Catalytic Methyl Transfer from Dimethylcarbonate to Carboxylic Acids

Abstract

Although methylation reactions are commonplace, currently used reagents are hazardous, toxic, and/or unstable. Dimethylcarbonate has been put forth as an inexpensive, nontoxic, and "green" potential methylating reagent. Herein we report a general, base-catalyzed methyl transfer from dimethylcarbonate to carboxylic acids. High selectivity for esterification is observed even in the presence of unprotected phenols, and the mild reaction conditions enable conservation of stereochemistry at epimerizable stereocenters. Isotope-labeling studies suggest a mechanism proceeding by direct methyl transfer from dimethylcarbonate to the substrate.

Aerobic Copper-Catalyzed O-Methylation with Methylboronic Acid

“…6 The use of a nucleophilic methyl source to replace typical reagents would avoid the intrinsic toxicity associated with electrophiles, offering a practical advantage. 7 Additionally, the selective oxidative cross-coupling of an alkylmetal(loid) reagent and an oxygen nucleophile might enable reaction selectivity and functional group compatibility that complement traditional methods.…”

Dimethyl sulfite a potential agent for methylation

“…Indeed, the general basecatalysed methylation of phenol performed at 90 °C did not proceed in liquid phase. 30 Octanoic acid reacts with 93% conversion to form the corresponding ester in a very high selectivity reaching 100% under our optimal conditions. Contrary to a base-catalyzed methylation of carboxylic acids at 90 °C in liquid phase 31 , octanoic acid can also play the role of acidic catalyst Indeed, the reaction was performed in the absence of catalyst showing 41% conversion after 22 hours giving the methyloctanoate in 76%.…”

Microwave-assisted methylation of dihydroxybenzene derivatives with dimethyl carbonate

“…Recognising that an equilibrium between DBU, DMC and the methoxide ion is established (Fig. 3, frame window, top), 38,39 a plausible mechanism for the formation of veratrole is illustrated at the bottom of Fig. 3: an initial transesterication promoted by CH 3 O À is followed by intramolecular decarboxylation producing the anion (ii); this is then methylated either by DMC or the Nmethoxycarbonylated salt of DBU (i) (paths a and b, respectively).…”