Dicationic Intermediates Research Articles

Friedel-Crafts Reactions with N-Heterocyclic Alcohols.

N-Heterocyclic alcohols are shown to be excellent substrates for superacid-promoted Friedel-Crafts reactions. The N-heterocyclic alcohols ionize to produce reactive, dicationic intermediates which provide good to excellent yields of arylation products.

Unbiased C3‐Electrophilic Indoles: Triflic Acid Mediated C3‐Regioselective Hydroarylation of N−H Indoles**

AbstractThe direct dearomative addition of arenes to the C3 position of unprotected indoles is reported under operationally simple conditions, using triflic acid at room temperature. The present regioselective hydroarylation is a straightforward manner to generate an electrophilic indole at the C3 position from unbiased indoles in sharp contrast to previous strategies. This atom‐economical method delivers biologically relevant 3‐arylindolines and 3,3‐spiroindolines in high yields and regioselectivities from both intra‐ and intermolecular processes. DFT computations suggest the stabilization of cationic or dicationic intermediates with H‐bonded (TfOH)n clusters.

Unbiased C3-Electrophilic Indoles: Triflic Acid Mediated C3-Regioselective Hydroarylation of N-H Indoles.

The direct dearomative addition of arenes to the C3 position of unprotected indoles is reported under operationally simple conditions, using triflic acid at room temperature. The present regioselective hydroarylation is a straightforward manner to generate an electrophilic indole at the C3 position from unbiased indoles in sharp contrast to previous strategies. This atom‐economical method delivers biologically relevant 3‐arylindolines and 3,3‐spiroindolines in high yields and regioselectivities from both intra‐ and intermolecular processes. DFT computations suggest the stabilization of cationic or dicationic intermediates with H‐bonded (TfOH) n clusters.

Access to Optically Pure Benzosultams by Superelectrophilic Activation.

Through superacid activation, N-(arenesulfonyl)-aminoalcohols derived from readily available ephedrines or amino acids undergo an intramolecular Friedel-Crafts reaction to afford enantiopure benzosultams bearing two adjacent stereocenters in high yields with fully controlled diastereoselectivity. Low-temperature NMR spectroscopy demonstrated the crucial role played by the conformationally restricted chiral dicationic intermediates.

Redox-Driven Folding, Unfolding, and Refolding of Bis(tetrathiafulvalene) Molecular Switch.

We report redox-driven folding, unfolding, and refolding motions of a synthetic molecular system, in which two tetrathiafulvalene (TTF) units are tethered onto a conformationally rigid yet torsionally flexible π-conjugated backbone. Upon one-electron oxidation, this molecular switch undergoes swiveling motions from a fully relaxed and freely rotating Z-shaped conformation to a compact folded conformation stabilizing π-stacked radical species. Subsequent one-electron oxidation produces dicationic intermediates, which either engage in intimate π-π interactions or transition to an open structure. Further oxidation, however, brings the molecule back to the initial conformation to minimize the repulsion between doubly-charged TTF units. Intriguingly, the reaction coordinates of this redox-driven structural change have strong dependence on the environment, such as the solvent (THF vs CH2Cl2) and supporting electrolyte (PF6- vs B(C6F5)4-). With a proper design, factors that are typically considered as "secondary effects" could dictate the solution dynamics and reaction pathways of structural folding and unfolding, all driven by controlled delivery of electrons.

Unsymmetric Twofold Scholl Cyclization of a 5,11-Dinaphthyltetracene: Selective Formation of Pentagonal and Hexagonal Rings via Dicationic Intermediates.

Even though the Scholl reaction is one of the most powerful processes for the synthesis of polycyclic aromatic hydrocarbons (PAHs), its mechanism still remains a subject of discussion. Herein, we report a unique twofold Scholl cyclization of a 5,11-dinaphthyltetracene. Single-crystal X-ray diffraction analysis of the cyclization product revealed that unsymmetric cyclizations of the two naphthyl groups resulted in the formation of fully unsaturated pentagonal and hexagonal rings. The thus obtained product exhibits a twisted π-surface and an absorption band that reaches up to 950 nm. A combined experimental and theoretical study showed that such unsymmetric Scholl cyclizations can be rationalized in terms of a mechanism that involves dicationic intermediates, which stands in contrast to previously reported pathways based on radical cations and arenium ions.

