Denmark Scott E, Pham Son M, Stavenger Robert A, Su Xiping, Wong Ken-Tsung, Nishigaichi Yutaka
Department of Chemistry, Roger Adams Laboratory, University of Illinois, Urbana, Illinois 61801, USA.
J Org Chem. 2006 May 12;71(10):3904-22. doi: 10.1021/jo060243v.
The mechanism of the catalytic, enantioselective addition of trichlorosilyl enolates to aldehydes has been investigated. Kinetic studies using ReactIR and rapid injection NMR (RINMR) spectroscopy have confirmed the simultaneous operation of dual mechanistic pathways involving either one or two phosphoramides bound to a siliconium ion organizational center. This mechanistic dichotomy was initially postulated on the basis of catalyst loading studies and nonlinear effects studies. This duality explains the difference in reactivity and stereoselectivity of various classes of phosphoramides. Determination of Arrhenius activation parameters revealed that aldol addition occurs through the reversible albeit unfavorable formation of an activated complex, and natural-abundance 13C NMR kinetic isotope effect (KIE) studies have determined that the turnover limiting step is the aldol addition. A thorough examination of a range of phosphoramides has established empirical structure-activity selectivity relationships. In addition, the effects of catalyst loading, rate of addition, solvents, and additives have been studied and together allow the formulation of a unified mechanistic picture for the aldol addition.
已对三氯硅基烯醇盐与醛的催化对映选择性加成反应机理进行了研究。使用ReactIR和快速注射核磁共振（RINMR）光谱进行的动力学研究证实了双机理途径的同时运行，该途径涉及与硅鎓离子组织中心结合的一个或两个磷酰胺。这种机理二分法最初是基于催化剂负载研究和非线性效应研究提出的。这种二元性解释了各类磷酰胺在反应性和立体选择性上的差异。阿累尼乌斯活化参数的测定表明，羟醛加成反应通过活化络合物的可逆但不利的形成而发生，天然丰度13C核磁共振动力学同位素效应（KIE）研究确定，周转限制步骤是羟醛加成反应。对一系列磷酰胺的深入研究建立了经验性的结构-活性-选择性关系。此外，还研究了催化剂负载量、添加速率、溶剂和添加剂的影响，这些共同为羟醛加成反应构建了一个统一的机理图景。
