Convenient Preparation of Polyfunctional Aryl Magnesium Reagents by a Direct Magnesium Insertion in the Presence of LiCl

Abstract

In the footsteps of Victor Grignard: The simple LiCl‐mediated insertion of magnesium into aryl chlorides and bromides at moderate temperatures leads to functionalized organomagnesium reagents (see scheme). An unprecedented range of functional groups may be present in the substrates (e.g. CN, CO2R, OTs, OBoc; Ts=p‐toluenesulfonyl, Boc=tert‐butylcarbonyloxy).

Preparation of Polyfunctional Arylmagnesium, Arylzinc, and Benzylic Zinc Reagents by Using Magnesium in the Presence of LiCl

“…Recently, we reported on the use of magnesium in the presence of LiCl for preparing various aryl-and heteroaryl-magnesium reagents 2 from the corresponding organic chlorides and bromides 3. [10] We have also reported that in the case of substrates bearing sensitive functional groups, the highly reactive magnesium intermediates can be efficiently trapped in situ by ZnCl 2 , leading to polyfunctional zinc compounds of type 4 (Scheme 1). [10,11] Herein, we wish to report the scope and limitations of this efficient insertion of magnesium into aryl, heteroaryl, and benzylic bromides (or chlorides).…”

“…[10] We have also reported that in the case of substrates bearing sensitive functional groups, the highly reactive magnesium intermediates can be efficiently trapped in situ by ZnCl 2 , leading to polyfunctional zinc compounds of type 4 (Scheme 1). [10,11] Herein, we wish to report the scope and limitations of this efficient insertion of magnesium into aryl, heteroaryl, and benzylic bromides (or chlorides). A new orthogonal regioselectivity pattern of zinc and magnesium insertions is also disclosed.…”

Radical Catalysis of Kumada Cross‐Coupling Reactions Using Functionalized Grignard Reagents

“…[7,8] Herein, we wish to report a new radical catalysis which makes it possible to perform a Kumada cross-coupling using aryl bromides at room temperature within a few minutes in the presence of an alkyl iodide. In preliminary experiments we observed that the reaction of PhMgCl (1 a), prepared by the insertion of magnesium in the presence of lithium chloride, [9] reacts slowly with 4-bromoanisole (2 a) in the presence of Pd(OAc) 2 and S-Phos (S-Phos = 2-dicyclohexylphosphanyl-2',6'dimethoxyphenyl) [10] or PEPPSI (PEPPSI = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene](3-chloropyridyl)palladium(II) dichloride), [11] leading to 4-methoxybiphenyl (3 a). A conversion of only 8 % was observed at 0 8C after 15 minutes.…”

A comprehensive study of the effects of spectator ligands, transition metals and lithium halide additives on the efficiency of iron, nickel and palladium-catalyzed cross-coupling reactions of cyclohexyl magnesium bromide with fluorinated bromobenzenes

“…If Grignard reagents are to be used as nucleophiles in coupling reactions with aryl bromides or chlorides it has been shown that lithium halide adducts of the Grignard reagents show an enhanced reactivity. [54][55][56][57][58] The aim of this research therefore was to gain an understanding of the mutual effects of various transition metals, different spectator ligands, lithium halide additives and the substitution pattern of the respective bromobenzene derivative on the efficiency of the cross-coupling reaction. Moreover, we were highly interested to find a synthetic protocol that allows for the use of iron catalysts with yields that should be comparable to the very well working palladium catalysts.…”