Intramolecular Nucleophilic Cyclization Research Articles

Vilsmeier Reaction of Enaminones: Efficient Synthesis of Halogenated Pyridin-2(1H)-ones

A facile and efficient one-pot synthesis of halogenated pyridin-2(1H)-ones from a series of readily available enaminones under Vilsmeier conditions is described, and a mechanism involving sequential halogenation, formylation, and intramolecular nucleophilic cyclization is proposed.

Synthesis of Cp−Re Complexes via Olefinic C−H Activation and Successive Formation of Cyclopentadienes

Treatment of an alpha,beta-unsaturated ketimine with an alpha,beta-unsaturated carbonyl compound in the presence of a rhenium complex, Re2(CO)10, gave a cyclopentadienyl-rhenium complex. This reaction proceeds via rhenium-catalyzed C-H bond activation of an olefinic C-H bond, insertion of an alpha,beta-unsaturated carbonyl compound into a Re-C bond of the alkenylrhenium intermediate, intramolecular nucleophilic cyclization, reductive elimination, elimination of aniline to give a cyclopentadiene derivative, followed by the formation of a cyclopentadienyl-rhenium complex from the cyclopentadiene derivative and the rhenium complex.

Vilsmeier−Haack Reaction of 1-Cyclopropyl-2-arylethanones

A convenient and efficient method to synthesize 3-(2-chloroethyl)-5-aryl-4H-pyran-4-ones 2 and 2-chloro-3-(2-chloroethyl)-1-naphthaldehydes 3 in moderate to good yields was developed via the Vilsmeier-Haack reaction of readily available 1-cyclopropyl-2-arylethanones 1 at different temperature. This reaction proceeds via sequential enolization, ring opening, haloformylation, and intramolecular nucleophilic cyclization or Friedel-Crafts alkylation reactions to produce 2 or 3.

Rhenium-catalyzed synthesis of indene derivatives via C-H bond activation

Abstract Rhenium complex, [ReBr(CO)3(thf)]2-catalyzed reactions between aromatic imines and either acetylenes or α,β-unsaturated carbonyl compounds gave indene derivatives in good to excellent yields. These reactions proceed via C-H bond activation, insertion of acetylenes or α,β-unsaturated carbonyl compounds, intramolecular nucleophilic cyclization, and reductive elimination. Indene derivatives were also obtained from aromatic ketones and α,β-unsaturated carbonyl compounds in the presence of catalytic amounts of the rhenium complex and p-anisidine. Sequential ruthenium-catalyzed hydroamination of aromatic acetylenes with anilines, and rhenium-catalyzed reactions of the formed aromatic ketimines with α,β-unsaturated carbonyl compounds also provided indene derivatives.

A Facile and Efficient Synthesis of Polyfunctionalized Pyridin-2(1H)-ones from β-Oxo Amides under Vilsmeier Conditions

A facile and efficient one-pot synthesis of polysubstituted pyridin-2(1H)-ones from a variety of beta-oxo amides under Vilsmeier conditions is described, and a mechanism involving sequential halogenation, formylation and intramolecular nucleophilic cyclization is proposed.

Vilsmeier−Haack Reactions of 2-Arylamino-3-acetyl-5,6-dihydro-4H-pyrans toward the Synthesis of Highly Substituted Pyridin-2(1H)-ones

A facile and efficient one-pot synthesis of highly substituted pyridin-2(1H)-ones was developed via Vilsmeier-Haack reactions of readily available enaminones, 2-arylamino-3-acetyl-5,6-dihydro-4H-pyrans, and a mechanism involving sequential ring-opening, haloformylation, and intramolecular nucleophilic cyclization reactions is proposed.

Efficient One‐Pot Synthesis of Highly Substituted Pyridin‐2(1H)‐ones via the Vilsmeier—Haack Reaction of 1‐Acetyl,1‐carbamoyl Cyclopropanes.

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Synthesis and Unusual Reactivity of N-Tosyl-4,5-benzoazacyclodeca-2,6-diyne, Yneamino-Containing Enediyne

Substitution of the propargylic carbon for nitrogen in cyclic 10-membered ring enediynes results in at least 2 orders of magnitude enhancement of reactivity. The mechanism of cycloaromatization of aza-enediynes, however, switches from radical (Bergman) to polar, which proceeds by initial protonation of a reactive yneamine moiety. Ketenimmonium cation produced on this step undergoes intramolecular nucleophilic cyclization. Reaction is strongly catalyzed by acids and exhibits substantial kinetic isotope effect.

Rhenium-catalyzed synthesis of naphthalene derivatives via insertion of aldehydes into a C–H bond

A rhenium complex, [ReBr(CO) 3(THF)] 2, catalyzed reactions of aromatic ketimines and aldehydes with dienophiles, followed by dehydration, to give naphthalene derivatives in good to excellent yields. This reaction proceeds via C–H bond activation, insertion of an aldehyde, intramolecular nucleophilic cyclization, reductive elimination, elimination of aniline and Diels–Alder reaction. After dehydration, naphthalene derivatives were formed.

