TY - JOUR
T1 - New in situ trapping metalations of functionalized arenes and heteroarenes with TMPLi in the presence of ZnCl2 and other metal salts
AU - Frischmuth, Annette
AU - Fernández, Maitane
AU - Barl, Nadja M.
AU - Achrainer, Florian
AU - Zipse, Hendrik
AU - Berionni, Guillaume
AU - Mayr, Herbert
AU - Karaghiosoff, Konstantin
AU - Knochel, Paul
PY - 2014/7/21
Y1 - 2014/7/21
N2 - The addition of TMPLi to a mixture of an aromatic or heteroaromatic substrate with a metal salt such as MgCl2, ZnCl2, or CuCN at -78 °C first leads to lithiation of the arene followed by transmetalation with the metal salt to afford functionalized organometallic compounds of Mg, Zn, or Cu. This in situ trapping method allows an expedited metalation (-78 °C, 5 min) of a range of sensitive pyridines (bearing a nitro, ester, or cyano group) and allows the preparation of kinetic regioisomers of functionalized aromatic compounds or heterocycles not otherwise available by standard metalating agents, such as TMPMgCl·LiCl or TMPZnCl·LiCl. Fast, faster, the fastest: Aromatic and heterocyclic substrates, when treated with TMPLi (TMP=2,2,6,6-tetramethylpiperidyl), undergo a kinetic lithiation and then a transmetalation with a metal salt such as MgCl2, ZnCl 2, or CuCN. This allows an expedited metalation of sensitive pyridines bearing a nitro, ester, or cyano group and allows the preparation of kinetic regioisomers of functionalized aromatic compounds or heterocycles.
AB - The addition of TMPLi to a mixture of an aromatic or heteroaromatic substrate with a metal salt such as MgCl2, ZnCl2, or CuCN at -78 °C first leads to lithiation of the arene followed by transmetalation with the metal salt to afford functionalized organometallic compounds of Mg, Zn, or Cu. This in situ trapping method allows an expedited metalation (-78 °C, 5 min) of a range of sensitive pyridines (bearing a nitro, ester, or cyano group) and allows the preparation of kinetic regioisomers of functionalized aromatic compounds or heterocycles not otherwise available by standard metalating agents, such as TMPMgCl·LiCl or TMPZnCl·LiCl. Fast, faster, the fastest: Aromatic and heterocyclic substrates, when treated with TMPLi (TMP=2,2,6,6-tetramethylpiperidyl), undergo a kinetic lithiation and then a transmetalation with a metal salt such as MgCl2, ZnCl 2, or CuCN. This allows an expedited metalation of sensitive pyridines bearing a nitro, ester, or cyano group and allows the preparation of kinetic regioisomers of functionalized aromatic compounds or heterocycles.
KW - amide bases
KW - cross-coupling
KW - metalation
KW - nitrogen heterocycles
KW - organometallic compounds
UR - http://www.scopus.com/inward/record.url?scp=84904692771&partnerID=8YFLogxK
U2 - 10.1002/anie.201403688
DO - 10.1002/anie.201403688
M3 - Article
AN - SCOPUS:84904692771
SN - 1433-7851
VL - 53
SP - 7928
EP - 7932
JO - Angewandte Chemie - International Edition
JF - Angewandte Chemie - International Edition
IS - 30
ER -