Index

The following index can be used to find topical information within the text. A comprehensive index of compounds, reagents, reactions and topics covered in graphical form on even-numbered pages is available at the following website: http:// www.worldscibooks.com/chemistry17815.html

Absolute stereochemistry, of Cecropia relationship between prostaglandins juvenile hormone, 453 and pyrrolizidines, 125 Absolute stereochemistry, reagent Acyclic stereogenic centers, control of, based control of, 185 29 Acetoacetic ester synthesis, of Acyl anion equivalents, 83, 185 substituted acetones, 53,451 metallated, dithiane as, 77, Acetylide addition, to ketone, 39 517 Activated cyclopropanes, opening with metallated cyanohydrins as, 103 thiolate anion, 123 metallated dihydropyran as, 527 Activating groups (SPh), 509 metallated furans as, 55 Acyclic diastereoselection, 3, 5, 13 Acylnitroso compounds, in approach and the prostaglandins, 123 to pumiliotoxin-C, 369 early application to synthesis, Aglycone, 537 455 Aldol condensation, 269 and juvabione, 5 and Cram's rule, 525 and prostaglandins, 5 and the Felkin-Ahn rule, 525 and pyrrolizidine alkaloids, 5 intramolecular, vinylogous, 81 and steroids, 5 intramolecular, 77, 79 relationship between prostaglandins minimization of ~-elimination and steroids, 125 during, 77

563 564 Organic Synthesis via Examination of Selected Natural Products

versus alkylation for carbon-carbon in planning synthesis of in conjugate addition I bond formation, 107 gephyrotoxin, 379 191 Aldol-dehydration, double, importance of in route to in intramolecular intramolecular, 51 pumiliotoxin-C, 369 cyclopropanations, 1 Aldol-dehydration, intramolecular, 27, role in determining relative, 95 39 stereochemistry of Diels-Alder, Asymmetric reduction, real Aldols, synthesis of using crotylation 361 controlled,61 reactions, 527 Allylsilanes, model for asymmetric Asymmetric synthesis, Alkaloids, total synthesis of, 281 addition to enones, 193 of aldols using crotylat Alkenes, as latent carbonyl groups, 233 Alternate or ambident functional reactions, 527 Alkylation groups (A-functions), examples of, of prostaglandins, 101 deconjugative, 35, 37 209,211 the chiral pool approa( ~-, diastereoselective of ester enolates Aminoketone, construction of via Aziridinium ions, prep; with arene-chromium Mannich reaction, 293 chemistry of, 435, 4, tricarbonyls, 179 Analgesics (painkillers), 405 Azomethine ylids, method intramolecular of enamine, 376 Androsterone, 29 generation for use in cyd intramolecular, of enolate, 253, Annulation reactions (annelation 149 261 reactions), 23 of enolate, stereoelectronics of, Anodic oxidation, of amides, 289 Baeyer-Villiger oxidation, 1 513 Anomeric effect, 505 309,327,511,523,539 of enolates, 1,2-asymmetric Anomeric effect, double Baeyer-Villiger oxidation, induction model, 157 as stereocontrol element in regioselective, 85 of imidate anion, 519 N,O-acetal formation, 289 Baker's yeast, 187, 195 versus aldol for carbon-carbon in spiroacetals, 523 Bamford-Stevens reaction, : bond formation, 107 Anthranilic acid, 371 Barbier-Wieland degradatio Alkyne, semi-hydrogenation to alkene, Arachidonic acid, 73 Barton reaction, 105, 339, 105 Arene-chromium tricarbonyl complex, Batrachotoxin, 337 Allenol ethers, synthesis and hydrolysis reaction with ester enolates, 179 Beckman rearrangement, 2; to cis-unsaturated aldehyde, 377 Aspirin, 75 Biomimetic synthesis, 41, 2 Allylation, Pd-mediated, 189 Asymmetric conjugate addition of morphine, 7,413 Allylic oxidation, using Corey-Fleet catalytic, of methyl group to of pumiliotoxin-C, 367 reagent, 427 enone, 373 of steroids, 3 Allylic rearrangement, promoted by of amide nucleophile to Biosynthesis HBr, 39 unsaturated ester, 373 of morphine, 411, 413 Allylic strain Asymmetric Diels-Alder, predictive proposal for Dentrobat as a conformational control model for, 93 367 element, 385 Asymmetric induction, 1,2-, 159 Biosynthetic pathway, 3 importance in 1,2-asymmetric Asymmetric induction, Bischler-Napieralski reactiOl induction model for enolate Cornforth model, 455 Blocking groups, 25 alkylation, 157 Felkin-Ahn model, 455 Brown allylation, 351 Index 565

