Résumé
The alpha-amidophosphonates (alpha-AmPs) and, more specifically, their alpha-C-alkylated derivatives are among the most promising bifunctional molecules used as ligands for the liquid-liquid extraction (LLE) of uranium (U) from various acidic media. However, the structure-activity relationship of such molecules has only been partially investigated to date, and it remains challenging when these ligands carry more than one chiral center. The work described therein aims to access enantio- and diastereopure alpha-AmPs. The extraction performance of these should subsequently be assessed in order to characterize the effect of chirality on U LLE. To the best of our knowledge, this article represents the first report of the chiral alpha-AmPs synthesis. The emphasis was placed on the stereochemistry of the alkylated alpha-carbon, and three synthesis routes were investigated. The first route involved enantioselective C-alkylation via chiral phase transfer catalysis (PTC), which failed to provide the expected compounds. The second route used the same chiral catalyst in a monophasic solvent in the presence of a strong base and yielded the alpha-C-alkylated amidophosphonate in low to average yields without enantioselectivity. The third route consisted of total synthesis starting from an enantiopure amino acid precursor and featured an Arbuzov reaction as a final key step. First trials led to the targeted molecules bearing one or three chiral centers in 9% overall yield with, respectively, enantiomeric excess ee similar to 30% (determined by chiral HPLC) and diastereoisomeric ratio dr similar to 65:35 (determined by NMR spectroscopy). Optimization of the method performed on substrates bearing a single chiral center could afford an enantiomeric excess ee <= 83%. Finally, new routes are open to access diastereopure alpha-AmP, besides a first limitation to the applicability of PTC and the unusual racemizing mechanism of the Arbuzov reaction are collaterally established.