Solid–Phase Organic Synthesis – Concepts, Strategies and Applications

PATRICK H. TOY , PhD, is an Associate Professor in the Department of Chemistry at the University of Hong Kong, where he was recognized as an Outstanding Young Researcher. Dr. Toy's review of the Mitsunobu reaction is one of the most frequently downloaded articles ever published in Chemistry-An Asian Journal . YULIN LAM , PhD, is an Associate Professor in the Department of Chemistry at the National University of Singapore. Dr. Lam is a reviewer for several major journals and is an Editorial Advisory Board member of ACS Combinatorial Science.

Preface xv Acknowledgments xvii Contributors xix Part I CONCEPTS AND STRATEGIES 1 1 LINKER STRATEGIES IN MODERN SOLID-PHASE ORGANIC SYNTHESIS 3 Peter J. H. Scott 1.1 Introduction 3 1.2 Classical Linker Strategies 5 1.3 Multifunctional Linker Strategies 28 1.4 Conclusions 73 2 COLORIMETRIC TEST FOR SOLID-PHASE ORGANIC SYNTHESIS 83 Yan Teng and Patrick H. Toy 2.1 Introduction 83 2.2 Functional Group Tests 84 2.3 Conclusions 92 3 PRACTICAL ASPECTS OF COMBINATORIAL SOLID-PHASE SYNTHESIS 95 Jan Hlavac, Miroslav Soural, and Viktor Krchnak 3.1 Introduction 95 3.2 Strategies in Combinatorial Solid-Phase Synthesis 101 3.3 Equipment and Instrumentation 112 3.4 Characterization and Purification 118 3.5 Conclusions 121 4 DIVERSITY-ORIENTED SYNTHESIS 131 Kieron M. G. O'Connell, Warren R. J. D Galloway, Brett M. Ibbeson, Albert Isidro-Llobet, Cornelius J. O'Connor, and David R. Spring 4.1 Introduction 131 4.2 Small Molecules and Biology 131 4.3 Diversity-Oriented Synthesis, Target-Oriented Synthesis, and Combinatorial Chemistry 133 4.4 Molecular Diversity 134 4.5 Diversity-Oriented Synthesis on Solid Phase 137 4.6 Diversity-Oriented Synthesis Around Privileged Scaffolds 146 4.7 Diversity Linker Units in Solid-Phase Organic Synthesis 147 4.8 Conclusions 148 5 DIVERSITY-ORIENTED SYNTHESIS OF PRIVILEGED HETEROCYCLES USING DIVERGENT STRATEGY 151 Seung Bum Park and Jonghoon Kim 5.1 Introduction 151 5.2 Divergent Synthesis of Natural Product-Like Polyheterocycles Using a Cyclic Iminium as a Single Key Intermediate 153 5.3 Conclusions 168 6 CHEMO- AND REGIOSELECTIVITY ENHANCEMENT IN SOLID-SUPPORTED REACTIONS 171 Douglas D. Young and Alexander Deiters 6.1 Introduction 171 6.2 Transition Metal-Mediated Solid-Supported Reactions 172 6.3 Non-transition Metal-Mediated Solid-Supported Reactions 186 6.4 Traceless Cleavage 192 6.5 Conclusions 201 Part II Applications 205 7 ASYMMETRIC SYNTHESIS ON SOLID SUPPORT 207 Baburaj Baskar and Kamal Kumar 7.1 Introduction 207 7.2 Asymmetric Chemical Transformations of Solid-Supported Substrates 208 7.3 Asymmetric Transformations Using Resin-Bound Chiral Catalysts and Auxiliaries 219 7.4 Conclusions 227 8 RECENT ADVANCES IN MICROWAVE-ASSISTED SOLID-PHASE SYNTHESIS OF HETEROCYCLES 231 Prasad Appukkuttan, Vaibhav, P. Mehta, and Erik Van der Eycken 8.1 Introduction 231 8.2 Fused 1,3-oxazin-6-ones 232 8.3 Thiazolo[4,5-d]pyrimidine-5,7-diones 233 8.4 Pyrazoles 234 8.5 HSP70 Modulators 234 8.6 Benzimidazo[2,1-b]quinazolin-12(5H)-ones 236 8.7 Imidazoles 237 8.8 1,4-Naphthoquinones 238 8.9 Phthalocyanines 238 8.10 