Facile synthesis of alkynyl-, aryl- and ferrocenyl-substituted pyrazoles via Sonogashira and Suzuki-Miyaura approaches

KARABIYIKOĞLU S., ZORA M.

APPLIED ORGANOMETALLIC CHEMISTRY, vol.30, no.10, pp.876-885, 2016 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 30 Issue: 10
  • Publication Date: 2016
  • Doi Number: 10.1002/aoc.3516
  • Journal Name: APPLIED ORGANOMETALLIC CHEMISTRY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.876-885
  • Keywords: pyrazole, ferrocene, alkyne, boronic acid, coupling, TOPOISOMERASE-I INHIBITION, ONE-POT SYNTHESIS, REGIOSELECTIVE SYNTHESIS, BIOLOGICAL EVALUATION, PHASE SYNTHESIS, DERIVATIVES, PYRIDINES, ANTITUMOR, KETONES, CYTOTOXICITY
  • Middle East Technical University Affiliated: Yes

Abstract

A concise and efficient synthesis of densely substituted novel pyrazoles with alkynyl, aryl and ferrocenyl functionalities is reported, providing a platform for biological studies. The general strategy involves Sonogashira and Suzuki-Miyaura cross-coupling reactions of easily obtainable 5-ferrocenyl/phenyl-4-iodo-1-phenylpyrazoles with terminal alkynes and boronic acids, respectively. The starting 4-iodopyrazoles were synthesized by electrophilic cyclization of alpha,beta-alkynic hydrazones with molecular iodine. Sonogashira reactions have been achieved by employing 5 mol% PdCl2(PPh3)(2), 5 mol% CuI, excess Et3N and 1.2 equiv. of terminal alkyne, relative to 4-iodopyrazole, in tetrahydrofuran at 65 degrees C, while Suzuki-Miyaura reactions have been accomplished using 5 mol% PdCl2(PPh3)(2) and 1.4 equiv. of both boronic acid/ester and KHCO3, with respect to 4-iodopyrazole, in 4:1 dimethylformamide-H2O solution at 110 degrees C. Both Sonogashira and Suzuki-Miyaura coupling reactions have proven effective for the synthesis of alkynyl-, aryl- and ferrocenyl-substituted pyrazoles and demonstrated good tolerance to a diverse range of substituents, including electron-donating and electron-withdrawing groups. These coupling approaches could allow for the rapid construction of a library of functionalized pyrazoles of pharmacological interest. Copyright (C) 2016 John Wiley & Sons, Ltd.