Eosin Y: Homogeneous Photocatalytic In-Flow Reactions and Solid-Supported Catalysts for In-Batch Synthetic Transformations
F. Herbrik, P. Camarero González, M. Krstic, A. Puglisi, M. Benaglia, M.A. Sanz, S. Rossi Appl. Sci., 2020, 10, 5596, [Link]
Abstract: In this paper, the most recent and significant applications of Eosin Y as an organo-photocatalyst will be discussed, focusing the attention on enabling technological aspects in homogeneous photochemical flow reactions, as well as on recent developments in solid-supported catalyst applications for batch synthetic transformations.
Solid supported chiral N-picolylimidazolidinones: recyclable catalysts for the enantioselective, metal- and H2-free reduction of imines in batch and in flow mode
R. Porta, M. Benaglia, R. Annunziata, A. Puglisi, G. Celentano Adv. Synth. Catal, 2017, 359, doi:10.1002/adsc.201700376 [Link]
Abstract: A new class of solid supported chiral imidazolidinones organocatalysts for the catalytic reduction of imines with trichlorosilane was developed. Polystyrene proved to be a more effective support than silica in terms of both chemical and stereochemical efficiency. Even with a loading as low as 1 mol % the best performing supported catalyst showed a remarkable activity and stereocontrol ability, promoting the reduction with stereoselectivities reaching 98% e.e. and in most cases ranging between 90-95% e.e. The general scope of the methodology and the good recyclability of the immobilized catalyst were demonstrated. The polystyrene-anchored chiral catalyst was also used to prepare packed bed reactors for the continuous flow synthesis of chiral amines, that were obtained in excellent yields and enantioselectivities. By exploiting the chiral organocatalytic reactor, the in-flow stereoselective synthesis of a common, immediate precursor of rivastigmine, of the calciomimetic (R)-NPS 568 and of Acrylamide (S)-A, currently under study for the treatment of neuropathic pain, was successfully accomplished.
Stereoselective Reduction of Imines with Trichlorosilane using Solid-Supported Chiral Picolinamides
S. D. Fernandes, R. Porta, P. C. Barrulas, A. Puglisi, A. J. Burke, M. Benaglia Molecules, 2016, 21, (9), 1490-1499. [Link]
Abstract: The stereoselective reduction of imines with trichlorosilane catalyzed by chiral Lewis bases is a well-established procedure for the synthesis of enantio-enriched amines. Five supported cinchona-based picolinamides have been prepared and their activity tested in a model reaction. The comparison of different supporting materials revealed that polystyrene gave better results than silica in terms of stereoselectivity. The applicability of the solid-supported catalyst of choice to the reduction of different imines was also demonstrated. Additionally, for the first time a catalytic reactor containing a polymer-immobilized chiral picolinamide has been employed for the stereoselective reduction of imines with trichlorosilane under continuous flow conditions.
Comparison of Different Polymer- and Silica-Supported 9-Amino-9-deoxy-epi-quinines as Recyclable Organocatalysts.
R. Porta, F. Coccia, R. Annunziata and A. Puglisi, ChemCatChem, 2015, 7, 1490-1499. [Link]
Abstract:9-Amino-9-deoxy-epi-quinine, properly modified by suitable linkers, was anchored on highly cross-linked polystyrene, poly(ethylene glycol), and silica. The resulting species were characterized by NMR spectroscopy and tested as supported organocatalysts in the reaction between isobutyric aldehyde and trans-߭nitrostyrene. Polystyrene- and poly(ethylene glycol)-supported catalysts outperformed their nonsupported counterpart affording the desired product in high yield and ee (>90% ee). Silica-supported catalysts proved to be less efficient in terms of both chemical yield and enantioselectivity. Polystyrene- and poly(ethylene glycol)-supported 9-amino-9-deoxy-epi-quinine were then used in the same reaction with different substrates, leading to the desired products in high yield and ee, as well as in three other reactions operating with different mechanism. An investigation of the recyclability of the polystyrene- and poly(ethylene glycol)-supported systems showed that these could be recovered and recycled with no loss of stereochemical activity but with a marked erosion of chemical efficiency occurring at the fifth reaction cycle. This was ascribed to chemical degradation of the alkaloid occurring during the reaction.
Chiral Hybrid Inorganic - Organic Materials: Synthesis, Characterization, and Application in Stereoselective Organocatalytic Cycloadditions.
