Reaction Conditions for the Regiodivergent Direct Arylations at C2‐ or C5‐Positions of Oxazoles using Phosphine‐Free Palladium Catalysts

Abstract Two sets of reaction conditions for the regiodivergent C2‐ or C5‐ direct arylations of oxazole are reported. In both cases, phosphine‐free catalysts and inexpensive bases were employed allowing the access to the arylated oxazoles in moderate to high yields. Using Pd(OAc) 2 /KOAc as catalyst and base, regioselective C5‐arylations were observed; whereas, using Pd(acac) 2 /Cs 2 CO 3 system, the arylation occurred at the C2‐position of oxazole. The higher reactivity of C5‐H bond of oxazole as compared to the C2‐H bond in the presence of Pd(OAc) 2 /KOAc system is consistent with a concerted metalation deprotonation mechanism; whereas the C2‐arylation likely occurs via a simple base deprotonation of the oxazole C2‐position. Then, from these C2‐ or C5‐arylated oxazoles, a second palladium‐catalyzed direct C−H bond arylation affords 2,5‐diaryloxazoles with two different aryl groups. We also applied these sequential arylations to the straightforward synthesis of 2‐arylphenanthro[9,10‐ d ]oxazoles via three C−H bond functionalization steps. The Ru‐catalyzed C−H arylation of the aryl unit of 2‐aryloxazoles is also described. magnified image