INDOLE BASED LIGANDS AND THEIR
PALLADACYCLES: SYNTHESIS, STRUCTURE AND CATALYTIC APPLICATIONS
MAHABIR PRATAP SINGH
DEPARTMENT OF CHEMISTRY
INDIAN INSTITUTE OF TECHNOLOGY DELHI
NEW DELHI-110016 MAY 2016
©Indian Institute of Technology Delhi (IITD), New Delhi, 2016
INDOLE BASED LIGANDS AND THEIR
PALLADACYCLES: SYNTHESIS, STRUCTURE AND CATALYTIC APPLICATIONS
by
MAHABIR PRATAP SINGH Department of Chemistry
Submitted
in fulfillment of the requirements of the degree of Doctor Of Philosophy
to the
INDIAN INSTITUTE OF TECHNOLOGY DELHI MAY 2016
i
CERTIFICATE
This is to certify that the thesis entitled, “INDOLE BASED LIGANDS AND THEIR
PALLADACYCLES: SYNTHESIS, STRUCTURE AND CATALYTIC
APPLICATIONS” being submitted by Mr. MAHABIR PRATAP SINGH to the Indian Institute of Technology Delhi for the award of the degree of Doctor of Philosophy, is a record of bonafide research work carried out by him. Mr. Mahabir Pratap Singh has worked under my guidance and supervision. He has fulfilled the requirements for the submission of this thesis, which to my knowledge has reached the requisite standard.
The results contained in this dissertation have not been submitted, in part or in full, to any other university or institute for award of any degree or diploma.
Date: Dr. AJAI K. SINGH
Professor
New Delhi Department of Chemistry
Indian Institute of Technology Delhi
New Delhi-110016
iii
ACKNOWLEDGEMENTS
I would like to begin by expressing my sincere thanks to my supervisor,
Professor Ajai Kumar Singh
for the years of invaluable supervision, magnanimous moral support, guidance and insight during the course of my dissertation.
His advice and instruction made this study possible. It has been a wonderful experience to work in his group during my tenure in IIT Delhi. A highly enriched, productive and motivational time of my student life has been spent in his laboratory under his never-ending enthusiasm, inspiration and personal guidance.I sincerely thanks to the Head, Department of Chemistry for providing necessary research facilities. I acknowledge the help extended by all faculty members and Keshav Sir during my stay here. I would like to thank my SRC committee members. I would also like to thank all staff and colleagues in Department of Chemistry IIT Delhi for their help and allowing me to be part of their family. I would like to express my heartfelt thanks to IIT Delhi for offering me an ideal environment in which I felt free and could concentrate on my research. Financial support by the “University Grants Commission” New Delhi, India for the award of Research Fellowships is duly acknowledged.
Sincere thanks to members of the research group Dr. Arun Kumar, Dr. V. V. Singh, Dr. U. Kumar, Dr. Poornima Singh, Dr. Neetu Singh, Dr. Om Prakash, Dr. Kamal Nayan Sharma, Dr. Fariha Saleem, Dr. Hemant Joshi, Alpesh Kumar Sharma, Pooja Dubey, Renu Bhaskar, Sonu Gupta, Mrinal Bhunia, Anirban Dutta, Ram Sahay Pal, Sourish Biswas, Pratibha Verma and Pratibha Sharma for their cooperation and help.
I would fail in my duties if do not thank to my senior Dr. G. K Rao for his valuable guidance and suggestions throughout the course of investigation.
The last 4.5 years haven’t been the easiest, but it is has been an awesome experience that I cannot imagine without my friends Pravesh, Ravi, Rohit, Saurav, Abadh, and Debdas. I would like to express my gratitude for the love, affection and support received from them.I would like to express my gratitude to my teachers Mr. Lalan Nishad, Mr. S Mahapatra, Mr. J. Mondal, Mr. Bhawani Shankar, Dr. Tazeen Mahmood and Dr.
Akhilesh Kumar Verma for tuning my life in a fruitful way.
Words fail to convey my heartfelt thanks to Soumee Bhattacharya, Ajeet Singh, Chandan Kumar and Satyendra Kumar who have been my pillar of strength throughout
iv
my work and makes the impossible to possible for me that I am able to see this day deserves a special mention.
