许多具有重要生物和生理活性的天然生物碱都含有手性哌啶环结构。但是，有效地构筑手性哌啶环结构在化学合成上具有很大的挑战性。胺基醛、胺基缩醛由于存在着两个非常重要的活泼官能团-胺基和醛基，它们在合成方法的研究以及药物化学中都占据着非常重要的地位。本论文利用既含有氨基又含有酚羟基的 Betti 碱作为辅助试剂，合成了一系列取代的手性哌啶类化合物，同时高效率地合成了极具挑战性的胺基缩醛类化合物。Betti 碱与苯甘氨醇等其它辅助试剂相比有以下优点：(1) 其酚羟基具有较强的酸性，因而在反应中往往表现出更强的活性；(2) Betti 碱含有苯环和萘环结构，有更大的刚性，在手性合成中具有更好的控制和诱导作用；(3) Betti 碱残基在脱除时比一般的苄基更容易。论文第 2 章中，以 (S)-Betti 碱的酒石酸盐为手性辅助试剂，与戊二醛反应生成氢化噁嗪中间体，然后在不同的反应条件下与格氏试剂反应，可选择性地分别获得2-位单取代、2,6-二相同取代、2,6-二不同取代的手性哌啶类化合物。而且，研究了碱性切苄基的条件，得出去苄基反应和生成盐酸盐的最佳反应条件为：底物:四氢呋喃:6M氢氧化钠:甲醇 = 1 g : 4 mL : 2 mL : 4 mL。利用碱性去苄基条件，可以容易地得到含有碳碳不饱和键的取代基，克服了催化氢化脱苄基只能得到饱和取代基的缺点。论文第 3 章利用外消旋Betti 碱为辅助试剂，在甲醇-水体系中，高效地合成了α-取代胺基缩醛类化合物。水的存在具有两方面的优点：(1) 使反应产物在体系中析出，促进了反应的进行；(2) 反应不用加吸水试剂或水分离器，克服了以往这类反应怕水的缺点。Pd-C 催化氢化脱苄基过程中，利用胺类底物控制的偕二氯化物氢化去氯反应，直接得到胺基缩醛的盐酸盐。这种方法具有以下优点：(1) 产物以盐的形式得到，产率高，后处理简单；(2) 反应中利用生成的干燥氯化氢直接成盐，避免了使用盐酸时对缩醛结构的破坏。
Chiral piperidine moieties are present in many natural alkaloids with important biological and/or physiological properties. Some N-containing compounds with new structures or biological activities have been obtained by modifying natural alkaloids, but the work of constructing chiral piperidine structures efficiently is still very challenging. Amino aldehydes and amino acetals bearing two important active groups-amino and aldehyde play a significant role in synthetic methods research and medicinal chemistry, which are widely used as intermediates in organic synthesis.Betti base is a natural alkaloid containing both amino and phenol hydroxyl group. In this thesis, a series of chirally substituted piperidine compounds as well as amino acetals have been synthesized employing Betti base as an auxiliary reagent. Compared to phenyl glycinol and other auxiliary reagents, Betti base has the following advavtages: (1) Phenol hydroxyl group is more acidic, which makes Betti base more reactive in reactions; (2) Betti base bearing both phenyl and naphthyl groups has stronger rigidity, thus, efficient chiral control and induction can be achieved in chiral synthesis; (3) Betti base residue can be removed more easily than common benzyl group due to the presence of both phenyl and naphthyl groups. In chapter 2, various chirally substituted piperidines were prepared using Betti base as auxiliary. Firstly, L-tartaric acid salt of (S)-Betti base reacted with glutaraldehyde to form hydrooxine intermediate. Then, under different conditions, the above intermediate and Grignard reagents underwent nucleophilic reactions to obtain 2-monosubstituted, 2,6-homo-disubstituted, 2,6-hetero-disubstituted chiral piperidines, respectively. Furthermore, debenzylation conditions in the basic environment have been studied, and the optimal reaction conditions are as follows: substrate : THF : 6M NaOH : MeOH = 1g : 4mL : 2mL : 4mL. Chiral piperidines bearing both saturated and unsaturated substitutents can be readily obtained by this debenzylation method, which overcome the drawbacks of catalytic hydrogenolysis. In MeOH-H2O system, α-substituted amino acetals have been synthesized in high effiency in chapter 3. The presence of water indicates two advantages of the method: (1) Precipitation of the products from reaction system will motivate the reaction to complete; (2) No water absorption agents or separator were required in the reaction, which solves the problem of avoiding the presence of water in previous reactions. In the removal of Betti base residue by Pd-C catalyzed hydrogenation, the amine-substrate-controlled hydrodechlorination reactions of gem-dichloride have been applied, and the amino acetal hydrochlorides were obtained straightforward as the products. In this process, two advantages are obvious: (1) The products were obtained in the form of their hydrochlorides, which made high product yields and simple workup. (2) Formation of hydrochloride salts have been implemented by in situ produced dry HCl, thus, possible hydrolysis of acetal structure in aqueous HCl was effectively avoided.
