Development of New Carbene Catalysts and Design of Organocatalytic Reactions

N-杂环卡宾(NHCs)由于其独特的性质引起了合成界的广泛关注。除了它们被广泛用作过渡金属的配体外，它们本身也被证明是催化剂。NHC催化剂的一个显着特征是它们能够实现醛的反应活性(Upolung)的逆转。虽然醛通常作为亲电体反应，但在NHC存在下，它们可以作为酰基阴离子的等价物。NHC催化的安息香反应是几十年前发现的，但在合成努力中的应用仍然很少，尽管它有能力形成碳-碳键。主要的限制来自于难以实现两种不同醛的交叉偶联。我们小组和其他人的最新进展使某些类型的交叉安息香反应成为可能。然而，可以化学选择性地偶联在一起的反应伙伴的范围仍然相当有限。在我们在α-氨基醛方面取得成功的基础上，我们建议设计新的催化剂和底物，使更多种类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。一个非常强大但具有挑战性的研究领域将是手性醛通过交叉安息香、Stetter和氮杂-安息香反应的动态动力学不对称转化，以化学、非对映和不对称方式提供产品。*尽管开发了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催化剂只属于四个密切相关的家族。由于即使是对催化剂结构的微小修改也可能导致显著不同的结果，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，这支持了更多的杂环卡宾可以在有机催化中发挥互补作用的观点。对杂环和取代基的系统研究将发现新的和有趣的反应活性。除了对新催化剂家族的综述外，还将从新的角度探索更多的传统杂环化合物。具体地说，将重新讨论噻唑烷和双(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。**

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.**