Department of Chemistry, Roger Adams Laboratory, University of Illinois, Urbana, IL 61801, USA.
Science. 2010 Jan 29;327(5965):566-71. doi: 10.1126/science.1183602.
Methylene C-H bonds are among the most difficult chemical bonds to selectively functionalize because of their abundance in organic structures and inertness to most chemical reagents. Their selective oxidations in biosynthetic pathways underscore the power of such reactions for streamlining the synthesis of molecules with complex oxygenation patterns. We report that an iron catalyst can achieve methylene C-H bond oxidations in diverse natural-product settings with predictable and high chemo-, site-, and even diastereoselectivities. Electronic, steric, and stereoelectronic factors, which individually promote selectivity with this catalyst, are demonstrated to be powerful control elements when operating in combination in complex molecules. This small-molecule catalyst displays site selectivities complementary to those attained through enzymatic catalysis.
亚甲基 C-H 键是最难选择性官能化的化学键之一，因为它们在有机结构中大量存在，并且对大多数化学试剂不活泼。它们在生物合成途径中的选择性氧化突出了这些反应对于简化具有复杂氧化模式的分子合成的威力。我们报告说，铁催化剂可以在各种天然产物环境中实现亚甲基 C-H 键氧化，具有可预测的、高的化学选择性、位置选择性，甚至是非对映选择性。电子、空间和立体电子因素，这些因素单独作用时可以提高催化剂的选择性，当在复杂分子中组合使用时，它们是强大的控制元件。这种小分子催化剂显示出与酶催化获得的位点选择性互补的位点选择性。
