Experimental evidence for the formation of cationic intermediates during iodine(iii)-mediated oxidative dearomatization of phenols

Article abstract of DOI:10.1039/c8ob01652f

Iodine(iii)-based oxidants are commonly used reagents for the oxidative dearomatization of phenols. Having a better understanding of the mechanism through which these reactions proceed is important for designing new iodine(iii)-based reagents, catalysts, and reactions. We have performed a Hammett analysis of the oxidative dearomatization of substituted 4-phenylphenols. This study confirms that iodine(iii)-mediated oxidative dearomatizations likely proceed through cationic phenoxenium ions and not the direct addition of a nucleophile to an iodine-bound phenol intermediate.

Full text of DOI:10.1039/c8ob01652f

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January 2016 Pages 1–372
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Takeharu Haino et al.
Solvent-induced emission of organogels based on tris(phenylisoxazolyl)
benzene
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DOI: 10.1039/C8OB01652F
JournalꢀNameꢀ
COMMUNICATIONꢀ
ꢀ
Experimentalꢀevidenceꢀforꢀtheꢀformationꢀofꢀcationicꢀintermediatesꢀ
duringꢀiodine(III)-mediatedꢀoxidativeꢀdearomatizationꢀofꢀphenolsꢀꢀ
Receivedꢀ00thꢀJanuaryꢀ20xx,ꢀ
Acceptedꢀ00thꢀJanuaryꢀ20xxꢀ
a
ꢀ a
TingꢀTang ꢀandꢀAndrewꢀM.ꢀHarned * ꢀ
DOI:ꢀ10.1039/x0xx00000xꢀ
www.rsc.org/ꢀ
6,7,8
Iodine(III)-basedꢀ oxidantsꢀ areꢀ commonlyꢀ usedꢀ reagentsꢀ forꢀ theꢀ catalysts. ꢀTryingꢀtoꢀdesignꢀaꢀchiralꢀenvironmentꢀaroundꢀanꢀ
intermediateꢀthatꢀreactsꢀthroughꢀaꢀunimolecularꢀpathwayꢀisꢀaꢀ
veryꢀ differentꢀ challengeꢀ thanꢀ oneꢀ involvingꢀ aꢀ bimolecularꢀ
oxidativeꢀ dearomatizationꢀ ofꢀ phenols.ꢀ Havingꢀ aꢀ betterꢀ
understandingꢀ ofꢀ theꢀ mechanismꢀ throughꢀ whichꢀ theseꢀ reactionsꢀ
pathway.ꢀ
proceedꢀisꢀimportantꢀforꢀdesigningꢀnewꢀiodine(III)-basedꢀreagents,ꢀ
Path A: bimolecular redox decomposition
