From Mono- to Tetraphosphines – A Contribution to the Development of Improved Palladium Based Catalysts for Suzuki- Miyaura Cross Coupling Reaction Von der Fakultät für Naturwissenschaften der Technischen Universität Chemnitz genehmigte Dissertation zur Erlangung des akademischen Grades Doktor rerum naturalium (Dr. ret. nat.) Vorgelegt von M. Sc. Albara I. S. Alrawashdeh geboren am 22.05.1981 in Al Tafila- Jordanien Chemnitz, eingereicht am 26.07.2011 Gutachter: Prof. Dr. Heinrich Lang Prof. Dr. Wolfgang Weigand Tag der Verteidigung: 09.11.2011 http://nbn-resolving.de/urn:nbn:de:bsz:ch1-qucosa-80110
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From Mono- to Tetraphosphines – A Contribution to the Development of
Improved Palladium Based Catalysts for Suzuki- Miyaura Cross Coupling
Reaction
Von der Fakultät für Naturwissenschaften der Technischen Universität Chemnitz
genehmigte Dissertation zur Erlangung des akademischen Grades
Die vorliegende Arbeit wurde in der Zeit von August 2008 bis Juli 2011 unter Leitung von Herrn Prof. Dr. Heinrich Lang am Lehrstuhl für Anorganische Chemie der Technischen Universität Chemnitz durchgeführt.
Herrn Prof. Dr. Heinrich Lang danke ich für die gewährte Freiheit bei der Bearbeitung des Themas, die anregenden Diskussionen und für die großzügige Unterstützung dieser Arbeit.
Dedication
To the spirit of my dear father,
To my great mother,
To my wife 'Asma' and my son 'Ibrahim'.
To my brothers; Alhassan, Alameen and Alrazi,
To my sisters; Lubaba and Afaq,
To The Hashemite Kingdome of Jordan.
Albara Alrawashdeh
Bibliographische Beschreibung und Referat
Albara I. S. Alrawashdeh
Von Mono- zu Tetraphosphane - Ein Beitrag zur Entwicklung von verbesserten
palladiumbasiereten Katalysatoren für die Suzuki–Miyaura Kreuzkupplung
Technische Universität Chemnitz, Fakultät für Naturwissenschaften
Dissertation 2011, 181 Seiten
Im ersten Teil der Arbeit wird die Synthese neopentyl- und neosilylsubstituierter Phosphane zur
Verwendung als Liganden in katalytisch aktiven Palladiumkomplexen beschrieben. Die Aktivität
wurde in der Suzuki-Miyaura Kreuzkupplungsreaktion getestet. Während die neosilylsubstituierten
Phosphane 2:1 Addukte (5b und 5d) mit geeigneten Palladiumsalzen bilden, welche moderate
Katalyseaktivität zeigen, untergehen die neopentylsubstituierten Komplexe schnelle
Cyclometalierungsreaktionen in Gegenwart von Basen und bilden die katalytisch wenig aktiven
Palladacyclen (6a, 6e, and 6g). Die deaktivierende Cylometallierung konnte durch Darstellung der
Palladiumcomplexe ausgehend von Pd(cod)Cl2 in Abwesenheit von Basen vermieden werden. Die
erhaltenen 2:1 Phosphaneaddukte zeigten deutlich verbesserte Aktivität. Daraus wurde gesch-
lossen, dass die Cyclomettalierung als Nebenreaktion eine wichtige Deaktiverungsmöglichkeit
darstellt, diese Überlegung veranlasste uns Trialkylphosphane mittlerer Größe, mit Substituenten die
nur schwer eine Cyclometallierungen eingehen können zu testen. Die Verwendung der
Phosphoniumsalze 4h (R = Cy, R‘ = neopentyl) und 4m (R = iPr, R‘ = CH2Cy) führt zu höheren
Aktivitäten in der Suzuki-Miyaura Kreuzkupplung, als bestes Katalysatorsystem hat sich die
Kombination aus Pd2(dba)3 oder Pd(OAc)2 und entsprechendem Phosphoniumsalz ergeben.
Im zweiten Teil dieser Arbeit werden Synthesen zu neuen biphenylbasierten Diphosphanen (70, 71,
76, and 77) vorgestellt. Die Palladiumkomplexe wurden ebenfalls auf ihre Eignung als Katalysatoren
in palladiumkatalysierten Suzuki-Miyaura Kreuzkupplungen getestet und zeigen für diese Klasse von
Komplexen gute Aktivität. Das Tetraphosphan 82 wurde für die Synthese des zweikernigen
Palladium(II)-komplex 83 eingesetzt. Durch die Koordination des D2h-symmetrischen
Tetraphosphanes an die Palladiumatome wird die Symmetrie des Moleküls erniedrigt und folglich
erhält man den formal D2-symmetrischen Komplex 83.
• Table of Contents……………………………………………………………………………………………………… i • List of Figures………………………………………………………………………………………………………….… v • List of Tables…………………………………………………………………………………………………………….. vii • List of Schemes…………………………………………………………………………………………………………. viii • Abbreviations……………………………………………………………………………………………………........ x 1 INTRODUCTION AND MOTIVATION……………………………………………………………………….. 1 1.1 Catalysis…………………………………………………………………………………………………………….. 1 1.2 Organometallic Chemistry and Homogenous Catalysis………………………………………. 6 1.3 Palladium in Homogenous Catalysis…………………………………………………………………… 7 1.4 Palladium Catalyzed Cross Coupling Reactions…………………………………………………… 8 1.5 Palladium Catalyzed Suzuki –Miyaura Cross Coupling Reactions………………………… 13 1.5.1 Phosphorous Ligands in Suzuki – Miyaura Cross Coupling Reactions……… 16
1.5.1.1 Trialkylphosphines…………………………………………………………………… 16 1.5.1.2 Biaryl Based Phosphine Ligands………………………………………………. 23 1.5.1.3 Palladacycles in The Suzuki Cross Coupling Reaction………………. 29 2 RESULTS AND DISCUSSION……………………………………………………………………………………… 36 2.1 Synthesis, Characterization and Applications of Trialkyl Monophosphine Ligands
in Palladium Catalyzed Cross Coupling Reactions………………………………………………
36 2.1.1 Synthesis and Characterization of Substituted Neopentyl and Neosilyl
Phosphine Ligands and their Phosphonium Salts……………………………………
36 2.1.2 Synthesis and Characterization of Substituted iPropyl and tButyl
Phosphonium Salts…………………………………………………………………………………
41
2.1.3 Synthesis and Characterization of Palladium Complexes……………………… 43 2.1.3.1 Synthesis of Substituted Neopentyl and Neosilyl Palladium
Complexes 5a-5d………………………………………………………………………
43 2.1.3.2 Characterization of the Synthesized Complexes 5a-5d…………….. 44 2.1.3.3 Molecular Structures of 5b and 5d……………………………................ 46
2.1.4 Cyclopalladated and Non-Cyclopalladated Complexes of Substituted Neopentyl phosphine…………………………………………………………………............
48
2.1.4.1 Coordination Behavior of Phosphonium Salt 4a ……………………… 49 2.1.4.2 Molecular Structure of the Cyclopalladated Complex 6a.………… 51 2.1.4.3 Coordination Behavior of Phosphonium Salt 4e………………………. 52 2.1.4.4 Molecular Structure of the Cyclopalladated Complex 6e………… 54 2.1.4.5 Coordination Behavior of Cyclopalladated Complex 6e…………… 56 2.1.4.6 Coordination Behavior of Phosphonium Salt 4g…………………….… 59 2.1.4.7 Coordination Behavior of Phosphonium Salt 4h…………………….… 60
2.1.5 Synthesis and Characterization of Substituted iPropyl and tButyl Dinuclear Palladium Complexes 6i-6o……………………………………………………
61
2.1.6 Effective Suzuki Cross Coupling Reactions Using Prepared Phosphonium Salts and Palladium Complexes……………………………………………………………..
67
2.1.6.1 Neopentyl and Neosilyl Phosphines Based Catalysts for Suzuki-Miyaura Cross-Coupling Reactions………………………………………....
67
2.1.6.2 Cyclometallated Palladium Complexes in Suzuki-Miyaura Cross-Coupling and Buchwald Amination Reactions………………..
75
Table of Contents
ii
2.1.6.3 Substituted Trialkylphosphonium Salts in Suzuki-Miyaura Cross
Coupling Reaction……………………………………………………………………
87 2.2 Synthesis, Characterization and Applications of New 2,2'-Bisphosphine and
2,2',6,6'-Tetraphosphine Biaryl Ligands in Palladium Catalyzed Suzuki Cross Coupling Reaction………………………………………………………………………………………………
97 2.2.1 Synthesis and Characterization of New 2,2'-Bisphosphine Ligands and
their Palladium and Platinum Complexes………………………………………………
97 2.2.1.1 Synthesis and Characterization of New 2,2'-
Bis(dimethylamino)-6,6'-Bisphosphinobiphenyl Ligands and their Palladium and Platinum Complexes…………………………………
97 2.2.1.2 Synthesis and Characterization of New 2,2'-Bis(dibromo)-6,6'-
Bisphosphino biphenyl Ligands and their Palladium and Platinum Complexes………………………………………………………………..
104 2.2.2 Bisphosphinbiphenyl Palladium Complexes in Suzuki-Miyaura Cross-
159 3.3 General Procedure for the Suzuki-Miyaura coupling…………………………………………. 160 3.4 General Procedure for the Buchwald-Hartwig coupling……………………………………. 160 3.5 General Procedure for the Suzuki-Miyaura coupling (Kinetic investigations)……. 161 3.6 General Procedure of 31P{1H} NMR studies of the Pd(0), 13e, complex……………… 161
APPENDIX…………………………………………………………………………….……………………………. 172 PERSONAL DATA……………………………………………………………………………………………….. 177 ACKNOWLEDGAMENT……………………………………………………………………………………….. 179
List of Figures
v
• List of Figures.
Figure 1.1: Effect of the catalysts in a thermodynamically favorable reaction…………... 2 Figure 1.2: History of catalysis of industrial process………………………………………………….. 4 Figure 1.3: The principle of cross coupling reaction……………………………………………..…... 9 Figure 1.4: Major cross coupling reactions…………………………………………………………..….… 11 Figure 1.5: Mechanism of a cross coupling reaction………………………………………………….. 13 Figure 1.6: General catalytic cycle for Suzuki-Miyaura coupling………………………………… 15 Figure 2.1: Molecular structure of 5b…………………………………………………………………….….. 47 Figure 2.2: Molecular structure of 5d…………………………………………………………………….….. 48 Figure 2.3: Molecular Structure of 6a (Cyclometallated palladium complex of
phosphine salt 4a (R = iPr, R' = Neopentyl))………………………………………….…..
51 Figure 2.4: Molecular Structure of 6e…………………………………………………………………….….. 54 Figure 2.5: Coordination behavior of cyclopalladated complex 6e……………………….….. 56 Figure 2.6: Molecular structure of 13e………………………………………………………………..….… 58 Figure 2.7: Molecular structure of 6m…………………………………………………………………..….. 64 Figure 2.8: Kinetic investigation of complex in the Suzuki Miyaura cross-coupling
reaction of 2-bromotoluene with phenylboronic acid ……………………..….…
72 Figure 2.9: Kinetic investigation of complexes 5 in the Suzuki Miyaura cross-coupling
reaction of 2-bromotoluene with phenylboronic acid ……………………….…...
