Moon Nicholas G, Harned Andrew M
Department of Chemistry, University of Minnesota-Twin Cities, 207 Pleasant St SE, Minneapolis, Minnesota 55455, USA.
Department of Chemistry, University of Minnesota-Twin Cities, 207 Pleasant St SE, Minneapolis, Minnesota 55455, USA and Department of Chemistry & Biochemistry, Texas Tech University, MS 41061, Lubbock, Texas 79409-1061, USA.
Org Biomol Chem. 2017 Feb 22;15(8):1876-1888. doi: 10.1039/c7ob00124j.
Two synthetic routes to the briarane stereotetrad have been investigated. The first route employed a boron aldol reaction to establish the stereogenic all-carbon quaternary carbon (C1). In this case, it was found that torsional steering in the transition state led to the formation of the undesired configuration at this position. The second route makes use of a highly diastereoselective acetylide conjugate addition/β-ketoester alkylation sequence to construct the vicinal C1 and C10 stereocenters with the correct relative configuration. Originally, it was proposed that torsional steering in the transition state for the ketoester alkylation step was the primary factor responsible for generating the major product. DFT calculations reveal that while torsional steering does play a role, larger conformational factors must also be considered. These calculations also reveal that an unusual C-Hπ(alkyne) interaction may contribute to lowering the energy of one transition state that leads to the observed stereoisomer. Ultimately, this strategy leads to a concise synthesis (under 10 steps) of the stereotetrad core common to the briarane diterpenoids.
已对两种合成蔷薇烷立体四元体的路线进行了研究。第一条路线采用硼醛醇反应来构建手性全碳季碳（C1）。在这种情况下，发现过渡态中的扭转导向导致该位置形成不需要的构型。第二条路线利用高度非对映选择性的乙炔共轭加成/β-酮酯烷基化序列来构建具有正确相对构型的邻位C1和C10立体中心。最初，有人提出酮酯烷基化步骤过渡态中的扭转导向是生成主要产物的主要因素。密度泛函理论计算表明，虽然扭转导向确实起作用，但也必须考虑更大的构象因素。这些计算还表明，一种不寻常的C-Hπ（炔烃）相互作用可能有助于降低导致观察到的立体异构体的一个过渡态的能量。最终，该策略实现了蔷薇烷二萜类化合物共有的立体四元体核心的简洁合成（少于10步）。