catalysts,ꢀandꢀreactions.ꢀWeꢀhaveꢀperformedꢀaꢀHammettꢀanalysisꢀ
2
ofꢀtheꢀoxidativeꢀdearomatizationꢀofꢀsubstitutedꢀ4-phenylphenols.ꢀ
Thisꢀ studyꢀ confirmsꢀ thatꢀ iodine(III)-mediatedꢀ oxidativeꢀ
dearomatizationsꢀ likelyꢀ proceedꢀ throughꢀ cationicꢀ phenoxeniumꢀ
ionsꢀ andꢀ notꢀ theꢀ directꢀ additionꢀ ofꢀ aꢀ nucleophileꢀ toꢀ anꢀ iodine-
boundꢀphenolꢀintermediate.ꢀ
OH
(R OH)
O
R1
OAc
I
O
+
+
Ph–I
+
Ph
Ph
I
AcOH
OAc
OAc
+
AcOH
R1 OR2
R1
2
1
3
Phenyliodine(III)ꢀ diacetateꢀ (PIDA)ꢀ andꢀ itsꢀ congenersꢀ areꢀ
powerfulꢀorganicꢀoxidantsꢀthatꢀhaveꢀbeenꢀemployedꢀinꢀaꢀwideꢀ
rangeꢀ ofꢀ interestingꢀ transformations. ꢀ Oneꢀ ofꢀ theꢀ moreꢀ
1
2
O
(R OH)
O
commonꢀ applicationsꢀ ofꢀ theseꢀ reagentsꢀ isꢀ inꢀ theꢀ oxidativeꢀ
dearomatizationꢀ ofꢀ phenolsꢀ toꢀ giveꢀ cyclohexadienonesꢀ (e.g.,ꢀ
=
irreversible step
+
+
Ph–I
2
→3,ꢀ Figureꢀ 1). ꢀ Curiously,ꢀ despiteꢀ theꢀ wideꢀ useꢀ ofꢀ thisꢀ
+
H
AcO
1
transformation,ꢀ itsꢀ mechanisticꢀ detailsꢀ areꢀ shroudedꢀ inꢀ
mystery.ꢀ Itꢀ isꢀ widelyꢀ acceptedꢀ thatꢀ thereꢀ isꢀ anꢀ initialꢀ ligandꢀ
exchangeꢀ betweenꢀ phenolꢀ 1ꢀ andꢀ PIDAꢀ toꢀ generateꢀ anꢀ
R1 OR2
R1
4
3
3
Path B: unimolecular redox decomposition
predicted by DFT calculations)
intermediateꢀaryl-λ -iodaneꢀ(2).ꢀWhatꢀhappensꢀnextꢀisꢀsubjectꢀ
toꢀ someꢀ debate,ꢀ andꢀ twoꢀ mechanisticꢀ proposalsꢀ areꢀ usuallyꢀ
(
3
encounteredꢀ inꢀ theꢀ literature. ꢀ Oneꢀ involvesꢀ aꢀ bimolecularꢀ
3
.222
redoxꢀ decompositionꢀ pathwayꢀ (Pathꢀ A,ꢀ 2→3)ꢀ inꢀ whichꢀ aꢀ
nucleophileꢀ(inꢀthisꢀcaseꢀR OH)ꢀattacksꢀtheꢀaromaticꢀringꢀofꢀtheꢀ
3.172
2
3
.239
4
activated”ꢀ phenol. ꢀ Thisꢀ S
3.242
“
directlyꢀ formꢀ dienoneꢀ 3ꢀ throughꢀ aꢀ singleꢀ transitionꢀ state.ꢀ
N
2´-likeꢀ mechanismꢀ isꢀ proposedꢀ toꢀ
3
3
.250
.282
2.643
2.650
3
Alternatively,ꢀ aryl-λ -iodaneꢀ 2ꢀ followsꢀ aꢀ unimolecularꢀ redoxꢀ
9
.27
3.375
.367
2
2
.829 10.02
.646
3
14.10
13.87
N
decompositionꢀ pathwayꢀ (Pathꢀ B,ꢀ 2→4→3).ꢀ Thisꢀ S 1-likeꢀ
TS1
5
