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Palladium Nanoparticles Supported on Smopex-234® as Valuable Catalysts for the Synthesis of Heterocycles

Gianluigi Albano
Claudio Evangelisti
2 and
Laura Antonella Aronica
Dipartimento di Chimica, Università degli Studi di Bari “Aldo Moro”, Via Edoardo Orabona 4, 70126 Bari, Italy
Istituto di Chimica dei Composti Organometallici—Consiglio Nazionale delle Ricerche (ICCOM- CNR), Via Giuseppe Moruzzi 1, 56124 Pisa, Italy
Dipartimento di Chimica e Chimica Industriale, Università di Pisa, Via Giuseppe Moruzzi 13, 56124 Pisa, Italy
CIRCC—Consorzio Interuniversitario per le Reattività Chimiche e la Catalisi, Via Celso Ulpiani 27, 70126 Bari, Italy
Author to whom correspondence should be addressed.
Catalysts 2021, 11(6), 706;
Submission received: 10 May 2021 / Revised: 28 May 2021 / Accepted: 31 May 2021 / Published: 3 June 2021
(This article belongs to the Section Catalysis in Organic and Polymer Chemistry)


Supported catalysts are important tools for developing green-economy-based processes. Palladium nanoparticles (NPs) that are immobilized on two fibers developed as metal scavengers (i.e., Smopex®-234 and Smopex®-111, 1% w/w) have been prepared and tested in copper-free cyclocarbonylative Sonogashira reactions. Their catalytic activity has been compared with that of a homogeneous catalyst (i.e., PdCl2(PPh3)2). Pd/Smopex®-234 showed high activity and selectivity in the synthesis of functionalized heterocycles, such as phthalans and isochromans, even when working with a very low amount of palladium (0.2–0.5 mol%). The extension of Pd/Smopex®-234 promoted cyclocarbonylative reactions to propargyl and homopropargyl amides afforded the corresponding isoindoline and dihydrobenzazepine derivatives. A preliminary test on Pd NPs leaching into the solution (1.7 × 10−3 mg) seems to indicate that, at the end of the reaction, almost all of the active metal is present on the fiber surface.

1. Introduction

Recently, the synthesis of heterocycles has received large attention [1,2] due to their increasing importance in the fields of pharmaceutical compounds and industrial chemicals. N- and O-containing heterocycles are structural motifs frequently found in biologically active compounds.
The 1,3-dihydroisobenzofuran [3,4] (phthalan, Figure 1a) nucleus is present in many natural and synthetic molecules, such as pestacin [5], citalopram [6,7], escitalopram [8,9,10], talopram [11], and egenine [12,13], which possess antidepressant, antioxidant, antimycotic, antihistaminic, antibacterial and antitumoral properties [5,8,14]. The phthalan derivative FR198248 was found to act as an anti-influenza agent [15,16], carbonylmethyleneisobenzofuran-1-imines have shown promising potential in herbicidal activity [17], and alkylidene functionalized 1,3-dihydroisobenzofurans have recently been tested as luminophores showing good fluorescence properties and remarkable Stokes shifts [18].
Isochroman [19,20,21] (Figure 1b) is the structural unit of a large number of compounds found in olive oil [22,23,24], leaves [25], and fungi [26,27,28,29,30]. Many isochromans exhibit anti-inflammatory [31,32,33], antibacterial [34,35], antifungal [36], antioxidant, and antiplatelet [37,38] activities, while some show cytotoxicity toward human cancer cell lines [39,40] and are used in the treatment of migraine headaches [41]. Moreover, isochroman is the nucleus of the commercial fragrance galaxolide [42,43,44], which is present in many products, including surface cleaners, laundry products, cosmetics, and perfumes.
Nitrogen-containing heterocycles are important substructures that are found in natural and synthetic alkaloids [45,46]. They also serve as an important source of pharmaceuticals and have inspired synthetic chemists to develop novel chemical transformations. For instance, indole [47,48,49] and its derivatives, such as isoindole [50,51] and isoindoline [52] (Figure 1c), are the basis for compounds possessing relevant biological activities. In particular, isoindoline derivatives are inhibitors of several enzymes involved in numerous diseases, including diabetes, obesity, heart failure, cancer, and mood disorders [53]. Moreover, isoindoline-based ligands are very interesting due to their modular set-up [54]. Finally, isoindoline pigments are particularly relevant, since they cover a wide range of colors from greenish-yellow to red and brown [55].
Owing to their great importance, there has been a continuous interest in developing new and efficient methods for the synthesis of such heterocycles. Several procedures are based on the palladium-promoted cyclization of suitable substrates, such as benzaldehydes [56], benzyl [57,58,59,60] and homobenzyl alcohols [61,62], propargyl ethers [63,64,65,66,67,68], benzylethers [58] and benzylamines [69], anilines [70], propargylamides [71], and arylimides [72].
In this field, Gabriele’s group has developed a very interesting methodology based on PdI2/KI-promoted oxidative cyclization-carbonylation reactions of different substrates affording O- and N-containing heterocycles [73,74,75,76,77,78,79,80,81,82]. Recently, we have described the use of transition-metal-promoted cyclocarbonylative coupling as a valuable tool for the synthesis of polyfunctionalized heterocyclic compounds [83,84,85,86,87,88].
In all cases described so far, homogeneous organometallic species have been employed as catalysts, thus making its recovery impossible and resulting in the metal contamination of the products. The research of greener methodologies prompted us to investigate the possible use of palladium nanoparticles (Pd NPs) deposited on metal scavengers as catalysts. Commercially available mercapto-functionalized polyolefin fibers, Smopex®-111 and Smopex®-234 (Figure 2), have been chosen as supports; they have been developed for the recovery of platinum group metals (Pt, Pd, Rh) from post-reaction solutions of cross-coupling processes, such as Mizoroki-Heck, Suzuki-Miyaura, and Sonogashira reactions [89,90,91,92]. Pd NPs supported on Smopex®-111 and Smopex®-234 were obtained through the metal vapor synthesis (MVS) technique. The versatility and feasibility of this synthetic approach in depositing size-controlled Pd NPs onto a wide range of supports, including organic polymers, have been previously established [93,94,95,96,97,98,99,100].
In the present work, we report that Pd/Smopex®-234 has resulted in an efficient catalyst for the synthesis of phthalan, isochroman, and isoindoline derivatives through cyclocarbonylative Sonogashira reactions. The Pd NPs’ dispersion, as well as the nature of the thiol moiety present on the polyolefin fibers, strongly influence the efficiency of the catalytic reactions.

