Sodium dithionite initiated reactions of 1-bromo-1-chloro-2,2,2-trifluoroethane with enol ethers of cyclic ketones

Sodium dithionite initiated reactions of 1-bromo-1-chloro-2,2,2-trifluoroethane (1) with methyl and trimethylsilyl ethers of cyclopentanone and cyclohexanone enols (2a-d) in a MeCN/H₂O system were investigated. 2-(2,2,2-Trifluoroethylidene)cyclopentanone (4a) and 2-(2,2,2-trifluoroethylidene)-cyclohexanone (4b), respectively, were obtained as the main products and isolated in reasonable yields. The reaction with a 1:1 mixture of 5- and 3-methyl substituted 1-methoxycyclohexenes, 2e and 2f, revealed strong influence of steric hindrance on the reaction rate; a mixture of 2-(2,2,2-trifluoroethylidene)-5-methylcyclohexanone (6) and 2-(2,2,2-trifluoroethylidene)-3-methylcyclohexanone (7) in a 9:1 ratio was formed. Ketones 4a and 4b were reduced to the corresponding alcohols 8 and 9 and the reaction of 4b with hydrazine gave an indazole derivative 10.     

Synthesis of functionalized benzothiophenes by twofold Heck and subsequent 6π-electrocyclization reactions of 2,3-dibromothiophene

The Heck reaction of 2,3-dibromothiophene afforded 2,3-di(alkenyl)thiophenes which were transformed into benzothiophenes by domino ′6π-electrocyclization/dehydrogenation′ reactions.     

Structure and reactions of photothebainehydroquinone

The structure of photothebainehydroquinone, which was obtained by unsensitized irradiation with UV light of thebainequinone (1) or thebainehydroquinone (2) has been shown by X-ray crystallography to be 3a, which arises from 2 through a di-π-methane to vinylcyclopropane rearrangement. Treatment of 3a with acid gave 5a, 6a, 5b and probably 6b. Studies using DCl showed that the opening of the cyclopropane in 3a to give 5a, 5b, and 6a involved ‘end-on’ approach of the D⁺. The mechanisms of the reactions are discussed.     

Novel triazinium-imidothioate zwitterions: intermediates in the reaction of [1,3,4]thiadiazolo[2,3-d][1,2,4]triazolo[1,5-a][1,3,5]triazinium cations with amines

Starting with bis([1,3,4]thiadiazolo)[1,3,5]triazinium halides 1, a novel class of heterocyclic compounds, the [1,3,4]thiadiazolo[2,3-d][1,2,4]triazolo[1,5-a][1,3,5]triazinium halides 5 were prepared. The reaction between 5 and primary or secondary amines 6 yielded highly substituted guanidines 8 and fused tricyclic bis([1,2,4]triazolo)[1,5-a:1′,5′-d][1,3,5]triazinium halides 9. The formation of the reactive triazinium-imidothioate zwitterions 7, which is controlled by the influence of negative hyperconjugation, was proven by NMR data and the X-ray structure of 7c. The subsequent ring-closure/ring-opening steps can be understood in terms of an S_N(ANRORC) process accompanied by intramolecular proton-transfer reactions. The zwitterions 7 were reacted with EtI forming cationic derivatives 10 or hydrolyzed at pH 6-7 to give novel heterocyclic ethanethioamides 11.     

Liquid crystals in the series of 2,4,6-tristyryl-1,3,5-triazines

Alkaline condensation reactions of 2,4,6-trimethyl-1,3,5-triazine (1) and substituted benzaldehydes (2a-n) yield 2,4,6-tristyryl-1,3,5-triazines (3a-n). A sufficient number and length of the alkoxy chains at the benzene rings provide liquid crystalline phases Col_hd. A special structure was found for compound 3i with 9 hexyloxy chains; it exists in the solid state in a helical columnar arrangement, which is transformed by heating to a hexagonal columnar mesophase. Irradiation of the mesophases of 3i-3m leads to partial cyclodimerization reactions, which cause different textures and lower the clearing points. The border line between the irradiated and the unirradiated zones is preserved in the solid and the liquid crystalline temperature range but also over a surprisingly long period in the molten state. A detailed study of this imaging technique was performed for the LC phase of 3i.     

