Transition Metal-catalyzed Synthesis Of Heterocyclic Compounds

Transition metal-mediated cyclization is one of the most attractive methodologies to synthesize heterocyclic compounds. It can construct complex molecules from readily accessible starting materials under mild conditions with high selectivity. Iron and copper have drawn much attention in organic synthetic chemistry due to their unique properties, such as low price, less toxicity and easy of synthesis. This thesis is focused on the synthesis of heterocyclic compounds catalyzed by iron or copper, including the following five parts:1. An efficient one-pot procedure for the preparation of 1,4-benzoxazine derivatives through copper-catalyzed three-component couplings was reported. The three-component coupling of aldehydes, amines and alkynes (A3 coupling) was a convenient method towards propargylamines. Arylamines with an ortho-oxygen nucleophile can also be employed in the A3 coupling reaction, and a sequential intramolecular nucleophilic attack of the oxygen to the triple bond furnished the benzoxazine derivatives in one-port. N-methyl, N-allyl and N-benzyl substituted 1, 4-benzoxazine derivatives were obtained in a high regio- and stereo selectivity manner with the yields from 30% to 85%.2. Iron-catalyzed high regioselective intramolecular O-H addition across C-C triple bond to affod 2H-1-benzopyran derivatives was described. Different additives could effect the reaction significantly. The use of aniline give 2H-1-benzopyran derivatives as the main products, while the use of butan-1-amine give benzofuran derivatives as the only products. The substrates with two aryl groups at the propargylic position and the triple bond terminus could afford the corresponding 2H-1-benzopyran derivatives with higher selectivity. In many cases, the 2H-1-benzopyran derivatives were the only product, others afforded a mixture of benzopyran and benzofunan with the selectivity from 87:13 to 95:5.3. Xathenes could be efficiently prepared using iron-catalyzed, microwave-promoted cascade benzylation-cyclization of phenols. Through the introd ucing of an ortho-halogen substitute to the benzylating reagents, a cascade benzylation/cyclization catalyzed by FeCl3 occurred to give xanthene derivatives in one port with the yields from 38% to 77%. And a variety of benzylating reagents such as benzyl acetates, benzyl bromides, and benzyl carbonates could afford 9-substituted xanthene derivatives conviently, especially 9-alkyl xanthenes, which were difficult to synthesize according to the reported methods.4. lndolizines are important nitrogen-containing heterocyclic compounds and many of them display important biological activities. Through Pd/Cu-catalyzed coupling/cycloisomerization reaction of 2-bromopyridine with propargyl ether, 3-substituted indolizines could be synthesized in one-pot. The reaction was carried out in a tandem manner without isolation of intermediates, 8 desired compounds were synthesized.5.2-allylsubstitued indolizines were obtained conviently through copper-catalyzed cyclic isomeriation/nucleophile addition of (3-(pyridin-2-yl) prop-2-ynyl) amine. The best condition was to use CuI as catalyst, Cesium carbonate as base, DMA as solvent. Under this condition, the desired products were obtained in 33%-68% yields, and there are no reports for the preparation of 2-allylsubstituted indolizines, to the best of our knowledge.In this thesis,8 designed 1,4-benzoxazine derivatives,15 designed 2H-1-benzopyran derivatives,14 designed xanthene derivatives, and 21 designed indolizines were synthesized. All compounds were characterized by 1H,13C NMR spectroscopy and mass spectroscopy.