2. Results and Discussion

2.1. Synthesis and Morphology of the Catalysts

Palladium NPs were obtained according to the MVS technique (Figure 3). This approach allowed for the generation of Pd nanoclusters that were weakly stabilized by organic solvents, which were then dispersed on Smopex®-111 and Smopex®-234 supports, respectively, by simple impregnation at 25 °C. Further reduction or thermal treatments of the catalysts were not required.
More in detail, Palladium vapors were co-condensed at a low temperature (77 K) with vapors of weakly stabilizing organic ligands (i.e., a mixture of mesitylene and 1-hexene) using a commercially available glass reactor. Upon warming, the frozen matrix melted and the nucleation and growth processes of the metal particles occurred, affording metal nanoclusters that were weakly stabilized by the solvent molecules, called solvated metal atoms (SMAs). The interaction of the metal vapors with the solvent matrix very quickly quenched the kinetic energy of metal atoms. The final sizes of the metal aggregates were greatly influenced by the solvent employed and the amount used, allowing for good control over their size. The Pd-SMA was handled at a low temperature (between 223 and 243 K) under an inert atmosphere, and it was used as a precursor for the preparation of supported Pd nanoparticles by simply mixing the SMA with the solid supports (i.e., Pd/Smopex®-234 and Pd/Smopex®-111) at room temperature. The metal quickly separated quantitatively from the solvent by interacting with the support surface, thus affording solid catalytic systems without the need for poisons (i.e., halide from metal salt precursors in catalysts prepared through reduction methods). One of the main advantages of the MVS approach is that it allows for the preparation of supported catalytic systems where the metal is deposited directly in its reduced form, so that the calcination and activation processes of the conventional wet deposition method are not required.
The morphology of Pd/Smopex®-111 and Pd/Smopex®-234 was investigated through transmission electron microscopy (TEM). Representative images of both systems are reported in Figure 4. The two systems exhibited different structural features, pointing out the crucial role of the organic support in controlling the final dispersion of the metal phase. Quite a low level of dispersion of Pd NPs was observed when supported on Smopex®-111. The presence of large agglomerates of roundish NPs, having diameters that were less than 10 nm in size (dm = 3.5 nm), was detected (Figure 4a).
On the other hand, the analysis of Pd/Smopex®-234 revealed the great affinity of this support for the as-prepared MVS-derived Pd NPs (Figure 4b), which prevents further NP aggregation phenomena during their immobilization. Indeed, a highly homogeneous dispersion of small Pd NPs (dm = 1.5 nm), which densely populated the surface of the organic fiber, was detected. Indeed, the mercaptoethyl acrylate group of Smopex®-234 is able to chelate the Pd NPs much better than the thiol functional group of Smopex®-111. Therefore, on Smopex®-234 Pd NPs are highly dispersed and stabilized. Moreover, assuming that the Pd NPs were spherical in shape, the theoretical exposed Pd fraction and metal-specific surface areas (SSAs) for both catalysts were calculated from HRTEM data through applying the following Equation (1):
dVS/dat = 3.32/(FE)1.23
where dVS is the size of Pd crystallites, dat is the atomic diameter of Pd (i.e., 0.275 nm), and FE is the exposed fraction of Pd [101], and Equation (2):
SSA = 3 Σniri2/(ΣρPdΣniri3) m2/g
where ri is the mean radius of the size class containing ni particles, and ρPd is the volumetric mass of Pd (12.02 g/cm3). As a result, Pd/Smopex®-234 exhibited a dispersion of 67% and an SSA = 116 m2/g, whereas Pd/Smopex®-111 exhibited a dispersion of 33% and an SSA = 48 m2/g.

2.2. Catalytic Activity of Pd/Smopex®-111 and Pd/Smopex®-234

First of all, the supported catalytic systems Pd/Smopex®-111 and Pd/Smopex®-234 were tested in the coupling between 2-ethynylbenzyl alcohol 1a and iodobenzene 2a, which were chosen as model compounds. The catalytic performance of the supported Pd NPs was compared with the activity of the PdCl2(PPh3)2 used as a homogenous reference catalyst. The reactions were performed in Et3N, which was used as a base and as a solvent, in a stainless-steel autoclave that was pressurized to 20 atm of carbon monoxide. While palladium nanoparticles that were supported on Smopex®-111 were totally inactive (Table 1, entry 2), those deposited on the Smopex®-234 fiber showed high catalytic efficiency in promoting the synthesis of phthalan derivative 3aa quantitatively, even in the presence of a very low amount of catalyst (0.2 mol%).
The unexpected difference observed in the catalytic activity of the Pd NPs deposited on the two Smopex® fibers (Table 1, entry 2 vs. entry 3) could be firstly related to the different morphological features of the two species (i.e., small particles well-dispersed for Pd/Smopex®-234 and the presence of large aggregates in the case of Pd/Smopex®-111). Moreover, a hypothetical mechanism of action of Pd/Smopex®-234 catalyst has been added in the Supplementary Materials.
The behavior of Pd/Smopex®-234 was also compared with that of homogeneous PdCl2(PPh3)2 (Table 1, entry 1 vs. entry 3): the reaction promoted by Pd NPs supported on Smopex®-234 took place with higher stereoselectivity toward the more stable isomer [102,103] (Z)-3aa (75%) with respect to the reaction carried out with the homogeneous catalyst (65%). The increase of the (Z) isomer amount after purification (i.e., silica column chromatography) may be due to the interconversion of (E) stereoisomer into the (Z) one, as already reported in the literature [104]. Indeed, as can be verified in the 1H-NMR of the crude product (see Supplementary Materials) the composition of the two isomers changes after purification, probably due to traces of acid.
The observed catalytic trend was confirmed by the reactions carried out using functionalized iodoarenes 2b and 2c (Table 1, entries 4–5), which possess different stereo-electronic features. Pd/Smopex®-234 was able to catalyze the cyclocarbonylative reactions quantitatively, affording the corresponding phthalans, (Z)-3ab and (Z)-3ac, in high yields (70–82%) after purification. Moreover, in the case of nitrile derivative 3ac, a complete stereoselectivity towards the (Z) isomer was observed.
The catalytic activity of Pd/Smopex®-234 was subsequently tested in the reaction of t-butylbenzyl alcohol 1b with iodobenzene 2a (Table 1, entries 8–9). The stereoselectivity of the process favored the formation of the (E) isomer in all the reactions ((Z)/(E) ratio of about 20/80), probably due to the steric hindrance of benzyl alcohol 1b. The same factor could be the reason for the overall reduced rate of the catalytic cycle. Indeed, in the cases of both PdCl2(PPh3)2- and Pd/Smopex®-234-promoted reactions, a substrate conversion of almost 20% was observed when a 0.2 mol% of palladium was used. (Table 1, entries 6 and 8). An increase of the catalytic amount to 0.5 mol% for the homogeneous complex determined a quantitative formation of phthalan 3ba (Table 1, entry 7). Analogously, an 82% conversion was observed when 1 mol% of Pd/Smopex®-234 was used (Table 1, entry 9).
Prompted by the good results obtained in the synthesis of phthalans 3 promoted by Pd/Smopex®-234 cyclocarbonylative Sonogashira reactions, we extended our investigation to the reaction of 2-(2-ethynylphenyl)ethanol 4 with iodoarenes 1a-c (Table 2), which was performed in the presence of homogeneous PdCl2(PPh3)2 and supported Pd/Smopex®-234 catalysts. In all cases, the reactions showed a complete conversion of the precursors and the exclusive formation of the (Z) stereoisomer of isochromans 6a-c, which were isolated as pure products in very high yields (90–95%). To our delight, a very low amount of Pd/Smopex®-234 (0.2 mol%) was able to catalyze the cyclocarbonylative reactions with complete chemo- and stereoselectivity.
Finally, the protocol based on Pd/Smopex®-234 cyclocarbonylative reactions was applied to the preparation of nitrogen-containing heterocycles. For this purpose, ortho-ethynylbenzyl tosylamide 6 and ortho-ethynylhomobenzyl tosylamide 7 were chosen as model compounds and tested in the reaction with iodobenzene 2a (Table 3). First of all, 0.2 mol% of homogeneous PdCl2(PPh3)2 (Table 3, entry 1) and supported Pd/Smopex®-234 (Table 3, entry 2) were employed in the reaction of tosylamide 6 with 2a, under the same experimental conditions (for 4 h at 100 °C, under 20 atm of CO, in Et3N, and using toluene as solvents). A relevant reduction of the reaction rate was detected when cyclocarbonylation was carried out with Pd NPs supported on Smopex®-234. Nevertheless, (E)-1-phenyl-2-(2-tosylisoindolin-1-ylidene) ethanone 8 was obtained as an exclusive product. In order to improve the conversion of the process, the reaction was repeated with 0.4 mol% of Pd/Smopex®-234 for a longer reaction time (24 h); under these experimental conditions, the quantitative formation of isoindoline derivative 8 was finally achieved (Table 3, entry 4).
The Pd/Smopex®-234 catalyst was subsequently applied to the cyclocarbonylative Sonogashira reaction between tosylamide 7 and iodobenzene 2a. The reaction took place with 0.4 mol% of supported Pd NPs and solely yielded dihydrobenzazepine 9, which is an important nucleus of many biologically active natural products and pharmaceutical compounds [105,106].
Finally, preliminary tests of Palladium leaching and catalyst recovery at the end of the reaction were carried out. With this aim, the autoclave was charged with iodobenzene 2a (0.6 mmol), tosylamide 6 (0.5 mmol), Et3N (1.5 mL), toluene (1.0 mL), and Pd/Smopex®-234 (0.4 mol% of Pd). After 24 h at 100 °C, the CO pressure was discharged (under fume hood), and the hot reaction mixture was filtered (using a Teflon filter, 0.2 mm) under nitrogen atmosphere. The palladium content in the resulting solution was determined by ICP-OES analysis and was found to be 0.8 w/w% of the initial Pd (i.e., 1.× 10−3 mg). This very low value will prompt us to carry out further experiments, such as recycling of the catalyst and Maitlis hot filtration tests [107,108], to evaluate the mechanism (homogeneous or heterogeneous) of the Pd/Smopex®-234 catalyst in the cyclocarbonylative Sonogashira reaction.

