Quinoxaline-based U-shaped septuple-bridged [7,7]orthocyclophanes: synthesis, solid-state structure, and self-assembly

We report a three-step synthesis of 12 septuple-bridged [7,7]orthocyclophanes 11 comprising (i) two quinoxaline-based sidewalls and (ii) a linker built-in with a succinimide ring that carries phenyl, p-methoxyphenyl, p-hydroxyphenyl, or p-methoxybenzyl appendants. The synthesis began from the Diels-Alder adduct of 1,2,3,4-tetrachloro-5,5-dimethoxycyclopentadiene (1) and succinimide ring-fused dioxatetracyclodecadiene 9, followed by ruthenium-promoted oxidation of dichloroetheno-bridges in the adduct to generate a bis-α-diketone, which was then condensed with an arene-1,2-diamine to construct sidewalls (phane parts), furnishing U-shaped septuple-bridged [7,7]orthocyclophanes 11 embedding quinoxaline, dimethylquinoxaline, or benzoquinoxaline rings. Concentration-variant ¹H NMR spectra of N-p-methoxybenzyl substituted orthocyclophanes (11zd, 11xd, and 11yd) and single-crystal structures of four orthocyclophanes (11xa, 11yd, 11zb, and 11zd) revealed that the U-shaped septuple-bridged [7,7]orthocyclophanes 11 have a tendency of self-assembly, forming V-shaped dimeric entities driven chiefly by intermolecular π-π stacking interaction in both solid state and solution of high concentration.     

SEAr-SNAr couplings of indolizines and related pyrrole derivatives with superelectrophilic nitrobenzoxadiazoles

The nucleophilic aromatic substitutions of 7-chloro-4,6-dinitrobenzofurazan (DNBZ-Cl) and 7-chloro-4,6-dinitrobenzofuroxan (DNBF-Cl) with a series of differently substituted indolizines (5a-f) and a series of dihyropyrroloisoquinolines (11a-f) have been investigated. In accord with previous reports emphasizing the superelectrophilic character of these compounds in σ-complexation processes, DNBZ-Cl and DNBF-Cl react very readily and quantitatively with the weak carbon nucleophiles 5a-f and 11a-f at room temperature in acetonitrile. In the case of DNBZ-Cl, the resulting products (7Z,a-f and 12Z,a-f) are those expected from the displacement of the chlorine atom through a S_EAr-S_NAr mechanism. A significant result is that these compounds, despite the lack of coplanarity of the two rings, are characterized by an intense intramolecular charge transfer between the donor pyrrole-type moiety and the electron-deficient acceptor DNBZ moiety. Contrasting with this behaviour, the DNBF-Cl reactions show a totally different pattern, proceeding with loss of the N-oxide functionality and expansion of the pyrrole moiety to afford stable zwitterionic spiro adducts (8F,a-f and 13F,a-f) of a so far unknown type. Rapid NMR recordings have revealed that the formation of these adducts occurs after initial formation of the expected substitution products 7F,a-f and 12F,a-f. A mechanism accounting for the overall rearrangement leading to the spirobenzofurazan adducts is suggested. It is based on an initial nucleophilic attack of the oxygen atom of the N-oxide functionality at the electron-deficient and strongly olefinic C-C coupling bond generated by the aforementioned intramolecular charge transfer. This results in the formation of an unstable five-membered isoxazole ring whose decomposition goes along with loss of the N-oxide functionality and enlargement of the pyrrole moiety into a pyridine one. Also discussed are the factors accounting for the high thermodynamic stability of the spiro adducts, and their relevance to the stability of previously reported spiro adducts.     

Synthesis of 2-amino-2,3-dihydrobenzofurans and fully substituted furans from modified Baylis-Hillman adducts

Syntheses of 2-amino-2,3-dihydrobenzofuran derivatives 3a-g and fully substituted furans 5a-f were achieved starting from the Baylis-Hillman adducts. We prepared 2-amino-2,3-dihydrobenzofurans from the Baylis-Hillman adducts of methyl and ethyl acrylates and fully substituted furans from the Baylis-Hillman adducts of alkyl vinyl ketones.     

