Acetic Acid 26, 254, 279, 289, 290, 316, 425, 446 Acetonitrile 47, 93

471

Index

a – four-component reaction 462 acetic acid 26, 254, 279, 289, 290, 316, 425, 446 – primordial electrophilic activation of 346 acetonitrile 47, 93, 101, 114, 266, 267, 272, 280, aldehyde–indole condensation 352 389, 412 aldehydes 19, 26, 34, 42, 80, 87, 90, 92, 112, 130, acetylated carbohydroxylation product 403 133, 167, 225, 283, 293, 357, 415, 416, 1-acetylcyclopropanecarboxamides 119 429, 444, 458 acetylene carboxylates 351 – 1,3-dipolar cycloaddition of 454 acetylenedicarboxylates 351 – DMSO, oxidation in situ 384 acetylenes 333, 351, 368, 374 – four-component reaction 462 achiral and racemic multicomponent – lithium bis(trimethylsilyl)amide 326 reactions 111 – three-component cycloaddition of 455 – involving four reactive sites 139–142 – three-component reaction of 443 – involving one pronucleophilic reactive – trimethylsilylimines 326 site 111–115 aldol condensation 367, 368, 383 – involving three reactive sites 134–138 aldol reaction 115, 188, 195, 197 – involving two reactive sites 115–134 – three-component aldol-type reaction 463 acid chlorides 215, 343, 344, 354, 357 aldol-type product 416 – catalytic transformation of 342 alicyclic ketones 429 Acm-S-protected cysteines 244 aliphatic amines 90 acrolein 116, 149 aliphatic ketones 79 acrylate 184, 411, 419 alkaline Boc deprotection 339 acyclic alkanes 423 alkaloid-like polycyclic moieties 29 acyclic allenes 305 alkaloids 29, 121, 146, 162, 164, 176, 404, acyclic analogs 232 446, 455 acyclic anhydrides 395–398 alkaloid-type polycycles 162 acyclic/cyclic benzylamines 274 alkane carbonylation 421 acylamino-1,3-butadiene 26 alkenol partner, trapping of 417 acylhydrazine 422 alkenylidene oxazolidinones acyl iodide 421 – A3-carboxylative cyclization 337 1-acyloxy-1,3-butadiene derivatives 396 – four-component synthesis 337 N-acyloxyphthalimide 412 alkenynes carbocyclization 416 5-acylpyrid-2-ones alkoxyallenes 324, 326, 327 – coupling–amination–aza-annulation – three-component reaction 327 four-component synthesis 345 1-(alkoxyarylmethyl)indole-3-carboxyl – four-component synthesis of 345 esters 293 acyl radicals, nucleophilic reactivity 423 α-alkoxy-β-hydroxy esters 188 o-acyl-substituted cyclohexenes 26 2-alkoxyfuro[2,3-c]quinolines 286 α-adduct intermediate 275 alkoxyoxazoles 444 alcohols 346, 429, 433, 460–462 – three-component synthesis of 444

Multicomponent Reactions in Organic Synthesis, First Edition. Edited by Jieping Zhu, Qian Wang, and Mei-Xiang Wang.  2015 Wiley-VCH Verlag GmbH & Co. KGaA. Published 2015 by Wiley-VCH Verlag GmbH & Co. KGaA. 472 Index

alkoxy radical 426 – three-component synthesis of 364, 365 2-alkoxy-substituted 2,5-dihydropyrroles 326 – transition metal-catalyzed processes 333 6-alkoxy-tetrahydropyridines 122 alkynols 464 α-alkyl-α-diazoacetates 186 alkynones 342 N-alkyl amines, oxidation of 266 – catalytic generation of 341, 342 2-alkylamino-3-arylquinoxalines 288 2-(1-alkynyl)-2-alken-1-ones 208 – synthesis, postulated mechanism 288 2-alkynylanilines 293 2-[1-alkyl-5,6-bis(alkoxycarbonyl)-1,2,3, 3-alkynylated β-amino acid ethyl esters 4-tetrahydro-2-oxopyridin-3-yl]acetic acid – three-component synthesis 352 derivatives 390 γ,δ-alkynyl-β-amino acid esters α-alkyl diazoacetates 189 – Cu(II)-catalyzed three-component synthesis alkyl halides 117, 429 of 352 – abstract halogens 431 alkynyl benzaldehyde hydrazine – carbonylation 419 – Fischer carbene mediates a cyclization of 369 N-alkyl hydroxylamine 279 2-alkynylbenzaldehydes 283 alkylidenecyclopropanes 424 ortho-alkynyl benzaldehydes 349 alkylidene malonates 112 2-alkynyl benzaldehyde substrate 346 alkyl iodides 420 2-alkynylbiaryls 67, 68 – one-carbon homologation of 419 α-alkynyl enaminyl Pd species 339 2-(3-alkyl-4-oxo-2-thioxo-1,3-thiazinan-5-yl) α-alkynyl indoles 337 acetic acids – three-component synthesis of 338 – generation of 389 ortho-alkynyl phenyl isonitrile 348 – three-component synthesis 389 alkynyl sulfones 404 alkyl radical 422 allene reaction 322 alkyne 370, 422 allenes – 1,3-dipolar cycloaddition 357 – in heterocycles synthesis 301 – titanium-catalyzed four-component reaction – intramolecular Michael addition 303 of 370 – multicomponent reactions of 314 alkyne–imine MCRs 160 – palladium-catalyzed reactions 307, 308 alkynes 343 – reactions with acceptor-substituted – in cycloadditions 356 allenes 301 ––in Cu(I)-catalyzed 1,3-dipolar azide–alkyne –– catalyzed multicomponent reactions cycloaddition 358–366 316–318 –– dienophiles in MCRs 366–370 –– uncatalyzed multicomponent –– as dipolarophiles 356–358 reactions 318–323 – electrophiles, conversion 341–345 – reactions with donor-substituted – as electrophilic partners 351–356 allenes 301, 323–328 – as nucleophilic, electrophilic, dipolarophilic, – reactions with 1,2-propadiene 302 and dienophilic reaction partners 334 –– copper-, nickel-, and rhodium-promoted – as nucleophilic, exempliﬁed reactivity multicomponent reactions 310–314 patterns of 334 –– multicomponent reactions without – π-nucleophilic reactivity 345–351 transition metals 314, 315 – σ-nucleophilic reactivity 335 –– palladium-catalyzed multicomponent –– alkyne–aldehyde–amine condensation– reactions 302–310 A3-coupling 335–337 α-allenic sulfonamides 306 –– alkyne–(hetero)aryl halide (sonogashira) allenic p-toluenesulfonamides coupling 337–341 – palladium-catalyzed carbonylation- –– electrophiles, acetylide additions 335 coupling-cyclization of 306 – organometallic MCRs, reaction rac-2,3-allenoates 455 partners 370–373 – 1,3-dipolar cycloaddition and kinetic – radical-mediated Cu-catalyzed three- resolution 456 component 366 allenoic acids 316 – terminal alkynyl C-H bonds 335 allenyl alcohols Index 473

– copper-mediated carbomagnesiation of 311 2-(1-aminoalkyl)-5-alkoxyoxazoles allenyl amidine 365 – Ugi-type three-component synthesis of 444 α-allenyl amines 2-(1-aminoalkyl)-5-aminoxazoles 443 – allenyl imine intermediates 310 α-amino amides 277, 412, 428 – palladium-catalyzed three-component – quaternary centers 429 cascade reaction 307 4-aminobenzo[b] [1,4]oxazepines allenyl imidothioate 324, 326 – three-component synthesis of 354, 355 allenyl imines 327 amino carbonyl compounds 273 1,2-allenyl ketones anti-β-amino carbonyls 440 – palladium-catalyzed carbonylative 2-amino-3,5-dicarbonitrile-6- dimerization of 316 thiopyridines 296 allenyl phosphonates 317 3-amino-3,4-dihydropyridinones 465 allenylsilane 315 amino esters – treatment 315 – 1,3-dipolar cycloaddition of 454 allyl acetoacetate 98 – three-component cycloaddition of 455 allyl chloride–aryne–alkyne coupling 60, 63 amino-functionalized ionic liquids 117 3-allyl N-cyanoindoles 348 2-amino-4-(5-hydroxy-3-methyl-1H-pyrazol- allylic alcohols 208 4-yl)-4H-chromene-3-carbonitrile allyl isocyanide 80 derivatives 138 π-allylpalladium species α-amino imides – cyclization of 310 – Ugi-type three-component reaction 277 – iodobenzene derivative, carbopalladation β-amino iso(thio)cyanates 17 of 303 α-aminomalonate 144 N-allylpyrimidines 103 5-aminooxazoles 244, 245 allyl-substituted hydroxypyrimidines 97 3-amino oxindoles 462 allyl sulfone 406 6-aminopenicillanic acid 4 allyl-tributylstannane 406 ortho-amino phenol 354 allyltrimethylsilane 395 – three-component synthesis of 354 Alternaria alternata 232 ortho-aminophenylacetylenes 368 alumina-promoted hydrolysis 287 4-amino-phthalazin-1(2H)-ones (APOs) 36 amide 277 – one-pot palladium-catalyzed MCR amidines toward 35, 36 – addition 423 5-aminopyrazole 21, 22 – formation 366 2-aminopyridines 292 – palladium-catalyzed synthesis 34 4-aminopyridines 84 amidinyl-substituted radicals 366 4-aminoquinolines 84 α-amido lactams α-amino-substituted alkoxyallenes 327 – oxidation–dehydration–Ugi reaction 273 4-amino-1,2,3,4-tetrahydroquinolines 447 amidomethyl-substituted 1,2,3-triazoles aminyl radicals 366 – three-component synthesis of 362, 363 ammonia 79, 94, 95, 109, 123, 126, 147, amido-substituted cyclohexadienes 367 386, 458 – substituted cyclohexadienes, pseudo-four- ammonium acetate 118 component synthesis of 367 – catalyzed, Hantzsch condensation reaction amines 26, 34, 36, 73, 90, 126, 222, 257, 305, of 459 389, 429, 430, 431, 432, 442 amphiphilic functionality, in situ – to 4CR products 387 generation 343 – four-component reaction 462 analgesic 393 – four-component reaction (4CR) 379 AnchorQueryTM 7 – Michael addition of 352 2- and 4-nitrophenols 78 syn-β-amino-αalkoxy esters 461 anellated azepines 357 aminoacetaldehyde dimethoxyacetal 96 anellated 4H-thiochromen-4-ones syn-β-amino-α-hydroxy esters 461 – three-component synthesis 343 1,2-amino alcohols 429 anellated isoquinolinium salts 346 474 Index

