Metal Free Catalytic Electrophilic Borylation

  • John Mcgough

Student thesis: Phd


In this thesis, the use of electrophilic boron reagents, generated from a catalytic amount of activator, in new carbon – carbon bond forming reactions is described. The first reaction developed herein is a trans-hydroboration reaction, being the stereo-chemically diverse equivalent of the classical cis-hydroboration. The adduct of 9-BBN and an NHC or MIC are activated with B(C6F5)3 to give borenium salts, which react with terminal alkynes in the presence of hydride donor to give the 1,2-trans-hydrobrated alkene product, which are characterised by 2-D NMR and X-ray crystallographic studies. Using a sterically small, less electron donating carbene species, the reaction turns over efficiently, allowing the use of only 5 mol% of the activator. This reaction is shown to hydroborate a range of terminal aryl acetylene species in high yields, with simple isolation methods which obviate the need for column chromatography. In addition, the limits of the reactivity are tested with alkyl acetylene and internal alkynes, and the key deactivation pathways are probed, with decomposition products being isolated and characterised. A full mechanistic study has been carried out to show the origin of selectivity and the 1,2- nature of the addition. The products from trans-hydroboration are air and moisture stable solids, which are readily de-protected by NHC removal to give species for use in the Suzuki-Miyaura cross coupling reaction. The need for strongly binding substituents on the boron centre is emphasised by the reactions of CatB-Amine and 9-BBN-amine species, which are not active in trans-hydroboration. The second reaction described is the borylation of heteroarenes using air and moisture stable carbene boranes activated with substoichiometric levels of iodine. This reaction proceeds at high temperature to give moderate yields of borylated indole and thiophene derivatives. In the reaction with indoles, the products are characterised as the C2- borylated species, as confirmed by 2-D NMR studies and X-Ray crystallography. The mechanism behind the regio-selectivity has been studied, including the formation of C3 isomer, and its in-situ isomerisation to the C2 isomer under the reaction conditions is described. Also described is the privileged nature of iodine as the initiator for this reaction, with strong Brønsted acid species or hydriophiles (species which have a high affinity for hydride) not being competent activators in this chemistry. The steric parameters of the NHC ligand are shown to play a key part in the chemistry, with the smallest carbenes showing deleterious a side reaction (one boron centre borylating 2 indole species). Larger carbenes show increased selectivity for the products, and the largest carbenes exhibit no reactivity due to increased kinetic barriers to reaction, and this is parametrised by calculation of representative buried volumes for the carbene-borane species used. The mechanism for this reaction is investigated using deuteration studies, rationalising the reactivity, substrate scope and selectivity seen.
Date of Award1 Aug 2017
Original languageEnglish
Awarding Institution
  • The University of Manchester
SupervisorMichael Ingleson (Supervisor) & David Mills (Supervisor)

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