Pd(II)-Catalyzed Ortho Trifluoromethylation of Arenes and Insights into the Coordination Mode of Acidic Amide Directing Groups

Abstract

A Pd(II)-catalyzed trifluoromethylation of ortho C-H bonds with an array of N-arylbenzamides derived from benzoic acids is reported. N-Methylformamide has been identified as a crucial promoter of C-CF(3) bond formation from the Pd center. X-ray characterization of the C-H insertion intermediate has revealed a rare coordination mode of acidic amides as directing groups and the origin of their capacity in directing C-H activation.

A combination of directing groups and chiral anion phase-transfer catalysis for enantioselective fluorination of alkenes

“…DGs have likewise been shown to play a central role in transition-metal catalysis, having recently been used for site-selective C-H activation (1)(2)(3)(4)(5)(6). The advantage of using a DG lies in the ability to functionalize nonpolar bonds (such as in alkenes) while maintaining beneficial polar interactions between the substrate and chiral source; however, DGs have rarely been used in organocatalysis.…”

First aromatic ring acetamidation by anodic oxidation

“…Conventional preparations of these acetamidated 1-(trifluoromethyl) benzenes have been recently described, as the Pd(II)-catalyzed trifluoromethylation of the aromatic C\H bond in acetanilides, which provides the highly biological potential key structure of ortho-CF 3 acetanilides [5] or the ortho-trifluoromethylation of N-aryl-benzamide catalyzed by Pd using the Umemoto reagent as the CF 3 source [6]. Direct Cu-catalyzed trifluoromethylation of pivalamido arenes with Togni reagent takes place with high selectivity at the ortho-position [7].…”

Regioselective trifluoromethylation of N-heteroaromatic compounds using trifluoromethyldifluoroborane activator

“…Although CF 3 groups can be regioselectively introduced to aromatic rings in cross-coupling reactions, requirement of multiple steps for the preparation of aryl halides and boronic acids/esters and generation of stoichiometric amounts of metal salts decrease synthetic efficiency. To overcome such drawbacks, direct C-H trifluoromethylation recently received much attention; however, examples of aromatic C-H trifluoromethylations are still limited [35][36][37][38][39][40][41][42][43][44][45][46] . These examples include the following: (1) directing groupassisted palladium 37,38 -or silver 39 -catalysed oxidative trifluoromethylation; (2) palladium 40 -or copper 41 -catalysed oxidative trifluoromethylation of heteroaromatic compounds; and (3) radical trifluoromethylation using NaSO 2 45,46 .…”

“…To overcome such drawbacks, direct C-H trifluoromethylation recently received much attention; however, examples of aromatic C-H trifluoromethylations are still limited [35][36][37][38][39][40][41][42][43][44][45][46] . These examples include the following: (1) directing groupassisted palladium 37,38 -or silver 39 -catalysed oxidative trifluoromethylation; (2) palladium 40 -or copper 41 -catalysed oxidative trifluoromethylation of heteroaromatic compounds; and (3) radical trifluoromethylation using NaSO 2 45,46 . The drawback to approach (1), however, is the requirement for directing groups that are not necessary in the target molecules 39 , and in approaches (2) and (3), regioselectivity is generally difficult to control, especially in the case of sixmembered heteroaromatic compounds except when using substrates with substituent(s) to block the possible reaction site(s) [40][41][42][43][44][45][46] .…”