Bulky Diphosphines in the Palladium Catalyzed Isomerizing Alkoxycarbonylation of Fatty Acids
Dissertation
zur Erlangung des akademischen Grades des Doktors der Naturwissenschaften (Dr. rer. nat.)
vorgelegt von
Josefine T. Christl aus Konstanz
an der Universität Konstanz
Mathematisch-Naturwissenschaftliche Sektion Fachbereich Chemie
Konstanz, 2016
1. Gutachter: Prof. Dr. Gerhard Müller 2. Gutachter: Prof. Dr. Stefan Mecking Tag der mündlichen Prüfung: 03. Juni 2016
meinem verstorbenen Großvater „Daddy“ gewidmet
der Leitung von Herrn Prof. Dr. Gerhard Müller im Fachbereich Chemie der Universität Konstanz angefertigt.
Herrn Prof. Dr. Gerhard Müller danke ich für den gewährten wissenschaftlichen Freiraum, seine großzügige Unterstützung sowie für seine freundliche Betreuung im Verlauf der gesamten Arbeit.
Herrn Prof. Dr. Stefan Mecking danke ich für die stets gute wissenschaftliche Zusammenarbeit.
Bei Herrn Dr. Inigo Göttker-Schnetmann möchte ich mich ganz herzlich für seine Diskussionsbereitschaft in fachlichen Fragen, Ideen und Anregungen sowie für die Einführung in die Einkristall-Röntgenstrukturanalyse und die Korrektur der vorliegenden Arbeit bedanken.
Philipp Roesle und Florian Stempfle danke ich für die Hilfe bei der Einarbeitung in die Reaktorexperimente, die chemischen Diskussionen sowie für die fruchtbare Zusammenarbeit bei der Erstellung und Ausarbeitung von Publikationen.
Des Weiteren bedanke ich mich bei Frau Prof. Dr. Lucia Caporaso von der Universität in Salerno für die Durchführung der DFT Rechnungen, die einen wichtigen Beitrag zur Erforschung der Struktur-Selektivitäts-Beziehungen geleistet haben.
Ich danke Lars Bolk für das Lösen aufgetretener PC-Probleme. Anke Friemel möchte ich für die Hilfe bei NMR-Messungen danken. Weiterer Dank gilt Herrn Dr. Werner Röll und Robin Kirsten für die zuverlässige Versorgung mit Laborutensilien aller Art.
Herrn Dr. Thomas Huhn und Frau Dipl.-Chem. Angelika Früh danke ich für Ihre freundschaftliche Verbundenheit und das stetige Interesse an meiner Arbeit sowie an meiner Person.
Ferner danke ich allen Kolleginnen und Kollegen, die durch ihre Hilfsbereitschaft zum Gelingen dieser Arbeit beigetragen haben.
Meinen Bürokollegen Alfred Straub und Dr. Amin Fallah sei für eine stets gute Büroatmosphäre gedankt.
Christl, J. T.; Roesle, P.; Stempfle, F.; Wucher, P.; Göttker-Schnetmann, I.; Müller, G.; Mecking, S. Chem. Eur. J. 2013, 19, 17131-17140. ,,Catalyst Activity and Selectivity in the Isomerizing Alkoxycarbonylation of Methyl Oleate”
Christl, J. T.; Roesle, P.; Stempfle, F.; Müller, G.; Caporaso, L.; Cavallo, L.; Mecking, S.
ChemSusChem 2014, 7, 3491 - 3495. ,,Promotion of Selective Pathways in Isomerizing Functionalization of Plant Oils by Rigid Framework Substituents”
Poster Presentations
5th Workshop on Fats and Oils as Renewable Feedstock for the Chemical Industry in Karlsruhe (March 18-20, 2012).
“Monomer Generation and Synthesis of Linear Polycondensates from Unsaturated Fatty Acids by Isomerizing Alkoxycarbonylation”
Josefine T. Christl, Philipp Roesle, Florian Stempfle, Gerhard Müller, Stefan Mecking, University of Konstanz, Konstanz, Germany.
7th Workshop on Fats and Oils as Renewable Feedstock for the Chemical Industry in Karlsruhe (March 23-25, 2014).
“Catalyst Structure-Productivity and Structure-Selectivity Relationship in the Isomerizing Methoxycarbonylation of HO-Sunflower Oil”
Josefine T. Christl, Philipp Roesle, Florian Stempfle, Inigo Göttker-Schnetmann, Gerhard Müller, Stefan Mecking, University of Konstanz, Konstanz, Germany
Poster Prize
7th Workshop on Fats and Oils as Renewable Feedstock for the Chemical Industry in Karlsruhe.
“Catalyst Structure-Productivity and Structure-Selectivity Relationship in the Isomerizing Methoxycarbonylation of HO-Sunflower Oil”
Josefine T. Christl, Philipp Roesle, Florian Stempfle, Inigo Göttker-Schnetmann, Gerhard Müller, Stefan Mecking, University of Konstanz, Konstanz, Germany
Die vorliegende Arbeit beschäftigt sich mit der Synthese neuartiger, sterisch anspruchsvoller, Diphosphin-Pd(II)-Komplexe und deren katalytischen Eigenschaften bei der isomerisierenden Methoxycarbonylierung von internen Fettsäuren, wie z.B. Methyloleat. Die aus dieser Reaktion resultierenden α,ω-Diester sind potentielle Ausgangsmaterialien für die industrielle Produktion von Polyester und Polyamiden. Das weltweite Interesse an der Entwicklung leistungsfähiger und kostengünstiger Herstellverfahren von α,ω-Diester ist deshalb stark angestiegen. In Laborversuchen führte der Einsatz des dtbpx-Katalysators [(dtbpx)Pd(OTf)2] (dtbpx = 1,2-Bis[(di- tert-butylphosphino)methyl]benzene) bisher zu den besten Ergebnissen hinsichtlich Produktivität und Selektivität. Diese Reaktion bietet allerdings noch Raum für Optimierung bei den genannten Parametern sowie auch hinsichtlich der relativ hohen Kosten.
Nach dem Vorbild des dtbpx-basierten Katalysators wurden zunächst sperrige elektronenreiche o- Tolyl-Diphosphine synthetisiert und nach erfolgter Komplexierung mit Pd(II) die katalytische Aktivität getestet. Das o-Tolyl-Rückgrad ermöglicht es hierbei auf einfache Weise selektiv verschiedene sperrige Alkylphosphine nacheinander einzuführen und dadurch eine Vielzahl neuer unsymmetrischer Diphosphin-Liganden zu erhalten. Folgende Alkylsubstituenten wurde eingesetzt: Adamantyl, tert-Butyl, iso-Propyl und Cyclohexyl. Die nachfolgende Testung der katalytischen Aktivität zeigte, dass neben dem dtbpx-Katalysator auch die meisten neu synthetisierten o-Tolyl-Pd(II)-Komplexe die Umwandlung einer internen Doppelbindung in einen endständigen Methoxy-Ester in guter Ausbeute und Selektivität katalysieren (Bildung von linearem 1,19-Diester).
Basierend auf Röntgenstrukturanalysen an Einkristallen der neuen katalytisch wirksamen Pd(II)- Komplexe konnten Struktur-Aktivitäts-Beziehungen der isomerisierenden Methoxy- carbonylierung aufgestellt werden. Daraus lässt sich ableiten, dass ein steigender sterischer Anspruch der Diphosphin Liganden vor allem die Produktivität des Katalysators erhöht, jedoch die Selektivität hinsichtlich des 1,19-Diesters deutlich weniger beeinflusst. Sogar für weniger sterisch anspruchsvolle Alkylsubstituenten am Phosphor konnte in der isomerisierenden Methoxycarbonylierung von Methyloleat eine starke Präferenz zum linearen Produkt festgestellt werden. Unter den angewandten Reaktionsbedingungen (90 °C, 120 h, MO:Pd = 125:1) wurden
97 % erzielt. Bei der Selektivität sind die Ergebnisse gegenüber dtbpx als Stand der Technik leicht vermindert (68 %-80 % versus 91 %).
