Smith Amos B, Pitram Suresh M, Boldi Armen M, Gaunt Matthew J, Sfouggatakis Chris, Moser William H
Department of Chemistry, Monell Chemical Senses Center and Laboratory for Research on the Structure of Matter, University of Pennsylvania, Philadelphia, PA 19104, USA.
J Am Chem Soc. 2003 Nov 26;125(47):14435-45. doi: 10.1021/ja0376238.
The development, application, and advantages of a one-flask multicomponent dithiane linchpin coupling protocol, over the more conventional stepwise addition of dithiane anions to electrophiles leading to the rapid, efficient, and stereocontrolled assembly of highly functionalized intermediates for complex molecule synthesis, are described. Competent electrophiles include terminal epoxides, epichlorohydrin, and vinyl epoxides. High chemoselectivity can be achieved with epichlorohydrin and vinyl epoxides. For vinyl epoxides, the steric nature of the dithiane anion is critical; sterically unencumbered dithiane anions afford S(N)2 adducts, whereas encumbered anions lead primarily to SN2' adducts. Mechanistic studies demonstrate that the SN2' process occurs via syn addition to the vinyl epoxide. Integration of the multicomponent tactic with epichlorohydrin and vinyl epoxides permits the higher-order union of four and five components.
本文描述了一种单瓶多组分二硫烷关键偶联方案的开发、应用及优势。该方案相较于更传统的将二硫烷阴离子逐步加成到亲电试剂的方法，能快速、高效且立体控制地组装用于复杂分子合成的高官能化中间体。适用的亲电试剂包括末端环氧化物、环氧氯丙烷和乙烯基环氧化物。使用环氧氯丙烷和乙烯基环氧化物可实现高化学选择性。对于乙烯基环氧化物，二硫烷阴离子的空间性质至关重要；空间位阻小的二硫烷阴离子生成(S(N)2)加合物，而位阻大的阴离子主要生成(SN2')加合物。机理研究表明，(SN2')过程通过对乙烯基环氧化物的顺式加成发生。多组分策略与环氧氯丙烷和乙烯基环氧化物的结合允许四组分和五组分的高阶联合。
