HFIP as a versatile solvent in resorcin[n]arene synthesis.

Herein, we present 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) as an efficient solvent for synthesizing resorcin[n]arenes in the presence of catalytic amounts of HCl at ambient temperature and within minutes. Remarkably, resorcinols with electron-withdrawing groups and halogens, which are reported in the literature as the most challenging precursors in this cyclization, are tolerated. This method leads to a variety of 2-substituted resorcin[n]arenes in a single synthetic step with isolated yields up to 98%.

Decarboxylative Cyclization of Proline with o-Alkynylbenzaldehyde through an Unexploited 8π-Electrocyclization: A DFT Study.

We employed density functional theory (DFT) methods to investigate the most plausible mechanism of cyclization/ring expansion of proline with o-alkynylbenzaldehyde. This one-pot reaction starts with the in situ formation of azomethine ylide, which can undergo three different reaction pathways to form the final product. Two mechanisms are based on nucleophilic addition and 4π-electrocyclization of the azomethine ylide, and our results indicate that the rate-determining step (RDS) of these two cyclizations are 40.1 and 40.2 kcal/mol, respectively. The third novel pathway relies upon 8π-electrocyclization as the key step of this reaction; interestingly, the RDS of this cyclization is ∼20.6 kcal/mol, which shows this route to be most feasible. Thus, we introduce a novel mechanism for the electrocyclization reaction of conjugated azomethine ylides that can help chemists to design and access a new series of compounds.

Synthesis of Spiro[chromene-imidazo[1,2-a]pyridin]-3'-imines via 6-exo-dig Cyclization Reaction.

A transition-metal-free postmodification of the Groebke-Blackburn-Bienaymé (GBB) reaction for the synthesis of spiro[chromene-imidazo[1,2-a]pyridin]-3'-imine was discovered. The unusual transformation represents the first example of activation and the reaction of the imidazole carbon atom. In this postcondensational modification, KOt-Bu acts as a base, which, after the isomerization of an alkyne moiety to allene, causes the next unique nucleophilic reaction of the imidazole carbon atom that results in spirocyclic structures. The proposed reaction mechanism was confirmed based on the DFT calculations.

Domino Decarboxylative Arylation and C-O Selective Bond Formation toward Chromeno[2,3-b]pyridine-2-one Skeletons.

Practical Pd-catalyzed 2-pyridones were designed to achieve chromeno[2,3-b]pyridine-2-ones. The reaction proceeds through domino nucleophilic addition and decarboxylative arylation, respectively. This methodology offers a moderately efficient approach to construct the bioactive, fused-heterocyclic skeletons via selective C-O bond formation and decarboxylative arylation in a single step with high selectivity and good yields.

Transition-metal-free oxidative cyclization reaction of enynals to access pyrane-2-one derivatives.

A novel and efficient metal-free C-H functionalization of enynals is developed to synthesize α-pyrone derivatives via the formation of two C-O bonds. In this project, K2S2O8 has been introduced as an efficient oxygen source and C-H functionalization agent in regioselective oxidative cyclization reaction with a relatively broad substrate scope.

Organocatalytic synthesis of enantiopure spiro acenaphthyl-pyrrolizidine/pyrrolidines: justifying the regioselectivity based on a distortion/interaction model.

An efficient organocatalytic [3 + 2] reaction with Schreiner's thiourea organocatalyst for the synthesis of a small library of novel enantiopure stable spiroacenaphthyl-pyrrolidines/pyrrolizidines with high regio- and diastereoselectivity (up to 99%) is described for the first time. These chiral compounds were synthesized by a three-component 1,3-dipolar cycloaddition of (E)-1-(2-oxoacenaphthylen-1(2H)-ylidene) pyrrolidin-1-ium-2-ide as a dipolar and (S)-cinnamoyl/crotonoyl oxazolidinone as a dipolarophile. The absolute configuration of cycloadducts was confirmed by X-ray diffraction analysis. The origin of catalyst reactivity and regio- and stereoselectivity was investigated through DFT calculations. DFT calculations showed that the regioselectivity was controlled by the distortion (deformation) of reactants and Schreiner's thiourea acts as a LUMO-lowering catalyst.

Catalytic formal [4 + 1] isocyanide-based cycloaddition: an efficient strategy for the synthesis of 1H-cyclopenta[b]quinolin-1-one derivatives.

An unprecedented catalytic isocyanide-based cycloaddition of alkyl and aryl isocyanides with (Z)-2-(2-hydroxy-2-alkylvinyl)quinoline-3-carbaldehydes was developed for the direct and efficient synthesis of 1H-cyclopenta[b]quinolin-1-one derivatives. On the basis of DFT calculations, a mechanism is proposed involving formal [4 + 1] cycloaddition of isocyanides, followed by imine-enamine tautomerization and air oxidation.

Regio- and chemo-selective cyclization of allenic-Ugi products for the synthesis of 3-pyrroline skeletons.

A highly efficient and stable novel class of allenic-Ugi products through a Crabbé homologation reaction is successfully demonstrated. Then, a regio- and chemo-selective cyclization of allenic-Ugi derivatives in a 5-exo-dig fashion to access 3-pyrroline skeletons is developed. Also, computational studies were performed and explained to provide insights into the reaction mechanism. This approach displays high bond-forming efficiency and atom economy with high yields.

Metal- and solvent-free domino reaction of 2-isocyanophenol esters to benzoxazines: long-range 1,5-acyl migration on 1,4-diazabutatriene.

The first example of intramolecular nucleophilic addition of 1,4-diazabutatriene to ester is disclosed. This approach provides a facile and versatile synthesis for functionalized 2H-1,4-benzoxazines under metal-, reagent-, and solvent-free conditions. Experimental and computational studies revealed the pivotal role of 1,5-acyl migration as the self-catalytic step in the reaction selectivity.