A. Puglisi, M. Benaglia, R. Annunziata, V. Chiroli, R. Porta, A. Gervasini J. Org. Chem., 2013, 78, 11326-11334. [Link]
Abstract: The synthesis of chiral imidazolidinones on mesoporous silica nanoparticles, exploiting two different anchoring sites and two different linkers, is reported. Catalysts 1-4 were prepared starting from L-phenylalanine or L-tyrosine methyl esters and supporting the imidazolidinone onto silica by grafting protocols or azide-alkyne copper(I)-catalyzed cycloaddition. The four catalysts were fully characterized by solid-state NMR, N2 physisorption, SEM,and TGA in order to provide structural assessments, including an evaluation of surface areas, pore dimensions, and catalyst loading. They were used in organocatalyzed Diels-Alder cycloadditions between cyclopentadiene and different aldehydes, affording results comparable to those obtained with the nonsupported catalyst (up to 91% yield and 92% ee in the model reaction between cyclopentadiene and cinnamic aldehyde). The catalysts were recovered from the reaction mixture by simple filtration or centrifugation. The most active catalyst was recycled two times with some loss of catalytic efficiency and a small erosion of ee.
Magnetic nanoparticles conjugated to chiral imidazolidinone as recoverable catalyst.
S. Mondini, A. Puglisi, M. Benaglia, D. Ramella, C. Drago, A. M. Ferretti, A. Ponti, Journal of Nanoparticle Research, 2013, 15, 2025-2036. [Link]
Abstract: The immobilization of an ad hoc designed chiral imidazolidin-4-one onto iron oxide magnetic nanoparticles (MNPs) is described, to afford MNPsupported MacMillan's catalyst. Morphological and structural analysis of the materials, during preparation, use, and recycle, has been carried out by transmission electron microscopy. The supported catalyst was tested in the Diels-Alder reaction of cyclopentadiene with cinnamic aldehyde, affording the products in good yields and enantiomeric excesses up to 93%, comparable to those observed with the non-supported catalyst. Recovery of the chiral catalyst has been successfully performed by simply applying an external magnet to achieve a perfect separation of the MNPs from the reaction product. The recycle of the catalytic system has been also investigated. Noteworthy, this immobilized MacMillan's catalyst proved to be able to efficiently promote the reaction in pure water.
Synthesis and catalytic activity of fluorous chiral primary amine-thioureas.
S. Orlandi, G. Pozzi, M. Ghisetti, M. Benaglia, New J. Chem., 2013, 37, 4140-4147. [Link]
Abstract: Three enantiopure fluorous thioureas featuring a free H2 group were synthesized by direct addition of aromatic isothiocyanates bearing a single n-C8F17 substituent in the ortho, meta and para position, respectively, to enantiopure (1R,2R)-1,2-diaminocyclohexane. The catalytic behavior of these bifunctional molecules was assessed in representative Michael-type reactions. The three fluorous thioureas performed similarly in all the reactions tested, thus showing that the position of the fluorous ponytail does not have a major influence on the catalytic behavior of this class of compounds. In particular, excellent enantioselectivities (up to 99% ee) and yields (up to 98%) were obtained for the addition of aliphatic aldehydes to maleimides to give a-substituted succinimides. Recyclability of these primary amine-based thioureas was found to be limited by the concurrent formation of imine-derivatives during the catalytic process, leading to a structural modification of the organic catalyst.
Immobilization of Chiral Bifunctional Organocatalysts on Poly(methylhydrosiloxane).
A. Puglisi, M. Benaglia, R. Annunziata, J. S. Siegel, Chem. Cat. Chem., 2012, 48, 3188-3190. [Link]
Abstract: Takemoto promotes: Enantiomerically pure bifunctional chiral catalysts are immobilized on poly(methylhydrosiloxane). A supported Takemoto-type catalyst promoted the diethyl malonate addition to nitrostyrene in fair to good yields and up to 83% ee, and its recyclability is demonstrated.
Hybrid inorganic-organic materials carrying tertiary amine and thiourea residues tethered on mesoporous silica nanoparticles: synthesis, characterization and cooperative catalysis.
A. Puglisi, R. Annunziata, M. Benaglia, F. Cozzi, A. Gervasini, V. Bertacche, M. C. Sala, Adv. Synth. Catal., 2009, 351, 219-229. [Link]
Abstract: Mesoporous silica nanoparticles carrying different loadings of tertiary amine and thiourea residues (residues ratios 53/47, 68/32, and 22/78, respectively) were synthesized by the co-condensation method and fully characterized by CP MAS NMR, powder XRD, SEM, BET, BJH and FT-IR techniques. These materials were tested as bifunctional catalysts in the conjugate addition of acetylacetone to 2-nitrostyrene, a reaction that under solvent-free conditions occurred in quantitative yield. By carrying out several experiments with the bifunctional catalysts featuring different molar ratios of active sites, and with different combinations of monofunctional supported and non-supported catalyst, the co-operativity of the tertiary amine and thiourea residues in catalyzing the reaction was demonstrated. The use of the bifunctional catalyst was extended to the addition of acetylacetone to an activated imine. Catalyst recycling for a total of three reaction cycles was demonstrated without significant erosion of activity.
Book chapter: Recoverable organic catalysts
M. Benaglia,ed. John Wiley and Sons, Recoverable and Recyclable Catalysts, 2009 [Link]