List of Contributors ................................... XXIII
Introduction ............................................ XXXV
1 Diversity-Oriented Syntheses of Natural Products and
Natural Product-Like Compounds ............................. 1
Ling-Min Xu, Yu-Fan Liang, Qin-Da Ye, and Zhen Yang
1.1 Introduction ............................................... 1
1.2 Diversity-Oriented Synthesis (DOS) ......................... 2
1.2.1 Diversity-Oriented Synthesis of Skeletally and
Stereochemically Diverse Small Molecules [10a] ...... 3
1.2.2 Biomimetic Diversity-Oriented Synthesis of
Galanthamine-Like Molecules ......................... 3
1.3 Diverted Total Synthesis (DTS) ............................. 7
1.3.1 Diverted Total Synthesis of the Migrastatins ........ 7
1.4 Function-Oriented Synthesis (FOS) .......................... 9
1.4.1 Syntheses of Novel and Highly Potent Analogs of
Bryostatin ......................................... 10
1.4.2 Discovery of Potent and Practical Antiangiogenic
Agents Inspired by Cortistatin A ................... 11
1.5 Target-Oriented Synthesis (TOS) ........................... 11
1.5.1 Synthetic Studies and Biological Evaluation of
Ecteinascidin 743 .................................. 13
1.5.2 Total Synthesis and Biological Evaluation of
Biyouyanagin A and Analogs ......................... 15
1.5.3 Total Synthesis of Vindoline, Related Natural
Products, and Structural Analogs ................... 18
1.5.4 Total Synthesis of Eudesmane Terpenes by Site-
Selective C-H Oxidations ........................... 19
1.5.5 Total Synthesis of Bipinnatin J, Rubifolide, and
Coralloidolides А, В, C, and E ..................... 21
1.5.6 Total Synthesis of Diverse Carbogenic Complexity
Within the Resveratrol Class from a Common
Building Block ..................................... 23
1.6 Conclusion and Perspectives ............................... 24
Acknowledgments ........................................... 26
References ................................................ 26
Commentary Part ........................................... 28
Comment 1 ................................................. 28
Michael Foley
Comment 2 ................................................. 29
Scott A. Snyder
Comment 3 ................................................. 30
Da-Wei Ma
Authors' Response to the Commentaries ..................... 31
References ................................................ 31
2 Total Synthesis of Natural Products and the Synergy with
Synthetic Methodology ..................................... 33
Qian Wang and Jie-Ping Zhu
2.1 Introduction .............................................. 33
2.2 Domino Process ............................................ 36
2.2.1 Introduction ....................................... 36
2.2.2 Total Synthesis of Hirsutellone В .................. 36
2.2.3 Total Synthesis of (±)-Minfiensine,
(-)-Phalarine, and Aspidophytine ................... 40
2.3 Multicomponent Reactions .................................. 43
2.3.1 Introduction ....................................... 43
2.3.2 Total Synthesis of (-)-Spirotryprostatin В ......... 46
2.3.3 Total Synthesis of Hirsutine ....................... 50
2.4 Oxidative Anion Coupling .................................. 52
2.4.1 Direct Coupling of Indole with Enolate, Total
Synthesis of Hapalindoles, Fischerindoles, and
Welwitindolinones .................................. 52
2.4.2 Total Synthesis of (±)- and (-)-Actinophyllic
Acid ............................................... 54
2.4.3 Total Synthesis of (-)-Communesin F ................ 56
2.5 Pattern Recognition ....................................... 60
2.5.1 Introduction ....................................... 60
2.5.2 Total Synthesis of (±)-Aplykurodinone-1 ............ 60
2.5.3 Total Synthesis of (±)-Vinigrol .................... 63
2.6 Conformation-Directed Cyclization ......................... 65
2.6.1 Introduction ....................................... 65
2.6.2 Cyclosporin and Ramoplanin A2 ...................... 65
2.7 Conclusion and Perspectives ............................... 69
Acknowledgments ........................................... 70
References ................................................ 70
Commentary Part ........................................... 72
Comment 1 ................................................. 72
Kyriacos C. Nicolaou
Comment 2 ................................................. 73
Henry N.C. Wong
Comment 3 ................................................. 75
Wei-Dong Li
References ................................................ 77
3 Interplay Between the Chemical Space and the Biological
Space ..................................................... 81
Ren-Xiao Wang
3.1 Chemical Biology: Historical and Philosophical Aspects .... 81
3.1.1 The Chemical Space and the Biological Space ........ 81
3.1.2 Historical Aspects of Chemical Biology ............. 83
3.1.3 Scope of Today's Chemical Biology .................. 85
3.1.4 Forward Chemical Genetics .......................... 88
3.2 Preparation of Chemical Libraries ......................... 90
3.2.1 Natural Product-Inspired Synthesis ................. 90
3.2.2 Diversity-Oriented Synthesis ....................... 92
3.2.3 Available Chemical Libraries ....................... 93
