the synthetic precursors (hetarenocyclopentanones).     

Condensed Pyridine Bases. Synthesis and Reactions of Benzofuro[2,3-c]indeno[2,1-e]-, Benzothieno[2,3-c]Indeno[2,1-e]-, Benzofuro-[3,2-c]Indeno[2,1-e]- and Thieno[2,3:4′,5′]-thieno[3,2-c]indeno[2,1-e]pyridines

Condensation of hetarene carboxaldehydes with phthalide gave 2-(3-hydroxy-1-oxoinden-2-yl)benzo[b]furan and 2-(3-hydroxy-1-oxoinden-2-yl)-5-ethylthieno[2,3-b]thiophene. Starting from hetaryl acetic acids gave 3-(3-hydroxy-1-oxoinden-2-yl)benzo[b]furan and 3-(3-hydroxy-1-oxoinden-2-yl)benzo[b]thiophene. Acylation of 3-hydroxy-1-oxoinden-2-yl-substituted heterocycles using acetic anhydride in the presence of 70% HClO₄ leads to the formation of pentacyclic pyrilium salts. Pentacyclic indenopyridines are prepared by treating the pyrilium salts with ammonia. The reaction of the carbonyl group in the indenopyridines with hydroxylamine, hydrazine hydrate, and in reduction using NaBH₄ has been studied.__________Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 435–443, March, 2005.     

New Method for the Synthesis and Reactivity of (5‐R‐1,3,4‐Oxadiazol‐2‐yl)furoxans

A new, simple and general one‐pot method for the preparation of (5‐R‐1,3,4‐oxadiazol‐2‐yl)furoxans has been developed on the basis of the interaction between accessible 3‐methylfuroxan‐4‐carboxylic acid hydrazide and aliphatic, aromatic and heterocyclic carboxylic acids or their chlorides in the presence of POCl₃. The synthesis and study of (5‐R‐1,3,4‐oxadiazol‐2‐yl)furoxans reactivity resulted in new polyheterocyclic ensembles incorporating furoxan, 1,3,4‐oxadiazole, pyrrole, triazole, furan, thiophene, pyrimidine, and other heterocycles in different combinations.