ADDITION OF AROMATIC THIOLS TO CONJUGATED CYCLOALKENONES, CATALYZED BY CHIRAL BETA-HYDROXY AMINES - A MECHANISTIC STUDY ON HOMOGENEOUS CATALYTIC ASYMMETRIC-SYNTHESIS
ADDITION OF AROMATIC THIOLS TO CONJUGATED CYCLOALKENONES, CATALYZED BY CHIRAL BETA-HYDROXY AMINES - A MECHANISTIC STUDY ON HOMOGENEOUS CATALYTIC ASYMMETRIC-SYNTHESIS
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DOI：
10.1021/ja00392a029
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发表时间：
1981-01-01
影响因子：
15
通讯作者：
WYNBERG, H
中科院分区：
文献类型：
--
作者：
HIEMSTRA, H;WYNBERG, H
当手性碱用作催化剂时，芳香硫醇和共轭环烯酮之间的反应产生光学活性的3-芳基硫代环烷酮。本文对该催化不对称合成的机理进行了详细的研究。该反应已在多种条件下进行。含有0-羟基胺部分（金鸡纳和麻黄生物碱）的催化剂比没有羟基功能的催化剂具有更高的反应速率和更高的对映体过量（ee 's）（高达75%）。极性溶剂、浓缩反应溶液和四正丁基铵盐的存在大大降低了ee 's。对奎宁在甲苯溶液中催化反应的动力学测量表明，这是一个三阶反应，每个反应物都是一级反应。活化焓很低（~ 0 kcal/mol），活化熵为负（-62 cal/(mol K)）。提出了硫醇加成反应的过渡态配合物模型，该模型很好地解释了反应速率、ee和绝对构型的实验数据。红金鸡和麻黄生物碱通过紧密过渡态配合物催化反应，该配合物由三种物质组成：硫醇、烯酮和催化剂。对于这些配合物的几何结构来说，重要的是三种稳定相互作用：硫醇阴离子和铵离子之间的静电相互作用，催化剂羟基和烯酮羰基之间的氢键，以及催化剂芳环系统和硫醇阴离子之间的分散相互作用。不同的空间条件导致烯酮的两种可能取向之间的自由能差，从而形成不相等数量的R和S产物。三种金鸡纳生物碱和没有羟基的催化剂缺乏至少一种稳定相互作用，导致结构过渡态较少，因此ee 's较低。建议这些不对称催化机制也适用于其他反应类型，由金鸡纳和麻黄生物碱催化。具有红- 0-羟基胺构型的生物碱可视为双功能催化剂。讨论了这类手性催化剂在催化不对称合成中的应用价值。催化不对称合成是制备纯对映体最具吸引力的方法，使用非手性起始材料。所述手性试剂的量与所合成的分子的数量相比是小的，并且不含任何手性辅助物质而获得所需的手性产物。2此外，催化不对称反应可以作为原始酶模型进行研究。酶是结构上最理想的手性催化剂，已成功地应用于有机领域
Reactionsbetween aromatic thiols and conjugated cycloalkenones afford optically active 3-arylthiocycloalkanones, when chiral bases are used as catalysts. This paper reports a detailed investigation into the mechanism of this catalytic asymmetric synthesis. The reaction has been performed under a variety of conditions. Catalysts containing the 0-hydroxy amine moiety (cinchona and ephedra alkaloids) give higher reaction rates and higher enantiomeric excesses (ee’s)(up to 75%) than catalysts without a hydroxyl function. Polar solvents, concentrated reaction solutions, and the presence of tetra-n-butylammonium salts lower the ee’s substantially. Kinetic measurements on a quinine-catalyzed reaction in toluene solution point to a third-order reaction, first order in each of the reactants. Activation enthalpies are very low (~ 0 kcal/mol) and activation entropies highly negative (—62 cal/(mol K)). Models of the transition-state complexes of the thiol addition reactions are proposed, which account well for the experimental data on reaction rate, ee, and absolute configuration. The erythro cinchonaand ephedra alkaloids catalyze the reaction via tight transition-state complexes, composed of three species: thiol, enone, and catalyst. Important for the geometry of these complexes are three stabilizing interactions: an electrostatic interaction between the thiol anion and theammonium cation, a hydrogen bond between the catalyst hydroxyl group and the enone carbonyl group, and a dispersion interaction between the catalyst aromatic ring system and the thiol anion. Different steric conditions cause a free-energy difference between two possible orientations of the enone, resulting in formationof unequal amounts of R and S products. The threo cinchona alkaloids and the catalysts without a hydroxyl group lackat least one of the stabilizing interactions, leading to less structured transition states and consequently lower ee’s. The suggestion is madethat these mechanisms of asymmetriccatalysis also hold for other reactiontypes, catalyzed by cinchona and ephedra alkaloids. The alkaloids having the erythro 0-hydroxy amine configuration can be viewed as bifunctional catalysts. The value of such chiral catalysts in catalytic asymmetric synthesis is discussed.Catalytic asymmetric synthesis is the most attractive method for the preparation of pure enantiomers, using achiral starting materials. The amount of the chiral reagent is small compared to thenumber of molecules synthesized, and the desired chiral product is obtained free from any chiral auxiliary substance. 2 Furthermore, a catalytic asymmetric reaction may be studied as a primitive enzyme model. Enzymes are structurally the most ideal chiral catalysts, and they are successfully applied in organic