【摘要】：許多具有生物活性分子、藥物、天然產(chǎn)物都具有手性季碳中心,季碳中心的構(gòu)建一直是不對稱催化領(lǐng)域研究的熱點,同時也是一項極具挑戰(zhàn)性的工作。近些年來,pyrroloindolines及furoindolines的不對稱合成,以及含三氟甲基的季碳中心的構(gòu)建引起了有機合成化學(xué)家們的廣泛關(guān)注。本論文通過用不對稱有機催化的方法實現(xiàn)了對其的合成,主要內(nèi)容包括： 1.通過手性雙環(huán)胍催化的相轉(zhuǎn)移烷基化反應(yīng),高立體選擇性合成具有手性季碳中心的pyrroloindolines和furoindolines 我們發(fā)展了手性雙環(huán)胍鹽與碘化鋅聯(lián)合催化體系,在相轉(zhuǎn)移條件下以3位單取代的吲哚酮及活化的溴代烷烴為底物,高立體選擇性合成具有生物活性及手性季碳中心的pyrroloindolines及furoindolines。該研究在以下幾方面取得重要突破：1)首次用不對稱有機催化的方法高立體選擇性集中合成了pyrroloindolines及furoindolines；2)首次報道了手性雙環(huán)胍鹽與碘化鋅聯(lián)合催化體系；3)首次證明了手性雙環(huán)胍鹽在弱的無機堿條件下可以作為相轉(zhuǎn)移催化劑使用,極大地豐富了手性雙環(huán)胍鹽在不對稱有機催化領(lǐng)域的應(yīng)用；4)通過改變催化劑的手性源可以高產(chǎn)率高立體選擇性得到目標(biāo)產(chǎn)物的兩個對映異構(gòu)體。 2.硫醇與酰胺活化的β-三氟甲基雙取代烯烴的不對稱共軛加成反應(yīng) 首次合成了酰胺活化的p-三氟甲基雙取代烯烴,并且發(fā)現(xiàn)生物堿衍生的手性催化劑與合適的無機堿聯(lián)用可以在不影響對映選擇性的前提下極大地提高反應(yīng)的活性。首次用酰胺活化的β-三氟甲基雙取代的烯烴與硫醇的不對稱共軛加成反應(yīng),合成了手性中心含有三氟甲基的叔硫醚及叔硫醇。反應(yīng)得到產(chǎn)物酰胺經(jīng)過簡單地結(jié)構(gòu)修飾可以轉(zhuǎn)化成相應(yīng)的酯、酸、酮、磺酰胺,有利于合成多種具有生物活性的化合物。
[Abstract]:Many bioactive molecules, drugs and natural products all have chiral quaternary carbon centers. The construction of quaterpillar carbon centers has always been a hot topic in the field of asymmetric catalysis, and it is also a very challenging work. In recent years, the asymmetric synthesis of pyrroloindolines and furoindolines and the construction of quaternary carbon centers containing trifluoromethyl have attracted the attention of organic synthetic chemists. In this paper, the synthesis of asymmetric organic catalysis was realized by using asymmetric organic catalysis, the main contents of which are as follows: 1. By phase transfer alkylation catalyzed by chiral dicycloguanidine, pyrroloindolines and furoindolines with chiral quaternary carbon center were synthesized by high stereoselectivity. We developed a combined catalytic system of chiral dicycloguanidine salt and zinc iodide. Under the condition of phase transfer, pyrroloindolines and furoindolines. with biological activity and chiral quaternary carbon center were synthesized with 3-position monosubstituted indolone and activated brominated alkane as substrate. This study has made important breakthroughs in the following aspects: 1) pyrroloindolines and furoindolines;2 were synthesized by asymmetric organic catalysis for the first time. The combined catalytic system of chiral dicycloguanidine salt and zinc iodide was reported for the first time. 3) it was proved for the first time that chiral dicycloguanidine salt can be used as phase transfer catalyst under weak inorganic base conditions, which greatly enriches the application of chiral dicycloguanidine salt in asymmetric organic catalysis. 4) two enantiomers of the target product can be obtained by changing the chiral source of the catalyst with high yield and high stereoselectivity. two銆，

本文編號：2507033