Microwave-Assisted Selective Nucleopalladation-Triggered Cascade Process: Synthesis of Highly Functionalized 3-Chloro-1H-indenes.

A nucleopalladation-triggered cascade transformation of internal alkynes bearing an amino nucleophile and an electrophilic enone was investigated under unconventional microwave-assisted conditions. Among the three possible pathways, the chloropalladation-triggered domino process proceeded selectively to furnish 3-chloro-1H-indenes in good to excellent yields. The reactions under microwave irradiation were completed in 30 min, and the conventional heating required 3-5 h for completion. The yields obtained under nonclassical heating using microwave irradiation are marginally higher (71-97%) than those of the conventional heating conditions (67-96%). The mechanism of this domino process involves chloropalladation of alkynes to deliver σ-vinylpalladium intermediates, intramolecular carbopalladation via Heck-type olefin insertion, and protodepalladation steps. The other two competitive intramolecular aminopalladation-initiated cascades via 7-endo-dig or 6-exo-dig cyclizations leading to oxazepine or benzoxazine scaffolds were not observed.

Revealing the Role of Solvent in anti-Oxypalladation-Triggered Regiocontrolled Domino Reactions for the Synthesis of Benzazepine- and Tetrahydroquinoline-Containing Scaffolds: A Combined Computational and Experimental Study.

Palladium-catalyzed regiocontrolled intramolecular oxypalladation-initiated cascades of multifunctional internal alkyne bearing an N-tosyl tether deliver functionalized benzazepine as an exclusive product via 6-endo-dig pathway in 1,4-dioxane solvent and tetrahydroquinoline scaffold as a major product via the 5-exo-dig pathway in the DMSO solvent. The role of the solvent in controlling the regioselectivity is still unknown which can be a major hurdle for further reaction development. Moreover, the reaction in DMSO suffered from having a mixture of products, and no exclusive formation of tetrahydroquinoline was achieved. Herein, we report a concerted computational and experimental study, revealing the role of the solvent in controlling the reaction outcome. DFT study revealed that the formation of the σ-vinylpalladium intermediate is reversible for the 5-exo-dig pathway while it is irreversible for the 6-endo-dig mechanism in 1,4-dioxane and consequently, the 5-exo-dig pathway is difficult to proceed. In contrast, both the 5-exo-dig and 6-endo-dig pathways are irreversible in DMSO. We predicted an exclusive formation of isobenzofuranone-fused chromane via the 5-exo-dig pathway when the N-tosyl tether is replaced by the O-tether in the internal alkyne in DMSO. The experimental study confirms the theoretical hypothesis and provides a highly chemo-divergent approach for the synthesis of biologically significant chromane with a large substrate scope and up to 95% yield at room temperature.

Electronically Robust Self-Assembled Supramolecular Gel as a Potential Material in Triboelectric Nanogenerators.

A series of self-assembling gluconamide conjugated naphthalimide amphiphiles (GCNA) was synthesized and the self-assembly of GCNA into gel rendered an increased electron density in naphthalimide moiety with an overall change in energy of 15.33×10-32  J via J-type aggregation. SEM analysis and X-ray diffraction underpinning the nanofibrillar formation, and rheological measurements confirmed the processablity and material fabrication. The enriched electron density in the aggregated GCNA4 via cooperative intermolecular non-covalent interactions makes it as effective electron donor in the fabrication of triboelectric nanogenerators (TENG). The TENG based on GCNA4-polydimethylsiloxane (PDMS) triboelectric pair generated an output voltage, current and power density of ∼250 V, 40 µA and ∼622 mW/m2 respectively, which is almost 2.4 times better in performance than the amorphous GCNA4 based TENG. The fabricated TENG can power-up 240 LEDs, wrist watch, thermometer, calculator and hygrometer.

Diversity-Oriented Synthesis of Benzo[f][1,4]oxazepine-, 2H-Chromene-, and 1,2-Dihydroquinoline-Fused Polycyclic Nitrogen Heterocycles under Microwave-Assisted Conditions.

