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

描述（由申请人提供）：拟议的研究涉及利用铜催化醛、酮和亚胺的二硼化反应的合成方法的发展。结果呢？-杂原子取代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新的-氨基硼酸酯和酸，已知的丝氨酸蛋白酶抑制剂和硼替佐米（Velcade）的基本成分，fda批准的多发性骨髓瘤治疗药物。拟议的综合方法将简化获得额外？-杂原子取代硼酸酯，可用于追求新的药物靶点，具有更高的效力和未实现的医学应用。概述的研究计划的目的是发展羰基化合物和亚胺的衍生物，并开发合成产物的合成用途，用于靶向合成。为实现这一目标，本研究计划的具体目标包括：1)建立介导醛类、酮类和亚胺类化合物合成的一般反应条件。2)利用手性二硼试剂或手性配体建立不对称二硼化反应条件。3)开发涉及硼化产物的合成应用，包括mattson型同源反应和支化硼酸乙烯酯的生成。

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.