73 Figure2.10: Kinetic investigation of complexes 5 in the Suzuki Miyaura cross-coupling
Reaction of 4-chloroacetophenone with phenylboronic acid…………………..
73 Figure 2.11: 31P{1H}-NMR investigation (25°C or 50°C, CD3CN) on the oxidative
addition of bromo benzonitrile to Pd(0) complex 13e in CD3CN……..………
78 Figure 2.12: 31P{1H}-NMR investigation (25°C or 60°C, CD3CN) on the oxidative
addition of 3,5-CF3-bromobenzene to Pd(0) complex 13e in CD3CN……..
78 Figure 2.13: 31P{1H}-NMR investigation (25°C or 50°C, CD3CN) on the oxidative
addition of iodobenzene to Pd(0) complex 13e in CD3CN…………………..…..
79 Figure 2.14: 31P{1H}-NMR investigation (25°C or 50°C, CD3CN) on the oxidative
addition of iodobenzene to Pd(0) complex (no.) in CD3CN ……………………..
80 Figure 2.15: Kinetic Investigation of 6k and 9k in the Buchwald-Hartwig amination
reaction of 2-bromotoluene with morpholine…………………………………………
83 Figure 2.16: Kinetic Investigation of 6k and 9k in the Buchwald- Hartwig amination
reaction of bromobenzene with diethyl amine………………………………..………
84 Figure 2.17: Kinetic investigation of the Suzuki Miyaura cross-coupling reaction of 4-
bromo- acetophenone with phenylboronic acid with 0.5 mol%Pd(OAc)2/1 mol% 4 ……………………………………………………………………..…………………………….
90 Figure 2.18: Kinetic investigation of the Suzuki Miyaura cross-coupling reaction of 3-
chloroanisol with phenylboronic acid with 0.5 mol% Pd(OAc)2/1 mol% 4
91 Figure 2.19: Kinetic investigation of the Suzuki Miyaura cross-coupling reaction of 2-
bromotoluene with phenylboronic acid with 0.5 mol% Pd(OAc)2/1mol% 4
92 Figure 2.20: 1H-NMR spectrum of bisphosphine ligand 71 CDCl3………………………………. 99 Figure 2.21: Variable temperature 1H NMR (500MHz) of 74 in CD2Cl2…………………..… 101 Figure 2.22: Variable temperature 31P{1H} NMR of 74 in CD2Cl2……..................………. 102 Figure 2.23: Molecular structure of 72…………………………………………………………………..…… 103 Figure 2.24: Molecular structure of 73 ………………………………………………………………………. 103
List of Figures
vi
Figure 2.25:
Molecular structure of 74……………………………………………………………………..…
104
Figure 2.26: Variable temperature 31P{1H} NMR of 79 in CD2Cl2/DMF........................ 108 Figure 2.27: The 31P{1H} NMR of 84 in CDCl3…………………….…………………………….….….. 108 Figure 2.28: Molecular structure of bisphosphinebiphenyl 77 ……………………………..……. 110 Figure 2.29: Molecular structure of palladium complex 78……………………………………..…. 110 Figure 2.30: Molecular structure of palladium complex 79 …………………………………..…… 111 Figure 2.31: Kinetic investigation of 72, 73, 78 and 79 in the Suzuki cross coupling
reaction of 2-bromotoluene with phenylboronic acid……………………….……
113 Figure 2.32: Kinetic Investigation of 79 in the Suzuki cross coupling reaction of 4-
bromoanisole with phenylboronic acid……………………………………………….….
114 Figure 2.33: Variable temperature 31P{1H} NMR spectra of complex 83 in d7-dmf
solution at 178, 198, 223, 248, 273, 298, 323, 348, and 373 K ……………...
117 Figure 2.34: Standard proton nmr spectrum, of 83, (top) and 1H selective NOE
spectrum (buttom) with irradiation at the aromatic proton at δ = 8.25 a mixing time of 0.5 sec and 64 transients recorded in d7-dmf at 398K……………………………………………………………………………………………………..…
118 Figure 2.35: 31P{1H} NMR spectrum of complex 83 in d7-dmf at 223K, signals were
grouped based on the signal intensity and line broadening…………………....
119 Figure 2.36: 31P{1H} EXSY spectrum of complex 83 at 208K in d7-DMF/CH2Cl2 mixture
(ratio 1:2)…………………………………………………………………………………………………
120 Figure 2.37: Molecular structure of complex 83………………………………………………………..… 121 Figure 2.38: Ortep drawing of the complete asymmetric unit of crystals of complex
83…………………………………………………………………………………………………..…………
122 Figure 3.1: Photo for preparation of Li/Na alloy…………………………………………..………….… 127
List of Tables
vii
• List of Tables.
Table 1.1: Types of the cross coupling reaction…………………………………………………….. 10 Table 1.2: Suzuki cross-couplings of aryl bromides by Fu………………………………………. 18 Table 1.3: Suzuki cross-couplings of aryl iodides by Fu………………………………………….. 18 Table 1.4: Suzuki cross-couplings of aryl chlorides by Fu………………………………………. 19 Table 1.5: Suzuki cross-couplings of aryl triflates by Fu…………………………………………. 19 Table 1.6: Suzuki cross-couplings of different aryl chlorides with phenylboronic 6
acid by Beller ligand 14………………………………………………………………………….
20 Table 1.7: Suzuki cross-couplings of aryl halides with phenylboronic 6 acid by
Shaughnessy ligands 15, 16 and 17……………………………………………………….
22 Table 1.8: Suzuki cross-couplings of aryl halides by Buchwald………………………………. 26 Table 1.9: Suzuki Cross-Couplings of Aryl Halides by Herrmann……………………………. 32 Table 2.1: 31P NMR data of phosphonium salts……………………………………………………… 43 Table 2.2: Selected bond lengths (Å) and angles (°) of 5b……………………………………… 47 Table 2.3: Selected bond lengths (Å) and angles (°) of 5d……………………………………… 48 Table 2.4: Data for single crystal X-ray structure analysis of 5b and 5d…………………. 172 Table 2.5: Selected bond lengths (Å) and angles (°) of palladacycle 6a.………………… 52 Table 2.6: Selected bond lengths (Å) and angles (°) of palladacycle 6e……………….… 55 Table 2.7: Data for single crystal X-ray structure analysis for 6a, 6e, 6m, and 13e.. 173 Table 2.8: Selected bond lengths (Å) and angles (°) of 12……………………………….…..… 58 Table 2.9: 31P NMR data of phosphonium salts and its dimeric palladium
complexes………………………………………………………………………………………….….
62 Table 2.10: Selected bond lengths (Å) and angles (°) of 6m…………………………………….. 65 Table 2.11: Selected bond lengths (Å) and angles (°) of 72-74, 77, 78 and 79…………. 112 Table 2.12: Selected bond lengths (Å) and angles (°) of 83………………………….………….. 121 Table 2.13: Data for single crystal x-ray structure analysis of 72-74, 77-79, and 83 … 174
List of Schemes
viii
• List of Schemes.
Scheme 1.1: The principle of catalysis…………………………………………………………………..…… 3 Scheme 1.2: Classification of catalysts………………………………………………………………………. 9
Scheme 1.13: Common dialkyl(biphenyl)phosphine for Suzuki cross coupling reactions 25
Scheme 1.14: Synthesis of biaryl backbone phosphines by Buchwald……………………….…. 27
Scheme 1.15: Synthesis of 2,2'-diphosphanesbiaryl…………………………………………………….. 28 Scheme 1.16: 2,2'-diphosphanesbiaryl bu Takaya and Achiwa…………………………………….. 28 Scheme 1.17: Structural definition of cyclometallation……………………………………………….. 29 Scheme 1.18: The first cyclometallated compound by Kleimann, Dubeck and Cope……. 30 Scheme 1.19:
Formation of trans-di(µ-acetato)-bis[di-o-tolylphosphino) benzyl] di- palladium by Hermann and co-workers………………………………………………….
31
Scheme 1.20: Ortho-metallated palladium complexes by Bedford and co-workers…….. 31
Scheme 1.21: Postulated mechanism for the formation of the catalytically active species [Pd{P(o-tol)3}2] during the amination reaction by Hartwig et al…
32
Scheme 1.22: Cyclometallated platinum complexes by Shaw et al. …………………………….. 33
Scheme 1.23: Cyclometallated palladium complexes by Kraus et al. …………………………… 34
Scheme 1.24: Cyclometallated palladium and platinum complexes by Kraus et al. ……… 34
Scheme 2.1: Synthesis of substituted neopentyl and neosilyl phosphines…………………. 37
Scheme 2.2: The mechanism of organomagnesium and organolithium compounds generation …………………………………………………………………………………………….
37
Scheme 2.3: Synthesis of substituted neopentyl and neosilyl phosphonium salts……… 39 Scheme 2.4: Substiuted iPropyl and tButyl phosphonium salts………………………………….. 42 Scheme 2.5: Synthesis of palladium complexes 5a, 5b, 5c and 5d via free phosphine
ligands 3a, 3b, 3c and 3d………………………………………………………………………
44 Scheme 2.6: Synthesis of palladium complexes 5a and 5b via phosphonium salts 4a
and 4b……………………………………………………………………………………………………
44 Scheme 2.7: Coordination behavior of phosphonium salts……………………………………….. 49 Scheme 2.8: Cyclopalladation of the phosphonium salt 4a by Pd(OAc)2……………………. 50
Scheme 2.9: Cyclopalladation of the phosphonium salt 4e by Pd(OAc)2……………………. 53 Scheme 2.10: Synthesis of palladium(0) complex 13e…………………………………………………. 57
Scheme 2.11: Cyclopalladation of the phosphonium salt 4g by Pd(OAc)2……………………. 59 Scheme 2.12: The dinuclear palladium complex of 4h………………………………………………… 60
List of Schemes
ix
Scheme 2.13: Coordination behavior of phosphonium salt's 4i-4o……………………………… 62 Scheme 2.14: Coordination behavior of phosphonium salt 4k…………………………………….. 65 Scheme 2.15: Coordination behavior of cyclopalladated complex 6k…………………………. 66 Scheme 2.16: Suzuki cross-coupling reaction of bromobenzene with phenylboronic
acid catalyzed by palladium complex 5b and 5d …………………………………….
68 Scheme 2.17:
Suzuki cross-coupling reaction of 4-bromoacetophenone with phenyl boronic acid catalyzed by palladium complex 5b and 5d ………………………
69
Scheme 2.18:
Suzuki cross-coupling reaction of 4-bromoanisole with phenylboronic acid catalyzed by 5………………………………………………………………………………..
70
Scheme 2.19:
Suzuki cross coupling reaction of 2-bromotoluene with phenylboronic acid catalyzed by palladium complexes 5 ………………………………………………
71
Scheme 2.20:
Suzuki cross coupling reaction of 2-chlorotoluene with phenylboronic acid catalyzed by palladium complexes 5 ………………………………………………
72
Scheme 2.21:
Screening of bases for Suzuki cross-coupling of 4-bromoacetophenon with phenylboronic acid using catalyst 5b and 5c…………………………………..
