Synthetic Studies Towards Benzo-[1.3]oxazines From Aryl Glycine Derivatives

The whole thesis is divided into three parts. In Part One, a review of generation methods, reactionpathways and applications in natural product syntheses of ortho-quinone methides as reactiveintermediates is presented.Part Two is focused on reaction conditions for the synthesis of aryl glycine derivatives. Byimplenting various (ortho-hydroxymethyl)aryl benzoates as substrates, aryl glycine derivatives wereobtained by treat with amines under ambient conditions. Merits of this method includes unnecessary ofpreliminary halogenation of the hydorxyl group and excellent yields (74%~93%). Aryl glycinederivatives were produced by in-situ generation of ortho-quinone methides under base conditions andsubsequently aza-Michael additions. Amines play two roles in this process, which is the reagent thatpromotes the rearrangement and the nucleophile of the conjugate addition. Tuning the ratio ofnucleophiles and tertiary amines could shorten reaction time. The addition of tertiary amines enhancedthe addition process for less basic nucleophiles with excellent yields. Substace could undergodimerization when nucleophiles are absent. Products are characterized by1H NMR,13C NMR, HRMSand IR analysis.Part Three described a method for the synthesis of1,3-benzoxazines. In the process of examine thechemical properties of N-substituted aryl glycine esters obtained in Part Two, a mixture of hydroxylprotection products and1,3-benzoxazines were observed under typical protection conditions. Afteroptimization of reaction conditions, a series of multisubstituted1,3-benzoxazines were synthesized withexcellent yields (70%~95%). Proposed reaction mechanism suggests that the intramolecular hydrogenbonding between hydroxyl and amino group plays vital role in the chemoselectivity. Modification ofester group gave aza-flavoid and polyring benzoxazines. Products are characterized by1H NMR,13CNMR, HRMS and IR analysis.