Linking Conformational Flexibility and Kinetics: Catalytic 1,4‐Type Friedel–Crafts Reactions of Phenols Utilizing 1,3‐Diamine‐Tethered Guanidine/Bisthiourea Organocatalysts |
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| Authors: | Dr Yoshihiro Sohtome Bongki Shin Natsuko Horitsugi Prof?Dr Keiichi Noguchi Prof?Dr Kazuo Nagasawa |
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| Institution: | 1. Department of Biotechnology and Life Science, Faculty of Technology, Tokyo University of Agriculture and Technology, 2‐24‐16 Naka‐cho, Koganei, Tokyo 184‐8588 (Japan), Fax: (+81)?42‐388‐7295;2. Present address: RIKEN Advanced Science Institute, 2‐1 Hirosawa, Wako‐shi Saitama 351‐0198 (Japan), Fax: (+81)?48‐467‐4666;3. Instrumentation Analysis Center, Tokyo University of Agriculture and Technology Institution, 2‐24‐16 Naka‐cho, Koganei, Tokyo 184‐8588 (Japan) |
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| Abstract: | Herein, we present details of our conformationally flexible, 1,3‐diamine‐tethered guanidine/bisthiourea organocatalysts for chemo‐, regio‐, and enantioselective 1,4‐type Friedel–Crafts reactions of phenols. These organocatalysts show a unique stereo‐discrimination governed by the differential activation entropy (ΔΔS≠), rather than by the differential activation enthalpy (ΔΔH≠). Extensive kinetic analyses using Eyring plots for a series of guanidine/bisthiourea organocatalysts revealed the key structural motif in the catalysts associated with a large magnitude of differential activation entropy (ΔΔS≠). A plausible guanidine–thiourea cooperative mechanism for the enantioselective Friedel–Crafts reaction is proposed. |
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| Keywords: | asymmetric synthesis entropy Friedel– Crafts reaction organocatalysis phenols |
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