Advanced organic chemistry

1176 Pages·2016·39.253 MB·English

by  Lewis, David E

Advanced
Organic Chemistry
David E. Lewis
University of Wisconsin–Eau Claire
New York Oxford
1

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Title: Advanced Organic Chemistry Short / Normal Publishing Services
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contents
Preface ix
chapter one
The Fundamentals Revisited: Structure, Bonding, and Reactivity
1.1 Organic Structure: A Brief History 1
1.2 Proton Transfers Revisited: Acids and Bases 7
1.3 Reactions and Reaction Mechanisms: “Electron Pushing” 13
1.4 Resonance 24
1.5 Spectroscopy and Chromatography 30
Chapter Summary 31
Key Terms 32
Additional Problems 33
chapter two
Stereochemistry
2.1 Stereoisomers and Chirality 37
2.2 Absolute Configuration 46
2.3 Optical Purity and Configuration 57
2.4 Conformation 63
2.5 An Introduction to Asymmetric Synthesis: Asymmetric Induction 67
2.6 How Well Did It Go? Measuring Enantiomer Ratios 77
2.7 Chirality at Atoms Other Than Carbon: Inversion of Pyramidal Centers 78
Chapter Summary 80
Key Terms 81
Additional Problems 81
chapter three
Organic Shorthand: Acronyms and Name Reactions
3.1 Organic Synthesis: A Brief Introduction 87
3.2 Name Reactions: A Historical Overview 87
3.3 Acronyms and Abbreviations 91
chapter four
Orbitals and Reactivity
4.1 Introduction 105
4.2 Atomic Orbitals: The History of the Modern Atomic Model 106
4.3 Covalent Bonding and Molecular Orbitals 111
Chapter Summary 125
Key Terms 126
Additional Problems 126
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iv contents
chapter five
Frontier Orbitals and Chemical Reactions
5.1 Chemical Reactions: Frontier Orbitals 129
5.2 Using Frontier Molecular Orbitals to Categorize Reactions and Reagents 137
5.3 Categorizing Reactions Using Frontier Molecular Orbital Pairings 142
5.4 Stereoelectronic Effects 156
5.5 Radical Reactions 159
Chapter Summary 160
Key Terms 160
Additional Problems 161
chapter six
Organic Reactions I: Pericyclic Reactions and the Conservation
of Orbital Symmetry
6.1 Introduction 163
6.2 π Molecular Orbitals of Conjugated Systems and Orbital Symmetry 165
6.3 Frontier Orbital Analysis: Stereochemical Consequences 167
6.4 Sigmatropic Rearrangements: More Details 170
6.5 Cycloaddition Reactions: More Details 180
6.6 Ene, Retro-Ene, and Similar Reactions 201
6.7 Orbital Correlation Diagrams 206
6.8 Combining Pericyclic Reactions in Sequence 209
Chapter Summary 214
Key Terms 215
Additional Problems 215
chapter seven
Aromaticity: The 150-Year Riddle
7.1 Benzene: The Beginning 221
7.2 Aromaticity and Antiaromaticity: The Hückel Molecular Orbital
Model of Cyclic Polyenes 222
7.3 How Does One Measure Aromaticity? Criteria for Aromaticity
and Its Quantification 233
7.4 Möbius Aromaticity 243
7.5 Homoaromaticity 246
7.6 The Rest of the Story: The History and Mythology of Benzene 250
Chapter Summary 254
Key Terms 254
Additional Problems 254
chapter eight
Physical Organic Chemistry and Reaction Mechanisms
8.1 Introduction 259
8.2 Solvents and Solubility 262
8.3 Reaction Kinetics 270
8.4 Activation Parameters from Kinetic Studies 279
8.5 Correlating Reaction Rates: Linear Free Energy Relationships 280
8.6 Isotope and Element Effects 291
8.7 Trapping and Crossover Experiments 299
8.8 The Variable Transition State and the Concept of the Mechanistic
Spectrum 301
8.9 Using Regiochemistry and Stereochemistry 307
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contents v
8.10 The Reactivity-Selectivity Principle 308
Chapter Summary 309
Key Terms 309
Additional Problems 309
chapter nine
Reactive Intermediates I: Carbocations
9.1 Carbocations 317
9.2 Rearrangements 327
9.3 Neighboring Group Participation 332
9.4 Nonclassical Carbocations 335
9.5 Methods for Generating Carbocations 339
Chapter Summary 342
Key Terms 343
Additional Problems 343
chapter ten
Organic Reactions II: Synthesis Using Carbocations to Form C—C Bonds
10.1 Introduction 347
10.2 The Friedel-Crafts Reactions 348
10.3 Formylation 364
10.4 Addition of Stabilized Carbocations: The Prins, Mannich,
and Mukaiyama Reactions 370
Chapter Summary 386
Key Terms 386
Additional Problems 387
chapter eleven
Reactive Intermediates II: Carbanions and Their Reactivity
11.1 Carbanions: Introduction and Overview 391
11.2 Metal Alkyls 397
11.3 Carbanions Stabilized by Heteroatoms 411
11.4 Formation of Enolate Anions 420
11.5 Rearrangements of Carbanions 430
Chapter Summary 434
Key Terms 434
Additional Problems 434
chapter twelve
Organic Reactions III: Synthetic Reactions of Carbon Nucleophiles:
