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 ortho-substituted iodoarenes using dimethyl carbonate as a methyl source.
In the presence of K2CO3 as a base, iodoarenes
are dimethylated at the ipso- and meta-positions of the iodo group, which represents a novel strategy for meta-C–H methylation. With KOAc as the base, subsequent
oxidative C(sp3)–H/C(sp3)–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.
3,4-Fused
tricyclic indole scaffolds are ubiquitous in bioactive
natural products and pharmaceuticals. A new protocol for the synthesis
of 3,4-fused tricyclic indoles has been developed through cascade
carbopalladation and C–H amination with N,N-di-tert-butyldiaziridinone. The protocol
allows access to a range of 3,4-fused tricyclic indoles, including
those containing various linkers and fused with medium-sized rings.
Rucaparib can be synthesized via this reaction, providing an advantageous
synthetic method for the FDA-approved cancer medicine.
A palladium-catalyzed cross-coupling reaction of aryl halides with 2-chlorobenzoic acids has been developed. The reaction forms C(sp3),C(sp2)-palladacycles through C(sp3)−H activation. The palladacycles react with 2-chlorobenzoic acids through two successive C−C...
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