NTOS 2021

Conference Speakers

Matthias Beller, Leibniz Institute for Catalysis (DE)

Development of Efficient Catalysts for Carbonylation Reactions: From Basic Research to Industrial Applications

The cost-effective and waste-free synthesis of materials, life science goods and all kinds of organic products require efficient chemical transformations. In this regard, development of more active and selective catalysts constitutes a key factor for achieving improved processes and providing the basis for a sustainable chemical industry. Despite continuous advancements in all areas of catalysis, still organic syntheses as well as the industrial production of many chemicals can be improved significantly in terms of sustainability and efficiency. In the talk, the development of a new class palladium catalysts for carbonylation reactions will be shown. Specifically, alkoxycarbonylations of olefins and alcohols applying cooperative catalysis will be addressed. These catalysts not only allow the development of new types of carbonylation reactions, but they also show improved performance in existing industrial processes and permit new applications.

Kasper Moth-Poulsen, Chalmers University of Technology (SE)

Molecular Solar Thermal Energy Storage Systems

In this talk, I will present and discuss our goal to develop new emission free solar energy storage materials. Molecular photoswitches can be used to store solar energy at up to 1 MJ/kg for several years. In this presentation, our efforts in improving molecular photoswitches towards efficient energy storage will be presented. I will discuss new ways to improve solar spectrum match and energy storage time without making compromises on energy storage densities. Moreover, I will present device concepts for lab scale demonstration of solar energy capture as well as heat release devices based on molecular photoswitches that perhaps one day can be used in real life application in solar thermal energy storage.

Phil Baran, Scripps Research Institute (US)

Electrifying Synthesis

Electrochemistry offers new and sustainable means to accomplish enabling reactions for organic synthesis. This presentation will cover some of our latest developments in this area.

Norio Shibata, Nagoya Institute of Technology (JP)

Transformations of Organic Fluorides to Organosilicon Compounds via Selective C-F Bond Activation

In recent years, various organofluorine compounds have become ubiquitous due to the rapid establishment of technologies for their synthesis. There are more than 340 registered fluoro-pharmaceuticals with complex structures and more than 425 registered fluoro-agrochemicals. In addition, it has been estimated that there are more than 8,800,000 commercially available fluoroarenes (SciFinder^®). Thus, the functionalization of organic fluorides via the cleavage/activation of C–F bonds in organic fluorides is a dynamic and emerging area of research that will expand the utility of organofluorine molecules. However, the chemical transformation of fluoro-organic compounds via C–F bond cleavage under very mild conditions is still rare. This presentation will report our recent progress on this topic based on the transformations of organic fluorides to organosilicon compounds via selective C-F bond activation. The key for these transformations is the use of silyl boronates with or without catalyst. Defluorosilylation of organic fluorides and carbosilylation of alkenes silyl boronates and organic fluorides with silyl boronates will be discussed.

Francesca Paradisi, University of Bern (CH)

Harnessing Biocatalysis for Sustainable Synthetic Processes

The rapid evolution of enzyme technology has enabled new reactions and processes with a level of efficiency which was unimaginable only a few years ago. However, to date only a few biocatalysed reactions have been implemented on an industrial level when compared to the vast majority of “traditional” organic methods. Flow chemistry offers a tremendous opportunity to dramatically increase enzymatic performance and bridge the gap from academic explorative research to intensive industrial productivity. Here the steady evolution of flow biocatalysis in our laboratory will be presented, moving towards systems of increasing complexity with combinations of several enzymes, including a breakthrough in the design and implementation of an ultra-efficient zero-waste and closed-loop process with unprecedented atom efficiency and automation.

Massimo Tasselli, SIR Industriale (IT)

Chemistry and Application of Thermo Setting Resins for Industrial Purposes

Synthesis and chemical nature of different thermo setting resins are illustrated with specifics information about polymers composition and cross linking systems, with an overview on the application properties and technical features.