mechanismꢀinvolvesꢀformsꢀphenoxeniumꢀionꢀ4, ꢀwhichꢀisꢀthenꢀ
rapidlyꢀtrappedꢀbyꢀtheꢀnucleophileꢀtoꢀgiveꢀdienoneꢀ3.ꢀ
2.502
.477
2
TS2
ꢀ
ꢀ
Althoughꢀ pathwaysꢀ Aꢀ andꢀ Bꢀ bothꢀ resultꢀ inꢀ theꢀ sameꢀ
Figureꢀ1.ꢀMechanisticꢀpictureꢀforꢀiodine(III)-mediatedꢀoxidativeꢀ
product,ꢀhavingꢀaꢀbetterꢀunderstandingꢀofꢀhowꢀtheseꢀreactionsꢀ
proceedꢀ isꢀ importantꢀ forꢀ theꢀ developmentꢀ ofꢀ newꢀ reactions.ꢀ
Answeringꢀ thisꢀ mechanisticꢀ questionꢀ isꢀ alsoꢀ ofꢀ criticalꢀ
importanceꢀ forꢀ developingꢀ nextꢀ generationꢀ chiralꢀ arylꢀ iodideꢀ
dearomatizations.ꢀ
ꢀ Recently,ꢀ weꢀ reportedꢀ aꢀ seriesꢀ ofꢀ DFTꢀ calculations,ꢀ usingꢀ
waterꢀ asꢀ aꢀ nucleophile,ꢀ aimedꢀ atꢀ probingꢀ theꢀ likelihoodꢀ ofꢀ
9
pathwaysꢀAꢀandꢀB. ꢀBriefly,ꢀweꢀwereꢀableꢀtoꢀlocateꢀtransitionꢀ
statesꢀ (TS1ꢀ andꢀ TS2,ꢀ Figureꢀ 1)ꢀ correspondingꢀ toꢀ theꢀ
unimolecularꢀ redoxꢀ decompositionꢀ ofꢀ iodaneꢀ 2.ꢀ Transitionꢀ
stateꢀ TS2,ꢀ inꢀ whichꢀ theꢀ acetateꢀ groupꢀ ofꢀ iodaneꢀ 2ꢀ isꢀ
protonated,ꢀ representsꢀ anꢀ attemptꢀ accountꢀ forꢀ potentialꢀ
1
0
hydrogenꢀ bondingꢀ effects ꢀ duringꢀ theꢀ decompositionꢀ ofꢀ theꢀ
Thisꢀjournalꢀisꢀ©ꢀTheꢀRoyalꢀSocietyꢀofꢀChemistryꢀ20xxꢀ
J.ꢀName.,ꢀ2013,ꢀ00,ꢀ1-3ꢀ|ꢀ1ꢀꢀ
Pleaseꢀdoꢀnotꢀadjustꢀmarginsꢀ

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COMMUNICATIONꢀ
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‡
‡
iodaneꢀandꢀisꢀlowerꢀinꢀenergyꢀ(ΔG TS1ꢀ~29ꢀkcal/mol;ꢀΔG TS2ꢀ~10ꢀ beꢀ detrimentalꢀ toꢀ aꢀ reactionꢀ mechanismꢀ thatꢀ inVvieowlvAertsicꢀledOirnelincetꢀ
kcal/mol).ꢀ Inꢀ contrast,ꢀ weꢀ wereꢀ unableꢀ toꢀ locateꢀ aꢀ transitionꢀ additionꢀofꢀaꢀnucleophileꢀtoꢀiodaneꢀ2.ꢀ DOI: 10.1039/C8OB01652F
stateꢀrepresentingꢀtheꢀdirectꢀadditionꢀofꢀaꢀnucleophileꢀ(H O)ꢀtoꢀ
2
ꢀ
Comparingꢀ ourꢀ resultsꢀ toꢀ literatureꢀ reportsꢀ ofꢀ relevantꢀ
theꢀphenolicꢀringꢀofꢀiodaneꢀ2.ꢀTheꢀreasonꢀforꢀthisꢀfailureꢀwasꢀ reactionsꢀ wasꢀ quiteꢀ instructive.ꢀ Hammettꢀ plotsꢀ forꢀ theꢀ
attributedꢀ toꢀ theꢀ overallꢀ negativeꢀ chargeꢀ ofꢀ theꢀ phenolicꢀ ionizationꢀofꢀphenolsꢀ(ρꢀ=ꢀ+1.819–3.197)ꢀandꢀaniliniumꢀionsꢀ(ρꢀ
