【作者】 郭娅静；

【导师】 周忠强；

【作者基本信息】 中南民族大学 ， 有机化学， 2007， 硕士

【摘要】 手性仲醇是药物、农药、香料等的重要合成中间体,对其各种合成方法的研究也日益增多。醛的不对称催化烷基化反应和前手性酮的不对称催化还原反应是制备手性仲醇的两种有效方法。这两种制备手性仲醇的方法无论在学术上还是工业应用方面都具有很重要的地位。不对称催化反应的核心是手性催化剂的设计合成。本论文从天然樟脑和L-氨基酸出发合成了一系列手性氨基醇,然后对这些氨基醇进行修饰,分别合成了相应的樟脑磺酰胺醇、樟脑酰胺醇、对甲苯磺酰胺醇以及羟基樟脑磺酰胺醇等配体,再将它们用于催化前手性芳酮的不对称还原反应和二乙基锌对芳香醛的不对称加成反应。具体内容如下:以L-苯丙氨酸、L-蛋氨酸、L-亮氨酸等与二氯亚砜低温反应生成相应的氨基酸甲酯盐酸盐,然后与格氏试剂加成制备了7个手性氨基醇。再经过磺酰化、酰化等过程对氨基醇上的氨基进行修饰得到6个手性樟脑磺酰胺醇、6个手性对甲苯磺酰胺醇和6个樟脑酰胺醇配体,其中四个配体经硼氢化钠还原得到了4个手性羟基樟脑磺酰胺醇。另外从天然樟脑出发合成了3个具有C2对称结构的手性羟基樟脑磺酰胺和1个手性羟基双磺酰胺醇。所得产物均为固体,通过熔点、比旋光度、IR和1H NMR确认。分别考察了手性氨基醇、手性樟脑磺酰胺醇和对甲苯磺酰胺醇与硼烷所形成的络合物在苯乙酮还原反应中的催化性能。选取其中催化效果最好的樟脑磺酰胺醇催化还原了苯丙酮、2-氯苯乙酮、2-溴苯乙酮、对氯苯乙酮、对溴苯乙酮和对甲基苯乙酮。实验表明,用手性氨基醇催化还原苯乙酮可获得90%~99%的化学产率和12.3%~70.4%e.e.;用手性樟脑磺酰胺醇催化则得到65.7%~99%的化学产率和0~33.0%e.e.。分别考察了樟脑磺酰胺醇与Ti(OiPr)4所成络合物和樟脑酰胺醇在二乙基锌对芳香醛的不对称加成反应中的催化性能。实验表明,樟脑磺酰胺醇在二氯甲烷中比在甲苯中催化效果相对较好,但e.e.最高只有19.6%;而具有C2对称结构的羟基樟脑磺酰胺则对不同芳醛有较好的催化活性,得到58%~89%的化学产率和17%~51%e.e.;樟脑酰胺醇分别以正己烷和二氯甲烷作溶剂直接催化苯甲醛加成得到48.4%~81.5%的化学产率和0~24.7%e.e.。更多还原

【Abstract】 The chiral secondary alcohols are important intermediates in the synthesis of drug, pesticide and spicery etc., and their numerous methods remain the focus of much research activity. Catalytic asymmetry addition of aldehydes and asymmetry reduction of prochiral ketones are two effective methods for preparation of chiral secondary alcohols. The methods play an important role in academic research and industry.The core of catalytic asymmetry reactions is design and synthesis of chiral catalyst. In this work, a series of chiral amino alcohols were synthesized from natural camphor and L-amino acids. And then camphor sulfonamide alcohols, camphor amide alcohols, p-toluene sulfonamide alcohols and hydroxyl camphor sulfonamide alcohols were respectively prepared by modified the amino alcohols. These ligands were used in asymmetry reduction of prochiral aromatic ketones and asymmetry addition of diethylzinc to aromatic aldehydes. Specific details are outlined as follows:Amino acid methyl ester hydrochlorides were prepared from L-phenylalanine, L-methionine, L-leucine and thionyl chloride in low temperature, and then seven chiral amino alcohols obtained by the reactions of amino acid methyl ester hydrochlorides with Grignard reagents. Six camphor sulfonamide alcohols, six p-toluene sulfonamide alcohols and six camphor amide alcohols were prepared by modifying the amino of these amino alcohols, such as sulfonylating, acylating etc. Four ligands of them were reduced by sodium borohydride to give four new chiral hydroxyl camphor sulfonamide alcohols. On the other hand, three new chiral hydroxyl camphor sulfonamides which have C2 symmetry structure and one chiral double hydroxyl sulfonamide alcohols were synthesized from natural camphor. All products were solid, and they were characterized with melting point, IR, specific rotation and 1H NMR.The catalytic performance of the complexes which were prepared from borane and chiral amino alcohols, chiral sulfonamide alcohols and p-toluene sulfonamide alcohols respectively was researched in asymmetry reduction of acetophenone. The best ligand was used to catalyze reduction of phenylethylketone, 2-chloroacetophenone, 2-bromoacetophenone, p-chloroacetophenone, p-bromoacetophenone, and p-methyl- acetophenone. The results showed that 90%~99% yield and 12.3%~70.4%e.e. were got when chiral amino alcohols were used as catalysts for reduction of acetophenone, 65.7%~99% yield and 0~33.0%e.e. obtained when chiral sulfonamide alcohols were used as catalysts for reduction of various prochiral ketones. Catalytic performance of the complexes of camphor sulfonamide alcohols and Ti(OiPr)4, and camphor amide alcohols in asymmetry addition of diethylzinc to aromatic aldehydes was researched. The results showed that better catalytic results were got in dichloromethane than in toluene when camphor sulfonamide alcohols were used as ligands, but the best asymmetric induction is only 19.6%e.e.; camphor sulfonamide alcohols with C2 symmetry structure catalyzed the addition of diethylzinc to aromatic aldehydes with 58%~89% yield and 17%~51%e.e.; camphor amide alcohols catalyzed the addition of diethylzinc to benzaldehyde with 48.4%~81.5% yield and 0~24.7%e.e. in hexane or dichloromethane.更多还原