Efficient and regioselective chromium(0)-catalyzed reaction of 2-substituted furans with diazo compounds: stereoselective synthesis of (2E,4Z)-2-aryl-hexadienedioic acid diesters

Pentacarbonyl(η²-cis-cyclooctene)chromium(0) (1) catalyzes efficiently reactions of diazo compounds with electron-rich furans. The reaction of 2-methoxyfuran (2) with alkyl α-diazoarylacetate (3a-g) furnishes the (2E,4Z)-2-aryl-hexadienedioic acid diesters (4a-g) in excellent yields. These reactions are highly regioselective. The cyclopropanation intermediates formed from 1 and diazo compounds 3a-g always arise from a carbene addition to the less substituted CC bond of 2. The resulting cyclopropanation product undergoes a ring opening reaction to form the corresponding (2E,4Z)-2-aryl-hexadienedioic acid diesters (4a-g). The pentacarbonylchromium(0)-catalyzed reactions of 2-alkylfuran (5a-b) with ethyl α-diazophenylacetate (3a) and 9-diazo-9H-fluorene (3h) produce the 1(E),3(E)-butadienes (6a-d) in very good yields.     

Photochromism of dihydroindolizines. Part 12: synthesis and photochromism of novel π-conjugated rigid dihydroindolizines as potential molecular electronic devices

Novel carbon-rich photochromic dihydroindolizine DHI derivatives and new spirocyclopropenes have been synthesized. Three alternative synthetic pathways for the synthesis of DHI 10 have been established. Different Sonogashira-mediated coupling reactions have been applied to optimize the reaction conditions and to obtain the best yields. Palladium-mediated Sonogashira coupling of DHIs with 4-(thioacetyl)iodobenzene 13 and iodobenzene 17 yielded coupling products, which have potential applications in molecular electronics. Irradiation of photochromic DHIs 10a-f, 12a-f, 14a-f, 16a-f and 18a-f with polychromatic light leads to betaines 9a-f, 13a-f, 15a-f, 17a-f and 19a-f. The coloured betaine forms are obvious in CH₂Cl₂ solution with concentration of 1×10⁻⁵ mol/L at room temperature because of their slower 1,5-electrocyclization. All the absorption maxima of the coloured betaines were found to be in the visible region and lie between 524 (betaine 9a) and 639 nm (betaine 15f). The kinetics of the thermal 1,5-electrocyclization was studied using multichannel UV-vis spectrophotometry. The kinetic measurements showed that the half-lives of the coloured betaines are in the second domain and lie between 112 and 1379 s. A highly pronounced increase in the half-lives of betaines bearing dimethyl substituted pyridazine compared with non-substituted pyridazine betaines was monitored. A large increase in the photostability of both DHIs and betaines under investigation compared with the standard DHI was observed. The charged zwitterionic betaine structures were stabilized by increasing the solvent polarity due to the electrostatic interactions between them. The tuning of the absorption maxima and the kinetic properties by changing the substitution in the fluorene part (region A) and pyridazine part (region C) will help these compounds to find their applications.     

An investigation of the scope of the 1,7-electrocyclization of α,β:γ,δ-conjugated azomethine ylides

Substituents on the diene component have little influence on the periselectivity of the cyclizations of α,β:γ,δ-conjugated azomethine ylides, with 1,7-electrocyclizations predominating. In some cases, subtle changes to these substituents can, however, influence the product formed, through their effect on the relative energies of the transition states for the 1,5- (6π) and 1,7-electrocyclization (8π) processes. The most striking changes in periselectivity occur for phenylethenyl-substituted azomethine ylides 3d–f, which can give either a pyrroline 4d,f or dihydrobenzazepine 6e, depending upon the alkene configuration.     

Deuterated ammonium formate as deuterium source in a mild catalytic deuterium transfer reaction of pyridines, pyrazines and isoquinolines

The application of deuterated ammonium formate as deuterium source in transfer deuteration reactions of aromatic heterocycles (4-6) for the synthesis of highly deuterated, substituted piperidines (1), piperazines (2) and tetrahydroisoquinolines (3) has been developed.     

