A Dissertation entitled orthoMetallated Acetophenone Imines as Ligands for Transition and Main Group Metals: Synthesis and Organometallic Reactivity and the Hydroamination of Allenes using a Palladium Allyl Triflate 3-Iminophosphine Precatalyst by John Frederick Beck Submitted to the Graduate Faculty as partial fulfillment of the requirements for the Doctor of Philosophy Degree in Chemistry ____________________________________ Dr. Joseph A.R. Schmidt, Committee Chair ____________________________________ Dr. Mark R. Mason, Committee Member ____________________________________ Dr. Terry P. Bigioni, Committee Member ____________________________________ Dr. Maria R. Coleman, Committee Member ____________________________________ Dr. Patricia R. Komuniecki, Dean College of Graduate Studies The University of Toledo December 2011 Copyright 2011, John Frederick Beck This document is copyrighted material. Under copyright law, no parts of this document may be reproduced without the expressed permission of the author. ii An abstract of orthoMetallated Acetophenone Imines as Ligands for Transition and Main Group Metals: Synthesis and Organometallic Reactivity and the Hydroamination of Allenes using a Palladium Allyl Triflate 3-Iminophosphine Precatalyst by John Frederick Beck Submitted to the Graduate Faculty as partial fulfillment of the requirements for the Doctor of Philosophy Degree in Chemistry The University of Toledo December 2011 orthoMetallated aryl imines have been used extensively as ligands for late transition metals such as palladium and iridium. Due to the lack of a direct synthetic pathway from the imine to the orthometallated imine, there are few examples of early metals utilizing orthometallated aryl imines as ligands. Early transition metals like titanium and zirconium are unable to undergo the necessary C-H activation step to form the orthometallated complex. In order to synthesize early metal complexes utilizing orthometallated imines, a new method was developed which activates the ortho-proton, via a regiospecific lithiation, prior to metal complexation. The inclusion of a methylenedioxy moiety directs the lithiation and stabilizes the product. A series of early transition metal complexes with orthometallated imines were produced and structurally characterized, using small molecule X-ray diffraction. Multiple metal complexes were synthesized by reacting a ortholithiated imine with early transition and main group metal t t synthons such as Ti(N Bu)Cl2py3, CpTi(N Bu)Clpy, HfCl4, EtMgBr, AlCl3, CuI, ZnCl2, n and Bu3SnCl. iii The synthesis of alicyclic 3-iminophosphine ligands was extended to include a new framework incorporating a cyclopentenyl backbone with a di-tert-butyl phosphine functionality (3IPtBu). The palladium complex [(3IPtBu)Pd(allyl)]OTf displayed excellent catalytic activity in the hydroamination of 3-methyl-1,2-butadiene (1,1- dimethylallene) with primary aryl amines (anilines), selectively producing the branched allylic amine product (kinetic product) in high conversion at ambient temperature for non-halogenated substrates. Hydroamination using halogenated anilines was successful at 70 °C, providing moderate yields, with the formation of little or no linear product (thermodynamic product). Additionally, a subsequent aromatic amino Claisen rearrangement of selected allylic amine products, employing catalytic triflic acid, proved to be an effective atom-economical method for the production of ortho-allylic anilines in a high yielding two-step, one-pot synthesis. iv For Dallas Frederick and Ann Beck, my parents, Frederick Dallas and Catherina Beck, my paternal grandparents, Clarence and Doris Rutledge, my maternal grandparents, William and Julie Rutledge, my uncle and aunt, and Bobbi Renstrom, without all of whom this would not have been possible. v Acknowledgments I cannot express in words the thanks I owe to my parents and grandparents for shaping me into the man I am today. Without the support of my mother, Ann R. Beck, my education would not have been possible. Although my father Dallas F. Beck died when I was young, his absence showed me that nothing is guaranteed in life and that you should live your life to the fullest because you never know when it all may end. I would like to express my deepest thanks to the Kalamazoo Community Foundation and Clarence L. Remynse for the endowment that supports the Clarence L. Remynse Scholarship. I acknowledge my advisor Dr. Joseph A.R. Schmidt and my committee members for their guidance. I also acknowledge my fellow group members Dr. Andrew Shaffer, Dr. Glenn Kuchenbeiser, Dr. Tamam Baiz, Dr. Abdollah Neshat, Mr. Matthew Hertel, Mr. Andrew Behrle, Mrs. Cheryl Seambos, Ms. Ksenia Kriatchkova, Mr. Aaron Jones, Mr. Nicholas Zingales, Mr. Pascal Marillier