Marquette University e-Publications@Marquette Dissertations (2009 -) Dissertations, Theses, and Professional Projects Synthetic and Mechanistic Studies of Ruthenium Catalyzed C-C, C-N and C-O Bond Activation Reactions Nishantha Kumara Kalutharage Marquette University Recommended Citation Kalutharage, Nishantha Kumara, "Synthetic and Mechanistic Studies of Ruthenium Catalyzed C-C, C-N and C-O Bond Activation Reactions" (2015). Dissertations (2009 -). Paper 506. http://epublications.marquette.edu/dissertations_mu/506 SYNTHETIC AND MECHANISTIC STUDIES OF RUTHENIUM CATALYZED C-C, C-N AND C-O BOND ACTIVATION REACTIONS By Nishantha Kalutharage, B.Sc. (Hons) A Dissertation Submitted to the Faculty of the Graduate School, Marquette University, in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy Milwaukee, Wisconsin May 2015 ABSTRACT SYNTHETIC AND MECHANISTIC STUDIES OF RUTHENIUM CATALYZED C-C, C-N AND C-O BOND ACTIVATION REACTIONS Nishantha Kalutharage, B.Sc. (Hons) Marquette University, 2015 Transition metal catalyzed selective C-C, C-N and C-O bond activation reactions are fundamentally important in organometallic chemistry and organic synthesis. Catalytic C-C, C-N and C-O activation are highly valuable for reforming processes of crude oils. Significant research has been devoted to transition metal mediated C-C, C-N and C-O bond cleavage reactions to form new compounds as these processes are expected to provide novel ways to transformation of inexpensive hydrocarbons into more commercially valuable products such as pharmaceuticals, agrochemicals and polymers. A few examples of transition metal catalyzed cross coupling reactions involving C- N bond cleavage have been reported. A well-defined Ru catalytic system has been developed for oxidative alkylation of alcohol by deaminative coupling reactions of amines to form alkylated ketones. The catalytic method was successfully applied to the decarboxylative and deaminative coupling of amino acids with ketones. Reductive deoxygenation of aldehydes and ketones has attracted considerable attention due to its many applications in fine-chemical synthesis and biofuel production. Classical methods for the deoxygenation of carbonyl compounds are generally associated with harsh reaction conditions and the use of stoichiometric amounts of toxic reagents, and poor functional-group tolerance. A well-defined Ru-H catalyst was found to mediate the reductive deoxygenation of carbonyl compounds to produce aliphatic compounds. Two different mechanistic pathways have been investigated in detail to probe the electronic nature of the catalysts and ligands. Reductive etherification of ketones/aldehydes and alcohols have been studied intensively as cheaper and greener ways to synthesize ethers. A method for the reductive coupling of carbonyl compounds with alcohols has been developed, which involved a highly chemoselective formation of unsymmetrically substituted ether products. The catalytic etherification method employs cheaply available molecular hydrogen as the reducing agent, tolerates a number of common functional groups, and uses environmentally benign water as the solvent. i ACKNOWLEDGMENTS Nishantha Kalutharage, B. Sc (Hons) I would like to express my special appreciation and thanks to my advisor, Professor Chae S. Yi, for his tremendous guidance during study at Marquette University. I would like to thank him for encouraging my research and for allowing me to grow as a research scientist. I would also like to thank my committee members Professors Adam Fiedler and Christopher Dockendoff, for their encouragement, insightful comments, and support. My special thanks goes to Professor William Donaldson who was on my thesis committee but is on sabbatical at the present time. I would like to thank my group members, Dr. Kwang- Min Choi, Junghwa Kim and Hanbin Lee, for being such good friends, and former group members as mentors Dr. Dong-Hwan Lee and Dr. Ki-Hyeok Kwon, for their support and valuable conversations during my first year. I thank my teachers and colleagues at the Ruhuna University, especially Dr. Sarath Wanniarachchi, who gave me precious help during my first year at Marquette. Two professors, Ruchira Cumaranatunga and Hema Pathirana, have inspired and encourage me choose chemistry as my future. My deepest gratitude goes to my parents for their unflagging love and support throughout my life. They have sacrificed their lives to provide the best possible environment for me to get the education. Most of all, I want to thank my wife Sugandhi Wasana for her love, sacrifice, and kind indulgence. To my beloved son Sandaru and daughter Hawanya, I would like to express my thanks for being such good children always cheering up, inspiring and astonishing me every day. I would like