18
portionꢀ ofꢀ iodaneꢀ 2ꢀ andꢀ theꢀ abilityꢀ ofꢀ thisꢀ partialꢀ negativeꢀ =ꢀ +2.767–3.558) ꢀ haveꢀ positiveꢀ ρꢀ values.ꢀ Thisꢀ indicatesꢀ thatꢀ
chargeꢀtoꢀrepelꢀanꢀincomingꢀnucleophile.ꢀTheseꢀresultsꢀstronglyꢀ ourꢀ resultsꢀ areꢀ notꢀ aꢀ directꢀ measureꢀ ofꢀ theꢀ
suggestedꢀthatꢀpathꢀBꢀwasꢀnotꢀonlyꢀtheꢀfavoredꢀpathwayꢀforꢀ stabilization/destabilizationꢀ ofꢀ theꢀ partialꢀ negativeꢀ chargeꢀ inꢀ
theꢀ decompositionꢀ ofꢀ iodaneꢀ 2,ꢀ butꢀ wasꢀ likelyꢀ theꢀ onlyꢀ iodaneꢀ 2.ꢀ Weꢀ areꢀ awareꢀ ofꢀ onlyꢀ oneꢀ otherꢀ Hammettꢀ studyꢀ
1
1
productiveꢀ pathwayꢀ available. ꢀ Althoughꢀ theseꢀ resultsꢀ putꢀ aꢀ involvingꢀ anꢀ iodine(III)-mediatedꢀ oxidation.ꢀ Thisꢀ reportꢀ usedꢀ
crackꢀinꢀtheꢀmechanisticꢀblackꢀbox,ꢀweꢀrecognizedꢀthatꢀaꢀmoreꢀ substitutedꢀphenyliodine(III)ꢀdiacetatesꢀ[RC H I(OAc) ]ꢀforꢀtheꢀ
6
4
2
19
substantialꢀ experimentalꢀ resultꢀ wasꢀ neededꢀ inꢀ orderꢀ toꢀ giveꢀ oxidativeꢀ cleavageꢀ ofꢀ vicinalꢀ diols. ꢀ Theꢀ resultingꢀ Hammettꢀ
weightꢀtoꢀthisꢀprediction.ꢀHerein,ꢀweꢀreportꢀsuchꢀaꢀresult.ꢀ
plotꢀ hadꢀ aꢀ positiveꢀ slopeꢀ (ρꢀ =ꢀ +1.475ꢀ vsꢀ σ).ꢀ Thisꢀ resultꢀ isꢀ
Basedꢀ onꢀ theꢀ computationalꢀ predictionꢀ thatꢀ theseꢀ consistentꢀ withꢀ aꢀ reactionꢀ inꢀ whichꢀ theꢀ iodineꢀ centerꢀ isꢀ
reactionsꢀ proceedꢀ throughꢀ aꢀ phenoxeniumꢀ ion,ꢀ weꢀ reasonedꢀ reducedꢀ(iodineꢀbecomeꢀlessꢀpositive).ꢀAꢀρꢀvalueꢀofꢀoppositeꢀ
ꢀ
1
2
thatꢀ aꢀ Hammettꢀ study ꢀ ofꢀ theꢀ oxidativeꢀ dearomatizationꢀ ofꢀ signꢀshouldꢀbeꢀexpectedꢀwhenꢀmonitoringꢀtheꢀoxidationꢀofꢀaꢀ
13
substitutedꢀ 4-phenylphenolsꢀ (5→6) ꢀ wouldꢀ beꢀ anꢀ idealꢀ substrate.ꢀ
(
A)
OH
OH
O
solutionꢀ (Figureꢀ 2A).ꢀ However,ꢀ theꢀ rapidꢀ reactionꢀ ratesꢀ
typicallyꢀ seenꢀ duringꢀ iodine(III)-mediatedꢀ oxidativeꢀ
dearomatizationꢀ reactionsꢀ precludeꢀ theꢀ measurementꢀ ofꢀ
individualꢀ rateꢀ constantsꢀ byꢀ traditionalꢀ means.ꢀ Instead,ꢀ weꢀ
PhI(OAc)
(0.1 mmol)
2
+
naphthalene
(int. std.)
