Phase II Environmentally greener, efficient, and safe synthetic platform for the

描述（由申请人提供）：我们建议继续扩大对铱催化芳香族碳氢活化/硼化的研究，并与其他化学转化相结合，作为一种目前难以达到的化学构建块的新方法，这将对各种实际应用非常有用，包括制药，农用化学，材料和精细化学开发。ir催化剂的温和性及其操作的反应条件允许含有各种官能团的芳烃的硼化。鉴于这种底物耐受性，大范围的后续同锅反应是可能的，目前正在开发中。我们新发明的“望远镜”碳氢活化/氧化硼化过程是这种以有效、可扩展的方式将硼化与其他化学转化结合起来的能力的一个主要例子。这个过程提供了快速和独特的途径来获得新的和高度功能化的酚类构建块，这些构建块目前在商业上是不可获得的，或者只能通过漫长、昂贵和其他不吸引人的途径来获得。酚类化合物是一种重要的商业化合物，被广泛利用，特别是在药物发现、开发和制造领域。即使有了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，已经建立的合成方法对于实际使用来说过于漫长和/或产量低。在该提案中，BoroPharm旨在通过专有技术的商业开发来解决这些困难，该技术已独家授权给BoroPharm， Inc.。具体来说，BoroPharm旨在验证铱催化的芳香硼化/氧化作为制药相关酚和羟基吡啶的商业途径。基于第一阶段目标的成功完成和BoroPharm不断增长的客户群的行业反馈，该第二阶段提案将解决以下具体目标：扩大硼化吡啶衍生物的组合，增加喹啉类、吡嗪类、嘧啶类、重氮类、咪唑类、吡唑类、恶唑类等。在适用的情况下生产氧化产物（如羟基喹啉）。2. 探索新的硼技术，包括三氟硼酸盐、三氟硼酸盐和MIDA衍生物的形成和利用。3. 增加苯酚组合，使更多以前未报告的产品可用。增加规模以生产公斤数量。4. 扩展组合中芳基硼酸盐的其他转化，并生产碳硼键被转化或保留的新产品。

DESCRIPTION (provided by applicant): We propose to continue expanding the study of iridium-catalyzed aromatic C-H activation/borylation in concert with other chemical conversions as a new approach to currently inaccessible chemical building blocks that will be highly useful for variety of practical applications, including pharmaceutical, agro-chemical, materials and fine chemical development. The mildness of the Ir-catalysts and the reaction conditions under which they operate, allows for the borylation of arenes containing a variety of functional groups. Given this substrate tolerance, a wide range of subsequent same-pot reactions is possible, and currently under development. Our newly invented process that "telescopes" C-H activation/borylation with oxidations serves as a prime example of this ability to couple borylation with other chemical transformations in an efficient, scaleable way. This process provides rapid and unique access to new and highly functionalized phenolic building blocks that are currently commercially unavailable or accessible only by protracted, costly, and otherwise unattractive routes. Phenols are commercially important compounds that are extensively utilized, 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. Based on the successful completion of Phase I objectives and industry feedback from BoroPharm's growing client base, the following specific aims will be addressed in this Phase II proposal: 1. Expand the portfolio of borylated pyridine derivatives and add quinolines, pyrazines, pyrimidines, diazenes, imidazoles, pyrazoles, oxazoles, etc. Produce oxidized products (e.g. hydroxyquinolines) where applicable. 2. Explore new boron technologies including the formation and utilization of trifluoroborate, triolate, and MIDA derivatives. 3. Augment the phenol portfolio to make more previously unreported products available. Increase the scale to produce kilogram quantities. 4. Expand upon additional transformations of aryl boronates in the portfolio, and to produce new products where the carbon-boron bonds are either transformed or retained. 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 the next phase of a 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. This project is a continuation of a phase I grant that succeeded with positive outcomes. Herein, we will expand upon the breadth, scope and scale of the chemical platform and expand on the synthesis of novel and useful pharmaceutical building blocks.