Catalytic Friedel–Crafts Reactions of Highly Electronically Deactivated Benzylic Alcohols

• Published in: Angewandte Chemie International Edition Vol. 56; no. 11; pp. 3085 - 3089
• Main Authors: Vuković, Vuk D., Richmond, Edward, Wolf, Eléna, Moran, Joseph
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 06.03.2017; Wiley Subscription Services, Inc; Wiley-VCH Verlag
• Edition: International ed. in English
• Subjects: Acids; Alcohol; Alcohols; Brønsted acid catalysis; carbenium ion; Catalysis; Chemical Sciences; Chemistry; Chemistry, Multidisciplinary; Deactivation; Dehydration; Friedel-Crafts reaction; Friedel–Crafts; hexafluoro-2-propanol; Organic chemistry; Physical Sciences; Propanol; Science & Technology; Titration; SUBSTITUTION; HEXAFLUOROISOPROPANOL; carbenium ion; CARBOCATIONS; PI-ACTIVATED ALCOHOLS; ALKYLATION; alcohols; AROMATIC-COMPOUNDS; SULFONATES; Bronsted acid catalysis; PROPARGYLIC ALCOHOLS; Friedel-Crafts; hexafluoro-2-propanol; FLUORINATED ALCOHOLS; CATION REACTIVITY; Brønsted acid catalysis
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201612573

Highly electronically deactivated benzylic alcohols, including those with a CF3 group adjacent to the OH‐bearing carbon, undergo dehydrative Friedel–Crafts reactions upon exposure to catalytic Brønsted acid in 1,1,1,3,3,3‐hexafluoro‐2‐propanol (HFIP) solvent. Titration and kinetic experiments support the involvement of higher order solvent/acid clusters in catalysis. More than a solvent: The use of the fluorinated solvent 1,1,1,3,3,3‐hexafluoro‐2‐propanol (HFIP) and a catalytic amount of a strong Brønsted acid enables dehydrative Friedel–Crafts reactions of highly deactivated benzylic alcohols. Mixed aggregates of acid and HFIP are likely to be involved in the catalysis.