3.3 Screening Strategies ...................................... 95
3.3.1 Phenotypic Assays .................................. 95
3.3.2 Binding Assays ..................................... 96
3.3.3 Challenges in Screening ........................... 100
3.3.4 Data Management and Informatics Analysis .......... 102
3.3.5 Chemical Approaches to Stem Cell Biology .......... 103
3.4 Target Elucidation and Validation ........................ 106
3.4.1 Strategies Employing Affinity Reagents ............ 106
3.4.1.1 Methods Employing Affinity
Chromatography ........................... 106
3.4.1.2 Methods Employing Biotinylated Probes .... 108
3.4.1.3 Methods Employing Radiolabeled/
Fluorescent and Photoaffinity Probes ..... 110
3.4.2 Hypothesis-Driven Approaches ...................... 112
3.4.3 Genetics-Based Approach ........................... 114
3.5 Conclusion and Perspectives .............................. 116
References ............................................... 117
Commentary Part .......................................... 121
Comment 1 ................................................ 121
Ke Ding
Comment 2 ................................................ 121
Li-He Zhang
Comment 3 ................................................ 122
Jun-Ying Yuan
Author's Response to the Commentaries .................... 122
References ............................................... 123
4 Biosynthesis of Pharmaceutical Natural Products and
Their Pathway Engineering ................................ 125
Michael J. Smanski, Xu-Dong Qu, Wen Liu, and Ben Shen
4.1 Introduction ............................................. 125
4.2 Expanded Paradigms in Biosynthetic Logic ................. 126
4.2.1 Thio-Template Biosynthesis ........................ 126
4.2.1.1 Archetypical PKS Paradigms ............... 126
4.2.1.2 Modular Type I PKSs and Their Broken
Colinearity Rule ......................... 129
4.2.1.3 New Enzymology Complementing the
Established Type I PKS Paradigms ......... 129
4.2.1.4 Iterative Type I PKSs in Bacteria ........ 134
4.2.1.5 ACP-Independent, Noniterative Type II
PKSs ..................................... 138
4.2.1.6 Archetypical NRPS Paradigms .............. 139
4.2.1.7 Atypical NRPS Paradigms .................. 139
4.2.1.8 Hybrid NRPS-PKS Paradigms ................ 141
4.2.2 Ribosomal Paradigms of Peptide NPs ................ 143
4.2.3 New Strategies for Peptide-Amide Bond Formation ... 146
4.3 New Approaches to NP Biosynthesis Research ............... 147
4.3.1 Comparative Gene Cluster Analyses Facilitate
Biochemical Characterization ...................... 148
4.3.2 Unique Combinatorial Strategies for Different
Pathways .......................................... 151
4.3.3 Synthetic Metagenomics for Improved Methyl
Halide Production ................................. 155
4.4 Better Understanding of the Scope and Diversity of NP
Production ............................................... 156
4.4.1 Genome Sequencing, Scanning, and Screening for
Chemical Potential ................................ 157
4.4.2 Genome Mining for Terpene Biosynthesis ............ 160
4.4.3 Genomisotopic Approach for Orphan Gene Clusters ... 162
4.4.4 Awakening Cryptic Gene Clusters through Global
Regulators ........................................ 163
4.4.5 Activation of NP Pathways Through Mixed
Culturing ......................................... 164
4.4.6 Heterologous Production ........................... 165
4.5 Future Perspectives ...................................... 168
Acknowledgments .......................................... 170
Abbreviations ............................................ 171
References ............................................... 171
Commentary Part .......................................... 178
Comment 1 ................................................ 178
Yi Tang
Comment 2 ................................................ 178
Yi Yu and Zi-Xin Deng
Authors' Response to the Commentaries .................... 179
Response to Yi Tang ...................................... 179
Response to Yi Yu and Zixin Deng ......................... 179
5 Carbohydrate Synthesis Towards Clycobiology .............. 181
Biao Yu and Lai-Xi Wang
5.1 Introduction ............................................. 181
5.2 Advances in Chemical Glycosylation ....................... 182
5.2.1 New Glycosyl Donors with Novel Leaving Groups ..... 183
5.2.1.1 Glycosylation with PTFAI Donors .......... 183
5.2.1.2 Glycosylation with 2'-Carboxybenzyl
Glycosides (CB Donors) ................... 184
5.2.1.3 Glycosylation with Glycosyl
o-Alkynylbenzoates ....................... 184
5.2.2 New Methods for Controlling the Stereochemistry
in Glycosylation .................................. 186
5.3 New Strategies in Oligosaccharide Assembly ............... 189
5.3.1 Automated Oligosaccharide Synthesis ............... 189
5.3.2 One-Pot Sequential Glycosylations ................. 192
5.4 Enzymatic and Chemoenzymatic Methods ..................... 193
5.5 Synthesis of Heparin and Heparan Sulfate
Oligosaccharides ......................................... 195
5.5.1 Chemical Synthesis of Heparin Oligosaccharides .... 196
5.5.2 Enzymatic Synthesis of Heparin Oligosaccharides ... 198
5.6 Synthesis of Homogeneous Glycoproteins ................... 200
