1. Sordello, F., Emanuele Azzi, E., Pellegrino, F., Deagostino, A., Renzi, P.,* Metal Centers Drive Selectivity of Electrocatalytic Oxygen Reduction Reaction Promoted by Tetrapyrazinoporphyrazine Complexes, Adv. Sustainable Syst. 2025, 9, 2400373.

https://onlinelibrary.wiley.com/doi/full/10.1002/adsu.202400373

Abstract: Fuel cells represent a promising technology for the future decarbonization of the mobility sector. However, the efficient use of H₂ and O₂ to produce electricity still requires noble metal catalysts such as platinum and ruthenium. In particular, the Oxygen Reduction Reaction (ORR) is complex and limiting due to its mechanism, which involves the transfer of four electrons and four protons to produce water. The search for alternative catalysts exhibiting high selectivity is progressing at a rapid pace. In this context, this group previously unveiled a homogeneous catalyst based on titanium-centered tetrapyrazinoporphyrazines (TPyzPz) for the ORR, noting a certain modularity in the selectivity toward either a two- or four-electron reduction reaction. In this study, the influence of different metal centers (magnesium (Mg), cobalt (Co), copper (Cu), and zinc (Zn)) and various substituents is investigated on the tetrapyrazinoporphyrazine ring. The findings indicate a strong dependence of activity and selectivity on these modifications. Notably, cobalt and copper catalysts exhibit a selectivity greater than 90% toward H₂O production in the ORR. However, alterations to the macrocycle structure significantly affected the reactivity of these catalysts. These new insights highlighted the importance of careful structural design in the development of the next generation of ORR catalysts.

 

1. Scarfiello, J., Caracciolo, S., Rusconi, M., Lanfranco, A., Azzi, E., Ghigo, G., Renzi, P.,* Deagostino, A., Catalyst-free Chloroamination Cyclization Cascade with Sodium Hypochlorite: from N‑(Pentenyl)sulfonylamides to 2‑(1-Chloromethyl)pyrrolidines, Eur. J. Org. Chem. 2024, 21, e202400108. Special Collection New Generation Methodologies in Organic Chemistry: A Focus on Italy.

https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/ejoc.202400108

Abstract: A mild and catalyst-free protocol to obtain several 2-chloromethylpyrrolidines by the use of a commercial solution of sodium hypochlorite is here reported, without the need for a light source. The choice of the solvent revealed to be crucial in the success of the reaction. Mechanistic studies, both experimental and computational, confirmed a radical mechanism, where the deprotonation step, followed by the oxidation of a N-centered anion to the corresponding radical, allowed 2-chloromethylpyrrolidines, by a very fast cyclization, to be obtained. Sodium hypochlorite plays the role of both the oxidant and the chlorine source.

 

1. Lanfranco, A., Rakhshan, S., Alberti, D., Renzi, P.,. Zarechian, A., Protti, N., Altieri, S.,^. Geninatti Crich, S.,* Deagostino, A.,* Combining BNCT with Carbonic Anhydrase Inhibition for Mesothelioma Treatment: Synthesis, In-vitro, and In-vivo Studies of Ureidosulfamido ortho-Carborane, Eur. J. Med. Chem. 2024, 270, 116334

https://www.sciencedirect.com/science/article/pii/S0223523424002149?via%...

Abstract: Mesothelioma is a malignant neoplasm of mesothelial cells caused by exposure to asbestos. The average survival time after diagnosis is usually nine/twelve months. A multi-therapeutic approach is therefore required to treat and prevent recurrence. Boronated derivatives containing a carborane cage, a sulfamido group and an ureido functionality (CA-USF) have been designed, synthesised and tested, in order to couple Boron Neutron Capture Therapy (BNCT) and the inhibition of Carbonic Anhydrases (CAs), which are overexpressed in many tumours. In vitro studies showed greater inhibition than the reference drug acetazolamide (AZ). To increase solubility in aqueous media, CA-USFs were used as inclusion complexes of hydroxypropyl β-cyclodextrin (HP-β-CD) in all the inhibition and cell experiments. BNCT experiments carried out on AB22 (murine mesothelioma) cell lines showed a marked inhibition of cell proliferation by CA-USFs, and in one case a complete inhibition of proliferation twenty days after neutron irradiation. Finally, in vivo neutron irradiation experiments on a mouse model of mesothelioma demonstrated the efficiency of combining CA IX inhibition and BNCT treatment. Indeed, a greater reduction in tumour mass was observed in treated mice compared to untreated mice, with a significant higher effect when combined with BNCT. For in vivo experiments CA-USFs were administered as inclusion complexes of higher molecular weight β-CD polymers thus increasing the selective extravasation into tumour tissue and reducing clearance. In this way, boron uptake was maximised and CA-USFs demonstrated to be in vivo well tolerated at a therapeutic dose. The therapeutic strategy herein described could be expanded to other cancers with increased CA IX activity, such as melanoma, glioma, and breast cancer.

