Annulative π-extension of indoles and pyrroles with diiodobiaryls by Pd catalysis: rapid synthesis of nitrogen-containing polycyclic aromatic compounds

Article abstract of DOI:10.1039/c8sc02802h

A palladium-catalyzed one-step annulative π-extension (APEX) reaction of indoles and pyrroles that allows rapid access to nitrogen-containing polycyclic aromatic compounds is described. In the presence of palladium pivalate and silver carbonate, diverse indoles or pyrroles coupled with diiodobiaryls in a double direct C-H arylation manner to be transformed into the corresponding π-extended compounds in a single step. The newly developed catalytic system enables the use of various pyrroles and indoles as templates with a series of diiodobiaryls to provide structurally complicated and largely π-extended nitrogen-containing polycyclic aromatic compounds that are otherwise difficult to synthesize.

Full text of DOI:10.1039/c8sc02802h

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Please Cꢀ dh oe ꢀmn oi c taꢀ al Sd cj ui es nt cꢀ me arginsꢀ
View Article Online
DOI: 10.1039/C8SC02802H
JournalꢀNameꢀ
ꢀ
ꢀ
ARTICLEꢀ
Annulativeꢀπ-ExtensionꢀofꢀIndolesꢀandꢀPyrrolesꢀwithꢀDiiodobiarylsꢀ
byꢀPdꢀCatalysis:ꢀRapidꢀSynthesisꢀofꢀNitrogen-ContainingꢀPolycyclicꢀ
AromaticꢀCompoundsꢀ
Receivedꢀ00thꢀJanuaryꢀ20xx,ꢀ
Acceptedꢀ00thꢀJanuaryꢀ20xxꢀ
#
†
,†,‡
,#,†,‡
HiroyukiꢀKitano, ꢀWataruꢀMatsuoka, ꢀHidetoꢀIto,* ꢀandꢀKenichiroꢀItami*
ꢀ
DOI:ꢀ10.1039/x0xx00000xꢀ
www.rsc.org/ꢀ
Aꢀpalladium-catalyzedꢀone-stepꢀannulativeꢀπ-extensionꢀ(APEX)ꢀreactionꢀofꢀindolesꢀandꢀpyrrolesꢀthatꢀallowsꢀrapidꢀaccessꢀtoꢀ
nitrogen-containingꢀ polycyclicꢀ aromaticꢀ compoundsꢀ isꢀ described.ꢀ Inꢀ theꢀ presenceꢀ ofꢀ palladiumꢀ pivalateꢀ andꢀ silverꢀ
carbonate,ꢀ diverseꢀ indolesꢀ orꢀ pyrrolesꢀ coupledꢀ withꢀ diiodobiarylsꢀ inꢀ aꢀ doubleꢀ directꢀ C–Hꢀ arylationꢀ mannerꢀ toꢀ beꢀ
transformedꢀ intoꢀ theꢀ correspondingꢀ π-extendedꢀ compoundsꢀ inꢀ aꢀ singleꢀ step.ꢀ Theꢀ newlyꢀ developedꢀ catalyticꢀ systemꢀ
enablesꢀ theꢀ useꢀ ofꢀ variousꢀ pyrrolesꢀ andꢀ indolesꢀ asꢀ templatesꢀ withꢀ aꢀ seriesꢀ ofꢀ diiodobiarylsꢀ toꢀ provideꢀ structurallyꢀ
complicatedꢀ andꢀ largelyꢀ π-extendedꢀ nitrogen-containingꢀ polycyclicꢀ aromaticꢀ compoundsꢀ thatꢀ areꢀ otherwiseꢀ difficultꢀ toꢀ
synthesize.ꢀ
directlyꢀ transformꢀ easilyꢀ availableꢀ unfunctionalizedꢀ
(hetero)arenesꢀ toꢀ polycyclicꢀ aromaticꢀ hydrocarbons,ꢀ
nanographenesꢀ andꢀ π-extendedꢀ heteroaromaticsꢀ inꢀ aꢀ doubleꢀ
Introductionꢀꢀ
ꢀ
ꢀꢀWithꢀ desirableꢀ electronicꢀ propertiesꢀ andꢀ diverseꢀ biologicalꢀ
directꢀ C–Hꢀ arylationꢀ manner,ꢀ theseꢀ protocolsꢀ offerꢀ largeꢀ
benefitsꢀ inꢀ theꢀ contextꢀ ofꢀ cost,ꢀ simplicity,ꢀ andꢀ step/atomꢀ
activities,ꢀnitrogen-containingꢀfusedꢀaromaticsꢀhaveꢀlongꢀbeenꢀ
recognizedꢀ asꢀ privilegedꢀ structuresꢀ inꢀ theꢀ fieldsꢀ ofꢀ organicꢀ
1
materialsꢀandꢀpharmaceuticalꢀscience. ꢀAsꢀtheseꢀpropertiesꢀcanꢀ
8
economy. ꢀꢀ
7 9-14
ꢀꢀRecently,ꢀwe ꢀandꢀothers ꢀhaveꢀreportedꢀtransition-metal-
ꢀ
catalyzedꢀAPEXꢀreactionsꢀofꢀindolesꢀandꢀpyrrolesꢀusingꢀvariousꢀ
beꢀ readilyꢀ tunedꢀ viaꢀ skeletalꢀ modificationꢀ ofꢀ theꢀ coreꢀ N-
heteroareneꢀ structure,ꢀ significantꢀ effortsꢀ haveꢀ beenꢀ devotedꢀ
toꢀ developꢀ newꢀ syntheticꢀ approachesꢀ forꢀ theꢀ π-extendedꢀ
nitrogen-containingꢀ polycyclicꢀ aromaticꢀ compoundsꢀ (N-PACs).ꢀ
Representativeꢀclassicalꢀapproachesꢀincludeꢀ(i)ꢀintramolecularꢀ
9
π-extensionꢀunitsꢀsuchꢀasꢀalkyne, ꢀalkene,
