Synthesis of 1,4-Benzoxazines by Domino S_N2 and Goldberg Coupling

Significance

Reported is a simple, efficient and alternative method to conventional multistep processes to prepare a 1,4-benzoxazine skeleton from aziridines 1 and ortho-iodophenol 2. The trans-1,4-benzoxazines 3 (stereochemistry established by X-ray structure analysis) are obtained in good to excellent yields using the easily available ethylenediamine-CuI complex as catalyst and K₂CO₃ as base. The reaction may be considered as initial aziridine ring opening (S_N2) followed by intramolecular copper-catalyzed Goldberg-type amination of the aryl iodides (S. L. Buchwald and co-workers J. Am. Chem. Soc. 2005, 127, 4120). A range of aziridines (6-, 7-, 8-membered ring with or without unsaturation) and substituted o-iodo­phenols (EWG and EDG) participate in this high-yielding and stereoselective reaction.