Reimagining theGrignard Reaction

Abstract

Grignard reagents count as the most widely used reagents in organic and organometallic chemistry. These reagents are easily available and exhibit a broad reactivity spectrum depending on the nature of the organic groups (bulkiness, electronic properties, nucleophilicity, and denticity owing to peripheral functionalities), solvent, temperature, and additives such as other organometallic components. In recent years, this Grignard‐type chemistry has moved in diverse directions to solve various synthetic challenges. For classic Grignard reactions, the spectrum of applicable solvents has been extended to ionic liquids and even aqueous media. The reactivity of Grignard‐type reagents can be altered by adding more electropositive alkali metal salts, leading to heterobimetallic alkaline earth metallates, or by formation of alkaline earth metal metalates with more electronegative p‐block or transition metals. Species with magnesium‐metal bonds (the so‐called inorganic Grignard reagents) exhibit enormous reactivity as reducing reagents. An attractive alternative to magnesium‐based Grignards is offered by the heavier homologous organoalkaline earth metal derivatives that represent very reactive organometallics. Within the heavier homologous Grignard reagents, the calcium congeners represent the most attractive compounds. Calcium is nontoxic, globally abundant, easily accessible, and inexpensive. Its use is hampered by the enormous reactivity difference of the metal itself (requiring activation procedures before use) and the organometallics derived from it (often leading to ether degradation reactions). Therefore, alkylcalcium complexes usually are stabilized by bulky trialkylsilyl (kinetic stabilization by steric protection) or phenyl groups (electronic protection by delocalization of the anionic charge). The arylcalcium derivatives are easily available and exhibit persistence in ethereal media comparable to organolithium complexes.

Trimethylsilylmethylcalcium Iodide, an Easily Accessible Grignard-Type Reagent of a Heavy Alkaline Earth Metal

“…Organocalcium chemistry has remained in the shadow of the widely used Grignard reagents , because these magnesium-based organometallics are easily accessible or in some cases even commercially available . The first trials to prepare organocalcium compounds via direct synthesis date back more than a hundred years; however, early reports on the synthesis of dimethylcalcium could not be reproduced .…”

“…Severe challenges hampered the development of calcium-based organometallics, such as the enormous discrepancy of the inertness of the metal and the extremely high reactivity of its organometallics. On the one hand, metal activation prior to use and extended reaction times are required; on the other hand, these factors lead to ether degradation and side reactions . The organometallic chemistry of calcium and, with limitations, that of its heavier congeners experienced a renaissance and vast interest after the determination of the molecular structure of [(diox) 2 Ca­{CH­(SiMe 3 ) 2 } 2 ] (diox = 1,4-dioxane) by Lappert and co-workers in 1991 .…”

“…Since alkylcalcium derivatives have a higher reactivity, especially a higher metalation potential, than arylcalcium derivatives and, hence, represent very interesting reagents for organic and organometallic chemistry, it is necessary to establish an efficient and reproducible synthesis of alkylcalcium compounds. On the basis of our experience of the preparation of aryl- and alkenylcalcium halides, the reduction of iodomethyl­trimethylsilane with activated calcium was investigated. Generally, the direct synthesis offers the preferred method for the synthesis of organocalcium derivatives in terms of atom economy and costs.…”

Reduction of Bromo- and Iodo-2,6-bis(diphenylphosphanylmethyl)benzene with Magnesium and Calcium

“…The insertion of magnesium into a carbon-halogen bond can be accompanied by ether cleavage with the initial α-or β-deprotonation step or a radical mechanism [1,2]. The organocalcium halides (heavy Grignard reagents) tend much more to degrade ethers and only diverse arylcalcium [3][4][5][6][7][8][9][10] and trimethylsilylmethylcalcium complexes [11] are easily prepared via the direct synthesis.…”

Reduction of Bromo- and Iodo-2,6-bis(diphenylphosphanylmethyl)benzene with Magnesium and Calcium

“…The insertion of magnesium into a carbon-halogen bond can be accompanied by ether cleavage with the initial α-or β-deprotonation step or a radical mechanism [1,2]. The organocalcium halides (heavy Grignard reagents) tend much more to degrade ethers and only selected arylcalcium [3][4][5][6][7][8][9][10] and trimethylsilylmethylcalcium complexes [11] are easily prepared via the direct synthesis.…”