BioPartnering 2006 PowerPoint Presentation

1. PEPPSI  Catalysts and Beyond: Highly Efficient Pd Catalysts for C  C and C  X Bond Formation Aaron G. Maestri, Ph.D. Product Manager - Catalysis Sigma-Aldrich Corporation Presented at the BioParterning Meetings, 2006

4. PEPPSI  is Readily Activated in situ enhance basicity of catalyst Coordinatively saturate the metal Increase the steric environment around the metal

7. PEPPSI  -IPr Exhibits Broad Utility in C–C and C–X Bond Forming Reactions

8. PEPPSI  Results in the Negishi Reaction: sp 3 -sp 3 couplings Organ, M. G. et al. Chem. Eur. J. 2006 , 12 , 4749.

9. Negishi Couplings – Extending PEPPSI  -IPr Versatility  sp 2 – sp 3 :  sp 3 – sp 2 : Organ, M. G. et al. Chem. Eur. J. 2006 , 12 , 4749.

10. Negishi Couplings – Execution of the Full Reaction Scope  sp 2 – sp 2 : Organ, M. G. et al. Chem. Eur. J. 2006 , 12 , 4749.

11. PEPPSI  Results in the Suzuki Reaction  sp 2 – sp 2 : Organ, M. G. et al. Chem. Eur. J. 2006 , 12 , 4743.

12. PEPPSI  Results in the Buchwald- Hartwig Amination Reaction • Alkyl amines readily transformed; anilines not so well Organ, M. G. et al. manuscript in preparation.

13. Extending PEPPSI  Reactivity in the Buchwald-Hartwig Amination Reaction • Aryl chlorides only • All reactions complete at room temperature Organ, M. G. et al. manuscript in preparation.

14. Kumada-Tamao-Corriu Coupling • Coupling works well at room temperature Organ, M. G. et al. Chem. Eur. J. 2006 , Accepted.

15. Kumada-Tamao-Corriu Coupling: Exploiting PEPPSI  ’s High Activity  First room temperature tetra ortho substituted cross coupling reported of any kind  Sequential Coupling Chemistry Organ, M. G. et al. Chem. Eur. J. 2006 , Accepted.

16. PEPPSI  Competition Experiment • PEPPSI- IPr is very reactive relative to other known strong catalysts in the literature

17. Heck-Amination Sequence - PEPPSI  Exhibits Robust Microwave Behavior • Yields > 75%, small library of 20 indoles prepared

18. Sonagashira Coupling – is PEPPSI  Versatile? • 1° Alkyl Centers: • 2° Alkyl Centers:

19. Enolate Arylation – Extending PEPPSI  Utility Under Mild Conditions

20. Hiyama Coupling • Note that the reaction of silanol and their respective Sodium salts are efficiently promoted in this reaction. • The Silanoates are available as a convenient solid that can be stored and dispensed directly into the reaction

21. What About Scale-up?? • Buchwald-Hartwig on Scale • Work Up • 1) filter thru Celite, 2) extract into acid, 3) titrate until basic 4) back extract into ether, 5) dry and remove solvent 26.5 G! 10 G! • Suzuki on Scale 10 G! • Kumada on Scale

22. Pd(AmPhos) 2 Cl 2 : A Highly Efficient, Air-Stable Catalyst for the Heteroaryl Suzuki Reaction