Click Reactions in Organic Synthesis

Srinivasan Chandrasekaran is an Honorary Professor and SERB Distinguished Fellow at the Department of Organic Chemistry, Indian Institute of Science, Bangalore, India. He received his M.Sc. and Ph.D. from the University of Madras, India, in 1967 and 1972, respectively. He was a research associate at Harvard University (USA) with Prof. E.J. Corey, and Syntex Research (Palo Alto, USA). He has published over 250 research papers in national and international journals and served as an elected member of the Bureau of IUPAC and Member of the Executive Committee of IUPAC. He is the Chairman of the National Organic Symposium Trust (NOST), India and was the President of the Chemical Research Society of India (CRSI) from 2012 to 2014. He was the editor-in-chief of Tetrahedron Letters published by Elsevier( 2007-14) and is currently on the Board of Consulting Editors. His major research interests lie in the areas of development of new synthetic methodologies and organometallic chemistry, total synthesis of natural products, homogeneous and heterogeneous catalysis, and organic materials.

• List of Contributors XIPreface XV1 Click Chemistry:Mechanistic and Synthetic Perspectives 1Ramesh Ramapanicker and Poonam Chauhan1.1 Cycloaddition Click Reactions 21.1.1 Azide–Alkyne Huisgen 1,3-Dipolar Cycloaddition 21.1.2 Copper-Catalyzed Azide–Alkyne Cycloaddition (CuAAC) Click Reaction 21.1.2.1 Mechanism of CuAAC Click Reactions 51.1.2.2 Catalysts used for CuAAC Click Reactions 61.1.2.3 Ligands used for CuAAC Click Reactions 71.1.3 Ruthenium-Catalyzed Azide–Alkyne Cycloaddition (RuAAC) Click Reactions 71.1.3.1 Mechanism of RuAAC Click Reactions 81.1.4 Strain-Promoted Azide–Alkyne Cycloaddition (SPAAC) Reactions 81.1.5 Organocatalytic Triazole Formation 101.2 Thiol-Based Click Reactions 121.2.1 Radical Click Reactions of Thiols 121.2.1.1 Thiol–Ene Radical Click Reaction 121.2.1.2 Thiol–Yne Radical Click Reaction 141.2.2 Nucleophilic Addition Click Reactions ofThiols 151.2.2.1 Thiol–Epoxide Click Reactions 171.2.2.2 Thiol–Isocyanate Click Reactions 171.2.2.3 Thiol–Michael Addition Click Reactions 181.2.2.4 Thiol–Halogen Nucleophilic Substitution Reaction 201.3 Miscellaneous Click Reactions 21References 222 Applications of Click Chemistry in Drug Discovery and Development 25Balasubramanian Gopalan and Kalpattu Kuppusamy Balasubramanian2.1 Introduction 252.2 Part A: Application of Click Chemistry to Drug Discovery and Development 252.2.1 Carbonic Anhydrase Inhibitors 302.2.2 Targeting Onchocerca Volvulus Chitinase-1 (OvCHT1) using the Hydroxytriazole Moiety within a Scaffold Hopping Approach 322.2.3 1,2,3-Triaole-Derived Anticancer Agents 342.2.3.1 Topoisomerase II Inhibitors 342.2.3.2 Histone Deacetylase Inhibitors 362.2.3.3 Protein Tyrosine Kinase Inhibitors 382.2.3.4 Antimicrotubule Agents 392.2.3.5 HSP 90 Inhibitors 402.2.3.6 Autophagy-Dependent Apoptosis in CancerTherapy 412.2.3.7 Anticancer Activity of 4β-Triazole-Podophyllotoxin 422.2.3.8 1,2,3-Triazole-Substituted Oleanolic Acid