Direct activation of alcohols via perrhenate ester formation for an intramolecular dehydrative Friedel–Crafts reaction. Issue 16 (1st July 2022)

• Record Type: Journal Article
• Authors: Zheng, Yuzhu; Fang, Xiong; Deng, Wen-Hao; Zhao, Bin; Liao, Rong-Zhen; Xie, Youwei
• Is Part Of: Organic chemistry frontiers. Volume 9:Issue 16(2022)
• Page Start: 4277
• Page End: 4286
• Publication Date: 2022-07-01
• Subjects: Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1039/d2qo00229a
• Languages: English
• ISSNs: 2052-4110

Abstract

Abstract : A general and highly efficient intramolecular dehydrative Friedel–Crafts reactions via Re2 O7 mediated hydroxyl group activation is described for the syntheses of tetrahydronaphthalene, tetrahydroquinoline, tetrahydroisoquinoline, chromane, and isochromane derivatives. Abstract : This manuscript describes a general method for the intramolecular dehydrative Friedel–Crafts reaction of alcohols catalyzed by Re2 O7 in hexafluoroisopropanol (HFIP). Under the optimized conditions, δ-aryl alcohols react with high efficiency to give various pharmaceutically significant organic scaffolds, such as tetrahydronaphthalene, tetrahydroquinoline, tetrahydroisoquinoline, chromane, and isochromane derivatives. The potential application of this methodology was exemplified by the formal or total synthesis of several commercially available drugs or biologically relevant molecules, including sertraline, nafenopin, etc . DFT calculations showed the preference for the activation of hydroxyl groups by Re2 O7 via perrhenate ester formation followed by heterolytic C–O bond cleavage over Brønsted acid-catalyzed dehydration.