An efficient, diversity-oriented synthesis of oxazepino[5,4-b]quinazolin-9-ones, 6H-chromeno[4,3-b]quinolines, and dibenzo[b,h][1,6]naphthyridines was established involving a substrate-based approach under microwave-assisted and conventional heating conditions in high yields (up to 88%). The CuBr2-catalyzed, chemoselective cascade annulation of O-propargylated 2-hydroxybenzaldehydes and 2-aminobenzamides delivered oxazepino[5,4-b]quinazolin-9-ones involving a 6-exo-trig cyclization-air oxidation-1,3-proton shift-7-exo-dig cyclization sequence. This one-pot process showed excellent atom economy (-H2O) and constructed two new heterocyclic rings (six- and seven-membered) and three new C-N bonds in a single synthetic operation. On the other side of diversification, the reaction between O/N-propargylated 2-hydroxy/aminobenzaldehydes and 2-aminobenzyl alcohols delivered 6H-chromeno[4,3-b]quinolines and dibenzo[b,h][1,6]naphthyridines involving sequential imine formation-[4 + 2] hetero-Diels-Alder reaction-aromatization steps. The influence of microwave assistance was superior to conventional heating, where the reactions were clean, rapid, and completed in 15 min, and the conventional heating required a longer reaction time at a relatively elevated temperature.

Rapid Assembly of Functionalized 2H-Chromenes and 1,2-Dihydroquinolines via Microwave-Assisted Secondary Amine-Catalyzed Cascade Annulation of 2-O/N-Propargylarylaldehydes with 2,6-Dialkylphenols.

An efficient, secondary amine-catalyzed cascade annulation of 2-O/N-propargylarylaldehydes with 2,6-dialkylphenols was established to access biologically relevant functionalized 2H-chromenes and 1,2-dihydroquinolines tethered with a synthetically useful p-quinone methide scaffold in high yields under microwave irradiation and conventional heating conditions. The microwave-assisted strategy was convenient, clean, rapid, and high yielding in which the reactions were completed in just 15 min, and the yields obtained were up to 95%. This highly atom-economical domino process constructed two new C-C double bonds and a six-membered O/N-heterocyclic ring in a single synthetic operation. Its mechanism process was rationalized as involving sequential iminium ion formation, nucleophilic addition, and intramolecular annulation steps. Furthermore, the synthesized 2H-chromene derivatives were transformed into valuable indeno[2,1-c]chromenes, 5H-indeno[2,1-c]quinolines, and oxireno[2,3-c]chromene via a palladium-catalyzed double C-H bond activation process and epoxidation, respectively.

A microwave-assisted intramolecular aminopalladation-triggered domino sequence: an atom economical route to 5,10-dihydroindeno[1,2-b]indoles.

A microwave-assisted, palladium(II)-catalyzed cascade reaction of 2-alkynylanilines tethered with an α,ß-unsaturated carbonyl moiety was established to access 5,10-dihydroindeno[1,2-b]indoles in high yields (up to 84%) in a short reaction time. This operationally simple cascade process shows 100% atom economy and allows the construction of two new five-membered rings and two new (1 C-C and 1 C-N) bonds in a single synthetic attempt. The mechanistic pathway of this reaction is visualized involving intramolecular aminopalladation (5-endo-dig) followed by carbopalladation (olefin insertion) and protonolysis steps. A systematic comparison between microwave irradiation and conventional heating methods was also performed to demonstrate the supremacy of the microwave-assisted approach. This domino reaction requires no protecting groups for the amino group and the palladium catalyst needs no ligands. To the best of our knowledge, this is the first report on microwave-assisted nucleopalladation-initiated cascade transformation.

Microwave-Assisted Copper(II)-Catalyzed Cascade Cyclization of 2-Propargylamino/Oxy-Arylaldehydes and O-Phenylenediamines: Access to Densely Functionalized Benzo[f]Imidazo[1,2-d][1,4]Oxazepines and Benzo[f]Imidazo[1,2-d][1,4]Diazepines.