My family members deserve special attention for their support and persistent confidence in me. I don’t have words to express my gratitude towards my father and mother, Shri Jainath Singh and Smt. Ramawati Singh. They have put high moral values inside me and made me strong enough to face any obstacle in life. My brother-in-laws Brijesh Singh, Durga Shankar Singh, Deepak Singh, Raghubir Singh and Tej Prakash Singh need a special mention for their deep affection. Thanks to my sisters Reena, Ranju, Neetu, Prity and Laxmi for their love and support. I express my love to Pratistha, Ankit, Anshit, Khusi, Happy, Harsh, Yash,Vaibhav and Aditya.
Thesis is dedicated to my favorite teacher Dr. Kalpana Mehrotra, Kirori Mal College, University of Delhi.
Last but not the least I thank almighty.
Mahabir Pratap Singh
v
ABSTRACT
Thesis is on indole based ligands and their palladacycles. Ligands in which palladation can be managed at C-2, C-3 and C-4 of indole moiety have been designed.
Mono-, bi- and tri-metallic Pd(II) complexes of indole based ligands have been prepared.
The catalytic potential of palladium complexes of indole based ligands for Suzuki- Miyaura coupling, Heck coupling and allylation reactions has been explored.
The first group is of chalcogenated indole based unsymmetrical hybrid (N,C,E)- pincer ligands (E = S/Se/Te) L1−L3. These ligands and their Pd(II) complexes 1−3 have been synthesized and characterized with 1H, 13C{1H}, 77Se{1H} and 125Te{1H} NMR and HR-MS. Single crystal structures of 1 and 2 have revealed square planar geometry of Pd.
The catalytic activities of 1–3 were tested for Heck coupling reactions of several aryl bromides (including deactivated ones) with n-butylacrylate. Palladacycles 1 and 2 was found to show better efficiency than complex 3. Palladium(II) complexes 1 and 2 were further tested as catalyst for allylation of aldehydes and found to show excellent catalytic activity (with 1 mol% of complex 1/2) for a wide substrate range.
vi
The second group of ligands prepared are unsymmetrical (N,C,N)-pincers L4 and L5. They were reacted with Na2PdCl4 to form Pd(II) complex 4 and 5. Synthesis of 3- sulfenylindole ligand L6 have been carried out by K2CO3 promoted sulfenylation of indole. They have been characterized with 1H, 13C{1H} and HR-MS. Single crystal structures of Pd(II) complexes 4−6 have been determined with X-ray diffraction.
The ligands L4 and L5 coordinate with Pd in a tridentate (N,C−,N) mode forming five- and six-membered rings with palladium. The ability of the L6 to coordinate with Pd(II) through nitrogen atom and C3 atom of the indole nucleus, forming a spiro ring is worth noting. The complexes 4 and 5 have been explored as catalyst for allylation of aldehydes and complex 6 for Suzuki-Miyaura coupling.
Thioamide based ligands L7−L11 constitute another class of indole based ligands.
Their coordination with Pd(II) has been investigated. The ligands and complexes have been characterized with 1H, 13C{1H} and 77Se{1H} NMR and X-ray diffraction (on single crystals of 7A,7B and 10). Sulphur in complex 7A bridge two palladium centers. For Suzuki-Miyaura coupling reactions the complexes of L7−L11 are efficient as catalyst as their 0.01−0.1 mol% was found sufficient for coupling.
vii
Terdendate ligands L12–L14 constitute the last group of indole based ligands reported in the thesis. Their Pd(II) complexes have been synthesized by their reaction with sodium tetrachloropalladate(II) in presence of anhydrous sodium acetate. These ligands and their Pd(II) complexes 1−3 have been synthesized and characterized with 1H, 13C{1H},
77Se{1H} and 125Te{1H} NMR and HR-MS. The structure of complex 12 has been established with X-ray crystallography. It has peri-palladation ( i.e or palladation at C-4 of the indole moiety) and distorted square-planar geometry around the metal centre.
