Synthesis of redox-active, intramolecular charge-transfer chromophores by the [2+2] cycloaddition of ethynylated 2H-cyclohepta[b]furan-2-ones with tetracyanoethylene

Ethynylated 2H-cyclohepta[b]furan-2-ones 5-15 have been prepared by Pd-catalyzed alkynylation of 3-iodo-5-isopropyl-2H-cyclohepta[b]furan-2-one (2) with the corresponding ethynylarenes or the reaction of 2-iodothiophene with 3-ethynyl-5-isopropyl-2H-cyclohepta[b]furan-2-one (4) under Sonogashira-Hagihara conditions. Compounds 5-15 reacted with tetracyanoethylene in a formal [2+2] cycloaddition reaction, followed by ring opening of the initially formed [2+2] cycloadducts, cyclobutenes, to afford the corresponding 1,1,4,4-tetracyanobutadienyl (TCBD) chromophores 16-26 in excellent yields. The intramolecular charge-transfer interactions between the 2H-cyclohepta[b]furan-2-one ring and TCBD acceptor moiety were investigated by UV/Vis spectroscopy and theoretical calculations. The redox behavior of the novel TCBD derivatives 16-26 was examined by cyclic voltammetry and differential pulse voltammetry, which revealed multistep electrochemical reduction properties, depending on the number of TCBD units in the molecule. Moreover, a significant color change was observed by UV/Vis spectroscopy under electrochemical reduction conditions.     

Photochemically induced [4+2]- versus [3+2]-cycloreversion reaction of hexasubstituted 2,3-diaza-bicyclo[3.1.0]hex-2-enes

Hexasubstituted 2,3-diaza-bicyclo[3.1.0]hex-2-enes containing large substituents at C-4 and C-6 upon irradiation undergo a novel [4+2]cycloreversion reaction leading to 2,3-diazahexatriens besides the normal [3+2]cycloreversion.     

An easy two step synthesis of macrocyclic peptidotriazoles via a four-component reaction and copper catalyzed intramolecular azide–alkyne [3+2] click cycloaddition

A two-step macrocyclization strategy for the synthesis of 12- and 14-membered cyclic peptidotriazoles by combining a one pot four-component reaction and an intramolecular [3+2] azide–alkyne click cycloaddition reaction is described. Macrocycles are obtained in good to excellent yield from the aqueous work-up of the reaction mixture and it is possible to expand or contract the ring size by adjusting the length of the nitrile moiety used in the MCR stage.     

Electron-transfer-induced intermolecular [2+2] cycloaddition reactions based on the aromatic "redox tag" strategy

Novel electron-transfer-induced intermolecular [2+2] cycloaddition reactions between an aliphatic cyclic enol ether and several unactivated olefins have been demonstrated on the basis of the aromatic "redox tag" strategy. The aromatic "redox tag" was oxidized during the formation of the cyclobutane ring, affording the relatively long-lived aromatic radical cation, which was then reduced to complete the overall reaction that constructed the corresponding [2+2] cycloadducts. The aromatic "redox tag" was also found to facilitate electron-transfer-induced cycloreversion reactions of cyclobutane rings.     

Synthesis of spirooxindoles bearing 2,3-(or 2,5-)dihydrothiophene-2-thione moiety via [3+2] annulation of carbon disulfide with Morita-Baylis-Hillman carbonates of isatins

Various spirooxindoles bearing 2,3-(or 2,5-)dihydrothiophene-2-thione moiety have been synthesized via [3+2] annulation reaction of carbon disulfide and the nitrogen ylides derived from Morita-Baylis-Hillman carbonates of isatins. 2,3-Dihydro- and 2,5-dihydrothiophene-2-thione moieties were formed selectively depending on steric hindrance around the nitrogen ylides.     

Synthesis of donor-acceptor chromophores by the [2 + 2] cycloaddition of arylethynyl-2H-cyclohepta[b]furan-2-ones with 7,7,8,8-tetracyanoquinodimethane

Arylethynyl-2H-cyclohepta[b]furan-2-ones reacted with 7,7,8,8-tetracyanoquinodimethane (TCNQ) in a formal [2 + 2] cycloaddition reaction, followed by ring opening of the initially formed cyclobutene derivatives, to afford the corresponding dicyanoquinodimethane (DCNQ) chromophores in excellent yields. The intramolecular charge-transfer (ICT) interactions between the 2H-cyclohepta[b]furan-2-one ring and DCNQ acceptor moiety were investigated by UV/Vis spectroscopy and theoretical calculations. The redox behavior of the novel DCNQ derivatives was examined by cyclic voltammetry (CV) and differential pulse voltammetry (DPV), which revealed their multistep electrochemical reduction properties depended on the number of DCNQ units in the molecule. Moreover, a significant color change was observed by visible spectroscopy under electrochemical reduction conditions.     

