The Chemistry of Zirconacycles and 2,6-Diazasemibullvalenes: Synthesis, Structures, Reactions, and Applications in the Synthesis of Novel N-Heterocycles (Springer Theses)

Zhang Shaoguang. The Chemistry of Zirconacycles and 2,6-Diazasemibullvalenes - Synthesis, Structures, Reactions, and Applications in the Synthesis of Novel N-Heterocycles [Springer Theses] 2015 [pdf 182sc 173c. 9.93mb]In this thesis, the author introduces two strategies used to construct various types of N-heterocycles, based on the chemistry of zirconacycles and 2,6-diazasemibullvalenes. In the first part, the author presents the development of multi-component cyclization of a zirconacyclobutene-silacyclobutene fused compound, nitriles and unsaturated compounds. These reactions provide synthetically useful methodology for various N-heterocycles such as 3-acyl pyrrole, pyrrolo[3,2-d]pyridazine and dihydropyrroloazepine, which are all difficult to synthesize by other means. The isolation and characterization of the key three-fused-ring Zr/Si-containing intermediates are also described in detail. These results show that the zirconacyclobutene-silacyclobutene fused compound behaves as a “chemical transformer” upon treatment with various substrates via the “coordination-induced skeleton rearrangement” mechanism. In the second part, the author demonstrates the synthesis and isolation of a series of 2,6-diazasemibullvalenes (NSBVs) from the reaction of 1,4-dilithio-1,3-dienes and nitriles, highlighting the significant progress made for the first time in this work: (1) determination of X-ray crystal structure of a substituted 2,6-diazasemibullvalene; (2) measurement of the activation barrier of its rapid intramolecular aza-Cope rearrangement in solution; (3) exploration of several reaction types of NSBV with diverse ring-expansion products and “bowl-shape” or “cage-shape” N-containing polycyclic skeletons; (4) demonstration of the localized structure as the predominant form and the homoaromatic delocalized structure as a minor component in the equilibrium using theoretical analysis. Based on well-founded results, this work sheds new light on this controversial topic. Supervisor’s Foreword 8 Contents 10 1 Introduction to Zirconacycle Chemistry 13 1.1 N-Heterocyclic Compounds 13 1.2 Zirconocene Chemistry 13 1.3 Zirconocene-Mediated Cyclization Reactions and Application in the Synthesis of N-Heterocycles 14 1.4 Zirconocene-Mediated Intramolecular Cyclization of Bis(Alkynyl)Silanes 21 1.5 Reaction Chemistry of Zirconacyclobutene--Silacyclobutene Complexes 24 1.5.1 Reaction of Zirconacyclobutene--Silacyclobutene Complexes with Alkynes (Class I) 25 1.5.2 Reaction of Zirconacyclobutene--Silacyclobutene Complexes with C=X Bond (Class II) 28 1.5.3 Reaction of Zirconacyclobutene--Silacyclobutene Complexes with Nitriles (Class III) 28 References 29 2 Zirconocene-Mediated Cyclization of Bis(alkynyl)silanes and Nitriles: Synthesis of N-Heterocycles and Isolation, Characterization, and Synthetic Application of Zr/Si-Containing Reactive Intermediates 33 2.1 Introduction 33 2.2 Results and Discussion 34 2.2.1 Formation of 5-Azaindoles from One Molecule of Bis(alkynyl)silane with Three Molecules of the Same Organonitrile 34 2.2.2 Isolation and Characterization of Zr/Si-Containing Organometallic Reactive Intermediates 36 2.2.3 Synthetic Application of Zr/Si-Containing Organometallic Reactive Intermediates 39 2.2.4 One-Pot Multi-component Coupling of Bis(alkynyl)silanes, Nitriles and Isocyanides and Synthesis