5.6.1 Convergent Glycopeptide Synthesis Coupled with
Native Chemical Ligation .......................... 200
5.6.2 Site-Selective Glycosylation via a Protein "Tag
and Modify" Strategy .............................. 202
5.6.3 Chemoenzymatic Glycosylation Remodeling of
Glycoproteins ..................................... 204
5.7 Synthesis of Carbohydrate-Containing Complex Natural
Compounds ................................................ 206
5.7.1 Total Synthesis of Carbohydrate Immune-Adjuvant
QS-21Aapi ......................................... 208
5.7.2 Total Synthesis of Lobatoside E ................... 208
5.7.3 Total Synthesis of Moenomycin A ................... 208
5.7.4 Total Synthesis of Lipoteichoic Acid .............. 210
5.8 Conclusion and Perspectives .............................. 212
Acknowledgments .......................................... 212
References ............................................... 212
Commentary Part .......................................... 218
Comment 1 ................................................ 218
Sam Danishefsky
Comment 2 ................................................ 218
David Crich
Authors' Response to the Commentaries .................... 219
References ............................................... 219
6 Chemical Synthesis of Proteins ........................... 221
Lei Liu
6.1 Introduction ............................................. 221
6.2 Brief History ............................................ 222
6.2.1 The Beginning ..................................... 222
6.2.2 Synthesis of Small Peptides ....................... 222
6.2.3 Total Synthesis of Insulin ........................ 223
6.2.4 Solid-Phase Peptide Synthesis ..................... 224
6.2.5 Chemical Ligation ................................. 224
6.2.6 Expressed Protein Ligation ........................ 226
6.3 Current Technology ....................................... 227
6.3.1 General Protocol .................................. 227
6.3.2 Thioester Synthesis ............................... 228
6.3.3 Overcome the Cys Limitation ....................... 231
6.3.4 Multiple Fragment Condensation .................... 232
6.3.5 An Illustrative Example ........................... 235
6.4 Applications ............................................. 236
6.4.1 Biophysics and Structural Biology ................. 236
6.4.2 Post-Translational Modifications .................. 237
6.4.3 Protein Probes .................................... 239
6.4.4 Protein Biopharmaceuticals ........................ 240
6.5 Conclusion and Perspectives ......................... 242
References ............................................... 242
Commentary Part .......................................... 244
Comment 1 ................................................ 244
Sam Danishefsky
Comment 2 ................................................ 244
David Crich
References ............................................... 245
7 CuAAC: the Quintessential Click Reaction ................. 247
Valery V. Fokin
7.1 Introduction ............................................. 247
7.2 Azide-Alkyne Cycloaddition: the Basics ................... 249
7.3 CuAAC: Catalysts and Ligands ............................. 251
7.4 Mechanistic Aspects of the CuAAC ......................... 258
7.5 Reactions of 1-Iodoalkynes ............................... 264
7.6 Examples of Application of the CuAAC Reaction ............ 266
7.6.1 Synthesis of Compound Libraries for Biological
Screening ......................................... 266
7.6.2 Copper-Binding Adhesives .......................... 268
7.7 Reactions of Sulfonyl Azides ............................. 269
7.7.1 1-Sulfonyl Triazoles: Convenient Precursors of
Azavinyl Carbenes ................................. 271
7.8 Outlook/Perspective ...................................... 273
Acknowledgments .......................................... 273
References ............................................... 273
Commentary Part .......................................... 276
Comment 1 ................................................ 276
Krzysztof Matyjaszewski
References ............................................... 276
8 Transition Metal-Catalyzed C-H Functionalization:
Synthetically Enabling Reactions for Building Molecular
Complexity ............................................... 279
Keary M. Engle and Jin-Quan Yu
8.1 Introduction ............................................. 279
8.2 Background and Early Work ................................ 281
8.2.1 The Challenges of Functionalizing C-H Bonds ....... 281
8.2.2 Mechanisms of C-H Cleavage by Transition Metals ... 282
8.2.3 Early Work in Metal-Mediated C(Aryl)-H Cleavage ... 285
8.2.4 С(aryl)-H Functionalization via Cyclometallation .. 288
8.2.5 Early Investigations of C(sp3)-H Cleavage ......... 289
8.3 First Functionalization: Challenges in Hydrocarbon
Chemistry ................................................ 293
8.3.1 Selective Functionlization of Methane and Higher
n-Alkanes ......................................... 294
8.3.2 Alkane Dehydrogenation ............................ 297
8.3.3 Alkane Metathesis ................................. 298
8.4 Further Functionalization: C-H Bonds as Reaction
Partners in Organic Synthesis ............................ 300