Substituted coumarin amidines: useful building blocks for the preparation of [1]benzopyrano[4,3-b]pyridin-5-one and [1]benzopyrano[4,3-d]pyrimidin-5-one derivatives

The synthesis of [1]benzopyrano[4,3-b]pyridin-5-ones 4a-f and 4g-j starting from 3-formylcoumarin and 3-cyanocoumarin N-functionalized amidines 3a-f and 3g-j, respectively, was reported. The ring-closure reaction mechanism, under basic or acidic media, was proposed. Furthermore, the reaction of 3-formylamidines 3a,c-f with ammonium acetate gave good yields of 2-substituted [1]benzopyrano[4,3-d]pyrimidin-5-ones 7.     

Substituted lithiumtrimethylsiloxysilanides LiSiRR′(OSiMe3) - Investigations of their synthesis, stability and reactivity

The reactions of the trimethylsiloxychlorosilanes (Me₃SiO)RR′SiCl (1a-h: R′ = Ph, 1a: R = H, 1b: R = Me, 1c: R = Et, 1d: R = ⁱPr, 1e: R = ^tBu, 1f: R = Ph, 1g: R = 2,4,6-Me₃C₆H₂ (Mes), 1h: R = 2,4,6-(Me₂CH)₃C₆H₂ (Tip); 1i: R = R′ = Mes) with lithium metal in tetrahydrofuran (THF) at −78 °C and in a mixture of THF/diethyl ether/n-pentane in a volume ratio 4:1:1 at −110 °C lead to mixtures of numerous compounds. Dependent on the substituents silyllithium derivatives (Me₃SiO)RR′SiLi (2b-i), Me₃SiO(RR′Si)₂Li (3a-g), Me₃SiRR′SiLi (4a-h), (LiO)RR′SiLi (12e, 12g-i), trisiloxanes (Me₃SiO)₂SiRR′ (5a-i) and trimethylsiloxydisilanes (6f^∗, 6h^∗, 6i^∗) are formed. All silyllithium compounds were trapped with Me₃SiCl or HMe₂SiCl resulting in the following products: (Me₃SiO)RR′SiSiMe₂R″ (6b-i: R″ = Me, 7c-i: R″ = H), Me₃SiO(RR′Si)₂SiMe₂R″ (8a-g: R″ = Me, 9a-g: R″ = H), Me₃SiRR′SiSiMe₂R″ (10a-h: R″ = Me, 11a-h: R″ = H) and (HMe₂SiO)RR′SiSiMe₂H (13e, 13g-i). The stability of trimethylsiloxysilyllithiums 2 depends on the substituents and on the temperature. (Me₃SiO)Mes₂SiLi (2i) is the most stable compound due to the high steric shielding of the silicon centre. The trimethylsiloxysilyllithiums 2a-g undergo partially self-condensation to afford the corresponding trimethylsiloxydisilanyllithiums Me₃SiO(RR′Si)₂Li (3a-g). (Me₃)Si-O bond cleavage was observed for 2e and 2g-i. The relatively stable trimethylsiloxysilyllithiums 2f, 2g and 2i react with n-butyllithium under nucleophilic butylation to give the n-butyl-substituted silyllithiums ⁿBuRR′SiLi (15g, 15f, 15i), which were trapped with Me₃SiCl. By reaction of 2g and 2i with 2,3-dimethylbuta-1,3-diene the corresponding 1,1-diarylsilacyclopentenes 17g and 17i are obtained.X-ray studies of 17g revealed a folded silacyclopentene ring with the silicon atom located 0.5 Å above the mean plane formed by the four carbon ring atoms.     

Studies on isocyanides: synthesis of tetrazolyl-isoindolinones via tandem Ugi four-component condensation/intramolecular amidation

The Ugi four-component condensation between methyl o-formylbenzoates 1, anilines 2a-c, isocyanides 3, and trimethylsilyl azide (4) afforded the expected Ugi adducts 5a-d, which were cyclized to the title compounds 6a-d upon treatment with sodium ethoxide in ethanol. Starting from aralkyl- or alkylamines 2d-g the Ugi adducts underwent a spontaneous cyclization to tetrazolyl-isoindolinones 6e-j.     

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.     

Facile generation method for conjugated allenyl esters based on retro-Dieckmann-type ring-opening reactions

α-Alkynyl-α-ethoxycarbonyl cyclopentanones 1a-c and cyclohexanones 2a-c were readily synthesized by the reaction of ethyl 2-oxocyclopentanonecarboxylate 6 and ethyl 2-oxocyclohexanonecarboxylate 7 with alkynyllead triacetates 5a-c obtained from lithium acetylides 4a-c and lead tetraacetate. Treatment of 1a-c and 2a-c with 1 N KOH in THF or with n-Bu₄N⁺OEt⁻ in EtOH and THF gave the corresponding conjugated allenyl esters 8a-c, 9a-c, 10a-c, and 11a-c in good to excellent yields, respectively.     

