Lewis acids: acidity scales and catalytic activity – ALEA

The catalytic activity of metal triflates and analogous salts, presenting low nucleophilicity and high Lewis acidity of the metal cation, has been examined in detail in several organic transformations. Novel cyclisation reactions involving the chemoselective activation of polyfunctional molecules showed interesting selectivity as a function of the metallic salts. Several electrophilic and/or nucleophilic functions such as olefins, allenes, enol ethers, allylic or carbonyl derivatives have been combined in various cyclisation reactions. Acidity/basicity
scales have been determined in order to rationalise the most efficient use of these Lewis superacids according to the functional groups present in the organic compounds.Data on coordination affinity of Lewis acids and superacids to organic substrates have been obtained using mass spectrometry methods, combined with theoretical calculations. In particular, an original ligand exchange method
involving metallic triflates developed via electrospray ionisation coupled with mass spectrometry has allowed the description of a quantitative basicity scale for organic ligands, such as unsaturated cyclic ketones, esters and diols. The interaction between metallic triflate-type catalysts and organic compounds has also been examined using nano-calorimetry.

Novel cycloisomerisation reactions with low catalyst loading have been
developed, aiming at high molecular diversity in atom economy processes, thus participating to the concept of “green chemistry”. In particular, cyclisations of unsaturated enol ethers leading to polycyclic ethers, cyclisations involving allenes and carbonyl compounds, as well as rearrangements giving access to polysubstituted cyclic enones have been published. Mass spectrometry has shown to be a well-adapted technique to examine the correlation between the organic substrates and the metal cations of the catalysts. Based on these data,
some acidity/basicity scales involving metal triflates have been established.These studies have opened new possibilities of academic and industrial cooperation. We also developed synthetic applications in the field of flavours and fragrances, by the synthesis of novel terpenoid-type compounds via the developed methodologies. Our industrial partners have evaluated these new odorant compounds.
The ALEA project has also opened interesting new perspectives concerning Lewis acid supported catalysts; it allowed for two industrial contracts and for three academic collaborations.

The main perspectives of the project can be summarised as follows :
- To set-up Lewis acidity and superacidity scales as well as Lewis basicity scales by combining the results of mass spectrometry, nano-calorimetry and theoretical calculations.
- To define the best adapted system between a substrate and a catalyst for a better control of the selectivity and efficiency of the processes.
- To describe novel and catalytic cyclisation reactions for polyfunctional substrates, adapting the affinity of the functional groups to the nature of the catalyst.
- To prepare a series of target compounds of potential interest in the field of fragrances.

The project mainly concerns fundamental research, aiming at publications in high ranking journals.
Synthetic applications in the area of flavours and fragrances are also foreseen.

We published 17 scientific articles in peer-reviewed journals (+ 2 in preparation), as well as a book chapter, 2 review articles and 2 patents. Moreover, 11 seminars and 30 communications to conferences and congresses have been presented. Among the publications, we can highlight 2 Angew. Chem.; one in the filed of mass spectrometry and the other in the field of synthetic methodology, giving evidence of the quality of the developed research.

Summary :

The present proposal deals with the synthetic and physicochemical aspects of the catalysis involving Lewis superacids, in view of their unique activity. The project involves the participation of two research groups at the Institut de Chimie de Nice. The first team is specialised in organic synthesis, catalysis and fine chemistry and the second one in physical organic chemistry.

Lewis superacids are metallic salts formed of a metal cation with the conjugated base of a superacid. They have shown exceptional catalytic potentiality for the electrophilic activation of organic substrates in the last years, in particular for the functionalisation of non activated olefins. We plan to focus our attention on the catalytic activity of metal triflates and triflimides, derived from triflic acid (CF3SO3H) and bis(trifluoromethane sulfonyl)imide (HN(SO2CF3)2), for their low nucleophilicity and the extremely strong Lewis acidity of the metal centres.

There is a need to establish adapted acidity scales for Lewis superacids in order to rationalise the choice of the best catalyst for a given process. Quantitative acidity scales of Lewis superacids will be established on the basis of mass spectrometry studies, using electrospray ionisation and competitive adduct formation of ionic species. A complementary approach will be based on the kinetic method, by means of collision induced dissociation of ionic clusters derived from metal triflimides and two different ligands. Acidity and basicity scales will also be obtained through thermochemical data from isothermal titration calorimetry measurements (ITC) for the interactions Lewis acid/organic ligand. In parallel to these experimental studies, quantum chemical calculations will be carried out in support of the energetic and structural aspects of stable ligand/Lewis acid adducts, in the frame of an international collaboration.

With the data acquired on substrate/catalyst interactions, we propose to examine the catalytic activity of a variety of metal triflimides and derivatives, mainly in novel cyclisation reactions at low catalyst loading. Catalytic cyclisations present a particularly high interest, due to high structural complexity generally attained in atom economy processes, thus participating to the general concept of “green chemistry”. The development of novel synthetic methodologies will involve cyclisations through the chemoselective activation of a particular functional group in polyfunctional molecules, including olefinic systems, allenes and allylic derivatives, for the synthesis of highly substituted polycyclic systems.

Synthetic applications of these catalytic methodologies in the field of flavours and fragrances will also be considered. Novel structures and analogues of natural terpenoid compounds will be prepared via the cyclisation methodologies and will be further functionalised. The obtained products will be tested for their fragrance properties. We will look for the valorisation (patent applications) of new compounds in the field of flavours and fragrances with companies, with which we are already in contact.