Unsymmetric Twofold Scholl Cyclization of a 5,11‐Dinaphthyltetracene: Selective Formation of Pentagonal and Hexagonal Rings via Dicationic Intermediates

AbstractEven though the Scholl reaction is one of the most powerful processes for the synthesis of polycyclic aromatic hydrocarbons (PAHs), its mechanism still remains a subject of discussion. Herein, we report a unique twofold Scholl cyclization of a 5,11‐dinaphthyltetracene. Single‐crystal X‐ray diffraction analysis of the cyclization product revealed that unsymmetric cyclizations of the two naphthyl groups resulted in the formation of fully unsaturated pentagonal and hexagonal rings. The thus obtained product exhibits a twisted π‐surface and an absorption band that reaches up to 950 nm. A combined experimental and theoretical study showed that such unsymmetric Scholl cyclizations can be rationalized in terms of a mechanism that involves dicationic intermediates, which stands in contrast to previously reported pathways based on radical cations and arenium ions.

Reactions of 2,3-naphthalenediol with cyclohexane in the presence of aluminum halides

2,3-Naphthalenediol (7) undergoes selective ionic hydrogenation with cyclohexane in the presence of excess AlCl3 or AlBr3 to afford 5,6,7,8-tetrahydro-2,3-naphthalenediol (8). Compound 8 can be further converted into 5,6,7,8-tetrahydro-1,2-naphthalenediol (9) and pyrocatechol (10). The discovered reactions represent new and efficient synthetic approaches to produce difficult to obtain derivatives of 7. The mechanistic aspects of the reactions, and the potential involvement of superelectrophilic dicationic intermediates, are discussed.

ChemInform Abstract: Superacid‐Promoted Cyclodehydration Leading to the Imidazo[2,1‐a]isoquinoline Ring System.

AbstractA mechanism for the title reaction is proposed involving dicationic intermediates.

Superacid‐Promoted Cyclodehydration Leading to the Imidazo[2,1‐a]isoquinoline Ring System

AbstractA series of heterocycle‐substituted acetophenones were prepared and reacted with the Brønsted superacid CF3SO3H (triflic acid=trifluoromethanesulfonic acid). Cyclodehydration provided aryl‐substituted imidazo[2,1‐a]isoquinolines and related products (28–85%, seven examples). A mechanism is proposed involving dicationic intermediates.

ChemInform Abstract: Ring Closing and Opening Reactions Leading to Aza‐Polycyclic Aromatic Compounds.

AbstractThe title compounds are obtained by a superacid‐promoted ring‐closing/ring‐opening cascade proceeding via a series of dicationic intermediates.

Ring closing and opening reactions leading to aza-polycyclic aromatic compounds

A series of functionalized aza-polycyclic aromatic compounds were prepared by a superacid-promoted ring closing and opening reaction cascade. A reaction mechanism is proposed, which involves reactive dicationic intermediates. A key step in the conversions involves ipso protonation of an aryl group and elimination of an alkyl phenyl group.

Dications in superacid HF/SbF 5: When superelectrophilic activation makes possible fluorination and/or C–H bond activation

The reactivity of aliphatic amides/ketones/imines and nitriles was studied in superacid HF/SbF 5 in the presence of CCl 4. After the identification of the reaction intermediates by in situ NMR experiments, we propose that the sp 3C–H bond functionalization (fluorination) by the superacid system is strongly dependant on the superelectrophilic character of the distonic dicationic intermediates.

Substitution Effect on the Cylization/Fluorination Reaction ofN-Dienes in Superacid

The novel cyclization/fluorination reaction of N-dienes in superacid was extended to substituted substrates. The influence of the substitution on superelectrophilic character of dicationic intermediates was shown and its dramatic effect on the synthesis of fluoropiperidines was studied. On the basis of new dicationic alpha-chloronium ammonium intermediates, starting from halogen-substituted dienes, high-valued fluorinated piperidines were synthesized.