Als Ergebnis weiterer Untersuchungen konnte gezeigt werden, dass sterisch anspruchsvolle Alkyl- Substituenten zur vollständigen Bildung der katalytisch aktiven Hydridspezies führen und diese mit zunehmender Raumfülle der Liganden stabilisieren. Damit lassen sich die geringeren Produktivitätsraten der Komplexe mit iso-Propyl- und Cyclohexyl-Gruppen im Vergleich zu den Komplexen mit tert-Butyl- und Adamantyl-Gruppen erklären.
Basierend auf den Ergebnissen des ersten Teils dieser Arbeit wurde der symmetrische Diphosphin Ligand dadpx (1,2-Bis[(di-1-adamantylphosphino)methyl]benzene) synthetisiert und nach Über- führung in den entsprechenden Pd-Komplex auf seine katalytischen Eigenschaften getestet. Der Admantyl-Substituent nimmt per se nicht mehr Raum ein als die tert-Butyl-Gruppe, stabilisiert jedoch durch seine Käfigstruktur den entsprechenden katalytisch aktiven Hydrid-Komplex. In der Methoxycarbonylierung von Methyloleat erwies sich der tetra-adamantyl-substituierte Komplex als hochselektiv, wobei die Menge gebildeter Ester-Nebenprodukte im Vergleich zum dtbpx- Katalysator sogar auf die Hälfte reduziert war. Dennoch konnte hinsichtlich der Produktivität pro Zeiteinheit keine Steigerung festgestellt werden. In einer zusätzlichen theoretischen Studie wurde der Zusammenhang zwischen Katalyseproduktivität und Selektivität hinsichtlich des 1,19-Diesters entschlüsselt. Durch die spezifische Interaktion des starren Adamantyl-Gerüsts mit dem Substrat (MeOH) werden die Übergangszustände unselektiver (und unerwünschter) Reaktionswege destabilisiert. Daraus resultiert die besonders hohe Produktselektivität und die verlangsamte Umsetzung des Edukts.
Im weiteren Verlauf dieser Arbeit wurde versucht durch die Kombination von tert-Butyl- und Adamantyl-Gruppen die Produktivität (pro Zeiteinheit) der '-Xylol basierten Diphosphin- Komplexe bei gleichzeitiger hoher Selektivität zu steigern. Im Zuge dieser Untersuchung wurden drei neue Diphosphin-Pd(II)-Komplexe jeweils mit Adamantyl- und tert-Butyl-Gruppen synthetisiert. Die katalytischen Ergebnisse zeigten, dass es durch die Kombination von Adamantyl- und tert-Butyl-Gruppen an einem Diphosphin möglich war, im Vergleich zum tetra-Adamantyl- System die Umsetzung des Eduktes zu beschleunigen, ohne die Selektivität negativ zu beeinflussen. Oberste Grenzen bezüglich der Produktivität pro Zeiteinheit und Selektivität
Ad)-Ligand.
Zum Schluss der Untersuchungen wurde der dtbpp (R = tert-Butyl)-Ligand mit unterschiedlichen Silizium-Alkylgruppen funktionalisiert, in den entsprechenden Pd(II)-Komplex transformiert und anschließend auf seine katalytische Aktivität getestet. Es wurde gefunden, dass die neuen Silizium- basierten Diphosphin-Pd(II)-Komplexe nur wenig die entsprechende, katalytisch aktive Hydrid- Spezies bilden. Deshalb entsteht der lineare 1,19-Diester nur in Spuren.
Abstract/Zusammenfassung ... XI
1 Introduction ... 3
1.1 Alternative to Fossil Feedstocks: Renewables ... 3
1.2 Alkoxycarbonylation ... 5
1.2.1 Ethylene / CO-Copolymerization ... 6
1.2.2 Methyl Propionate Formation ... 6
1.3 Diphosphine Synthesis ... 10
1.4 Highly Active and Selective Catalysts for the Production of Methyl Propionate ... 11
1.5 Catalysts for the Methoxycarbonylation of Terminal Olefins ... 13
1.6 Possible -Functionalization of Internal Olefines ... 14
1.6.1 Isomerizing Alkoxycarbonylation of Monofunctional Olefines ... 14
1.6.2 Isomerizing Alkoxycarbonylation of -Functionalized Olefines ... 15
1.6.3 Isomerizing-Endfunctionalization Reactions ... 17
1.6.4 ,-Functionalized Long-Chain Alkanes as Building Blocks for Polymers ... 19
2 Scope of this Thesis ... 21
3 Results and Discussion ... 23
3.1 Previous Studies ... 23
3.2 Novel Complexes of Bulky Diphosphine Ligands with an Unsymmetric Backbone ... 27
3.2.1 Synthesis of o-Tolyl-Tetra-Adamantyl Diphosphine ... 31
3.2.2 Synthesis and Molecular Structure of Diphosphine Pd(II) Complexes ... 35
3.2.3 Methoxycarbonylation of Methyl Oleate ... 38
3.2.4 Time Dependency of the Methyl Oleate Content ... 44
3.2.5 Formation and Isolation of Pd(II) Hydride Species ... 46
Precursor ... 63
3.2.7 Summary ... 64
3.3 Synthesis and Properties of [(dadpx)Pd(OTf)2] as a Catalyst Precursor ... 66
3.3.1 Synthesis of the Tetra Adamantyl Ligand and the Corresponding Pd(II) Complex ... 67
3.3.2 Effect of Reaction Conditions on the Catalytic Performance ... 68
3.3.3 Hydride Complex Formation ... 71
3.3.4 DFT Studies ... 74
3.3.5 Summary ... 76
3.4 Catalysis with Mixed Adamantyl and tert-Butyl substituted Diphosphines ... 77
3.4.1 Diphosphine Ligand Syntheses ... 80
3.4.2 Generation of Pd(II) Catalyst Precursors and Determination of their Molecular Structures ... 87
3.4.3 Catalytic Methoxycarbonylation of Methyl Oleate... 90
3.4.4 Time Dependency of Methyl Oleate Content ... 92
3.4.5 Formation of the Catalytically Active Hydride Species ... 93
3.4.6 Summary ... 96
3.5 Diphosphines with a Hetero-substituted Backbone ... 97
3.5.1 Synthesis of Si-Diphosphines and Transformation into their Pd(II) Complexes ... 99
3.5.2 Catalytic Methoxycarbonylation of Methyl Oleate... 100
4 Summary and Outlook ... 106
5 Experimental Section ... 111
5.1 Materials and General Considerations ... 111
5.2 Synthetic Procedures ... 112
5.2.1 Synthesis of Diphosphine Ligands with an o-Tolyl-Backbone... 112
5.2.2 Synthesis of Diphosphine Ligands with an -Xylene Backbone ... 123
5.2.4 Synthesis of Palladium(II) Complexes... 133
5.2.5 General Synthesis of MeOH Coordinated Hydride Pd(II) Complexes ... 146
5.2.6 General Synthesis of PPh3 Coordinated Pd(II) Complexes ... 149
5.2.7 General Procedure for the Monoprotonation of Diphosphine Ligands ... 153
5.2.8 Synthesis of Phosphonium Salts 68 and 69 ... 155
5.2.9 Carbonylation Procedures ... 156
5.2.10 General Procedure for NMR Tube Experiments ... 157
5.2.11 Isomerization Experiments ... 157
5.2.12 In-situ Generation of [(115)Pd(µ-H)(µ-CO)Pd(115)]+OTf- ... 158
5.3 The Half Cone Angle[25] ... 158
5.4 Crystal Structure Determinations ... 160
5.5 Computational Details ... 171
6 Supplementary Material ... 173
7 References ... 217
acac Acetylacetone
AIBN 2,2′-Azobis(2-methylpropionitril)
biphephos 6,6′-[(3,3′-Di-tert-butyl-5,5′-dimethoxy-1,1′-biphenyl-2,2′-diyl)bis(oxy)]
bis(dibenzo[d,f][1,3,2]dioxaphosphepin) BQ Cyclohexa-2,5-diene-1,4-dione
Cg 6-Phospha-2,4,8-trioxa-1,3,57-tetramethyladamantane
CO Carbonmonoxide
COSY Correlation spectroscopy
Chemical shift in ppm
COD Cycloocta-1,5-diene
COE Cyclooctene
DABCO 1,4-Diazabicyclo[2.2.2]octane
dadpx 1,2-Bis[(di-1-adamantylphosphino)methyl]benzene dapp 1,3-Bis(phospha-oxa-adamantyl)propane
