PdII-Catalyzed methoxylation of C(sp3)–H bonds adjacent to benzoxazoles and benzothiazoles

Abstract

The Pd(OAc)₂/PhI(OAc)₂ catalyst system promotes the highly regioselective dehydrogenative methoxylation of a C(sp³)–H bond adjacent to benzoxazole and benzothiazole rings. The title transformation constitutes the first example of a Pd-catalyzed C(sp³)–H activating methoxylation at the proximal-selective α-position with regard to a directing auxiliary and provides expedient access to an important class of azole-decorated methyl ethers (up to 90% isolated yield). The synthetic practicality of the methodology was demonstrated by achieving α-methoxyacetic acids via the elimination of the benzoxazole auxiliaries and by obtaining the precursor of an O-methylated Breslow intermediate.