Iowa State University Capstones, Theses and Retrospective Theses and Dissertations Dissertations 2001 Palladium-catalyzed annulations, ternary couplings, and migration chemistry Daniel Edward Emrich Iowa State University Follow this and additional works at: https://lib.dr.iastate.edu/rtd Part of the Organic Chemistry Commons Recommended Citation Emrich, Daniel Edward, "Palladium-catalyzed annulations, ternary couplings, and migration chemistry " (2001). Retrospective Theses and Dissertations. 1039. https://lib.dr.iastate.edu/rtd/1039 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 Retrospective Theses and Dissertations by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. INFORMATION TO USERS This manuscript has been reproduced from the microfilm master. UMI films the text directly from the original or copy submitted. Thus, some thesis and dissertation copies are in typewriter face, while others may be from any type of computer printer. The quality of this reproduction is dependent upon the quality of the copy submitted. Broken or indistinct print, colored or poor quality illustrations and photographs, print bleedthrough, substandard margins, and improper alignment can adversely affect reproduction. In the unlikely event that the author did not send UMI a complete manuscript and there are missing pages, these will be noted. Also, if unauthorized copyright material had to be removed, a note will indicate the deletion. Oversize materials (e.g., maps, drawings, charts) are reproduced by sectioning the original, beginning at the upper left-hand corner and continuing from left to right in equal sections with small overlaps. Photographs included in the original manuscript have been reproduced xerographically in this copy. Higher quality 6" x 9" black and white photographic prints are available for any photographs or illustrations appearing in this copy for an additional charge. Contact UMI directly to order. ProQuest Information and Learning 300 North Zeeb Road, Ann Arbor, Ml 48106-1346 USA 800-521-0600 Palladium-catalyzed annulations, ternary couplings, and migration chemistry by Daniel Edward Emrich A dissertation submitted to the graduate faculty in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Major: Organic Chemistry Major Professor: Richard C. Larock Iowa State University Ames, Iowa 2001 UMI Number: 3016703 UMI UMI Microform 3016703 Copyright 2001 by Bell & Howell Information and Learning Company. All rights reserved. This microform edition is protected against unauthorized copying under Title 17, Uniteid States Code. Bell & Howell Information and Learning Company 300 North Zeeb Road P.O. Box 1346 Ann Arbor, Ml 48106-1346 ii Graduate College Iowa State University This is to certify that the Doctoral dissertation of Daniel Edward Emrich has met the dissertation requirements of Iowa State University Signature was redacted for privacy. Major Professor Signature was redacted for privacy. Signature was redacted for privacy. For the Gçâdua College iii To Rebecca iv TABLE OF CONTENTS LIST OF ABBREVIATIONS vi GENERAL INTRODUCTION 1 Dissertation Organization 2 CHAPTER 1. PALLADIUM(0)-CATALYZED HETEROANNULATION OF CYCLIC AND BICYCLIC ALKENES BY FUNCTIONALLY- SUBSTITUTED ARYL IODIDES 4 Abstract 4 Introduction 5 Results and Discussion 9 Conclusion 43 Experimental 43 Acknowledgement 59 References 59 CHAPTER 2. SYNTHESIS OF TETRASUBSTITUTED ALKENES BY THE PALLADIUM-CATALYZED TERNARY COUPLING OF ARYL IODIDES, ALKYNES, AND ORGANOMETALLICS 63 Abstract 63 Introduction 64 Results and Discussion 72 Conclusion 117 Experimental 117 Acknowledgement 131 References 131 CHAPTER 3. PALLADIUM MIGRATION FROM AN ARYL GROUP TO AN ACYL GROUP 139 Abstract 139 Introduction 140 Results and Discussion 144 Conclusion 167 Experimental 168 Acknowledgement 178 References 179 GENERAL CONCLUSIONS 182 ACKNOWLEDGEMENTS 184 LIST OF ABBREVIATIONS atm atmosphere aq aqueous BINAP 2,2'-bis(diphenyIphosphino)-l,r-binaphthyl brs broad singlet Bu butyl C Celsius cat. catalytic calcd calculated d days d doublet dba dibenzylideneacetone dd doublet of doublets ddd doublet of doublets of doublets DMA MN-dimethylacetamide DME ethylene glycol dimethyl ether DMF A/.N-dimethylformamide DMG MN-dimethylglycine DMSO dimethyl sulfoxide DPPB 1,2-bis(dipheny lphosphino)butane DPPE 1,2-bis(diphenylphosphino)ethane DPPF 1,1'-bis(diphenylphosphino)ferrocene DPPM 1,2-bis(dipheny lphosphino)methane vi DPPP 1,3-bis(diphenylphosphino)propane EDG electron-donating group EI Electron Ionization eq equation equiv equivalent Et ethyl EtOAc ethyl acetate eV electron volts EWG electron-withdrawing group g gram GC Gas Chromatography GC-MS Gas