Mechanochemical Activation of Zinc and Application to Negishi Cross‐Coupling

Abstract

A form independent activation of zinc, concomitant generation of organozinc species and engagement in a Negishi cross‐coupling reaction via mechanochemical methods is reported. The reported method exhibits a broad substrate scope for both C(sp3)–C(sp2) and C(sp2)–C(sp2) couplings and is tolerant to many important functional groups. The method may offer broad reaching opportunities for the in situ generation organometallic compounds from base metals and their concomitant engagement in synthetic reactions via mechanochemical methods.

Direct Mechanocatalysis: Palladium as Milling Media and Catalyst in the Mechanochemical Suzuki Polymerization

“…In most cases, the catalyzed reactions are run homogeneously, although there are discussions and studies in the literature about heterogeneous analogues . In the recent past, several of the aforementioned reactions have been performed in a solvent‐free manner in ball mills . These mechanochemical reactions proved advantageous, being extremely swift and consuming less energy while the solvent‐free reaction environment significantly reduces the amount of waste produced and circumvents any possible solubility issues .…”

“…[12][13][14] In the recent past, several of the aforementioned reactions have been performed in asolvent-free manner in ball mills. [15][16][17][18][19] These mechanochemical reactions proved advantageous,being extremely swift and consuming less energy while the solvent-free reaction environment significantly reduces the amount of waste produced and circumvents any possible solubility issues. [20,21] However, often the catalyst salts used in these solvent-free protocols are still the same as those in conventional solution-based processes.…”

A Ball‐Milling‐Enabled Reformatsky Reaction

“… A) Formation and use of organzinc reagents. B) Previous work: one‐jar two‐step Negishi coupling . C) This work: one‐jar one‐step mechanochemical Reformatsky reaction.…”

“…[3] Recently,w ei dentified mechanochemistry and ball-milling as at ool for the straightforward generation of organozinc speciesw ithout the requirement for carefullyp repareds olvents or inert gases.U nder these conditions the input of mechanical energy is enough to break down the resilient metal oxide surface and, in the presenceo ft he alkyl/aryl halide,g enerate the corresponding organozinc species (Scheme 1B). [4] These organozinc speciesm ay then be intercepted by opening the grinding jar,a dding both catalyst and coupling partner beforet hen running at elescoped Negishic oupling reaction; such ap rocess is applicable to both sp 3 Àsp 3 ands p 3 Àsp 2 coupling reactions. We have exploited this concept to carry out the one-jar,o ne-step preparation andu se of organozinc species in ar obust mechanochemical Reformatsky reaction (Scheme 1C).…”

“…B) Previous work: one-jar two-step Negishi coupling. [4] C) This work:one-jar one-step mecha-nochemicalR eformatsky reaction. bromoethane, [11] or chlorotrimethylsilane.…”