PEPPSI

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.{{cite journal |last1=Nasielski |first1=J. |last2=Hadei |first2=N. |last3=Achonduh |first3=G. |last4=Kantchev |first4=E.A.B.|last5=O'Brien |first5=C.J. |last6=Lough |first6=A. |last7=Organ |first7=M.G. |title=Structure-Activity Relationship Analysis of Pd-PEPPSI Complexes in Cross-Couplings: A Close Inspection of the Catalytic Cycle and the Precatalyst Activation Model |journal=Chem. Eur. J. |volume=16 |pages=10844–10853 |year=2010 |doi=10.1002/chem.201000138 |pmid=20665575}} Commonly used PEPPSI catalysts such as Pd-PEPPSI-IPr[https://www.sigmaaldrich.com/US/en/product/aldrich/669032 PEPPSI™-IPr catalyst], Sigma-Aldrich contain an unsubstituted imidazole core (R₂=H) and a 3-chloro substituted pyridine ligand (R₃=3-Cl). However, structural modifications of the imidazole backbone{{cite journal |last1=Pompeo |first1=M. |last2=Froese |first2=R.D.J |last3=Hadei |first3=N. |last4=Organ |first4=M.G. |title=Pd-PEPPSI-IPent^Cl: A Highly Effective Catalyst for the Selective Cross-Coupling of Secondary Organozinc Reagents |journal=Angew. Chem. Int. Ed. |volume=51 |pages=11354–11357 |year=2012 |doi=10.1002/anie.201205747 |pmid=23038603}}{{cite journal |last1=Pompeo |first1=M. |last2=Farmer |first2=J.L. |last3=Froese |first3=R.D.J |last4=Organ |first4=M.G. |title=Room-Temperature Amination of Deactivated Aniline and Aryl Halide Partners with Carbonate Base Using a Pd-PEPPSI-IPent^Cl-o-Picoline Catalyst |journal=Angew. Chem. Int. Ed. |volume=53 |pages=3223–3226 |year=2014 |doi=10.1002/anie.201310457 |pmid= 24677620}}{{cite journal |last1=Atwater |first1=B. |last2=Chandrasoma |first2=N. |last3=Mitchell |first3=D. |last4=Rodriguez |first4=M.J. |last5=Pompeo |first5=M. |last6=Froese |first6=R.D.J. |last7=Organ |first7=M.G. |title=The Selective Cross-Coupling of Secondary Alkyl Zinc Reagents to Five-Membered-Ring Heterocycles Using Pd-PEPPSI-IHept^Cl |journal=Angew. Chem. Int. Ed. |volume=127 |pages=9638–9642 |year=2015 |doi=10.1002/anie.201503941 |pmid= 26110577}}{{cite journal |last1=Lu |first1=D.-D. |last2=Xu |first2=X.-X. |last3=Liu |first3=F.-S. |title=Bulky Yet Flexible Pd-PEPPSI-IPent^An for the Synthesis of Sterically Hindered Biaryls in Air |journal=J. Org. Chem. |volume=82 |pages=10898–10911 |year=2017 |doi=10.1021/acs.joc.7b01711 |pmid= 28925697}} and pyridine ligand can profoundly affect the catalytic activity of these complexes.

The synthesis and structure of Pd-PEPPSI catalysts were presented in 2005 and published in 2006.{{cite journal |last1=O'Brien |first1=C.J. |last2=Kantchev |first2=E.A.B. |last3=Valente |first3=C. |last4=Hadei |first4=N. |last5=Chass |first5=G.A. |last6=Lough |first6=A. |last7=Hopkinson |first7=A.C. |last8=Organ |first8=M.G. |title=Easily Prepared Air- and Moisture-Stable Pd–NHC (NHC=N-Heterocyclic Carbene) Complexes: A Reliable, User-Friendly, Highly Active Palladium Precatalyst for the Suzuki–Miyaura Reaction |journal=Chem. Eur. J. |volume=12 |pages=4743–8 |year=2006 |doi=10.1002/chem.200600251 |pmid=16568494}} 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%.[http://www.sigmaaldrich.com/chemistry/chemical-synthesis/technology-spotlights/peppsi.html PEPPSI Catalysts], Sigma-Aldrich Contrary to other common palladium-based catalysts, such as tetrakis(triphenylphosphine)palladium(0), PEPPSI is stable to exposure to air{{cite book |last1=Li |first1=Jia Jack |last2=Corey |first2=E.J. |title=Name reactions for homologations, Part 1 |publisher=John Wiley and Sons |year=2009 |isbn=978-0-470-48701-3 }} and moisture.{{cite journal |last1=Valente |first1=C. |last2=Belowich |first2=M.E. |last3=Hadei |first3=N. |last4=Organ |first4=M.G. |title=Pd-PEPPSI Complexes and the Negishi Reaction |journal=Eur. J. Org. Chem. |year=2010 |pages=4343–4354 |doi=10.1002/ejoc.201000359}} Even heating in dimethyl sulfoxide at 120 °C for hours does not result in significant decomposition or deactivation of PEPPSI catalysts.

