Organic Chemistry Organic Chemistry—online support Each chapter in this book is accompanied by a set of problems, which are available free of charge online. To access them visit the Online Resource Centre at www.oxfordtextbooks.co.uk/orc/clayden2e/ and enter the following: Username: clayden2e Password: compound 2069_Book.indb i 12/12/2011 8:21:29 PM This page intentionally left blank ORGANIC CHEMISTRY SECOND EDITION Jonathan Clayden Nick Greeves Stuart Warren University of Manchester University of Liverpool University of Cambridge 1 2069_Book.indb iii 12/12/2011 8:21:35 PM 1 Great Clarendon Street, Oxford OX2 6DP Oxford University Press is a department of the University of Oxford. It furthers the University’s objective of excellence in research, scholarship, and education by publishing worldwide in Oxford New York Auckland Cape Town Dar es Salaam Hong Kong Karachi Kuala Lumpur Madrid Melbourne Mexico City Nairobi New Delhi Shanghai Taipei Toronto With offi ces in Argentina Austria Brazil Chile Czech Republic France Greece Guatemala Hungary Italy Japan Poland Portugal Singapore South Korea Switzerland Thailand Turkey Ukraine Vietnam Oxford is a registered trade mark of Oxford University Press in the UK and in certain other countries Published in the United States by Oxford University Press Inc., New York © Jonathan Clayden, Nick Greeves, and Stuart Warren 2012 The moral rights of the authors have been asserted Crown Copyright material reproduced with the permission of the Controller, HMSO (under the terms of the Click Use licence.) Database right Oxford University Press (maker) First published 2001 All rights reserved. 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Ltd ISBN 978-0-19-927029-3 10 9 8 7 6 5 4 3 2 1 2069_Book.indb iv 12/12/2011 8:21:40 PM Abbreviations xv Preface to the second edition xvii Organic chemistry and this book xix 1 What is organic chemistry? 1 2 Organic structures 15 3 Determining organic structures 43 4 Structure of molecules 80 5 Organic reactions 107 6 Nucleophilic addition to the carbonyl group 125 7 Delocalization and conjugation 141 8 Acidity, basicity, and pKa 163 9 Using organometallic reagents to make C–C bonds 182 10 Nucleophilic substitution at the carbonyl group 197 11 Nucleophilic substitution at C=O with loss of carbonyl oxygen 222 12 Equilibria, rates, and mechanisms 240 13 1H NMR: Proton nuclear magnetic resonance 269 14 Stereochemistry 302 15 Nucleophilic substitution at saturated carbon 328 16 Conformational analysis 360 17 Elimination reactions 382 18 Review of spectroscopic methods 407 19 Electrophilic addition to alkenes 427 20 Formation and reactions of enols and enolates 449 21 Electrophilic aromatic substitution 471 22 Conjugate addition and nucleophilic aromatic substitution 498 23 Chemoselectivity and protecting groups 528 24 Regioselectivity 562 25 Alkylation of enolates 584 26 Reactions of enolates with carbonyl compounds: the aldol and Claisen reactions 614 27 Sulfur, silicon, and phosphorus in organic chemistry 656 28 Retrosynthetic analysis 694 29 Aromatic heterocycles 1: reactions 723 30 Aromatic heterocycles 2: synthesis 757 31 Saturated heterocycles and stereoelectronics 789 32 Stereoselectivity in cyclic molecules 825 Brief contents 2069_Book.indb v 12/12/2011 8:21:40 PM 33 Diastereoselectivity 852 34 Pericyclic reactions 1: cycloadditions 877 35 Pericyclic reactions 2: sigmatropic and electrocyclic reactions 909 36 Participation, rearrangement, and fragmentation 931 37 Radical reactions 970 38 Synthesis and reactions of carbenes 1003 39 Determining reaction mechanisms 1029 40 Organometallic chemistry 1069 41 Asymmetric synthesis 1102 42 Organic chemistry of life 1134 43 Organic chemistry today 1169 Figure acknowledgements 1182 Periodic table of the elements 1184 Index 1187 vi BRIEF CONTENTS 2069_Book.indb vi 12/12/2011 8:21:41 PM Contents Abbreviations xv Preface to the second edition xvii Organic chemistry and this book xix What is organic chemistry? 1 Organic chemistry and you 1 Organic compounds 2 Organic chemistry and industry 6 Organic chemistry and the periodic table 11 Organic chemistry and this book 13 Further reading 13 2 Organic structures 15 Hydrocarbon frameworks and functional groups 16 Drawing molecules 17 Hydrocarbon frameworks 22 Functional groups 27 Carbon atoms carrying functional groups can be classifi ed by oxidation level 32 Naming compounds 33 What do chemists really call compounds? 