angularly annulated furoquinolines – Diels–Alder adducts 390 – three-component synthesis of 369 β-aryloximes 403 anhydride-based multicomponent arylpalladium species 305 reactions 379 1-aryl-4-(2-phenylethynyl)[1,2,4]triazolo[4, anhydride used, in MCRs 3-a]quinoxalines – structures of 380 – four-component synthesis 339 anilines 188, 196, 464 N-aryl proline amides 30 – aldol-type reaction of 462 N-aryl-pyrrolidine-2-carboxamide 90, 91 – as amino substrates 335 N-arylpyrrolidine-2-thiocarboxamides 91 – aza-Diels-Alder reaction of 453 N-aryl thiocarboxamides 96 – Michael addition of 352 arynes 39 – three-component cycloaddition of 455 – based multicomponent reactions 41 – three-component reaction of 443 – 2,3-didehydrobenzofuran 39 annulated cyclohexadiene 372 – transition metal-catalyzed multicomponent annulated furoquinolines reactions 60 – ortho-aminophenylacetylenes 368 –– annulations 60, 61, 63–65 annulated hydroquinone 371, 372 –– cross-coupling-type reactions 65, 66 annulation reactions –– insertion into σ-bond 65–68 – cyclic anhydrides, MCRs of 392 –– Mizoroki–Heck-type reactions 65, 67 – phthalic anhydrides 393–395 Asinger reaction 4 – succinic anhydrides 393–395 anti-α-substituted α,β-diamino acid 4,5-anti-substituted lactam derivatives 462 – radical reductive desulfurization 387 atom-transfer radical carbonylation aromatic aldehydes 22, 188, 293 (ATC) 421 – Hantzsch condensation reaction of 459 Au(I)-Cu(I) cocatalytic system 66 aromatic spiroacetals 464 azabicyclo[3.3.1]nonanones 115 aromatization 167 aza-Darzens reaction aryl aldehyde 131, 311, 318, 368 – three-component synthesis 442 arylalkynes 434 aza-Diels-Alder reaction 447 arylamine 402 – enantioselective inverse electron demand aryl and heteroaryl pyridines (IED) 450 – from “dual heterogeneous catalyzed” – five-component 447 3CR 290 1-azadiene 167 3-arylbenzoquinoline derivatives 125 aza-ene reaction 440 3-arylbenzo[f]quinolinyl-1, azaindolines 102 2-dicarboxylates 368 azasteroids 164 – benzoquinolines, three-component synthesis azatitanacycle 370 of 368 azide aryl diazoacetates 188, 189, 196 – 1,3-dipolar cycloaddition 323 – rhodium(II)-catalyzed aziridination 187 – α-insertion of 348 aryl diazonium 402 azidoacetonitrile 360 α-arylglycine ester 458 azido sulfones 404 aryl halides 60, 131 aziridines – one-carbon homologation of 419 – derivatives 441 arylidene cyclopentanes 348 – enantioselective one-pot synthesis of aryl iodides 200, 306, 419, 420 441, 442 – NHC-boranes 419 – synthesis of 441 – palladium-catalyzed three-component azlactones 465 cascade reaction 307 1,1´-azobis(cyclohexane-1-carbonitrile) – secondary amines of 303 (V-40) 409 – silver phosphate 307 azodicarboxylates 187, 188 β-aryl isoserine derivatives 189 azomethine 144, 184, 225 N-arylmaleimides 186 azomethine imine 1,3-dipole 134 Index 475 azomethine ylide 184, 185, 225, 456 Biginelli reactions 165, 280, 444 – copper-catalyzed three-component – acyclic/cyclic ketones 440, 445 reaction 185 – asymmetric 445 – rhodium-catalyzed three-component – chiral phosphoric acid-catalyzed 445 reaction 186 – cyclic ketones 445 – ruthenium-catalyzed asymmetric three- – enantioselective, organocatalysts for 149 component reaction 185 – mechanism 130 azomethine ylides 225 – preparation of heterocycles, variations – cycloaddition of 356 in 131 – 1,3-dipolar cycloaddition of 454 – for preparation of other heterocycles 131 – dipole 357 – trifluoromethylated ketones 130 bimacrocycles b – igloo-shaped, synthesis of 260 Barton carbonate PTOC-OMe 408 – by threefold Ugi-4CR-based Barton reaction 426 macrocyclizations Beller’s cataCXium ligand 345 –– syntheses of 258 benzaldehydes 102, 140, 431 biocatalysis 15, 23, 25, 26, 30, 32, 33 – 4CR of 386 biology-oriented synthesis (BIOS) design benzamidine hydrochloride 98 strategies benzenoids 168 biotransformation 8, 25, 34 benzimidazoles 95 2,2´-bipyridines 290 – synthesis 95 bis(α-isocyanoacetamide) 248 benzimidazolopiperazine 96 bisallenes palladium-catalyzed coupling- benzo-annulated cycloalkanones 372, 373 cyclization of 307 – three-component synthesis of 373 1,5-bisallenes, palladium-catalyzed reaction benzo[a] quinolizidine derivatives 467 of 316 benzodiazepine 103 rac-2,4-bis(diphenylphosphino)pentane 1,5-benzodiazepine derivatives 125 (bdpp) 313 benzo[f]quinolones 125 bispropargylamine 373 benzofurans 118 3,5-bis(trifluoromethyl)benzyl bromide 448 benzofused heterocycles 304 2,2´-bis(trimethylstannyl) biaryls 65 – exo-trig-cyclization–allenylation–amination Boc derivatives 326 sequence 303 BODIPY dyes 10 benzoquinolines 131 Bohlmann–Rahtz reaction 124 benzoquinone 316, 432 borane 408 benzoquinoxaline 98 boron derivatives 415 benzothiazole 175 boronic acids 316 benzotriazole 95 boronoacrolein 167 benzylamines 95 boryl enamine 416 – acyclic 274 bromine atom-transfer process 410 – biomimetic three-component 1,3-dipolar 1-bromoalkynes 354 cycloaddition 459 – electron-deficient alkynes 354 – imine intermediate from 304 – three-component synthesis of 354 benzylation 448 bromobenzene 34 benzylic alcohols 271, 272 3-bromobenzofuran 39 benzylic carbocation 417 bromodimethyl-sulfonium bromide 125 benzylidene acetone 143 bromomalonate 410 4-benzylpiperidine Brønsted acids 19, 148, 456 – oxidation of 275 – chiral 161, 439 – Ugi-Smiles reaction of 275 – combination of with transition metals biaryl ether–cyclopeptoid macrocycles 254 192–196 bicyclic system 425 – ionic liquid (1-methylimidazolinium bidirectional Ugi-MiB 247 hydrogen sulfate [Hmim]HSO4) 280 476 Index

Buchwald–Hartwig amination 337 – aza-Diels–Alder reaction 446–453 t-BuOK 22, 212, 221, 315, 419, 420 – azlactones 465 2,3-butadienoates 318 – Biginelli reaction 444–446 t-butyl hydroperoxide (TBHP) 277 – 1,3-dipolar cycloaddition 454–458 tert-butyl isocyanide 26, 34 – Friedel–Craft alkylation of indoles 465 – hantzsch dihydropyridine synthesis 458, 459 c – Mannich reaction 439–442 calixarenes 232 – metal/chiral phosphoric acid 459–465 CAN-catalyzed synthesis of 1, – Ugi four-component reaction (U-4CR) 4-dihydropyridines 296 442–444 Candida antarctica lipase B (CAL-B)-catalyzed chiral reagent induction 190 aminolysis 362 5-chloro- and 5-trifluoromethyl- carbalkoxypiperidone 116 2-hydroxypyridines 84 carbamate component 315 p-chlorobenzylamine 77 carboallylation, of electron-poor olefins chloroquine 97 406, 407 N-chlorosuccinimide (NCS) carboaminohydroxylation product 402 – 4-benzylpiperidine, oxidation of 275 carbodiazenylation product 402 cinchona 146 carbon disulfide 95 cinnamyl bromide 80 carbonitrosation 403 3,4-cis-substituted meso-amines 91 carbonylative four-component heterocycle clam-shaped bimacrocycles 260 synthesis 216 click–Goldberg amidation–Camps cyclization carbonyl ylides 185–187, 225 sequence. 361 carbopalladation–β-hydride elimination–6π- πC=N bonds 427 electrocyclization–oxidative aromatization – free-radical Strecker process 427–429 sequence 310 – Mannich-type processes 429–431 carbopalladation–exo-cyclization cobalt-catalyzed reaction, of acetonitrile 114 sequence 323 C,O-bis-nucleophilic reactivity 139 carboxylic acids 81, 277, 278 cocrystal structures – Ugi-type reaction 277 – of MCR molecules bound to biological –– surrogates in 74–76 receptors 7 cascade Mannich-type reaction 440 combinatorial library, of small molecules 2 Castro–Stevens coupling 335 combinatorial synthesis – Pd-catalyzed variation of 335 – of natural product-inspired biaryl ether– catalyzed multicomponent reactions 316–318 cyclopeptoid macrocycles 254 C-centered radicals 404 – steroid–peptoid hybrid macrocycles 255 cerium ammonium nitrate (CAN) 120, 295, condition-based divergence (CBD) 15, 18, 21 296, 387 4,5-cis-configured dihydropyrrole derivatives

cerium(III) triﬂate catalyzes 337 – BF3–etherate in propionitrile 315 cerium(IV) sulfate 394 copper-catalyzed synthesis 278