in conjugate addition reactions, Cahn-Ingold-Prelog (CIP) convention, 191 167 in intramolecular Calcimycin (A23187), 11, 505-529 cyclopropanations, 139 Carbene generation, by a-elimination relative, 95 reaction, 433 Asymmetric reduction, reagent Carbocation, vinylic, nucleophilic controlled,61 capture of, 57 Asymmetric synthesis, Carbocycle synthesis, 3 of aldols using crotylation Carbohydrates, as source of chirality, reactions, 527 517 of prostaglandins, 101 Carbon-hydrogen activation, via Barton the chiral pool approach, 181 reaction, 339 Aziridinium ions, preparation and Carbon-hydrogen insertion, of carbene chemistry of, 435, 437, 439 (vinylidene) in approach to Azomethine ylids, method of morphine, 433 generation for use in cycloadditions, Carbopalladation, approach to 149 prostaglandins, III Cecropia juvenile hormone, 11,445­ Baeyer-Vi11iger oxidation, 187,235, 474 309,327,511,523,539,541 Celebrex, as COX inhibitor, 75 Baeyer-Vil1iger oxidation, Charge affinity inversion (charge regioselective, 85 reversal),211 Baker's yeast, 187, 195 Chiral auxiliary, Bamford-Stevens reaction, 287 for Diels-Alder reaction, 91 Barbier-Wieland degradation, 29 phenylglycinol as in synthesis of Barton reaction, 105, 339, 381 pumiliotoxin-C, 367, 369 Batrachotoxin, 337 proline as in synthesis of Beckman rearrangement, 235,339 pumiliotoxin-C, 371 Biomimetic synthesis, 41, 291 Chiral pool of morphine, 7,413 approach to asymmetric synthesis, ofpumiliotoxin-C, 367, 369 181, 183, 185, 187 of steroids, 3 definition, 103 Biosynthesis in approach to lasonolide A, of morphine, 411, 413 485 proposal for Dentrobatid alkaloids, in calcimycin synthesis, 517 367 Chiral reducing agent, design of, 97 Biosynthetic pathway, 3 Chiral, crotylborane, 527 BiscWer-Napieralski reaction, 299, 305 Chirality transfer, issues of geometry in Blocking groups, 25 Ireland-Claisen,513 Brown al1ylation, 351 Chirality, transfer of, 121 'l

566 Organic Synthesis via Examination of Selected Natural Products

Chloroacrylonitrile, a-, as ketene Conformations, of allylic alcohols and Crotylborane, chiral, 527 equivalent in Diels-Alder, 85 effect on epoxidation Cuprate addition, stereoel Chloronitrile, a-, conversion to ketone, stereochemistry, 471 517 85 Conjugate addition, to enone for Curtin-Hammett Principle Cholesterol, 3, 17, 19 introduction of PG sidechain, 101 Curtius rearrangement, 2( Cholesterol, biosynthesis of, 41 Conjugate addition-molate trapping, to establish ketene eql Cholesterol, synthesis of, 29 105,373 Cyanohydrin, metallated a Cholic acid, 17 Convergence, importance in planning a equivalent, 103 Cladinose, L-, in erythromycin A, synthesis, 493 Cyclic structures, for cont 537 Convergent synthesis, 517, 527, 537 multiple acyclic stereoge Claisen condensation, crossed, 311 comparison with linear synthesis, 515,521 Claisen condensations, iterative in 99 Cyclization, base-initiated, biosynthesis of polyacetates, 483 importance in synthesis design, Cycloaddition, [2+2] OfYl Claisen rearrangement, 197, 343 204,205 enone, 169 and transfer of chirality, 121,513 of prostaglandins, 105 Cycloalkene synthesis, gen

as enforced SN 2' reaction, 55,451 Cope elimination, 143,267 103 enolate, 513 Cope rearrangement, 311 Cycloalkenes, as latent die< how to see potential for use in in plan for synthesis of reserpine, compounds, 233 synthesis, 451 309 Cyclohexenes, conversion 1 Johnson-Faulkner, 55 stereochemistry of, 171 acylcyclopentanes, 20 stereochemical course of, 171, Corey lactone, for prostaglandin Cyclohexenone, from cycle 451 synthesis, 89 51 Codeine, as cough suppressant, 405 Corey-Fuchs reaction, 349 Cyclooxygenase (COX) Codeine, conversion to morphine, 411, Corey-Nicolaou lactonization, 549 in biosynthesis of prost 413,421 Corey-Rucker reagent, in Peterson 75 Colchicine, 561 olefination, 389 inhibitors of, 75 Collins oxidation, 509 Corey-Suggs reduction, 115 Cyclopentane, from cyclohc Computer-assisted synthesis design, Corey-Winter reaction, 263 Cyclopropanation, of alkenl 282,283 Cornforth model, for 1,2­ Cyclopropanation, stereoch Configurational stability, of 5,5­ diastereoselection, 455 intramolecular carbene-al

hemiacetal, 543 Corticosteroids, introduction of Cll reactions, 139 Conformational analysis oxygen, 31, 35 Cyclopropane, geminally ac in allylic systems within context of Corticosteroids, preparation by 127,139,141 ester enolate alkylation, 57 polyolefin cyclization, 59 of allylic alcohols, 471 Cortisone, 17, 19, 31,39 Dart-poison frogs, 337 of N-acyltetrahydroisoquinolines, Crabtree's catalyst, for directed Decahydroquinoline alkaloi, 417 hydrogenation, 371 Deconjugation, ofenone, 2 of substituted cyclohexane, 379, Cram selectivity, 509, 525 Demerol, as analgesic, 405 381 Crotylation-oxidative cleavage, strategy Desosamine, D-, in erythro Conformational mobility, 543 for polypropionate synthesis, 527 537 Index 567

