新型β-氨基手性膦催化剂的设计、合成及应用

发布时间：2017-12-27 14:08

  本文关键词：新型β-氨基手性膦催化剂的设计、合成及应用　出处：《华东师范大学》2017年博士论文　论文类型：学位论文

  更多相关文章： 手性膦催化 β-氨基手性膦 手性叔丁基亚磺酰胺 Rauhut-Currier反应 [3+2]环加成反应

【摘要】：在过去的几十年里,不对称手性膦催化已发展成为构建官能化的手性分子和合成砌块的重要策略。在众多的手性膦催化剂中,β-氨基手性膦是一种高效且用途广泛的催化剂,在很多不对称反应中都具有优异表现。但是,β-氨基手性膦催化剂的传统合成路线具有反应条件苛刻、路线冗长和结构不易修饰等缺点。因此,发展构建β-氨基手性膦催化剂的新策略具有十分重要的意义。本文中,我们通过Ph2PCH2Li和手性亚磺酰亚胺的加成反应,高非对映选择性、高产率地得到了一系列结构新颖的β-氨基手性膦催化剂,并考察了其在不对称Rauhut-Currier反应和[3+2]环加成反应中的应用。主要内容包括以下五个方面:1.Xiao-Phos的设计、合成及其在不对称Rauhut-Currier反应中的应用商业易得的醛和手性叔丁基亚磺酰胺在钛酸四异丙酯作为脱水剂的条件下缩合得到手性亚磺酰亚胺,然后再与Ph2PCH2Li发生亲核加成反应,高非对映选择性、高产率地得到了一系列结构新颖的β-氨基手性膦催化剂(Xiao-Phos)。进一步的研究结果表明,Xiao-Phos在环己二烯酮衍生物的分子内Rauhut-Currier反应以及芳基烯酮和缺电子烯烃的分子间Rauhut-Currier反应中具有优异的表现。2.Wei-Phos的设计、合成及其在不对称分子间Rauhut-Currier反应中的应用邻位二芳基膦取代的醛和手性叔丁基亚磺酰胺在钛酸四异丙酯作为脱水剂的条件下缩合得到相应的手性亚磺酰亚胺,然后再与Ph2PCH2Li发生亲核加成反应,高非对映选择性、高产率地得到了一系列结构新颖的片氨基手性双膦催化剂(Wei-Phos)。进一步的研究结果表明,Wei-Phos在烯酮和缺电子烯烃的分子间Rauhut-Currier反应中表现出了优异的催化活性和底物广普性:在2.5 mol%的Wei-Phos作为催化剂的条件下,烯酮和缺电子烯烃可以顺利地发生不对称分子间交叉Rauhut-Currier反应,最高以98%的产率和99%的ee得到一系列手性多羰基化合物。3.Peng-Phos催化丙烯醛和缺电子烯烃的不对称分子间Rauhut-Currier反应邻位芳基取代的醛和手性叔丁基亚磺酰胺在钛酸四异丙酯作为脱水剂的条件下缩合得到相应的手性亚磺酰亚胺,然后再与Ph2PCH2Li发生亲核加成反应,高非对映选择性、高产率地得到了一系列邻位含有大位阻芳基取代基的β-氨基手性膦催化剂(Peng-Phos)。研究结果表明,Peng-Phos在丙烯醛和缺电子烯烃的不对称分子间Rauhut-Currier反应中表现出了优异的化学选择性、区域选择性以及对映选择性。4.手性膦催化γ-无取代基联烯酸酯和β-全氟烷基取代烯酮的不对称[3+2]环加成反应叔丁基亚磺酰胺类手性膦催化剂经过四步简单转化就可以方便转化成一系列含有不同酰基保护基的新型手性催化剂。手性膦催化剂(S)-P3在β-全氟烷基取代烯酮和联烯酸乙酯不对称环加成反应表现出了最高的催化活性和对映选择性:一系列含有不同官能团的β-三氟甲基取代烯酮和联烯酸酯均可以顺利发生不对称[3+2]环加成反应,以优异的收率和对映选择性生成相应的三氟甲基取代环戊烯类化合物。当反应规模为10 mmol时,催化剂的用量可以降为1 mol%而不影响收率和对映选择性。5.手性膦催化γ-取代联烯酸酯和β-全氟烷基取代烯酮的不对称[3+2]环加成反应商业可得的单功能手性双膦催化剂(R,R)-DIPAMP在γ-芳基取代联烯酸酯与三氟甲基取代不饱和烯酮的[3+2]环加成反应中具有很高的催化活性和底物广普性,高区域选择性、非对映选择性和对映选择性地构建了一系列含有3个连续手性中心的环己烯类化合物。另一方面,对于产烷基取代联烯酸酯与三氟甲基取代不饱和烯酮的[3+2]环加成反应,多功能手性膦催化剂(S)-P3具有更优异地表现。此外,通过对反应历程的研究,我们发现在单功能手性双膦(R,R)-DIPAMP作为催化剂的条件下,γ-芳基取代联烯酸酯与三氟甲基取代不饱和烯酮的[3+2]环加成反应是一个去外消旋化的过程;而多功能β-氨基手性膦(S)-P3作为催化剂的条件下,我们观察到了明显的动力学拆分现象。
[Abstract]:In the past few decades, asymmetric chiral phosphine catalysis has developed into an important strategy for the construction of functionalized chiral molecules and synthetic blocks. Among many chiral phosphine catalysts, beta Aminophosphine is a highly efficient and versatile catalyst, which has excellent performance in many asymmetric reactions. However, the traditional synthesis route of beta Aminophosphine catalyst has some shortcomings, such as harsh reaction conditions, long route and difficult to modify structure. Therefore, it is of great significance to develop a new strategy for the construction of a beta Aminophosphine catalyst. In this paper, we through the Ph2PCH2Li reaction and chiral sulfinyl imines with high diastereoselectivity and high yield from a series of novel chiral beta amino phosphine catalyst, and investigated its in asymmetric Rauhut-Currier reaction and [3+2] cycloaddition reaction application. The main contents include the following five aspects: the design and synthesis of 1.Xiao-Phos and its application in commercial asymmetric Rauhut-Currier reaction of aldehyde and easy chiral tert butyl sulfenamides as dehydrating agent under the condition of condensation to obtain chiral sulfinyl imines in four isopropyl titanate, then Ph2PCH2Li nucleophilic addition reaction, high diastereoselective, high yield from a series of novel chiral beta amino phosphine catalyst (Xiao-Phos). Further studies show that Xiao-Phos has excellent performance in the intramolecular Rauhut-Currier reaction of cyclohexadienone derivatives, as well as the intermolecular Rauhut-Currier reaction between aryl ketene and electron deficient olefin. The design and synthesis of 2.Wei-Phos and its application in asymmetric vicinal intermolecular Rauhut-Currier reaction of two aryl phosphine substituted chiral tert