36 How should you name compounds? 40 Further reading 42 Determining organic structures 43 Introduction 43 Mass spectrometry 46 Mass spectrometry detects isotopes 48 Atomic composition can be determined by high-resolution mass spectrometry 50 Nuclear magnetic resonance 52 Regions of the 13C NMR spectrum 56 Different ways of describing chemical shift 57 A guided tour of the 13C NMR spectra of some simple molecules 57 The 1H NMR spectrum 59 Infrared spectra 63 Mass spectra, NMR, and IR combined make quick identifi cation possible 72 Double bond equivalents help in the search for a structure 74 Looking forward to Chapters 13 and 18 78 Further reading 78 Structure of molecules 80 Introduction 80 Electrons occupy atomic orbitals 83 Molecular orbitals—diatomic molecules 88 Bonds between different atoms 95 Hybridization of atomic orbitals 99 Rotation and rigidity 105 Conclusion 106 Looking forward 106 Further reading 106 Organic reactions 107 Chemical reactions 107 Nucleophiles and electrophiles 111 Curly arrows represent reaction mechanisms 116 Drawing your own mechanisms with curly arrows 120 Further reading 124 Nucleophilic addition to the carbonyl group 125 Molecular orbitals explain the reactivity of the carbonyl group 125 Attack of cyanide on aldehydes and ketones 127 The angle of nucleophilic attack on aldehydes and ketones 129 Nucleophilic attack by ‘hydride’ on aldehydes and ketones 130 Addition of organometallic reagents to aldehydes and ketones 132 Addition of water to aldehydes and ketones 133 Hemiacetals from reaction of alcohols with aldehydes and ketones 135 Ketones also form hemiacetals 137 Acid and base catalysis of hemiacetal and hydrate formation 137 Bisulfi te addition compounds 138 Further reading 140 Delocalization and conjugation 141 Introduction 141 The structure of ethene (ethylene, CH2=CH2) 142 Molecules with more than one C=C double bond 143 1 2 3 4 5 6 7 2069_Book.indb vii 12/12/2011 8:21:41 PM The conjugation of two ππ bonds 146 UV and visible spectra 148 The allyl system 150 Delocalization over three atoms is a common structural feature 154 Aromaticity 156 Further reading 162 Acidity, basicity, and pKa 163 Organic compounds are more soluble in water as ions 163 Acids, bases, and pKa 165 Acidity 165 The defi nition of pKa 168 Constructing a pKa scale 171 Nitrogen compounds as acids and bases 174 Substituents affect the pKa 175 Carbon acids 176 pKa in action—the development of the drug cimetidine 178 Lewis acids and bases 180 Further reading 181 Using organometallic reagents to make C–C bonds 182 Introduction 182 Organometallic compounds contain a carbon–metal bond 183 Making organometallics 184 Using organometallics to make organic molecules 189 Oxidation of alcohols 194 Looking forward 196 Further reading 196 Nucleophilic substitution at the carbonyl group 197 The product of nucleophilic addition to a carbonyl group is not always a stable compound 197 Carboxylic acid derivatives 198 Why are the tetrahedral intermediates unstable? 200 Not all carboxylic acid derivatives are equally reactive 205 Acid catalysts increase the reactivity of a carbonyl group 207 Acid chlorides can be made from carboxylic acids using SOCl2 or PCl5 214 Making other compounds by substitution reactions of acid derivatives 216 Making ketones from esters: the problem 216 Making ketones from esters: the solution 218 To summarize.. . 220 And to conclude. . . 220 Further reading 220 Nucleophilic substitution at C=O with loss of carbonyl oxygen 222 Introduction 222 Aldehydes can react with alcohols to form hemiacetals 223 Acetals are formed from aldehydes or ketones plus alcohols in the presence of acid 224 Amines react with carbonyl compounds 229 Imines are the nitrogen analogues of carbonyl compounds 230 Summary 238 Further reading 239 Equilibria, rates, and mechanisms 240 How far and how fast? 240 How to make the equilibrium favour the product you want 244 Entropy is important in determining equilibrium constants 246 Equilibrium constants vary with temperature 248 Introducing kinetics: how to make reactions go faster and cleaner 250 Rate equations 257 Catalysis in carbonyl substitution reactions 262 Kinetic versus thermodynamic