74
Scheme 2.22: Postulated mechanism for the formation of the catalytically active monophosphine palladiumd(0) species in Suzuki cross-coupling……………
76
Scheme 2.23: Proposed reaction pathways for the oxidative additions of aryl halides to the Pd(0) complex 13e……………………………………………………………………….
77
Scheme 2.24:
Suzuki coupling of 4-chloroacetophenon with phenylboronic acids catalyzed by mixtures of complex 6e and two equivalents of PPh3 or PPh2(o-tolyl)…………………………………………………………………………………………..
81 Scheme 2.25:
Suzuki cross-coupling reaction of 4-chloroacetophenone with phenyl boronic acid catalyzed by 6k, 9k and 10k………………………………………………..
82
Scheme 2.26: Amination of aryl bromides and chlorides catalyzed by 6k…………………….. 85 Scheme 2.27:
Influence of catalyst loading of 6m ((P(iPropyl)2CH2Cy)2Pd2Cl4) in Suzuki coupling of 4-bromocetophenon with phenylboronic acid ……………………
86
Scheme 2.28:
Suzuki coupling of 4-bromoacetophenon with phenylboronic acids catalyzed by mixtures of Pd(OAc)2 and two equivalents of phosphonium salts [HPR2R'][BF4]; 4b, 4k, 4l, 4m, 4n and 4o.......................................
89 Scheme 2.29:
Suzuki coupling of 2-bromotoluene with phenylboronic acids using phosphonium salts 4………………………………………………………………………………
93
Scheme 2.30:
Suzuki coupling of aryl halides with phenylboronic acids catalyzed by 4h([HPCy2CH2C(CH3)3])/Pd(OAc)2…………………………………………………………….
94
Scheme 2.31:
The comparison of a variety of phosphine ligands as reported by Fu et al. and phosphonium salts 4h, 4m and 4n in Suzuki coupling of 4-chlorotoluene and Phenylboronic acid …………………………………………….……
95 Scheme 2.32: Synthesis of Biaryl backbone phosphines 70 and 71…………………….………… 98 Scheme 2.33: Synthesis of palladium and platinum biarylbackbone phosphines
complexes 72-74……………………………………………………………………………….……
100 Scheme 2.34: Synthesis of biaryl backbone phosphines 76 and 77………………………….…… 105 Scheme 2.35: Synthesis of palladium and platinum biaryl backbone phosphines
complexes 78-81……………………………………………………………………………….……
106 Scheme 2.36: Synthesis of 2,2’,6,6’-tetraphosphinobiphenyl 82 and its related complex
83…………………………………………………………………………………………………………..
115
Abbreviations
x
• Abbreviations.
Ac acetyl
Å angstrom
Ar aryl
br broad
Cat catalysis
CataCXium® A di-1-adamantyl-n-butylphosphine
COSY correlated spectroscopy
Cy cyclohexyl
d doublet (1H NMR)
dd
dt
doublet of doublet
doublet of triplet
DMF dimethylformamide
DMSO dimethylsulfoxide
dppf 1,1'-bis(diphenylphosphino)ferrocene
dsept doublet of septet
DTBNP ditertbutyl neopentyl phosphine
Et ethyl
Et2O diethyl ether
EWG electron with drawing group
EXSY exchange spectroscopy
Hz hertz iPr Iso-propyl
J coupling constant
L ligand
m medium (IR)
M metal
m multiplet (1H NMR)
M.p melting point
MeOH methanol
MHz mega hertz
mmol millimol
MS mass spectrometry nBu n-butyl nBuLi n-butyllithium
Hz, and 2JHH = 6.69 Hz, respectively. Finally, the CH(CH3)2 was appeared at δ = 1.37 ppm.
Chapter 2: Results and Discussion
51
2.1.4.2 Molecular Structure of the Cyclopalladated Complex 6a. The solid state structures of 6a (Cyclometallated palladium complex for phosphnume salt 4a
(R = iPr, R' = Neopentyl) was determined by single crystal X-ray analysis. Crystals suitable for
X-ray studies for complexes 6a were grown by slow diffusion of pentane or diethyl ether
into a solution of dichloromethane containing the complex at room temperature. The
molecular structure of 6a is shown in Figure 2.3, selected bond lengths (Å) and angels (°) are
given in Table 2.5. Crystal data, together with the data collection and refinement
parameters are presented in Table 2.7 (in the appendix). The structure of palladacycle 6a
consists of two halves, in which each half of the dimer is the inverted mirror image of the
other. Moreover, the central four – membered {Pd2(μ-Cl)2} cycle was flat and the four atoms
(two Pd and two Cl) form a perfect plane. Each palladium atom in complex 6a (Figure 2.3) is
in a square planner configuration with the total bond angel around each palladium atom;
360°, and each of them has four atoms in its coordination sphere; one phosphorus, the
metallated carbon and two chlorides. The Pd-Cl (trans to P) bond length was 2.4176(4) Å
(compared with 2.4168(6)Å in Palladacycle 6e), while the Pd-Cl (trans to metallated C) bond
length was 2.4626(4) Å (compared with 2.4754(6) Å in Palladacycle 6e). In addition the Pd-P
bond length was 2.1974(4) Å (compared with 2.2318(6) Å in Palladacycle 6e) and all of them
fall in the expected range of values for similar phosphametallacycle complexes.[166]
Figure 2.3: Molecular structure of 6a (Cyclometallated palladium complex of phosphonium
salt 4a (R = iPr, R' = Neopentyl)), (Pd; orange, P; yellow, Cl; green and C; gray).
Chapter 2: Results and Discussion
52
Table 2.5: Selected bond lengths (Å) and angles (°) of palladacycle 6a.
The Pd – Pd distance within the dimer 6a (Cyclometallated palladium complex of phosphine
salt 4a; R = iPr, R' = Neopentyl) was 3.510 Å (compared with 3.61 Å in Palladacycle 6e;
cyclometallated palladium complex of phosphine salt 4e; R = tBu, R' = Neopentyl) and like
those of the Palladacycle 6e, the crystal structure also confirms the trans-geometry of the
phosphorous atoms along the Pd–Pd axis. As expected for a d8 complex, both palladium
centers were found to be in square planar coordination geometries (the sum of the angles
around Pd in the complex 6a was 360°). Due to the steric strain between a square planar Pd
coordination and an almost planar five membered metallacycle, the Pd–P bond lengths in
cyclometallated palladium complexes 6a were shorter than that expected for a non-
cyclometallated palladium complex 6m (R = iPr, R' = CH2Cy; 2.236 Å) as well as
cyclometallated palladium complex 6e (2.232 Å). On the other hand, the Pd-Cl-Pd-P dihedral
angles was 167.48(15)°, while the Pd-Cl-Pd-C (metallated carbon atom) was 179.67(6)°.
2.1.4.3 Coordination Behavior of Phosphonium Salt 4e.
In common with the previous method used for the cyclopalladation of ligand 4a, the
prepared phosphonium salt 4e was directly treated with a stoichiometric amount of
palladium(II) acetate (1:1 molar ratio) in tetrahydrofuran in the presence of sodium acetate
Pd-P 2.1974(4) Cl-Pd-Cl 98.165(15)
Pd-Cl(trans to P) 2.4176(4) Pd-Pd 3.510
Pd-Cl(trans to metallated C) 2.4626(4) Cl-Pd-P (trans to metallated C) 98.165(15)
Pd-C3 2.0436(18) P-Pd-Cl (trans to p) 173.670(16)
P-C1 1.8373(18) C3 Pd1 Cl1 92.87(5)
P- C6 1.8393(17) C3 Pd1 P1 80.94(5)
P-C9 1.8412(18) Pd-P-C1 106.77(6)
C2 C3 Pd1 115.15(16) C3 Pd1 Cl1 179.06(5)
Chapter 2: Results and Discussion
53
as a base, to yield the cyclopalladated dimer 6e as analytically pure pale yellow crystals in an
overall yield of 83 % after work-up (Scheme 2.9).
Scheme 2.9: Cyclopalladation of the phosphonium salt 4e by Pd(OAc)2.
Like those of the palladacycle 6a, the 31P{1H} NMR spectroscopic observations were thus
indicative of two important points. Firstly, the coordination shift (Δδ) of the phosphine
ligand was supportive of the five – membered chelate ring formation upon cyclopalladation
of the phosphonium 4e and, therefore, provided support to palladated structure of the
ligand via oxidative addition to carbon-hydrogen bonds of methyl in neopentyl group.
Secondly, the appearance of one singlet peak (δ = 94.02 ppm) was in accordance with the
dimeric structure of complex 6e.
Looking at the 1H NMR of the dimeric complex 6e, the CH3 protons of the rest of the
neopentyl group appeared as singlet at δ = 1.21 ppm. Consequently the metallated methyl
protons of the neopentyl group appears as a singlet at δ = 2.35 ppm. Moreover, peak due to
the methyl protons of the tButyl group was appeared as a doublet at δ = 1.44 ppm due to
the spin-spin coupling with the phosphorus atom with coupling constant of 3JHP = 10 Hz,
whereas in the ligand 4e was appeared at δ = 1.49 ppm with coupling constant of 3JHP = 20
Hz. These data clearly sign that complexation has taken place. Finally, the linker methyl
group adjacent the phosphorus atom was appeared as a doublet at δ = 1.83 ppm with
coupling constant of 3JHP = 10 Hz. The 1H NMR signals of the dimer 6e in solution were clear
and easily to be resolved which helped us to get full NMR spectroscopic characterization of
the cyclopalladated structure of the phosphine ligand 4e as mentioned in the above
paragraph. The doublet resonance of the CH2 protons is adequately resolved though and the
efficiency of the spin – spin coupling with the adjacent phosphorus nucleus has improved as
Chapter 2: Results and Discussion
54
a consequence of C-H palladation. This was noted from the 2JPH coupling constant of 10 Hz
for the palladated structure, which is more than twice as large as that of the uncoordinated
ligand (5Hz).
2.1.4.4 Molecular Structure of the Cyclopalladated Complex 6e.
The solid state structure of 6e was determined by single crystal X-ray crystallography.
Crystals suitable for X-ray studies for complexe 6e were grown by slow diffusion of pentane
diethyl ether into a solution of dichloromethane containing the complex at room
temperature. The molecular structure of 6e is shown in Figure 2.4, selected bond lengths (Å)
and angels (°) are given in table 2.6. Crystal data, together with the data collection and
refinement parameters are presented in table 2.7 (in the appendix). Each palladium atom in
complex 6e (Figure 2.4) has four atoms in its coordination sphere; one phosphorus, the
metallated carbon and two chlorides. The Pd-Cl bond length was 2.4168(6) Å, while the Pd-P
bond length was 2.2318(6) Å.
Figure 2.4: Molecular structure of 6e (Pd; orange, P; yellow, Cl; green and C; gray).
Chapter 2: Results and Discussion
55
Table 2.6: Selected bond lengths (Å) and angles (°) of palladacycle 6e.
The Pd–Pd distance within the dimer 6e was 3.610 Å. The crystal structure also confirms the
trans-geometry of the phosphorous atoms along the Pd–Pd axis. As expected for a d8
complex, both palladium centers were found to be in square planar coordination geometries
(the sum of the angles around Pd in the complex 6e was 360°). Due to the steric strain
between a square planar Pd coordination and an almost planar five membered metallacycle,
the Pd–P bond lengths in cyclometallated palladium complexes 6e were shorter than
expected for a non-cyclometallated palladium complex 6m (2.236 Å).
