Synthesis of α-(Trifluoromethyl)styrenes and 1,3-Di(trifluoromethyl)indanes via Electrophilic Activation of TMS Ethers of (Trifluoromethyl)benzyl Alcohols in Brønsted Acids.

TMS ethers of CF3-benzyl alcohols (and their heterocyclic analogues) undergo elimination of TMSOH molecule with the formation of α-(trifluoromethyl)styrenes in yields of up to 90% under the action of strong Brønsted acids TfOH or H2SO4. Under the acidic conditions upon prolongation of the reaction, the α-(trifluoromethyl)styrenes are further dimerized into cis-/trans-1,3-di(trifluoromethyl)indanes in yields of up to 100%. Plausible reaction mechanisms of these electrophilic transformations including the intermediate formation of CF3-benzyl carbocations are discussed.

Synthesis of bis-spirocyclic derivatives of 3-azabicyclo[3.1.0]hexane via cyclopropene cycloadditions to the stable azomethine ylide derived from Ruhemann's purple.

A reliable method for the synthesis of bis-spirocyclic derivatives of 3-azabicyclo[3.1.0]hexanes through the 1,3-dipolar cycloaddition (1,3-DC) reactions of cyclopropenes to the stable azomethine ylide - protonated form of Ruhemann's purple (PRP) has been developed. Both 3-substituted and 3,3-disubstituted cyclopropenes reacted with PRP, affording the corresponding bis-spirocyclic 3-azabicyclo[3.1.0]hexane cycloadducts in moderate to good yields with high diastereofacial selectivity. Moreover, several unstable 1,2-disubstituted cyclopropenes were successfully trapped by the stable 1,3-dipole under mild conditions. The mechanism of the cycloaddition reactions of cyclopropenes with PRP has been thoroughly studied using density functional theory (DFT) methods at the M11/cc-pVDZ level of theory. The cycloaddition reactions have been found to be HOMOcyclopropene-LUMOylide controlled while the transition-state energies for the reaction of 3-methyl-3-phenylcyclopropene with PRP are fully consistent with the experimentally observed stereoselectivity.

Rhodium-Catalyzed Denitrogenative Diazole-Triazole Coupling toward Aza-Bridged Structures and Imidazole-Based Chelating Ligands.

1,4,8-Triazaocta-1,3,5,7-tetraenes, generated in situ by Rh2(Piv)4-catalyzed denitrogenative coupling of pyrazoles with 1-sulfonyl-1,2,3-triazoles, smoothly form 2,6,8-triazabicyclo[3.2.1]octa-3,6-dienes via intramolecular aza-Diels-Alder cycloaddition. This domino reaction, combined with the subsequent thermal or acid-catalyzed rearrangement of the cycloadducts, provides direct and flexible access to N-sulfonylated (Z)-2-(2-aminovinyl)imidazoles.

The carbene transfer to strong Lewis acids: copper is better than silver.

A new convenient approach to the synthesis of useful N-heterocyclic carbene complexes of group 13 metals was successfully developed. We demonstrate that air-stable copper(i) diaminocarbene complexes are excellent carbene transfer reagents for the synthesis of (IMes or IPr)MCl3 with high yields (M = Al, Ga). Use of this simple method allowed for the first time to obtain (IPr)AlCl3, inaccessible via a free carbene route. In contrast to copper complexes, under the same conditions the more commonly used silver analog (IPr)AgCl reacts with MCl3 (M = Al, Ga, In) yielding only the homoleptic cationic complexes [(IPr)2Ag]+MCl4-.

TfOH-Promoted Reactions of TMS-Ethers of CF3-Pentenynoles with Arenes. Synthesis of CF3-Substituted Pentenynes, Indenes, and Other Carbocyclic Structures.

Trimethylsilyl ethers of 1,5-diaryl-3-(trifluoromethyl)-pent-1-en-4-yn-3-oles [Ar-C≡C-C(CF3)(OSiMe3)-CH═CH-Ar'] in the superacid TfOH give rise to reactive conjugated CF3-allylic-propargylic cations [Ar-C≡C-C+(CF3)-CH═CH-Ar']. These species react with arenes in the presence of 1.5 equiv of TfOH forming regio- and stereoselectively E-1,1,5-triaryl-3-(trifluoromethyl)-pent-2-en-4-ynes [Ar-C≡C-C(CF3)═CH-CHAr'(Ar″)] in good yields. In the excess of TfOH, these CF3-pentenynes are further intramolecularly cyclized into CF3-bicyclic dihydroanthracene derivatives ("helicopter"-like molecules). The CF3-pentenynes may also react with arenes, as external nucleophiles, leading to CF3-indenes. These two main reaction pathways depend on internal nucleophilicity of aryl substituents in CF3-pentenynes and external nucleophilicity of aromatic molecules. Plausible cationic reaction mechanisms have been discussed. CF3-bicyclic dihydroanthracene derivatives have been studied regarding their cytotoxicity and virus-inhibiting activity against influenza virus A/Puerto Rico/8/34 (H1N1) in MDCK cell line.