Trimethyl borate/magnesium halide complex-induced one-pot homologation reactions of isoquinoline with dialkyl-TMP-zincate

Novel one-pot homologation reactions of isoquinoline with lithium dialkyl-TMP-zincate⋅2MgBrCl/trimethyl borate are described. 1-Alkylisoquinolines (2, 3A, 4A, 5A, 6, and 7) and 1-alkyl-3,4-dihydroisoquinolines (3B, 4B, and 5B) are easily prepared under the presented reaction conditions. The role of the B(OMe)₃/MgBrCl complex is examined in these homologation reactions. The specific reaction mechanisms, including 1,2-migration of the alkyl ligands from 1-isoquinolylzincates, are proposed. The migratory aptitudes of ligands of 1-isoquinolylzincates are also discussed.     

A tandem decarboxylation and inverse electron-demand Diels-Alder reaction of amino-thiophenecarboxylic acids with 1,3,5-triazines

The scope of 1,3,5-triazine inverse electron-demand Diels-Alder (IDA) reactions was expanded to include aminothiophenecarboxylic acids as latent dienophiles. A series of 2-amino-3-thiophenecarboxylic acids (1a-d) and a 3-amino-2-thiophenecarboxylic acid (5) were introduced as productive dienophiles in IDA reactions with various 1,3,5-triazines (2a-e). This method is useful for the one-step synthesis of both thieno[2,3-d]pyrimidines and thieno[3,2-d]pyrimidines, which should complement existing methods.     

Approaches to the synthesis of arisugacin A

Approaches to the synthesis of the important acetylcholinesterase inhibitor, arisugacin A, are described. Two different routes to the key AB ring system are described: the first utilizes an intramolecular Diels-Alder reaction on a furan substrate and the second a 6π-electrocyclization of a substituted triene followed by cycloaddition with singlet oxygen. The successful synthesis of a fully functionalized AB ring system of arisugacin A, the tetraol 52 from hydroxy-β-ionone 22 in 16 steps and 9.3% overall yield is described. Several useful synthetic transformations to this molecule and its analogues are reported, e.g., the formation of the furan Diels-Alder cycloadduct 14 and its conversion into the oxa-bridged structures 17 and 21, the preparation of the dienes 25 and 26 and the conversion of the later into the endoperoxide 30 and its diol 36, the preparation of the endoperoxide 40 and the oxa-bridged system 42, and finally the use of the enelactone 43 and its ultimately successful conversion into 52. In addition, several novel rearrangements are described, producing the unusual compounds 62, 65, and 67. Finally, the successful coupling of the pyrone unit to the AB ring system is described to give compounds 70 and 71. The novel reduction of these compounds to the cyclic ether 74 is described.     

Environment friendly organic synthesis using bismuth compounds. An efficient method for carbonyl-ene reactions catalyzed by bismuth triflate

Bismuth triflate (0.1 mol %) is a highly efficient catalyst for the cyclization of citronellal 1, a reaction that yields a ratio of 80:20 of isopulegol 2 and neoisopulegol 3. This methodology has also been extended to the synthesis of substituted piperidines. The bismuth triflate catalyzed ene reaction of aldehyde 4 gives a 70:30 mixture of piperidines 5 and 6. The advantages of these methods include the use of a highly efficient catalyst that is relatively nontoxic, cheap and easy to handle.     

An efficient route for the synthesis of 2-arylthiazino[5,6-b]indole derivatives

Substituted 2-thiobenzamidomethylindole derivatives (14a-e) were prepared by the reaction of 2-aminomethylindole (9) with substituted benzoyl chlorides, followed by sulfurization using Lawesson's reagent. Alternatively, these thioamides were obtained from the amine in one step in an efficient manner by using substituted benzaldehydes in the presence of sulfur, or at room temperature with the aid of substituted methyl dithiobenzoates. The Hugerschoff reactions of thiobenzamides (14a-e) with phenyltrimethylammonium tribromide provided the rare title 2-arylthiazino[5,6-b]indoles (15a-e) in good yields. A convenient one-pot approach for the synthesis of 2-phenyl-1,3-thiazino[5,6-b]indole (15a) from 2-aminomethylindole (9) is also described.     

