Development of New Carbene Catalysts and Design of Organocatalytic Reactions

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。除了它们作为过渡金属的配体的广泛用途之外，它们已经被证明以其自身的权利作为催化剂。NHC催化剂的一个显著特征是它们能够实现醛的反应性逆转（upolung）。而醛类通常作为亲电试剂反应，它们在NHC存在下可以表现为酰基阴离子等价物。NHC催化的苯偶姻反应在几十年前就被发现了，但尽管它能够形成碳-碳键，但在合成方面的应用仍然很少。主要的限制来自于难以实现两种不同醛的交叉偶联。我们小组和其他人最近的进展使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伴侣的范围仍然非常有限。基于我们在α-氨基醛方面的成功，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，还需要解决非对映体和对映体选择性问题，以便这些反应充分发挥其潜力。一个非常强大的，尽管具有挑战性的研究领域将包括通过交叉苯偶姻，Stetter和氮杂苯偶姻反应的手性醛的动态动力学不对称转化，以化学，非对映体和对映体选择性方式提供产品。尽管已经开发出数量惊人的用于有机金属络合物的新卡宾，但目前使用的NHC催化剂仅属于四个密切相关的家族。由于即使是催化剂结构的微小修改也会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，恶唑盐可以催化苯偶姻，Stetter和其他反应支持的概念，更多的杂环卡宾可以在有机催化中发挥互补作用。杂环和取代基的系统研究将揭示新的和有趣的反应活性。除了新的催化剂家族的调查，更传统的杂环将在一个新的光探索。具体来说，我们将重新审视噻唑亚基和双（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。**

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.**