ꢀ
7a,10
ꢀ1-vinylpropargylꢀ
13ꢀ
alcohols, ꢀα-diazocarbonylꢀcompounds, ꢀα-bromochalcone,
1
1
12
1
3
14
α-bromocinnamate, ꢀ
cyclicꢀ
diaryliodoniumꢀ
salts, ꢀ
7b
7c
2
dibenzogermoles ꢀandꢀdiiodobiphenyls ꢀ(Figureꢀ1b).ꢀHowever,ꢀ
theseꢀAPEXꢀreactionsꢀareꢀlimitedꢀinꢀtermsꢀofꢀlackꢀofꢀvarietyꢀinꢀ
π-extendingꢀ agents,ꢀ narrowꢀ substrateꢀ scope,ꢀ andꢀ lowꢀ
functionalꢀgroupꢀtolerance.ꢀHerein,ꢀweꢀreportꢀaꢀnewꢀcatalyticꢀ
APEXꢀreactionꢀthatꢀallowsꢀefficientꢀpyrrole-to-indole,ꢀpyrrole-
to-carbazoleꢀandꢀindole-to-carbazoleꢀπ-extensions.ꢀOurꢀnewlyꢀ
establishedꢀ catalyticꢀ systemꢀ featuringꢀ palladiumꢀ pivalateꢀ andꢀ
silverꢀ carbonateꢀ inꢀ aꢀ mixedꢀ DMF/DMSOꢀ solventꢀ systemꢀ
enabledꢀtheꢀrapidꢀsynthesisꢀofꢀstructurallyꢀcomplicatedꢀN-PACsꢀ
fromꢀ readilyꢀ availableꢀ unfunctionalizedꢀ pyrroles/indolesꢀ andꢀ
diiodobiaryls.ꢀ
carbon–nitrogenꢀ bondꢀ formationꢀ ofꢀ biarylꢀ amines, ꢀ (ii)ꢀ
intramolecularꢀ carbon–carbonꢀ bondꢀ formationꢀ ofꢀ diarylꢀ
3
amines, ꢀandꢀ(iii)ꢀstepwiseꢀfunctionalizationꢀandꢀπ-extensionꢀofꢀ
4
indolesꢀ andꢀ pyrroles. ꢀ However,ꢀ theseꢀ methodsꢀ requireꢀ theꢀ
useꢀofꢀprefunctionalizedꢀheteroaromaticsꢀsuchꢀasꢀhalogenatedꢀ
pyrroles,ꢀ anilinesꢀ andꢀ indoles,ꢀ andꢀ stepwiseꢀ transformationsꢀ
fromꢀunfuctionalizedꢀ(hetero)aromatics.ꢀToꢀachieveꢀmaximumꢀ
efficiencyꢀinꢀN-PACꢀconstruction,ꢀaꢀmoreꢀdirectꢀandꢀ‘intuitive’ꢀ
methodꢀ forꢀ π-extensionꢀ ofꢀ unfunctionalizedꢀ pyrrolesꢀ andꢀ
indolesꢀisꢀcalledꢀfor.ꢀ
ꢀ
forꢀ theꢀ annulativeꢀ π-extensionꢀ (APEX)ꢀ ofꢀ unfuctionalizedꢀ
ꢀꢀRecently,ꢀweꢀhaveꢀintroducedꢀseveralꢀnewꢀone-stepꢀmethodsꢀ
ꢀ
5
hetero)aromaticsꢀ(Figureꢀ1a). ꢀBecauseꢀsuchꢀAPEXꢀreactionsꢀ
-7
(
#
InstituteꢀofꢀTransformativeꢀBio-Moleculesꢀ(WPI-ITbM),ꢀNagoyaꢀUniversity,ꢀChikusa,ꢀ
Nagoyaꢀ464-8602,ꢀJapanꢀ
†
GraduateꢀSchoolꢀofꢀScience,ꢀNagoyaꢀUniversity,ꢀChikusa,ꢀNagoyaꢀ464-8602,ꢀJapanꢀ
‡
JST-ERATO,ꢀItamiꢀMolecularꢀNanocarbonꢀProject,ꢀNagoyaꢀUniversity,ꢀChikusa,ꢀNagoyaꢀ
4
64-8602,ꢀJapanꢀ
Thisꢀjournalꢀisꢀ©ꢀTheꢀRoyalꢀSocietyꢀofꢀChemistryꢀ20xxꢀ
J.ꢀName.,ꢀ2013,ꢀ00,ꢀ1-3ꢀ|ꢀ1ꢀꢀ
Pleaseꢀdoꢀnotꢀadjustꢀmarginsꢀ

Please Cꢀ dh oe ꢀmn oi c taꢀ al Sd cj ui es nt cꢀ me arginsꢀ
Page 2 of 6
ARTICLEꢀ
JournalꢀNameꢀ
temperatureꢀ acceleratedꢀ theꢀ consumptionꢀ ofꢀ rt
a) One-step annulative π-extension (APEX) reaction
View Article Online
theꢀ sta ingꢀ
DOI: 10.1039/C8SC02802H
material,ꢀtheꢀyieldꢀofꢀ3aaꢀwasꢀdecreasedꢀ(entriesꢀ12ꢀandꢀ13).ꢀ
Finally,ꢀweꢀconfirmedꢀthatꢀtheꢀAPEXꢀreactionꢀdidꢀnotꢀproceedꢀ
H
H
Ar
Ar
annulative
π-extension
2 3
inꢀ theꢀ absenceꢀ ofꢀ Pdꢀ catalystꢀ orꢀ Ag CO ꢀ (entriesꢀ 14ꢀ andꢀ 15).ꢀ
(APEX)
unfunctionalized
hetero)aromatics
π-extended
(hetero)aromatics
Althoughꢀtheꢀuseꢀofꢀadditionalꢀ ligandsꢀforꢀPdꢀandꢀtheꢀuseꢀofꢀ
dibromobiphenylꢀinꢀplaceꢀofꢀdiiodobiphenylꢀasꢀtheꢀπ-extensionꢀ
reagentꢀ wereꢀ alsoꢀ investigated,ꢀ theseꢀ modificationsꢀ provedꢀ
ineffectiveꢀ (seeꢀ ESIꢀ forꢀ details).ꢀ Ultimatelyꢀ theꢀ conditionsꢀ inꢀ
entryꢀ 8ꢀ wereꢀ deemedꢀ optimalꢀ forꢀ theꢀ presentꢀ indole-to-
carbazoleꢀAPEXꢀreaction.ꢀ
(
b) Reported transition-metal-catalyzed APEX reaction of indoles and pyrroles
cat. Pd, Cu, Rh, Ru, Ir, Au
or
π-extending agents
N
R1
N
N
R1
R1
Tableꢀ1ꢀꢀScreeningꢀofꢀreactionꢀconditionsꢀforꢀtheꢀPd-catalyzedꢀindole-to-carbazoleꢀAPEXꢀ
reactionꢀofꢀN-methylindoleꢀ(1a)ꢀandꢀdiiodobiphenylꢀ(2a).ꢀꢀ
π-extending agents =
O
O
Me
R2
R2
R2
Ge
TfO
I
Pd cat. (5 mol%)
Ag salt
O
R2
Me
I
I
N2
N
DMF/DMSO
Temp., 19 h
etc.
N
1
a
2a
1.5 eq.