CpCo(dithiolene) complexes of highly flexible oxddt ligand with two different Z-shaped and U-shaped structures

[CpCo(oxddt)] complex (2, oxddt = o-xylenediyldithioethylene-1,2-dithiolate, Cp = η⁵-cyclopentadienyl) was obtained from o-xylenediyldithioethylene-1,3-dithiol-2-one (OC(oxddt)) (1). 2 further reacted with diazoalkanes (N₂CHR) to form some alkylidene-bridged adducts [CpCo(CHR)(oxddt)] (R = H (3a), SiMe₃ (3b)). Adduct 3a further reacted with protic acids (HX) to give some S-methylated adducts [CpCo(X)(oxddt)(S-Me)] (X = Cl (4a), OCOCF₃ (4c)), followed by the Co-C bond cleavage in the three-membered cobaltathiirane ring. Two different Z-shaped and U-shaped molecular structures were observed by X-ray diffraction studies. In the former structure (Z), the dithiolene and o-xylylene planes are located at almost parallel position each other, and in the latter structure (U), both planes are not parallel but the o-xylylene moiety is located closer to the dithiolene plane than the Z-shaped one. The Z-shaped structure involves 1 and 2. The U-shaped structure involves 3a, 3b, 4a and 4c. Complex 1 showed a one-dimensional chain through intermolecular π-π interaction in the crystal. Complex 2 had a dimeric interaction between dithioethylenedithiolate moieties (S₂C₂S₂) in the oxddt. The SiMe₃ group in 3b was placed at an exo-position with respect to the cobaltadithiolene ring due to a steric hindrance from the U-shaped oxddt ligand. In 4a, the X and Me groups are located at the opposite side of the dithiolene plane (anti-form) but in 4c, both groups are presented at the same side of the dithiolene plane (syn-form). The NMR analysis of 4a in solution indicated existence of both anti- and syn-isomers (7:1).     

Chiral binuclear copper(II) catalyzed nitroaldol reaction: scope and mechanism

Chiral binuclear copper(II) Schiff base complexes 4a-g have been prepared from aldehydes 1a,b, (S)-amino alcohols 2a-f, and Cu(OAc)₂·1H₂O in high yield. Their catalysis is studied for the addition of nitroalkanes to aldehydes at ambient conditions with 76:24 er.     

A Pd[0]-catalyzed Ullmann cross-coupling/reductive cyclization approach to C-3 mono-alkylated oxindoles and related compounds

The Pd[0]-catalyzed Ullmann cross-coupling of o-nitrohaloarenes 1a-e with the brominated heterocycles 2a-f delivers the expected products 3a-j in good to excellent yields. The reductive cyclization of such products, as well as N-acyl derivatives 3k, l, and m, has been investigated and provided the C-3 mono-substituted oxindoles 5a-d, f, g, k, and m, the direct reduction products 4i and j or indole 5l.     

Regioselective synthesis of 1,3,4,5-tetrasubstituted pyrazoles from Baylis-Hillman adducts

Tetrasubstituted pyrazole derivatives 3a-j were synthesized regioselectively in good yields from the reaction of Baylis-Hillman adducts 1a-f and hydrazine hydrochlorides 2a-d in 1,2-dichloroethane.     

3-Amino- and 3-acylamido-2-phosphonopyridines: synthesis by Pd-catalyzed P-C coupling, structure and conversion to pyrido[b]-anellated PC-N heterocycles

Palladium catalyzed cross-coupling of 3-amino- and 3-acylamido-2-bromopyridines 1a-f with triethyl phosphite allowed the synthesis of 3-amino- and 3-acylamido pyridine-2-phosphonic acid diethyl esters 2a-f, whereas nickel catalysts, although providing access to related anilido-2-phosphonates, proved inactive. Reduction of the aminophosphonate 2a with LiAlH₄ afforded 3-amino-2-phosphinopyridine (3a), which was cyclocondensed with dimethylformamide dimethyl acetal (DMFA) via phosphaalkene intermediates 4a to the novel pyrido[b]-anellated 1,3-azaphosphole 5a. Reaction of amidophosphonates 2b-f with LiAlH₄ did not result in the expected reductive cyclization, as shown by closely related anilido-2-phosphonates, but led to product mixtures containing N-secondary 3-amino-2-phosphinopyridines 3b-f as the main or major component. The conversion of 3b,d,e with DMFA to 5b,d,e provides first examples of N-substituted pyrido[b]-anellated azaphospholes. Structures were confirmed by multinuclear NMR and X-ray crystallography (for 2c, 3b).     