The catalytic efficiency of 12−14 for Suzuki-Miyaura coupling appears promising as their 0.05−1.0 mol % was sufficient for good conversions. Palladacycles containing S/Se donor site are better catalysts for SMC than that having Pd−Te bond.
ix
TABLE OF CONTENTS
Certificate ... i
Acknowledgements ... iii
Abstract ... ...v
List of Contents ... ix
List of Figures ... xiii
List of Tables ... xvii
Glossary of Symbols and Abbreviations ... xxi
Chapter 1 Introduction ... 1.1 Palladacycles ... 2
1.2 Indole Based Ligands ... 5
1.2.1 Indolylphosphine Ligands...5
1.2.2 Palladium(II) Complexes of Indolylphosphines...10
1.2.3 Indole Ligands Having Nitrogen/Oxygen/Sulfur Co-donor Sites …...12
1.2.3.1 Indole Ligands Undergoing C-2 Palladation and their Palladacycles ... 12
1.2.3.2 Indole Ligands Undergoing C-3 and C-4 Palladation and their Palladacycles ... 16
1.3 Catalytic Applications ... 19
1.3.1 Catalysis of Suzuki-Miyaura Coupling ... 19
1.3.2 Catalysis of Mizoroki-Heck Coupling ... 21
1.3.3 Catalysis of Allylation of Aldehydes and Imines ... 22
1.4 Objectives and Scope of the Present Work ... 24
References ... 26
Chapter 2 Materials and Methods ... 2.1 Chemicals and Reagents ... 37
2.2 Synthesis of Precursors ... 37
2.2.1 1-Pyridin-2-ylmethyl-1H-indole-3-carbaldehyde ... 37
2.2.2 1-Prop-2-ynyl-1H-indole-3-carbaldehyde... 38
2.2.3 1-Benzyl-1H-indole-3-carbaldehyde ... 38
x
2.2.4 1-(1-benzyl-1H-[1,2,3]-triazole-4ylmethyl)-1H-indole-3-carbaldehyde .... 38
2.2.5 Azidomethylbenzene... 39
2.2.6 1H-Indole-3-carbothioic acid dimethylamide ... 39
2.2.7 2-(Phenylthio)ethylamine ... 39
2.2.8 2-(Phenylseleno)ethylamine ... 40
2.2.9 2-(Phenyltelluro)ethylamine ... 40
2.3 Characterization Techniques ... 41
2.3.1 Melting Point ... 41
2.3.2 Nuclear Magnetic Resonance Spectra ... 41
2.3.3 Mass Spectrometery ... 41
2.3.4 Single Crystal X-ray Diffraction Studies ... 42
References ... 43
Chapter 3 Indole Based Unsymmetrical Pincers and their Palladacycles in Mizoroki- Heck Coupling and Allylation of Aldehydes ……….. 3.1 Introduction ... 45
3.2 Experimental ... 47
3.2.1 Synthesis of 1-(2-Chloro-ethyl)-1H-indole-3-carbaldehyde ... 47
3.2.2 Synthesis of 1-(2-(Phenylthio)ethyl)-1H-indole-3-carbaldehyde ... 47
3.2.3 Synthesis of 1-(2-(Phenylselanyl)ethyl)-1H-indole-3-carbaldehyde ... 48
3.2.4 Synthesis of Synthesis of 1-(2-((4-Methoxyphenyl)tellanyl)ethyl)-1H- indole-3-carbaldehyde ... 49
3.2.5 Syntheses of Ligands L1−L3 ... 50
3.2.6 Syntheses of Complexes 1−3 ... 52
3.2.7 General Procedure for Mizoroki-Heck Coupling ... 53
3.2.8 General Procedure for Allylation of Aldehydes ... 54
3.3 Results and Discussion ... 54
3.3.1 NMR and Mass Spectra ... 56
3.3.2 Crystal Structures ... 57
3.3.3 Catalytic Applications ... 68
3.3.3.1 Pincer Complexes 1−3 in Mizoroki-Heck Coupling ... 68
3.3.3.2 Palladium(II) Complexes 1 and 2 in Allylation of Aldehydes ... 71
3.4 Conclusions ... 74
xi
References ... 75
Chapter 4 Monometallic and Bimetallic Palladium(II) Complexes of Indole Based Ligands for Catalytic Activation of Allylation of Aldehydes and Suzuki-Miyaura Coupling ………..……... ... 4.1 Introduction ... 81
4.2 Experimental ... 83
4.2.1 Synthesis of Ligand L4 ... 83
4.2.2 Synthesis of Ligand L5 ... 84
4.2.3 Synthesis of Ligand L6 ... 85
4.2.4 Synthesis of Complex 4 and 5 ... 86
4.2.5 Synthesis of Complex 6 ... 86