3. Materials and Methods

3.1. Preparation of Solvated Palladium Atoms Solutions

Palladium vapors were generated under reduced pressure (10−5 mBar) through the resistive heating of 500 mg of the metal in an alumina-coated tungsten crucible; they were then co-condensed at liquid N2 temperature (−195 °C) with vapors of 1-hexene (30 mL) and mesitylene (30 mL) in a glass reactor [109]. The reactor chamber was heated to the melting point of the solid matrix (−40 °C), and the resulting brown solution (called Pd-SMA) was siphoned and handled at a low temperature (about −40 °C). The palladium content of the obtained Pd-SMA, determined through an ICP-OES analysis, was 2.3 mg of Pd/mL.

3.2. Preparation of Supported Palladium Catalysts

In a Schlenk tube, Pd-SMA (27 mL, 62.1 mg of Palladium) was added to a suspension of the support (Smopex®-111 or Smopex®-234) (6.2 g) in mesitylene (20 mL). The resulting mixture was stirred for 6 h at 25 °C. The colorless solution was then removed, and the light-brown solid was washed with n-pentane (3 × 20 mL) and dried under reduced pressure. The metal content of Pd/Smopex®-111 and Pd/Smopex®-234 (i.e., 1% w/w) was confirmed through ICP-OES analysis.

3.3. Synthesis of Phthalans: General Procedure

In a typical run (see Table 1), ortho-ethynylbenzyl alcohol 1 (2.0 mmol), iodoarene 2 (2.0 mmol), and Et3N (5 mL) were mixed, under CO atmosphere, into a Schlenk tube. This solution was siphoned in a 25 mL stainless steel autoclave, previously charged with the Pd catalyst (0.2–1 mol%), and placed under vacuum (0.1 Torr). The reactor was pressurized with carbon monoxide (20 atm), and the resulting mixture was stirred at 100 °C for 24 h. After the removal of excess CO (under fume hood), the reaction mixture was diluted with CH2Cl2 (20 mL), washed with brine (20 mL), dried over anhydrous Na2SO4, and the solvent was removed under reduced pressure. Reagent conversion and product composition were determined through 1H-NMR analysis. Crude products were purified through column chromatography on silica gel and were characterized by 1H-NMR and 13C-NMR techniques.

3.4. Synthesis of Isochromans: General Procedure

In a typical run (see Table 2), 2-(2-ethynylphenyl)ethanol 4 (2.0 mmol), iodoarene 2 (2.0 mmol), and Et3N (5 mL) were mixed, under CO atmosphere, into a Schlenk tube. This solution was siphoned in a 25 mL stainless steel autoclave, previously charged with the Pd catalyst (0.2 mol%), and placed under vacuum (0.1 Torr). The reactor was pressurized with carbon monoxide (20 atm), and the resulting mixture was stirred at 100 °C for 24 h. After the removal of excess CO (under fume hood), the reaction mixture was diluted with CH2Cl2 (20 mL), washed with brine (20 mL), dried over anhydrous Na2SO4, and the solvent was removed under reduced pressure. Reagent conversion and product composition were determined through 1H-NMR analysis. Crude products were purified through column chromatography on silica gel and were characterized by 1H-NMR and 13C-NMR techniques.

3.5. Synthesis of N-Heterocyclic Compounds: General Procedure

In a typical run (see Table 3), ortho-ethynyl(homo)benzyl tosylamide 6 or 7 (2.0 mmol), iodobenzene 2a (2.5 mmol), Et3N (3 mL), and toluene (2 mL) were mixed, under CO atmosphere, into a Schlenk tube. This solution was siphoned in a 25 mL stainless steel autoclave, previously charged with the Pd catalyst (0.2–0.4 mol%), and placed under vacuum (0.1 Torr). The reactor was pressurized with carbon monoxide (20 atm), and the resulting mixture was stirred at 100 °C for a selected time (4–24 h). After the removal of excess CO (under fume hood), the reaction mixture was diluted with CH2Cl2 (20 mL), washed with brine (20 mL), dried over anhydrous Na2SO4, and the solvent was removed under reduced pressure. Reagent conversion and product composition were determined through 1H-NMR analysis. Crude products were purified through column chromatography on silica gel or neutral alumina and were characterized through 1H-NMR and 13C-NMR techniques.

4. Conclusions

In conclusion, we have reported that Pd NPs, prepared according to the MVS technique, can be easily deposited on commercial thiol-based metal scavengers Smopex®-111 and Smopex®-234, affording Pd/Smopex®-111 and Pd/Smopex®-234 systems. The latter material exhibits a very high homogeneous dispersion of small Pd NPs (dm = 1.5 nm) without the presence of Pd NP aggregates, as observed for Pd/Smopex®-111. Both systems were initially studied as supported catalysts in the cyclocarbonylative reaction of 2-ethynylbenzyl alcohol with iodoarenes to generate phthalans. Pd/Smopex®-234 showed a catalytic efficiency comparable to that observed with the PdCl2(PPh3)2 organometallic complex, which was used as a reference homogeneous catalyst. On the other hand, Pd/Smopex®-111 was completely unable to promote the reaction. Pd/Smopex®-234 also proved to be very efficient in the synthesis of isochroman, isoindoline, and dihydrobenzazepine derivatives with high chemo- and stereoselectivity.
Almost all the cyclocarbonylative Sonogashira reactions were carried out with a very small amount of catalyst (0.2–0.4 mol% of Pd) in both phosphine-free and Cu-free conditions, thus enhancing the potentialities of Pd/Smopex®-234 as a promising catalyst for heterocycle synthesis.

Supplementary Materials

The following are available online at additional experimental details; supplementary figures; 1H-NMR and 13C-NMR spectra of the pure products of cyclocarbonylative reactions.

Author Contributions

Conceptualization, L.A.A. and C.E.; validation, C.E. and G.A.; formal analysis, C.E. and G.A.; investigation, G.A.; data curation, L.A.A. and G.A.; writing—original draft preparation, L.A.A. and C.E.; writing—review and editing, C.E and G.A.; supervision, L.A.A. All authors have read and agreed to the published version of the manuscript.


This research was funded by the University of Pisa, grant number PRA_ 2020_21.

Conflicts of Interest

The authors declare no conflict of interest.


