Skeletal diversity in small-molecule synthesis using ligand-controlled catalysis
Skeletal diversity in small-molecule synthesis using ligand-controlled catalysis
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DOI：
10.1021/cc7001028
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发表时间：
2007-11-01
影响因子：
--
通讯作者：
Schreiber, Stuart L.
中科院分区：
文献类型：
--
作者：
Gray, B. Lawrence;Schreiber, Stuart L.
通过硅醚连接的双炔进行了两个pd催化的还原转化，其中反应结果仅由膦配体的选择控制。我们筛选了钯预催化剂、配体和添加剂，以优化这类底物的还原环化或氢化的选择性条件。制备了16种硅醚系链双炔，并对每种途径进行了最佳的催化剂/配体组合。这些反应的硅环二烯和硅基系链烯产物在1-3个合成步骤中被加工成密集取代的、立体化学和附体丰富的双环和三环小分子。这些研究说明了如何对过渡金属催化剂进行微小的修饰，以类似于萜烯生物合成等生物合成途径的方式，获得各种小分子，其中酶结构的微小变化直接导致骨骼分化。
Two Pd-catalyzed reductive transformations of diynes tethered through a silyl ether linkage were developed, where the reaction outcomes were controlled solely by selection of phosphine ligand. We screened Pd precatalysts, ligands, and additives to optimize conditions selective either for reductive cyclization or hydrogenation of this substrate class. Sixteen silyl ether-tethered diynes were prepared and subjected to the best catalyst/ligand combinations for each pathway. Silacyclic dienes and silyl-tethered enyne products of these reactions were elaborated to densely substituted, stereochemically- and appendage-rich, bicyclic and tricyclic small molecules in 1-3 synthetic steps. These studies illustrate how small modifications to a transition-metal catalyst can be used to access a diverse set of small molecules, in a fashion analogous to biosynthetic pathways such as terpene biosynthesis, where minor changes to enzyme structure direct skeletal differentiation.