Convenient Synthesis of 1,4-Dihydro-2H-3,1-benzoxazin-2-ones by Iodocyclization of t-Butyl 2-Vinylphenylcarbamate

Abstract

It has been found that t-butyl 2-vinylphenylcarbamate derivatives underwent iodocyclization on treatment with iodine in the presence of sodium hydrogencarbonate to afford 4-iodomethyl-1,4-dihydro-2H-3,1-benzoxazin-2-one derivatives in generally good yields. The reduction of these 4-iodomethyl derivatives with tributyltin hydride gave the corresponding 4-methyl derivatives in good yields.We previously demonstrated that the preparation of 4H-1,3-benzodioxin-2-one derivatives could be achieved by iodocyclization of t-butyl 2-vinylphenyl carbonate derivatives, derived from t-butoxycarbonylation of 2-vinylphenol derivatives. 1 As an extension of this cyclization reaction, we anticipated that a similar sequence starting with 2-aminostyrene derivatives should lead to formation of 1,4-dihydro-2H-3,1-benzoxazin-2-one derivatives. We report here on details concerning the results of our investigation which provide a new and simple method for constructing the 1,4-dihydro-2H-3,1benzoxazin-2-one skeleton. 2 Compounds having this skeleton have attracted considerable attention of medicinal and synthetic organic chemists, because some of them have been reported to exhibit a variety of biological activities, 3 such as HIV-1 reverse transcriptase inhibitory 3a and progesterone receptor antagonistic activities. 3b,e 1-Substituted 1,4-dihydro-2H-3,1-benzoxazin-2-one derivatives have been used as precursors for the generation of the corresponding aza-o-quinodimethane intermediates. 4 Most of the previous syntheses of 1,4-dihydro-2H-3,1-benzoxazin-2-one derivatives have been based on the reaction of 2-aminobenzyl alcohol derivatives with phosgene, 3,5,6 though Nishiyama, Naitoh, and Sonoda have recently reported a synthesis of 4-nonsubstituted derivatives by selenium-catalyzed carbonylation of 2-nitrobenzyl alcohols. 7 We conducted reactions of t-butyl 2-vinylphenylcarbamates (2), which were easily prepared by t-butoxycarbonylation of 2-aminostyrene derivatives (1) with di-t-butyl dicarbonate under the conditions