Iron‐Catalyzed Coupling of Aryl Grignard Reagents with Alkyl Halides: A Competitive Hammett Study

Catalysis for Total Synthesis: A Personal Account

“…[70] In contrast, higher alkylmagnesium halides reduce the chosen iron precatalyst to low-valent species, the exact nature of which is still a matter of debate. [71] In any case, we were able to emulate for the very first time all of the elementary steps of a possible catalytic cycle (Scheme 5), [72] starting from well-defined low-valent iron complexes such as 10 which had previously been prepared in Mülheim by Jonas et al; [73] all proposed organoiron intermediates of the chosen model cross-coupling reaction were obtained in crystalline form, despite their exceptional sensitivity (Figure 3). [72] Despite this success, it became apparent that different redox manifolds must be considered.…”

Substrate‐Selective Catalysis

“…In two consecutive publications, Norrby and co‐workers investigated the mechanisms of the aryl–alkyl cross‐coupling reaction using Fe III as a pre‐catalyst. The first reaction studied was the reaction of aryl electrophiles with alkyl Grignard reagents88 and the second reaction studied was between alkyl electrophiles and aryl Grignard reagents 89. The research methodology used in the investigations was based on the use of competitive Hammett studies, reaction monitoring using GC and density functional theory (DFT) calculations.…”

“…The first reaction studied was the reaction of aryl electrophiles with alkyl Grignard reagents [88] and the second reaction studied was between alkyl electrophiles and aryl Grignard reagents. [89] The research methodology used in the investigations was based on the use of competitive Hammett studies, reaction monitoring using GC and density functional theory (DFT) calculations. The first study indicated that Fe I behaved as the catalytic species and that the oxidative addition of the aryl electrophile to the catalysts constituted the rate-limiting step.…”

New insights into the mechanism of iron-catalyzed cross-coupling reactions

“…Recently, interest in iron-catalyzed coupling reactions has increased significantly because of their environmentally benign character, low cost, and low toxicity. 12,13 Subsequently, the current study investigates the possible reaction pathways that might occur during the rate-limiting step and not during the stages that might have occurred prior to that step. Subsequently, transmetalation and reductive elimination processes reproduce the active Fe(I) catalyst.…”

“…3-5 Kochi initially suggested an Fe(I) species as a potential intermediate in the iron-catalyzed cross-coupling reaction that is converted to Fe(III) through oxidative addition. 13 To allow for an in-depth study, the investigation of two possible paths for the rate-limiting step has been proposed: regular oxidative addition (OA) and atom transfer (AT) paths. [6][7][8][9][10] On the other hand, Furstner and co-workers suggested the involvement of Fe(−II)/Fe(0) species, due to the low activity of the used Fe(I) complexes containing Cp ligands.…”