Thiourea Derivatives as Brønsted Acid Organocatalysts

Ádám Madarász, Zsolt Dósa, Szilárd Varga, Tibor Soós, Antal Csámpai, Imre Pápai

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40 Citations (Scopus)

Abstract

Combined computational-experimental studies were carried out to parallel two mechanistic models for tetrahydropyranylation of alcohols catalyzed by Schreiner's thiourea. The results challenge the common mechanistic view that the catalytic effect is related to stabilizing double hydrogen-bonding interactions between the thiourea and the alcohol, which promote the attack on 3,4-dihydro-2H-pyran (DHP) (hydrogen bonding (HB) mechanism). In the alternative mechanism that we propose, thiourea acts as a Brønsted acid, protonating DHP to form an oxacarbenium ion, which reacts with the alcohol (Brønsted acid (BA) mechanism). Computations point to clear preference of transition states associated with the BA mechanism and, accordingly, predict similar catalytic activity for N-methylated thiourea and thiouracil. These predictions are confirmed experimentally. Reactions with deuterated alcohols yield both syn and anti products, providing further support for the Brønsted acid mechanism.

Original languageEnglish
Pages (from-to)4379-4387
Number of pages9
JournalACS Catalysis
Volume6
Issue number7
DOIs
Publication statusPublished - Jul 1 2016

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Keywords

  • acid-base catalysis
  • computational analysis
  • hydrogen bonding interactions
  • mechanism
  • organocatalysis
  • tetrahydropyranylation
  • thiourea

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)

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