Iowa State University Capstones, Theses and Graduate Theses and Dissertations Dissertations 2014 Greener and renewable methods for Pd-catalyzed cross-coupling and alkoxycarbonylation reactions Gina M. Roberts Iowa State University Follow this and additional works at: https://lib.dr.iastate.edu/etd Part of the Chemistry Commons Recommended Citation Roberts, Gina M., "Greener and renewable methods for Pd-catalyzed cross-coupling and alkoxycarbonylation reactions" (2014). Graduate Theses and Dissertations. 13808. https://lib.dr.iastate.edu/etd/13808 This Dissertation is brought to you for free and open access by the Iowa State University Capstones, Theses and Dissertations at Iowa State University Digital Repository. It has been accepted for inclusion in Graduate Theses and Dissertations by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. Greener and renewable methods for Pd-catalyzed cross-coupling and alkoxycarbonylation reactions by Gina M. Roberts A dissertation submitted to the graduate faculty in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Major: Organic Chemistry Program of Study Committee: L. Keith Woo, Major Professor Andreja Bakac William S. Jenks Aaron D. Sadow Yan Zhao Iowa State University Ames, Iowa 2014 Copyright © Gina M. Roberts, 2014. All rights reserved. ii DEDICATION To Betty Jean, The memories with you I will cherish, Since it was last year that you did perish, And ever since my world has been a little more nightmarish iii TABLE OF CONTENTS Page LIST OF ABBREVIATIONS ............................................................................. v ABSTRACT ................................................................................................... viii CHAPTER 1 IMPORTANCE OF GREEN CHEMISTRY ................................ 1 Transition Metal Catalyzed Carbon-Carbon Bond Formation via Coupling Reactions .................................................................................. 2 Palladium Catalyzed Cross-Coupling reactions ......................................... 3 Transition Metal Catalyzed Carbon-Carbon Bond Formation via Carbonylation .................................................................... 9 Palladium Catalyzed Alkoxycarbonylation ............................................... 10 Palladium Catalyzed Alkoxycarbonylation for Biorenewable Production of Adipate ........................................................ 15 Alternatives to Organic Solvent ................................................................ 17 Molecular Structure Of Normal and Cholate Surfactants .......................... 19 Aggregation Of Normal and Cholate Surfactants in Water ...................... 21 Influence of Micelles on Organic Reactions ........................................... 24 Summary and Outlook ............................................................................ 26 References ............................................................................................ 27 CHAPTER 2 SONOGASHIRA COUPLING OF ARYL HALIDES WITH 1-ALKYNES UNDER MILD AQUEOUS CONDITIONS: SURVEY OF SURFACTANT ROLE IN CROSS-COUPLING REACTIONS ...................... 32 Abstract ................................................................................................... 32 Introduction ............................................................................................ 33 Results and Discussion ............................................................................. 36 Summary and Outlook ............................................................................ 57 Experimental Section ................................................................................ 60 References ............................................................................................. 71 Supporting Information ............................................................................ 79 CHAPTER 3 PHOSPHINE-MODIFIED CHOLATE LIGANDS FOR PALLADIUM CATALYZED CROSS-COUPLING REACTIONS UNDER AQUEOUS CONDITIONS ............................................................................ 80 Abstract ................................................................................................... 80 Introduction ............................................................................................ 81 Results and Discussion ............................................................................. 82 Summary and Outlook ............................................................................. 93 iv Experimental Section ................................................................................ 98 References ............................................................................................. 