Environmentally greener, efficient, and safe synthetic platform for the productio

描述(由申请人提供)：我们建议研究Ir催化的芳香族C-H活化/硼化反应与其他化学事件的结合，作为一种新的方法，以获得新的和高度有用的，但目前无法获得的药物开发基础。红外催化剂的温和和它们的反应条件允许含有各种官能团的芳烃的硼化反应。考虑到底物的耐受性，随后的大范围同锅反应也是可以容忍的。新发明的工艺通过氧化“望远镜”C-H活化/硼化，允许独特地获得新的、高度功能化的酚醛构建块，这些构建块在商业上是不可获得的，或者只能通过漫长、昂贵或其他不具吸引力的路线才能获得。酚类化合物是具有广泛商业价值的重要化合物，特别是在药物发现、开发和制造领域。即使有一系列的方法来生产它们，仍然有许多相对简单的例子，在这些例子中，已建立的合成对于实际应用来说是令人望而却步的长和/或低产率。在这项提案中，BoroPharm公司旨在通过独家授权给BoroPharm公司的专有技术的商业开发来克服这些困难。具体地说，BoroPharm公司的目标是验证Ir催化的芳香族硼化/氧化作为一种商业路线来获得与药物相关的苯酚和羟基吡啶。利用现代合成化学的工具，将实现以下目标：1.评估BoroPharm的苯酚产品可扩展到100克苯酚产品。2.优化了硼化催化剂/配体组合和负载量。3.氧化剂对苯酚产率影响的评价。4.扩大BoroPharm的苯酚产品组合，包括氟取代酚和氰基取代酚。5.将硼化氧化延伸到吡啶和喹啉底物。 与公共健康相关：新药的发明在很大程度上取决于化学家从分子构件组装独特化合物的能力。在这方面，新的药物需要新的组成部分，而成本较低的药物将需要更有效和更环保的途径来获得这些关键中间体。在此，我们建议开发新技术来创建独特和多功能的化学构建块，其发明将有助于新药的发现和开发。

DESCRIPTION (provided by applicant): We propose to study the combination of Ir-catalyzed aromatic C-H activation/borylation with other chemical events as a new approach to novel and highly useful, but currently inaccessible building blocks for pharmaceutical development. The mildness of the Ir-catalysts and reaction conditions under which they operate allows the borylation of arenes containing a variety of functional groups. Given this substrate tolerance, wide ranges of subsequent same-pot reactions are also tolerated. Newly invented processes that "telescope" C-H activation/borylation with oxidations allow unique access to new and highly functionalized phenolic building blocks that are commercially unavailable or only accessible by protracted, costly, and otherwise unattractive routes. Phenols are important compounds with broad commercial importance, especially in the area of drug discovery, development, and manufacture. Even with an array of methods for their production, there are still many relatively simple examples where the established syntheses are prohibitively long and/or low yielding for practical use. In this proposal BoroPharm aims to combat these difficulties through the commercial development of proprietary technology that has been exclusively licensed to BoroPharm, Inc. Specifically, BoroPharm aims to validate iridium-catalyzed aromatic borylation/oxidation as a commercial route to pharmaceutically relevant phenols and hydroxypyridines. Using the tools of modern synthetic chemistry, the following objectives will be pursued: 1. Assessment of scalability of BoroPharm's phenol offerings to 100 g of phenol products. 2. Optimization of borylation catalyst/ligand combinations and loadings. 3. Evaluation of the effects of oxidant on phenol yield. 4. Expansion of BoroPharm's phenol portfolio including fluoro and cyano substituted phenols. 5. Extension of borylation oxidation to pyridine and quinoline substrates. PUBLIC HEALTH RELEVANCE: The invention of new drugs rests heavily on the chemist's ability to assemble unique compounds from molecular building blocks. In this regard, new pharmaceuticals call for new building blocks, while lower cost drugs will require more efficient and environmentally friendly routes to these key intermediates. Herein we propose to develop novel technology for the creation of unique and versatile chemical building blocks, the invention of which will aid the discovery and development of new medicines.