275 Index a antiaromatic systems acetals and hemiacetals – benzo-annulation 264 – aldehyde hydrates 267 – compounds 262–263 – chloral hydrate 267 – cyclobutadiene 263 – cyclohexanone hydrate 267 – cyclooctatetraene 264 – cyclopropanones 267, 268 – cyclopropene 263 – definitions 267 – 3-cyclopropenyl anion 263 – formation mechanisms 268, 269 – dimerization 263–264 – protecting group 268, 269 – energetically destabilized, conjugation activation energy 17 262, 264 addition reactions, carbenes aryne–metal complexes 227–228 – bicyclic olefins 172–173 arynes – carbene to alkene, stereospecific – 1,2-, 1,3-and 1,4-didehydrobenzenes addition 170 229–230 – dibromocarbene 168, 169 – allylic hydrogen 228 – hexafluorobenzene 172, 173 – 1-aminobenzotriazole, oxidation 235 – pyrroles and indoles 172, 173 – benzenediazonium-2-carboxylate 232, – Simmons–Smith reactions 174, 175 233–234 – Simmons–Smith reagent 173–174 – Bergman cyclization 229 – singlet carbenes 168, 169 – coupled cluster (CC) 225 – stereochemistry 170–171, 172 – cycloaddition reactions 227, 240–243 – stereoselectivity 173 – density functional theory (DFT) 225 – triplet carbenes 168, 169–170 – 1,3-dipolar cycloaddition 243–244 aldol condensation – generation 230 – aldehyde/ketone 78, 79 – and heteroarynes 225 – aromatic ketones 78, 79 – isolable zwitterion 234 – Claisen condensation 78, 80 – lowest unoccupied molecular orbitals – Dieckmann condensation 80 (LUMOs) 227 – esters 78 – meta-benzyne 228, 229 – fluoroacetonitrileCOPYRIGHTED 78, 79 – nomenclature MATERIAL 226 – Knoevenagel condensation 81 – nucleophilic addition 237–238 – Michael reaction 81 – in organic synthesis 245–246 alkene 30 – ortho-, meta-and para-benzynes alkyl and dialkyl carbenes 185 227 allenes (cycloaddition to 1,2-dienes) – ortho-benzyne 226 176 – para-benzyne 228, 229 allylic hydrogen 228 – reactions 228 amine 29–30 – representative 226 Reactive Intermediates in Organic Chemistry: Structure, Mechanism, and Reactions, First Edition. Maya Shankar Singh. c 2014 Wiley-VCH Verlag GmbH & Co. KGaA. Published 2014 by Wiley-VCH Verlag GmbH & Co. KGaA. 276 Index arynes (contd.) – classification 154 – transition metals 227–228 – cycloaddition to alkynes 177 – triple bond formation, regiochemistry – cycloaddition to 1,2-diene 176 239–240 – cycloaddition to 1,3-diene 176–177 – difluorocarbene 157–158 b – dimerization 160 Bamford–Stevens reaction 162, 163, 185 – dimethoxycarbene, stabilization 158 Bergman cyclization 229 – electron repulsion energy 156–157 biomedicinal application 269, 270 – α-elimination 163–164 biradicals 142–146 – EPR measurements 156 bromination, radicals reactions – formation 160 – allylic 120 – ‘‘intersystem crossing’’ 157 – benzylic 120, 121 – linear 155 – regioselective, 2-methylpropane 125–126 – methylene 153–160 – steroid structure, testosterone acetate – neutral conditions, formation 165–166 120, 122 – nomenclature 154 – Wohl–Ziegler reaction 120, 121 – nucleophilic, ambiphilic, and electrophilic 158 c – nucleophilic and electrophilic character camphor tosylhydrazone 162 155 carbanions – persistent carbene 158–159 – C–H bond deprotonation 70 – rearrangement 181–182 – chiral carbanions 90–91 – singlet carbenes 157 – C–X bond reduction 69 – small rings, generation 166–167 – enolate reactions, carbonyl groups. See – substituents 157 enolate reactions, carbonyl groups – triplet methylene 156 – homoallylic rearrangements. See carbenoids 165 homoallylic rearrangements carbocations – metal reaction, alkene 70–71 – alcohol 29 – negative ion, carbon–carbon double/triple –alkene 30 bonds 71 – alkyl groups 27 – reactions 77–78 – amine 29–30 – stability. See stability, carbanions – bonding and solvation 23–24 – structure and geometry. See structure and – carbenium ions 23 geometry, carbanions – carbonium ions 22, 23 – and tautomerism 91–95 – carbonyl compounds 30 carbene ligands, organometallic chemistry – cationic polymerization 50–51 – definition 188–189 – detection 36–37 –Dotz¨ benzannulation 191 – electronegative atom 28 – Fischer carbenes 189, 190 – feature 37 – NHC types, representative 192 – gas phase 26 – Schrock carbenes 189, 190 – halide 29 – Tebbe’s reagent 190 – hyperconjugation 27 – triazol-5-ylidene carbene 192 – hypervalent and hypovalent cations 24 carbene precursors 160 – hypovalent and hypervalent 25 carbenes – intermediates 21 – addition reactions. See addition reactions, – methanonium ion 24 carbenes – methyl cation 26 – bent and linear, electronic configurations – NMR spectrum 23 155 – nonclassical 51–55 – bond angle and frontier orbitals nature 156 – nucleophile 38 – carbenoids 165 – PMO description stabilization 28 – characteristics 153–154 – proton elimination. See proton elimination – chemistry 153 – reaction pathways 38 Index 277 – rearrangements. See rearrangements, – furan 