3aa
0
.20 mmol
c) This work
ꢀ
Yield ꢀ(%)ꢀ
a
cat. Pd(OPiv)2
Ag2CO3
entryꢀ
Pdꢀcat.ꢀ
Agꢀsaltꢀ
Temp.ꢀ(°C)ꢀ
80ꢀ
Ar
Ar
I
I
1ꢀ
2ꢀ
Pd(OAc)
2
ꢀ
Ag
Ag
Ag
Ag
Ag
Ag
Ag
Ag
2
2
2
2
2
2
2
2
CO
3
CO
3
CO
3
CO
3
CO
3
CO
3
CO
3
CO
3
ꢀ(3.0ꢀeq.)ꢀ
ꢀ(3.0ꢀeq.)ꢀ
ꢀ(3.0ꢀeq.)ꢀ
ꢀ(3.0ꢀeq.)ꢀ
ꢀ(3.0ꢀeq.)ꢀ
ꢀ(3.0ꢀeq.)ꢀ
ꢀ(3.0ꢀeq.)ꢀ
ꢀ(1.5ꢀeq.)ꢀ
54ꢀ
61ꢀ
3ꢀ
N
DMF/DMSO, 80 ˚C
Ar
Pd(OPiv)
2
ꢀ
80ꢀ
R
Ar
N
3
4
5
6
7
8
9
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
PdCl
2
ꢀ
80ꢀ
R
indoles
or
pyrroles
nitrogen-containing
polycyclic aromatic
compounds
PdI
2
ꢀ
80ꢀ
2ꢀ
Pd(PPh
3
)
4
ꢀ
80ꢀ
4ꢀ
(
N-PACs)
ꢀ
ꢀ
Pd(OCOCF
Pd(CH CN)
3
)
2
ꢀ
80ꢀ
0ꢀ
Figureꢀ 1ꢀ a)ꢀ Generalꢀ schemeꢀ ofꢀ annulativeꢀ π-extensionꢀ (APEX)ꢀ reactionꢀ ofꢀ
unfunctionalizedꢀ(hetero)aromatics.ꢀb)ꢀPreviousꢀtransition-metal-catalyzedꢀAPEXꢀ
reactionsꢀofꢀindolesꢀandꢀpyrroles.ꢀc)ꢀPalladium-catalyzedꢀAPEXꢀreactionꢀofꢀindolesꢀ
andꢀpyrrolesꢀwithꢀdiiodobiarylsꢀ(thisꢀwork).ꢀ
3
4
(BF
4
)
2
ꢀ
80ꢀ
0ꢀ
cꢀ
Pd(OPiv)
Pd(OPiv)
Pd(OPiv)
Pd(OPiv)
Pd(OPiv)
Pd(OPiv)
noneꢀ
2
2
2
2
2
2
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
80ꢀ
78ꢀ(66)
AgOAcꢀ(3.0ꢀeq.)ꢀ
AgOPivꢀ(3.0ꢀeq.)ꢀ
80ꢀ
33ꢀ
0ꢀ
1
0ꢀ
11ꢀ
2ꢀ
80ꢀ
Resultsꢀandꢀdiscussionꢀ
AgOCOCF
3
ꢀ(3.0ꢀeq.)ꢀ
80ꢀ
0ꢀ
1
Ag
2
Ag
2
Ag
2
CO
3
CO
3
CO
3
ꢀ(1.5ꢀeq.)ꢀ
ꢀ(1.5ꢀeq.)ꢀ
ꢀ(1.5ꢀeq.)ꢀ
100ꢀ
100ꢀ
80ꢀ
57ꢀ
58ꢀ
0ꢀ
ꢀ
ꢀꢀꢀWeꢀ beganꢀ ourꢀ studyꢀ byꢀ optimizingꢀ theꢀ reactionꢀ conditionsꢀ
forꢀindole-to-carbazoleꢀextensionꢀofꢀN-methylindoleꢀ(1a)ꢀusingꢀ
,2ʹ-diido-1,1ʹ-biphenylꢀ(2a)ꢀasꢀaꢀπ-extendingꢀagentꢀ(Tableꢀ1).ꢀ
Afterꢀ extensiveꢀ screening,ꢀ weꢀ discoveredꢀ thatꢀ 1aꢀ (1.0ꢀ equiv)ꢀ
coupledꢀ withꢀ 2aꢀ (1.5ꢀ equiv)ꢀ inꢀ theꢀ presenceꢀ ofꢀ Pd(OAc)
mol%)ꢀ andꢀ Ag CO ꢀ (3.0ꢀ equiv)ꢀ atꢀ 80ꢀ °Cꢀ inꢀ 7:3ꢀ mixtureꢀ ofꢀ
bꢀ
ꢀ13
1
4ꢀ
5ꢀ
2
1
Pd(OPiv)
2
ꢀ
1
noneꢀ
80ꢀ
0ꢀ
a
b
Yieldꢀ wasꢀ determinedꢀ byꢀ Hꢀ NMRꢀ analysisꢀ usingꢀ dodecaneꢀ asꢀ anꢀ internalꢀ standard.ꢀ
c
ꢀ (5ꢀ Reactionꢀtimeꢀwasꢀ1ꢀh.ꢀ Isolatedꢀyieldꢀinꢀtheꢀparenthesis.ꢀPivꢀ=ꢀpivaloyl.ꢀ
2
2
3
ꢀ
ꢀ
dimethylformamideꢀ (DMF)ꢀ andꢀ dimethylsulfoxideꢀ (DMSO)ꢀ toꢀ
provideꢀ N-methyldibenzo[a,c]carbazoleꢀ (3aa)ꢀ inꢀ 54%ꢀ yieldꢀ
ꢀꢀAꢀ possibleꢀ reactionꢀ mechanismꢀ ofꢀ currentꢀ indole-to-
carbozoleꢀ APEXꢀ reactionꢀ isꢀ shownꢀ inꢀ Schemeꢀ 1.ꢀ Oxidativeꢀ
additionꢀofꢀ2aꢀtoꢀpalladiumꢀspeciesꢀ(Pd(0)ꢀorꢀPd(II))ꢀoccursꢀtoꢀ
(
entryꢀ 1).ꢀ Useꢀ ofꢀ palladiumꢀ pivalateꢀ [Pd(OPiv)
Pd(OAc) ꢀ improvedꢀ theꢀ yieldꢀ toꢀ 61%ꢀ (entryꢀ 2),ꢀ butꢀ otherꢀ
palladiumꢀsourcesꢀsuchꢀasꢀPdCl
andꢀPd(CH CN) (BF ꢀfailedꢀtoꢀgiveꢀmoreꢀthanꢀtraceꢀamountsꢀ
ofꢀproductꢀ(entriesꢀ3–7).ꢀDecreasingꢀtheꢀamountꢀofꢀAg
2
]ꢀ insteadꢀ ofꢀ
2
1
formꢀbiphenylylpalladiumꢀintermediateꢀA. ꢀThen,ꢀtheꢀremovalꢀ
5
2
,ꢀPdI ,ꢀPd(PPh ) ,ꢀPd(OCOCF ) ꢀ
2 3 4 3 2
1
ofꢀ iodideꢀ byꢀ silverꢀ saltꢀ mayꢀ activateꢀ Pdꢀ complexꢀ A ꢀ toꢀ formꢀ
