Catalytic Asymmetric Hydroboration: Uncapping the Potential with Two-Point Bindin

催化不对称硼氢化：通过两点结合释放潜力

基本信息

批准号：
8840270
负责人：
JAMES M TAKACS
金额：
$ 21.98万
依托单位：
UNIVERSITY OF NEBRASKA LINCOLN
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-05-01 至 2017-04-30
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Developing efficient methods for the reliable, stereocontrolled synthesis of small molecules via asymmetric catalysis is central to providing the means to prepare potential mechanistic probes and pharmaceuticals. These are essential tools that enable the better understanding and control of biological processes relevant to human health. The development of new catalytic asymmetric reactions is therefore of both practical and fundamental importance to the NIH mission. Chiral organoboranes are finding increasing use as synthetic intermediates en route to other useful functionality via stereospecific functional group interconversion, reagents for asymmetric synthesis, and synthetic targets for pharmaceutical applications. The stereochemistry of carbon-boron bond is retained upon transmetallation or conversion to other useful functional groups. Organoboranes are therefore seen as important intermediates for incorporating a variety of functional groups with defined stereochemistry in natural product, pharmaceutical intermediate, and drug synthesis. Recent breakthroughs in the development of methods for the stereospecific conversion of carbon-boron to carbon-carbon bonds increase the demand for efficient methods to synthesize chiral organoboronates. While stoichiometric asymmetric hydroboration is useful for asymmetric synthesis, its ultimate replacement, the greener direct catalytic asymmetric hydroboration (CAHB), remains as one of the unsolved problems in asymmetric catalysis. Notwithstanding a series of impressive recent advances using pinacol diborane as a (mono)borane surrogate, the lack of a versatile direct method for catalytic asymmetric hydroboration remains a critical barrier to the use of chiral organoboranes. The proposed studies build on recent breakthroughs in the catalytic asymmetric hydroboration of two-point binding substrates. Accomplishing the specific aims of the proposal will develop and expand the generality of that methodology and better define the mechanism through computational studies supported by experimental data. The computational studies will be carried out in collaboration with faculty and undergraduate students from the Department of Chemistry and Physics at Purdue University Calumet.

描述（由申请人提供）：开发有效的方法，用于通过不对称催化对小分子的可靠，立体控制的合成，对于提供准备潜在的机械探针和药物的手段至关重要。这些是必不可少的工具，可以更好地理解和控制与人类健康相关的生物学过程。因此，新的催化不对称反应的发展对NIH任务既实用又至关重要。手性有机体正在通过立体特定功能组互转换，非对称合成试剂和用于药物应用的合成靶标，在通往其他有用功能的合成中间体中发现了越来越多的使用。碳键的立体化学在跨化或转换为其他有用官能团时保留。因此，有机烷被视为重要的中间体，用于在天然产物，药物中间体和药物合成中融合具有定义的立体化学的各种官能团。在开发碳碳键的立体特异性转化方法的方法方面的最新突破增加了对合成手性有机体的有效方法的需求。虽然化学计量数不对称的混合液可用于不对称合成，但其最终替代物，绿色的直接催化不对称液压（CAHB）仍然是不对称催化中未解决的问题之一。尽管使用Pinacol Diborane作为（单声道）硼烷替代物的一系列令人印象深刻的进步，但缺乏用于催化不对称液压材料的多功能直接方法仍然是使用手性有机体的关键障碍。拟议的研究基于两点结合底物的催化不对称水合的最新突破。实现该提案的具体目的将发展和扩大该方法的一般性，并通过实验数据支持的计算研究更好地定义机制。计算研究将与普渡大学Calumet化学与物理系的教职员工和本科生合作进行。