Levin Mark D, Chen Tiffany Q, Neubig Megan E, Hong Cynthia M, Theulier Cyril A, Kobylianskii Ilia J, Janabi Mustafa, O'Neil James P, Toste F Dean
Department of Chemistry, University of California, Berkeley, CA 94720, USA.
Chemical Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
Science. 2017 Jun 23;356(6344):1272-1276. doi: 10.1126/science.aan1411.
The biological properties of trifluoromethyl compounds have led to their ubiquity in pharmaceuticals, yet their chemical properties have made their preparation a substantial challenge, necessitating innovative chemical solutions. We report the serendipitous discovery of a borane-catalyzed formal C(sp)-CF reductive elimination from Au(III) that accesses these compounds by a distinct mechanism proceeding via fluoride abstraction, migratory insertion, and C-F reductive elimination to achieve a net C-C bond construction. The parent bis(trifluoromethyl)Au(III) complexes tolerate a surprising breadth of synthetic protocols, enabling the synthesis of complex organic derivatives without cleavage of the Au-C bond. This feature, combined with the "fluoride-rebound" mechanism, was translated into a protocol for the synthesis of F-radiolabeled aliphatic CF-containing compounds, enabling the preparation of potential tracers for use in positron emission tomography.
三氟甲基化合物的生物学特性使其在药物中广泛存在，然而其化学性质使其制备成为一项重大挑战，需要创新的化学解决方案。我们报告了一个意外发现，即硼烷催化从金（III）进行形式上的C（sp）-CF还原消除反应，该反应通过一种独特的机制生成这些化合物，该机制包括氟化物提取、迁移插入和C-F还原消除，以实现净C-C键构建。母体双（三氟甲基）金（III）配合物能耐受令人惊讶的多种合成方案，能够在不切断Au-C键的情况下合成复杂的有机衍生物。这一特性与“氟化物回弹”机制相结合，转化为一种合成含氟脂肪族CF化合物的F放射性标记方案，能够制备用于正电子发射断层扫描的潜在示踪剂。