6
3
4
4 2
)
17
electron-deficientꢀ aryl-Pdꢀ species ,ꢀ whichꢀ thenꢀ reactꢀ withꢀ
indoleꢀatꢀtheꢀC2ꢀpositionꢀtoꢀaffordꢀintermediateꢀB.ꢀThroughꢀtheꢀ
controlꢀ experimentsꢀ onꢀ theꢀ C–Hꢀ arylationsꢀ ofꢀ 1,2-
dimethylindoleꢀandꢀ1,3-dimethylindoleꢀwithꢀiodobenzene,ꢀtheꢀ
presentꢀAPEXꢀreactionꢀseemsꢀtoꢀoccurꢀthroughꢀtheꢀC2-arylationꢀ
ofꢀindoleꢀratherꢀthanꢀC3-arylationꢀinꢀtheꢀfirstꢀstepꢀ(seeꢀESIꢀforꢀ
details).ꢀ Finalꢀ stepꢀ wouldꢀ beꢀ well-establishedꢀ Pd-catalyzedꢀ
intramolecularꢀ C–H/C–Iꢀ couplingꢀ toꢀ affordꢀ theꢀ cyclizedꢀ
2
CO
.5ꢀequivꢀ(relativeꢀtoꢀ1a)ꢀfurtherꢀincreasedꢀtheꢀyieldꢀofꢀ3aaꢀtoꢀ
8%ꢀ (entryꢀ 8).ꢀ Theꢀ useꢀ ofꢀ silverꢀ carboxylateꢀ saltsꢀ (AgOAc,ꢀ
)ꢀ insteadꢀ ofꢀ Ag CO ꢀ resultedꢀ inꢀ muchꢀ
lowerꢀyieldꢀ(entriesꢀ9–11).ꢀTheꢀsilverꢀcationꢀitselfꢀwasꢀessentialꢀ
forꢀthisꢀreaction;ꢀtheꢀuseꢀofꢀNa CO ,ꢀK CO ꢀorꢀCs CO ꢀinsteadꢀofꢀ
Ag CO ꢀ failedꢀ toꢀ giveꢀ anyꢀ productꢀ (seeꢀ Electronicꢀ Supportingꢀ
3
ꢀtoꢀ
1
7
AgOPiv,ꢀ orꢀ AgOCOCF
3
2
3
2
3
2
3
2
3
2
3
Informationꢀ(ESI)ꢀforꢀdetails).ꢀTheꢀuseꢀofꢀtheꢀDMF/DMSOꢀmixedꢀ
solventꢀ systemꢀ wasꢀ importantꢀ forꢀ obtainingꢀ maximumꢀ
conversion;ꢀ highlyꢀ polarꢀ singleꢀ solventsꢀ suchꢀ asꢀ N,N-
1
8
compoundꢀ3aaꢀ(Figureꢀ2). ꢀ
ꢀ
3
dimethylacetamideꢀ(DMAc),ꢀDMF,ꢀDMSO,ꢀCH CNꢀprovidedꢀ3aaꢀ
inꢀ diminishedꢀ yieldꢀ (29–10%,ꢀ seeꢀ ESIꢀ forꢀ details),ꢀ whileꢀ lessꢀ
polarꢀ solventsꢀ suchꢀ asꢀ 1,2-dichloroethane,ꢀ 2,2,2-
trifluoroethanol,ꢀ 1,4-dioxaneꢀ andꢀ ꢀ tolueneꢀ completelyꢀ
suppressedꢀ theꢀ reaction.ꢀ Althoughꢀ higherꢀ reactionꢀ
2
ꢀ|ꢀJ.ꢀName.,ꢀ2012,ꢀ00,ꢀ1-3ꢀ
Thisꢀjournalꢀisꢀ©ꢀTheꢀRoyalꢀSocietyꢀofꢀChemistryꢀ20xxꢀ
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Page 3 of 6
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JournalꢀNameꢀ
ꢀARTICLEꢀ
n+
View Article Online
DOI: 10.1039/C8SC02802H
I
Pd(OPiv)2 (5.0 mol%)
Ag2CO3 (1.5 eq.)
I
I
2
a
1a + Ag CO
I
2
3
[
Pd]n+
N
R1
[
Pd]
DMF/DMSO
80 ˚C, 19 h
I
−[Pd]
n = 0 or 2
N
N
−
AgI
R1
−
AgHCO3
A
B
indoles 1a-m
pyrroles 4a-b
2a
1.5 eq.
carbazoles 3aa-3ma
indoles 5aa-5ba
isolated yield
n+
0.20 mmol
I
[
Pd]
[
Pd]
−
−
[Pd]
[HI]
N
N
C
3aa
ꢀ
N
N
N
Schemeꢀ1ꢀProposedꢀreactionꢀmechanismꢀforꢀtheꢀPd-catalyzedꢀAPEXꢀreactionꢀofꢀ
N-methylindoleꢀ(1a)ꢀwithꢀ2,2ʹ-diiodo-1,1ʹ-biphenylꢀ(2a).ꢀ
3
aa
3ba
71%
3ca
70%
6
6%
ꢀ
ꢀ
ꢀꢀUnderꢀtheꢀoptimizedꢀconditions,ꢀvariousꢀtypesꢀofꢀπ-extendedꢀ
carbazoles/indolesꢀ3,ꢀ5ꢀwereꢀpreparedꢀfromꢀtheꢀcorrespondingꢀ
indole/pyrroleꢀderivativesꢀ1,ꢀ 4ꢀandꢀdiiodobiarylsꢀ2.ꢀSchemeꢀ2ꢀ
illustratesꢀ theꢀ scopeꢀ ofꢀ applicableꢀ indoleꢀ andꢀ pyrroleꢀ
derivativesꢀ(1a–1m).ꢀN-Alkylꢀ(2a,ꢀ2b),ꢀN-benzylꢀ(2c),ꢀN-phenylꢀ
N
N
N
O
3
da
3ea
3fa
(
2d)ꢀ indolesꢀ andꢀ cross-linkedꢀ lilolidineꢀ (2e)ꢀ wereꢀ convertedꢀ
47%
72%
N.D.
