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

描述（由申请人提供）：碳-碳键的构造在有机合成中至关重要。因此，开发允许温和和选择性形成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。在羰基化合物中加入1,2-亲核试剂是构建碳-碳键的主要方法。在这些转化中常用的试剂是格氏试剂、有机锂或有机锌试剂。这些试剂的缺点包括低官能团耐受性，空气和水分敏感性，高碱度和有限的台架稳定性。另一种方法是用金属催化将有机硼化合物1,2加成羰基。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、水分和色谱的稳定性。迄今为止，只有高度活化的羰基被证明在铑催化下与有机硼化合物进行1,2-加成。我们希望扩展该反应的范围，包括使用Rh(I)催化将蒎烯硼酸酯添加到未活化的酮中。最初的目标将包括为这种类型的添加和反应条件的优化建立概念证明，以及调查这种转化的分子内和分子间变异的范围。在成功完成这项研究后，将开发一种不对称变体，允许获得对映体富集的叔醇。初步结果表明，芳香族和异芳香族双酚硼酸酯经过1,2加成成酮，可以顺利地得到所需的叔醇。

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.