 

1. Renzi, P.,* Rusconi, M., Ghigo, G., Deagostino, A. Purple-Light Promoted Thiol-ene Reaction of Alkenes, Adv. Synth. Catal. 2023, 365, 4623. Featured in Org. Chem. Highlights 2024, May 27.

https://onlinelibrary.wiley.com/doi/10.1002/adsc.202300990

Abstract: Here we present a catalyst-free protocol for the purple light-mediated anti-Markovnikov functionalization of alkenes with thiols. Crucial to the generation of the thiyl radical was the formation of a key photo-active complex. More than 30 thioether products were obtained, demonstrating tolerance towards different functional groups and scalability up to 5 mmol of alkene. Two different reaction conditions have been developed, varying both the solvent and the amount of thiol. Depending on the alkene structure, water can be used as an alternative to dichloromethane as a solvent, thus increasing the sustainability of the whole process.

 

1. Lanfranco, A., Renzi, P., Rusconi, M., Deagostino, A., Carboranes meet photochemistry: Recent progresses in light-mediated cage functionalisation, Tetrahedron Lett. 2023, 131, 154782

https://www.sciencedirect.com/science/article/pii/S0040403923004926

Abstract: Carboranes are intriguing structures which show an excellent in vivo stability and high chemical versatility. Furthermore, thanks to their structural and electronic properties they find many applications in several fields, as smart materials, bioisosters of aryl rings in knows drugs and BNCT (Boron Neutron Capture Therapy) agents, for example. Recently, the reactivity of these boron rich icosahedral cages, promoted by UV–visible light, has encountered the interest of some research groups, which described new pathways based on the formation of B- and C-centred radicals. In these way, properly functionalised carboranes have been prepared, increasing the applications of these precious moieties.

1. Renzi, P.,* Scarfiello, J., Lanfranco, A., Deagostino, A., Light-Induced Domino and Multicomponent Reactions: How to Reach Molecular Complexity without a Catalyst, Eur. J. Org. Chem. 2023, 26, e202300713

https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/ejoc.202300713

Abstract: Achieving high molecular complexity can be not trivial, but the exploitation of domino reactions provides an atom- and step-economical method to reach this target. Over the past decades, a lot of efforts have been put on the development of photocatalytic cascades employing both metal-based and purely organic catalysts. Despite the effectiveness of these protocols, catalyst- and additive-free light-induced domino reactions are gaining momentum thank to their efficiency, operational simplicity and sustainability. The increasing number of papers published on this field in the last years is a proof of the appeal of these transformations. In this Review, we discuss domino and multicomponent reactions mediated by light with a focus on photocatalyst- and additive-free processes. The most recent advances in the synthesis of complex nitrogen-, oxygen-, sulphur- and selenium-heterocycles together with multicomponent cascades are analysed with an emphasis on both experimental and mechanistic studies.

 

1. Sordello, F., Prantsidou Georgiadou, P., Azzi, E., Tschauder, Y., Pellegrino, F., Formenti, D., Renzi, P.,* Electrocatalytic oxygen reduction reaction promoted by titanium-based tetrapyrazinoporphyrazines, Appl. Organomet. Chem., 2023, e7116

             https://onlinelibrary.wiley.com/doi/full/10.1002/aoc.7116

 

Abstract: In this study, we unveiled titanium-based tetrapyrazinoporphyrazines as a valuable alternative to noble metals in the oxygen reduction reaction (ORR). By simply modifying the synthetic conditions, we were able to tune the ORR selectivity while showing that the introduction of substituents on the macrocycle periphery is detrimental to the ability of the complex to reduce molecular oxygen. A complete electrochemical characterization in different conditions is reported together with rotating ring-disk electrode measurements, which assessed the possibility of selectively switching from 2- to a 4-electron reduction product changing the titanium precursor amounts during the complex synthesis.

