Préparation d'organoaluminiques fonctionnels et applications en synthèse organique – AluMeth

The search for new original synthetic tools, especially for diversity-oriented synthesis and polyfunctional complex molecules eleboration, is a very active field. One of the challenging goals in this area of investigation is to develop reagents that combine good reactivity and functional group tolerance, in order to minimize the number of steps necessary to create complex molecular structures. In this context, the aim of this project is to investigate new routes to organoaluminum reagents and to evaluate their scope in synthetic organic chemistry. The covalent nature of the carbon-aluminum bound, associated with the excellent Lewis acidity of the metal and its rich coordination chemistry make organoaluminum reagents good candidates for the elaboration of functional organometallic reagents. However, despite considerable work in the field of inorganic chemistry, their use in preparative organic synthesis for the formation of carbon-carbon bonds is still scarce when compared to the corresponding group I and II organometallic reagents. A major reason for the lack of applications of these compounds in organic synthesis is their mode of preparation, which is very often restricted to a salt-metathesis from the corresponding organoalkali, more reactive but less function-tolerant. We have recently developed a new access to mixed dialkylalkynylaluminum reagents via a triethylamine-catalyzed terminal alumination of alkynes. This synthetic route avoids the use of strong, nucleophilic bases and a transmetalation step, delivering the organoaluminum species in non-coordinating solvents. The aim of this project is to exploit this new route as a starting point for the elaboration of more elaborated, functional organoaluminum reagents. In the first part of this project, the scope and limitation of the metalation step will be investigated. Only a few Lewis bases have been described to assist the terminal alumination of alkynes. Investigation of this parameter could lead to a more efficient metalation step, with lower activation energy, and thus a faster and/or more function-tolerant process. The use of chiral bases in this process is also unexplored, and could lead to interesting application in asymmetric synthesis. This mechanistic investigation will enable the study of the preparation of functional mixed alkynylaluminum reagents. Thus, functional group tolerance of the metalation step will be studied as well as the reactivity of such new species under various experimental conditions. In the third part of this project, access to more complex aluminum acetylides will be attempted by conducting selective chemical transformations of functional groups functional or pre-functional aluminum acetylides, after the metalation step, in the presence of the carbon-metal bond. Such a strategy should enable the elaboration of alkynylaluminum reagents with increased molecular complexity while maintaining the integrity of the carbon-metal bond before its ultimate transformation after decomplexation in a divergent bidirectional synthesis. The last part of this project will focus on the triple bond transformation of mixed alkynyl aluminum reagents into more functional unsaturated systems, included or not into aromatic or heterocyclic frameworks, in the presence of the carbon-metal bond. Among the different possibilities, the access to bismetallic species and aromatic organoaluminum compounds will be our major objectives in this task.