Strategies and Methods for the Synthesis of Aromatic Molecules

芳香分子占已上市药品的80%，并且越来越多地成为新材料的组成部分，例如传感器和智能手机电池。基于定向邻位金属化（DoM）反应的芳香族化合物构造新方法的发明和发展一直是我们研究的中心主题。DoM取代了传统的亲电取代，成为制造取代芳环的主要手段，并且该技术或单独或与过渡金属催化化学结合，已转移到商业药物的合成中。我们的研究将集中在1。多取代萘酚和二氢苯并呋喃的金属化途径。这些协议旨在取代传统路线，并建立新的通用方法来构建a-萘酚，生物活性天然产物和一类配体。2. DoM-DMG在杂芳烃合成中的舞蹈。该项目开发了新的官能团迁移（舞蹈）反应，用于构建具有药用价值的杂环类，克服了漫长的路线。3. 含dmg芳烃的光氧化还原反应。该项目旨在发现和开发光氧化催化反应，以补充或取代我们的DoM化学。4. DoM-Kulinkovich反应链接。该项目旨在开发一种新的具有光学活性的环丙醇的一般途径，并发现dom衍生的具有药用价值的芳香分子的Kulinkovich反应。5. 氮杂核糖合成的DoM。项目2的分子将为合成一类新的B-N杂环提供前体，这些杂环具有独特的性质，对有机电子和传感材料具有未来的价值。6. 天然产物的全合成。该项目涉及几种生物活性天然产物的全合成，例如生物碱，芳香聚酮)。这些综合将展示我们的DoM和DreM策略的广泛适用性。7. Biaryl Atropisomerism。二芳基反旋体是由于围绕中心芳基-芳基键的受限旋转而具有旋光性的分子。我们的目标是合成和关联简单和大环双芳基分子的实验计算旋转屏障，这些分子目前在药物发现计划中很感兴趣。8. 酰胺dmg定向ir催化的C-H键活化/硼化偶联。在本项目中，将研究反应的范围/局限性以及C-H正交活化- suzuki - miyaura工艺。申请资金将支持7名硕士、3名博士、10名本科生和几名访问研究生（澳大利亚、法国、德国和西班牙）的研究活动。

Aromatic molecules constitute 80% of marketed drugs and increasingly are components of new materials, eg sensors and smartphone batteries. Invention and development of new methodology for construction of aromatic compounds based on directed ortho metalation (DoM) reaction has been a central theme of our research. DoM has overtaken traditional electrophilic substitution as the principal means for making substituted aromatic rings and the technology, alone or aligned with transition metal-catalyzed chemistry, has been transferred to the synthesis of commercial drugs. Our research will focus on 1. Metalation Routes to Polysubstituted -Naphthols and Dihydrobenzofurans. These protocols aim to supercede traditional routes and establish new general methods for the construction of a-naphthols, bioactive natural products, and a class of ligands. 2. DoM-DMG Dance in the Synthesis of Heteroaromatics. This project develops new functional group migration (dance') reactions for the construction of valuable classes of pharmaceutically relevant heterocycles, overcoming lengthy routes. 3. Photoredox Reactions of DMG-bearing Aromatics. The project aims to discover and develop photoredox-catalyzed reactions to complement or supercede our DoM chemistry. 4. DoM-Kulinkovich Reaction link. The project aims to develop a new general route to optically-active cyclopropanols and to discover a Kulinkovich reaction on DoM-derived aromatic molecules of pharmaceutical value. 5. DoM for Azaborinine Synthesis. Molecules of Project 2 will provide precursors for the synthesis of a new class of B-N heterocycles that have distinct properties of future value for organic electronic and sensing materials. 6. Total Synthesis of Natural Products. The project concerns the total synthesis of several bioactive natural products, e.g. alkaloids, aromatic polyketides). The syntheses will showcase our DoM and DreM strategies of broad applicability. 7. Biaryl Atropisomerism. Biaryl atropisomers are molecules that are optically active by virtue of restricted rotation about the central aryl-aryl bond. We aim to synthesize and correlate experimental-computational rotational barriers of simple and macrocyclic biaryls, molecules that are of current interest in drug discovery programs. 8. Amide DMG-directed Ir-catalyzed C-H Bond Activation/Borylative Coupling. In this project, the scope/limitations of the reaction and the orthogonal C-H activation-Suzuki-Miyaura process will be studied. The requested funding will support research activity of 7 MSc, 3 PhD, 10 undergrads, and several visiting grad students (Australia, France, Germany, and Spain).