Alkali-metal-mediated zincation of anisole: synthesis and structures of three instructive ortho-zincated complexes

W Clegg, S H Dale, A M Drummond, E Hevia, G W Honeyman, R E Mulvey

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

The new concept of alkali-metal-mediated zincation (AMMZ), formally a zinc−hydrogen exchange reaction but one that requires the participation of an alkali metal, is applied here to the alkyl aryl ether anisole, an important molecule for studying directed ortho-metalation (DoM) chemistry. Treating one molar equivalent of anisole with the lithium dialkyl-TMP zincate reagent [THF·Li(μ-TMP)(μ-tBu)Zn(tBu)] (1) in hexane solution affords the mono-ortho-zincated complex [THF·Li(μ-TMP)(μ-o-C6H4OMe)Zn(tBu)] (2), which establishes that 1 functions as an alkyl base although previously it was regarded as an amido (TMP) base in other DoM applications. Treating two molar equivalents of anisole with 1, and increasing the reaction time, affords the bis-ortho-zincated complex [THF·Li(μ-TMP)(μ-o-C6H4OMe)Zn(o-C6H4OMe)] (3), which establishes that 1 can also function as a dual alkyl base. Omitting THF and rerunning the reaction with one or two molar equivalents of anisole affords [Ph(Me)O·Li(μ-TMP)(μ-o-C6H4OMe)Zn(tBu)] (4), which remarkably contains a combination of neutral and ortho-deprotonated anisole ligands. On isolating crystalline 4 from solution and adding THF, it converts to 2 and then to 3 on further stirring of the solution, as determined by NMR studies. This fact, along with other observations, would suggest that a complex-induced proximity effect does not need to be invoked to explain the observed zincation of anisole. The crystal structures of 2−4 are presented, as are their 1H, 13C, and 7Li NMR spectra recorded in C6D6 solution.
LanguageEnglish
Pages7434-7435
Number of pages2
JournalJournal of the American Chemical Society
Volume128
Issue number23
DOIs
Publication statusPublished - 14 Jun 2006

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Thymidine Monophosphate
Alkali Metals
Alkali metals
Nuclear magnetic resonance
Hexane
Ethers
Lithium
Zinc
Crystal structure
Ligands
Hexanes
Crystalline materials
Ether
Hydrogen
Molecules
anisole

Keywords

  • directed ortho-metalation
  • tertiary aromatic amides

Cite this

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title = "Alkali-metal-mediated zincation of anisole: synthesis and structures of three instructive ortho-zincated complexes",
abstract = "The new concept of alkali-metal-mediated zincation (AMMZ), formally a zinc−hydrogen exchange reaction but one that requires the participation of an alkali metal, is applied here to the alkyl aryl ether anisole, an important molecule for studying directed ortho-metalation (DoM) chemistry. Treating one molar equivalent of anisole with the lithium dialkyl-TMP zincate reagent [THF·Li(μ-TMP)(μ-tBu)Zn(tBu)] (1) in hexane solution affords the mono-ortho-zincated complex [THF·Li(μ-TMP)(μ-o-C6H4OMe)Zn(tBu)] (2), which establishes that 1 functions as an alkyl base although previously it was regarded as an amido (TMP) base in other DoM applications. Treating two molar equivalents of anisole with 1, and increasing the reaction time, affords the bis-ortho-zincated complex [THF·Li(μ-TMP)(μ-o-C6H4OMe)Zn(o-C6H4OMe)] (3), which establishes that 1 can also function as a dual alkyl base. Omitting THF and rerunning the reaction with one or two molar equivalents of anisole affords [Ph(Me)O·Li(μ-TMP)(μ-o-C6H4OMe)Zn(tBu)] (4), which remarkably contains a combination of neutral and ortho-deprotonated anisole ligands. On isolating crystalline 4 from solution and adding THF, it converts to 2 and then to 3 on further stirring of the solution, as determined by NMR studies. This fact, along with other observations, would suggest that a complex-induced proximity effect does not need to be invoked to explain the observed zincation of anisole. The crystal structures of 2−4 are presented, as are their 1H, 13C, and 7Li NMR spectra recorded in C6D6 solution.",
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author = "W Clegg and Dale, {S H} and Drummond, {A M} and E Hevia and Honeyman, {G W} and Mulvey, {R E}",
year = "2006",
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Alkali-metal-mediated zincation of anisole: synthesis and structures of three instructive ortho-zincated complexes. / Clegg, W ; Dale, S H ; Drummond, A M ; Hevia, E ; Honeyman, G W ; Mulvey, R E .

