Directed C-H Bond Functionalization

Debabrata Maiti is Professor and Institute Chair in the Department of Chemistry, IIT Bombay, India. His research interests are focused on the development of new and sustainable synthetic and catalytic methodologies. He is an Associate Editor for the Journal of Organic Chemistry (ACS). Supriya Rej is a Ramanujan faculty in the Department of Chemistry at IIT Dharwad, India. His current research focuses on bond activation and synthetic methodology development.

• Preface xiii1 History of Directed C—H Bond Activation and its Discovery 1Susmita Mondal, Sumit Ghosh, Asim Kumar Ghosh, and Alakananda Hajra1.1 Introduction 11.2 Importance of C—H Activation 21.3 Early Discoveries in Stoichiometric Metal-promoted Proximal C—H Bond Functionalization 31.4 Directing Group-assisted Catalytic Proximal C—H Bond Functionalization 31.4.1 In-built Functional-Group-directed Proximal C—H Bond Functionalization 31.4.2 Removable Directing Group-assisted Proximal C—H Bond Functionalization 111.4.2.1 Pre-installed and Post-removable Directing Groups-assisted C—H Bond Activation 111.4.2.2 Traceless Directing Group-assisted C—H Bond Functionalization 131.4.2.3 Transient Directing Group (TDG)-assisted C—H Bond Activation 151.5 Directed Distal C—H Bond Functionalization 171.5.1 meta-C—H Bond Functionalization 171.5.2 para-C—H Bond Functionalization 201.5.3 Remote C—H Functionalization 241.6 Conclusions 28Acknowledgments 29References 292 Pd-catalyzed In-built Functional Group-directed C—H Functionalization 37Ananya Dutta and Masilamani Jeganmohan2.1 Introduction 372.2 In-built Nitrogen Atom in a Heterocycle as the Efficient Directing Group 392.3 Aliphatic Amines as the In-built Functional Group 392.3.1 Pd-catalyzed Amine-directed Intramolecular C(sp3)—H Amination 402.3.2 Pd-catalyzed In-built Amine-directed C—H Arylation 402.3.3 Pd-catalyzed Amine-directed C—H Acetoxylation 442.3.4 Pd-catalyzed Amine-directed Alkenylation Reaction 452.3.5 Amine Group-directed Carbonylation Reactions 472.4 Carboxylic Acids as the In-built Functional Group in C—H Activation 482.4.1 Pd-catalyzed C(sp2)—H Bond Functionalization of Benzoic and Phenyl Acetic Acids 502.4.1.1 Pd-catalyzed Carboxylate Group-directed C(sp2)—H Bond Arylation of Benzoic Acids 502.4.1.2 Pd-catalyzed Carboxylate Group-directed Benzolactone and Isocoumarin Formation Using Benzoic Acids 502.4.1.3 Pd-catalyzed Carboxylate-assisted Halogenation, Amidation, Carboxylation, and Acylation Reaction of Benzoic Acids 532.4.1.4 Pd-catalyzed Carboxylate-assisted C(sp2)—H Bond Arylation of Phenyl Acetic Acids 552.4.1.5 Ligand-assisted Pd-catalyzed Olefination of Substituted Phenyl Acetic Acids 572.4.1.6 Pd-catalyzed ortho-C(sp2)—H Functionalizations of Phenyl Acetic Acids 572.4.2 Benzylic C(sp3)—H Activation of Carboxylate Directing Group 602.4.2.1 External ligand-assisted Benzylic C(sp3)—H Activation of Carboxylate Motifs 602.4.3 Pd-catalyzed C(sp3)—H Activation of Aliphatic Acids Assisted by In-built Carboxylate Group 612.4.3.1 Pd-catalyzed Carboxylate-assisted Arylation of Proximal Aliphatic C(sp3)—H Bonds 612.4.3.2 Pd-catalyzed External Ligand-assisted Lactonization of Proximal C(sp3)—H Bonds 632.4.3.3 Pd-catalyzed Carboxylate-assisted β-C(sp3)—H Acetoxylation 632.4.3.4 Pd-catalyzed β-C(sp3)—H Alkynylation and Deuteration of Free Carboxylic Acids 652.4.3.5 Pd-catalyzed Ligand-assisted Distal C(sp3)—H Bond Arylation 662.4.3.6 Pd-catalyzed Ligand-assisted Distal C(sp3)—H Bond Lactonization 662.4.3.7 Pd-catalyzed Enantioselective Carboxylate-directed C(sp3)—H Activation 682.5 Aldehyde as the In-built Functional Group in C—H Activation 692.5.1 Pd-catalyzed C(sp2)—H Functionalization of Free Aldehydes 712.6 Sulfonic Acid as the In-built Functional Group