Light-induced one-pot synthesis of pyrimidine derivatives from vinyl azides.

A one-pot procedure for the synthesis of tetrasubstituted dihydropyrimidine and pyrimidine derivatives from α-azidocinnamates was developed. The synthesis is based on the finding that the outcome of LED photolysis of α-azidocinnamates depends on the light wavelength employed. Blue light (455 nm) leads to the formation of 2H-azirines only, but violet light (395 nm), UV-A light (365 nm), or sunlight result in the transformation of the in situ formed 2H-azirines to 1,3-diazabicyclo[3.1.0]hex-3-enes. Under basic catalysis (DBU), the latter were isomerized to 1,6-dihydropyrimidines which were oxidized to pyrimidines using DDQ. A successful use of Cs2CO3 as a base and air as an oxidant was also demonstrated.

Generation and NMR Study of Short-Lived and Reactive Trifluoroalkyl Carbocations of the α-Halogenothiophene Series in Brønsted Superacids: Reactions of the Cations with Arenes.

Protonation of oxygen in the side chain of the Me3SiO group (followed by the elimination of Me3SiOH) and protonation of the thiophene ring in 2-chloro(or bromo)-5-(1'-Me3SiO-1'-trifluoromethyl-alkyl)thiophenes in Brønsted superacids (CF3SO3H, FSO3H) gave rise to short-lived and reactive trifluoroalkyl carbocations of the thiophene series. These cations were studied by low-temperature NMR spectroscopy in the superacids, which shed light on their reactivity and reaction mechanisms. The cations may react with (hetero)aromatic π-nucleophiles in various directions, depending on their structures as well as the reaction temperature and time. These transformations resulted in the formation of novel fluoro-organics of the thiophene family, namely, products of arylation of both the thiophene system and its side chain, hydrodehalogenation of halothiophenes, or electrophilic "dimerization".

2H-Azirine-2-carbonyl Azides: Preparation and Use as N-Heterocyclic Building Blocks.

2H-Azirine-2-carbonyl azides, new reactive heterocyclic building blocks, were synthesized in high yield by the reaction of sodium azide with 2H-azirine-2-carbonyl chlorides, generated by the Fe(II)-catalyzed isomerization of 5-chloroisoxazoles. 2-(Azidocarbonyl)-1H-pyrroles, prepared by the Ni(II)-catalyzed reaction of 2-(azidocarbonyl)-2H-azirines with 1,3-diketones, easily undergo the Curtius rearrangement in boiling tBuOH to give Boc-protected α-aminopyrroles in high yield. Heating of 2-(azidocarbonyl)-1H-pyrroles for a short time in inert solvents leads to the high-yield formation of benzo- and hetero-fused 1H-pyrrolo[2,3-b]pyridin-6(7H)-ones, which are formed via a 6π electrocyclization involving the vicinal aryl or hetaryl substituent and the N═C bond of isocyanate, generated by the Curtius rearrangement of the azidocarbonyl group. The Pd-catalyzed cross-coupling reaction of 1-acetyl-2-methyl-3H-pyrrolo[2,3-c]isoquinolin-5-yl triflate, easily prepared from the corresponding pyrroloisoquinolone, leads to variously 5-substituted 3H-pyrrolo[2,3-c]isoquinolines in excellent yields.

How Strong is Hydrogen Bonding to Amide Nitrogen?

The protonation of the carboxamide nitrogen atom is an essential part of in vivo and in vitro processes (cis-trans isomerization, amides hydrolysis etc). This phenomenon is well studied in geometrically strongly distorted amides, although there is little data concerning the protonation of undistorted amides. In the latter case, the participation of amide nitrogen in hydrogen bonding (which can be regarded as the incipient state of a proton transfer process) is less well-studied. Thus, it would be a worthy goal to investigate the enthalpy of this interaction. We prepared and investigated a set of peri-substituted naphthalenes containing the protonated dimethylamino group next to the amide nitrogen atom ("amide proton sponges"), which could serve as models for the study of an intramolecular hydrogen bond with the amide nitrogen atom. X-Ray analysis, NMR spectra, basicity values as well as quantum chemical calculations revealed the existence of a hydrogen bond with the amide nitrogen, that should be attributed to the borderline between moderate and weak intramolecular hydrogen bonds (2-7 kcal ⋅ mol-1 ).

Isoxazole Strategy for the Synthesis of α-Aminopyrrole Derivatives.