A highly efficient microwave-assisted copper(II)-catalyzed cyclization cascade was established starting from readily accessible O/N-propargylated 2-hydroxy or 2-aminobenzaldehydes and o-phenylenediamines to synthesize densely functionalized imidazo[1,2-d][1,4]oxazepines and imidazo[1,2-d][1,4]diazepines in high yields (up to 93%). This one-pot two-step process was found to be highly atom economical (-H2O, -H2) and operationally simple and enabled the generation of two new heterocycle rings (seven- and five-membered) and three new C-N bonds in a single synthetic operation. These reactions well tolerated a variety of substituents including electron-donating and electron-withdrawing groups and furnished the desired fused heterocycles in high yields under microwave irradiation in a very short reaction time. The mechanism of the established protocol involves sequential imine formation-intramolecular cyclization-air oxidation followed by 7-exo-dig cyclization steps. A comparative study between the microwave-assisted approach and conventional heating was also performed to demonstrate the advantages of the microwave-assisted protocol in terms of high yield and shorter reaction time.

Microwave-assisted one-pot two-step imine formation-hetero-Diels-Alder-detosylation/aromatization sequence: direct access to dibenzo[b,h][1,6]naphthyridines.

A microwave-assisted, copper-catalyzed, one-pot, two-step reaction is established to access functionalized [1,6]naphthyridines in high yields (up to 96%) starting from 2-(N-propargylamino)benzaldehydes and arylamines. This rapid and operationally simple sequential reaction allowed the construction of two new heterocyclic rings and three new (2 C-C and 1 C-N) bonds in a single synthetic operation. This reaction tolerated various electron-donating and electron-withdrawing substituents well and delivered the desired products in a shorter reaction time under microwave irradiation. This reaction proceeds through a sequential imine formation, intramolecular [4 + 2] hetero-Diels-Alder reaction, and air oxidation, followed by detosylation-aromatization steps.

Progress in the Chemistry of Tetrahydroquinolines.

Tetrahydroquinoline is one of the most important simple nitrogen heterocycles, being widespread in nature and present in a broad variety of pharmacologically active compounds. This Review summarizes the progress achieved in the chemistry of tetrahydroquinolines, with emphasis on their synthesis, during the period from mid-2010 to early 2018.

Direct Access to Bridged Tetrahydroquinolines and Chromanes via an InCl3-Catalyzed Sequential Three-Component Cascade.

A sequential three-component cascade process was developed for the synthesis of bridged tetrahydroquinolines and chromanes bearing 2,6-methanobenzo[d][1,3]diazocine and 2,6-methanobenzo[g][1,3]oxazocine scaffolds, respectively, in good yields from readily available materials. The InCl3-catalyzed reaction progressed via enamine formation, Michael addition, intramolecular cyclization, and intramolecular iminium ion cyclization steps. Notably, this high atom economic approach (-2H2O) allowed the generation of four new bonds (1 C-C and 3 C-N or 1 C-C, 1 C-O and 2 C-N) and two heterocyclic rings in a single operation.

Regioselective synthesis of tetrahydroquinolines via syn- and anti-nucleopalladation-initiated cascade processes.

Palladium(ii)-catalyzed regioselective syn-chloropalladation and anti-acetoxypalladation-initiated cascade processes were developed for the synthesis of functionalized tetrahydroquinolines. A series of N-propargyl arylamines tethered with an α,ß-unsaturated carbonyl scaffold underwent atom economical cascade reactions to deliver chloro- and acetoxy-substituted tetrahydroquinolines bearing an exocyclic double bond in high yields. A mechanism is proposed for these cascade processes involving a sequential syn-chloropalladation or anti-acetoxypalladation of alkynes followed by intramolecular olefin insertion (6-exo-trig) and protonolysis steps. The reaction was completely regioselective and the terminal aryl/alkyl group of the propargyl moiety dictated the regiochemistry of the initial nucleopalladation. The role of the bidentate nitrogen ligand is crucial to trigger the acetoxypalladation-initiated cascade sequence in contrast to the chloropalladation-initiated process.

Diastereoselective ABB' Three-Component Synthesis of Highly Functionalized Spirooxindoles Bearing Five Consecutive Asymmetric Carbons.

