發(fā)布時(shí)間：2018-05-03 21:14

  本文選題：苯并異噻唑衍生物 + 亞甲胺葉立德�。� 參考：《青島科技大學(xué)》2017年碩士論文

【摘要】：1,3-偶極環(huán)加成反應(yīng)因具有立體選擇性好和反應(yīng)條件溫和的特點(diǎn),成為合成五元雜環(huán)化合物的常用方法。自二十世紀(jì)六十年代Huisgen提出1,3-偶極環(huán)加成反應(yīng)概念,環(huán)加成反應(yīng)的機(jī)理及應(yīng)用研究一直是化學(xué)領(lǐng)域研究的熱點(diǎn)。近年來以非手性的1,3-偶極體和烯烴為底物,利用手性金屬絡(luò)合物催化劑獲得具有光學(xué)活性化合物的合成方法,受到有機(jī)合成化學(xué)家的廣泛關(guān)注。受天然吲哚啉類螺環(huán)化合物合成方法及生物活性的啟發(fā),提出以亞甲胺葉立德為偶極體,與苯并異噻唑衍生物進(jìn)行1,3-偶極環(huán)加成反應(yīng)合成新型吡咯螺苯并異噻唑類化合物。同時(shí)對以苯并異噻唑衍生物為骨架的1,3-偶極環(huán)加成反應(yīng)進(jìn)行深入研究,探索手性催化條件下反應(yīng)的非對映選擇性和對映選擇性,建立進(jìn)行此類反應(yīng)的一般方法。為構(gòu)建具有類似結(jié)構(gòu)的化合物提供方法學(xué)依據(jù),并為進(jìn)一步研究此類化合物的不對稱1,3-偶極環(huán)加成反應(yīng)打下重要基礎(chǔ)。本論文主要完成的工作有:(1)以鄰溴苯胺為原料,經(jīng)分子內(nèi)N-烷基化、N-甲基化以及環(huán)化反應(yīng)合成1,3-二氫-2,1-苯并異噻唑-2,2-二氧化物。通過脂肪醛和芳香醛與1,3-二氫-2,1-苯并異噻唑-2,2-二氧化物的Knoevenagel縮合反應(yīng)合成含有雙鍵結(jié)構(gòu)的3-取代亞甲基-2,1-苯并異噻唑-2,2-二氧化物親偶極體。(2)以甘氨酸甲酯鹽酸鹽及甘氨酸叔丁酯為底物,通過與脂肪醛、含有不同取代基的芳香醛及具有雜環(huán)結(jié)構(gòu)的醛類物質(zhì)進(jìn)行縮合反應(yīng),制備不同種類的亞胺。(3)以3-取代亞甲基-2,1-苯并異噻唑-2,2-二氧化物為親偶極體,與亞甲胺葉立德進(jìn)行非手性條件下的1,3-偶極環(huán)加成反應(yīng)以及在三氟甲磺酸銅/DM-Segphos催化體系作用下的不對稱1,3-偶極環(huán)加成反應(yīng),合成新型吡咯螺苯并異噻唑類化合物,獲得通過一步反應(yīng)構(gòu)建具有四個(gè)手性中心、三個(gè)叔碳原子和一個(gè)螺碳原子的吡咯螺苯并異噻唑類化合物的新方法。探討不同種類路易斯酸、配體、堿、溶劑、溫度和反應(yīng)時(shí)間對反應(yīng)的影響,確定較佳反應(yīng)條件。該方法具有高度對映選擇性,ee值最高可達(dá)99%。通過X-射線單晶衍射確定了產(chǎn)物的絕對構(gòu)型,提出了三氟甲磺酸銅/DM-Segphos催化體系參與不對稱反應(yīng)的催化作用機(jī)理。
[Abstract]:Due to its good stereoselectivity and mild reaction conditions, 1H _ 3-dipolar cycloaddition reaction has become a common method for the synthesis of five-member heterocyclic compounds. Since Huisgen put forward the concept of 1 ~ (3) -dipolar cycloaddition reaction in 1960s, the mechanism and application of cycloaddition reaction have been a hot topic in the field of chemistry. In recent years, the synthesis of optically active compounds by using chiral metal complex catalysts using non-chiral 1 / 3 dipolar and olefin as substrates has attracted extensive attention of organic synthesis chemists. Inspired by the synthetic method and biological activity of natural indolines, a new type of pyrrolidine benzoisothiazole compounds was synthesized by using methylamine ylide as dipole and benzoisothiazole derivatives as dipole cycloaddition reaction. At the same time, the dipolar cycloaddition reaction with benzoisothiazole derivatives as the skeleton was studied in depth. The enantioselectivity and enantioselectivity of the reaction under chiral catalysis were explored, and a general method for such reactions was established. It provides a methodological basis for the construction of compounds with similar structures and lays an important foundation for the further study of asymmetric 1 ~ (3) -dipolar cycloaddition reactions of these compounds. The main work of this thesis is: (1) using o-bromoaniline as the raw material, the intramolecular N-alkylation, N-methylation and cyclization reaction are used to synthesize 1o _ 3-dihydro-2o _ 1-benzoisothiazole-2o _ 2-dioxo _ 2. Knoevenagel condensation of aliphatic aldehydes and aromatic aldehydes with 1o 3-dihydro-2o 1-benzoisothiazole-2o 2-dioxide to synthesize 3- substituted methylene methylene-1-benzoisothiazole-2-dioxide-dipolar hydrophilic dipolar compound with double bond structure.) Methyl glycine hydrochloride And tert-butyl glycine as substrate, By condensation reaction with aliphatic aldehydes, aromatic aldehydes with different substituents and aldehydes with heterocyclic structures, different kinds of imines were prepared. A new type of pyrrolidine benzoisothiazole compounds was synthesized by the non-chiral 1o 3- dipolar cycloaddition reaction with methylamine ylide and the asymmetric 1 + 3 dipolar cycloaddition reaction with copper trifluoromeresulfonate / DM-Segphos catalyst system. A new method for the construction of pyrrole spirobenzoisothiazole compounds with four chiral centers, three tertiary carbon atoms and one snail carbon atom was obtained by one step reaction. The effects of different kinds of Lewis acid, ligand, alkali, solvent, temperature and reaction time on the reaction were discussed, and the optimum reaction conditions were determined. The method has a high enantioselectivity of ee value up to 99. The absolute configuration of the product was determined by X-ray single crystal diffraction, and the catalytic mechanism of copper trifluorosulfonate / DM-Segphos catalyst system for asymmetric reaction was proposed.
【學(xué)位授予單位】：青島科技大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：O621.251

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1 周容;肖微;尹祥;詹固;陳應(yīng)春;;環(huán)狀烯酮與環(huán)狀1-氮雜二烯的非對映及對映選擇性[4+2]環(huán)加成反應(yīng)[J];化學(xué)學(xué)報(bào);2014年07期

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本文編號：1840114