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Index

References to tables are given in bold type.

acetals 23symmetrical cyclic 209210

acetylenes see alkynesAchilles Heel strategy 6364acids, halogenation 47acyl anion equivalents 167170,

187189acylation

by ketene dimers 254Friedel-Crafts 89, 209

acyloin reaction 180182adipic acid 199adrenaline 50AIDS drugs 119120alcohols

C-C disconnections 69 76dehydration to alkenes 107derivatives 27 28oxidation 72protecting groups for 6566symmetrical 78 80

synthesis 7071, 74751,2 C-C disconnections 7374examples 7475

aldehydesfrom alcohols 72synthesis by acylation 9396

aldol reaction 134, 321322alkaloids 275alkenes

cyclisation by carbene insertion 231234from alkynes by reduction 116117hydrationsynthesis

of 1,2-difunctionalised compounds 170171by elimination 107108by Wittig reaction 108112

alkylation reactionsamination 5657aromatic compounds 910, 1011

alkynesin anti-AIDS drug 119120reduction to alkenes 116117

Organic Synthesis: The Disconnection Approach. Second Edition Stuart Warren and Paul Wyatt

2008 John Wiley & Sons, Ltd

allylic carbons 177179amides, as protecting groups 6264amines

overview 5354primary 55, 5657secondary 55, 57

tertiary 56from nitro compounds by reduction 161162monomorine I synthesis 5759reductive amination 5556

amino acids 3132Aphox 306Arndt-Eistert procedure 237238aromatic compounds

acylation 89disconnection 78functional group addition, general strategy

1722functional groups, and reactivity 18reduction 273277

aspartame 64

axial attack 8990azides 56

Baeyer-Villiger reaction 203204, 253Beckmann rearrangement 253benzene rings, Birch reduction 274275benzocaine 78benzoin condensation 174175biotin 177179Birch reduction 274275

aromatic carboxylic acids 276277brevianamide 194bromohexanoic acid 47t-butyloxycarbonyl group 64

carbenesmetal complexes 233synthesis by -elimination 232233

carbobenzyloxy (Cbz) groups 63carbon acids 131132carbon nucleophiles 70

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326 Index

carbonyl compounds1,2 di- 1731741,3 di- 1361371,4 di- 1901911,5 di- 1511591,6 di- 199204and amination 54-hydroxy 133135by conjugate addition 98100cyclisation to five-membered rings 255256derivatives 23 25dicarbonyl 129132intramolecular reactions 140141nucleophilicity 129,-unsaturated 135136-functionalisation 172173

carbonyl condensations, compounds whichcannot enolise 141144

carboxylic acids

C-C disconnection 7273reduction 276277

Cbz group 63chemoselectivity 2934chirality see stereochemistrychloroacetyl chloride 47cis-chrysanthemic acid 230citronellal 196197Claisen rearrangement 265267clopirac 302303columbiasin A 271272conformational control 8990conjugate addition 36, 3738, 321322

of acyl anion equivalents 187189carbon nucleophiles 104106

nitro-alkanes 163convergence 314318, 319copaene 293295Cope rearrangement 265coriolin 292, 292293cyanide ion 169170, 187cyclisation 4849, 217219

three-membered rings 219cyclopropanes 229231sulfonium ylids 234235

four-membered rings 220221, 245, 280282by ionic reactions 248

five-membered rings 221223, 255258six-membered rings 223224, 270271

Diels-Alder reaction 201202

seven-membered rings 224 226disconnections for small rings 280282general considerations 217219ketenes 251254kinetic and thermodynamic factors 218ring expansion and contraction 238240Robinson annelation 156157salbutamol 50 51and selectivity control 279280

cyclomethycaine 3031

cyclopentanes 257258by conjugate addition 258

cyclopropanes 229231

damascenone 262darifenacin 75dendrimers 267diarylketones 182183diastereoisomers 8385diazoalkanes 237238, 238240dicarbonyl compounds 193196dichlorocarbene 232dicyclomine 273274Diels-Alder reaction 121127, 269, 271273,

3203211,6-dicarbonyl compounds 201202functional group interconversion (FGI) of

products 126

molecules with several chiral centres 291nitroalkene synthesis 164165regioselectivity 124125in water 126127

dienesstereospecificity 122123synthesis 117

by Wittig reaction 112dienoestrol 180difunctionalised compounds

1,1-difunctionalised 41431,2-difunctionalised 39411,3-difunctionalised 37, 38see also disconnections, two-group

dihydropyran 63

dimedone 230disconnections1,5-difunctionalised compounds 151158overview 12, 80symbol 7example 24guidelines 80order of events 1718C-C

one-group1, 1 70731, 2 7375other 7576simplification 7778starting materials 7879symmetry 78two-group

1,2-difunctionalised compounds 1671761,3-difunctionalised compounds 1331381,4-difunctionalised compounds 1851921,5-difunctionalised compounds 1511591,6-difunctionalised compounds 199205Diels-Alder reactions 129132

C-heteroatom 301303polarity reversal 4546

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Index 327

carbonyl compounds 207214heterocyclic compounds 301304two functional groups

as analytic preliminary 4344overview 3536recognition 36see also Diels-Alder reactions;

disconnections, C-C, two-groupdisparlure 111DMF 9497

electrocyclic reactions 261263elm bark beetle 2enamines 147148enantiomers 83 85enolates