datbux 1,2-Bis[(1-adamantyl-tert-butylphosphino)methyl]benzene DBU 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine
dba 1,5-Diphenylpenta-1,4-dien-3-on dppe 1,3-Bis(diphenylphosphino)ethane dppp 1,3-Bis(diphenylphosphino)propane
DPEphos [Oxybis(2,1-phenylene)]bis(di-phenylphosphine) dppf 1,1'-Bis(diphenylphosphino)-ferrocene
dppmx 1,2-Bis(diphenylphosphino-1-ethyl)benzene dppx 1,2-Bis(diphenylphosphinomethyl)benzene dtbpp 1,3-Bis(di-tert-butylphosphino)propane
dtbpmSi Bis[(di-tert-butylphosphino)methyl]dialkylsilane dtbpx 1,2-Bis[(di-tert-butylphosphino)methyl]benzene
equiv equivalent
HMBC Heteronuclear multiple bond correlation
HMPA Hexamethylphosphoramide
HSQC Heteronuclear single quantum coherence
MALDI-TOF Matrix-Assisted Laser Desorption Ionization Time-of-Flight
MeOH Methanol
MMA Methyl Methacrylate
MP Methylpropionate
m/z Mass-to-Charge Ratio
NBS 1-Bromo-2,5-pyrrolidinedione
NMR Nuclear Magnetic Resonance
PK Polyketones
ppm Parts per million
r.t. Room temperature
THF Tetrahydrofuran
TMS Trimethylsilyl
TON Turn over number mol [(monomer) / mol (metal center)]
TOF Turn over frequency mol [(monomer) / mol (metal center) and time]
Xantphos 4,5-Bis-(diphenylphosphino)-9,9-dimethylxanthene
1 Introduction
Most of the present chemical commodities including daily used household items such as shampoo, creams, lubricants and plastics like thermoplastic polymers (e.g. polyethylene, polyamides, polystyrene), are currently prepared almost exclusively from fossil feedstocks (e.g. crude oil or natural gas). In the view of limited availability of such feedstocks the chemical industry has an enormous responsibility not only to use these resources very efficiently but also to find new strategies to mitigate the dwindling fossil resources.
Regarding the increasing plastic production worldwide, for ecological sustainability it becomes unavoidable to search for alternative renewable resources in the long term.[1,2,3] Well known polymers from renewable resources are cellulose esters and ethers, poly(lactic acid) (PLA) and poly(hydroxyl alkanoates) (PHAs), which are manufactured nowadays on a large scale.[1,2]
Likewise, sugar cane based polyethylene is now produced industrially. All these polymers are based on carbohydrate feedstock and production often includes a fermentation step. Concerning feedstock utilization and reaction space-time yields, chemical synthetic routes in which the original molecular structure of the plant biomass employed is substantially retained are attractive alternatives. Catalysis plays a central role in the conversion of biomass as it is more economical beneficial by reducing the number of synthetic steps to reach a preferable high adding value and at the same time producing less waste than a non catalytic route.
1.1 Alternative to Fossil Feedstocks: Renewables
The utilization of renewable resources as a source of chemicals requires their efficient transformation to useful building blocks such as α,ω-functionalized compounds.[4] In principle plant oil derived fatty acids (base catalyzed saponification of the triglycerides release the fatty acids) are attractive substrates, which exhibit long-chain, crystallizable linear CH2 segments as well as two functional groups (double bond and ester functionalility). Their transformation into linear α,ω-functionalized compounds is of interest for the generation of semicrystalline aliphatic polyesters and hydrophobic polyamides (Scheme 1).
Scheme 1. -Functionalization possibilities of oleic acid (X = CHO, COOMe).
One example for the long-standing utilization of a fatty acid based renewable feedstock is illustrated by the preparation of the difunctional monomer sebacic acid from base-catalyzed cleavage of ricinoleic acid, which is converted to aliphatic polyamides like Nylon-6,10.[5]
Cleavage reactions such as ozonolysis or catalytic oxidation of the olefin functionality in the fatty acid chain yield α,ω-dicarboxylic acids and derivatives of medium chain length along with monofunctional oxygenates as stoichiometric by-products, which are of limited industrial interest.
Self-metathesis of oleates can yield 1,18-dioctadecanoates after subsequent hydrogenation of the double bond. However, stoichiometric amounts of the C18 alkene are formed. As an equilibrium reaction only 50 % conversion can be attained unless one of the reaction products is selectively removed from the reaction mixture. Other entirely chemical catalytic approaches such as hydrogenation, isomerization as well as dimerization are also studied to this end.[4b,6]
However, in the examples mentioned above not the complete fatty acid chain is incorporated into the corresponding monomer. In order to employ the potential of the long-chain linear feedstock to provide crystallizable segments and to utilize the feedstock most efficiently, a full linear incorporation of the entire fatty acid chain would be desirable. Given that the double bond in unsaturated fatty acids is located in the center of the molecule, complete utilization of the monomer can only be achieved by functionalization at the chain end. One possible biotechnological approach
is the enzymatic ω-oxidation in which the entire fatty acid chain remains intact. Limited space-time yields and complicated work up of the reaction mixture is the major shortcoming of this route.[7,8]
This example clearly shows that an efficient and highly regio- as well as chemoselective conversion of an internal double bond into a terminal functional group remains a synthetic challenge, as terminal olefins are thermodynamically disfavored versus internal double bonds of the substrate.[7,8]
1.2 Alkoxycarbonylation
Some of the most important industrial processes using homogeneous transition metal catalysts are the hydroformylation of olefins and the alkoxycarbonylation.[9] The latter reaction converts the olefin into an ester by employing carbon monoxide in the presence of an alcohol and a suitable catalyst. In this regard, the methoxycarbonylation of ethylene to methyl propionate and polyketones, respectively are remarkable reactions (Scheme 2). This reaction is catalyzed by diphosphine based Pd(II) complexes. Polyketones (AKROTEK® PK, AKRO-PLASTIC GmbH) are used inter alia as thermoplastic materials in mechanical engineering,[10] methyl propionate (MP) is a precursor of methyl methacrylate (MMA), which in turn is used for the production of acrylic plastic like Plexiglas®.[11]
Scheme 2. Carbonylation reaction to methyl methacrylate and thermoplastics.
The carbonylation reaction outlined in Scheme 2 is sensitive for the kind of catalyst precursor used.
