本文關(guān)鍵詞：新型β-氨基手性膦催化劑的設(shè)計、合成及應用　出處：《華東師范大學》2017年博士論文　論文類型：學位論文

  更多相關(guān)文章： 手性膦催化 β-氨基手性膦 手性叔丁基亞磺酰胺 Rauhut-Currier反應 [3+2]環(huán)加成反應

【摘要】：在過去的幾十年里,不對稱手性膦催化已發(fā)展成為構(gòu)建官能化的手性分子和合成砌塊的重要策略。在眾多的手性膦催化劑中,β-氨基手性膦是一種高效且用途廣泛的催化劑,在很多不對稱反應中都具有優(yōu)異表現(xiàn)。但是,β-氨基手性膦催化劑的傳統(tǒng)合成路線具有反應條件苛刻、路線冗長和結(jié)構(gòu)不易修飾等缺點。因此,發(fā)展構(gòu)建β-氨基手性膦催化劑的新策略具有十分重要的意義。本文中,我們通過Ph2PCH2Li和手性亞磺酰亞胺的加成反應,高非對映選擇性、高產(chǎn)率地得到了一系列結(jié)構(gòu)新穎的β-氨基手性膦催化劑,并考察了其在不對稱Rauhut-Currier反應和[3+2]環(huán)加成反應中的應用。主要內(nèi)容包括以下五個方面:1.Xiao-Phos的設(shè)計、合成及其在不對稱Rauhut-Currier反應中的應用商業(yè)易得的醛和手性叔丁基亞磺酰胺在鈦酸四異丙酯作為脫水劑的條件下縮合得到手性亞磺酰亞胺,然后再與Ph2PCH2Li發(fā)生親核加成反應,高非對映選擇性、高產(chǎn)率地得到了一系列結(jié)構(gòu)新穎的β-氨基手性膦催化劑(Xiao-Phos)。進一步的研究結(jié)果表明,Xiao-Phos在環(huán)己二烯酮衍生物的分子內(nèi)Rauhut-Currier反應以及芳基烯酮和缺電子烯烴的分子間Rauhut-Currier反應中具有優(yōu)異的表現(xiàn)。2.Wei-Phos的設(shè)計、合成及其在不對稱分子間Rauhut-Currier反應中的應用鄰位二芳基膦取代的醛和手性叔丁基亞磺酰胺在鈦酸四異丙酯作為脫水劑的條件下縮合得到相應的手性亞磺酰亞胺,然后再與Ph2PCH2Li發(fā)生親核加成反應,高非對映選擇性、高產(chǎn)率地得到了一系列結(jié)構(gòu)新穎的片氨基手性雙膦催化劑(Wei-Phos)。進一步的研究結(jié)果表明,Wei-Phos在烯酮和缺電子烯烴的分子間Rauhut-Currier反應中表現(xiàn)出了優(yōu)異的催化活性和底物廣普性:在2.5 mol%的Wei-Phos作為催化劑的條件下,烯酮和缺電子烯烴可以順利地發(fā)生不對稱分子間交叉Rauhut-Currier反應,最高以98%的產(chǎn)率和99%的ee得到一系列手性多羰基化合物。3.Peng-Phos催化丙烯醛和缺電子烯烴的不對稱分子間Rauhut-Currier反應鄰位芳基取代的醛和手性叔丁基亞磺酰胺在鈦酸四異丙酯作為脫水劑的條件下縮合得到相應的手性亞磺酰亞胺,然后再與Ph2PCH2Li發(fā)生親核加成反應,高非對映選擇性、高產(chǎn)率地得到了一系列鄰位含有大位阻芳基取代基的β-氨基手性膦催化劑(Peng-Phos)。研究結(jié)果表明,Peng-Phos在丙烯醛和缺電子烯烴的不對稱分子間Rauhut-Currier反應中表現(xiàn)出了優(yōu)異的化學選擇性、區(qū)域選擇性以及對映選擇性。4.手性膦催化γ-無取代基聯(lián)烯酸酯和β-全氟烷基取代烯酮的不對稱[3+2]環(huán)加成反應叔丁基亞磺酰胺類手性膦催化劑經(jīng)過四步簡單轉(zhuǎn)化就可以方便轉(zhuǎn)化成一系列含有不同�；Ｗo基的新型手性催化劑。手性膦催化劑(S)-P3在β-全氟烷基取代烯酮和聯(lián)烯酸乙酯不對稱環(huán)加成反應表現(xiàn)出了最高的催化活性和對映選擇性:一系列含有不同官能團的β-三氟甲基取代烯酮和聯(lián)烯酸酯均可以順利發(fā)生不對稱[3+2]環(huán)加成反應,以優(yōu)異的收率和對映選擇性生成相應的三氟甲基取代環(huán)戊烯類化合物。當反應規(guī)模為10 mmol時,催化劑的用量可以降為1 mol%而不影響收率和對映選擇性。5.手性膦催化γ-取代聯(lián)烯酸酯和β-全氟烷基取代烯酮的不對稱[3+2]環(huán)加成反應商業(yè)可得的單功能手性雙膦催化劑(R,R)-DIPAMP在γ-芳基取代聯(lián)烯酸酯與三氟甲基取代不飽和烯酮的[3+2]環(huán)加成反應中具有很高的催化活性和底物廣普性,高區(qū)域選擇性、非對映選擇性和對映選擇性地構(gòu)建了一系列含有3個連續(xù)手性中心的環(huán)己烯類化合物。另一方面,對于產(chǎn)烷基取代聯(lián)烯酸酯與三氟甲基取代不飽和烯酮的[3+2]環(huán)加成反應,多功能手性膦催化劑(S)-P3具有更優(yōu)異地表現(xiàn)。此外,通過對反應歷程的研究,我們發(fā)現(xiàn)在單功能手性雙膦(R,R)-DIPAMP作為催化劑的條件下,γ-芳基取代聯(lián)烯酸酯與三氟甲基取代不飽和烯酮的[3+2]環(huán)加成反應是一個去外消旋化的過程;而多功能β-氨基手性膦(S)-P3作為催化劑的條件下,我們觀察到了明顯的動力學拆分現(xiàn)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.
【學位授予單位】：華東師范大學
【學位級別】：博士
【學位授予年份】：2017
【分類號】：O643.36
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本文編號：1342007