The structure of palladacycle 6e consists of two halves, in which each half of the dimer is the
inverted mirror image of the other. Moreover, the central four – membered {Pd2(μ-Cl)2}
cycle was flat and the four atoms (two Pd and two Cl) form a perfect plane. The Pd-C, Pd-P
and Pd-Cl bond lengths fall in the expected range of values for similar phosphametallacycle
complexes.[166] Looking at the bond lengths and angels, the Pd-C (metallated atom), Pd-P,
Pd-Cl (bridging trans to P) and Pd-Cl (bridging trans to metallated carbon atom) in
palladacycle 6e were 2.043(2) Å, 2.2318(6) Å, 2.4754(6) Å and 2.4168(6) Å , respectively. On
the other hand, the Pd-Cl-Pd-P dihedral angles was 174.43(17)°, while the Pd-Cl-Pd-C
(metallated carbon atom) was 179.81(7)°.
Pd-P 2.2318(6) Cl-Pd-Cl 84.92(2)
Pd-Cl(trans to P) 2.4168(6) Pd-Pd 3.610
Pd-Cl(trans to metallated C) 2.4754(6) Cl-Pd-P (trans to metallated C) 102.47(2)
Pd-C3 2.043(2) P-Pd-Cl (trans to p) 172.57(2)
P-C1 1.853(2) C3 Pd1 Cl1 175.95(7)
P- C6 1.886(2) C3 Pd1 P1 81.58(7)
P-C11 1.879(2) Pd-P-C1 115.57(7)
C2 C3 Pd1 115.15(16) C3 Pd1 Cl1 91.03(7)
Chapter 2: Results and Discussion
56
2.1.4.5 Coordination Behavior of Cyclopalladated Complex 6e. The metal-carbon σ bond in cyclometalated palladium complexes is remarkably robust[185],
and a variety of conventional reactions can be successfully carried out. For example, the
chlorine-bridged dimer 6e undergoes the usual adduct formation at mild reaction conditions
with either triphenylphosphine via cleavage of the μ-chloro bridges to yield 9e, or with
PPh2(o-Tolyl) to yield 10e. Both of the mononuclear complexes 9e and 10e were crystalline
and well-characterized product with a trans-configuration whith respect to the phosphorus.
As usual, this geometries were indicated by the 31P{1H} NMR spectra for 9e and 10e which
were presented as a pair of doublets with slightly different 31P-31P couplings. Such that the
coupling constant has a large value (2JPP = 379 Hz, trans PPh3 ligand and 2JPP = 377 Hz, trans
PPh2(o-tolyl) ligand). In addition, the chlorine anions in palladacycle complex 6e were
exchanged easily by salt metathesis with silver acetate and silver trifloroacetate to give the
dimeric complexes 11e and 12e respectively (Figure 2.5).
Figure 2.5: Coordination behavior of cyclopalladated complex 6e.
Chapter 2: Results and Discussion
57
Looking at the 1H NMR of the dimeric complex 11e and 12e, the CH3 protons of the rest of
the neopentyl group were appeared as a singlet at δ = 1.21 ppm and at δ = 1.18 ppm,
respectively. Consequently the metallated methyl protons of the neopentyl group appears
as a singlet at δ = 2.16 ppm in 11e and at δ = 2.29 ppm in 12e. Moreover, peaks due to the
methyl protons of the tButyl group was appeared as a doublet in 11e at δ = 1.41 ppm due to
the spin-spin coupling with the phosphorus atom with coupling constant of 3JHP = 13.5 Hz,
whereas in the complex 12e was appeared at δ = 1.49 ppm with coupling constant of 3JHP =
13.8 Hz. Finally, the linker methyl group adjacent the phosphorus atom was papered as a
doublet, in 11e, at δ = 1.80 ppm with coupling constant of 3JHP = 9 Hz, and at δ = 1.80 ppm in
12e with coupling constant of 3JHP = 8 Hz. These data clearly signs that chloride displacement
has taken place. The methyl protons of acetate group in 11e were appeared at δ = 2.35 ppm
too. On the other hand, we reported the synthesis and the structure of 14VE palladium(0)
complex of ligand 4e, firstly by deprotonation of phosphonium salt 4e by means of a base to
regenerate the free phosphine 3e, then by the reaction of this phosphine with
(tmeda)PdMe2, which was prepared according to the published procedure, to yield
(PtBu2CH2CCMe3)2Pd 13e as colourless solid in an overall yield of 88 % after work-up.
As usual, the reaction of phosphine with (tmeda)PdMe2[186] (tmeda; tetramethylethylene
diamine) often give bisphosphine-dimethylpalladium complexes, but in our case for bulky
phosphine, like 3e, these readily reductively eliminate ethane to yield a slightly air-sensitive
(PtBu2CH2CMe3)2Pd(0) 13e (Scheme 2.10).
Scheme 2.10: Synthesis of palladium(0) complex 13e.
The room temperature 31P{1H} NMR spectra of 13e in C6D6 showed one sharp signal at 45.09
ppm, in addition, the 1H NMR spectra at room temperature showed three peaks appears at
δ = 1.51 ppm as doublet, δ = 1.48 ppm as singlet and at δ = 1.43 ppm. In June 2010, at the
same period of our investigation of palladium (0) complex 13e, Shaughnessy and co-worker
Chapter 2: Results and Discussion
58
[184] have synthesized the same complex by different procedure; they added a methanolic
solution of NaOH to Pd(cod)Br2 suspended in toluene at -5°C. Then they reacted the
resulting solution with phosphine in toluene at a certain temperature, and they succeeded
to precipitate the complex as off-white solid by methanol.
The solid state structure of 13e was determined by single crystal X-ray crystallography.
Crystals suitable for X-ray studies of complex 13e were grown upon recrystallization from
cold pentane at -20°C. The molecular structure of 13e is shown in figure 2.6, selected bond
lengths (Å) and bond angels (°) are given in table 2.8. Crystal data, together with the data
collection and refinement parameters are presented in table 2.7. An obvious different of
this structure and those of the few other reported structure of (PR3)2Pd was the (C2-C1-P-
Pd) dihedral angel near the zero (-0.17(18) Å)[184], whereas in the palladium(II) dichloride
complex of phosphine 3e this angle was 126.52(9) Å[184], due to the steric strain in this
system.
Figure 2.6: Molecular structure of 13e (Pd; orange, P; yellow, and C; gray).
Table 2.8: Selected bond lengths (Å) and angles (°) of 13e.
Pd-P 2.2974(6) C2-C1-P 120.03(15)
P-C1 1.865(2) P-Pd-P 180(5)
P- C6 1.890(2) Pd-P-C6 111.32(7)
P-C10 1.892(2) Pd-P-C1 117.93(7)
Chapter 2: Results and Discussion
59
The Pd-P bond length was 2.2974(6) Å (compared with 2.2318(6) Å in palladacycle 6e, and
2.4148(4) Å in the palladium (II) dichloride complex of phosphine 3e [184]), while the P-C1
bond length was 1.865(2) Å (compared with 1.853(2) Å in palladacycle 6e, and 1.8522(14) Å
in the palladium(II)dichloride complex of phosphine 3e [184]). In addition the C2-C1-P bond
angel was 120.03(15)° (compared with 126.24(9)° in the palladium(II) dichloride complex of
phosphine 3e [184]) .
2.1.4.6 Coordination Behavior of Phosphonium Salt 4g.
Like those of the phosphapalladacycle 6a and 6e, the cyclometallated palladium complex 6g
have been prepared by a direct treatment of the phosphonium salt 4g with a stoichiometric
amount of palladium(II) acetate (1:1 molar ratio) in tetrahydrofuran in the presence of
sodium acetate as a base, followed by chloride ion metathesis (by washing the reaction
mixture a couple of times with sodium chloride solution) to yield the cyclopalladated dimer
as analytically pure off white crystals in an overall yield of 86 % after work-up (Scheme
2.11).
Scheme 2.11: Cyclopalladation of the phosphonium salt 4g by Pd(OAc)2.
By a combination of 1H and 31P{1H} NMR spectroscopic analyses of the crude product, a
good indication of the presence of the product as cyclometallated palladium complex 6g (R
= trineopentyl) was provided, by the appearance of one singlet at δ = 1.28 ppm for CH3 of
two neopentyl group, as well as a simple doublet of doublet resonance representative of the
CH2 protons of neopentyl arms which appeared at δ = 1.93 ppm. In addition, one doublet
appeared at δ = 2.47 ppm for the CH2 protons of the third neopentyl arm which was
Chapter 2: Results and Discussion
60
responsible for cyclometallation process, also with spin-spin coupling with phosphorus atom
with coupling constants 3JPH = 11.7 Hz. Finally, one singlet was appeared at δ = 1.179 ppm-
which belong to the two methyl group of the rest of the cyclometallated neopentyl arm.
Moreover, the room temperature 31P{1H} NMR spectrum (CDCl3) of the analytically pure
product was presented as a singlet peaks at δ = 33.66 ppm.
2.1.4.7 Coordination Behavior of Phosphonium Salt 4h.
In the case of phosphonium salt 4h, when palladium acetate was treated with this salt like
the above protocol which described for preparation of cyclometallated palladium complexes
6a, 6e and 6g, it only afforded the 1:1 dinuclear, chlorine-bridged palladium complexe (non-
cyclometallated palladium complex) 6h as a pale yellow powder in an over yield of 84%
(Scheme 2.12).
Scheme 2.12: The Dinuclear Palladium Complex of 4h.
The 1H NMR signals of the dimmer 6h in solution were clear and easily to be resolved. For
instance, the CH3 protons of the neopentyl group was appeared as a singlet at δ = 1.33 ppm,
whereas in the ligand 4h was appeared at δ = 1.15 ppm. Moreover, the linker CH2 group
adjacent the phosphorus atom was appeared as a doublet at δ = 2.314 ppm due to the spin-
spin coupling with the phosphorus atom with coupling constant of 3JHP = 11.8 Hz, whereas in
the ligand 4h (R = Cy, R' = Neopentyl) was appeared at δ = 2.11 ppm with coupling constant
of 3JHP = 12 Hz. More two set of multiplet was appeared in the range of δ = 1.4-2.48 ppm for
the cyclohexyl group. The 31P{1H} NMR spectroscopic observations were thus indicative of
two important features. Firstly, the coordination shift (Δδ) of the phosphine ligand at
Chapter 2: Results and Discussion
61
approximately δ = 4.28, was supportive of the formation dimmer complex 6h. Secondly, the
appearance of one singlet peaks (δ = 17.33 ppm) was in accordance with the dimeric
structure of complex 6h (non-cyclometallated palladium complex) and clearly signs that
complexation has taken place.
2.1.5 Synthesis and Characterization of Substituted iPropyl and tButyl Dinuclear
Palladium Complexes 6i-6o.
An easy and common way to obtain most metallacycles is the direct formation from the free
ligand and a metal salt in protic solvents at ambient temperature. [14, 29]
In this part of our investigation, we began studying the behaviors of a broad range of
substituted iPropyl and tButyl phosphonium salts to know weather they undergo
cyclometallated to form four or five membered ring metallated palladium complexes (type
A), or the dimeric non-cyclometallated palladium complexes (type B).
