Alpha-Tertiary Amines and Amino Acids via Rearrangement of Ureas

通过尿素重排生成α-叔胺和氨基酸

• 批准号: 191285586
• 负责人: Dr. Nicole Volz
• 金额: --
• 依托单位: School of Chemistry
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2011-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/191285586?language=en
• 关键词: Alpha; Tertiary; Amines; Amino; Acids

The wide occurrence of alpha-tertiary amines in naturally occurring and synthetic bioactive molecules has provided an impetus for the development of a number of synthetic strategies over the last 50 years. They pose a surprisingly difficult synthetic challenge - especially when the quaternary carbon centre has to be synthesised in an enantioselective way. The most convenient approach has been the 1,2 addition of nucleophiles to ketimines, but the lack of reactivity of these species coupled with difficulties of achieving good stereoselectivity has encouraged the exploration of alternative ways of constructing of the quaternary centre. A powerful alternative approach makes use of the rearrangement of readily available precursors, often (but not always) with formation of a new tertiary carbon to nitrogen bond (for example Curtius or sigmatropic rearrangement). Another useful method for synthesising hindered amines is the rearrangement of lithiated ureas that was developed by Clayden et al. The aim of the project will be to investigate the scope, limitations, and applicability of this previously unreported rearrangement. The project consists of three important aspects: Part I is the synthesis of free unnatural amino acids. Starting from vinylureas, enantioselective rearrangement and further transformations will be a new access to amino acids. Part II will deal with the scope of the substrates for the rearrangement. New substrates (nitrile/acid substituted ureas) will be investigated as well as the new non aromatic migrating groups. Part III is the literature unknown enantioselective hydrogenation of vinyl ureas to synthesise new starting material for the enantioselective rearrangement chemistry.

在过去的50年中，α-叔胺在天然存在的和合成的生物活性分子中的广泛存在为许多合成策略的发展提供了动力。它们提出了一个令人惊讶的困难的合成挑战-特别是当季碳中心必须以对映选择性的方式合成时。最方便的方法是将亲核试剂1，2加成到酮亚胺上，但这些物质缺乏反应性，难以实现良好的立体选择性，这鼓励了探索构建季中心的替代方法。一种强有力的替代方法是利用容易获得的前体的重排，通常（但不总是）形成新的叔碳-氮键（例如Curtius重排或σ迁移重排）。合成受阻胺的另一种有用的方法是由Clayden等人开发的锂化脲的重排。该项目的目的是调查这种以前未报道的重排的范围，限制和适用性。该项目包括三个重要方面：第一部分是游离非天然氨基酸的合成。从乙烯脲类化合物出发，对映体选择性重排和进一步转化将成为氨基酸合成的一条新途径。第二部分将讨论重新安排的基础的范围。将研究新的底物（腈/酸取代脲）以及新的非芳族迁移基团。第三部分是文献中未知的乙烯基脲的不对称选择性氢化反应，合成了新的不对称重排反应的起始原料。