587

Index

a acyl halides 52–55 ab initio calculations 24, 40, 41 O-acyl isoimides 49–51 Acantkella acuta 21 S-acyl isoimides 50, 51 acetals 188, 189, 401 acyl transfer reactions see Mumm acetylenedicarboxylates rearrangements – nonclassical IMCRs 315, 316 acylating agents 129–133 – zwitterions 264–267, 269, 271, 274–277 2-acylbenzazepines 54 achiral isocyanides 1 1-acyl-3,4-dihydroisoquinolines 54 acid addition reactions 49–52 α-acyloxyaminoamides 367 acid-mediated polymerization 25 acylpiperazines 352 acid-promoted condensations 355 2-acylpyrrolines 54 α-acidic isocyanides 75–108 acylthioamides 53, 54 – dihydropyridone MCR 95–97 2-adamantyl isocyanide 37 – 4,5-disubstituted oxazole MCR 83, 84 ADC see acyclic diaminocarbenes – 2-imidazoline MCR 91–95 AFM see atomic force microscopy – isocyanide reactivity 78–80 AIBN see azo-bis-isobutyronitrile – multicomponent reactions 75–108 alcohols – nitropyrrole MCR 83, 84 – carbene coupling reactions – oxazole MCR and in situ Domino process 532–537 88–91 – chiral nonracemic isocyanides 2 – synthesis 76–78 – isocyanide reactivity 64–66 – 2,4,5-trisubstituted oxazole MCR 84–88 – zwitterions 273–275 – 2,6,7-trisubstituted quinoxaline MCR 82, aldazines 204 83 aldehyde-acids 362, 366–371 – union of MCRs 93–95 aldehydes – van Leusen imidazole MCR 81, 82 – amine surrogates 199 acrylonitriles 116 – carboxylic acid surrogates 180–184 activated alkenes – chiral nonracemic isocyanides 4, 5 – isocyanide reactivity 55–58 – isocyanide reactivity 58–60 – α-isocyanoacetic acid derivatives 116, – α-isocyanoacetic acid derivatives 116, 117 121–126, 141, 142 – pyrrole synthesis 386–390 – nonclassical IMCRs 305, 317 – zwitterions 279–281, 284–286, 288 – zwitterions 275, 276, 283 activated alkynes 55–58, 390 aldol reactions 18, 121–126 activated azines 220–223 alginate-coated gold electrodes 241, activated heterocumulenes 60, 61 242 activated isocyanides 299, 308–320 aliphatic isocyanide reactivity 36–41, acyclic diaminocarbenes (ADC) 531–533, 43–46, 52 537, 546 aliphatic nitriles 37–39

Isocyanide Chemistry: Applications in Synthesis and Material Science, First Edition. Edited by Valentine Nenajdenko. © 2012 Wiley-VCH Verlag GmbH & Co. KGaA. Published 2012 by Wiley-VCH Verlag GmbH & Co. KGaA. 588 Index

alkenes amino isocyanides 11, 12 – isocyanide reactivity 55–58 N-aminolactams 214 – pyrrole synthesis 386–390 5-aminooxazoles 140, 141 – zwitterions 279–281, 284–286, 288 2-amino-4H-pyrans 270 5-alkoxyoxazoles 80 2-aminopyrazoles 466 alkyl isocyanoacetates 109, 110 aminopyrroles 278, 279 alkyl 2-nitroethanoates 268 5-aminothiazoles 132 alkyl phenylglyoxylates 316 anthracenes 410, 411 alkylamines 281 anti-fouling activity 20, 21 N-alkylated quinolines 220, 221 antitubulin chalcones 471 alkylation reactions 113–115, 351, 352 Arbuzov reactions 10 alkyne–azide cycloaddition reactions arenesulfenyl chlorides 138 442–444 Armstrong benzodiazepine synthesis 433 alkynes aromatic nitro compounds 402–407 – isocyanide reactivity 55–58 aromatic substitution reactions 355, 356 – α-isocyanoacetic acid derivatives 119–121 aryl transfer reactions see Smiles – pyrrole synthesis 390, 401, 402 rearrangements – zwitterions 263–282 N-aryl amidation reactions 437, 438 allylation reactions 114 N-aryl arylimines 64 alternating peptoid–peptide chimeras 253 N-aryl carboxamides 171, 172 ambiguine H 22, 23 aryl isocyanide reactivity 36, 39–41, 43–46, amides 50, 51, 271–273 52, 53, 65 amidines aryl nitriles 39, 40 – carbene coupling reactions 538, 539 arylsulfenyl chlorides 55 – carboxylic acid surrogates 179, 184 arylsulfonylmethyl isocyanides 76–80 – chiral nonracemic isocyanides 15 N-aryl thiocarboxamides 175, 176 – molecular diversity 371–373 arynes 283, 284, 316–318 – nonclassical IMCRs 324 Asinger reactions 362 aminals 188, 189 atomic force microscopy (AFM) amine surrogates 195–231 – chiral nonracemic isocyanides 26 – activated azines 220–223 – polyisocyanides 558, 563, 567, 572 – enamines, masked imines and cyclic atropisomerism 23, 557 imines 223–227 Axinella cannabina 18 – hydrazines 200–218 axisonitrile-1 16 – hydroxylamines 196–200 axisonitrile-3 18 – isocyanide reactivity 220–223 aza-Diels–Alder reactions 89, 90 – miscellaneous surrogates 218–220 1-azadienes 269 amines 6-azaindolines 89, 91 – carbene coupling reactions 532–537 aza-β-lactams 212 – chiral nonracemic isocyanides 2, 3 azasugar imines 225, 226 – isocyanide reactivity 64–66 aza-Wittig reactions 358, 359, 439, 440 – zwitterions 264 azepine tetrazoles 170 amino acids azetidinones 186 – amine surrogates 203 azides – α-isocyanoacetic acid derivatives 111 – amine surrogates 226 – molecular diversity 362–365 – chiral nonracemic isocyanides 11, 12 – polyisocyanides 563 – polyisocyanides 570, 571 α-aminoaldehydes 436, 437 – tetrazole synthesis 471–473 aminoboranes 184 2-azidophenyl isocyanide 540 aminocarbenes see carbenes azines N-aminocarbonyl amides 218 – amine surrogates 220–223 amino carboxamides 182 – nonclassical IMCRs 300, 304–306 aminocarbynes 532 azinium salts 300 2-aminofurans 451–453 azoalkenes 206 Index 589 azo-bis-isobutyronitrile (AIBN) 14, 47 – tethered aldehyde and keto acids 362, azolium salts 306 366–371 azomethines 59, 60, 310–312 – tethered heterocyclic amidines 371–373 Biginelli reactions 76 b binucleation of mononuclear ligands 515, Barton–Zard pyrrole synthesis 116, 117, 516 386, 390–410, 420–424, 458 biocatalytic desymmetrization 13 base-promoted condensations 355 bioconjugates 240, 241, 258 BBN see 9-borabicyclononanes biomimetic syntheses 20, 21 BCOD see bicyclo[2.2.2]octadiene bipyrroles 396, 397 benzamides 284 bis(aminofuryl)bicinchoninic amides 274, benzazepines 342, 343 275 benzhydrylium ions 36 Bischler–Napiralski synthesis 48 benzimidazoles 2,3-bis-iminoazetidines 59, 60 – IMCR examples and protocols 473 block copolymers – molecular diversity 338, 340, 341, 345 – chiral nonracemic isocyanides 26 benzimidazolium salts 307, 308 – polyisocyanides 556, 557, 565, 574 benzochromenes 274 BODIPY see boron–dipyrromethene 1,5-benzodiazepine-2,4-diones 443–446 bond-forming effi ciency 336 1,4-benzodiazepine-2,5-diones (BZD) 9-borabicyclononanes (BBN) 22, 23 337–339, 345, 433–439 boron–dipyrromethene (BODIPY) dyes benzodiazepines 431–449 385, 386, 391, 420–424 – 1,4-benzodiazepine scaffolds via IMCRs boron trifl uoride 186 433–443 borylative cyclization reactions 326 – 1,5-benzodiazepine scaffolds via IMCRs bovine serum albumin (BSA) 240, 241 443–446 bridging ligands – fused-ring systems 440–443 – carbenes 534, 535 – molecular diversity 337–340, 343–347, – isocyanoarenes 494, 495, 514–517 349, 350 2-bromobenzoic acids 437 – two-ring systems 433–440 β-bromo-α-isocyanoacrylates (BICA) 135, benzodiazepinones 353, 359, 437, 438, 445 136 benzofurans 473 Brønsted acids benzofused heterocycles 175, 176 – carboxylic acid surrogates 180, 181, 187 benzofused γ-lactams 366, 367 – molecular diversity 372 benzopiperazinones 176, 177, 357 BSA see bovine serum albumin benzoporphyrins 410 BTPP see t-butyl-iminotris(pyrrolidino) benzoquinones 317 phosphorane 1,4-benzothiazepines 368, 369 Burgess reagent 2 benzoxazepines 342, 343 butylated hydroxy toluene (BHT) 393 benzoxazepinones 353 t-butyl-iminotris(pyrrolidino)phosphorane benzoxazinones 351, 353 (BTPP) 401, 403, 404 benzoyl isothiocyanate 280, 281 BZD see 1,4-benzodiazepine-2,5-diones benzyl isocyanide 38 BHT see butylated hydroxy toluene c BICA see β-bromo-α-isocyanoacrylates carbamoylated dihydroisoquinolines 301 bicyclic lactams 338, 339, 358, 364, 373 carbenes bicyclic tetrazoles 343, 344 – amine and alcohol coupling reactions bicyclo[2.2.2]octadiene (BCOD) 385, 386, 532–537 409, 410, 414–416, 419, 423, 424 – dipole–isocyanide couplings 543, 544 bifunctional approach (BIFA) 361–374 – functionalized amine and alcohol – amino acids 362–365 couplings 537 – combined bifunctional and post- – hydrazine and hydrazone couplings 537, condensation modifi cations 373, 374 538 – cyclic imines 362, 365 – imine and amidine couplings 538, 539 590 Index

