SYNTHESIS, COORDINATION CHEMISTRY, AND REACTIVITY OF FUNCTIONALIZED PHOSPHINES: TOWARD WATER-SOLUBLE MACROCYCLIC PHOSPHINE COMPLEXES by CHARLES D. SWOR A DISSERTATION Presented to the Department of Chemistry and the Graduate School of the University of Oregon in partial fulfillment of the requirements for the degree of Doctor of Philosophy March 2011 DISSERTATION APPROVAL PAGE Student: Charles D. Swor Title: Synthesis, Coordination Chemistry, and Reactivity of Functionalized Phosphines: Toward Water-soluble Macrocyclic Phosphine Complexes This dissertation has been accepted and approved in partial fulfillment of the requirements for the Doctor of Philosophy degree in the Department of Chemistry by: Dr. Michael M. Haley Chairperson Dr. David R. Tyler Advisor Dr. Darren W. Johnson Member Dr. Shih-Yuan Liu Member Dr. Mark H. Reed Outside Member and Richard Linton Vice President for Research and Graduate Studies/Dean of the Graduate School Original approval signatures are on file with the University of Oregon Graduate School. Degree awarded March 2011 ii © 2011 Charles David Swor iii DISSERTATION ABSTRACT Charles David Swor Doctor of Philosophy Department of Chemistry March 2011 Title: Synthesis, Coordination Chemistry, and Reactivity of Functionalized Phosphines: Toward Water-soluble Macrocyclic Phosphine Complexes Approved: _______________________________________________ Dr. David R. Tyler Macrocyclic phosphine compounds have long been sought as ligands for transition metal complexes because of their strong binding properties. Despite considerable effort in this field, no general methods for synthesizing phosphine macrocycles or their complexes have been developed. This dissertation describes attempts to synthesize an iron complex with a water-soluble macrocyclic tetraphosphine ligand for use in separating nitrogen from natural gas. Chapter I reviews previous syntheses of macrocyclic phosphine ligands and their complexes, focusing on ligand synthesis, coordination chemistry, and demetallation of the complexes. Chapter II reports on the synthesis of water-soluble secondary bidentate phosphine ligands, their coordination chemistry with iron(II), and attempts to use these complexes as templates for forming a macrocyclic iron-phosphine complex by reactions with carbon electrophiles. Over the course of treating these iron complexes with various carbon electrophiles, an interesting reaction between bromomaleic anhydride and proton sponge was discovered. Chapter III explores the product, 4-maleicanhydrido-1,8-bis- iv (dimethylamino)naphthalene (MAPS). Due to its conjugated donor-acceptor network, which is disrupted upon protonation, MAPS acts as a colorimetric version of a proton sponge. The attachment of MAPS to amine-functionalized solid supports, forming solid- supported proton sponge reagents, is also described. Chapter IV discusses the synthesis of an iron(II) complex of the water-soluble phosphine 1,2-bis(di(hydroxymethyl)phosphino)ethane (DHMPE). Although unbound hydroxymethylphosphines commonly react with NH-functional amines via the phosphorus Mannich reaction, this and other complexes of DHMPE do not undergo this reaction. Further investigation with hydroxymethylphosphine-boranes suggests that the currently-accepted mechanism of the phosphorus Mannich reaction is incorrect, and an alternate mechanism is proposed. Chapter V discusses the synthesis and functionalization of copper(I) complexes of water-soluble phosphines. Unlike the complexes described in Chapter I, these complexes readily react with -dihalides or di(acyl chloride)s, forming complexes whose mass spectra correspond to those with macrocyclic phosphine ligands. Unlike most macrocyclic tetraphosphine complexes, these complexes can be demetallated by treatment with sulfide. Finally, a new synthesis of water-soluble macrocycles, based on lessons learned during the course of these investigations, is proposed. This dissertation includes previously published and unpublished co-authored material. v CURRICULUM VITAE NAME OF AUTHOR: Charles David Swor GRADUATE AND UNDERGRADUATE SCHOOLS ATTENDED: University of Oregon, Eugene, OR Tennessee Technological University, Cookeville, TN DEGREES AWARDED: Doctor of Philosophy in Chemistry, 2011, University of Oregon Master of Science in Chemistry, 2007, University of Oregon Bachelor of Science in Chemistry, 2004, Tennessee Technological University AREAS OF SPECIAL INTEREST: Phosphine Synthesis Coordination Chemistry Macrocyclic Ligands Reactions of Coordinated Ligands PROFESSIONAL EXPERIENCE: Co-op Engineer, Fleetguard, Inc., 2004-2005 Graduate Teaching Fellow, University of Oregon, 2005-2007 Graduate Research Assistant, University of Oregon, 2010-2011 GRANTS, AWARDS, AND HONORS: NSF GK-12 Fellowship, University of