H
X
14
MeOH
25±0.5 ºC
Ar OMe
turnedꢀ toꢀ theꢀ "one-pot"ꢀ methodꢀ reportedꢀ byꢀ Harper, ꢀ inꢀ
whichꢀtheꢀnecessaryꢀrelativeꢀratesꢀ(k /k )ꢀareꢀobtainedꢀusingꢀaꢀ
competitionꢀ experiment ꢀ andꢀ areꢀ related,ꢀ byꢀ equationꢀ 1,ꢀ toꢀ
5
a
5b-g
6a-g
X
H
15
X = OMe, CH
3
, F, Br, CO
(0.2 mmol)
2
Et, CF
3
(0.2 mmol)
ꢀ
theꢀamountꢀofꢀeachꢀcompoundꢀpresentꢀatꢀtheꢀbeginningꢀofꢀtheꢀ (B)
experimentꢀ andꢀ atꢀ theꢀ timeꢀ ofꢀ theꢀ analysis.ꢀ Comparedꢀ toꢀ
traditionalꢀ methodsꢀ ofꢀ obtainingꢀ rateꢀ data,ꢀ thisꢀ modelꢀ hasꢀ
0
0
.500
.400
14
0.300
OMe
manyꢀ practicalꢀ benefits, ꢀnotꢀleastꢀofꢀwhichꢀisꢀthatꢀaccurateꢀ
measurementsꢀ ofꢀ substrateꢀ orꢀ productꢀ concentrationsꢀ isꢀ notꢀ
necessary.ꢀ Onlyꢀ theꢀ ratioꢀ atꢀ theꢀ beginningꢀ andꢀ endꢀ ofꢀ theꢀ
reactionꢀisꢀneeded.ꢀ
0
0
0
.200
.100
.000
CH3
s
◆
igm
σ
a-p
p
s
■
igm
σ
a+
+
-
0.100
-0.200
0.300
-0.400
y = -0.5965x - 0.083
R² = 0.96348
F
!
–
!
sigma-
!
"(
)
̖
σ
!!,!!!
CO2Et
!
!
Br
-
y = -0.7261x + 0.0223
= !"(
!
(1)
!
R² = 0.88358
!
!
)
!
!
,!!!
y = -0.9224x + 0.0209
CF3
-
0.500
R² = 0.95289
1
6
ꢀ
Inꢀ ourꢀ study, ꢀ naphthaleneꢀ wasꢀ usedꢀ asꢀ anꢀ internalꢀ
-
0.600
-
1.00
-0.80
-0.60
-0.40
-0.20
0.00
0.20
0.40
0.60
0.80
standardꢀtoꢀmeasureꢀtheꢀratioꢀ(byꢀHPLC)ꢀofꢀphenolsꢀ5aꢀandꢀ5b-
gꢀatꢀtheꢀbeginningꢀandꢀendꢀofꢀtheꢀreaction.ꢀEachꢀreactionꢀwasꢀ
runꢀtoꢀpartialꢀconversion,ꢀbyꢀusingꢀaꢀlimitingꢀamountꢀofꢀPIDA,ꢀ
inꢀ orderꢀ toꢀ ensureꢀ someꢀ ofꢀ eachꢀ startingꢀ materialꢀ remained.ꢀ
sigma
(C)
0
.400
+
–
0.300
0.200
0.100
OMe
Theꢀ resultingꢀ Hammettꢀ plots,ꢀ withꢀ respectꢀ toꢀ σ
values, ꢀ areꢀ shownꢀ inꢀ Figureꢀ 2B.ꢀ Asꢀ canꢀ beꢀ seen,ꢀ plottingꢀ
p
,ꢀ σ ,ꢀ andꢀ σ ꢀ
y = -0.5106x + 0.0576
17
