Synthesis of 1,4-benzoxazines via Y(OTf)3-catalyzed ring opening/annulation cascade reaction of benzoxazoles with propargylic alcohols

A convenient Y(OTf)(3)-catalyzed cascade formal [4 + 2] cyclization approach for the formation of 1,4-benzoxazine scaffolds from benzoxazoles and propargyl alcohols through a ring-opening and regioselective ring-closure process has been developed. By using this mild and practical protocol, a broad range of aldehyde-containing 1,4-benzoxazine compounds were prepared in moderate to excellent yields with good functional group tolerance. Mechanistic studies indicated that an S(N)1 nucleophilic substitution of benzoxazole with a propargyl cation was involved in this transformation.

Automated summary

A convenient Y(OTf)(3)-catalyzed cascade formal [4 + 2] cyclization approach for the formation of 1,4-benzoxazine scaffolds from benzoxazoles and propargyl alcohols has been developed. The mild and practical protocol allows for the preparation of a broad range of aldehyde-containing 1,4-benzoxazine compounds in moderate to excellent yields. Mechanistic studies revealed an S(N)1 nucleophilic substitution of benzoxazole with a propargyl cation in this transformation.