Ni-Catalyzed Reduction of Inert C-O Bonds: A New Strategy for Using Aryl Ethers as Easily Removable Directing Groups

Ni-Catalyzed Reduction of Inert C-O Bonds: A New Strategy for Using Aryl Ethers as Easily Removable Directing Groups

Most synthetic chemists are used to employ aryl methyl ethers as directing groups. They are powerful directors in substitution reactions, metallations and others. But once you are done, you are stick with them. They are not easy to remove, though some methods existed. Now, Martin et al. (ICIQ, Spain) have developed a catalytic method for the reduction of those ‘inert’ C-O bonds.
The method relies in the use of Ni(COD)2 (5-10 mol%), PCy3 (10-20 mol%), TMDSO as reducing agent (1 equiv) in toluene at 110 °C for 8-14 h. The results are quite good and a number of substrates are demethoxylated. The protocol leaves benzylic methyl ethers, methyl esters and others untouched. As demonstration of its applicability, the authors have prepared some substrates by ortho-metallation, removing then the OMe group to reach ‘magically’ prepared substrates, even with the troublesome 1,3-substitution pattern. I have already in mind a couple of substrates which we would like to test…
J. Am. Chem. Soc., 2010, 132 (49), pp 17352–17353. See: 10.1021/ja106943q


Combined experimental and theoretical study on the reductive cleavage of inert C?O bonds with silanes: Ruling out a classical Ni(0)/Ni(II) catalytic couple and evidence for Ni(I) intermediates

J. Cornella, E. Gómez-Bengoa, R. Martin
J. Am. Chem. Soc. 2013, 135, 1997-2009

A mechanistic and computational study on the reductive cleavage of C-OMe bonds catalyzed by Ni(COD)2/PCy3 with silanes as reducing agents is reported herein. Specifically, we demonstrate that the mechanism for this transformation does not proceed via oxidative addition of the Ni(0) precatalyst into the C-OMe bond. In the absence of an external reducing agent, the in-situ-generated oxidative addition complexes rapidly undergo β-hydride elimination at room temperature, ultimately leading to either Ni(0)-carbonyl- or Ni(0)-aldehyde-bound complexes. Characterization of these complexes by X-ray crystallography unambiguously suggested a different mechanistic scenario when silanes are present in the reaction media. Isotopic-labeling experiments, kinetic isotope effects, and computational studies clearly reinforced this perception. Additionally, we also found that water has a deleterious effect by deactivating the Ni catalyst via formation of a new Ni-bridged hydroxo species that was characterized by X-ray crystallography. The order in each component was determined by plotting the initial rates of the C-OMe bond cleavage at varying concentrations. These data together with the in-situ-monitoring experiments by 1H NMR, EPR, IR spectroscopy, and theoretical calculations provided a mechanistic picture that involves Ni(I) as the key reaction intermediates, which are generated via comproportionation of initially formed Ni(II) species. This study strongly supports that a classical Ni(0)/Ni(II) for C-OMe bond cleavage is not operating, thus opening up new perspectives to be implemented in other related C-O bond-cleavage reactions.

Read all about Organic Spectroscopy on ORGANIC SPECTROSCOPY INTERNATIONAL 


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