RICERCA ITALIANA     

Synthesis and reactivity/activity of functionalized unsaturated systems. Part II.

Università degli Studi di Genova

Abstract

In prosecution of research projects in which the single RU’s are currently engaged, the investigation of the chemistry of activated unsaturated systems, either electron-rich or electron-poor, is the pivotal subject of the present research program. Indeed, the examined systems exhibit an extremely diversified reactivity allowing the synthesis (often by innovative and/or environmentally friendly processes) of new classes of compounds which are often polyfunctionalized and consequenly show practical interest both as synthons and as biologically-active molecules. Therefore, the main target of the project is to achieve the synthesis of unsaturated building-blocks which, due to the contemporaneous presence of several functional groups which interact with each other (being, e.g., in relative conjugate positions), are prone to a number of synthetic applications. The success of the project should be guaranteed by the long-term experience acquired by the various RU’s in specific sectors of this field and by the fact that they will actively collaborate with each other, as far as both know-how exchange and sharing of the scientific instruments in charge of each RU are concerned. Among the activated unsaturated systems under investigation (as substrates, intermediates or final targets) we can mention nitroenamines, dinitrodienamines, nitroalkenes, 2-nitro- and 2,3-dinitro-1,3-butadienes, carbonyl compounds, enones, hydrazones, 1,2-diaza-1,3-butadienes. Among the heterocycles >>>

Principal Investigator

Giovanni PETRILLO Università degli Studi di GENOVA

Research Objectives

This research project is grounded on the development of new synthetic methodologies and processes using activated unsaturated electron-rich or electron-poor systems to prepare target compounds of various kind. Indeed unsaturated (poly)functionalized systems, thanks to the presence of more reactive sites in their molecules, are prone to structural changes, providing the access to new organic molecules which could have useful applications either as synthons (for further synthetic developments) or as final products exhibiting biological or pharmacological activity. The main targets of the present project can be summarized in the following research lines, fully detailed in the B models of the various RU's:
-- synthesis of unsaturated, highly-functionalized building-blocks;
-- use of such building-blocks for the synthsesis of target molecules, exhibiting cyclic or acyclic structures and possibly susceptible of biological/pharmaceutical applications;
-- optimization of known synthetic processes and design of new and innovative ones, also on the grounds of previsions based on quantum-mechanical (e.g., ab-initio) calculations; studies on the stereoselectivity of the reactions employed; structural analysis of the compounds involved (substrates, intermediates, products).
The common efforts which will be devoted to the achievement of the proposed targets, guaranteed by the complementarity of the cultural interests and of the expertises of the single RU's >>>

First Results

The results expected from Phase 1 are mainly represented by publications (papers and/or reviews on the specific research fields) and communications to Meetings, to be judged by the scientific community and, of course, by the "Collegio dei Garanti" and by the Referees. At the end of the first phase of the project a Meeting of the five Research Units will be organized in order to present and discuss the results obtained, to verify the effectiveness of the ongoing collaborations and of the desirable exchange of expertises, as well as to prepare the scheduled scientific and financial annual report.As stated at the end of Phase 1, the results expected from Phase 2 are likewise represented by publications (papers and/or reviews) and communications to Meetings to be judged by the scientific community and, of course, by the "Collegio dei Garanti" and by the Referees.
As done at the end of Phase 1, also at the end of the second phase of the project a Meeting of all the five Research Units will be organized, in order to verify and evaluate the results obtained as well as to prepare the scheduled final scientific and financial report.

Timescale

24 months

National and international background

Multiple bonds, either in acyclic or in aliphatic and aromatic cyclic structures, are pillars of organic synthesis [1]. The involvement of heteroatoms in the multiple bonds or their proximity to them, or the activation by proper substituents greatly influence the reactivity of such bonds, making them suitable for the syntheses of a large variety of compounds, either electron-rich or electron-deficient ones, much enlarging the scope of their practical use.

Dehydration of beta-nitroalcohols deriving from nitroaldol reactions (Henry reactions) [2] is the most classic path to nitroalkenes [3]. In this framework, the RU of Camerino has set up a number of new procedures to synthesize beta-nitroalcohols either in heterogeneous phase [4] or, alternatively, via Henry-type reactions in water, so as to avoid using organic solvents within environmentally-friendly processes [5]. More recently the RU has achieved a one-pot synthesis of nitroalkenes without isolating the intermediate nitroalcohols [6]. Another interesting feature of nitroalkene reactivity is the possible addition of nucleophilic reagents, which produces functionalized nitroalkanes [7]: such a process can be accompanied by the transformation of the nitro group into a carbonyl (Nef reaction) [8]. Another interesting possibility comes from the fact that the electron-withdrawing character of the nitro group makes nitroalkenes very good dienophile systems in cycloaddition reactions [9].

The >>>