of N-Containing Heterocycles via Intramolecular Cyclization of Iminoacyl--Zr Intermediates 41 2.2.4.1 Isolation and Structural Characterization of Iminoacyl-Zr and Bis(iminoacyl)--Zr Intermediates via Mono- and Double Insertion of Isocyanides into Azazirconacycles 43 2.2.4.2 Intramolecular Cyclization of eta 2-Iminoacyl--Zr Complexes to Form Tetra-substituted 5-Azaindoles or Dihydropyrrolo[3,2-c]azepine Derivatives 45 2.2.5 One-Pot Synthesis of Pyrrolo[3,2-d]pyridazines and Pyrrole-2,3-Diones via Zirconocene-Mediated Four-Component Coupling of Bis(alkynyl)silane, Nitriles, and Azide 48 2.2.5.1 One-Pot Synthesis of Pyrrolo[3,2-d]pyridazine Derivatives via Zirconocene-Mediated Cyclization of One Bis(alkynyl)silane, Two Nitriles, and One Azide 48 2.2.5.2 One-Pot Synthesis of Pyrrole-2,3-Dione Derivatives via Zirconocene-Mediated Cyclization of One Bis(alkynyl)silane, Two Nitriles, and One TMSN3 51 2.3 Summary 53 2.4 Experimental Section 54 References 70 3 Bulky Nitrile Coordination-Induced Skeleton Rearrangement of Zr-/Si-Containing Metallacycles and Selective Synthesis of 5-Azaindoles 74 3.1 Introduction 74 3.2 Results and Discussion 76 3.2.1 Bulky Nitriles Coordination-Induced Skeleton Rearrangement of Zirconacyclopropene--Azasilacyclopentadiene Complexes 76 3.2.2 Reaction and Synthetic Application of Zirconacyclopropene--Azasilacyclopentadiene Complexes: Reactions of the Zirconacyclopropene Moiety 78 3.2.3 Reaction and Synthetic Application of Zirconacyclopropene--Azasilacyclopentadiene Complexes: Reactions Involving Both the Zirconacycle and Silacycle Moiety 81 3.2.3.1 Reaction of 3-2 with Acid Chloride 81 3.2.3.2 Reaction of 3-2 with Second Molecule of Nitrile 82 3.2.3.3 Reactions of Intermediate 3-2 with the Second and Third Molecules of Nitrile: Formation of 5-Azaindoles from One Si-Tethered Diyne, One t-BuCN, and Two Identical or Different Organonitriles 83 3.3 Summary 86 3.4 Experimental Section 87 References 100 4 Introduction to Semibullvalenes and Azasemibullvalenes 102 4.1 Homoaromaticity 102 4.2 Cope Rearrangement 104 4.3 Semibullvalene 105 4.3.1 Electronic Stabilization by Substituents (Dewar--Hoffmann SBV) 106 4.3.2 Destabilization of Localized Structure by Small Ring Annulation 111 4.3.3 Coordination with Metal Ion 112 4.3.4 Stabilization of Delocalized Structure by Solvation 113 4.3.5 Introduction of Heteroatom into Skeleton 113 4.3.6 Azasemibullvalene 114 References 116 5 2,6-Diazasemibullvalenes: Synthesis, Structural Characterization, and Theoretical Analysis 119 5.1 Introduction 119 5.2 Result and Discussion 120 5.2.1 2,6-Diazasemibullvalenes: Synthesis 120 5.2.2 2,6-Diazasemibullvalenes: Structural Characterization 122 5.2.3 2,6-Diazasemibullvalenes: Theoretical Analysis and Computational Results 125 5.3 Summary 126 5.4 Experimental Section 127 References 134 6 2,6-Diazasemibullvalenes: Reaction Chemistry and Synthetic Application 136 6.1 Introduction 136 6.2 Result and Discussion 137 6.2.1 Insertion Reaction of Unsaturated Compounds or Low-Valent Metals into the Weakened C--N Bonds of 2,6-Diazasemibullvalenes 137 6.2.2 Lewis Acid-Catalyzed Cycloadditions of 2,6-Diazasemibullvalenes with Isocyanides, Azides, and Diazo Compounds: Novel Reaction Patterns Leading to N-Heterocyclic Cage-Shaped Compounds 140 6.2.2.1 Zinc Triflate-Catalyzed [5 + 1] Cycloadditions of 2,6-Diazasemibullvalenes with Isocyanides: Synthesis of Diazabrexadienes 141 6.2.2.2 Lanthanum Triflate-Catalyzed Rearrangement--Cycloaddition of 2,6-Diazasemibullvalenes and