PHOTOCHEMISTRYOF HETEROCYCLES
MAURIZIO D’AURIA
UniversityofBasilicata,Potenza,Italy
AMBRA GUARNACCIO
InstituteofStructureofMatter(ISM)attheCNR-ISM,TitoScalo,Italy
ROCCO RACIOPPI
UniversityofBasilicata,Potenza,Italy
SONIA STOIA
ITT"16Agosto1860",CorletoPerticara,Potenza,Italy
LUCIA EMANUELE
DepartmentofArtandRestoration,UniversityofDubrovnik,Dubrovnik,Croatia
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1.Photochemicalsynthesisofheterocyclic compounds1
1.1Introduction3
1.2Azetidines3
1.2.1SynthesisbyazaPaterno ` Buchireaction3
1.2.2Synthesisbyintramolecularclosureof N-formil-α-oxoamides4
1.2.3SynthesisbyNorris-Yangrearrangement4
1.2.4Reactionbetweenfullereneand formamidines5
1.2.5Synthesisbyciclizationofaminoketones6
1.3Aziridines6
1.3.1Synthesisbyrearrangementofpyridinium salts6
1.3.2Synthesisbyinsertionofnitreneinto doublebonds7
1.3.3Synthesisfromhomoallylpyrroles7
1.3.4Synthesisbyrearrangementoftriazolines8
1.3.5Synthesisofaziridinesbyvisible-light induceddecarboxylativecyclizationof N-arylglycinesanddiazocompounds8
1.3.6Photoinducedaziridinationofalkeneswith N-sulfonyliminoiodinane9
1.3.7Photochemicalaziridinationoffullerenes9
1.3.8Synthesisfromsugarderivativesand azides10
1.3.9Synthesisfromazidesbyphotocatalysis10
1.3.10Synthesisfromazidoformates11
1.4Diazepinesandbenzodiazepines11
1.4.1Synthesisfrom4-pyridylazides11 1.5Furans13
1.5.1Furansfrom α-bromo-β-dicarbonyl compoundsandalkynes13
1.5.2Benzofuransfrom2-chlorophenolsand alkynes13
1.5.3Dihydroandtetrahydrofuransfrom cyclopropanederivatives14
1.5.4Dihydrofuranfromphotodimerizationof β-carbonylketones15
1.5.5Tetrasubstitutedfuransfromsilylenolethers and α-bromodiketones15
1.5.6Synthesisof5H-furanonesfrom substitutedcyclobutenones16
1.5.7Photochemicalcatalyticalsynthesisof dihydrofuransfromvinylandaryl cyclopropanes16
1.5.8Tetrahydrofuransfromcyclobutanones andnitrilecompounds16
1.5.9Reactionofpropargylderivativeswith alkenes17
1.5.10Tetrahydrofuransfrom α,β-unsaturated ketones18
1.5.11 γ-Lactonesfromallylicalcoholsand α,β-unsaturatedketoester18
1.5.12Synthesisfromcinnamicacidandketones18
1.5.13Synthesisfrom α-chloroalkylketones andstyrenes19
1.5.14Synthesisbyisomerizationofalkenes20 1.6Imidazolesandderivatives20
1.6.1Synthesisofanimidazoleintermediated byHCN20
1.6.2Synthesisofdihydroimidazolesfrom pyridiniumsaltsandanalkene21
1.6.3Synthesisofanimidazolinoneby cyclizationofalinearcompound22
1.6.4Synthesisofpurinesbyirradiationof urea/acetylene22
1.6.5Onepotsynthesisfromaldehydes, α-aminonitrilesandisoxazoles23
1.6.6Reactionof N-(1-methylpyrimidin-2-one) pyridiniumchloride.Contractiontoan imidazolidinone23
1.7Synthesisofoxadiazoles24
1.7.11,2,4Oxadiazolesfrom2H-azirinesand nitrosoarenes24
1.7.2Photooxidationof N-acylhydrazonesto 1,3,4-oxadiazoles25
1.8Synthesisofoxazolesandrelatedsystems26
1.8.1Synthesisofoxazolesbyconversionof 1-acyltriazoles26
1.8.2Synthesisfrom α-bromoketonesand benzylamines26
1.8.3Threecomponentscondensationof silylenolethers,fluoroalkylhalidesand chiralaminoalcoholstoobtainoxazolidines27
1.8.4Oxazolidinonesfrompropargylicamines andCO2 28
1.8.5Conversionofbenzoilformamidesto oxazolidin4-ones29
1.8.6Synthesisofphosphoniumsubstituted oxazolesfromphosphonium-iodonium ylides30
1.8.7Synthesisfromazirinesandaldehydes30
1.9Oxetanes:thePaterno ` Bu¨chireaction31
1.9.1 Exo-oxetanesfromcarbonylcompounds withvinylenecarbonates31
1.9.2Photocycloadditionof N-acylenaminesto aldehydes32
1.9.3Oxetanesfromcarbonylcompoundsand 2,5dimethyl-4-isobutyl-oxazoles33
1.9.4Reactionof2,3-dihydrofuran34
1.9.5Reactionofasilylderivativeofcinnamyl alcohol35
1.9.6Reactionofgeraniolderivatives35
1.9.7Reactionwithisoxazolederivatives36
1.9.8Synthesisofanelusiveoxetaneby photoadditionofbenzophenoneto thiopheneinthepresenceofaLewis acid37
1.9.9Reactionof2-furylmethanolderivatives38
1.9.10Reactionofsilylenolethers39 1.10Piperidines40
1.10.1Iodinecatalyzedsp3-Hamination40
1.10.2Synthesisfrom2,6-diaminopimelicacidto piperidine-2,6-dicarboxylicacid42
1.10.3Aphotochemicalreactioninthesynthesis ofazasugarderivatives43
1.10.4Piperidinesfromring-contactionof N-chlorolactams43
1.10.5Synthesisof2-piperidinonecatalyzed fromahydrophobicanalogofvitamin B12 44
1.11Pyrazoles44
1.11.1Aromatizationof1,3,5trisubstituted pyrazolines44