1,2,3,4-Tetrahydroquinolines 242 8.11 1,2,3-Triazoles 243 8.12 2,8-Diaminopurines 244 8.13 Imidazolidin-4-ones 245 8.14 Indoles 247 8.15 1,2,3,4-Tetrahydroquinolines Using a SmI2-Cleavable Linker 248 8.16 Hydantoins 249 8.17 Imatinib 250 8.18 Isoindolines 252 8.19 2-(Benzylthio)imidazo[1,2a]-pyrimidin-5-ones 253 8.20 2-Aminobenzothiazoles 254 8.21 Pyrimidines, Pyrazoles, and Isoxazoles 255 8.22 Quinolin-2(1H)-ones and Coumarins 256 8.23 Benzofurans 257 8.24 i-Condensed Purines 258 8.25 2(1H)-Pyrazinones 259 8.26 Conclusions 260 References 261 9 SOLID-PHASE SYNTHESIS OF HETEROCYCLES FROM PEPTIDES AND AMINO ACIDS 269 Zhi Li, Marc Giulianotti, Wenteng Chen, Richard A. Houghten, and Yongping Yu 9.1 Introduction 269 9.2 Synthesis of Various Heterocycles 269 10 GENERATION OF DRUG-LIKE FIVE-MEMBERED HETEROCYCLIC LIBRARIES USING CARBON DISULFIDE AND MERRIFIELD RESIN 319 Young-Dae Gong and Taeho Lee 10.1 Introduction 319 10.2 Solid-Phase Synthesis of Related Thiazole Compounds 320 10.3 Solid-Phase Synthesis of Benzoxazoles 333 10.4 Solid-Phase Synthesis of Related Pyrazole Compounds and 1,3,4-Triazoles via a Dithiocarbazate Linker 334 10.5 Solid-Phase Synthesis of 1,3,4-Oxadiazoles and 1,3,4-Thiadiazoles via Selective Cyclization 342 10.6 Solid-Phase Synthesis of 1,2,4-Thiadiazoles 347 10.7 Summary 350 11 RECENT ADVANCES IN SOLID-PHASE 1,3-DIPOLAR CYCLOADDITION REACTIONS 355 Kirsi Harju and Jari Yli-Kauhaluoma 11.1 Introduction 355 11.2 Solid-Phase Synthesis of Pyrrolidines, Pyrrolines, and Pyrroles 356 11.3 Synthesis of Pyrazolines and Pyrazoles 361 11.4 Solid-Phase Synthesis of Imidazoles, 1,2,4-Triazoles, and 1,2,3-Triazoles 364 11.5 Solid-Phase Synthesis of Isoxazolidines, Isoxazolines, and Isoxazoles 369 11.6 Conclusions 378 12 SULFONES IN SOLID-PHASE HETEROCYCLE SYNTHESIS 383 Chai Hoon Soh and Yulin Lam 12.1 Introduction 383 12.2 Linkers 384 12.3 Conclusions 411 13 SOLID-PHASE ORGANIC RADIOSYNTHESIS 415 Rapha el Hoareau and Peter J. H. Scott 13.1 Introduction 415 13.2 Solid-Phase Organic Radiosynthesis with Fluorine-18 416 13.3 Solid-Phase Organic Radiosynthesis with Carbon-11 421 13.4 Solid-Phase Organic Radiosynthesis with Other Radioisotopes 422 13.5 Conclusions 424 14 SOLID-PHASE SYNTHESIS OF DYES AND THEIR APPLICATION AS SENSORS AND BIOIMAGING PROBES 427 Marc Vendrell, Hyung-Ho Ha, Sung Chan Lee, and Young-Tae Chang 14.1 Introduction 427 14.2 On-Bead Sensors 428 14.3 Solid-Phase Approaches in Fluorescent Labeling 429 14.4 Solid-Phase Derivatization of Fluorescent Scaffolds 430 14.5 Diversity-Oriented Fluorescent Libraries 433 14.6 Conclusions 437 14.7 Acknowledgments 437 15 DENDRITIC MOLECULES ON SOLID SUPPORT: SOLID-PHASE SYNTHESIS AND APPLICATIONS 441 Kerem Goren and Moshe Portnoy 15.1 Introduction 441 15.2 Synthesis 442 15.3 Applications of Dendronized Supports 464 15.4 Conclusions 480 16 OLIGOSACCHARIDE SYNTHESIS ON SOLID, SOLUBLE POLYMER, AND TAG SUPPORTS 489 Katsunori Tanaka and Koichi Fukase 16.1 Introduction 489 16.2 Solid-Phase Methods for Synthesis of Oligosaccharides 490 16.3 Polymer-Supported and Tag-Assisted Oligosaccharide Synthesis in Solution 516 16.4 Conclusions 526 16.5 Acknowledgments 527 References 527 Index 531