The synthesis of spirooxindoles bearing tetrahydro-4 H-cyclopenta[ b]furan framework was established starting from isatin-derived aldehydes and 2 equiv of 1,3-dicarbonyl compounds involving a piperidine-catalyzed ABB' three-component domino process. This reaction was highly diastereoselective affording a single diastereomer of spirooxindoles with five consecutive asymmetric carbons including spiro and tetrasubstituted carbon centers. In addition, this waste-free (-2H2O) reaction showed high atom economy and step economy by creating four new bonds, including three C-C bonds and one C-O bond, and two rings (one carbo- and one heterocyclic) in a single operation. The mechanism of this three-component domino process involved sequential Knoevenagel condensation-Michael addition-intramolecular oxa-Michael addition-intramolecular aldol reactions.

Heterogeneous Amberlyst-15-catalyzed synthesis of complex hybrid heterocycles containing [1,6]-naphthyridine under metal-free green conditions.

An efficient green protocol for the synthesis of complex hybrid heterocycles containing [1,6]-naphthyridine and coumarin/pyrazole moieties was established, involving an intramolecular [4 + 2] hetero Diels-Alder reaction as the key step. The biologically significant 12,13-dihydro-6H-benzo[h]chromeno[3,4-b][1,6]naphthyridin-6-ones and 6,10-dihydro-5H-benzo[h]pyrazolo[3,4-b][1,6]naphthyridines were synthesized starting from 2-(N-propargylamino)-arylaldehydes and 3-aminocoumarins or 3-methyl-1-aryl-1H-pyrazol-5-amines in the presence of an Amberlyst-15 catalyst in PEG-200 in good yields. The easy access to diverse complex molecules in a single operation from readily available starting materials, a commercially available, transition metal-free and recyclable catalyst, the use of a green solvent, a very high atom economy and the release of water as the only side product are the highlights of this protocol.

Synthesis of 5,6-Dihydrodibenzo[b,h][1,6]naphthyridines via Copper Bromide Catalyzed Intramolecular [4 + 2] Hetero-Diels-Alder Reactions.

A highly efficient synthesis of 5,6-dihydrodibenzo[b,h][1,6]naphthyridines was achieved by reaction between 2-(N-propargylamino)benzaldehydes and arylamines in the presence of CuBr2. The in situ generated electron-deficient heterodienes bearing a tethered alkyne partner underwent an intramolecular inverse electron-demand hetero-Diels-Alder reaction followed by air oxidation to furnish the products in high yields. This reaction tolerated a large number of substituents to afford diverse products under mild conditions. This strategy was also successfully extended to the synthesis of 12,13-dihydro-6H-benzo[h]chromeno[3,4-b][1,6]naphthyridin-6-ones starting from 3-amino-2H-chromen-2-one, again in high yields.

Synthesis of 6,12-Epiminodibenzo[b,f][1,5]diazocines via an Ytterbium Triflate-Catalyzed, AB2 Three-Component Reaction.

An efficient and selective procedure for the synthesis of epiminodibenzo[b,f][1,5]diazocines involving a AB2 three-component reaction is developed. Two equivalents of suitably substituted 2-aminoarylaldehydes reacted with arylamines in the presence of Yb(OTf)3 to afford the desired products in high yields. The reaction is highly atom-economic and waste-free, in addition to allowing the generation of two heterocyclic rings and four C-N bonds in a single operation. Significantly, this approach is complementary to the existing literature procedures, affording arylamine-derived products that could not be accessed previously. A plausible mechanism is proposed involving an imine formation-intermolecular annulation-intramolecular iminium ion cyclization sequence.

Metal-free oxidative amidation of aldehydes with aminopyridines employing aqueous hydrogen peroxide.

The first metal free report on the amidation of aldehydes with aminopyridines was accomplished using simple aqueous hydrogen peroxide (aq. H2O2) as the oxidant. No catalysts or additives were needed for this transformation and the reaction proceeded in water, an environmentally benign reaction medium. Green oxidant and reaction conditions, and the ability to construct diverse N-(pyridin-2-yl)benzamide by this elegant method render it a practical alternative for the synthesis of these amides.

Palladium(II)-catalyzed intramolecular carboxypalladation-olefin insertion cascade: direct access to indeno[1,2-b]furan-2-ones.