  1. Albano, G.; Aronica, L.A. From alkynes to heterocycles through metal-promoted silylformylation and silylcarbocyclization reactions. Catalysts 2020, 10, 1012. [Google Scholar] [CrossRef]
  2. Albano, G.; Aronica, L.A. Acyl sonogashira cross-coupling: State of the art and application to the synthesis of heterocyclic compounds. Catalysts 2020, 10, 25. [Google Scholar] [CrossRef] [Green Version]
  3. Karmakar, R.; Pahari, P.; Mal, D. Phthalides and phthalans: Synthetic methodologies and their applications in the total synthesis. Chem. Rev. 2014, 114, 6213–6284. [Google Scholar] [CrossRef]
  4. Ilya, E.; Kulikova, L.; Van der Eycken, E.V.; Voskressensky, L. Recent advances in phthalan and coumaran chemistry. ChemistryOpen 2018, 7, 914–929. [Google Scholar] [CrossRef] [Green Version]
  5. Harper, J.K.; Arif, A.M.; Ford, E.J.; Strobel, G.A.; Porco, J.A.; Tomer, D.P.; Oneill, K.L.; Heider, E.M.; Grant, D.M. Pestacin: A 1,3-dihydro isobenzofuran from Pestalotiopsis microspora possessing antioxidant and antimycotic activities. Tetrahedron 2003, 59, 2471–2476. [Google Scholar] [CrossRef]
  6. Sánchez, C.; Bøgesø, K.P.; Ebert, B.; Reines, E.H.; Braestrup, C. Escitalopram versus citalopram: The surprising role of the R-enantiomer. Psychopharmacology 2004, 174, 163–176. [Google Scholar] [CrossRef]
  7. Larsen, M.A.B.; Plenge, P.; Andersen, J.; Eildal, J.N.; Kristensen, A.S.; Bøgesø, K.P.; Gether, U.; Strømgaard, K.; Bang-Andersen, B.; Loland, C.J. Structure–activity relationship studies of citalopram derivatives: Examining substituents conferring selectivity for the allosteric site in the 5-HT transporter. Br. J. Pharmacol. 2016, 173, 925–936. [Google Scholar] [CrossRef] [Green Version]
  8. Waugh, J.; Goa, K.L. Escitalopram. CNS Drugs 2003, 17, 343–362. [Google Scholar] [CrossRef]
  9. Baldwin, D.S.; Reines, E.H.; Guiton, C.; Weiller, E. Escitalopram therapy for major depression and anxiety disorders. Ann. Pharmacother. 2007, 41, 1583–1592. [Google Scholar] [CrossRef]
  10. Leonard, B.; Taylor, D. Review: Escitalopram—Translating molecular properties into clinical benefit: Reviewing the evidence in major depression. J. Psychopharmacol. 2010, 24, 1143–1152. [Google Scholar] [CrossRef] [Green Version]
  11. Eildal, J.N.N.; Andersen, J.; Kristensen, A.S.; Jørgensen, A.M.; Bang-Andersen, B.; Jørgensen, M.; Strømgaard, K. From the selective serotonin transporter inhibitor citalopram to the selective norepinephrine transporter inhibitor talopram: Synthesis and structure−activity relationship studies. J. Med. Chem. 2008, 51, 3045–3048. [Google Scholar] [CrossRef]
  12. Huang, Q.; Chen, J.; Zhang, W.; Zhou, B.; Zhang, C.; Gerwick, W.H.; Cao, Z. Alkaloids from Corydalis decumbens suppress neuronal excitability in primary cultures of mouse neocortical neurons. Phytochemistry 2018, 150, 85–92. [Google Scholar] [CrossRef]
  13. Zhang, C.-L.; Huang, Q.-L.; Chen, J.; Zhang, W.-J.; Jin, H.-X.; Wang, H.-B.; Naman, C.B.; Cao, Z.-Y. Phthalideisoquinoline hemiacetal alkaloids from corydalis decumbens that inhibit spontaneous calcium oscillations, including alkyl derivatives of (+)-egenine that are strikingly levorotatory. J. Nat. Prod. 2019, 82, 2713–2720. [Google Scholar] [CrossRef]
  14. Praveen, C.; Lyyappan, C.; Perumal, P.T.; Girija, K. AgOTf as an alternative catalyst for the regioselective cyclization of 2-(alkynyl)benzyl alcohols: Synthesis and biological evaluation of phthalans. Indian J. Chem. Sect B 2012, 51B, 498–507. [Google Scholar] [CrossRef]
  15. Nishihara, Y.; Tsujii, E.; Yamagishi, Y.; Sakamoto, K.; Tsurumi, Y.; Furukawa, S.; Ohtsu, R.; Kino, T.; Hino, M.; Yamashita, M.; et al. FR198248, a new anti-influenza agent isolated from aspergillus terreus No. 13830. J. Antibiot. 2001, 54, 136–143. [Google Scholar] [CrossRef] [Green Version]
  16. Nishihara, Y.; Takase, S.; Tsujii, E.; Hatanaka, H.; Hashimoto, S. New anti-influenza agents, FR198248 and its derivatives II. characterization of FR198248, its related compounds and some derivatives. J. Antibiot. 2001, 54, 297–303. [Google Scholar] [CrossRef] [Green Version]
  17. Araniti, F.; Mancuso, R.; Ziccarelli, I.; Sunseri, F.; Abenavoli, M.R.; Gabriele, B. 3-(Methoxycarbonylmethylene)isobenzofuran-1-imines as a new class of potential herbicides. Molecules 2014, 19, 8261–8275. [Google Scholar] [CrossRef] [Green Version]
  18. Mandali, P.K.; Pati, A.K.; Mishra, A.K.; Chand, D.K. Fluorescent 1-Arylidene-1,3-dihydroisobenzofuran: Ligand-Free palladium nanoparticles, catalyzed domino synthesis and photophysical studies. ChemistrySelect 2017, 2, 5259–5265. [Google Scholar] [CrossRef]
  19. Albano, G.; Aronica, L.A. Potentiality and synthesis of O- and N-heterocycles: Pd-catalyzed cyclocarbonylative sonogashira coupling as a valuable route to phthalans, isochromans, and isoindolines. Eur. J. Org. Chem. 2017, 2017, 7204–7221. [Google Scholar] [CrossRef]
  20. Larghi, E.L.; Kaufman, T.S. The oxa-pictet-spengler cyclization: Synthesis of isochromans and related pyran-type heterocycles. Synthesis 2006, 2006, 187–220. [Google Scholar] [CrossRef]
  21. Zhao, Z.; Kang, K.; Yue, J.; Ji, X.; Qiao, H.; Fan, P.; Zheng, X. Research progress in biological activities of isochroman derivatives. Eur. J. Med. Chem. 2021, 210, 113073. [Google Scholar] [CrossRef]
  22. Bianco, A.; Coccioli, F.; Guiso, M.; Marra, C. The occurrence in olive oil of a new class of phenolic compounds: Hydroxy-isochromans. Food Chem. 2002, 77, 405–411. [Google Scholar] [CrossRef]
  23. Guiso, M.; Marra, C.; Arcos, R.R. An investigation on dihydroxy-isochromans in extra virgin olive oil. Nat. Prod. Res. 2008, 22, 1403–1409. [Google Scholar] [CrossRef] [PubMed]
  24. Bendini, A.; Cerretani, L.; Carrasco-Pancorbo, A.; Gómez-Caravaca, A.M.; Segura-Carretero, A.; Fernández-Gutiérrez, A.; Lercker, G. Phenolic molecules in virgin olive oils: A survey of their sensory properties, health effects, antioxidant activity and analytical methods. An overview of the last decade alessandra. Molecules 2007, 12, 1679–1719. [Google Scholar] [CrossRef]