8.4.1 Philosophy ........................................ 300
8.4.2 Steroid Functionalization Using Free Radical
Chemistry ......................................... 301
8.4.3 Building Molecular Complexity Using Transition
Metal-Mediated Reactions .......................... 303
8.5 Catalytic C-H Functionalization via Metal Insertion ...... 303
8.6 Other Emerging Metal-Catalyzed Further
Functionalization Methods ................................ 311
8.6.1 Biomimetic C-H Oxidation Methods .................. 312
8.6.2 Metallocarbenoid Insertion ........................ 315
8.6.3 Metallonitrenoid Insertion ........................ 318
8.7 Outlook and Conclusion ................................... 321
Acknowledgments .......................................... 322
Abbreviations ............................................ 322
References ............................................... 323
Commentary Part .......................................... 328
Comment 1 ................................................ 328
Huw M.L. Davits
Comment 2 ................................................ 329
Zhenfeng Xi
Comment 3 ................................................ 330
Shu-Li You
Comment 4 ................................................ 332
Zhang-Jie Shi
Authors' Response to the Commentaries .................... 333
References ............................................... 333
9 An Overview of Recent Developments in Metal-Catalyzed
Asymmetric Transformations ............................... 335
Christian A. Sandoval and Ryoji Noyori
9.1 Introduction ............................................. 335
9.2 Asymmetrie Carbon-Carbon Bond Formation .................. 336
9.2.1 Asymmetric Hydroformylations ...................... 336
9.2.2 Asymmetric Additions Involving Carbon
Nucleophiles ...................................... 337
9.2.2.1 Direct Aldol and Aldol Type .............. 338
9.2.2.2 1,2-Additions ............................ 339
9.2.2.3 1,4-Additions ............................ 340
9.2.3 Cycloadditions .................................... 341
9.2.3.1 Cyclopropanation ......................... 341
9.2.3.2 Diels-Alder Reaction ..................... 342
9.2.3.3 Other Addition Reaction .................. 343
9.2.4 Allylic Alkylations ............................... 344
9.2.5 Asymmetric Catalysis Involving Coupling
Processes ......................................... 345
9.2.6 Asymmetric Catalysis Involving Metathesis ......... 348
9.3 Asymmetric Reductions and Oxidations ..................... 348
9.3.1 Asymmetric Reductions ............................. 348
9.3.1.1 Asymmetric Hydrogenation (AH) ............ 348
9.3.1.2 Asymmetric Transfer Hydrogenation ........ 350
9.3.1.3 Other Asymmetric Reductions .............. 351
9.3.2 Asymmetric Oxidations ............................. 351
9.3.2.1 Asymmetric Oxidation ..................... 351
9.3.2.2 Asymmetric Epoxidation ................... 351
9.3.2.3 Asymmetric Amination and Halogenation .... 351
9.4 Conclusion ............................................... 353
References ............................................... 353
Commentary Part .......................................... 363
Comment 1 ................................................ 363
Qi-Lin Zhou
Comment 2 ................................................ 363
Andreas Pfaltz
Comment 3 ................................................ 365
Xue-Long Hou
Comment 4 ................................................ 365
Hisashi Yamamoto
References ............................................... 366
10 The Proline-Catalyzed Mannich Reaction and the Advent
of Enami Catalysis ....................................... 367
Benjamin List and Sai-Hu Liao
10.1 Introduction ............................................. 367
10.2 The Proline-Catalyzed Mannich Reaction ................... 367
10.3 Conclusion ............................................... 374
References ............................................... 374
Commentary Part .......................................... 375
Comment 1 ................................................ 375
Seiji Shirakawa and Keiji Maruoka
Comment 2 ................................................ 377
The Early Status of Asymmetric Organocatalysis ........... 377
Liu-Zhu Gong
Milestone in Asymmetric Organocatalysis .................. 378
Enamine Catalysis ........................................ 378
Iminium Catalysis ........................................ 378
Domino Reactions by Amine Catalysis ...................... 378
Hydrogen Bonding Catalysis ............................... 378
Conclusion ............................................... 379
Comment 3 ................................................ 379
Wen-Jing Xiao
References ............................................... 382
11 Recent Topics in Cooperative Catalysis: Asymmetric
Catalysis, Polymerization, Hydrogen Activation, and
Water Splitting .......................................... 385
Motomu Kanai
11.1 Introduction ............................................. 385
11.2 Cooperative Catalysis in Asymmetric Reactions ............ 387
11.2.1 On the Shoulder of Giants in the Twentieth
Century ........................................... 387
11.2.2 Catalyst Higher Order Structure as a Determinant
of Function: Catalytic Enantioselective Strecker
