Development and Synthetic Applications of [1,3] and [3,3] Rearrangements of O-Vinyl Oximes

本研究由化学系化学合成项目资助，劳拉·L.芝加哥伊利诺伊大学化学系的安德森将探索O-乙烯基肟的[1，3]和[3，3]重排的合成应用，以更有效地获得重要的立体定向有机片段，如α-氨基酮，1，4-亚氨基酮，β-氨基醇，γ-氨基醇和杂环。 O-乙烯基肟在有机合成中的应用由于缺乏通用的制备方法而受到阻碍。 该计划建立在最近发现的制备O-乙烯基肟的简单方法及其重排反应的可调性的初步观察的基础上。 收集的基本反应性和机械数据将用于指导立体选择性和催化过程的发展，并利用这些未充分利用的重要的催化剂的潜力。 O-乙烯基肟的重排产物将利用σ迁移重排过程中的立体化学信息集进一步衍生化，以提供快速获得复杂的、立体定向的有机片段的途径。该项目可以将未使用的有机化合物转化为有价值的和通用的有机合成子，为合成目标的逆合成分析和阐明重要药物的新的有效途径提供了新的工具，材料. 提案中概述的基础研究可以迅速阐明这些未充分利用的中间体的最有效应用，这种合成方法开发的方法也将作为一种手段，培养一个种族和性别多样化的研究生和本科生群体，为合成挑战找到创造性的解决方案，并为他们积极影响化学界做好准备。

In this project, funded by the Chemical Synthesis Program of the Chemistry Division, Professor Laura L. Anderson of the Department of Chemistry at the University of Illinois at Chicago will explore the synthetic applications of the [1,3] and [3,3] rearrangements of O-vinyl oximes for more efficient access to important stereodefined organic fragments such as alpha-amino ketones, 1,4-imino ketones, beta-amino alcohols, gamma-amino alcohols, and heterocycles. Prior use of O-vinyl oximes in organic synthesis has been hampered by a lack of general methods for their preparation. This program builds on recent discoveries of simple methods for the preparation of O-vinyl oximes and initial observations of the tunability of their rearrangement reactions. Collection of fundamental reactivity and mechanistic data will be used to guide the development of stereoselective and catalytic processes and to harness the potential of these underutilized important synthons. Rearrangement products of O-vinyl oximes will be further derivitized using the stereochemical information set during the sigmatropic rearrangements to provide rapid access to complicated, stereodefined, organic fragments.This project could transform an unused organic compound into a valuable and versatile organic synthon, providing new tools for the retrosynthetic analysis of synthetic targets and the elucidation of new efficient pathways to important pharmaceuticals and materials. The fundamental studies outlined in the proposal could rapidly elucidate the most potent applications of these underutilized intermediates and this approach to synthetic method development will also function as a means to train an ethnic and gender diverse group of graduate and undergraduate students to find creative solutions to synthetic challenges and prepare them to positively impact the chemical community.