Bocknack Brian M, Wang Long-Cheng, Krische Michael J
Department of Chemistry and Biochemistry, University of Texas, Austin, TX 78712, USA.
Proc Natl Acad Sci U S A. 2004 Apr 13;101(15):5421-4. doi: 10.1073/pnas.0307120101. Epub 2004 Mar 15.
Catalytic tandem conjugate addition-enolate trapping represents an effective strategy for the design of catalytic transformations that enable formation of multiple C-C bonds. Recently, using enantioselective rhodium-catalyzed conjugate addition methodology, we developed a catalytic tandem conjugate addition-aldol cyclization of keto-enones. Here, we report related desymmetrizations and parallel kinetic resolutions involving the use of diones as terminal electrophiles. The Rh-enolate generated on enone carbometallation effectively discriminates among four diastereotopic pi-faces of the appendant dione, ultimately providing products that embody four contiguous stereocenters, including two adjacent quaternary centers, with quantitative diastereoselection and high levels of enantiomeric excess. This methodology allows concise entry to optically enriched seco-B ring steroids possessing a 14-hydroxy cis-fused C-D ring junction, as found in naturally occurring cardiotonic steroids derived from digitalis.
催化串联共轭加成-烯醇化物捕获是一种设计催化转化的有效策略，可实现多个碳-碳键的形成。最近，我们利用对映选择性铑催化的共轭加成方法，开发了一种酮烯酮的催化串联共轭加成-羟醛环化反应。在此，我们报道了相关的去对称化反应和平行动力学拆分反应，其中使用二酮作为末端亲电试剂。烯酮碳金属化生成的铑-烯醇化物能有效区分附属二酮的四个非对映异位π-面，最终提供包含四个相邻立体中心（包括两个相邻季碳中心）的产物，具有定量的非对映选择性和高水平的对映体过量。这种方法可以简洁地合成光学富集的具有14-羟基顺式稠合C-D环连接的开链B环甾体，就像在源自洋地黄的天然强心甾体中发现的那样。