R² = 0.14932
+
–
p
againstꢀσ ꢀgaveꢀtheꢀbestꢀlinearꢀfit.ꢀTheꢀplotsꢀusingꢀσ ꢀandꢀσ
CH3
0
.000
bothꢀdisplayedꢀsignificantꢀcurvature.ꢀImportantly,ꢀtheꢀlinearꢀfitꢀ
forꢀallꢀthreeꢀofꢀtheꢀplotsꢀreturnedꢀnegativeꢀρꢀvalues,ꢀwhichꢀisꢀ
consistentꢀ withꢀ theꢀ developmentꢀ ofꢀ positiveꢀ chargeꢀ inꢀ theꢀ
phenolicꢀringꢀofꢀiodaneꢀ2ꢀduringꢀtheꢀrateꢀdeterminingꢀstep.ꢀ
-
-
-
-
0.100
0.200
0.300
0.400
F
Br
y = -0.7693x - 0.2272
R² = 0.54784
CO2Et
◆ σR
sigmaR
ꢀ
areꢀmoreꢀimportant,ꢀweꢀplottedꢀtheꢀrelativeꢀrateꢀdataꢀagainstꢀ
Inꢀorderꢀtoꢀgaugeꢀwhetherꢀresonanceꢀorꢀinductiveꢀeffectsꢀ
-0.500
sigmaI
■ σ
I
CF3
1
7
σ
R
ꢀ andꢀ σ
correlationꢀ (R ꢀ value),ꢀ butꢀ visualꢀ inspectionꢀ ofꢀ theꢀ σ
revealsꢀitꢀisꢀveryꢀscattered,ꢀcomparedꢀtoꢀtheꢀcorrespondingꢀσ
I
ꢀ values ꢀ (Figureꢀ 2C).ꢀ Neitherꢀ gaveꢀ aꢀ veryꢀ goodꢀ
-0.600
-
0.80
-0.60
-0.40
-0.20
0.00
0.20
0.40
0.60
2
I
ꢀ plotꢀ
sigma
ꢀ
R
ꢀ
Figureꢀ2.ꢀ(A)ꢀCompetitionꢀexperimentꢀusedꢀtoꢀmeasureꢀrelativeꢀrateꢀ
data.ꢀ(B)ꢀHammettꢀplotsꢀofꢀrelativeꢀrateꢀdata.ꢀ(C)ꢀEvaluationꢀofꢀ
resonanceꢀandꢀinductiveꢀeffectsꢀonꢀrelativeꢀrates.ꢀ
plot.ꢀResonanceꢀeffectsꢀareꢀexpectedꢀtoꢀbeꢀmoreꢀimportantꢀforꢀ
stabilizing/destabilizingꢀaꢀdevelopingꢀcharge,ꢀbutꢀwillꢀnotꢀbeꢀasꢀ
importantꢀforꢀnucleophilicꢀattackꢀonꢀaꢀ"neutral"ꢀmolecule.ꢀOurꢀ
resultsꢀ alsoꢀ showꢀ thatꢀ theꢀ methoxyꢀ substituent,ꢀ aꢀ resonanceꢀ
donatingꢀgroup,ꢀfacilitatesꢀtheꢀreaction.ꢀItꢀisꢀdifficultꢀtoꢀimagineꢀ
howꢀ suchꢀ aꢀ groupꢀ wouldꢀ facilitateꢀ direct,ꢀ nucleophilicꢀ attackꢀ
ontoꢀ iodaneꢀ 2.ꢀ Inꢀ contrast,ꢀ stronglyꢀ electron-withdrawingꢀ
ꢀ
WeꢀalsoꢀperformedꢀaꢀseriesꢀofꢀDFTꢀcalculationsꢀinꢀorderꢀtoꢀ
furtherꢀcorroborateꢀourꢀexperimentalꢀresults. ꢀForꢀthisꢀworkꢀ