Crotylborane, chiral, 527 Dess-Martin periodinane oxidation, Cuprate addition, stereoelectronics of, 493 517 Desulfurization, 253 Curtin-Hammett Principle, 295 Desymmetrization Curtius rearrangement, 267, 353 in enzyme-mediated reduction, 35 to establish ketene equivalency, 91 of cyclohexanone, 165 Cyanohydrin, metallated as acyl anion in synthesis of erythronolide A, equivalent, 103 539 Cyclic structures, for controlling Deuterium labeling experiments, in multiple acyclic stereogenic centers, design of calcimycin synthesis, 507 515,521 Diastereoselection, Cyclization, base-initiated, 523 in carbene-alkene addition Cycloaddition, [2+2] ofynamine with reactions, 139 enone, 169 reagent control of, 95 Cycloalkene synthesis, general strategy, relative within context of 103 prostaglandin synthesis, 95 Cycloalkenes, as latent dicarbonyl substrate control of, 95 compounds, 233 Diastereoselective hydrogenation, in Cyclohexenes, conversion to cyclic system to control acylcyclopentanes, 20 stereochemistry, 177 Cyclohexenone, from cyclopentene, Diastereoselectivity, 1,2-, 513 51 Diastereoselectivity, 1,4-, 513 Cyclooxygenase (COX) Diastereoselectivity, in crotylation in biosynthesis of prostaglandins, reaction, 527 75 Diastereoselectivity, in prostaglandin inhibitors of, 75 synthesis, 119 Cyclopentane, from cyclohexene, 77 Dicarbonyl compounds, 1,4-, synthesis Cyclopropanation, of alkenes, 123 of, 55 Cyclopropanation, stereochemistry of Diels-Alder reaction, 21, 165, 197 intramolecular carbene-alkene aromaticity as a driving force, 393 reactions, 139 in plan for synthesis of reserpine, Cyclopropane, geminally activated, 309 127, 139, 141 ketene equivalents, 83 Lewis acid promoted, 83, 91 Dart-poison frogs, 337 lowering temperature through use Decahydroquinoline alkaloids, 359 of more reactive dienophile, 91 Deconjugation, of enone, 29, 107 of nitroalkene and butadiene, 77 Demerol, as analgesic, 405 of acylnitroso compounds, 145 Desosamine, D-, in erythromycin A rate as a function of dienophile, 537 91 568 Organic Synthesis via Examination of Selected Natural Products

retro, for generation of acylnitroso in retrosynthetic analysis of Enantioselective reduction, compound,147 twistane, 247 enzymes, 35 stereocontrol in, 85 in synthesis of triquinacene, 271 Enantioselective synthesis, ( Diels-Alder-retro-aldol, strategy for reinforcing and interfering, 215 using enzymatic reductio controlling vicinal stereochemistry, Dipolar cycloaddition, 1,3­ Enantioselectivity, in croty!: 165 importance of reversibility in reaction, 527 Diels-Alder-retro-Diels-Alder, in plan nitrone approach to HTX, 357 Ene-reactions, intramolecul for synthesis of reserpine, 315 azomethine ylid in approach to acylnitroso compounds, ~ Dienamide synthesis, 361, 363 pyrrolizidine alkaloids, 149 Enolate alkylation, stereoch Difunctional relationships, 5, 7, 205 of nitrones in approach to course of, 513 1,2-, construction of, 219 pyrrolizidine alkaloids, 143 Enolate protonation, kineti, 1,3-, construction of, 217 Dipole-dipole repulsion, importance in stereochemistry in, 549 1,3-, relevance to Mannich asymmetric Diels-Alder, 93 Enolate-Claisen, importanc reaction, 281 Directed reactions, 307 geometry, 513 1,4-, and construction of 5­ addition offree radicals, 116 Enyne synthesis, via Petersc membered rings, 227 addition to unactivated alkenes, olefination, 383 1,4-, construction of, 221, 223 III Enzymatic reduction, 35 1,5-, and construction of6­ hydrogenation, heterogenous, of ketone to alcohol US] membered rings, 225, 227 376 yeast, 187, 195 1,5-, construction of, 223 hydrogenation, in synthesis of using horse liver alcoho and construction of pumiliotoxin-C, 371 dehydrogenase (HLA cyclohexanones, 225 Dodecahedrane, relationship to Epimerization and thermod and construction of triquinacene, 265 control stereochemistry ir cyclopentanones, 227 spiroacetals, 529 classification of, 213 Electrochemistry, anodic oxidation of Epoxidation, stereochemistr generation by insertion reactions, amides, 289 corticosteroid synthesis, 1 235 Electrophilic addition, Epoxide opening, regioselec importance in retrosynthetic iodolactonization, 87 351 analysis, 247 Electrophilic addition, selectivity Equilenin, 3, 19 importance in synthetic plan for between alkenes, 39 Equivalency concept porantherine, 281 Electrophilic functional groups iodonium ion as proton importance in synthetic plan for (E-functions), examples of, 209 87 porantheridine, 287 Elimination, P-, avoidance of, 87 ketene equivalents, 83 in analysis of lasonolide A Enantiomer production, of natural 1,2-bis-sulfonylethylene substructures, 483 products depending upon plant equivalent, 391 in approach to pumiliotoxin-C, source, 377, 379 of terminal alkene to ale 371 Enantiomers, separation by Erythromycin, 13, 537-555 in Diels-Alder route to chromatography of chiral support, Eschenmoser sulfide contrae pumiliotoxin-C, 365 429 Eschweiler-Clark methylatio Estrone, 3, 19 Index 569

