1,2-Oxazines and their Benzo Derivatives

Abstract

This chapter covers all significant developments concerning 1, 2-oxazines and their benzo derivatives which appeared in the literature during the period 1996–2005. In this chapter, most of the information refers to the mono- and bicyclic oxazines and benzo-fused bi- and tricyclic ring systems. The 1,2-oxazines containing fused heterocyclic and bi- or tricyclic bridgehead ring systems with nitrogen at the bridgehead are not covered. Several research groups have investigated the ring synthesis of dihydro- and tetrahydro- 1,2-oxazines via intra- and intermolecular cycloaddition of nitroalkanes, nitroalkenes, nitrones, cyclization of oximes, hydroxamates, and appropriately substituted O -, N -alkylhydroxylamines. In addition, several 1,2-oxazine containing compounds have been prepared via the following cycloaddition reactions: [4+2] hetero-Diels–Alder, tandem [4+2][3+2], domino [4+2][4+2][3+2], homo [3+2], and [3+3]. Very useful synthetic methods have been developed for the preparation of highly substituted nitrogen-containing compounds (amino acid esters, pyrrolidines, piperidine, and indolizidines) via reductive cleavage of N–O bonds. The most common reagents employed for such reductive N–O bond cleavage reactions are H 2 /Pd/C, Mg(Hg)/TiCl 4 , Al/Hg, Li/Hg, Na/Hg, and SmI 2 . The cis- or trans -4,5-dihydroxy-6 H -1,2-oxazines are derived from 3,4-dihydro-6 H -1,2-oxazines via OsO 4 and epoxidation followed by ring opening by acid, respectively. The following reactions at the ring nitrogen of the 1,2-oxazine have been reported: N-alkylation, N-acylation, N-oxidation, etc. 1,4-Addition of alkyl- and aryllithium compounds to 1,2-oxazines proceeded without detectable interference of competing 1,2-addition to the C N bond. Several core ring transformations involving oxazines have been encountered in natural products and pharmaceuticals via ring expansion and ring contraction reactions.