in C—H Activation 712.6.1 Pd-catalyzed C(sp2)—H Functionalization of Free Sulfonic Acids 712.7 Alcohols as the In-built Functional Group in C—H Activation 722.7.1 Phenethyl Alcohol as the In-built Functional Group 722.7.2 Phenol as the In-built Functional Group 732.7.3 Hydroxyl Moiety of Salicylaldehyde as the In-built Functional Group 742.7.4 Miscellaneous Examples of Free Alcohol as the In-built Functional Group 742.8 Conclusion 75References 763 Traceless Directing Group in C—H Bond Functionalization 85Shuvojit Haldar and Debasis Banerjee3.1 Introduction 853.2 Classification of the Traceless Groups 873.3 Carbonyl Group as a Traceless Directing Group 873.3.1 Carboxylic Acid as a Traceless Directing Group for Various Organic Transformations 873.3.1.1 Carboxylic Acid as a Traceless Directing Group Toward Biaryl Synthesis 873.3.1.2 Carboxylic Acid as a Traceless Directing Group: Alkylation of Indole 903.3.1.3 Carboxylic Acid as a Traceless Directing Group in Alkylation/Alkenylation 933.3.2 Aldehyde and Ketone as a Traceless Directing Group 953.3.3 Ester as a Traceless Directing Group 963.3.4 Amide as a Traceless Directing Group 963.3.5 CO2 as a Traceless Directing Group in C—H Bond Activation 973.3.6 tert-Butoxycarbonyl (BOC) Group as a Traceless Directing Group 973.4 Nitrogen-containing Functional Groups as a Traceless Directing Group 983.4.1 Amine as a Traceless Directing Group 983.4.2 Hydrazone as a Traceless Directing Group 993.4.3 N–O Group as a Traceless Directing Group 1003.4.4 Alkene-tethered Aldoxime as a Traceless Directing Group 1013.5 Miscellaneous Groups as a Traceless Directing Group 1023.5.1 ((Pinacolato)boron (Bpin)) Group as a Traceless Directing Group 1023.5.2 Acetal as a Traceless Directing Group 1023.5.3 Sulfur-based Group as a Traceless Directing Group 1033.5.4 Silicon Group as a Traceless Directing Group 1033.5.5 Halides as a Traceless Directing Group 1043.6 Conclusions 106Acknowledgments 106References 1064 Removable Directing Group in Proximal C—H Functionalization 111Vikash Kumar, Malati Das, Sivakumar Sudharsan, and Parthasarathy Gandeepan4.1 Introduction 1114.2 Removable Directing Groups 1124.2.1 C—H Functionalization of Amino Compounds 1124.2.2 C—H Functionalization of Hydroxyl Compounds 1164.2.3 C—H Functionalization of Aldehyde and Ketone Compounds 1194.2.4 C—H Functionalization of Carboxylic Acids 1234.2.5 C—H Functionalization of Sulfonic Acid 1284.2.6 C—H Functionalization of Heterocycles 1314.2.7 Silicon Tethers for C—H Functionalization 1354.3 Summary and Conclusions 137References 1385 Removable Template-assisted Transition Metal-catalyzed Distal C—H Functionalization 165Ke Yang, Dan Yuan, Faith Herington, and Haibo Ge5.1 Introduction 1655.2 Distal C(sp2)—H Bond Functionalization 1665.2.1 Distal C(sp2)—H Functionalization of Arylalkyl and Aryl Acid Derivatives 1665.2.2 Distal C(sp2)—H Functionalization of Arylalkyl and Aryl Amines 1735.2.3 Distal C(sp2)—H Functionalization of Arylalkyl Alcohols and Phenols 1785.2.4 Distal C(sp2)—H Functionalization of Arylalkyl Silanes 1815.3 Distal C(sp3)—H Bond Functionalization 1845.3.1 γ-C(sp3)—H Bond Functionalization of Carboxylic Acids 1845.3.2 γ-C(sp3)—H Bond Functionalization of Aliphatic Ketones 1905.3.3 δ-C(sp3)—H Bond Functionalization of Aliphatic Amines 1925.4 Conclusions 195Funding 196References 1966 Non-covalent Template-assisted C—H Bond Functionalization 203Yoichiro Kuninobu6.1 Introduction 2036.2 Control of Site Selectivity 2056.2.1 C(sp2)—H Transformations 2056.2.1.1 Controlled by Hydrogen Bond 2056.2.1.2 Controlled by Lewis Acid–Base Interaction 2136.2.1.3 Controlled by Electrostatic Interaction 2186.2.1.4 Controlled by Other Non-covalent Interactions 2216.2.2 C(sp3)—H Transformations 2266.2.2.1 Controlled