Enantioselective reduction, using Felkin-Ahn model, for 1,2­ enzymes, 35 diastereoselection, 455, 509, 525 (in Enantioselective synthesis, of twistane aldol) using enzymatic reduction, 255 Finkelstein reaction, 321,455 Enantioselectivity, in crotylation Formyl anion equivalent, lithiated reaction, 527 dithiane as, 219 Ene-reactions, intramolecular of N­ Free radical addition acylnitroso compounds, 345 approach to prostaglandins, 115 Enolate alkylation, stereochemical intermolecular, 115, 117 course of, 513 Free radical allylation, in approach to Enolate protonation, kinetic control of perhydrohistrionicotoxin, 345 stereochemistry in, 549 Free radical cyclization Enolate-Claisen, importance of enolate conformational analysis of, 485 geometry, 513 of N-centered radical in morphine Enyne synthesis, via Peterson-type synthesis, 425 olefination, 383 stereochemistry of, 321 Enzymatic reduction, 35 Free radical intermediate, to avoid \3­ of ketone to alcohol using Baker's elimination, 87 yeast, 187, 195 Functional group relationships, and using horse liver alcohol appearance of synthetic approaches, dehydrogenase (HLAD), 255 395 Epimerization and thermodynamics, to Functional group transformation control stereochemistry in (FGT), to establish equivalency, 85, spiroacetals, 529 219 Epoxidation, stereochemistry in Functional groups, importance of corticosteroid synthesis, 13 compatability in synthesis design, Epoxide opening, regioselectivity in, 205 351 Functionality, level of, 20 Equilenin, 3, 19 Furans, metalated, as acyl anion Equivalency concept equivalents, 55 iodonium ion as proton equivalent, Furst-Plattner rule 87 in epoxide openings, 295 ketene equivalents, 83 variation of for nucleophilic 1,2-bis-sulfonylethylene as ethylene opening of bromonium ion, equivalent, 391 303 of terminal alkene to aldehyde, 283 Fusidic acid, 17 Erythromycin, 13, 537-555 Eschenmoser sulfide contraction, 383 Geminally activated cyclopropanes, Eschweiler-Clark methylation, 267 reactions with amines, 139, 141 Estrone, 3, 19 Gennari-Still reaction 487, 495 570 Organic Synthesis via Examination of Selected Natural Products

Gephyrotoxin, 9, 374-395, 337 Hydrazones, as A-functional groups, Julia olefin synthesis, 453,4 difunctional relationships in, 375 211 relationship to Grob enantioselective synthesis, debate Hydrogenation, semi, of alkyne, 39 fragmentation, 459 over absolute stereochemistry, Hydrogenation, stereochemistry of, 25 variations of, 457 377 Julia-Lythgoe-Kocienski olel structure and determination of Imide, size as a cyclohexane synthesis, 485, 489,491, ' absolute configuration, 377 substituent, 381 Juvabione, 5,29,159-197 Grieco-Sharpless method, formal Imides, ketone-like reactivity of, 375 determination of absolu' dehydration of terminal alcohol, 485, Iminium ion, stereoelectronic model configuration via syntl 547 for addition of nucleophile to, 285, Juvenile hormones, 159,44: Grob fragmentation, relationship to 289 Julia olefin synthesis, 459 Insect sex hormones, 447 Ketene equivalent Insertion reactions, for generation of chiral, 93 Hastanecine, 141 difunctional relationships, 235 unsaturated ester as, 91 Heck reaction, intramolecular, as Intramolecular a-chloroacrylonitrile as i oxidative phenolic coupling alkylation, of enamine, 393 Alder reaction, 293 alternative, 427 conjugate addition, to construct a-chloroacryloyl cWorid4 Henry reaction, 77 pyrrolidine, 387 for Diels-Alder reaction, example of nitro group as an N­ delivery of nucleophile in epoxide Ketone reduction, axial deliv function, 209 opening, 301 hydride, 29 Heroin, as analgesic, 405 delivery, of nucleophile via N,N­ Kinetic control, of stereochel Heterogenous catalytic hydrogenation, acetal formation, 295 enolate protonation, 311, ~ stereocontrol of, 376, 377 Ionophores, as a family of natural Kornblum oxidation, 219, 4~ Histrionicotoxin, 7, 335-357, 337 products, 505 enantioselective synthesis via Ionophores, introduction to, 497 Lanosterol, 41 double-alkylation strategy, 351, Ireland-Claisen, importance of enolate Lasolocid A (X537A), as an i 353 geometry, 513 509 of ene-yne substructure via Isomerization, of cyclopentadienes, 83 Lasonolide A, 11,479-497, ! Sonogashira reaction, 351 Isomerization, Pd-mediated, 37 biological activity of enar synthesis of ene-yne substructure Isonitriles, as free radical traps, 117 481 via Wittig reaction, 349 Isotope dilution method, application to Latent Craxis ofsymmetry, i synthesis via intramolecular nitrone morphine synthesis, 413 of calcimycin synthesis, 50? cycloaddition, 355, 357 Iterative reactions, in Cecropia juvenile Latent carbonyl groups, alken Histrionicotoxins, 337 hormone syntheses, 473 233 Homosteroid, D-, 20,33 Iterative synthesis, 449 Laudanosine, 411 Horner-Wadsworth-Emmons reaction, of trisubstituted olefins, 463 LeChatelier's Principle, 21 81,363,447,497,523,525 Limonene, R-, 181, 183 Gennari-Still modification of, 487, Johnson-Faulker Claisen, 451 Linear strategy, 517 495 Johnson-Lemieux oxidation, 283, 437 Linear synthesis, comparison' Hydration of nitriles, catalytic, 371 Jones oxidation, 297 convergent synthesis, 99 Index 571

