View source for PEPPSI

{{Short description|Group of chemical compounds}}
{{distinguish|Pepsi}}
[[File:Generic PEPPSI.png|thumb|right|alt=A schematic of a generic Pd-PEPPSI type precatalyst|A schematic of a generic Pd-PEPPSI type precatalyst. R<sub>1</sub>, R<sub>2</sub>, and R<sub>3</sub> represent carbon or heteroatom substituents.]]
'''PEPPSI''' is an abbreviation for '''p'''yridine-'''e'''nhanced '''p'''recatalyst '''p'''reparation '''s'''tabilization and '''i'''nitiation. It refers to a family of commercially available<ref name=sigma-PEPPSI/><ref name=sigma-PEPPSI-IPent>[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</ref><ref name=Aldrich-ChemFiles>[https://www.sigmaaldrich.com/deepweb/assets/sigmaaldrich/product/documents/670/622/al_chemfile_v6_n3.pdf PEPPSI Catalyst], Sigma-Aldrich ChemFiles</ref> palladium [[Catalysis|catalysts]] developed around 2005 by Prof. Michael G. Organ and co-workers at [[York University]],<ref name="Organ-ACS-2005">{{cite conference |url=http://oasys2.confex.com/acs/230nm/techprogram/P891899.HTM |title=Rational catalyst design and its application in sp<sup>3</sup>-sp<sup>3</sup> couplings |author1=Hadei, N. |author2=Kantchev, E.A.B. |author3=O'Brien, C.J. |author4=Chass, G. |author5=Hunter, H.H. |author6=Penner, G. |author7=Hopkinson, A.C.|author8=Organ, M.G. |date=2005 |publisher=American Chemical Society |pages=Abstract 308 |location=Washington, DC |conference=230th ACS National Meeting}}</ref><ref name=Hadei-2005>{{cite journal|last1=Hadei|first1=N. |last2=Kantchev |first2=E.A.B.|last3=O'Brien |first3=C.J. |last4=Organ |first4=M.G. |title=The First Negishi Cross-Coupling Reaction of Two Alkyl Centers Utilizing a Pd−N-Heterocyclic Carbene (NHC) Catalyst |journal=[[Org. Lett.]] |volume=7 |pages=3805–3807 |year=2005 |pmid=16092880 |doi=10.1021/ol0514909}}</ref> which can accelerate various carbon-carbon and carbon-[[heteroatom]]<ref name=OPRD-2014>{{cite journal |last1=Valente |first1=C. |last2=Pompeo |first2=M. |last3=Sayah |first3=M. |last4=Organ |first4=M.G. |title=Carbon–Heteroatom Coupling Using Pd-PEPPSI Complexes |journal=[[Organic Process Research & Development]] |volume=18 |pages=180–190|year=2014 |doi=10.1021/op400278d}}</ref> bond forming cross-[[coupling reaction]]s. In comparison to many alternative [[palladium]] catalysts, Pd-PEPPSI-type complexes are stable to air and moisture and are relatively easy to synthesize and handle.
==Structure and synthesis==
In the basic structure of  Pd-PEPPSI, R<sub>1</sub> can be a [[Methyl group|methyl]] (CH<sub>3</sub>, Me), [[ethyl group|ethyl]] (C<sub>2</sub>H<sub>5</sub>, Et), iso[[propyl]] ([[Carbon|C]]<sub>3</sub>[[Hydrogen|H]]<sub>7</sub>, <sup>''i''</sup>Pr), iso[[pentyl]] (C<sub>5</sub>H<sub>11</sub>, <sup>''i''</sup>Pent), or iso[[heptyl]] (C<sub>7</sub>H<sub>15</sub>, <sup>''i''</sup>Hept) 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.<ref name=Nasielski-2010>{{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}}</ref> Commonly used PEPPSI catalysts such as Pd-PEPPSI-IPr<ref name=Aldrich-PEPPSI-IPr>[https://www.sigmaaldrich.com/US/en/product/aldrich/669032 PEPPSI™-IPr catalyst], Sigma-Aldrich</ref> contain an unsubstituted imidazole core (R<sub>2</sub>=H) and a 3-chloro substituted pyridine ligand (R<sub>3</sub>=3-Cl). However, structural modifications of the imidazole backbone<ref name=Pompeo-2012>{{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<sup>Cl</sup>: 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}}</ref><ref name=Sayah-2013/><ref name=Pompeo-2014>{{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<sup>Cl</sup>-o-Picoline Catalyst |journal=[[Angew. Chem. Int. Ed.]] |volume=53 |pages=3223–3226 |year=2014 |doi=10.1002/anie.201310457 |pmid= 24677620}}</ref><ref name=Atwater-2015>{{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<sup>Cl</sup> |journal=[[Angew. Chem. Int. Ed.]] |volume=127 |pages=9638–9642 |year=2015 |doi=10.1002/anie.201503941 |pmid= 26110577}}</ref><ref name=Lu-2017>{{cite journal |last1=Lu |first1=D.-D. |last2=Xu |first2=X.-X. |last3=Liu |first3=F.-S. |title=Bulky Yet Flexible Pd-PEPPSI-IPent<sup>An</sup> 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}}</ref> and pyridine ligand<ref name=Nasielski-2010/><ref name=Sayah-2013/><ref name=Pompeo-2014/> can profoundly affect the catalytic activity of these complexes.
