Mechanisms of Nucleophilic Substitution at Tricoordinate Sulfur

这个项目是由芝加哥伊利诺伊大学的Paul Young在有机动力学计划范围内进行的，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种反应的详细途径将被研究，并特别注意单步和多步路线之间的竞争。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。有大量数据表明，在某些条件下，简单硫酸盐的烷基转移反应可能通过配体偶联机制发生，包括从中间体四配位硫烷还原消除。这一建议很容易通过监测选定反应的产物分布和立体化学来检验。合成了一系列在苯基周围具有已知手性的手性S-甲基-S-(取代α-甲基苄基)-S-(取代苯基)硫盐，并与下列亲核试剂反应：(1)取代乙醇(利用溶剂化条件，反应过程用核磁共振进行)，(2)取代吡啶和伯基，在非质子性溶剂和质子性溶剂中的仲胺和叔胺，(3)包括膦和碳离子在内的强亲核剂，(4)在观察到亲核试剂浓度二级依赖的条件下取代醋酸酯和苯甲酸酯的高浓度，和(5)双功能亲核试剂，包括α-吡啶酮和α-吡啶硫酮。对于每一类亲核试剂，将获得产物分布，并特别强调转移的苄基的手性。对于每个观察到的路径，将使用经典的Hammett和Bronsted关联式来研究结构对反应性的影响。将测定亲核速率常数的二次氚同位素效应和C-13同位素效应，以与观察到的对儿茶酚-O-甲基转移酶催化的甲基转移的同位素效应进行比较。亲核强度对分配路径的影响将被研究，既在给定的系列内(布朗斯特德关联)，也在所研究的亲核试剂阵列上(N+型关联)。作为一套完整的数据，这些数据将定义在三配位硫发生的取代反应中“配体偶联”途径的限制，并将使人们更全面地了解亲核结构在烷基转移过程的每一条潜在途径上的作用。

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.