Reaction of Ketimines by Poly-Rare Earth Metal
Complexes ......................................... 389
11.2.3 Cooperative Asymmetric Catalysis Involving the
Anion Binding Concept ............................. 391
11.3 Cooperative Catalysis in Alkene Polymerization ........... 393
11.4 Cooperative Catalysis in Hydrogen Activation/
Generation ............................................... 394
11.4.1 Ligand-Metal Cooperation .......................... 394
11.4.2 Frustrated Lewis Pairs ............................ 396
11.5 Conclusion and Perspectives .............................. 398
References ............................................... 398
Commentary Part .......................................... 401
Comment 1 ................................................ 401
Takao Ikariya
Comment 2 ................................................ 402
Takashi Ooi
Comment 3 ................................................ 405
Kuiling Ding
Comment 4 ................................................ 409
David Milstein
Authors' Response to the Commentaries .................... 410
References ............................................... 411
12 Flourishing Frontiers in Organofluorine Chemistry ........ 413
G.K. Surya Prakash and Fang Wang
12.1 Introduction ............................................. 413
12.2 Synthetic Approaches for the Introduction of Fluorine-
Containing Functionalities and Related Chemistry ......... 415
12.2.1 Novel Fluorinating Reagents and C-F Bond
Formation Reactions ............................... 416
12.2.1.1 Nucleophilic Fluorinations ............... 416
12.2.1.2 Electrophilic Fluorinations .............. 423
12.2.2 Efficient Trifluoroalkylation Reactions ........... 428
12.2.2.1 Nucleophilic Trifluoromethylating
Reagents, Trifluoromethyl-Metal
Reagents, and Related Chemical
Transformations .......................... 429
12.2.2.2 Electrophilic Trifluoromethylating
Reagents and Reactions ................... 433
12.2.2.3 Recent Developments in the Construction
of CF3-C Bonds ........................... 437
12.2.3 Novel Methods for the Introduction of
Difluoromethyl Motifs ............................. 445
12.2.3.1 Nucleophilic Difluoromethyl Building
Blocks and Approaches .................... 445
12.2.3.2 Electrophilic Difluoromethyl Reagents
and Approaches ........................... 451
12.2.4 Catalytic Asymmetric Synthesis of Chiral
Monofluoromethylated Organic Molecules via
Nucleophilic Fluoromethylating Reactions .......... 452
12.3 Conclusion and Perspectives .............................. 459
Acknowledgment ........................................... 460
References ............................................... 460
Commentary Part .......................................... 470
Comment 1 ................................................ 470
David O'Hagan
Comment 2 ................................................ 471
Jinbo Нu
Comment 3 ................................................ 472
Kuiling Ding and Li-Xin Dai
Authors' Response to the Commentaries .................... 472
References ............................................... 473
Addendum ................................................. 473
13 Supramolecular Organic Chemistry: the Foldamer Approach .. 477
Zhan-Ting Li
13.1 Introduction ............................................. 477
13.2 Foldamers: the Background ................................ 479
13.3 Molecular Recognition .................................... 480
13.3.1 m-Phenyleneethynylene Oligomers ................... 480
13.3.2 Naphthalene-Incorporated Ethylene Glycol
Oligomers ......................................... 483
13.3.3 Heterocyclic Oligomers ............................ 484
13.3.4 Cholate Oligomers ................................. 486
13.3.5 Aromatic Hydrazide and Amide Oligomers ............ 487
13.3.5.1 Hydrazide Foldamers ...................... 487
13.3.5.2 Benzamide Foldamers ...................... 488
13.3.5.3 Heteroaromatic Amide Foldamers ........... 490
13.3.5.1 Flexible Arylamide Oligomers ............. 492
13.3.5.5 Modified Arylamide Oligomers:
Molecular Tweezers ....................... 494
13.3.5.6 Reaction Acceleration .................... 497
13.4 Homoduplex ............................................... 497
13.5 Organogels ............................................... 499
13.6 Vesicles ................................................. 501
13.7 Supramolecular Liquid Crystals ........................... 502
13.8 Macrocycles .............................................. 503
13.8.1 Formation of Coordination Bonds ................... 503
13.8.2 Formation of 1,2,3-Triazoles ...................... 503
13.8.3 Formation of Amides ............................... 506
13.8.4 Formation of Reversible Imine and Hydrazone
Bonds ............................................. 508
13.9 Catalysis ................................................ 510
13.9.1 β-Peptides ........................................ 510
13.9.2 Chiral N-Substituted Glycine Peptoids ............. 511
13.9.3 Cholate Oligomers ................................. 512
13.10 Macromolecular Self-Assembly ............................ 514
13.11 Conclusion and Perspectives ............................. 516
Acknowledgments .......................................... 517
