Scientific background. The search for new methods for C-C or C-X (X = O, N,..) bond formations is of utmost importance in the field of total synthesis. Within the context of discovering efficient synthetic strategies, a major advance would be the design of a new reaction allowing the direct transformation of a particular C-H bond. Such a selective CH functionalization reaction would enhance the value of simple alkanes as starting materials in synthesis. This quest, however, still remains challenging since the reagent should be active enough to induce C-H bond cleavage but also sufficiently mild to allow this event to occur at a given position. Several groups have recently reported the discoveries of catalytic C-H bond functionalizations involving either CH activation or CH insertion. These two mechanistically different processes are complementary in terms of regioselectivity but they also display the same major drawback related to their efficiency and selectivity. The latter are almost always dependent upon the involvement of an internal tether that directs the reagent into the proximity of the C-H bond to be cleaved. This is particularly true in the field of CH insertion where major developments have benefited from recent progress made in the chemistry of nitrenes and carbenes. These species were until recently considered as non-selective and unstable agents. Their reactivity can now be fine-tuned in the presence of transition metal complexes but their applications are confined to intramolecular C-N or C-C bond formations. The mechanism of these nitrene and carbene insertions, moreover, remains a subject of debate since the postulated metal-coordinated intermediates have never been characterized. Objectives. In the context of the highly competitive field of CH functionalization, one of the partners of this project has disclosed new procedures for the generation of nitrenes under mild conditions using hypervalent iodine reagents. This has recently culminated with the production of chiral nitrenes for the first time starting from sulfonimidamides, chiral sulfur(VI) reagents rarely used in organic chemistry. These nitrene precursors exhibit unprecedented reactivity and have been shown to react with chiral rhodium(II) dimers to afford CH aminated products in excellent yields and exceptional selectivities. This pioneering but preliminary intermolecular CH amination therefore offers unique opportunities for the development of efficient CH functionalizations of alkanes while it has raised new mechanistic questions that remain to be addressed and answers to which will be helpful for the design of new reagents. This project therefore aims at designing asymmetric nitrene insertions to C-H bonds of alkanes from sulfonimidamides and investigate the related carbene transfer starting from the analogous sulfoximines. This will be envisaged through the combination of experiments and theoretical studies. A special attention will be paid to the characterization of the metalla-nitrene and carbene intermediate in order to gain key information on their structures likely to help in the design of more reactive species. Application of these methodologies in total synthesis will be also developed.
Monsieur Philippe DAUBAN (Institut de chimie des substances naturelles)
The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.
Institut de chimie des substances naturelles
Laboratoire Hétérochimie Fondamentale et Appliquée
Institut Pluridisciplinaire de Recherche sur l'Environnement et les Matériaux
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Beginning and duration of the scientific project: December 2007 - 36 Months