Direct Arylation of Oxazoles at C2. A Concise Approach to Consecutively Linked Oxazoles

Abstract

The synthesis of bis- and trisoxazoles via direct arylation is discussed. A variety of aryl groups can be installed at the 2-position of 5-aryl and 5-carboxy-substituted oxazoles under mild conditions using palladium catalysis on water. The direct arylation method can be extended to the synthesis of bis- and trisoxazoles if 2-triisopropylsilyl-4-iodooxazole is used as the electrophile in the arylation.

Recent advances in direct C–H arylation: Methodology, selectivity and mechanism in oxazole series

“…Hoarau selected Cy-JohnPhos and P( o -tol) 3 electron-rich ligands for the direct, C2-selective arylation of ethyl oxazole-4-carboxylate with iodides, bromides and chlorides (Scheme 9) [49–50]. Greaney and Ackermann further revealed the high performance of the Herrmann–Beller precatalyst (HBP) as well as the (1-Ad) 2 P(O)H/Pd(OAc) 2 combination for the direct coupling of ethyl oxazole-4-carboxylate, with iodides and bromides, respectively (Scheme 9) [51–52]. …”

Intermolecular and Selective Synthesis of 2,4,5‐Trisubstituted Oxazoles by a Gold‐Catalyzed Formal [3+2] Cycloaddition

“…[13] This is seemingly due to poor chemoselectivity in the formation and application of the required 1,3-N,O-dipole equivalent, acyl nitrenes, for instance by thermal or photochemical decomposition of acyl azides in the presence of alkynes. [19] The novel reactivity of the aminide as a potentially controllable N-acyl nitrene equivalent to form oxazoles was studied (Table 1). [16] Similarly convergent one-step or one-pot methods to prepare functionalized 1,3oxazoles are rare, [8] and often require the use of highly reactive species with consequent structural limitations.…”

Recent Developments in Pd-Catalyzed Direct Arylations of Heteroarenes with Aryl Halides

“…Searching for direct arylation routes to bioactive polyazoles, Greaney and co-workers synthesized C2 TIPS-protected 4-iodooxazole, which was then employed in a short synthesis of the trisoxazole core of the antifungal ulapualide A (Scheme 24) [39].…”