Development of New Carbene Catalysts and Design of Organocatalytic Reactions

新型卡宾催化剂的开发及有机催化反应的设计

• 批准号: RGPIN-2017-06230
• 负责人: Gravel, Michel
• 金额: $ 3.28万
• 依托单位: University of Saskatchewan
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=688919
• 关键词: Development; New; Carbene; Catalysts; Design

Due to their unique properties, N-heterocyclic carbenes (NHCs) have attracted a lot of attention from the synthetic community. In addition to their widespread use as ligands for transition metals, they have been shown to act as catalysts in their own right. A remarkable feature of NHC catalysts is their ability to effect a reversal of reactivity (umpolung) for aldehydes. Whereas aldehydes normally react as electrophiles, they can behave as acyl anion equivalents in the presence of NHCs.******The NHC-catalyzed benzoin reaction was discovered several decades ago but applications in synthetic endeavours remain scarce despite its ability to form carbon-carbon bonds. The main limitation comes from the difficulty to achieve the cross-coupling of two different aldehydes. Recent developments by our group and others have made certain types of cross-benzoin reactions possible. Nevertheless, the range of reaction partners that can be coupled together chemoselectively remains quite limited. Building on our success with alpha-amino aldehydes, we propose to design new catalysts and substrates that will make a wider variety of cross-benzoin reactions possible. In addition to issues of chemoselectivity, diastereo- and enantioselectivity need to be addressed in order for these reactions to achieve their full potential. One very powerful, albeit challenging, area of investigation will consist in the dynamic kinetic asymmetric transformation of chiral aldehydes via cross-benzoin, Stetter, and aza-benzoin reactions to deliver products in a chemo-, diastereo- and enantioselective fashion.******Despite the astounding number of new carbenes that have been developed for use in organometallic complexes, NHC catalysts currently in use belong to only four closely related families. As even minor modifications of the catalyst structure can lead to dramatically divergent outcomes, we propose to conduct a rational catalyst discovery program. Our recent discovery that oxazolium salts can catalyze the benzoin, Stetter, and other reactions supports the notion that many more heterocyclic carbenes can play complementary roles in organocatalysis. A systematic survey of heterocycles and substituents will uncover new and interesting reactivities. Alongside this survey of new catalyst families, more conventional heterocycles will be explored in a new light. Specifically, thiazolylidenes and bis(amino)carbenes (BACs) will be revisited as we believe interesting new reactivity can be uncovered using these frameworks.**

由于其独特的特性，N-杂环卡宾斯（NHC）吸引了合成社区的很多关注。除了将其广泛用作过渡金属的配体使用外，它们本身还可以作为催化剂。 NHC催化剂的一个显着特征是它们能够影响醛反应（Umpolung）的逆转。尽管醛通常以电力为反应，但在NHC存在的情况下，它们可以作为酰基阴离子等效物的作用。****** ****** NHC催化的苯并反应是几十年前被发现的，但尽管它能够形成碳碳碳键，但在合成努力中的应用仍然很少。主要限制来自于实现两种不同醛的交叉偶联的困难。我们小组和其他人的最新发展使某些类型的交叉反应成为可能。然而，可以将化学选择性耦合在一起的反应伙伴的范围仍然非常有限。在我们在Alpha-Amino醛中取得成功的基础上，我们建议设计新的催化剂和底物，以使更广泛的跨苯并反应成为可能。除了化学选择性问题外，还需要解决映射和对映选择性，以使这些反应充分发挥其潜力。一个非常有力的，尽管具有挑战性的调查领域将包括通过交叉苯并醛，静态，Stetter和Aza-benzoin反应的动态动态性不对称转化，以在化学，非洲映射和对含有式的时尚中传递产物，以提供新型的carbornes。目前正在使用的催化剂仅属于四个密切相关的家庭。由于催化剂结构的微小修饰也会导致巨大的分歧，我们建议进行一个理性的催化剂发现程序。我们最近发现的是，恶作剂盐可以催化苯甲酸酯，斯特特和其他反应支持这样的观念，即更多的杂环卡宾斯可以在有机催化中起互补作用。对杂环和取代基的系统调查将发现新的有趣的反应性。除了对新催化剂家庭的调查外，还将以新的方式探索更多传统的杂环。具体而言，将重新审视噻唑基烯和二苯甲酸（氨基）碳烯（BAC），因为我们认为使用这些框架可以发现有趣的新反应性。**