Organic Synthesis Reagents on Transition Metals

描述（由申请人提供）：药物和生物活性分子的构建依赖于碳-碳键形成的方法。在过去的十年中，烯烃复分解已成为形成这些键的有力手段，应用范围从但不限于小有机分子，复杂的天然产物，以及控制良好的聚合物结构。高活性、高效、稳定和选择性强的催化剂的可用性是进一步发展这些广泛应用的关键。在上一个授权期内，催化剂的制备促进了(a)在水溶液中，(b)在空间阻碍底物中，(c)在较低的催化剂负载下，以及(d)具有更高水平的对映体选择性。提出了一种构造n -杂环羰基配体的简便方法。该方法将在下一个资助期内用于立体选择性复分解催化剂的开发（控制碳-碳双键的反：顺比）和催化剂稳定性的改善（以降低催化剂负载），以及其他提出的改进。这种催化剂的设计和制备将进一步使生物相关化合物的快速和选择性形成成为可能。公共卫生相关性：生物活性分子的制备仍然是人类健康和相关领域研究中的一个重大挑战。烯烃复分解现在通常用于这类分子的构造。该反应催化剂的开发是推进这种强大的碳-碳键形成技术的关键。

DESCRIPTION (provided by applicant): The construction of pharmaceutical and bioactive molecules relies on methods for the formation of carbon-carbon bonds. Over the past decade olefin metathesis has emerged as a powerful means by which to form these bonds in applications ranging from, but not limited to, small organic molecules, complex natural products, and well-controlled polymer architectures. The availability of robust catalysts that are highly active, efficient, stable, and selective is key to the further development of these wide-ranging applications. Over the last granting period catalysts were prepared that facilitate metathesis (a) in aqueous solutions, (b) with sterically hindered substrates, (c) at lower catalyst loadings, and (d) with higher levels of enantioselectivity. A powerfully simple method for the construction of N-heterocyclic carbene ligands was developed. This method will be exploited over the next granting period for the development of stereoselective metathesis catalysts (controlling the trans:cis ratio of the carbon-carbon double bonds), and improvement of catalyst stability (to lower catalyst loadings), among other proposed improvements. The design and preparation of such catalysts would further enable the rapid and selective formation of biologically-relevant chemical compounds. PUBLIC HEALTH RELEVANCE: The preparation of bioactive molecules remains a significant challenge in the study of human health and related fields. Olefin metathesis is now routinely used for the constructions of such molecules. Development of catalysts for this reaction is key to the advancement of this powerful carbon-carbon bond forming technology.