smoothlyꢀtoꢀdibenzocarbazolesꢀ3ba–3daꢀinꢀgoodꢀtoꢀmoderateꢀ
yield,ꢀ howeverꢀ theꢀ reactionꢀ ofꢀ N-acetylꢀ indoleꢀ 2fꢀ didꢀ notꢀ
provideꢀtheꢀexpectedꢀπ-extensionꢀproductꢀ3fa.ꢀTheꢀpresenceꢀofꢀ
substituentsꢀatꢀtheꢀ5-,ꢀ6-,ꢀorꢀ7-positionsꢀofꢀtheꢀindoleꢀringꢀwasꢀ
well-tolerated,ꢀ givingꢀ variousꢀ nitro-ꢀ (3ga),ꢀ cyano-ꢀ (3ha,ꢀ 3la),ꢀ
bromo-ꢀ (3ia),ꢀ methoxy-ꢀ (3ja,ꢀ 3ka),ꢀ andꢀ benzyloxy-substitutedꢀ
O2N
NC
Br
N
N
N
3
ga
45%
3ha
44%
3ia
62%
(
3ma)ꢀ dibenzocarbazolesꢀ inꢀ moderateꢀ yieldsꢀ (40-62%).ꢀ Theseꢀ
resultsꢀsuggestꢀthatꢀsubstituentsꢀonꢀtheꢀbenzeneꢀringꢀofꢀindoleꢀ
doꢀnotꢀcriticallyꢀaffectꢀtheꢀreactionꢀprogress.ꢀInterestingly,ꢀweꢀ
foundꢀ thatꢀ theꢀ currentꢀ APEXꢀ reactionꢀ betweenꢀ N-substitutedꢀ
pyrrolesꢀ andꢀ 2aꢀ wasꢀ mono-selectiveꢀ forꢀ theꢀ formationꢀ ofꢀ
dibenzoindolesꢀ5aaꢀandꢀ5baꢀinꢀ39%ꢀandꢀ43%ꢀyields;ꢀonlyꢀtraceꢀ
amountsꢀ ofꢀ theꢀ di-APEXꢀ tetrabenzocarbazoleꢀ products,ꢀ theꢀ
MeO
N
N
N
MeO
CN
3
4
ja
9%
3ka
52%
3la
42%
7c,19
mainꢀ productsꢀofꢀourꢀpreviousꢀreport, ꢀwereꢀobserved.ꢀAsꢀ
syntheticꢀmethodsꢀtoꢀprepareꢀtheꢀdibenzo[e,g]indoleꢀskeletonꢀ
2
remainꢀ limitedꢀ andꢀ inefficient, ꢀ theꢀ currentꢀ APEXꢀ protocolꢀ
0
N
O
N
providesꢀaꢀvaluable,ꢀstreamlinedꢀentryꢀtoꢀthisꢀcompoundꢀclass.ꢀ
ꢀ
N
3
ma
5aa
5ba
4
0%
39%
42%
ꢀ
Schemeꢀ2ꢀSubstrateꢀscopeꢀofꢀindolesꢀandꢀpyrrolesꢀinꢀtheꢀAPEXꢀreactionꢀwithꢀ2,2ʹ-
diiodo-1,1ʹ-biphenylꢀ(2a).ꢀ
ꢀ
ꢀ
ꢀꢀTheꢀ scopeꢀ ofꢀ diiodobiarylsꢀ inꢀ theꢀ currentꢀ APEXꢀ reactionꢀ isꢀ
shownꢀinꢀSchemeꢀ3.ꢀTheꢀreactionꢀofꢀN-methylindoleꢀ(2a)ꢀwithꢀ
unsymmetricalꢀ 4-chloro-2,2ʹ-diiodo-1,1ʹ-biphenylꢀ (2b)ꢀ gaveꢀ aꢀ
1
:1.4ꢀregioisomericꢀmixtureꢀofꢀ3abꢀandꢀ3abʹꢀinꢀ94%ꢀcombinedꢀ
yield.ꢀ APEXꢀ reactionsꢀ ofꢀ 1aꢀ andꢀ 4aꢀ withꢀ 4,4ʹ-dibromo-2,2ʹ-
diiodo-1,1ʹ-biphenylꢀ (2c)ꢀ smoothlyꢀ occurredꢀ toꢀ giveꢀ
dibromodibenzocarbazoleꢀ3acꢀandꢀdibromodibenozoindoleꢀ5ccꢀ
inꢀ81%ꢀandꢀ44%ꢀyield,ꢀrespectively.ꢀToꢀourꢀdelight,ꢀtheꢀreactionꢀ
ofꢀ 1aꢀ withꢀ 2,2ʹ-diiodo-1,1ʹ-binaphthaleneꢀ (2d)ꢀ gaveꢀ
dinaphthocarbazoleꢀ 3adꢀ containingꢀ aꢀ [5]heliceneꢀ moietyꢀ inꢀ
2
5%ꢀ yield,ꢀ whoseꢀ helicalꢀ structureꢀ wasꢀ confirmedꢀ byꢀ X-rayꢀ
crystallographicꢀanalysis.ꢀAsꢀthisꢀexampleꢀclearlyꢀdemonstrates,ꢀ
theꢀlate-stageꢀattachmentꢀofꢀcomplex,ꢀextendedꢀpolyaromaticꢀ
unitsꢀ isꢀ oneꢀ ofꢀ theꢀ mostꢀ remarkableꢀ characteristicsꢀ inꢀ theꢀ
presentꢀAPEXꢀreaction.ꢀ
Thisꢀjournalꢀisꢀ©ꢀTheꢀRoyalꢀSocietyꢀofꢀChemistryꢀ20xxꢀ
J.ꢀName.,ꢀ2013,ꢀ00,ꢀ1-3ꢀ|ꢀ3ꢀ
Pleaseꢀdoꢀnotꢀadjustꢀmarginsꢀ

Please Cꢀ dh oe ꢀmn oi c taꢀ al Sd cj ui es nt cꢀ me arginsꢀ
Page 4 of 6
ARTICLEꢀ
JournalꢀNameꢀ
di(benzothieno)carbazoleꢀ8ꢀinꢀ32%.ꢀToꢀourꢀdelight,ꢀ
ꢀ
View Article Online
theꢀreactionꢀ
DOI: 10.1039/C8SC02802H
ofꢀ N-methylpyrroleꢀ (4c)ꢀ withꢀ diiodo-2,2ʹ-bibenzothiopheneꢀ 7ꢀ
affordedꢀaꢀdoubleꢀAPEXꢀproduct,ꢀtetra(benzothieno)carbazoleꢀ
9,ꢀinꢀ15%ꢀyield.ꢀWhileꢀtheꢀyieldsꢀwereꢀlow,ꢀtheꢀgenerationꢀofꢀ
theseꢀ novelꢀ N-S-PACꢀ structures,ꢀ whichꢀ areꢀ highlyꢀ interestingꢀ
fromꢀtheꢀviewpointꢀofꢀoptoelectronicꢀpropertiesꢀyetꢀotherwiseꢀ
difficultꢀ toꢀ synthesizeꢀ byꢀ conventionalꢀ organicꢀ reactions,ꢀ isꢀ
notable.ꢀꢀ
Ar
Ar
Pd(OPiv)2 (5.0 mol%)
Ag2CO3 (1.5 eq.)
Ar
I
I
N
DMF/DMSO
80 ˚C, 19 h
Ar
N
N-methylndole 1a
N-methypyrrole 4c
2b-d
1.5 eq.
carbazoles 3ab-3ad
indole 5cc
isolated yield
0
.10 mmol
Cl
Br
ꢀ
Pd(OPiv)2 (5.0 mol%)
Ag2CO3 (1.5 eq.)