and Ms. Danielle Samblanet. I would also like to thank Dr. Nicholas Kingsley, Mr. Christopher Yeisley and the entire research group of Dr. Mark Mason for their comradery. I have also been blessed by the opportunities that have been made available to me and by the many coworkers and friends who are too numerous to mention here. vi Contents Abstract iii Acknowledgments vi Contents vii List of Tables x List of Figures xi List of Schemes xiii Chapter 1 orthoMetallation and the Hydroamination Reaction 1.1 orthoMetallation 1 1.2 Group 4 orthoMetallation 5 1.3 orthoLithiation 6 1.4 orthoLithiation of Imines 11 1.5 Hydroamination 14 References 19 Chapter 2 Structural Characterization of Novel orthoLithiated Imines 2.1 Introduction 25 2.2 Results and Discussion 27 vii 2.3 Conclusion 42 2.4 Experimental 43 2.4.1 General Methods and Instrumentation 43 2.4.2 Ligand Synthesis 44 2.4.3 Ligand Lithiation 45 2.5 Crystallography of orthoLithiated Imines 47 References 54 Chapter 3 Isolation and Characterization of Titanium Imido Complexes using orthoMetallated Imine Ligands 3.1 Introduction 59 3.2 Results and Discussion 62 3.3 Conclusion 73 3.4 Experimental 74 3.4.1 General Methods and Instrumentation 74 3.4.2 Synthesis of Starting Materials 75 n 3.4.3 General Synthetic Procedure for complexes (L )2Ti(NR”) 76 3.5 Crystallography of 3-4a, 3-7a, 3-8a and 3-9 82 References 88 Chapter 4 Isolation and Characterization of Main Group and Late Transition Metal Complexes using orthoMetallated Imine Ligands 4.1 Introduction 97 4.2 Results and Discussion 99 4.3 Conclusion 119 4.4 Experimental 119 viii 4.4.1 General Methods and Instrumentation 119 4.4.2 Synthesis and Characterization of Reaction Products 121 4.5 Crystallography of 4-2a, 4-2b, 4-4, 4-5, 4-6, 4-7 and 4-10 132 References 137 Chapter 5 Hydroamination of 1,1-Dimethylallene with Primary Aryl Amines Under Mild Conditions: An Atom-Economical Route to N-(1,1- Dimethyl-2-Propenyl)-Anilines 5.1 Introduction 144 5.2 Results and Discussion 146 5.3 Conclusion 153 5.4 Experimental 154 5.4.1 General Methods and Instrumentation 154 5.4.2 Catalyst Synthesis 155 5.4.3 General Procedure for Catalytic Hydroamination of 1,1- 159 Dimethylallene 5.4.3.1 Characterization of Hydroamination Products 159 5.4.4 General Catalytic Procedure for Aryl Amino Claisen 162 Rearrangement 5.4.4.1 Characterization of Aryl Amino Claisen 162 Rearrangement Products 5.5 Crystallography of [(3IPtBu)Pd(allyl)]OTf (5-5) 165 References 167 ix List of Tables 2.1 Lithium NMR chemical shifts 33 2.2 τ values for 5-coordinate lithium centers 38 2.3 Twist angles for lithium complexes 40 2.4 Selected bond lengths and angles 41 1 2 6 2.5 Crystallographic data for compounds (Li-L )4, (Li-L )4, (Li-L )2●Et2O, 47 6 7 8 8 8 (Li-L )2, (Li-L )2, (Li-L )2, (Li-L )2●DME and H-L 3.1 Crystal data and collection parameters of 3-1a, 3-3b, 3-5a and 3-7 87 4.1 Crystallographic data for compounds 4-2, 4-4a, 4-4b, 4-5, 4-6, 4-7 and 4-10 135 5.1 Hydroamination of 1,1-dimethylallene with anilines 151 5.2 Hydroamination of 1,1-dimethylallene coupled with aryl amino Claisen 152 rearrangement 5.3 Crystallographic data for 5-5 166 x List of Figures 1 2-1 ORTEP diagram of (Li-L )4 29 8 2-2 ORTEP diagram of coordination polymer of (Li-L )2 32 8 2-3 ORTEP diagram of (Li-L )2 32 6 2-4 ORTEP diagram of “donor” dimer of (Li-L )2 34 6 2-5 ORTEP diagram of coordination polymer of (Li-L )2•Et2O 36 4 2-6 ORTEP diagram of (Li-L )2●Et2O 36 8 2-7 ORTEP diagram of (Li-L )2●DME 37 8 2-8 ORTEP diagram of ((Li-L )2●DME)n 38 3-1 ORTEP diagram of 3-4b 65 3-2 ORTEP diagram of 3-7a 67 3-3 ORTEP diagram of 3-8a 68 3-4 The 1H NMR spectrum of 3-7a 69 3-5 The 1H NMR spectrum of 3-1a 71 3-6 ORTEP diagram of 3-9 73 4-1 ORTEP diagram of 4-2a 104 xi 4-2 ORTEP diagram of 4-2b 105 4-3 ORTEP diagram of 4-4 108 4-4 ORTEP diagram of 4-5 109 4-5 ORTEP diagram of 4-6 112 4-6 ORTEP diagram of 4-7 113 4-7 ORTEP diagram of 4-10 117 5-1 ORTEP diagram of 5-5 148 xii List of Schemes 1.1 Synthesis of cyclopentadienyl [o-(phenylazo)phenyl] nickel 2 1.2 C-H activation of a triphenylphosphine ligand of IrCl(PPh3)3 3 1.3 Insertion of a cyano group into a metal-benzyne 5 1.4 The isolation of a titanium-benzyne via the use of trimethyl phosphine 6 1.5 The reaction of anisole with n-butyl lithium and an electrophile 7 1.6 An early mechanism for the ortholithiation of anisole via n-butyllithium 8 1.7 A proposed mechanism for the lithiation of anisole 9 1.8 The solvent dependent reaction of an aryl carbamate and n-butyl lithium 11 1.9 The regiospecific lithiation of piperonal cyclohexylimine 11 1.10 The nucleophilic attack of n-butyl lithium on an imine 12 1.11 The regiospecific lithiation of an aryl imine using LiTMP 13 1.12 The zirconium catalyzed hydroamination of an alkyne and primary amine 14