DyCat3

镝猫3

• 批准号: EP/X022862/1
• 负责人: Andrew Smith
• 金额: $ 26万
• 依托单位: University of St Andrews
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FX022862%2F1
• 关键词: DyCat3

Kinetic resolution is a useful process in industry and academia for the preparation of enantiomerically pure compounds. Despite its widespread use, a recognised drawback is that the theoretical maximum yield of a single enantiomer is 50%. This limitation can potentially be overcome by using dynamic kinetic resolution (DKR), in which the individual enantiomers of the racemic starting material interconvert dynamically. This process needs to be coupled with a selective KR event that allows the faster reacting enantiomer of the racemate to be selectively derivatised. The current state-of-the-art in this area has been reported by Bäckvall, who has reported and explored extensively the dual catalytic acylative DKR of secondary alcohols using chemoenzymatic methods. In contrast, the DKR of tertiary alcohols is a widely recognized challenge in the area of enantioselective catalysis as both enantiomerization and KR steps are difficult individually, but need to work synergistically and without inhibition for an effective DKR. The current state-of-the-art with respect to tertiary alcohol DKR has been demonstrated in a single isolated example by Gröger, using a metal-supported racemization catalyst coupled with enzymatic KR. Although moderate selectivity due to catalyst deactivation was observed, a sequential iterative batch process was successful and shows proof of principle that this challenging transformation is feasible. This proposal aims to develop a range of effective tertiary alcohol dynamic kinetic resolution strategies. Racemization approaches will rely upon either reversible nucleophilic addition to a carbonyl group, or boronic acid catalysis to reversibly prepare racemic tertiary alcohols, that coupled with a Lewis-base catalysed kinetic resolution will lead to efficient tertiary alcohol DKR.

动力学分辨率是工业和学术界的有用过程，用于制备对映体纯化合物的准备。尽管使用了宽度，但公认的缺点是单个对映异构体的理论最大产量为50％。可以通过使用动态动力学分辨率（DKR）来克服这种限制，在这种动态动力学分辨率（DKR）中，外消旋起始材料的各个对映异构体动态互动。此过程需要与选择性的KR事件结合起来，该事件允许种族主义者的更快的反应艺人选择性地衍生。 Bäckvall报道了该领域的最新最新面积，他使用化学酶方法报告并广泛探索了二次醇的双重催化酰基DKR。相比之下，第三级醇的DKR在对映体化领域是一个广泛认可的挑战，因为对映异构化和KR步骤既困难又单独，但需要协同工作，并且不抑制有效的DKR。 Gröger在单个孤立的示例中使用金属支持的种族化催化剂与酶促KR相结合的单个孤立示例中证明了有关第三级酒精DKR的最新最新。尽管观察到由于催化剂失活而导致的中等选择性，但顺序迭代的批次过程是成功的，并证明了原理的证据，表明这种挑战转化是可行的。提案旨在制定一系列有效的高等教育动态动力学分辨率策略。种族化方法将依赖于羰基的可逆核能抗性添加，或者硼酸催化剂可逆地制备外消旋第三级酒精，并与刘易斯碱基础催化的动力学分辨率相结合，将导致有效的第三醇DKR。

项目成果

Enantioselective Synthesis of Tetra-substituted 3-Hydroxyphthalide Esters by Isothiourea-Catalysed Acylative Dynamic Kinetic Resolution

异硫脲催化酰化动态动力学拆分对映选择性合成四取代 3-羟基苯酞酯

• DOI: 10.26434/chemrxiv-2024-tjwhm
• 发表时间: 2024
• 作者: Agrawal S