Chromatography-Mass Spectrometry h hours H hydrogen Hex hexanes HRMS High-Resolution Mass Spectrometry Hz Hertz IR infrared m multiplet m meta Me methyl mg milligram MHz megaHertz vii mL milliliters mmol miUimole(s) mol mole(s) mp melting point nm nanometer NMP l-methyl-2-pyrrolidinone NMR Nuclear Magnetic Resonance NOSEY Two-Dimensional Nuclear Overhauser Spectroscopy o ortho p para Pd(0) palladium(O) Ph phenyl PPh3 triphenylphosphine q quartet s singlet S^l substitution, nucleophiiic, unimoiecuiar soin solution t triplet t or ten tertiary r-Bu rerr-butyl temp temperature Tf trifluoromethanesulfonyl viii THF tetrahydrofiiran TLC thin layer chromatography TMS trimethylsilyl tt triplet of triplets UV ultraviolet 1 GENERAL INTRODUCTION Over the past decades, synthetic organic chemists have taken advantage of organometallics in their synthetic methodologies. Methodologies which employ an organometallic have proven useful for the formation of carbon-carbon single bonds—a typically difficult bond to form in synthetic chemistry in good yield under mild conditions. Organolithium and organomagnesium (or Grignard reagents) have been used extensively to form carbon-carbon single bonds. Typically these organometallic reagents are employed in stoichiometric amounts. Additionally, organotransition metal chemistry has been used extensively in organic synthesis; however, transition metals are usually (but not always) employed in catalytic amounts. These reagents consist of a transition metal and organic group bonded directly by either a a or n metal-carbon bond. One example of these reagents is the organocopper compounds, which have been used a lot with Grignard reagents. Other organometallic compounds, such as organonickel, organomercury, and organoiron compounds, have also been widely used to form carbon-carbon bonds. Even organoruthenium and organorhodium compounds, which are typically employed as hydrogénation catalysts, have recently been used to form carbon-carbon bonds. Similarly, organopalladium compounds have progressed from being used in hydrogénation reactions to being employed in forming carbon-carbon single bonds. Much attention has been focused on palladium in synthetic chemistry due to its low toxicity, high tolerance of functional groups, and ability to be employed catalytically in reactions. 2 Although palladium is expensive, it is still attractive in organic synthesis, because it can be used in a small amount catalytically. The current literature is full of synthetic methodologies where palladium has been used to form carbon-carbon bonds both regio- and sterioselectively, some of which have familiar names, such as the Heck, Sonogashira, Suzuki, and Stille reactions. The Larock group has done extensive, basic research on organopalladium methodologies. These methodologies have involved palladium-catalyzed annulations of organic halides onto 1,2-, 1,3-, and 1,4-dienes, as well as alkynes, for the synthesis of carbo- and heterocycles. This dissertation serves to expand the scope and utility of earlier methodologies. The dissertation is organized into three different papers, which are suitable for publication, and the author of the publication was the primary investigator and author of the papers. Dissertation Organization This dissertation is divided into three chapters, and each chapter is written as an independent paper following the guidelines for the Journal of Organic Chemistry. The papers are composed of an abstract, introduction, results and discussion, conclusion, experimental, acknowledgements, and references. Chapter 1 extends earlier Larock group, palladium-catalyzed methodology, o- Amino- and o-hydroxyaryl iodides, which were previously annulated onto norbomene and bicyclo[2.2.2]oct-2-ene, are annulated onto other cyclic and bicyclic alkenes. The reaction has been optimized, and a reaction mechanism is proposed. 3 Chapter 2 presents preliminary results on new palladium-catalyzed methodology for the synthesis of tetrasubstituted alkenes. These alkenes are formed via the ternary coupling of aryl iodides, alkynes, and organometallics. The reaction conditions are optimized and the scope and limitations of the reaction are discussed. A reaction mechanism is proposed, and the regio- and stereoselectivity of the reaction is investigated. Chapter 3 presents work on palladium migration chemistry wherein the palladium migrates from an aryl group to an acyl group. Different substrates, which undergo this new kind of palladium migration, are investigated. The reaction conditions are optimized, and a reaction mechanism is proposed. General conclusions and acknowledgements are included. 4 CHAPTER