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 internal PEPPSI) were synthesized.

File:PyNHC-PEPPSI-water.png

PEPPSI catalyze various cross-coupling reactions including Negishi coupling, Suzuki coupling, Sonogashira coupling, Kumada coupling,{{cite book |last=Ackerman |first=Lutz |title=Modern Arylation Methods |publisher=Wiley-VCH |place=Verlag |year=2009 |isbn=9783527319374 |doi=10.1002/9783527627325}} and the Buchwald–Hartwig amination as well as aryl sulfination{{cite journal |last1=Sayah |first1=M. |last2=Organ |first2=M.G. |title=Carbon–Sulfur Bond Formation of Challenging Substrates at Low Temperature by Using Pd-PEPPSI-IPent |journal=Chem. Eur. J. |volume=12 |year=2011 |pages=11719–11722 |doi=10.1002/chem.201102158 |pmid=21898625}}{{cite journal |last1=Sayah |first1=M. |last2=Lough |first2=A.J. |last3=Organ |first3=M.G. |title=Sulfination by Using Pd-PEPPSI Complexes: Studies into Precatalyst Activation, Cationic and Solvent Effects and the Role of Butoxide Base |journal=Chem. Eur. J. |volume=19 |year=2013 |pages=2749–2756 |doi=10.1002/chem.201203142 |pmid=23296748}} and the Heck reaction.{{cite book |last1=Luis |first1=Santiago V. |last2=Garcia-Verdugo |first2=Eduardo |title=Chemical Reactions and Processes Under Flow Conditions |series=Green Chemistry Series |publisher=Royal Society of Chemistry |year=2009 |isbn=978-0-85404-192-3 |doi=10.1039/9781847559739}} In Negishi coupling, PEPPSI promotes reaction of alkyl halides, aryl halides or alkyl sulfonates with alkylzinc halides,{{cite book |last=Cazin |first=Catherine S.J. |date=2010 |title=N-Heterocyclic Carbenes in Transition Metal Catalysis and Organocatalysis |url=https://books.google.com/books?id=eptAg5POIxMC&pg=PA169 |location=Netherlands |publisher=Springer |pages=169–173 |isbn=978-90-481-2866-2 |doi=10.1007/978-90-481-2866-2 |series=Catalysis by Metal Complexes |volume=32}} 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. Once activated, the NHC-Pd(0) species becomes rather air-sensitive.{{cite journal |last1=Organ |first1=M.G. |last2=Avola |first2=S. |last3=Dubovyk |first3=I. |last4=Hadei |first4=N. |last5=Kantchev |first5=E.A. |last6=O'Brien |first6=C.J. |last7=Valente |first7=C. |title=A User-Friendly, All-Purpose Pd–NHC (NHC=N-Heterocyclic Carbene) Precatalyst for the Negishi Reaction: A Step Towards a Universal Cross-Coupling Catalyst |journal=Chem. Eur. J. |volume=12 |pages=4749–4755 |year=2006 |pmid=16568493 |doi=10.1002/chem.200600206}}[https://www.sigmaaldrich.com/deepweb/assets/sigmaaldrich/marketing/global/documents/172/720/al_peppsi_activation_guide.pdf PEPPSI: Instructions for Use], Sigma-Aldrich

File:Peppsi-couplings.png (a) and Buchwald-Hartwig reaction (b) can be activated by PEPPSI complexes.]]

iPEPPSI (internal PEPPSI) type catalyse the copper-free Sonogashira reaction in aqueous solution.{{cite journal |author1=Gazvoda, M. |author2=Virant, M. |author3=Pevec, A. |author4=Urankar, D. |author5=Bolje, A. |author6=Kočevar, M. |author7=Košmrlj, J. |journal=Chem. Commun. |title= A mesoionic bis(Py-tzNHC) palladium(II) complex catalyses green Sonogashira reaction through an unprecedented mechanism |year=2016 |volume=52 |pages=1571–1574 |doi= 10.1039/c5cc08717a|pmid=26575368 |doi-access=free}}

File:Sonogashira-peppsi.png

Additionally, the cationic palladium iPEPPSI complex shown above was used in the hydroamination of alkynes as well.{{cite journal |author1=Virant, M. |author2=Mihelač M. |author3=Gazvoda M. |author4=Cotman, A.E. |author5=Pinter, B. |author6=Košmrlj, J. |journal=Org. Lett. |title= Pyridine Wingtip in [Pd(Py-tzNHC)₂]²⁺ Complex Is a Proton Shuttle in the Catalytic Hydroamination of Alkynes |year=2020 |volume=22 |pages=2157-2161 |doi= 10.1021/acs.orglett.0c00203|pmc=7308070 |pmid=31999464 |doi-access=free}}

File:Virant-OrgLett-2020.png |url=https://repozitorij.uni-lj.si/Dokument.php?id=124988&lang=slv}}]]

{{Reflist|colwidth=30em}}

• [http://www.yorku.ca/organ/peppsi_1.htm PEPPSI homepage at Prof. Michael G. Organ's research group]

Category:Catalysts

Category:Organopalladium compounds