Pd-Catalyzed ,-Dimethylation of -Substituted Iodoarenes via a Base-Controlled C-H Activation Cascade with Dimethyl Carbonate as the Methyl Source.

A methyl group can have a profound impact on the pharmacological properties of organic molecules. Hence, developing methylation methods and methylating reagents is essential in medicinal chemistry. We report a palladium-catalyzed dimethylation reaction of -substituted iodoarenes using dimethyl carbonate as a methyl source. In the presence of KCO as a base, iodoarenes are dimethylated at the - and -positions of the iodo group, which represents a novel strategy for -C-H methylation. With KOAc as the base, subsequent oxidative C(sp)-H/C(sp)-H coupling occurs; in this case, the overall transformation achieves triple C-H activation to form three new C-C bonds. These reactions allow expedient access to 2,6-dimethylated phenols, 2,3-dihydrobenzofurans, and indanes, which are ubiquitous structural motifs and essential synthetic intermediates of biologically and pharmacologically active compounds.