4<i>H</i>-1,2-Benzoxazines with Electron-Withdrawing Substituents on the Benzene Ring:  Synthesis and Application as Potent Intermediates for Oxygen-Functionalized Aromatic Compounds

A new general method for synthesizing functionalized 4<i>H</i>-1,2-benzoxazine derivatives is described. Although 4<i>H</i>-1,2-benzoxazine is one of the fundamental structure of the oxazine group, no general synthetic method for the heterocycle has been established. We found that 3-methoxycarbonyl-4<i>H</i>-1,2-benzoxazine was obtained in good yield when methyl 2-nitro-3-phenylpropionate was treated with an excess amount of trifluoromethanesulfonic acid. This methodology was also applicable for the synthesis of 4<i>H</i>-1,2-benzoxazine rings functionalized with various electron-withdrawing substituents on the benzene ring. Furthermore, we also show that the resulting 4<i>H</i>-1,2-benzoxazines can be used as precursors of functionalized <i>o</i>-quinone methides and multisubstituted phenols. This type of heterocycle can be a potent intermediate to oxygen-fuctionalized aromatic compounds.