A catalytic, atom-economical, domino 5-endo-dig cyclization-intramolecular olefin insertion sequence was developed under mild conditions. Aryl alkynoic acids bearing a tethered enone partner afforded the indeno[1,2-b]furan-2-ones, the core skeleton present in a number of biologically significant molecules including the natural product solanacol, under ligand-free, palladium-catalyzed reaction conditions in high yields. The competitive ß-hydride elimination in the final step leading to the conjugated analogs was avoided by the addition of lithium bromide. A plausible mechanism for this domino sequence is proposed involving intramolecular carboxypalladation and olefin insertion steps.

Fully diastereoselective synthesis of polysubstituted, functionalized piperidines and decahydroquinolines based on multicomponent reactions catalyzed by cerium(IV) ammonium nitrate.

The cerium(IV) ammonium nitrate (CAN)-catalyzed, three-component reaction between primary amines, ß-dicarbonyl compounds, and α,ß-unsaturated aldehydes in ethanol heated to reflux, constitutes a general, one-pot synthesis of 1,4-dihydropyridines. Their reduction with sodium triacetoxyborohydride furnished piperidine derivatives bearing up to five substituents with full diastereoselectivity in a hitherto inaccessible stereochemical arrangement. The reaction proceeded with no significant loss of enantiomeric purity under mild reduction conditions that are compatible with several functional groups that are normally sensitive to reduction. Octahydroquinolin-5-one derivatives, which were prepared by a modified version of the initial multicomponent reaction, were not suitable substrates for the sodium triacetoxyborohydride mediated reduction, but they were transformed into the corresponding decahydroquinolines, including a precursor of the amphibian alkaloid pumiliotoxin C, by catalytic hydrogenation under a variety of conditions.

Remediation of Dyes Using Supramolecular Material Derived from Carbohydrate Based π-Gelator Using the Bottom-Up Assembly Approach.

As a consequence of rapid population growth, the earth has faced numerous environmental sustainability issues and crises, water pollution is one of the important points of concern because of industrialization. In particular, effluents discharged from dying industries are rated top among the various industrial effluents, especially by their volume and composition. Annually >7.5 × 105 metric tons of different dyes are produced and consumed in different industries. In order to dye 1 kg of fabric, approximately 100-150 L of water is required, and after the dying process, it is discharged as an effluent either on a landfill or in water bodies. It is our responsibility to conserve environmental sustainability. In this line, we have developed a simple protocol to generate carbohydrate-based amphiphile using D-sorbitol, and pyrene-1-carboxaldehyde in good yield. This carbohydrate-based π-gelator is prone to forming a gel in various solvents and oils by the bottom-up assembly process. Morphological analysis of the self-assembled structure was identified by using optical microscopy and SEM. The viscoelastic behavior of the gel was examined by using rheology. In this paper, we explored the dye adsorption and desorption characteristics of the gel. Further, we have developed a cartridge based on cellulose using a template-assisted assembly phenomenon and demonstrated its potential in adsorbing dyes such as methylene blue, crystal violet, rhodamine B, and Congo red.

A ß-enaminone-initiated multicomponent domino reaction for the synthesis of indoloquinolizines and benzoquinolizines from acyclic precursors.

The cerium(IV) ammonium nitrate (CAN)-catalyzed sequential multicomponent reaction between tryptamine, α,ß-unsaturated aldehydes, and ß-dicarbonyl compounds affords highly substituted indolo[2,3-a]quinolizines in a single synthetic operation. Two rings are generated through the creation of two C-C and two C-N bonds by a domino process comprising initial ß-enaminone formation, followed by individual Michael addition, 6-exo-trig cyclization, iminium formation, and Pictet-Spengler steps. Furthermore, the reaction is diastereoselective and affords exclusively compounds with a trans relationship between the H-2 and H-12b protons. The use of amines bearing a less nucleophilic side chain aromatic ring (5-bromotryptamine, 3,4-dimethoxyphenylethylamine) prevents the Pictet-Spengler final step and leads to N-indolylethyl or N-phenylethyl-1,4-dihydropyridines, which are cyclized to the corresponding indolo[2,3-a]quinolizines or benzo[a]quinolizines in the presence of HCl in methanol/water. Treatment of the fused quinolizine derivatives with sodium triacetoxyborohydride led to the corresponding indolo[2,3-a]quinolizidines or benzo[a]quinolizidines, possessing four stereogenic centers, as mixtures of two diastereomers.