1,3-dicarbonyl compounds 9798alkylation to cyclopropanes 229231

anionic 131132, 132lithium 9697, 145146enols

alkylation 9698specific 144148

enones, spiro 210211epoxides 4546

rearrangement reactions 241equilibrium reactions 148149esters

lithium enolates 145146synthesis by acylation 9396

ethersas protecting groups 62synthesis 25 26

Favorskii rearrangement 242243fencamfamin 164fentiazac 303304fluconazole 40fluoxetine 1213folded molecules 90

stereochemistry 292293formaldehyde, Mannich reaction 143144Friedel-Crafts reactions 8 9, 209functional group addition (FGA)

1,4-difunctionalised compounds 196197aromatic compounds 1011carbonyl compounds 191order of events 1718

functional group interconversion (FGI) 7 8Diels-Alder products 126

functional groupschoice and yields 33functionalisation, allylic and benzylic

177179interaction 17 18and reactivity 18two-group disconnections 3536see also protecting groups

furans, electrophilic substitution309310

furfural 119

gingerol-6 146grandisol 168guanacastetepenes 272273

halicholactone 235halogenation

acids 47ketones 4647

Henry reaction 163heterocyclic compounds

1,5-dicarbonyl compounds 158aromatic 301311indoles 307saturated 217227

substitution reactions 308311homoenolates 1891904-hydroxyketones 187

indoles, electrophilic substitution 309310indomethacin 307308intramolecular reactions, cyclisations

217226

jasmone 116117juvabione 295298

ketenes 251254ketones

alkylation, regiospecific 101103

cyclopentyl 256257from alcohols 7172halogenation 46 47synthesis 95

by acetylene hydration 118by acylation at carbon 9396by alkylation of enolates 9698by conjugate addition 98100by oxidation of alcohols 72

unsaturated 133149Knoevenagel reaction 144

lactones 148149, 208209laulimalide 65LHASA program 2

lithium enolates 9697, 145146-lycorane, stereochemistry 323324

Mannich reaction 143144maritidine 275metal carbenoids 233234metaproterenol 172methoxatin 315318methylenomycin 186187

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328 Index

Michael reactionsacceptors suitable for conjugate addition

155156enol equivalents suitable for conjugate

addition 155156MIV-150 319monomorine I 5759multistriatin 24, 8385, 8788

Nazarov reaction 261263nitro compounds 161, 162164, 165,

188189Novartis PKI 166 anti-cancer drug 310311

oblivon 115

Palanil 111paracetamol 29 30

pentalenoactone 201permethrin 230pH, and chemoselectivity 3031Pharaohs ant 5758phenaglycodol 169phensuximide 188photochemistry, cycloadditions 245248pinacol reaction 179180, 240242piquindone 212214pKa of bases and carbon acids 132polarity, synthons 130131Prelog-Djerassi lactone 289291propanil 24protecting groups 31, 6162, 67

for alcohols 6566

for amines 6264literature 66 67pyrazoles 313318pyridines 304306

nucleophilic substitution 310pyrimidines 306, 310pyrroles 302303

electrophilic substitution 309310

radical reactionsC-C bond formation 179182strategy 177183

reactivity, functional groups, and selectivity2930

rearrangement reactions 238240

Claisen 265267Cope 265Favorskii 242243pinacol 240242sigmatropic 263267

reconnection 193197definition 194

regioselectivity 101 106, 124125of cyclisation reactions 283in photochemical cyclisations 247248enones 103106

Reissert synthesis 317, 318Reppe process 116reserpine 19Robinson annelation 156157, 269,

270271

saccharine 15salbutamol 20, 5051sarracenin 4344, 284286sigmatropic rearrangements 263267silyl groups, as protecting groups 65spiro-enones 210211starting materials 7880

1,2-dicarbonyl 173174

1,4-dicarbonyl 190191enantiomeric purity 8384steganone 233234stereochemistry 45-lycorane 323324conformational control 89folded molecules 90, 292293molecules with many chiral centres

289291ortho- and para- product mixtures 1415stereoselectivity 8889

Claisen rearrangment 266267stereospecificity 8588, 86

Diels-Alder reaction 122123stereoselectivity 88 89, 266267stereospecificity 8588, 86, 266267substitution reactions

difficult-to-add substituents 19electrophilic

aromatic compounds 1920reagents 11

nucleophilicallylic halides 26aromatic compounds 1112, 1315,

2021sulfides, synthesis 27surfynol 115116symmetrical compounds, alcohols 7880synthesis design, general strategy 4synthons 910

definition 9

polarity 130131

t-butyldimethylsilyl (TBDMS) group 65tandem processes 313Taxol 283284thiazoles 303304

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Index 329

thiols 32tri-iso-propylsilyl groups 65triethylsilyl group 65tropinone 12

vernolepin 207208vinyl cyclopropane

263264vinyl halides 105106vulpinic acid 169170

Wittig reaction 108112and lithium enolates 146147

X-506 antibiotic 194

ylidsstabilised, Wittig reaction 110112sulfur 234235

Z group 63