Photoreactions of 1,2,4,5-benzenetetracarbonitrile with arylethenes—photo- olefin dimerization-aromatic substitution reactions

Irradiation of 1,2,4,5-tetracyanobenzene (TCNB) with styrene derivatives 1-4, respectively, leads to a photochemical olefin dimerization-aromatic substitution reaction to give the corresponding (2,4,5-tricyanophenyl)tetralin derivative (8, 12, 16, 17, and 20) as the main product. Further irradiation of the primary product with alkene results in substitution of the meta-CN group by another phenyltetralinyl to give the corresponding 4:1 (alkene-TCNB) product. According to the effect of the codonor (biphenyl) and salt (magnesium perchlorate) on reaction rate, the result of photoinduced reactions of TCNB with tetralin (6) and 1-phenyltetralin (7) and analysis of the known kinetic data for relevant processes in the cyanoarene-alkene reactions, the mechanism for the formation of the olefin dimerization-aromatic substitution products (such as 8) is proposed to involve radical pair combination of the alkene cyclodimer radical (the corresponding 4-phenyl-1-tetralinyl radical) with TCNB⁻ followed by expulsion of a CN⁻. Photoreactions of TCNB with the alkene photocyclodimer (1-phenyltetralin) may also make minor contributions. Photoinduced reaction of TCNB with 1-phenylcyclohexene (5) takes a different pathway from 1-4 to afford the 1:1 (5-TCNB) primary product 21 by deprotonation of 5⁺ and radical pair combination with TCNB⁻ followed by elimination of HCN.     

Pd-catalyzed boronations and cross-coupling reactions of aromatic cobaltadithiolene complexes with aryl halides

The Pd-catalyzed reaction of [CpCo(S2C2(Ph)(Bpin))] (1, Bpin = 4,4,5,5-tetramethyl-1,3,2-dioxaboronate) with 1-iodonaphthalene or 2-bromothiophene gave the cross-coupling product [CpCo(S2C2(Ph)(Ar))] (Ar = 1-Np (4) or 2-Th (5)), although an early paper described the reaction of 1 with 3-bromopyridine or 9-bromoanthracene (Ar = 3-Py (2) or 9-Anth (3)). The boronation of the brominated precursor [CpCo(S2C2(p-C6H4Br)(H))] (7) with Bpin-H in the presence of Pd catalyst gave the expected boronated product [CpCo(S2C2(p-C6H4Bpin)(H))] (8) but also underwent an unexpected direct boronation on the dithiolene carbon to form [CpCo(S2C2(p-C6H4Br)(Bpin))] (9). The brominated complex 7 or [CpCo(S2C2(Ph)(p-C6H4Br))] (10) was synthesized by thermal reaction and the microwave-enhanced reaction relatively gave better yield with shorter reaction time than that of the conventional heating reaction. The cross-coupling reactions of the boronated or [CpCo(S2C2(Ph)(p-C6H4Bpin))] (11) with aryl halides successfully produced the corresponding cross-coupling products such as [CpCo(S2C2(p-C6H4Py)(H))] (12) or [CpCo(S2C2(p-C6H4Anth)(H))] (13) from 8 and [CpCo(S2C2(Ph)(p-C6H4Py))] (14) from 11. The structures of 7, 9, 11, 12, 13 and 14 were determined by X-ray diffraction studies. Electronic absorption maxima (λ_max) due to dithiolene LMCT in dichloromethane solution can be modified in the range of 574-602 nm by a substituent effect on the dithiolene ring. Redox potentials obtained from CV measurement were also reported.     

Biomimetic syntheses of ineleganolide and sinulochmodin C from 5-episinuleptolide via sequences of transannular Michael reactions

Treatment of a solution of the macrocyclic norcembranoid 7 with lithium hexamethyldisilazide in THF at −78 °C to 0 °C, leads to the polycyclic norcembranoids ineleganolide 1 and sinulochmodin C (2) (65%), which are found in the corals Sinularia inelegans and Sinularia lochmodes, respectively. The conversions are believed to be biomimetic, and occur by successive transannular Michael reactions in 7. Under different temperature conditions the novel polycycle 30 is the main product, alongside small quantities of 1 and 2. The polycycle 30 is possibly produced from ineleganolide 1, following a reverse oxy-Michael reaction and two successive aldol reactions. The significance of the synthesis of ineleganolide 1, sinulochmodin C (2) and the structure 30 from 5-episinuleptolide 7, to the likely biosynthesis of the related norcembranoids scabrolide A (3), scabrolide B (4) and horiolide 31 found in Sinularia sp. is discussed.     

