Van Leusen oxazole synthesis

T10425>. Through a proper use of the Suzuki-Miyamura and van Leusen oxazole synthesis it was possible to synthesize a wide variety of aromatic derivatives substituted with oxazole rings. The strategy was based on the initial synthesis of the aromatic scaffold and the subsequent reaction of the carbonyl functions with toluenesulfonylmethyl isocyanide (TosMIC) as depicted in the following scheme<07S3653>. 

In related studies on the transformations of tosylmethyl isocyanide (24 TosMIC), van Leusen and co-workers found that the based-mediated condensation of 24 and a range of aldehydes yielded the corresponding 5-substituted oxazoles (c/, 28). This methodology thus provided an alternative to the Schollkopf reaction in the preparation of these compounds, and has subsequently become known as the van Leusen oxazole synthesis. 

In analogy to the van Leusen oxazole. synthesis (cf. p. 173), the anion of TosMIC adds to the imine function and the addition product 46 cyclizes to the imidazoline 47, which undergoes base-induced elimination of sulfinic acid producing the imidazole 45. 

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