Organic Synthesis Reagents on Transition Metals

描述(申请人提供)：药物和生物活性分子的构建依赖于碳-碳键的形成方法。在过去的十年中，烯烃化合作用已经成为形成这些键的一种强有力的手段，其应用范围包括但不限于有机小分子、复杂的天然产物和可控的聚合物结构。获得高活性、高效率、稳定和选择性强的催化剂是进一步发展这些广泛应用的关键。在最后的授权期内，制备的催化剂促进了(A)在水溶液中的歧化反应，(B)与空间受阻的底物，(C)在较低的催化剂负载量下，以及(D)具有较高的对映选择性水平。发展了一种非常简单的N-杂环卡宾配体的合成方法。这种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)，以及改善催化剂稳定性(以降低催化剂负载量)，以及其他拟议的改进措施。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。与公共健康的相关性：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。烯烃化合反应现在通常用于构建这种分子。开发用于该反应的催化剂是推进这一强大的碳-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.