Directed C-H Functionalization Reactions with a Picolinamide Directing Group: Ni-Catalyzed Cleavage and By-Product Recycling.

An efficient strategy for the cleavage of the picolinamide directing group (DG) and recycling of the byproduct generated has been developed. In this protocol, picolinamides were first Boc activated into tertiary N-Boc-N-substituted picolinamides. These were then cleaved via a Ni-catalyzed esterification reaction with EtOH to give valuable N-Boc protected amines. Ni(cod)(2) was used as a catalyst without any ligands or base additives. The byproduct, ethyl 2-picolinate can be used to install the picolinamide DG in a direct or indirect manner on amines. The protocol exhibits a broad functional group tolerance and high yields. To demonstrate the utility of this approach, it was applied on many selected examples from the recent C-H functionalization literature featuring 2-picolinamide as a DG.