1. Renzi, P., Ascensio, A., Azzi, E., Parisotto, S., Sordello, F., Pellegrino, F., Ghigo, G., Deagostino, A., Unveiling the Synthetic Potential of Inexpensive and Bench Stable Diarylmethylium Tetrafluoroborates in the Light Mediated Hydrosulfonylation of Alkenes, Chem. Sci. 2023, 14, 2721

https://pubs.rsc.org/en/content/articlelanding/2023/sc/d3sc00182b

Abstract: In this paper, we present the synthetic potential of diarylmethylium tetrafluoroborates as catalysts for the visible light promoted hydrosulfonylation of unactivated alkenes. For the first time, these salts, which are bench stable and easily preparable on a multi-gram scale, were employed as organocatalysts. Interestingly, a catalyst loading of only 1 mol% allowed sulfone products to be efficiently obtained from good-to-excellent yields with high functional-group tolerance and scalability up to 15 mmol of alkene. The mechanistic study, both experimental and computational, presented here, revealed an alternative mechanism for the formation of the key sulfonyl radical. Indeed, the photoactive species was proved not to be the diarylcarbenium salt itself, but two intermediates, a stable S–C adduct and an ion couple, that were formed after its interaction with sodium benzenesulfinate. Upon absorbing light, the ion couple could reach an excited state with a charge-transfer character which gave the fundamental sulfonyl radical. A PCET (proton-coupled electron transfer) closes the catalytic cycle reforming the diarylcarbenium salt.

 

1. Sforzi, J., Lanfranco, A., Stefania, R. Alberti, D., Bitonto, V., Parisotto, S., Renzi, P., Protti, N., Altieri, S., Deagostino, A., Geninatti Crich, S., A novel pH sensitive theranostic PLGA nanoparticle for Boron Neutron Capture Therapy in Mesothelioma treatment, Scientific Reports 2023, 13 (1), 620

https://www.nature.com/articles/s41598-023-27625-0

Abstract: This study aims to develop poly lactic-co-glycolic acid (PLGA) nanoparticles with an innovative imaging-guided approach based on Boron Neutron Capture Therapy for the treatment of mesothelioma. The herein-reported results demonstrate that PLGA nanoparticles incorporating oligo-histidine chains and the dual Gd/B theranostic agent AT101 can successfully be exploited to deliver a therapeutic dose of boron to mesothelioma cells, significantly higher than in healthy mesothelial cells as assessed by ICP-MS and MRI. The selective release is pH responsive taking advantage of the slightly acidic pH of the tumour extracellular environment and triggered by the protonation of imidazole groups of histidine. After irradiation with thermal neutrons, tumoral and healthy cells survival and clonogenic ability were evaluated. Obtained results appear very promising, providing patients affected by this rare disease with an improved therapeutic option, exploiting PLGA nanoparticles.

 

1. Azzi, E., Ghigo, G., Sarasino, L., Parisotto, S., Moro, R., Renzi, P.,* Deagostino, A., Photoinduced Chloroamination Cyclization Cascade with N-Chlorosuccinimide: from N-(Allenyl)sulfonylamides to 2-(1-Chlorovinyl)pyrrolidines, J. Org. Chem. 2023, 88, 6420. JOC Special Issue Progress in Photocatalysis for Organic Chemistry

https://pubs.acs.org/doi/10.1021/acs.joc.2c01963

Abstract: Here, we present an intriguing photoinduced chloroamination cyclization of allenes bearing a tethered sulfonylamido group to afford 2-(1-chlorovinyl)pyrrolidines and related heterocycles in the presence of N-chlorosuccinimide (NCS) as the chlorine source. An in depth experimental and computational mechanistic study revealed the existence of multiple reaction pathways leading to a common nitrogen centered radical (NCR). This key NCR can be, in fact, originated from (a) the oxidation of the deprotonated allene by the photoexcited state of the Ru-catalyst and (b) the photodissociation of the in situ formed N-chloroallene. The NCR formation triggers an intramolecular cyclization to a highly reactive pyrrolidine vinyl radical, which upon chlorination delivers the final product. Thus, NCS plays a dual role, serving both as an activator of the sulfonamido functionality and as the chlorinating agent.