Substitution and Addition
12.1 Carbon-Carbon Bond Formation: Carbon Nucleophiles and Electrophiles 439
12.2 Substitution and Addition with Metal Alkyl Reagents Having
C—M σ Bonds 439
12.3 Metal Enolates: Versatile Carbon Nucleophiles 458
12.4 The Aldol Addition Reaction 466
12.5 Conjugate Addition of Enolates and Similar Compounds 481
12.6 Azaenol Derivatives: Imines, Hydrazones, and Enamines 486
Chapter Summary 492
Key Terms 493
Additional Problems 493
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chapter thirteen
Reactive Intermediates III: Free Radicals, Carbenes, Arynes, and Nitrenes
13.1 Free Radicals 497
13.2 Carbenes 505
13.3 Nitrenes 516
13.4 Arynes 518
Chapter Summary 528
Key Terms 528
Additional Problems 528
chapter fourteen
Organic Reactions IV: Applications of Free Radical Chemistry in Synthesis
14.1 Methods for Site-Specific Generation of Free Radicals 533
14.2 Reactions of Free Radicals 542
14.3 Reactions of Free Radicals Useful for Synthesis 548
14.4 Additions and Cyclizations of Free Radicals 557
14.5 Diradicals: Formation and Uses in Synthesis 567
Chapter Summary 569
Key Terms 570
Additional Problems 570
chapter fifteen
Organic Synthesis: Retrosynthetic Analysis, Protecting
Groups, and the Strategy of Organic Synthesis
15.1 What Is Organic Synthesis? 577
15.2 Organic Reactions: Tools of the Synthetic Chemist 583
15.3 Retrosynthetic Analysis: An Introduction to the Vocabulary
and Strategy of Organic Synthesis 591
15.4 Applying RetrosyntheticAnalysis to a Real Example 605
15.5 Selectivity Revisited 610
15.6 Protection of Alcohols 614
15.7 Protection of Aldehydes, Ketones, and Carboxylic Acids 624
15.8 Protection of Amines 631
15.9 Protecting Groups for Hydrocarbons 635
Chapter Summary 638
Key Terms 638
Additional Problems 639
chapter sixteen
Organic Reactions V: Condensations and Cascade Reactions
of Carbon Nucleophiles
16.1 Addition, Condensation, Cascade Reactions: Definitions 647
16.2 The Aldol Condensation and Related Reactions 647
16.3 Condensations Where the Initial Adduct Is Intercepted 650
16.4 The Claisen Condensation and Related Reactions 656
16.5 The Wittig, Horner-Wadsworth-Emmons, and Related Reactions 661
16.6 Cascade Reactions Initiated by Carbon Nucleophiles 677
Chapter Summary 682
Key Terms 682
Additional Problems 683
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chapter seventeen
Organic Reactions VI: Metal-Catalyzed Reactions for C—C Bond Formation
17.1 Catalysis and “Green” Chemistry 689
17.2 Bonding in Organometallic Complexes 690
17.3 Basic Organometallic Reactions I: Reactions at the Metal 697
17.4 Basic Organometallic Reactions II: Reactions at the Ligand 704
17.5 Hydrometalation: Making the Organometallic Reagents by Addition 716
17.6 Palladium-Catalyzed Substitution: Tsuji-Trost and Buchwald-Hartwig
Reactions 730
17.7 Cross-Coupling Reactions to Form C—C Bonds 737
Chapter Summary 752
Key Terms 753
Additional Problems 753
chapter eighteen
Redox Reactions I: Oxidation
18.1 Introduction 761
18.2 Overview of Oxidation 765
18.3 Oxidation of Alcohols to Aldehydes and Ketones with Stoichiometric
Metal-Based Reagents 766
18.4 Oxidation of Alcohols Using Non-Metal-Based Reagents 775
18.5 Oxidations to Carboxylic Acids 784
18.6 Oxidation of Ethers and Amines 789
18.7 Oxidative Rearrangements 792
18.8 Oxidation of Unsaturated Hydrocarbons 801
18.9 Oxidative Cleavage of Carbon-Carbon Bonds 815
18.10 Oxidative Substitution of Carbon-Hydrogen σ Bonds 821
18.11 Oxidation of Alkanes 834
18.12 A Catalogue of Oxidation Reactions: Oxidation at a Glance 838
Chapter Summary 842
Key Terms 842
Additional Problems 842
chapter nineteen
Redox Reactions II: Reduction with Molecular Hydrogen or Its Equivalent
19.1 Overview of Reduction 855
19.2 Catalytic Hydrogenation 855
19.3 Hydrogenolysis 877
Chapter Summary 883
Key Terms 883
Additional Problems 883
chapter twenty
Redox III: Reduction with Complex Metal Hydrides and Active Metals
20.1 Reductions with Metal Hydrides 891
20.2 Reduction by Hydrogen Transfer from Carbon 905
20.3 Stereochemistry and Stereoselectivity in Hydride Reductions 910
20.4 Reduction Using Metals 912
20.5 Reduction of Carbonyl Compounds to Hydrocarbons 924
20.6 A Catalog of Reduction Reactions: Reduction at a Glance 932
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Chapter Summary 935
Key Terms 935
Additional Problems 935
chapter twenty-one
Asymmetric Oxidation and Reduction
21.1 Asymmetric Redox Reactions: An Overview 943
21.2 Sharpless Asymmetric Epoxidation of Allylic Alcohols 944
