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Heterocyclic Synthesis  

Heterocyclic compounds are the backbone of a number of natural and synthetic molecules. In many cases, the skeleton of drugs, bioactive molecules and even advanced materials is constituted by hetero(poly)cyclic rings of various sizes. Since the time when this section of DiSFarm was the Institute of Organic Chemistry of the Faculty of Pharmacy, the heterocyclic synthesis was one of the main subjects for many research groups and it is still a growing and evolving topic. In particular, the different groups are devoted both to the synthesis of new heterocyclic molecules as well as to the study of new strategies for the synthesis of new/known-structures by alternative and sustainable approaches. The synthesis is often supported and enhanced by in-depth spectroscopic and computational studies addressed to an accurate characterization of the obtained products and to the explanation of the reaction mechanisms involved.

 

Stereoselective  synthesis  of  4, 5 or  6-membered heterocycles

Concetta La Rosa

This line of research involves the synthesis and transformations of new heterocyclic compounds with four, five or six atoms, obtained by means of synthetic methodologies such as the [2+2]π ketene-imine reactions, the 1,3-dipolar cycloaddition or the [4+2]π Diels-Alder cycloaddition reactions. In particular are taken into consideration stereoselective synthesis of heterocyclic compounds having spiranic junction with hetero or carbocycles of particular interest for their biological activity both as such, e.g. spiro-b-lactams, both as derivatives obtained after transformations, such as b-amino acids variously functionalized.

 Synthesis of N-heterocycles via transition metals catalysis and green chemistry

Egle Beccalli, Elena Borsini, Alberto Mazza

Within the heterocyclic chemistry most of the researches are finalized to study the reactivity and to obtain heteropolycyclic bioactive molecules and alkaloids. The indole derivatives and the isoxazole nucleus are the more studied heterocyclic systems due to the high versatility in ring transformation to give different heterocyclic systems. The indole derivatives are used as a synthons for several carbazole alkaloids and on these substrates started the studies on the metals-transition catalyzed reactions. This topic has become the focus of the research area, in particular the palladium(II)-complexes are interesting allowing the use of unfunctionalized substrates, through the CH bond activation, with economical and procedural benefits.

Nowadays studies dealing with green chemistry, such as the use of eco-friendly conditions, aqueous solvents, solvent-free reactions, microwaves assisted reactions are in progress.

 

 azidi e enamines cycloaddition reactions

Emanuela Erba, Alessandro Contini

Our group studied for a long time cycloaddition reactions and the subsequent rearrangement of the cycloadducts of aryl and sulfonyl azides with enamines of various aldehydes and linear or cyclic ketones. The primary thermolabile dihydrotriazole cycloadduct underwent a transformation yielding mainly amidines. The obtained amidines, syntetized by a efficient multicomponent reaction protocol, were extensively used as syntones in heterocycle synthesis. Aiming to obtain new synthetically useful starting materials, a number of carbonylic compounds have been used.

It is known that the nature of the starting carbonyl reactant appears to rule the outcome of the reaction, and cyclic ketones containing a nitrogen atom showed an unexpected behavior. With the aim to explian all the examined results an in-depth computational study of the reaction mechanism was performed.

Alkynes in domino and multicomponent reactions.

G Abbiati, E. Rossi
Collaborators:  Dell’Acqua, V. Pirovano

This line of research concerns the synthesis of various nitrogen and oxygen containing heterocycles by cascade reactions involving intramolecular cyclization. Simple building-blocks characterized by the presence of C-C triple bond proximal to a proper nucleophilic center are the starting products of choice. The development of new strategies for the preparation of starting materials in a simple and efficient fashion is part and parcel of the line of work. The final cyclization steps often involve a hydrofunctionalization of the triple bond (hydroamination, hydroalkoxylation, etc.) promoted by salts and complexes of transition metals, in particular palladium, titanium, gold and silver. In many cases the domino approaches are transformed in multicomponent processes in which the catalytic activity of the transition metal is involved in the synthesis of the starting material as well as in the cyclization reaction, everything in a single operation step. Where the synthesis leads to the formation of a new stereocenter, particular attention is dedicated to the study of the stereoselective version of the transformation, by means of suitable catalysts with chiral ligands, capable to direct the stereochemical course of the reaction. In some cases, the optimized methodologies are applied to the synthesis of specific compounds, e.g. the total synthesis of natural compounds or the preparation of new molecules with particular photophysical properties.

 

 

Coinage metal catalyzed cycloaddition reaction of vinylheterocycles

E. Rossi, G. Abbiati
Collaborators: V. Pirovano, M. Dell’Acqua

In this line of research, vinylheterocyclesare evaluated as dienes in cycloaddition reactions with various dienophiles such as a,b-unsaturated carbonyl compounds, allenes, etc. Many efforts are devoted to the study of the reactions catalyzed by salts and complexes (also chiral) of gold and silver in order to synthesize new heteropolycyclic molecules in a regio-, diastereo- and enantioselective fashion. In this context, the development of efficient strategies for the preparation of starting materials is an essential part of the research.

 

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