Visible Light-Enabled Synthesis of Heterocycles through Energy Transfer - Equipment Supplement

项目摘要/摘要 氮杂环丁烷、氮杂环己烷和氧杂环己烷是四元杂环化合物，具有良好的药代动力学。 影响并代表着当前药物化学中的重要组成部分。环加成反应 在烯烃和亚胺或羰基之间，也称为(Aza)Paternó-Büchi反应，代表 最直接的合成方法来获得这些化合物，然而这些化合物目前的用途 由于对紫外光和竞争反应路径的严格要求，转化受到高度限制 通过光化学激发即可使用。因此，能够结合官能化氮杂环丙烷，氮杂环丙烷， 由于缺乏有效的合成方法，目前进入医药铅结构的氧杂环己烷受到严重限制。 方法：研究方法。到目前为止，还没有基于可见光的通用合成平台用于烯烃之间的环加成反应 亚胺或羰基的存在。拟议的研究计划的目标是确定和开发 能够使这些官能团之间的有效环加成反应获得氮杂替丁的化学策略， 氮杂环己烷，以及基于可见光促进的能量转移催化的氧杂环己烷。 这些新的合成方法将为合成各种不同的化合物提供通用和模块化的方案 在当前药物化学中非常受欢迎的杂环基元。此外，这些战略 所描述的将使烯烃与亚胺或羰基在温和反应下发生环加成反应 具有高官能团耐受性的条件，因为它们放弃了紫外线的要求。的实用程序 可获得的四元杂环作为构筑基团将在二次修饰和 通过从商业上可获得的起始材料合成生物活性靶标结构。 在该研究计划内制备的化合物将被纳入化合物库中 由密歇根大学化学基因组学中心(CCG)维护，并成为 用于生物研究和新药发现项目的高通量筛选(HTS)方法。 总而言之，所描述的研究将使Aza Paternó-Büchi和 Paternó-Büchi反应依赖于可见光激发下的能量传递。这些新的 转化是能够直接获得官能化氮杂环丁烷的理想合成工具， 氮杂环己烷和氧杂环己烷，预计将在药物化学领域产生广泛的影响。

Project Summary/Abstract Azetidines, azetines, and oxetanes are four-membered heterocycles that exhibit desirable pharmacokinetic effects and represent important building blocks in current medicinal chemistry. Cycloaddition reactions between alkenes and imines or carbonyls, also referred to as (aza) Paternò-Büchi reactions, represent the most direct synthetic approach to access these compounds, however the current utility of these transformations is highly restricted due to the stringent requirement of UV-light and competing reaction paths accessible upon photochemical excitation. Thus, the ability to incorporate functionalized azetidines, azetines, and oxetanes into pharmaceutical lead structures is currently severely limited due to a lack of efficient synthetic methods. To date, no visible light-based platform of general synthetic utility for cycloadditions between alkenes and imines or carbonyls exists. The objective of the proposed research program is to identify and develop chemical strategies that enable efficient cycloadditions between these functional groups to access azetidines, azetines, and oxetanes based on energy transfer catalysis facilitated by visible light. These new synthetic methods will provide general and modular protocols for the synthesis of a large variety of heterocyclic motifs that are highly desirable in current medicinal chemistry. Additionally, the strategies described will enable cycloaddition reactions between alkenes and imines or carbonyls under mild reaction conditions with high functional group tolerance as they forego the requirement of UV-light. The utility of the accessible 4-membered heterocycles as building blocks will be demonstrated in secondary modifications and by enabling the synthesis of biologically active target structures from commercially available starting materials. The compounds prepared within this research program will be incorporated into the compound library maintained by the Center for Chemical Genomics (CCG) at the University of Michigan and become part of high-throughput screening (HTS) approaches for biological research and new drug discovery projects. In summary, the research described will enable general, catalytic strategies for aza Paternò-Büchi and Paternò-Büchi reactions relying on energy transfer upon excitation with visible light. These new transformations represent desirable synthetic tools that will enable direct access to functionalized azetidines, azetines, and oxetanes, and are expected to have broad implications in the area of medicinal chemistry.