Enantioselective Synthesis Of Nitrogen-Containing Heterocycles And α-Substituted Phosphonates

N-Heterocycles and chiral phosphonates are two important classes of heteroatomic compounds possessing extremely rich biological activities, which play important roles in the Pharmaceuticals, agricultural chemicals and natural bioactive compounds. Therefore, efficient synthesis of N-heterocycles and chiral phosphonates is the focus of research interests of organic chemists. With the development of modern organic synthesis, more and more new organic synthetic methodologies have been applied in the synthesis of heteroatomic and heterocyclic compounds. In this thesis, we will present the application of asymmetric organocatalysis, olefin cross-metathesis, aza-Wittig reaction, and catalytic asymmetric hydrogenation toward the synthesis of optically active 1,2,3,4-tetrahydro-quinolines and chromans, pyrazolo[3,4-d]pyrimidin-4-ones, and chiralα-oxophosphonate derivatives which possess potential biological activities. The purpose of this research is to expand the application scope of new methodologies and to synthesize biologically active heteroatomic and heterocyclic compounds.1. Asymmetric synthesis of tetrahydroquinolines and chromans via tandem Grubbs Ru-catalyzed olefin cross-metathesis reaction and organocatalytic intramolecular Friedel-Crafts alkylation has been described. With the use of MacMillan chiral imidazolidinone as catalysts, this novel tandem reaction gave the corresponding tetrahydroquinolines and chromans in 30-95% yields and up to 90% ee in Et₂O at room temperature.2. Synthesis of novel pyrazolo[3,4-d]pyrimidin-4-one derivatives possessing potential herbicidal activity has been carried out via the tandem aza-Wittig and annulation reactions. The title compounds 6-(4-alkoxycarbonylalkoxy)phenoxy-3-alkylthio (alkylsulfonyl)-1-phenyl-5-(substituted phenyl)-pyrazolo[3,4-d]pyrimidin-4-ones 3-6 and 3-7 have been synthesized by the reaction of the corresponding substituted phenols 3-2 with carbodiimide 3-5 in 52-98% yields in the presence of K₂CO₃ as base. The title compounds bear both the skeletons of pyrazolo[3,4-d]pyrimidin-4-one and aryloxyphenoxypropionate (APP).3. Highly enantioselective synthesis of herbicidal activeα-oxophosphonates has been achieved via catalytic asymmetric hydrogenation. With the use of Rh(I)/Me-DuPhos as the catalytic system, the prochiralα-acyloxy-α,β-unsaturated vinyl phosphonates could be hydrogenated to the corresponding a-substituted phosphonates in high enantiomenc purity (89-96% ee) in methanol at room temperature.4. One hundred and seventy Compounds (totally six series) have been designed and synthesized. Their structures were clearly verified by spectroscopic data (NMR, IR, MS, Elemental analysis or X-ray diffraction crystallography). Among which one hundred and eighteen compounds have been preliminarily biologically investigated. The results of preliminary bioassay indicated that the title compounds 3-6, 3-7, and 4-4 showed good herbicidal activity which could be potential herbicides. And R or S isomers of 4-5 have little difference in the herbicidal activity compared to the racemates.