to thank ii all of my friends who have been helping me to keep my mind peacefully under difficult situations, especially Mohamed El-Mansy and Wei Hu. My gratefulness to the countless technical support from Dr. Sheng Cai (for his support and his help running special NMR studies) and Dr. Sergey Lindeman (for providing single crystal diffraction analysis data). I am extremely appreciative of the financial assistance and the research assistantship given by Marquette University, the Arthur J. Schmitt Foundation, and the National Science Foundation which provided me with more time to focus on my research. Also, I would like to thank the Graduate School and all of the Marquette University administration. iii DEDICATION I dedicate this work to my wife, son, daughter and my mother, for their patience and support. Thank you for your understanding and your love. TABLE OF CONTENTS ACKNOWLEDGEMENT………………………………………………………………...i DEDICATION……………………………………………………………………………iii LIST OF TABLES……………………………………………………………………….iv LIST OF FIGURES…………………………………………………………………..…viii LIST OF SCHEMES…………………………………………………………………….xvi CHAPTER 1 ....................................................................................................................... 1 INTRODUCTION .............................................................................................................. 1 1.1 C-C Bond Activation of Hydrocarbon Molecules................................................ 1 1.1.1 Stoichiometric C-C Bond Activation Reaction .......................................... 3 1.1.2 Catalytic C-C Bond Activation Reactions ................................................. 4 1.1.2.1 C-C Bond Activation of Strained Molecules ....................................... 4 1.1.2.2. Catalytic C-C Activation of Unstrained Molecules ............................ 7 1.1.2.3. Chelate Assisted C-C Bond Activation Reactions of Unstrained Molecules…………………………………………………………………….8 1.1.2.4 Alkene/Alkyne Insertion Reactions via C-C Bond Cleavage ............ 12 1.2. Catalytic C-N Bond Activation Reactions ................................................. 14 1.2.1 Heterogeneous Hydrodenitrogenation of Nitrogen Heterocycles ........ 14 1.2.1 Hydrodenitrogenation Reactions Catalyzed by Soluble Metal Complexes…….…………………………………………………………….14 1.2.2. Catalytic Deaminative C-N Cleavage Reactions ................................. 18 1.2.2.1 C-N Bond Cleavage of Allylic Amines…………………....…..18 1.2.2.2 C-N Cleavage of Arylamines……………………………….…22 1.2.2.3 C-N Cleavage of Secondary and Tertiary Amines………….....23 1.2.2.4 Biochemical Deamination Reactions………………...…….…..25 CHAPTER 2: PART 1: Transition Metal Catalyzed C-O Bond Activation Reactions .... 31 2.1 Transition Metal Catalyzed Hydrogenolysis of Carbonyl Compounds. ......... 31 2.1.1 Classical Carbonyl Reduction Methods ................................................... 31 2.1.2 Wolff–Kishner Reduction..................................................................... 31 2.1.2.1 Catalytic Modification to Wolff-Kishner Reduction…………....32 2.1.3 Clemmensen Reduction ........................................................................ 33 2.1.4 Reduction of ketone/aldehydes using aluminum, silane etc. ................ 35 2.1.5 Homogeneous Catalytic Reduction Methods ....................................... 36 2.1.6 Reductive Deoxygenation of Ester, Amide, and other Carbonyl Compounds …………………………………………………………………38 2.1.7 Hydrogenolysis of C-O Bonds ................................................................. 43 2.1.7.1 Hydrogenolysis of Aryl Ethers .......................................................... 43 CHAPTER 2: PART 2: Transition Metal Catalyzed Ether Synthesis .............................. 53 2.2.1 Introduction .............................................................................................. 53 2.2.2 Classical Methods .................................................................................... 54 2.2.2.1 O-Alkylation.......................................................................................... 54 2.2.2.2 Mitsunobu Etherification ................................................................... 54 2.2.2.3 Etherification by Using DialkylPhosphites ....................................... 55 2.2.3 Cross-coupling Reactions ......................................................................... 57 2.2.3.1 Ullman Reaction ................................................................................ 57 2.2.4 Catalytic Etherification Methods ............................................................. 60 2.2.5 Etherification by [IrCl 2Cp*(NHC)] Catalyst ............................................ 63 2.2.6 dehydrative Etherification of Alcohols ...................................................