A convenient microwave-assisted synthesis of cinchona alkaloid-derived ligands

An efficient synthesis of cinchona alkaloid-derived ligands based on solvent-free microwave-assisted reaction was described. The coupling of 1,4-dichlorophthalazine or 3,6-dichloropyridazine with quinine, cinchonine or cinchonidine provide bis-or monocinchona alkaloid-derived ligands in moderate to good yields （52-89%） within 15 min under optimum microwave conditions.

Computational studies of cinchona alkaloid-catalyzed asymmetric Michael additions

Cinchona alkaloid is one of the most effective organocatalysts that facilitate a wide range of transformations. To elucidate the mechanistic details and especially the origins of the observed high enantio- and diastereoselectivities, computational chemists have contributed dramatic efforts in this important area. This review covers the recent computational studies on the cinchona alkaloid-catalyzed asymmetric Michael additions, including both C-C and C-S bond formations, to present a general viewpoint of these fruitful advances. Based on the types of bond formation and the cinchona alkaloid catalysts, key information regarding the activation model and the origins of enantioselectivities is discussed.

Using Natural Cinchona Alkaloids to Promote the Enantioselective Addition of Dialkylzinc to N-Diphenylphosphinylimines

Cinchona alkaloids are utilized as chiral ligands to promote the enantioselective addition of dialkylzinc to N-diphenylphos-phinylimines affording enantiomerically enriched N-diphenyl-phosphinylamines in up to 91% ee.

Cinchona Alkaloid-catalyzed Asymmetric Direct Mannich Reaction of Malononitrile to Imine for Synthesis of β-Amino Malononitrile

The first direct asymmetric Mannich reaction of malononitrile to N-Boc-protected imines has been developed with cinchona alkaloid as catalyst. The procedure could tolerate a relatively wide range of substrates, and results in excellent yields and good enantioselectivities even in the presence of only 1 mol% of catalyst loading. The present work provides an easy access to β-amino malononitrile derivatives.

Chiral Cinchona Alkaloid-Thiourea Catalyzed Mannich Reaction for Enantioselective Synthesis of β-Amino Ketones Bearing Benzothiazol Moiety

Mannich reactions of imine with acetylacetone were effectively catalyzed by the modified chiral cinchona alka-loid-derived thiourea. The reactions led to chiral r-amino carbonyl compounds in high yields and good enantiose-lectivities. The study demonstrated for the first time that Mannich reactions of unmodified acetylacetone with het-erocyclic imine derived from benzothiazole can be promoted by chiral bifunctional organocatalyst.

An easy route to exotic 9-epimers of 9-amino-(9-deoxy) cinchona alkaloids with(8S,9R) and(8R,9S)-configurations through two inversions of configuration

Four exotic chiral organocatalysts, 9-amino-（9-deoxy） cinchona alkaloids with （8S, 9R） and （8R, 9S）- configurations, were conveniently synthesized for the first time in 27-72% total yields through two conversions of configuration at the 9-stereogenic centers of commercially available cinchona alkaloids.

A green access to supported cinchona alkaloid amide catalysts for heterogeneous enantioselective allylsilylation of aldehydes and process intensity evaluation in batch and flow

We report herein a new class of polystyrene-supported cinchona alkaloid amide catalysts for enantioselective allylation of various aldehydes using allyltrichlorosilane under both batch and continuous flow conditions.The supported catalyst was synthesized using an environmentally benign coupling agent with a surfactant in aqueous media.Under batch conditions,consistently high yields and enantioselectivity were obtained for the allylation of aliphatic aldehydes with recycling and reuse of the catalyst for more than 10 runs.Subsequently,this catalytic system was successfully implemented into a packed bed flow reactor with similar efficiency and enantiose-lectivity.While flow is a viable option,the batch methodology has better potential for application at a larger-scale setting upon the comparison of space-time yield and catalyst loadings.With the sustainable synthesis and great recyclability of our polymeric catalyst,this methodology holds great potential for the large-scale delivery of valuable enantiopure homoallylic alcohols.