The conversion of 2-cyano cyanothioformanilides into 3-aminoindole-2-carbonitriles using triphenylphosphine

2-Cyano cyanothioformanilide 3a reacts with triphenylphosphine in the presence of water to give 2-(cyanomethyleneamino)benzonitrile 4a, 2-(cyanomethylamino)benzonitrile 5, 3-aminoindole-2-carbonitrile 2a and (2-cyanoindol-3-yl)iminotriphenylphosphorane 6a. In the presence of p-toluenesulfonic acid in MeOH the reaction between 2-cyano cyanothioformanilide 3a and triphenylphosphine (2 equiv) gives 3-aminoindole-2-carbonitrile 2a in 90% yield. Under the same conditions 2-(cyanomethyleneamino)benzonitrile 4a gives anthranilonitrile 8a, 3-aminoindole-2-carbonitrile 2a and N-(2-cyanophenyl)formamide 9. In addition, substituted 2-cyano cyanothioformanilides 3b-f react with triphenylphosphine and p-toluenesulfonic acid in MeOH to give 3-aminoindole-2-carbonitriles 2b-f in 63-75% yields. Under analogous conditions 2-cyano-4,5-dimethoxyphenyl cyanothioformanilide 2g gives only 4,5-dimethoxyanthranilonitrile 8g and 4,6,7-trimethoxyquinazoline-2-carbonitrile 14g, but in refluxing dry PhMe in the absence of p-toluenesulfonic acid 2-cyano-4,5-dimethoxyphenyl cyanothioformanilide 3g, (2-cyano-5,6-dimethoxyindol-3-yl)iminotriphenylphosphorane 6g and 2-(cyanomethyleneamino)-4,5-dimethoxybenzonitrile 4g are obtained. The structure of 2-(cyanomethyleneamino)-4,5-dimethoxybenzonitrile 4g is supported unambiguously via independent synthesis and comparison to the isomeric 6,7-dimethoxyquinazoline-2-carbonitrile 15. All new compounds are fully characterised and a tentative mechanism for the transformation of 2-cyano cyanothioformanilides to indoles is proposed.     

Thermal and microwave assisted reactions of 2,5-disubstituted thienosultines with [60]fullerene: non-Kekulé biradicals and self-sensitized oxygenation of the cycloadduct

Refluxing an o-dichlorobenzene solution of 2,5-disubstituted thienosultines 10a-f with [60]fullerene for 2-24 h gave both 1:1 and 2:1 cycloadducts in 37-79% isolated yields. The reaction was highly accelerated by microwave irradiation giving comparable yields of cycloadducts. Sultines 10a-f underwent cheletropic extrusion of SO₂ to form the corresponding non-Kekulé biradical intermediates 11a-f, which were subsequently trapped by [60]fullerene to form corresponding cycloadducts. The activation energy barriers (ΔG_c^≠) determined for the boat-to-boat inversion of these 4′,5′,6′,7′-tetrahydrobenzo[c]thieno-[5′,6′:1,2][60]fullerene adducts 12a-f were found to be in the range of 13.5-14.8 kcal/mol. Unexpectedly, one of the monoadduct 12a was found to be labile when kept in air under ambient light. Two new products 15 (a sulfine-enone) and 16 (an endione) were isolated from the decomposed 12a and were found to derive from self-sensitized singlet oxygen reaction on the 2,5-dimethylthieno moiety of 12a.     

A highly α-regioselective In(OTf)3-catalyzed N-nucleophilic substitution of cyclic Baylis-Hillman adducts with aromatic amines

The highly α-regioselective N-nucleophilic substitution of B-H adducts bearing five (1a-f) or six-membered ring (5a-e) moieties with aromatic amines (2a-e) was developed under the catalysis of In(OTf)₃ (10 mol%). During the reaction the allylic rearrangement from γ-product to α-product occurred, resulting in thermodynamically stable α-product predominately.     