Oregon, 2007-2010 Ferris U. Foster Scholarship, Department of Chemistry, Tennessee Technological University, 2004 Outstanding Senior Award, Department of Chemistry, Tennessee Technological University, 2004 vi PUBLICATIONS: Swor, C. D.; Hanson, K. R.; Zakharov, L. N.; Tyler, D. R. Reactions of Coordinated Hydroxymethylphosphines with NH-Functional Amines: Investigation of the Phosphorus Mannich Reaction. Submitted to Inorganic Chemistry. Swor, C. D. and Tyler, D. R. Solid-supported proton sponges. U.S. Patent Application No. 61/383,688. September 16, 2010. Swor, C. D.; Zakharov, L. N.; Tyler, D. R. A colorimetric proton sponge. J. Org. Chem. 2010, 75, 6977-6999. vii ACKNOWLEDGMENTS I would first like to thank my advisor, Professor David R. Tyler, for his guidance over the course of my graduate studies. He has been a great mentor, and has provided an excellent environment for me to enhance my knowledge and skills in science. By setting a lofty example, he has given me the commitment, motivation, and the desire to conduct scientific research which will provide an important contribution to society. Thanks also to all members of my committee, who have demonstrated a genuine interest in my project and in my development as a chemist. I would also like to thank previous graduate students in the Tyler Group, especially Justin Crossland, Bevin Daglen, and Takiya Ahmed, who mentored me throughout my graduate career. Thanks also to rotation students Brandy Fox, Kyle Hanson, Jesse Gavette, and Andy Hughett, as well as undergraduates McKenzie Floyd, Erika Hanson, and Ian Doxsee, for the work they contributed to the project. Thanks also to Bryan Nell, who is continuing this research project after I leave, and I wish him the best of luck in his graduate career. I thank Lev Zakharov for the crystal structures presented in this dissertation. Thanks also to Mike Strain for all his help with NMR spectrometers, and Tim Carter and Erich Chapman for their help with the mass spectrometers. Thank you to all the wonderful friends I have met during my graduate career. There are too many of you to mention by name, but because of you I will always remember my graduate school experience as a great one. I was fortunate to receive funding through the UO GK-12 program (NSF Grant # DGE-0742540). I am also deeply grateful to directors Anae Rosenberg and Dean viii Livelybrooks for allowing me to participate in this program. The GK-12 does an excellent job promoting science in schools across Oregon. In addition, my experience as a GK-12 fellow in these schools has helped immensely with my development as a science educator. I am privileged to have been a part of this program. Finally, I would like to thank my family. Thanks to my parents Tom and Sallie, and my brother Steve, for their continued love and encouragement during my graduate career. I would especially like to thank my beautiful wife Rachel for being my steadfast partner throughout this endeavour. She has provided me with support, confidence, and stability during these challenging years. I am grateful and blessed that she has chosen me to accompany her on this adventure of life, and I can’t wait to see what’s next. ix Dedicated to every good teacher I’ve ever had. I could never have achieved any of my success without the skills they have given me. x TABLE OF CONTENTS Chapter Page I. SYNTHESIS AND COORDINATION CHEMISTRY OF MACROCYCLIC PHOSPHINE LIGANDS ............................................................................................. 1 1.1. Introduction ..................................................................................................... 1 1.2. Synthesis of Macrocyclic Phosphine Ligands ................................................ 5 1.2.1. Cyclocondensation Reactions ................................................................ 5 1.2.1.1. Early Syntheses ............................................................................. 5 1.2.1.2. Cyclocondensations Using Rigid Linkers ..................................... 13 1.2.1.3. Stereochemical Control ................................................................. 15 1.2.1.4. Self-Assembling Phosphine Macrocycles ..................................... 20 1.2.1.5. Summary ....................................................................................... 22 1.2.2. Template Syntheses ............................................................................... 22 1.2.2.1. Triphosphine Macrocycles ............................................................ 23 1.2.2.2. Tetraphosphine Macrocycles ........................................................ 29 1.2.2.3. Larger Macrocycles ...................................................................... 39 1.3. Coordination Chemistry of Macrocyclic Phosphine