Julia olefin synthesis, 453, 457 Luciduline intermediate, structural relationship to Grob relationship to reserpine fragmentation, 459 intermediate, 309 variations of,457 Lycopodium alkaloids, examples of, Julia-Lythgoe-Kocienski olefin 293 synthesis, 485, 489, 491,493 Lysine, as chiral pool starting material Juvabione, 5,29,159-197 for porantheridine, 287 determination of absolute configuration via synthesis, 181 Macrolactonization, 497, 537, 543, Juvenile hormones, 159,447 549,551 Macrolides, 11 Ketene equivalent Mannich reaction chiral,93 and 1,3-difunctional relationships, unsaturated ester as, 91 281 a-chloroacrylonitrile as in Diels- double intramolecular in sparteine Alder reaction, 293 synthesis, 291 a-chloroacryloyl chloride as, 91 in alkaloid synthesis and for Diels-Alder reaction, 83 biosynthesis, 281 Ketone reduction, axial delivery of Mass spectrometry, in structure hydride, 29 determination of dart-poison Kinetic control, of stereochemistry in alkaloids, 337 enolate protonation, 311, 549 McGarvey-Fleming model, for Kornblum oxidation, 219, 437 asymmetric alkylation of enolates, 157 Lanosterol, 41 Mechanisms, importance in synthesis Lasolocid A (X537A), as an ionophore, design, 204, 205 509 Meerwein-Pondorf-Verley reduction, Lasonolide A, 11,479-497,537 301 biological activity of enantiomers, Methadone, as analgesic, 405 481 Michael addition, deconjugative, Latent Craxis of symmetry, in design 33 of calcimycin synthesis, 507 Michael reaction, 23 Latent carbonyl groups, a1kenes as, Michael-Michael reaction, of dienolate 233 with acrylate as Diels-Alder Laudanosine, 411 equivalent, 327 LeChatelier's Principle, 21 Midland reduction, 61 Limonene, R-, 181, 183 Mislow-Evans rearrangement, and Linear strategy, 517 transfer of chirality, 121 Linear synthesis, comparison with Mitsunobu reaction, 107,419,423 convergent synthesis, 99 Moffatt-type oxidation, 487 572 Organic Synthesis via Examination of Selected Natural Products

Monensin, as an ionophore 505, 509, NMR spectroscopy, in structure regiochemical problem of morphine, 415, 4: 561 determination of dart-poison Morphine, 7 alkaloids, 337 site selective equivalent Morphine, 403-439 Nonactin, as an ionophore 509 diazonium chemistry and analgesics, 405 Nucleophilic functional groups Oxime derivatives, as A-fun groups, 211 biosynthesis of, 411, 413 (N-functions), examples of, 209 synthesis via intramolecular Oxy-Cope rearrangement electrophilic aromatic Olefin geometry, importance in in synthesis oflucidulir substitution, 435 establishing vicinal stereochemical stereochemistry of, 17l Ozonolysis, 523, 527 synthesis via relationships, 447 perhydrophenanthrene-based Olefin metathesis, 497 approach, 429 Olefin stereochemistry, as function of Painkillers (analgesics), 405 Perhydrohistionicotoxin boat versus chair transition states in N,O-relationships, 1,3-, in alkaloids, oxy-Cope, 175 retrosynthetic analyses, 297 Olefin synthesis via N-acyliminium ions N-acyliminium ion cyclizations classification of according to acylnitroso compoun Perhydroindan, 20 in Mannich-type reactions with method of construction, 474 alkenes, 341 trisubstituted, 11 Perhydronaphthalene (deca Perillaldehyde, 185 in synthesis of gephyrotoxin, 379 Organopalladium chemistry, Ill, 113 N-acylnitroso compounds, Oxetane formation, in competition Periodate cleavage, ofvicino Peterson olefination, 357 intramolecular ene reactions of, with Grob fragmentation, 461 PGA, structure of, 77 345 Oxidation state Nef reaction, for conversion of adjustment of in PG synthesis, PGA1, synthesis of, 79 N-function to E-function, 209, 221 105 PGA1 , the problem of acycL Neighboring group participation, adjustments, in synthesis of diastereoselection, 123 PGE structure of, 77 301 reserpine, 317 b PGE synthesis of, 79 Neuroscience, importance of dart­ changes at carbon, 21, 23 b PGE , structure of, 75 poison frogs to, 337 importance of in synthesis of 1 PGE , synthesis of, 109 Nitrile chemistry, comparison of reserpine, 311 1 PGF , synthesis of, 79 pumiliotoxin-C and reserpine role in selection of starting 1a syntheses, 367 materials for synthesis, 185 PGF1a, synthesis of, 117 Nitroalkanes Oxidation, 511 PGF1a, synthesis of, 87 as A-functions, 209 Oxidation, conversion of amine to PGF1/3, synthesis of, 79 importance of tautomers, 209 ketone, 79 PGG1 , structure of, 75 Nitrone cycloaddition Oxidation, Saegusa, 117 PGH1, structure of, 75 Photochemistry, in triquina( intramolecular, 297 Oxidative cleavage of alkene to synthesis, 269, 273 in pyrrolizidine alkaloid synthesis, ketoaldehyde, 79 143 Oxidative phenolic coupling Photocycloadditions, directe to establish 1,3-N,D-relationship, a mechanistic interpretation, 413 intramolecular, 307 Pictet-Spengler reaction, 29' 297 alternatives to, 419 Index 573