CF3 radical 422 – of pyrroles from primary amines 226 chemoinformatics 261 copper-promoted multicomponent C-H functionalization in multicomponent reactions 310 reactions 218–221 coumarins 164 chiral amines 286 coupling–amination–aza-annulation– chiral dirhodium(ii) catalysis 190 Pictet–Spengler sequence 343 chiral HPLC analysis 269 coupling–isomerization–Stetter–Paal–Knorr chiral imidazolidines 455 synthesis 345 chiral 8-phenylmenthol diazoacetate 185 coupling reagent (CR) 234, 235, 241 chiral phosphoric acid-catalyzed asymmetric cross-coupling transformations 200 multicomponent reactions 439, 441, 445, crown ethers 232 453, 457 C4-substituted 1,4-dihydropyridines 458 – aryl ethylamine derivatives 466 Cu-carbenoid 357 Index 477

Cu–ferrite nanoparticles 117 cyclohex-2-ene-1-ols 396 1,4-cuprate addition–alkylation tandem cyclohexenols 26 process 406 cyclohexenone 149, 446 Cu-sulfonyl ketenimines 363 cyclohexyl isonitrile 77, 238, 250, 287 – nitrogen extrusion 362 cyclooctane 422 N-cyano-3-allylindoles cyclo-oligomerization 241 – insertion-[1,2]-shift-insertion-allylation cyclopentanone derivatives 136, 292 synthesis, mechanistic rationale 350 cyclopeptoids – three-component synthesis 350 – biaryl ether–cyclopeptoid macrocycles 250, N-(cyanomethyl)amides 19 253, 254 cyanomethyl-1,2,3-triazole 360 – containing, photoswitching unit 253 cyclic acyliminium ion 344 – RGD cyclopeptoid 239 cyclic anhydrides 393 cyclophanes 232 cyclic (D,L)-α-peptide 233 – synthesis 249 cyclic β-keto esters 116 cyclopropenes 187 cyclic 1,3-dicarbonyl 141 cyclopropyl fragmentation 101 cyclic 1,3-diketones 21, 22 cyclic enaminones 396 d cyclic enethiourea derivative 449 decarboxylation 291 cyclic imines 276 9-deoxy-9-aminoquinine 148 – nucleophilic isocyanide 276 diacids 250, 254 cyclic ketones 429 dialcohols 257 – Biginelli-like reaction 445 dialkyl acetylenedicarboxylates 367, 393, 398 cyclic oleﬁns 187, 426 – p-dimethylaminopyridine 353 cyclic tertiary enecarbamate 449 dialkylzinc reagents 416, 431 exo-trig-cyclization–allenylation–amination diamine 97, 390 sequence 303 diamine/diisocyanide combination 251 cyclization reaction 1,3-diamines – on biological activity 232, 233 – chiral 441 – of cross-coupling reaction products – three-component synthesis of 442 216–218 2,5-diaminofuran derivatives 397 – of peptide, silver-mediated 233 2,3-diarylpyrroles 127 – via palladium–allyl complexes 210 anti-diastereomer 382 – via three-component coupling 466 endo-diastereomer 446 cycloaddition reactions 132, 166, 169, 184, 185, syn-diastereomer 381, 382 235, 356, 366, 398, 457 diastereoselectivities 26, 29, 90, 113, 134, 135, cycloadduct 184–186, 282, 364, 365, 370, 455 145, 150, 190, 195, 225, 241, 311, 386, 387, cyclocarbonylation reaction 305 416, 451, 462 cyclocondensation 165, 216, 280, 281, 335, 2,6-diazabicyclo[2.2.2]octane (2,6-DABCO) 342, 360, 371 core 135 cyclodehydration 120, 125 trans-diazadecalines 122 cyclodextrins 126, 232 diazaheterocyclic structures 390 cyclodimerization 233 1,4-diazepanes 125 cycloheptane 422 diazirine aldehyde, isolation 270 cycloheptatrien-1-ones 90 diazirine-modiﬁed α-acyloxyamides 270 cycloheptene carboxylic acids 136 – synthesis of 270 cyclohexadienes 135 diazoacetates 184, 200 1,3-cyclohexadiones 128 – chiral phosphoric acid-catalyzed cyclohexane 422 aza-Darzens reactions of 442 cyclohexane-1,3-dione 123 diazo compounds cyclohexanols 135 – alcohol, Mannich-type reaction 461 cyclohexenedione moiety 372 – four-component reaction 462 – tautomerization 372 – three-component reaction 462 478 Index

2-diazo-1,3-diketone 134 – 1,4-dihydropyridines (1,4-DHPs) 115, diazoindan-1,3-dione 185 116, 283 diazonium salt 402 –– plausible reaction mechanism for – carbodiazenylation reaction 402 synthesis 285 3-diazo oxindoles 462 –– synthesis from aldehydes, anilines, and dibenzylamines 274, 276 alkenes 284 dibenzyl azodicarboxylate (DBAD) 311 – 1,6-dihydropyridines 122 β,β´-dibromo-ortho-bromostyrenes 337 – 2,3-dihydropyridines 324 1,3-dicarbonyls 109, 127, 135 – 3,4-dihydropyrimidin-2(1H)-ones 280, 444 – compounds 110, 111, 116, 117, – three-component cyclization 460 149, 317 dihydropyrimidinethiones 446 –– as bis-nucleophiles in MCRs 115 dihydropyrimidinones 165 – derivatives 128 2,5-dihydropyrroles 327 – potential reaction sites 110 – derivatives 458 β-dicarbonyls 109 2,5-dihydroxy-1,4-benzoquinone 139 – chemistry 164 2,2-dihydroxyindene-1,3-dione 396 2,3-dichloro-5,6-dicyanobenzoquinone diisocyanide 80 (DDQ) 432 diisonitrile 254, 257 1,2-dichloroethane (DCE) 283 1,4-diketones 345 2,3-didehydrobenzofuran 40 diketopiperazines 241 Diels–Alder adducts 390 dimedone Diels–Alder cycloaddition 391 – 5,5-dimethylcyclohexane-1,3-dione 394 – with isoprene 390 – Hantzsch condensation reaction of 459 – stereoselectively 453 dimethyl acetylenedicarboxylate (DMAD) 123, Diels–Alder products 322 184, 186 Diels–Alder reaction 26, 28, 353, 368, 444 – dipolar MCRs 175, 176 – dihydropyrans via a hetero reaction 118 dimethyl allenedicarboxylate 320 – MCR of anhydrides, aldehydes, and N,N-dimethylamino nitrene 370 dienophiles involving 28 N,N-dimethylformamide (DMF) 28, 49, 77, 96, – retro 357 101, 102, 219, 324, 341, 383, 406 dienes 426 dimethyl malonate 143 dienophiles 26 dimethyl 3-oxo-pentanedioate 149 – acylating agents 379 dimethyl sulfomycinamate 124 dienophilic reaction partners, exemplified dimethyl sulfoxide (DMSO) 35, 77, 86, 143, reactivity patterns 334 238, 273, 367, 384, 426 diester 421 1,3-dioxane derivatives 1,3-diester derivatives 130–132 – N-heterocyclic carbene (NHC)-catalyzed diethyl α-aminomalonate 144 annulation 318 diethyl acetylene-dicarboxylate 356 1,3-dioxan-4-ylidene acetates, synthesis 318 diethyl maleate 422 4H-1,3-dioxin-6-yl propanoates difuranyl ketones 316 – bicyclic guanidine-catalyzed synthesis trans-dihydrofuran 118 of 318 dihydrofurans 118 2,4-dioxo-benzodiazepines 137 – ring 117 dioxolane, bismuth-catalyzed allylation 395 dihydrofuroquinoline 369 dioxygen–copper system 292 ´ 2,5-dihydro-5-imino-2-methylfuran-3, 3,3 -diphenyl H8-BINOL 445 4-dicarboxylates 397 1,6-dipolar cyclization 353 1,6-dihydronaphthyridines 116 1,3-dipolar cycloadditions 184–186, 269, 304, dihydro-1,3-oxazines 315 356, 358, 454 9,10-dihydrophenanthrenes 60 – catalyzed by (R,R)-bisphosphoric acid dihydropyridines (DHPs) 171, 288, 324, catalyst 454 324, 458 dipolarophiles 133, 175, 185 – derivatives 459 – electron-deficient 455 Index 479 dipolarophilic exemplified reactivity patterns enamides 327 of 334 enamine 283, 327 1,3-dipole 357 – oxidation of 417 1,4-dipole 353 β-enamino ester 352 dipole-mediated processes 175, 176 enaminone 344 directionality in Ugi-MiB reactions 247 enantioenriched allene (Ra) 314 dirhodium(II) catalyst 188 – rhodium-catalyzed intramolecular dispirooxindole anellated heterocycles reaction 313 – pseudo-four-component synthesis of 353 enantioenriched allenylsilane 314 dispirooxindole-annulated enantioenriched spiroacetals tetrahydroquinolizidines – catalytic three-component reaction 464 – pseudo-four-component synthesis of 353 enantioselective MCRs 142, 143 1,3-disubstituted allenes – involving one reactive site 143–145 – palladium-catalyzed three-component – involving three reactive sites 149, 150 coupling of 316 – involving two reactive sites 146–149 N,N-disubstituted anilines 277, 278 enantioselective palladium(II) phosphate- 2,4-disubstituted ethyl thiophene- catalyzed three-component reaction 5-carboxylates – of diazoacetates, pyrroles, and imines 200 – three-component synthesis 342 enantioselective synergistic catalysis 190, 191 cis-disubstituted tetrahydroquinolines 450 enantioselectivity 147, 148, 150, 396, 443, 447, 2,4-disubstituted thiophene ethyl carboxylates 450, 456, 462, 465 – three-component synthesis of 342 enecarbamate 410, 449 disulfide-bridged peptidomimetic enoates 414 macrocycle 244 enolate 432 dithiocarbamates 389 enolizable ketones 212, 445 diversity-oriented synthesis (DOS) design enones 407, 412, 414 strategies 14 – system 406 1,4-diynes, pseudo-four-component enoximes, carbohydroxylation of 416 synthesis 354 enynes 416, 423, 426 docking, of Ugi ligand 9 enzyme-catalyzed hydrolysis 28 domino oxidation, Ugi-type reaction 274 – optically pure tertiary alcohol acetates, donor-substituted allenes 323 synthesis of 28 droplet-based microfluidic technique 242 epimerization 234, 286, 382, 388 drug discovery 5, 7, 8, 173, 252, 254, 380, 396 epoxidation reaction 188 drugs under (pre)clinical development, and epoxide 65, 171, 188 incorporating MCR chemistry 5 epoxy-tetrahydropyrrolo[3,4-b]pyridin- 5-ones 444 e esters 419 electrocatalysis 117 – t-BuOK 420 electron-deficient olefins 458 ethanol (EtOH) 22, 24, 97, 110, 112, 120, 127, electron-poor alkene 401 141, 343, 385, 389, 410, 441, 442 electron-poor olefins 422 ethoxide 22, 39 electron-rich indolyl moiety 344 ethoxycarbonylation 448 electron-rich olefins 432 5-ethoxy oxazole electron-rich organo-Pd species 350 – three-component formation of 369 electrophiles 345 ethyl α-aryl-α-isocyanoacetate electrophilic acyliminium ion 357 – with pivalaldehyde/ – Pd-catalyzed carbonylative cyclization cyclohexanecarboxaldehyde and of 357 anilines 444 electrophilic, exemplified reactivity patterns ethyl acetate 276 of 334 ethyl acetoacetate 138, 147, 459 electrophilic nitrilium ion 412 ethyl allenoates 319 electrophilic radical 404 N-ethylaniline 142 480 Index