butyl aldehyde and sulfenamides as dehydrating agent under the condition of condensation of the corresponding chiral sulfinyl imine in four isopropyl titanate, Ph2PCH2Li and nucleophilic addition reaction, high non enantioselective, high yield from a series of novel chiral amino phosphine catalyst tablets (Wei-Phos). Further study indicated that Wei-Phos in ketene and electron deficient olefins intermolecular Rauhut-Currier reaction showed excellent catalytic activity and substrate popularity: in 2.5 mol% Wei-Phos as catalyst under the conditions of ketene and electron deficient alkenes can cross Rauhut-Currier reaction successfully asymmetric molecules, the highest to 98% the yield of 99% EE and a series of chiral carbonyl compounds. 3.Peng-Phos catalytic acrolein and electron deficient olefins asymmetric intermolecular Rauhut-Currier reaction of ortho substituted aryl aldehydes and chiral tert butyl sulfenamides as dehydrating agent under the condition of condensation of the corresponding chiral sulfinyl imine in four isopropyl titanate, Ph2PCH2Li and nucleophilic addition reaction, high diastereoselectivity, high yield from a series of ortho containing sterically hindered aryl substituents of beta amino chiral phosphine catalyst (Peng-Phos). The results show that Peng-Phos exhibits excellent chemical selectivity, regioselectivity and enantioselectivity in the asymmetric intermolecular Rauhut-Currier reaction of acrolein and electron deficient olefins. Asymmetric [3+2] ring 4. chiral phosphine catalyzed gamma no substituent allenic ester and beta perfluoroalkyl substituted ketene addition reaction of tert butyl sulfenamide type chiral phosphine catalyst through four simple steps you can easily transformed into a series of different acyl radical protection containing chiral catalyst. Chiral phosphine catalyst (S) -P3 in beta perfluoroalkyl substituted ketene and acid ethyl ester asymmetric cycloaddition reaction showed the highest catalytic activity and enantioselectivity: a series of different functional group containing beta three fluorine substituted ketene and allenic ester can occur easily in the asymmetric [3+2] ring the reaction with excellent yield and enantioselectivity to generate three fluorine corresponding substituted cyclopentene compounds. When the reaction scale is 10 mmol, the amount of catalyst can be reduced to 1 mol% without affecting the yield and enantioselectivity. The single function of chiral phosphine catalysts for asymmetric [3+2] ring 5. chiral phosphine catalytic gamma - substituted allenes ester and beta perfluoroalkyl substituted ketene addition reaction of commercially available (R, R) -DIPAMP in gamma aryl substituted allenes ester and three fluorine methyl substituted ethylenically unsaturated ketone ring with [3+2] the reaction has high catalytic activity and substrate of broad spectrum, high regioselectivity, diastereoselectivity and enantioselectivity to build a series of compounds containing cyclohexene 3 consecutive chiral centers. On the other hand, for the [3+2] cycloaddition reaction of alkyl substituted dienes with three fluoromethyl substituted unsaturated ketene, the multifunctional chiral phosphine catalyst (S) -P3 has better performance. In addition, through the study on the reaction process, we found that in the single function of chiral Biphosphine (R, R) -DIPAMP as catalyst, gamma aryl substituted allenes ester and three fluorine methyl substituted ethylenically unsaturated ketone [3+2] cycloaddition reaction is a process of deracemization; and the function of beta amino phosphine (S) -P3 as catalyst, we observed the phenomenon of apparent kinetic resolution.
【学位授予单位】：华东师范大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：O643.36
，

本文编号：1342007