Rhodium-Catalyzed 1,2-Addition of Pinacolboronic Esters into Ketones

描述(申请人提供)：碳-碳键的结构在有机合成中至关重要。因此，开发能够温和和选择性地形成C-C键的新方法是非常可取的，特别是在天然产物和药物合成的背景下。1，2-碳亲核加成反应是构筑碳-碳键的重要方法。在这些转化中常用的试剂有格氏试剂、有机锂试剂或有机锌试剂。这些试剂的缺点是官能团耐受性低，对空气和湿气敏感，碱度高，工作台稳定性有限。另一种方法是金属催化的有机硼化合物与羰基的1，2-加成反应。有机硼试剂在许多方面都有优势，包括它们的易得性、低碱度、对空气、水分和层析的稳定性。到目前为止，只有高活性的羰基与有机硼化合物在铑催化下发生了1，2-加成反应。我们希望扩大这个反应的范围，以包括在Rh(I)催化下向未活化酮中加成频碳硼酸酯。最初的目标将包括为这种类型的加成建立概念证明和反应条件的优化，以及调查这种转化的分子内和分子间变体的范围。在这项研究成功完成后，将开发一种不对称变体，使其能够获得富含对映体的叔醇。初步结果表明，芳香族和杂芳族频碳硼酸酯与酮发生了1，2-加成反应，从而顺利地合成了所需的叔醇。 与公众健康相关：碳-碳键的构建在有机合成中至关重要。因此，开发能够温和和选择性地形成C-C键的新方法是非常可取的，特别是在天然产物和药物合成的背景下。在这里，我们提出了一种新的Rh(I)催化的芳基频碳硼酸酯与未活化酮的1，2-加成反应。初步目标的成功将为合成催化的、对映体选择性的1，2-品那多硼酸酯提供一条途径。

DESCRIPTION (provided by applicant): The construction of carbon-carbon bonds is of paramount importance in organic synthesis. As such, the development of new methods which allow for mild and selective C-C bond formation are highly desirable, especially in the context of the syntheses of natural products and pharmaceuticals. 1,2-additions of carbon nucleophiles into carbonyl compounds is a premier method for constructing carbon-carbon bonds. Common reagents employed in these transformations are Grignards, organolithium or organozinc reagents. Drawbacks of these reagents include low functional group tolerance, air and moisture sensitivity, high basicity and limited bench stability. An alternative approach is the metal catalyzed 1,2-addition of organoboron compounds into carbonyls. Organoboron reagents are advantageous in many ways including their ready availability, low basicity, stability to air, moisture and chromatography. To date, only highly activated carbonyls have been shown to undergo 1,2- additions with organoboron compounds under rhodium-catalysis. We wish to extend the scope of this reaction to include additions of pinacolboronic esters into unactivated ketones using Rh(I) catalysis. Initial goals will include establishing proof of concept for this type of addition and optimization of the reaction conditions as well as investigating the scope of both intra- and intermolecular variants of this transformation. Upon the successful completion of this investigation, an asymmetric variant will be developed allowing access to enantio-enriched tertiary alcohols. Preliminary results have shown aromatic and heteroaromatic pinacolboronic esters have undergo 1,2-addition into ketones, to smoothly afford the desired tertiary alcohols. PUBLIC HEALTH RELEVANCE: The construction of carbon-carbon bonds is of paramount importance in organic synthesis. As such, the development of new methods which allow for mild and selective C-C bond formation are highly desirable, especially in the context of the syntheses of natural products and pharmaceuticals. Herein, we propose a novel Rh(I)-catalyzed 1,2-addition of arylpinacolboronic esters into unactivated ketones. The success of the initial goals will provide a pathway for the development of catalytic, enantioselective 1,2-additions of pinacolboronic esters.