Synthesis of thiophene-based TAK-779 analogues by C-H arylation

Anna Junker, Junichiro Yamaguchi, Kenichiro Itami, Bernhard Wünsch

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

A rapid synthesis of thiophene-based TAK-779 analogues 1 is reported using a late-stage diversification strategy. At the end of the synthesis, the key building block 2, which was prepared in six steps from thiophene, was arylated regioselectively at the α-position directly with iodoarenes. Since 2 offers several reactive positions, various established catalyst systems were tested. It was found that Crabtree catalyst (an Ir catalyst) converted efficiently and selectively the thiophene system 2 into 2-aryl-substituted compounds 9. The direct C-H arylation of 2 with electron-rich iodoarenes led to high yields, whereas electron-deficient iodoarenes required longer reaction times for complete conversion. A small set of diverse amides 1 was synthesized by hydrolysis of 9 and subsequent HATU coupling with primary amines 4.

Original languageEnglish
Pages (from-to)5579-5586
Number of pages8
JournalJournal of Organic Chemistry
Volume78
Issue number11
DOIs
Publication statusPublished - 2013
Externally publishedYes

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Thiophenes
Catalysts
Electrons
Amides
Amines
Hydrolysis
TAK 779

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Synthesis of thiophene-based TAK-779 analogues by C-H arylation. / Junker, Anna; Yamaguchi, Junichiro; Itami, Kenichiro; Wünsch, Bernhard.

In: Journal of Organic Chemistry, Vol. 78, No. 11, 2013, p. 5579-5586.

Research output: Contribution to journalArticle

Junker, Anna ; Yamaguchi, Junichiro ; Itami, Kenichiro ; Wünsch, Bernhard. / Synthesis of thiophene-based TAK-779 analogues by C-H arylation. In: Journal of Organic Chemistry. 2013 ; Vol. 78, No. 11. pp. 5579-5586.
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