Robert W. Huigens III, University of Florida (US)

Indole Alkaloids and Phenazine Antibiotics as Synthetic Platforms for Discovery

Various natural products, such as taxol, morphine and vancomycin, play a prominent role in medicine due to their ability to modulate biological targets critical to human disease. Our lab has two natural product inspired synthetic medicinal chemistry programs, driven by the structural complexity of indole alkaloids and the function of phenazine antibiotics. These programs aim to address major biomedical problems, including: (1) enhancing the chemical diversity of screening libraries used to drive drug discovery in screening campaigns and (2) the discovery of small molecules capable of targeting and eradicating surface-attached bacterial biofilms. Our first program is focused on rapidly generating diverse and complex compounds, which can be accessed through short synthetic sequences motivated by the dramatic alteration of the inherent complex ring system of indole alkaloids. From these efforts, we have generated a library of >350 complex and diverse small molecules, which are producing an array of interesting hit compounds in diverse disease areas. Our second program is focused on targeting bacterial biofilms, which contain metabolically-dormant persister cells that demonstrate tolerance towards every class of conventional antibiotic available. Biofilms are the underlying cause of chronic and recurring bacterial infections. Our lab has discovered that the marine phenazine antibiotic 2-bromo-1-hydroxyphenazine is a tunable molecular scaffold that provides access to highly potent antibacterial agents that are able to eradicate drug-resistant and antibiotic-tolerant bacterial biofilms.

Manuel Alcarazo, Georg August University of Göttingen (DE)

Synthetic Applications of Cationic Phosphines and Sulfonium Salts

In α-cationic phosphines at least one of the three substituents at phosphorus corresponds to a cationic (normally, but not always heteroaromatic) group, which is attached without any spacer by a relatively inert P-C bond. This unique architecture confers the resulting ligand strong acceptor properties, which frequently surpass those of traditional acceptor ligands such as phosphites or polyfluorinated phosphines. In addition, the fine tuning of the stereoelectronic properties of α-cationic phosphines is also possible by judicious selection of the number and nature of the cationic groups. The opportunities offered in catalysis by α-cationic ligands arise from this ability to deplete electron density from the metals they coordinate. Thus, if in a hypothetical catalytic cycle the step that determines the rate is facilitated by an increase of the Lewis acidity at the metal center then, an acceleration of the whole process is expected by their use as ancillary ligands. Interestingly, this situation is found more frequently than one might think; many common elementary steps involved in catalytic cycles, such as reductive eliminations, coordination of substrates to metals, or the attack of nucleophiles to coordinated substrates, belong to this category and are often fostered by electron poor metal centers. In this regard our group has observed remarkable ligand acceleration effects by the employment of α-cationic phosphines in Au(I) and Pt(II)-promoted hydroarylation and cycloisomerization reactions. These results seem to be general in π-acid catalysis when the nucleophile used is not especially electron rich because their attack to the activated alkene or alkyne is normally rate determining. The application of this concept to the enantioselective synthesis of helicenes will be discussed as well.

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Flash Presentations

First Session (29^th November, 16:45-17.30 UTC+1)

1. Kinetically Controlled Stereoselective Access to Branched 1,3-Dienes by Ru-Catalyzed Remote Conjugative Isomerization

Simone Scaringi, C. Mazet
University of Geneva (CH)

Conjugated dienes are ubiquitous building blocks and their stereoselective synthesis is challenging. We recently reported a Ru-catalyzed long-range conjugative isomerization of remote alkenes that affords branched 1,3-dienes (10.1021/acscatal.1c02144). These kinetic products are obtained in high yields, regio- and stereoselectivity. A broad range of functional groups are compatible. Two one-pot multimetallic selective catalytic sequences are reported underscoring the potential of the method.

2. Catalytic Enantioselective Reduction of Nitroalkenes in DESs

Chiara Faverio, M. Benaglia
University of Milano (IT)

The first organocatalytic reduction involving hydrogen bonding interactions among the substrate, the reagent and the catalyst in deep eutectic solvents was developed. We studied the reduction of β,β-disubstituted nitroalkenes with Hantzsch ester in the presence of thiourea-based chiral catalysts to promote the formation of enantioenriched β-branched nitroalkanes, that was published by List (10.1021/ja074045c), employing DESs as reaction medium instead of traditional organic solvents.

3. Cu(OTf)₂-Mediated Difunctionalization of C3-Synthons en Route to 1-aryl-2-aminopropanes

Camilla Loro, G. Poli, G. Broggini
University of Insubria (IT)

Following our interest toward alkene difunctionalization (10.1021/acs.orglett.0c00010), we have developed a copper-mediated decarboxylative arylation/hydroamination reaction of O-allyl carbamates providing a direct synthesis of N-substituted phenethylamine derivatives. In the presence of Cu(OTf)₂ as additive, O-allyl carbamates behaved as C3-1,2-dication equivalents allowing the generation of 1-aryl-2-aminopropanes through a Friedel-Crafts arylation and an anti-Markovnikov hydroamination pathway.