 

1. Lanfranco, A., Alberti, D., Parisotto, S., Renzi, P., Lecomte, V., Geninatti-Crich, S., Deagostino, A., Biotinylation of a MRI/Gd BNCT Theranostic Agent to Access a Novel Tumor-Targeted Delivery System, Org. Biomol. Chem. 2022, 20, 5342

https://pubs.rsc.org/en/content/articlelanding/2022/ob/d2ob00764a

Abstract: A new biotin based BNCT (Boron Neutron Capture Therapy)-MRI theranostic is here reported (Gd-AL01) in order to exploit the high tumour specificity of biotin and the selectivity of BNCT in a synergistic manner. The key is the preparation of an intermediate where an o-carborane is linked to two amino groups orthogonally protected via the exploitation of two consecutive Mitsunobu reactions. The aim is its functionalisation in two different steps with biotin as the biological vector and Gd-DOTA as the MRI probe and GdNCT agent. Cell uptake was evaluated on HeLa tumour cells overexpressing biotin receptors. The internalised boron is proportional to the concentration of the theranostic agent incubated in the presence of cells. A maximum value of 77 ppm is reached and a well detectable signal intensity increase in the T₁ weighted image of HeLa cells was observed, differently from clinically used GdHPDO3A, where no contrast is detected. These excellent results indicate that Gd-AL01 can be applied as a theranostic probe in BNCT studies.

 

1. Parisotto, S., Azzi, E., Lanfranco, A., Renzi, P., Deagostino, A., Recent Progresses in the Preparation of Chlorinated Molecules: Electrocatalysis and Photoredox Catalysis in the Spotlight, Reactions 2022, 3 (2), 233

https://www.mdpi.com/2624-781X/3/2/18

Abstract: Among halogenated molecules, those containing chlorine atoms are fundamental in many areas such as pharmaceuticals, polymers, agrochemicals and natural metabolites. Despite the fact that many reactions have been developed to install chlorine on organic molecules, most of them rely on toxic and hazardous chlorinating reagents as well as harsh conditions. In an attempt to move towards more sustainable approaches, photoredox catalysis and electrocatalysis have emerged as powerful alternatives to traditional methods. In this review, we collect the most recent and significant examples of visible-light- or current-mediated chlorination published in the last five years.

 

1. Renzi, P., Azzi, E., Bessone, E., Ghigo, G., Parisotto, S., Pellegrino, F., Deagostino, A., Blue light enhanced Heck arylation at room temperature applied to allenes, Org. Chem. Front., 2022, 9, 906; (cover picture)

https://pubs-rsc-org.bibliopass.unito.it/en/content/articlelanding/2022/...

Abstract: An unprecedented visible light enhanced room temperature Heck reaction between aryl halides and allenyl tosyl amines is here reported. A simple catalytic system (Pd(OAc)₂/PPh₃) is employed to afford arylated vinyl pyrrolidines and piperidines. A broad scope with high tolerance towards functional groups is observed. Electronic effects play an important role in the efficiency of this process. Mechanistic studies, both experimental and computational, indicate no evidence for a radical mechanism and a pivotal role of light in promoting the carbo-palladation step.

 

1. Azzi, E., Lanfranco, A., Moro, R., Deagostino, A., Renzi, P.,* Visible Light as the Key for the Formation of Carbon–Sulfur Bonds in Sulfones, Thioethers, and Sulfonamides: An Update, Synthesis (Germany), 2021, 53 (19), 3440

https://www-thieme-connect-de.bibliopass.unito.it/products/ejournals/abs...

Abstract: This review summarizes the most relevant advancements made in the photocatalyzed synthesis of sulfones, thioethers, and sulfonamides from 2017 to the beginning of 2021. Synthetic strategies towards the construction of sulfur–carbon bonds are discussed together with the proposed reaction mechanisms. Interestingly, sulfur-based functional groups, which are of fundamental importance for the pharmaceutical field, can be assembled by photocatalysis in an easy and straightforward way under milder reaction conditions employing less toxic and expensive sulfur sources in comparison with common strategies.

