Transition-Metal-Catalyzed C-H Functionalization of Heterocycles, 2 Volumes

Contents List of Contributors xiii 8 Functionalization of Pyridines, Quinolines, and Isoquinolines 357 Jun Zhou and Bing-Feng Shi 8.1 Introduction 357 8.2 C2-Selective Functionalization 358 8.2.1 Alkylation 358 8.2.2 Arylation 361 8.2.2.1 Pyridine Derivatives as Substrates 361 8.2.2.2 Pyridine N-oxides as Substrates 363 8.2.2.3 N-iminopyridinium Ylides as Substrates 365 8.2.3 Alkenylation 365 8.2.4 Acylation, Amination, and Aminomethylation 367 8.3 C3-Selective Functionalization 370 8.3.1 Alkylation 370 8.3.2 Arylation 371 8.3.3 Alkenylation 374 8.3.4 Borylation 377 8.4 C4-Selective Functionalization 378 8.4.1 Alkylation 378 8.4.2 Arylation 380 8.4.3 Alkenylation 381 8.4.4 Borylation 382 8.5 C8-Selective Functionalization 382 8.6 Summary and Conclusions 387 9 Transition Metal-Catalyzed C-H Bond Functionalization of Diazines and Their Benzo Derivatives 393 Christian Bruneau and Rafael Gramage-Doria 9.1 Introduction 393 9.2 Carbon-carbon Bond Formation 394 9.2.1 C-H Bond (Hetero)arylations 394 9.2.2 C–H Bond Olefinations 406 9.2.3 C–H Bond Alkylations 415 9.2.4 C–H Bond Alkynylations 418 9.2.5 C–H Bond Carboxylations 419 9.3 Carbon-nitrogen Bond Formation 420 9.4 Carbon-oxygen Bond Formation 424 9.5 Carbon-sulfur Bond Formation 424 9.6 Carbon-boron Bond Formation 425 9.7 Carbon-silicon Bond Formation 425 9.8 Carbon-halogen Bond Formation 427 9.9 Conclusions 428 Acknowledgments 429 10 Functionalization of Chromenes and Their Derivatives 435 Laura Cunningham, Sundaravel Vivek Kumar, and Patrick J. Guiry 10.1 Introduction 435 10.2 2 H-Chromenes 435 10.3 2 H-Chromene-ones (Coumarins) 437 10.3.1 C3-Selective Functionalization 437 10.3.1.1 Alkenylation 437 10.3.1.2 Arylation 438 10.3.1.3 Other 441 10.3.1.4 Annulation/Cyclization 442 10.3.2 C4–H Selective Functionalization 449 10.3.3 C5-Selective Functionalization 456 10.4 4 H-Chromene 459 10.5 4 H-Chromenones (Chromones) 462 10.5.1 C2-Selective C–H Activation 462 10.5.2 C3-Selective C–H Activation 463 10.5.3 C5-Selective C–H Activation 468 10.5.3.1 Alkenylation 468 10.5.3.2 Alkylation 471 10.5.3.3 (Hetero)arylation 473 10.5.3.4 Amination/Amidation 474 10.5.3.5 Others 477 10.5.4 C6-Selective C–H Activation 478 10.5.5 Conclusions 478 11 Transition Metal-Catalyzed C–H Functionalization of Imidazo-fused Heterocycles 485 Rajeev Sakhuja and Anil Kumar 11.1 Introduction 485 11.2 C–C Bond Formation 486 11.2.1 Alkylation 486 11.2.1.1 Fluoro Alkylation 486 11.2.1.2 Alkoxycarbonyl Alkylation 488 11.2.1.3 Aryl/heteroaryl Alkylation 489 11.2.1.4 Amino Alkylation 493 11.2.1.5 Sulfonyl/Carbonyl/Cyano Alkylation 496 11.2.2 Alkenylation/Alkynylation/Allenylation 498 11.2.3 Cyanation/Carbonylation 503 11.2.4 Arylation/Heteroarylation 509 11.3 C–S/Se Bond Formation 525 11.4 C–N Bond Formation 532 11.5 C–P Bond Formation 533 11.6 C–Si Bond Formation 535 11.7 Conclusions 535 Acknowledgments 536 12 Dehydrogenative Annulation of Heterocycles: Synthesis of Fused Heterocycles 543 Neha Jha and Manmohan Kapur 12.1 Dehydrogenative Coupling: An Overview 543 12.2 Importance of Heterocycles and Their Fused Congeners 545 12.3 Metal-Catalyzed Dehydrogenative-coupling Reactions: Formation of C–Z Bonds 546 12.3.1 C–C Bond Formation 546 12.3.1.1 Synthesis of Large-sized Molecules: COTs 549 12.3.2 Formation of C–N Bonds 550 12.3.3 Formation of C–B Bonds 557 12.4 Conclusions 562 13 C–H Functionalization of Saturated Heterocycles Beyond the C2 Position 567 Amalia-Sofia Piticari, Natalia Larionova, and James A. Bull 13.1 Introduction 567 13.2 Heterocycle Functionalization with a C2 Directing Group 567 13.2.1 Carboxylic Acid-Linked C2 Directing Groups 567 13.2.2 Applications of N-Heterocycle Functionalization with C2 Directing Groups 580 13.3 Heterocycle Functionalization with C3 