  25. Feng-Lin, H.; Jhy-Yih, C. Phenolics from tectaria subtriphylla. Phytochemistry 1993, 34, 1625–1627. [Google Scholar] [CrossRef]
  26. Malmstrøm, J.; Christophersen, C.; Frisvad, J.C. Secondary metabolites characteristic of Penicillium citrinum, Penicillium steckii and related species. Phytochemistry 2000, 54, 301–309. [Google Scholar] [CrossRef]
  27. Chen, G.; Lin, Y.; Vrijmoed, L.L.P.; Fong, W.-F. A new isochroman from the marine endophytic fungus 1893#. Chem. Nat. Compd. 2006, 42, 138–141. [Google Scholar]
  28. Khamthong, N.; Rukachaisirikul, V.; Phongpaichit, S.; Preedanon, S.; Sakayaroj, J. Bioactive polyketides from the sea fan-derived fungus Penicillium citrinum PSU-F51. Tetrahedron 2012, 68, 8245–8250. [Google Scholar] [CrossRef]
  29. McMullin, D.R.; Nsiama, T.K.; Miller, J.D. Secondary metabolites from Penicillium corylophilum isolated from damp buildings. Mycologia 2014, 106, 621–628. [Google Scholar] [CrossRef]
  30. Kock, I.; Draeger, S.; Schulz, B.; Elsässer, B.; Kurtán, T.; Kenéz, Á.; Antus, S.; Pescitelli, G.; Salvadori, P.; Speakman, J.-B.; et al. Pseudoanguillosporin A and B: Two new isochromans isolated from the endophytic fungus pseudoanguillospora sp. Eur. J. Org. Chem. 2009, 2009, 1427–1434. [Google Scholar] [CrossRef]
  31. Trefiletti, G.; Rita Togna, A.; Latina, V.; Marra, C.; Guiso, M.; Togna, G.I. 1-Phenyl-6,7-dihydroxy-isochroman suppresses lipopolysaccharide-induced pro-inflammatory mediator production in human monocytes. Br. J. Nutr. 2011, 106, 33–36. [Google Scholar] [CrossRef] [Green Version]
  32. Togna, A.R.; Latina, V.; Trefiletti, G.; Guiso, M.; Moschini, S.; Togna, G.I. 1-Phenil-6,7-dihydroxy-isochroman inhibits inflammatory activation of microglia. Brain Res. Bull. 2013, 95, 33–39. [Google Scholar] [CrossRef]
  33. Li, W.; Lee, C.; Bang, S.H.; Ma, J.Y.; Kim, S.; Koh, Y.-S.; Shim, S.H. Isochromans and related constituents from the endophytic fungus annulohypoxylon truncatum of zizania caduciflora and their anti-inflammatory effects. J. Nat. Prod. 2017, 80, 205–209. [Google Scholar] [CrossRef]
  34. Trisuwan, K.; Rukachaisirikul, V.; Sukpondma, Y.; Phongpaichit, S.; Preedanon, S.; Sakayaroj, J. Furo[3,2-h]isochroman, furo[3,2-h]isoquinoline, isochroman, phenol, pyranone, and pyrone derivatives from the sea fan-derived fungus Penicillium sp. PSU-F40. Tetrahedron 2010, 66, 4484–4489. [Google Scholar] [CrossRef]
  35. Niaz, S.-I.; Zhang, P.; Shen, H.; Li, J.; Chen, B.; Chen, S.; Liu, L.; He, J. Two new isochromane derivatives penisochromanes A and B from ascidian-derived fungus Penicillium sp. 4829. Nat. Prod. Res. 2019, 33, 1262–1268. [Google Scholar] [CrossRef]
  36. He, G.; Matsuura, H.; Takushi, T.; Kawano, S.; Yoshihara, T. A new antifungal metabolite from penicillium expansum. J. Nat. Prod. 2004, 67, 1084–1087. [Google Scholar] [CrossRef]
  37. Togna, G.I.; Togna, A.R.; Franconi, M.; Marra, C.; Guiso, M. Olive oil isochromans inhibit human platelet reactivity. J. Nutr. 2003, 133, 2532–2536. [Google Scholar] [CrossRef] [PubMed]
  38. Mateos, R.; Madrona, A.; Pereira-Caro, G.; Domínguez, V.; Cert, R.M.; Parrado, J.; Sarriá, B.; Bravo, L.; Espartero, J.L. Synthesis and antioxidant evaluation of isochroman-derivatives of hydroxytyrosol: Structure–activity relationship. Food Chem. 2015, 173, 313–320. [Google Scholar] [CrossRef] [PubMed]
  39. Kuramochi, K.; Tsubaki, K.; Kuriyama, I.; Mizushina, Y.; Yoshida, H.; Takeuchi, T.; Kamisuki, S.; Sugawara, F.; Kobayashi, S. Synthesis, structure, and cytotoxicity studies of some fungal isochromanes. J. Nat. Prod. 2013, 76, 1737–1745. [Google Scholar] [CrossRef] [PubMed]
  40. Tobe, M.; Tashiro, T.; Sasaki, M.; Takikawa, H. A concise synthesis of (±)-pseudodeflectusin, an antitumor isochroman derivative isolated from Aspergillus sp. Tetrahedron 2007, 63, 9333–9337. [Google Scholar] [CrossRef]
  41. Ennis, M.D.; Ghazal, N.B.; Hoffman, R.L.; Smith, M.W.; Schlachter, S.K.; Lawson, C.F.; Im, W.B.; Pregenzer, J.F.; Svensson, K.A.; Lewis, R.A.; et al. Isochroman-6-carboxamides as highly selective 5-HT1D agonists:  Potential new treatment for migraine without cardiovascular side effects. J. Med. Chem. 1998, 41, 2180–2183. [Google Scholar] [CrossRef] [PubMed]
  42. Fráter, G.; Müller, U.; Kraft, P. Preparation and olfactory characterization of the enantiomerically pure isomers of the perfumery synthetic Galaxolide®. Helv. Chim. Acta 1999, 82, 1656–1665. [Google Scholar] [CrossRef]
  43. Kraft, P.; Fráter, G. Enantioselectivity of the musk odor sensation. Chirality 2001, 13, 388–394. [Google Scholar] [CrossRef] [PubMed]
  44. David, O.R.P. A chemical history of polycyclic musks. Chem. Eur. J. 2020, 26, 7537–7555. [Google Scholar] [CrossRef] [PubMed]
  45. Kochanowska-Karamyan, A.J.; Hamann, M.T. Marine indole alkaloids: Potential new drug leads for the control of depression and anxiety. Chem. Rev. 2010, 110, 4489–4497. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  46. Thokchom Prasanta, S.; Okram Mukherjee, S. Recent progress in biological activities of indole and indole alkaloids. Mini Rev. Med. Chem. 2018, 18, 9–25. [Google Scholar]
  47. Sravanthi, T.V.; Manju, S.L. Indoles—A promising scaffold for drug development. Eur. J. Pharm. Sci. 2016, 91, 1–10. [Google Scholar] [CrossRef]
  48. Kaushik, N.K.; Kaushik, N.; Attri, P.; Kumar, N.; Kim, C.H.; Verma, A.K.; Choi, E.H. Biomedical importance of indoles. Molecules 2013, 18, 6620–6662. [Google Scholar] [CrossRef]
  49. Mancuso, R.; Dalpozzo, R. Recent progress in the transition metal catalyzed synthesis of indoles. Catalysts 2018, 8, 458. [Google Scholar] [CrossRef] [Green Version]
  50. Speck, K.; Magauer, T. The chemistry of isoindole natural products. Beilstein J. Org. Chem. 2013, 9, 2048–2078. [Google Scholar] [CrossRef]
  51. Csende, F.; Porkoláb, A. Antiviral activity of isoindole derivatives. J. Med. Chem. Sci. 2020, 3, 254–285. [Google Scholar]
  52. Albano, G.; Aronica, L.A. Cyclization reactions for the synthesis of phthalans and isoindolines. Synthesis 2018, 50, 1209–1227. [Google Scholar]
