Development of New Carbene Catalysts and Design of Organocatalytic Reactions

n -杂环碳因其独特的性质，引起了合成界的广泛关注。除了广泛用作过渡金属的配体外，它们还被证明具有催化剂的作用。NHC催化剂的一个显著特征是它们对醛类的反应性逆转的能力。虽然醛通常以亲电试剂的形式反应，但在NHCs的存在下，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，尽管它能够形成碳-碳键，但在合成领域的应用仍然很少。主要的限制是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发展使某些类型的交叉苯并酮反应成为可能。然而，可以化学选择性耦合在一起的反应伙伴的范围仍然相当有限。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，使更广泛的交叉苯甲酸反应成为可能。除了化学选择性问题外，为了使这些反应充分发挥其潜力，还需要解决非映体和对映体选择性问题。一个非常强大的，尽管具有挑战性的研究领域将包括手性醛通过交叉苯甲酸、Stetter和氮杂苯甲酸反应的动态动力学不对称转化，以化学、非映对和对映选择性的方式传递产物。******尽管已开发用于有机金属配合物的新碳烯数量惊人，但目前使用的NHC催化剂仅属于四个密切相关的家族。由于即使是催化剂结构的微小修改也可能导致显著不同的结果，我们建议进行一个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，这支持了更多杂环碳化合物在有机催化中可以发挥互补作用的观点。对杂环和取代基的系统研究将会发现新的有趣的反应。除了对新催化剂家族的调查外，还将以新的视角探索更传统的杂环化合物。具体地说，我们将重新研究噻唑苄基和双（氨基）羰基（BACs），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.**