In: Journal of the American Chemical Society, Vol. 128, No. 23, 14.06.2006, p. 7434-7435.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Alkali-metal-mediated zincation of anisole: synthesis and structures of three instructive ortho-zincated complexes

AU - Clegg, W

AU - Dale, S H

AU - Drummond, A M

AU - Hevia, E

AU - Honeyman, G W

AU - Mulvey, R E

PY - 2006/6/14

Y1 - 2006/6/14

N2 - The new concept of alkali-metal-mediated zincation (AMMZ), formally a zinc−hydrogen exchange reaction but one that requires the participation of an alkali metal, is applied here to the alkyl aryl ether anisole, an important molecule for studying directed ortho-metalation (DoM) chemistry. Treating one molar equivalent of anisole with the lithium dialkyl-TMP zincate reagent [THF·Li(μ-TMP)(μ-tBu)Zn(tBu)] (1) in hexane solution affords the mono-ortho-zincated complex [THF·Li(μ-TMP)(μ-o-C6H4OMe)Zn(tBu)] (2), which establishes that 1 functions as an alkyl base although previously it was regarded as an amido (TMP) base in other DoM applications. Treating two molar equivalents of anisole with 1, and increasing the reaction time, affords the bis-ortho-zincated complex [THF·Li(μ-TMP)(μ-o-C6H4OMe)Zn(o-C6H4OMe)] (3), which establishes that 1 can also function as a dual alkyl base. Omitting THF and rerunning the reaction with one or two molar equivalents of anisole affords [Ph(Me)O·Li(μ-TMP)(μ-o-C6H4OMe)Zn(tBu)] (4), which remarkably contains a combination of neutral and ortho-deprotonated anisole ligands. On isolating crystalline 4 from solution and adding THF, it converts to 2 and then to 3 on further stirring of the solution, as determined by NMR studies. This fact, along with other observations, would suggest that a complex-induced proximity effect does not need to be invoked to explain the observed zincation of anisole. The crystal structures of 2−4 are presented, as are their 1H, 13C, and 7Li NMR spectra recorded in C6D6 solution.

AB - The new concept of alkali-metal-mediated zincation (AMMZ), formally a zinc−hydrogen exchange reaction but one that requires the participation of an alkali metal, is applied here to the alkyl aryl ether anisole, an important molecule for studying directed ortho-metalation (DoM) chemistry. Treating one molar equivalent of anisole with the lithium dialkyl-TMP zincate reagent [THF·Li(μ-TMP)(μ-tBu)Zn(tBu)] (1) in hexane solution affords the mono-ortho-zincated complex [THF·Li(μ-TMP)(μ-o-C6H4OMe)Zn(tBu)] (2), which establishes that 1 functions as an alkyl base although previously it was regarded as an amido (TMP) base in other DoM applications. Treating two molar equivalents of anisole with 1, and increasing the reaction time, affords the bis-ortho-zincated complex [THF·Li(μ-TMP)(μ-o-C6H4OMe)Zn(o-C6H4OMe)] (3), which establishes that 1 can also function as a dual alkyl base. Omitting THF and rerunning the reaction with one or two molar equivalents of anisole affords [Ph(Me)O·Li(μ-TMP)(μ-o-C6H4OMe)Zn(tBu)] (4), which remarkably contains a combination of neutral and ortho-deprotonated anisole ligands. On isolating crystalline 4 from solution and adding THF, it converts to 2 and then to 3 on further stirring of the solution, as determined by NMR studies. This fact, along with other observations, would suggest that a complex-induced proximity effect does not need to be invoked to explain the observed zincation of anisole. The crystal structures of 2−4 are presented, as are their 1H, 13C, and 7Li NMR spectra recorded in C6D6 solution.

KW - directed ortho-metalation

KW - tertiary aromatic amides

U2 - 10.1021/ja061898g

DO - 10.1021/ja061898g

M3 - Article

VL - 128

SP - 7434

EP - 7435

JO - Journal of the American Chemical Society

T2 - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

SN - 0002-7863

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ER -