The Mallat Family Laboratory of Organic Chemistry, Schulich Faculty of Chemistry and the Lise Meitner-Minerva Center for Computational Quantum Chemistry, Technion-Israel Institute of Technology, Haifa 32000, Israel.
Institut Für Organische und Biomolekulare Chemie, Georg-August-Universität, Göttingen, Tammannstrasse 2, 37077 Göttingen, Germany.
Nature. 2014 Jan 9;505(7482):199-203. doi: 10.1038/nature12761. Epub 2013 Dec 8.
Since the nineteenth century, many synthetic organic chemists have focused on developing new strategies to regio-, diastereo- and enantioselectively build carbon-carbon and carbon-heteroatom bonds in a predictable and efficient manner. Ideal syntheses should use the least number of synthetic steps, with few or no functional group transformations and by-products, and maximum atom efficiency. One potentially attractive method for the synthesis of molecular skeletons that are difficult to prepare would be through the selective activation of C-H and C-C bonds, instead of the conventional construction of new C-C bonds. Here we present an approach that exploits the multifold reactivity of easily accessible substrates with a single organometallic species to furnish complex molecular scaffolds through the merging of otherwise difficult transformations: allylic C-H and selective C-C bond activations. The resulting bifunctional nucleophilic species, all of which have an all-carbon quaternary stereogenic centre, can then be selectively derivatized by the addition of two different electrophiles to obtain more complex molecular architecture from these easily available starting materials.
自 19 世纪以来，许多合成有机化学家一直致力于开发新策略，以可预测且高效的方式对碳-碳和碳-杂原子键进行区域、立体和对映选择性构建。理想的合成应使用最少数量的合成步骤，且官能团转化和副产物少或没有，原子利用率最高。对于合成难以制备的分子骨架，一种潜在的有吸引力的方法可能是通过选择性激活 C-H 和 C-C 键，而不是通过传统方法构建新的 C-C 键。在这里，我们提出了一种利用容易获得的底物的多重反应性与单一有机金属物种相结合的方法，通过合并原本难以进行的转化来提供复杂的分子支架：烯丙基 C-H 和选择性 C-C 键活化。然后，所得的双功能亲核物种，所有这些都具有全碳季碳立体中心，可通过添加两个不同的亲电试剂进行选择性衍生化，从而从这些易得的起始原料获得更复杂的分子结构。
