Chiral Bifunctional Reagents for 1,3-Functionalization

该项目由美国德克萨斯大学圣安东尼奥分校的韩铉洙教授资助，由化学学部化学合成项目资助，正在开发用于合成复杂有机化合物的新型双功能试剂。这些双功能试剂的工作不依赖于官能团调整或使用保护基团（两个主要的合成效率低下的罪魁祸首），同时保持高选择性。因此，未来的双功能试剂和相应的合成策略为许多化学和生物学上重要的化合物（包括天然产物和药物）的高效不对称合成提供了一个多功能工具箱。这发生在圣安东尼奥德克萨斯大学化学系一个新兴的年轻科学家培训项目的背景下。开发不需要官能团操纵和保护基团的不对称醛烯丙基化/丁基化和烯丙基取代/迈克尔加成两种基本有机反应的方法是本项目的主要重点。这些目标包括：(1)简明的双功能试剂合成路线；(2)将双功能试剂在醛烯丙基化/丙烯基化反应中的应用扩展到多种脂肪和芳香族醛；(3)展示了该合成策略在2-烷基-1,3-二醇/氨基醇以及更复杂和迄今为止难以接近的环体系的高效不对称合成中的力量和多功能性。与更传统的B-、Si-和/或sn基试剂相比，这些双功能试剂在酸性或氧化条件下通过[3,3]-异位重排起作用，并且是完全“有机”的（都是c基的），使它们对环境无害且空气稳定。

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.