Sustainable development now plays an increasingly important role in the strategy of chemical industries. As a part of this preoccupation, the search for more economic and more ecofriendly new efficient synthetic methods is of vital concern. The development of iron-catalyzed cross-coupling reactions is one of the current promising fields of research, as these reactions are very attractive compared to the related palladium-or nickel-catalyzed procedures extensively used until now. This is well illustrated by the numerous results published by us [1] and others. [2] Note that for large-scale applications, it is not enough to use iron salts as catalysts; it is also important to use cheap ligands in small amounts as well as solvents that are compatible with industrial processes.We recently became interested in the iron-catalyzed alkylation of aromatic Grignard reagents for large-scale applications. During the course of our studies, some related reports appeared in the literature. Hayashi and Nagano [3a] and Bedford et al. [3c,d] reported the cross-coupling reaction between primary and secondary alkyl bromides and aromatic Grignard reagents in the presence of catalytic amounts of FeCl 3 . The group of Bedford also showed that a [FeCl(salen)] complex can be used as a catalyst.[3b] However, yields are generally lower than 80 % and the Grignard reagent has to be used in large excess and added at once. Moreover, the reactions are performed in diethyl ether under reflux. Therefore, these methods are not suitable for large-scale applications.Two other reports suggested that the coupling could be carried out in THF. Fürstner [3e] showed that the complex [Li(tmeda)] 2 [Fe(C 2 H 4 ) 4 ] is a very efficient catalyst (TMEDA: N,N,N',N'-tetramethylethylenediamine). From a mechanistic point of view, this elegant example is very interesting as it demonstrates that a Fe 2À species can be used successfully. However, the use of a sophisticated non-commercial iron complex is a major drawback for large-scale applications. The catalytic system used by Nakamura and co-workers [3f] (FeCl 3 / TMEDA) seems more attractive. Nevertheless, it is necessary to use a large quantity of TMEDA (26 equiv relative to FeCl 3 ). Also, during our investigations we found that the use of FeCl 3 leads to variable yields according to its purity and its commercial origin (see Supporting Information). Moreover, this salt is not very easy to handle on a large scale as it is highly hygroscopic.Herein, we report our results concerning two new catalytic systems that can be used on a large scale to perform this reaction very efficiently.Nakamura and co-workers reported that the use of [Fe(acac) 3 ] (acac: acetylacetonate) as a catalyst gave unsatisfactory yields of the substitution product.[4] We found this very surprising because during our investigations the reaction proceeded very efficiently in the presence of TMEDA and [Fe(acac) 3 ], whatever the origin of the salt (Scheme 1). Moreover, these results concord well with our experience in the field of iron catal...

Sustainable development now plays an increasingly important role in the strategy of chemical industries. As a part of this preoccupation, the search for more economic and more ecofriendly new efficient synthetic methods is of vital concern. The development of iron-catalyzed cross-coupling reactions is one of the current promising fields of research, as these reactions are very attractive compared to the related palladium-or nickel-catalyzed procedures extensively used until now. This is well illustrated by the numerous results published by us [1] and others. [2] Note that for large-scale applications, it is not enough to use iron salts as catalysts; it is also important to use cheap ligands in small amounts as well as solvents that are compatible with industrial processes.We recently became interested in the iron-catalyzed alkylation of aromatic Grignard reagents for large-scale applications. During the course of our studies, some related reports appeared in the literature. Hayashi and Nagano [3a] and Bedford et al. [3c,d] reported the cross-coupling reaction between primary and secondary alkyl bromides and aromatic Grignard reagents in the presence of catalytic amounts of FeCl 3 . The group of Bedford also showed that a [FeCl(salen)] complex can be used as a catalyst.[3b] However, yields are generally lower than 80 % and the Grignard reagent has to be used in large excess and added at once. Moreover, the reactions are performed in diethyl ether under reflux. Therefore, these methods are not suitable for large-scale applications.Two other reports suggested that the coupling could be carried out in THF. Fürstner [3e] showed that the complex [Li(tmeda)] 2 [Fe(C 2 H 4 ) 4 ] is a very efficient catalyst (TMEDA: N,N,N',N'-tetramethylethylenediamine). From a mechanistic point of view, this elegant example is very interesting as it demonstrates that a Fe 2À species can be used successfully. However, the use of a sophisticated non-commercial iron complex is a major drawback for large-scale applications. The catalytic system used by Nakamura and co-workers [3f] (FeCl 3 / TMEDA) seems more attractive. Nevertheless, it is necessary to use a large quantity of TMEDA (26 equiv relative to FeCl 3 ). Also, during our investigations we found that the use of FeCl 3 leads to variable yields according to its purity and its commercial origin (see Supporting Information). Moreover, this salt is not very easy to handle on a large scale as it is highly hygroscopic.Herein, we report our results concerning two new catalytic systems that can be used on a large scale to perform this reaction very efficiently.Nakamura and co-workers reported that the use of [Fe(acac) 3 ] (acac: acetylacetonate) as a catalyst gave unsatisfactory yields of the substitution product.[4] We found this very surprising because during our investigations the reaction proceeded very efficiently in the presence of TMEDA and [Fe(acac) 3 ], whatever the origin of the salt (Scheme 1). Moreover, these results concord well with our experience in the field of iron catal...