Ruthenium(ii)-catalyzed selective C–H difluoroalkylation of aniline derivatives with pyrimidyl auxiliaries

Abstract

A ruthenium-catalyzed alternative para- and meta-difluoroalkylation of anilines is herein reported. The reaction tolerates a broad range of aniline derivatives and provides a convenient approach for accessing the corresponding para/meta-selective difluoroalkylated products. Mechanism studies demonstrated that the initial CAr-H and N-H cycloruthenation is the pivotal step in achieving remote C-H difluoroacetylation.

A Ligand‐Enabled Palladium‐Catalyzed Highly para‐Selective Difluoromethylation of Aromatic Ketones

“…Although heteroaromatic compounds are capable of achieving site‐selective fluorinated products because of their intrinsic electronic effects,, general aromatic compounds usually suffer from poor site selectivity,, (Figure a). Until recently, research into site‐selective C−H difluoromethylation of arenes has been of a preliminary nature . For example, the Ackermann group developed a ruthenium‐catalyzed meta ‐selective C−H difluoromethylation of 2‐arylpyridine derivatives .…”

“…Until recently,r esearch into site-selective C À Hd ifluoromethylation of arenes has been of ap reliminary nature. [8][9][10] Fore xample,t he Ackermann group developed ar uthenium-catalyzed meta-selective CÀH difluoromethylation of 2-arylpyridine derivatives. [8] A paraselective difluoromethylation of acetanilides and ketoximes by modulating the coordination ability of the directing group was developed by our group.…”

Remote Fluorination and Fluoroalkyl(thiol)ation Reactions

“…A series of mechanistic studies and DFT calculations suggested that the chelation‐assisted cycloruthenation is the key factor in achieving the para ‐selectivity. Subsequently, Liang and co‐workers reported a similar Ru‐catalyzed para C−H difluoromethylation of pyrimidyl‐protected aniline derivatives [38c] …”

para‐Selective Palladium‐Catalyzed C−H Difluoroalkylation by Weak Oxazolidinone Assistance

“…Subsequently, the same group expanded the substrate scope to anilide, indoline and tetrahydroquinoline derivatives under similar conditions [14] . Besides, Liang reported a ruthenium‐catalyzed para‐selective C−H difluoromethylation using pyrimidyl and quinazoline auxiliaries [15] . Moreover, Zhao and Lou further achieved para ‐selective C−H difluoromethylation of electron‐deficient aromatic carbonyls in the presence of palladium catalysts [16] .…”