4. Merging DOS with LSF: a Simple Pathway Towards Constrained Peptidomimetics

Lorenzo Baldini, A. Trabocchi
University of Firenze (IT)

Making a precise nonacidic C-H bond reacting allows to generate a site of functionalization otherwise unexploitable. Many substrates, including amino acids (10.1021%2Facs.orglett.0c02331), have been employed in TM-assisted C-H bond activation reactions (10.1073/pnas.1903048116), exploiting the use of Directing Groups to achieve chemoselectivity. We combined the DOS-compatible Castagnoli-Cushman Reaction with Pd-catalyzed C(sp³)-H bond activation reaction, and we developed a range of heterocyclic arylated peptidomimetics.

5. Chemoenzymatic Stereodivergent Synthesis of all the Stereoisomers of the 2,3-dimethylglyceric Acid Ethyl Ester

Francesco Presini, P.P. Giovannini
University of Ferrara (IT)

The 2,3-dimethylglyceric acid, constitutes the acyl and/or the alcoholic moiety of many bioactive natural esters. We will describe a chemoenzymatic methodology which gives access to all the four possible stereoisomers of the 2,3-dimethylglyceric acid ethyl ester using both NHC/TEMPO-organocatalysts (10.1016/j.tet.2011.08.056) and biocatalysts like Novozymes-435 and acetylacetoin reductase, AAR (10.1002/ejoc.202001542). The entire procedure, allowed to obtain the four enantiopure stereoisomers with overall yields ranging from 20% to 42%.

6. Rieche Formylation of Phenyl Boronic Acids

Alessandro Santarsiere, M. Funicello, P. Lupattelli, L. Chiummiento
University of Basilicata (IT)

The formylation of unsubstituted phenyl boronic acid did not give any reaction while electron-rich aryl boronic acids lead to the regioselective formation of the corresponding ipso-substituted aryl aldehyde when the boron is placed in an activated position, while, when the boron is in a deactivated position, the formation of a formylated boronic acids has been observed, therefore the product obtained retains the boronic functionality. Electron-poor phenyl boronic acids results to be unreactive.

7. Application of Bifunctional Iminophosphorane Organocatalysts in Enantioselective Aza-Henry Reaction

Milena Krstic, M. Benaglia, M. Sanz
University of Milano (IT)

The new family of chiral Brønsted bases, named BIMPs (Bifunctional IMinoPhosphoranes) has shown great efficiency for the synthesis of chiral α-quaternary amino acid building blocks. Herein, we report the asymmetric addition of nitromethane to BOC-protected trifluoromethyl ketimines promoted by iminophosphorane organocatalysts. The products, featuring quaternary stereocenter, were isolated in good yields and high enantioselectivity (10.1021/acs.accounts.0c00369).

8. New Nanoparticles Endowed with Antibiofilm Activity

Arianna Gelain, P. Molino, P. Hayes, S. Villa
University of Milano (IT)

Besides the positive role in the human health, biofilm presence is often associated to the infections. To prevent biofilm formation and the selection of resistant strains, we prepared several functionalized nanoparticles starting from colloidal silica and natural compounds (salicylic and cinnamic acids) derivatives, characterized by a significant antibiofouling properties (10.1080/08927014.2017.1286649 and 10.1371/journal.pone.0131519), aiming to overcome the limits of the available coatings.

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Second Session (30^th November, 14:45-15.30 UTC+1)

9. Functionalization of Cyclic Trimidazole for Optoelectronic and Biological Applications

Daniele Malpicci, E. Lucenti, A. Forni, D. Marinotto, L. Carlucci, C. Giannini, P. Zhang, E. Cariati
University of Milano (IT)

In the present communication we report our recent achievements in the functionalization of the cyclic trimidazole scaffold (C₉H₆N₆, TT, 10.1021/acs.jpclett.7b00503) with various chromophoric groups (10.1002/chem.202102839), to prepare new AIEgens and RTP emitters for both optoelectronic and biological applications.