2 + 2] cycloaddition reaction to Sc3N@I(h)-C80. The formation of very stable [5,6]- and [6,6]-adducts

The [2 + 2] cycloaddition reaction of Sc(3)N@I(h)-C(80) with benzyne was successfully conducted for the first time. The reaction affords both the [5,6]- and [6,6]-monoadducts with a four-membered ring attached to the cage surface on 5,6- and 6,6-ring fusions, respectively. The compounds were characterized by MALDI-TOF, NMR, UV-vis-NIR spectroscopy and single-crystal X-ray structure determination. The electrochemical behavior of both monoadducts was investigated. The [5,6]-regioisomer displays reversible cathodic behavior similar to that observed for the fulleropyrrolidines with a 5,6-addition pattern. Surprisingly, the [6,6]-regioisomer also exhibits reversible cathodic behavior. The interconversion reaction of the isomers was also explored, and the results showed that both monoadducts are thermally very stable.     

Acid-catalyzed transannular cyclization of 3aH-cyclopentene[8]annulene-1,4-(5H,9aH)-diones and some proposed mechanisms

Bicyclic 3aH-cyclopentene[8]annulene-1,4-(5H,9aH)-diones underwent three types of acid-induced transannular reactions, Michael cyclization, [3 + 2] cycloaddition, and Friedel-Crafts ipso-alkylation, depending on the cyclopentenone ring substituent (Me or Ph) and the position of [8]annulenone substituent as well as the nature of acids (BF3, MeSO3H, CF3SO3H). The Me-substituent permitted the Michael reaction for all acids used to give tricyclic diones by the activation of cyclopentenone carbonyl group. However, the Ph-substituent inhibited the Michael reaction for BF3 and MeSO3H but allowed the [3 + 2] cycloaddition and Friedel-Crafts reaction for CF3SO3H depending on the position of annulenone substituent. These CF3SO3H reactions exhibited the following novel rearrangements, affording 2-naphthalenone and 7-acenaphthylene derivatives, respectively. The factors that control the reaction mode of these transannular cyclizations were discussed in view of the constraint twist-boat conformation of [8]annulenone ring as well as the ring substituent effects on the intramolecular cyclization. In addition, these [8]annulenone rings were found to easily undergo the intramolecular [2 + 2] photocyclization to provide the tetracyclic cage compounds which exhibited the facile cycloreversion under the influence of acid.     

Generation and reactions of 2-alkyl-3-carboethoxycyclopentadienones

Thermolysis of 6-alkyltricyclo[5.2.1.0^2,6]decadienone esters 3 in DMF produces 2-alkyl-3-carboethoxycyclopentadienones 8 in an efficient [4+2]cycloreversion reaction. These cyclic dienones can be trapped by cyclopentadiene to afford regioselectively tricyclodecadienones 9 in high yields.     

Carbon-carbon bond formation reaction of ethereal oxonium ylides via metal-enolate intermediates

First, the carbon-carbon (C-C) bond-forming reaction of aldehydes with bicyclo[m.n.0]-1-oxonium ylides was studied as the ylide was transiently formed in the Rh(II)-catalyzed reaction of a nonenolizable diazoketone, namely, 2-(3-diazo-1,1-dimethyl-2-oxopropyl)-2-methyldioxolane (1). The reaction of 1 with benzaldehyde in the presence of ClTi(Oi-Pr)3 gave the three-carbon, ring-enlarged, and C-C-bonded product 2a (53%). Second, enolizable diazoketone 5 bearing no methyl substituents at the alpha-position was studied under similar catalytic conditions, and the ring-enlarged and C-C-bonded products 19a and 20a were also formed (87%) when titanium compound ClTi(Oi-Pr)3 or Ti(Oi-Pr)4 was used. Similar reactions of diazoketones 27, 29, and 31 bearing a cyclic acetal ring and a longer tethering chain than 5 gave C-C-bonded products 28 (74%), 30 (8%), and 32 and 33 (overall 48%), respectively, albeit 28 and 30 possessed a spiro bisacetal structure. Thus, the hitherto unclarified C-C bond formation of ethereal oxonium ylides with carbonyl electrophiles was realized with the use of an appropriate Lewis acid, for example, ClTi(Oi-Pr)3.     

