University of California Los Angeles Phosphine Catalysis using Allenoates with pro-Nucleophiles or Arylidenes; Development of an Asymetric Phosphine Catalyst; and Allenes as π-Ligands in Copper-Mediated Cross-Coupling A dissertation submitted in partial satisfaction of the requirements for the degree Doctor of Philosophy in Chemistry by Tioga Martin 2014 Abstract of Dissertation Phosphine Catalysis using Allenoates with pro-Nucleophiles or Arylidenes; Development of an Asymetric Phosphine Catalyst; and Allenes as π-Ligands in Copper-Mediated Cross-Coupling by Tioga Jarrett Martin Doctor of Philosophy in Chemistry University of California, Los Angeles, 2014 Professor Craig A. Merlic, Chair The unique characteristics of 1,2-dienes have proven to be a dynamic and ever growing field of study in organic chemistry. Allenes have been manipulated into a myriad of transformations, and have offered their unique characteristics to a number of fields of study. Chapter 1 discusses a phosphine catalyzed annulation between allenoates and alkenes to form cyclohexenes. In Chapter 2 the new phosphine catalyzed β’-Addition of a Pronucleophile to an allenoate is examined. Chapter 3 presents the development of a proline derived phosphine catalyst and its application in asymmetric synthesis of dihydropyrroles. A review on allene complexes with transition metals is presented in Chapter 4. Chapter 5 explores the effect of allene ligands upon copper, and subsequent copper-mediated vinyl ether synthesis. ii The dissertation of Tioga Martin is approved. Michael E. Jung Selim M. Senkan Craig A. Merlic, Committee Chair University of California, Los Angeles 2014 iii Table of Contents Chapter 1. Phosphine-Catalyzed [4 + 2] Annulations of 2-Alkylallenoates and Olefins: Synthesis of Multisubstituted Cyclohexenes ...................................................................................1 I. Introduction ......................................................................................................................1 II. Results and Discussion .....................................................................................................4 A. Preparation of Arylidenemalonates, Arylidenemalononitriles, and (E)-2-cyano-3- arylacrylates ........................................................................................................................4 B. Survey of Phosphine Catalysts for the [4 + 2] Annulation .................................................6 C. Survey of Solvents for the [4 + 2] Annulation ...................................................................8 III. Conclusion ......................................................................................................................11 Experimental Section: General Information...............................................................................12 General Procedure for Formation of Dimethyl Arylidenemalonate ...........................................13 General Procedure for Formation of Arylidenemalononitriles and 2-Cyano-3-arylacrylates ....13 General Procedure for Formation of Cyclohexenes ...................................................................14 References ..................................................................................................................................17 Chapter 2. Phosphine-Catalyzed β’-Functionalization with Pronucleophiles on Activated α- Alkyl Allenes .................................................................................................................................20 I. Introduction ....................................................................................................................20 II. Results and Discussion ...................................................................................................21 A. Proposed Mechanism of the β’-Addition of Pronucleophiles to Allenes .........................21 B. Survey of Phenolic Pronucleophiles .................................................................................22 C. Attempt at Trapping the Diels-Alder Adduct ...................................................................24 D. Access to Functionalized Coumarin .................................................................................25 iv E. Survey of Amine Pronucleophiles ....................................................................................26 F. Survey of Carboxylic Acid Pronucleophiles ....................................................................28 G. Survey of Carbon Pronucleophiles ...................................................................................30 H. Furfuryl Alcohol, Benzaldehyde Oxime, and Thiophenol Pronucleophiles ....................32 I. Dimerization of Ethyl 2-(cyanomethyl)buta-2,3-dienoate ...............................................33 III. Conclusion ......................................................................................................................34 Experimental Section: General Information...............................................................................35 General Procedure for the Phosphine-Catalyzed β’-Addition of Pronucleophiles to Activated Allenes ........................................................................................................................................36 General Procedure for the Cope Rearrangement of Compound 4a ............................................37 General Procedure for the Dimerization of Ethyl 2-(cyano)but-2,3-dienoate............................38 General Procedure for the In Situ Heck Coupling .....................................................................39 References ..................................................................................................................................40 Chapter 3. Amino Acid Derived [2.2.1] Bicyclic Phosphine: Asymmetric Synthesis of Dihydropyrroles .............................................................................................................................44 I. Introduction ....................................................................................................................44 II. Results and Discussion ...................................................................................................46 A. Synthesis of [2.2.1] Bicyclic Phosphines .........................................................................46 B. Substrate Optimization of the Phosphine-Catalyzed [3 + 2] Annulation of Allenoates and Imines ...............................................................................................................................49 C. Survey of the Asymmetric Phosphine-Catalyzed [3 + 2] Annulation of Allenoates and Imines ...............................................................................................................................51 v D. De-tosylation and in situ N-Benzylation ..........................................................................53 III. Conclusion ......................................................................................................................55 Experimental Section: General Information...............................................................................56 Synthesis of Protected Catalyst ..................................................................................................57 Reductive Deprotection of Phosphines ......................................................................................63 Allenoate Synthesis ....................................................................................................................68 Phosphine-Catalyzed [3 + 2] Allenoate/Imine Annulation ........................................................69 Tables of HPLC conditions for Separating Pyrrolines ...............................................................81 References ..................................................................................................................................83 Chapter 4. Common Coordination Complexes of Allenes as π-Bond Ligands to Transition Metals .............................................................................................................................................86 I. Introduction ................................................................................................................86 II. Allene Coordinated Transition-Metal Complexes......................................................87 A. Examples of the Fluxional Behavior of Allene Ligands ............................................89 B. Examples and Characteristics of η2-vinyl Coordination ............................................91 C. Examples of μ-η2,η2-parallel and –oblique Coordination...........................................96 D. An Example of μ-η2-Coordination .............................................................................99 E. Examples of μ-η1,η3-Allyl Complexes ............................................................................ 99 F. Other Ligation Motifs of Allene-Metal Coordination ................................................. 101 G. Insertion of Allenes to give Metal-Allyl Complexes................................................103 III. Conclusion ................................................................................................................106 References ................................................................................................................................107 vi Chapter 5. Allenes as π-Bond Ligands in Copper-Mediated