Generation and suppression of 3-/4-functionalized benzynes using zinc ate base (TMP-Zn-ate): New approaches to multisubstituted benzenes

Masanobu Uchiyama, Yuri Kobayashi, Taniyuki Furuyama, Shinji Nakamura, Yumiko Kajihara, Tomoko Miyoshi, Takao Sakamoto, Yoshinori Kondo, Keiji Morokuma

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

We present full details of our new methods for preparing functionalized benzynes with lithium di-alkyl(2,2,6,6-tetramethylpiperidino)zincate (R 2Zn(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 tBu 2Zn(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.

Original languageEnglish
Pages (from-to)472-480
Number of pages9
JournalJournal of the American Chemical Society
Volume130
Issue number2
DOIs
Publication statusPublished - 2008 Jan 16

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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