S
S
S
I
I
N
S
N
Cl
N
N
DMF/DMSO
Br
80 ˚C, 19 h
N
3
ab
3ab′
3ac
8
1%
3
3
ab+3ab′: 94%
ab/3ab′ = 1:1.4
1
a
7
8
32%
0
.10 mmol
1.5 eq.
Br
S
Pd(OPiv)2 (5.0 mol%)
Ag2CO3 (3.0 eq.)
S
I
S
S
N
N
S
Br
N
I
DMF/DMSO
80 ˚C, 19 h
cca
S
N
5
3ad
X-ray structure
4
4%
25%
of 3ad
ꢀ
a
Schemeꢀ3ꢀSubstrateꢀscopeꢀofꢀdiiodobiaryls.ꢀ 0.20ꢀmmolꢀscale.ꢀ
4
c
7
9
15%
0
.20 mmol
3.0 eq.
ꢀ
ꢀ
Schemeꢀ5ꢀAPEXꢀreactionsꢀofꢀN-methylindoleꢀ(1a)ꢀandꢀN-methylpyrroleꢀ(4c)ꢀwithꢀ
,3ʹ-diiodo-2,2ʹ-bibenzothiopheneꢀ(7)ꢀforꢀtheꢀsynthesisꢀofꢀN-S-PACs.ꢀ
3
ꢀ
ꢀꢀToꢀdemonstrateꢀtheꢀpowerꢀofꢀtheꢀcurrentꢀAPEXꢀreactionꢀtoꢀ
buildꢀ complex,ꢀ unsymmetricalꢀ N-PACsꢀ fromꢀ simpleꢀ startingꢀ
materials,ꢀ weꢀ employedꢀ aꢀ two-stepꢀ sequenceꢀ toꢀ synthesizeꢀ
tetrabenzocarbazoleꢀ 6,ꢀ aꢀ compoundꢀ difficultꢀ toꢀ prepareꢀ viaꢀ
knownꢀ methodsꢀ (Schemeꢀ 4).ꢀ First,ꢀ APEXꢀ reactionꢀ ofꢀ N-
methylpyrroleꢀ (4c)ꢀ withꢀ 2aꢀ wasꢀ carriedꢀ outꢀ toꢀ giveꢀ theꢀ
correspondingꢀ N-methyldibenzoindoleꢀ (5ca)ꢀ inꢀ 37%ꢀ yield.ꢀ
Notably,ꢀthisꢀreactionꢀdidꢀnotꢀgiveꢀdouble-APEXꢀproductꢀwhichꢀ
isꢀtheꢀmajorꢀproductꢀinꢀtheꢀpreviouslyꢀdevelopedꢀAPEXꢀreactionꢀ
ꢀꢀꢀꢀTheꢀ structuralꢀ andꢀ electronicꢀ propertiesꢀ ofꢀ 8ꢀ andꢀ 9ꢀ wereꢀ
elucidatedꢀ viaꢀ X-rayꢀ crystallography,ꢀ UV-
Vis/photoluminescenceꢀ spectroscopy,ꢀ andꢀ DFT/TD-DFTꢀ
calculationsꢀatꢀtheꢀB3LYP/6-31G(d)ꢀlevelꢀofꢀtheoryꢀ(Figureꢀ2).ꢀꢀ
SingleꢀcrystalꢀX-rayꢀstructuresꢀ(Figuresꢀ2a,ꢀ2b,ꢀS2ꢀandꢀS3)ꢀrevealꢀ
thatꢀcompoundꢀ8ꢀadoptsꢀaꢀrelativelyꢀflattenedꢀstructureꢀinꢀtheꢀ
solidꢀstateꢀ(Figureꢀ2a),ꢀwhileꢀcompoundꢀ9ꢀpossessesꢀaꢀtwistedꢀ
structureꢀowingꢀtoꢀtheꢀembeddedꢀheteroheliceneꢀmoiety.ꢀꢀDFTꢀ
calculationsꢀ forꢀ 8ꢀ (Figureꢀ 2c)ꢀ revealꢀ delocalizationꢀ ofꢀ theꢀ
HOMOꢀ(–5.23ꢀeV)ꢀoverꢀtheꢀentireꢀmolecule,ꢀwhileꢀtheꢀLUMOꢀ(–
1.49ꢀ eV)ꢀ localizesꢀ onꢀ aꢀ benzothienocarbazoleꢀ wing.ꢀ Onꢀ theꢀ
otherꢀ hand,ꢀ theꢀ HOMOꢀ andꢀ LUMOꢀ ofꢀ 9ꢀ areꢀ delocalizedꢀ overꢀ
entireꢀmolecule,ꢀandꢀthusꢀtheꢀenergyꢀlevelꢀofꢀLUMOꢀ(–1.72ꢀeV)ꢀ
isꢀslightlyꢀlowerꢀthanꢀthatꢀofꢀ8.ꢀTheꢀUV–visꢀabsorptionꢀspectraꢀ
8b
ofꢀN-phenylpyrrole. ꢀThen,ꢀ5caꢀwasꢀfurtherꢀreactedꢀwithꢀ4,4ʹ-
dibromo-2,2ʹ-diiodo-1,1ʹ-biphenylꢀ (2c)ꢀ byꢀ usingꢀ
Pd(CH CN) (BF /AgOPiv/TfOHꢀ catalyticꢀ system ꢀ toꢀ giveꢀ theꢀ
8b
3
4
4 2
)
2
1
desiredꢀproductꢀ6ꢀinꢀ33%ꢀyield. ꢀRapidꢀaccessꢀtoꢀaꢀnewꢀclassꢀofꢀ
unsymmetricallyꢀ substitutedꢀ tetrabenzocarbazoleꢀ isꢀ notable,ꢀ
andꢀshouldꢀcontributeꢀtoꢀtheꢀexplorationꢀofꢀnewꢀcompoundsꢀ
forꢀorganicꢀelectronicsꢀapplication.ꢀ
2 2
ofꢀ8ꢀandꢀ 9ꢀinꢀCH Cl ꢀshowꢀthatꢀbothꢀcompoundsꢀhaveꢀbroadꢀ
ꢀ
Pd(CH3CN)4(BF4)2
Br
absorptionꢀ bandsꢀ betweenꢀ 300ꢀ andꢀ 450ꢀ nmꢀ (Figureꢀ 3e).ꢀ
Absorptionꢀmaximaꢀwereꢀfoundꢀatꢀ294,ꢀ317,ꢀ339,ꢀ357,ꢀ381ꢀandꢀ
(
5.0 mol%)
Pd(OPiv)2 (5.0 mol%)
a (1.5 eq.)
Ag2CO3 (1.5 eq.)