References ............................................... 517
Commentary Part .......................................... 520
Comment 1 ................................................ 520
Peter J. Stang
Comment 2 ................................................ 521
Liang Zhao and Mei-Xiang Wang
Introduction ............................................. 521
Macrocyclic Compounds .................................... 522
Cycloparaphenylenes ...................................... 522
Pillar[n]arenes .......................................... 524
Heteracalixaromatics ..................................... 525
Noncovalent Interactions ................................. 527
Quadruple Hydrogen Bonding ............................... 527
Halogen Bonding .......................................... 528
Anion-π Interaction ...................................... 529
Perspectives ............................................. 530
Acknowledgements ......................................... 531
Comment 3 ................................................ 531
Chen-Ho Tung
Author's Response to the Commentaries .................... 532
Reply to Zhao and Wang's Comments ........................ 532
Reply to Tung's Comments ................................. 533
Reply to Stang's Comments ................................ 533
References ............................................... 533
14 Novel Catalysis for Alkene Polymerization Mediated by
Post-Metallocenes: a Gateway to New Polyalkenes .......... 537
Hiromu Kaneyoshi, Haruyuki Makio, and Terunori Fujita
14.1 Introduction ............................................. 537
14.2 Late Transition Metal Complexes .......................... 538
14.2.1 Diimine-Ligated Ni and Pd Complexes ............... 538
14.2.2 Pyridyldiimine-Ligated Fe and Co Complexes ........ 540
14.2.3 Phenoxyimine-Ligated Ni Complexes ................. 542
14.3 Early Transition Metal Complexes ......................... 544
14.3.1 Phenoxyimine-Ligated Group 4 Metal Complexes ...... 544
14.3.1.1 High Activity for Ethylene
Polymerization ........................... 544
14.3.1.2 Wide-Ranging Control over the Molecular
Weight of the PE ......................... 545
14.3.1.3 Living Polymerization Mediated by
Fluorinated Ti-FI Catalysts .............. 546
14.3.1.4 Effect of Catalyst Activator ............. 547
14.3.1.5 Stereospecific Polymerization of
Propylene ................................ 547
14.3.1.6 Copolymerization of Ethylene with
Cyclic Alkenes ........................... 548
14.3.1.7 Selective Production of 1-Hexene by
Ethylene Trimerization ................... 548
14.3.2 Chelating Bis(phenoxy)-Ligated Group 4 Metal
Complexes ......................................... 549
14.3.3 Pyridylamine-Ligated Hf Complexes ................. 551
14.4 Conclusion and Perspectives .............................. 553
Acknowledgment ........................................... 554
References ............................................... 554
Commentary Part .......................................... 555
Comment 1 ................................................ 555
Robert Grubbs
Comment 2 ................................................ 556
Jun Okuda
General .................................................. 556
Early Work on Late Metals ................................ 556
Ligand Design Principles for Post-metallocenes ........... 556
Comment 3 ................................................ 557
Eugene Y.-X. Chen
Authors' Response to the Commentaries .................... 559
References ............................................... 559
15 Chem Is Try Computationally and Experimentally: How
Will Computational Organic Chemistry Impact Organic
Theories, Mechanisms, and Synthesis in the Twenty-First
Century? ................................................. 561
Zhi-Xiang Yu and Yong Liang
15.1 Introduction ............................................. 561
15.2 Developing New Theories, Concepts, and Understandings
for Organic Chemistry .................................... 561
15.2.1 Bifurcations on Potential Energy Surfaces of
Organic Reactions ................................. 563
15.2.2 Computational Prediction of Carbon Tunneling ...... 566
15.2.3 Predictions of Contra-Steric Stereochemistry in
Cyclobutene Ring-Opening Reactions by the Theory
of Torquoselectivity .............................. 568
15.3 Understanding Reaction Mechanisms ........................ 571
15.3.1 Mechanism of Phosphine-Catalyzed [3 + 2]-
Reactions of Allenoates and Electron-Deficient
Alkenes: Discovery of Water-Catalyzed [1, 2]-
Proton Shift ...................................... 574
15.3.2 Mechanism of Metal Carbenoid O-H Insertion into
Water: Why Is a Copper(I) Complex More Competent
Than a Dirhodium(II) Complex in Catalytic
Asymmetric O-H Insertion Reactions? ............... 577
15.3.3 Mechanism of the Nazarov Cyclization of Aryl
Dienyl Ketones: Pronounced Steric Effects of
Substituents ...................................... 580
15.4 Computation-Guided Development of New Catalysts, New
Reactions, and Synthesis Planning for Ideal Synthesis .... 583
15.4.1 Discovery of Catalysts for бтт
Electrocyclizations ............................... 586
15.4.2 Computational Design of a Chiral Organocatalyst
for Asymmetric Anti-Mannich Reactions ............. 588