– intramolecular cyclizations 536, 537, chiral polyisocyanides 551–553 540–543 chiral racemic isocyanides 1 – α-isocyanoacetic acid derivatives 122, chiral stationary phases (CSP) 572 128 chlorination reactions 22, 53 – metal-bound isocyanides 531–550 chlorination–elimination strategy 226 – miscellaneous reactions 544–546 α-chloroketones 173, 174 – polyisocyanides 554 cholanic peptide–steroid hybrids 239, 240 – reactivity modes 531, 532 chromenes 274 derivatives 163–165 chromenylfurandicarboxylates 277 carbonimidyl chlorides 52, 53 chromium complexes carbonylmetalate complexes 493–497, – carbenes 540 502–505, 514, 515 – isocyanoarenes 511–516, 519–521 carboxamides 368–370 chromophore-functionalized polyisocyanides carboxylation reactions 110 563–570 carboxylic acid surrogates 159–194 cinchona alkaloid catalysts 117 – carbonic acid derivatives 163–165 circular dichroism (CD) spectroscopy – cyanamide 179 – chiral nonracemic isocyanides 24, 26 – hydrazoic acid 167–171 – polyisocyanides 557–559, 561–563, 565, – derivatives 166, 167 570, 573, 574 – mineral and Lewis acids 180–189 Claisen rearrangements 18, 77 – phenols and derivatives 171–179 click chemistry 361, 569–572 – selenide and sulfi de 165, 166 cobalt complexes – silanol 165, 166 – α-isocyanoacetic acid derivatives 126 – thiocarboxylic acids 160–163 – isocyanoarenes 497–501, 522 carboxylic acids collagenase-I 340, 341 – chiral nonracemic isocyanides 2 compound chemical tractability 336 – isocyanide reactivity 49–52 concanavalin A 237 – zwitterions 274, 275 conformation memory 560, 561 carvone 21 conformational constraints 96, 97 cationotropic 1,2-shifts 37, 38 contracted porphyrins 414, 417–420 cavitands 49, 50 convergent approach to natural product CD see circular dichroism mimics 256, 257 chalcogenation reactions 321–323 copper catalysts chiral auxiliaries 3, 4 – carboxylic acid surrogates 185 chiral nonracemic isocyanides 1–33 – α-isocyanoacetic acid derivatives 120, – amino and alcoholic functionalized 121, 128, 140 11–16 – isocyanoarenes 517 – amino isocyanides 11, 12 – molecular diversity 360, 361 – applications 26 – nonclassical IMCRs 326 – azido isocyanides 11, 12 – polyisocyanides 569 – carboxylic, sulfonyl and phosphonyl corannuleneopyrroles 403, 404 functionalized 4–10 core-modifi ed porphyrins 414, 416, 418 – hydroxy isocyanides 12–16 Cotton effects 559, 573 – α-isocyano amides 7–9 crosslinking 242, 243 – α-isocyano esters 4–7 crown ethers 536 – β-isocyano esters and amides 9 cryptands 246, 247, 255, 256 – isolation and natural sources 16, 17 CSP see chiral stationary phases – natural isocyanides 16–23 CTV see cyclotriveratrylene – phosphonylmethyl isocyanides 10 Curtius rearrangements 2, 3, 11, 20 – polyisocyanide synthesis 23–26 CV see cyclic voltammetry – racemization in synthesis 4–6 cyanamides 40, 179 – simple unfunctionalized isocyanides 1–4 α-cyano-divinylketones 118, 119 – sulfonylmethyl isocyanides 10 α-cyano-α-isocyanoacetates 137 – synthesis 1–23 N-(cyanomethyl)amides 85, 86 Index 591 cyclic imines cylindrical nanocapsules 49, 50 – amine surrogates 223–227 cysteine-based polyisocyanides 26 – chiral nonracemic isocyanides 5, 6 – molecular diversity 362, 365 d cyclic iminium derivatives 169 Davydov solitons 562 cyclic ketones 198 DBU see 1,8-diazabicyclo[5.4.0]undec-7-ene cyclic peptoids 254, 255, 358 DCC see N,N-dicyclohexylcarbodiimide cyclic thioimidic esters 282 DDQ see 2,3-dichloro-5,6-dicyano-1,4- cyclic voltammetry (CV) 555 benzoquinone cyclization reactions Debye–Scherrer X-ray analyses 557 – α-acidic isocyanides 80, 83–85 decarboxylation reactions 9 – amine surrogates 203, 216, 217 dehydration reactions – benzodiazepine synthesis 432, 435, 436, – α-acidic isocyanides 77, 78 438–441 – chiral nonracemic isocyanides 1, 2, 4, 9, – carbenes 536, 537, 540–543 14, 15, 18 – carboxylic acid surrogates 160, 161, 166, – α-isocyanoacetic acid derivatives 112 167, 177–179 dendrimers 253, 254, 258 – indole synthesis 474–477 Dendrobinium nobile 54 – isocyanide reactivity 48, 53–56, 58–61, density functional theory (DFT) 56, 65, 66 512–514 – α-isocyanoacetic acid derivatives 114, 2-deoxy-2-isocyano sugars 15 115, 118, 119, 122, 129–132, 135, 136, deoxypyrrololine 394 139–143 depsipeptides – molecular diversity 337–350, 355 – α-acidic isocyanides 96, 97 – nonclassical IMCRs 314, 315, 321–323, – α-isocyanoacetic acid derivatives 137 326 – multiple IMCRs 234, 251, 252 – pyrrole synthesis 385, 395, 396 DFT see density functional theory – quinoline synthesis 477–479 DHOP see dihydrooxazolopyridines – thiazole synthesis 464–466 DHP see dihydropyridines cycloaddition reactions DIA see 2,6-diisocyanoazulene – α-acidic isocyanides 78–82 gem-diactivated olefi ns 288 – amine surrogates 198 diarylglyoxal 205 – benzodiazepine synthesis 442–444 3,4-diarylpyrroles 395 – chiral nonracemic isocyanides 11, 12 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) – isocyanide reactivity 35, 55–61 389–406, 455, 456 – α-isocyanoacetic acid derivatives 117, diazaborolidines 310 118, 120, 121 diazadiborinines 309 – isoxazole synthesis 461, 464 DIB see 1,4-diisocyanobenzene – molecular diversity 357, 359–361, DIBA see 2,2´-diisocyano-6,6´-biazulenyl 371–373 2,3-dichloro-5,6-dicyano-1,4-benzoquinone – nonclassical IMCRs 303, 310–312, (DDQ) 318–320 – multiple IMCRs 252, 253 – polyisocyanides 569 – nonclassical IMCRs 301 – pyrrole synthesis 385, 414–416 – pyrrole synthesis 408, 409, 419 – zwitterions 264, 265, 280, 281, 285, 286 – quinoxaline synthesis 479 cyclobutenediones 277, 278 N,N-dicyclohexylcarbodiimide (DCC) cyclobutyl isocyanide 38 2, 51 cyclocondensation reactions 122 Diels–Alder reactions cycloelimination reactions 303 – α-acidic isocyanides 88–90 cyclopropanes 288, 289 – chiral nonracemic isocyanides 20 cyclopropenimines 55 – molecular diversity 360 cyclo[8]pyrroles 385, 386, 419, 420 – pyrrole synthesis 397–400, 410, 411 cyclosporines 6, 51, 144 2-diethylaminoquinazolines 65, 66 cyclotriveratrylene (CTV) 238 dihalogeno isocyanides 52, 53 592 Index