products 264 Summary of mechanisms from Chapters 6–12 266 Further reading 267 1H NMR: Proton nuclear magnetic resonance 269 The differences between carbon and proton NMR 269 Integration tells us the number of hydrogen atoms in each peak 270 Regions of the proton NMR spectrum 272 Protons on saturated carbon atoms 272 The alkene region and the benzene region 277 The aldehyde region: unsaturated carbon bonded to oxygen 281 Protons on heteroatoms have more variable shifts than protons on carbon 282 Coupling in the proton NMR spectrum 285 To conclude 301 Further reading 301 Stereochemistry 302 Some compounds can exist as a pair of mirror- image forms 302 8 9 10 11 12 13 14 CONTENTS viii 2069_Book.indb viii 12/12/2011 8:21:42 PM Diastereoisomers are stereoisomers that are not enantiomers 311 Chiral compounds with no stereogenic centres 319 Axes and centres of symmetry 320 Separating enantiomers is called resolution 322 Further reading 327 Nucleophilic substitution at saturated carbon 328 Mechanisms for nucleophilic substitution 328 How can we decide which mechanism (SN1 or SN2) will apply to a given organic compound? 332 A closer look at the SN1 reaction 333 A closer look at the SN2 reaction 340 Contrasts between SN1 and SN2 342 The leaving group in SN1 and SN2 reactions 347 The nucleophile in SN1 reactions 352 The nucleophile in the SN2 reaction 353 Nucleophiles and leaving groups compared 357 Looking forward: elimination and rearrangement reactions 358 Further reading 359 Conformational analysis 360 Bond rotation allows chains of atoms to adopt a number of conformations 360 Conformation and confi guration 361 Barriers to rotation 362 Conformations of ethane 363 Conformations of propane 365 Conformations of butane 365 Ring strain 366 A closer look at cyclohexane 370 Substituted cyclohexanes 374 To conclude. .. 381 Further reading 381 Elimination reactions 382 Substitution and elimination 382 How the nucleophile affects elimination versus substitution 384 E1 and E2 mechanisms 386 Substrate structure may allow E1 388 The role of the leaving group 390 E1 reactions can be stereoselective 391 E2 eliminations have anti-periplanar transition states 395 The regioselectivity of E2 eliminations 398 Anion-stabilizing groups allow another mechanism—E1cB 399 To conclude 404 Further reading 406 Review of spectroscopic methods 407 There are three reasons for this chapter 407 Spectroscopy and carbonyl chemistry 408 Acid derivatives are best distinguished by infrared 411 Small rings introduce strain inside the ring and higher s character outside it 412 Simple calculations of C=O stretching frequencies in IR spectra 413 NMR spectra of alkynes and small rings 414 Proton NMR distinguishes axial and equatorial protons in cyclohexanes 415 Interactions between different nuclei can give enormous coupling constants 415 Identifying products spectroscopically 418 Tables 422 Shifts in proton NMR are easier to calculate and more informative than those in carbon NMR 425 Further reading 426 Electrophilic addition to alkenes 427 Alkenes react with bromine 427 Oxidation of alkenes to form epoxides 429 Electrophilic addition to unsymmetrical alkenes is regioselective 433 Electrophilic addition to dienes 435 Unsymmetrical bromonium ions open regioselectively 436 Electrophilic additions to alkenes can be stereospecifi c 439 Adding two hydroxyl groups: dihydroxylation 442 Breaking a double bond completely: periodate cleavage and ozonolysis 443 Adding one hydroxyl group: how to add water across a double bond 444 To conclude. . .a synopsis of electrophilic addition reactions 447 Further reading 447 Formation and reactions of enols and enolates 449 Would you accept a mixture of compounds as a pure substance? 449 Tautomerism: formation of enols by proton transfer 450 Why don’t simple aldehydes and ketones exist as enols? 