BF3·OEt2-TFAA Mediated Tetra-Functionalization of Amino Acids - Synthesis of Di- and Tri-Substituted 2-Trifluoromethyl Oxazoles in One Pot.

A highly efficient, TFAA-BF3·OEt2 mediated multicomponent coupling of amino acid, TFAA, and aromatics provides a broad library of 2-trifluoromethyl equipped 2,5-disubstituted/2,4,5-trisubstituted oxazoles or N-(trifluoroacetyl)-β-aminoalkyl ketones. This amino acid tetra-functionalization approach involves amidation (C-N), anhydride (C-O), Friedel-Crafts acylation (C-C), and Robinson-Gabriel annulation (C-O) followed by dehydrative aromatization. This reaction takes place under operationally simple, mild, and metal-free conditions using readily available amino acids and aromatic compounds.