Gold-Catalyzed [3+2]-Cycloaddition Approach to 2,4,5-Trisubstituted Oxazoles

Significance

Reported is the gold-catalyzed synthesis of 2,4,5-trisubstituted oxazoles 3 via the formal [3+2] cycloaddition of ynamides 1 with pyridine-N-aminides 2. N-Alkyl, -benzyl, and -aryl groups on the ynamide are all well tolerated. Excellent chemoselectivity in the addition to the yn­amide π-system is observed, even in the presence of another alkene or alkyne (R^² = CH₂C≡CTMS, allyl). With regard to alkyne R^³ substitution, both alkyl (including a primary alkyl bromide) and conjugated systems perform equally well. The reaction is not limited to ynamides since the cyclization of an ynol ether was shown to give 4-ethoxyoxazole 4 in moderate yield.