451 15 16 17 18 19 20 CONTENTS ix 2069_Book.indb ix 12/12/2011 8:21:42 PM Evidence for the equilibration of carbonyl compounds with enols 451 Enolization is catalysed by acids and bases 452 The intermediate in the base-catalysed reaction is an enolate ion 452 Summary of types of enol and enolate 454 Stable enols 456 Consequences of enolization 459 Reaction with enols or enolates as intermediates 460 Stable equivalents of enolate ions 465 Enol and enolate reactions at oxygen: preparation of enol ethers 467 Reactions of enol ethers 468 To conclude 470 Further reading 470 Electrophilic aromatic substitution 471 Introduction: enols and phenols 471 Benzene and its reactions with electrophiles 473 Electrophilic substitution on phenols 479 A nitrogen lone pair activates even more strongly 482 Alkyl benzenes also react at the ortho and para positions 484 Electron-withdrawing substituents give meta products 486 Halogens show evidence of both electron withdrawal and donation 489 Two or more substituents may cooperate or compete 491 Some problems and some opportunities 492 A closer look at Friedel–Crafts chemistry 492 Exploiting the chemistry of the nitro group 494 Summary 495 Further reading 497 Conjugate addition and nucleophilic aromatic substitution 498 Alkenes conjugated with carbonyl groups 498 Conjugated alkenes can be electrophilic 499 Summary: factors controlling conjugate addition 509 Extending the reaction to other electron- defi cient alkenes 510 Conjugate substitution reactions 511 Nucleophilic epoxidation 513 Nucleophilic aromatic substitution 514 The addition–elimination mechanism 515 The SN1 mechanism for nucleophilic aromatic substitution: diazonium compounds 520 The benzyne mechanism 523 To conclude. . . 526 Further reading 527 Chemoselectivity and protecting groups 528 Selectivity 528 Reducing agents 530 Reduction of carbonyl groups 530 Hydrogen as a reducing agent: catalytic hydrogenation 534 Getting rid of functional groups 539 Dissolving metal reductions 541 Selectivity in oxidation reactions 544 Competing reactivity: choosing which group reacts 546 A survey of protecting groups 549 Further reading 561 Regioselectivity 562 Introduction 562 Regioselectivity in electrophilic aromatic substitution 563 Electrophilic attack on alkenes 570 Regioselectivity in radical reactions 571 Nucleophilic attack on allylic compounds 574 Electrophilic attack on conjugated dienes 579 Conjugate addition 581 Regioselectivity in action 582 Further reading 583 Alkylation of enolates 584 Carbonyl groups show diverse reactivity 584 Some important considerations that affect all alkylations 584 Nitriles and nitroalkanes can be alkylated 585 Choice of electrophile for alkylation 587 Lithium enolates of carbonyl compounds 587 Alkylations of lithium enolates 588 Using specifi c enol equivalents to alkylate aldehydes and ketones 591 Alkylation of β-dicarbonyl compounds 595 Ketone alkylation poses a problem in regioselectivity 598 Enones provide a solution to regioselectivity problems 601 Using Michael acceptors as electrophiles 605 To conclude. . . 612 Further reading 613 Reactions of enolates with carbonyl compounds: the aldol and Claisen reactions 614 Introduction 614 The aldol reaction 615 Cross-condensations 618 21 22 23 24 25 26 CONTENTS x 2069_Book.indb x 12/12/2011 8:21:42 PM Specifi c enol equivalents can be used to control aldol reactions 624 How to control aldol reactions of esters 631 How to control aldol reactions of aldehydes 632 How to control aldol reactions of ketones 634 Intramolecular aldol reactions 636 Acylation at carbon 640 Crossed ester condensations 643 Summary of the preparation of keto-esters by the Claisen reaction 647 Controlling acylation with specifi c enol equivalents 648 Intramolecular crossed Claisen ester condensations 652 Carbonyl chemistry—where next? 654 Further reading 654 Sulfur, silicon, and phosphorus in organic chemistry 656 Useful main group elements 656 Sulfur: an element of contradictions 656 Sulfur-stabilized anions 660 Sulfonium salts 664 Sulfonium ylids 665 Silicon and carbon compared 668 Allyl silanes as nucleophiles 675 The selective synthesis of alkenes 677 The properties of alkenes depend on their geometry 677 Exploiting cyclic compounds 678 Equilibration of alkenes 679 E and Z alkenes can be made by stereoselective addition to alkynes 681 Predominantly E alkenes can be formed by stereoselective elimination reactions 684 The Julia olefi nation is regiospecifi c and connective 686 Stereospecifi c eliminations can give pure single isomers of alkenes 688 Perhaps the most important way of making alkenes—the Wittig reaction 689 To conclude 693 Further reading 693 Retrosynthetic analysis 694 Creative chemistry 694 Retrosynthetic analysis: synthesis backwards 694 Disconnections must correspond to known, reliable reactions 695 Synthons are idealized reagents 695 Multiple step syntheses: avoid chemoselectivity problems 698 Functional group interconversion 699 Two-group disconnections are better than one-group disconnections 702 C–C disconnections 706 Available starting materials 711 Donor and acceptor synthons 712 Two-group C–C disconnections 712 1,5-Related functional groups 719 ‘Natural reactivity’ and ‘umpolung’ 719 To conclude. . . 