We showed that when palladium acetate was treated with phosphonium salts (4i, 4j, 4l, 4m,
4n or 4o), by approved protocol to prepare the cyclometallated palladium complexes, they
only afforded the 1:1 dinuclear complexes (6i, 6j, 6l, 6m, 6n or 6o), (Scheme 2.13).
Chapter 2: Results and Discussion
62
Scheme 2.13: Coordination behavior of phosphonium salts 4i-o.
The 31P NMR spectra of the dimmer complexes (6i-l and 6m-n) each show one single
resonance, which suggests the presence of only one isomer in solution, in the region δ = -
10.54 to 94.02 ppm and well removed from the chemical shift of the phosphonium salts
starting materials 4. In addition, there is a significant difference between the chemical shift
of cyclometallated and non cyclometallated palladium complexes. The 31P NMR
spectroscopic data for new complexes, together with that for the parent new and known
phosphonium salts are shown in table 2.9.
Table 2.9: 31P NMR data of phosphonium salts and its dimeric palladium complexes.
Chapter 2: Results and Discussion
63
The dinuclear palladium complexes described in table 2.9 were fully characterized by 1H, 13C,
and 31P NMR, and IR, elemental analyses and MS as well as melting point.
In the case of phosphonium salt 4m (R = iPr, R' = CH2Cy), when palladium acetate was
treated with this salt; it only afforded the 1:1 dinuclear chlorine-bridged palladium
complexe 6m (non-cyclometallated palladium complex) as a pale yellow powder in an over
all yield of 79% (Scheme 2.13).
By a combination of 1H and 31P{1H} NMR spectroscopic analyses of the crude product, it was
immediately obvious that we got the non-cyclometallated palladium complex 6m (non-
cyclometallated palladium complex of phosphonium salt 4m (R = iPr, R' = CH2Cy). For
instance, in solution, the 31P{1H} NMR spectrum (CDCl3) of the analytically pure product was
presented as a singlet peak at δ = 57.36 ppm at room temperature, whereas in the ligand
appeared at δ = 27.41 ppm, and from this value thus indicative of an important point; the
appearance of one singlet peaks (δ = 57.36 ppm) was in accordance with the dimeric
structure for the complex 6m. In addition, the 1H NMR signals were cleared and easily to
resolved. For instance, the doublet resonance of the CH2 (δ = 2.25 ppm) proton is
adequately resolved though and the efficiency of the spin – spin coupling with the adjacent
phosphorus nucleus has improved as a consequence of non C-H palladation. This was noted
from the 2JPH coupling constant of 12 Hz for the non cyclometallated structure. Moreover,
the methyl protons of the isopropyl protons were appeared as duplet of duplet at δ = 1.43
ppm and δ = 1.38 ppm with coupling constants 3JPH = 13.6 Hz and 3JPH = 12 Hz, respectively,
In addition, 2JHH = 6.9 Hz and 2JHH = 6 Hz, respectively. Also the protons of cyclohexyl group
were appeared in the range of δ = 1.21-1.87ppm. Finally, the CH(CH3)2 protons were
appeared at δ = 2.39 ppm.
The solid state structure of 6m was determined by single crystal X-ray crystallography.
Crystals suitable for X-ray studies for complex 6m was grown by slow diffusion of pentane
into a solution of dichloromethane containing the complex 6m at room temperature. The
molecular structure of 6m is shown in figure 2.7, selected bond lengths (Å) and angels (°) are
given in table 2.10. Crystal data, together with the data collection and refinement
parameters are presented in table 2.7. The structure of palladacycle 6m consists of two
halves, in which each half of the dimer is the inverted mirror image of the other.
Chapter 2: Results and Discussion
64
Like those of the cyclometallated palladium complexes 6a, 6e and 6g, in the non-
cyclometallated palladium complex 6m (Figure 2.7), each palladium atom in complex was
in a square planner configuration with the total bond angels around each palladium atom =
360°, and each of them has four atoms in its coordination sphere; one phosphorus and
three chlorides. The Pd–Pd distance within the dimer 6m was 3.50 Å (compared with 3.61 Å
and 3.510 Å in palladacycle 6e and 6a, respectively.) and like those of the palladacycle 6e
and 6a, the crystal structure also confirms the trans-geometry of the phosphorous atoms
along the Pd–Pd axis. The Pd–P bond lengths in non cyclometallated palladium complexes
6m were longer than expected for a cyclometallated palladium complex 6e (2.232 Å) as well
as in the cyclometallated palladium complex 6a (2.197 Å). On the other hand, the Pd-Cl-Pd-P
dihedral angles was 175.04(3)°, while the torsion angel Cl2-Pd-Cl1-Pd was 10.4(3)°. The
structure of non-cyclometallated palladium complex 6m consists of two halves, in which
each half of the dimer is the inverted mirror image of the other. Moreover, the Pd-P and Pd-
Cl bond lengths fall in the expected range of values for similar phospha metallacycle
complexes.[166]
Figure 2.7: Molecular structure of 6m (Pd; orange, P; yellow, Cl; green and C; gray).
Chapter 2: Results and Discussion
65
Table 2.10: Selected bond lengths (Å) and angles (°) of 6m.
Looking at the bond lengths, the Pd-P, Pd-Cl1 (bridging trans to P), Pd-Cl1 (bridging trans to
Cl2 atom) and Pd-Cl2 in 6m were 2.2356(8) Å, 2.3190(7) Å, 2.4754(6) Å, 2.4353(8) Å and
2.2751(8) Å, respectively.
In the case of the phosphonium salt 4k, we were pleased to find that the reaction of this salt
proceeded cleanly to afford four membered ring cyclometallated palladium complex 6k as a
pale yellow solid in an over all yield of 95% (Scheme 2.14). In addition to our work, Goel and
co-worker have prepared the cyclometallated palladium complex 6k directly by treatment of
the free phosphine P(tBu)3 with PdCl2 or Na2PdCl4 in DMF, and stirring at room temperature
for long period of time (48h).[177]
Compared to previous protocol for the synthesis of 6k, the procedure does not require
stirring for long period of time. An investigation on the preparation and characterization of
authentic samples of 6k showed that it readily undergoes intramolecular metalation in
solution.
Scheme 2.14: Coordination behavior of phosphonium salt 4k.
Pd-P 2.2356(8) Cl1-Pd-Cl2 175.19(3)
Pd-Cl(trans to P) 2.3190(7) Pd-Pd 2.232
Pd-Cl(trans to Cl2) 2.4754(6) P-Pd-Cl1(trans to P) 174.96(3)
Pd-Cl2 2.2751(8) P-Pd-Cl1(trans to Cl2) 93.83(3)
P-C1 1.839(3) P-Pd-Cl2 90.80(3)
P- C5 1.837(3) Pd-P-C7 116.17(10)
P-C7 1.834(3) Pd-Cl1-Pd 94.78(3)
Chapter 2: Results and Discussion
66
The metal-carbon σ bond in cyclometalated palladium complex 6k is remarkably robust, and
a variety of conventional reactions can be successfully carried out. For example, the
treatment of a dichloromethane solution of 6k with two equivalents of either PPh3 or
PPh2(o-Tolyl) resulted in the precipitation of monomeric palladium complexes 9k and 10k,
respectively (Scheme 2.15). In addition, a color changes from pale yellow to light yellow was
observed. After evaporation, an off-white solid was obtained whose 31P NMR spectrum in
CDCl3 showed a pair of doublets with different 31P-31P couplings. Such that the coupling
constant has a large value (2JPP = 379 Hz, trans PPh3 ligand and 2JPP = 252 Hz, trans PPh2(o-
Tol) ligand) and the chemical shift being consistent with the formation of the monomeric
complexes 9k and 10k.
Scheme 2.15: Coordination behavior of cyclopalladated complex 6k.
From above results, it can be stated that a broad range of trialkylphosphonium salts
undergo cyclometallation either as five and four membered ring metallated palladium
complexes or the dimeric non-cyclometallated palladium complexes. Interestingly, the tri-
tButyl substituted phosphonium salt 4k, [HP(tBu)3][BF4], undergo cyclometallation process
via C-H activation. In contrast, the mono and di-substituted tButyl phosphonium salt 4i (R =
iPr, R' = tBu) and 4j (R = tBu, R' = iPr) afforded only the 1:1 dinuclear complexes. In summery
the formation of five membered palladacycle by cyclometallation of a neopentyl group
proceeds more easily than the same process leading to four membered palladacycle on
tButyl group. Obviously steric crowding on the phosphine as well as methyl groups in the
right position to form five membered palladacycle lead to very fast and easy C-H activation
and subsequent cyclopalladation.
Chapter 2: Results and Discussion
67
2.1.6 Effective Suzuki Cross Coupling Reactions Using Prepared Phosphonium Salts
and Palladium Complexes.
Interest in the studying of palladium (II) complexes mainly focuses on the ability to
exploitation their electronic and steric effects to tune the acidity and reactivity of such
complexes for their probable utility as catalysts [159, 162]. It has been shown that the catalytic
activity depends on the donor atom around the metal present in the complex as well as the
steric environment around the metal too. In general, an electron rich metal complex
accelerates the oxidative addition and the steric around the metal center facilitates
reductive elimination and stabilizes the complex. Therefore, phosphines serve as useful
reagents and catalysts, in a wide array of important organic synthesis resulting from
different types of cross coupling reaction. In the early studies, triarylphosphines (e.g., PPh3),
which are typically air stable, have been the predominant focus of study over
trialkylphosphines, probably as a result in large part of the fact that many of them are air-
sensitive, which makes them more difficult to handle than triarylphosphines.[4,89, 93]
Therefore, we focused our interest, in the second part of this thesis, in a simple but
powerful strategy for handling these phosphines would be to protect them as their
conjugate acids. According to this approach, a stable, easily handled phosphonium salt
would be employed as a precursor, and insitu deprotonation in the reaction mixture would
liberate the desired free phosphine. In this section we described the application and efficacy
of prepared complexes and phosphonium salts in the Suzuki Miyaura cross coupling
reaction.
2.1.6.1 Neopentyl and Neosilyl Phosphines based Catalysts for Suzuki-Miyaura Cross-Coupling Reaction. As an obvious model reaction we have examined the formation of substituted biphenyls
from phenylboronic acid and different types of alkyl halides in the presence of palladium
= Neopentyl) and 5d (R = Ph, R' = Neosilyl); section 2.4.1) or Beller and Herrmann
Palladacycle. [147, 159, 162] Unfortunately, this system doesn't showed any significant catalytic
activity in Suzuki cross coupling and failed to yield any isolable product in the applied
conditions, except in the case of activated aryl bromide. Coupling reactions performed with
4-bromoacetophenone just showed some limited activity (21% conversion by 2 mol% Pd of
6e) after more than 48h at 100°C. In contrast, 8% conversion was achieved by use of 6a
(cyclometallated palladium complex of phosphonium salt 4a (R = iPr, R' = Neopentyl)) under
the same conditions. The very low conversions observed with these catalysts can be
ascribed to the difficultness to generate the Pd(0) active species by reductive C-H or C-C
elimination.[87, 147, 188]. The P-based palladacyclic Suzuki catalysts rapidly generate Pd(0) by
nucleophilic attack of the aryl boronic acid at the palladium center, followed by reductive
elimination and C-C bond formation to yield the catalytic active Pd(0) monophosphine
species [87, 188-189]. We suggested a similar process which is operative in the case of
trialkylphosphines based palladacycles (Scheme 2.22).
