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: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=712102
• 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.

由于其独特的性质，N-杂环卡宾（NHC）引起了合成界的广泛关注。除了广泛用作过渡金属配体之外，它们本身也被证明可以充当催化剂。 NHC 催化剂的一个显着特征是它们能够逆转醛的反应性（umpolung）。虽然醛通常作为亲电子试剂发生反应，但在 NHC 存在下，它们可以表现为酰基阴离子等价物。 NHC 催化的安息香反应在几十年前就被发现了，但尽管它能够形成碳-碳键，但在合成领域的应用仍然很少。主要限制来自于难以实现两种不同醛的交叉偶联。我们小组和其他人的最新进展使得某些类型的交叉安息香反应成为可能。然而，可以化学选择性偶联在一起的反应配偶体的范围仍然相当有限。基于我们在α-氨基醛方面取得的成功，我们建议设计新的催化剂和底物，使更广泛的交叉安息香反应成为可能。除了化学选择性问题外，还需要解决非对映选择性和对映选择性问题，以便这些反应充分发挥其潜力。一个非常强大但具有挑战性的研究领域将包括通过交叉苯偶姻、Stetter 和氮杂苯偶姻反应进行手性醛的动态动力学不对称转化，以化学、非对映和对映选择性方式提供产物。 尽管已开发用于有机金属配合物的新型卡宾数量惊人，但目前使用的 NHC 催化剂仅属于四个密切相关的家族。由于即使对催化剂结构进行微小的修改也可能导致截然不同的结果，因此我们建议进行合理的催化剂发现计划。我们最近发现恶唑盐可以催化安息香、Stetter 和其他反应，这支持了更多杂环卡宾可以在有机催化中发挥补充作用的观点。对杂环和取代基的系统研究将发现新的、有趣的反应性。除了对新催化剂家族的调查之外，还将以新的视角探索更传统的杂环化合物。具体来说，我们将重新审视噻唑基和双（氨基）卡宾（BAC），因为我们相信使用这些框架可以发现有趣的新反应性。