Azides: Synthesis of Triazabrexadienes 144 6.2.2.3 Scandium Triflate-Catalyzed Rearrangement--Cycloaddition of 2,6-Diazasemibullvalenes and Diazo Compounds: Synthesis of Triazabrexadienes 146 6.2.3 Oxidation of 2,6-Diazasemibullvalenes by O2 or N-Oxides: Synthesis of Delta 1-Bipyrrolinones and Pyrrolino[3,2-b]Pyrrolinones 148 6.2.3.1 Oxidation of 2,6-Diazasemibullvalenes by O2: Synthesis of Delta 1-Bipyrrolinones 150 6.2.3.2 Oxidation of 2,6-Diazasemibullvalenes by N-Oxides: Synthesis of Pyrrolino[3,2-b]Pyrrolinones 151 6.2.3.3 Synthetic Applications of Delta 1-Bipyrrolinones and Pyrrolino[3,2-b] Pyrrolinones 152 6.2.4 Nucleophilic Ring-Opening Reactions of 2,6-Diazasemibullvalenes for the Synthesis of Diverse Functionalized Delta 1-Bipyrroline Derivatives 155 6.2.4.1 Nucleophilic Ring Opening of 2,6-Diazasemibullvalenes with Proton-Bearing Nucleophiles 155 6.2.4.2 Nucleophilic Ring Opening of 2,6-Diazasemibullvalenes with Sulfoxonium Ylides 156 6.3 Summary 158 6.4 Experimental Section 159 References 179 In this thesis, the author introduces two strategies used to construct various types of N-heterocycles, based on the chemistry of zirconacycles and 2,6-diazasemibullvalenes. In the first part, the author presents the development of multi-component cyclization of a zirconacyclobutene-silacyclobutene fused compound, nitriles and unsaturated compounds. These reactions provide synthetically useful methodology for various N-heterocycles such as 3-acyl pyrrole, pyrrolo[3,2-d]pyridazine and dihydropyrroloazepine, which are all difficult to synthesize by other means. The isolation and characterization of the key three-fused-ring Zr/Si-containing intermediates are also described in detail. These results show that the zirconacyclobutene-silacyclobutene fused compound behaves as a ĺlchemical transformerĺl upon treatment with various substrates via the ĺlcoordination-induced skeleton rearrangementĺl mechanism. In the second part, the author demonstrates the synthesis and isolation of a series of 2,6-diazasemibullvalenes (NSBVs) from the reaction of 1,4-dilithio-1,3-dienes and nitriles, highlighting the significant progress made for the first time in this work: (1) determination of X-ray crystal structure of a substituted 2,6-diazasemibullvalene; (2) measurement of the activation barrier of its rapid intramolecular aza-Cope rearrangement in solution; (3) exploration of several reaction types of NSBV with diverse ring-expansion products and ĺlbowl-shapeĺl or ĺlcage-shapeĺl N-containing polycyclic skeletons; (4) demonstration of the localized structure as the predominant form and the homoaromatic delocalized structure as a minor component in the equilibrium using theoretical analysis. Based on well-founded results, this work sheds new light on this controversial topic Front Matter....Pages i-xi Introduction to Zirconacycle Chemistry....Pages 1-20 Zirconocene-Mediated Cyclization of Bis(alkynyl)silanes and Nitriles: Synthesis of N -Heterocycles and Isolation, Characterization, and Synthetic Application of Zr/Si-Containing Reactive Intermediates....Pages 21-61 Bulky Nitrile Coordination-Induced Skeleton Rearrangement of Zr-/Si-Containing Metallacycles and Selective Synthesis of 5-Azaindoles....Pages 63-90 Introduction to Semibullvalenes and Azasemibullvalenes....Pages 91-107 2,6-Diazasemibullvalenes: Synthesis, Structural Characterization, and Theoretical Analysis....Pages 109-125 2,6-Diazasemibullvalenes: Reaction Chemistry and Synthetic Application....Pages 127-173