Derivatives as Anticancer Agents 422.2.3.9 Anti-Infective Agents 432.2.3.10 1,2,3-Triazole Nucleoside 442.2.3.11 1,2,3-Triazole Carbonucleosides 452.2.3.12 β-Lactamase Inhibitors as Antibacterial Agents 472.2.3.13 1,2,3-Triazole-Linked Carbazoles as Antitubercular Agents 482.2.3.14 1,4-Diaryl-Substituted 1,2,3-Traizoles as Antimycobacterial (Mtb) Agents 482.2.3.15 1,2,3-Triazole-Adamantylacetamide Hybrids as Antitubercular Agents 502.2.3.16 Non-Nucleoside HIV Integrase Inhibitors 502.2.3.17 MiscellaneousTherapeutic Segments: 1,2,3-Triazole-Linked Dopamine D3 Receptor (D3R) 532.2.3.18 Peptidomimetics: 1,2,3-Triazole as a Disulfide Bond Mimetic 532.3 Part B: Synthesis of Triazole-Based Drugs Currently in use 542.2.1 Tazobactam 542.3.1.1 Synthesis of tazobactam from intermediate 102 552.3.1.2 Other reports on Tazobactam synthesis 552.3.2 Solithromycin 562.3.2.1 Synthesis of Solithromycin 572.3.3 Cefatrizine 602.3.4 Radezolid 612.3.5 Molidustat 632.3.5.1 Synthesis of Molidustat 632.3.6 Tradipitant 632.3.7 Carboxyamidotriazole 662.3.8 Rufinamide 662.3.8.1 Rufinamide–Novartis Process 662.3.8.2 An Efficient Synthesis of Rufinamide 682.3.8.3 Continuous-Flow Total Synthesis of Rufinamide 68References 703 Green Chemical Synthesis and Click Reactions 77Maria José Arévalo, Óscar López, and Maria Victoria Gil3.1 Introduction 773.2 Huisgen 1,3-Dipolar Cycloaddition 773.2.1 Green Perspectives on Reaction Conditions 783.2.1.1 Copper(I) Catalysts 783.2.1.2 Copper(I) Complexes with Nitrogen- and Phosphorous-Donating Ligands 793.2.1.3 Metalated Reagents as Catalysts 823.2.1.4 Immobilized Copper Species 823.2.1.5 Copper Nanocatalysis 833.2.1.6 Other Metals as Catalysts 843.2.1.7 Nonconventional Energy Sources 853.2.2 Applications to Synthesis 853.2.2.1 Regioselectivity of the Alkyne–Azide Cycloaddition 853.2.2.2 Different Substitution Patterns on Triazole 863.2.2.3 Strain-Promoted Cycloadditions 873.2.2.4 Sulfonyl Azides in Huisgen Cycloaddition 873.2.2.5 Synthesis of Vinyl-1,2,3-Triazoless 873.2.2.6 Triazole Derivative Ligands for Coordination Chemistry 883.2.2.7 Tetrazole Synthesis 883.2.2.8 Synthesis of Chiral Triazoles 883.2.2.9 Synthesis of Triazoles with Luminescent Properties 893.2.2.10 Synthesis of Triazole Libraries 893.2.2.11 Synthesis of Phosphorylated Triazoles 893.3 Other 1,3-Dipolar Cycloadditions 903.4 Atom Economy and Simplicity of Procedures in Multicomponent Reactions 903.4.1 Reaction Conditions 913.4.1.1 Copper Compounds as Catalysts 913.4.1.2 Copper Complexes with Nitrogen- and Phosphorous-Donating Ligands 913.4.1.3 Immobilized Copper Species 913.4.1.4 Copper Nanocatalysis 923.5 Summary and Conclusions 92References 934 Synthesis of Substituted 1,2,3-Triazoles through Organocatalysis 99Kengadarane Anebouselvy and Dhevalapally B. Ramachary4.1 Introduction 994.2 Preformed-Enolate-Based Synthesis of Substituted 1,2,3-Triazoles 1014.3 Preformed-Enamine-Based Synthesis of Substituted 1,2,3-Triazoles 1064.4 Synthesis of Substituted 1,2,3-Triazoles via Catalytic Enolate Intermediates 1094.5 General Mechanistic