Directing Groups 586 13.3.1 Carboxylic Acid-Linked C3 Directing Groups 586 13.3.2 Amine-Linked C3 Directing Groups 590 13.3.3 Alcohol-Linked C3 Directing Groups 592 13.4 Heterocycle Functionalization with a C4 Directing Group 594 13.5 Transannular Heterocycle Functionalization with N-linked Directing Groups 598 13.6 Conclusions 603 14 Asymmetric Functionalization of C–H Bonds in Heterocycles 609 Olena Kuleshova and Laurean Ilies 14.1 Introduction 609 14.2 Enantioselective C–H Activation 609 14.2.1 Activation of C(sp2)–H Bonds 609 14.2.2 Activation of C(sp3)–H Bonds 611 14.3 C–H Activation Followed by Enantioselective Functionalization 615 14.3.1 Intramolecular Coupling 615 14.3.1.1 Indoles and Pyrroles as Coupling Partners 615 14.3.1.2 Imidazoles and Benzoimidazoles as Coupling Partners 618 14.3.1.3 Pyridines and Pyridones as Coupling Partners 618 14.3.2 Intermolecular Coupling 619 14.3.2.1 Directing-Group-Free C–H Functionalization 619 14.3.2.2 Functionalization Assisted by a Directing Group at the C3 Site 621 14.3.2.3 Functionalization Assisted by a Directing Group at the N-1 Site 623 14.3.3 Atropo-enantioselective Synthesis of Heterobiaryls 624 14.4 Conclusions and Perspectives 627 15 Transition Metal-Catalyzed C–H Functionalization of Nucleoside Bases 631 Yong Liang and Stanislaw F. Wnuk 15.1 Introduction 631 15.2 Direct Functionalization of the C5-H Bond in Uracil Nucleosides 632 15.2.1 Cross-Dehydrogenative Alkenylation at the C5 Position 632 15.2.2 Direct C–H Arylation at the C5 Position 634 15.2.3 Direct C–H Alkylation at the C5 Position 635 15.2.4 Miscellaneous Direct C–H Functionalizations 636 15.3 Direct Functionalization of C6-H Bond in Uracil 637 15.3.1 Stepwise C6-H Functionalization of Pyrimidine Nucleoside via Lithiation and Alkylation 637 15.3.2 Direct C6-H Functionalization of the Uracil Base 637 15.3.2.1 Functionalization with Aryl Halides 637 15.3.2.2 Cross-Dehydrogenative Functionalization with Arenes 638 15.3.2.3 Functionalization with Aryl Boronic Acid 639 15.3.2.4 Intramolecular C6-H Functionalization of Uracil Derivatives 639 15.4 Inverted C–H Functionalization of Uracil Nucleosides 640 15.4.1 Inverted C5-H Functionalization of Uracil Nucleosides 640 15.4.2 Inverted C6-H Functionalization of Uracil 641 15.5 Direct C2-H Functionalization of Adenosine 641 15.6 Direct C6-H Functionalization of Purine Nucleoside 642 15.6.1 Direct C6-H Alkylation 642 15.6.1.1 With Cycloalkanes 642 15.6.1.2 With Boronic Acid 643 15.6.1.3 With Alkyltrifluoroborate 643 15.6.1.4 With Alkyl Carboxylic Acid 643 15.6.1.5 With tert-Alkyl Oxalate Salts 644 15.6.2 Direct C6-H Arylation 644 15.6.3 Other Direct C6-H Functionalization 645 15.7 Direct Activation of C8-H Bond in Purine and Purine Nucleosides 645 15.7.1 Cross-Coupling of Adenine Nucleosides with Aryl Halides 645 15.7.2 Cross-Coupling of Inosine and Guanine Nucleosides with Aryl Halides 647 15.7.3 Cross-Coupling of Adenine Nucleosides with Alkanes 648 15.7.4 Miscellaneous Functionalization of Adenosine-related Substrates 649 15.8 Conclusions 650 16 C–H Activation for the Synthesis of C1-(hetero)aryl Glycosides 657 Morgane de Robichon, Juba Ghouilem, Angélique Ferry, and Samir Messaoudi 16.1 General Introduction 657 16.2 Classical Methods to Prepare C-aryl Glycosides 657 16.3 Directed C-H Activation Approach 658 16.3.a Directed Csp2-Csp2 Bond Formation 659 16.3.a.1 Directing Group Attached to the Aryl Partner 659 16.3.a.2 Directing Group Attached to the Sugar Nucleus 661 16.3.b Directed Csp2-Csp3 Bond Formation 662 16.3.b.1 The Directing Group (DG) Attached to the Coupling Partner 662 16.3.b.2 The Directing Group Attached to the Sugar Nucleus 675 16.4 Conclusions and Perspectives 679 17 Late-stage C–H Functionalization: Synthesis of Natural Products and Pharmaceuticals 683 Harshita Shet and Anant R. Kapdi 