 

1. Lanfranco, A., Moro, R., Azzi, E., Deagostino, A., Renzi, P.,* Unconventional approaches for the introduction of sulfur-based functional groups, Org. Biomol. Chem., 2021, 19 (32), 6926

https://pubs-rsc-org.bibliopass.unito.it/en/content/articlelanding/2021/...

Abstract: Organosulfur compounds have a pivotal role in the functionalities of many natural products, pharmaceuticals and organic materials. For these reasons, the search for new methodologies for the formation of carbon–sulfur bonds has been the object of intensive work for organic chemists. However, the proposed strategies suffer from various drawbacks, such as volatility, toxicity, and instability of the sulfur sources or the use of VOC solvents. In this review, we summarise the recent protocols which have the goal of obtaining sulfones, thioethers, thiazines, thiazepines and sulfonamides in an unconventional and/or sustainable way. The use of starting materials less invasive and toxic with respect to the traditional reagents, alternative solvents such as water, ionic liquids or deep eutectic solvents, the exploitation of ultrasound and electrochemistry, increasing the efficiency of the process, are reported. Moreover, representative reaction mechanisms are also discussed.

 

1. Antenucci, A., Dughera, S., Renzi, P.,* Green Chemistry Meets Asymmetric Organocatalysis: A Critical Overview on Catalysts Synthesis, ChemSusChem, 2021, 14 (14), 2785

https://chemistry-europe-onlinelibrary-wiley-com.bibliopass.unito.it/doi...

Abstract: Can green chemistry be the right reading key to let organocatalyst design take a step forward towards sustainable catalysis? What if the intriguing chemistry promoted by more engineered organocatalysts was carried on by using renewable and naturally occurring molecular scaffolds, or at least synthetic catalysts more respectful towards the principles of green chemistry? Within the frame of these questions, this Review will tackle the most commonly occurring organic chiral catalysts from the perspective of their synthesis rather than their employment in chemical methodologies or processes. A classification of the catalyst scaffolds based on their E factor will be provided, and the global E factor (E_G factor) will be proposed as a new green chemistry metric to consider, also, the synthetic route to the catalyst within a given organocatalytic process.

 

1. Azzi, E., Ghigo, G., Parisotto, S., Pellegrino, F., Priola, E., Renzi, P., Deagostino, A., Visible Light Mediated Photocatalytic N-Radical Cascade Reactivity of γ,δ-Unsaturated N Arylsulfonylhydrazones: A General Approach to Structurally Diverse Tetrahydropyridazines, J. Org. Chem., 2021, 86, 3300

https://pubs-acs-org.bibliopass.unito.it/doi/abs/10.1021/acs.joc.0c02605

Abstract: Tetrahydropyridazines are of particular interest for their versatility as intermediates in organic synthesis and display pharmacological activity in several domains. Here, we describe the photocatalytic synthesis of different tetrahydropyridazines starting from γ,δ-unsaturated N-arylsulfonylhydrazones. Simple structural changes of substrates result into three different pathways beginning from a common N-hydrazonyl radical, which evolves through a domino carboamination/dearomatization, a HAT process, or a photoinduced radical Smiles rearrangement to afford diverse tetrahydropyridazines. All reactions are carried out in very mild conditions, and the quite inexpensive Cl₂ is used as the catalyst. Preliminary mechanism studies are presented, among them luminescence and electrochemical characterization of the involved species. Computational studies allow to rationalize the mechanism in accord with the experimental findings.

