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/硼基化与其他化学事件的组合，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的结构单元。Ir-催化剂的温和性和它们操作的反应条件允许含有各种官能团的芳烃的硼基化。考虑到这种底物耐受性，也可以耐受宽范围的后续同锅反应。新发明的将C-H活化/硼基化与氧化“伸缩”的方法允许独特地获得新的和高度官能化的酚类结构单元，所述酚类结构单元在商业上不可用或仅可通过延长的、昂贵的和另外没有吸引力的途径获得。酚类是具有广泛商业重要性的重要化合物，特别是在药物发现、开发和制造领域。即使有一系列的生产方法，仍然有许多相对简单的例子，其中建立的合成是令人望而却步的长和/或低产量的实际应用。在本提案中，BoroPharm旨在通过专有技术的商业开发来克服这些困难，该专有技术已独家授权给BoroPharm，Inc.。具体而言，BoroPharm旨在验证铱催化的芳族硼基化/氧化作为药学相关酚类和羟基吡啶的商业途径。利用现代合成化学的工具，将追求以下目标：1。评估BoroPharm的苯酚产品可扩展到100 g苯酚产品。2.硼化催化剂/配体组合和负载的优化。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，包括氟代和氰基取代的苯酚。5.吡啶和喹啉底物硼化氧化的扩展。 公共卫生相关性：新药的发明在很大程度上依赖于化学家从分子构件组装独特化合物的能力。在这方面，新的药物需要新的构件，而成本较低的药物将需要更有效和环境友好的途径来获得这些关键中间体。在此，我们建议开发新技术，以创造独特和通用的化学结构单元，其发明将有助于发现和开发新药。

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.