ethyl 2,3-butadienoate 316, 318 – free-radical carbonylation – [2+2+1]-cycloaddition reaction 319 –– alkane carbonylation 421–423 ethyl 4-chloroacetoacetate 138 –– alkyl halide carbonylation 419, 420 ethyl diazoacetate 186, 189, 202, 203, 357 –– allyl moiety, radical addition of 424 ethyl esters 390 –– metal-mediated atom-transfer radical ethyl glyoxylate 304 carbonylation 420, 421 ethyl 2,3-pentadienoate 318 –– nucleophilic reactivity of acyl ethyl radical 432 radicals 423

– Et3B, decomposition of 432 – free-radical oxygenation 424–427 ethynyl triﬂone 422 – oleﬁnC=C bonds

Et4NOTs salt 425 –– aryl radicals, addition 402, 403 ETPO (4-ethyl-2,6,7-trioxa-1-phosphabicyclo –– carbohydroxylation/sulfenylation/ [2.2.2]octane) 65 phosphorylation 407–410 exo-cyclized pyrrolidines 307 –– electron-poor olefins, carboallylation 5-exo-trig cyclization 417 of 406, 407 –– photoredox catalysis 410–414 f –– radical–polar crossover processes facile manganese(III)-catalyzed photochemical 414–418 reaction 318 –– sulfonyl derivatives as terminal trap 4-ferrocenyl quinolines 338 404–406 – three-component synthesis of 338 – πC=N bonds 427 Fischer carbenes 369 –– free-radical Strecker process 427–429 five-membered heterocycles –– Mannich-type processes 429–431 – from nucleophile-tethered alkenes or – PhSeSePh 434 alkyne 209 – polar effects 406 five-membered ring hydroxy heteroaromatic – zwitterionic hydroquinone-fused [1,4]- – and related mercaptans 88, 89 oxaziniums 432, 433 s-cis fixed diamino diene 353 free-radical oxygenation 424–427 fluorescent pharmacophores 10 Friedel-Crafts reaction 450 fluoride ions 117 – acylation 394 fluorinated compounds 413 – alkylation 111 – olefins, light irradiation 412 – cyclization 451 fluorobenzaldehyde 101 functionalized cyclohex-2-ene-1-ols 397 p-fluorobenzaldehyde 101 furans formaldehyde 142, 250 – coupling–isomerization–Stetter–Paal– 2-formyl benzoic acid 384 Knorr synthesis 345 four-component reaction. see Ugi four- – multicomponent approach toward 397 component reaction (U-4CR) – polyfunctionalized 397 free-radical carbonylation – polysubstituted 208 – alkane carbonylation 421–423 – substituted, palladium-catalyzed synthesis – alkyl halide carbonylation 419, 420 of 209 – allyl moiety, radical addition of – three-component synthesis of 346 424 furo[3,2-c]coumarins – metal-mediated atom-transfer radical –“green” synthesis 291 carbonylation 420, 421 furocoumarin – nucleophilic reactivity of acyl – adduct 291 radicals 423 – synthesis by a one-pot oxidative pseudo-3C free-radical multicomponent reactions condensation 291 401 furopyridines 328 – alkynes 433 cis-fused bicyclic nitrogen products 309 – donor and acceptor radical species fused-ring heterocycles 402 – for ortho-substituted arene building – ethyl radical 432 blocks 211–214 Index 481 g 2-(1H-indol-3-yl)arylmethyl-3-arylamino Garner’s aldehyde 272 acrylates 351 GBB-3CR-derived fluorescent homoallyl azide 102 pharmacophores 9 homoallyl esters 396 glycocyclodepsipeptides 246 homoallyl ethers 395 glyco-macrocycle 253 homoallylic alcohols 316 glycosyl bromides 411 homophthalic anhydrides glyoxylates 462 – dual electrophilic and nucleophilic Goldberg amidation 361 reactivity 381 Grignard reagents 53, 311 – imine–anhydride reactions of 380, 381 Groebke–Blackburn–Bienaymé MCR – MCRs employing 382, 383 reactions 10, 36, 173, 346 – quinolones 380 – postcondensation 174 Hoveyda–Grubbs second-generation catalyst 98 h H-pyrazolo[5,1-α]isoquinoline 283 4H-anellated thiochromen- 4-ones 343 Huisgen reaction 360 Hantzsch dihydropyridine synthesis 165, 458 Hünig base 305 Hantzsch ester 411, 412 hydrazine hydrate 393 Hantzsch-like, MCR 165 – 4CR by Mosaddegh 394 Hantzsch product 22 hydrazines 36, 128, 137, 167, 370, 371 Hantzsch reactions involving enamino – homophthalic anhydride 383 derivatives 121 – titanium-catalyzed four-component Hantzsch’s pyrrole synthesis 126 reaction of 370 Hantzsch synthesis of dihydropyridines 129 hydrazone 134 Hantzsch-type reaction 460 hydrogen Hayashi–Jørgensen catalyst 146 – abstraction 422 HCV protease inhibitor 8 – atom donor 417 Heck-type approach 98 – bonding interactions 447, 449, 450 heteroaryl Heck-type process 99 – selenide 17, 75 N-heteroaryl thiocarboxamides 87 hydrogenolysis 94 heterocycle–isocyanide MCRs 171 hydroiodic acid 346 heterocycles 126, 184 hydroperoxides 427 – eight-membered ring 384 – C-centered radical species 424 – in MCRs, role of 160 hydroquinone 372 – syntheses with allenes 210 hydroxamic acid 426, 427 – synthesis via münchnones 226 N-(hydroxyalkyl)formamides 273 N-heterocyclic carbene (NHC)-catalyzed α-hydroxyalkylpiperidine derivative 167 annulation α-hydroxyamides 19, 279 – [2+2+2]-annulation 318 2-hydroxybenzaldehydes 140 – 1,3-dioxane derivatives 318 2-hydroxybenzoate 82 Hetero-Diels–Alder/allylboration 3-hydroxy-β-lactam derivatives 189 protocol 167 α-hydroxy hydroxamate 427 hetero-Diels-Alder cycloadditions hydroxyl ether 432 164, 166 hydroxymethylation product 419 – and related processes 166 4-hydroxy-6-methyl-2H-pyran-2-one hetero-Diels–Alder MCRs 167, 446 119, 138 hexahydrocoumarins 142 4-hydroxy-3-nitrobenzoic acid 80 – derivatives 141 hydroxypyrimidines 85 hexahydroisoindolyl benzoic acids 390 – 2-hydroxypyridines 84 hexahydropyrrolo[3,2-c]quinolines 449 – 4-hydroxypyridines 84 high-throughput screening (HTS) 7 – 2-hydroxypyrimidine 85 1H-3-indenamines – 4-hydroxypyrimidines 85 – three-component synthesis 351 3-hydroxypyrroles 126 482 Index

