An Efficient Synthesis Of Polysubstituted Oxazoles Via A Copper(Ⅰ)/Amino Acid-catalyzed Intramolecular C-O Coupling Reaction

Oxazoles are a very important class of five-membered heterocyclic compounds.Its special structure makes many of oxazole-containing compounds exhibit uniqueproperties and biological activities in the pharmaceutical, pesticide, materials, andmany other areas. As a result, oxazole synthesis has drawn considerable attentionwith a number of new synthetic methodologies developed.Besides Robinson-Gabriel condensation, the most straightforward ways toconstruct oxazole rings are oxidative or coupling cyclization of N-acylenamidederivatives. In recent years, although a number of oxidative cyclization approachesby oxidants (e.g. TBHP, I2, hypervlent iodine reagent, K2S2O8, NBS and O2) orcatalyzed by transition-metals for oxazole synthesis have been reported; However,despite the elegance of these oxidative strategies, the non-oxidative coupling strategyremains an important alternative, particularly in the context of constructing oxazolescontaining oxidant-sensitive substructures, which is still not sufficiently developed.In this dissertation, we have developed an efficient approach to constructoxazoles via copper(I)/amino acids-catalyzed Ullmann-type reactions. The requiredsubstrate were obtained via ring-opening reactions of easily accessableErlenmeyer-Pl chl azlactones precursors by nucleophiles (e.g. primary amines,cyclic or acyclic secondary amines, ammonia, amino acid esters and alcohols),followed by bromination. Under optimal conditions, all the substrates were allcyclized to the corresponding oxazoles smoothly in high yields (86－99%). Themethodology has a number of advantages, such as easy preparation of substrates,mild reaction conditions, high yields, and good tolerance of substrate scope. Withthis protocol, we have prepared a series of4-position functionalized (with ester,carboxamide groups, etc.)2,4,5-trisubstituted oxazole derivatives..