Synthesis of functionalised oxazoles and bis-oxazoles

A new method for the synthesis of oxazoles, and in particular chiral non-racemic oxazoles derived from amino acids, has been developed. Thus, rhodium(II) catalysed reaction of diazocarbonyl compounds 6 and 11 in the presence of amides 8 and 10 results in regioselective insertion of the carbenoid into the amide N-H bond with formation of the beta-carbonyl amides 9 and 12. Cyclodehydration of amides 9 and 12 using triphenylphosphine-iodine-triethylamine gives functionalised oxazoles 7 and 13. The oxazoles 13e and 13f were converted into the bis-oxazoles 17a and 17b by a second rhodium(II) catalysed regioselective N-H insertion reaction on the amides 15, followed by cyclodehydration.