Cyclization Reactions of 1‐Amino‐5‐trifluoromethyl‐5‐thienyl‐1‐azapenta‐1,4‐dien‐3‐ones under Superelectrophilic Conditions: Synthesis of Novel Benzothiophenols, Cyclopentenols and Dihydrodiazepinols

AbstractTrifluoromethyl‐substituted 1‐amino‐5‐thienyl‐1‐aza‐1,4‐dien‐3‐ones 5, which are accessible in good yields from keto esters 1 in a three‐step procedure, undergo three different types of cyclization reactions upon treatment with a large excess of trifluoromethanesulfonic acid, depending on the substitution pattern. Thus, starting materials 5a–f without a halogen substituent at the 3‐position of the thienyl subunit undergo 1,6‐cyclization reactions (hydroxyannulation) to give benzothiophenol derivatives 6. In contrast, 5‐(3‐bromothienyl)‐substituted compounds 5g–j undergo Nazarov 1,5‐cyclization reactions to produce cyclopentenols 7a–d. Finally, 1‐dimethylamino‐substituted 1‐azadienones 5k,l undergo 1,7‐cyclization reactions to form novel dihydrodiazepinones 8a,b after tautomerization. On the basis of quantum chemical calculations we interpret these different types of multistep reactions to be cyclization reactions that proceed under superelectrophilic conditions through both mono‐ and dicationic intermediates. Electrophilic and pericyclic cyclization modes are discussed on the basis of the results of NICS calculations. Several of the compounds 6, 7 and 9 were characterized by X‐ray diffraction.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Superelectrophilic Intermediates in the Synthesis of Novel Indenole Derivatives via 1,5-Cyclization Reactions of 5-Aryl-1-azapenta-1,4-dien-3-ones

Oximes of 5,5-disubstituted 1-azapenta-1,4-dien-3-ones 3 underwent 1,5-cyclization reactions yielding indenole derivatives 4 in moderate to good yields upon treatment with an excess of tri­fluoromethanesulfonic acid. Similarly, the hydrazone 3g led to indenole 4f upon protonation. The reaction could also be successfully applied to the synthesis of benzo[b]cyclopenta[d]thiophene 5 starting from 3f. Products of a competing aza-Nazarov reaction were not observed. The reaction mechanism is explained by assuming the involvement of dicationic intermediates, generated by superelectrophilic solvation, similar to that of known Nazarov and aza-Nazarov-type transformations. Quantum chemical calculations of reaction energies and activation barriers are discussed with respect to the experimental results.

Preparation of Aza-Polycyclic Aromatic Compounds via Superelectrophilic Cyclizations

Alkenyl-substituted N-heterocycles react in superacidic CF3SO3H (triflic acid) to produce dicationic intermediates. These superelectrophiles undergo cyclizations to give varied aza-polycyclic aromatic compounds in generally good yields (27-99%, 16 examples). Theoretical calculations indicate a preference for charge-separated dicationic intermediates.

Superacidic and HUSY-zeolite activation of 1,3-indandione: reactions with benzene and cyclohexane

1,3-Indandione ( 1) readily condenses with benzene and undergoes selective ionic hydrogenation with cyclohexane when activated by superacids, such as CF 3SO 3H, AlCl 3 and AlBr 3 to give 3,3-diphenyl-1-indanone ( 4) and 1-indanone ( 7), respectively. Combination of these reactions in ‘one-pot’ yields 3-phenyl-1-indanone ( 5). In addition, similar reactions have been carried out using the regenerable solid acid, HUSY-zeolite, providing an effective excess of acidic sites. The mechanism of these reactions, with potential involvement of superelectrophilic dicationic intermediates, is discussed.

Superacidic Activation of Maleimide and Phthalimide and Their Reactions with Cyclohexane and Arenes

AbstractWhen activated in the CF3SO3H/SbF5 acid system maleimide (1) and phthalimide (2) undergo selective ionic hydrogenation with cyclohexane to give 1,5‐dihydropyrrol‐2‐one (3) and phthalimidine (11), respectively. When treated with aluminum halides, N‐phenylmaleimide (4) reacts with cyclohexane to give N‐phenylsuccinimide (5), whereas 2 still gives 11. Imide 1 also condenses with benzene in trifluoromethanesulfonic acid (CF3SO3H) to give 1,5‐dihydro‐5,5‐diphenylpyrrol‐2‐one (7) as the major product. However, in the presence of aluminum halides 1 reacts with benzene, toluene, and o‐dichlorobenzene to give 3‐arylsuccinimides 8–10, respectively. Imide 2 reacts with benzene under the influence of trifluoromethanesulfonic acid as well as aluminum halides to yield 3,3‐diphenylphthalimidine (12). The mechanism of these reactions, with potential involvement of superelectrophilic dicationic intermediates, is discussed. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

Superacid‐Catalyzed Reactions of Pyridinecarboxaldehydes.

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