1.11.2Photochemicalbrominationforpreparation ofmono,bisandfusedpyrazolederivatives45
1.11.3PyrazolesfromhydrazinesandMichael acceptors47
1.11.4Synthesisofpyrazolederivativesviaformal [4 1 1]annulationandaromatization48
1.11.5Reactionofhydrazonesand α-bromoketones49
1.11.6Onepotsynthesisofpyrazolesfrom alkynesandhydrazines51
1.11.7Sunlight-promoteddirectirradiationof N-centeredanion:thephotocatalyst-free synthesisofpyrazoles52
1.11.8Efficientphotooxidationofaryl(hetaryl) pyrazolinesbybenzoquinone53
1.11.9Synthesisofpyrazolesviaphotochemical ringopeningofpyridazine N-oxides54 1.12Pyridines55
1.12.1Pyridinesfromringclosureof acyloximes55
1.12.2Synthesisofnaphthylpyridinesfrom heptadynesandnitriles57
1.12.3Synthesisofsubstitutedpyridinefrom arylketoneandbenzylamines58
1.12.4Pyridinesfromtrimerizationoftwo alkenesandanitrile60 1.13Pyrimidines61
1.13.1Synthesisofbenzo-fusedpyrimidines4-onesfrom1,2,4oxadiazoles61
1.13.2Fluoroalkylatespyrimidinesfromsilyl enolethers,amidines,and fluoroalkylhalides63
1.13.3Threecomponentsynthesisfromactive methylenecompounds,perfluoroalkyl iodidesandguanidines66
1.13.4Synthesisofpyrimidonesfrom4-allyltetrazolones67 1.14Pyrroles69
1.14.1Dehydrogenativearomatizationand sulfonylationofpyrrolidines69
1.14.2Synthesisofnitrogenheterocycles generatedfrom α-silylsecondaryamines undervisiblelightirradiation71
1.14.3Synthesisofsubstitutedpyrrolesby dimerizationofacylazirines71
1.14.4Photochemicalisomerizationsof N-substituted2-halopyrroles:synthesesof N-substituted3-halopyrroles73
1.14.5Synthesisofpentacyclesincorporatinga pyrroleunit73
1.14.6Synthesisof1,3,4trisubstitutedpyrroles bycondensationofarylazidesand aldheydes76
1.15Pyrrolidines78
1.15.1Pyrrolydinonesfromsuitableamidesand aniridiumcatalyst78
1.15.2[3 1 2]Cycloadditionbetweena cyclopropylketoneandanimine79
1.15.3Synthesisofpyrrolidinesfromalkanes andnitrogenderivatives80
1.15.4Aroylchlorinationof1,6dienesto obtain2-pyrrolidinones82
1.15.5Synthesisofpyrrolidinonesfusedwitha cyclobutanering82 1.16Thiophenesandbenzothiophenes85
1.16.1Cyclizationof2-alkynylanilineswith disulfidetoaffordbenzothiophenes85
1.16.2Cyclizationofdiethynilsulfideto thiophene87 References87
2.Photoisomerizationofheterocycliccompounds91
2.1Photoisomerizationofpentaatomicheterocycles91
2.1.1Isomerizationoffuranderivatives91
2.1.2Isomerizationofpyrrole99
2.1.3Isomerizationofthiophene105
2.1.4Isomerizationofisoxazole108
2.1.5Isomerizationofoxazole114
2.1.6Isomerizationofpyrazole115
2.1.7Isomerizationofimidazole118
2.1.8Isomerizationofthiazoles118
2.1.9Isomerizationofisothiazoles124
2.1.10Isomerizationofoxadiazoles127
2.1.11Otherpentaatomicheterocycles133
2.2Photoisomerizationofhexatomicheterocycles133
2.2.1Isomerizationofpyridines133
2.2.2Isomerizationofdiazines144 References152
3.Photochemicalbehaviorof diheteroarylethenesandphotochromism161
3.1Photochemistryofolefins:Anoverview161
3.2Photoinducedpericyclicreactions:Stilbeneandits diheteroarylethenesderivatives174
3.2.1SomeapplicationsoftheMalloryreaction177
3.3The[2 1 2]photocycloadditionreactionson heteroarylethenes179
3.4Photochromismofdiheteroarylethenes183
3.4.1Abriefhistoricaloverviewandbasic reactionmechanism183
3.4.2Photochromism:Tuningwithethene bridges187
3.4.3Photochromism:Tuningwithfuntionalised heteroarylgroups192
3.4.4Photocyclizationreactionsandsolvent effect196
3.4.5Photochromisminchiral diheteroarylethenes198
3.4.6Ringclosureprocessesinducedbyvisible radiationandall-visiblephotochromism201
3.5Applicationsofphotochromicmoleculesof diheteroarylethenes:Switchesandoptical memories205
3.5.1Switches205
3.5.2Switchableelectricconduction206
3.5.3Switchablesupramolecularsystems208
3.5.4Switchableliquidcrystals210
3.5.5Switchablechemicalpropertiesand bioactivity211
3.5.6Opticalmemories212 References214
4.1.1Fromnaturaltoartificialphotoactive systems219
4.1.2Explanationofphotoactivitythroughthe comprehensionofthenatureoflight220
4.1.3Explanationofmolecularphotoactivity throughlight matterinteractionmodels220
4.1.4Themolecularskeletonofphotoactive moleculesdefinethebehavioroflight absorptionandemissioninmolecules222
4.2Mainclassesofheterocyclicphotoactive compounds:synthesisandphotochemical reactions224
4.2.1Three-memberedheterocycles224
4.2.2Four-memberedheterocycles232
4.2.3Five-memberedheterocycles239