weꢀ madeꢀ useꢀ ofꢀ theꢀ relationshipꢀ betweenꢀ theꢀ Hammettꢀ
equationꢀ andꢀ freeꢀ energyꢀ (e.g.,ꢀ equationꢀ 2). ꢀ First,ꢀ weꢀ
determinedꢀtheꢀoverallꢀfreeꢀenergyꢀchangeꢀforꢀtheꢀconversionꢀ
ofꢀ phenolsꢀ 5a-gꢀ toꢀ theꢀ phenoxeniumꢀ ionsꢀ 7a-gꢀ (Figureꢀ 3A).ꢀ
1
6
2
0
3 2
groupsꢀlikeꢀCF ꢀandꢀCO Etꢀslowꢀtheꢀreactionꢀrate.ꢀAgain,ꢀitꢀisꢀ
difficultꢀtoꢀimagineꢀhowꢀanꢀelectron-withdrawingꢀgroupꢀwouldꢀ
+
–
p
Plottingꢀ theꢀ freeꢀ energyꢀ changesꢀ againstꢀ σ ,ꢀ σ ,ꢀ andꢀ σ ꢀ
2
ꢀ|ꢀJ.ꢀName.,ꢀ2012,ꢀ00,ꢀ1-3ꢀ
Thisꢀjournalꢀisꢀ©ꢀTheꢀRoyalꢀSocietyꢀofꢀChemistryꢀ20xxꢀ
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O rP gl ea na is ce &ꢀ d Bo i ꢀon mo to ꢀ lae dc juu l sa tr ꢀ Cm h ae r mg i ins ts rꢀ y
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returnedꢀnegativeꢀρꢀvaluesꢀinꢀallꢀcases.ꢀAsꢀshouldꢀbeꢀexpected,ꢀ
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Conflictsꢀofꢀinterestꢀ
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DOI: 10.1039/C8OB01652F
+ 16
theꢀbestꢀcorrelationꢀwasꢀseenꢀwhenꢀσ ꢀwasꢀused. ꢀꢀ
Thereꢀareꢀnoꢀconflictsꢀtoꢀdeclare.ꢀ
‡
‡
!
!
–∆!
∆!
!
!
log !
=
+
= ꢀꢁ (2)
!
!.!!"
!.!!"
‡
Nextꢀ weꢀ plottedꢀ theꢀ calculatedꢀ ΔG ꢀ valuesꢀ forꢀ theꢀ
Notesꢀandꢀreferencesꢀ
ꢀ
ꢀ
protonatedꢀ unimolecularꢀ transitionꢀ statesꢀ (e.g.,ꢀ TS2).ꢀ Onceꢀ
againꢀ(Figureꢀ3B),ꢀnegativeꢀρꢀvaluesꢀwereꢀreturnedꢀinꢀallꢀcases.ꢀ 1ꢀ (a)ꢀ Hypervalentꢀ Iodineꢀ Chemistry:ꢀ Modernꢀ Developmentsꢀ inꢀ
+
Althoughꢀtheꢀcorrelationꢀwithꢀσ ꢀwasꢀnotꢀasꢀgoodꢀinꢀthisꢀcase,ꢀ
OrganicꢀSynthesis,ꢀed.:ꢀT.ꢀWirth,ꢀSpringer,ꢀBerlin,ꢀ2003.ꢀ(b)ꢀV.ꢀV.ꢀ
Zhdankin,ꢀ Hypervalentꢀ Iodineꢀ Chemistry,ꢀ Wiley,ꢀ Westꢀ Sussex,ꢀ
2014.ꢀ
