Shedding new light on ZnCl2-mediated addition reactions of Grignard reagents to ketones: structural authentication of key intermediates and diffusion-ordered NMR studies

David R. Armstrong, William Clegg, Pablo Garcia-Alvarez, Matthew D. McCall, Lorraine Nuttall, Alan R. Kennedy, Luca Russo, Eva Hevia

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38 Citations (Scopus)

Abstract

Building on recent advances in synthesis showing that the addition of inorganic salts to Grignard reagents can greatly enhance their performance in alkylation reactions to ketones, this study explores the reactions of EtMgCl with benzophenone in the presence of stoichiometric or catalytic amounts of ZnCl2 with the aim of furthering the understanding of the role and constitution of the organometallic species involved in these transformations. Investigations into the metathesis reactions of three molar equivalents of EtMgCl with ZnCl2 led to the isolation and characterisation (X-ray crystallography and H-1 and C-13 NMR spectroscopy) of novel magnesium "zinc-rich" zincate [{(THF)(6)Mg2Cl3}(+){Zn2Et5}(-)] (1), whose complicated constitution in THF solutions was assessed by variable-temperature H-1 DOSY NMR studies. Compound 1 reacted with one equivalent of benzophenone to yield magnesium magnesiate [{(THF)(6)Mg2Cl3}(+){Mg-2(OC(Et)Ph-2)(2)Cl-3(THF)}(-)] (3), whose structure was determined by Xray crystallography. H-1 NMR monitoring of this reaction showed two equivalents of ZnEt2 formed as a co-product, which together with the "magnesium only constitution" of 3 provides experimental insights into how zinc can be efficiently recycled in these reactions, and therefore used catalytically. The chemoselectivity of this reaction can be rationalised in terms of the synergic effect of magnesium and zinc and contrasts with the results obtained when benzophenone was allowed to react with EtMgCl in the absence of ZnCl2, where the reduction of the ketone takes place preferentially. The reduction product [{(THF)(5)Mg3Cl4{OC(H)Ph(CF3)}(2)] (4) obtained from the reaction of EtMgCl with 2,2,2-trifluoroacetophenone was established by X-ray crystallography and multinuclear (H-1, C-13 and F-19) NMR spectroscopy. Compounds 3 and 4 exhibit new structural motifs in magnesium chemistry having MgCl2 integrated within their constitution, which highlights the new role of this inorganic salt in providing structural support for the newly generated alkoxide ligand.

Original languageEnglish
Pages (from-to)4470-4479
Number of pages10
JournalChemistry - A European Journal
Volume17
Issue number16
DOIs
Publication statusPublished - 11 Apr 2011

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Keywords

  • addition reactions
  • Grignard reagents
  • mixed-metal chemistry
  • NMR spectroscopy
  • zincates
  • carbonyl-compounds
  • organomagnesium reagents
  • tertiary alcohols
  • ate complexes
  • organometallic reagents
  • zincate complex
  • magnesium
  • metalation

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