722 Further reading 722 Aromatic heterocycles 1: reactions 723 Introduction 723 Aromaticity survives when parts of benzene’s ring are replaced by nitrogen atoms 724 Pyridine is a very unreactive aromatic imine 725 Six-membered aromatic heterocycles can have oxygen in the ring 732 Five-membered aromatic heterocycles are good at electrophilic substitution 733 Furan and thiophene are oxygen and sulfur analogues of pyrrole 735 More reactions of fi ve-membered heterocycles 738 Five-membered rings with two or more nitrogen atoms 740 Benzo-fused heterocycles 745 Putting more nitrogen atoms in a six-membered ring 748 Fusing rings to pyridines: quinolines and isoquinolines 749 Aromatic heterocycles can have many nitrogens but only one sulfur or oxygen in any ring 751 There are thousands more heterocycles out there 753 Which heterocyclic structures should you learn? 754 Further reading 755 Aromatic heterocycles 2: synthesis 757 Thermodynamics is on our side 758 Disconnect the carbon–heteroatom bonds fi rst 758 Pyrroles, thiophenes, and furans from 1,4-dicarbonyl compounds 760 How to make pyridines: the Hantzsch pyridine synthesis 763 Pyrazoles and pyridazines from hydrazine and dicarbonyl compounds 767 Pyrimidines can be made from 1,3-dicarbonyl compounds and amidines 770 Unsymmetrical nucleophiles lead to selectivity questions 771 Isoxazoles are made from hydroxylamine or by cycloaddition 772 Tetrazoles and triazoles are also made by cycloadditions 774 The Fischer indole synthesis 775 27 28 29 30 CONTENTS xi 2069_Book.indb xi 12/12/2011 8:21:43 PM Quinolines and isoquinolines 780 More heteroatoms in fused rings mean more choice in synthesis 784 Summary: the three major approaches to the synthesis of aromatic heterocycles 785 Further reading 788 Saturated heterocycles and stereoelectronics 789 Introduction 789 Reactions of saturated heterocycles 790 Conformation of saturated heterocycles 796 Making heterocycles: ring-closing reactions 805 Ring size and NMR 814 Geminal (2J ) coupling 817 Diastereotopic groups 820 To summarize.. . 824 Further reading 824 Stereoselectivity in cyclic molecules 825 Introduction 825 Stereochemical control in six-membered rings 826 Reactions on small rings 832 Regiochemical control in cyclohexene epoxides 836 Stereoselectivity in bicyclic compounds 839 Fused bicyclic compounds 841 Spirocyclic compounds 846 Reactions with cyclic intermediates or cyclic transition states 847 To summarize.. . 851 Further reading 851 Diastereoselectivity 852 Looking back 852 Prochirality 856 Additions to carbonyl groups can be diastereoselective even without rings 858 Stereoselective reactions of acyclic alkenes 865 Aldol reactions can be stereoselective 868 Single enantiomers from diastereoselective reactions 871 Looking forward 876 Further reading 876 Pericyclic reactions 1: cycloadditions 877 A new sort of reaction 877 General description of the Diels–Alder reaction 879 The frontier orbital description of cycloadditions 886 Regioselectivity in Diels–Alder reactions 889 The Woodward–Hoffmann description of the Diels–Alder reaction 892 Trapping reactive intermediates by cycloadditions 893 Other thermal cycloadditions 894 Photochemical [2 ++ 2] cycloadditions 896 Thermal [2 + 2] cycloadditions 898 Making fi ve-membered rings: 1,3-dipolar cycloadditions 901 Two very important synthetic reactions: cycloaddition of alkenes with osmium tetroxide and with ozone 905 Summary of cycloaddition reactions 907 Further reading 908 Pericyclic reactions 2: sigmatropic and electrocyclic reactions 909 Sigmatropic rearrangements 909 Orbital descriptions of [3,3]-sigmatropic rearrangements 912 The direction of [3,3]-sigmatropic rearrangements 913 [2,3]-Sigmatropic rearrangements 917 [1,5]-Sigmatropic hydrogen shifts 919 Electrocyclic reactions 922 Further reading 930 Participation, rearrangement, and fragmentation 931 Neighbouring