title: Mechanistic studies into amine-mediated electrophilic arene borylation and its application in MIDA boronate synthesis.
abstract: Direct electrophilic borylation using Y(2)BCl (Y(2) = Cl(2) or o-catecholato) with equimolar AlCl(3) and a tertiary amine has been applied to a wide range of arenes and heteroarenes. In situ functionalization of the ArBCl(2) products is possible with TMS(2)MIDA, to afford bench-stable and easily isolable MIDA-boronates in moderate to good yields. According to a combined experimental and computational study, the borylation of activated arenes at 20 °C proceeds through an S(E)Ar mechanism with borenium cations, [Y(2)B(amine)](+), the key electrophiles. For catecholato-borocations, two amine dependent reaction pathways were identified: (i) With [CatB(NEt(3))](+), an additional base is necessary to accomplish rapid borylation by deprotonation of the borylated arenium cation (σ complex), which otherwise would rather decompose to the starting materials than liberate the free amine to effect deprotonation. Apart from amines, the additional base may also be the arene itself when it is sufficiently basic (e.g., N-Me-indole). (ii) When the amine component of the borocation is less nucleophilic (e.g., 2,6-lutidine), no additional base is required due to more facile amine dissociation from the boron center in the borylated arenium cation intermediate. Borenium cations do not borylate poorly activated arenes (e.g., toluene) even at high temperatures; instead, the key electrophile in this case involves the product from interaction of AlCl(3) with Y(2)BCl. When an extremely bulky amine is used, borylation again does not proceed via a borenium cation; instead, a number of mechanisms are feasible including via a boron electrophile generated by coordination of AlCl(3) to Y(2)BCl, or by initial (heteroarene)AlCl(3) adduct formation followed by deprotonation and transmetalation.
authors.affiliation: Department of Chemistry, University of Manchester, Manchester, M13 9PL, United Kingdom.
authors.forename: Viktor
authors.initials: V
authors.lastname: Bagutski
authors.forename: Alessandro
authors.initials: A
authors.lastname: Del Grosso
authors.forename: Josue Ayuso
authors.initials: JA
authors.lastname: Carrillo
authors.forename: Ian A
authors.initials: IA
authors.lastname: Cade
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Helm
authors.forename: James R
authors.initials: JR
authors.lastname: Lawson
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Singleton
authors.forename: Sophia A
authors.initials: SA
authors.lastname: Solomon
authors.forename: Tommaso
authors.initials: T
authors.lastname: Marcelli
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Ingleson
mesh_terms: D000588:Amines / Q000737:chemistry*; D001896:Boron Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D006841:Hydrocarbons, Aromatic / Q000737:chemistry*; D007098:Imino Acids / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure
chemical_list: D000588:Amines; D001896:Boron Compounds; D006841:Hydrocarbons, Aromatic; D007098:Imino Acids; C533766:N-methyliminodiacetic acid