Oxazole Stille coupling reaction

Oxazole compounds can also be produced by use of the Stille reaction. Clapham and Sutherland describe the use of tri-2-furylphosphine/Pd2(dba)3-catalyzed Stille coupling reactions (Scheme 12) to produce a range of oxazole-containing derivatives, including 58, with an 85% yield [56]. 

Bromo- and 4-bromoalkyl-2,5-diphenyloxazole 38 were subjected to the Stille coupling with a range of commercially available tributyltin reagents. Tri-2-furylphosphine/ Pd2(dba)3 was used as an effective catalyst. Copper(n) oxide enhanced the Stille coupling reactions of 2,5-diphenyl-4-tributylstannanyloxazole with various electrophiles [41]. Such method offered an efficient synthetic route to prepare resins from oxazole-containing monomers such as 2,5-diphenyl-4-vinyloxazole. 

The intermolecular Heck reactions of oxazoles and thiazoles with olefins are not too common. They are rarely high yielding since in several cases they are biased by dehalogenation. Due to this reason the olefination of these systems is usually achieved through Stille coupling with vinylstannanes. 

The 2-aryloxazoles have also been synthesized under microwave activation by the direct Stille and Suzuki cross-coupling reactions of 1,3-oxazoline (OXT) [17]. Nolt et al. [18] utilized the microwave-assisted Cornforth rearrangements for the preparation of substituted 5-amino-oxazole-4-carboxylate (v). 

Smith 111 et al. reported an effective synthesis of a variety of 2,4-orthogonally functionalized oxazoles with shorter reaction times and modest to excellent overall yields (48-90%). 2-Chloromethyl-4-vinyloxazole (36) was obtained in 78% yield via the Stille coupling of 2-chloromethyl-4-triflate with vinyltributyltin [40]. 

The Hantzch-Panek condensation of ethylpyruvate with acrylamide followed by treatment with trifluoroaceticanhydride (TFAA) provided 2-vinyloxazole-4-ethylcarboxylate 37 in good yield [57]. The Stille coupling of 2-chlorooxazole-4-ethylcarboxylate with vinyltrimetbylstannane also provided 2-vinyloxazole 37 [26]. The reactivity of 37 towards cycloaddition reactions with enone and coupling reactions with aryl halides were explored [57]. Heck reaction of vinyloxazole with p-iodoanisole gave the cinnamyl oxazole 97 in 71% yield [57]. 

Vinyl oxazoles are efficiently prepared through Stille reaction of a halooxazole with a vinyl stannane therefore, there are relatively few reported Heck reactions of halooxazoles with olefins. Yamanaka s 1987 Sonogashira paper included a section of Heck coupling reactions. The authors noted poor yields with 2-bromooxazoles, and yields that were variable at best for 4-and 5-bromooxazoles. 

The use of organostannyl oxazoles in Stille reactions has also been reported <2001JOC9033>. 4-Tributylstannyl oxazole 53 can be generated via an organolithium deprotonation of oxazole 52 which underwent a Pd-mediated crosscoupling with a benzyl chloride to give a coupled product in good yield (Scheme 6). 

In total synthesis papers, most reported Stille reactions involving oxazoles occur remotely to the oxazole ring. Most papers detailing direct Stille reaction of an oxazole ring are methodology papers. Williams showed that 2-phenylsulfonyl-5-stannyloxazole is a competent coupling partner with a vinyl iodide in a Stille reaction, and Taylor utilized a series of 2-chlorooxazoles as coupling partners for Stille reaction with... 

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