regiochemical problems in synthesis Pictet-Spengler reaction of morphine, 415, 417 in biosynthesis of morphine, 411 site selective equivalent via aryl Polyacetates, natural products derived diazonium chemistry, 415 from acetic acid, 483 Oxime derivatives, as A-functional Polyketides, 13 groups, 211 Polymers, polypropionates as, 537 Oxy-Cope rearrangement Polyolefin cyclizations, 43 in synthesis of luciduline, 293 acetal as initiator, 51 stereochemistry of, 171 alkynes as terminators, 53 Ozonolysis, 523, 527 allylic alcohol as initiator, 49 effect of Cll substitutents in Painkillers (analgesics), 405 approach to corticosteroids, 59 Perhydrohistionicotoxin rates as a function of substituents, retrosynthetic analyses, 339 63 via N-acyliminium ions and N­ termination with an allylic silane, acylnitroso compounds, 339 63 Perhydroindan, 20 termination with ethylene Perhydronaphthalene (decalin), 20 carbonate, 57 Perillaldehyde, 185 termination with nitroethane, 57 Periodate cleavage, of vicinal diol, 525 Polypropionate natural products, 13, Peterson olefination, 357 505,537 PGA, structure of, 77 calcimycin as, 505

PGA1, synthesis of, 79 introduction to, 497 PGA2, the problem of acyclic repeating unit in, 527 diastereoselection, 123 synthesis via crotylation-oxidative PGEl> structure of, 77 cleavage strategy, 527 PGEl> synthesis of, 79 Porantherilidene, 285

PGE2, structure of, 75 Porantherine,281

PGE2 , synthesis of, 109 Practical synthesis, of juvabione, 63

PGF1u, synthesis of, 79 Principle ofvinylogy, 375 PGF2u, synthesis of, 117 Progesterone synthesis, analysis in PGF2u, synthesis of, 87 terms of difunctional relationships, PGF2p, synthesis of, 79 229

PGG2 , structure of, 75 Progesterone, 17

PGH2, structure of, 75 Propargylic alcohols, use in Photochemistry, in triquinacene trisubstituted olefin synthesis, synthesis, 269, 273 463 Photocycloadditions, directed and Prostaglandin synthesis, analysis in intramolecular, 307 terms of difunctional relationships, Pictet-Spengler reaction, 299, 329 231 574 Organic Synthesis via Examination of Selected Natural Products

Prostaglandins, 3, 71-127 Relative stereochemistry, use of cyclic Ring synthesis from arachidonic acid, 73 compounds to control, 521 five-membered, 3 strategies for synthesis of, 99 Relay synthesis, 27 six-membered, 3 Protecting group selection, of erythromycin A, 551 Robinson annulation, appli compatability in complex synthesis, of morphine, 409 perhydrophenanthrene al 545 Research, the search part of, 387 morphine, 429 Pumiliotoxin, comparison of Diels- Reserpine intermediate, structural Alder routes to, 359, 365 relationship to luciduline Saegusa oxidation, 117 Pumiliotoxin-C, 7, 358-373 intermediate, 309 Sakurai, reaction, 193 Pummerer rearrangement, 219 Reserpine, 9, 299-329 Salutaridine,413 Pyrrolizidine alkaloids,S, 137-151 as substituted cyclohexane, 299 ScWosser modification ofV introduction to, 299 reaction, 55 Quinic acid, as starting material for synthetic plan, 299 Schlosser's base, 527 reserpine, 321 Reserpine-isoreserpine, stereochemical Seeo-acid relationship between, 313, 319, cyclization of, 545 Reaction classification, 207 325 definition of, 537 Reaction conditions, as tool for Resolution Semi-hydrogenation, of alk achieving thermodynamic or kinetic in enantioselective approach to Sex hormones, 17 control, 329 twistane, 257 Sharpless epoxidation, 351 Reaction sequencing, importance of in of acid as ephedrine salt, 89 Sigmatropic rearrangement

reserpine synthesis, 327, 329 of ketone via chiral acetal 2,3- as formal SN2' real Reactive intermediates, tactics for formation and diastereomer 471 generation of, 145, 147 separation, 433 and transfer of chirality Reagent-controlled asymmetric of S,S-hemiacetal in synthesis of Singlet oxygen, use in pros1 synthesis, in allylation reactions, 491 erythronolide A, 545 synthesis, 101