 

1. Renzi, P.,* Mazzapioda, L., Nardelli, F., Martini, F., Geppi, M., Mancone, C., Navarra, M. A., D'Acunzo, F., Gentili, P., Titanium-Based Tetrakis-2,3--porphyrazine: Synthesis and Characterization, Eur. J. Inorg. Chem. 2020, 2020 (25), 2417

https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/ejic.202000193

Abstract: Tetrapyrazinoporphyrazine (TPysPz) ligands and metal complexes find, generally, application as electronic materials and catalysts. Considering the limited application of Titanium (Ti), we prepared and characterized a family of ligands and Ti-based complexes of tetrakis-2,3-porphyrazine (R = H, 2-Py, Ph). UV/Vis measurements in different solvents confirm molecular aggregation, which results more pronounced in the presence of 2-pyridil and phenyl substituents on the macrocycle edge. Because of low solubility, solid state NMR was applied for structure characterization. Additional IR and MALDI-TOF were carried out to complete the characterization. Cyclic voltammetry in DMSO/Bu₄NBF₄ 0.1 m unveiled that our Ti complexes can take part in up to five redox events. The first two quasi-reversible reductions involve Ti(IV), whereas the further to or three occur at the expense of the TPysPz macrocycle. To test the applicability of our compounds as catalytic materials, we performed a preliminary cyclic voltammetry investigation in the solid-state, which showed typical peaks of hydrogen redox reactions.

 

1. D’Acunzo, F., De Santis, S., Masci, G., Nardi, M., Renzi, P., Sobolov, A., A remarkably large phase-transition effect in a random copolymer of OEGMA500 induced by the photochemistry of the 2-(hydroxyimino)aldehyde group, Macromol. Chem. Phys. 2019, 220, 1900200

https://onlinelibrary.wiley.com/doi/10.1002/macp.201900200

Abstract: The effect of UV irradiation on the cloud points (CP) of aqueous solutions of a random 1:1 copolymer of oligo(ethylene glycol) methyl ether methacrylate (OEGMA₅₀₀) and a 2-(hydroxyimino)aldehyde (HIA) functionalized methacrylate is presented. CPs are determined by visible spectroscopy and dynamic light scattering (DLS). ¹H and ¹³C NMR experiments are carried out in D₂O and DMSO-d₆ on the polymer and on an HIA-functionalized model of the photoresponsive repeat unit. UV-irradiated solutions exhibit an unprecedented increase of the phase-separation temperature for an OEGMA photoresponsive copolymer (10–22 °C, depending on concentration and irradiation conditions). Phase separation is reversible with little hysteresis. With both pristine and irradiated polymer solutions, aggregate dimensions are <10 nm (DLS) at room temperature. Aggregates of >100 nm form at the CP and gradually grow as temperature increases, whereas the light-induced processes of the repeat unit model in DMSO-d₆ are well identified (e.g., oxime E/Z isomerization and Norrish-Yang cyclization of the aldehyde moiety), it is not straightforward to extrapolate such behavior to the polymeric solution in water. The remarkably large phototriggered thermal effect in the present work motivates further investigations on the solvent-dependent photochemistry of HIA as a promising functional group for the synthesis of multi-stimuli responsive materials.

 

1. Streitferdt, V., Haindl, M. H., Hioe, J., Morana, F., Renzi, P., Rekowski, F. v. R., Zimmermann, A., Nardi, M., Zeitler, K., Gschwind, R. M., Unprecedented Mechanism of an Organocatalytic Route to Conjugated Enynes with a Junction to Cyclic Nitronates, Eur. J. Org. Chem. 2019, 2, 328; (cover picture)

           https://onlinelibrary.wiley.com/doi/full/10.1002/ejoc.201801153

            Abstract: Conjugated enynes as well as cyclic nitronates are crucial building blocks for numerous natural products and pharmaceuticals. However, so far, no common and metal-free synthetic route to both conjugated enynes and cyclic nitronates has been reported. Herein, in situ NMR, labelling studies and theoretical calculations were combined to investigate the mechanism of the unusual triple bond formation towards conjugated enynes. Starting from nitroalkene dimers, first an isoxazolidine-2,5-diol derivative is formed as central intermediate. From this, enynes were generated by a combination of oxidation, dehydration, and retro 1,3-dipolar cycloaddition, whereas for nitronates a base induced intramolecular reorganization is proposed. While the product distribution could be controlled and high yields of nitronate were achieved, only medium to good yields for enynes were obtained due to polymerization losses. Nevertheless, we hope that these mechanistic investigations may provide a basis for further developments of organocatalytic or metal-free preparations of conjugated enynes and nitronates.

