title: C(sp2)-H Borylation of Fluorinated Arenes Using an Air-Stable Cobalt Precatalyst: Electronically Enhanced Site Selectivity Enables Synthetic Opportunities.
abstract: Cobalt catalysts with electronically enhanced site selectivity have been developed, as evidenced by the high ortho-to-fluorine selectivity observed in the C(sp2)-H borylation of fluorinated arenes. Both the air-sensitive cobalt(III) dihydride boryl 4-Me-(iPrPNP)Co(H)2BPin (1) and the air-stable cobalt(II) bis(pivalate) 4-Me-(iPrPNP)Co(O2CtBu)2(2) compounds were effective and exhibited broad functional group tolerance across a wide range of fluoroarenes containing electronically diverse functional groups, regardless of the substitution pattern on the arene. The electronically enhanced ortho-to-fluorine selectivity observed with the cobalt catalysts was maintained in the presence of a benzylic dimethylamine and hydrosilanes, overriding the established directing-group effects observed with precious-metal catalysts. The synthetically useful selectivity observed with cobalt was applied to an efficient synthesis of the anti-inflammatory drug flurbiprofen.
authors.affiliation: Department of Chemistry, Princeton University , New Jersey 08544, United States.
authors.forename: Jennifer V
authors.initials: JV
authors.lastname: Obligacion
authors.affiliation: Department of Chemistry, Princeton University , New Jersey 08544, United States.
authors.forename: Máté J
authors.initials: MJ
authors.lastname: Bezdek
authors.affiliation: Department of Chemistry, Princeton University , New Jersey 08544, United States.
authors.forename: Paul J
authors.identifier: 0000-0001-8473-2898
authors.initials: PJ
authors.lastname: Chirik
mesh_terms: D000388:Air; D000475:Alkenes / Q000737:chemistry*; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry; D001895:Boron / Q000737:chemistry*; D002384:Catalysis; D003035:Cobalt / Q000737:chemistry*; D004355:Drug Stability; D005480:Flurbiprofen / Q000138:chemical synthesis / Q000737:chemistry; D054879:Halogenation; D007495:Iridium / Q000737:chemistry*; D015394:Molecular Structure
chemical_list: D000475:Alkenes; D000893:Anti-Inflammatory Agents; D003035:Cobalt; D007495:Iridium; D005480:Flurbiprofen; D001895:Boron