【摘要】：以5,6-二氫菲啶為主要骨架的化合物是一種重要的氮雜環(huán)化合物,具有廣泛的生物活性,如抗癌、抗菌、消炎等。雖然這一類化合物的合成方法已有很多報(bào)道,但是都集中于非手性化合物的合成,有關(guān)含手性結(jié)構(gòu)5,6-二氫菲啶的合成方法卻鮮有涉及。本論文以手性6-取代-5,6-二氫菲啶類化合物的合成為研究目標(biāo),開展有關(guān)方法學(xué)研究。采用聯(lián)苯-2-胺和具有較高親電性的羰基化合物,在手性磷酰亞胺酸催化劑的作用下,通過(guò)Pictet-Spengler反應(yīng)合成出較高產(chǎn)率和高對(duì)映選擇性的6-取代-5,6-二氫菲啶類化合物。我們首先將10種手性磷酰亞胺酸和手性磷酸的催化劑運(yùn)用到3’,5’-二甲氧基-[1,1’-聯(lián)苯]-2-胺和對(duì)硝基苯甲醛的不對(duì)稱Pictet-Spengler反應(yīng)中。常溫下,以甲苯為溶劑,篩選出3,3’位為二萘取代基的(R)-H8-BINOL磷酰亞胺酸作為最佳催化劑。之后依次進(jìn)行溶劑、催化劑用量、反應(yīng)溫度的篩選,得出了最佳的反應(yīng)條件,即0℃時(shí),在5mol%3,3’位為2-萘取代基的(R)-H8-BINOL磷酰亞胺酸催化劑的作用下,以氯仿為反應(yīng)溶劑,5?分子篩為添加劑。最后我們分別對(duì)不同取代基的兩種底物進(jìn)行擴(kuò)展,在最佳反應(yīng)條件的基礎(chǔ)上,得到了20種不同取代基的6-芳基-5,6-二氫菲啶的不對(duì)稱產(chǎn)物,產(chǎn)率最高達(dá)到了95%,ee值更是達(dá)到了99%,并通過(guò)單晶衍射,確認(rèn)了產(chǎn)物的最終構(gòu)型。由此,我們可以看出手性磷酰亞胺酸對(duì)此類不對(duì)稱化合物的合成有著較強(qiáng)的催化活性和手性控制能力。在此基礎(chǔ)上,我們繼續(xù)考察了3’,5’-二甲氧基-[1,1’-聯(lián)苯]-2-胺和親電性更強(qiáng)的丙酮酸酯作為起始原料,以手性磷酰亞胺酸為催化劑,通過(guò)不對(duì)稱Pictet-Spengler反應(yīng)合成手性6-烷氧羰基-5,6-二氫菲啶化合物的反應(yīng)活性,同樣依次考查了催化劑、反應(yīng)溶劑、催化劑用量以及反應(yīng)溫度對(duì)于結(jié)果的影響。我們由此得到了最佳的反應(yīng)條件:-40℃時(shí),仍然在3,3’位為2-萘取代基的(R)-H8-BINOL磷酰亞胺酸催化劑的作用下,以CCl4為反應(yīng)溶劑,5?分子篩為添加劑,得到了90%的最高產(chǎn)率,以及83%的ee值。綜上所述,我們利用手性磷酰亞胺酸做催化劑,通過(guò)不對(duì)稱Pictet-Spengler反應(yīng),合成所需要的具有高對(duì)映選擇性的6-取代-5,6-二氫菲啶類化合物,已經(jīng)取得了較理想的研究成果,豐富了這類不對(duì)稱氮雜環(huán)化合物的合成方法。
[Abstract]:The compound with 5-dihydrophenanthroline as the main skeleton is an important nitrogen heterocyclic compound, which has a wide range of biological activities, such as anti-cancer, antibacterial, anti-inflammatory and so on. Although there have been many reports on the synthesis of this kind of compounds, they are mainly focused on the synthesis of non-chiral compounds. In this thesis, the synthesis of chiral 6-substituted-5-5-dihydrophenanthroline compounds was studied. The high yield and high enantioselectivity of 6- substituted-5-dihydrophenanthroline compounds were synthesized by Pictet-Spengler reaction with biphenyl-2-amine and carbonyl compounds with high electrophilic activity under the action of chiral phosphoimide acid catalyst. We first applied 10 kinds of chiral phosphoimide and chiral phosphoric acid catalysts to asymmetric Pictet-Spengler reactions of 3H5, dimethoxy-[1hlO- biphenyls] -2-amine with p-nitrobenzaldehyde, and the results were as follows: (1) Chiral phosphoimide and chiral phosphoric acid were used in the asymmetric Pictet-Spengler reaction of p-nitrobenzaldehyde. Using toluene as solvent, (R) H 8 BINOL phosphorimide at 3'3 'position was selected as the best catalyst at room temperature. Then the solvent, catalyst dosage and reaction temperature were screened in turn, and the optimum reaction conditions were obtained, namely, chloroform was used as the reaction solvent at 0 鈩，

本文編號(hào)：2211752