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Efficient Catalytic Syntheses of Organoboronate
Esters Ubiquitous building blocks for the fine
chemical and pharmaceutical industries NORSC
Sustainable Chemistry Initiative Ramside Hall,
Durham 24th April 2012 Patrick Steel Department
of Chemistry, Durham University,
UK p.g.steel_at_durham.ac.uk
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Why make aryl boronates?
Hall, Boronic Acids, Wiley-VCH, 2nd Ed 2011
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Why make aryl boronates?

• Non-toxic
• Tolerant to air and water
• Stable in the absence of a catalyst
• React under mild conditions
• Reaction by-product is inert and benign to humans

Hall, Boronic Acids, Wiley-VCH, 2nd Ed 2011
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Classical Aryl Boronate Synthesis a Sustainable
Chemistry Challenge?
Asher et al., Tetrahedron Lett., 2003, 44, 7719
Snieckus et al., J. Org. Chem., 2009, 74, 4094
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Functional Group Tolerant Aryl Boronate Synthesis
Ishiyama, Miyaura et al., J. Org. Chem., 1995,
60, 7508
Kleeberg, Marder et al., Angew. Chem. Int. Ed.,
2009, 48, 5350
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Iridium Catalysed Arene C-H Borylation
Mkhalid, Barnard, Marder, Murphy, Hartwig, Chem.
Rev., 2010, 110, 890
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Iridium Catalysed Arene C-H Borylation
Mkhalid, Barnard, Marder, Murphy, Hartwig, Chem.
Rev., 2010, 110, 890
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Iridium Catalysed Borylation An Atom Economical
Process
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Iridium Catalysed Borylation An Atom Economical
Process
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Iridium Catalysed Borylation An Atom Economical
Process
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One-pot Transformations from Arenes
Maleczka, Smith et al., Tetrahedron, 2008, 64,
6103
Ishiyama, Miyaura et al., Tetrahedron, 2008, 64,
4967
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One-pot C-H Borylation/Suzuki-Miyaura
Cross-Coupling
Solvent Temp ( C) Time (h) GC-MS Conversion ()
DMF 80 6 0
1,4-dioxane 80 6 25
MeCN 80 6 37
2-MeTHF 80 6 85
MTBE 80 6 100
Peter Harrisson
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One-pot C-H Borylation/Suzuki-Miyaura
Cross-Coupling
Peter Harrisson
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One-pot C-H Borylation/Suzuki-Miyaura
Cross-Coupling
Peter Harrisson
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One-pot C-H Borylation/Suzuki-Miyaura
Cross-Coupling
Peter Harrisson
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One-pot C-H Borylation/Suzuki-Miyaura
Cross-Coupling
Peter Harrisson
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Microwave Accelerated One-Pot Biaryl Synthesis
Peter Harrisson
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Challenges for Ir-Catalysed Arene C-H
Borylation Regiocontrol
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Challenges for Ir-Catalysed Arene C-H
Borylation Heterocyclic Organoboronic Acids
Data Courtesy David Blakemore Pfizer - Neusentis
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Challenges for the Synthesis of Heterocyclic
Boronate Esters
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Challenges for the Synthesis of Heterocyclic
Boronate Esters
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Quinoline Boronate Esters
Peter Harrisson
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Where Now for Cleaner Greener Aromatic C-H
Borylation?
Other sequential chemistries Faster more
effective Catalysts. Better ligand sets to
control regiochemistry.
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Where Now for Cleaner Greener Aromatic C-H
Borylation?
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Where Now for Cleaner Greener Aromatic C-H
Borylation?
Other sequential chemistries Faster more
effective Catalysts. Better ligand sets to
control regiochemistry. Cheaper metals than Ir
Cu????
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Alkyl Boronate Esters via Cu-Catalysed C-X
Activation
Hazmi Tajuddin
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2012 Durham Lectures
Prof John Hartwig University of California,
Berkeley

Monday 14th May Tuesday 15th May Wednesday 16th
May Department of Chemistry, Durham
University All Lectures Commence at 4pm
Visitors Welcome For Further Details
p.g.steel_at_durham.ac.uk
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Understanding and Optimising Chemical Processes
2nd 3rd July 2012 Department of
Chemistry Durham University
This two-day programme provides delegates with an
opportunity to augment their process knowledge
using Principal Components Analysis (PCA) and
Design of Experiments (DoE) methodologies to
expand process understanding, establish and
develop capability, ensure robust and in-control
processes, improve quality and reduce operational
and environmental costs.
Keynote Speaker Martin Owen Product Development,
GlaxoSmithKline, Stevenage
Further Information Registration Contact
Matthew Linsley, ISRU, Newcastle
University matthew.linsley_at_newcastle.ac.uk
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Acknowledgements
Prof Todd Marder

Peter Harrisson Hazmi Tajuddin Bianca
Bitterlich Prof Lei Liu (Tsinghua University,
Beijing)
James Morris (Syngenta) Aoife Maxwell (GSK) Lena
Shukla (GSK)
Alan Kenwright (NMR) Jackie Mosely (MS) Andrei
Batsanov (X-ray)
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Understanding and Optimising Chemical Processes
2nd 3rd July 2012 Department of
Chemistry Durham University
This two-day programme provides delegates with an
opportunity to augment their process knowledge
using Principal Components Analysis (PCA) and
Design of Experiments (DoE) methodologies to
expand process understanding, establish and
develop capability, ensure robust and in-control
processes, improve quality and reduce operational
and environmental costs.
Keynote Speaker Martin Owen Product Development,
GlaxoSmithKline, Stevenage
Further Information Registration Contact
Matthew Linsley, ISRU, Newcastle
University matthew.linsley_at_newcastle.ac.uk
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