4.2.4Six-memberedheterocycles266
4.3Applicationsandtechnologyofthemain classesofheterocyclicphotoactivecompounds268
4.3.1Heterocyclicconjugatedbackbonesfor efficientemergingorganicphotovoltaics268
4.3.2Lightstabilityofnon-fullereneacceptors: photo-oxidationandphotophysical degradations275
4.3.3Majorclassesofnon-fullereneacceptors: rylenediimides279
4.3.4Majorclassesofnon-fullereneacceptors: perylenediimidesmallmolecules279
4.3.5Majorclassesofnon-fullereneacceptors: fused-ringelectronacceptors280
4.3.6Polymersandsmall-moleculedonors281
4.3.7Nonlinearopticalmaterials282 References290
5.Photodegradationofdrugsandcrop protectionproducts297
5.1Introduction297
5.2Generalmechanismsofphotodegradationof drugs298
5.3Anti-inflammatory,analgesic,and immunosuppressantdrugs299
5.3.1Nonsteroidalanti-inflammatorydrugs299
5.3.2Pyrazoloneanalgesicandantipyreticdrugs300
5.3.3Immunosuppressantandanti-histamic drugs302
5.4Drugsactingonthecentralnervoussystem304
5.4.1Barbituricacidderivatives304
5.4.2Benzodiazepines306
5.4.3Thioxantheneandphenothiazine psychotherapeuticagents308
5.5Cardiovasculardrugs310
5.5.1Cardiacagents310
5.5.2Bloodpressure-regulatingdrugs310
4.Heterocyclic-basedphotoactivematerials219
4.1Overviewofphotoactivematerials219
5.5.3Adrenergics311
5.5.4Diuretics312
5.6Chemotherapeuticagents313
5.6.1Antibacterialdrugs313
5.6.2Antibacterialsandantivirals:aromatic derivatives315
5.6.3 β-Lactamantibiotics316
5.6.4Antiprotozoal,anti-amebic,antimycotic drugs317
5.6.5Antineoplasticdrugs317
5.6.6Furocoumarins318
5.7Generalmechanismsofphotodegradationofcrop protectionproducts319
5.7.1Azolefungicides320
5.7.2Dicarboximidefungicides321
5.7.3Imidazolinoneherbicides323
5.7.4Macrocycliclactoneinsecticide324
5.7.5N-Methylcarbamateinsecticides325
5.7.6Neonicotinoidinsecticides327
5.7.7Organophosphateinsecticides328
5.7.8Triazineherbicides329
5.7.9Triazinoneherbicides330
5.7.10Triazolopyrimidineherbicide332
5.7.11Unclassifiedpesticides334 References335 Index337
Photochemicalsynthesisofheterocyclic compounds
OUTLINE
1.1Introduction3
1.2Azetidines3
1.2.1SynthesisbyazaPaterno ` Buchireaction3
1.2.2Synthesisbyintramolecularclosureof N-formil-α-oxoamides4
1.2.3SynthesisbyNorris-Yangrearrangement4
1.2.4Reactionbetweenfullereneand formamidines5
1.2.5Synthesisbyciclizationofaminoketones6
1.3Aziridines6
1.3.1Synthesisbyrearrangementofpyridinium salts6
1.3.2Synthesisbyinsertionofnitreneintodouble bonds7
1.3.3Synthesisfromhomoallylpyrroles7
1.3.4Synthesisbyrearrangementoftriazolines8
1.3.5Synthesisofaziridinesbyvisible-lightinduced decarboxylativecyclizationof N-arylglycines anddiazocompounds8
1.3.6Photoinducedaziridinationofalkeneswith N-sulfonyliminoiodinane9
1.3.7Photochemicalaziridinationoffullerenes9
1.3.8Synthesisfromsugarderivativesand azides10
1.3.9Synthesisfromazidesbyphotocatalysis10
1.3.10Synthesisfromazidoformates11
1.4Diazepinesandbenzodiazepines11
1.4.1Synthesisfrom4-pyridylazides11
1.5Furans13
1.5.1Furansfrom α-bromo-β -dicarbonyl compoundsandalkynes13
1.5.2Benzofuransfrom2-chlorophenolsand alkynes13
1.5.3Dihydroandtetrahydrofuransfrom cyclopropanederivatives14
1.5.4Dihydrofuranfromphotodimerizationof β -carbonylketones15
1.5.5Tetrasubstitutedfuransfromsilylenolethers and α-bromodiketones15
1.5.6Synthesisof5H-furanonesfromsubstituted cyclobutenones16
1.5.7Photochemicalcatalyticalsynthesisof dihydrofuransfromvinylandaryl cyclopropanes16
1.5.8Tetrahydrofuransfromcyclobutanonesand nitrilecompounds16
1.5.9Reactionofpropargylderivativeswith alkenes17
1.5.10Tetrahydrofuransfrom α,β -unsaturated ketones18
1.5.11 γ -Lactonesfromallylicalcoholsand α,β -unsaturatedketoester18
1.5.12Synthesisfromcinnamicacidandketones18
1.5.13Synthesisfrom α-chloroalkylketonesand styrenes19
1.5.14Synthesisbyisomerizationofalkenes20 1.6Imidazolesandderivatives20
1.6.1Synthesisofanimidazoleintermediatedby HCN20
1.6.2Synthesisofdihydroimidazolesfrompyridinium saltsandanalkene21
1.6.3Synthesisofanimidazolinonebycyclization ofalinearcompound22
1.6.4Synthesisofpurinesbyirradiationofurea/ acetylene22
1.6.5Onepotsynthesisfromaldehydes, α-aminonitrilesandisoxazoles23
1.6.6Reactionof N-(1-methylpyrimidin-2-one) pyridiniumchloride.Contractiontoan imidazolidinone23
1.7Synthesisofoxadiazoles24
1.7.11,2,4Oxadiazolesfrom2H-azirinesand nitrosoarenes24