4.2.6 General Procedure for Allylation of Aldehydes ... 87
4.2.7 General Procedure for the Suzuki-Miyaura Coupling ... 88
4.3 Results and Discussion ... 88
4.3.1 NMR and Mass Spectra ... 90
4.3.2 Crystal Structures ... 92
4.3.3 Catalytic Applications ... 107
4.3.3.1 Palladium(II) Complexes 4 and 5 in Allylation of Aldehydes ... 107
4.3.3.2 Dimeric Complex 6 in Suzuki-Miyaura Coupling ... 109
4.4 Conclusions ... 111
References ... 113
Chapter 5 Cyclopalladated Dimethylamide of Indole-3-Carbothioic Acid: Synthesis, Structures and Catalytic Applications ………... 5.1 Introduction ... 117
5.2 Experimental ... 119
5.2.1 Synthesis of Ligand L7 ... 119
5.2.2 Synthesis of Ligand L8 and L9 ... 119
5.2.3 Synthesis of Ligand L10 ... 120
5.2.4 Synthesis of Ligand L11 ... 121
5.2.5 Synthesis of Complex 7A... 123
xii
5.2.6 Synthesis of Complex 7B... 124
5.2.7 Synthesis of Complex 8 and 9 ... 124
5.2.8 Synthesis of Complex 10 and 11 ... 126
5.2.9 General Procedure for Suzuki-Miyaura Coupling ... 127
5.3 Results and Discussion ... 128
5.3.1 NMR and Mass Spectra ... 131
5.3.2 Crystal Structures ... 133
5.3.3 Catalytic Applications ... 141
5.3.3.1 (C,S)-Palladacycle 7A and 7B in Suzuki-Miyaura Coupling ... 142
5.3.3.2 Pincer complexes (8−11) in Suzuki-Miyaura Coupling ... 144
5.4 Conclusions ... 145
References ... 146
Chapter 6 Cyclopalladated Chalcogenated Schiff Bases of 1-Benzyl-Indole-3- Carbaldehyde: Synthesis, Structure and Catalytic Activity………. 6.1 Introduction ... 149
6.2 Experimental ... 150
6.2.1 Syntheses of Ligands L12−L14 ... 150
6.2.2 Syntheses of Complexes 12−14 ... 152
6.2.3 General Procedure for Suzuki-Miyaura Coupling ... 154
6.3 Results and Discussion ... 154
6.3.1 NMR and Mass Spectra ... 156
6.3.2 Crystal Structures ... 157
6.3.3 Catalytic Applications ... 163
6.4 Conclusion ... 165
References ... 167
Bio-data …. ... 171 Encl. Supporting Information in CD
xiii
LIST OF FIGURES
Figure 3.1 Molecular structure of 1-(2-chloro-ethyl)-1H-indole-3- carbaldehyde with ellipsoids at 30% probability level
59
Figure 3.2 Molecular structure of 1-(2-(phenylthio)ethyl)-1H- indole-3-carbaldehyde with ellipsoids at 30%
probability level
59
Figure 3.3 Molecular structure of complex 1 with ellipsoids at 30%
probability level
60
Figure 3.4 Molecular structure of complex 2 with ellipsoids at 30%
probability level
60
Figure 3.5 Molecular packing framework showing non-covalent C–
H∙∙∙O and C–H∙∙∙π interactions in the crystal lattice of 1- (2-chloro-ethyl)-1H-indole-3-carbaldehyde
65
Figure 3.6 Molecular packing framework showing non-covalent C–
H∙∙∙O and C–H∙∙∙π interactions in the crystal lattice of 1- (2-(phenylthio)ethyl)-1H-indole-3-carbaldehyde
65
Figure 3.7 Molecular packing framework showing non-covalent C–
H···Cl, C–H∙∙∙π and Cl∙∙∙Cl interactions in the crystal lattice of complex 1
66
Figure 3.8 Molecular packing framework showing non-covalent C–
H∙∙∙Cl, C–H∙∙∙π and Cl∙∙∙Cl interactions in the crystal lattice of complex 2
66
Figure 4.1 Molecular structure of 1-pyridin-2-ylmethyl-1H-indole- 3-carbaldehyde with ellipsoids at 30% probability level
93
Figure 4.2 Molecular structure of 1-(prop-2-yn-1-yl)-1H-indole-3- carbaldehyde with ellipsoids at 30% probability level
94
xiv
Figure 4.3 Molecular structure of 1-(1-benzyl-1H-[1,2,3]-triazole- 4ylmethyl)-1H-indole-3-carbaldehyde with ellipsoids at 30% probability level.
