Nickel‐Catalyzed Benzylation of C−H Bonds in Aromatic Amides with Benzyltrimethylammonium Halides

Abstract

Nickel‐catalyzed benzylation reactions of C−H bonds in aromatic amides with benzyltrimethylammonium halides are developed by using a 5‐chloro‐8‐aminoquinoline derivative as a bidentate directing group. Benzylation occurs selectively at the ortho‐C−H bonds in aromatic amides, and no methylation was detected. The presence of a 5‐chloro‐8‐aminoquinoline moiety is essential for the success of this reaction, in which a variety of functional groups can be tolerated.

Bidentate Directing Groups: An Efficient Tool in C–H Bond Functionalization Chemistry for the Expedient Construction of C–C Bonds

“…In addition to alkyl halides or alkenes, other alkylating reagents have also been employed for the alkylation of C­(sp 2 )–H and C­(sp 3 )–H bonds, which are briefly described in Table . ,− In 2014, Chatani reported the Ni­(II)-catalyzed oxidative coupling between ortho -C–H bonds of aromatic amides and C­(sp 3 )–H bonds of toluene derivatives (entry 1) . Heptafluoroisopropyl iodide was used as a radical initiator.…”

“…In 2016, Chatani reported the Ni-catalyzed methylation of ortho -C–H bonds in aromatic amides using dicumyl peroxide ( E ) as a methylating reagent (entry 6) . Chatani and Wei independently reported that benzyltrimethylammonium halides ( F ) could be used as a benzylating reagent for the Ni-catalyzed C–H benzylation of aromatic amides (entry 7 and 8). , To avoid the unprecedented C5-activation conferred by the quinoline directing group, a 5-chloro-8-aminoquinoline (8-AQ′) derivative was used as a directing group in the former report (entry 7) . Hirano and Miura established a copper-mediated strategy for the decarboxylative coupling of ortho -C–H bonds in aromatic amides with potassium malonate monoesters G (entry 9) .…”

Understanding Ni(II)-Mediated C(sp3)–H Activation: Tertiary Ureas as Model Substrates

“…Much less is known about the mechanism of Ni­(II)-mediated CMD reactions, despite the increasing focus on Ni-based catalysis. The most well-studied examples use Daugulis’s 8-aminoquinoline (8AQ) directing group (Scheme A, Scheme ) to make new C–C, − C–N, ,, C–O, C–S, − and even C–X − cross-coupling products. This strategy has been applied to β-C­(sp 2 )–H − ,,,,,,− and β-C­(sp 3 )–H ,,− ,,,,,− , bonds in amides.…”

Nickel-catalyzed oxidative C–H/N–H annulation of N-heteroaromatic compounds with alkynes

“…In fact, Ni-catalyzed C–H functionalization reactions were limited to specific substrates that contain an acidic C–H bond, such as pentafluorobenzene, pyridine derivatives, and azoles 5 a . However, since our initial report in 2013 on the use of an 8-aminoquinoline directing group8 in Ni( ii )-catalyzed C–H alkylation with alkyl halides,9 a a combination of Ni( ii ) catalysts and N , N ′-bidentate directing groups has now emerged as a powerful methodology for use in Ni-catalyzed C–H functionalization reactions 5b,c. Since then, the Ni( ii ) catalyst/8-aminoquinoline directing system has been extensively used for the development of Ni-catalyzed C–H functionalizations 5b,c,9,10…”

“…5b , c Since then, the Ni( ii ) catalyst/8-aminoquinoline directing system has been extensively used for the development of Ni-catalyzed C–H functionalizations. 5b , c , 9 , 10 …”