Bronsted Acid Catalysis in Enantioselective Acyl Substitution

化学催化项目支持华盛顿大学Vladimir B. Birman教授的一个项目，该项目将探索Brønsted酸在催化、不对称酰基取代反应中的应用，如对映选择性O-和s -酰化以及手性酰基供体的对映选择性醇解。将应用于几种酰基供体的两种基本激活模式是酸辅助酰基转移催化和使用轴向手性磷酸的直接Brønsted酸催化。酰基转移催化将主要利用非手性羧酸与先前在伯曼实验室开发的基于脒的对映选择性酰化催化剂相结合。这些研究将导致几种底物的非酶动力学分解（KR）、动态动力学分解（DKR）、去对称化和去消旋化的新方法的发展。一个简单的过渡态模型的可用性将有助于向学生介绍不对称催化的基础知识。Vladimir B. Birman教授将研究一个被称为不对称有机催化的热门领域，该领域在工业界和学术界都有相当大的潜在影响。这项研究将有助于更好地理解化学群落中的非共价相互作用。对于学术界以外的过程开发来说，更广泛的科学影响可能相当重要。研究生和本科生将在合成有机化学方面得到更多样化的培训。最近开发的4-芳基内酯的DKR方案操作简单，使用易于获得的起始材料和催化剂，并提供了讨论有机化学许多基本概念的机会。这使它成为华盛顿大学本科实验课程的理想选择。这些措施将进一步提高华盛顿大学化学研究生和本科课程的质量，并帮助其成为中西部地区领先的研究机构之一。

The Chemical Catalysis Program supports Professor Vladimir B. Birman of Washington University for a project that will explore the application of Brønsted acids to catalytic, asymmetric acyl substitution reactions, such as enantioselective O- and S-acylation and enantioselective alcoholysis of chiral acyl donors. The two basic modes of activation that will be applied to several classes of acyl donors are acid-assisted acyl transfer catalysis and direct Brønsted acid catalysis using axially chiral phosphoric acids.The acyl transfer catalysis will utilize primarily achiral carboxylic acids in combination with amidine-based enantioselective acylation catalysts previously developed in the Birman laboratory. These studies will lead to the development of new methods for the nonenzymatic kinetic resolution (KR), dynamic kinetic resolution (DKR), desymmetrization and deracemization of several classes of substrates. The availability of a simple transition state model will be helpful for introducing students to the basics of asymmetric catalysis. Professor Vladimir B. Birman will work in a topical area called asymmetric organocatalysis that is having considerable potential impact in both industry and academia. The research will lead to a better understanding of non-covalent interactions in the chemical community. The broader scientific impact, for process development outside of academia, could be quite significant. Graduate and undergraduate students will be provided more diverse training in synthetic organic chemistry. The recently developed protocol for the DKR of 4-aryl-azlactones is operationally simple, utilizes easily obtainable starting materials and catalysts, and presents an opportunity to discuss many fundamental concepts of organic chemistry. This makes it an ideal candidate for incorporation into the undergraduate laboratory curriculum at Washington University. These steps will further improve the quality of the graduate and undergraduate programs in chemistry at Washington University and help build its strength as one of the leading research institutions in the Midwest.