Diastereoselective Synthesis Of Propagylamine Via Three Component Couplings Of α-oxyaldehyde, Alkynes, And Amines In Water

High yield and low cost were major concerns in traditional organic synthesis. According to the concept of Green Chemistry, many factors such as low toxic and vaporized solvent, reduction of waste, mild condition, recyclable materials as well as atom-economy should be considered. For these concerns, more cheap reactions should be explored. Choosing an environmentally benignant cleaning reaction solvent is an important part of Green Chemistry research. Water is the cheapest and mildest reaction solvent. Water is an ideal green solvent because it has advantages in terms of cost, safety, environmental concerns and simple operation. Meanwhile, water is the basis and bearer of life, and numerous biochemical organic reaction and inorganic reactions take place in water. Recently, metal organic reaction in aqueous media provided many opportunities to synthetic chemistry with high efficiency and high selectivity, which is significant study field. Based on the principles of Green Chemistry, requirement of atom-economy, this thesis developed diastereoselective synthetic method of propargylamine which contained chiral nitrogen by three coupling of aldehyde-amine-alkyne. By using Cu, Ag and Au as transition metal catalysts, we investigated their catalytic and chelate mechanism in synthesis of propargylamine, and then studied the influence of latter transition metal catalyst and aqueous media on selectivity of the reaction.Chiral nitrogen compound widely exist in nature. The propargylamine which containα-amino alcohol structural unit is of importance in terms of bioactivities. It is one of the major goals to develop synthetic method of enantio- or diatereo- pure amine. On the basis of previous studies on A3 coupling, this thesis investigated diatereoselectivity of propargylamine containingα-oxyamine, which was synthesized fromα-oxyaldehyde.To obtainα-oxyaldehyde, we got allylic alcohols from reactions of aldehyde and vinyl magnesium bromide, and then protected allylic alcohols by different group, finally achievedα-oxyaldehydes via ozonolysis from allylic alcohols.In Three-Component couplings of aliphatic aldehyde with alky side chain inα-position, piperidine and phenylacetylene, catalytic activity in A3 reactions involvingαsubstituted aliphatic aldehyde. Variation among copper, silver and gold catalysts as well as reaction temperature influence diastereoselectivity very slightly, while affect reaction yield apparently. Type of substituent is the key factor impaction diastereoselectivity in this kind of A3 reaction, when oxygen was introduced intoαposition of aldehyde, desired propargylamine was not obtained due to chelation effect between silver and oxygen. However, gold catalyst gave very high yield. AuI catalyst gave the highest yield and good diastereoselectivity even at room temperature. The highest yield and the best selectivity were obtained in water solvent at room temperature. So it is ideal atom-economy in aqueous media under mild condition.Based on investigation on A3 reaction involvingα-oxyaldehyde, three components coupling of carbohydrate, piperidine and phenylacetylene was also studied. Through these researches, we tried to explore the reaction's biological scope. When the optically pure protected glyceraldehydes were used, the corresponding propargylamine was obtained in high diastereoselectivity and good yield. But in terms of glucose pentacetate and benzyl protected glucose, A3 reaction didn't work, which reaction activity was much worse than that of glyceraldehydes. Probably the main reason is glucose could transform into stable six-ring hemiacetal.In the thesis, the mechanism of Three-Component coupling ofα-oxyaldehyde, piperidine and phenylacetylene was analyzed. It was also investigated that transition metal could activate C-H bond of terminal alkynes and activate double bond of amine to improve the reaction of amine and terminal alkynes. The chelating mechanism of A3 reaction with Cu, Ag and Au as catalysts was further explored.Relative conformation of propargylamine that containedα-hydroxyl amino structural unit was determined by comparing coupling constant of proton. The ratio of anti/syn was also obtained.By means of GC, NMR, IR, MS and HRMS, we isolated and analyzed all the diastereomers in this thesis.