1.7.2Photooxidationof N-acylhydrazonesto1,3,4oxadiazoles25
1.8Synthesisofoxazolesandrelatedsystems26
1.8.1Synthesisofoxazolesbyconversionof1-acyl triazoles26
1.8.2Synthesisfrom α-bromoketonesand benzylamines26
1.8.3Threecomponentscondensationof silylenolethers,fluoroalkylhalidesandchiral aminoalcoholstoobtainoxazolidines27
1.8.4Oxazolidinonesfrompropargylicaminesand CO2 28
1.8.5Conversionofbenzoilformamidestooxazolidin 4-ones29
1.8.6Synthesisofphosphoniumsubstitutedoxazoles fromphosphonium-iodoniumylides30
1.8.7Synthesisfromazirinesandaldehydes30
1.9Oxetanes:thePaterno ` Bu ¨ chireaction31
1.9.1 Exo-oxetanesfromcarbonylcompounds withvinylenecarbonates31
1.9.2Photocycloadditionof N-acylenaminesto aldehydes32
1.9.3Oxetanesfromcarbonylcompoundsand2,5 dimethyl-4-isobutyl-oxazoles33
1.9.4Reactionof2,3-dihydrofuran34
1.9.5Reactionofasilylderivativeofcinnamyl alcohol35
1.9.6Reactionofgeraniolderivatives35
1.9.7Reactionwithisoxazolederivatives36
1.9.8Synthesisofanelusiveoxetaneby photoadditionofbenzophenonetothiophene inthepresenceofaLewisacid37
1.9.9Reactionof2-furylmethanolderivatives38
1.9.10Reactionofsilylenolethers39
1.10Piperidines40
1.10.1Iodinecatalyzedsp3-Hamination40
1.10.2Synthesisfrom2,6-diaminopimelicacidto piperidine-2,6-dicarboxylicacid42
1.10.3Aphotochemicalreactioninthesynthesisof azasugarderivatives43
1.10.4Piperidinesfromring-contactionof Nchlorolactams43
1.10.5Synthesisof2-piperidinonecatalyzedfroma hydrophobicanalogofvitaminB12 44
1.11.1Aromatizationof1,3,5trisubstituted pyrazolines44
1.11.2Photochemicalbrominationforpreparationof mono,bisandfusedpyrazolederivatives45
1.11.3PyrazolesfromhydrazinesandMichael acceptors47
1.11.4Synthesisofpyrazolederivativesviaformal [4 1 1]annulationandaromatization48
1.11.5Reactionofhydrazonesand α-bromoketones49
1.11.6Onepotsynthesisofpyrazolesfromalkynes andhydrazines51
1.11.7Sunlight-promoteddirectirradiationof Ncenteredanion:thephotocatalyst-freesynthesis ofpyrazoles52
1.11.8Efficientphotooxidationofaryl(hetaryl) pyrazolinesbybenzoquinone53
1.11.9Synthesisofpyrazolesviaphotochemicalring openingofpyridazine N-oxides54
1.12Pyridines55
1.12.1Pyridinesfromringclosureofacyloximes55 1.12.2Synthesisofnaphthylpyridinesfrom heptadynesandnitriles57
1.12.3Synthesisofsubstitutedpyridinefromaryl ketoneandbenzylamines58
1.12.4Pyridinesfromtrimerizationoftwoalkenes andanitrile60
1.13Pyrimidines61
1.13.1Synthesisofbenzo-fusedpyrimidines-4-ones from1,2,4oxadiazoles61
1.13.2Fluoroalkylatespyrimidinesfromsilylenol ethers,amidines,andfluoroalkylhalides63
1.13.3Threecomponentsynthesisfromactive methylenecompounds,perfluoroalkyliodides andguanidines66
1.13.4Synthesisofpyrimidonesfrom4-allyltetrazolones67
1.14Pyrroles69
1.14.1Dehydrogenativearomatizationand sulfonylationofpyrrolidines69
1.14.2Synthesisofnitrogenheterocyclesgenerated from α-silylsecondaryaminesundervisible lightirradiation71
1.14.3Synthesisofsubstitutedpyrrolesbydimerization ofacylazirines71
1.14.4Photochemicalisomerizationsof N-substituted 2-halopyrroles:synthesesof N-substituted 3-halopyrroles73
1.14.5Synthesisofpentacyclesincorporatingapyrrole unit73
1.14.6Synthesisof1,3,4trisubstitutedpyrrolesby condensationofarylazidesandaldheydes76
1.15Pyrrolidines78
1.15.1Pyrrolydinonesfromsuitableamidesandan iridiumcatalyst78
1.15.2[3 1 2]Cycloadditionbetweena cyclopropylketoneandanimine79
1.15.3Synthesisofpyrrolidinesfromalkanesand nitrogenderivatives80
1.15.4Aroylchlorinationof1,6dienestoobtain 2-pyrrolidinones82
1.15.5Synthesisofpyrrolidinonesfusedwitha cyclobutanering82
1.16Thiophenesandbenzothiophenes85
1.16.1Cyclizationof2-alkynylanilineswithdisulfide toaffordbenzothiophenes85
1.16.2Cyclizationofdiethynilsulfideto thiophene87 References87
1.1Introduction
Heterocycliccompoundsareofenormousinterest,especiallyinpharmaceuticalchemistry.Infact,themajority ofcurrentdrugscontainsaheterocyclicring.Despitethegreatimportanceofthesecompounds,onlyfewmethodsexistforthesynthesisofheterocyclesusingphotochemicalmethodthoughphotochemicalreactionsareoften easytorealize,clean,andenvironmentallybenign.Amongthevariousmethodstobuildaheterocycle,cyclizationoflinearcompounds,[x 1 y]cyclizationandringclosurearethemajorones.Theresearchinthisfieldhas significantlyincreasedcomparedtothepast,todiscovernewmethodsandclarifythereactionmechanisms.