hydroxyquinoline 97 indium-mediated 3CR 396 4-hydroxyquinolines 84 indoles 432 hydroxyquinoxalines 85 – aza-Diels-Alder reaction of 453 hydroxysulfenylation product 416 – derivatives, heterocycles of 396 α-hydroxytrifluoromethyl radical 413 – propargylation–iodocyclization synthesis –– mechanistic rationale of 347 i – three-component aza-Diels–Alder IBX/TBAB-mediated oxidative Strecker reaction 453 reaction 285 indoline derivative 366 IMCR-based protocols 236 indol-2-yl carboxamides 346 imidazo[2,1-a]phthalazin-6-one 36 in situ oxidation, multicomponent imidazole formation reactions 266 – ytterbium triflate catalysis for 346 – intermediate reaction 284 imidazole formation–cycloaddition sequence –– mediated by transition metal catalysis – imidazotriazolobenzodiazepines 292–295 –– four-component synthesis of 362 –– without transition metal-mediated imidazoles 227 oxidation 285–292 – ketenimine formation-addition-cyclization – isocyanide-based multicomponent synthesis of 365 reactions 266 – three-component synthesis of 365 –– Passerini reactions 266–271 – trifluoromethanesulfonic acid, in –– synthesis of derivatives 279, 280 dichloromethane 327 –– Ugi reactions with alcohols 271–273 imidazolidinone derivatives, highly –– Ugi reactions with secondary amines functionalized 307 273–275 imidazolidin-4-ones –– Ugi smiles reaction with secondary – three-component synthesis 364 amines 275, 276 imidazolo heterocycles 97 –– Ugi smiles reaction with tertiary imidazolyl dipole 365 amines 277–279 imidazopyridine derivatives 292 – as Lewis acids 295–297 imidazotriazolobenzodiazepines – Wittig olefination–Diels–Alder – four-component synthesis of 361, 362 multicomponent reaction 281

imides 277, 412 –– MnO2-/PCC-mediated multicomponent – copper-catalyzed synthesis 278 oxidation 282 – isocyanide nitrogen 277 in situ oxidative aromatization 288 – products cyclization 391 intramolecular cyclization 161 imines 273, 357 intramolecular H-bonding 81 – from dibenzylamine 275 inverse electron demand (IED) 450 – NXN-7, synthesis of 381 iodide reaction 419 – with singlet oxygen 275 iodinated 2,5-dihydropyrroles, formation 327 – in situ forming 429 iodine 291, 346 – three-component reaction 462 – NHC-boranes 419 – Ugi-Smiles reaction 276 – transfer reaction 419 iminium ions 277, 337, 350 – tributyltin radical 404 – alkynyl copper species, formation of 353 iodoanilines 99 – nucleophilic attack on 350 – Pd(0), oxidative addition of 305 – proposed mechanism for synthesis 278 2-iodoanilines, cyclocarbonylation α-iminonitriles 285, 286 reaction 305 iminospiro-γ-lactones 392 iodobenzene derivative 302 iminoyl-Pd species 356 – carbopalladation of 303 immunoglobulins (Igs) 10 iodoester 402 2H-indazolo[2,1-b] phthalazine-1,6,11(13H)- iodo(het)aryl aldehydes 304 triones 394 – synthesis of 304 1H-3-indenamines 349, 350 2-iodo(het)aryloxyallenes 323 Index 483 iodoheterocycles 168 isopyrrole 313 4-iodoindolazepinones isoquinoline 176, 320 – three-component synthesis of 346, 347 isoquinolinium-2-ylamide 283 iodonium species 346 isoquinolinone 103 o-iodopyrimidinols 101 isoxazoles 89 iodosobenzoic acid (IBA) 267 itaconic anhydride 388, 389, 390 iodovinyl-substituted dihydroimidazole derivatives 327 j iron porphyrins 188 Joullié–Smiles coupling 90, 91 isatins 188, 384 Joullié–Ugi coupling reaction 171 – [2+2+1]-cycloaddition reaction 319 Julia–Kocienski olefination reactions 89 – derivatives 117, 144 julolidine derivatives 463 –– nucleophilic addition to 319 isatoic anhydrides 384 k – dual electrophilic and nucleophilic Kabachnik–Fields reaction reactivity 381 – three-component 466 – imine–anhydride reactions of 383–385 Keck’s procedure 234 – MCRs of 388–390 ketoamides 102, 119, 125, 279 – quinolones 380 keto esters 109, 125, 135, 137, 280, 422, 458 isatoic anhydrides, form quinazolinones 383 – aza-Diels-Alder reaction of 447 isatylidene malononitriles 319 – biomimetic three-component 1,3-dipolar isocyanacetamide 80 cycloaddition 459 isocyanates 176, 210, 307, 391 – 1,3-dipolar cycloaddition 458 isocyanide–azine MCRs 172 – formation 419 isocyanides 34, 80, 90, 254, 267, 273, 278, 280, – products 200 393, 412 ketones 87, 167, 427 – based reactions 171–175 γ-keto ynoate 354 – cyclic imines react with 275 ketyl radicals 429 – MCRs with oxiranes, aziridines, oxazolidines, Knoevenagel adduct 130 and imines 172 – from 1,3-indanedione and the aldehyde 112 – Ugi-type reaction 277 Knoevenagel condensation 112, 296 N-isocyaniminotriphenylphosphorane 132 – 1,3-dicarbonyls with arylglyoxals 112 α-isocyanoacetamides 244, 245 Knoevenagel–hetero-Diels–Alder – three-component reaction of 443 reaction 110, 164 isoeugenol derivatives 450 Kobayashi’s silylaryl triflates 41 isoindolines – derivatives 455 l – pseudo-six-component synthesis of 373 lactamizations 173, 234, 235 – rhodium-copper-catalyzed pseudo-six- γ-lactams component synthesis 372 – multicomponent assembly 386 – synthesis, 1,3-dipolar cycloaddition 456 – NH, synthesis of 386, 387 isoindolinone 103 – Shaw’s diastereoselective total synthesis 387 isonitriles 128, 140, 236, 257, 370, 383 – synthesis of 386 – [2 +2]-cycloaddition 370 – tetra- and pentasubstituted 385 – [2+2+1]-cycloaddition reaction 319 lactones 421 – four-component cycloaddition of 319 – synthesis of 311 – three-component synthesis of 354 – yields 317 – titanium-catalyzed four-component reaction lactonization 432 of 370 Langlois’s reagent 413 isoprene 390, 391 lanthanide triflates 161 isopropyl 2,3-butadienoate Lewis acids 19, 142, 148, 207, 345 – trimethylphosphine-catalyzed annulation – catalyst 394, 439 of 318 – combination with transition metals 192 484 Index

– Et3B 432 malonyl coenzyme A 109 – mediated annulation reactions 314 mandipropamide 6 – multicomponent reactions involving Mannich products 461 oxidants as 295–297 Mannich reactions 429, 439–442, 450, 458, 465 Lewis base 449, 456 – anti/syn-selective enantioselective 463 library members, for diacid/diisocyanide – double 136 combinations 248 – ethyl oxaloacetate with primary amines lipase-catalyzed acylation, followed by and 113 Ugi-4CR 27 – leading to spirocyclic product 114 lipases 26 – nucleophilic component 440 lipid peroxidation inhibition 396 – phosphoric acid-catalyzed 451 Lipinski’s rule 231 – and related processes 160–164 lithiated methoxyallene 326 – sequential vinylogous 450 lithium bis(trimethylsilyl)amide 326 – three-component 440 lithium bromide 316 MAO–Ugi–Smiles sequence 30 luminescent pyrroles 345 MARDi cascade 136 luminescent symmetrical terthiophenes 342 materials science, application of MCRs in 10 matrix metalloproteinase 232 m – MMP-8 inhibitor peptide 233 macrocyclic drugs 231, 232, 235 MCRs. see multicomponent reactions macrocyclization 232, 233, 235 Meerwein reaction 402 – chemoselectivity of peptide 233 Meldal–Sharpless click reaction 339, 360 – comparison of methodologies 235 Meldal–Sharpless Cu(I)-catalyzed 1,3-dipolar – IMCR-based 237 azide–alkyne cycloaddition (CuAAC) 358 –– macrocyclizations of trifunctionalized Meldrum’s acid 132, 137, 140, 141, 164 building blocks (MiB-3D) 256–259 MeO radical 408 ––sequential, of multiple bifunctional building 3-mercapto-4-alkyl-1,2,4-triazoles 89 blocks 259, 260 β-mercaptoamides 287 –– of single bifunctional building blocks – one-pot synthesis from α,β-unsaturated 237–245 aldehydes, amines, and thiols 288 – multiple MCR-based, bifunctional building mercapto benzimidazole 95 blocks 245–256 2-mercapto imidazoles 89 – parameters signiﬁcant role in 234 5-mercapto pyrazoles 89 – Ugi-4CR-based of single bifunctional 4-mercapto pyridine 87 building blocks 237 4-mercaptoquinolines 97 – utilizing Ugi reaction pass through a tethered mercapto triazines 87 α-adduct 236 mesityl acridinium 413