The nature of phosphine ligands employed, can direct the reaction either to polyketones or methyl propionate.[12] It was proposed that cationic Pd(II) catalysts in the presence of excess monodentate phosphine (e.g. PPh3) and Brønsted acids of weakly coordinating anions favor hydroesterfication
of ethylene to afford methyl propionate, whereas bidentate ligands almost exclusively lead to polyketones. Further investigations showed that the chemoselectivity of the reaction originates from the bite angle and the steric bulk of the bidentate ligand.[13,14]
1.2.1 Ethylene / CO-Copolymerization
The development of new bidentate phosphines for specific catalytic applications has been subject of research for several decades. Since the late 1980’s Shell developed new bidentate phosphine ligands which lead selectively to polyketones. Drent et al. found that among the ligands of the series Ph2P(CH2)nPPh2 (n = 1-6), the one with n = 3 is the most effective in terms of both productivity and molecular weight of the polymers. It was proposed that the energy barrier for insertion reactions is lower for a diphosphine with a natural bite angle close to 90°, which is better met by the (CH2)3 backbone (n=3).[12,15]
Scheme 3. Diphosphine ligand (dppp) which is selective for polyketone production.
1.2.2 Methyl Propionate Formation
Later, Drent found that the substitution of the phenyl groups by sterically demanding tert-butyl groups (dtbpp) lead to a change in selectivity of the reaction in favor of the production of methyl propionate (Scheme 4) with 97.4 % yield at 120 °C, 40 bar, CO:ethylene = 2:1, TOF = 25.000 h-1 (turn over frequency).[13] The most effective ligand up to now was developed in 1990. The diphosphine ligand (dtbpx) consists of an -xylene backbone and sterically demanding tert-butyl substituents.[16] The catalyst is generated in-situ from Pd(dba)2, the dtbpx ligand and methanesulfonic acid. The production process provides methyl propionate with a high production rate of TOF = 50.000 h-1 and selectivities greater than 99.9 % under mild conditions (80°C, 10 bar, pressure, CO:ethylene, 1:1).
Scheme 4. Diphosphine ligands (dtbpp and dtbpx) which are selective for methyl propionate production.
Recently, Lucite International (Mitsubishi Rayon) developed a MMA process which exhibits as a key step the low-pressure ethylene carbonylation to methyl propionate with the homogeneous dtbpx diphosphine based catalytic system. This is followed by reaction of the methyl propionate formed with formaldehyde in the gase phase over a fixed-bed heterogeneous catalyst in the presence of methanol to produce MMA and water. This so-called Alpha process is claimed to reduce the total production cost by 40 % and operates at mild conditions. It was first commercialized at the Alpha 1 plant in Singapore in 2008 with an annual capacity of 250kte.[17]
The mechanism of the methoxycarbonylation of ethylene as outlined in Scheme 5 was studied intensively by NMR and infrared spectroscopic techniques.[12,18,19] In principle, there are two possible pathways widely accepted today: The hydride cycle (A) involving a Pd(II) hydride species and the methoxy cycle (B) involving a methoxy Pd species.
Scheme 5. Mechanism of the methoxycarbonylation of ethylene to methyl propionate (v, MP) or polyketones (vii, PK), respectively.
The hydride cycle (A) starts with the formation of the Pd-H (i) species in which ethylene is inserted (ii). Further coordination (step ii-iii) and migratory-insertion of a CO molecule (step iii-iv) into the Pd-C bond of the Pd-ethyl complex (ii) generates the Pd-acyl complex (iv). Subsequent inter- or intramolecular nucleophilic attack of methanol at the Pd-acyl species irreversibly leads to the formation of methyl propionate (v, MP) under regeneration of the Pd-hydride species (i).
Depending on the diphosphine ligand of the Pd(II) catalyst, instead of competing methanolysis termination, a further ethylene molecule can coordinate to the Pd-acyl complex (iv) forming vi and thus leading via subsequent chain growth to polyketones (vii, PK).
Starting point of the methoxy cycle (B) is the CO insertion to the Pd-OMe (viii) bond leading to the formation of the methoxy-carbonyl complex (ix). Subsequent coordination and insertion of ethylene in combination with the methanolysis yields the final product methyl propionate (v, MP).
For both mechanisms all individual steps have been observed in model compounds and depending on the catalytic system and reaction conditions both mechanisms might in principle occur.
However, up to now it seems that the hydride mechanism is the major operative pathway, which is based on mechanistical evidence.[20,21,22 ]
The reaction rate and chemoselectivity towards methylpropionate are mainly controlled by steric factors and thus the bite angle and the steric demand of the bidentate ligands are important issues.
DFT investigations (density functional theory) showed a strong influence of the steric bulk and the bite angle on the methanolysis as rate-determing step. The high electron density caused by the - donor diphosphine stabilizes the 14e--η2-acyl intermediate (iv) and suppresses at the same time the formation of the 16e- complex (e.g. the ethylene complex (vi)). By increasing the steric demand of the catalyst, the resting states of the preceding insertion of the olefin are destabilized, thus easing the rate-determining step. The bulky tert-butyl groups restrict the available space around the other two coordination sites of the square-planar Pd(II) center and consequently inhibit the ethylene coordination forming vi which leads, after subsequent insertion into the resulting Pd-acyl complex, to a growing chain (vii). The chemoselectivity of this reaction is mainly a steric problem. After insertion of just one molecule of each monomer, fast methanolysis of the Pd-acyl iv intermediate occurs with selective formation of methyl propionate (v, MP).[23]
The key role in governing the selectivity of the carbonylation of ethylene is the steric hindrance of the catalytic system. The steric environment in metal complexes is often considered to be more important than electronic factors in determining the structure and the reactivity of complexes. In this regard the steric demand of phosphines can be quantified by the concept of Tolman’s cone angle θ (Figure 1).[24]
Figure 1. Tolman’s cone angle θ and half cone angle φ of diphosphine ligands.
The cone angle is defined as the apex angle of a cylindrical cone centred 2.28 Å from the center of the phosphorus atom and just touching the van der Waals radii of the outermost atoms of the
molecule. We have transferred the principle of Tolman’s cone angle to diphosphine ligands and quantified the catalytic pocket around the palladium center by measurement of the half cone angle
. For this purpose we measured the angles between a vector V defined by the center of the two phosphorus atoms and the Pd(II) center, and four vectors R1, R2, R3, and R4 defined by the Pd(II) center and the substituents on the phosphorus moiety (see right side of Figure 1). The arithmetic average of these angles is the ‘half cone angle’ (for details cf. Exp. Section).[25]
1.3 Diphosphine Synthesis
The synthesis of the dtbpx ligand has already been described by Shaw[26] et al. in 1976 and some of its reactions have been explored by Spencer[27] and coworkers in 1992. In the 1990s ICI developed a carbonylation process based on this ligand.[16a] The published synthetic pathways are summarized in Scheme 6.
Scheme 6. Synthetic pathways to the dtbpx ligand and its derivatives.
The methyl groups of a can be deprotonated/lithiated (i) with a strong base (e.g. NatBu, KOtBu, BuLi) followed by subsequent treatment with two equivalents of di-tert-butylchlorophosphine
(ii).[28a,b] Another possibility is the bromination or chlorination (iii) of a and the further conversion to the desired borane protected diphosphine e with two equivalents of a lithium phosphide (iv).[28c]
This route contains an additional synthesis step because the borane adduct (e) has to be removed from the reaction mixture releasing the free diphosphine dtbpx. In addition dtbpx can be synthesized via a Grignard reaction (vi).
According to Shaw and Moulton[26] (viii), the secondary phosphine is reacted with ,’-dibromo- o-xylene (c) in acetone to yield the diphosphonium bromide (f). Treatment with an excess of sodium acetate in degassed water liberates the desired phosphine dtbpx. Basically, the formation of large quantities of the cyclized phosphonium salt (g) as by-product makes this approach inefficient considering the expense of the di-tert-butylphosphine starting material.
