Expanding Mg-Zn hybrid chemistry

inorganic salt effects in addition reactions of organozinc reagents to trifluoroacetophenone and the implications for a synergistic lithium-magnesium-zinc activation

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

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Numerous organic transformations rely on organozinc compounds made through salt-metathesis (exchange) reactions from organolithium or Grignard reagents with a suitable zinc precursor. By combining X-ray crystallography, NMR spectroscopy and DFT calculations, this study sheds new light on the constitution of the organometallic species involved in this important synthetic tool. Investigations into the metathesis reactions of equimolar amounts of Grignard reagents (RMgX) and ZnCl2 in THF led to the isolation of novel magnesium-zinc hybrids, [{(thf)(2)(mu-Cl)(3)ZnR}(2)] (R = Et, tBu, nBu or o-OMe-C6H4), which exhibit an unprecedented structural motif in mixed magnesium-zinc chemistry. Furthermore, theoretical modelling of the reaction of EtMgCl with ZnCl2 reveals that formation of the mixed-metal compound is thermodynamically preferred to that of the expected homometallic products, RZnCl and MgCl2. This study also assesses the alkylating ability of hybrid 3 towards the sensitive ketone trifluoroacetophenone, revealing a dramatic increase in the chemoselectivity of the reaction when LiCl is introduced as an additive. This observation, combined with recent related breakthroughs in synthesis, points towards the existence of a trilateral Li/Mg/Zn synergistic effect.

Original languageEnglish
Pages (from-to)8333-8341
Number of pages9
JournalChemistry - A European Journal
Volume17
Issue number30
DOIs
Publication statusPublished - 18 Jul 2011

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Addition reactions
Lithium
Magnesium
Zinc
Salts
Chemical activation
Magnesium Chloride
X ray crystallography
Organometallics
Ketones
Discrete Fourier transforms
Nuclear magnetic resonance spectroscopy
Metals
Inorganic Chemistry

Keywords

  • addition reactions
  • cooperative effects
  • Grignard reaction
  • magnesium
  • salt effect
  • zincates
  • alkali-metal-magnesium
  • grignard-reagents
  • functionalized aryl
  • structural elucidation
  • asymmetric-synthesis
  • chloride catalysis
  • tertiary alcohols

Cite this

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title = "Expanding Mg-Zn hybrid chemistry: inorganic salt effects in addition reactions of organozinc reagents to trifluoroacetophenone and the implications for a synergistic lithium-magnesium-zinc activation",
abstract = "Numerous organic transformations rely on organozinc compounds made through salt-metathesis (exchange) reactions from organolithium or Grignard reagents with a suitable zinc precursor. By combining X-ray crystallography, NMR spectroscopy and DFT calculations, this study sheds new light on the constitution of the organometallic species involved in this important synthetic tool. Investigations into the metathesis reactions of equimolar amounts of Grignard reagents (RMgX) and ZnCl2 in THF led to the isolation of novel magnesium-zinc hybrids, [{(thf)(2)(mu-Cl)(3)ZnR}(2)] (R = Et, tBu, nBu or o-OMe-C6H4), which exhibit an unprecedented structural motif in mixed magnesium-zinc chemistry. Furthermore, theoretical modelling of the reaction of EtMgCl with ZnCl2 reveals that formation of the mixed-metal compound is thermodynamically preferred to that of the expected homometallic products, RZnCl and MgCl2. This study also assesses the alkylating ability of hybrid 3 towards the sensitive ketone trifluoroacetophenone, revealing a dramatic increase in the chemoselectivity of the reaction when LiCl is introduced as an additive. This observation, combined with recent related breakthroughs in synthesis, points towards the existence of a trilateral Li/Mg/Zn synergistic effect.",
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year = "2011",
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day = "18",
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Expanding Mg-Zn hybrid chemistry : inorganic salt effects in addition reactions of organozinc reagents to trifluoroacetophenone and the implications for a synergistic lithium-magnesium-zinc activation. / Armstrong, David R.; Clegg, William; Garcia-Alvarez, Pablo; Kennedy, Alan R.; McCall, Matthew D.; Russo, Luca; Hevia, Eva.