  53. Richa Kaur, B. Isoindole derivatives: Propitious anticancer structural motifs. Curr. Top. Med. Chem. 2017, 17, 189–207. [Google Scholar]
  54. Csonka, R.; Speier, G.; Kaizer, J. Isoindoline-derived ligands and applications. RSC Adv. 2015, 5, 18401–18419. [Google Scholar] [CrossRef]
  55. Radtke, V.; Erk, P.; Sens, B. Isoindoline pigments. In High Performance Pigments; Smith, H.M., Ed.; Wiley-VCH: Weinheim, Germany, 2002; pp. 211–230. [Google Scholar]
  56. Dell’Acqua, M.; Facoetti, D.; Abbiati, G.; Rossi, E. From domino to multicomponent: Synthesis of dihydroisobenzofurans. Tetrahedron 2011, 67, 1552–1556. [Google Scholar] [CrossRef]
  57. Ammann, S.E.; Rice, G.T.; White, M.C. Terminal olefins to chromans, isochromans, and pyrans via allylic C–H oxidation. J. Am. Chem. Soc. 2014, 136, 10834–10837. [Google Scholar] [CrossRef] [Green Version]
  58. Petrone, D.A.; Malik, H.A.; Clemenceau, A.; Lautens, M. Functionalized chromans and isochromans via a diastereoselective Pd(0)-catalyzed carboiodination. Org. Lett. 2012, 14, 4806–4809. [Google Scholar] [CrossRef]
  59. Zanardi, A.; Mata, J.A.; Peris, E. Domino approach to benzofurans by the sequential sonogashira/hydroalkoxylation couplings catalyzed by new n-heterocyclic-carbene-palladium complexes. Organometallics 2009, 28, 4335–4339. [Google Scholar] [CrossRef]
  60. Buxaderas, E.; Alonso, D.A.; Nájera, C. Synthesis of dihydroisobenzofurans via palladium-catalyzed sequential alkynylation/annulation of 2-bromobenzyl and 2-chlorobenzyl alcohols under microwave irradiation. Adv. Synth. Catal. 2014, 356, 3415–3421. [Google Scholar] [CrossRef]
  61. Lu, Y.; Wang, D.-H.; Engle, K.M.; Yu, J.-Q. Pd(II)-catalyzed hydroxyl-directed c−h olefination enabled by monoprotected amino acid ligands. J. Am. Chem. Soc. 2010, 132, 5916–5921. [Google Scholar] [CrossRef] [Green Version]
  62. Ammann, S.E.; Liu, W.; White, M.C. Enantioselective allylic C−H oxidation of terminal olefins to isochromans by palladium(ii)/chiral sulfoxide catalysis. Angew. Chem. Int. Ed. 2016, 55, 9571–9575. [Google Scholar] [CrossRef] [Green Version]
  63. Nandakumar, A.; Balakrishnan, K.; Perumal, P.T. Palladium-catalyzed intramolecular hydroarylation of 2-bromobenzyl propargyl ethers: A new access to exocyclic isochromans. Synlett 2011, 2011, 2733–2739. [Google Scholar] [CrossRef]
  64. Shen, R.-W.; Yang, J.-J.; Zhang, L.-X. Facile synthesis of phthalan derivatives via a Pd-catalyzed tandem hydroalkynylation, isomerization, Diels–Alder cycloaddition and aromatization reaction. Chin. Chem. Lett. 2015, 26, 73–76. [Google Scholar] [CrossRef]
  65. Ghosh, M.; Singha, R.; Dhara, S.; Ray, J.K. Synthesis of 4,5,6-trisubstituted-1,3-dihydroisobenzofurans by virtue of palladium-catalyzed domino carbopalladation of bromoenynes and internal alkynes. RSC Adv. 2015, 5, 85911–85914. [Google Scholar] [CrossRef]
  66. Yamamoto, Y.; Nagata, A.; Nagata, H.; Ando, Y.; Arikawa, Y.; Tatsumi, K.; Itoh, K. Palladium(0)-catalyzed intramolecular [2+2+2] alkyne cyclotrimerizations with electron-deficient diynes and triynes. Chem. Eur. J. 2003, 9, 2469–2483. [Google Scholar] [CrossRef] [PubMed]
  67. Zhou, P.; Zheng, M.; Jiang, H.; Li, X.; Qi, C. An aerobic [2 + 2 + 2] cyclization via chloropalladation: From 1,6-diynes and acrylates to substituted aromatic carbocycles. J. Org. Chem. 2011, 76, 4759–4763. [Google Scholar] [CrossRef]
  68. Tsubakiyama, M.; Sato, Y.; Mori, M. Synthesis of bicyclic heterocycles from propargyl esters using a palladium catalyst bearing a bidentate ligand. Heterocycles 2004, 64, 27–31. [Google Scholar] [CrossRef]
  69. Solé, D.; Serrano, O. Selective synthesis of either isoindole- or isoindoline-1-carboxylic acid esters by Pd(0)-catalyzed enolate arylation. J. Org. Chem. 2010, 75, 6267–6270. [Google Scholar] [CrossRef] [PubMed]
  70. Zhou, P.-X.; Luo, J.-Y.; Zhao, L.-B.; Ye, Y.-Y.; Liang, Y.-M. Palladium-catalyzed insertion of N-tosylhydrazones for the synthesis of isoindolines. Chem. Commun. 2013, 49, 3254–3256. [Google Scholar] [CrossRef] [PubMed]
  71. Zhang, Y.; Wu, W.; Fu, C.; Huang, X.; Ma, S. Benzene construction via Pd-catalyzed cyclization of 2,7-alkadiynylic carbonates in the presence of alkynes. Chem. Sci. 2019, 10, 2228–2235. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  72. Williams, F.J.; Jarvo, E.R. Palladium-catalyzed cascade reaction for the synthesis of substituted isoindolines. Angew. Chem. Int. Ed. 2011, 50, 4459–4462. [Google Scholar] [CrossRef]
  73. Gabriele, B.; Salerno, G.; Fazio, A.; Pittelli, R. Versatile synthesis of (Z)-1-alkylidene-1,3-dihydroisobenzofurans and 1H-isochromenes by palladium-catalyzed cycloisomerization of 2-alkynylbenzyl alcohols. Tetrahedron 2003, 59, 6251–6259. [Google Scholar] [CrossRef]
  74. Bacchi, A.; Costa, M.; Della Cà, N.; Fabbricatore, M.; Fazio, A.; Gabriele, B.; Nasi, C.; Salerno, G. Synthesis of 1-(Alkoxycarbonyl)methylene-1,3-dihydroisobenzofurans and 4-(Alkoxycarbonyl)benzo[c]pyrans by palladium-catalysed oxidative carbonylation of 2-Alkynylbenzyl alcohols, 2-Alkynylbenzaldehydes and 2-Alkynylphenyl Ketones. Eur. J. Org. Chem. 2004, 2004, 574–585. [Google Scholar] [CrossRef]
  75. Gabriele, B.; Salerno, G.; Costa, M. PdI2-Catalyzed synthesis of heterocycles. Synlett 2004, 2004, 2468–2483. [Google Scholar] [CrossRef]
  76. Della Ca’, N.; Campanini, F.; Gabriele, B.; Salerno, G.; Massera, C.; Costa, M. Cascade reactions: Catalytic synthesis of functionalized 1,3-dihydroisobenzofuran and tetrahydrofuran derivatives by sequential nucleophilic ring opening–heterocyclization–oxidative carbonylation of alkynyloxiranes. Adv. Synth. Catal. 2009, 351, 2423–2432. [Google Scholar] [CrossRef]
  77. Gabriele, B.; Mancuso, R.; Ziccarelli, I.; Salerno, G. A new approach to isoindolinone derivatives by sequential palladium iodide-catalyzed oxidative aminocarbonylation–heterocyclization of 2-ethynylbenzamides. Tetrahedron Lett. 2012, 53, 6694–6696. [Google Scholar] [CrossRef]
  78. Mancuso, R.; Ziccarelli, I.; Armentano, D.; Marino, N.; Giofrè, S.V.; Gabriele, B. Divergent palladium iodide catalyzed multicomponent carbonylative approaches to functionalized isoindolinone and isobenzofuranimine derivatives. J. Org. Chem. 2014, 79, 3506–3518. [Google Scholar] [CrossRef] [PubMed]
