Asymmetric Induction in Organocopper Conjugate Addition Reactions

这项研究将开发出在有机铜共轭加成反应和形式等价的SN2‘取代反应中实现不对称诱导的通用、有效的方法。该项目有四个具体目标。首先，将合成和研究几个初步研究建议的潜在有效的手性不可转移配体。其中包括手性双环ı3.3.0！八氢环戊烷ıb！吡咯环体系和手性联萘酰胺配体可能为不对称诱导提供了电子基础。其次，将进行机理研究，包括1H，13C和7Li核磁共振实验和分子量测定，以探索各种铜酸盐试剂的结构和组成。第三，将考察手性可转移配体的方法，这些配体可以通过简单的官能团操作很容易地转化为各种取代基。第四，将探索易于制备的手性底物及其与有机铜试剂在共轭加成和SN2‘取代反应中的反应方法。这些方法涉及手性α，β-不饱和肼和烯丙基缩醛。这项研究最初是在波士顿大学发起的，然后转移到克莱姆森大学。这将导致开发新的、高效的天然产物合成方法。它已经出版了九种出版物。

This investigation will develop general, efficient methods for effecting asymmetric induction in organocopper conjugate addition reactions and formally equivalent SN2' substitution reactions. The project has four specific goals. First, several potentially effective chiral non-transferable ligands, suggested by the preliminary study, will be synthesized and examined. These include a chiral bicyclic ı3.3.0! octahydrocyclopentaıb!pyrrole ring system and a chiral binaphthyl amido ligand that may provide an electronic basis for the asymmetric induction. Second, mechanistic studies involving 1H, 13C, and 7Li NMR experiments and molecular weight determinations will be undertaken to probe the structures and compositions of the various cuprate reagents. Third, methods involving chiral transferable ligands that can be readily transformed into a variety of substituents by facile functional group manipulations will be examined. Fourth, methods involving readily prepared chiral substrates and their reactions with organocopper reagents in conjugate addition and SN2' substitution reactions will be explored. These methods involve chiral alpha, beta-unsaturated hydrazones and allylic acetals. This research was initiated at Boston University and then transferred to Clemson University. It will lead to the development of new, efficient methods for synthesizing natural products. It has resulted in nine publications.