Theaimofthischapteristoexplorethephotochemicalsyntheticmethodsforthesynthesisofthemostcommonheterocycliccompounds.
1.2Azetidines
1.2.1SynthesisbyazaPaterno ` Buchireaction
TheazaPaterno ` Buchireactionisaphotochemicalreactionbetweenanalkeneandanimineoranoxime.Not muchinformationexistsintheliteratureaboutthisreaction.Beckeretal.developedamethodforanintramolecularazaPaterno ` Buchireactioninwhichinthesamemoleculesadoublebondandanoximearepresentto obtainabicyclicazetidine(Fig.1.1).1
Usually,thesereactionsaredifficult,becausethepreferredreactionisthe E/Z isomerizationofimineoroxime, andarelimitedtorigidsystemswithirradiationwithhighenergyUVradiation.Theuseofacatalyst(PF6)permitstousevisiblelightviaatripletenergytransfertothedoublebondofthealkene.Controlreactionsrevealed thatbothlightandphotocatalystwerenecessaryforthe[2 1 2]photocycloadditiontoproceed.
Othersubstrateswiththesamebasicstructurewereinvestigated.Ineverycase,thereactionprocedeswell withhighyield(upto98%)andexcellentdiastereoselectivity(20:1).Furthermore,itisindependentfromthe E/Z configurationoftheoxime.2
In2020,thesameresearchgrouppointeditsattentiontointermolecularazaPaterno ` Buchireactions.3 The firstdifficultyencounteredwasthattheexcitedalkenehasatooshortlifetimebeforereactingwithanoxime.So, thechoicewastoselectacyclicoximethatcannotgive E/Z isomerization(Fig.1.2).
FIGURE1.1 IntramolecularazaPaterno ` Buchireaction.
FIGURE1.2 Cyclicoxime.
ThecatalystofchoicewasalwaysPF6.Anexampleisgiveninthe Scheme1.1
SCHEME1.1 Azetidinefromcyclicoxime.
Manyazetidinesweresynthesizedinthisway,insomecaseswithexcellentregioanddiastereoselectivity.
1.2.2Synthesisbyintramolecularclosureof N-formil-α-oxoamides
Irradiationofabenzenesolutionof N-formyl-N-methylbenzoylformamidewithahighpressuremercurylamp gaveacyclizationproduct,3-hydroxy-1-methyl-3-phenylazetidine-2,4-dione.4 Whenother N-formyl-α-oxoamides wereirradiatedunderthesameconditions,thecorrespondingcyclicimideswereobtained(Scheme1.2).
Intramolecularclosureof N-formil-α-oxoamides.
Theformationofazetidineisrationalizedintermsofhydrogenabstractionbytheketonecarbonylfromthe formylgroupandsubsequentcyclizationoftheresulting1,4diradical(Fig.1.3).
1.2.3SynthesisbyNorris-Yangrearrangement
Anothersimplewaytoconstruct3-hydroxyazetidinesisdescribedbyBaxendaleetal.5 Asimpleacyclic2aminoketonefollowingphotochemicalexcitationinvolvingan - π*transitionwithformationofadiradicalthat abstractsaprotonfromoneoftheavailablesites(usuallythe δ-proton)leadingtoanewdiradicalwhichcancombinetoformthecyclicproduct(Scheme1.3).
Norris-Yangrearrangment.
Performingthereactioninbatch,oftenlongreactiontimesandverydiluteconditionsarenecessary.Sothe reactionwasperformedwithaflowreactorataspeedof1mL/min.Thispermitstoobtainconversionupto95% andisolatedyieldsof70%/80%.ConcerningtheusedwavelengthananalysisofUVspectrashowsthatthenπ*transitioncorrespondstoabout300nmsoasuitablefilterwasused.Aboutthechosensubstrate,theauthors findthebestresultswhennitrogenisderivatizedassulfonamide(Fig.1.4).
FIGURE1.3 Diradicalintermediateinthereactionof Scheme1.2
SCHEME1.2
SCHEME1.3
About30compoundsofthiskindwerepreparedandsubmittedtophotochemicalreaction.Theisolatedyields varyfrommoderatetoexcellent.ThelowestyieldswereobtainedwhenRwasanortochloroorbromophenyl. Maybe,itcanbeduetoalackofplanarityinthetransitionstatebetweenphenylandcarbonyl.