2c (1.5 eq.)
AgOPiv (2.0 eq.)
TfOH (2.0 eq.)
2
3
99ꢀnmꢀinꢀ8,ꢀandꢀtheꢀcorrespondingꢀpeaksꢀwereꢀalsoꢀfoundꢀinꢀ9ꢀ
N
atꢀ 305,ꢀ 332,ꢀ 348,ꢀ 393ꢀ andꢀ 412ꢀ nm.ꢀ Theꢀ TD-DFTꢀ calculationsꢀ
revealedꢀthatꢀtheꢀlongest-wavenumberꢀabsorptionsꢀinꢀ8ꢀandꢀ9ꢀ
(399ꢀandꢀ412ꢀnm)ꢀareꢀattributedꢀtoꢀtheꢀallowedꢀHOMO–LUMOꢀ
transitionsꢀ(seeꢀESIꢀforꢀdetails).ꢀTheꢀfluorescenceꢀspectraꢀofꢀ8ꢀ
andꢀ9ꢀinꢀCH Cl ꢀdisplayꢀbroadꢀemissionsꢀwithꢀemissionꢀmaximaꢀ
DMF/DMSO
ClCH2CH2Cl
50 ˚C, 12 h
N
80 ˚C, 19 h
N
Br
4
c
5ca
7%
6
33%
3
ꢀ
Schemeꢀ4ꢀSequentialꢀAPEXꢀreactionsꢀofꢀN-methylpyrroleꢀ(4c)ꢀforꢀtheꢀsynthesisꢀofꢀ
usymmetricallyꢀsubstitutedꢀtetrabenzocarbazoleꢀ6.ꢀ
2
2
ofꢀ427ꢀandꢀ437ꢀnm,ꢀrespectivelyꢀ(Figureꢀ2e).ꢀꢀ
ꢀꢀTheꢀ currentꢀ APEXꢀ reactionꢀ alsoꢀ providedꢀ aꢀ facileꢀ routeꢀ toꢀ
ꢀ
ꢀ
polycyclicꢀaromaticꢀcompoundsꢀcontainingꢀbothꢀnitrogenꢀandꢀ
sulfurꢀ (N-S-PACs)ꢀ (Schemeꢀ 5).ꢀ ꢀ N-methylindoleꢀ (1a)ꢀ coupledꢀ
withꢀ 3,3ʹ-diiodo-2,2ʹ-bibenzothiopheneꢀ (7)ꢀ toꢀ giveꢀ
4
ꢀ|ꢀJ.ꢀName.,ꢀ2012,ꢀ00,ꢀ1-3ꢀ
Thisꢀjournalꢀisꢀ©ꢀTheꢀRoyalꢀSocietyꢀofꢀChemistryꢀ20xxꢀ
Pleaseꢀdoꢀnotꢀadjustꢀmarginsꢀ

Page 5 of 6
Please Cꢀ dh oe ꢀmn oi c taꢀ al Sd cj ui es nt cꢀ me arginsꢀ
JournalꢀNameꢀ
ꢀARTICLEꢀ
a) ꢀ
b) ꢀ
e) ꢀ
View Article Online
DOI: 10.1039/C8SC02802H
side viewꢀ
side viewꢀ
top viewꢀ
top viewꢀ
c) ꢀ
d) ꢀ
LUMO
1.49 eVꢀ
HOMO
–5.23 eVꢀ
LUMO
–1.72 eVꢀ
HOMO
5.26 eVꢀ
–
–
ꢀ
Figureꢀ2ꢀTopꢀandꢀsideꢀviewsꢀofꢀtheꢀX-rayꢀcrystalꢀstructuresꢀofꢀa)ꢀ8ꢀandꢀb)ꢀ9.ꢀThermalꢀellipsoidsꢀareꢀdrawnꢀatꢀ50%ꢀprobability.ꢀPictorialꢀfrontierꢀmolecularꢀorbitalsꢀandꢀ
2 2
energyꢀlevelsꢀofꢀc)ꢀ8ꢀandꢀd)ꢀ9ꢀcalculatedꢀusingꢀtheꢀB3LYP/6-31G(d)ꢀlevelꢀofꢀtheory.ꢀe)ꢀNormalizedꢀUV–visꢀabsorptionꢀandꢀfluorescenceꢀspectraꢀofꢀ8ꢀandꢀ9ꢀinꢀCH Cl ꢀatꢀ
rt._ꢀ
ꢀ
ꢀ
theꢀ Worldꢀ Premierꢀ Internationalꢀ Researchꢀ Centerꢀ Initiativeꢀ
WPI),ꢀJapan.ꢀꢀ
(
Conclusionsꢀ
Notesꢀandꢀreferencesꢀ
ꢀ
Inꢀ summary,ꢀ weꢀ haveꢀ developedꢀ aꢀ novelꢀ palladium-
catalyzedꢀAPEXꢀreactionꢀtoꢀenableꢀtheꢀannulativeꢀπ-extensionꢀ
ofꢀ indoles/pyrrolesꢀ withꢀ diiodobiaryls.ꢀ Useꢀ ofꢀ theꢀ
1
(a)ꢀ H.-J.ꢀ Knölkerꢀ andꢀ K.ꢀ R.ꢀ Reddy,ꢀ Chem.ꢀ Rev.,ꢀ 2002,ꢀ 102,ꢀ
4
2
303–4427;ꢀ (b)ꢀ M.ꢀ Someiꢀ andꢀ F.ꢀ Yamada,ꢀ Nat.ꢀ Prod.ꢀ Rep.,ꢀ
003,ꢀ 20,ꢀ 216–242;ꢀ (c)ꢀ S.ꢀ Deslandes,ꢀ S.ꢀ Chassaingꢀ andꢀ E.ꢀ
2 2 3
Pd(OPiv) /Ag CO ꢀ catalyticꢀ systemꢀ inꢀ aꢀ mixedꢀ DMF/DMSOꢀ
solventꢀallowsꢀtheꢀpreparationꢀofꢀaꢀdiverseꢀrangeꢀofꢀN-PACsꢀinꢀ
aꢀ singleꢀ step,ꢀ includingꢀ severalꢀ previouslyꢀ unsynthesizedꢀ
structures.ꢀ Rapidꢀ accessꢀ toꢀ exoticꢀ scaffoldsꢀ suchꢀ asꢀ complex,ꢀ
unsymmetricallyꢀ substitutedꢀ tetrabenzocarbazolesꢀ andꢀ
extendedꢀN-heteroarenesꢀfeaturingꢀmultipleꢀheliceneꢀmoietiesꢀ
isꢀ aꢀ particularꢀ highlightꢀ ofꢀ theꢀ presentꢀ APEXꢀ protocol.ꢀ
DevelopedꢀAPEXꢀmethodologyꢀalsoꢀhasꢀgreatꢀpotentialꢀforꢀtheꢀ