15.4.3 Computation-Guided Development of Gold-Catalyzed
Cycloisomerizations Proceeding via 1,2-Si
Migrations ........................................ 590
15.4.4 A Computationally Designed Rh (I)-Catalyzed
[(5 + 2) + 1] Cycloaddition for the Synthesis
of Cyclooctenones ................................. 593
15.5 Conclusion ............................................... 595
Acknowledgments .......................................... 597
References ............................................... 597
Commentary Part .......................................... 600
Comment 1 ................................................ 600
K.N. Houk
Comment 2 ................................................ 600
Yun-Dong Wu and Xin-Hao Zhang
References ............................................... 601
16 Case Study of Mechanisms in Synthetic Reactions .......... 603
Ai-Wen Lei and Li-Qun Jin
16.1 Introduction ............................................. 603
16.2 Mechanistic Study of Coupling Reactions .................. 604
16.2.1 Oxidative Addition ................................ 605
16.2.1.1 Influence of Ligands on Oxidative
Addition ................................. 605
16.2.1.2 Oxidative Addition of Haloarenes to
Trialkylphosphine-Pd(0) Complexes ........ 608
16.2.2 Transmetallation .................................. 615
16.2.2.1 General Aspects of the Transmetallation
Step ..................................... 615
16.2.2.2 Investigation of the Transmetallation
Step in Coupling Reactions ............... 617
16.2.3 Reductive Elimination ............................. 624
16.2.3.1 General Aspects of Reductive
Elimination .............................. 624
16.2.3.2 Case Study of the Reductive Elimination
Step of the Oxidative Coupling Reaction .. 626
16.3 Mechanistic Study of Aerobic Oxidation ................... 627
16.3.1 Recent Progress in Aerobic Oxidation .............. 627
16.3.2 Mechanistic Characterization of Aerobic
Oxidation ......................................... 629
16.3.2.1 Kinetic Investigations ................... 629
16.3.2.2 Conclusion ............................... 634
16.4 Conclusion and Perspective ............................... 634
Acknowledgments .......................................... 635
References ............................................... 635
Commentary Part .......................................... 638
Comment 1 ................................................ 638
Xin Mu, Guo-Sheng Liu, and Qi-Long Shen
Comment 2 ................................................ 640
Yoshinori Yamamoto
Authors' Response to the Commentaries .................... 640
References ............................................... 640
17 Organic Materials and Chemistry for Bulk Heterojunction
Solar Cells .............................................. 643
Chun-Hui Duan, Fei Huang, and Yong Cao
17.1 Introduction ............................................. 643
17.2 Molecular Design and Engineering of Donor Materials ...... 645
17.2.1 Molecular Design and Engineering of Conjugated
Polymers .......................................... 645
17.2.1.1 Homopolymers ............................. 645
17.2.1.2 Push-Pull Copolymers ..................... 650
17.2.1.3 Conjugated Polymers with Pendant
Conjugated Side Chains ................... 655
17.2.1.4 Block Conjugated Copolymers .............. 656
17.2.2 Solution-Processed Small-Molecule Donor
Materials ......................................... 660
17.3 Molecular Design and Engineering of Acceptor Materials ... 662
17.3.1 Fullerene-Based Acceptors ......................... 662
17.3.2 Non-Fullerene-Based Acceptors ..................... 669
17.4 Conclusion and Outlook ................................... 671
Acknowledgments .......................................... 671
References ............................................... 671
Commentary Part .......................................... 676
Comment 1 ................................................ 676
Niyazi Serdar Sariciflci
Comment 2 ................................................ 677
Yongfang Li
Comment 3 ................................................ 681
Guillermo C. Bazan
Comment 4 ................................................ 682
Xiong Gong
Authors' Response to the Commentaries .................... 682
References ............................................... 682
18 Catalytic Utilization of Carbon Dioxide: Actual Status
and Perspectives ......................................... 685
Albert Boddien, Felix Gärtner, Christopher Federsel,
Irene Piras, Henrik Junge, Ralf Jackstell, and Matthias
Beller
18.1 Introduction ............................................. 685
18.2 Catalytic Reductions of CO2 to Formic Acid and
Methanol ................................................. 686
18.2.1 Electrochemical CO2 Reduction ..................... 686
18.2.2 Photochemical CO2 Reduction ....................... 689
18.2.3 Catalytic Reduction of CO2 to Methanol ............ 691
18.2.3.1 Heterogeneous Catalysis .................. 692
18.2.3.2 Homogeneous Catalysis .................... 693
18.2.3.3 Enzymatic Approaches ..................... 694
18.2.4 Catalytic Reduction of CO2 to Formic Acid ......... 695
18.2.4.1 Heterogeneous Catalysis .................. 696
18.2.4.2 Homogeneous Catalysis .................... 697