Efficient One-Pot Synthesis of Highly Substituted Pyridin-2(1H)-ones via the Vilsmeier−Haack Reaction of 1-Acetyl,1-Carbamoyl Cyclopropanes

A facile and efficient one-pot synthesis of highly substituted pyridin-2(1H)-ones is developed via the Vilsmeier-Haack reaction of readily available 1-acetyl,1-carbamoyl cyclopropanes, and a mechanism involving sequential ring-opening, haloformylation, and intramolecular nucleophilic cyclization reactions is proposed.

Reactions of perfluoro(2-methylpent-2-ene) and perfluoro(5-azanon-4-ene) with primary amines containing a 2,6-di-tert-butylphenol fragment

Reactions of perfluoro(2-methylpent-2-ene) and perfluoro(5-azanon-4-ene) with 4-(2-aminoethyl)-2,6-di-tert-butylphenol and 4-(3-aminopropyl)-2,6-di-tert-butylphenol in acetonitrile in the presence of triethylamine gave the corresponding azetidine, 1,2-dihydroazete, and 1,2-dihydro-1,3-diazete derivatives, respectively. The reaction mechanisms, role of triethylamine, and factors affecting the intramolecular nucleophilic cyclization process are discussed.

5,6,7,8-Tetrafluoro-3λ4δ2,1,2,4-benzothiaselenadiazine, 5,6,7,8-Tetrafluoro-1,3λ4δ2,2,4-benzodithiadiazine, and Their Hydrocarbon Analogues: Molecular and Crystal Structures

5,6,7,8-Tetrafluoro-3lambda4delta2,1,2,4-benzothiaselenadiazine (1) is prepared by the intramolecular nucleophilic cyclization of C6F5SeN=S=NSiMe3 (2) mediated by CsF. According to an X-ray diffraction analysis, the heterocycle of 1 is bent along the Se(1)...N4 line by 6.0(2) degrees in the crystal. Despite the obvious similarities between 1 and its 1,3-dithia analogue (7) with respect to molecular composition and shape, the crystal packing of 1 is substantially different from that of 7. An interesting consequence of this is the inclusion of atmospheric N2 in the crystal lattice of the selenium derivative 1. The molecular structure and bonding of 1 have been investigated using quantum-chemical calculations at the DFT/B3LYP/6-311+G level of theory, and the results have been compared to those of 5,6,7,8-tetrafluoro-1,3lambda4delta2,2,4-benzodithiadiazine (7) and their hydrocarbon analogues (5 and 8).

Rhenium‐Catalyzed Formation of Indene Frameworks via C—H Bond Activation: [3 + 2] Annulation of Aromatic Aldimines and Acetylenes.

A rhenium complex, [ReBr(CO)3(thf)]2, catalyzes the reaction of an aromatic aldimine with an acetylene to give an indene derivative in a quantitative yield. The reaction proceeds via C-H bond activation, insertion of the acetylene, intramolecular nucleophilic cyclization, and reductive elimination. In contrast to ruthenium and rhodium catalysts, which are usually employed in this type of reaction, the rhenium catalyst promotes the intramolecular nucleophilic cyclization of the alkenylmetal species generated by insertion of the acetylene.

Insertion of Polar and Nonpolar Unsaturated Molecules into Carbon−Rhenium Bonds Generated by C−H Bond Activation: Synthesis of Phthalimidine and Indene Derivatives

A rhenium complex, [ReBr(CO)(3)(thf)](2), catalyzes the reaction of an aromatic aldimine with an isocyanate and an acetylene to give a phthalimidine and an indene derivative in a quantitative yield, respectively. The reactions proceed via C-H bond activation, insertion of the isocyanate or the acetylene, intramolecular nucleophilic cyclization to the aldimine of the generated amido- or alkenyl-rhenium species, and reductive elimination. In contrast to ruthenium and rhodium catalysts, which are usually employed in this type of reaction, the rhenium catalyst promotes the insertion of a polar unsaturated molecule. This occurs more easily than the insertion of a nonpolar unsaturated molecule.