  79. Mancuso, R.; Della Ca’, N.; Veltri, L.; Ziccarelli, I.; Gabriele, B. PdI2-Based catalysis for carbonylation reactions: A personal account. Catalysts 2019, 9, 610. [Google Scholar] [CrossRef] [Green Version]
  80. Gabriele, B.; Mancuso, R.; Veltri, L.; Ziccarelli, I.; Della Ca, N. Palladium-catalyzed double cyclization processes leading to polycyclic heterocycles: Recent advances. Eur. J. Org. Chem. 2019, 2019, 5073–5092. [Google Scholar] [CrossRef]
  81. Mancuso, R.; Ziccarelli, I.; Brindisi, M.; Altomare, C.D.; Frattaruolo, L.; Falcicchio, A.; Della Ca’, N.; Cappello, A.R.; Gabriele, B. A stereoselective, multicomponent catalytic carbonylative approach to a new class of α,β-Unsaturated γ-Lactam derivatives. Catalysts 2021, 11, 227. [Google Scholar] [CrossRef]
  82. Gabriele, B.; Mancuso, R.; Salerno, G. Oxidative carbonylation as a powerful tool for the direct synthesis of carbonylated heterocycles. Eur. J. Org. Chem. 2012, 2012, 6825–6839. [Google Scholar] [CrossRef]
  83. Aronica, L.A.; Giannotti, L.; Giuntini, S.; Caporusso, A.M. Synthesis of 2-Alkylideneisochromans by cyclocarbonylative sonogashira reactions. Eur. J. Org. Chem. 2014, 2014, 6858–6862. [Google Scholar] [CrossRef] [Green Version]
  84. Aronica, L.A.; Giannotti, L.; Tuci, G.; Zinna, F. Cyclocarbonylative sonogashira reactions of 1-ethynylbenzyl alcohols: Synthesis of 1-Carbonylmethylene-1,3-Dihydroisobenzofurans. Eur. J. Org. Chem. 2015, 2015, 4944–4949. [Google Scholar] [CrossRef]
  85. Aronica, L.A.; Albano, G.; Giannotti, L.; Meucci, E. Synthesis of N-heteroaromatic compounds through cyclocarbonylative sonogashira reactions. Eur. J. Org. Chem. 2017, 2017, 955–963. [Google Scholar] [CrossRef]
  86. Albano, G.; Morelli, M.; Aronica, L.A. Synthesis of functionalised 3-Isochromanones by silylcarbocyclisation/desilylation reactions. Eur. J. Org. Chem. 2017, 2017, 3473–3480. [Google Scholar] [CrossRef]
  87. Albano, G.; Morelli, M.; Lissia, M.; Aronica, L.A. Synthesis of functionalised indoline and isoquinoline derivatives through a silylcarbocyclisation/desilylation sequence. ChemistrySelect 2019, 4, 2505–2511. [Google Scholar] [CrossRef]
  88. Albano, G.; Giuntini, S.; Aronica, L.A. Synthesis of 3-Alkylideneisoindolin-1-ones via sonogashira cyclocarbonylative reactions of 2-Ethynylbenzamides. J. Org. Chem. 2020, 85, 10022–10034. [Google Scholar] [CrossRef]
  89. Jiang, X.; Sclafani, J.; Prasad, K.; Repič, O.; Blacklock, T.J. Pd−Smopex-111:  A new catalyst for heck and suzuki cross-coupling reactions. Org. Process. Res. Dev. 2007, 11, 769–772. [Google Scholar] [CrossRef]
  90. Colacot, T.J. Palladium based FibreCat and SMOPEX® as supported homogenous catalyst systems for simple to challenging carbon–carbon coupling reactions. Top. Catal. 2008, 48, 91–98. [Google Scholar] [CrossRef]
  91. Frankham, J. The use of metal scavengers for recovery of precious, base and heavy metals from waste streams. Platin. Metals Rev. 2010, 54, 200–202. [Google Scholar] [CrossRef]
  92. Phillips, S. The use of metal scavengers for recovery of palladium catalyst from solution. Platin. Metals Rev. 2010, 54, 69–70. [Google Scholar] [CrossRef]
  93. Caporusso, A.M.; Innocenti, P.; Aronica, L.A.; Vitulli, G.; Gallina, R.; Biffis, A.; Zecca, M.; Corain, B. Functional resins in palladium catalysis: Promising materials for Heck reaction in aprotic polar solvents. J. Catal. 2005, 234, 1–13. [Google Scholar] [CrossRef]
  94. Albano, G.; Evangelisti, C.; Aronica, L.A. Hydrogenolysis of benzyl protected phenols and aniline promoted by supported palladium nanoparticles. ChemistrySelect 2017, 2, 384–388. [Google Scholar] [CrossRef]
  95. Aronica, L.A.; Caporusso, A.M.; Tuci, G.; Evangelisti, C.; Manzoli, M.; Botavina, M.; Martra, G. Palladium nanoparticles supported on Smopex® metal scavengers as catalyst for carbonylative Sonogashira reactions: Synthesis of α,β-alkynyl ketones. Appl. Catal. A 2014, 480, 1–9. [Google Scholar] [CrossRef] [Green Version]
  96. Albano, G.; Interlandi, S.; Evangelisti, C.; Aronica, L.A. Polyvinylpyridine-supported palladium nanoparticles: A valuable catalyst for the synthesis of alkynyl ketones via acyl sonogashira reactions. Catal. Lett. 2020, 150, 652–659. [Google Scholar] [CrossRef]
  97. Evangelisti, C.; Panziera, N.; D’Alessio, A.; Bertinetti, L.; Botavina, M.; Vitulli, G. New monodispersed palladium nanoparticles stabilized by poly-(N-vinyl-2-pyrrolidone): Preparation, structural study and catalytic properties. J. Catal. 2010, 272, 246–252. [Google Scholar] [CrossRef]
  98. Evangelisti, C.; Balerna, A.; Psaro, R.; Fusini, G.; Carpita, A.; Benfatto, M. Characterization of a Poly-4-vinylpyridine- supported cupd bimetallic catalyst for sonogashira coupling reactions. ChemPhysChem 2017, 18, 1921–1928. [Google Scholar] [CrossRef] [PubMed]
  99. Fusini, G.; Rizzo, F.; Angelici, G.; Pitzalis, E.; Evangelisti, C.; Carpita, A. Polyvinylpyridine-supported palladium nanoparticles: An efficient catalyst for suzuki–miyaura coupling reactions. Catalysts 2020, 10, 330. [Google Scholar] [CrossRef] [Green Version]
  100. Oberhauser, W.; Evangelisti, C.; Jumde, R.P.; Petrucci, G.; Bartoli, M.; Frediani, M.; Mannini, M.; Capozzoli, L.; Passaglia, E.; Rosi, L. Palladium-nanoparticles on end-functionalized poly(lactic acid)-based stereocomplexes for the chemoselective cinnamaldehyde hydrogenation: Effect of the end-group. J. Catal. 2015, 330, 187–196. [Google Scholar] [CrossRef]
  101. Borodziński, A.; Bonarowska, M. Relation between crystallite size and dispersion on supported metal catalysts. Langmuir 1997, 13, 5613–5620. [Google Scholar] [CrossRef]
  102. Chai, Z.; Xie, Z.-F.; Liu, X.-Y.; Zhao, G.; Wang, J.-D. Tandem addition/cyclization reaction of organozinc reagents to 2-Alkynyl aldehydes:  Highly efficient regio- and enantioselective synthesis of 1,3-dihydroisobenzofurans and tetrasubstituted furans. J. Org. Chem. 2008, 73, 2947–2950. [Google Scholar] [CrossRef] [PubMed]
