Mechanistic insights into entropy-driven 1,2-type Friedel-Crafts reaction with conformationally flexible guanidine-bisthiourea bifunctional organocatalysts

Katsuhiro Nakano, Tatsuya Orihara, Masaki Kawaguchi, Keisuke Hosoya, Shogo Hirao, Ryosuke Tsutsumi, Masahiro Yamanaka, Minami Odagi, Kazuo Nagasawa

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

In some asymmetric catalytic reactions, the enantio-discrimination step is dominated by the change in entropy, in contrast to the usual enthalpy-driven process, but the origin of this entropy-dependent behavior is unclear. Here, we first conducted Eyring analysis to confirm the entropy-driven character of our previously reported 1,2-type Friedel-Crafts (FC) reaction of sesamol with imine, catalyzed by conformationally flexible guanidine-bisthiourea bifunctional organocatalyst, and then we carried out computational studies to compare the transition states leading to the two enantiomers. We found no significant temperature dependence of ΔH or -TΔS for TS-R, the transition state leading to the R enantiomer. In TS-S, on the other hand, -TΔS was increased at higher temperature, although ΔH was unchanged. Furthermore, the benzyl groups of the catalyst increase the contribution of the enthalpy term to the enantioselectivity, albeit with retention of the entropy-driven behavior arising from the conformationally flexible catalyst structure.

Original languageEnglish
Article number132281
JournalTetrahedron
Volume92
DOIs
Publication statusPublished - 2021 Jul 16
Externally publishedYes

Keywords

  • DFT calculation
  • Entropy
  • Friedel-crafts reaction
  • Guanidine
  • Organocatalyst

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

Fingerprint

Dive into the research topics of 'Mechanistic insights into entropy-driven 1,2-type Friedel-Crafts reaction with conformationally flexible guanidine-bisthiourea bifunctional organocatalysts'. Together they form a unique fingerprint.

Cite this