Synthesis of α/ß dipeptides containing linear or cyclic α-dehydro-ß-amino acids as scaffolds for bioactive compounds.

The synthesis of α/ß dipeptides containing linear or cyclic α-dehydro-ß-amino acids has been performed starting from alkylidene acetacetamides, which were obtained from α-amino esters via Ir-catalyzed allylic amination. Differently hindered carbonates were synthesized via a protocol involving chemoselective Luche's reduction, acylation, and allylic amination. Depending on the nature of the selected α-amino acid, we observed strong influence on the product regiochemistry due to the carbonate size and the amino-acid side chain. In particular, complete regioselectivity was observed in the aminic allylation of carbonates deriving from amino acids possessing a methylene unit in ß-position. On the contrary, methyl carbonates deriving from ß-branched amino acid afforded different results depending on the hindrance of the carbonate. Moreover, spontaneous cyclization was observed for carbamate-containing intermediates, allowing to obtain peptidomimetic polyfunctionalized dihydropyrimidine-2,4-dione. Finally, by inverting the order of reduction/acylation steps on the starting alkylidene acetoacetamides, the formation of polyfunctionalized 1,3-oxazinane-2,4-dione was obtained demonstrating the wide applications of these substrates for the preparation of bioactive peptidomimetics.

Regioselective Iridium-Catalyzed Asymmetric Monohydrogenation of 1,4-Dienes.

A highly efficient regio- and enantioselective monohydrogenation of 1,4-dienes has been realized using an iridium catalyst with a chiral N,P-ligand under mild conditions. The substrate scope was studied and included both unfunctionalized as well as functionalized substituents on the meta- or para-position. Substrates having substituents with functionalities such as silyl protected alcohols or ketals were monohydrogenated in high regioselectivity and high enantiomeric excess (up to 98% ee).