Exhaustive Reduction of Esters Enabled by Nickel Catalysis

Abstract

We report a one-step procedure to directly reduce unactivated aryl esters into their corresponding tolyl-derivatives. This is achieved by the action of a Ni/NHC catalyst and an organosilane reducing agent that is activated in situ by stoichiometric KOtBu. The resulting conditions provide a direct and efficient alternative to multi-step procedures for this transformation that often require use of hazardous metal hydrides. Applications in the synthesis of-CD3 containing products, derivatization of bioactive molecules, and chemoselective reduction in the presence of other CO bonds is demonstrated. File list (2) download file view on ChemRxiv Manuscript.pdf (1.92 MiB) download file view on ChemRxiv Supporting information.pdf (4.97 MiB)

Standardized Stirring for Small Scale Surveys

“…Catalytic reactions are sensitive to a wide range of experimental conditions, even in homogeneous systems. [1][2][3][4][5][6][7][8][9] These conditions include variables, such as concentration of reactants and catalyst, [10] stirring rate, [11] reaction time and temperature, [12] which contribute to the outcome of a catalytic system after optimization. This study focuses on the influence of stirring in a small-scale crosscoupling reaction.…”

Standardized Stirring for Small Scale Surveys**

“…Catalytic reactions are sensitive to a wide range of experimental conditions, even in homogeneous systems. [1][2][3][4][5][6][7][8][9] These conditions include variables, such as concentration of reactants and catalyst, [10] stirring rate, [11] reaction time and temperature, [12] which contribute to the outcome of a catalytic system after optimization. This study focuses on the influence of stirring in a small-scale cross-coupling reaction.…”

Nickel-Catalyzed Reductive Deoxygenation of Diverse CO Bond-Bearing Functional Groups

“…While aryl esters (S11) could be deoxygenated effectively to form tolyl derivatives (S12), 33 we found that esters present on carbons beyond the aryl position (S13) were only reduced to the alcohol oxidation state.…”

“…Extending previous research that employs d2-TMDSO to install trideuteromethyl (-CD3) groups in the place of esters, 33 we were able to install deuterium atoms in positions previously held by C-O bonds in alcohols, ketones and ethers.…”

“…Column chromatography was performed using a gradient of 1→20% ethyl acetate in hexanes to afford product as a pale-yellow oil (23 mg, 78% yield). The procedure was repeated on 4-methoxycinnamaldehyde (33), the corresponding aldehyde, to reveal the same product (21 mg, 79% yield). Characterization data matched those previously reported.…”