Enantioselective direct aldol-type reaction of 4-hydroxycoumarin with ethyl trifluoropyruvate catalyzed by modified cinchona alkaloids

A new enantioselective aldol-type reaction of 4-hydroxycoumarins and ethyl trifluoropyruvate has been developed. In the presence of (DHQD)2PHAL (5 mol%), ethyl trifluoropyruvate could react with various 4-hydroxycoumarins to afford novel 4-hydroxycoumarin derivatives containing a tertiary trifluoromethyl alcohol center in good yields with moderate enantioselectivities.

A new free recoverable and reusable mono-alkaloid-type ligand and its use in preparation of ethyl(2R,3S)-2,3-dihydroxy-3-phenylpropionate

A new free recoverable and reusable mono-alkaloid-type ligand has been synthesized by a simple method. With highly polar groups, the ligand can be recycled and reused eight times to prepare ethyl （2R,3S）-2,3-dihydroxy-3-phenylpropionate with high yield and ee via asymmetric dihydroxylation （AD） reaction. C 2009 Sheng Yong Zhang. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

绿色化学理念下奎宁苯甲酰酯金鸡纳生物碱衍生物的微波无溶剂合成的有机化学自主设计性教学实验

目的探讨绿色化学理念下开设有机化学自主设计性教学实验的意义。方法基于绿色化学理念,设计奎宁苯甲酰酯类金鸡纳生物碱衍生物的微波无溶剂合成,完成自主设计性教学实验。结果实验内容新颖,涵盖酯类微波无溶剂合成方法、产物后处理、柱层析纯化等操作步骤,与医药学专业的有机化学理论知识契合度高,同时,实验中利用核磁共振氢谱、高分辨质谱等波谱学数据对产物结构进行了表征,对于培养学生将理论课中所学知识点灵活用于实践解决问题的能力起到了积极促进作用,且使学生建立起绿色合成化学的理念。结论该实验不仅能有效提升学生学习的自主性,激发学习兴趣,强化其实验基本操作技能,也使学生对科学研究工作的思路有更好地认识,为其后续其他专业课程的学习打牢基础。

铜催化不对称合成螺环吡唑啉酮的反应因素评价研究

利用炔系硝基烯烃和吡唑酮的迈克尔加成/Conia-ene环化反应立体选择性合成手性螺环吡唑啉酮,并对影响反应的因素进行考察,比较了过渡金属、不同骨架的配体、溶剂、温度对反应的影响.结果表明,当以金鸡纳碱和廉价金属铜为催化剂,三氯甲烷为溶剂在-40℃下,反应可以达到97%的产率、大于20:1的dr值和91%的ee值.

辛可宁-方酰胺催化剂的合成及应用

以9-氨基-(9-脱氧)表辛可宁(2)和方酸二乙酯(3)为原料,经缩合反应得到一种结构新颖的辛可宁-方酰胺催化剂(1),并将其应用于催化β-硝基苯乙烯(4)和乙酰丙酮(5)的不对称Michael加成反应,得到手性3-(2-硝基-1-苯基乙基)戊-2,4-二酮(6),通过1HNMR、^(13)CNMR、MS等手段对辛可宁-方酰胺催化剂及催化产物6的结构进行了表征,并对催化产物6的合成条件进行了优化。结果表明,在辛可宁-方酰胺催化剂用量n(辛可宁-方酰胺催化剂)∶n(β-硝基苯乙烯)为0.08∶1、溶剂为二氯甲烷、室温下反应12 h的最佳条件下,催化产物6收率达到90%,ee值>99%。

高分子支载的金鸡纳生物碱催化剂在不对称催化反应中的应用进展

综述了近年来高分子支载的金鸡纳生物碱催化剂在不对称双羟基化反应、不对称Michael加成反应、活性亚胺的不对称烷基化反应以及潜手性酮的不对称还原反应中的应用及最新进展。

金鸡纳生物碱衍生手性双胺配体的合成及其在不对称氢转移反应中的催化作用

以价廉易得的天然金鸡纳生物碱奎宁和辛可宁为原料,在温和条件下容易地合成了6种手性双胺配体. 考察了它们与过渡金属Ir和Rh形成的配合物在苯乙酮不对称氢转移反应中的催化活性和不对称诱导作用. 结果表明, 9-氨基金鸡纳生物碱配体具有良好的不对称催化活性,而当配体中的氨基被取代后其对映选择性降低. 将9-氨基（9-脱氧）表辛可宁的Ir配合物用于其它芳香酮的不对称氢转移反应时,该配体也显示了很高的催化活性（80%～90%收率）和对映选择性（除对氯苯乙酮ee值为72%外,其余芳香酮ee值均为95%～97%）.