1.4 Highly Active and Selective Catalysts for the Production of Methyl Propionate
The high performance of the dtbpx based catalyst prompted much interest in developing even more efficient catalysts. Several complexes with symmetrical and unsymmetrical ligands of the dtbpx type (Figure 2), which do not differ in the bite angle with respect to the benchmark dtbpx ligand, showed significant differences in selectivity towards methyl propionate. Ligands with one PtBu2
group reach similar activities and selectivies as compared to the dtbpx catalyst. By changing both PtBu2 moieties against PR2 groups with less bulky substituents selectivity and activity are significantly lower, the main products being oligomers and polyketones. Pringle[29] concluded that only one PtBu2 group is required to achieve both selectivity and activity. The chemoselectivity- determining step is dictated by a Pd-acyl intermediate with a PtBu2 group trans to the acyl substituent.
Figure 2. Ligands for the methoxycarbonylation of ethylene leading to methyl propionate (MP) and polyketones (PK).
Eastham[30]et al. developed a series of new diphosphine ligands with structural similarities to dtbpx comprising cycloalkyl-backbones of varying ring size (Figure 3). The catalytic activity of the in-situ generated catalyst was investigated in the methoxycarbonylation of ethylene using two different acid systems: CF3CO2H (pKa = 0.5) and MeSO3H (pKa = -1.9). Variation of the acids has significant influence on the outcome of the experiments. Using equimolar amounts of MeSO3H the complexes incorporating ligands with three-, four- and six-membered rings were more active than the benchmark dtbpx system (TON: up to 997 versus 630 for the dtbpx ligand).
In the presence of excess amounts of MeSO3H the cycloalkyl catalysts were deactivated, in contrast to the dtbpx catalyst, which remained highly productive (TOF = 50.000 h-1).[16b] Moreover, an excess of MeSO3H led to a sharp activity increase of the dtbpx catalyst favoring the formation of catalytically active species as compared to the equimolar reaction conditions (TON = 630).
According to the authors, this result can be explained with the higher basicity of the cycloalkyl diphosphine ligands as compared to the dtbpx ligand (the bite angles of the four new systems are virtually identical with the dtbpx ligand): Under the mentioned conditions the cycloalkyl diphosphines are protonated leading to the formation of inactive Pd black.
When employing a large excess of the weaker acid CF3CO2H no protonation of the diphosphines occurs and good catalytic results were obtained for the four-, five- and six-membered ring cycloalkyl diphosphines (TON: ca. 850 versus 603 for the dtbpx ligand).
Figure 3. Diphosphine ligands with aliphatic cyclic backbones and corresponding bite angles .
1.5 Catalysts for the Methoxycarbonylation of Terminal Olefins
Recently Beller[31]et al. reported the preparation of novel N-heterocyclic diphosphine ligands with benzene, tetralin, lutidine, pyrazine, quinoxaline and maleimide backbones and their initial catalytic performance in methoxycarbonylation reactions of 1-octene (Scheme 7). Under the described conditions the new catalysts gave the linear methoxycarbonylated product in low to moderate total ester yield of 4-64 % (linear selectivity in the range of 69-92 %). Changing the substituents on phosphorus atoms from phenyl to cyclohexyl to tert-butyl enhance the selectivity towards the linear ester.
Scheme 7. Pd-catalyzed methoxycarbonylation of 1-octene.
1.6 Possible -Functionalization of Internal Olefines
As mentioned in Section 1.1, for a most efficient utilization of the fatty acid feedstock a complete incorporation of the entire fatty acid chain is desirable. Two main requirements have to be fulfilled:
A) An isomerization process which shifts the internal double bond to the terminal chain end.
B) The chain-end functionalization must be ensured which can be realized by the methoxycarbonylation process as explained in Section 1.2.
The combination of both processes A and B is referred to as isomerizing alkoxycarbonylation, which enables the efficient transformation of an internal double bond to a terminal ester functionality simultaneously by using a single catalyst only.
1.6.1 Isomerizing Alkoxycarbonylation of Monofunctional Olefines
The beginning of the isomerizing alkoxycarbonylation reaches back to the work of Pringle and Cole-Hamilton.[32] They found not only that terminal 1-olefines can be selectively transformed into linear esters, but also internal olefins such as 2-octene, 3-octene as well as 4-octene were converted into the corresponding linear monoesters in high yields of 94-99 %. In this connection in-situ generated Pd(II) complexes of electron rich diphosphines such as meso/rac-dapp[32a] or the aforementioned dtbpx[32b] were used (Scheme 8).
Scheme 8. Isomerizing methoxycarbonylation of internal olefines.
Thereby the double bond is isomerized to the terminal end of the chain via chain walking[33]
followed by the methoxycarbonylation step. The combination of isomerization and end-functionalization was further extended to longer chains with internal alternating double bond systems.
1.6.2 Isomerizing Alkoxycarbonylation of -Functionalized Olefines
Cole Hamilton[34] et al. transferred the basic principle of the alkoxycarbonylation of unsaturated olefins to unsaturated fatty acids (Scheme 9). Using Pd(II) catalysts derived from the dtbpx ligand,[16] high selectivities towards the linear diester (dimethyl-1,19-nonadecanedioate) starting from methyl oleate (MO) were achieved.[35] This remarkable reaction fully incorporates an unsaturated fatty acid starting material into an α,ω-diester. Taking all together the chemoselective transformation of an internal double bond to the terminal chain end is particularly challenging for the chemical synthesis.
Scheme 9. Conversion of methyl oleate to dimethyl-1,19-nonadecanedioate.
The essential mechanistic features responsible for the unusual selectivity towards the linear α,ω- diester have been revealed by the Mecking group (Scheme 10).[22] Important results are summarized in the following:
Scheme 10. Mechanistic investigations in the isomerizing methoxycarbonylation of methyl oleate.[22]
The insertion of methyl oleate into the hydride species (i) firstly results in a branched alkyl species (ii). After rapid isomerization the linear alkyl species (iii) and the chelate (iv) are formed in an equimolar ratio. Insertion of CO into the alkyl complexes (iii and iv) forms the linear alkanoyl species (v) and a five-membered chelate (vi) which is not opened even with excess of CO. Due to the reversibility of the CO insertion the resting state of the dormant catalyst species (vi) can interconvert into the productive catalytic cycle. Computational studies showed that due to the steric demand of the ligand, first the linear alkyl species (iii) is energetically favored over the branched ones and second the four-membered chelate (iv) is favored over the five-membered chelate. For this increasing difference of the barrier G≠ between the methanolysis of the linear (v) and branched alkanoyl (vi), the final step, the methanolysis preferably occurs from the linear alkanoyl species (v), even with a large excess of MeOH.
1.6.3 Isomerizing-Endfunctionalization Reactions
Other examples of isomerization-endfunctionalization processes include Nozaki’s highly n- selective three-step one-pot reaction of several internal olefins such as (Z)-2 decene, (Z)-2- tridecene and methyl oleate to the corresponding n-alcohols using a Rh/Ru dual catalyst-system (Scheme 11). The conversion comprise the isomerization of the double bond, hydroformylation to the aldehydes and subsequent hydrogenation to the corresponding alcohols.[36]
Scheme 11. One-pot isomerization, hydroformylation and hydrogenation.[36]
Olefin metathesis tandem processes have attracted particular attention in recent years (Scheme 12).
Gooßen et al. described the conversion of oleic acid via isomerizing self- and cross-metathesis reactions into compound mixtures with varying chain length distribution. In analogy to olefin blends available from petrochemical sources the chain length distribution with regard to the mean and span could be adjusted.[37]
Scheme 12. Isomerizing olefin metathesis.[37]
An effective catalyst system was identified that continuously equilibrates the position of the double bond in olefinic substrates such as methyl oleate. At the same time the catalyst system metathesize the olefin mixture in order to obtain defined distributions of functionalized products. The dimeric Pd(I) complex [Pd(-Br)tBu3P]2 turned out to be an uniquely active isomerization catalyst, which retains its activity in the presence of state-of-art olefin metathesis catalysts without loosing activity.[37]
Angelici[38] et al. explored the behavior of methyl oleate in the selective isomerizing hydroboration reaction in order to produce the boronated ester group exclusively on the terminal end of the carbon chain. Scheme 13 (A) shows the reaction sequence with an in-situ generated catalyst. The catalytic system [Ir(COE)2Cl]2 / dppe promotes both the rapid isomerization of methyl oleate and the selective hydroboration of the terminal isomer in 45 % yield.[38]
Another example describes the isomerizing hydroformylation of methyl oleate in the presence of a rhodium catalyst (Scheme 13 (B).[39]
Scheme 13. One-pot isomerizing, hydroboration (A)[38] and hydroformylation (B).[6c,39]
Under the given conditions (115 °C, 20 bar syngas) the best yield of the -aldehyde is 26 %.