In: Chemistry - A European Journal, Vol. 17, No. 30, 18.07.2011, p. 8333-8341.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Expanding Mg-Zn hybrid chemistry

T2 - inorganic salt effects in addition reactions of organozinc reagents to trifluoroacetophenone and the implications for a synergistic lithium-magnesium-zinc activation

AU - Armstrong, David R.

AU - Clegg, William

AU - Garcia-Alvarez, Pablo

AU - Kennedy, Alan R.

AU - McCall, Matthew D.

AU - Russo, Luca

AU - Hevia, Eva

PY - 2011/7/18

Y1 - 2011/7/18

N2 - Numerous organic transformations rely on organozinc compounds made through salt-metathesis (exchange) reactions from organolithium or Grignard reagents with a suitable zinc precursor. By combining X-ray crystallography, NMR spectroscopy and DFT calculations, this study sheds new light on the constitution of the organometallic species involved in this important synthetic tool. Investigations into the metathesis reactions of equimolar amounts of Grignard reagents (RMgX) and ZnCl2 in THF led to the isolation of novel magnesium-zinc hybrids, [{(thf)(2)(mu-Cl)(3)ZnR}(2)] (R = Et, tBu, nBu or o-OMe-C6H4), which exhibit an unprecedented structural motif in mixed magnesium-zinc chemistry. Furthermore, theoretical modelling of the reaction of EtMgCl with ZnCl2 reveals that formation of the mixed-metal compound is thermodynamically preferred to that of the expected homometallic products, RZnCl and MgCl2. This study also assesses the alkylating ability of hybrid 3 towards the sensitive ketone trifluoroacetophenone, revealing a dramatic increase in the chemoselectivity of the reaction when LiCl is introduced as an additive. This observation, combined with recent related breakthroughs in synthesis, points towards the existence of a trilateral Li/Mg/Zn synergistic effect.

AB - Numerous organic transformations rely on organozinc compounds made through salt-metathesis (exchange) reactions from organolithium or Grignard reagents with a suitable zinc precursor. By combining X-ray crystallography, NMR spectroscopy and DFT calculations, this study sheds new light on the constitution of the organometallic species involved in this important synthetic tool. Investigations into the metathesis reactions of equimolar amounts of Grignard reagents (RMgX) and ZnCl2 in THF led to the isolation of novel magnesium-zinc hybrids, [{(thf)(2)(mu-Cl)(3)ZnR}(2)] (R = Et, tBu, nBu or o-OMe-C6H4), which exhibit an unprecedented structural motif in mixed magnesium-zinc chemistry. Furthermore, theoretical modelling of the reaction of EtMgCl with ZnCl2 reveals that formation of the mixed-metal compound is thermodynamically preferred to that of the expected homometallic products, RZnCl and MgCl2. This study also assesses the alkylating ability of hybrid 3 towards the sensitive ketone trifluoroacetophenone, revealing a dramatic increase in the chemoselectivity of the reaction when LiCl is introduced as an additive. This observation, combined with recent related breakthroughs in synthesis, points towards the existence of a trilateral Li/Mg/Zn synergistic effect.

KW - addition reactions

KW - cooperative effects

KW - Grignard reaction

KW - magnesium

KW - salt effect

KW - zincates

KW - alkali-metal-magnesium

KW - grignard-reagents

KW - functionalized aryl

KW - structural elucidation

KW - asymmetric-synthesis

KW - chloride catalysis

KW - tertiary alcohols

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DO - 10.1002/chem.201100866

M3 - Article

VL - 17

SP - 8333

EP - 8341

JO - Chemistry - A European Journal

JF - Chemistry - A European Journal

SN - 0947-6539

IS - 30

ER -