Chiral Bifunctional Reagents for 1,3-Functionalization

在这项由化学系化学合成计划资助的项目中，德克萨斯大学圣安东尼奥分校的韩贤秀教授正在开发用于合成复杂有机化合物的新的双功能试剂。这些双功能试剂在不依赖官能团调整或使用保护基团(合成效率低下的两个主要原因)的情况下起作用，同时保持高选择性。因此，未来的双功能试剂和伴随的合成策略为许多化学和生物重要化合物的高效不对称合成提供了一个通用的工具箱，包括天然产物和药物。这是在德克萨斯大学圣安东尼奥分校化学系正在兴起的年轻科学家培训计划的背景下进行的。发展两种基本的有机反应，不对称醛的烯丙基化/巴豆基反应和烯丙基取代/Michael加成反应，而不需要官能团的操作和保护基团，是本项目的主要重点。这些目标包括：(1)双功能试剂的简明合成路线；(2)将醛的烯丙化/巴豆基化反应中的双功能试剂扩展到一系列不同的脂肪醛和芳香醛；(3)展示合成策略在2-烷基-1，3-二醇/氨基醇的高效不对称合成中的威力和通用性，以及更复杂和迄今难以接触的环系。与更传统的B-、Si-和/或Sn基试剂不同，这些双官能团试剂在酸性或氧化条件下通过[3，3]-Sigmatrotic重排操作，并且完全是有机的(全部基于C)，使它们对环境友好，对空气稳定。

In this project funded by the Chemical Synthesis Program of the Chemistry Division, Prof. Hyunsoo Han of the University of Texas at San Antonio is developing new bifunctional reagents for the synthesis of complex organic compounds. These bifunctional reagents work without relying on functional group adjustments or on the use of protecting groups (two chief culprits of synthetic inefficiency), while maintaining high selectivity. Consequently, the prospective bifunctional reagents and accompanying synthetic strategies provide a versatile tool box for efficient asymmetric synthesis of many chemically and biologically important compounds, including natural products and pharmaceuticals. This occurs within the context of an emerging program for the training of young scientists in the Department of Chemistry at the University of Texas at San Antonio. The development of methods for carrying out two fundamental organic reactions, asymmetric aldehyde allylation/crotylation and allylic substitution/Michael addition, without functional group manipulations and protection groups is a main focus of this project. These targets include: (1) concise synthetic routes for bifunctional reagents; (2) extension of bifunctional reagents in the aldehyde allylation/crotylation reactions to a diverse array of aliphatic and aromatic aldehydes; (3) demonstration of the power and versatility of the synthetic strategies in the efficient asymmetric syntheses of 2-alkyl-1,3-diols/aminoalcohols as well as more complex and heretofore inaccessible ring systems. In contrast to more traditional B-, Si-, and/or Sn-based reagents, these bifunctional reagents operate through [3,3]-sigmatropic rearrangement under either acidic or oxidative conditions, and are totally "organic" (all C-based), making them environmentally benign and air-stable.