Palladium-Catalyzed Selective β-Arylation of Aliphatic Amides Using a Removable N,O-Bidentate Auxiliary

Abstract

A new method for palladium-catalyzed β-arylation of aliphatic and cycloaliphatic amides without conventional silver salts utilizing 2-aminopyridine-1-oxide moiety (PyO) as an N,O-bidentate group has been developed. Reactions proceeded smoothly in DMSO solvent in the presence of K 2 HPO 4 ·3H 2 O, providing the β-arylated aliphatic amide products in a moderate-to-good yield. An important cyclopalladium intermediate, successfully obtained with a modest yield, could be converted to the monoarylation product and be used as catalyst in arylation reaction. Moreover, the PyO directing group was easily removed under base condition to generate aliphatic acids.

Transition-Metal-Catalyzed, Coordination-Assisted Functionalization of Nonactivated C(sp3)–H Bonds

“…In 2015, Song, Niu, and coworkers disclosed a palladium-catalyzed β-methyl C(sp 3 )−H arylation directed by a 2-aminopyridine-1-oxide moiety that proceeds without using silver salt additives as is required in comparable N,N-bidentate-directed reactions (Scheme 86a). 255 At nearly the same time, the Lu group reported a palladiumcatalyzed, pyridine-N-oxide-directed β-methylene C(sp 3 )−H arylation (Scheme 86b). 256 In this case, the addition of AgOAc significantly promoted this transformation and enabled the arylation of more challenging methylene C(sp 3 )−H bonds.…”

“…As a complement to the extensively studied N , N -bidentate DGs, N , O -bidentate DGs have also been explored as they likely facilitate the oxidation of Pd­(II) to Pd­(IV) because of increased electron density at the Pd­(II) center. In 2015, Song, Niu, and co-workers disclosed a palladium-catalyzed β-methyl C­(sp 3 )–H arylation directed by a 2-aminopyridine-1-oxide moiety that proceeds without using silver salt additives as is required in comparable N , N -bidentate-directed reactions (Scheme a) . At nearly the same time, the Lu group reported a palladium-catalyzed, pyridine- N -oxide-directed β-methylene C­(sp 3 )–H arylation (Scheme b) .…”

Decoding Directing Groups and Their Pivotal Role in C−H Activation

“…In these cases, the N-oxide-pyridyl amides can be easily obtained from a DMAP-catalyzed carboxylic substitution between benzoic acid and a 2-amine-(N-oxide)-pyridine. Another synthetic pathway was described in 2015 by Niu and Song, [242] this time starting from an acyl chloride. The obtained substrate was used for a successful palladium-catalyzed C(sp 3 )À H arylation in the presence of iodobenzene, from which the arylated product was obtained in 70 % yield (Scheme 46).…”

Palladium-Catalyzed, N-(2-Aminophenyl)acetamide-Assisted Ortho-Arylation of Substituted Benzamides: Application to the Synthesis of Urolithins B, M6, and M7

“…In 2005, the pioneering discovery of 8-aminoquinoline as a bidentate directing group by Daugulis paved the way for site-selective C–H functionalization reactions, particularly ortho -arylation of benzamide derivatives . Subsequently, various N , N -, N , S -, and N , O -bidentate directing groups such as 8-aminoquinoline, picolinamide, pyridin-2-ylmethanamine/(pyridine-2-yl)­isopropyl amine (PIP), triazole, 2-thiomethylaniline, peptide derivatives, 2-aminopyridine 1-oxide, and others were reported and utilized for C–H activation/C–C bond formation. In particular, Q, PA, and PIP were shown to be highly active bidentate directing groups with diverse substrates. − , More recently, tremendous progress has been made by Daugulis, Yu, Chatani, , Ackermann, Nakamura, Shi, and others ,, in bidentate directing-group-assisted C–H ortho -arylation reactions.…”