Ni-catalyzed Iterative Alkyl Transfer from Nitrogen Enabled by the In Situ Methylation of Tertiary Amines.

Current methods to achieve transition-metal-catalyzed alkyl 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 C-C 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 Csp3-Csp3 bonds. We demonstrate PO(OMe)3 (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)3, Ni-catalyzed C-N bond cleavage and concurrent Csp3-Csp3 bond formation.