Structural and reactivity insights in Mg–Zn hybrid chemistry

Zn–I exchange and Pd-catalysed cross-coupling applications of aromatic substrates

Tobias D. Bluemke, William Clegg, Pablo García-Alvarez, Alan R. Kennedy, Konrad Koszinowski, Matthew D. McCall, Luca Russo, Eva Hevia

Research output: Contribution to journalArticle

17 Citations (Scopus)
78 Downloads (Pure)

Abstract

Expanding the synthetic potential of Mg-Zn hybrid organyl reagents (generated via transmetallation reactions), this study uncovers a versatile approach, involving a sequence of direct Zn-I exchange and Pd catalysed cross-coupling reactions which grants access to a wide range of asymmetric bis(aryls). By combining X-ray crystallography with ESI-MS and non-deuterium NMR spectroscopic studies, new light is shed on the heterobimetallic constitution of the intriguing organometallic species [(THF)4MgCl 2Zn(tBu)Cl] (1) and [{Mg2Cl3(THF) 6}+{ZntBu3}-] (2), formed through transmetallation of tBuMgCl with n equivalent amounts of ZnCl2 (n = 1 and 3 respectively). Operating by cooperative effects, alkyl-rich hybrid 2 can effectively promote direct Zn-I exchange reactions with aromatic halides in short periods of time at room temperature in THF solution. The structural elucidation of key organometallic intermediates involved in some of these Zn-I exchanges, provides new reactivity insights into how these bimetallic systems operate. Thus, while the reaction of 2 with 3 equivalents of 2-iodoanisole (3b) gives magnesium dizincate [{Mg(THF)6}2+{Zn(o-C 6H4-OMe)3}2 -] (4) which demonstrates the 3-fold activation of the tBu groups attached to Zn in 2, using 2-iodobenzonitrile (3i), only two tBu groups react with the substrate, affording [(THF)4MgCl(NC-o-C6H4)ZnI(o-C 6H4-CN)(THF)] (7). In 7 Mg and Zn are connected by an aryl bridge, suggesting that the formation of contacted ion-pair hybrids may have a deactivating effect on the outcome of the Zn-I exchange process. A wide range of homoleptic tris(aryl) zincate intermediates have been prepared in situ and used as precursors in Pd catalysed cross-coupling reactions, affording bis(aryls) 6a-s in excellent yields under mild reaction conditions without the need of any additive or polar cosolvent such as NMP or DMI.

Original languageEnglish
Pages (from-to)3552-3562
Number of pages11
JournalChemical Science
Volume5
Issue number9
Early online date16 Jun 2014
DOIs
Publication statusPublished - 1 Sep 2014

Fingerprint

Organometallics
X ray crystallography
Substrates
Magnesium
Chemical activation
Nuclear magnetic resonance
Ions
Temperature

Keywords

  • transmetallation reactions
  • hybrid chemistry
  • X-ray crystallography

Cite this

Bluemke, Tobias D. ; Clegg, William ; García-Alvarez, Pablo ; Kennedy, Alan R. ; Koszinowski, Konrad ; McCall, Matthew D. ; Russo, Luca ; Hevia, Eva. / Structural and reactivity insights in Mg–Zn hybrid chemistry : Zn–I exchange and Pd-catalysed cross-coupling applications of aromatic substrates. In: Chemical Science. 2014 ; Vol. 5, No. 9. pp. 3552-3562.
@article{d9a00e8dcb0b43e7a251dc77ce1b3420,
title = "Structural and reactivity insights in Mg–Zn hybrid chemistry: Zn–I exchange and Pd-catalysed cross-coupling applications of aromatic substrates",
abstract = "Expanding the synthetic potential of Mg-Zn hybrid organyl reagents (generated via transmetallation reactions), this study uncovers a versatile approach, involving a sequence of direct Zn-I exchange and Pd catalysed cross-coupling reactions which grants access to a wide range of asymmetric bis(aryls). By combining X-ray crystallography with ESI-MS and non-deuterium NMR spectroscopic studies, new light is shed on the heterobimetallic constitution of the intriguing organometallic species [(THF)4MgCl 2Zn(tBu)Cl] (1) and [{Mg2Cl3(THF) 6}+{ZntBu3}-] (2), formed through transmetallation of tBuMgCl with n equivalent amounts of ZnCl2 (n = 1 and 3 respectively). Operating by cooperative effects, alkyl-rich hybrid 2 can effectively promote direct Zn-I exchange reactions with aromatic halides in short periods of time at room temperature in THF solution. The structural elucidation of key organometallic intermediates involved in some of these Zn-I exchanges, provides new reactivity insights into how these bimetallic systems operate. Thus, while the reaction of 2 with 3 equivalents of 2-iodoanisole (3b) gives magnesium dizincate [{Mg(THF)6}2+{Zn(o-C 6H4-OMe)3}2 -] (4) which demonstrates the 3-fold activation of the tBu groups attached to Zn in 2, using 2-iodobenzonitrile (3i), only two tBu groups react with the substrate, affording [(THF)4MgCl(NC-o-C6H4)ZnI(o-C 6H4-CN)(THF)] (7). In 7 Mg and Zn are connected by an aryl bridge, suggesting that the formation of contacted ion-pair hybrids may have a deactivating effect on the outcome of the Zn-I exchange process. A wide range of homoleptic tris(aryl) zincate intermediates have been prepared in situ and used as precursors in Pd catalysed cross-coupling reactions, affording bis(aryls) 6a-s in excellent yields under mild reaction conditions without the need of any additive or polar cosolvent such as NMP or DMI.",
keywords = "transmetallation reactions, hybrid chemistry, X-ray crystallography",
author = "Bluemke, {Tobias D.} and William Clegg and Pablo Garc{\'i}a-Alvarez and Kennedy, {Alan R.} and Konrad Koszinowski and McCall, {Matthew D.} and Luca Russo and Eva Hevia",
year = "2014",
month = "9",
day = "1",
doi = "10.1039/c4sc01263a",
language = "English",
volume = "5",
pages = "3552--3562",
journal = "Chemical Science",
issn = "2041-6520",
number = "9",

}

Structural and reactivity insights in Mg–Zn hybrid chemistry : Zn–I exchange and Pd-catalysed cross-coupling applications of aromatic substrates. / Bluemke, Tobias D.; Clegg, William; García-Alvarez, Pablo; Kennedy, Alan R.; Koszinowski, Konrad; McCall, Matthew D.; Russo, Luca; Hevia, Eva.

