Solid-Phase Synthesis of Benzoxazoles

In SPOS, the choice of the linker that serves to attach the library scaffold to the polymer support is critical. As a result, a variety of elegant linking methods have been developed that enable the introduction of additional diversity into the products during the cleavage reactions. The sulfone linker is an example of a safety-catch linker that can be cleaved from resins by using nucleophilic substitution reactions with amines. 

We reasoned that a possible solution to this problem would be to accelerate the cyclization reaction. Therefore, we examined the effects of various additives, including 

---

SOLID-PHASE SYNTHESIS OF BENZOXAZOLES VIA MITSUNOBU REACTION... 

Solid-Phase Synthesis of Benzoxazoles via Mitsunobu Reaction... 

Wan1997a Wang, F. and Hauske, J.R., Solid Phase Synthesis of Benzoxazoles via Mitsunobu Reaction, Tetrahedron Lett., 38 (1997) 6529-6532. 

A solid-phase preparation of benzoxazoles by the Mitsunobu reaction, suitable for the synthesis of a combinatorial library, has been described 2-aminophenol attached to a solid support is converted into the conesponding benzoxazoles by treatment with carboxylic acids in the presence of triphenylphosphine and diethyl azodicarboxylate in THF at room temperature <97TL6529>. Heating diacylated 2-aminophenols with toluene-p-sulfonic acid in boiling xylene gives high yields of benzoxazoles 61 <97T457>. 

H. Hioki, K. Matsushita, M. Kubo, K. Harada, M. Kodama, Y. Fukuyama, Solid-phase combinatorial synthesis of benzothiazoles, benzimidazoles, and benzoxazoles using a traceless linker. Tetrahedron 63 (2007) 11315-11324. 

---