Umicore CX Catalysts Palladium catalyzed cross-coupling reactions 2 3 Specific, well-defined precatalysts and ready-made catalysts UMICORE PMC WILL ASSIST YOU WITH OUR EXPERTISE IN ACTIVITY EXACTLY AS FAR AS IT IS NEEDED TO MEET YOUR NEEDS Palladium catalyzed C-C- and C-X bond forming reactions have undergone remarkable developments in the last 25 years [1]. Numerous research groups, inspired by the 2010 Chemistry Nobel Prize awardees Heck, Negishi and Suzuki [2], have developed new palladium precursors, ligands and catalysts to fully utilize this versatile, synthetic tool in organic chemistry. Some of these palladium complexes have transitioned into a broad range of applications spanning from synthesis of agrochemicals, use in natural products and active pharmaceutical ingredients down to appearing in materials for electronic applications. Umicore CX catalysts at glance: • Alternative Palladium precursors • Well-defined, ready-to-use Palladium phosphine complexes • Selective & active Palladium N-heterocyclic carbene complexes • Efficient Palladium recovery streams [1] a) Handbook of Organopalladium Chemistry for Organic Synthesis, (Eds.: E. Negishi, F. Diederich) Wiley-VCH, 2002, b) Metal-Catalyzed Cross Coupling Reactions, (Eds.: A. de Meijere, F. Diederich) Wiley-VCH, 2004, c) Angew. Chem. Int. Ed. 2012, 51, 5062 [2] http://www.nobelprize.org/nobel_prizes/chemistry/laureates/2010/popular-chemistryprize2010.pdf 4 5 CROSS-COUPLING REACTIONS ARE A TRANSITION METAL CATALYZED COUPLING OF AN ORGANIC ELECTROPHILE (I.E. ORGANIC HALIDE) WITH AN ORGANIC NUCLEOPHILE. SEVERAL NAME REACTIONS HAVE BEEN DEVELOPED USING ORGANOMETALLIC CARBON NUCLEOPHILES HALOGEN BONDS. Kumada Sonogashira-Hagihara Stille Mizoroki-Heck Carbonylation Buchwald - Hartwig -Amination Cyanation Suzuki -Miyaura Negishi Hiyama In addition to conventional product offerings Regardless of whether you need to perform a such as the palladium precursors and highly Suzuki coupling with strongly hindered and/or active phosphine catalysts, Umicore has deactivated substrates or a Negishi coupling developed a number of stable, user-friendly, with substrates carrying sensitive functional well-defined and powerful Palladium(0) and groups, or you are searching for a catalyst for LEGEND Palladium(II) N-heterocyclic carbene (NHC) a Buchwald-Hartwig Amination reaction, we catalysts that are commercially available at will provide you with the appropriate catalytic X = I, Br, Cl, or OTf industrial scale. active complex. 6 7 Examples Buchwald-Hartwig amination reaction(3) Mizoroki-Heck Coupling(6) OMe OMe 5 mol% [Pd(dppf)Cl2] 1.2 eq.NaOtBu + N THF, 3 h, 100 °C N substrate 1: substrate 2 2:1 substrate 1: substrate 2 1:1 I H2N O H 5 mol% Pd(OAc)2 2.5 mol% Pd2dba3 t 1 N 1.2 eq. 96% yield 5 mol% HBF4*P Bu3 5 mol% XPhos t 1.5 eq. K2CO3 3 eq. NaO Bu N + toluene, 110 °C toluene, mW N O 45 min, 110 °C O Br O O 89% yield 79% yield 5 mol% [Pd(dppf)Cl2] 2 1.2 eq. NaOtBu + H2N THF, 3 h, 100 °C Br N H 1.2 eq. 