In: Chemical Science, Vol. 5, No. 9, 01.09.2014, p. 3552-3562.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Structural and reactivity insights in Mg–Zn hybrid chemistry

T2 - Zn–I exchange and Pd-catalysed cross-coupling applications of aromatic substrates

AU - Bluemke, Tobias D.

AU - Clegg, William

AU - García-Alvarez, Pablo

AU - Kennedy, Alan R.

AU - Koszinowski, Konrad

AU - McCall, Matthew D.

AU - Russo, Luca

AU - Hevia, Eva

PY - 2014/9/1

Y1 - 2014/9/1

N2 - Expanding the synthetic potential of Mg-Zn hybrid organyl reagents (generated via transmetallation reactions), this study uncovers a versatile approach, involving a sequence of direct Zn-I exchange and Pd catalysed cross-coupling reactions which grants access to a wide range of asymmetric bis(aryls). By combining X-ray crystallography with ESI-MS and non-deuterium NMR spectroscopic studies, new light is shed on the heterobimetallic constitution of the intriguing organometallic species [(THF)4MgCl 2Zn(tBu)Cl] (1) and [{Mg2Cl3(THF) 6}+{ZntBu3}-] (2), formed through transmetallation of tBuMgCl with n equivalent amounts of ZnCl2 (n = 1 and 3 respectively). Operating by cooperative effects, alkyl-rich hybrid 2 can effectively promote direct Zn-I exchange reactions with aromatic halides in short periods of time at room temperature in THF solution. The structural elucidation of key organometallic intermediates involved in some of these Zn-I exchanges, provides new reactivity insights into how these bimetallic systems operate. Thus, while the reaction of 2 with 3 equivalents of 2-iodoanisole (3b) gives magnesium dizincate [{Mg(THF)6}2+{Zn(o-C 6H4-OMe)3}2 -] (4) which demonstrates the 3-fold activation of the tBu groups attached to Zn in 2, using 2-iodobenzonitrile (3i), only two tBu groups react with the substrate, affording [(THF)4MgCl(NC-o-C6H4)ZnI(o-C 6H4-CN)(THF)] (7). In 7 Mg and Zn are connected by an aryl bridge, suggesting that the formation of contacted ion-pair hybrids may have a deactivating effect on the outcome of the Zn-I exchange process. A wide range of homoleptic tris(aryl) zincate intermediates have been prepared in situ and used as precursors in Pd catalysed cross-coupling reactions, affording bis(aryls) 6a-s in excellent yields under mild reaction conditions without the need of any additive or polar cosolvent such as NMP or DMI.

AB - Expanding the synthetic potential of Mg-Zn hybrid organyl reagents (generated via transmetallation reactions), this study uncovers a versatile approach, involving a sequence of direct Zn-I exchange and Pd catalysed cross-coupling reactions which grants access to a wide range of asymmetric bis(aryls). By combining X-ray crystallography with ESI-MS and non-deuterium NMR spectroscopic studies, new light is shed on the heterobimetallic constitution of the intriguing organometallic species [(THF)4MgCl 2Zn(tBu)Cl] (1) and [{Mg2Cl3(THF) 6}+{ZntBu3}-] (2), formed through transmetallation of tBuMgCl with n equivalent amounts of ZnCl2 (n = 1 and 3 respectively). Operating by cooperative effects, alkyl-rich hybrid 2 can effectively promote direct Zn-I exchange reactions with aromatic halides in short periods of time at room temperature in THF solution. The structural elucidation of key organometallic intermediates involved in some of these Zn-I exchanges, provides new reactivity insights into how these bimetallic systems operate. Thus, while the reaction of 2 with 3 equivalents of 2-iodoanisole (3b) gives magnesium dizincate [{Mg(THF)6}2+{Zn(o-C 6H4-OMe)3}2 -] (4) which demonstrates the 3-fold activation of the tBu groups attached to Zn in 2, using 2-iodobenzonitrile (3i), only two tBu groups react with the substrate, affording [(THF)4MgCl(NC-o-C6H4)ZnI(o-C 6H4-CN)(THF)] (7). In 7 Mg and Zn are connected by an aryl bridge, suggesting that the formation of contacted ion-pair hybrids may have a deactivating effect on the outcome of the Zn-I exchange process. A wide range of homoleptic tris(aryl) zincate intermediates have been prepared in situ and used as precursors in Pd catalysed cross-coupling reactions, affording bis(aryls) 6a-s in excellent yields under mild reaction conditions without the need of any additive or polar cosolvent such as NMP or DMI.

KW - transmetallation reactions

KW - hybrid chemistry

KW - X-ray crystallography

UR - http://www.scopus.com/inward/record.url?scp=84905175581&partnerID=8YFLogxK

U2 - 10.1039/c4sc01263a

DO - 10.1039/c4sc01263a

M3 - Article

VL - 5

SP - 3552

EP - 3562

JO - Chemical Science

JF - Chemical Science

SN - 2041-6520

IS - 9

ER -