Chapter 2: Results and Discussion
76
Scheme 2.22: Postulated mechanism for the formation of the catalytically active
monophosphine Palladiumd(0) species in Suzuki cross-coupling of 4-bromoacetophenon
with phenylboronic acid by reductive C-C bond formation from cyclometallated palladium
complex 6e.
To obtain a detailed and clear view about the nature and the role of P(tBu)2CH2C(CH3)3
ligand 3e in catalytic cycle steps; the oxidative addition process of the Pd(0) complex 13e of
this ligand have been studied. The oxidative addition of haloarenes to d10 Pd(0) phosphine
complexes is a key step in Suzuki cross coupling reaction process.[87, 147, 188] Therefore, we
have examined this reaction by 31P{1H} NMR monitoring. Firstly, we tried to achieve
oxidative addition of activated aryl bromide (Scheme 2.23), such as bromobenzonitrile, to
the 14VE Pd(P(tBu)2CH2C(CH3)3)2 13e. Figure 2.11 shows the 31P{1H} NMR spectroscopic
monitoring. The reaction of Pd(P(tBu)2CH2C(CH3)3)2 13e with bromobenzonitrile is
accompanied by the growth of a singlet at δ = 15.98 ppm and of a singlet at δ = 53.59 ppm,
while the signals of Pd(P(tBu)2CH2C(CH3)3)2 13e at δ = 41.26 ppm constantly decrease. We
Chapter 2: Results and Discussion
77
assigned the signal at δ = 53.59 ppm to oxidative addition product 13c and the singlet at δ =
15.98 ppm to free phosphine 3e. Next we tried to achieve oxidative addition of 3,5-CF3-
bromobenzene to Pd(0) complex 13e. Similarly upon addition of an excess of 3,5-CF3-
bromobenzene to a solution of Pd(0) complex 13e in CD3CN; we observed a change in the
31P{1H}-NMR resonances (Figure 2.12). The signal for Pd(0) decrease with time and two new
signals appeared in a ratio of about 1:1, the free Phosphine and the postulated complex
13d. In the case of oxidative addition of iodobenzen to the Pd(0) a direct formation of two
sharp signal were observed at room temperature (Figure 2.13 and 2.14). As the sole
products in oxidative addition were only the free phosphine and the complex 13f, we tried
to force this reaction to completeness by increasing the temperature to 70°C in hope to
isolate the pure complex 13f by simple removing the free phosphine, solvent as well as the
iodobenzene by oil pump vacuum. These attempts were hampered by the formation of
another two sharp signals after 20 minutes at 70°C. We know from our investigation (vide
supra) that Pd(II) complexes with neopentyl decorated phosphines do easily undergo
cyclometallation by C-H activation. Indeed the signal at δ = 91.80 ppm (compared with δ =
94.02 ppm of related cyclometallated palladium complex 6e, where X = Cl) can be assigned
to complex 13g. Another typical side reaction is the reductive elimination of a biaryl by C-C
bond formation accompanied by the formation of a dimeric Pd(I) complex 13h (Figure 2.14),
we assigned the signal at δ = 58.34 ppm to this complex based on the reported shifts for
similar complexes.[87, 188-189]
Scheme 2.23: Proposed reaction pathways for the oxidative additions of aryl halides to the
Pd(0) complex 13e.
Chapter 2: Results and Discussion
78
Figure 2.11: 31P{1H}-NMR investigation (25°C or 50°C, CD3CN) on the oxidative addition of bromobenzonitrile to Pd(0) complex 13e in CD3CN solution by using PPh3 as external standard: (A) at the start; (B) after 48h at 25°C; (C) after 48h at 60°C.
Figure 2.12: 31P{1H}-NMR investigation (25°C or 60°C, CD3CN) on the oxidative addition of 3,5-CF3-bromobenzene to Pd(0) complex 13e in CD3CN solution by using PPh3 as external standard: (A) at the start at 25°C; (B) after 48h at 25°C; (C) after 48h at 60°C.
Chapter 2: Results and Discussion
79
Figure 2.13: 31P{1H}-NMR investigation (25°C or 50°C, CD3CN) on the oxidative addition of
iodobenzene to Pd(0) complex 13e in CD3CN solution by using PPh3 as external standard: (A)
after 5min. at 25°C; (B) after 10min. at 25°C; (C) after 5min. at 60°C; (D) after 10min. at 60°C;
(E) after 20min. at 60°C.
Chapter 2: Results and Discussion
80
Figure 2.14: 31P{1H}-NMR investigation (25°C or 50°C, CD3CN) on the oxidative addition of iodobenzene to Pd(0) complex 13e in CD3CN solution by using PPh3 as external standard: (F) after 22min. at 60°C; (G) after 25min. at 60°C; (H) after 5min. at 70°C; (I) after 10min. at 70°C; (J) after 20min. at 70°C.
Chapter 2: Results and Discussion
81
In an effort to determine whether phosphine adducts of the complex 6e (either PPh3 or
PPh2(oTolyl) generally perform better than palladacycle analogue 6e, we compared the
performances of catalysts formed in situ with these phosphines with activated aryl chloride
substrate. The P : Pd ratios were maintained at 2 : 1 for both phosphines used and the
results are summarised in scheme 2.24. As can be seen, in all cases the PPh2(o-Tolyl) ligand
did indeed performed better than PPh3. As mentioned earlier, the activity shown with these
substrates is not as high as that shown by triarylphosphine-based Palladacycle. [159, 162]
Scheme 2.24: Suzuki coupling of 4-chloroacetophenon with phenylboronic acids catalyzed
by mixtures of complex 6e and two equivalents of PPh3 or PPh2(o-Tolyl).
In order to test the catalytic activity of the four membered palladacycles, we have used the
dimmer 6k (cyclometallated palladium complex of P(tBu)3) and monomeric palladium
complexe 9k (monomeric phosphane adduct 6k with PPh3) and 10k (monomeric phosphane
adduct of 6k with PPh2P(o-Tolyl)) in the Suzuki coupling reaction of 4-chloroacetophenone
with phenyl boronic acid to get the coupling product 4-acetylbiphenyl. Coupling reactions
performed with 4-chloroacetophenone just show some limited activity (31% conversion by 1
mol% Pd of 6k) after more than 20h at 100°C. In contrast, 36% and 38% conversion were
achieved by monomeric palladium complex 9k and 10k, respectively, under the conditions
employed here too (Scheme 2.25). From these limited data, we cannot rule out a specific
Chapter 2: Results and Discussion
82
rule on the effectiveness of four and five membered ring cyclometallated palladium
complexes 6e or 6k as catalyst in Suzuki cross coupling reaction, but we can judge from
these limited examples that the cyclometallated palladium complexes 6e (cyclometallated
palladium complex of 4e (R = tBu, R' = Neopentyl) and 6k (R = R' = tBu) have been found to
be less effective in Suzuki cross coupling reaction than ortho metallated palladium
complexes.[159, 162] In addition, the very low conversions observed with the using of either
four or five membered palladacycles 6e and 6k as catalysts in such cross coupling reaction
may be ascribed to the difficultness of generating the palladium active species through
reductive elimination.[159, 164-165]
Scheme 2.25: Suzuki cross-coupling reaction of 4-chloroacetophenone with phenyl boronic
acid catalyzed by 6k, 9k and 10k.
From this limited data set (Scheme 2.24), it would appear as though no significant different
between using dimmer or monomer palladium complexes in Suzuki cross coupling of
activated aryl chloride 7i. In addition, without further studies we could not completely rule
out the efficiency of cyclometallated palladium complexes 6k in Suzuki cross coupling
reaction. However, we then decided to examine the dimmer 6k and monomer 9k as catalyst
in Buchwald amination coupling reaction of different types of aryl halides with amines. In
Chapter 2: Results and Discussion
83
general, the test reactions were performed in dioxan using KOtBu as a base at 95°C and 1
mol% catalyst loading. In the first example, we reacted 2-bromotoluene with morpholine in
order to evaluate the difference in activity of the dimmer palladium complex 6k as well as
the monomer one 9k over time. Figurer 2.15 shows the profile of these time dependent
reactions. We also reported kinetic investigation of the amination cross coupling reaction of
diethyl amine with bromobenzene (Figure 2.16). Each pair of substrates was heated at 95°C
with vigorous stirring. After 2.5, 5, 10, 20, 30, 60, 90, 120, 150, 180, 210, 240 and 300 min,
samples (~1 mL) were taken for characterization. The conversions were determined by
GC/MS spectroscopy.
0 20 40 60 80 100 120 140 1600
20
40
60
80
100
% C
on
vers
ion
Time(min)
30
30b
6k
9k
Figure 2.15: Kinetic Investigation of 6k and 9k in the Buchwald- Hartwig amination reaction
of 2-bromotoluene with morpholine (1 mol% [Pd], 95°C).
As shown in figure 2.15, we observed that the coupling reaction with deactivated or
sterically hindered aryl bromide, for example; 2-bromotoluene, was successfully coupled
after less than 120min by using of 6k (cyclometallated palladium complex of P(tBu)3) and the
monomeric palladium complexes 9k (monomer of 6k/PPh3) as catalysts. Moreover, no
significant differences were observed by using the di- or mononuclear palladium complexes
6k and 9k, respectively. Also an over all yield of 93% within 2.5h was achieved. Fu et al. also
reported the use of Pd(OAc)2 with a sterically hindered and electron rich trialkylphosphine
Chapter 2: Results and Discussion
84
ligand, PtBu3, yielded the cross coupling product in excellent yield, 96%, within 6h at
elevated temperature.[83, 89-90]
0 50 100 150 200 250 3000
20
40
60
80
100
% C
on
vers
ion
Time(min)
30
30b
6k
9k
Figure 2.16: Kinetic Investigation of 6k and 9k in the Buchwald- Hartwig amination reaction
of bromobenzene with diethyl amine (1 mol% [Pd], 95°C).
In contrast, coupling reaction of diethyl amine with neutral aryl halide, such as
bromobenzene, was less successful and only led to approximately 49% and 16% conversions
after 120min by 6k and 9k, respectively. In contrast to previous studies [200], simple acyclic
secondary amines were poor substrates. Reactions carried out with 4-bromoacetophenone
and 4-chloroacetophenone with morpholine also showed some conversion rates.
For example, complete conversion of 4-bromoacetophenone at 95°C with 1 mol% catalyst
6k was observed in overall yield of 90% (Scheme 2.25, entry 3). In contrast, complete
conversion of 4-chloroacetophenone was less successful and only led to approximately 59%
(Scheme 2.25, entry 5). By using 6k and KOtBu in dioxane in the coupling reaction of
morpholine with 4-bromotoluene the product was obtained in 61% isolated yield (Scheme
2.26, entry 1). On the other hand, the cross coupling reaction of morpholine and
deactivated aryl chloride (such as 2-chlorotoluene) in presence of either 6k or 9k was
unsuccessful and yielded no product (just 14% conversion was observed) when our
Chapter 2: Results and Discussion
85
optimized conditions were used. In addition, coupling reaction with more crowded and
sterically hindered aryl bromides, such as bromomesitylene, was less successful and only led
to approximately 24% isolated yield by 6k in boiling dioxane.
Scheme 2.26: Amination of aryl bromides and chlorides catalyzed by 6k (R = R' = tBu).
