Nickel-Catalyzed Reductive Methylation of Alkyl Acid with Methyl p-Tosylate

Abstract

Methyl group is the smallest carbon substituent that plays important roles in many compounds. Conversion of a carboxylic acid into a ketone is a fundamental transformation in organic chemistry. This functional group change is usually performed indirectly by activating the carboxylic acid into an acyl chloride or into a Weinreb amide, and then by nucleophilic attack with an organometallic reagent. However, direct conversion of a carboxylic acid into a ketone can be achieved in one-step reaction using at least 2 equiv. of an organolithium reagent at low temperature and producing much tertiary alcohol. Herein, methylation of alkyl acid under Ni-catalyzed reductive coupling conditions using methyl p-methyl tosylate as the methylation reagent was reported to yield methylated ketones. Moderate yields as well as good functional group tolerance were observed under the present mild and easy-to-operate reaction conditions.