Catalytic Regioselective Functionalization of Alkane and Arenes

在这个由化学部化学催化项目资助的项目中，加州大学伯克利分校的John F. Hartwig教授将在典型的不反应的碳氢键（C-H）上进行反应。Hartwig教授的研究小组发现了甲基C-H键在烷烃和功能化分子的烷基中的硼化，并开发了铱配合物，该配合物在温和的条件下催化芳基和烷基C-H键的硼化，具有立体控制的选择性，包括高周转率发生的反应。提出的研究建立在几组关于C-H键的硅基化，脂肪族C-H键的硼化与一种新的铱催化剂的初步数据，以及控制这些C-H键功能化选择性的因素。拟议的研究将扩大烷基C-H键硼化的范围，包括二级C-H键和活化的初级C-H键的硼化，通过与该组最近发现的烷基C-H键的定向硅化相关的策略进行定向硼化，以及芳烃、杂芳烃和烯烃的分子间C-H键硅化。该研究还将通过制备硼基和硅基配合物来深入了解C-H键的硅化和硼化机制，这些配合物可以作为最近发现的脂肪族C-H键的硼化和脂肪族和芳香族C-H键的硅化的中间体。多年来，化学合成一直专注于分子特定点上的反应，这些反应包含一组被称为“官能团”的反应性原子。这些官能团远端的C-H键通常与用于常规合成化学的试剂不反应。提出的研究重点是选择性地发生在分子的C-H键上的反应，这些反应通常是不反应的。实现这一目标必须面对的一个挑战是分子中特定C-H键的选择性功能化。在某些情况下，一个碳氢键的选择性是由键的空间可用性决定的，在某些情况下是由键周围电子的分布决定的，在其他情况下是由离碳氢键几个原子远的官能团的位置决定的。将揭示利用这些特性进行选择性的方法。这项研究将带来新的方法，以更少的步骤、更少的浪费、更少的依赖于官能团的安装和保护来进行化学合成。此外，这项研究还为未来设计更有效的合成催化剂和工艺奠定了基础。这可能会影响有用材料的合成，如含有新性质的聚合物、具有增强发光能力的有机分子、用于其他反应的催化剂组分、用于理解生物系统的有机探针和重要药用分子的组分。所提出的研究工作已成为新课程的一部分，包括课堂、短期课程、许多外部讲座，以及PI最近完成的一个主要教科书项目。

In this project funded by the Chemical Catalysis Program of the Chemistry Division, Professor John F. Hartwig at the University of California, Berkeley will develop reactions at typically unreactive carbon-hydrogen (C-H) bonds. Prof. Hartwig's group discovered the borylation of methyl C-H bonds in alkanes and alkyl groups of functionalized molecules and developed iridium complexes that catalyze the borylation of aryl and alkyl C-H bonds under mild conditions, with sterically controlled selectivity, including reactions that occur with high turnovers. The proposed research builds upon several sets of preliminary data on the silylation of C-H bonds, the borylation of aliphatic C-H bonds with a new iridium catalyst, and the factors that control selectivity in these C-H bond functionalizations. The proposed research will broaden the scope of the borylations of alkyl C-H bonds to include the borylation of secondary C-H bonds and activated primary C-H bonds, directed borylations by strategies related to this group's recently discovered directed silylations of alkyl C-H bonds, and aspects of intermolecular C-H bond silylations of arenes, heteroarenes, and alkenes. The proposed research will also gain insight into the mechanism of silylations and borylations of C-H bonds by preparing boryl and silyl complexes that are competent to be intermediates in the recently discovered borylations of aliphatic C-H bonds and silylations of aliphatic and aromatic C-H bonds.For many years, chemical synthesis has focused on reactions at particular points of a molecule that contains a reactive array of atoms called "functional groups." The C-H bonds distal from these functional groups are usually unreactive with reagents used for conventional synthetic chemistry. The proposed research focuses on reactions that occur selectively at the C-H bonds of a molecule that are typically unreactive. One challenge that must be met to achieve this goal is the selective functionalization of a specific C-H bond in a molecule. In some cases, the selectivity for one C-H bond results from the spatial availability of the bond, in some cases from the distribution of electrons around the bond, and in other cases from the position of a functional group several atoms away from the C-H bond. Methods to exploit each of these properties for selectivity will be uncovered. This research will lead to new methods to conduct chemical synthesis in fewer steps, with less waste, and with less reliance on the installation and protection of functional groups. In addition, this research creates the underlying principles on which future design of catalysts and processes for more efficient synthesis are based. This may impact the synthesis of useful materials such as polymers containing new properties, organic molecules with enhanced abilities to emit light, components of catalysts for other reactions, organic probes for understanding biological systems, and components of medicinally important molecules. Work emanating from the proposed research has become part of new curricula for the classroom, short-courses, many external lectures, and a major textbook project that was recently completed by the PI.