 

1. Bella, F., Renzi, P., Cavallo, C., Gerbaldi, C., Caesium for perovskite solar cells: an overview, Chem. Eur. J. 2018, 24, 12183; (Special Issue: Young Chemists 2018, cover picture)

https://doi.org/10.1002/chem.201801096

Abstract: Perovskite solar cells have the potential to revolutionize the world of photovoltaics, and their efficiency close to 23 % on a lab-scale recently certified this novel technology as the one with the most rapidly raising performance per year in the whole story of solar cells. With the aim of improving stability, reproducibility and spectral properties of the devices, in the last three years the scientific community strongly focused on Cs-doping for hybrid (typically, organolead) perovskites. In parallel, to further contrast hygroscopicity and reach thermal stability, research has also been carried out to achieve the development of all-inorganic perovskites based on caesium, the performances of which are rapidly increasing. The potential of caesium is further strengthened when it is used as a modifying agent of charge-carrier layers in solar cells, but also for the preparation of perovskites with peculiar optoelectronic properties for unconventional applications (e.g., in LEDs, photodetectors, sensors, etc.). This Review offers a 360-degree overview on how caesium can strongly tune the properties and performance of perovskites and relative perovskite-based devices.

 

1. Renzi, P., Hioe, J., Gschwind, R. M., Enamine/Dienamine and Brønsted Acid Catalysis: elusive intermediates, reaction mechanisms and stereoinduction modes based on in situ NMR spectroscopy & computational study, Acc. Chem. Res. 2017, 50, 2936

http://pubs.acs.org/doi/10.1021/acs.accounts.7b00320

Abstract: Over the years, the field of enantioselective organocatalysis has seen unparalleled growth in the development of novel synthetic applications with respect to mechanistic investigations. Reaction optimization appeared to be rather empirical than rational. This offset between synthetic development and mechanistic understanding was and is generally due to the difficulties in detecting reactive intermediates and the inability to experimentally evaluate transition states. Thus, the first key point for mechanistic studies is detecting elusive intermediates and characterizing them in terms of their structure, stability, formation pathways, and kinetic properties. The second key point is evaluating the importance of these intermediates and their properties in the transition state.

 

1. Renzi, P., Hioe, J., Gschwind, R. M., Decrypting Transition States by Light: Photoisomerization as a Mechanistic Tool in Brønsted Acid Catalysis, J. Am. Chem. Soc. 2017, 139, 6752

http://pubs.acs.org/doi/abs/10.1021/jacs.7b02539

Abstract: Despite the wide applicability of enantioselective Brønsted acid catalysis, experimental insight into transition states is very rare, and most of the mechanistic knowledge is gained by theoretical calculations. Here, we present an alternative approach (decrypting transition state by light = DTS-hν), which enables the decryption of the transition states involved in chiral phosphoric acids catalyzed addition of nucleophiles to imines. Photoisomerization of double bonds is employed as a mechanistic tool. For this class of reactions four pathways (Type I Z, Type I E, Type II Z, Type II E) are possible, leading to different enantiomers depending on the imine configuration (E- or Z-imine) and on the nucleophilic attack site (top or bottom). We demonstrated that the imine double bond can be isomerized by light (365 nm LED) during the reaction leading to a characteristic fingerprint pattern of changes in reaction rate and enantioselectivity. This characteristic fingerprint pattern is directly correlated to the transition states involved in the transformation. Type I Z and Type II Z are demonstrated to be the competing pathways for the asymmetric transfer hydrogenation of ketimines, while in the nucleophilic addition of acetylacetone to N-Boc protected aldimines Type I E and Type II E are active. Accelerations on reaction rate up to 177% were observed for ketimines reduction. Our experimental findings are supported by quantum chemical calculations and noncovalent interaction analysis.

 

1. Renzi, P.,* Organocatalytic synthesis of axially chiral atropisomers, Org. Biomol. Chem. 2017, 15, 4506

http://pubs.rsc.org/en/content/articlelanding/2017/ob/c7ob00908a/unauth#!divAbstract

Abstract: This Review summarises the recent progress made in the organocatalytic synthesis of atropisomeric compounds. Methodologies based on dynamic kinetic resolution and direct access to BINOL-like biaryls are described. A particular emphasis is given to reaction mechanisms and to the development of strategies to obtain stable products by increasing the barrier to atropisomer interconversion during the reaction.