1.2.4Reactionbetweenfullereneandformamidines
Fullerene(C60)isaveryinterestingmolecule,nononlyforitsshape,butalsoforthepossibilitythatfuctionalizedfullerenescouldhavebiologicalactivity.6 Theauthorsreportnovelfullerenederivativeshavinganazetidinimineframeworkandcharacterizedtheproduct.Thereaction(Scheme1.4)wasperformedusing N,N0 -bis(2,2dialkylphenyl)formamidinesandawavelength . 400nm.
Thereactiondidnotproceedwhen 1a or 1b wasusedbecauseoftheirpoorsolubilityinthesolventthatwas used(toluene).Moreover,thereactiondidnotproceedintheabsenceofoxygen.
Inthisregard,thereactionmechanismcanbeproposedasshownin Scheme1.5.Initially,asingleelectron transferoccurredfromtheformationofastableC60anionradicalandanamidiniumcationradicalthroughan electrontransferfromaformamidine.Oncegenerated,theC60anionradicalreducesmolecularoxygentogeneratesuperoxideanionradical.C60andanamidiniumcationreacttogethertoformaprotonatedintermediate.The superoxideanionthendeprotonatedradical;theresultingO2H mustbeasufficientlypowerfuloxidanttoconverttheintermediateintoazetidinimine.
FIGURE1.4 Sulfonamideusedin Scheme1.3
SCHEME1.4 Reactionoffullerene.
SCHEME1.5 Mechanismofthereaction.
1.Photochemicalsynthesisofheterocycliccompounds
1.2.5Synthesisbyciclizationofaminoketones
Azetidinescanalsopreparedinopticallypureformstartingfromaminoketones.6 Afteraseriesofsynthetic steps,compoundAwaspreparedandsubmittedtoirradiationtoobtainanazetidinewithconfiguration 2R (Scheme1.6).
SCHEME1.6 Azetidinesfromaminoketones.
Forthesynthesisof 2S enantiomer,itwasstartedfromserine,thatwassubmittedtoaseriesofsyntheticsteps: inanalogousmatter,itispossibletoobtaintheenantiomeroftheazetidinecarboxylicacidwithconfiguration 2S (Scheme1.6).
1.3Aziridines
1.3.1Synthesisbyrearrangementofpyridiniumsalts
Aziridinecanbeobtainedbyrearrangementofpyridiniumsaltsalsoinadiastereoselectivemanner.7,8 An exampleisoutlinedbelow(Scheme1.7).
SCHEME1.7 Rearrangmentofpyridiniumsalts.
Iftheaziridineistreatedwithanucleofile,insomecasesitispossibletheopeningofaziridineringtoafforda cyclopentene(Scheme1.8).
SCHEME1.8 Openingofaziridinetocyclopentene.
Thereactionworkswellalsowithtetrahydroquinolines(Fig.1.5).
FIGURE1.5 Reactionoftetrahydroquinolines.
FIGURE1.6 Synthesisofaziridinesfromenolethers.
FIGURE1.7 Aziridinesfromhomoallylpyrroles.
Thereactionfurnishesalmostexclusivelyaziridinesinthecaseinwhichreactionisperformedinabasic medium.Thus,itallowstominimizetheringopeningtocyclopentene.
1.3.2Synthesisbyinsertionofnitreneintodoublebonds
When2-azido-1,3-thiazolereactswithadoublebond,atripletnitreneisformed,whichcaninsertinthedouble bondtoformanaziridine.9 Thereactionworksparticularlywithenolethers(Fig.1.6).
1.3.3Synthesisfromhomoallylpyrroles
In2016,Blackamandcoworkerssynthesizedasetofhomoallylpirroles,withtheaimtoobtainamethatesis reaction,asithappenedforpyrrolesalkylsubstitutedwithalongerchain.10 Withtheirgreatsurprisetheproductsobtainedwereaziridine.Inthefigurebelowisobtainedthegeneraloutcomeofreaction(Fig.1.7). Thereactionproceedswithgoodyields.TheonlyrequirementisthepresenceofanEWGgroupinposition2 ofpyrroles.Varyingthegradeofsubstitution,itispossibletoobtainverycomplexmoleculeswithquaternary centers.Aproposedmechanismisthefollowing:theexcitationofthegenericpyrrolesubstitutedwithanEWGat C2resultsinaninitial[2 1 2]cycloadditionacrosstheC2 C3bondtogiveacyclobutane.Thentheformationof abiradicalhappens,andthislatterundergoesC2 C5toaffordtheaziridine(Scheme1.9).
SCHEME1.9 Mechanismofthereaction.
Thereactionisscalable-up.Usingabatteryofflowreactors,itispossibletoobtainupto100gperdayof aziridine.
1.3.4Synthesisbyrearrangementoftriazolines
Usually,photochemicalreactionsareperformedinsolution.DeLoeraetal.triedinsteadtomakethereaction insolidphase.11 Thereactionstartsfromatriazolinetoobtain,afterlossofnitrogen,anaziridine.Thereaction canbefollowedmonitoringthedevelopmentofgaseousnitrogen.Themechanismofdenitrogenationoftriazolineisreportedinthe Scheme1.10.
SCHEME1.10 Mechanismofthereaction.
Thetriazolineswereobtainedby[1,1]dipolarcycloadditionbetweenmaleimideandsubstitutephenylazides, andthenirradiatedwithamediumpressureHglampwhitaquartzfilter(Scheme1.11and1.12).
SCHEME1.11 [1,1]dipolarcycloadditionbetweenmaleimideandsubstitutephenylazides.