17.1 Introduction 683 17.2 Synthesis of (±)-Ibogamine 684 17.3 Synthesis of YD-3 and YC-1 (C–H Arylation of Indazoles) 685 17.4 Synthesis of Complanadine A 685 17.5 Synthesis of Diptoindonesin G (C–H Arylation of Benzofuran) 686 17.6 Synthesis of Dragmacidin D (C–H Arylation of Indoles at the C3 Position) 687 17.7 Synthesis of Celecoxib (C–H Arylation of Pyrazoles) 688 17.8 Synthesis of Aspidospermidine 689 17.9 Synthesis of Pipercyclobutanamide A 690 17.10 Synthesis of Nigellidine Hydrobromide 691 17.11 Synthesis of (+)-Linoxepin 691 17.12 Synthesis of (±)-Rhazinal 692 17.13 Synthesis of Podophyllotoxin (C–H Arylation) 693 17.14 Synthesis of (±)-Rhazinilam 694 17.15 Synthesis of Aeruginosins (sp3 C–H Alkenylation and Arylation) 694 17.16 Synthesis of Gamendazole 696 17.17 Synthesis of Beclabuvir (BMS-791325) 697 17.18 Conclusions 698 18 Late-stage Functionalization of Pharmaceuticals, Agrochemicals, and Natural Products 703 François Richard, Elias Selmi-Higashi, and Stellios Arseniyadis 18.1 C–H Methylation and Alkylation 704 18.2 C–H Arylation and Olefination 705 18.3 Formation of Other C−C Bonds 711 18.4 C–H Hydroxylation 714 18.5 C–H Amination 715 18.6 C–H Trifluoromethylation 716 18.7 C–H Difluoromethylation 716 18.8 C–H Fluorination 718 18.9 C–H Silylation 718 18.10 C–H Phosphorylation 719 18.11 C–H Deuteration and Tritiation 720 18.12 Conclusions 723 Index 727 Brief Contents Volume 1: List of Contributors xiii Preface xvii 1 Historical Perspective and Mechanistic Aspects of C–H Bond Functionalization 1 Tariq M. Bhatti, Eileen Yasmin, Akshai Kumar, and Alan S. Goldman 2 Recent Advances in C–H Functionalization of Five–Membered Heterocycles with Single Heteroatoms 61 B. Prabagar and Zhuangzhi Shi 3 Functionalization of Five-membered Heterocycles with Two Heteroatoms 109 Jung Min Joo 4 Transition Metal-Catalyzed C–H Functionalization of Indole Benzenoid Ring 155 Vikash Kumar, Rajaram Maayuri, Lusina Mantry, and Parthasarathy Gandeepan 5 Transition Metal-Catalyzed C2 and C3 Functionalization of Indoles 193 Pinki Sihag, Meledath Sudhakaran Keerthana, and Masilamani Jeganmohan 6 C(sp2)–H Functionalization of Indolines at the C7-Position 251 Neeraj Kumar Mishra and In Su Kim 7 Transition Metal-Catalyzed C–H Functionalization of Benzofused Azoles with Two or More Heteroatoms 319 Tanumay Sarkar, Subhradeep Kar, Prabhat Kumar Maharana, Tariq. A. Shah, and Tharmalingam Punniyamurthy Volume 2: List of Contributors xiii 8 Functionalization of Pyridines, Quinolines, and Isoquinolines 357 Jun Zhou and Bing-Feng Shi 9 Transition Metal-Catalyzed C-H Bond Functionalization of Diazines and Their Benzo Derivatives 393 Christian Bruneau and Rafael Gramage-Doria 10 Functionalization of Chromenes and Their Derivatives 435 Laura Cunningham, Sundaravel Vivek Kumar, and Patrick J. Guiry 11 Transition Metal-Catalyzed C–H Functionalization of Imidazo-fused Heterocycles 485 Rajeev Sakhuja and Anil Kumar 12 Dehydrogenative Annulation of Heterocycles: Synthesis of Fused Heterocycles 543 Neha Jha and Manmohan Kapur 13 C–H Functionalization of Saturated Heterocycles Beyond the C2 Position 567 Amalia-Sofia Piticari, Natalia Larionova, and James A. Bull 14 Asymmetric Functionalization of C–H Bonds in Heterocycles 609 Olena Kuleshova and Laurean Ilies 15 Transition Metal-Catalyzed C–H Functionalization of Nucleoside Bases 631 Yong Liang and Stanislaw F. Wnuk 16 C–H Activation for the Synthesis of C1-(hetero)aryl Glycosides 657 Morgane de Robichon, Juba Ghouilem, Angélique Ferry, and Samir Messaoudi 17 Late-stage C–H Functionalization: Synthesis of Natural Products and Pharmaceuticals 683 Harshita Shet and Anant R. Kapdi 18 Late-stage Functionalization of Pharmaceuticals, Agrochemicals, and Natural Products 703 François Richard, Elias Selmi-Higashi, and Stellios Arseniyadis Index 727