Novel synthetic methodologies based on carbon dioxide: alpha-amino acid derivatives from nitrone umpolung, an atom-economic process, catalysed by transition metals

基于二氧化碳的新型合成方法：来自硝酮umpolung的α-氨基酸衍生物，硝酮umpolung是一种由过渡金属催化的原子经济过程

• 批准号: 68851291
• 负责人: Dr. Olaf Walter
• 金额: --
• 依托单位: Joint Research Centre Karlsruhe
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2008
• 资助国家: 德国
• 起止时间: 2007-12-31 至 2012-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/68851291?language=en
• 关键词: Novel; synthetic; methodologies; based; carbon

The chemical recycling of CO2 would provide a cheap, non toxic, and abundant carbon source for chemical industries. Therefore, there is a need for chemists to develop novel methodologies that use CO2 as a C1 building-block, despite its poor intrinsic reactivity. We aim to participate in this challenge through the proposed original approach for the synthesis of α-amino acid derivatives from nitrones and CO2. Nitrones are stable, easy to manipulate intermediates, which are readily available from a large variety of carbonyl compounds. Consequently, the scope of this reaction is potentially broad as it could give access to highly diverse α-amino acid derivatives, including α-N-hydroxyamino acids and α, α-disubstituted amino acids. The latter are highly valuable building blocks for pharmaceutical research. Should this project be successful, the developed synthetic method would be highly attractive compared to the current processes for preparing α-amino acids and would contribute to the valorisation of CO2 as a feedstock for chemical industries.Our project stems from the recent discovery of the SmI2-promoted nitrone umpolung in Grenoble and its success will depend strongly on our capacity to find appropriate conditions for reaction of the resulting intermediates with CO2. The expertise of the Karlsruhe chemists in the use and activation of CO2 will thus be essential for the achievement of this program’s objectives. While the partners in Grenoble will input their competence in the field of nitrone umpolung for scope, limitations, mechanistic and stereochemical aspects, the role of the partners in Karlsruhe will be to delineate the optimal conditions for performing the reactions with CO2 in terms of temperature, pressure, and possibly activation by transition metals. Once the feasibility of the reaction is demonstrated, research will focus on avoiding the use of excess SmI2, in order to translate this process into an economical and environmentally sustainable one.

CO2的化学回收将为化学工业提供廉价、无毒、丰富的碳源。因此，有必要为化学家开发新的方法，使用二氧化碳作为C1积木，尽管其固有的反应性差。 我们的目标是通过提出的从硝酮和CO2合成α-氨基酸衍生物的原始方法参与这一挑战。硝酮是一种稳定的、易于操作的中间体，可从多种羰基化合物中容易地获得。因此，该反应的范围可能很广，因为它可以获得高度多样化的α-氨基酸衍生物，包括α-N-羟基氨基酸和α，α-二取代氨基酸。后者是药物研究的极有价值的基石。如果这个项目成功，与目前制备α-氨基酸的方法相比，开发的合成方法将具有很大的吸引力，并将有助于将CO2作为化学工业的原料。我们的项目源于最近发现的SmI 2-促进硝酮umpolung在格勒诺布尔和它的成功将在很大程度上取决于我们的能力，以找到适当的条件，反应的结果中间体与CO2。卡尔斯鲁厄化学家在二氧化碳使用和活化方面的专业知识对于实现该计划的目标至关重要。格勒诺布尔的合作伙伴将在硝酮的范围、限制、机理和立体化学方面投入他们的能力，而卡尔斯鲁厄的合作伙伴的作用将是在温度、压力和可能的过渡金属活化方面描述与CO2进行反应的最佳条件。一旦反应的可行性得到证明，研究将集中在避免使用过量的SmI 2，以将该过程转化为经济和环境可持续的过程。