The synthesis of methyl 5-aminopyrrole-3-carboxylates from 4-methyleneisoxazol-5-ones via "cyanide Michael addition/methylation/reductive isoxazole-pyrrole transformation" is developed. The last step occurs in a domino mode involving Mo(CO)6-mediated reductive isoxazole ring-opening, Mo(CO)6-catalyzed cis-trans-isomerization of the enamine intermediate followed by 1,5-exo-dig cyclization. 5-Amino-1H-pyrrolo-3-carboxylates react with 1,3-diketones, affording pyrrolo[1,2-a]pyrimidine-7-carboxylates, and are easily converted into 2-diazo-2H-pyrrole-4-carboxylates. These compounds demonstrate the reactivity of both diazo compounds, giving pyrrole-containing products of intra/intermolecular azo coupling, and carbenes to give pyrrole-containing insertion products into CH and OH bonds under photolysis.

Stereo- and Regioselective 1,3-Dipolar Cycloaddition of the Stable Ninhydrin-Derived Azomethine Ylide to Cyclopropenes: Trapping of Unstable Cyclopropene Dipolarophiles.

A stereo- and regioselective 1,3-dipolar cycloaddition of the stable ninhydrin-derived azomethine ylide [2-(3,4-dihydro-2 H-pyrrolium-1-yl)-1-oxo-1 H-inden-3-olate, DHPO] to differently substituted cyclopropenes has been established. As a result, an efficient synthetic protocol was developed for the preparation of biologically relevant spiro[cyclopropa[ a]pyrrolizine-2,2'-indene] derivatives. DHPO has proved to be an effective trap for such highly reactive and unstable substrates as parent cyclopropene, 1-methylcyclopropene, 1-phenylcyclopropene, and 1-halo-2-phenylcyclopropenes. It has also been found that 3-nitro-1,2-diphenylcyclopropene undergoes a nucleophilic substitution reaction in alcohols and thiols to afford 3-alkoxy- and 3-arylthio-substituted 1,2-diphenylcyclopropenes, which can be captured as corresponding 1,3-dipolar cycloadducts in the presence of DHPO. These new approaches provide a straightforward strategy for the synthesis of functionally substituted cyclopropa[ a]pyrrolizine derivatives. The factors governing regio- and stereoselectivity have been revealed by means of quantum mechanical calculations (M11 density functional theory), including previously unreported Nylide- Hcyclopropene second-orbital interactions. The outcome of this work contributes to the study of 1,3-dipolar cycloaddition, as well as enriches chemistry of cyclopropenes and methods for the construction of polycyclic compounds with cyclopropane fragments.

Synthesis of 1,2,4-Oxadiazoles by Tandem Reaction of Nitroalkenes with Arenes and Nitriles in the Superacid TfOH.

The tandem reaction of nitroalkenes with arenes and nitriles in the superacid CF3SO3H (TfOH) results in the formation of 1,2,4-oxadiazole derivatives in yields up to 96%. This reaction proceeds via the consequent interaction of arenes and nitriles, as nucleophiles, with intermediate cationic species derived by the protonation of nitroalkenes in TfOH. This is novel and general synthesis of 1,2,4-oxadiazoles, which are very important compounds for medicinal chemistry.

Generation of 1,2-oxathiolium ions from (arysulfonyl)- and (arylsulfinyl)allenes in Brønsted acids. NMR and DFT study of these cations and their reactions.

In strong Brønsted acids (CF3SO3H, FSO3H, D2SO4), (arysulfonyl)allenes (ArSO2-CR1=C=CR2R3) and (arylsulfinyl)allenes (ArSO-CR1=C=CR2R3) undergo cyclization into the corresponding stable 1,2-oxathiolium ions, which were studied by means of NMR and DFT calculations. Quenching of solutions of these cations with low nucleophilic media, aqueous HCl, leads to their deprotonation with a stereoselective formation of (arysulfonyl)butadienes (for instance, ArSO2-CR1=C-C(Me)=CH2, for R2 = R3 = Me, yields of 87-98%). Reactions of (arysulfonyl)allenes in the system TfOH (0.1 equiv)-HFIP (hexafluoropropan-2-ol) followed by hydrolysis give rise to allyl alcohols (ArSO2-CR1=CH-C(OH)R2R3, yields of 78-99%). Reflux of solutions of (arysulfonyl)allenes in the presence of TfOH (1 equiv) in 1,2-dichlorobenzene leads to the cyclization into thiochromene 1,1-dioxides in high yields. Under the action of TfOH or AlX3 (X = Cl, Br) followed by hydrolysis of reaction mixtures, (arylsulfinyl)allenes give allyl alcohols (ArSO2-CR1=CH-C(OH)R2R3). Plausible reaction mechanisms have been proposed for all studied reactions.