103 Supporting Information ............................................................................ 105 CHAPTER 4 Pd COMPLEXES WITH N-HETEROCYCLIC CARBENE LIGANDS AS CATALYSTS FOR THE ALKOXYCARBONYLATION OF OLEFINS ............................................................................................. 114 Abstract ................................................................................................... 114 Introduction ............................................................................................ 115 Results and Discussion ............................................................................. 117 Summary ............................................................................................. 124 Experimental Section ................................................................................ 126 References ............................................................................................. 130 Supplementary Information ...................................................................... 133 CHAPTER 5 CONCLUSION ...................................................................... 137 APPENDIX A 12 Principles of Green Chemistry ......................................... 140 v LIST OF ABBREVIATIONS CO carbon monoxide CMC critical micelle concentration CTAB Cetyl trimethylammonium bromide dba dibenzylideneacetone DEAD diethyl azodicarboxylate DiPEA N,N-diisopropylethylamine DIAD diisopropyl azodicarboxylate DMA dimethylacetamide DMSO dimethylsulfoxide dtbpmb Ditertbutyl phosphine methyl benzene dppp 1,3-diphenylphosphino propane dtbpp 1,3-ditertbutylphosphino propane dppm 1,3-diphenylphosphinomethane ESI electrospray ionization Et ethyl EtOAc Ethyl Acetate EtOH ethanol eqn equation g gram mg milligram vi GC gas chromatography GC-MS gas chromatography coupled with mass spectrometry h hour L liter LMS lutidinium mesylate MsOH methane sulfonic acid MSA methane sulfonic acid Me methyl MeOH methanol Mes mesitylene MHz megahertz mL milliliter nBu n-butyl OAc acetate OTf triflate OTs tosylate [ox] oxidation 2-PisMS 2-picolinium mesylate 4-PisMS 4-picolinium mesylate psi pounds per square inch PMS pyridinium mesylate ppm parts per million vii NaC Sodium Cholate µL microliter mL milliliter min minute mo. month mol mole mmol millimole µmol micromole NEt3 triethylamine NHC N-heterocyclic carbene NMR nuclear magnetic resonance Ph phenyl Ph3P triphenyl phosphine rt room temperature rxn reaction SDS Sodium dodecyl sulfate TEA triethylamine THF tetrahydrofuran TsOH p-toluenesulfonic acid PTSA p-toluenesulfonic acid wt% weight percent viii ABSTRACT In response to current environmental issues and concerns, an abundance of chemical literature focuses upon green, benign methodologies. Considering these issues, work presented within this thesis focuses upon development of greener synthetic techniques that are robust and versatile in both and Pd-catalyzed cross- coupling reactions and alkoxycarbonylation. Sonogashira coupling between terminal alkynes and aryl bromides or o iodides was high yielding with Pd(PPh3)2Cl2 in water at 40 C using commercially available surfactants such as SDS and CTAB. An iodide and Cu(I) inhibition was observed under these micellar conditions with aryl bromide substrates, leading to development of Cu(I)-free conditions. Studies under Cu(I)-free conditions suggest two competing mechanistic cycles. Both cycles (deprotonation and carbopalladation) lead to traditional Sonogashira products, but the carbopalladation cycle also produces an enyne product. The surfactant solution (either 2 wt% SDS or CTAB) can be recycled up to 3 times without reduction in yield when coupling 1-iodoanpthalene with 1-octyne in the presence of excess piperidine, 5 mol% CuI, and 2 mol% Pd(PPh3)2Cl2. The effect of the phosphine ligand structure was evaluated in aqueous phase Heck cross-coupling reactions. A methyl cholate derivative was modified with a tri-aryl phosphine moiety, creating a novel ligand that effectively coordinated to Pd(OAc)2 when dissolved in methanol. The cholate-Pd complex proved to be an ix efficient catalyst for Heck cross-coupling between various olefins and aryl iodide substrates under basic aqueous conditions with mild heating. The cholate ligand appears to enhance reaction yields by creating a localized hydrophobic environment around the Pd center, which attracts and increases the local concentration of nonpolar coupling reagents near the active catalytic site. Homogeneity studies show that the catalytically active Pd species remains heterogeneous throughout the reaction duration. Finally, palladium catalysts can also be effective in the conversion of olefinic molecules to aliphatic esters. Palladium complexes, generated