SCHEME1.12 Obtainingoftheaziridine.
1.3.5Synthesisofaziridinesbyvisible-lightinduceddecarboxylativecyclizationof N-arylglycines anddiazocompounds
Theauthorsenvisionedthatthevisible-lightphotoredox-mediateddecarboxylationof N-arylglicinewould affordan α-aminoalkylradicalwhichcouldbefurtheroxidizedinthepresenceofoxygentogeneratedactive imine.12 TheattackofiminebydiazocompoundswouldleadtointermediateA.IntermediateAcontaininga negativeamineanionmightundergoan exo-tet cyclization,whichultimatelyformaziridineastheproduct (Fig.1.8).Thereactioniscompleteafter60minwithayieldof80%.
Aftervarioustentative,theauthorsfoundthebestconditionforthereaction:RoseBengalascatalyst,methanol,O2,r.tandblueLEDS.
FIGURE1.8 Reactionof N-arylglicine.
Synthesisofiminoiodinanes.
Synthesisofaziridines via imidoiodinanes.
1.3.6Photoinducedaziridinationofalkeneswith N-sulfonyliminoiodinane N-Sulfonyliminoiodinanesarepowerfulcatalystsforthephotoinducedaziridinationofalkenes.Theycaneasilysynthesizedfrom2-nitroiodobenzenediacetateandthecorrespondingsulfonamide(Fig.1.9).13 Inthesamewayweresynthesizediminoiodinane 3a-c (Scheme1.13).
SCHEME1.13 Synthesisofiminoiodinane.
Withthesereactantsinhand,theauthorstriedphotochemicalreactionat0 CwithLEDsat375nm(Fig.1.10). Thereactionofstyrene 4a with 3a gaveaziridine 5a in73%yield,whilethesamereactionwith 2a improved chemicalyieldupto98%.Otherexamplesarereportedin Scheme1.14.
SCHEME1.14 Otherexamples.
1.3.7Photochemicalaziridinationoffullerenes
Fullerenesareveryinterestingcompoundsfromachemistryofheterocyclespointofviewbecausetheyare abletoincorporateheteroatomsbyreactionsofcycloadditions.14,15 Inparticular,fullerenecanthermally
FIGURE1.9
FIGURE1.10
1.Photochemicalsynthesisofheterocycliccompounds
incorporatearylazidestogivetriazolineswhichinturncanphotochemicallyextrudenitrogentogiveaziridinofullerene(Scheme1.15).
SCHEME1.15 Synthesisofazidofullerenes.
Theaziridinationprocesswasnotdisturbedbytheintroductionofgroupsuchanalkyl,ester,ketone,andfluorine.
1.3.8Synthesisfromsugarderivativesandazides
Aminosugarsarecomponentofvarycompoundsofgreatimportanceinmedicine.Amongthese,daunosamineandristosaminearecomponentofafamilyofantibiotics(Fig.1.11).
Manysynthesesexistofthesecompounds,butonlyinonecaseanaziridineispresentinacrucialsynthetic step.16 Thesyntheticpassagesforthesynthesisofdaunosamineglicosideareshowedin Scheme1.16
SCHEME1.16 Synthesisofdaunosamine.
1.3.9Synthesisfromazidesbyphotocatalysis
Inaworkconcerningthesynthesisofpyrrolederivatives,certainparticularsubstrates,withadoublebond nearanazidegroup,canreacttogiveaziridines,attheconditionthatbeusedtheappropriatephotocatalyst[Ir (df(CF3)(ppy)2(dtbbpy)]PF6 (Scheme1.17).17
SCHEME1.17 Pyrrolederivativesfromazidogroup.
FIGURE1.11 Daunosamineandristosamine.
1.3.10Synthesisfromazidoformates
Aziridinescanalsobeobtainedbyazidoformates.Itinterestingtonotethatwhenthesubstituentin ortho positioninthephenylringisHoralkyltheproductsobtainedareamidoesters(Fig.1.12).18
Onthecontrary,whenthesubstituentisanallyl,thereactiontakesacompletelydifferentwaywithformation ofaziridines(Fig.1.13).Otherexamplesarereportedin Fig.1.14.
1.4Diazepinesandbenzodiazepines
1.4.1Synthesisfrom4-pyridylazides
Amongthethreeisomersofdiazepines,only1,2-and1,3-diazepinesarewellknownintheliterature.Thesynthesisoflesssubstituted6H-1,4-diazepinesfrom4-pyridylazidesbyirradiationinthepresenceofmethoxideion hasbeendescribed.Thestarting4-azidopyridineswerepreparedfromthecorresponding4-chloropyridinesby treatmentwithhydrazinehydratefollowedbydiazotization(Fig.1.15).19
FIGURE1.12 Reactionofazidoformates.
FIGURE1.13 Azidoformatehavinganallylgroup.
FIGURE1.14 Otherexamplesofthesynthesisofaziridinesthroughazidoformates.
FIGURE1.15 Diazotizationofpyridinederivatives.
FIGURE1.16 Synthesisof1,4-diazepines.
FIGURE1.17 Possibleintermediatesinthesynthesisof1,4-diazepines.
Irradiation(400W,highpressureHglamp;pyrexfilter)(Fig.1.16)oftheazidesresultedintheformationof thedesired6H-1,4-diazepinesin35% 70%yields,asthesoleringexpansionproducts. Unsymmetricalazidesmayringcloseineitheroftwodirectiontoaffordtwoisomericproducts.However,the authorsobservedtheformationofasoleproductasdepictedin Fig.1.17. Inthesameway,theauthorssynthesizedsome1H-2,4-benzodiazepines.20 Thesyntheticroutestothestarting 4-azidoquinolinesaredepictedinthe Scheme1.18
SCHEME1.18 Synthesisofthestarting azidoquinolines.