TfOH-Promoted Reaction of 2,4-Diaryl-1,1,1-Trifluorobut-3-yn-2-oles with Arenes: Synthesis of 1,3-Diaryl-1-CF3-Indenes and Versatility of the Reaction Mechanisms.

The TfOH-mediated reactions of 2,4-diaryl-1,1,1-trifluorobut-3-yn-2-oles (CF3-substituted diaryl propargyl alcohols) with arenes in CH2Cl2 afford 1,3-diaryl-1-CF3-indenes in yields up to 84%. This new process for synthesis of such CF3-indenes is complete at room temperature within one hour. The synthetic potential, scope, and limitations of this reaction were illustrated by more than 70 examples. The proposed reaction mechanism invokes the formation of highly reactive CF3-propargyl cation intermediates that can be trapped at the two mesomeric positions by the intermolecular nucleophilic attack of an arene partner with a subsequent intramolecular ring closure.

Reactions of 3,3,3-Trihalogeno-1-nitropropenes with Arenes in the Superacid CF3SO3H: Synthesis of ( Z)-3,3,3-Trihalogeno-1,2-diarylpropan-1-one Oximes and Study on the Reaction Mechanism.

3,3,3-Trihalogeno-1-nitropropenes C(Hal3)CH═CH(NO2) (Hal = F, Cl, Br) in reaction with arenes in the superacid CF3SO3H (TfOH) at room temperature in 1 h afford 3,3,3-trihalogeno-1,2-diarylpropan-1-one oximes C(Hal3)CH(Ar)-C(Ar)═NOH (CHal3-oximes) in yields of 23-99%. Such CHal3-oximes having one ortho-substituent in the aryl ring exist as atropoisomers in solutions at room temperature. Several cationic intermediates of this reaction were studied by means of NMR and DFT calculations, which proves the detailed reaction mechanism of the formation of CHal3-oximes in TfOH. CHal3-oximes (for Hal = Cl, Br) with DBU in DMF at microwave or thermal activation are cyclized into 5-halogeno-3,4-diarylisoxazoles in yields of 37-59%. CHal3-oximes under the conditions of Beckmann rearrangement with PCl5 in benzene at room temperature in 24 h are turned at first into imidoyl chlorides (yields of 94-96%), which undergo transformation into the corresponding benzamides PhCONHCHPh(CHal3) on silica gel (yields of 46-47%).

Reactions of 1,5-Diaryl-3-(trifluoromethyl)pent-1-en-4-yn-3-yl Cations with Benzene in TfOH. Synthesis of CF3-"Helicopter"-Like Molecules.

Trimethylsilyl ethers of 1,5-diaryl-3-(trifluoromethyl)pent-1-en-4-yn-3-oles in superacid CF3SO3H (TfOH) give rise to the corresponding intermediate CF3-pentenynyl cations. These species react with benzene to afford conjugated CF3-pentenynes, which undergo subsequent cyclization, first, into CF3-cycloheptadienes and, finally, into unusual CF3-"helicopter"-like bicyclic structures.

Versatile structures of group 13 metal halide complexes with 4,4'-bipy: from 1D coordination polymers to 2D and 3D metal-organic frameworks.

A systematic structural study of complexes formed by aluminium and gallium trihalides with 4,4'-bipyridine (bipy) in 2 : 1, 1 : 1, and 1 : 2 stoichiometric ratios has been performed. Molecular structures of 11 complexes in the solid state have been determined for the first time. Complexes of 2 : 1 composition are molecular, while complexes of 1 : 1 composition form metal-organic frameworks of different kinds: an ionic 3D network (three interpenetrated lvt nets for AlCl3bipy), an ionic 2D network for AlBr3bipy and GaBr3bipy and a 1D coordination polymer in the case of GaCl3bipy. Thus, the nature of the Lewis acid plays a critical role in the structural type of the complex in the solid state. Incorporation of excess bipy molecules into (GaCl3bipy)∞ (formation of crystallosolvate) leads to an unprecedented change of the molecular structure from a non-ionic 1D coordination polymer to an ionic 2D metal organic framework [GaCl2bipy2](+)[GaCl4](-)·2bipy. As indicated by the temperature-dependent XRD study, removal of bipy by heating in a vacuum restores the non-ionic 1D structure. Quantum chemical computations for simple cluster model systems (up to eight Al and Ga atoms) reveal that ionic forms are slightly favourable, although the energy differences between the ionic and non-ionic structures are not large. These theoretical predictions are in good agreement with experimental findings. Thus, even relatively simple cluster models may be used to indicate the structural preferences in the solid state. Both experimental and computational IR frequency shifts of the in-plane ring bending mode of bipy upon complexation correlate well with the M-N bond distances in the complexes.