dihydroazaphenanthrene-fused 2,5-disubstituted oxazoles 461 benzodiazepinediones 440, 441 disubstituted pyrroles 453, 454 4,5-dihydro-3H-1,4-benzodiazepin-5-ones 2,3-disubstituted quinolines 65, 66 436 disubstituted thiazoles 465 dihydroisoindoles 398, 399 diterpenes 16, 18 3,4-dihydroisoquinolines 48 dithiocarbamate 282 dihydroisoquinoxalinones 338, 339 divinyl ketones 118, 119 dihydrooxazolopyridines (DHOP) 96, 97 DMAD see dimethyl acetylenedicarboxylate dihydropyridines (DHP) 54, 307, 308 DMBQ see dimethyl-1,4-benzoquinone dihydropyridones 95–97 DMSO see dimethyl sulfoxide dihydroquinazoline–benzodiazepine Domino process 88–91, 321 tetracycles 442, 443 double isocyanide insertions 318–320, 324, dihydroquinazolines 345–347, 359 325 diisocyanoarenes 514–521 double MCRs 235, 244–246 2,6-diisocyanoazulene (DIA) 514–516, DPPA see diphenyl phosphorylazide 518–521 drug discovery 335, 336, 374 1,4-diisocyanobenzene (DIB) 515, 516, 519 dye-sensitized solar cells 423, 424, 464–467 2,2´-diisocyano-6,6´-biazulenyl (DIBA) dynamic kinetic resolution 7 515–519, 522 N,N-diisopropylethylamine (DIPEA) 571 e diketopiperazines 338–340, 345, 352, 355, electrocyclization reactions 167 365 electron paramagnetic resonance (EPR) dimethyl acetylenedicarboxylate (DMAD) spectroscopy 499, 500 – furan synthesis 451–453 electron spin resonance (ESR) spectroscopy – isocyanide reactivity 56 39, 555 – nonclassical IMCRs 315, 316 electronic structure 35, 36 – zwitterions 264–266, 276 electrophilic reactions dimethylamino isocyanoacrylates 135, 466, – chiral nonracemic isocyanides 22 467 – isocyanide reactivity 35, 36, 47–61 N-dimethylamino peptoids 202 – α-isocyanoacetic acid derivatives 138, 139 β-dimethylamino-α-isocyanoacrylates 134 – nonclassical IMCRs 317 dimethyl-1,4-benzoquinone (DMBQ) 2 eledoisin 203 dimethyl 3-oxopentanedioate 269, 270 elemental sulfur 281, 282 dimethyl sulfoxide (DMSO) Ellman benzodiazepine synthesis 431, 432 – isocyanide reactivity 42, 65 enamines 223–227 – polyisocyanides 560–562 enantiomerically pure isocyanides see chiral – zwitterions 264 nonracemic isocyanides Dimroth-type rearrangements 276 encapsulation complexes 49, 50 dioxaphosphorinanes 10 endothiopeptides 161 DIPEA see N,N-diisopropylethylamine 7-epi-14-isocyano-isodauc-5-ene 21 dipeptides epoxides 288, 320 – amine surrogates 226, 227 EPR see electron paramagnetic resonance – multiple IMCRs 234, 257 ESR see electron spin resonance – polyisocyanides 26 (ethoxycarbonylmethyl) diphenyl phosphorylazide (DPPA) 131 triphenylphosphonium bromide 270, 271 diphenylketene 60 ethyl acetoacetate 203 dipolar acid fl uorides 306 ethyl isocyanoacetate 202, 203 dipolar compounds 263, 264 eurystatin A 4, 5 dipolarophiles 279, 280, 310–313 expanded porphyrins 414, 417–420 dipole–isocyanide couplings 543, 544 exploratory power 336, 368, 369, 374 dipole moments 494 disaccharides 15 f disubstituted imidazoles 467, 468 F-SPE see fl uorous solid-phase extraction 4,5-disubstituted oxazoles 83, 84, 459–461 ferrocenyl carbene complexes 533 Index 593 ferrocenyl isocyanoarenes 509, 510, 514 gold complexes ferrocenyl polyisocyanides 573, 574 – carbenes 535–537, 543 ferrocenylphosphine complexes 125, 126, – α-isocyanoacetic acid derivatives 125, 128 126, 128 fi le-enhancement strategies 336, 374 – isocyanoarenes 517–522 Fischer carbene complexes 545 – nonclassical IMCRs 325, 326 fi ve-coordinate isocyanidemetalates grafting on strategy 563, 564 502–504 Grignard reagents 62 fl ash vacuum pyrolysis (FVP) 3, 13 Groebke–Bienaymé reactions 160, 180 fl uorescence spectroscopy 566, 569, 570 Groebke–Blackburn reactions 252, 253 fl uoro-benzaldehydes 286, 287 2-fl uoro-5-nitrobenzoic acid 342, 343 h N-fl uoropyridinium fl uorides 222, 471–473 half-wave redox potentials 513, 514 fl uorous solid-phase extraction (F-SPE) 438 halogenation reactions 22, 53, 387, 388 formamides 77, 78, 112 Hammett correlations 39, 40, 56 formamidine salts 313 Hantzsch reactions 76 formylation reactions hapalindole alkaloids 17, 18, 21, 22 – chiral nonracemic isocyanides 1, 2, 14, Heck coupling reactions 356, 357, 543 15, 18 Heck-type cyclization–isomerizations 178 – α-isocyanoacetic acid derivatives 111, helical polymer confi gurations 112 – chiral nonracemic isocyanides 23–26 – pyrrole synthesis 387, 388 – polyisocyanides 551, 552, 556–561, four-coordinate isocyanidemetalates 564 497–502 helix inversion barriers 552 fourfold MCRs 245, 246 heme 386, 393 free-radical see radical hemicryptophanes 247 Friedel–Crafts annulations 22 Henry reactions 392, 393 fullerenes 280, 281 Hermann’s catalyst 22 functional dendrimers 253, 254 N-heteroaryl thiocarboxamides 175, 176 functional dyes 385, 386, 391, 420–424 heteroarynes 283, 284 functional polyisocyanides 570–575 heterocumulenes 60, 61, 132 functionalized benzodiazepinediones 437 heterocyclic amidines 371–373 furanone hydrazone pathway 276 N-heterocyclic carbenes (NHC) 93, 94, 531, furans 532, 537, 540, 541, 546 – IMCR examples and protocols 451–453 heterocyclization reactions – α-isocyanoacetic acid derivatives 130 – α-acidic isocyanides 83, 84 – zwitterions 275–279 – isocyanide reactivity 54, 58–61, 65 furopyrrolones 89, 90 – α-isocyanoacetic acid derivatives 118, 136 fused 3-amino imidazoles 372 hexaphyrinogens 408, 409 fused-ring benzodiazepines 440–443 high exploratory power 336, 368, 369, 374 FVP see fl ash vacuum pyrolysis highly oriented pyrolytic graphite (HOPG) 558 g homoleptic isocyanide complexes 493–497, gallium trichloride 288, 319, 320 510–514 GCNF see germ cell nuclear factors homolytic bond breaking 39 gem-diactivated olefi ns 48, 49, 288 HOPG see highly oriented pyrolytic graphite germ cell nuclear factors (GCNF) 432 Horner–Wadsworth–Emmons reactions glutamate analogues 360 252, 387 glycoconjugates 236, 237 horseradish peroxidase (HRP) 240–242, glycosyl isocyanides 575 – chiral nonracemic isocyanides 13–16 Huisgen cycloaddition reactions – isocyanide reactivity 41–43 – chiral nonracemic isocyanides 11, 12 glyoxaldehydes 349 – molecular diversity 360, 361 glyoxylic acids 341 – polyisocyanides 569 594 Index