efficientꢀ andꢀ rapidꢀ synthesisꢀ ofꢀ planarꢀ andꢀ non-planarꢀ π-
extendedꢀ N-PACsꢀ suchꢀ asꢀ π-extendedꢀ azacorannulenes,ꢀ aza-
buckybowlsꢀandꢀpyrrolopryrrolesꢀwhichꢀareꢀregardedꢀasꢀoneꢀofꢀ
Delfourne,ꢀMar.ꢀDrugs,ꢀ2009,ꢀ7,ꢀ754–786;ꢀ(d)ꢀA.ꢀW.ꢀSchmidt,ꢀ
K.ꢀR.ꢀReddyꢀandꢀH.-J.ꢀKnölker,ꢀChem.ꢀRev.,ꢀ2012,ꢀ112,ꢀ3193–
3328;ꢀ(e)ꢀN.ꢀBlouinꢀandꢀM.ꢀLeclerc,ꢀAcc.ꢀChem.ꢀRes.,ꢀ2008,ꢀ41,ꢀ
1
2
110–1119;ꢀ(f)ꢀP.ꢀM.ꢀBeaujugeꢀandꢀJ.ꢀR.ꢀReynolds,ꢀChem.ꢀRev.,ꢀ
010,ꢀ110,ꢀ268–320;ꢀ(g)ꢀC.ꢀWang,ꢀH.ꢀDong,ꢀW.ꢀHu,ꢀY.ꢀLiuꢀandꢀ
D.ꢀZhu,ꢀChem.ꢀRev.,ꢀ2012,ꢀ112,ꢀ2208–2267;ꢀ(h)ꢀM.ꢀBashir,ꢀA.ꢀ
Bano,ꢀ A.ꢀ S.ꢀ Ijazꢀ andꢀ B.ꢀ A.ꢀ Chaudhary,ꢀ Molecules,ꢀ 2015,ꢀ 20,ꢀ
13496–13517;ꢀ(i)ꢀS.ꢀM.ꢀThomas,ꢀA.ꢀPurmal,ꢀM.ꢀPollastriꢀandꢀK.ꢀ
Mensa-Wilmot,ꢀSci.ꢀRep.,ꢀ2016,ꢀ6,ꢀ32083;ꢀ(j)ꢀH.ꢀLi,ꢀF.ꢀZhe-Ling,ꢀ
W.ꢀYi-TaoꢀandꢀL.ꢀLi-Gen,ꢀChin.ꢀJ.ꢀNat.ꢀMed.,ꢀ2017,ꢀ15,ꢀ881–
888;ꢀ (k)ꢀ K.ꢀ Karonꢀ andꢀ M.ꢀ Lapkowski,ꢀ J.ꢀ Solidꢀ Stateꢀ
Electrochem.,ꢀ2015,ꢀ19,ꢀ2601–2610.ꢀ
22
promisingꢀmaterialsꢀforꢀoptelectronics. ꢀFurtherꢀinvestigationsꢀ
intoꢀ theꢀ reactionꢀ mechanismꢀ andꢀ applicationsꢀ ofꢀ thisꢀ APEXꢀ
methodꢀ towardsꢀ theꢀ synthesisꢀ ofꢀ largerꢀ π-extendedꢀ
heteroaromaticsꢀareꢀcurrentlyꢀunderway.ꢀ
2
(a)ꢀZ.ꢀChen,ꢀB.ꢀWang,ꢀJ.ꢀZhang,ꢀW.ꢀYu,ꢀZ.ꢀLiuꢀandꢀY.ꢀZhang,ꢀOrg.ꢀ
Chem.ꢀFront.,ꢀ2015,ꢀ2,ꢀ1107–1295;ꢀ(b)ꢀG.ꢀSong,ꢀF.ꢀWangꢀandꢀ
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Conflictsꢀofꢀinterestꢀ
Thereꢀareꢀnoꢀconflictsꢀtoꢀdeclare.ꢀ
3
4
(a)ꢀ J.ꢀ Yamaguchi,ꢀ A.ꢀ D.ꢀ Yamaguchiꢀ andꢀ K.ꢀ Itami,ꢀ Angew.ꢀ
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Acknowledgementsꢀ
Thisꢀ workꢀ wasꢀ supportedꢀ byꢀ theꢀ ERATOꢀ programꢀ fromꢀ JSTꢀ
(
(
JPMJER1302ꢀ toꢀ K.I.),ꢀ theꢀ JSPSꢀ KAKENHIꢀ Grantꢀ Numbersꢀ
JP26810057,ꢀ JP16H00907,ꢀ JP17K19155ꢀ andꢀ JP18H02019ꢀ toꢀ
2
447–2464;ꢀ (d)ꢀ L.ꢀ Ackermann,ꢀ R.ꢀ Vicenteꢀ andꢀ A.ꢀ R.ꢀ Kapdi,ꢀ
Angew.ꢀChem.,ꢀInt.ꢀEd.,ꢀ2009,ꢀ48,ꢀ9792-9826;ꢀ(e)ꢀY.ꢀSegawa,ꢀT.ꢀ
MaekawaꢀandꢀK.ꢀItami,ꢀAngew.ꢀChem.,ꢀInt.ꢀEd.,ꢀ2015,ꢀ54,ꢀ66–
H.I.),ꢀ theꢀ SUMITOMOꢀ Foundationꢀ (141495ꢀ toꢀ H.I.)ꢀ andꢀ theꢀ
DAIKOꢀFoundationꢀ(H.I.).ꢀWeꢀalsoꢀthankꢀDr.ꢀYasutomoꢀSegawaꢀ
andꢀ Mr.ꢀ Kentaꢀ Katoꢀ forꢀ assistanceꢀ ofꢀ X-rayꢀ crystallographicꢀ
analysisꢀ andꢀ Dr.ꢀ Davidꢀ R.ꢀ Levineꢀ forꢀ proofreading.ꢀ Theꢀ
computationsꢀwereꢀperformedꢀusingꢀtheꢀResearchꢀCenterꢀforꢀ
ComputationalꢀScience,ꢀOkazaki,ꢀJapan.ꢀITbMꢀisꢀsupportedꢀbyꢀ
8
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J.ꢀName.,ꢀ2013,ꢀ00,ꢀ1-3ꢀ|ꢀ5ꢀ
Pleaseꢀdoꢀnotꢀadjustꢀmarginsꢀ

Please Cꢀ dh oe ꢀmn oi c taꢀ al Sd cj ui es nt cꢀ me arginsꢀ
Page 6 of 6
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ꢀ|ꢀJ.ꢀName.,ꢀ2012,ꢀ00,ꢀ1-3ꢀ
Thisꢀjournalꢀisꢀ©ꢀTheꢀRoyalꢀSocietyꢀofꢀChemistryꢀ20xxꢀ
Pleaseꢀdoꢀnotꢀadjustꢀmarginsꢀ