Unfortunately, hydrogenation of the double bonds occurred as a dominant reaction pathway, which was attributed to an ester group effect. The ester function makes hydroformylation in the immediate vicinity of this group impossible. For this reason hydrogenation predominates over formation of branched aldehydes.[6c]
1.6.4 ,-Functionalized Long-Chain Alkanes as Building Blocks for Polymers
The use of vegetable oils and fatty acids for polymer applications has a long tradition. Important examples are building blocks for thermoplastic polymers (e. g. dicarboxylic acids such as sebacic acid and oleic acid) as well as polymer additives (e.g. epoxidized soybean oil as plasticizer).[6a]
A particular efficient route leading to polyesters has recently been developed by the Mecking group (Scheme 14).[40] Technical plant oils (such as high oleic sunflower oil) can be employed as a substrate without prior separation of the different fatty acids present. The approach is based on readily available methyl oleate and the first step takes advantage of the isomerizing alkoxycarbonylation reaction. The monomer building block (α,ω-diester, dimethyl-1,19-nona- decanedioate) is obtained highly selectively on a 100 g scale in the lab. Further reduction of this monomer either by LiAlH4 or ruthenium catalyzed hydrogenation lead to the corresponding diol, which is used as second monomer partner in the following step-grow polycondensation polymerization reaction leading to polyesters with molecular weights M typically being 2×104 g mol-1 and a crystallinity of around 75 %. Other chemical reactions include the transformation of the α,ω-diesters to α,ω-diamines and α,ω-acetals which are all obtained in polycondensation grade purities of > 99 %.[40]
Scheme 14. Thermoplastic polyesters from renewable resources with complete feedstock utilization.
Polyesters generated from 1,19-dimethyl-nondecaneedioate as monomer building block posess useful mechanical properties such as high crystallinity, which are comparable to linear polyethylene (HDPE) their thermal properties being compatible with thermoplastic processing.
Due to their hydrophobicity and crystallinity such long-chain aliphatic polycondensates can be subject to a desirable slow hydrolytic degradation in the environment, e.g. in marine environments.
Although with the dtbpx catalyst system high reaction productivities and selectivities in the isomerizing methoxycarbonylation of olefines can be obtained, the reaction is rather slow.
Especially for long chain molecules such as methyl oleate the reaction times increase greatly (ethylene (TOF: 12,000 h-1, at 80 °C, 10 bar, CO : ethylene = 1:1) < 2-octene (3 hours, 80°C, 30 bar, TON: 255) < 3/4-octene (16 hours, 80°C, 30 bar, TON : 255) < methyl oleate (18 hours, 90
°C, 20 bar CO, TON: 125).[16b,22,32b,34,40] Furthermore, the dtbpx based catalytic active hydride species is sensitive towards the reaction conditions (e. g. CO pressure). Carbon monoxide can induce the formation of inactive neutral Pd(0) complexes which can couple with other cationic palladium species to form catalytically inactive bridged [(P^P)Pd]22+ complexes or reductive elimination of the Pd(II) hydride complex to the protonated ligand and Pd metal. These processes limit the overall yield of the linear product and decrease the catalytic performance of the catalyst.[41,42] These problems might be overcome by changing the nature of the diphosphine ligand.
The specific design of the ligand structure and substitution pattern could generate Pd complexes of greater stability, which are more active and more selective when used in the isomerizing methoxycarbonylation of methyl oleate.
2 Scope of this Thesis
In the view of the worldwide constantly growing demand for polymers, a fast and simple access to the plastic products is desirable. Plant oils offer a unique starting material structure with their long methylene sequences. If those can be converted to a linear difunctional chain this provide unique building blocks for semicrystalline polymers. This challenge is achieved by the isomerizing alkoxycarbonylation reaction of fatty acids such as methyl oleate, which is readily available from plant oils. Therby the entire fatty acid chain is converted into the linear -diester as versatile long chain monomer building block for polymers. For this pivotal single-step transformation on a large scale efficient catalysts are required (Scheme 15). So far, no robust process suitable for large- scale production of the long chain 1,19-diester has been developed. On the lab scale promising results were achieved with the use of dtbpx derived catalysts.
In this context the goal of the present thesis was to synthesize novel diphosphine based Pd(II) catalyst precursor complexes, which are highly selective in the 1,19-diester production and less sensitive towards deactivation processes. The focus was on unsymmetrical bidentate ligands with an o-tolyl backbone bearing different bulky and electron rich alkyl substituents on the phosphorus donor atom. The orthogonal reactivity pattern of the unsymmetrical o-tolyl backbone (Scheme 15) opens a simple way to a rich library of different unsymmetrical diphosphine ligands. The influence of their steric bulk on the selectivity to the linear 1,19-diester formation and their productivity has not been investigated yet.
Structure productivity relationships can give hints as to how the catalysts’ diphosphine substitution pattern impacts on selectivity and productivity of this remarkable reaction. Consequently, the most effective substitution pattern R and R’ of the unsymmetrical o-tolyl diposphines should be transferred on a second generation of Pd(II) catalysts based on the known -xylene backbone, followed by investigations of their catalytic behavior in the isomerizing methoxycarbonylation of methyl oleate.
Scheme 15. Transformation of plant oil derived methyl oleate into polymers via the Pd(II) catalyzed isomerizing alkoxycarbonylation process.
3 Results and Discussion 3.1 Previous Studies
Important previous studies directly related to the new results reported in this thesis shall be briefly summarized here.
Pd(II) complexes bearing the sterically demanding dtbpx ligand are known to be very productive catalysts in the isomerizing alkoxycarbonylation of plant oils.[33-35] The favorable properties of the dtbpx ligand (type I wih R = tBu, 1) and its unsymmetrical derivatives lead to the decision to explore the performance of catalysts based on the o-tolyl backbone (II) (Figure 4). o-Tolyl diphosphine ligands II are in a mid-position between the rather rigid diphosphines of type III and the more flexible dtbpx type I ligands. Metal complexes with ligands of this type might be suitable for efficient catalyst precursors. In addition, they could be more resistant towards catalyst decomposition as they are less basic than complexes based on type I and less sensitive towards protonation and Pd black formation.[30] To investigate whether the coordination chemistry of the unsymmetrical o-phosphino-benzyl-diorgano-phosphine ligands would provide insight into the catalytic performances of its Pd complexes is of further interest.
Figure 4. Diphosphine structures (R = alkyl, e.g. tert-butyl, iso-propyl).
Known syntheses leading to unsymmetrical diphosphines are outlined in the following Schemes 16-18. A suitable starting material for the diphosphine synthesis is o-bromotoluene 2. G. Müller[43]
et al. developed a photochemical route to convert 2 to 3 (Scheme 16). The starting material is easiliy accessible and inexpensive. Moreover, dihalogene-phosphine 3 is an interesting and versatile substrate that can be used in large scale for transformation into further phosphine ligands.
UV light induces the formation of an exo-methyl radical of 2, which reacts finally with PCl3 or PBr3 to 3. Treatment of di-bromo-phosphine 3 with two equivalents of a Grignard reagent leads to the double substituted benzylphosphine 4, which is lithiated in the presence of n-BuLi (5).
