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

Research output: Contribution to journalArticle

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.

LanguageEnglish
Pages4470-4479
Number of pages10
JournalChemistry - A European Journal
Volume17
Issue number16
DOIs
Publication statusPublished - 11 Apr 2011

Fingerprint

Addition reactions
Ketones
Magnesium
Authentication
Nuclear magnetic resonance
Zinc
X ray crystallography
Nuclear magnetic resonance spectroscopy
Salts
Magnesium Chloride
Crystallography
Alkylation
Organometallics
Ligands
Monitoring
benzophenone
Temperature

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

Cite this

Armstrong, David R. ; Clegg, William ; Garcia-Alvarez, Pablo ; McCall, Matthew D. ; Nuttall, Lorraine ; Kennedy, Alan R. ; Russo, Luca ; Hevia, Eva. / Shedding new light on ZnCl2-mediated addition reactions of Grignard reagents to ketones : structural authentication of key intermediates and diffusion-ordered NMR studies. In: Chemistry - A European Journal. 2011 ; Vol. 17, No. 16. pp. 4470-4479.
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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.",
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Shedding new light on ZnCl2-mediated addition reactions of Grignard reagents to ketones : structural authentication of key intermediates and diffusion-ordered NMR studies. / Armstrong, David R.; Clegg, William; Garcia-Alvarez, Pablo; McCall, Matthew D.; Nuttall, Lorraine; Kennedy, Alan R.; Russo, Luca; Hevia, Eva.

In: Chemistry - A European Journal, Vol. 17, No. 16, 11.04.2011, p. 4470-4479.

Research output: Contribution to journalArticle

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T1 - Shedding new light on ZnCl2-mediated addition reactions of Grignard reagents to ketones

T2 - Chemistry - A European Journal

AU - Armstrong, David R.

AU - Clegg, William

AU - Garcia-Alvarez, Pablo

AU - McCall, Matthew D.

AU - Nuttall, Lorraine

AU - Kennedy, Alan R.

AU - Russo, Luca

AU - Hevia, Eva

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Y1 - 2011/4/11

N2 - 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.

AB - 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.

KW - addition reactions

KW - Grignard reagents

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KW - NMR spectroscopy

KW - zincates

KW - carbonyl-compounds

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KW - tertiary alcohols

KW - ate complexes

KW - organometallic reagents

KW - zincate complex

KW - magnesium

KW - metalation

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