PEPPSI

Structure and synthesis

In the basic structure of Pd-PEPPSI, R1 can be a methyl (CH3, Me), ethyl (C2H5, Et), isopropyl (C3H7, iPr), isopentyl (C5H11, iPent), or isoheptyl (C7H15, iHept) group, and starting from the second in the row the resulting catalysts are thus labeled as PEPPSI-IEt, PEPPSI-IPr, PEPPSI-IPent, and PEPPSI-IHept respectively, with or without "Pd-" added in front. Commonly used PEPPSI catalysts such as Pd-PEPPSI-IPr contain an unsubstituted imidazole core (R2=H) and a 3-chloro substituted pyridine ligand (R3=3-Cl). However, structural modifications of the imidazole backbone and pyridine ligand can profoundly affect the catalytic activity of these complexes.

The synthesis and structure of Pd-PEPPSI catalysts were presented in 2005 PEPPSI catalysts are organopalladium complexes containing N-heterocyclic carbene (NHC) ligands. They can be obtained by reacting an imidazolium salt, palladium(II) chloride, and potassium carbonate in 3-chloropyridine as a solvent, under vigorous stirring at 80 °C for 16 hours in air. The yield of PEPPSI in this reaction is 97–98%. Contrary to other common palladium-based catalysts, such as tetrakis(triphenylphosphine)palladium(0), PEPPSI is stable to exposure to air and moisture. Even heating in dimethyl sulfoxide at 120 °C for hours does not result in significant decomposition or deactivation of PEPPSI catalysts.

''i''PEPPSI

Examples of abnormal NHCs based on the mesoionic 1,2,3-triazol-5-ylidene structure have been used for palladium catalysis. In this manner, pyridine fused tzNHCs were prepared to yield palladium complexes with pyridine attached to the carbene core. With this ligand, air stable and highly active palladium complexes of iPEPPSI (as in 'i'''''nternal PEPPSI) were synthesized.

Properties and reactions

PEPPSI catalyze various cross-coupling reactions including Negishi coupling, and the Buchwald–Hartwig amination In Negishi coupling, PEPPSI promotes reaction of alkyl halides, aryl halides or alkyl sulfonates with alkylzinc halides, and the important advantage of PEPPSI over alternative catalysts is that the reaction can be carried out in a general chemical laboratory, without a glove box. PEPPSI contains palladium in the +2 oxidation state and is thus a "precatalyst", that is the metal must be reduced to the active Pd(0) form in order to enter the cross-coupling catalytic cycle. This is usually achieved in situ in the presence of active transmetalating agents such as organo-magnesium, -zinc, -tin, or -boron reagents.

iPEPPSI ('i'''''nternal PEPPSI) type catalyse the copper-free Sonogashira reaction in aqueous solution.

Additionally, the cationic palladium iPEPPSI complex shown above was used in the hydroamination of alkynes as well.

References

References

1. [https://www.sigmaaldrich.com/US/en/technical-documents/technical-article/chemistry-and-synthesis/cross-coupling/peppsi-ipent PEPPSI™-IPent for Demanding Cross-Coupling Reactions], Sigma-Aldrich
2. [https://www.sigmaaldrich.com/deepweb/assets/sigmaaldrich/product/documents/670/622/al_chemfile_v6_n3.pdf PEPPSI Catalyst], Sigma-Aldrich ChemFiles
3. (2005). "Rational catalyst design and its application in sp³-sp³ couplings". American Chemical Society.
4. (2005). "The First Negishi Cross-Coupling Reaction of Two Alkyl Centers Utilizing a Pd−N-Heterocyclic Carbene (NHC) Catalyst". [[Org. Lett.]].
5. (2014). "Carbon–Heteroatom Coupling Using Pd-PEPPSI Complexes". [[Organic Process Research & Development]].
6. (2010). "Structure-Activity Relationship Analysis of Pd-PEPPSI Complexes in Cross-Couplings: A Close Inspection of the Catalytic Cycle and the Precatalyst Activation Model". [[Chem. Eur. J.]].
7. [https://www.sigmaaldrich.com/US/en/product/aldrich/669032 PEPPSI™-IPr catalyst], Sigma-Aldrich
8. (2012). "Pd-PEPPSI-IPent^Cl: A Highly Effective Catalyst for the Selective Cross-Coupling of Secondary Organozinc Reagents". [[Angew. Chem. Int. Ed.]].
9. (2014). "Room-Temperature Amination of Deactivated Aniline and Aryl Halide Partners with Carbonate Base Using a Pd-PEPPSI-IPent^Cl-o-Picoline Catalyst". [[Angew. Chem. Int. Ed.]].
10. (2015). "The Selective Cross-Coupling of Secondary Alkyl Zinc Reagents to Five-Membered-Ring Heterocycles Using Pd-PEPPSI-IHept^Cl". [[Angew. Chem. Int. Ed.]].
11. (2017). "Bulky Yet Flexible Pd-PEPPSI-IPent^An for the Synthesis of Sterically Hindered Biaryls in Air". [[J. Org. Chem.]].
12. [http://www.sigmaaldrich.com/chemistry/chemical-synthesis/technology-spotlights/peppsi.html PEPPSI Catalysts], Sigma-Aldrich
13. (2009). "Name reactions for homologations, Part 1". John Wiley and Sons.
14. (2010). "Pd-PEPPSI Complexes and the Negishi Reaction". [[Eur. J. Org. Chem.]].
15. Ackerman, Lutz. (2009). "Modern Arylation Methods". Wiley-VCH.
16. (2011). "Carbon–Sulfur Bond Formation of Challenging Substrates at Low Temperature by Using Pd-PEPPSI-IPent". [[Chem. Eur. J.]].
17. (2013). "Sulfination by Using Pd-PEPPSI Complexes: Studies into Precatalyst Activation, Cationic and Solvent Effects and the Role of Butoxide Base". [[Chem. Eur. J.]].
18. Cazin, Catherine S.J.. (2010). "N-Heterocyclic Carbenes in Transition Metal Catalysis and Organocatalysis". Springer.
19. (2006). "A User-Friendly, All-Purpose Pd–NHC (NHC=N-Heterocyclic Carbene) Precatalyst for the Negishi Reaction: A Step Towards a Universal Cross-Coupling Catalyst". [[Chem. Eur. J.]].
20. [https://www.sigmaaldrich.com/deepweb/assets/sigmaaldrich/marketing/global/documents/172/720/al_peppsi_activation_guide.pdf PEPPSI: Instructions for Use], Sigma-Aldrich
21. (2016). "A mesoionic bis(Py-''tz''NHC) palladium(II) complex catalyses green Sonogashira reaction through an unprecedented mechanism". [[Chem. Commun.]].
22. (2020). "Pyridine Wingtip in [Pd(Py-''tz''NHC)₂]²⁺ Complex Is a Proton Shuttle in the Catalytic Hydroamination of Alkynes". [[Org. Lett.]].
23. Virant, Miha. (2019). "Development of homogeneous palladium catalytic systems for selected transformations of terminal acetylenes". [[University of Ljubljana]].