Enaminone-based Synthesis Of Heterocycles

Aza-heterocycles are important cores in many natural products,pharmaceuticals and agrochemical products. The condensation of carbonyl compounds with ammonia is well-documented as the traditional method to synthesize N-heterocycles. But they suffer from harsh reaction conditions and low efficiency. Recently, transition-metal-catalyzed cycloaddition reactions have provided complementary pathways. However, transition metals as catalysts may cause potential contamination of the products. Therefore, the development of more operationally simple method using readily available starting materials with broad functional group tolerability under metal-free conditions is still highly desirable. Recently, enaminone has emerged as a versatile synthetic intermediate for building various N-heterocycles due to their ambident nucleophilicity of enamineand the ambident electrophilicity of enone. This thesis focus on the enaminone-based synthesis of N-heterocycles,the main results obtained are as follows:(1) The base-promoted direct N-α,β-C(sp3)-H functinalization of enaminones was achieved for the synthesis of polysubstituted pyridines from1-arylethyl amines and ynones. Various polysubstituted pyridines were provided with high regioselectivity, high efficiency, and environmentalfriendliness.(2) A novel protocol to synthesize multisubstituted benzo[b][1,4]oxazepines from N-(2-haloaryl)enaminones was developed.With 2 equiv. of Cs2CO3, the iminoenol tautomer of N-(2-haloaryl)enaminone was captured by the C–X bond via an intramolecular O-arylation to afford substituted benzo[b][1,4]oxazepines.(3) Two classical heterocycles, pyrrole and pyridine, were simultaneously installed by the interception of in situ generated 1,4-oxazepinewith the in situ formed pyrrole from N-Propargylic β-enaminones for the preparation of N-(2-pyridyl)pyrroles.(4) A convenient “one-pot” regiospecific synthesis of substituted quinoxalines from o-phenylenediamines and ynones under metal-free conditions was developed. An intermolecular Micheal addition reaction,dehydration condensation and a base-promoted C-α-CH2-extrusion were involved in this procedure, which features high regioselectivity, efficiency and environmental friendliness.