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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 24 th April 2012 Patrick Steel Department of Chemistry, Durham University, UK

∂ Why make aryl boronates? Hall, Boronic Acids, Wiley-VCH, 2 nd Ed 2011

∂ Why make aryl boronates? Hall, Boronic Acids, Wiley-VCH, 2 nd Ed 2011 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

∂ 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

∂ 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

∂ Iridium Catalysed Arene C-H Borylation Mkhalid, Barnard, Marder, Murphy, Hartwig, Chem. Rev., 2010, 110, 890

∂ Iridium Catalysed Arene C-H Borylation Mkhalid, Barnard, Marder, Murphy, Hartwig, Chem. Rev., 2010, 110, 890

∂ 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

∂ SolventTemp ( ˚C)Time (h)GC-MS Conversion (%) DMF8060 1,4-dioxane80625 MeCN MeTHF80685 MTBE One-pot C-H Borylation/Suzuki-Miyaura Cross-Coupling Peter Harrisson

∂ One-pot C-H Borylation/Suzuki-Miyaura Cross-Coupling

∂ Peter Harrisson One-pot C-H Borylation/Suzuki-Miyaura Cross-Coupling

∂ Peter Harrisson One-pot C-H Borylation/Suzuki-Miyaura Cross-Coupling

∂ Peter Harrisson One-pot C-H Borylation/Suzuki-Miyaura Cross-Coupling

∂ Peter Harrisson Microwave Accelerated “One-Pot” Biaryl Synthesis

∂ Challenges for Ir-Catalysed Arene C-H Borylation Regiocontrol

∂ Challenges for Ir-Catalysed Arene C-H Borylation Heterocyclic Organoboronic Acids Data – Courtesy David Blakemore Pfizer - Neusentis

∂ Challenges for the Synthesis of Heterocyclic Boronate Esters

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∂ Peter Harrisson Quinoline Boronate Esters

∂ Where Now for ‘Cleaner Greener’ Aromatic C-H Borylation? Other sequential chemistries Faster more effective Catalysts. Better ligand sets to control regiochemistry.

∂ 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????

∂ Hazmi Tajuddin Alkyl Boronate Esters via Cu-Catalysed C-X Activation

∂ 2012 Durham Lectures Monday 14 th May Tuesday 15 th May Wednesday 16 th May Department of Chemistry, Durham University All Lectures Commence at 4pm – Visitors Welcome For Further Details Prof John Hartwig University of California, Berkeley

∂ Understanding and Optimising Chemical Processes 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. Further Information & Registration Contact: Matthew Linsley, ISRU, Newcastle University 2 nd & 3 rd July 2012 Department of Chemistry Durham University Keynote Speaker Martin Owen Product Development, GlaxoSmithKline, Stevenage 29

∂ Acknowledgements Peter Harrisson Hazmi Tajuddin Bianca Bitterlich Prof Lei Liu (Tsinghua University, Beijing) Prof Todd Marder James Morris (Syngenta) Aoife Maxwell (GSK) Lena Shukla (GSK) Alan Kenwright (NMR) Jackie Mosely (MS) Andrei Batsanov (X-ray)

∂ Understanding and Optimising Chemical Processes 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. Further Information & Registration Contact: Matthew Linsley, ISRU, Newcastle University 2 nd & 3 rd July 2012 Department of Chemistry Durham University Keynote Speaker Martin Owen Product Development, GlaxoSmithKline, Stevenage 31

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