Exploration of Mechanochemical Activation in Solid-State Fluoro-Grignard Reactions

Abstract

Owing to the strength of the C–F bond, the ‘direct’ preparation of Grignard reagents, i.e., the interaction of elemental magnesium with an organic halide, typically in an ethereal solvent, fails for bulk magnesium and organofluorine compounds. Previously described mechanochemical methods for preparing Grignard reagents have involved ball milling powdered magnesium with organochlorines or bromines. Activation of the C–F bond through a similar route is also possible, however. For example, milling 1- and 2-fluoronaphthalene with an excess of magnesium metal for 2 h, followed by treatment with FeCl3 and additional milling, produces the corresponding binaphthalenes, albeit in low yields (ca. 20%). The yields are independent of the particular isomer involved and are also comparable to the yields from corresponding the bromonaphthalenes. These results may reflect similar charges that reside on the α-carbon in the naphthalenes, as indicated by density functional theory calculations.

Benzene Ring Knitting Achieved by Ambient‐Temperature Dehalogenation via Mechanochemical Ullmann‐Type Reductive Coupling

“…[27,45,46] It is known that Grignard reagents are a subclass of organomagnesium compound, which is a kind of popular reagent in organic synthesis with the generic formula RMgX for creating new CC bonds. [47][48][49] We envisaged that energy generated by mechanical treatment could initiate and stimulate the insertion of Mg species into the CBr bond, leading to rapid and efficient solid-state formation of the Grignard reagent intermediates and final CPN construction via reductive Ullmann-type coupling. Mg was proved to be an efficient reagent in our previous works to promote the solid-state denitriding reaction and crystallization of boron nitride.…”

Grignard reagent formation via C–F bond activation: a centenary perspective

“…Recently, Speight and Hanusa reported a C–F bond activation in fluoronaphthalene with magnesium under ball milling conditions (Scheme 6b). 67 Formation of naphthalene upon quenching with water and of binaphthyl upon subsequent addition of iron( iii ) chloride indicated the presence of a fluoro-Grignard reagent intermediate. Neither optimization of the reaction conditions nor a demonstration of synthetic applicability was done so far.…”

Mechanochemical Grignard Reactions with Gaseous CO2 and Sodium Methyl Carbonate

“…or a) Pinhas and co-workers (2011) [7] b) Métro and co-workers (2020) [8] NH 3 Harrowfield and co-workers (2001) [11] X Ph R O CO Speight and Hanusa (2020) [12] 2 X: F, Br…”

“…[12,13] Scheme 1. Previously reported mechanochemical reactions with CO2 (a and b), [7,8] mechanochemical Grignard reactions (c and d), [11,12] and mechanochemically conducted Grignard reactions with CO2 in this work.…”

“…In search of a mechanochemical way to conduct Grignard reactions which hardly occur, if at all, in solution, Speight and Hanusa found that ball milling facilitates the insertion of magnesium into a C-F-bond as detected by the respective binaphthyls, albeit in low yields (Scheme 1, d). [12,13] Scheme 1. Previously reported mechanochemical reactions with CO2 (a and b), [7,8] mechanochemical Grignard reactions (c and d), [11,12] and mechanochemically conducted Grignard reactions with CO2 in this work.…”