Thesis Advisor徐宝华
Degree Grantor中国科学院大学
Degree Name硕士
Degree Discipline化学工程

亚胺,一般指分子结构中含有C=N双键,亦叫Schiff碱,广泛存在于大自然中,是许多具有生物活性分子中的关键结构单元,亦在有机合成领域中占据重要地位。有机胺C(sp3) -H键直接官能化是目前亚胺合成方法中最具前景的方向之一,主要包含交叉脱氢偶联和氧化还原中性两种策略。本文报道了一种新颖的合成α,β-不饱和亚胺路径,选择硝酮作为原料,在路易斯酸碱催化体系中一步实现醛和硝酮β 位C(sp3)-H键官能化反应,并进行了详细的条件筛选、底物拓展及机理研究。(1)以强路易斯酸In(OTf)3为催化剂,在高温(120 oC)以及过量硝酮(3.0 equiv.)为底物的条件下,实现PR3(R = Et, NMe2)协助的硝酮β位sp3碳氢键烯基化反应,α,β-不饱和亚胺的收率为85%;(2)以弱路易斯酸SiCl4为催化剂,在低温(60 oC)以及硝酮(2.0 equiv.)为底物的条件下,实现PR3(R = Et, NMe2)协助的硝酮β 位sp3碳氢键烯基化反应,得到高收率(92%)的α,β-不饱和亚胺,催化体系的底物官能团兼容性良好。同时,六元硝酮为底物,发生两次[1,3]-氢转移和羟醛缩合得到芳构化产物,即3,5-二烷基吡啶,底物官能团兼容性良好;(3)机理研究表明:有机膦试剂作为路易斯碱,与弱的路易斯酸SiCl4协同作用于硝酮的脱氧过程;此外,催化体系中大量存在的碱(有机膦氧、硝酮)对SiCl4的配位离子化作用,同时增强了SiCl4路易斯酸酸性和耐水性;由此构建了路易斯酸碱协同催化体系,实现温和条件下硝酮与有机醛的高效偶联官能化反应。;Imines with valuable containing C=N bonds, also called Schiff bases, play privileged role as structural motifs of many bioactive materials and synthetic origins. Different strategies are available for the construction of such structural motifs, yet direct β-C(sp3)-H bond functionalization of proper amines has drawn unwavering attentions, including cross dehydrogenation coupling and redox-neutral strategies. Herein, we reported a novel method to synthesize α,β-unsaturated imines by β-C(sp3)-H functionalization of nitrones. The reaction conditions in terms of Lewis acids, Lewis bases, temperature and solvents were screened and optimized. The limit and scope of carbonyl substrates was examined, and a mechanistic proposal was presented and discussed.(1) A novel approach of β-C(sp3)-H alkenylation of cyclic nitrones catalyzed by strong Lewis acid In(OTf)3 in the presence of Lewis base PR3 (R = Et or NMe2) with aldehydes to α,β-unsaturated imines was developed. It provides a choice to obtain α,β-unsaturated imines with a yield of 85%, when both of the loading of nitrone (3.0 equiv.) and the temperature (120 oC) were relatively high.(2) An alternative method of β-C(sp3)-H alkenylation of cyclic nitrones catalyzed by weak Lewis acid SiCl4 was developed. The optimized yield of 92% was obtained from the reaction of aldehyde and nitrone (2.0 equiv.) at 60 oC. In addition, in the case of 6-membered nitrone, a [1,3]-hydride shift within the resulted α,β-unsaturated imines renders the aromatization leading to 3,5-dialkylpyridines. The generation of unsaturated imines or aromatic heterocyclics accompanied with β-functionalization from nitrones and carbonyl substrates was therefore attained with satisfactory substrates tolerance.(3) Mechanistic studies show that: the synthesis of α,β-unsaturated imines mainly involves deoxygenation and aldol condensation, each proceeding under a cooperation effect between Lewis acid and Lewis base. Besides, both the acidity and hydrolytic stability of the weak SiCl4 were supposed to be enhanced by coordination with phosphine oxide (R = Et) or phosphoric triamide (R = NMe2) that originated from deoxygenation of nitrones by PR3. Therefore, an efficient Lewis base activated Lewis acid system of SiCl4-catalyzed/PR3-mediated was constructed to achieve a mild transformation of nitrones to α,β-unsaturated imine via β-C(sp3)-H functionalization with aldehydes/ketones.

Document Type学位论文
Recommended Citation
GB/T 7714
朱德萍. 硝酮β位sp3碳氢键官能化反应研究[D]. 中国科学院大学,2018.
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