Nickel‐Catalyzed CH Alkylations: Direct Secondary Alkylations and Trifluoroethylations of Arenes

Abstract

A versatile nickel catalyst allowed for C-H alkylations of unactivated arenes with challenging secondary alkyl bromides and chlorides. The high catalytic efficacy also set the stage for direct secondary alkylations of indoles as well as C-H trifluoroethylations with ample substrate scope.

Nickel Catalysts/N,N′-Bidentate Directing Groups: An Excellent Partnership in Directed C–H Activation Reactions

“…21b Ackermann recently reported on the nickel(II)-catalyzed alkylation with secondary alkyl halides and trifluoroethylation of CH bonds using an 8-aminoquinoline as the directing group (Scheme 5). 23 The more active nickel source for this type of transformation was [(DME)NiCl 2 ] (DME: dimethoxyethane) with BDMAE [bis(2-dimethylaminoethyl) ether] as the stabilizing ligand using LiO t Bu as a base in toluene at 160°C for 20 h. The catalytic system tolerated a variety of functional groups with excellent selectivities for monoalkylated products. The metasubstituted amides gave 81 and 84 exclusively through the cleavage of the less-hindered CH bonds.…”

Nickel‐Catalyzed Monofluoromethylation of Aryl Boronic Acids

“…Notably, many biologically active molecules, including the widely prescribed afloqualone, fluticasone propionate, and the anaesthetic sevoflurane, contain a CH 2 F group as an essential motif. [3] Although a variety of methods for the transition-metalcatalyzed trifluoromethylation [4] and difluoromethylation [3b, 5] of arenes have been developed in the past several decades, the incorporation of methyl groups containing a single fluorine (CH 2 F) into arenes has been studied to a lesser extent and remains a challenge. [6] The only example of a palladiummediated direct monofluoromethylation of pinacol phenylboronate was reported by the Suzuki group in 2009.…”

“…(2), Scheme 4), which further implicated the generation of the fluoro(phenylsulfonyl)methyl radical in the catalytic cycle. Furthermore, catalytic (5 mol %) and stoichiometric amounts of [Ni(PPh 3 ) 4 ] were subjected to the standard conditions, respectively, but gave none or only trace amounts of 3 a, thus indicating that the Ni 0 species might not be involved in the catalytic cycle (see the Supporting Information for a detailed discussion).…”

Nickel-Catalyzed C–H Bond Functionalization Utilizing an N,N′-Bidentate Directing Group

“…However, Ackermann recently successfully found the optimal reaction conditions for the Ni(II)-catalyzed alkylation of C-H bonds with secondary alkyl halides using essentially the same chelation system (Scheme 8) [32]. The reaction gave the monoalkylation products 22 with excellent selectivity.…”

“…It was found that a variety of groups, such as alkyl, benzyl, allyl, and methyl groups, can be installed at the ortho-position in the Ni-catalyzed reaction of C-H bonds with alkyl halides or pseudohalides (Schemes 6 and 8) [29,30,32]. Zeng recently reported on the Ni(0)-catalyzed ortho-allylation of C-H bonds in aromatic amides using an 8-aminoquinoline as the directing group with allyl phosphates (Scheme 9) [33].…”