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Junaid MS Thesis Mechanistic Investigations of Zinc and Titanium Catalyzed Oxidation, Hydroamination and Cycloaddition Reactions By Riffat Un Nisa CIIT/FA13-R66-002/ATD PhD Thesis In Chemistry COMSATS University Islamabad Abbottabad Campus - Pakistan Spring, 2017 i COMSATS University Islamabad Mechanistic Investigations of Zinc and Titanium Catalyzed Oxidation, Hydroamination and Cycloaddition Reactions A Thesis Presented to COMSATS University Islamabad, Abbottabad Campus In partial fulfillment of the requirement for the degree of PhD (Chemistry) By Riffat Un Nisa CIIT/FA13-R66-002/ATD Spring, 2017 ii Mechanistic Investigations of Zinc and Titanium Catalyzed Oxidation, Hydroamination and Cycloaddition Reactions A Post Graduate Thesis submitted to the Department of Chemistry as partial fulfillment of the requirement for the award of Degree of Ph.D in Chemistry Name Registration Number Riffat Un Nisa CIIT/FA13-R66-002/ATD Supervisor Dr. Khurshid Ayub Associate Professor Department of Chemistry COMSATS University Islamabad Abbottabad Campus Co-Supervisor Dr. Tariq Mehmood Associate Professor Department of Chemistry COMSATS University Islamabad Abbottabad Campus iii iv v vi vii DEDICATION Dedicated to my Parents, Husband and daughters Omima and Ayesha viii ACKNOWLEDGEMENTS In the name of Allah, Most Gracious, Most Merciful All praise and glory to Almighty Allah who bestowed me with everything and gave me courage to carry out this work. Peace and blessings of Allah be upon our last Prophet Hazrat Muhammad (Peace Be upon Him) the source of knowledge and blessing for entire mankind. I feel great honor to express my utmost sincerest gratitude to my supervisor Dr. Khurshid Ayub, whose constant guidance, kindness, encouragement, excellent suggestions, valuable advices, enthusiasm, and great patience helped me to complete this thesis successfully and gave me extraordinary experience throughout the work. I offer my enthusiastic gratitude to my research co-supervisor Dr. Tariq Mehmood whose guidance, positive appreciation and affectionate behavior helped me to complete the present assignment in time. I am really thankful to Prof. Dr. Abdur Rahman for his great co-operation, help and encouragement. I am also grateful to all my honorable teachers. I wish to acknowledge the members of Khurshid research group, especially Maria, Naveen, Saima, Saira, Rida and Sajida for their joyful gathering, positive criticism, and kind assistance in the whole work. I gratefully acknowledge the funding source i.e. Higher Education Commission that made my PhD work possible. I owe my profound thanks to my husband, Khaliq ur Rehman whose unconditional support remained with me throughout this work and for encouragement in removing the impediments came in my way during this strenuous work. I appreciate my little daughters Omima and Ayesha for abiding my ignorance and the patience they showed during my research work. Words would never say how grateful I am to all of you. A special thanks to my beloved late father, mother, sister, step father for their endless love, support, efforts and prayers for which I am forever grateful. My regard also goes to my in-laws for their moral support. Riffat Un Nisa CIIT/FA13-R66-002/ATD ix ABSTRACT Mechanistic Investigations of Zinc and Titanium Catalyzed Oxidation, Hydroamination and Cycloaddition Reactions The mechanism of the Zn(II) catalyzed oxidation of benzylic alcohol to benzaldehyde, ester and amide by three different oxidants (H2O2, TBHP, and CH3OOH) is investigated through density functional theory methods and compared with the similar oxidation mechanisms of other late transition metals. Inner sphere, intermediate sphere and outer sphere mechanisms have been analyzed. The effect of pyridine-2- carboxylic acid (ligand) and halides (Br2 and I2) is studied for benzaldehyde and ester formation reactions. Two new reactions are predicted such as oxidation of thiol to thioester and oxidation of benzylamine to benzaldimine and guanidine. The same set of calculations is repeated for newly predicted reactions as were performed for ester and amide formations. The inner sphere mechanism involving β-hydride elimination is found kinetically more demanding in all oxidation reactions. Ligand showed profound effect on rate of the reaction. In the presence of a ligand, intermediate sphere mechanism is found more plausible because of steric effect. In the absence of a ligand, the outer sphere mechanism is found more favorable. Mechanism of Zn(OTf)2 catalyzed hydroamination-hydrogenation of alkynes with amines is investigated through density functional theory methods. Both inner sphere and outer sphere mechanisms for nucleophilic attack of nitrogen on electrophilic alkyne centre to deliver imine have been investigated for the hydroamination reaction. Four different