Thermal [2 + 2] cycloreversion of a cyclobutane moiety via a biradical reaction

The nature of the Woodward-Hoffmann-forbidden, thermal activated cycloreversion mechanism of cyclobutane has long been the subject of speculation and intense research. We were now able to prove the theoretically postulated biradicalic mechanism directly from radical scavenging reactions and electron paramagnetic resonance (EPR) experiments on [2 + 2] heterodimers of 5-fluoro-1-heptanoyluracil and 7-methoxy-1,1-dimethylnaphthalenon. The dimers show both the "allowed" photochemically as well as the "forbidden" thermally triggered [2 + 2] cycloreversion of the cyclobutane ring. The quantum efficiency of the photochemical cleavage is about 1%. The thermal cycloreversion reaction is independent from solvent and occurs at low activation energies of about 13 kcal/mol, even in the solid state. The radical scavenger and EPR results are further supported by the finding, that the reaction products are solely the educts for the anti-head-to-tail heterodimer. But for the syn-head-to-head heterodimer two additional products are observed, which require a sufficiently stable biradical intermediate to facilitate the required intramolecular rearrangements. Because of the surprisingly high lifetime of the radical species of these heterodimers it was possible to prove the long-discussed biradical mechanism experimentally.     

Cooperative diastereoselectivity of palladium- and platinum-promoted intramolecular [4 + 2] Diels-Alder cycloaddition reactions of 3,4-dimethyl-1-phenylphosphole

The complexes [(DMPP)2M(CH3CN2)]X2 (DMPP = 3,4-dimethyl-1-phenylphosphole; M = Pd, Pt; X = BF4-, NO3-, ClO4-) react with 2 equiv of the dienophiles N,N-dimethylacrylamide (DMAA), 2-vinylpyridine (VyPy), and diphenylvinylphosphine (DPVP) to form bis-[4 + 2] Diels-Alder cycloaddition products. The [M(DMPP)2(DMAA)2]2+ and [M(DMPP)2(VyPy)2]2+ complexes form exclusively as the cis-geometric isomers, whereas for [M(DMPP)2(DPVP)2]2+, both cis- and trans-geometric isomers are formed. The two Diels-Alder cycloadditions occur sequentially, and the absolute configuration of the first reaction influences the absolute configuration of the second. In all cases, recemic mixtures of the (R,R) and (S,S) diastereomers are formed; none of the meso (R,S) diastereomer is observed. New complexes were characterized by elemental analyses, physical properties, infrared spectroscopy, 1H, 1H(31P), 13C(1H), and 31P(1H) NMR spectroscopy, and, in most cases, X-ray crystallography.     

Oxorhenium(V) and oxotechnetium(V) [NN][S]3 complexes of 2-phenylbenzothiazole derivatives

The reaction of 2-(2'-pyridyl)benzothiazole, [NN], with the ReO(V)(3+) and TcO(V)(3+) cores in the presence of thiophenols, [S] (RC(6)H(4)SH, R = H, 4-CH(3), 4-OCH(3)), as coligands led to the isolation of hexacoordinated complexes of the MO[NN][S](3) type (M = Re, Tc). In all cases, two geometric mer isomers were formed, as evidenced by NMR spectroscopy and confirmed by X-ray crystallography. In both isomers, the coordination geometry about the metal ion is a distorted octahedral defined by the two nitrogen atoms of the bidentate ligand, the three sulfur atoms of the monodentate thiols, and the oxygen atom of the oxo group. The apical positions of the octahedron are occupied by the oxygen of the oxo group and, in one of the isomers, the nitrogen of the pyridyl moiety of 2-(2'-pyridyl)benzothiazole, while, in the second isomer, the imine nitrogen of 2-(2'-pyridyl)benzothiazole. The complexes are stable, neutral, and lipophilic. Complete (1)H and (13)C NMR assignments are reported for all complexes. The synthetic reaction was also successfully transferred at the technetium-99m tracer level by ligand exchange reaction using (99m)Tc-glucoheptonate as precursor in the presence of 2-(2'-pyridyl)benzothiazole and 4-CH(3)C(6)H(4)SH. The structure of the technetium-99m complex was established by high-performance liquid chromatographic comparison with the analogous oxotechnetium and oxorhenium complexes. The 2-(2'-pyridyl)benzothiazole ligand serves as a preliminary model for 2-(4-aminophenyl)benzothiazole, which possesses interesting properties for the development of technetium and rhenium radiopharmaceuticals for tumor imaging and/or radiotherapy as well as in vivo diagnosis of Alzheimer's disease.     