The synthesis and structure of Pd-PEPPSI catalysts were presented in 2005<ref name="Organ-ACS-2005"/><ref name=sigma-PEPPSI/> and published in 2006.<ref name=O'Brien-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}}</ref> 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&nbsp;°C for 16 hours in air. The yield of PEPPSI in this reaction is 97–98%.<ref name=sigma-PEPPSI>[http://www.sigmaaldrich.com/chemistry/chemical-synthesis/technology-spotlights/peppsi.html PEPPSI Catalysts], Sigma-Aldrich</ref><ref name=O'Brien-2006/> Contrary to other common palladium-based catalysts, such as [[tetrakis(triphenylphosphine)palladium(0)]], PEPPSI is stable to exposure to air<ref name=Li-2009>{{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 }}</ref> and moisture.<ref name=Valente-2010>{{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}}</ref> Even heating in [[dimethyl sulfoxide]] at 120&nbsp;°C for hours does not result in significant decomposition or deactivation of PEPPSI catalysts.<ref name=sigma-PEPPSI/>
===''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 ''i''PEPPSI (as in '''i'''''nternal'' PEPPSI) were synthesized.<ref name="Gazvoda-Chem-Commun-2016" />
[[File:PyNHC-PEPPSI-water.png|thumb|center|253 px|An example of ''i''PEPPSI complex.<ref name="Gazvoda-Chem-Commun-2016"/>]]
==Properties and applications==
PEPPSI can catalyze various palladium cross-[[coupling reaction]]s including [[Negishi coupling]],<ref name=Li-2009/> [[Suzuki reaction|Suzuki coupling]], [[Sonogashira coupling]], [[Kumada coupling]],<ref name=Ackerman-2009>{{cite book |last=Ackerman |first=Lutz |title=Modern Arylation Methods |publisher=Wiley-VCH |place=Verlag |year=2009 |isbn=9783527319374 |doi=10.1002/9783527627325}}</ref> and the [[Buchwald–Hartwig amination]]<ref name=OPRD-2014/> as well as aryl sulfination<ref name=Sayah-2011>{{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}}</ref><ref name=Sayah-2013>{{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}}</ref><ref name=OPRD-2014/> and the [[Heck reaction]].<ref name=sigma-PEPPSI/><ref name=Luis-2009>{{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}}</ref> In Negishi coupling, PEPPSI promotes reaction of [[alkyl]] halides, [[aryl]] [[halide]]s or alkyl [[sulfonate]]s with alkylzinc halides,<ref name=Cazin-2010>{{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}}</ref> 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#Chemistry and chemical engineering|''in situ'']] in the presence of active transmetalating agents such as organo-magnesium, -zinc, -tin, or -boron reagents.<ref name=Nasielski-2010 /> Once activated, the NHC-Pd(0) species becomes rather air-sensitive.<ref name=Li-2009/><ref name=sigma-PEPPSI/><ref name=Organ-2006>{{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}}</ref><ref>[https://www.sigmaaldrich.com/deepweb/assets/sigmaaldrich/marketing/global/documents/172/720/al_peppsi_activation_guide.pdf PEPPSI: Instructions for Use], Sigma-Aldrich</ref>
[[File:Peppsi-couplings.png|thumb|center|446 px|[[Suzuki coupling]] (a)  and [[Buchwald-Hartwig reaction]] (b) can be activated by PEPPSI complexes.]]
An efficient, cationic palladium catalyst of ''i''PEPPSI ('''i'''''nternal'' PEPPSI) type was demonstrated to efficiently catalyse the [[Sonogashira coupling#Copper-free Sonogashira coupling|copper-free Sonogashira reaction]] in water as the only solvent, under aerobic conditions, in the absence of copper, amines, phosphines and other additives.<ref name="Gazvoda-Chem-Commun-2016">{{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-''tz''NHC) 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}}</ref>
[[File:Sonogashira-peppsi.png|thumb|center|620 px|Sonogashira coupling under green reaction conditions using ''i''PEPPSI.<ref name="Gazvoda-Chem-Commun-2016" />]]
Additionally, the cationic palladium ''i''PEPPSI complex shown above was used in the [[hydroamination|hydroamination of alkynes]] as well. The authors have demonstrated that the ligands actively participate in the reaction mechanism since the pyridine group acts as an internal base to enable the intramolecular proton transfer between active sites of intermediates.<ref name=Virant-2020>{{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-''tz''NHC)<sub>2</sub>]<sup>2+</sup> 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}}</ref><ref name=Virant-thesis-2019>{{cite thesis |type=PhD |last=Virant |first=Miha |date=2019|title=Development of homogeneous palladium catalytic systems for selected transformations of terminal acetylenes |publisher=[[University of Ljubljana]] |url=https://repozitorij.uni-lj.si/Dokument.php?id=124988&lang=slv}}</ref>
[[File:Virant-OrgLett-2020.png|thumb|center|400px|Palladium ''i''PEPPSI complex with designated catalytic region and pyridine wingtip that actively participates in the catalytic reactions as internal base.<ref name=Virant-2020/><ref name=Virant-thesis-2019/>]]
==References==
{{Reflist|colwidth=30em}}
==External links==
*[http://www.yorku.ca/organ/peppsi_1.htm PEPPSI homepage at Prof. Michael G. Organ's research group]
[[Category:Catalysts]]
[[Category:Organopalladium compounds]]