Mechanisms of Nucleophilic Substitution at Tricoordinate Sulfur

这个项目由芝加哥伊利诺伊大学的Paul Young负责，属于有机动力学项目，旨在研究含有三配位（即三个键）硫原子的有机化合物的反应。这些化合物与带负电荷的物质反应的详细途径将被研究，特别注意单步和多步途径之间的竞争。这项工作将使化学家能够更好地预测和控制涉及硫原子的复杂反应。有大量的数据表明，在一定条件下，简单磺酸盐的烷基转移反应可能通过配体偶联机制发生，涉及中间四配位硫烷的还原消除。这个建议很容易通过监测产物分布和选定反应的立体化学来验证。将合成一系列手性已知的s -甲基- s -（取代-甲基苄基）- s -（取代苯基）磺酸盐，并与以下亲核试剂反应：(1)取代乙基醇（将利用溶剂溶解条件和反应进展跟踪核磁共振），(2)取代吡啶和伯、仲、叔胺在非质子溶剂和发现支持最小溶剂溶解活性的质子溶剂中，(3)强亲核试剂包括磷化氢和碳离子，(4)在观察到亲核试剂浓度二阶依赖的条件下，高浓度的取代乙酸酯和苯甲酸酯；(5)双功能亲核试剂，包括-吡啶酮和-吡啶乙硫酮。对于每一类亲核试剂，将得到产物分布，特别强调转移苯基的手性。对于每一个观察到的途径，结构对反应性的影响将使用经典的Hammett和Bronsted关联进行研究。将确定次级氘同位素效应和C-13同位素对亲核速率常数的影响，并与儿茶酚- o -甲基转移酶催化的甲基转移所观察到的同位素效应进行比较。将研究亲核试剂强度对分配途径的影响，包括给定序列（Bronsted相关性）和所研究的亲核试剂阵列（N+型相关性）。这些数据作为一个完整的集合，将定义在三配位硫发生的取代反应中“配体偶联”途径的极限，并将允许更完整地理解亲核试剂结构在烷基转移过程的每个潜在途径中的作用。

This project by Paul Young of the University of Illinois, Chicago, is within the Organic Dynamics Program, and is aimed at a study of the reactions of organic compounds containing tricoordinate (i.e., three bonds) sulfur atoms. The detailed pathway by which these compounds react with negatively charged species will be investigated with special attention given to the competition between single and multiple step routes. This work should allow chemists to better predict and control complex reactions involving sulfur atoms. There is a significant body of data suggesting that, under certain conditions, alkyl transfer reactions from simple sulfonium salts may occur through a ligand coupling mechanism involving reductive elimination from an intermediate tetracoordinate sulfurane. This suggestion is easily testable by monitoring the product distribution and stereochemistry of selected reactions. A series of chiral S-methyl-S-(substituted alpha-methylbenzyl)-S-(substituted phenyl)sulfonium salts with known chirality around the benzyl group will be synthesized, and reacted with the following nucleophiles: (1) substituted ethyl alcohols (solvolysis conditions will be utilized and the progress of the reaction followed by NMR), (2) substituted pyridines and primary, secondary and tertiary amines in aprotic solvents and protic solvents found to support minimal solvolysis activity, (3) strong nucleophiles including phosphines and carbanions, (4) high concentrations of substituted acetates and benzoates under conditions where a second-order dependence on nucleophile concentration is observed, and (5) bifunctional nucleophiles including alpha- pyridones and alpha-pyridinethiones. For each class of nucleophile, product distributions will be obtained with special emphasis on the chirality of the transferred benzyl group. For each of the observed pathways, the effects of structure on reactivity will be investigated using classical Hammett and Bronsted correlations. Secondary deuterium isotope effects and C-13 isotope effects on the nucleophilic rate constants will be determined for comparison with isotope effects observed for methyl transfers catalyzed by the enzyme, catechol-O-methyltransferase. The effect of nucleophile strength on the partitioning pathways will be investigated, both within a given series (Bronsted correlations) and across the array of nucleophiles investigated (N+-type correlations). These data, taken as a complete set, will define the limits of the "ligand coupling" pathway in substitution reactions occurring at tricoordinate sulfur and will allow a more complete understanding of the role of nucleophile structure on each of the potential pathways for the alkyl transfer process.