macrocyclodepsipeptide 245 Me3Sn radical 409 macrolactonization 235 metalated alkoxyallenes 323 – of linear precursor 234 – organic synthesis 323 magnetic nanoparticle-supported TEMPO metal carbene 184 catalyst metallacycles, in multicomponent – separation of 272 reactions 221–223 maleates 454 metal–ligand complexes 170 maleic anhydride 390 metallocatalyzed cycloisomerization 128 – 4CR of 386 metal-mediated processes 168–170 – one-pot 3CR-Diels-Alder cycloaddition methanol 77, 276 reaction of 391 methoxy alkenyl N-dimethylamino maleimide isoindole 370 – alkyl radical 406 p-methoxybenzaldehyde 102, 386 – cyclohexene 407 p-methoxybenzylamine 387 malonate 145 methyl acrylate 284 malononitrile radical 418 methyl benzoates 36 Index 485 methylbenzylamine 80 Morita–Baylis–Hillman reactions 318 (R)-α-methylbenzylamine 302 morpholine 429 methyl carbamate 315 – derivative 322 α-methylene-β-lactone derivatives 312 morpholinoethyl isocyanide 19 4-methylene-3,4-dihydro-1(2H)-isoquinolin- multicomponent cross-coupling and 1-ones carbonylation reactions 208 – facile synthesis of 302 – cyclization with alkyne- or alkene-containing 2-methyleneindanones 61 nucleophiles 208 methyleneindolinone 456 multicomponent cyclocarbonylations 3-methylenepyrrolidine derivative 455 214–216 4-methylene-tetrahydroisoquinolines 302 multicomponent reactions 1, 4, 5, 14, 439 methyl 2-iodobenzoate 302 – of arynes, β-ketosulfones and electron- methyl isocyanoacetate 26 deﬁcient alkenes 53 methyl 2-methylbut-3-yn-2-yl carbonate 309 – of arynes via electrophilic coupling methyl-4-nitro-2-benzoate 103 41, 42 methyl pyruvates 188 – based computational methods 6 methyl thioisocyanate 326 – under basic conditions 53, 58–62 Mg/La mixed oxide 117 – and biocatalysis 23, 25 Michael acceptor functionality – catalytic enantioselective 449 – in ortho-position 302 – chemistry for easy/cheap synthesis and Michael acceptors 53, 112, 115, 124, 289, 303, process improvement of marketed drug 8 352, 379 – complex chromanone products 383 Michael addition 53, 110, 112, 124, 126, 197, – copper-, nickel-, and rhodium- 289, 344, 352, 353, 416, 446 promoted 310–314 – based three-component access to – developed by Hantzsch and Biginelli 110 pyrroles 127 – with 1,3-diester derivatives 132 – cyclizing carbocupration–cross-coupling – and (dynamic) enzymatic kinetic sequence 349 resolution 26 – initiated three-component synthesis of – and enzymatic desymmetrization 29–31 pyridines 124 – general concept 15 – thiols onto enones 416 – homophthalic anhydride 383 Michael/aldol (dehydration) sequences 136 – involving α-oxoketene generated by Wolff Michael–aldol-type reaction 197 rearrangement for 134 Michael-initiated MCRs 166 – involving α-oxoketene generated from Michael–Michael–cyclization–Diels–Alder Meldrum’s acid 132 sequence 353 – involving β-keto esters in Michael/aldol Michael reaction 143, 318 sequences 137 – decarboxylative 412 – involving in situ generated enamino esters as – intramolecular 318 bis-nucleophiles in 136 – reﬂexive ynones 143 – isatoic anhydrides 384, 385 microwave heating – isonitriles and 1,3-dicarbonyls for synthesis – aldehyde with IBX 270 of pyrrole 128 Mizoroki–Heck-type multicomponent – maleic anhydride 385 reactions 65 – in material chemistry 9

MnO2-/PCC-mediated multicomponent – microwave-assisted 34 oxidation–Wittig oleﬁnation–Diels–Alder – under neutral conditions 42 reactions 282 –– amine-based multicomponent modular reaction sequences (MRS) 17–19 reactions 47, 48 monoamine oxidase N (MAO-N) 91 –– carbonyl compound-based 49, 50 monocarbonylation product 421 –– ether-based multicomponent reactions monoclonal antibodies (mAbs) 10 50, 52 monosubstituted triazoles, synthesis 323 –– imine-based multicomponent monoterpene 425 reactions 46, 47 486 Index

–– isocyanide-based multicomponent β-nitro alcohol 425 reactions 42–46 nitroalkenes 144, 167 – nickel-promoted 310 3-nitro-2-arylimidazo[1,2-a]pyridines 293 – palladium-catalyzed MCR – derivatives from aminopyridines, aromatic –– of aryl iodides, diazoacetates, CO, and aldehydes, and nitromethane 293 triethylsilane via a carbonylation/ p-nitrobenzaldehyde 95 acyl migratory insertion process 201 (see nitrogen-containing heterocycles 306 also palladium-catalyzed reactions) – synthesis 310 –– of N-substituted o-iodoanilines, diazo nitrogen-substituted allenes 323 compounds, and CO via 202 nitroketene dithioacetal 390 – photoredox 278 nitromethane 293 – Povarov MCRs (see Povarov reaction) nitrones 274, 315, 364 – Reissert-type 164 – three-component synthesis 364 – rhodium-promoted 310 nitroolefin 145 – Sonogashira-initiated 169 2-nitrophenol 77, 81, 96 – synthesis of bis-pyranobenzoquinones and 3-nitrophenylpropynoic acid 270 ZD0947 141 nitrosation 95 – uncatalyzed 318–323 β-nitrostyrenes 185 – union 18, 23 nitrothiophenols 83 –– based on 2-imidazoline and NO addition product N-(cyanomethyl)amide MCRs 24 – tautomerization of 403 – via 1,3-dipolar cycloaddition 223–227 nonrepetitive macrocyclic architectures 232 – via metal carbene migratory insertion norbornene, enantioselective rhodium- 199–201 catalyzed hydroboration of 408 – without transition metals 314, 315 nucleophile (NuH) 380, 421 multicomponent synthesis of substituted – acylating agents 379 pyrrolidines and tetrahydrofurans 209 nucleophilic multimacrocycles – aromatic substitution 343 – sequential MiBs applied to the synthesis – pivaloyloxymethyl radical 431 of 260 – radical 407 multiple bond-forming transformations –– species 428 (MBFTs) 109 – reaction 351 multiple multicomponent macrocyclization 245 o Mumm rearrangement 80, 273, 277 octyl iodide 421 münchnones 226 olefins 402, 416, 421, 426 – biomimetic three-component 1,3-dipolar n cycloaddition 459 nanozeolite catalyst 117 – carboazidation 404 naphthalenes 369 – carbodiazenylation reaction 402 2-naphthol 129 – C=C bonds 2-naphthylamine 368 –– aryl radicals, addition 402, 403 natural product-inspired biaryl ether– –– carbohydroxylation/sulfenylation/ cyclopeptoid macrocycles 253 phosphorylation 407–410 natural product, use of MCR in total synthesis –– electron-poor olefins, carboallylation of 4 of 406, 407 NHC-boranes 419 –– photoredox catalysis 410–414 NH γ-lactam 386, 387 –– radical–polar crossover processes Ni-catalyzed [2 +2+2]-cycloaddition 373 414–418 nickelacyclopentadiene 372 –– sulfonyl derivatives as terminal trap nifedipine 5 404–406 β-nitrate 425 – electron-deficient 406 nitrilium intermediate 279 – electron-poor 455 Index 487

– excellent diastereocontrol 406 p – ketooxygenation of 427 palladacyclopentadiene 66, 67 – oxidative nitration of 425 palladium acetate 102 – radical alkylphosphanylation of 409 palladium-catalyzed reactions 34, 168, oligomerization 233 304, 421 one-pot oxidative Biginelli reaction, plausible – carbonylation, of aryl iodide 200 mechanism 281 – [2 +2 +2]-cycloaddition of arynes 39 one-pot palladium-catalyzed MCR toward – enolates 102 APOs 35 – iminoacylation 34 o-phenylenediamines 125 – multicomponent reactions 26, 29, 34, optically pure tertiary alcohol acetates, 302–310 synthesis of 28 –– allene dipolar cascades 170 organoborane ––of allenes, aryl iodides, and diazoacetates via – alkyl radical 406 a carbopalladation/allyl migratory insertion – precursor 407 process 203 organoboronic acids 65 –– with heterocyclic reactants 168 organocatalysts 148 –– to synthesize amidines 34 – for enantioselective Biginelli – oxidative 5-endo-dig cyclization– reactions 149 alkoxycarbonylation 293 organolithium 53 – Pd–Cu catalysis 101, 340 ortho-phenylenediamine 94 – Pd-cyanamide 348 ortho-(triﬂuoromethyl)aryl iodides 53 – Pd-iminoyl azide 348 ortho-(triﬂuoromethyl)arylsilver species 53 paraformaldehyde 292 oxadiazolidine 365 Parikh–Doering (Pyr SO3/DMSO) oxaloacetic acid 109 conditions 273 oxanickelacycle 312 Passerini adducts 267, 268, 270 [1,4]-oxazinium 433 Passerini condensation oxazinones 133 – under aerobic oxidation 270 1,3-oxazin-4-ones 133 Passerini product 28 oxazoles Passerini reactions 265, 266–271. see also – moiety 443 P-3CR – synthesis of heterocycles 328 – alcohols and N-alkyl amines 266 oxazolidinones 335 – derived acrylic acid monomers 9 1,3-oxazolium-5-oxides (Münchnones) 226, – postulated mechanism for 271 227, 357 –– aerobic oxidative catalytic 2-(3-oxetanyl)benzaldehydes 453 conditions 271 oxidative aromatization 128, 372 Passerini–Smiles reaction 91–94 oxidative Biginelli-3CR, catalyzed by acidic Passerini three-component reaction ionic liquid 281 (P-3CR) 10, 236, 379 oxidative domino cross-coupling reaction – with alcohols 266 – between indoles, β-keto esters, and aryl – β-azido alcohols 269 boronates 294 – dihydrooxazinones, synthesis of 269 oxidative multicomponent annulation 292 – MiB approach 255 oxime 416 – oxidative 267 – electron-rich radical species 406 –– building blocks 267 – sequential multicomponent reaction 406 –– multiple multicomponent 8-oxo-bicyclo[3.2.1]octane derivatives 136 macrocyclization 268 4-oxo-enoates 196 –– with phenylethanol, benzyl isocyanide, 2-oxo-1H-indol-3-ylidenes 320 and benzoic acid 266 4-oxo-1,3-thiazinan-5-yl acetic acids 388 Passerini–Zhu protocol 267–269 N-oxyl radical 407 PEG-diamine 250 oxypalladation–carbonylation sequence 316 penicillin 4 oxytocin receptor antagonists 5 pentacyclic products 488 Index

