羟基噁唑啉催化的二乙基锌与芳香醛不对称加成反应和坦洛新合成初探

【作者】 李志亭；

【导师】 李新生； 李良超；

【作者基本信息】 浙江师范大学 ， 有机化学， 2006， 硕士

【摘要】 本论文包括两部分 第一部分 羟基噁唑啉催化的二乙基锌与芳香醛不对称加成反应 第二部分 坦洛新合成初探 从手性苦杏仁酸出发，对羟基进行酯化反应，得到乙酰氧基苯乙酸，再将其依次与2-氨基丙醇(a)、2-氨基-3-甲基戊醇(b)、苯甘胺醇(c)、2-氨基-3-苯丙醇(d)、2-氨基-3-甲基丁醇(e)、1-氨基-3.3-二甲基丁醇(f)、缬胺醇(g)反应，依次得到4-甲基-[2-(4.5-二氢噁唑啉基)]苯基甲酸乙酯(Ⅱa产率86.3％)、4-异丁基-[2-(4.5-二氢噁唑啉基)]苯基甲酸乙酯(Ⅱb产率79.7％)等一系列中间体(Ⅱc-Ⅱg)；然后在氢氧化钠强碱作用下对羟基去保护，相应得到了含羟基的两个手性中心的噁唑啉催化剂4-甲基-[2-(4.5-二氢噁唑啉基)]苯基甲醇(Ia产率80％)，4-异丁基-[2-(4.5-二氢噁唑啉基)]苯基甲醇(Ⅰb产率90％)等催化剂(Ⅰc-Ⅰg)；随后将催化剂(Ⅰa-Ⅰg)用于催化芳基醛与二乙基锌的不对称加成反应，其中催化剂苯基-[4-苯基-2-(4.5-二氢噁唑啉基)]甲醇(Ⅰc)催化苯甲醛与二乙基锌的不对称加成反应，得到很好的产率和51％ee，4-叔丁基-[2-(4.5-二氢噁唑啉基)]苯基甲醇(Ⅰf)催化苯甲醛与二乙基锌的不对称加成反应，有较好的对映选择性(66％ee)；考察了(Ⅰf)催化邻氯苯甲醛、对氯苯甲醛、肉桂醛和2-萘醛等不同芳香醛与二乙基锌的加成反应，都表现出良好的催化效果；而催化剂(Ⅰf)对供电子取代基和空间位阻大的基团的芳香醛的对映选择性表现较差，而对吸电子取代基团的芳香醛则表现出较好的对映选择性。催化剂(Ⅰf)催化对氯苯甲醛与二乙基锌的不对称加成反应，获得了最好的结果，产物1-对氯苯基丙醇的产率高达94％，对映体过量达到91％。更多还原

【Abstract】 The dissertation consists of two parts. One is asymmetric addition of diethylzinc to aromatic aldehydes in the presence of hydroxymethyl oxazoline ligands, The other is study on synthesis of tamsulosin.We use the cheap available L- or D-mandelic acids as our preliminary materials. After protection of hydroxyl group with acetyl chloride by esterification, the esters were treated with L-alaninol (a), D-phenylglycinol (b) et al. in chlorobenzene under reflux to obtain correspondingly 4-mehtyl-4,5-dihydrooxazol-2-yl)(phenyl) methyl acetate IIa in 86.3% yield . The other acetates (IIb-IIg) could beachieved with high yields using the same method. Deprotection of acetyl under condition of 20% sodium hydroxide to afford 4-methyl-4,5-di hydrooxazol-2yl)(phenyl) methanol Ia in 80% yield, 4-isobutyl-4,5-dihydrooxazol-2-yl) (phenyl) methanol Ib in 90% yield. Hydroxymethyl oxazolines Ic-Ig are also obtained in high yield. The seven chiral ligands Ia-Ig were used in catalytic asymmetric addition of diethylzinc to benzaldehydes. Among these oxazolines, the catalyst phenyl (4-phenyl-4,5-dihydrooxazol-2-yl)methanol Ic showed good catalytic effectiveness and achieved 51% enantiomeric excess, 4-tert-butyl-4,5 -dihydromethyloxazol-2-yl)(phenyl)methanol If obtained the best enantiomeric excess (up to 66%). Alkylation of other aromatic aldehydes were investigated with 10% mol If as catalyst. It is seen that this compound is fairly effective with respect to both para-and ortho-substituted benzaldehydes, as well as to cinnamaldehyde and 2-naphthaldehyde. The presence of electron-donor substitutents and bulky substituents in the ortho position appreciably reduces the enantioselectivity, whereas electron-withdrawing groups increase ee value. The best result was obtained in the reaction with更多还原