Efficient Catalytic Syntheses of Organoboronate Esters

2. 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@durham.ac.uk

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

4. 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

5. Classical Aryl Boronate Synthesis a Sustainable Chemistry Challenge? Asher et al., Tetrahedron Lett., 2003, 44, 7719 Snieckuset al., J. Org. Chem., 2009, 74, 4094

6. Functional Group Tolerant Aryl Boronate Synthesis Ishiyama, Miyauraet al., J. Org. Chem., 1995, 60,7508 Kleeberg, Marder et al., Angew. Chem. Int. Ed., 2009, 48, 5350

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

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

9. Iridium Catalysed Borylation – An Atom Economical Process

10. Iridium Catalysed Borylation – An Atom Economical Process

11. Iridium Catalysed Borylation – An Atom Economical Process

12. ‘One-pot’ Transformations from Arenes Maleczka, Smith et al., Tetrahedron, 2008, 64, 6103 Ishiyama, Miyaura et al., Tetrahedron, 2008, 64, 4967

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

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

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

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

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

18. Microwave Accelerated “One-Pot” Biaryl Synthesis Peter Harrisson

19. Challenges for Ir-Catalysed Arene C-H Borylation Regiocontrol

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

21. Challenges for the Synthesis of Heterocyclic Boronate Esters

22. Challenges for the Synthesis of Heterocyclic Boronate Esters

23. Quinoline Boronate Esters Peter Harrisson

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

25. Where Now for ‘Cleaner Greener’ Aromatic C-H Borylation?

26. 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????

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

28. 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@durham.ac.uk

29. ISRU 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@newcastle.ac.uk

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

31. ISRU 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@newcastle.ac.uk