94
Figure 4.4 Molecular structure of L4 with ellipsoids at 30%
probability level
94
Figure 4.5 Molecular structure of L6 with ellipsoids at 30%
probability level
95
Figure 4.6 Molecular structure of complex 4 95
Figure 4.7 Molecular structure of complex 5 with ellipsoids at 30%
probability level
96
Figure 4.8 Molecular structure of complex 6 with ellipsoids at 30%
probability level
96
Figure 4.9 Molecular packing framework showing non-covalent C–
H∙∙∙O interactions in the crystal lattice of 1-(Pyridin-2- ylmethyl)-1H-indole-3-carbaldehyde.
102
Figure 4.10 Molecular packing framework showing non-covalent C–
H∙∙∙O interactions in the crystal lattice of 1-(prop-2-yn- 1-yl)-1H-indole-3-carbaldehyde
103
Figure 4.11 Molecular packing framework showing non-covalent C–
H∙∙∙O, C–H∙∙∙N and C–H∙∙∙π interactions in the crystal lattice of 1-(1-benzyl-1H-[1,2,3]-triazole-4ylmethyl)- 1H-indole-3-carbaldehyde
103
Figure 4.12 Molecular packing framework showing non-covalent C–
H∙∙∙π interactions in the crystal lattice of ligand L4
104
Figure 4.13 Molecular packing framework showing non-covalent C–
H∙∙∙S and N–H∙∙∙N secondry interactions in the crystal lattice of ligand L6
104
Figure 4.14 Molecular packing framework showing non-covalent C–
H∙∙∙Cl secondry interactions in the crystal lattice of complex 5
105
xv
Figure 4.15 Molecular packing framework showing non-covalent C–
H∙∙∙Cl secondary interactions in the crystal lattice of complex 6.
105
Figure 5.1 Molecular structure of L7 with ellipsoids at 30%
probability level.
134
Figure 5.2 Molecular Structure of 7A 135
Figure 5.3 Molecular structure of 7B with ellipsoids at 30%
probability level.
135
Figure 5.4 Molecular structure of 10 with ellipsoids at 30%
probability level.
135
Figure 5.5 Molecular packing framework showing non-covalent C–
H··· π, N–H··· π interactions in the crystal lattice of ligand L7
139
Figure 5.6 Molecular packing framework showing non-covalent C–
H··· π, C–H···Cl and N–H···Cl interactions in the crystal lattice of complex 7B
139
Figure 5.7 Molecular packing framework showing non-covalent π··
π, C–H···Cl and C–H···S interactions in the crystal lattice of complex 10.