Hulme benzodiazepine synthesis 433 – α-isocyanoacetic acid derivatives 132, hybrid macrocycles 244–246, 255, 256 133, 135, 138–140 hybrid peptide–peptoid podands 237–240 – nonclassical IMCRs 314, 315 hybrid peptide–steroid architectures – polyisocyanides 26 238–240 imidazolidines 52, 186, 223, 224 hydantoins imidazolidinetriones 350 – carboxylic acid surrogates 163, 164, 166, imidazolines 167, 184 – α-acidic isocyanides 78, 79, 91–95 – molecular diversity 349, 350 – carboxylic acid surrogates 186 hydantonimides 249 – α-isocyanoacetic acid derivatives 126– hydration reactions 537 129, 134 hydrazines – molecular diversity 340 – amine surrogates 200–218 – multiple IMCRs 251, 252 – carbene coupling reactions 537, 538 imidazolinones 115, 140, 141 – carboxylic acid surrogates 169 imidazolium salts 306, 307 hydrazino turns 207 imidazolo[1,2-a]quinoxalines 252, 253 hydrazinopeptides 203, 204, 206, 207, imidazopyridines 357 209–215, 250 imidazoquinoxalinones 356 hydrazo-Ugi reactions 200–218 imidoyl anions 65, 66 hydrazoic acid 51, 52, 167–171 imidoyl chlorides 185, 313–315 hydrazones 218, 537, 538 imine surrogates 195, 196, 223–227 hydride ion transfer 57 imines hydrochloric acid addition reactions 52 – carbene coupling reactions 538, 539 hydrogels 241–243 – isocyanide reactivity 58–60 bonding – α-isocyanoacetic acid derivatives 126–129 – amine surrogates 210, 215, 219 – molecular diversity 336, 346, 347, 349, – polyisocyanides 561–563, 566, 575 362, 365 hydrogen sulfi de 165, 166 – nonclassical IMCRs 302, 303 hydrogenation reactions 13 iminium intermediates hydroselenide 160, 165, 166 – amine surrogates 201, 223–227 hydroxides 64–66 – carboxylic acid surrogates 169 hydroxy amides 181, 182 – nonclassical IMCRs 300, 307 hydroxy benzaldehydes 286, 287 – zwitterions 279, 280 hydroxy heterocycles 175 iminoacyl species 532 hydroxy isocyanides 12–16 iminoboranes 309–312 α-hydroxy-β-isocyano esters 10 iminofurans 317 hydroxylamines 196–200 iminoindenones 284 α-hydroxylamino acetamides 199–200 2-iminoisoindolines 317 α-hydroxylaminoamides 367 iminolactones 288, 315, 316 hydroxylaminomethyl tetrazoles 198 5-iminooxazolines 87, 88 Hymeniacidon spp. 21 iminooxetanes 58, 59 iminophorphoranes 470 i iminopyrones 277, 278 ibuprofen 3 in situ Domino process 88–91 IBX see 2-iodoxybenzoic acid in situ-generated hydrazoic acid 169 IEDDA see inverse electron demand incident-photon-to-electron conversion Diels–Alder effi ciency (IPCE) 423 IEP see iterative effi ciency potential indazolinones 342, 343 imidate esters 284 Indinavir 352 imidates 324 indium trifl ate 188 imidazoisoquinolines 287 indole-2-carboxylic esters 142 imidazoketopiperazines 370, 371 indoles imidazoles – carboxylic acid surrogates 178 – α-acidic isocyanides 78, 79, 81, 82 – IMCR examples and protocols 473–477 – IMCR examples and protocols 466–469 – isocyanide reactivity 59 Index 595 indolinones 357 – halogen and acyl halide reactions 52–55 indolizines 357 – hydroxide, alcohol and amine reactions indoloketopiperazines 370, 371 64–66 infrared (IR) spectroscopy – isocyanide–cyanide rearrangements 35, – isocyanide reactivity 49, 50 37–41 – isocyanoarenes 497, 500, 505, 506, 513, – nonclassical IMCRs 299, 300, 308–320 519–522 – nucleophilic reactions 35, 36, 62–66 – polyisocyanides 560, 562, 563 – organometallic reagents 46, 47, 62–64 insertion reactions 318–327 – oxidation reactions 35, 41–45 intramolecular cyclizations – reduction reactions 35, 45–47 – α-acidic isocyanides 80, 85 – sulfur and selenium reactions 42–45 – amine surrogates 216 isocyanide resins 312, 313 – benzodiazepine synthesis 435, 436, 438, isocyanoacetamides 111, 112, 128, 129, 440, 441 142, 143 – carbenes 536, 537, 540–543 isocyanoacetates 109, 110, 112, 115, 116, – isocyanide reactivity 56 391–407 – α-isocyanoacetic acid derivatives 118, α-isocyanoacetic acid derivatives 109–158 119, 139 – acylating agents 129–133 – molecular diversity 337 – additional functional group chemistries – nonclassical IMCRs 314, 322, 323 134–137 intramolecular cycloadditions 117, 118, 198 – alkylation reactions 113–115 intramolecular elimination reactions 119 – alkyne reactions 119–121 intramolecular hydrazo-Ugi reactions 212, – allylation reactions 114 213 – carbonyl and imine reactions 116, intramolecular hydrogen bonding 210, 215, 121–129 219 – imidazoline synthesis 126–129, 134 inverse electron demand Diels–Alder – Michael addition reactions 115–119, 122, (IEDDA) reactions 360 123, 135 iodocarbamoylation reactions 307, 308 – miscellaneous reactions 139–144 2-iodoxybenzoic acid (IBX) 301, 302 – multicomponent reactions 133, 134, 137, ionic liquids 459–461 141, 142 IPCE see incident-photon-to-electron – organometallic reagents 121–124 conversion effi ciency – oxazole synthesis 118, 119, 129–132, 138, IR see infrared 142, 143 iron complexes – oxazoline synthesis 122–126, 131 – carbenes 533, 541, 542 – pyrrole synthesis 116, 117, 119–121 – chiral nonracemic isocyanides 13 – sulfur electrophile reactions 138, 139 – isocyanoarenes 501, 502 – synthesis 109–113 – quinoxaline synthesis 479 – transition metal catalysts 124–127 isocyanates 41–43, 278, 279 isocyanoacetonitriles 112, 113 isocyanic acid derivatives 166, 167 isocyanoamides 7–9, 40, 79–80 isocyanide-cyanide rearrangements 35, isocyanoarenes 37–41 – bridging ligands 494, 495, 514–517 isocyanide dichlorides 52, 53 – fi ve-coordinate isocyanidemetalates isocyanide reactivity 35–73 502–504 – acid reactions 49–52 – four-coordinate isocyanidemetalates – α-acidic isocyanides 78–80 497–502 – activated alkene and alkyne reactions – historical perspective 493–497 55–58 – homoleptic organometallic complexes – activated heterocumulene reactions 60, 493–497, 510–514 61 – isocyanoazulenes 508–514, 518–521 – amine surrogates 220–223 – η5-isocyanocyclopentadienide ligands – carbonyl and imine reactions 58–60 509, 510, 522 – electronic structure 35, 36 – low-valent complexes 497–508 – electrophilic reactions 35, 36, 47–61 – nonbenzenoid isocyanoarenes 508–521 596 Index