groups can accelerate substitution reactions 931 Rearrangements occur when a participating group ends up bonded to a different atom 937 Carbocations readily rearrange 940 The pinacol rearrangement 945 The dienone-phenol rearrangement 949 The benzilic acid rearrangement 950 The Favorskii rearrangement 950 Migration to oxygen: the Baeyer–Villiger reaction 953 The Beckmann rearrangement 958 Polarization of C–C bonds helps fragmentation 960 Fragmentations are controlled by stereochemistry 962 Ring expansion by fragmentation 963 Controlling double bonds using fragmentation 965 The synthesis of nootkatone: fragmentation showcase 966 Looking forward 969 Further reading 969 Radical reactions 970 Radicals contain unpaired electrons 970 Radicals form by homolysis of weak bonds 971 31 32 33 34 35 36 37 CONTENTS xii 2069_Book.indb xii 12/12/2011 8:21:43 PM Most radicals are extremely reactive. . . 974 How to analyse the structure of radicals: electron spin resonance 975 Radical stability 977 How do radicals react? 980 Radical–radical reactions 980 Radical chain reactions 984 Chlorination of alkanes 986 Allylic bromination 989 Reversing the selectivity: radical substitution of Br by H 990 Carbon–carbon bond formation with radicals 992 The reactivity pattern of radicals is quite different from that of polar reagents 997 Alkyl radicals from boranes and oxygen 998 Intramolecular radical reactions are more effi cient than intermolecular ones 999 Looking forward 1002 Further reading 1002 Synthesis and reactions of carbenes 1003 Diazomethane makes methyl esters from carboxylic acids 1003 Photolysis of diazomethane produces a carbene 1005 How do we know that carbenes exist? 1006 Ways to make carbenes 1006 Carbenes can be divided into two types 1010 How do carbenes react? 1013 Carbenes react with alkenes to give cyclopropanes 1013 Insertion into C–H bonds 1018 Rearrangement reactions 1020 Nitrenes are the nitrogen analogues of carbenes 1022 Alkene metathesis 1023 Summary 1027 Further reading 1027 Determining reaction mechanisms 1029 There are mechanisms and there are mechanisms 1029 Determining reaction mechanisms: the Cannizzaro reaction 1031 Be sure of the structure of the product 1035 Systematic structural variation 1040 The Hammett relationship 1041 Other kinetic evidence for reaction mechanisms 1050 Acid and base catalysis 1053 The detection of intermediates 1060 Stereochemistry and mechanism 1063 Summary of methods for the investigation of mechanism 1067 Further reading 1068 Organometallic chemistry 1069 Transition metals extend the range of organic reactions 1069 The 18 electron rule 1070 Bonding and reactions in transition metal complexes 1073 Palladium is the most widely used metal in homogeneous catalysis 1078 The Heck reaction couples together an organic halide or trifl ate and an alkene 1079 Cross-coupling of organometallics and halides 1082 Allylic electrophiles are activated by palladium(0) 1088 Palladium-catalysed amination of aromatic rings 1092 Alkenes coordinated to palladium(II) are attacked by nucleophiles 1096 Palladium catalysis in the total synthesis of a natural alkaloid 1098 An overview of some other transition metals 1099 Further reading 1101 Asymmetric synthesis 1102 Nature is asymmetric 1102 The chiral pool: Nature’s chiral centres ‘off the shelf’ 1104 Resolution can be used to separate enantiomers 1106 Chiral auxiliaries 1107 Chiral reagents 1113 Asymmetric catalysis 1114 Asymmetric formation of carbon–carbon bonds 1126 Asymmetric aldol reactions 1129 Enzymes as catalysts 1132 Further reading 1133 Organic chemistry of life 1134 Primary metabolism 1134 Life begins with nucleic acids 1135 Proteins are made of amino acids 1139 Sugars—just energy sources? 1142 Lipids 1147 Mechanisms in biological chemistry 1149 Natural products 1156 Fatty acids and other polyketides are made from acetyl CoA 1161 Terpenes are volatile constituents of plants 1164 Further reading 1167 38 39 40 41 42 CONTENTS xiii 2069_Book.indb xiii 12/12/2011 8:21:43 PM Organic chemistry today 1169 Science advances through interaction between disciplines 1169 Chemistry vs viruses 1170 The future of organic chemistry 1179 Further reading 1181 Figure acknowledgements 1182 Periodic table of the elements 1184 Index 1187 43 CONTENTS xiv 2069_Book.indb xiv 12/12/2011 8:21:44 PM