possibilities of hydrogen activation for the hydrogenation of imine to deliver amine have also been studied. These competitive reactions differ regarding the fate of proton and hydride generated from heterolytic cleavage of H2. The inner sphere mechanism is kinetically more demanding and is not believed to contribute significantly to the progress of the reaction under the experimental conditions. Outer sphere route for nucleophilic attack of non-coordinated amine on coordinated alkyne is found the most plausible. The overall energy barrier for outer sphere mechanism in amine adduct can also be surpassed under the reaction conditions, therefore this mechanism cannot be excluded safely. For hydrogenation reaction, heterolytic hydrogen cleavage involving proton shift on triflate ligand and hydride to metal is found most plausible over the competitive H2 cleavage reactions. The mechanism of TiCl4 mediated formal [3 + 3] cyclization of 1,3-bis(silyl enol ethers) with 1,3- dielectrophiles is also studied with B3LYP method of density functional theory (DFT) to rationalize the experimental regioselectivity. Methyl and trifluoromethyl substituted 1,3 dielectrophiles are studied theoretically since they show different regioselectivities. Four different mechanisms involving direct-direct, direct-conjugate, conjugate-direct and conjugate-conjugate addition of 1,3-bis(silyl enol ethers) on 1,3-dielectrophiles are studied for each dienophile. The intramolecular transition metal catalyzed and non-catalyzed dynamic shift of the silyl moiety are also studied. The structure of the 1,3 dienophile and the x associated Mulliken charges are the driving forces for different regioselectivities in methyl and trifluoromethyl dienophiles. xi TABLE OF CONTENTS 1 Introduction ....................................................................................................... 1 1.1 Catalyst and Catalysis .....................................................................................2 1.1.1 Role of a Catalyst ......................................................................................2 1.2 Importance of Catalysis...................................................................................2 1.3 Characteristic Features of a Catalyst ...............................................................3 1.4 Classification of Catalysis ...............................................................................3 1.4.1 Heterogeneous Catalysis ...........................................................................3 1.4.2 Homogeneous Catalysis ............................................................................4 1.5 Transition Metals in Homogeneous Catalysis.................................................4 1.6 Zinc Catalysis ..................................................................................................5 1.6.1 Zinc Catalyzed Copolymerization of Carbon Dioxide with Epoxide .......6 1.6.2 Zinc Catalysis in C-N Bond Formation Reactions ...................................8 1.6.3 Zinc Catalysis in Reactions of C-C Bond Formation .............................10 1.6.4 Zinc Catalysis in C-O Bond Formation Reactions .................................14 1.6.5 Zinc Catalysis in Friedel Crafts Reactions..............................................16 1.6.6 Organozinc in Oxidative Cross Coupling Reactions ..............................17 1.6.7 Zinc Catalyzed Oxidation Reactions.......................................................17 1.6.8 Zinc Catalyzed Hydroamination Reactions ............................................22 1.6.9 Zinc Catalyzed Reduction Reactions ......................................................27 1.7 Titanium Catalysis.........................................................................................31 xii 1.7.1 Titanium Catalyzed Intramolecular Cross Coupling Reaction ...............32 1.7.2 Titanium Catalyzed C-X Bond Formation Reaction ..............................33 1.7.3 Titanium Catalyzed C-C Bond Formation Reactions .............................35 1.8 Theoretical Approaches for the Mechanisms of Zn Catalyzed Reactions ....40 1.9 Theoretical Approaches for the Mechanisms of Ti Catalyzed Reactions .....43 1.10 Objectives ......................................................................................................44 1.10.1 Rationalization of the Experimental Regioselectivity ............................44 1.10.2 Rationalization of the Product Distribution in Zn(II) Catalyzed Oxidative Esterification ...........................................................................................45 1.10.3 Comparison of Zn Catalysis with other Late Transition Metals Catalysis …………………………………………………………………………45 1.10.4 Prediction of New Reactions...................................................................46
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