金鸡纳碱衍生物修饰的负载铱催化剂催化芳香酮不对称加氢

以金鸡纳碱衍生物作为手性修饰剂,研究了三苯基膦稳定的Ir/SiO2催化剂催化芳香酮多相不对称加氢.通过电感耦合等离子体原子发射发谱(ICP-AES)、高分辨透射电镜(HRTEM)、X射线光电子能谱(XPS)、Brunauer-Emmett-Teller(BET)比表面积测试等固体表面分析手段对负载铱催化体系进行了表征;利用红外(IR)光谱、固体核磁共振(NMR)等分析手段初步表征了负载铱多相催化体系中手性修饰剂-金属-稳定剂在载体上的相互作用;利用'均相与多相催化体系的对比'、'催化剂稳定性实验'、'汞中毒实验'等方法阐明了手性修饰的负载铱催化体系是多相催化体系.还考察了稳定剂种类、修饰剂种类、金属负载量、溶剂、碱添加剂种类等因素对不对称加氢反应的影响.结果表明,金鸡纳碱衍生物对Ir/SiO2催化剂具有较好的修饰作用,在优化反应条件下苯乙酮及其衍生物加氢反应的对映选择性为52%-96%,4-乙酰基吡啶、2-乙酰基噻吩及2-乙酰基呋喃加氢反应的对映选择性可分别达到74%、75%及63%.

多相不对称催化氢化研究进展

本文综述了多相不对称催化氢化反应的最新研究进展。特别是对最近几年来两个典型的多相不对称催化氢化体系即酒石酸盐修饰镍催化剂催化 β-酮酸酯的不对称氢化反应体系和金鸡纳生物碱修饰铂催化剂催化 α-酮酸酯的不对称氢化反应体系进行了详细的介绍和讨论 ,同时展望了多相不对称催化氢化反应研究的前景。

超声法提取金鸡纳生物碱的工艺

研究金鸡纳总生物碱的超声提取工艺.采用L9(34)正交设计通过正交试验得出了超声提取的最佳工艺条件.超声提取的影响因素顺序为提取次数>提取时间>料液比,其最佳提取条件为A2B2C2,即8倍量的甲苯提取液提取4次,每次45 min.实验证明该提取工艺方法经济合理.

手性胺盐催化的α,β-不饱和酮的不对称环氧化反应

以手性胺衍生的有机催化剂催化α,β-不饱和酮的不对称环氧化反应,考察了手性胺的结构、氧化剂的种类和溶剂对反应立体选择性的影响.结果表明金鸡纳碱衍生9-氨基(9-脱氧)表辛可宁(A6)催化α,β-不饱和酮的不对称环氧化反应时,其光学产率可达84%ee.通过共价键负载于β-环糊精的手性胺在查尔酮的不对称环氧化反应中也显示出立体诱导作用.

两种不对称二羟化反应的新型手性配体的合成及其应用

目的 :设计两种新的桥联基以合成两种新的不对称二羟化反应的金鸡纳碱衍生物配体并将其用于催化四种烯烃的不对称二羟化反应 ,考察催化效果 .方法 :以苯酚、α 萘酚和氰尿酰氯为原料 ,制备两种新桥联基 ,然后在氮气保护下 ,于5 0℃分别与奎宁反应生成两个新配体 ,并将其用于锇酸钾 铁氰化钾、H2 O tBuOH(1∶1 )体系 ,催化四种烯烃的不对称二羟化反应 .结果 :结果表明 ,化学产率为 75 %～ 98% ,对映体过量均大于 80 % .结论 :以氰尿酰氯衍生物为桥联基合成的两种奎宁金鸡纳碱衍生物配体 ,方法简便、成本低廉 。