– organometallic reagents 493–529 kinetic resolution 7 – redox-related complexes 497–502, Knoevenagel reactions 504–508 – amine surrogates 205 – self-assembled monolayers 517–521 – α-isocyanoacetic acid derivatives 121, – six-coordinate isocyanidemetalates 122 504–508 – molecular diversity 355 isocyanoazulenes 508–514, 518–521 Knorr pyrrole synthesis 385 10-isocyano-4-cadinene 19, 20 Knorr-type pyrazolone syntheses 218 η5-isocyanocyclopentadienide ligands 509, 510, 522 l isocyano esters 4–7, 9, 77–80, 86 lactamization reactions 354 ent-2-(isocyano)trachyopsane 19–21 β-lactams isoindoles 402–407 – chiral nonracemic isocyanides 17, 21 isoindolinones 356 – molecular diversity 353, 354, 364, 368 isomeric porphyrins 414, 417–421 γ-lactams 338, 366, 367 isoquinolines lactonization reactions 354 – amine surrogates 221–223 lanthanide catalysts 184 – nonclassical IMCRs 301, 302, 304, 305, LC see liquid crystal 317, 318 LDA see lithium diisopropylamide – zwitterions 287, 288 levulinic acid 95 isoselenocyanates 45 Lewis acids isotactic polypropylene 552 – carboxylic acid surrogates 180, 181, isothiocyanates 42–45, 132 184–189 isotwistane dione 21 – molecular diversity 372 isoxazoles 361, 461, 464 – nonclassical IMCRs 313, 314 isoxazolines 361 – zwitterions 288, 289 iterative effi ciency potential (IEP) 336, library development 336, 339–343, 374 374 Liebeskind–Srogl cross-coupling reactions 93 j Lindsey method 407, 412–414 Joullie–Ugi reactions 225 liquid crystal (LC) systems 572–574 lithium diisopropylamide (LDA) 321, 479 k living polymerizations 555, 556 Kennedy benzodiazepine synthesis 435 ketazines 204 m ketenes 60, 129, 130 MacDonald condensations 420 ketenimines McFarland amidine synthesis 182–184 – isocyanide reactivity 61 macrobicycles 246, 247, 255, 256 – nonclassical IMCRs 313, 314 macrocycles – zwitterions 267, 269, 271–274 – α-acidic isocyanides 88 keto-acids 362, 366–371 – carbenes 535 3-ketoamides 118, 119 – molecular diversity 352, 361 2-keto-5-aminooxazoles 142, 143 – multiple IMCRs 243–247, 254–256 ketoimidoyl halides 53 manganese complexes 502–504, 510, 537 ketones Mannich reactions – amine surrogates 198, 199 – α-acidic isocyanides 76, 91, 92 – chiral nonracemic isocyanides 5 – amine surrogates 205, 206 – isocyanide reactivity 58–60 – carboxylic acid surrogates 169, 175 – α-isocyanoacetic acid derivatives 116, mannosides 237 121–126, 142 Marcaccini benzodiazepine synthesis – nonclassical IMCRs 305, 317 436 – zwitterions 283 masked imines 223–227 ketopiperazines 338, 339, 343, 370, 371 matrix metalloproteinases (MMP) 340, kinetic isotope effect 38 341 Index 597 merry-go-round mechanism 25, 554, 555, – nucleophilic additions and substitutions 575 351–356 metal-bound isocyanides – palladium-mediated reactions 356–358 – amine and alcohol couplings 532–537 – ring-closing metathesis 358, 373 – carbenes 531–550 – secondary reactions of Ugi products – dipole–isocyanide couplings 543, 544 350–361 – functionalized amine and alcohol – Staudinger–aza-Wittig reactions 358, 359 couplings 537 – tethered aldehyde and keto acids 362, – hydrazine and hydrazone couplings 537, 366–371 538 – tethered heterocyclic amidines 371–373

– imine and amidine couplings 538, 539 – TMSN3-modifi ed Ugi-4CC/one internal – intramolecular cyclizations 536, 537, nucleophile 343, 344 540–543 – Ugi-4CC/one internal nucleophile – miscellaneous reactions 544–546 337–343 – reactivity modes 531, 532 – Ugi-4CC/three internal nucleophiles 347, metal-to-ligand charge transfer (MLCT) 348 515, 516 – Ugi-4CC/two internal nucleophiles N-methylated peptides 6 344–347 methyl tert-butyl ether (MTBE) 393 – Ugi-5CC/one internal nucleophile methyl trans-iminocrotonates 57, 58 348–350 N-methylmorpholine (NMM) 4, 7 molecular weight distribution (MWD) 572 – α-acidic isocyanides 78 molybdenum complexes – α-isocyanoacetic acid derivatives – carbenes 540, 544, 545 110–112 – isocyanide reactivity 44 MiB see multiple multicomponent monamphilectine A 17, 21 macrocyclizations MTBE see methyl tert-butyl ether Michael addition reactions multicomponent polymerization 243 – α-acidic isocyanides 77 multicomponent reactions (MCR) – benzodiazepine synthesis 437, 438 – α-acidic isocyanides 75–108 – chiral nonracemic isocyanides 21 – benzimidazole synthesis 473 – α-isocyanoacetic acid derivatives 115– – benzodiazepine synthesis 431–449 119, 122, 123, 135 – benzofuran synthesis 473 – pyrrole synthesis 392, 393 – chiral nonracemic isocyanides 1, 3, 4, 7, – zwitterions 271–273, 284, 286 9, 12–16, 21 microwave-assisted coupling reactions 143, – convergent approach to natural product 144, 346–348, 438, 439, 441–443 mimics 256, 257 mineral acids 180–184 – dihydropyridones 95–97 Mitsunobu reactions 352–354 – 4,5-disubstituted oxazoles 83, 84 MLCT see metal-to-ligand charge transfer – early examples 76 MMP see matrix metalloproteinases – formal isocyanide insertion reactions molecular diversity 335–384 320–327 – alkylation reactions 351, 352 – furan synthesis 451–453 – amino acids 362–365 – heterocycle synthesis 451–492 – aromatic substitutions 355, 356 – hybrid peptide–peptoid podand synthesis – base- or acid-promoted condensations 237–240 355 – imidazole synthesis 466–469 – bifunctional approach 361–374 – 2-imidazolines 91–95 – combined bifunctional and post- – indole synthesis 473–477 condensation modifi cations 373, 374 – isocyanide activation 299, 308–320 – cyclic imines 362, 365 – isocyanide attack on activated species – cycloaddition reactions 357, 359–361, 299, 300–308 371–373 – isocyanide reactivity 35, 48, 49, 56–58, 67 – lactonizations and lactamizations 354 – α-isocyanoacetic acid derivatives 133, – Mitsunobu reactions 352–354 134, 137, 141, 142 598 Index