Migratory cycloisomerization of 1,3-dien-5-ynes conjugated with pseudopeptides in assembly of benzo[7]annulenes.

A novel domino cycloisomerization of 1,3-dien-5-ynes for the synthesis of 7H-benzo[7]annulenes is reported. The noticeable feature of this domino reaction involves the assembly of the fused bicyclic motifs through a transamidation/5-exo-trig cyclization/8π-electrocyclization sequence in a single step. Finally, mechanistic investigations were conducted experimentally and supported by DFT calculations.

Asymmetric hydroalkylation of alkynes and allenes with imidazolidinone derivatives: α-alkenylation of α-amino acids.

This work reports a new method for the synthesis of quaternary α-alkenyl substituted amino acids by the enantio- and diastereoselective addition of imidazolidinone derivatives to alkynes and allenes. Further hydrolysis of the imidazolidinone products under acidic conditions afforded biologically relevant amino acid derivatives. This method is geometry-selective (E-isomer), enantio- and diastereoselective, and products were obtained in good to excellent yields. The utility of this new methodology is proved by its operational simplicity and the successful accomplishment of gram-scale reactions. Experimental and computational studies suggest the key role of Li in terms of selectivity and support the proposed reaction mechanism.

Metal-Free Domino Oligocyclization Reactions of Enynals and Enynones with Molecular Oxygen.

A novel metal-free direct addition of molecular oxygen to the C-C triple bond toward benzannulated oxygen-bridged seven-membered ring systems and aza[3.1.0]bicycle skeletons under 3O2 atmosphere has been described. The reaction proceeds through at least three intramolecular C-O and C-C bond forming steps via green, simple, and unprecedented domino radical processes with high selectivity and good yields.

Copper-Catalyzed Cycloisomerization of Unactivated Allene-Tethered O-Propargyl Oximes: A Domino Reaction Sequence toward the Synthesis of Hexahydropyrrolo[3,4-b]azepin-5(4H)-ones.

A novel copper-catalyzed cycloisomerization of unactivated allene-tethered O-propargyl oximes has been developed for the synthesis of hexahydropyrrolo[3,4-b]azepin-5(4H)-ones. This one-pot domino reaction proceeds via a [2,3]-sigmatropic rearrangement, a [3 + 2] cycloaddition, and another [3,3]-sigmatropic rearrangement. The methodology offers a practical and straightforward route for the rapid assembly of both ring components of the fused bicyclic motifs from acyclic precursors by simultaneously forming four new bonds (a C═O, a C═N, and two C-C bonds) in a single step.

Synthesis of N-(Isoquinolin-1-yl)sulfonamides via Ag2O-Catalyzed Tandem Reaction of ortho-Alkynylbenzaldoximes with Benchtop Stabilized Ketenimines.

In this project, a moderately efficient approach to multisubstituted N-(isoquinolin-1-yl)sulfonamide derivatives was illustrated, utilizing ortho-alkynylbenzaldoximes and zwitterionic ketenimine salts in a tandem reaction catalyzed by silver oxide. The oxophilicity of Ag2O, along with its nature as Lewis acid, pave the way for a smooth [3 + 2] cycloaddition between isoquinoline N-oxides and ketenimine species, which is a key step in this reaction. DFT calculation suggests that 1,3-dipolar cycloaddition of nitrone and ketenimine proceeds through a selective stepwise mechanism.

An Aminopyridinium Ionic Liquid: A Simple and Effective Bifunctional Organocatalyst for Carbonate Synthesis from Carbon Dioxide and Epoxides.

An aminopyridinium ionic liquid is presented as a green, tunable, and active metal-free one-component catalytic system for the atom-efficient transformation of oxiranes and CO2 to cyclic carbonates. Inclusion of a positively charged moiety into aminopyridines, through a simple single-step synthesis, provides a one-component ionic liquid catalytic system with superior activity; effective in ring opening of epoxide, CO2 inclusion, and stabilization of oxoanionic intermediates. An efficiency assessment of a variety of positively charged aminopyridines was pursued, and the impact of temperature, catalyst loading, and the kind of nucleophile on the catalytic performance was also investigated. Under solvent-free conditions, this bifunctional organocatalytic system was used for the preparation of 18 examples of cyclic carbonates from a broad range of alkyl- and aryl-substituted oxiranes and CO2 , where up to 98 % yield and high selectivity were achieved. DFT calculations validated a mechanism in which nucleophilic ring-opening and CO2 inclusion occur simultaneously towards cyclic carbonate formation.

An Electrostatically Enhanced Phenol as a Simple and Efficient Bifunctional Organocatalyst for Carbon Dioxide Fixation.

An electrostatically enhanced phenol as a simple and competent bifunctional organocatalyst for the atom-economical conversion of epoxides to cyclic carbonates under environmentally benign conditions is described. Incorporating a positively charged center into phenols through a modular one-step synthesis results in a bifunctional system with enhanced acidity and reactivity, capable of epoxide activation, a halide nucleophilic ring-opening process, and CO2 incorporation in a synergistic fashion. A rational survey of the efficiency of different positively charged phenols and the influence of different parameters, such as temperature, catalyst loading, and the nature of the nucleophile, on catalytic activity was conducted. In addition, the time-dependent conversion of epoxide into the corresponding cyclic carbonate was further explored by FTIR-ATR and 1 H NMR spectroscopy. This bifunctional catalytic platform is among one of the mildest and most efficient metal-free systems that is capable of converting a variety of epoxides into cyclic carbonates under virtually ambient conditions. The 1 H NMR titration experiment validated the bifunctional catalytic mechanism wherein both the epoxide activation and the nucleophilic ring-opening process occur in concert en route to carbon dioxide fixation.