140
Figure 6.1 Molecular structure of L12 with ellipsoids at 30%
probability level
158
Figure 6.2 Molecular structure of L13 with ellipsoids at 30%
probability level
158
Figure 6.3 Molecular structure of 12 with ellipsoids at 30%
probability level
158
Figure 6.4 Molecular packing framework showing non-covalent C–
H···π interactions in the crystal lattice of ligand L12
161
xvi
Figure 6.5 Molecular packing framework showing non-covalent C–
H···π interactions in the crystal lattice of ligand L13
161
Figure 6.6 Molecular packing framework showing non-covalent C–
H···Cl interactions in the crystal lattice of complex 12
162
xvii
LIST OF TABLES
Table 3.1 Crystal data and structural refinements for ligand precursors A and B1
61
Table 3.2 Crystal data and structural refinements for complex 1 and 2
62
Table 3.3 Bond lengths [Ǻ] and bond angles [o] for complex 1 63 Table 3.4 Bond lengths [Ǻ] and bond angles [o] for complex 2 64 Table 3.5 Distances [Å] of non-covalent interactions for
complexes A and B1
67
Table 3.6 Distances [Å] of non-covalent interactions for complex 1 and 2
67
Table 3.7 Optimization of reaction conditions 69
Table 3.8 Mizoroki-Heck coupling reaction catalyzed by palladacycles 1−3
70
Table 3.9 Allylation of aldehydes catalyzed by complex 1 and 2 73 Table 4.1 Crystal data and structural refinement parameters for
ligand precursors aldehydes
97
Table 4.2 Crystal data and structural refinement parameters for ligands L4 and L6
98
Table 4.3 Crystal data and structural refinement parameters for complex 5 and 6
99
Table 4.4 Selected bond lengths [Ǻ] and bond angles [o] for complex 5
100
Table 4.5 Selected bond lengths [Ǻ] and bond angles [o] for complex 6
101
Table 4.6 Distances [Å] of inter-molecular interactions for 1- 106
xviii
(pyridin-2-ylmethyl)-1H-indole-3-carbaldehyde and 1- (prop-2-yn-1-yl)-1H-indole-3-carbaldehyde.
Table 4.7 Distances [Å] of inter-molecular interactions for 1-((1- Benzyl-1H-1,2,3-triazol-4-yl)methyl)-1H-indole-3- carbaldehyde, L4 and L6.
106
Table 4.8 Distances [Å] of inter-molecular interactions for5 and 6 107 Table 4.9 Allylation of aldehydes catalyzed by complex 4 and 5 108 Table 4.10 Suzuki-Miyaura coupling reaction catalyzed by catalyst
6
110
Table 5.1 Crystal data and structural refinement parameters for L7, 7B and 10
136
Table 5.2 Selected bond lengths [Ǻ] and bond angles [o] for complex 7B
137
Table 5.3 Distances [Å] of inter and intra-molecular interactions for complex 10
138
Table 5.4 Distances [Å] of inter-molecular interactions for ligand L7
140
Table 5.5 Distances [Å] of inter-molecular for complex 7B and 10 141
Table 5.6 Optimization of reaction conditions 142
Table 5.7 Suzuki-Miyaura coupling reaction catalyzed by (C,S)- palladacycles 7A and 7B
143
Table 5.8 Suzuki-Miyaura coupling reaction catalyzed by unsymmetrical pincer palladacycles 8−11
144
Table 6.1 Crystal data and structural refinement parameters for ligands L12, L13 and complex 12
159
xix
Table 6.2 Selected bond lengths [Ǻ] and bond angles [o] for complex 12
160
Table 6.3 Distances [Å] of inter-molecular interactions for L12, L13 and 12
162
Table 6.4 Optimization of reaction conditions 163
Table 6.5 Suzuki-Miyaura coupling reaction catalyzed by 12−14 164
xxi
GLOSSARY OF SYMBOLS AND ABBREVIATIONS
% percent
δ chemical shift
ν frequency
Å angstrom
Ar Aryl
µL microlitre
C degree centigrade
br broad signal
n-Bu n-butyl
Cq quaternary carbon
C−C carbon−carbon
cm centimeter
CH2Cl2 dichloromethane
CHCl3 chloroform
CH3CN acetonitrile
d doublet
DCM dichloromethane
DMA dimethylacetamide
DMF dimethylformamide
DMSO dimethyl sulfoxide
e.g. for example
g gram
h hour
HR high resolution
Hz hertz
HC Heck coupling
i.e. that is
kV kilovolt
m multiplet
m/z mass/charge
xxii
MHz megahertz
M+ molecular ion
M molar
mmol millimole
mol mole
mL milliliter
m.p. melting point
NMP N-methyl-2-pyrrolidone
NMR nuclear magnetic resonance
Pd palladium
Ph phenyl
n-Pr n-propyl
S sulphur
Se selenium
SMC Suzuki-Miyaura Coupling
t triplet
Te tellurium
THF tetrahydrofuron
TLC thin layer chromatography
TMS tetrametylsilane
XRD x-ray diffraction
