University of Illinois Urbana-Champaign

Iridium-catalyzed borylation of aromatic and aliphatic C-H bonds: methodology and mechanism

Liskey, Carl

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https://hdl.handle.net/2142/45525

Description

Title
Iridium-catalyzed borylation of aromatic and aliphatic C-H bonds: methodology and mechanism
Author(s)
Liskey, Carl
Issue Date
2013-08-22T16:43:10Z
Director of Research (if dissertation) or Advisor (if thesis)
Hartwig, John F.
Doctoral Committee Chair(s)
Hartwig, John F.
Committee Member(s)
  • Denmark, Scott E.
  • Rauchfuss, Thomas B.
  • Hergenrother, Paul J.
Department of Study
Chemistry
Discipline
Chemistry
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Date of Ingest
2013-08-22T16:43:10Z
Keyword(s)
  • borylation
  • C-H borylation
  • C-H activation
  • iridium
  • iridium-catalyzed borylation
Abstract
A method to conduct the one-pot, meta cyanation of arenes by iridium-catalyzed C-H borylation and copper-mediated cyanation of the resulting arylboronate esters is described in Chapter 2. This process relies on a previously unknown method to conduct the cyanation of arylboronic esters, and conditions for this new transformation are reported. Conditions for the copper-mediated cyanation of arylboronic acids are also reported. By the resulting sequence of borylation and cyanation, 1,3-disubstituted and 1,2,3-trisubstituted arenes and heteroarenes containing halide, ketone, ester, amide and protected alcohol functionality are converted to the corresponding meta-substituted aryl nitriles. The utility of this methodology is demonstrated through the conversion of a protected 2,6-disubstituted phenol to 4-cyano-2,6-dimethylphenol, which is an intermediate in the synthesis of the pharmaceutical Etravirine. The utility of the method is further demonstrated by the conversion of 3-chloro-5-methylbenzonitrile, produced through the one-pot C-H borylation and cyanation sequence, to the corresponding 3,5-disubstituted aldehydes, ketones, amides, carboxylic acids, tetrazoles, and benzyl amines. The properties and reactivities of iridium-trisboryl complexes containing different ancillary ligands and boryl ligands are reported in Chapter 3. A large difference in reactivity towards the borylation of C-H bonds is observed for a series of trisboryl complexes, and this difference is attributed to the electron-donating properties of the pinacolate vs. catecholate groups on the boryl ligands, and the steric and electronic properties of bipyridine vs. bisphosphine ancillary ligands. In addition, other boron reagents besides the common bis(piacolato)diboron were studied in the C-H borylation of arenes. A different diboron reagent, bis(hexyleneglycol)diboron, reacts with arenes to form arylboronate esters in good yields. The borylation of secondary C-H bonds, specifically secondary C-H bonds of cyclic ethers, with a catalyst generated from tetramethylphenanthroline and an iridium precursor is reported in Chapter 4. This borylation occurs with unique selectivity for the C-H bonds located β to the oxygen atoms over the weaker C-H bonds located α to oxygen atoms. Mechanistic studies imply that the C-H bond cleavage occurs directly at the β position rather than at the α position followed by isomerization of a reaction intermediate. The preparation of aminoalkyl and alkoxyalkylboronate esters is described in Chapter 5. The products of these reactions directly undergo Suzuki-Miyaura cross-coupling reactions. Alternatively, the products can be isolated as air stable potassium trifluoroborate salts. Selective borylation between similar methyl groups is observed, based on subtle differences in the electronic properties of the substrate. Finally, the borylation of cyclopropanes catalyzed by the combination of (η6-mes)IrBpin3 or [Ir(COD)OMe]2 and a phenanthroline derivative is reported in Chapter 6. The borylation occurs selectively at the methylene C-H bonds of the cyclopropane ring over methine or methyl C-H bonds. High diasteroselectivities were observed from reactions catalyzed by the combination of iridium and 2,9-Me2-phenanthroline. The cyclopropylboronate esters that are generated are versatile synthetic intermediates that can be converted to trifluoroborate salts, boronic acids, cyclopropylarenes, cyclopropylamines, and cyclopropanols.
Graduation Semester
2013-08
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http://hdl.handle.net/2142/45525
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Copyright 2013 Carl Liskey

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