Scheme 16. Photo-catalytic synthesis of unsymmetrical diphosphines by G. Müller et al.[43]
After subsequent conversion with dialkylphophine chlorides, the desired o-tolyl diphosphines (II) can be obtained. Moreover, derivate 3 even offers the possibility of a stepwise P-alkylation by adding 1 equivalent of a certain Grignard reagent (Cl-Mg-R) followed by the addition of another Grignard reagent (1 equiv., Cl-Mg-R’) to achieve diphosphine ligands carrying different alkyl residues attached on the benzyl phosphorus. In addition, by using Grignard reagents (e.g.
Cl-Mg-Me, Cl-Mg-tBu) as alkylation agents for the phosphorus atom the application of expensive starting materials such as dialkyl-chlorophosphines can be avoided.[44] The reaction sequence outlined in Scheme 16 clearly shows the advantages of an orthogonal reactivity principle (represented in II). Targeted introduction of both phosphine moieties succeed stepwise, one after another, via two different carbon reactivity patterns. The carbon atom at the benzyl position acts as electrophile and the o-carbon benzene atom operates as a nucleophile attacking the dialkyl- chlorophosphine. However, the use of the photo reaction (2 to 3) is limited due to long reaction times (6 hours) and harsh reaction conditions (e.g. 160 °C) which causes the formation of unwanted side products.
Starting with tolyl-bromide 2 Gosh et al. developed an approach for the synthesis of the tetraphenyl substituted diphosphine 9 in several steps (Scheme 17).[45] The pivotal step is the substitution
reaction of benzyl bromide 7 and borane-diphenylphosphine complex using highly carcinogenic HMPA (step 3). On the one hand, the broad application of this route is limited due to the use of HMPA, which is essential for the reaction. On the other hand, step 1 (substitution with HP(O)Ph2) as well as step 4 (reduction of phosphine oxide 8) are limited to less electron donating substituents such as phenyl.
Scheme 17. Synthesis of 9 by Gosh et al.[45]
Alternatively, o-bromo-benzylbromide 10 has been used as starting material to synthesize several unsymmetrical diphosphine ligands (examples shown in Figure 5). Three different initial steps leading to benzyl phosphine derivative 12 were elaborated and published (Scheme 18), respectively, comprising the two-step formation of a Grignard intermediate (a),[46a,47d] usage of metallated phosphines (b)[16a,46] as well as the addition of dialkyl phosphine (c).[47] The straightforward chemistry is characterized by the lithiation (13) using n-BuLi followed by the direct phosphorylation with dialkylchlorophosphines giving rise to the target ligands II.
Scheme 18. Synthesis of diphosphines type II.
According to synthesis (c), Pringle et al. described very recently the manufacture of several target ligands (two examples are shown in Figure 5),[48] which were used for generating catalysts suitable for the methoxycarbonylation of ethylene. The catalytic performance of the corresponding Pd(II) and Pt(II) complexes illustrates that the results strongly depend on the substitution pattern on the phosphorus atom. Compared to others, diphosphines bearing more sterically demanding groups were highly active.
Figure 5. Diphosphines for the methoxycarbonylation of ethylene.
3.2 Novel Complexes of Bulky Diphosphine Ligands with an Unsymmetric Backbone
At the same time as Pringle’s investigations we have independently chosen route c (Shell patent)[47]
as basis of own research activities. The Shell route seemed to be most efficient for the introduction of bulky substituents (which are generally unreactive) leading to new unsymmetrical diphosphine ligands (Scheme 19).
2-Bromo-benzylbromide 10 is treated with secondary bulky phosphines such as HP(tBu)2 (14), HP(Ad)2 (15) and HP(Cy)2 (16) giving rise to the corresponding mono-substituted intermediates, which were easily isolated as hydrobromic acid salts 17-19 (white solids and in the case of 18 colorless crystals).
Scheme 19. Efficient route to monophosphines 20, 21 and 22.
The highest yields could be obtained with acetonitrile as solvent, facilitating the nucleophilic attack of the bulky monophosphines at the benzylbromide 10. Treatment of the formed hydrobromides (17-19) with trimethylamine in toluene release the resulting neutral monophosphines 20 (86 %) and 21 (65 %), which could directly be used in the next step without further purification (purity by
1H NMR > 98 %). Crude 22 was received as a pale yellow oil, which was recrystallized from hot ethanol yielding 22 as colorless crystals (45 %).
Scheme 20. Synthesis of unsymmetrical diphosphines 29-34.
Monophosphine 20 was lithiated at room temperature in pentane by adding n-BuLi, resulting in the immediate formation of a white precipitate that has been isolated by simple filtration (Scheme 20).
Further treatment of 23 with chlorophosphines (Cl-tBu2P, Cl-PiPr2 and Cl-PCy2) in THF at -80 °C afforded the desired unsymmetrical diphosphines 29, 30 and 31, respectively, as crude products, which were recrystallized from ethanol or other organic solvents (see Table 1, with detailed crystallization conditions and behavior) as colorless needles suitable for X-ray diffraction.
Table 1. Crystallization behavior of the diphosphines 29-34.
Ligand Crude product Crystallization Ligand properties 29 (tBu-tBu) Colorless oil EtOH, r.t. -> -20 °C Waxy colorless crystal 30 (tBu-Cy) Colorless solid Hot EtOH -> r.t -> -20 °C Colorless needles 31 (tBu-iPr) Waxy solid EtOH, r.t. -> -20 °C Waxy colorless crystal 32 (Ad-tBu) Yellow foam Hot EtOH, CH2Cl2 -> r.t. Colorless crystal 33 (Ad-Cy) Colorless solid Extraction with H2O Colorless solid 34 (Cy-Cy) Colorless foam Hot pentane, CH2Cl2 -> r.t. Colorless crystal
Alternatively, monophosphines 20, 21 and 22 can be lithiated with n-BuLi in THF solution (instead of pentane) without precipitation. This in-situ generation of the lithium aryls turned out to be advantageous as compared to the limited stability of the isolated lithium aryls. The formation of the lithium salts was checked on completeness and the “in process control” (IPC) was made by NMR measurements. NMR samples were taken after 15 minutes when the lithiation was initiated.
The lithium salt has been identified as hydrolyzed compound o-deuterium-benzyl-di(tert- butyl)phosphine after quenching with methanol-d4.
In case the lithiation turned out to be incomplete, the formation of undesired side products such as the alkylated phosphine n-butyl-di(tert-butyl)phosphine (36) is likely (Figure 6).
Figure 6. Example of a 1H NMR spectrum of a crude product mixture after incomplete lithiation.
As is shown in Figure 6, incomplete lithiation gave the following compound mixture: diphosphine 29 (7.2 %), hydrolyzed monophosphine 35 (21.4 %) and alkylated phosphine 36 (71.4 %) derived from n-BuLi and Cl-PtBu2. Increasing temperature will lead to -lithiation and thus facilitate the formation of impurities. Elongation of the reaction time completes the o-lithiation and thus decreases the formation of impurities. The presence of sterically hindered residues lead to prolonged reaction times of the o-lithiation of 30-60 minutes (e.g. 29, 32). Alternatively to n-BuLi the more reactive tert-BuLi has been tested in the lithiation reaction. In this regard, the isolation of the lithium salts can be advantageous as the addition of equimolar reagents (next step) does not generate side products.
The target compounds 29-34 were obtained in yields of 34 up to 94 % by quenching the in-situ generated lithium aryls with chlorophosphines 26-28 followed by subsequent recrystallization. The
31P NMR shifts of all synthesized diphosphine ligands (Figure 7) nicely correlate with the nature of the alkyl substituent in the following order δ: tBu ≈ Ad > Cy> iPr.
Figure 7. 31P NMR data for ligands 29-34 in C6D6, 25 °C, for 33 in CDCl3.