1. Renzi, P., Bella, M., Design of Experiments: A rational approach toward non-covalent asymmetric organocatalysis, SYNLETT 2017, 28, 306

https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-0036-1588654

Abstract: This account describes, from a personal point of view, the possible strategies to tackle and optimize non-covalent organocatalyzed reactions. When chemical intermediates are covalently bound, predictive mechanistic scenarios can be depicted. In contrast, there are several organocatalyzed transformations (e.g., those employing cinchona alkaloids) for which optimization is essentially based on a trial-and-error approach. The experience of the authors is that these reactions can be tackled with a rational approach employing Design of Experiments (DoE). This tool is widely exploited in industrial process chemistry, but is little known within academia. The purpose of this account is to show the effectiveness and utility of DoE in asymmetric non-covalently organocatalyzed reactions, discussing selected examples.

 

1. Renzi, P., Kronig, C., Carlone, A., Esöksüz, S., Berkessel, A., Bella, M., Kinetic resolution of oxazinones: Rational exploration of chemical space through the design of experiments, Chem. Eur. J. 2014, 37, 11768

http://onlinelibrary.wiley.com/doi/10.1002/chem.201402380/abstract

Abstract: The organocatalytic kinetic resolution of 4-substituted oxazinones has been optimised (selectivity factor S up to 98, chiral oxazinone ee values up to 99.6 % (1 a–g) and product ee values up to 90 % (3 a–g)) in a rational way by applying the Design of Experiments (DoE) approach.

 

1. Silvi, M.,^¥ Renzi, P.,^¥ Rosato, D., Margarita, C., Vecchioni, A., Bordacchini, I., Morra, D., Nicolosi, A., Cari, R., Sciubba, F., Scarpino Schietroma, D. M., Bella, M., Enantioselective aza-Michael addition of imides by using an integrated strategy involving the synthesis of a family of multifunctional catalysts, usage of multiple catalysis, and rational design of experiment, Chem. Eur. J. 2013, 30, 9973 (^¥ co-first)

http://onlinelibrary.wiley.com/doi/10.1002/chem.201301493/abstract

Abstract: A challenging asymmetric reaction (aza-Michael addition of imides to enones) has been optimized through an integrated approach involving the synthesis of a family of organocatalysts, multiple catalysis (usage of additives), and finally with rational exploration of the chemical space by the application of the experiment design.

1. Renzi, P., Bella, M., Non-asymmetric organocatalysis, Chem. Commun. 2012, 48 (55), 6881

http://pubs.rsc.org/en/Content/ArticleLanding/2012/CC/c2cc31599h#!divAbstract

Abstract: Asymmetric organocatalysis is now an established methodology for the preparation of chiral compounds. However, these are not the only valuable molecules which can be conveniently obtained. Organocatalytic reactions affording achiral compounds are gaining momentum, opening unexplored pathways in the synthesis of densely functionalized aromatic moieties, olefins and useful molecules such as natural substances.

 

1. Monaco, M. R., Renzi, P., Scarpino Schietroma, D. M., Bella, M., Biomimetic organocatalytic asymmetric synthesis of 2-substituted piperidine-type alkaloids and their analogues, Org. Lett., 2011, 13, 4546

http://pubs.acs.org/doi/abs/10.1021/ol2017406

Abstract: Natural substances such as pelletierine and its analogues have been prepared in up to 97% ee and good yield by a protective-group-free, biomimetic approach. Usage of benzonitrile or acetonitrile as solvents effectively prevents product racemization.

 

1. Renzi, P., Overgaard, J., Bella, M., Multicomponent asymmetric reactions mediated by proline lithium salt, Org. Biomol. Chem., 2010, 8, 980; (cover picture)

http://pubs.rsc.org/en/Content/ArticleLanding/2010/OB/b924158b#!divAbstract

Abstract: The multicomponent reaction between proline lithium salt, 2-cyclohexen-1-one and aliphatic aldehydes affords the 4-alkylidene-2-cyclohexen-1-ones, which are interesting fragrances, and bicyclic amino acids that bear four additional stereocenters, obtained as single stereoisomer.