18.3 CO2 as a Cl-Building Block in C-C Coupling Reactions ..... 702
18.4 Catalytic C-0 Bond Formation Utilizing Carbon Dioxide .... 703
18.4.1 Synthesis of Linear Carbonates .................... 704
18.4.2 Synthesis of Cyclic Carbonates .................... 707
18.5 Current Industrial Processes Using CO2 ................... 710
18.5.1 Urea .............................................. 711
18.5.2 Methanol .......................................... 713
18.5.3 Carboxylic Acids .................................. 713
18.5.4 Carbonates ........................................ 714
18.6 Conclusion and Outlook ................................... 715
References ............................................... 716
Commentary Part .......................................... 722
Comment 1 ................................................ 722
Gábor Laurenczy
Comment 2 ................................................ 723
Min Shi
References ............................................... 724
19 Synthetic Chemistry with an Eye on Future
Sustainability ........................................... 725
Guo-Jun Deng and Chaojun Li
19.1 Introduction ............................................. 725
19.1.1 Chemical Feedstocks ............................... 726
19.1.2 Green Solvents .................................... 727
19.1.3 Reactions ......................................... 728
19.2 Cross-Dehydrogenative Coupling ........................... 729
19.2.1 CDC Reaction of the α-C-H Bond of Nitrogen in
Amines ............................................ 730
19.2.1.1 Alkynylation (sp3-sp Coupling) ........... 730
19.2.1.2 Arylation (sp3-sp2 Coupling) ............. 732
19.2.1.3 Alkylation(sp3-sp3) ...................... 732
19.2.2 CDC Reaction of α-C-H Bond of Oxygen in Ethers
(sp3-sp3) ......................................... 734
19.2.3 CDC Reaction of Allylic and Benzylic C-H Bonds .... 735
19.2.3.1 Allylic Alkylation (sp3-sp3) ............. 735
19.2.3.2 Benzylic Alkynylation (sp3-sp) ........... 736
19.2.3.3 Benzylic Alkylation (sp3-sp3) ............ 736
19.2.4 CDC Reaction of Alkane C-H Bonds .................. 737
19.2.4.1 Alkane Alkylation (sp3-sp3) .............. 737
19.2.4.2 Alkane Arylation (sp3-sp2) ............... 737
19.2.5 CDC Reaction of Aryl C-H Bonds .................... 739
19.3 Nucleophilic Addition of Terminal Alkynes in Water ....... 741
19.3.1 Direct Nucleophilic Addition of Terminal
Alkynes to Aldehydes .............................. 741
19.3.2 Direct Addition of Terminal Alkynes to Ketones
in Water .......................................... 743
19.3.3 Addition of Terminal Alkynes to Imines,
Tosylimines, Iminium Ions, and Acyliminium Ions ... 744
19.3.3.1 Imines ................................... 744
19.3.3.2 Iminium Ions ............................. 744
19.3.3.3 Acylimine and Acyliminium Ions ........... 747
19.3.3.4 Multiple and Tandem Addition of
Terminal Alkynes to C=N Bonds ............ 747
19.3.4 Direct Conjugate Addition of Terminal Alkynes
in Water .......................................... 748
19.4 Conclusion and Perspectives .............................. 749
Acknowledgments .......................................... 750
References ............................................... 750
Commentary Part .......................................... 754
Comment 1 ................................................ 754
Roger A. Sheldon
Comment 2 ................................................ 756
Таk Hang Chan
References ............................................... 758
20 Organic л-Conjugated Molecules for Organic
Semiconductors and Photovoltaic Materials ................ 759
De-Qing Zhang, Xiao-Wei Zhan, Zhao-Hui Wang, Jian Pei,
Guan-Xin Zhang, and Dao-Ben Zhu
20.1 Introduction ............................................. 759
20.2 Conjugated Molecules for p-Type Organic Semiconductors ... 760
20.3 Conjugated Molecules for n-Type Organic Semiconductors ... 766
20.4 Conjugated Molecules for Photovoltaic Materials .......... 769
20.5 Conclusion and Outlook ................................... 773
References ............................................... 774
20.1 Commentary Part I ........................................ 777
Comment 1 ................................................ 777
Seth R. Marder
Comment 2 ................................................ 777
Tien Yau Luh
Authors' Response to the Commentaries .................... 779
References ............................................... 779
21 The Future of Organic Chemistry-an Essay ................. 781
Ronald Breslow
21.1 Introduction ............................................. 781
21.2 The Field of Organic Chemistry Will Broaden .............. 781
21.2.1 Synthesis ......................................... 781
21.2.2 Reactions Mechanisms and Theory ................... 782
21.2.3 Physical Chemistry ................................ 782
21.2.4 Biology ........................................... 783
21.2.5 Medicinal Chemistry ............................... 783
21.2.6 Multimolecular Systems ............................ 785
21.2.7 Pollution and Toxicity ............................ 787
21.3 Conclusion ............................................... 789
Index .................................................... 791
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