It was known from the work of Herrmann and co-worker that the using of orthometallated
triaryl phosphine palladium complexes in amination reactions of a wide range of aryl halides
and amines can be easily be achieved at high temperatures (100-135°C) in good yields. [162]
From this limited data set it would appear as though that cyclometallated palladium
complex 6k has been found to be less effective, for the coupling of aryl halides with amine,
than ortho metallated palladium complexes in spite of the presence of the electron rich and
sterically demanding ligand in cyclometallated palladium complex 6k. This result may be
suggests that the steric property could be more important in determining catalyst activity
toward aryl halides than the electronic properties of the ligand.
Then we expand our investigation to see what is the behaviour of the dinuclear
noncyclometallated palladium complex 6m ((P(iPr)2CH2Cy)2Pd2Cl4) as catalyst in Suzuki cross
Chapter 2: Results and Discussion
86
coupling reaction. Firstly, the dinuclear palladium complex 6m was screened for their ability
to promote the Suzuki coupling of 4-bromoacetophenone and phenylboronic acid using
0.5% mol/Pd and sodium carbonate in dioxane/water mixture. This complex served as an
air-stable precatalyst that is highly effective for the coupling of 4-bromoacetophenone and
phenylboronic acid. In this reaction; complex 6m ((P(iPr)2CH2Cy)2Pd2Cl4) gave complete
conversion within 20 minutes. It is significant to accomplish good conversion and/or yields
using minimum amounts of catalysts. Therefore, we have examined the effect of catalyst
loading, of 6m ((P(iPr)2CH2Cy)2Pd2Cl4), on a convenient coupling between 4-bromoaceto-
phenone and phenylboronic acid at 80°C. Good conversion (100%, 98% and 93%) was
obtained from normal catalyst loads (0.5% mol) down to a level of 0.1 and 0.05 mol%,
respectively (Scheme 2.27). A low conversion (18%) was obtained even at catalyst loading as
low as 0.01 with a TON and TOF of 1800 and 3600, respectively. These are the indications of
an effective catalytic system that merits more downstream explorations.
Scheme 2.27: Influence of catalyst loading of 6m ((P(iPr)2CH2Cy)2Pd2Cl4) in Suzuki coupling of
4-bromocetophenon with phenylboronic acid .
Chapter 2: Results and Discussion
87
Based in success of 6m in the test reaction, coupling of aryl bromides and chlorides with
phenylboronic acid were carried out. Complete conversions were obtained with activated
and deactivated aryl bromide as well as deactivated aryl chlorides. For example, complete
conversions of 4-chloroacetophenone at 90°C and 4-bromoanisol at 80°C with 0.5 mol%
catalyst 6m was observed within 120 min and 300 min, respectively. No significant
conversions to product occurred in attempts to couple sterically hindered aryl chloride using
0.5 mol% of 6m even at high temperature (110°C in toluene).
From this limited data set it would appear as though the dinuclear palladium complex 6m
has the greatest effect on the couplings involving electron deficient aryl bromide and
chloride than the cyclometallated one (e.g.; 6e and 6k). In addition, no significant effect on
the coupling of electron rich aryl chloride was obtained.
2.1.6.3 Substituted Trialkylphosphonium Salts in Suzuki-Miyaura Cross Coupling
Reaction.
As mentioned in the first chapter of this thesis, several groups have established that the
combination of bulky and electron rich phosphines with different type of palladium salts
show high catalytic activity in cross coupling reactions.[4, 89, 93-95] In our investigations,
selected examples of the prepared phosphonium salts were shown to be excellent ligands
for the palladium catalyzed Suzuki cross-coupling reaction, may be due to the possibility of
in situ deprotonation of the phosphonium salts under catalytic conditions. In order to test
the catalytic activity of phosphonium salts 4a (R = iPr, R' = Neopentyl), 4b (R = iPr, R' =
In order to test and compare the catalytic activity of substituted iso-propyl phosphonium
salts 4a, 4b and 4o, we have used these phosphonium salts in the Suzuki coupling reaction
of 2-bromotoluene with phenylboronic acid with 0.5 mol% Pd(OAc)2/1 mol% phosphonium
salt in presence of K2CO3 as a base and dioxane/water (2:1) as a solvent (Figure 2.19). We
were pleased to find that the coupling reaction with 2-bromotoluene led to 98%, 8.7% and
71% conversions within 10 minutes by phosphonium salts 4a, 4b and 4o, respectively. On
the other hand, complete conversions of 2-bromotoluene at 80°C with 4a, 4b and 4o were
observed after 20, 240 and 45 minutes, respectively (Figure 2.19).
Reactions carried out with 4-chloroacetophenone also showed some conversion rates. For
example, complete conversions of 4-chloroacetophenone, at 90°C with 0.5 mol% Pd(OAc)2
/1 mol% phosphonium salts in presence of K2CO3 as a base and dioxane/water(2:1) as a
solvent, were observed after 60, 120, 90 and 90 minutes by 4a, 4i, 4l and 4o, respectively.
Chapter 2: Results and Discussion
92
0 50 100 150 200 2500
20
40
60
80
100
4a
4b
34
% C
on
vers
ion
Time(min)
4a
4b
4o
Figure 2.19: Kinetic investigation of the Suzuki Miyaura cross-coupling reaction of 2-bromo- toluene with phenylboronic acid with 0.5 mol% Pd(OAc)2/1 mol% 4 (4a (R = iPr, R' = Neopentyl), 4b (R = iPr, R' = Neosilyl), and 4o (R = iPr, R' = iBu). From this limited data set it would appear as though the phosphonium salts have the
greatest effect on the couplings involving electron deficient aryl bromide and chloride and
low (or not significant) effect on the coupling of electron rich aryl chloride. A comparison of
the catalytic activity of the phosphonium salts, (Scheme 2.27, Figures 2.17, 2.18 and 2.19)
shows that in general the phosphonium salts 4l (R = iPr, R' = CH(Et)2) and 4o (R = iPr, R' = iBu)
gave better results in cross coupling of activated aryl halides compared to non or
deactivated ones. Nevertheless, with regard to a general use, the combinations of
phosphonium salts and Pd(OAc)2 constitute interesting catalyst systems due to the high
stability of all components towards air and water and thus the easy handling of the catalyst.
Next, the best two phosphonium salts 4l and 4m of substituted iPropyl were used for Suzuki
reactions of various activated and deactivated aryl halides. For electron-deficient aryl
bromides, e.g., acetyl substituted bromobenzene; excellent yields are obtained both in the
presence of substituted iPropyl and tButyl phosphonium salts. In the case of more
challenging substrates, e.g. 3-chloroanisole (Figure 2.18) the using of phosphonium salt 4l (R
= iPr, R' = CH(Et)2) gave the best result. In addition, the catalyst derived from phosphonium
salt 4a and Pd(OAc)2 gave very good yield of coupled product in the coupling of 2-
Chapter 2: Results and Discussion
93
bromotoluene with phenylboronic acid. Similar yields are obtained by the catalyst system 4n
(R = iPr, R' = CH2Cy)/Pd(OAc)2, while the catalyst system derived from phosphonium salt 4l (R
= iPr, R’ = CH(Et)2) and Pd(OAc)2 gave the low yield of cross coupling product 2-
methylbiphenyl (Scheme 2.29).
Scheme 2.29: Suzuki coupling of 2-bromotoluene with phenylboronic acids using
C1-4 (δ = 53.5; 40.4; 49.7; 46.2 ppm) and one D1-2 (δ = 51.9; 48.3) with two signals indicating
that one C2 axis is still appropriate (Figures 2.35 and 2.36). Conformers A - D are found in the
ratio of 13:21:17:49 at 223 K; at lower temperature signals for conformers A, and B,
respectively, are weaker and the signals for C and D become dominant (at 198 K:
11:17:20:51 and at 178 K: 11:8:24:57). That means the energy minimum conformer of
complex 83 is either C or D. Down to the lowest accessible temperature for solution studies
the signals sharpen which indicate that the rotation of the isopropyl groups is frozen at the
Chapter 2: Results and Discussion
119
31P NMR time scale (Figure 2.38). P-P exchange in conformer D must occur through at least
one conformer higher in energy and lower in symmetry, which might be one assigned to the
signal groups A, B, or C, respectively. To deepen knowledge of this process, we recorded 2D
31P{1H} EXSY NMR spectra at 208 K in a d7-DMF/CH2Cl2 mixture (ratio 1:2) (Figure 2.36).
Figure 2.35: 31P{1H} NMR spectrum of complex 83 in d7-dmf at 223K, signals were grouped based on the signal intensity and line broadening.
The observed exchange signals for the direct P-P exchange are very small, although they
should be the strongest as conformer D is the dominant species. Exchange crosses peaks of
signal D1 with B1/2 and C1/2 as well as D2 with B3/4 and C3/4, respectively, are found. However,
this alone does not explain the P-P exchange. Due to limitation in the solubility of complex
83 and the necessary low temperatures we have not been able to obtain a signal to noise
ratio allowing detection of cross peaks between other conformers. However, a good guess
of the reaction rate is the coalescence point, and that gives k = 0.5 kHz at 298K for the P-P
exchange.
Chapter 2: Results and Discussion
120
Figure 2.36: 31P{1H} EXSY spectrum of complex 83 at 208K in d7-DMF/CH2Cl2 mixture (ratio 1:2), the cross peaks for the P-P exchange within conformer D is marked with green boxes, note that this cross peaks would have higher intensity due to the dominant conformer D if the P-P exchange would be comparable fast within D. The colored lines on the top should indicate the correlation between the exchanging signals. This spectrum has been recorded with 2048 transients in F2 and 128 transients in F1 and a mixing time of 0.6 sec. Conformer A does not show exchange signals in this spectrum.
By diffusion of n-pentane vapor into a solution of complex 83 in CH2Cl2/MeOH crystals
suitable for single crystal X-ray structure determination could be obtained. Complex 83
crystallized in the monoclinic crystal system, space group P1 (Figure2.37) and selected bond
lengths (Å) and bond angles (°) of 83 are presented in table 2.12. Crystal data, together with
the data collection and refinement parameters for all complexes are presented in the
appendix (Table 2.13). The asymmetric unit includes two molecules of 83 and five molecules
of CH2Cl2 and one of methanol (Figure 2.38). In contrast to the results of the low
temperature NMR spectra, in the solid state none of the molecules of complex 83 has
crystallographic symmetry. The isopropyl groups of the ligand are tightly packed and show
Chapter 2: Results and Discussion
121
short contacts to neighboring methyl groups as well as to the aromatic protons at the
biphenyl moiety.
Figure 2.37: Molecular structure of complex 83.
Table 2.12: Selected bond lengths (Å) and angles (°) of 83.
Pd1-Pd2 7.7430(4) C27-P3 1.857(4)
Cl1-Pd1 2.3738(9) P1-Pd1-P2 91.46(3)
Cl2-Pd1 2.3628(9) P1-Pd1-Cl2 170.51(4)
Cl3-Pd2 2.3640(9) P2-Pd1-Cl2 95.37(3)
Cl4-Pd2 2.3327(12) P1-Pd1-Cl1 86.78(3)
C32-P4 1.853(4) P2-Pd1-Cl1 176.01(4)
C30-P3 1.855(4) Cl2-Pd1-Cl1 85.98(3)
P1-Pd1 2.2744(9) P4-Pd2-P3 92.80(4)
P2-Pd1 2.2782(9) P4-Pd2-Cl3 167.49(4)
P3-Pd2 2.2993(11) P3-Pd2-Cl4 172.56(4)
P4-Pd2 2.2492(9) P4-Pd2-Cl4 90.84(4)
C36-P4 1.853(4) P4-Pd2-P3 92.80(4)
C21-P2 1.873(4) P3-Pd2-Cl3 89.65(4)
C24-P 1.860(4) Cl4-Pd2-Cl3 88.18(4)
Chapter 2: Results and Discussion
122
Figure 2.38: Ortep drawing of the complete asymmetric unit of crystals of complex 83.
