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During the PhD Luca Mengozzi studied reactions involving carbocations or carbocationic intermediates to develop new synthetic methodologies, and a new generation of quantum cellular automata (QCA) candidates in the context of the European Project Molarnet. Concerning the development of new asymmetric methodologies, he studied in detail the stereoselective alkylation of aldehydes with isoquinolinium and quinolinium ions generated in situ. These reactions were promoted by chiral secondary amine catalysts and no metals are needed. The first alkylation of acyl isoquinolinium ions with aldehydes was reported and it was applied to the first enantioselective synthesis of 13-alkyl tetrahydroprotoberberine alkaloids. Preliminary tests on resistant tumor cell lines performed by prof. Calonghi revealed promising cytotoxic activities. An asymmetric Pictet Spengler reaction to access 1-allyl isoquinolines was also reported. He studied the activation of carboxylic acids and their alkylation with stable carbenium ions promoted by chiral isothioureas and the development of the first photocatalytic alkylation of aldehydes promoted by iron photosensitizers. He spent five months as a visiting PhD student in Prof. Pericás Research group at ICIQ, Tarragona, Spain. During this period he studied the use of flow chemistry techniques for the synthesis of antiviral agent (-)-oseltamivir. In particular he studied the use of supported organocatalsyts in the enantiodetermining step of the synthetic pathway. QCA are a new paradigm for molecular computation and he worked on the synthesis of new candidates applying the knowledge of the research group on SN1 reactions. Through this strategy a new class of ferrocene guanines conjugates, ferrocene porphyrins, and ferrocene containing aluminium salophen complexes were obtained. The study of their properties on different surfaces that revealed the formation of interesting self-assembled monolayers for both salophen complexes and porphyrins. One paper was published and three are in preparation with our Molarnet partners.

The alpha-alkylation of aldehydes is an important transformation. It was and in some way it is still considered the " Holy Grail" of organocatalysis. However, it is still not possible to introduce methyl groups by using methyl iodide as electrophile in a stereoselective organocatalytic promoted alkylation of aldehydes or ketones. The stabilization of carbenium ion by sulfur allowed us to introduce a quite straightforward methodology for a formal a-methylation of aldehydes. The commercially available benzodithiolylium tetrafluoborate is a stable carbenium ion with a rich chemistry and interesting properties. Furthermore, it can be easily removed by nickel Raney or it can be oxidized to the corresponding carbonyl group.

Isoquinoline derivatives have a leading role in medicinal and natural products chemistry. However, only a few examples of catalytic asymmetric synthesis of these compounds by the attack of carbon nucleophiles to activated isoquinolinium intermediates are reported. Organocatalytic methodologies to access enantioenriched dihydroisoquinolines were also described, but were not general, and of limited use. Herein, we present an effective, simple enantioselective organocatalytic alkylation of isoquinoline with aldehydes, combining simple enamine catalysis with the formation of N-acyl isoquinolynium ions. We have discovered a practical, efficient, and general methodology that allows the use of chiral secondary amine-based organocatalysts in the presence of acylating agents such as Boc2O and CbzCl. With this methodology a straightforward access to stable 1,2-dihydro- and 1,2,3,4-tetrahydroisoquinoline building blocks in high enantiomeric excesses (ee up to 99%) was established. In addition, we have found a simple and efficient procedure for the synthesis of enantioenriched isoquinoline derivatives.

Salophens and Salens are Schiff bases generated through the condensation of two equivalents of salicylaldehyde with either 1,2-phenylenediamines or aliphatic diamines, respectively. Both ligands have been extensively exploited as key building blocks in coordination chemistry and catalysis. In particular, their metal complexes have been widely used for various catalytical transformations with high yield and selectivity. Through the modification of the phenol unit it is possible to tune the steric hindrance and electronic properties of Salophen and Salen. The introduction of long aliphatic chains in salicylaldehydes can be used to promote their self-assembly into ordered supramolecular structures on solid surfaces. Herein, we report a novel method towards the facile synthesis of robust and air-stable [Al(Salophen)] derivatives capable of undergoing spontaneous self-assembly at the graphite/solution interface forming highly-ordered nanopatterns. The new synthetic approach relies on the use of [MeAlIII (Salophen)] as a building unit to introduce, via a simple acid/base reaction with functionalized acidic phenol derivatives, selected frameworks integrating multiple functions for efficient surface decoration. STM imaging at the solid/liquid interface made it possible to monitor the formation of ordered supramolecular structures. In addition, the redox properties of the Salophen derivatives functionalized with ferrocene units in solution and on surface were unraveled by cyclic voltammetry. The use of a five-coordinate aluminum alkyl Salophen precursor enables the tailoring of new Salophen molecules capable of undergoing controlled self-assembly on HOPG, and thereby it can be exploited to introduce multiple functionalities with subnanometer precision at surfaces, ultimately forming ordered functional patterns.

A mechanism based on the sequential absorption of two photons by the components of a redox couple has been recently proposed for catalysis of the energetically demanding reduction of aryl halides. Here, we analyze the suggested photochemical mechanism of this reaction, which employs perylenediimide (PDI) as a photocatalyst, on the basis of spectroscopic, electrochemical and electron paramagnetic resonance data. Our results indicate that the photoexcited PDI radical anion (*PDI˙−) cannot play the role of a photosensitizer in the aforementioned process. Instead, the reduction of 4′-bromoacetophenone likely involves *PDI˙− decomposition products. The extremely short lifetime of the photoexcited transient species, as *PDI˙−, is a major general limitation for photocatalytic schemes based on sequential two-photon excitation. In order to better understand the potential of such schemes, we discuss them in the context of the Z-scheme in natural photosynthesis.

The frequent occurrence of chiral 1-substituted-1,2,3,4-tetrahydroisoquinoline ring systems in a large number of alkaloids, possessing a broad spectrum of biological and pharmaceutical properties, has prompted out a considerable interest in their synthesis. Economical and valuable stereoselective processes based on organocatalytic transformations represent a new avenue for approaching isoquinoline alkaloids with efficiency and creativity.

The compatibility of indium(III) Lewis acids with water and amines allows their employment in synergistic and cooperative catalysis. Stereoselective organocatalytic S(N)1-type reactions, in which carbenium ions are generated, are promoted by the presence of indium salts. The peculiar properties of indium salts can be exploited in organocatalysis for the design of water-compatible, benign, green processes. The development of such indium(III)-promoted organocatalytic procedures is the focus of our recent research, a summary of which is presented in this article. The compatibility of indium(III) Lewis acids with water and amines allows their employment in synergistic and cooperative catalysis. Stereoselective organocatalytic SN1-type reactions, in which carbenium ions are generated, are promoted by the presence of indium salts. The peculiar properties of indium salts can be exploited in organocatalysis for the design of water-compatible, benign, green processes. The development of such indium(III)-promoted organocatalytic procedures is the focus of our recent research, a summary of which is presented in this article. © Georg Thieme Verlag Stuttgart.New York.

Imidazolininone organocatalysts (MacMillan catalysts) are one of the most effective catalysts, used in many interesting organocatalytic reactions. Their robustness, easy preparation from amino acids, and widespread use, make them one of the most powerful catalysts for general enantioselective transformations. The imidazolidinone catalysts promote new reaction modes in organocatalysis, such as SOMO activation and enantioselective photocatalytic reactions. Herein, the key principles underpinning their functionality and their reported use are summarised.