21.3 Asymmetric Epoxidation of Unfunctionalized Alkenes 950
21.4 Oxidation with Chiral Three-membered Heterocycles 955
21.5 Asymmetric Dihydroxylation 965
21.6 Kinetic Resolution of Alcohols 967
21.7 Enantioselective Insertion into C—C and C—H Bonds 972
21.8 Asymmetric Hydrogenation 973
21.9 Asymmetric Reductions with Metal Hydrides and Metal Alkyls 980
21.10 Enzymes: Biocatalysis of Redox Reactions 983
Chapter Summary 985
Key Terms 986
Additional Problems 986
chapter twenty-two
The Organic Compounds of Silicon, Phosphorus,
Sulfur, Selenium, and Tin
22.1 Introduction 993
22.2 Silanes and Stannanes as Directing Groups: Carbocation Chemistry 999
22.3 Heteroatom-Centered Nucleophiles: Silyllithiums, Stannyllithiums,
Sulfides and Selenides 1008
22.4 Reactions of Organophosphorus, Organosulfur and Organoselenium
Compounds 1010
Chapter Summary 1021
Key Terms 1022
Additional Problems 1022
chapter twenty-three
Modern Asymmetric Synthesis
23.1 Controlling Absolute Stereochemistry 1027
23.2 Asymmetric Synthesis with Chiral Auxiliaries: Additions 1038
23.3 Asymmetric Substitution at Carbon: Alkylation of Enolates and
Related Nucleophiles 1051
23.4 Catalytic Asymmetric Synthesis 1055
23.5 Representative Asymmetric Syntheses 1066
Chapter Summary 1086
Key Terms 1086
Additional Problems 1086
Appendix 1: Named Reactions, Named Reagents, and Named Rules 1095
Appendix 2: Glossary of Key Terms 1119
Appendix 3: Selected Physical Constants 1133
Index 1137
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preface
Over the past three decades of my career, I have seen introductory organic chemistry
change from a foundation course for chemists and chemical professionals, to a service
course for students planning on careers in the medical field. This change in emphasis has
been accompanied, in my opinion, by an erosion of the level of the course material, so that
students who do go on to graduate school in chemistry are no longer well prepared for the
introductory courses in organic chemistry at the graduate level. At the same time, the
amount and level of material that confronts new graduate students in organic chemistry
has become more demanding, and this has further widened the gap between the introduc-
tory courses at the undergraduate and graduate levels.
This book specifically targets advanced undergraduate students and entering graduate
students, and is an attempt to bridge that gap—to provide upper-level undergraduate stu-
dents with an advanced textbook that addresses a number of important topics in more
depth than now occurs in most introductory textbooks, while providing both a useful
review, and then a much more substantial discussion of these topics for beginning gradu-
ate students.
Organization
This book has been written explicitly as a textbook, and its organization reflects this. The
book is divided loosely into four sections: 1) introductory materials and general concepts
of bonding and stereochemistry; 2) physical organic chemistry, reactive intermediates,
and their reactions; 3) redox reactions; and 4) modern asymmetric reactions and synthe-
sis. This last section also contains a chapter on the chemistry of the elements in the lower
periods of the main groups, as well as a chapter on modern catalytic reactions for the
formation of carbon–carbon bonds.
Each chapter concludes with a list of key terms introduced in the chapter. In chapters
where new organic reactions are introduced, there are Reaction Synopses that contain the
general reaction and typical reagents and reaction conditions to effect the reaction. I also
feel that the humanity of our science is often overlooked in an effort to impart the most
factual information possible. To counter this, I have included footnotes where biographi-
cal information about the chemists who developed the science can be found. For the most
part, these footnotes contain references to longer biographical works or obituaries, but on
a few occasions, these biographies are somewhat more expansive because additional infor-
mation is so scarce.
Among the introductory chapters are discussions of stereochemistry and molecular
orbital theory, including frontier orbital theory and the question of aromaticity. This sec-
tion also contains a chapter (Chapter 3) containing the most frequently used acronyms in
organic chemistry. In many books, the acronyms list is relegated to an appendix, but their
use has become so widespread in modern synthetic organic chemistry that I have chosen
to include them explicitly in the body of the book.
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