Iron-catalyzed C(sp²)–C(sp³) cross-coupling at low catalyst loading

Abstract

An operationally-simple protocol for the selective C(sp2)–C(sp3) iron-catalyzed cross-coupling of aryl chlorides with Grignard reagents at low catalyst loading is reported.

Iron-Catalyzed C(sp2)–C(sp3) Cross-Coupling of Aryl Chlorobenzoates with Alkyl Grignard Reagents

“…We became interested in developing the iron-catalyzed cross-coupling of aryl chlorobenzoates as part of our program in iron catalysis [36][37][38][39][40][41][42][43] and the cross-coupling of C(acyl)-X (X = N, O) electrophiles [44,45]. Recently, several groups have reported methods for the nickel and palladium-catalyzed C(acyl)-O bond activation of aryl benzoates, leading to the selective formation of acyl-metal intermediates (Scheme 2, box) [46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64].…”

“…Spectroscopic data matched literature values. General methods have been published [36][37][38][39][40][41][42][43]. All new compounds have been characterized by established guidelines by 1 H-NMR, 13 C-NMR, HRMS, and Mp as appropriate.…”

“…The success of the iron-NMP reagent relies in large part on the outstanding functional group tolerance of this catalyst, the high toxicity of NMP notwithstanding [34,35]. In this vein, our laboratory has reported iron-catalyzed cross-couplings with alkyl Grignard reagents using benign urea ligands that represent an effective alternative to the reprotoxic NMP [36][37][38][39][40][41][42][43].…”

Additive and Counterion Effects in Iron-Catalyzed Reactions Relevant to C–C Bond Formation

“…As a result, alternatives to NMP are now being sought. Toward this goal, Szostak and co-workers have been exploring alternatives to NMP, in particular urea derivatives. − The additives 1,3-dimethyl-3,4,5,6-dimethylpropyleneurea (DMPU), 1,3-dimethyl-2-imidazolidinone (DMI), N -methyl-caprolactam ( N -Me-CPL), and 1,1,3,3-tetramethylurea (TMU) were successfully used as alternatives to NMP in the iron-catalyzed cross-coupling of heteroaryl chlorides and organotosylates with alkyl Grignard reagents (Scheme ). When exploring alternatives to NMP, it was hypothesized that successful substitutes would possess the same amide O-coordinating moiety as NMP.…”

Ligand Effect on Iron‐Catalyzed Cross‐Coupling Reactions: Evaluation of Amides as O‐Coordinating Ligands

“…Next, on the basis of the initial screen, we selected ten most effective ligands (TMU, 1 ; DMBA, 3 ; DEBA, 4 ; Mor‐BA, 6 ; Pyrr‐BA, 7 ; Pip‐BA, 8 ; DMAC, 13 ; C9‐DMAC, 15 ; i Pr‐DMAC, 16 ; Bis(OMeEt)BnA, 19 ) and evaluated their effect on the more challenging cross‐coupling at low catalyst loading (Tables –) . Initially, the cross‐coupling of 4‐chloro‐4‐(trifluoromethyl)benzene ( 26 ) at 0.10 mol% loading was examined (Table ).…”