Content area
Abstract
This dissertation describes the fundamental study of Ni-catalyzed cross-coupling reactions. Ni-catalyzed cross-coupling has emerged as a versatile platform to construct C-C bonds, which transforms simple chemical feedstocks into complex functional molecules. The ability of nickel stabilizing radical intermediates opens new pathways in catalysis, while understanding and characterization of the unique reactivity of nickel catalysis is nascent, which has restricted rational catalyst design. A better mechanistic study would build insight into how reactions take place and inform the design of more sustainable catalysts to address synthetic limitations.
A comprehensive mechanistic study was conducted on Ni-catalyzed cross-electrophile couplings, where the rate-limiting factors were elucidated as the heterogenous re-duction of Ni(II) and proposed Ni(I)/Ni(II) intermediates were either isolated or character-ized via various spectroscopic techniques. The origin of chemoselectivity toward cross-coupling lies in the sequential activation of electrophiles via different Ni(I) intermediates where Ni(I)-halide preferentially reacts with aryl halides, and Ni(I)-aryl reacts with alkyl halides faster to form radicals.
Radical formation from carbon halides at Ni(I) center is a key step in cross-electrophile and stereoconverging couplings, while the detailed mechanism is unknown on a catalytic relevant system due to the unstability of Ni(I) intermediate. Electroanalytic methods were applied to generate active Ni(I) in situ and determine kinetics on transient unstable Ni intermediates. The kinetic results suggest a concerted halogen atom abstraction to afford carbon radical where the rate is directly correlated to the bond dissociation energy of carbon halide bonds.
Following the radical formation step, radical capture on Ni(II) center is the final key step in C–C bond formation, for which a highly reactive Ni(III) intermediate is commonly proposed to facilitate the reductive elimination. Despite a handful DFT studies having been conducted on this elemental step, there is generally a lack of experimental characterization of radical capture at catalytically competent nickel(II) complexes to benchmark those computational results. A comprehensive mechanistic study was performed on catalytically relevant Ni(II) complexes. The study demonstrated the rate of radical capture, the direct observation of a Ni(III) intermediate and revealed the stereoselectivity of this fundamental transformation step.
