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

Xinzhe Shi (1) , Jean-François Soulé (1) , Henri Doucet (1)

1 ISCR - Institut des Sciences Chimiques de Rennes

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)/Cs2CO3 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.

Keywords: C-H bond functionalization; C-C bond formation; oxazole; direct arylation; palladium

Domains: Chemical Sciences

Xinzhe Shi, Jean-François Soulé, Henri Doucet. Reaction Conditions for the Regiodivergent Direct Arylations at C2-or C5-Positions of Oxazoles using Phosphine-Free Palladium Catalysts. Advanced Synthesis and Catalysis, 2019, 361 (20), pp.4748-4760. ⟨10.1002/adsc.201900641⟩. ⟨hal-02303396⟩