Synthesis and properties of 3-arylcyclohepta[4,5]imidazo[1,2-a]-1,3,5-triazine-2,4(3H)-diones and related compounds: photo-induced autorecycling oxidation of some amines

Novel 3-phenyl- and 3-(4-nitrophenyl)cyclohepta[4,5]imidazo[1,2-a]-1,3,5-triazine-2,4(3H)-diones and the corresponding imino derivatives 5a,b and 6a,b were synthesized in modest to moderate yields by the abnormal and normal aza-Wittig reaction of 2-(1,3-diazaazulen-2-ylimino)triphenylphosphorane with aryl isocyanates and subsequent heterocyclization reaction with a second isocyanate. The related cationic compound, 1-methyl-3-phenylcyclohepta[4,5]imidazo[1,2-a]-1,3,5-triazine-2,4(3H)-dionylium tetrafluoroborate 7a, was also prepared. The electrochemical reduction of these compounds exhibited more positive reduction potentials as compared with those of the related compounds of 3,10-disubstituted cyclohepta[4,5]pyrrolo[2,3-d]pyrimidine-2,4(1H,3H)-dione systems. In a search of the oxidizing ability, compounds 5a, 6a, and 7a were demonstrated to oxidize some amines to give the corresponding imines in more than 100% yield under aerobic and photo-irradiation conditions, while even benzylamine was not oxidized under aerobic and thermal conditions at 100 °C. The oxidation reactions by cation 7a are more efficient than that by 5a and 6a. Quenching of the fluorescence of 5a was observed, and thus, the oxidation reaction by 5a probably proceeds via electron-transfer from amine to the excited singlet state of 5a. In the case of cation 7a, the oxidation reaction is proposed to proceed via formation of an amine-adduct of 7a and subsequent photo-induced radical cleavage reaction.     

Quantum chemical study of ethylene addition to group-7 oxo complexes MO2(CH3)(CH2) (M = Mn, Tc, Re)

Quantum chemical calculations using DFT at the B3LYP level have been carried out for the reaction of ethylene with the group-7 compounds ReO₂(CH₃)(CH₂) (Re1), TcO₂(CH₃)(CH₂) (Tc1) and MnO₂(CH₃)(CH₂) (Mn1). The calculations suggest rather complex scenarios with numerous pathways, where the initial compounds Re1-Mn1 may either engage in cycloaddition reactions or numerous addition reactions with concomitant hydrogen migration. There are also energetically low-lying rearrangements of the starting compounds to isomers which may react with ethylene yielding further products. The [2 + 2]_Re,C cycloaddition reaction of the starting molecule Re1 is kinetically and thermodynamically favored over the [3 + 2]_C,O and [3 + 2]_O,O cycloadditions. However, the reaction which leads to the most stable product takes place with initial rearrangement to the dioxohydridometallacyclopropane isomer Re1a that adds ethylene with concomitant hydrogen migration yielding Re1a-1. The latter reaction has a slightly higher barrier than the [2 + 2]_Re,C cycloaddition reaction. The direct [3 + 2]_C,O cycloaddition becomes more favorable than the [2 + 2]_M,C reaction for the starting compounds Tc1 and Mn1 of the lighter metals technetium and manganese but the calculations predict that other reactions are kinetically and thermodynamically more favorable than the cycloadditions. The reactions with the lowest activation barriers lead after rearrangement to the ethyl substituted dioxometallacyclopropanes Tc1a-1 and Mn1a-1. The manganese compound exhibits an even more complex reaction scenario than the technetium compounds. The thermodynamically most stable final product of ethylene addition to Mn1 is the ethoxy substituted metallacyclopropane Mn1a-2 which has, however, a high activation barrier.     

Cycloaddition reactions of 3-fluorobutenone

3-Fluorobutenone (8) reacted as a dienophile with several dienes 9, 11, 13, 15, 17 to give cycloaddition products in moderate yields. The regio- and stereoselectivity of the reactions are given. Compound 8 is slightly less reactive than methyl vinyl ketone.