Recycling, of stereoisomeric alcohols Reticuline, 411 SN 2' reactions via oxidation-reduction, 87 Retroaldol condensation, 165, 167 Claisen rearrangements Reduction Retro-Aldol condensation, in plan for equivalent of, 343 of alkynes, control of synthesis of reserpine, 307 in approaches to Cecro stereochemistry, 171 Retro-Claisen condensation, 169 hormone, 467 of iodide in presence of ester and Retro-Diels-Alder, to generate N­ Solvolysis lactone, 87 acylnitroso reactive intermediate, of allylic alcohol, 49 selective, of nitroalkane, 79 345 of unsaturated nosylate. Reductive homologation, of ketone, Retronecine, 143, 145 Sonogashira reaction, 351 337 Retrosynthetic analysis, 20, 205 Sparteine, biomimetic syntb Regiochemistry, of N-acyliminium ion Ring expansion, cyclopentanone to Spiroacetals, 505 cyclizations, 343 lactam via Beckmann rearrangement thermodynamic control Regioselective hydration of alkene, of nitrone, 439 stereochemistry of, 51 directed, 87 Ring opening reaction, of cyclobutane and the anomeric effect Relative asymmetric induction, 191 with relief of strain, 169 Squalene oxide, 43 Index 575

Ring synthesis Squalene, 41 five-membered, 3 Stacking, 1t-1t, importance in six-membered, 3 asymmetric Diels-Alder, 93 Robinson annulation, application to Starting materials, importance of perhydrophenanthrene approach to recognition in synthesis design, 204, morphine, 429 205 Stereochemical control, importance of Saegusa oxidation, 117 kinetics and thermodynamic Sakurai, reaction, 193 considerations, 325 Salutaridine, 413 Stereochemical relationship, control of Schlosser modification ofWittig 1,2 by addition reactions, 123, 139 reaction, 55 1,4 by transfer of chirality, 123 Schlosser's base, 527 by thermodynamics or kinetics, 37 Seco-acid vicinal relationships through Diels- cyclization of, 545 Alder reaction, 167 definition of, 537 vicinal relationships, 139 Semi-hydrogenation, of alkyne, 141 through bowl-shaped nature of Sex hormones, 17 reactant, 189 Sharpless epoxidation, 351 through molecular shape, 301, 321 Sigmatropic rearrangements starting material vs

2,3- as formal SN 2' reactions, 467­ thermodynamics, 521 471 Stereochemistry and transfer of chirality, 121 importance of controlling relative, Singlet oxygen, use in prostaglandin 29 synthesis, 101 in formation of bromohydrin, 39

SN 2' reactions kinetic vs thermodynamic control Claisen rearrangements as of, 435 equivalent of, 343 of addition of acetylide to steroidal in approaches to Cecropia juvenile ketone, 39 hormone, 467 of enolate alkylation, 513 Solvolysis of irninium ion reduction in of allylic alcohol, 49 reserpine synthesis, 305 of unsaturated nosylate, 45 reagent control of, 97 Sonogashira reaction, 351 remote control of in Sparteine, biomimetic synthesis of, 291 hydrogenation, 383 Spiroacetals, 505 thermodynamic control in thermodynamic control over spiroacetal formation, 507 stereochemistry of, 507 thermodynamic control of and the anomeric effect, 505 epimerization, 527 Squalene oxide, 43 thermodynamic control over, 505 576 Organic Synthesis via Examination of Selected Natural Products

