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1、第五章第五章 不对称合成不对称合成2010年年10月月内容提要内容提要不对称合成及立体化学基本概念不对称合成及立体化学基本概念非对映择向合成非对映择向合成 对映择向合成对映择向合成双不对称合成双不对称合成 绝对不对称合成绝对不对称合成 不对称合成及立体化学基本概念不对称合成及立体化学基本概念不对称合成的定义：不对称合成的定义：由由Morrison和和Mosher提出：提出： “不对称合成是这样一个反应，其不对称合成是这样一个反应，其中底物分子整体中的非手性单元，经过反应剂不等量地生成立体中底物分子整体中的非手性单元，经过反应剂不等量地生成立体异构产物的途径，转化为手性单元。异构产物的途径，转化
2、为手性单元。 ”不对称合成的效率不对称合成的效率 （在不对称合成反应中，产物的两种对映体或非（在不对称合成反应中，产物的两种对映体或非对映体的数量差别越大，即立体选择性越高，合成效率越大对映体的数量差别越大，即立体选择性越高，合成效率越大 ）用对）用对映体（映体（% e.e.）或非对映体）或非对映体(% d.e.)过量百分数或光学纯度（过量百分数或光学纯度（%O.P.）来表示如下：来表示如下：旋光性旋光性 能使平面偏振光的偏振面旋转的性质叫做光活性或旋光性能使平面偏振光的偏振面旋转的性质叫做光活性或旋光性 ; ;手性手性 实物与其镜像不等同或不重合的性质称为手性或者不对称性。实物与其镜像不等同
3、或不重合的性质称为手性或者不对称性。右旋化合物右旋化合物 以顺时针方向旋转偏振光的对映体为右旋化合物，用（以顺时针方向旋转偏振光的对映体为右旋化合物，用（+ +）或）或字母字母d d表示；表示；左旋化合物左旋化合物 以逆时针方向旋转偏振光的对映体为左旋化合物，用（以逆时针方向旋转偏振光的对映体为左旋化合物，用（- -）或）或字母字母l l表示。表示。外消旋体外消旋体 左旋和右旋对映体的等摩尔混合物称为外消旋体（旋光值左旋和右旋对映体的等摩尔混合物称为外消旋体（旋光值=0=0），），用放在分子名称前面的（用放在分子名称前面的（）或）或racrac表示。表示。分子结构具备以下三个条件之一的才具有手
4、性：分子结构具备以下三个条件之一的才具有手性：（1 1）有不对称碳原子）有不对称碳原子（2 2）有四价共价键连的不对称原子，如：）有四价共价键连的不对称原子，如：SiSi，GeGe，N N（在季铵盐中或（在季铵盐中或N N氧化物氧化物中），中），MnMn，CuCu，BiBi，ZnZn，四个价键指向四面体的四个角，且互不相同，四个价键指向四面体的四个角，且互不相同（3 3）有三价的不对称原子，孤对电子看作是第四个基团（在）有三价的不对称原子，孤对电子看作是第四个基团（在CIPCIP优先序列中排优先序列中排末尾），且因某些固定键的存在而不能翻转。例如下列三元杂环，杂原子含末尾），且因某些固定键的存
5、在而不能翻转。例如下列三元杂环，杂原子含未共用电子对：未共用电子对：手性化合物的命名手性化合物的命名 (1)Fischer惯例或惯例或D/L结构结构(2)CIP惯例或惯例或R/S结构结构u 手性中心构型手性中心构型u 手性轴构型手性轴构型u 手性面构型（手性面构型（planar chirality）u 螺旋手性结构（螺旋手性结构（helical chirality） （R）-苯基乳酸（S）- -碘带乙基磺酸（S）-1，3-二氯丙二烯 （R）-1，3-二氯丙二烯 （S）2，6二甲基螺3，3庚烷 （R）2，6二甲基螺3，3庚烷判断构型的具体步骤如下：判断构型的具体步骤如下：确定分子的手性面，该平面
6、应为分子的自然平面，如化合物确定分子的手性面，该平面应为分子的自然平面，如化合物2 2中的苯环中的苯环平面；平面；确定指示原子或确定指示原子或P P原子（原子（pilot atompilot atom或或leading atomleading atom）和优势边，）和优势边，P P原原子是手性面外直接与所选手性面相连的所有原子中优先性最高的原子，子是手性面外直接与所选手性面相连的所有原子中优先性最高的原子，优势边是在手性平面内与优势边是在手性平面内与P P原子较近的边；原子较近的边；从与从与P P原子直接相连的手性面上的原子开始，在手性面内与原子直接相连的手性面上的原子开始，在手性面内与P P
7、原子直接原子直接相连的序数最优的原子称为第一原子；与第一原子直接相连序数最优相连的序数最优的原子称为第一原子；与第一原子直接相连序数最优先的原子称为第二原子；第三原子就是直接与第二原子（而非第一原先的原子称为第二原子；第三原子就是直接与第二原子（而非第一原子）相连的序数最优先的原子。分别用子）相连的序数最优先的原子。分别用1 1，2 2，3 3标记第一、二、三原子；标记第一、二、三原子；从从P P原子处观察优势边，沿原子处观察优势边，沿123123的顺序为顺时针，记作的顺序为顺时针，记作RpRp，逆时针，逆时针为为S SP P。立体化学中其它概念和表示法的含义立体化学中其它概念和表示法的含义(
8、1)不对称（asymmetric）分子和非对称（dissymmetric）分子 (2) 对映（异构）体和非对映（异构）体 (3)外消旋体和内消旋体(4)DL与的区别(5)Re/Si面(6)syn（同侧位）/anti（反侧位）(7)赤式/苏式（erythro/threo）5.2 非对映择向合成非对映择向合成5.2.1 含含-不对称碳原子的醛、酮的亲核加成反应不对称碳原子的醛、酮的亲核加成反应 CramCram规则一规则一 例如：例如：CramCram规则二规则二 Cornforth规则 主要考虑R与Cl之间的斥力主要考虑R与Cl之间的斥力主要考虑Ph,Cl与O之间的斥力举例：举例：5.2.2 不
9、对称环己酮的亲核加成不对称环己酮的亲核加成5.3 对映择向合成对映择向合成 引入手性辅基进行对映择向合成引入手性辅基进行对映择向合成 5.3.2 利用不对称试剂进行对映择向合成 烯烃醇20D%e.e.构型 顺式烯烃-11.8(-13.3)-8.6-6.5(-6.7)-2.087(98.4)8291(95)67-70(40)RRR1S,2S 反式烯烃+1.44+0.751314SS不对称硼试剂控制的硼氢化不对称硼试剂控制的硼氢化 手性亲双烯体控制的不对称手性亲双烯体控制的不对称Diels-AlderDiels-Alder反应反应 手性试剂诱导的醇醛缩合反应 醛的不对称烯丙基化反应 5.3.3应用
10、不对称催化剂的对映择向合成应用不对称催化剂的对映择向合成 手性膦配体产物e.eR=C6H5R=H1234596(S)99(R)95(S)85(R)100(R)94(S)91(R)90(R)73(R)98(R)配体溶剂时间（h）产物构型%e.e7a7a7a7a7b7c7dTHF/MeOH(9:1)THF/MeOH(8:2)i-PrOHMeOHTHF/MeOH(8:2)THF/MeOH(8:2)THF/MeOH(8:2)3020205203030SSSSSSS98.497.697.095.897.998.198.2RPh p-Cl-Ph o-MeO-Ph p-MeO-Ph p-Me-Ph E-Ph
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