by Hydrogen Bond 2266.2.2.2 Controlled by Electrostatic Interaction 2286.2.2.3 Controlled by Other Non-covalent Interactions 2306.3 Acceleration of Reactions and Substrate and Functional Group Specificities 2306.4 Summary and Conclusions 235References 2367 Pd/Norbornene (NBE) Cooperative Catalysis in C—H Bond Activation 241Zhibo Yan and Zhe Dong7.1 Introduction 2417.2 The Early Organometallic Study and Reaction Discovery 2427.2.1 The Stoichiometric Organometallic Study 2427.2.2 The Initial Reaction Discovery by Catellani 2467.3 Pd(0)/Pd(II)/Pd(IV) Catalytic Cycle: A Series of Chemoselectivity Puzzle 2487.3.1 The S N -2-type Oxidative Addition vs Concerted Oxidative Addition: Electrophile Scope 2507.3.2 Migratory Insertion vs β-carbon Elimination: Norbornene Modification 2537.4 Palladium(II)-initiated Palladium/Norbornene Catalysis 2547.4.1 N—H Bond-initiate Palladium/Norbornene Catalysis 2557.4.2 C—H Bond-initiated Palladium/Norbornene Catalysis 2587.4.2.1 Directed C—H Bond Activation 2587.4.2.2 Non-directed C—H Bond Activation 2687.5 Summary and Conclusions 271References 2718 Transient Directing Groups in C—H Bond Functionalization 277Tsz-Kan Ma, Hannan M. Seyal, and James A. Bull8.1 Introduction 2778.1.1 The Concept of Transient Directing Groups for C—H Functionalization 2778.1.2 Early Developments Using Stoichiometric Imine to Direct C—H Functionalization 2798.2 Transient C(sp3)—H Functionalization 2828.2.1 C(sp3)—H Functionalization of Aldehydes 2828.2.2 C(sp3)—H Functionalization of Ketones 2878.2.3 C(sp3)—H Functionalization of Amines 2898.3 Transient C(sp2)—H Functionalization 2948.3.1 C(sp2)—H Functionalization of Aldehydes 2948.3.1.1 Palladium Catalysis 2948.3.1.2 Rhodium and Ruthenium Catalysis 2998.3.1.3 Iridium and Cobalt Catalysis 3018.3.1.4 Copper Catalysis 3018.3.2 C(sp2)—H Functionalization of Ketones 3018.3.2.1 Rhodium Catalysis 3018.3.2.2 Rhenium Catalysis 3038.3.2.3 Iridium Catalysis 3048.3.2.4 Palladium Catalysis 3048.3.3 C(sp2)—H Functionalization of Amines 3058.4 Conclusions and Outlook 306References 3079 Redox Reactions in Ru(II)-Catalyzed C—H Activations 315Suman Dana, Suman Ghosh, Mainak Koner, Nityananda Ballav, and Mahiuddin Baidya9.1 Introduction 3159.2 Background and Early Findings 3169.3 Aromatic C—H Bond Activation Through Ru(II/IV)-catalyzed Reactions 3189.4 Standard Ru(II/0)-catalyzed Reactions 3279.5 Aerobic Ru(II/0)-catalyzed Reactions 3349.6 Ru(II)-catalyzed C—H Activations with the Directing Group as the Internal Oxidant 3389.7 Ru(II)-catalyzed meta- and para-C—H Activations with Ru(II/III)-manifold 3429.8 Ru(II)-catalyzed C—H Activations Under Photocatalysis 3499.9 Ru(II)-catalyzed C—H Activations Under Electrocatalysis 3519.10 Conclusion and Future Outlook 355References 35910 Emerging Metal-free Directed C—H Functionalization 373Rahul Bangari and Supriya Rej10.1 Introduction 37310.2 Metal-free Directed Oxidative C—H Functionalization 37410.3 Directed C—N Bond Formation 37510.3.1 C(sp2)—N Bond Formation 37510.3.2 C(sp3)—H Bond Formation 37910.4 Directed C—O Bond Formation 38010.4.1 C(sp2)—O Bond Formation 38010.4.2 C(sp3)—O Bond Formation 38210.5 Directed C—C Bond Formation 38310.6 Directed C—H Borylation 38410.6.1 C(sp2)—H Borylation 38410.6.2 C(sp3)—H Borylation 39010.7 Directed C—H Silylation 39110.8 Summary and Outlook 393Acknowledgments 394References 39411 Directed C(sp3)—H Functionalization in Asymmetric Synthesis 405Floris Buttard, Balu Ramesh, Javid Rzayev, and Tatiana Besset11.1 Introduction 40511.2 Asymmetric Transition Metal-catalyzed C(sp3)—H Bond Activation with Chiral Catalysts 40511.2.1 Palladium Catalysis 40611.2.1.1 Classical Directing Group-directed Asymmetric C(sp3)—H Activation 40611.2.1.2 Transition Metal-catalyzed C(sp3)—H Activation