Department of Chemistry, University of Utah, 315 South 1400 East, Salt Lake City, Utah 84112, United States.
J Org Chem. 2020 Aug 7;85(15):9979-9992. doi: 10.1021/acs.joc.0c01274. Epub 2020 Jul 30.
Current methods to achieve transition-metal-catalyzed alkyl carbon-nitrogen (C-N) bond cleavage require the preformation of ammonium, pyridinium, or sulfonamide derivatives from the corresponding alkyl amines. These activated substrates permit C-N bond cleavage, and their resultant intermediates can be intercepted to affect carbon-carbon bond-forming transforms. Here, we report the combination of in situ amine methylation and Ni-catalyzed benzalkyl C-N bond cleavage under reductive conditions. This method permits iterative alkyl group transfer from tertiary amines and demonstrates a deaminative strategy for the construction of Csp-Csp bonds. We demonstrate PO(OMe) (trimethylphosphate) to be a Ni-compatible methylation reagent for the in situ conversion of trialkyl amines into tetraalkylammonium salts. Single, double, and triple benzalkyl group transfers can all be achieved from the appropriately substituted tertiary amines. Transformations developed herein proceed via recurring events: the in situ methylation of tertiary amines by PO(OMe), Ni-catalyzed C-N bond cleavage, and concurrent Csp-Csp bond formation.
目前实现过渡金属催化的烷基碳-氮（C-N）键断裂的方法需要从相应的烷基胺预先形成铵、吡啶鎓或磺酰胺衍生物。这些活化的底物允许 C-N 键断裂，并且它们的中间体可以被拦截以影响碳-碳键形成转化。在这里，我们报告了原位胺甲基化和 Ni 催化的还原条件下苄基 C-N 键断裂的组合。该方法允许叔胺的迭代烷基转移，并证明了用于构建 Csp-Csp 键的脱氨策略。我们证明 PO(OMe)（三甲磷酸酯）是 Ni 相容的甲基化试剂，可将三烷基胺原位转化为四烷基铵盐。单、双和三苄基转移都可以从适当取代的叔胺中实现。本文所开发的转化通过反复发生的事件进行：PO(OMe)的原位叔胺甲基化、Ni 催化的 C-N 键断裂以及同时的 Csp-Csp 键形成。