– isocyanoarenes 496 multivalent glycoconjugates 236, 237 – isoxazole synthesis 461, 464 Mumm rearrangements – linear and branched scaffolds 248–254 – amine surrogates 195, 198–200 – macrocyclizations 243–247, 254–256 – carboxylic acid surrogates 160, 161, 186 – molecular diversity 335–384 – molecular diversity 336, 363, 364, 367, – multicomponent polymerization 243 368 – multiple IMCRs 233–262 – multiple IMCRs 250, 251 – multivalent glycoconjugate synthesis 236, muraymicyn D2 11 237 MWD see molecular weight distribution – nitropyrroles 83, 84 – nonclassical IMCRs 299–334 n – one-pot multiple IMCRs 234–243 nanocapsules 49, 50 – oxadiazole synthesis 470, 471 nanoreactors 574, 575 – oxazole MCR and in situ Domino process naphthoporphyrins 398, 410 88–91 naproxen 3 – oxazole synthesis 459–461 natural isocyanides – protein modifi cation and immobilization – chiral nonracemic isocyanides 16–23 240, 241, 258 – isolation and natural sources 16, 17 – pyrazole synthesis 466, 470 – synthesis 17–23 – pyrrole synthesis 391, 453–459 Nef reactions – quinoline synthesis 477–479 – α-isocyanoacetic acid derivatives 129, – quinoxaline synthesis 479 135 – sequential IMCRs 248–257 – nonclassical IMCRs 313, 314 – tetrazole synthesis 471–473 – pyrrole synthesis 392, 393 – thiazole synthesis 464–466 NHC see N-heterocyclic carbenes – triazole synthesis 470, 471 nickel complexes – 2,4,5-trisubstituted oxazoles 84–88 – carbenes 545, 546 – 2,6,7-trisubstituted quinoxalines 82, 83 – isocyanide reactivity 41, 42 – type I processes 299–308 – isocyanoarenes 522 – type II processes 299, 308–320 – polyisocyanides 553, 554, 560, 563, 575 – type III processes 299 nicotinamides 274, 275 – union of MCRs 93–95 ningalin B 386, 395 – van Leusen imidazole MCR 81, 82 niobium complexes 506–508 – zwitterions 263–265 nitrilium intermediates – see also Passerini reactions; Ugi reactions – carboxylic acid surrogates 160, 181, multiple isocyanide-based MCRs 186 233–262 – molecular diversity 336, 343, 373, 574 – convergent approach to natural product – nonclassical IMCRs 300, 302, 303, 306, mimics 256, 257 316, 317 – hybrid peptide–peptoid podand synthesis nitroalkenes 389–396, 458 237–240 3-nitroindoles 404, 405 – linear and branched scaffolds 248–254 nitroketenes 401 – macrocyclizations 243–247, 254–256 nitrophenols 172–175 – multicomponent polymerization 243 2-nitrophenyl isocyanide 540, 541 – multivalent glycoconjugate synthesis 236, β-nitroporphyrins 405, 406 237 nitropyrroles 83, 84, 389, 390 – one-pot multiple IMCRs 234–243 nitroso compounds 320 – polysaccharide hydrogel assembly NLO see nonlinear optical 241–243 NMM see N-methylmorpholine – protein modifi cation and immobilization NMR see nuclear magnetic resonance 240, 241, 258 NOESY see nuclear Overhauser effect – sequential IMCRs 248–257 spectroscopy multiple multicomponent macrocyclizations non-Evans syn-aldol reactions 18 (MiB) 243–247 nonbenzenoid isocyanoarenes 508–521 Index 599 nonclassical isocyanide-based MCRs organolithium reagents 299–334 – chiral nonracemic isocyanides 3, 4 – formal isocyanide insertion reactions – isocyanide reactivity 62, 63 320–327 – nonclassical IMCRs 309, 310, 321 – isocyanide activation 299, 308–320 organometallic reagents – isocyanide attack on activated species – α-acidic isocyanides 77 299–308 – bridging isocyanoarene ligands 494, 495, – type I processes 299–308 514–517 – type II processes 299, 308–320 – carboxylic acid surrogates 185, 186 – type III processes 299 – chiral nonracemic isocyanides 3, 4, 14, nonlinear optical (NLO) materials 567, 15 575 – fi ve-coordinate isocyanidemetalates norbornenes 360 502–504 Norcardicin 363, 364 – four-coordinate isocyanidemetalates Norrish-type homolytic cleavages 22, 23 497–502 nuclear magnetic resonance (NMR) – historical perspective 493–497 spectroscopy – homoleptic isocyanide complexes – amine surrogates 209, 210 493–497, 510–514 – carbenes 536 – isocyanide reactivity 46, 47, 62–64 – chiral nonracemic isocyanides 24 – α-isocyanoacetic acid derivatives – isocyanide reactivity 49, 50 121–124 – isocyanoarenes 494–496, 505, 506, 511, – isocyanoarenes 493–529 512 – isocyanoazulenes 508–514, 518–521 – multiple IMCRs 236 – η5-isocyanocyclopentadienide ligands – polyisocyanides 559–563 509, 510, 522 nuclear Overhauser effect spectroscopy – low-valent complexes 497–508 (NOESY) 253 – nonbenzenoid isocyanoarenes 508–521 nucleophilic reactions – redox-related complexes 497–502, – amine surrogates 200 504–508 – carbenes 531, 532 – self-assembled monolayers 517–521 – isocyanide reactivity 35, 36, 62–66 – six-coordinate isocyanidemetalates – α-isocyanoacetic acid derivatives 129, 504–508 135, 137 organosamarium reagents 64 – molecular diversity 337–356 organozinc reagents 64 – zwitterions 264, 266–271 oxadiazepins 269 nucleophilicity parameters 36 oxadiazoles 470, 471 Nutlins 93 oxazepinones 367 oxazines 187 o oxazoles OBO-esters 111 – α-acidic isocyanides 78–80, 83–91 OFET see organic fi eld effect transistors – IMCR examples and protocols 459–461 oligomerization reactions – α-isocyanoacetic acid derivatives 118, – isocyanide reactivity 35, 57, 58 119, 129–132, 138, 142, 143 – multiple IMCRs 243–247 – nonclassical IMCRs 302 – porphyrins 419–421 oxazolidines oligonucleotides 306 – amine surrogates 223, 224 oligopyrroles 395, 396 – nonclassical IMCRs 310–313, 320 one-pot multiple IMCRs 234–243 oxazolines Ono method 407 – α-acidic isocyanides 78, 79, 87, 88 OPV see organic photovoltaic – chiral nonracemic isocyanides 13 organic fi eld effect transistors (OFET) 420, – α-isocyanoacetic acid derivatives 423, 424 122–126, 131 organic photovoltaic (OPV) devices 420, oxetanes 186, 187 423, 424, 545–547 oxidation reactions 35, 41–45 600 Index

oxidation–substitution reactions 2 pentafuranoses 14, 15 oximes 199 peptide-based hybrid macrocycles 244, 245 2-oxocarbapenems 364 peptide nucleic acid (PNA) oligomers 248, oxodiazepines 359 249 oxyaminocarbene ligands 542, 543 peptide–peptoid podands 237–240 peptide–steroid hybrids 238–240 p peptidic tetrazoles 249, 250 palladium catalysts peptidomimetics – α-acidic isocyanides 77 – α-acidic isocyanides 97 – benzodiazepine synthesis 437, 440 – amine surrogates 203, 204, 206, 207, – carbenes 534, 535, 537–539, 542–544 209–215, 226, 227 – carboxylic acid surrogates 178 – chiral nonracemic isocyanides 12, 13 – indole synthesis 474–476 – molecular diversity 352, 354, 358 – isocyanide reactivity 53, 64 – multiple IMCRs 240, 255–257 – α-isocyanoacetic acid derivatives 114, peptoid–peptide chimeras 253 127, 128 peptoids – isocyanoarenes 522 – amine surrogates 202 – molecular diversity 356–358 – hybrid peptide–peptoid podands 237–240 – nonclassical IMCRs 324, 325 – molecular diversity 358 palladium–platinum catalysts 554–556, – multiple IMCRs 250, 251, 253–255 560, 565, 572 Perkow reactions 313, 314 PAMAM see Passerini–amine perylene diimides 565–567 deprotection–acyl migration perylene-functionalized polyisocyanides parallel synthesis 336, 367 564–569, 575 Parr–Knorr synthesis 385 phase-transfer catalysis 76 Passerini reactions phenanthroline-Ru(III) complexes 414, 417 – α-acidic isocyanides 75, 76, 94–97 phenols 171–179 – benzodiazepine synthesis 431, 432 phenoxyiminoisobenzofurans 317, 318 – carbonic acid derivatives 163–165 phenylalanine methyl esters 202, 203 – carboxylic acid surrogates 159–194 phosgenes 77, 78, 109–112 – chiral nonracemic isocyanides 3–5, 10, phosphazene super bases 130, 393, 403 12, 13, 16 phosphines – cyanamide 179 – carbenes 532, 533, 545, 546 – hydrazoic acid 167–171 – zwitterions 264 – isocyanic acid derivatives 166, 167 phosphonylmethyl isocyanides 10 – α-isocyanoacetic acid derivatives 111, photochemical cyclizations 479 133, 134, 137 phthalazinones 204, 205 – mineral and Lewis acids 180–189 Phyllidia varicosa 21 – multiple IMCRs 233–235, 242, 243, 252, phytochromobolin 394, 395 253, 257 Pictet–Spengler-type cyclizations 355 – nonclassical IMCRs 320 Plasmodium falciparum 367 – oxazole synthesis 461 platinum complexes 538, 539, 542, 543, – phenols and derivatives 171–179 545, 546 – selenide and sulfi de 165, 166 PNA see peptide nucleic acid – silanol 165, 166 podand architectures 237–240 – thiocarboxylic acids 160–163 polyacetylenes 552 – zwitterions 265 poly(tert-butylisocyanide) 23 Passerini–amine deprotection–acyl polychlorals 552 migration (PAMAM) strategies 5, 8 polydentate isocyanides 494–496 PBG see porphobilinogen polydispersity index (PDI) 556, 566 PDI see polydispersity index polyguanidines 552 penicillin derivatives 362 polyisocyanides 551–585 Penicillium notatum 16 – applications 26 pentacenes 410, 411 – chiral nonracemic isocyanides 23–26 Index 601