10. Turning Renewable Feedstocks into a Valuable and Efficient Punctually Chiral Phosphate Salt Catalyst

Achille Antenucci, M. Bella, A. Carlone, S. Dughera, R. Salvio
University of Torino (IT)

The recent assignment of the Nobel Prize for Chemistry to the development of asymmetric organocatalysis is food for thought about the relationship between organocatalysis and green chemistry. Indeed, organocatalysis has not yet reached the level of industrial application of organometallic catalysis and biocatalysis. Indeed, most of the chiral organocatalysts are not designed and synthesized in a sustainable fashion (10.1002/cssc.202100573). On this purpose, one of our recent achievements is the design of a novel recyclable punctually chiral phosphate from natural compounds from the chiral pool and its application in the solventless and room temperature addition of TMSCN to aldehydes (10.1002/ajoc.202100624).

11. Direct, Asymmetric Synthesis of Carbocycle-Fused Uracils via [4+2] Cycloadditions: a Noncovalent Organocatalysis Approach

Enrico Marcantonio, C. Curti, F. Zanardi
University of Parma (IT)

Herein, we report the development of an asymmetric [4+2] cycloaddition between remotely enolizable 6-methyluracil-5-carbaldehydes as vinylogous pronucleophiles and nitroolefins, under the strategic exploitation of a noncovalent bifunctional organocatalysis. A series of functional group-rich rich and chiral carbocycle-fused uracils embedding three contiguous stereocenters were achieved in one step in good yields, with good enantioselectivities and complete diastereocontrol (10.1002/adsc.202100082).

12. Effective Promotion of Proline-Catalyzed Aldol Reaction in Water by Bile Acid Salt Surfactants and their Derivatives

Venanzio Raglione, A. D'Annibale
University of Roma La Sapienza (IT)

Proline-catalysed aldol reaction of aromatic aldehydes with ketones was successfully carried out in water without any cosolvent in presence of catalytic amounts of bile acid salt surfactants and L-Proline bile acid conjugated derivatives. Product yields showed to be generally high. The reaction promoting effect in water exerted by bile acid salts was due to their ability to effectively disperse non polar substrates, thus affording the typical “in presence of water” (10.1002/anie.200603378) reaction conditions.

13. Photocatalytic Redox-Neutral CO₂ Fixation for the Synthesis of Carboxylic Acids

Pietro Franceschi, A. Scopano, A. Vega-Peñaloza, A. Sartorel, L. Dell’Amico
University of Padova (IT)

Utilisation of carbon dioxide (CO₂) for carboxylation of organic compounds is a challenging process of great importance since CO₂ is a sustainable and non-toxic C1 source (10.1002/cssc.201801063). Herein, we report the photoredox carboxylation of 4-benzylic-1,4-dihydropyridines for the synthesis of phenylacetic acids. Mechanistic investigations showed the importance of activating the substrate by deprotonation with a base, and the involvement of benzyl radicals and carbanions in the interception of CO₂.

14. Gold-Catalyzed Hydroarylation of Alkynes: Application for the Synthesis of Coumarins

Pietro Bax
University of Padova (IT)

Gold catalyzed hydroarylation of alkynes has emerged in organic synthesis as a powerful tool to construct complex molecules of practical interest and use. Indeed, alkynes are well known to be activated by gold towards the (intra/intermolecular) external nucleophilic attack. Generally gold(I) and gold(III) species are chosen for the scope, and in this case electron-rich phenols and electron-poor alkynes bearing a carboxylic/ester group are chosen for the synthesis of different coumarin derivatives under mild conditions and in ionic liquids (10.1038/nature05592, 10.1002/ejoc.200801054).

15. Synthesis of Indoles by Reductive Cyclization of o-Nitrostyrenes Using Formate Esters as Efficient CO Surrogates

Manar Ahmed Fouad Abdellatif, F. Ferretti, F. Ragaini
University of Milan (IT)

In 1986, Cenini and co-workers reported the first reductive cyclization reaction of o-nitrostyrenes to indoles using carbon monoxide as the reductant, employing different transition metals as catalysts under forcing conditions (10.1039/C39860000784). In spite of the high efficiency and the high atom-economical character of these reactions, they have not become of widespread use. This might be also due to the need to use pressurized CO. Our group presented alkyl and aryl formates as efficient, powerful, low-toxic and cheap in situ CO-releasers for the reductive cyclization of ortho-nitrostyrenes to indoles using Pd-based catalytic systems (10.1002/ejoc.202100789). Here we report the results of a further optimization that allowed us to improve both selectivity and yield.