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形成碳-碳键的方法。在过去的十年中，烯烃复分解已经成为一种强有力的手段，通过该手段在从但不限于小有机分子、复杂的天然产物和良好控制的聚合物结构的应用中形成这些键。高活性、高效、稳定和选择性的耐用催化剂的可用性是这些广泛应用的进一步发展的关键。在最后一个授权期内，制备了促进复分解的催化剂（a）在水溶液中，（B）与空间位阻底物，（c）在较低催化剂负载下，和（d）具有较高水平的对映选择性。发展了一种简单有效的N-杂环卡宾配体的合成方法。该方法将在下一个授权期内用于开发立体选择性复分解催化剂（控制碳-碳双键的反式：顺式比率）和改进催化剂稳定性（以降低催化剂负载量）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得能够快速和选择性地形成生物相关的化合物。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此类分子的构造。该反应催化剂的开发是这种强大的碳-碳键形成技术进步的关键。

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.