The crystal and molecular structures of diphosphines 29, 32 and 34 were determined by X-ray diffraction (Figure 8). Selected bond lengths and angles are summarized in Table 2. Bond lengths are in the typically range of P-C(alkyl) and differ only marginally for the diphosphines 29, 32 and 34, respectively. As expected the P-C(aryl) bonds are slightly shorter than the P-C(alkyl) bonds.
The bond angle between the two cyclohexyl groups and P1 (C(14)-P(1)-C(8)) shows a value of 102.91(11), which is smaller as compared to the corresponding angles in the diphosphines 29 and 32. This is due to less steric hindrance of the cyclohexyl rings.
Figure 8. Molecular structure of 29, 32 and 34 in the solid state. Ellipsoids are drawn at the 50%
probability level. Hydrogen atoms have been omitted for clarity.
Regarding the P2-C7-axis in 29 (see Figure 8), the substituents C12 and C6 form a torsion angle of almost 180° (C(6)-C(7)-P(2)-C(12): 173.0°). The tert-butyl groups on C12 are placed at the maximum distance to the benzene ring at P2 (diphosphine 29, Figure 8).
Table 2. Selected bond lengths [Å] and angles [°] for 29, 32 and 34.
29 32 34
Bond lengths
C(1)-P(1) 1.855(17) C(7)-P(2) 1.868(17)
C(1)-P(1) 1.852(2) C(7)-P(2) 1.862(19)
C(1)-P(1) 1.847(2) C7)-P(2) 1.867(2) Bond
angles
C(1)-P(1)-C(16) 106.94(8) C(20)-P(1)-C(16) 110.55(8) C(8)-P(2)-C(12) 109.92(8)
C(1)-P(1)-C(8) 105.40(9) C(12)-P(1)-C(8) 111.00(10) C(16)-P(2)-C(26) 111.40(8)
C(1)-P(1)-C(8) 100.17(11) C(14)-P(1)-C(8) 102.91(11) C(20)-P(2)-C(7) 100.56(10) Torsion
angle
C(5)-C(6)-C(7)-P(2) 49.2(19) C(6)-C(7)-P(2)-C(12) 173.0(13)
C(5)-C(6)-C(7)-P(2) 33.9(2) C(6)-C(7)-P(2)-C(26) -150.10(14)
C(5)-C(6)-C(7)-P(2) 63.5(2) C(6)-C(7)-P(2)-C(20)-155.80(17)
3.2.1 Synthesis of o-Tolyl-Tetra-Adamantyl Diphosphine
To further explore the potential of bulky alkyl substituents a chelating ligand with diadamantylphosphine groups on both phosphorus atoms was synthesized. To carry out the final step, the corresponding lithium salt 24 should be converted to the target ligand 38 using chloro- diadamantyl phosphine 37 as reagent for the nucleophilic attack (Scheme 21).[49,50,51]
Scheme 21. Synthesis of diphosphine 38 using Cl-PAd2.
Chlorophosphine 37 is commercially available, but expensive,[52] and is described in the literature to be generated in high yield by mixing diadamantylphosphine 15 and DBU in the presence of either highly reactive phosgene or carbon tetrachloride (CCl4) (Scheme 22). Due to the high toxicity of the chlorinating reagents - phosgene, triphosgene[51b] as well as carbon tetrachloride - alternative sources for the chlorination or other halogenations were considered.[49,50,51]
Scheme 22. Synthesis of Cl-PAd2 37.
According to the literature attempts to halogenate the phosphine with gaseous chlorine, bromine and/or iodine were not successful and led to product mixtures as the diadamantylphosphine turned out to be extremely unreactive, probably because of the +I-effect of the adamantyl cage.
Unfortunately, the use of inorganic chlorination agents like PCl5[53a,c] or C2Cl6[53b,c] resulted in unidentified product mixtures and hydrochlorinated adamantyl phosphine.
The search for alternative halogenations of diadamantyl phosphine 15 led to the use of solid CBr4
as reagent, having good dissolution properties in methylene chloride (Scheme 23). Indeed, the desired bromo-derivative 39 could be synthesized in 95 % yield after the side product bromoform was removed by evaporation (b.p.: 149.5°C).
Scheme 23. Brominaton of 15.
As bromophosphine 39 suffers from slow decomposition,[49] which was observed by NMR after 24 hours, it turned out to be obligatory to react 39 directly after its synthesis. It should be noted that phosphine oxide 40 (31P NMR (400 MHz, CDCl3): 68.8, s) and hydrobromide 41 (1H NMR (400 MHz, CDCl3): 6.2, d 1J(P,H) = 468.8 Hz) are the major impurities resulting from decomposition reaction of 39. For the next step isolated lithiated benzylphosphine 24 (Table 3, entry i) as well as o-Br-benzylphosphine 21 (Table 3, entry iii, iv and v) were used as starting materials for the substitution reaction with bromophosphine 39. In addition, a Cu+ catalyzed bromo-aryl activation (Table 3, entry vi and vii) was also conducted. [54] Corresponding approaches and detailed reaction conditions are summarized in Table 3.
Table 3. Several attempts synthesizing diphosphine 38.
In order to generate the target ligand 38 only two reaction conditions (Table 3, entry iii and vi) were successful, although only very poor yields in the range of 10 % after recrystallization could be achieved. All other attempts failed completely and/or came along with large amounts of the hydrolyzed monophosphine 42.
However, most importantly sufficient amounts of ligand 38 could be manufactured according to the reaction conditions where using tert-BuLi (Table 3, entry iii) for testing its catalytic activity in the isomerizing alkoxycarbonylation reaction. In total, the obtained results show that the P-aryl coupling is quite challenging for the highly sterically demanding - and thus unreactive - diadamantylphosphine 15. Typical 1H and 31P NMR data of the starting material 21, the hydrolyzed phosphine 42 and the product 38 are given in Figure 9.
Figure 9. NMR data for the product mixture.
In parallel Pringle et al. investigated alternative Pd catalyzed P-C(aryl) couplings (conditions:
[Pd(PPh3)4], HPCg, DABCO, 140 °C, 24 hours) with the aim of synthesizing similar phosphine ligands with bulky substituents (Section 3.1, Figure 5).[48] Pringle’s results are characterized by obtaining rather low yields in the range of 14 %, whenever particularly bulky substituents such as phospha-trioxa-adamantane (Cg) were involved. These findings support our preference for other reaction conditions as already described.[48]
3.2.2 Synthesis and Molecular Structure of Diphosphine Pd(II) Complexes
Starting from the diphosphine ligands 29-34, 38 the desired Pd(II) complexes were synthesized in two steps, initially in the presence of [Pd(dba)2], followed by adding two equivalents of trifluoromethanesulfonic acid (TfOH) and p-benzoquinone (BQ) (Pd(0) -> Pd(II)) in the final step (Scheme 24).[22,63a]
Scheme 24. Synthesis of diphosphine Pd(II) complexes 51-(OTf)2-57-(OTf)2.
The diphosphines 29-34, 38 and [Pd(dba)2] were dissolved in THF and stirred at room temperature for 12 hours. After filtration of small amounts of Pd black and removal of the solvent, the reddish residue obtained was washed with pentane to remove residual diphosphine. The generated diphosphine Pd(0) complexes were reacted further without additional characterization. Crystals of 47 (R = Ad, R’ = tBu) suitable for X-ray crystallography (Figure 10) could be isolated by adding pentane to a solution of 47 in methylene chloride. Dissolution of the [(P^P)Pd(0)(dba)] complexes 44-50 in diethylether and addition of trifluoromethanesulfonic acid in the presence of benzoquinone as an oxidizing agent afforded the desired diphosphine Pd(II) ditriflate complexes (51-(OTf)2-57-(OTf)2) after 12 hours as off-white to yellow solids. The complexes were analyzed
