Generation and suppression of 3-/4-functionalized benzynes using zinc ate base (TMP-Zn-ate): new approaches to multisubstituted benzenes.
We present full details of our new methods for preparing functionalized benzynes with lithium di-alkyl(2,2,6,6-tetramethylpiperidino)zincate (R2Zn(TMP)Li) through deprotonative zincation as a key reaction. In this system, by choosing appropriate ligands for the zincate, either regioselective zincation of functionalized haloaromatics or the generation of substituted benzynes can be controlled in good yields with excellent chemoselectivity, using the same substrate. Zincation with (t)Bu2Zn(TMP)Li followed by electrophilic trapping or zincation with Me2Zn(TMP)Li followed by nucleophilic or diene trapping is shown to be a powerful tool for the chemoselective preparation of 1,2,3-/1,2,4-trisubstituted benzene derivatives. These methods offer far greater generality than previous methods for the synthesis of multifunctionalized benzenes. Computational/theoretical studies of the reaction mechanism of this unique benzyne formation indicated that preferential coordination of the dialkylzinc moiety of zincate to halogen is the reason for the reduced activation energy of the elimination, that is, for the formation of the benzyne. The role of the ligands on Zn in accelerating/decelerating the elimination is also discussed.
Uchiyama
Masanobu
M
Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. uchiyama@mol.f.u-tokyo.ac.jp
Kobayashi
Yuri
Y
Furuyama
Taniyuki
T
Nakamura
Shinji
S
Kajihara
Yumiko
Y
Miyoshi
Tomoko
T
Sakamoto
Takao
T
Kondo
Yoshinori
Y
Morokuma
Keiji
K
D001555:Benzene Derivatives / Q000138:chemical synthesis*; D006219:Halogens / Q000737:chemistry; D018020:Lithium Compounds / Q000737:chemistry*; D015032:Zinc / Q000737:chemistry
D001555:Benzene Derivatives; D006219:Halogens; D018020:Lithium Compounds; D015032:Zinc