Réaction d’amination intramoléculaire de liens C-H à partir de N-mésyloxycarbamates catalysée par des complexes de rhodium et d’autres métaux de transition : s
ynthèse verte d’oxazolidinones
C-H amination reactions, i.e. the direct transformation of a C-H bond into a C-N bond, represents a very promising synthetic approach to prepare nitrogen-containing compounds. The strategy, when applied to intramolecular transformations, represents a powerful method for the preparation of heterocycles. In particular, oxazolidinones (5-membered carbamate heterocycles), which are a novel class of promising antimicrobials, could be easily accessed using C-H amination. Nearly a decade ago, our research group developed methods for metal nitrene-mediated C-H aminations, for both intra- and intermolecular transformations. N-Tosyloxycarbamates, in the presence of a tetracarboxylate rhodium (II) dimer catalyst and a base, were found to be good precursors to metal nitrenes; the latter being able to perform C(sp3)-H insertions. In the present thesis, we have worked on developing a “greener” method for C-H amination reactions. N-Mesyloxycarbamates, lighter than their N-tosyloxycarbamate homologues, were identified as nitrene precursors. The methodology requires only 3 mol % of rhodium dimer Rh2(tpa)4 and 1.5 equivalents of an aqueous saturated solution of K2CO3, in AcOEt and provides the cyclized product in good yields. The scope of the reaction was investigated, illustrating the tolerance and limitations of the catalytic system: heteroatoms are not a problem except for nucleophilic nitrogens, which should be protected, in order to allow for efficient transformation. We observed that secondary C-H bonds were less reactive than tertiary ones. After attempting to develop specific conditions for non-activated bonds, we showed that propargylic C-H bonds can be chemoselectively aminated; and the C-C triple bond can easily be further derivatized, allowing for structural diversification. With regards to replacing rhodium complexes by complexes of other metals, which are more abundant and cheaper, we focused first on iron complexes and then on nickel pincer complexes. Iron phthalocyanin complexes are viable catalysts for the intramolecular C-H amination using N-mesyloxycarbamates. Iron (III) phthalocyanin chloride, along with AgBF4 salt and K2CO3, in anhydrous 1,1,2,2-tetrachloroethane, allows the formation of phenyloxazolidin-2-one in 63% yield. Likewise, the same product can be generated in 49% yield, when a POCN nickel pincer is used as a catalyst, along with a sodium mesylate salt and a base, in anhydrous DCM. Some mechanistic clues could be collected while studying the catalytic systems.
Oxazolidinones C-H Amination N-Mesyloxycarbamates Rhodium dimers Iron phtalocyanin Nickel pincers