Not unexpectedly one of the molecules shows disorder that could not be fully resolved;
however, the other has been refined without disordered parts (Figure 2.38). The most
striking feature is the almost square planar coordination of the two palladium complex
fragments. Contrary to the expectation for a 2,2’-diphosphine biphenyl ligated palladium
complex but in accordance with NMR spectroscopy the palladium atoms are bent away from
the expected C2(x) axes through the midpoints of the phosphorus atoms in 2,2’- and 6,6’-
positions, respectively, and the centroid of the central C-C bond in the biphenyl moiety.
Therefore, the two palladium complex fragments are C1 symmetric, similar observations
have been found in mononuclear transition metal complexes with related structure.[199] The
isopropyl groups do not show clear preference for edge or face orientation, however, in
nearly all PdP-CH(Me)2 moieties stacked conformation is found. The found multitude of
orientations of the isopropyl groups in the solid state raises the question which conformer is
the dominant one assigned to signal group D observed in the low temperature 31P NMR
Chapter 2: Results and Discussion
123
spectrum. As the crystals have been grown at ambient temperature different conformers
are thermally accessible. Moreover, the one with the highest entropy will become the
dominant conformer in solution and also the one fitting the best in the crystal lattice will be
depicted from the mixture and subsequently found in the solid state structure. For those
reasons it is not wise to draw too many correlations between conformers observed in
solution and in solid state. But if one omits the orientation of the isopropyl groups, the
molecular structure of all molecules found in solid state point to the assumption that the
former C2(z)-axes remain valid. Hence, most likely conformer D is C2-symmetric with the C2-
axis in line with the central C-C bond. However, clearly the spatial arrangement of the
isopropyl groups is highly interdependent as the observation of only four conformers in the
31P NMR spectrum with the C2 symmetric conformer D as the dominant species
demonstrates. The two complex fragments combined in 83 cannot simply be treated as
combination of two fluxional fragments but are cross linked and sense each other.
In summary, we have for the first time synthesized a highly symmetric 2,2’,6,6’-
tetraphosphane biphenyl and a related dinuclear palladium complex 83 employing 82 as
ligand. The complex shows complicate temperature dependent NMR spectra that have been
rationalized by intramolecular interaction of the isopropyl groups (gear effect). Only a minor
number of possible conformers of complex 83 are observed at low temperatures with more
than 50 % of the molecules adopting the C2 symmetric conformation D.
As the spatial arrangement of the ligands around a metal center often controls the reactivity
and properties (e. g. color, spin state) the found interaction can be recognized as a kind of
communication or coupling pathway between the palladium complex fragments through
the ligand skeleton similar to the allosteric interaction in enzymes. Systems that are able to
couple magnetic or electronic properties of metal complexes are of high interest in material
science.
Chapter 3: Experimental Section
124
Chapter
3
3. Experimental Section.
3.1 General Remarks: Equipment, Chemicals and Work Technique. 3.1.1 Chemicals and Work Technique.
All reactions handling sensitive chemicals were carried out under an argon inert gas
atmosphere using standard Schlenk and cannula techniques. All solvents were distilled by
standard methods. Tetrahydrofuran and diethyl ether were freshly distilled from sodium
benzophenone ketyl under argon, and solvents that are commercially available, ethanol and
dimethylforamide, were used without further purification unless otherwise noted.
Methylene chloride was distilled freshly from calcium hydride under argon. All other
chemicals were purchased by commercial suppliers (Merck®, Aldrich®, Arcos® and others)
and were used without further purification. Silica gel (230-400 mesh) 122 was used for flash
column chromatography. All air stable compounds were concentrated using a rotary
evaporator and reduced pressure.
Chapter 3: Experimental Section
125
3.1.2 NMR Spectroscopy.
All NMR spectra have been recorded on a 500MHz Bruker AVANCE III spectrometer. Proton
spectra are referenced to the residual protons of the deuterated solvent (d7-dmf: δ = 8.18
C14H10Br2N2O4 (430.049 g∙mol-1): C 39.10, H 2.34, N 6.51.; found C 40.9, H 2.36, N 6.79.
3.2.41 Synthesis of 6,6'-dibromo-4,4'-dimethylbiphenyl-2,2'-diamine 68. To a solution of 2,2'-dibromo-4,4'-dimethyl-6,6'-dinitrobiphenyl (4.2 g, 9.66 mmol) in 25 mL
of absolute ethanol was added 32 % w/w aqueous HCl (15.0 mL). Zink powder (4.93g, 75.3
mmol) was then added in portions over 15 min, and the reaction mixture was heated to
reflux at 100°C for 2 h. After cooling, the mixture was poured into ice water (50 mL) and
then made alkaline with 20% w/w aqueous NaOH solution(or ammonia) until pH = 9.0. The
product was next extracted with CH2Cl2, and the organic layer was washed with brine, dried
over anhydrous MgSO4, filtered, and then evaporated to dryness to give crude product as
brown solids, then purified by column chromatography (Alox., hexane) yielding the title
mmol) of acetylferrocene and were dissolved in 9 mL of a 1,4-dioxan/water mixture (2:1),
thf or toluene. After addition (0.1-1 mol %) of the respective catalyst (or Pd:L), the reaction
mixture was heated at the given temperature with vigorous stirring for the given time. After
3, 8, 15, 20, 30, 60, 90, 120, 150, 180, 210, 240 and 300 min, samples (~1 mL) were taken for
characterization, evaporate the solvent and chromatographed on silica gel with diethyl
ether (or CH2Cl2) as eluent, and all volatiles were evaporated under reduced pressure. The
conversions were determined by 1H NMR spectroscopy.
3.6. General procedure of 31P{1H} NMR studies of the Pd(0), 13e, complex:
Kinetic experiments were performed at room temperature, 50°C, 60°C and 70°C with 0.013
M solutions of palladium(0) complex, Pd[(tBu2)PCH2C(CH3)3] 13e, in CD3CN with two drops of
THF. After addition of the aryl halides at certain temperature, spectra were then recorded at
regular time intervals until the conversion reached about 50%. The data were acquired by
following the growing of the free phosphine signals, decreasing the intensity of Pd(0)
complex and formation of new signals as described in details in the chapter 2; section
(2.1.6.2).
Chapter 4: Symmary
162
4. Summary.
Bulky, electron-rich phosphines are effective ligands in palladium-catalyzed cross-coupling
reactions, which are most useful organic transformations. For industrial palladium-catalyzed
processes, phosphine ligands have to be stable and easy to be synthesized from cost-
effective starting materials. For these and other reasons, new and excellent precursors for
the generation of new phosphines are required, especially those which are stable, easy to
produce and handle and very efficient in a wide range of organic synthesis under mild
conditions. In this study, a new method that fulfils most of these requirements had been
developed.
In the first part of the this thesis, we were pleased to find that neopentyl and neosilyl
substituted phosphines palladium complexes, as well as additionlly trialkylphosphine ligand,
were conveniently prepared by a modular synthesis and successfully tested in Suzuki
coupling of different type of aryl halides under mild reaction conditions. Their efficiency
prompted us to study their coordination behaviour to afford cyclometallated palladium
complexes. Whereas the neosilyl substituted phospines form 2:1 adducts with palladium
salts which showed moderate activity, the neopentyl complexes quickly undergo
cyclometallation in presence of bases to form palladacycles (6a, 6e, and 6g) which showed
only moderate catalytic activity. Cyclometallation could be avoided by the preparation
starting from Pd(cod)Cl2 in the absence of bases. The obtained 2:1 phosphine adducts
showed superior activity. We concluded that cyclometallation process is an important
deactivation pathway; this prompted us to test trialkyl phosphine ligands with medium size
but substituents not reliable to cyclometallation. We have been pleased to find that (4h, 4l
and 4m) showed good activity in Suzuki cross-coupling reaction. The best results have been
obtained by in situ preparation of active catalyst from Pd2(dba)3 or Pd(OAc)2 and the
appropriate phosphonium salt. In addition, the palladacycle complexes 6k and 9k have been
tested in Buchwald amination and showed moderate to good activity.
Chapter 4: Symmary
163
We then set our focus on the development of a new family of novel phosphine ligands being
suitable for Pd-catalyzed cross couplings (especially Suzuki cross coupling reaction).
Encouraged by the success of the biphenyl-based phosphines (70, 71, 76, and 77) and their
dichloride palladium and platinum complexes (72, 73, 74, 78, 79, 80 and 81). Ligand (70 and
76) were remarkably stable towards air, while ligands 71 and 77 were high sensitive to air.
Systematically, the scope of the novel phosphine ligands was expanded to other class of
phosphine; the first synthesis of a highly symmetric 2,2',6,6'-tetraphosphinobiphenyl 82 has
been reported, and used as ligand in a dinuclear palladium(II) complex 83. We gained access
to the isopropyl decorated tetraphosphane 82 by a one-pot-two-step synthesis starting
from 2,2'-dibromo-6,6'-diiodo-4,4'-dimethylbiphenyl followed by a convenient lithiation-
phosphorylation method to afforded the tetraphosphine as analytical pure white solid in
over yield of 84%. We reported that the 2,2’,6,6’-tetraphosphane had D2h symmetric, while
the dinuclear palladium complex was D2 symmetric and hence chiral. Due to the crowded
phosphine substituent's in 2,2’,6,6’-tetraphosphane; different conformers are observed at
low temperature with either C2 or C1 symmetry. Herein, it was demonstrated that all steps
of the synthesis protocol of the 2,2'-dibromo-6,6'-diiodo-4,4'-dimethylbiphenyl and its
dinuclear palladium complex can proceed under very special conditions. Within the class of
bisphosphine based palladium complexes they show good activity, especially the isopropyl
substituted phosphines are promising chiral ligands in Suzuki-Miyaura cross-coupling
reaction.
As the spatial arrangement of the ligands around a metal center often controls the reactivity
and properties (e. g. colour, spin state) the found interaction can be recognized as a kind of
communication or coupling pathway between the palladium complex fragments through
the ligand skeleton similar to the allosteric interaction in enzymes. Systems that are able to
couple magnetic or electronic properties of metal complexes are of high interest in material
science and they may have good applications in spin crossover studies, so spin crossover
studies can be carried out employing 2,2’,6,6’-tetraphosphinobiphenyls as bridging ligands
by using other metal ions such as nickel.
Chapter 4: Symmary
164
Finally, despite of most of the catalyst systems depending upon their electronic and steric
properties proceed cleanly toward cross coupling product; there is a wide range of them can
not be regionalized simply by looking on their electronic and steric properties but also must
be related to on the resistance of phosphine ligands toward side reaction. As we observed
from our investigations, the less electron donating and electron crowding performed, in
some examples, better than the more electron donating monophosphine system.
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