CATALYSIS AND LIGAND DESIGN: LIVING RING OPENING POLYMERIZATION OF LACTIDE WITH CHIRAL DINUCLEAR INDIUM CATALYSTS AND TEMPLATE SYNTHESIS OF FUNCTIONALIZED CARBENES ON IRON COMPLEXES by Insun Yu M.Sc., The University of Manitoba, 2005 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in THE FACULTY OF GRADUATE STUDIES (Chemistry) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) November 2012 © Insun Yu, 2012 Abstract A family of indium complexes were synthesized and their catalytic activity towards the ring opening polymerization of lactide to form poly(lactic acid), a biodegradable polymer, were assessed. Racemic and enantiopure mono- and bis-alkoxy-bridged complexes bearing bulky chiral diaminoaryloxy ligands were synthesized and characterized. The reaction of the bis-alkoxy-bridged complexes with water produced mono-hydroxy-alkoxy-bridged dinuclear indium complexes. Investigation of both the mono- and bis-alkoxy-bridged complexes confirmed dinuclear structures in solution and in the solid state. These dinuclear complexes were highly active catalysts for the ring-opening polymerization of lactide to form poly(lactic acid) at room temperature. A detailed mechanistic investigation showed that the selectivities obtained for the ROP of racemic LA with the mono- and bis-alkoxy-bridged complexes are different and, along with kinetics investigations, suggest a dinuclear propagating species for these complexes. Additionally, neutral and cationic alkyl indium complexes bearing a chiral diaminophenoxy ligand were synthesized and characterized. Investigation of the cationic complexes in solution by NMR spectroscopy showed the counter anions influenced the different chemical environments at the metal center in solution. The preliminary polymerization of methyl methacrylate with neutral dialkyl and cationic alkyl indium complexes produced poly(methyl methacrylate). This is the first demonstration of cationic indium complexes for catalytic reactivity not only in solution but also in neat monomer. Finally, a family of cyclic and acyclic Fischer-type carbenes were generated via nucleophilic attack at the carbon atom of a coordinated isocyande on a piano-stool iron(II) complex. All complexes were characterized by IR and NMR spectroscopy and, where possible, by single-crystal X-ray diffraction. In particular, rare donor-functionalized acyclic (phosphino)(amino)- and (silyl)(amino)carbenes were generated by a two-step template synthesis on the iron(II) complex. The methodology involves the initial formation of ylidene complexes followed by reduction of the resulting imine to yield the desired carbene complexes. The reversible conversion of an acyclic (sily)(amino)carbene complex to its ylidene precursor via slow deprotonation with hydride was demonstrated. i Preface Chapter 2 I synthesized the majority of the racemic and enantiopure mono- and bis-ethoxy-bridged complexes [(NNOR)InX(μ-OEt)]2 and [(NNOR)InX]2[μ-Y][μ-OEt] (NNOR = 2-t-butyl-4-R-6- (((2-(dimethylamino)cyclohexyl)amino)methyl)phenolate, R = t-Bu, Me; X = Cl, I; Y = Cl, I, OEt), respectively, and characterized them using a variety of techniques. I solved all the molecular structures using single-crystal X-ray crystallography and performed the reactivity studies of the dinuclear indium complexes. Dr. Alberto Acosta-Ramirez, a former postdoctoral fellow, synthesized and characterized the racemic dinuclear indium complexes [(NNOtBu)In(I)(μ-OEt)]2 and [(NNOtBu)In(I)]2(μ-OH)(μ-OEt) and their single crystals that I collected the single crystal X-ray data for these compounds and solved the molecular structure. The work in Chapter 2 has been published in the Journal of American Chemical Society.1 I was the major contributor to the writing of the this manuscript, with significant input from Prof. Mehrkhodavandi. Chapter 3 I performed all the kinetic and mechanistic studies and the large-scale polymerization of LA, with the exception of the data presented in Figure 3.16 for a plot of PLA Mn and molecular weight distribution (PDI) as functions of added rac- or L-LA for catalyst (±)-5, (±)-[(NNOtBu)InCl]2(µ-Cl)(µ-OEt), Figure 3.20 for plots of PLA Mn and Pm as functions of conversion for catalysts (±)-5 and (R,R/R,R)-5, and Figure 2.25 for a plot of PLA Mn with [(NNOtBu)In(Cl)]2(μ-Cl)(μ-OEt) in the presence of the different equivalent of (NNOtBu)InCl2 which were performed Dr. Alberto Acosta-Ramirez. Chapter 3 has been published in its entirety in the Journal of American Chemical Society.1 I also contributed synthesis and characterization of the work with the achiral indium complexes [(NMe2NMeOtBu)In(Cl)]2(μ- Cl)(μ-OEt) as well as the kinetic and polymerization studies published in Dalton Transactions.2 Kimberly Osten and I were the major contributors to the writing of the this manuscript, with significant input from Prof. Mehrkhodavandi. ii Chapter 4 I performed all of the studies in this chapter, and synthesis and single crystal X-ray crystallographic characterization of the indium complex (NNOtBu)InMe2 of Chapter 4 has been published in Inorganic Chemistry.3 I was a minor contributor to the writing of the this manuscript, however the remainder of the chapter was written exlusively by myself. Chapter 5 I performed all of the work in Chapter 5, except for DFT calculations performed by professor Paula Diaconescu and molecular structures of 35 and 36 solved by Dr. B. Patrick. This work has been published in Organometallics in 20094 and 2010.5 I was the major contributor to the writing of the this manuscript, with contributions to the discussion of DFT by Prof. Diaconescu and with significant input from Prof. Mehrkhodavandi. iii Table of Contents Abstract ..................................................................................................................................... i Preface ...................................................................................................................................... ii Table of Contents ................................................................................................................... iv List of Tables ......................................................................................................................... vii List of Figures ......................................................................................................................... ix List of Schemes ..................................................................................................................... xvi List of Abbreviations and Symbols .................................................................................. xviii List of Compounds .............................................................................................................. xxii Acknowledgements ............................................................................................................ xxiv Dedication ........................................................................................................................... xxvi Cahpter 1: General Introduction .......................................................................................... 1 Cahpter 2: Structural Characterizations of Chiral Alkoxy-Bridged Dinuclear Indium(III) Complexes in Solution and Solid State ............................................................ 6 2.1 Introduction ............................................................................................................................... 6 2.1.1 Indium catalysts for the polymerization of cyclic esters ................................................... 6 2.1.2 Comparison with aluminum analogues ........................................................................... 10 2.1.3 Determination of catalyst nuclearity in solution ............................................................. 12 2.2 Results ..................................................................................................................................... 14 2.2.1 Synthesis and characterization of proligands .................................................................. 14 2.2.2 Synthesis and characterization of racemic alkoxy-bridged indium complexes ............... 16 2.2.3 Synthesis and characterization of enantiopure alkoxy-bridged indium complexes ........ 21 2.2.4 Dinuclear nature of ethoxy-bridged complexes in solution ............................................ 25 2.3 Conclusion .............................................................................................................................. 38 2.4 Experimental section ............................................................................................................... 39 Cahpter 3: Mechanistic and Selectivity Studies of the Ring Opening Polymerization of Lactide with Chiral Alkoxy-Bridged Dinuclear Indium Catalysts .................................. 54 3.1 Introduction ............................................................................................................................. 54 iv 3.1.1 Lactide ............................................................................................................................. 54 3.1.2 Poly(lactic acid) ............................................................................................................... 56 3.1.3 Metal-catalyzed coordination-insertion mechanisms for ring opening polymerization (ROP) of lactide (LA) .................................................................................................................