Catalytic and Enantioselective Synthesis of Chiral Multisubstituted Tribenzothiepins by Intermolecular Cycloadditions

• Published in: Angewandte Chemie International Edition Vol. 55; no. 14; pp. 4552 - 4556
• Main Authors: Tahara, Yu-ki, Matsubara, Riku, Mitake, Akihito, Sato, Tatsuki, Kanyiva, Kyalo Stephen, Shibata, Takanori
• Format: Journal Article
• Language: English
• Published: WEINHEIM Blackwell Publishing Ltd 24.03.2016; Wiley; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Chemistry; Chemistry, Multidisciplinary; chirality; cycloaddition; enantioselectivity; Physical Sciences; rhodium; Science & Technology; synthetic methods; enantioselectivity; D-2-SYMMETRIC DIMER; cycloaddition; ASYMMETRIC-SYNTHESIS; HEXAYNES; chirality; THIAAZULENOCYCLONE; CONSTRUCTION; INTRAMOLECULAR CYCLOADDITIONS; synthetic methods; rhodium; DIYNES
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201511876

The first catalytic and highly enantioselective synthesis of tribenzothiepin derivatives was achieved. Two types of intermolecular cycloadditions using either diphenyl‐sulfide‐tethered diynes or 2‐phenyl sulfanylbenzene‐tethered diynes with a monoalkyne successfully gave chiral multisubstituted tribenzothiepins in good to excellent ee values under mild conditions. The inversion energy of this saddle‐shaped molecule was calculated by measurement of the racemization rate of chiral tribenzothiepins using the Eyring kinetic equation under heating conditions. The present protocol could also be used to prepare a chiral tribenzoselenepin. End of the tether: The first catalytic and highly enantioselective synthesis of tribenzothiepin derivatives was achieved. Two types of intermolecular cycloadditions, either using diphenyl‐sulfide‐tethered diynes or 2‐phenyl sulfanylbenzene tethered diynes with a monoalkyne, led to chiral multisubstituted tribenzothiepins in good to excellent ee values under mild reaction conditions. The present protocol was used to prepare a chiral tribenzoselenepin.