title: Unsymmetrical Diarylmethanes by Ferroceniumboronic Acid Catalyzed Direct Friedel-Crafts Reactions with Deactivated Benzylic Alcohols: Enhanced Reactivity due to Ion-Pairing Effects.
abstract: The development of general and more atom-economical catalytic processes for Friedel-Crafts alkylations of unactivated arenes is an important objective of interest for the production of pharmaceuticals and commodity chemicals. Ferroceniumboronic acid hexafluoroantimonate salt (1) was identified as a superior air- and moisture-tolerant catalyst for direct Friedel-Crafts alkylations of a variety of slightly activated and neutral arenes with stable and readily available primary and secondary benzylic alcohols. Compared to the use of classical metal-catalyzed alkylations with toxic benzylic halides, this methodology employs exceptionally mild conditions to provide a wide variety of unsymmetrical diarylmethanes and other 1,1-diarylalkane products in high yield with good to high regioselectivity. The optimal method, using the bench-stable ferroceniumboronic acid salt 1 in hexafluoroisopropanol as cosolvent, displays a broader scope compared to previously reported catalysts for similar Friedel-Crafts reactions of benzylic alcohols, including other boronic acids such as 2,3,4,5-tetrafluorophenylboronic acid. The efficacy of the new boronic acid catalyst was confirmed by its ability to activate primary benzylic alcohols functionalized with destabilizing electron-withdrawing groups like halides, carboxyesters, and nitro substituents. Arene benzylation was demonstrated on a gram scale at up to 1 M concentration with catalyst recovery. Mechanistic studies point toward the importance of the ionic nature of the catalyst and suggest that factors other than the Lewis acidity (pKa) of the boronic acid are at play. A SN1 mechanism is proposed where ion exchange within the initial boronate anion affords a more reactive carbocation paired with the non-nucleophilic hexafluoroantimonate counteranion.
authors.affiliation: †Department of Chemistry, Centennial Center for Interdisciplinary Science, University of Alberta, Edmonton, Alberta T6G 2G2, Canada.
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Mo
authors.affiliation: †Department of Chemistry, Centennial Center for Interdisciplinary Science, University of Alberta, Edmonton, Alberta T6G 2G2, Canada.
authors.forename: Joshua
authors.initials: J
authors.lastname: Yakiwchuk
authors.affiliation: †Department of Chemistry, Centennial Center for Interdisciplinary Science, University of Alberta, Edmonton, Alberta T6G 2G2, Canada.
authors.forename: Julien
authors.initials: J
authors.lastname: Dansereau
authors.affiliation: ‡Department of Chemistry, University of Winnipeg, Winnipeg, Manitoba R3B 2E9, Canada.
authors.forename: J Adam
authors.initials: JA
authors.lastname: McCubbin
authors.affiliation: †Department of Chemistry, Centennial Center for Interdisciplinary Science, University of Alberta, Edmonton, Alberta T6G 2G2, Canada.
authors.forename: Dennis G
authors.initials: DG
authors.lastname: Hall
mesh_terms: D019905:Benzyl Alcohol / Q000737:chemistry*; D001897:Boronic Acids / Q000737:chemistry*; D002384:Catalysis; D005296:Ferrous Compounds / Q000737:chemistry*; D008697:Methane / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure
chemical_list: D001897:Boronic Acids; D005296:Ferrous Compounds; D019905:Benzyl Alcohol; D008697:Methane