The first reductive cyclization by lithium aluminum hydride: stereospecific reductive cyclization of 1-(methoxycarbonylmethyl)imidazolidin-4-ones

The first LiAlH₄-driven reductive cyclization of the bifunctional 1-(methoxycarbonylmethyl)imidazolidin-4-ones, (−)-1a-c or(+)-1a-c, stereospecifically generated the corresponding 1,6-diaza-4-oxa-bicyclo[3.2.1]octanes, (−)-3a-c or(+)-3a-c, with a novel bicyclic system.     

A clay-mediated, regioselective synthesis of 2-(aryl/alkyl)amino-thiazolo[4,5-c]carbazoles

The 3-aminocarbazoles 1a-e were condensed with phenyl and benzyl isothiocyanates on montmorillonite K10 clay or TLC-grade silica gel at room temperature to furnish efficiently the N-phenyl and N-benzylthioureidocarbazoles, 2a-e and 2f, respectively, within minutes. When adsorbed on montmorillonite K10 clay impregnated with para-toluene sulfonic acid (1:1, w/w) and heated at 60-70 °C, 2a-e and 2f furnished the 2-anilino and 2-benzylaminothiazolo[4,5-c]carbazoles, 3a-e and 3f, respectively, regioselectively in high yields. The cyclisation was also effective for the N-methylthioureidocarbazoles 2g-i.     

Naphthyridines. Part 3: First example of the polyfunctionally substituted 1,2,4-triazolo[1,5-g][1,6]naphthyridines ring system

Treatment of 1,2,4-triazoles (1) with diethylmalonate in bromobenzene gave 1,2,4-triazolo-[1,5-a]pyridines 2. Chlorination of 2 using POCl₃/DMF (Vilsmeier reagent) led to the isolation of 7-chloro-6-formyl-1,2,4-triazolo[1,5-a]pyridine derivative 4, which reacted with the stabilized ylid 5 to afford 6-ethoxycarbonylvinyl-1,2,4-triazolo[1,5-a]-pyridines 6. Azidation of 6 yielded the corresponding azido compound 7, (Scheme 2). Reduction of 7 with Na₂S₂O₄ gave the corresponding 7-amino compound 8, which cyclized in boiling DMF to give the novel 1,2,4-triazolo[1,5-g][1,6]naphthyridines 9. On the other hand, reacting 7 with one equivalent of PPh₃ (aza-Wittig reaction) in CH₂Cl₂ gave 7-imino-phosphorane derivative 10, and subsequent cyclization in boiling DMF afforded the new 1,2,4-triazolo[1,5-g][1,6]naphthyridine derivative 11 (Scheme 3). However, treatment of 10 with phenyl isothiocyanate in 1,2-dichlorobenzene at reflux temperature gave the new 1,2,4-triazolo[1,5-g][1,6]naphthyridine derivative 14 (Scheme 4). Refluxing 6 with excess of a primary amines 15a,b in absolute. EtOH yielded the corresponding 7-alkyl-amino-1,2,4-triazolo[1,5-a]pyridines 16a,b. These obtained amines 16a,b underwent intramolecular heterocyclization in boiling DMF to give the novel 9-alkyl-1,2,4-triazolo[1,5-g][1,6]-naphthyridines 17a,b, in excellent yields (Scheme 5).     

Regioselective synthesis of 1- and 4-substituted 7-oxopyrazolo[1,5-a]pyrimidine-3-carboxamides

The synthesis of 7-substituted pyrazolo[1,5-a]pyrimidine-3-carboxamides was studied. First, methyl 7-hydroxypyrazolo[1,5-a]pyrimidine-3-carboxylate (5) was prepared in three steps from methyl 5-amino-1H-pyrazole-4-carboxylate (3). Treatment of 5 with POCl₃ gave the highly reactive 7-chloro derivative 10, which was reacted with amines, benzyl alcohol, and phenylboronic acid in the presence of Pd-catalyst to give the corresponding 7-substituted derivatives 11. Hydrolysis of the esters 5 and 11 followed by amidation gave the corresponding carboxamides 16a–h and 15. Regioselectivity of N-alkylation of 7-hydroxypyrazolo[1,5-a]pyrimidine-3-carboxylic acid derivatives 5 and 16 was tunable by the carboxy function. Alkylation of the secondary amides 16a–f furnished the 1-alkyl derivatives 17a–f, whereas the ester 5 and the tertiary amides 16g,h gave the 4-alkyl derivatives 14a–d and 16m,n, selectively.