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：
8654345
负责人：
JAMES M TAKACS
金额：
$ 22万
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 2016-04-30
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）：开发通过不对称催化可靠、立体控制合成小分子的有效方法对于提供制备潜在机械探针和药物的手段至关重要。这些是能够更好地理解和控制与人类健康相关的生物过程的重要工具。因此，新的催化不对称反应的发展对于 NIH 的使命具有实际意义和根本重要性。手性有机硼烷越来越多地用作合成中间体，通过立体特异性官能团互变、不对称合成试剂和药物应用的合成靶标获得其他有用的功能。碳-硼键的立体化学在金属转移或转化为其他有用的官能团时得以保留。因此，有机硼烷被视为在天然产物、药物中间体和药物合成中掺入具有确定立体化学的各种官能团的重要中间体。最近在碳-硼到碳-碳键的立体定向转化方法的开发方面取得的突破增加了对合成手性有机硼酸酯的有效方法的需求。虽然化学计量不对称硼氢化可用于不对称合成，但其最终替代品，更环保的直接催化不对称硼氢化（CAHB），仍然是不对称催化中未解决的问题之一。尽管最近使用频哪醇乙硼烷作为（单）硼烷替代物取得了一系列令人印象深刻的进展，但缺乏催化不对称硼氢化的通用直接方法仍然是使用手性有机硼烷的关键障碍。拟议的研究建立在两点结合底物催化不对称硼氢化作用的最新突破的基础上。实现该提案的具体目标将发展和扩展该方法的通用性，并通过实验数据支持的计算研究更好地定义该机制。计算研究将与普渡大学卡鲁梅特化学和物理系的教师和本科生合作进行。