Vinyl Ethers Containing an Epoxy Group: XXII. Synthesis and Base-Catalyzed Transformations of 1-(Allyloxy)- and 1-[2-(Vinyloxy)ethoxy]-3-(2-propynyloxy)propan-2-ols

Reactions of 2-(allyloxymethyl)- and 2-[2-(vinyloxy)ethoxy]methyloxiranes with 2-propynol (∼3 wt % of t-BuOK, 75–85°C, 5–10 h) lead to formation of new 1-organyloxy-3-(2-propynyloxy)propan-2-ols (yield 65–95%). On heating to 45–100°C in the presence of bases (KOH, t-BuOK), 1-allyloxy- and 1-[2-(vinyloxy)ethoxy]-3-(2-propynyloxy)propan-2-ols are transformed into the corresponding 2-vinyl-1,3-dioxolane, 6-methyl-2,3-dihydro-1,4-dioxine, 6-methylene-1,4-dioxane, and 2,3-dihydro-5H-1,4-dioxepine derivatives, whose yield and ratio strongly depend on the solvent nature, catalyst, and substituent at the hydroxy group. 2-Vinyl-1,3-dioxolane and 6-methyl-2,3-dihydro-1,4-dioxine derivatives are formed as the major products (yield 70–99%) in the presence of t-BuOK in aprotic media (toluene, THF, DMSO) or in the absence of a solvent as a result of prototropic isomerization followed by intramolecular heterocyclization. Intramolecular nucleophilic cyclization of 3-(2-propynyloxy)propan-2-ols to 6-methylene-1,4-dioxane is the predominant process in water in the presence of KOH. In all cases, the fraction of 2,3-dihydro-5H-1,4-dioxepine derivatives among the cyclization products ranges from 0 to 5% (KOH) or to 14% (t-BuOK).

Rhenium-Catalyzed Formation of Indene Frameworks via C−H Bond Activation: [3+2] Annulation of Aromatic Aldimines and Acetylenes

A rhenium complex, [ReBr(CO)3(thf)]2, catalyzes the reaction of an aromatic aldimine with an acetylene to give an indene derivative in a quantitative yield. The reaction proceeds via C-H bond activation, insertion of the acetylene, intramolecular nucleophilic cyclization, and reductive elimination. In contrast to ruthenium and rhodium catalysts, which are usually employed in this type of reaction, the rhenium catalyst promotes the intramolecular nucleophilic cyclization of the alkenylmetal species generated by insertion of the acetylene.

Dynamic Resolution of α‐Bromo Tertiary Amides for Stereoselective Preparation of Dipeptide Analogues.

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Dynamic Resolution of α-Bromo Tertiary Amides for Stereoselective Preparation of Dipeptide Analogues

Dynamic resolution of -bromo tertiary acetamides in asymmetric nucleophilic substitution reaction is described. Intermolecular substitution of -bromo tertiary acetamides with dibenzylamine in the presence of TBAI and gave the dipeptide analogues 7-10 with high stereoselectivities up to 90 : 10 dr. Also, cyclic dipeptide analogues 20-29 were produced by the intramolecular nucleophilic cyclization of -bromo tertiary acetamides with low stereoselectivities in 84-42% yields.

Stereocontrolled total synthesis of (+)-vincristine.

An efficient total synthesis of (+)-vincristine has been accomplished through a stereoselective coupling of demethylvindoline and the eleven-membered carbomethoxyverbanamine presursor. Demethylvindoline was prepared by oxidation of 17-hydroxy-11-methoxytabersonine, followed by regioselective acetylation with mixed anhydride method. Although an initial attempt of coupling by using demethylvindoline formamide was not successful and resulted in recovery of the starting compounds, the reaction using demethylvindoline took place smoothly to furnish the desired bisindole product with the correct stereochemistry at C18'. After formation of the piperidine ring by sequential removal of the protective groups and intramolecular nucleophilic cyclization, the total synthesis of vincristine was completed by formylation of N1.

Gas‐Phase Thermolysis of Benzotriazole Derivatives. Part 2. Synthesis of Benzimidazo[1,2‐b]cinnolines, a Novel Heterocyclic Ring System, by Pyrolysis of Benzotriazole Derivatives. Kinetic and Mechanistic Study.

Abstract Gas-phase pyrolysis of benzotriazolyl ketones and their arylhydrazones gave indole, benzimidazole and benzimidazo[1,2-b]cinnoline derivatives via interesting novel routes. The homogeneous first-order gas-phase pyrolysis of 10 arylhydrazono derivatives of α-benzotriazol-1-yl ketones was investigated over the temperature range 420–530 K. Five of these substrates were 2-(arylhydrazono)-2-(benzotriazol-1-yl)-1-phenylethanone derivatives (Series 1), and the remaining five were the corresponding acetone analogues (Series 2). The values of the Arrhenius frequency factor (log A/s−1) for the pyrolysis of the compounds of Series 1 and 2 were, respectively, 12.27±1.44 and 9.07±1.20, while the values of the Arrhenius activation energy (Ea/kJ mol−1) were 132.8±8.4 and 123.2±23.0, respectively. Besides, reaction pathways are offered to rationalize the kinetic results and to account for the products of pyrolysis of the substrates under study, namely: (i) extrusion of N2 and formation of a 1,3-biradical reactive intermediate leading to substituted imidazoles (Series 1); (ii) intramolecular nucleophilic addition, cyclization and subsequent fragmentation with or without loss of H2O/N2 fragments (Series 1 and 2).