96% yield NC (7) NC 5 mol% [Pd(dppf)Cl2] Negishi Coupling 1.2 eq. NaOtBu + H2N THF, 3 h, 100 °C N Br H CN CN O 1.2 eq. 93% yield t Cl 2 mol% [Pd(P Bu3)2] + ClZn NMP/THF 18 h, 100 °C O O O O 1.5 eq. 76% yield t s (4) Cl 2 mol% [Pd(P Bu3)2] Bu + ClZn sBu Palladium catalyzed decarboxylation NMP/THF 24 h, 100 °C t 5 mol% Pd[P( Bu3)]2 H 1.5 eq. 70% yield 1 eq. TBACl N N O 1.5 eq. Cs2CO3 N Ph + PhBr + DMF, µW, Ph OH 8 min, 170 °C Ph 2 eq. 74% yield trace Newman-Kwartz rearrangement(8) O NMe2 S NMe2 t 2 mol% [Pd(P Bu3)2] S toluene, 4 h, 100 °C O Palladium catalyzed oxidative coupling(5) F3C F3C > 99% yield OH 5 mol% Umicore CX21 OH t 2.2 eq.KO Bu O NMe S NMe + 2 t 2 toluene, 1.5 h, 80 °C 2 mol% [Pd(P Bu3)2] Cl S toluene, 4 h, 100 °C O 2.1 eq. 92% yield > 99% yield [3] J. Am. Chem. Soc. 1996, 118, 7217 [6] J. Am. Chem. Soc. 2008, 130, 3266 [4] J. Am. Chem. Soc. 2006, 128, 11350 [7] J. Am. Chem. Soc. 2001, 123, 2719 [5] J. Org. Chem. 2011, 76, 1390 [8] Angew. Chem. Int. Ed. 2009, 48, 7612 8 9 Suzuki-Miyaura Coupling(9,10) First Class Palladium metal 50 ppm Umicore CX21 N Cl t 1.1 eq. KO Bu N + (HO)2 B tech. grade IPA 3 h, 80 °C recycling technology 1.05 eq. 92% yield UMICORE’S PRECIOUS METAL RECYCLING CAPABILITIES CAN GIVE 1 mol% Umicore CX32 (HO)2B 1.1 eq. KOtBu MORE VALUE TO YOUR PROCESS. THE SOONER THE BETTER! + Br tech. grade IPA 1.5 h, rt 1.05 eq. 92% yield Planning to associate a metal recycling loop to your industrial scale Palladium catalyzed cross-coupling re- action will bring significant additional cost effective- Cl 50 ppm Umicore CX21 1.1 eq. KOt Bu ness to your process. The earlier we speak, the better + (HO)2B tech. grade IPA we can adjust the separation and recycling processes 3 h, 80 °C to offer you maximized precious metal savings. Con- 1.05 eq. 92% yield tact us to discover the accuracy and efficiency of our Palladium recycling technologies and their impact on the economics of your chemical synthesis. Palladium catalyzed oxidative carbonylation(11) [Pd]/ligand O H 0.5 eq. TBP + OH + CO 16 h, 120 °C O Umicore PMC cross-couplings 15 eq. 10 atm 81% yield with 5 mol% PdCl2 and 5 mol% Xantphos 80% yield with 2 mol% Pd(Xantphos)Cl2 precatalysts and ready-to-use catalysts ADVANTAGES READY TO USE EMPIRICAL FORMULA CHEMICAL NAME CAS-No PRODUCT-No VERSUS IN SITU FORMED CATALYSTS: +2 Palladium(II) chloride 7647-10-1 3000036292 PdCl2 • higher reactivity +2 • consistent reactivity profile for optimum reactivity control Diacetylacetonatopalladium(II) 14024-61-4 3000034510 [Pd(acac)2] • no catalytically inactive palladium-ligand species +2 Bis(acetonitrile)dichloropalladium(II) 14592-56-4 3000036037 • higher subsequent end-product purity level [Pd(CH3CN)2Cl2] +2 • no impurities from palladium precursor and no ligand by Bis(benzonitrile)dichloropalladium(II) 14220-64-5 3000036142 incomplete in situ transformation [Pd(C6H5CN)2Cl2] +2 • efficient utilization of stable, pure & active catalyst with Dichloro(1,5-cyclooctadiene)palladium(II) 12107-56-1 