Palladium Cross-Couplings of Oxazoles

Abstract

A review covering the literature until April 2008 concerning organometallic reactions to funcionalise oxazoles is described. A protocol for the functionalisation of the oxazole 2- and 4-positions using the Suzuki coupling reaction is described. 2- Aryl-4-trifloyloxazoles undergo rapid, microwave-assisted coupling with a range of aryl and heteroaryl boronic acids in good to excellent yields. The methodology is similarly effective using 4-aryl-2-chlorooxazoles as the coupling partner and has been extended to the synthesis of a novel class of homo- and heterodimeric 4,4- linked dioxazoles. In addition, a regioselective Suzuki-Miyaura cross-coupling of 2,4-dihalooxazoles followed by a Stille coupling has been successfully developed. The procedure affords convergent syntheses of trisoxazoles in high yield and in a minimum number of steps. Furthermore, C-2 direct arylation of oxazoles is discussed. This methodology is extended to the synthesis of C2-C4’ linked bis and tris oxazoles of the type found in the Ulapualide A family of natural products.