Irradiationoftheazides(9a-e)inmethanol-dioxanecontainingsodiummethoxidefor30 40minresultedin theformationofthedesired2,4-benzodiazepines(14a-e)in45% 70%yields,asthesolering-expansionproducts. Inthecaseofthe1-chloroisoquinoline(9e),thechlorineatomwasreplacedbymethoxideunderthepresentbasic reactionconditiontoaffordthesame1-methoxydiazepine(14d)asthatobtainedfrom 9d.Themechanismofformationofbenzodiazepinesisreportedin Scheme1.19.
SCHEME1.19 Mechanismofthereaction.
FIGURE1.18 Synthesisofdiazepinones.
Azidoterpyridinescanphotochemicallyconvertedindiazepinones(Fig.1.18).21 IfR1 isdifferentfromR2,both isomersofdiazepinoneswereobtained.
1.5Furans
1.5.1Furansfrom α-bromo-β-dicarbonylcompoundsandalkynes
Anunusualreactionpermitstoobtainfuransfrom α-bromo-β-dicarbonylsandalkynes.22 Thereactionoccurs withvisiblelightandacomplexofiridiumascatalyst,accordingtothe Scheme1.20
SCHEME1.20 Furansfrom α-bromo-β-dicarbonylsandalkynes.
ThereactionworkswellifR1 isanalkylwhile,ifitisanaryl,anaphtholisobtained.Anotherexampleis reportedin Scheme1.21.Theyieldsvaryfromgood(40% 50%)toexcellent(80% 90%).
SCHEME1.21 Anotherexample.
1.5.2Benzofuransfrom2-chlorophenolsandalkynes
2-Substitutedbenzofuransweresynthesizedbyaone-stepmetal-freephotochemicalreactionbetween2chlorophenolderivativesandterminalalkynesbytandemformationofanaryl CandaC Obondviaanaryl cationintermediate.23 Areasonablemechanismforthisreactionisdepictedin Scheme1.22
SCHEME1.22 Reactionof2-chlorophenolderivatives.
Thefirstpartofthisstudyaimedtoindividuatetheconditionforasuccessfulsynthesisbyusingthereaction of2-chlorophenolinpresenceof1-hexyneunderdifferentconditions.Thebestsolventrevealedtobe5:1MeCN/ waterinpresenceofacetonewhichactsasatripletsensitizer.Thisconsentstomaximizetheyields(42% 49%) andtominimizetheformationofthemainby-product(phenol).Theyieldofbenzofuransfurtherincreased whenstartingfrom4-t-butyl-2-chlorophenol.Furthermore,goodyields(upto85%)wereobtainedwhenoxygen basedsubstituent,suchamethoxyoranhydroxylgroup,wereintroduced.Finally,acceptableyieldswere obtainedalsobyusingtrimethylacetyleneinsteadof1-hexyne.
1.5.3Dihydroandtetrahydrofuransfromcyclopropanederivatives
Thephotochemistryofcyclopropaneinvolvesmainlythe cis-trans isomerization.Infewcases,with suitablesubstituents,aringexpansioncouldhappentocyclopentenesorfuranderivatives.24 Aseriesofderivativesstartingfromethylchrysantemateswassinthesized(Fig.1.19).
Whenthereactionistripletsensitizedwithbenzophenone,compound 16 givesonlyrecoveredmaterialanda cyclopentene.Thesamewasobservedwith 16b, 16c,and 16d,that,besidescyclopentene,affordsalsofuranderivatives 19 and 20 (Fig.1.20).
Oxime 16e doesnotreact,givingonlyamixtureofdiastereoisomers.Alcohol 16f givesamixtureofhighly polarcompoundswhichdoesnotwereidentified.Itwasalsotriedtomakethereactionwithoutsensitizer. 16a furnishesamixtureofstereoisomerofthestartingproductanda19%of2-furanone 21 (Fig.1.21).
Ketone 16d doesnotgivethecyclopentenederivativeobservedininthetriplet-sensitizedreactionbutproducesthetetrahydrofuran 20 (19%)alongwithstartingmaterial.
Derivativesofchrisanthemates.
Dihydroandtetrahydrofuransfromcyclopropanederivatives.
FIGURE1.21 2-Furanoneobtainedfrom 16a
FIGURE1.19
FIGURE1.20
FIGURE1.22 Dimerizationofacetylacetone.
FIGURE1.23 Amorecomplexexample.
1.5.4Dihydrofuranfromphotodimerizationof β-carbonylketones
Highlyfunctionalizedfuranscanbeobtainedbyaerobicoxidativedimerizativeannulationsof β-carbonyl ketones(Fig.1.22).25
Aplausiblemechanismofreactionshouldbethatreportedin Scheme1.23
SCHEME1.23 Mechanismofthereaction.
ThereactionoccursirradiatingthemixturewithblueLEDsunderoxygen,and,insomecases,excellentyields canbeobtainedadding4A ˚ molecularsieves.Anotherexampleofthisprocedureisreportedin Fig.1.23
1.5.5Tetrasubstitutedfuransfromsilylenolethersand α-bromodiketones
Thesameauthorsthatobtainedfuransfrom α-bromo-β-dicarbonylcompoundsandalkynesusedinsteadof alkynessilylenolethers(Scheme1.24).26
SCHEME1.24 Reactionwithsilylenolethers.