Directed via the Oxidative Addition of Palladium on Aryl Halides or Pseudo Halides 41311.2.1.3 Native Group-directed Asymmetric C(sp3)—H Activation 41611.2.2 Use of Other Transition Metal Catalysts 41811.3 Chiral Transient Directing Groups for Asymmetric Transition Metalcatalyzed C(sp3)—H Activation 42111.4 Supramolecular Assembly-directed Hydrogen Atom Abstractions for Asymmetric C(sp3)—H Bond Functionalization 42311.5 Summary and Conclusions 424References 42512 Photoredox Catalysis in C—H Bond Functionalization 431Sayak Ghosh, James Mortimer, and Patricia Z. Musacchio12.1 Introduction 43112.2 Direct Activation of Substrates via Oxidative SET 43312.3 Oxygen-centered Radicals 43412.3.1 Processes Utilizing Peroxide 43412.3.1.1 Tert-butyl Hydroperoxide (TBHP) as an Oxygen Radical Source 43612.3.1.2 Di-tert-butyl Peroxide (DTBP) as an Oxygen Radical Source 43612.3.1.3 Dicumylperoxide (DCP) and Benzoyl Peroxide (BPO) as an Oxygen Radical Source 43712.3.1.4 Tert-butyl Peroxybenzoate (TBPB) as an Oxygen Radical Source 43712.3.1.5 Persulfate Salts as Oxygen Radical Source 43812.3.2 Processes Using Pyridine N-Oxides and their Derivatives 43812.3.3 Processes Using Carboxylate Radicals 43912.3.4 Processes Utilizing Phosphate Radicals 43912.3.5 Direct and Indirect Use of Alcohols as Precursors 44112.4 Decatungstate Catalysis 44512.4.1 Application to Giese-Type Hydroalkylation and Olefin Addition 44612.4.2 Application to Minisci Alkylation 44712.4.3 Heteroatom Incorporation via Electrophilic Radical Trapping 44712.4.4 Application to Metallaphotoredox Cross-Coupling 44912.4.5 Application to Radical–Polar Crossover 45012.5 Halogen Radicals 45012.6 Thiyl Radicals 45612.7 Nitrogen-centered Radicals 45812.7.1 Processes Utilizing Aminyl Radicals 45812.7.2 Processes Utilizing Iminyl Radicals 46112.7.3 Processes Utilizing Amidyl and Sulfonamidyl Radicals 46112.7.4 Processes Utilizing Nitrogen Radical Cations 46412.7.5 Processes Utilizing Azidyl Radical 46412.8 Carbon-centered Radicals 46612.9 Summary and Conclusions 467References 46713 Dual Transition Metal/Photoredox Catalysis for Directed C(sp2)—H Activations 477Akshay M. Nair and Martin Fañanás-Mastral13.1 Introduction 47713.2 Photocatalysis for Transition Metal Catalyst Reoxidation 47913.3 Photocatalysis for Coupling Partner Activation 49413.4 Summary and Conclusions 502References 50414 Industrial and Flow Application of Directed C—H Bond Functionalization 509Aritra Mukherjee, Rahul Bangari, and Supriya Rej14.1 Introduction 50914.2 Directed C(sp2)—H Functionalization 51014.2.1 Homogeneous Catalysis 51014.2.2 Heterogeneous Catalysis 51614.3 Directed C(sp3)—H Functionalization 51714.4 Summary and Conclusions 518Acknowledgments 520References 52115 Applications of Directed C—H Functionalization in Medicinal and Process Chemistry 525Krishnamay Pal, Rajesh Sahu, and Anant R. Kapdi15.1 Introduction 52515.2 C—H Functionalization in Medicinal Chemistry 52615.2.1 Synthesis of Tie2 Tyrosine Kinase Inhibitor 52615.2.2 Synthesis of Angiotensin II Receptor Blocker 52815.2.3 Synthesis of BRD 3914 52915.2.4 Synthesis of Zafirlukast (Accolate) 53015.2.5 Synthesis of Palomid 529 53115.2.6 Synthesis of Febuxostat 53215.2.7 Synthesis of Tryprostatin A 53315.2.8 Synthesis of Adiphenine 53415.3 C—H Functionalization in Process Chemistry 53515.3.1 Kilogram-Scale Synthesis of Beclabuvir 53515.3.2 Commercial Synthesis of BMS- 911543 53715.3.3 Commercial Synthesis of BMS- 919373 53915.3.4 Multikilogram-Scale Preparation of AZD 4635 54015.3.5 Developed Synthetic Procedure of LSZ 102 54115.3.6 Developed Scalable Process of YLF466D 54315.3.7 Multikilogram-Scale Synthetic Process of Nemiralisib 54415.3.8 Kilogram-Scale Synthetic Process of AZD 4573 54515.4 Conclusion 546References 547Index 553