Nitriles 2.4.5- trisubstituted oxazoles

Kawano Y, Togo H (2009) lodoarene-catalyzed one-pot preparation of 2,4,5-trisubstituted oxazoles from alkyl aryl ketones with mCPBA in nitriles. Tetrahedron 65 6251-6256 Jarikote DV, Siddiqui SA, Rajagopal R, Daniel T, Lahoti RJ, Srinivasan KV (2003) Room temperature ionic liquid promoted synthesis of 1,5-benzodiazepine derivatives under ambient conditions. Tetrahedron Lett 44 1835-1838... 

TABLE 1 18. 2.4,5-TRISUBSTITUTED OXAZOLES FROM OXIDATION OF KETONES WITH IRON(III) solvates of NITRILES" ... 

Kim and co-workers prepared a series of 2,4,5-trisubstituted oxazoles 1614 in low to good yields from desoxybenzoins 1613 and nitriles (Scheme 1.411). This Ritter-like reaction works best in the presence of a 1 1 mixture of trifluoromethane-sulfonic acid-sulfuric acid. Trifluoromethanesulfonic acid or sulfuric acid alone is ineffective. Fuming sulfuric acid gave < 10% of an oxazole. The authors proposed that sulfuric acid acts as an oxidant, analogous to Tl(OTf)3 or Cu(OTf)2. ... 

As described in Sect. 2.1.2, the a-functi(Mialization (tosylation, triflation) of ketones with hypervalent iodine, followed by nucleophilic attack by diverse nucleophiles in an intramolecular fashion offers a convenient entry to various heterocycles [6]. Such a transformation can also be realized in an intermolecular fashion. Along these lines, Togo and coworkers [97] reported an elegant one-pot synthesis of 2,4,5-trisubstituted oxazoles 142 from alkyl aryl ketones 140 and nitriles 141 via an iodoarene-catalyzed oxidation reaction (Scheme 35). In this reaction sequence, reactive aryliodonium species were generated in situ by the reaction of aryl iodide with mCPBA and trifluoromethanesulfonic acid (TfOH). Afterwards, aryliodOTiium species reacted with alkyl aryl ketone to form a fi-keto aryliodonium species. 

A new approach to the synthesis of 2,4,5-trisubstituted and 2,5-disubstituted oxazoles, 97 and 98, used l-(methylthio)acetone 95 with nitriles in the presence of trifluoromethanesulfonic anhydride. The proposed mechanism involves an unstable 1-(methylthio)-2-oxopropyl triflate 96 which was detected using NMR spectroscopy <06JOC3026>. 

---