The Extending Of The JWang’s Tandem Reaction

Phosphonate as one part of the nucleic acid is found in plants and animals in large quantities. Arylphosphonates are widely widely employed in materials, such as fuel cell membrane materials, optical materials, polymer materials, etc.; Some of them also show biological activities and have been used in medicinal chemistry and nucleic acid chemistry. Furthermore, they are also important intermediates for the synthesis of heterocyclic compounds. But as far as we know, researches on the synthesis of arylphosphonates are limited. Most reports synthesize arylphosphonates by introducing phosphate ester to synthesized aromatic ring compounds. But synthetic methods in the literatures suffer strict operation conditions or make metal catalysts needed.On the other hand, Bridgehead nitrogen-containing heterocycles has drawn more and more attention of medicinal chemists and organic chemists due to their similarities and diversions in structure to indole.Our team accidentally discovered a new type of JWang’s tandem reaction during the restructuring losartan as an antihypertensive drug. The advantages of the JWang’s tandem reaction are easily available reactants, mild reaction conditions and simple post-processing. A few series bridgehead nitrogen-containing heterocycles were synthesized through the reaction and their optical properties and antitumor activities were also investigated.On the basis of previous work, this dissertation make γ-bromine-α,β-unsaturated phosphate instead of γ-bromine-α,β-unsaturated carbonate to obtain series of arylphosphonates. indolizine, pyrazole[1,5-a]pyridine and pyridine[1,2-a]benzimidazole phosphonates were synthesized under the optimized reaction conditions. In the case of pyridine[1,2-a]benzimidazole, a series of condensed ring compounds with no phosphonate were obtained. After the test of1H and13C NMR, IR, MS, X-ray crystallographic analysis, the structures were defined as follows:The product was obtained by a new tandem reaction. Instead of water-elimination in Jwang’s reaction, Horner-Emmons reaction occurred as the last stage in the new tandem reaction.A plausible reaction course with five stages was proposed based on previous work and the results of the reaction:Sn2, deprotonation, electron flow, nucleophic addition, Horner-Emmons reaction. The effect of reactant on the selectivity of the last stage in the reaction was also discussed.In summary, this thesis make sence in four aspects:1. To expand our previous work, we found a new tandem reaction and the reaction mechanism was also proposed;2. a few series of bridgehead nitrogen-containing heterocycles and arylphosphonates were obtained with potential biological activity and optical properties;3. provide a new novel method for synthesizing bridgehead nitrogen-containing heterocycles;4. bring the phosphate to the bridgehead nitrogen-containing heterocycles by a sample tandem reaction. Thus, this work has important implications in organic synthesis.