Developing the Synthetic Utility of the Copper-Catalyzed Diboration of Aldehydes

描述（由申请方提供）：拟定研究涉及开发利用醛、酮和亚胺的铜催化二硼化的合成方法。结果呢？杂原子取代的硼酸酯具有已知的药物性质和在靶向合成中的潜在应用。所提出的方法的一个优点是提供了获得新的氨基硼酸酯和酸、已知的丝氨酸蛋白酶抑制剂和Bortezaline（Velcade）（FDA批准的多发性骨髓瘤治疗）的基本组分的途径。拟议的综合方法将简化获得额外的？杂原子取代的硼酸酯，其可用于追求具有增加的效力和未实现的医药应用的新的药物靶标。 概述的研究计划的目标是开发羰基化合物和亚胺的二硼化反应，并利用所得产物的合成效用进行靶向合成。为了实现这一目标，研究计划的具体目标包括：1）建立介导醛，酮和亚胺的二硼化的一般反应条件。2)开发使用手性二硼试剂或手性配体的不对称二硼化反应条件。3)开发涉及二硼化产物的合成应用，包括Matteson型同系反应和支化乙烯基硼酸酯的形成。 公共卫生相关性：C-B键的合成多功能性导致其在无数天然产物和药物靶标的合成中的使用。将硼取代基结合到有机基质中的新方法将增加可以通过这些转化获得的分子类型。拟议的研究计划涉及铜催化的羰基化合物和亚胺的二硼化反应，以及将所得产物开发成有机合成中合成可行的中间体。

DESCRIPTION (provided by applicant): The proposed research involves the development of synthetic methods that utilizes the copper-catalyzed diboration of aldehydes, ketones, and imines. The resulting ?-heteroatom- substituted boronate esters have known pharmaceutical properties and potential applications in target-directed synthesis. One advantage of the proposed methodology is to provide access to new -aminoboronate esters and acids, known serine protease inhibitors and an essential component of Bortezomib (Velcade), an FDA-approved treatment of multiple myeloma. The proposed synthetic methodology would simplify access to additional ?-heteroatom-substituted boronate esters that could be used in the pursuit of new pharmaceutical targets with increased potency and unrealized medicinal applications. The objective of the outlined research plan is to develop the diboration of carbonyl compounds and imines and to exploit the synthetic utility of the resulting products for target- directed synthesis. To achieve this goal, the specific aims of the research plan include: 1) Establish general reaction conditions that mediate the diboration of aldehydes, ketones, and imines. 2) Develop asymmetric diboration reaction conditions using chiral diboron reagents or chiral ligands. 3) Develop synthetic applications involving the diboration products including Matteson-type homologation reactions and formation of branched vinyl boronate esters. PUBLIC HEALTH RELEVANCE: The synthetic versatility of the C-B bond has led to its use in the synthesis of countless natural products and pharmaceutical targets. New methods to incorporate boron substituents into organic substrates would increase the types of molecules that could be accessed through these transformations. The proposed research plan involves the copper-catalyzed diboration of carbonyl compounds and imines, and the development of the resulting products into synthetically viable intermediates in organic synthesis.