Mechanistic insights into entropy-driven 1, 2-type Friedel-Crafts reaction with conformationally flexible guanidine-bisthiourea bifunctional organocatalysts. (16th July 2021)

• Record Type: Journal Article
• Authors: Nakano, Katsuhiro; Orihara, Tatsuya; Kawaguchi, Masaki; Hosoya, Keisuke; Hirao, Shogo; Tsutsumi, Ryosuke; Yamanaka, Masahiro; Odagi, Minami; Nagasawa, Kazuo
• Is Part Of: Tetrahedron. Volume 92(2021)
• Publication Date: 2021-07-16
• Subjects: Organocatalyst -- Guanidine -- Entropy -- Friedel-crafts reaction -- DFT calculation; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tet.2021.132281
• Languages: English
• ISSNs: 0040-4020

Abstract

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 -T ΔS for TS- R, the transition state leading to the R enantiomer. In TS- S, on the other hand, -T ΔS 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. Graphical abstract: Image 1