– chiral polymers 551–553 pyran-2-ones 267 – functional 570–575 pyrazoles – helical polymer confi gurations 551, 552, – amine surrogates 205, 206, 215, 216 555–561, 564 – IMCR examples and protocols 466, 470 – monomeric isocyanides 553 pyrazol-3-ones 217, 218 – multiple IMCRs 238–240 pyrazolo[1,2-a]pyridazines 274 – polyisocyanopeptides 561–563 pyrazoloquinoxalinones 356 – polymerization mechanism 553–556 pyridazinones 205 – properties 24 pyridine N-oxide 42 – scaffolds for anchoring chromophores pyridine-2,6-dicarboxyclic acid 240 563–570 pyridines – synthesis 25, 26 – nonclassical IMCRs 303, 304, 317, 318 polyisocyanopeptides 561–563 – zwitterions 264, 288 polymer-supported IMCRs 312, 313, 339, pyridinium ylides 313, 314 340, 366–371, 434–436 pyridinyl–imidoyl adducts 181 polymerization reactions pyrrenopyrroles 403, 404 – chiral nonracemic isocyanides 25, 26 pyrrole-2-carbaldehydes 395, 396 – isocyanide reactivity 35, 65 pyrrole-2-carboxylates 391–393, 400, 401 – multiple IMCRs 243 pyrroles 385–429 – polyisocyanides 553–556 – α-acidic isocyanides 79, 80, 83, 84 polymersomes 574, 575 – alkyne-based synthesis 390, 401, 402 poly(methacrylate ester)s 552 – aromatic nitro compound-based synthesis polypropylene 552 402–407 polypyrroles 387, 391, 421, 422 – IMCR examples and protocols polysaccharide networks 241–243 453–459 poly(triphenylmethyl methacrylate) 552 – isocyanoacetate-based synthesis porphobilinogen (PBG) 386, 388, 393 391–407 porphyrin-fused phenanthroline-Ru(III) – α-isocyanoacetic acid derivatives 116, complexes 414, 417 117, 119–121 porphyrinogens 408, 409 – isoindole synthesis 402–407 porphyrins – nitroalkene-based synthesis 389–396 – cycloaddition reactions 414–416 – nonclassical IMCRs 302, 303 – expanded, contracted and isomeric 414, – porphyrin synthesis 385–387, 391, 395, 417–421 396, 398, 407–424 – functional dyes 420–424 – tetramerization 407–412 – Lindsey method 407, 412–414 – TosMIC-based syntheses 386–390 – oligomerization 419–421 – α,β-unsaturated sulfone-based synthesis – polyisocyanides 558, 559, 563–565, 575 396–401 – pyrroles 385–387, 391, 395, 396, 398, pyrrolizidines 118, 119 407–423 pyrrolo[1,2-a] [1,4]diazepines 369, 370 – tetramerization of pyrroles 407–412 pyrroloketopiperazines 370, 371 Povarov reactions 301 pyrrolostatin 394 powder X-ray diffraction (PXRD) 563 pyruvamides 53 prodigiosin 386 prolines 365 q propiolyl chlorides 89 quinazolines 338 proteins quinolines 220–223, 477–479 – covalent modifi cation and immobilization quinoxalines 62, 82, 83, 479 240, 241, 258 quinoxalinones 341, 342, 347 – multiple IMCRs 240, 241, 258 pseudo-peptidic imidazolines 251, 252 r pump-probe spectroscopy 562 radical inhibitors PXRD see powder X-ray diffraction – isocyanide reactivity 37–39 2H-pyran-3,4-dicarboxylates 282 – pyrrole synthesis 393 602 Index

radical reactions semiconducting materials 567, 574, 575 – chiral nonracemic isocyanides 14, 15 sequential IMCRs 248–257 – indole synthesis 474–477 – amine surrogates 197, 210 – isocyanide reactivity 35, 38, 39, 47 – linear and branched scaffolds 248–254 random copolymerization 571 – macrocycles 254–256 RCM see ring-closing metathesis – natural product mimics 256, 257 redox potentials 513, 514 sesquiterpenes 16, 18–20 redox-related complexes 497–502, 504–508 Shaabani benzodiazepine synthesis reduction reactions 35, 45–47 443–445 reductive amination reactions 22 silaaziridines 323, 324 reductive cleavage reactions 18 silanol 165, 166 Reissert-type processes 300–307 siloxyamides 166 resin-bound isocyanides 434–436 silver catalysts resonance light scattering (RLS) 565 – α-acidic isocyanides 92, 93 retro Diels–Alder reaction 410, 420 – isocyanide reactivity 48, 54 retro-Michael reactions 89, 90 – α-isocyanoacetic acid derivatives 117, rhodium catalysts 126, 139, 140 – carbenes 545 – isocyanoarenes 517 – isocyanide reactivity 44, 45 silyl isocyanides 40, 41 – α-isocyanoacetic acid derivatives 122 single-crystal X-ray analyses 210, 369, 535 ring-closing metathesis (RCM) single reactant replacement (SRR) strategy – carboxylic acid surrogates 177 86–88 – molecular diversity 358, 373 six-coordinate isocyanidemetalates 504–508 ring-opening reactions size-exclusion chromatography (SEC) 563 – carboxylic acid surrogates 186–189 Smiles rearrangements – isocyanide reactivity 58, 59 – carboxylic acid surrogates 160, 171–179 – nonclassical IMCRs 323, 324 – multiple IMCRs 250, 251 – zwitterions 288, 289 – zwitterions 285, 286 Ritter reactions 21 sodium azide 198 RLS see resonance light scattering sodium naphthalene/1,2-dimethoxyethane ruthenium complexes 46 – carbenes 541 solid-phase extraction (SPE) 341, 438 – indole synthesis 474–476 solid-phase synthesis – isocyanoarenes 501 – benzodiazepines 431 – pyrrole synthesis 414, 417 – molecular diversity 366, 367 rylideneindolinones 356, 357 – multiple IMCRs 248, 249, 253 – nonclassical IMCRs 302 s solid-supported IMCRs 312, 313, 339, 340, Saegusa deamination reactions 47 366–371, 434–436 safety-catch linker isocyanides 338, 339 solution-phase synthesis 248–250, 253 SAM see self-assembled monolayers Sonogashira cross-coupling reactions 356, samarium catalysts 326, 327 357, 539 samarium(II) iodide 38 Soret bands 564, 565 sapphyrins 414, 417–420 SPE see solid-phase extraction Schollköpf isocyanides 161–163, 170, 171 spirocyclic iminolactones 277 screening collections 335, 336 γ-spiroiminolactams 278, 279 SEC see size-exclusion chromatography spiroisoindolines 178, 179 selenium derivatives 321–323 spiroisoquinolines 178, 179 seleno-carbamoylation reactions 307 spirostanic peptide–steroid hybrids 239, selenocyanates 132, 167 240 selenoesters 132 SRR see single reactant replacement seleno-oxidation reactions 45 Staudinger–aza-Wittig reactions 358, 359 self-assembled monolayers (SAM) 517–521 steric factors 217 self-trapping states 562 steroidal cages 247, 255 semicarbazones 219, 220 Straudinger reactions 439, 440 Index 603

