Practical Organocatalytic Synthesis of Functionalized Non-C2-Symmetrical Atropisomeric Biaryls

Hongyin Gao, Qing Long Xu, Craig Keene, Muhammed Yousufuddin, Daniel H. Ess, Lászlõ Kürti

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

An organic acid catalyzed direct arylation of aromatic C(sp2)H bonds in phenols and naphthols for the preparation of 1,1′-linked functionalized biaryls was developed. The products are non-C2-symmetrical, atropoisomeric, and represent previously untapped chemical space. Overall this transformation is operationally simple, does not require an external oxidant, is readily scaled up (up to 98mmol), and the structurally diverse 2,2′-dihydroxy biaryl (i.e., BINOL-type), as well as 2-amino-2′-hydroxy products (i.e., NOBIN-type) are formed with complete regioselectivity. Density-functional calculations suggest that the quinone and imino-quinone monoacetal coupling partners are exclusively arylated at their α-position by an asynchronous [3,3]-sigmatropic rearrangement of a mixed acetal species which is formed insitu under the reaction conditions. An organic acid catalyzed direct arylation of aromatic C(sp2)H bonds in phenols and naphthols was developed. This transformation is operationally simple, does not require an external oxidant, is readily scaled up, and the structurally diverse biaryls are formed with complete regioselectivity. Density functional calculations suggest a mechanism involving a mixed-acetal formation/[3,3]-sigmatropic rearrangement sequence.

Original languageEnglish (US)
Pages (from-to)566-571
Number of pages6
JournalAngewandte Chemie - International Edition
Volume55
Issue number2
DOIs
StatePublished - Jan 11 2016

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Naphthols
Naphthol
Regioselectivity
Acetals
Phenols
Organic acids
Oxidants
Density functional theory
benzoquinone
naphthol BINOL

Keywords

  • atropisomerism
  • biaryls
  • organocatalysis
  • rearrangements
  • synthetic methods

ASJC Scopus subject areas

  • Chemistry(all)
  • Catalysis

Cite this

Practical Organocatalytic Synthesis of Functionalized Non-C2-Symmetrical Atropisomeric Biaryls. / Gao, Hongyin; Xu, Qing Long; Keene, Craig; Yousufuddin, Muhammed; Ess, Daniel H.; Kürti, Lászlõ.

In: Angewandte Chemie - International Edition, Vol. 55, No. 2, 11.01.2016, p. 566-571.

Research output: Contribution to journalArticle

Gao, Hongyin ; Xu, Qing Long ; Keene, Craig ; Yousufuddin, Muhammed ; Ess, Daniel H. ; Kürti, Lászlõ. / Practical Organocatalytic Synthesis of Functionalized Non-C2-Symmetrical Atropisomeric Biaryls. In: Angewandte Chemie - International Edition. 2016 ; Vol. 55, No. 2. pp. 566-571.
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