Synthesis And Application Of Chiral N, P-ligands

Chiral compounds are very important for physiological activity of the organism. It is importance to gain pure chiral molecules by isolation from natural resources or artificial synthesis. Too many studies indicated that is a attractive way to obtain the desired chiral compounds by transition metal-catalyzed asymmetric reaction in high yield, excellent enantioselectivity and diastereoselectivity. Desigan, synthesis, development and application of new chiral ligands are the topics of transition metal- catalyzed asymmetric reaction. More attentions were paid to chiral N, P-ligands because of its high catalytic activityNitrogen heterocycle is one of the most important units for synthesis of many natural products, pharmaceuticals and Proline derivatives. What's more, the asymmetric cycloaddition reaction is considered as one of the most simple and effective methods to gain heterocyclic compounds. Now, transition metal-catalyzed cycloaddition reactions have been broadly focused by chemist due to its fascinating catalytic activity and stereoselectivity.In the thesis, we prepared three serious of new chiral N, P-ligands with L-Proline framwork, then examined the catalytic efficience and the steroselectivity in Cu(I) and/or Ag(I) catalyzed aza Diels-Alder reactions and 1,3-dipolar cycloadditions. The thesis was divided into two parts.In the frist part of the thesis, we studied the synthesis of chiral N, P-ligands. Synthesis of chiral N, P-ligands (2, 4, 5). First, we used L-Proline as the chiral source to synthesize (2-((diphenylphosphino)methyl)pyrrolidine) according to repo- rted method. Then, the (2-((diphenylphosphino)methyl)pyrrolidine) was coupled with differents substituented 2-ethoxy-4, 5-dihydrooxazole to give the desired ligands. Synthesis of chiral N, P-ligands 1 and 3. Compounds 1and 3 were obtained by the reaction between 2-methoxypyridine or 2-methyoxy-6-methylpyridine and lithium amide of (2-((diphenylphosphino)methyl)pyrrolidine).Synthesis of chiral N, P-ligand 6 and 7. The reaction of (2-((diphenylphosphin o)me thyl)pyrrolidine) with pivaloyl chloride gave the amide. The amide was reduction by NaBH4 to give the chiral N, P-ligand 6. The chiral N, P-ligand 7 was obtained by alkylation of (2-((diphenylphosphino)methyl)pyrrolidine) using diphenylmthyl bromide as alkylation reagent and triethylamine as base.Secondly, a comprehensive examines of effects on Cu or Ag complexes catalyzed asymme- tric cycloaddition reactions were taken. It was very interesting to find that the desired cycloaddition product can be obtained in high yield in the asymmetric [4+2] cycloaddition reaction under the best conditions, that is using AgOTf and chiral ligand1 could provide. Meanwhile, we found that the complex formed from CuOTf and chiral ligand 1 is a better altertive to catalyze asymmetric [3+2] cycloaddition reaction to give the taget compound in excellent yield.In present, the enantioselectivity of the cycloaddition is not so high. However, it is important to note that more higher enantioselectivity would be obtained by further modification of the ligand or in the others asymmetric catalytic reactions.