Synthesis and antibacterial activity of new N-[2-(thiophen-3-yl)ethyl] piperazinyl quinolones

As a part of continuing search for potential antibacterial agents in the quinolones field, we have synthesized novel quinolone agents bearing N-[2-(thiophen-3-yl)ethyl] piperazinyl moiety in the 7-position of the quinolone ring. In vitro antibacterial evaluation of the target compounds showed that N-[2-(thiophen-3-yl)ethyl] group attached to piperazine ring served as promising C-7 substituent for piperazinyl quinolone antibacterials. Among these derivatives, ciprofloxacin analogues, containing N-[2-(thiophen-3-yl)-2-hydroxyiminoethyl] or N-[2-(thiophen-3-yl)-2-methoxyiminoethyl] residue provided a high inhibition against all the tested Gram-positive organisms including methicillin-resistant Staphylococcus aureus comparable or superior with respect to the reference drugs norfloxacin and ciprofloxacin.     

Stereospecific and Stereoselective Rhodium(I)‐Catalyzed Intramolecular [2+2+2] Cycloaddition of Allene‐Ene‐Ynes: Construction of Bicyclo[4.1.0]heptenes

Treatment of the allene‐ene‐yne substrates with [{RhCl(CO)₂}₂] effected the intramolecular [2+2+2]‐type ring‐closing reaction to produce various of tri‐ and tetracyclic derivatives containing a cyclopropane ring. The reaction is highly stereoselective as well as stereospecific with good to excellent yields.     

The synthesis of optically pure β-lactams derived from sugars. High-pressure [2+2] cycloaddition of toluene-4-sulphonyl isocyanate to glycals.

[2+2] Cycloaddition of toluene-4-sulphonyl isocyanate to glycals 1 - 4 at room temperature under 10 kbar pressure gave respective β-lactams 5 - 8 in good yields. The reaction proceeds regio- and stereospecifically to afford the four-membered ring in position trans to the acetoxy group at C-3 of the glycal moiety.     

Catalytic enantiospecific [3+2] annulation of aminocyclopropanes with ketones

An almost familiar ring: The first enantiospecific [3+2] annulation of donor-acceptor aminocyclopropanes with ketones is reported (see scheme; Phth=phthaloyl). The reaction is catalysed by tin(IV) chloride (5?mol?%) at -78?°C and gives aminotetrahydrofurans bearing a quaternary C5 atom in high yield, diastereoselectivity and enantiospecificity (see scheme).     

Organometallic compounds : XII. stereochemical interconversion reactions between 1,1′−bis(α-hydroxyalkyl)ferrocenes and 7-oxa[3]ferrocenophanes

Meso and racemic isomers of 1,1′-bis(α-hydroxyalkyl)ferrocene derivatives, and trans and cis isomers of 7-oxa[3]ferrocenophanes have been isolated. The configurations of these isomers have been determined both by spectroscopy and from their reaction behavior. It has been found that the ring-closure and ring-opening interconversion reactions between 1,1′-bis(α-hydroxyalkyl)ferrocenes and 7-oxa[3]ferrocenophanes are stereospecific. PMR spectra of the diols and ethers have been examined at 100 MHz in CF₃COOH, and the existence of α-[1′-(α-hydroxyalkyl)ferrocenyl]carbonium ions has been demonstrated in this acid. A mechanism for the various interconversion reactions is proposed on the basis of their stereospecific reactivity and from the PMR spectra of the carbonium ions.     

Pt(II)- or Au(III)-catalyzed [3+2] cycloaddition of metal-containing azomethine ylides: highly efficient synthesis of the mitosene skeleton

[reaction: see text] Only 1-3 mol % of PtCl(2) or AuBr(3) was sufficient to promote generation and [3+2] cycloaddition of transition-metal-containing azomethine ylides derived from N-(o-alkynylphenyl)imines bearing an internal alkyne moiety. A highly efficient method for the preparation of synthetically useful tricyclic indole derivatives having a substituent at the 3-position of the indole nucleus was established by this method.