  103. Lu, D.; Zhou, Y.; Li, Y.; Yan, S.; Gong, Y. Copper(II)-catalyzed asymmetric henry reaction of o-alkynylbenzaldehydes followed by Gold(I)-mediated cycloisomerization: An enantioselective route to chiral 1H-isochromenes and 1,3-dihydroisobenzofurans. J. Org. Chem. 2011, 76, 8869–8878. [Google Scholar] [CrossRef] [PubMed]
  104. Duan, S.; Cress, K.; Waynant, K.; Ramos-Miranda, E.; Herndon, J.W. Synthesis of alkylidenephthalans through fluoride-induced cyclization of electron-deficient 2-siloxymethylphenylacetylene derivatives. Tetrahedron 2007, 63, 2959–2965. [Google Scholar] [CrossRef] [Green Version]
  105. Danyliuk, I.Y.; Vas’kevich, R.I.; Vas’kevich, A.I.; Vovk, M.V. Hydrogenated benzazepines: Recent advances in the synthesis and study of biological activity. Chem. Heterocycl. Compd. 2019, 55, 802–814. [Google Scholar] [CrossRef]
  106. Kawase, M.; Saito, S.; Motohashi, N. Chemistry and biological activity of new 3-benzazepines. Int. J. Antimicrob. Agents 2000, 14, 193–201. [Google Scholar] [CrossRef]
  107. Hamlin, J.E.; Hirai, K.; Millan, A.; Maitlis, P.M. A Simple Practical Test for Distinguishing a Heterogeneous Component in an Homogeneously Catalysed Reaction. J. Mol. Catal. A Chem. 1980, 7, 543–544. [Google Scholar]
  108. Rizzo, G.; Albano, G.; Lo Presti, M.; Milella, A.; Omenetto, F.G.; Farinola, G.M. Palladium supported on silk fibroin for suzuki–miyaura cross-coupling reactions. Eur. J. Org. Chem. 2020, 2020, 6992–6996. [Google Scholar] [CrossRef]
  109. Evangelisti, C.; Schiavi, E.; Aronica, L.A.; Psaro, R.; Balerna, A.; Martra, G. Solvated metal atoms in the preparation of supported gold catalysts. In Gold Catalysis, Preparation, Characterization, and Applications; Prati, L., Villa, A., Eds.; Jenny Stanford Publishing: New York, NY, USA, 2015; pp. 73–97. [Google Scholar]
Figure 1. Chemical structure of: (a) phthalan; (b) isochroman; (c) isoindoline.
Figure 1. Chemical structure of: (a) phthalan; (b) isochroman; (c) isoindoline.
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Figure 2. Structure of the supports for the Pd NPs used in this work: (a) styril thiol-grafted polyolefin fiber (Smopex®-111); (b) mercaptoethyl acrylate-grafted polyolefin fibers (Smopex®- 234).
Figure 2. Structure of the supports for the Pd NPs used in this work: (a) styril thiol-grafted polyolefin fiber (Smopex®-111); (b) mercaptoethyl acrylate-grafted polyolefin fibers (Smopex®- 234).
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Figure 3. Schematic representation of the MVS approach to obtain supported Pd NPs.
Figure 3. Schematic representation of the MVS approach to obtain supported Pd NPs.
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Figure 4. Representative TEM micrograph and histogram of the particle size distribution of Pd/Smopex®-111 (a) and Pd/Smopex®-234 (b).
Figure 4. Representative TEM micrograph and histogram of the particle size distribution of Pd/Smopex®-111 (a) and Pd/Smopex®-234 (b).
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Table 1. Palladium-promoted synthesis of phthalans via cyclocarbonylative Sonogashira reactions.
Table 1. Palladium-promoted synthesis of phthalans via cyclocarbonylative Sonogashira reactions.
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Entry 11R2RCatalyst 2Pd Loading (mol%)Conversion (%) 33Selectivity (%) 3,4
1aHaHPdCl2(PPh3)20.2100aa65 (68)35 (25)
4aHbo-MePd/Smopex®-2340.2100ab79 (70)21 (18)
5aHco-CNPd/Smopex®-2340.2100ac100 (82)/
6bt-BuaHPdCl2(PPh3)20.228ba22 78
7bt-BuaHPdCl2(PPh3)20.5100ba24 (15)76 (57)
1 The reactions were performed with ortho-ethynylbenzyl alcohol 1 (2 mmol) and iodoarene 2 (2 mmol), in Et3N (5 mL) under CO atmosphere (20 atm), at 100 °C for 24 h. 2 Supported catalysts contain 1% w/w of palladium. 3 Conversion and selectivity were determined by 1H-NMR analysis. 4 In parentheses, the yields of pure products are reported.
Table 2. Palladium-promoted synthesis of isochromans via cyclocarbonylative Sonogashira reactions.
Table 2. Palladium-promoted synthesis of isochromans via cyclocarbonylative Sonogashira reactions.
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Entry 1R2Catalyst 2Yield (%) 3R5
1 The reactions were performed with ortho-ethynylhomobenzyl alcohol 4 (2 mmol) and iodoarene 2 (2 mmol), in Et3N (5 mL), under CO atmosphere (20 atm), and in the presence of 0.2 mol% of Pd, at 100° for 24 h. 2 Pd/Smopex®-234 contains 1% w/w of palladium. 3 The yields of pure products are reported.
Table 3. Palladium-promoted synthesis of N-heterocyclic compounds via cyclocarbonylative Sonogashira reactions.
Table 3. Palladium-promoted synthesis of N-heterocyclic compounds via cyclocarbonylative Sonogashira reactions.
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Entry 1nTosylamideCatalyst 2Pd Loading (mol%)Reaction Time (h)Conversion (%) 3Product 4
116PdCl2(PPh3)20.241008 (75%)
527Pd/Smopex®-2340.424929 (63%) 5
1 The reactions were performed with tosylamide 6 or 7 (2 mmol) and iodobenzene 2a (2.5 mmol), in Et3N (3 mL) and toluene (2 mL), under CO atmosphere (20 atm), at 100 °C. 2 Pd/Smopex®-234 contains 1% w/w of palladium. 3 Conversion was estimated through the 1H-NMR analysis of crude products. 4 The yields of pure products are reported in parentheses. 5 Dihydrobenzazepine 9 was obtained as a mixture of two conformers: s-trans/s-cis (60/40 molar ratio).
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Albano, G.; Evangelisti, C.; Aronica, L.A. Palladium Nanoparticles Supported on Smopex-234® as Valuable Catalysts for the Synthesis of Heterocycles. Catalysts 2021, 11, 706.

AMA Style

Albano G, Evangelisti C, Aronica LA. Palladium Nanoparticles Supported on Smopex-234® as Valuable Catalysts for the Synthesis of Heterocycles. Catalysts. 2021; 11(6):706.

Chicago/Turabian Style

Albano, Gianluigi, Claudio Evangelisti, and Laura Antonella Aronica. 2021. "Palladium Nanoparticles Supported on Smopex-234® as Valuable Catalysts for the Synthesis of Heterocycles" Catalysts 11, no. 6: 706.

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