240–241 carbocations – ortho-benzyne 240, 241, 243 – solvent effects 30–31 – taxodione synthesis 242, 243 –sp2-hybridized model 26 difluorocarbene 157–158 – stability. See stability, carbocations 1,2-diiodobenzene/phthalic anhydride, – structure and reactivity 21, 22 formation 235–236 – superacids 22 dimerization, carbenes 160 – tert butyl cation 25 dimethoxycarbene, stabilization 158 – trifluoromethoxide anion 28 1,3-dipolar cycloaddition 243–244 – triphenylmethanol 22 Dotz¨ benzannulation 191 – tropylium bromide 22 carbonyl compounds 30 e catalysts 3 electron paramagnetic resonance (EPR), cationic polymerization 50–51 radicals chemical reaction 3 – detection 103 chemically induced dynamic nuclear – energy absorption 104, 105 polarization (CIDNP) 107 – ethyl radical. See ethyl radical chemistry 1–3 – hyperfine splitting 104 chemoselectivity 7 – and PMR 104 chlorination – principle 104 – bromination, radical-catalyzed 119 – second-derivative spectrum, methyl radical – cyclohexane 119 104, 105 – 2,3-dimethylbutane 129 – spin polarization 104, 105 – iso-butane and 2-methylbutane 119 electron paramagnetic resonance (EPR) CIDNP. See chemically induced dynamic measurements 156 nuclear polarization (CIDNP) electron repulsion energy 156–157 coupled cluster (CC) 225 electrophile 4 cyclic carbenes 184 enolate reactions, carbonyl groups cycloaddition reactions, nitrenes – aldol condensation. See aldol condensation – alkenes 209–210 – enamines 81, 83 – alkynes 211–212 – Robinson ring-forming reaction. See – arenes 212, 213 Robinson ring-forming reaction – 1,3-dienes 210–211 ethyl radical – hyperconjugation model 106 d – location 106 density functional theory (DFT) 225 diadamantylcarbene 186 f diastereoselective 6 Favorskii rearrangement 87, 88 diazo compounds, photolysis Fischer carbenes 189, 190 – carbene precursors 160 FMO theory. See frontier molecular orbital – diazocarbonyl compounds, decomposition (FMO) theory 161 free radicals. See radical(s) – diazomethane 160–161 frontier molecular orbital (FMO) theory 117 – and ketene compounds, decomposition 161 h diazocarbonyl compounds, decomposition halide 29 161 homoallylic rearrangements diazomethane 160–161 – allylic and 86–87 Dieckmann condensations 80 – carbanion 87 Diels–Alder reaction – contraction of rings 88–89 – alkenes 242, 243 – Favorskii rearrangement 87, 88 – aryne, unexpected formation 241–242 – Neber rearrangement 89 – benzyne, diradical excited state 242 – Sommelet–Hauser rearrangement 89 – cycloaddition 240 – Wittig and Stevens rearrangements 87, 88 278 Index i linear carbenes 155 insertion reactions, carbenes lowest unoccupied molecular orbitals – alkylcarbenes 178 (LUMOs) 227 – alkylidene carbenes 180 – C–C bond 179 m – cyclic transition state 177 malonic anhydrides, thermal decomposition – hydrogen abstractions 177 250 – intramolecular 180 meta-benzyne 228, 229 – O–H bonds 179–180 methanonium ion 24 – single bonds 177–178 methylene 153, 178, 183 insertion reactions, nitrenes Michael reaction 81 – aryl nitrenes 214 – carbamates 212 n – carbazole formation 215 N-bromosuccinimide (NBS) 120 – cyclization 215 NBS. See N-bromosuccinimide (NBS) – functionalization, cyclohexanes 214 Neber rearrangement 89 – H abstraction-recombination mechanism neuropeptide S receptors (NPSRs) 258 213 N-heterocyclic carbenes (NHCs) 248–249 – intramolecular 214–215 nitrenes – saturated hydrocarbon 213, 214 – alkyl and arylcarbonyl 200 – selectivity 214 – azides and isocyanates 203 – sulfonylnitrenes 215 – azides, formation 203–205 ‘‘intersystem crossing’’ 157 – azides reaction 197 – carbenes 198 k – chemical reaction, ground state 199–201 ketene reaction 182, 183 – common derivaties 197–198 ketenes and cumulenes – cycloaddition reactions. See cycloaddition – acylketenes 249 reactions, nitrenes – bis-imine, methylketene reaction 252 – delocalized structure, triplet phenylnitrene – cycloaddition 251–252 201 – difluoroketene 248 – donor substituents, stabilization 200 – dimerization 251 – electronic structures 199 – diphenylketene, generation and trapping – electronic/steric effects, aromatic 201–202 247 – generation and trapping 198 – dissociation 248 – generation methods 203 – fluoroketene formation 247 – heterocycles 206–207 – β-lactams formation 253 – insertion reactions. See insertion reactions, keto-enol interconversion mechanism nitrenes – acetone 92 – IR spectroscopy 200 – acidic solution 91–92 – isocyanates 205 – benzoyl acetone 94–95 – isomerization and hydrogen shifts 197 – bicyclic and alkyl diketones 95 – LFP 201 – carbon–carbon double bond 92–93 – molecular entities 197 – carbonyl and ester groups 93–94 – nucleophiles. See nucleophiles – cyclopentane-1,2-dione 95 – nucleophilic reagents, aryl 197 – diethyl malonate 94 – organic reaction mechanisms 202–203 – 1,3-diketones