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Synthesis 2021; 53(20): 3847-3861
DOI: 10.1055/a-1516-8745
paper

Highly Efficient Synthesis of 2-Substituted Benzo[b]furan Derivatives from the Cross-Coupling Reactions of 2-Halobenzo[b]furans with Organoalane Reagents

Chang Wen
a   College of Chemistry and Environment, Southwest Minzu University, Chengdu 610041, P. R. of China
b   Key Laboratory of General Chemistry of the National Ethnic Affairs Commission, College of Chemistry and Environment, Southwest Minzu University, Chengdu 610041, P. R. of China
c   Key Laboratory of Pollution Control Chemistry and Environmental Functional Materials for Qinghai-Tibet Plateau of the National Ethnic Affairs Commission, College of Chemistry and Environment, Southwest Minzu University, Chengdu 610041, P. R. of China
,
Chuan Wu
a   College of Chemistry and Environment, Southwest Minzu University, Chengdu 610041, P. R. of China
b   Key Laboratory of General Chemistry of the National Ethnic Affairs Commission, College of Chemistry and Environment, Southwest Minzu University, Chengdu 610041, P. R. of China
c   Key Laboratory of Pollution Control Chemistry and Environmental Functional Materials for Qinghai-Tibet Plateau of the National Ethnic Affairs Commission, College of Chemistry and Environment, Southwest Minzu University, Chengdu 610041, P. R. of China
,
Ruiqiang Luo
a   College of Chemistry and Environment, Southwest Minzu University, Chengdu 610041, P. R. of China
b   Key Laboratory of General Chemistry of the National Ethnic Affairs Commission, College of Chemistry and Environment, Southwest Minzu University, Chengdu 610041, P. R. of China
c   Key Laboratory of Pollution Control Chemistry and Environmental Functional Materials for Qinghai-Tibet Plateau of the National Ethnic Affairs Commission, College of Chemistry and Environment, Southwest Minzu University, Chengdu 610041, P. R. of China
,
Qinghan Li∗
a   College of Chemistry and Environment, Southwest Minzu University, Chengdu 610041, P. R. of China
b   Key Laboratory of General Chemistry of the National Ethnic Affairs Commission, College of Chemistry and Environment, Southwest Minzu University, Chengdu 610041, P. R. of China
c   Key Laboratory of Pollution Control Chemistry and Environmental Functional Materials for Qinghai-Tibet Plateau of the National Ethnic Affairs Commission, College of Chemistry and Environment, Southwest Minzu University, Chengdu 610041, P. R. of China
,
Feng Chen
a   College of Chemistry and Environment, Southwest Minzu University, Chengdu 610041, P. R. of China
b   Key Laboratory of General Chemistry of the National Ethnic Affairs Commission, College of Chemistry and Environment, Southwest Minzu University, Chengdu 610041, P. R. of China
c   Key Laboratory of Pollution Control Chemistry and Environmental Functional Materials for Qinghai-Tibet Plateau of the National Ethnic Affairs Commission, College of Chemistry and Environment, Southwest Minzu University, Chengdu 610041, P. R. of China
› Author AffiliationsWe thank the Sichuan Provincial Department of Science and Technology support program (No. 2015NZ0033), the Fundamental Research Funds for the Central Universities, and the Southwest Minzu University (No. 2018NZD06) for financial support.
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Abstract

A highly efficient and simple route for the synthesis of 2-substituted benzo[b]furans has been developed by palladium-catalyzed cross-coupling reaction of 2-halobenzo[b]furans with aryl, alkynyl, and alkylaluminum reagents. Various 2-aryl-, 2-alkynyl-, and 2-alkyl-substituted benzo[b]furan derivatives can be obtained in 23–97% isolated yields using 2–3 mol% PdCl2/4–6 mol% XantPhos as the catalyst under mild reaction conditions. The aryls bearing electron-donating or electron-withdrawing groups in 2-halobenzo[b]furans gave products in 40–97% isolated yields. In addition, aluminum reagents containing thienyl, furanyl, trimethylsilanyl, and benzyl groups worked efficiently with 2-halobenzo[b]furans as well, and three bioactive molecules with 2-substituted benzo[b]furan skeleton were synthesized. Furthermore, the broad substrates scope and the typical maintenance of vigorous efficiency on gram scale make this protocol a potentially practical method to synthesize 2-substituted benzo[b]furan derivatives. On the basis of the experimental results, a possible catalytic cycle has been proposed.

Key words

2-substituted benzo[b]furans - palladium - organoalane reagents - 2-halobenzo[b]furan - cross-coupling reaction

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/a-1516-8745.
  • Supporting Information

Primary Data

    Primary data for this article are available online at https://zenodo.org/record/4972809 and can be cited using the following DOI: 10.5281/zenodo.4972809.



Publication History

Received: 07 May 2021

Accepted after revision: 25 May 2021

Accepted Manuscript online:
25 May 2021

Article published online:
24 June 2021

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