vicinal, control through kinetic Steroids, ring juncture stereochemistry, as template for reaction protonation, 169 17 development, 179, 18 vicinal, the problem of control in Stitching methodology, using boranes, as tool for understandin acyclic systems, 161 185 stereochemistry, 193 Stereocontrol Stork-Danheiser synthesis, 327 biomimetic, 3,41 acyclic using ring-opening strategy, Stork-Eschenmoser hypothesis, 43 importance of mechanis 537 Strategy, 13,205 stereochemical princiF acyclic and cyclic, 3 3-component coupling for PG design, 204, 205 importance of order of operations, synthesis, 105 selection of key interme, 45 allylation-oxidation for use in to meet demand for sup importance of, 25 polyacetate synthesis, 491 compound, 561 of cyclic stereogenic centers by for control of vicinal olefin geometry, 53 stereochemistry, 119 Tactics, 13,205 Stereoelectonics for molecules containing multiple improvement of for prol analysis ofimine addition reactions, acyclic stereogenic centers, 515 prostaglandin synthesi 385 for synthesis of lasonolide A via Tamao-Fleming oxidation, 3 considerations, 329 intramolecular Stille coupling, Tandem reactions, 197 control in nucleophilic opening of 483 aldol-dehydration-alkyla epoxide, 295, 301 for synthesis of lasonolide via approach to morphine control, of stereochemistry in macrolactonization reaction, 495 radical cyclization-additi ketone reduction, 541 Structure determination, by synthesis, elimination approach 1 model for addition of nucleophile 11,447,449,481 morphine, 423 to imine, 285 Sulfonium salts, as A-functional groups, reduction-hydrogenolysi of N-acyliminium ion cyclizations, 211 formation-reduction, ; 341,343 Sulfoxides, as A-functional groups, stereochemistry controU of cuprate addition, 517 211 thermodynamics versu Stereoelectronic effects, on reserpine­ Sulfur-containing heterocycles, use to 523 isoreserpine oxidation-reduction set stereochemistry in acyclic systems, sulfone addition-alkylatie chemistry, 319 473 approach to morphine Stereorandom synthesis Sween oxidation, 425, 491 Target-oriented synthesis, ne purpose of, 447, 451 Symmetry considerations, 205 value to medicinal chemistry, 81 as a consideration in retrosynthetic Tautomerization, importance Stereoselective olefin synthesis, 447 analysis, 375 determining functional gee Steric effects, in cis-decalin in approach to porantherine, 281 reactivity, 213 conformational equilibria, 295 in synthetic approaches to Terpenoids, side chain sterec Steroid side chain problem, 157, 159 triquinacene, 265, 269, 273 problem,S Steroid synthesis use of in erythronolide A strategy, Testosterone, 29 annulation strategy, 35 539 Thermodynamic control industrial scale, 35 Synthesis of epimerization stereoc] Steroids, 3 and structure determination, 11 527 Index 577

as template for reaction of stereochemistry in ketone development, 179, 185 alkylation, 541 as tool for understanding reaction of stereochemistry, 521 stereochemistry, 193 as a stereochemical control biomimetic, 3, 41 element, 305 importance of mechanistic, control of intramolecular aldol stereochemical principles during regiochemistry, 79 design, 204, 205 control over stereochemistry, 505 selection of key intermediates, 19 for controlling spiroacetal to meet demand for supply of stereochemistry, 507 compound, 561 Thiele's acid, 269 Three-component coupling, strategy Tactics, 13, 205 for PG synthesis, 99, 107, 109 improvement of for problems in Thromboxanes,93 prostaglandin synthesis, 89 Tin hydride reductions, catalytic in tin, Tamao-Fleming oxidation, 327,485 93 Tandem reactions, 197 Todomatuic acid, 163 aldol-dehydration-alkylation Torsional strain approach to morphine, 431 importance in enolate alkylations, radical cyclization-addition­ 157 elimination approach to in macrocycle, 543 morphine, 423 Total synthesis, as a tool for reduction-hydrogenolysis-imine methodology development, 151 formation-reduction, 363 Transannular strain, in macrocycle, 543 stereochemistry controlled by Transfer of chirality, 1,2- to 1,4, 513 thermodynamics versus kinetics, Transfer of chirality, 121, 513 523 in Claisen rearrangement, 513 sulfone addition-alkylation Triquinacene, 7 approach to morphine, 419, 421 Triquinacene Target-oriented synthesis, necessary origin of 5-membered rings in considerations, 205 synthesis of, 267, 269 Tautomerization, importance ofin relationship to dodecahedrane, 265 determining functional group synthesis of, 265-273 reactivity,213 Trisubstituted olefin synthesis, Gennari­ Terpenoids, side chain stereochemistry Still compared with normal HWE problem,S reactions, 487 Testosterone, 29 Twistane, 7 Thermodynamic control Diels-Alder route to, 249, 257 of epimerization stereochemistry, retrosynthetic analysis of, 247 527 synthesis of, 249-263 578 Organic Synthesis via Examination of Selected Natural Products

Umpolung, 211 Weinreb amide synthesis, 485 Weiss reaction, in triquinacene VanRheenan oxidation, 541 synthesis, 271 Vicinal diastereoselection, in addition Williamson ether synthesis, 317,453, of metallated vinyl sulfoxide to 455 enone, 195 Wittig reaction, 187,261,289,349, Vicinal dihydroxylation, with OS04, 39 353,489,495,517, Vicinal stereochemistry for introduction of prostaglandin control by ring-opening strategy sidechain, 87 using Baeyer-Villiger, 177, 187 modifications of in stereoselective control of by addition to alkenes, olefin synthesis, 465 123 Schlosser modification of, 55, control of in oxy-Cope 465 rearrangement, 175 stereochemistry of, 55 control through alkene addition Wolf-Kishner reduction, 249, 257, 291, reactions, 119 409 control through cycloaddition-ring opening strategy, 169 Yamamoto-Peterson olefination Vinylogy, the principle of, 215 (ene-yne synthesis), 383 Vioxx, as COX inhibitor, 75 Ynamine cycloaddition, 169

Water scavenger, use to improve yield ZOlefin synthesis, via Wittig reaction in sensitive Diels-Alder reaction, 361 of unstabilized phosphoranes, 55