Strecker reactions 76 1,1,3,3-tetramethylbutyl isocyanide (TMBI) structure–reactivity relationships 39 62, 63 styrylfuran derivatives 276, 277 tetranaphtho[2,3]porphyrins (TNP) 413, 5-substituted oxazoles 459 414 sugar-amino acid conjugates 15 tetraphenylporphyrin (TPP) 410–412, 423 sugar isocyanides 13–16 tetrasubstituted imidazoles 468, 469 sugar polyisocyanides 26 tetrasubstituted pyrroles 453, 458 sulfated glycoconjugates 236, 237 tetrathiafulvalenes (TTF) 26, 573 sulfenyl thiocyanates 138, 139 tetrazoles sulfonamides 218, 219 – amine surrogates 198, 200, 201 sulfones 396–401 – carboxylic acid surrogates 167, 170, sulfonylimines 317 171 N-sulfonylimines 129 – IMCR examples and protocols 471–473 sulfonylmethyl isocyanides 10 – isocyanide reactivity 51–53, 55 sulfur 281, 282 – molecular diversity 343, 344 sulfur electrophile reactions 138, 139 – multiple IMCRs 249, 250 sulfuration reactions 42–45 tetrazolo[1,5-a][1,4]benzodiazepines super-amphiphiles 574 441–443 supramolecular macrocycles 535 TFA see trifl uoroacetic acid Suzuki coupling reactions TFAA see trifl uoroacetic anhydride – benzodiazepine synthesis 438, 439 TFT see thin-fi lm transistors – carbenes 543 1,4-thiazepines 368, 369 – isocyanide reactivity 53 thiazoles – pyrrole synthesis 420 – α-acidic isocyanides 78, 79 Suzuki–Miyaura cross-coupling reactions – IMCR examples and protocols 464–466 538 – α-isocyanoacetic acid derivatives 137, 138 syn–anti isomerism 559, 560 thiazolidines 223–225 syndio conformation 24, 559, 560 thiazolines 78, 79 synthetic hydrogels 241–243 thin-fi lm transistors (TFT) 567 thiocarbonic acid 164, 165 t thiocarboxylic acids 160–163 Taft correlations 39, 40 52 tandem MCRs 326, 327 thioketones 124 tantalum complexes 504–508 thiophenols 48, 49, 175 TAP see tetraanthra[2,3]porphyrins threefold MCRs 235 TBAF see tetra-n-butylammonium fl uoride TIMC see tetraisocyano-meta-cyclophane TBP see tetrabenzoporphyrin tin complexes 502, 503 TCAA see trichloroacetic anhydride titanium catalysts 325, 326 telaprevir 10 titanium tetrachloride 184, 185, 187, 188 tellurium derivatives 321–323 TMBI see 1,1,3,3-tetramethylbutyl tethered aldehyde and keto acids 362, isocyanide 366–371 TNP see tetranaphtho[2,3]porphyrins tethered heterocyclic amidines 371–373 Tolypocladium infl atum gams 51, 144 tetraanthra[2,3]porphyrins (TAP) 413, 414 TON see turnover number meso-tetraarylporphyrins 407, 410–414 Torroba benzodiazepine synthesis 439, 440 tetrabenzoporphyrin (TBP) 385, 410–416, N-tosylguanidines 314, 315 423 α-tosylpyrroles 389, 390 tetra-n-butylammonium fl uoride (TBAF) TPP see tetraphenylporphyrin 77 transition metal catalysts tetracyclic scaffolds 345, 346 – chiral nonracemic isocyanides 13, 25 tetrahydroisoquinolines 301 – isocyanide reactivity 35, 41, 42, 44, 45 tetrahydropyridazine-3,6-diones 212, 213 – α-isocyanoacetic acid derivatives tetrahydropyridines 54 124–127 tetraisocyano-meta-cyclophane (TIMC) – isocyanoarenes 493–496 518–520 – nonclassical IMCRs 324–326 604 Index

trapping agents – chiral nonracemic isocyanides 4–6, 8, – carbonyl compounds 275–278, 283, 284 11–13, 16 – CH-acids 266–271 – cyanamide 179 – electron-defi cient olefi ns 279–281 – hydrazines 200–218 – imines 278–280 – hydrazoic acid 167–171 – isocyanides 287–289 – hydroxylamines 196–200 – miscellaneous compounds 280–282 – imine surrogates 195, 196, 223–227 – NH-acids 271–273 – isocyanic acid derivatives 166, 167 – nonclassical IMCRs 313, 315–318 – α-isocyanoacetic acid derivatives 111, – OH-acids 273–275 133, 134, 137 – zwitterions 265–282 – mineral and Lewis acids 180–189 TREN see tris(2-aminoethyl)amine – molecular diversity 335–361 triacid building blocks 238–240 – multiple IMCRs 233–258 triazadibenzoazulenones 441 – nonclassical IMCRs 300–307, 320 triazines 52, 220 – phenols and derivatives 171–179 triazoles 361, 470, 471 – secondary reactions of Ugi products tributyltin hydride 14, 15, 46, 47 350–361 trichloroacetic anhydride (TCAA) 305 – selenide and sulfi de 165, 166 trifl uoroacetic acid (TFA) – silanol 165, 166 – amine surrogates 204–208, 219 – tetrazole synthesis 471–473 – molecular diversity 337, 341, 348 – thiocarboxylic acids 160–163 – multiple IMCRs 250, 257 – zwitterions 265, 285, 286 – nonclassical IMCRs 313 Ugi–Reissert reactions 301–304 – polyisocyanides 562, 563 Ugi/de-Boc/cyclize (UDC) strategy trifl uoroacetic anhydride (TFAA) 303–307 – amine surrogates 204 α-trifl uoromethyl ketones 173, 174 – benzodiazepine synthesis 434, 435, 441 triiminothietanes 61 – carboxylic acid surrogates 163 triisocyanide building blocks 238–240 – molecular diversity 337–350

trimethylsilyl azide 471–473 – TMSN3-modifi ed Ugi-4CC/one internal 9-triptycyl isocyanide 39 nucleophile 343, 344 tris(2-aminoethyl)amine (TREN) 238–240 – Ugi-4CC/one internal nucleophile trisubstituted imidazoles 468, 469 337–343 2,4,5-trisubstituted oxazoles 84–88, 93, – Ugi-4CC/three internal nucleophiles 347, 461–463 348 trisubstituted pyrroles 453, 455–457 – Ugi-4CC/two internal nucleophiles 2,6,7-trisubstituted quinoxalines 82, 83 344–347 trisubstituted thiazoles 466 – Ugi-5CC/one internal nucleophile Trypanosoma brucei 367 348–350 TTF see tetrathiafulvalenes Ullmann cyclizations 161, 177 tungsten complexes 514–516, 540 ultraviolet (UV)-visible spectroscopy 515, turnover number (TON) 537 564–566, 570, 573, 574 two-component coupling reactions 35, 143, union of MCRs 93–95 144 universal isocyanides 335 α,β-unsaturated aldehydes 276, 277 u α,β-unsaturated ketones 116 UDC see Ugi/de-Boc/cyclize α,β-unsaturated sulfones 396–401 Ugi reactions ureas 349 – α-acidic isocyanides 75, 76, 94–97 ureido-linked disaccharides 15 – activated azines 220–223 urethanes 349 – amine surrogates 195–231 UV see ultraviolet – benzodiazepine synthesis 431–446 – bifunctional approach 361–374 v – carbonic acid derivatives 163–165 van Leusen reaction 81, 82, 386–390, 458, – carboxylic acid surrogates 159–194 466–471 Index 605 vanadium complexes 504–508 zinc catalysts variolins 53 – amine surrogates 199 vibrational circular dichroism (VCD) 558 – carboxylic acid surrogates 187 Vilsmeier–Haack reactions 395, 396 – oxadiazole and triazole synthesis 470, vinigrol 47 471 – tetrazole synthesis 471–473 w zinc porphyrins 565 Walborsky reagent 62, 63, 252 zirconium catalysts 474–476 Wang resins 366, 367 zwitterions 263–298 Welwitindolinones 17, 21, 22 – carbonyl compounds as trapping agents Wolff rearrangements 142, 143 275–278, 283, 284 – CH-acids as trapping agents 266–271 x – electron-defi cient olefi ns as trapping X-ray diffraction (XRD) agents 279–281 – carbenes 535 – imines as trapping agents 278–280 – chiral nonracemic isocyanides 24 – isocyanide reactivity 47, 48, 56, 57 – molecular diversity 369 – isocyanide–alkyne reactions 263–282 – multiple IMCRs 253 – isocyanide–aryne reactions 283, 284 – polyisocyanides 560, 561, 563, 572 – isocyanide–electron-defi cient olefi n X-ray structural spectroscopy 499, 500, reactions 284–286 513 – isocyanides as trapping agents 287–289 xanthocillin 16 – miscellaneous reactions 286, 287 – miscellaneous trapping agents 280–282 z – NH-acids as trapping agents 271–273 Zhu three-component reactions 244, 245 – nonclassical IMCRs 313, 315–318 zinc bromide 52 – OH-acids as trapping agents 273–275