– [1,3]-hydrogen shift 321 polymerization 233 peptide-based compounds 6 polymer-supported triphenylphosphine peptide nucleic acid (PNA) 10 (PSTPP) 268 peptidomimetics 31 polysubstituted perhydrofuropyrans 140 – acrylates, four-component synthesis of 352 – derivatives 141 – furans and pyrroles 208 pericyclic reactions 356 – pyrazolidin-3-ones 134 Petasis reaction 304 – pyrroles 226 – using hetarylboronic acids 304 –– four-component synthesis, mechanistic pharmaceutical production rationale of 358 – E-factors 31 – pyrrolidines 145 – standard guidelines 31 – tetrahydrofurans 208 3-phenacylideneoxindoles 126 postcondensation 2. see also Ugi-Smiles phenanthrenes 60 postcondensations phenols 81 potassium carbonate 102 – nucleophilic addition of 354 potassium persulfate 291 – Ugi-type reaction with 276 potassium tert-butoxide 22 phenoxy radical, irradiation 433 Povarov–oxidation sequence 368 phenylacetylene 101 Povarov reaction 451, 462 phenylethynyl iodide 53 – adducts 161 phenyl isocyanate 391 – with β-substituted (E)-enecarbamates 449 phosphine ligand 277 – chiral phosphoric acid-catalyzed phosphoric acid –– aniline with methyl pyruvate 451 – azomethine ylides catalyzed 455 – cyclic enethioureas as dienophiles 449 – catalyzed Biginelli reaction 148 – dihydropyridines and unsaturated lactams phosphorus 409 in 162 photoafﬁnity-labeled peptoids 270 – with 2-hydroxystyrenes 451 photoinduced electron transfer (PET) 410 –– as dienophiles 450 photosensitizer 274 – indoles 163 PhSeSePh 433, 434 – involving isatin o-phthalaldehyde 119 –– four-component, anilines with methyl phthalazinones 393, 395 pyruvates 452 phthalic anhydride –– three-component 448, 452 – 4CR by Mosaddegh 394 – mechanistic variations 163 picolinamide–nicotinamide hybrids 290 – reaction involving cyclic enol ethers and Pictet–Spengler reactions 8, 122, 160, 173, esters. 162–166 344, 466 – total synthesis of martinelline by 162 piperidine 117, 118 – using enecarbamates 447 – access via Mannich-type reaction/cyclization praziquantel, three-step synthesis involving 8 cascade reactions 441 primary amine – trans-isomer 441 – Ti precursor complex 370 piperidine derivatives 441 – titanium-catalyzed four-component reaction piperidines 307 of 370 piperidinones 406 proline-derived secondary amines 148 PNA synthesis, using sequential Ugi reaction 9 pronucleophilic reactive site 111 polar effects 401 1,2-propadiene polycyclic benzimidazoles 128, 129 – secondary amines of 303 polycyclic products 453 – three-component reaction 302 polyfunctionalized furans 397 n-propanol 429 polyfunctional substrate 424 propargyl alcohols 346 polyheterocyclic scaffold 353 propargyl amidine 365 polyheterocyclic systems 175 propargylamines 103, 335 polyheterocyclic zwitterions 173 – A3-coupling for synthesis 336 Index 489

– furnishing propargylamides 362 pyrrolidine-2,3-diones 113 – synthesis 336 pyrrolidines 138, 208, 454 – three-component synthesis of 365 – derivatives 454, 458 propargyl bromide 67, 68 – Ugi-Smiles reaction of 276 propargyl carbonates 307 – yielding multisubstituted, 1,3-dipolar propiolic acids cycloaddition of 454 – 1,3-dipolar cycloaddition 269 pyrrolines 225 propionaldehyde 77, 102 3-pyrrolines 2-(2-propynyl)aniline derivatives 463 3-pyrrolines, three-component synthesis protein–protein interactions 7, 232 of 356, 357 protons pyrrolo[3,4-b]pyridin-5-ones, synthesis 392 – primordial electrophilic activation of 346 pyrrolopiperazines 122 – transfer process 197 pyrrolopyrimidines 103 N-pyrazinyl derivatives 84 pyrroloquinoline library 162 pyrazoles – four-component synthesis of 371 q – Ti-catalyzed vinamidine formation- quinolines 87, 99, 175 cyclocondensation synthesis of 371 – ferrocenyl-substituted 337 pyrazolidine derivatives 311 quinolinyl moieties, as antimalarial – diastereoisomers (3R,5R) 311 pharmacophore 337 pyrazolidinones 133 quinones 185, 455 1H-pyrazolo[1,2-b]phthalazine-1, quinoxaline derivatives 339 2-dicarboxylates 393, 394 quinquethiophenes 342 pyrazolones 137 1H-pyrazolo[1,2-a]pyridazine-1, r 2-dicarboxylates 393 racemic esters 396 pyridazinones 393, 395 racemization 302 – synthesis of 393 radical–polar crossover processes 414 pyridines 97, 98, 123, 124, 288 reaction design concept 15–17 – containing structures, generation of 390 regiodivergent reaction 315 – heterocycles 309 regioisomers 306, 307

–– synthesis of 327 Rh2(OAc)4 461 – MCR synthesis of 289 rhodium- and ruthenium-catalyzed – mechanism proposed for three-component synthesis synthesis 289 – of heterocycles from azomethine and pyrido[1,2-a]pyrimidin-4-imines 364 carbonyl ylides 225 – three-component synthesis 364 rhodium carbenes 188 pyrido[1,2-a]-fused 1,3-diazaheterocycles 389 rhodium catalysis, usages 313 pyrido[2´,1´:2,3]imidazo[5,1-a]isoquinolinium rhodium-catalyzed three-component reactions triflates 347 – of alcohols, aryl diazoacetates pyridoxal phosphate (PLP)-dependent –– and aromatic aldehydes 189 enzymes 458 –– and N-(tert-butylsulfinyl)imines 190 pyridyl-stabilized carbanion 357 – of aryl diazoacetates, anilines, and pyrimidine-N-oxides 4-oxo-enoates via switchable reaction – oxygen substituents 328 pathways 197 – synthesis of heterocycles 328 – of diazo compounds with anilines and pyrimidines 97, 98 β,γ-unsaturated α-keto esters and – synthesis of heterocycles 328 subsequent cyclizations 196 N-pyrimidinyl carboxamides 85 – intramolecular cascade Michael–aldoltype pyrroles 127, 128, 225, 318, 325 reaction 197 – derivatives 313, 315, 318, 326 – rhodium(II) chiral, catalyzed reaction of –– synthesis 312, 317 anilines, diazophosphonates, and electron- – four-component synthesis of 346, 357 deficient aromatic aldehydes 191 490 Index

– via trapping of ammonium ylides with SPINOL-phosphoric acid 148, 448 imines 188 spiroanellated dihydrofuran 357 – of water, diazo compounds, and aryl spirocyclic oxindole-butenolides imines 189 – [2+2+1]-cycloaddition reaction 319 ring-closing metathesis (RCM) 97, 235 spirocyclic oxindoles Ritter reaction 163, 327, 412 – one-pot synthesis of 320 Robinson–Schöpf synthesis 109 spirocyclohexenones 144 Ru-based metathesis 97, 98 spirodihydrofurans 118 ruthenium carbene 184 4-spiro-3,5-disubstituted cyclohexanones 143 ruthenium carbonyl-catalyzed pseudo-four- spiroheterocycles 113 component reaction 371 spiroheterocyclic systems 165 spiro[indolin-3,2´-quinolines] 451 s spirolactones 244, 393

(Sa)-allenylsilane spiro[4,6]-lactones 115, 116 – with aldehyde and tert-butyl carbamate 315 – synthesis 117 sacrificial reagent 279 spirooxindoles 146, 353, 384 salicylaldehydes 464 – derivatives 144, 456, 457 salicylaldehydimines 465 – pyranochromenediones 142 salicylic aldehyde 360 – skeletons 456 samarium diiodide complex spiropyranoxindoles 146 – with HMPA reacts 432 spiropyrazolidin-3-one 134 saponification 245 spiro[pyrrolidin-3,3´-oxindole] ring scandium triflate 120 system 455 Schiff bases 254 spiro[pyrrolidin-3,2´-oxindoles] synthesis secondary amine 431 – 1,3-dipolar cycloaddition 457 Sepharose solid support-bound Ugi products 9 spiro[pyrrolidin-3,3´-oxindoles] synthesis sequence-specific polymer synthesis 9, 10 – 1,3-dipolar cycloaddition 457 sequential palladium-catalyzed cyclization– spiropyrroloxindoles 145 azide 323 3-spiro-1,2,3,4-tetrahydroquinolines 114 S-H bond dissociation enthalpy 413 spiro-type polyheterocycles 122 [1,5]-sigmatropic rearrangement 325 Staudinger–aza-Wittig step 268 single-component two-center reaction (SCR)- stereomeric oxazolines 269 based approach 235 steroid–peptoid hybrid macrocycles 249 single-electron transfer (SET) 402 – with hydrophilic and lipophilic moieties 252 – oxidation 278 steroid–peptoid hybrid macrocycles, by Ugi- single reactant replacement 17–19 4CRs 251 – strategy 15 Strecker reaction 427, 429 ––replacing aldehyde/ketone for an imine 19 structure–activity relationships (SARs) 1 six-membered ring hydroxy styrenes 412, 417, 426 heteroaromatics 84 – hydroxytrifluoromethylation of 413 Smiles rearrangements 76, 77 N-substituted o-iodoanilines 201 sodium ethoxide 22 N-substituted 3-pyrrolines 357 sodium 2-iodobenzenesulfonate 272 – imine and dimethyl sodium methoxide 85 acetylenedicarboxylate 357 sodium nitrite, removal of 271 succinic anhydrides 380 solubility problems 85 sulfones 422 SOMO catalysis 417 – cyclic enecarbamates and enamides 404 Sonogashira coupling 101, 335, 337, 342 sulfonohydrazide 283 – at E-configured bromostyrene position 337 sulfonyl azides 362 – of heteroaromatic halides 339 – radical-mediated Cu-catalyzed three- Sonogashira-Glaser reaction 340 component 366 – cyclization synthesis – radical-mediated Cu-catalyzed three- –– pseudo-five-component 341 component reaction of 366 Index 491