3000034509 correct stoichiometry [Pd(cod)Cl2] +2 • no loss of palladium and ligand by incomplete in situ Palladium(II) acetate 3375-31-3 3000034514 transformation or ligand decomposition [Pd(OAc)2]3 +2 • no in situ catalyst preformation step Palladium(II) pivalate 106224-36-6 3000020655 [Pd(OOCtBu) ] • Easy catalyst operation for improved 2 3 process safety & simplicity +2 Bis(η3-allyl)di(μ-chloro)dipalladium(II) 12012-95-2 3000034516 [Pd(allyl)Cl]2 +2 Di(μ-chloro)bis(η3-cinnamyl)dipalladium(II) 12131-44-1 3000034515 [Pd(cinnamyl)Cl]2 0 Tris(dibenzylideneacetone)dipalladium(0) 51364-51-3 3000034523 [9] [Pd (dba) ] x dba Chem. Eur. J. 2006, 12, 5142 2 3 [10] J. Am. Chem. Soc. 2006, 128, 4101 [11] J. Am. Chem. Soc. 2012, 134, 9902 10 11 READY TO USE PALLADIUM PHOSPHINE CATALYSTS PALLADIUM N-HETEROCYCLIC CARBENE CATALYSTS Palladium Vinylsiloxane TRADE NAME EMPIRICAL FORMULA CAS-No PRODUCT-No TRADE NAME EMPIRICAL FORMULA CAS-No PRODUCT-No Catalysts 0 Si Si O Umicore CX11 NHC = IPr 649736-75-4 3000034519 Si Si [(IPr)Pd(NQ)] O 0 O 2 O Pd Pd O Umicore CX61 252062-59-2 3000036051 Pd(vs)c NHC Pd Pd NHC Si Si O 0 Umicore CX12 NHC = IMes 467220-49-1 3000034521 O [(IMes)Pd(NQ)]2 iPr i 0 P Pr US 6 316 380 and Umicore CX14 NHC = SIMes 955998-76-2 3000036042 Si WO 2004 014550 apply. [(SIMes)Pd(NQ)]2 O Fe Pd 0 Si Umicore CX62 1708984-17-1 3000036052 +2 P [Pd(dippf)(vs)tol] Umicore CX21 NHC = IPr 478980-03-9 3000034520 iPr NHC [(IPr)Pd(allyl)CI] iPr Pd WO2015 059049 and foreign equivalents apply. +2 Umicore CX22 NHC = IMes 478980-04-0 3000034522 Cl [(IMes)Pd(allyl)CI] Palladium Monodentate TRADE NAME EMPIRICAL FORMULA CAS-No PRODUCT-No +2 Phosphine Catalysts US 6 316 380, WO 2004 014550 and Umicore CX23 NHC = SIPr 478980-01-7 3000034526 foreign equivalents apply. [(SIPr)Pd(allyl)CI] PPh 3 NHC +2 0 Pd PPh3 Umicore CX31 NHC = IPr 884879-23-6 3000034528 Pd-Tetrakis 14221-01-3 3000034517 Pd Ph3P [(IPr)Pd(cinnamyl)CI] [Pd(PPh3)4] Cl PPh3 +2 Umicore CX32 NHC = SIPr 884879-24-7 3000034527 [(SIPr)Pd(cinnamyl)CI] 0 P Pd P Fu catalyst 53199-31-8 3000034529 t US 6 316 380, WO 2004 014550 and +2 [Pd[P( Bu3)]2] Umicore CX33 NHC = IPr* 1380314-24-8 3000036301 foreign equivalents apply. [(IPr*)Pd(cinnamyl)CI] +2 Br NHC Cl Cl Umicore CX41 NHC = IPr 444910-17-2 3000034518 +1 [(IPr)PdCI ] tBu P Pd Pd PtBu Pd Pd 2 2 3 3 Umicore CX71 t 185812-86-6 3000036049 [PdBr[P( Bu3)]]2 Cl Cl NHC Br +2 US 6 316 380, WO 2004 014550 and Umicore CX42 NHC = SIPr 627878-09-5 3000034610 +2 foreign equivalents apply. [(SIPr)PdCI2]2 Umicore CX72 29934-17-6 3000034513 R1= PCy3 [Pd(PCy ) CI ] 3 2 2 NHC 0 Umicore CX51 NHC = IPr 478019-87-3 3000036038 +2 Pd [(IPr)Pd(vs)] R1= PPh3 Umicore CX73 13965-03-2 3000034512 [Pd(PPh3)2CI2] 0 Umicore CX52 NHC = IMes 441018-46-8 3000036039 +2 Si Si [(IMes)Pd(vs)] Cl R1 R1= P(o-tol)3 Umicore CX74 40691-33-6 3000034511 O Pd [Pd[P(o-tol)3]2CI2] R1 Cl US 6 316 380, WO 2004 014550 and 0 +2 Umicore CX54 NHC = SIMes 1004291-85-3 3000036043 foreign equivalents apply.