Synthesis of Oxazoles via TBHP/I₂-Mediated Reaction of Alkenes with Benzylic Amines

Significance

Reported is an efficient synthesis of polysubstituted oxazoles 3 by a TBHP/I₂-mediated oxidative cyclization of aryl alkenes 1 with benzylic amines 2. The reaction involves three sequential steps, halogenation and oxidation of the olefin followed by cyclization to give product 3. Optimization studies indicated the requirement of t-BuOOH (TBHP) as oxidant, I₂ as halogen source, and DMSO as solvent as involved in the Kornblum oxidation (N. Kornblum et al. J. Am. Chem. Soc. 1957, 79, 6562). An excess of benzylamines is necessary to overcome the oxidation of benzyl­amine to benzaldehyde. The scope of the reaction shows that reactions of alkenes bearing EWGs or EDGs on the aromatic ring proceed smoothly in good yield to afford the expected oxazoles 3. Moreover, terminal heterocyclic alkenes can be used as substrates. With respect to the benzyl­amine substrates, EDGs were shown to be unfavorable for the formation of oxazoles, whereas EWGs showed an increase in the reaction yields. A plausible mechanism was proposed without evidence.