– three-component synthesis 364 – multicomponent synthesis of 417 – three-component synthesis of 365 – products 187 N-sulfonyl-N,N-disubstituted amidines 366 tetrahydroisoindolo[1,2-a]isoquinoline – three-component synthesis 366 amides 391, 392 sulfonyl group, fragmentation 423 tetrahydroisoquinoline 273 2-(N-sulfonylimino)indolines 366 – domino oxidation/Ugi-type reaction – three-component synthesis of 367 of 274 sulfonyl ketenimines 362, 364, 365, 366 tetrahydroisoquinoline-containing – formation 365 peptidomimetics 274 – intermediate, [3+2]-cycloaddition of 364 1,2,3,4-tetrahydropyrazine 96 – nitrogen extrusion 362 tetrahydropyridines 447 sulfur-based binucleophiles 342 tetrahydroquinolines 451 sulfur nucleophiles 342 – with chiral quaternary stereogenic Suzuki-type coupling reaction 309 centers 450 symmetrical 2,5-di(hetero)arylthiophenes tetramethylammonium hydroxide 117 – pseudo-ﬁve-component 341 meso-tetraphenylporphyrin 274 synthetic organic chemistry 13 tetrasubstituted pyrroles 127 2,3,4,6-tetrasubtituted pyridines 289 t – exploiting dual catalysis by activated tandem oxidation–Wittig oleﬁnation–Diels– carbon 290 Alder reaction with α-hydroxy tetrazoles 17 ketones 281 thiazoles 89 tautomerization 17, 117, 125 thiazolium salt deprotonation 345 TBHP/Cu(I) oxidizes amine 277 thioamides 97 telaprevir 8 – adducts 97 – using two MCRs and biocatalysis 33 thiocresol 386 TEMPO (2,2,6,6-tetramethylpiperidine- thioether 408 1-oxyl) 270 – electron-rich radical species 406 tentoxin acyclic precursor 232 thiol–monoterpene co-oxygenation reaction terminal alkynes 360, 362 (TOCO) 425 terpene 136 thiols 416 tertiary alcohol acetates, optically pure 28 thiophenes 168 tertiary alcoholate 354 thiophosphinylation 434 tertiary amines 283 thiosalicylate derivatives 84 – radical-mediated Cu-catalyzed three- thiourea 148 component 366 three-component reactions (3CRs) 7, 30, 236, – Ugi-type reaction 277 269, 382, 397, 402 tetrabutylammonium bromide (TBAB) 280 – 2-alkynylbenzaldehydes, sulfonohydrazide, tetrabutylammonium decatungstate and tertiary amines 282 (TBADT) 422 – anilines predominate 382 tetrabutylammonium tribromide 135 – catalysts and mediators 382 tetracyclic chromenes – tuning by adapting reaction conditions 22 – isonitriles and acetylenedicarboxylates 383 – Ugi-3CR adduct 392 tetracyclic compounds 304 – of vinyl iodides, ethyl diazoacetate, and tetracyclic indeno[1,2-b]indole 396 amines 203 tetracyclic products 384 – water 462 tetrahydro-β-carbolines 343 Ti-imino species 370

– coupling-addition-aza-annulation-Pictet- Ti(IV)/Et3N systems 111 Spengler synthesis of 344 TiO2 catalyst 278 – diastereoselective formation of 343 Togni’s reagents 407, 412 – four-component synthesis 344 toluene 77 tetrahydrobenzoxanthones 128, 129 p-toluene sulfonic acid 125 tetrahydrofuran (THF) 266 N-tosyl benzodiazepine 292 492 Index

N-tosyl imine 227 tropolone 90 tosylimines 322 Truce–Smiles rearrangemen 103 N-tosyl-substituted imines 226 tryptamine derivatives 343 1-tosyl-1,2,3-triazoles 312 tryptophyl derivatives 164, 165 transformations, involving metal carbene tungstophosphoric acid 113 migratory insertion 200 two-dimensional multicomponent transition metal catalysis 41, 207, 208 sequence 295 trialkylamines 410 tyrosine 233 trialkylboranes 415, 416 triazine 97 u 1,2,4-triazine 167 Ugi-5C-4CR variation 3 triazoles 313, 360 Ugi–deprotection–cyclization (UDC) 2 – derivatives 362 Ugi diketopiperazines 6 – retro-Diels-Alder step furnished 323 Ugi four-component reaction (U-4CR) triazolo-fused dihydrooxazinones 269 236, 442 3-triazolyl-2-iminochromenes – based approach to RGD cyclopeptoids 239 – three-component synthesis of 360 –– sequential elongation/cyclization 239 triazol-1-yl-quinolin-2(1H)-ones 361 – macrocyclization of glycine oligomers 238 – three-component synthesis of 360, 361 – stoichiometric and catalytic oxidative 272 3-triazolyl-substituted N-heterocycles Ugi–intramolecular Diels–Alder MCRs 175 – three-component synthesis 340 Ugi-MiB-based quenching approach tributylstannyl(diethyl)amine 34 – of macrocyclic oligoimine-based dynamic tributyltin radical 404 combinatorial libraries 256 2,4,6-trichlorobenzoyl chloride 234 Ugi-MiB combinatorial approach 255 tricyclic anellated azepines 359 – biaryl ether bisisonitriles in 253 tricyclic pyridines, obtained with 3CR Ugi-modified stationary phases 10 approach 289 Ugi postcondensations 94 trifluoroacetic anhydride (TFAA) 397 Ugi reactions 74 trifluoroborane 466 – with alcohols 271–273 1,1,1-trifluoro-2-butanone 26 – alcohols and N-alkyl amines 266 trifluoroethanol (TFE) 413 – with hydrazines 74 trifluoromethanesulfonic acid 327 – in organic synthesis 73 trifluoromethylating agent 413 – with secondary amines 74, 273–275 trifluoromethylation–iodination, of – variation of 4 arynes 53 Ugi reagents 272 trifluoromethyl-containing compounds Ugi–Smiles couplings – three-component reaction 465 – of 2-nitrophenols. 78 trifluoromethyl-ketones 318 Ugi–Smiles postcondensations 94 trifluoromethylsilver 53 – cycloaddition 103–105 3,4,5-trimethoxyaniline 465 – involving reduction of nitro trimethylsilyl azide 348 group 94–96 trimethylsilyl cyanide 285 – involving transition metal-catalyzed

trimethylsilyldiazomethane (TMSCHN2) 202 processes 97 trimethylsilyl triﬂate 315 –– palladium-catalyzed processes 98–101 triphenylene derivatives 39 –– Ru-based metathesis 97, 98 tris(2-aminoethyl)amine (TREN) 257 – radical reactions 103 2,3,4-trisubstituted 4-aryl – reactivity of peptidyl unit 101–103 tetrahydroquinolines 450 – Ugi–Smiles thioamides, transformations 1,4,5-trisubstituted pyrazoles 370 96, 97 – titanium-catalyzed four-component reaction Ugi-Smiles reaction of 370 – adduct 80 2,3,4-trisubstituted 1,2,3,4- – based strategies 74 tetrahydroquinolines 448 – energy proﬁle Index 493

–– in methanol 82, 83 vinyl sulfones 404 –– in toluene 82, 83 vinyl zinc 417 – mechanism 275 – with secondary amines 275, 276 w – with tertiary amines 277–279 Wittig-type oleﬁnation 120 Ugi-type reaction involving tertiary amines, Wolff rearrangement 134 isocyanides, and carboxylic acids or – cyclic 2-diazo-1,3-diketones 133 water 277 Ullmann coupling 98, 366 x Umemoto’s reagents 412 1,2-undecadiene 313 xanthate 406 xylocaine 2 unidirectional Ugi-MiB 247, 251 α,β-unsaturated acid chlorides 343, 344 α,β-unsaturated aldehyde 391 y α,β-unsaturated cyclic anhydrides Yamaguchi’s conditions 234 – Diels–Alder reactions 390–392 Yb(III)-catalyzed, synthesis of fully substituted – isatoic anhydrides pyrazoles 129 –– MCRs of 388–390 Yonemitsu reaction 111, 164, 165 – maleic anhydride MCRs 385–388 α,β-unsaturated esters 416 z 5,6-unsubstituted 1,4-DHPs 122 Zhu-3CR–[4+2]-cycloaddition–[4+2]- cycloreversion–oxidation sequence 369 v Z-protected glycine 257 vabicaserin 292 zwitterionic acid ﬂuorides 397, 398 vinamidine 371 zwitterionic hydroquinone-fused [1,4]- vinylazide 318 oxaziniums 432, 433 vinyl bromophenol ether 354 Zwitterionic intermediates 198 vinyl copper specie, transmetalation – MCRs via electrophilic trapping of 348 198, 199 vinyl pivalate 406 zwitterions 319, 320, 354