具有生物活性的呋喃环与吡咯环衍生物的合成研究
发布时间：2019-06-18 11:28
【摘要】：本论文主要研究手性氮膦配体、2,3-二取代-5-乙烯基-4,5-二氢呋喃衍生物以及2-次甲基吡咯环衍生物的合成。1.合成了一系列酰胺类及亚胺类手性氮膦配体。首先,将生物碱辛可宁衍生为伯胺化合物,然后与2-(二苯基氧膦)苯甲酸通过脱水缩合合成最简单的酰胺类手性氮膦配体,紧接着通过插入不同氨基酸合成了一系列酰胺键类手性配体。同时,将辛可宁伯胺化合物与不同氨基酸及2-(二苯基膦)苯甲醛通过脱水缩合反应合成不同系列的亚胺类手性氮膦配体。2.在金属催化剂与配体协同催化下,利用烯丙基二碳酸酯与β-酮酯通过分子间的C-烯丙基化反应与分子内的O-烯丙基化反应合成2,3-二取代-5-乙烯基-4,5-二氢呋喃衍生物。通过对实验反应参数进行优化,最终选择以2 mol%Pd(PPh3)4与2 mol%1,2-双(二苯基膦)乙烷作为高效催化体系,并在此高效催化体系下合成一系列2,3-二取代-5-乙烯基-4,5-二氢呋喃衍生物。结果表明,反应底物含有吸电子基团时反应具有较高的反应活性及产率。随后,又利用所合成的手性氮膦配体与金属协同作用合成手性2,3-二取代-5-乙烯基-4,5-二氢呋喃衍生物,虽然没有得到较高ee值的手性目标产物,但为后续的研究提供了实验经验和理论指导。3.在合成的手性氮膦配体、金属以及碱的共同催化下,以末端炔基二碳酸酯与保护的亚胺为底物,通过Mannich反应及炔氢胺化串联环化反应合成2-次甲基吡咯环衍生物,并对反应条件-金属催化剂、手性配体及反应溶剂进行筛选优化,在优化的条件下成功得到目标产物,其产率为83%,ee值为65%。
[Abstract]:This paper mainly deals with the synthesis of chiral nitrogen-derived ligands, 2,3-disubstituted-5-vinyl-4,5-dihydro-derivatives and 2-methomorphin derivatives. A series of chiral amine and imine chiral nitrogen-derived ligands were synthesized. First, the alkaloid cinchonine is derived as a primary amine compound, and then is synthesized by dehydration condensation with 2-(diphenyl oxide) benzoic acid to synthesize the simplest triamine-like chiral nitrogen-derived ligand, followed by the synthesis of a series of amine-like chiral ligands by inserting different amino acids. In that same time, the compound of the primary amine of the cinchonine and the different amino acid and 2-(diphenylmethyl) benzaldehyde are synthesized by a dehydration condensation reaction to synthesize a different series of imine chiral nitrogen-based ligands. 2,3-disubstituted-5-vinyl-4,5-dihydro-derivatives are synthesized by the C-allylation reaction between the molecules and the O-allylation reaction in the molecule with the co-catalysis of the metal catalyst and the ligand. The experimental reaction parameters were optimized,2 mol% Pd (PPh3)4 and 2 mol% 1,2-bis (diphenylmethyl) ethane were selected as the high efficiency catalytic system, and a series of 2,3-disubstituted-5-vinyl-4,5-dihydro-derivatives were synthesized in this efficient catalytic system. The results show that the reaction substrate has higher reaction activity and yield when the electron-withdrawing group is contained in the reaction substrate. Subsequently, the chiral 2,3-disubstituted-5-vinyl-4,5-dihydro-derivatives of the chiral 2,3-disubstituted-5-vinyl-4,5-dihydro-derivatives was synthesized by the combination of the synthesized chiral nitrogen-base ligand and the metal, although the chiral target product of the higher ee value was not obtained, the experimental experience and the theoretical guidance were provided for subsequent studies. under the co-catalysis of the synthesized chiral nitrogen-base ligand, the metal and the base, the terminal alkynyl dicarbonate and the protected imine are used as a substrate, and the 2-methomorphin ring derivative is synthesized through the Mannich reaction and the hydroamination series cyclization reaction, and the reaction condition-metal catalyst is prepared, The chiral ligand and the reaction solvent are screened and optimized, and the target product is successfully obtained under the optimized conditions, and the yield is 83% and the ee value is 65%.
【学位授予单位】：湖南工业大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R914.5
本文编号：2501451
[Abstract]:This paper mainly deals with the synthesis of chiral nitrogen-derived ligands, 2,3-disubstituted-5-vinyl-4,5-dihydro-derivatives and 2-methomorphin derivatives. A series of chiral amine and imine chiral nitrogen-derived ligands were synthesized. First, the alkaloid cinchonine is derived as a primary amine compound, and then is synthesized by dehydration condensation with 2-(diphenyl oxide) benzoic acid to synthesize the simplest triamine-like chiral nitrogen-derived ligand, followed by the synthesis of a series of amine-like chiral ligands by inserting different amino acids. In that same time, the compound of the primary amine of the cinchonine and the different amino acid and 2-(diphenylmethyl) benzaldehyde are synthesized by a dehydration condensation reaction to synthesize a different series of imine chiral nitrogen-based ligands. 2,3-disubstituted-5-vinyl-4,5-dihydro-derivatives are synthesized by the C-allylation reaction between the molecules and the O-allylation reaction in the molecule with the co-catalysis of the metal catalyst and the ligand. The experimental reaction parameters were optimized,2 mol% Pd (PPh3)4 and 2 mol% 1,2-bis (diphenylmethyl) ethane were selected as the high efficiency catalytic system, and a series of 2,3-disubstituted-5-vinyl-4,5-dihydro-derivatives were synthesized in this efficient catalytic system. The results show that the reaction substrate has higher reaction activity and yield when the electron-withdrawing group is contained in the reaction substrate. Subsequently, the chiral 2,3-disubstituted-5-vinyl-4,5-dihydro-derivatives of the chiral 2,3-disubstituted-5-vinyl-4,5-dihydro-derivatives was synthesized by the combination of the synthesized chiral nitrogen-base ligand and the metal, although the chiral target product of the higher ee value was not obtained, the experimental experience and the theoretical guidance were provided for subsequent studies. under the co-catalysis of the synthesized chiral nitrogen-base ligand, the metal and the base, the terminal alkynyl dicarbonate and the protected imine are used as a substrate, and the 2-methomorphin ring derivative is synthesized through the Mannich reaction and the hydroamination series cyclization reaction, and the reaction condition-metal catalyst is prepared, The chiral ligand and the reaction solvent are screened and optimized, and the target product is successfully obtained under the optimized conditions, and the yield is 83% and the ee value is 65%.
【学位授予单位】：湖南工业大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R914.5
【参考文献】
相关期刊论文 前1条
1 ;New Chiral Metal Cluster Systems for Catalytic AsymmetricSyntheses of Chiral Alcohols[J];Chemical Research in Chinese Universities;2004年02期
，本文编号：2501451
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