Aspects of Enolate Route 1134.6 Synthesis of Substituted 1,2,3-Triazoles via Enamine Intermediates 1144.7 General Mechanistic Aspects of Enamine Route 1234.8 Synthesis of Substituted 1,2,3-Triazoles via Iminium Intermediate 1234.9 Miscellaneous Routes for the Synthesis of 1,2,3-Triazoles 1244.10 Conclusions 136Acknowledgments 136References 1375 Applications of the Cu-Catalyzed Azide–Alkyne Cycloaddition (CuAAC) in Peptides 141Freek A. B. M. Hoogstede and Floris P. J. T. Rutjes5.1 Introduction 1415.2 CuAAC-Mediated Peptide Conjugation Strategies 1425.3 CuAAC-Mediated Peptide Backbone Modification Strategies 1485.4 Conclusions 157References 1576 Synthesis of Diverse Carbohydrate-Based Molecules using Click Chemistry 161Anoop S. Singh, Kunj B.Mishra, AmritaMishra, and Vinod K. Tiwari6.1 Introduction 1616.2 Cu-Catalyzed Click Chemistry in the Synthesis of Diverse Glycoconjugates 1626.3 Synthesis of Carbohydrate-Based Simple to Complex Macrocycles 1816.4 Click-Inspired Synthesis of Diverse Neoglycoconjugates 1856.5 Conclusion and Future Perspective 195Acknowledgment 196References 1967 Azide–Alkyne Click Reaction in Polymer Science 203Joydeb Mandal and S. Ramakrishnan7.1 Introduction 2037.2 Linear, Dendritic, and Hyperbranched Polymers 2057.3 Telechelic and Block Copolymers 2207.4 Star and Star-Block Polymers 2267.5 Cyclic Polymers 2307.6 Side-Chain Clickable Polymers 2357.7 Cross-linked Polymeric Systems 2387.8 Porous Organic Polymers 2427.9 Surface Modification using CuAAC Reaction 2447.10 Strain-Promoted Click Reaction 2477.11 Topochemical Azide–Alkyne Cycloaddition (TAAC) Reactions 2497.12 Summary and Outlook 251References 2518 Thiol-Based “Click” Chemistry for Macromolecular Architecture Design 255Weidong Zhang, Kui Chen, and Gaojian Chen8.1 Introduction 2558.2 Thiol Chemistry for Macromolecular Architecture Design 2568.2.1 Linear Polymers 2568.2.2 Graft and Comb Polymers 2588.2.3 Star Polymers 2618.2.4 Cyclic Polymers 2638.2.5 Dendritic and Hyperbranched Polymers 2658.2.6 Conjugated and Hybrid Polymers 2708.3 Conclusion 276Acknowledgments 284References 2849 Synthesis of Macrocycles and Click Chemistry 287Dario Pasini9.1 Introduction 2879.1.1 Peptide- and Sugar-Containing Click Macrocycles 2899.1.2 Click Macrocycles for Anion Binding and Supramolecular Recognition 2979.1.3 Clicking Macrocycles to form Mechanical Bonds 3009.1.4 Cyclic Polymers Obtained by the CuAAC Click Reaction 3029.2 Summary and Conclusions 304References 30410 Modifications of Nucleosides, Nucleotides, and Nucleic Acids using Huisgen’s [3+2] Azide–Alkyne Cycloaddition: Opening Pandora’s Box 309Franck Amblard, Ozkan Sari, Sebastien Boucle, Ahmed Khalil, and Raymond F. Schinazi10.1 Introduction 30910.1.1 Nucleoside Modifications 30910.1.1.1 Nucleoside Analogs as Potential Drugs 30910.1.1.2 Nucleoside Bioconjugates 31110.2 Nucleotide and Nucleic Acid Modifications 31610.2.1 “Artificial” DNA 31610.2.2 Presynthetic Modification DNA 31610.2.3 Postsynthetic Modification 31810.3 Conclusion 331Acknowledgments 332References 332Index 337