Nickel-Catalysed Sequential Hydrodefluorination of Pyridines: Mechanistic Insights Led to the Discovery of Bench-Stable Precatalysts

The nickel(0) complex [Ni(iPrPN)(COD)] (iPrPN = 2-[(N-diisopropylphosphino)methylamino]pyridine, COD = 1,5-cyclooctadiene) was an efficient precatalyst for the hydrodefluorination of pyridines employing pinacolborane (HBPin). 2-fluoro and 2,6-difluoropyridines were hydrodefluorinated at the 2- and 6-positions at room temperature in 3 h 30 min. The impact of the number of fluorine atoms and their position at the pyridyl ring in the efficiency of the catalyst was explored. Mechanistic experiments for the hydrodefluorination of 2,6-difluoropyridine allowed to identify COD decoordination followed by C-F oxidative addition as the catalyst entry pathway to the cycle and the [Ni(iPrPN)(COD)] complex as the catalyst resting-state. The Ni(II) fluoride complexes, [NiF(iPrPN)(6-Fpy)] (6-Fpy = 6-fluoropyrid-2-yl) and [NiF(iPrPN)(py)] (py = 2-pyridyl) were independently synthesized and identified as intermediates in the two subsequent hydrodefluorination cycles operative through single-turnover experiments. Both Ni(II) fluoride complexes were found to be bench-stable precatalysts for the process with a comparable efficiency to [Ni(iPrPN)(COD)] in the presence of a substoichiometric amount of COD to prevent catalyst deactivation.