visualꢀinspectionꢀrevealsꢀtheꢀplotꢀisꢀmoreꢀlinearꢀthanꢀthoseꢀforꢀ
–
–
ꢀ andꢀ σ .ꢀ Importantly,ꢀ theꢀ plotsꢀ forꢀ σ
σ
curvatureꢀthatꢀisꢀveryꢀsimilarꢀtoꢀthatꢀseenꢀwhenꢀplottingꢀourꢀ
p
p
ꢀ andꢀ σ ꢀ haveꢀ aꢀ
2
3
ꢀ Reviews:ꢀ (a)ꢀ A.ꢀ Pelterꢀ andꢀ R.ꢀ S.ꢀ Ward,ꢀ Tetrahedron,ꢀ 2001,ꢀ 57,ꢀ
2
3
4
73;ꢀ(b)ꢀR.ꢀM.ꢀMoriartyꢀandꢀO.ꢀPrakash,ꢀOrg.ꢀReact.,ꢀ2001,ꢀ57,ꢀ
27;ꢀ(c)ꢀS.ꢀQuideau,ꢀL.ꢀPouysegu,ꢀandꢀD.ꢀDeffieux,ꢀSynlett,ꢀ2008,ꢀ
67;ꢀ(d)ꢀL.ꢀPouysegu,ꢀD.ꢀDeffieux,ꢀandꢀS.ꢀQuideau,ꢀTetrahedron,ꢀ
21
experimentalꢀresults. ꢀThisꢀsuggestsꢀthatꢀwhileꢀourꢀtransitionꢀ
stateꢀ modelꢀ mayꢀ notꢀ beꢀ completelyꢀ accurate,ꢀ itꢀ isꢀ aꢀ goodꢀ
approximationꢀofꢀwhatꢀoccursꢀinꢀtheꢀflask.ꢀAnyꢀdiscrepanciesꢀ
areꢀlikelyꢀdueꢀtoꢀourꢀhandlingꢀofꢀtheꢀprotonationꢀstateꢀofꢀtheꢀ
2010,ꢀ66,ꢀ2235;ꢀ(e)ꢀS.ꢀQuideau,ꢀL.ꢀPouysegu,ꢀP.ꢀA.ꢀPeixoto,ꢀandꢀD.ꢀ
DeffieuxꢀinꢀHypervalentꢀIodineꢀChemistry,ꢀed:ꢀT.ꢀWirth,ꢀSpringer,ꢀ
Berlin,ꢀ2016,ꢀpp.ꢀ25–74.ꢀ
ꢀ Sometimesꢀ aꢀ radicalꢀ pathwayꢀ isꢀ invoked.ꢀ However,ꢀ Kitaꢀ hasꢀ
shownꢀthatꢀsuchꢀaꢀmechanismꢀonlyꢀappliesꢀtoꢀoxidationsꢀofꢀarylꢀ
ethersꢀandꢀrequiresꢀveryꢀspecificꢀconditions.ꢀSee:ꢀ(a)ꢀY.ꢀKita,ꢀH.ꢀ
Tohma,ꢀK.ꢀHatanaka,ꢀT.ꢀTakada,ꢀS.ꢀFujita,ꢀS.ꢀMitoh,ꢀH.ꢀSakurai,ꢀ
andꢀS.ꢀOka,ꢀJ.ꢀAm.ꢀChem.ꢀSoc.,ꢀ1994,ꢀ116,ꢀ3684;ꢀ(b)ꢀH.ꢀTohma,ꢀH.ꢀ
Morioka,ꢀ S.ꢀ Takizawa,ꢀ M.ꢀ Arisawa,ꢀ andꢀ Y.ꢀ Kita,ꢀ Tetrahedron,ꢀ
3
intermediateꢀ aryl-λ -iodanesꢀ (2)ꢀ andꢀ theꢀ unimolecularꢀ redoxꢀ
decompositionꢀtransitionꢀstateꢀ(TS1ꢀvs.ꢀTS2).ꢀ
(A)
OH
O
PhI(OAc)2
(ρ = –12.653 vs σp)
(
ρ = –8.4632 vs σ+)
MeOH
X/H
(ρ = –9.9488 vs σ )
–
X/H
5a-g
7a-g
2
001,ꢀ57,ꢀ345;ꢀ(c)ꢀT.ꢀDohi,ꢀM.ꢀIto,ꢀN.ꢀYamaoka,ꢀK.ꢀMorimoto,ꢀH.ꢀ
Fujioka,ꢀandꢀY.ꢀKita,ꢀTetrahedron,ꢀ2009,ꢀ65,ꢀ10797;ꢀ(d)ꢀreferenceꢀ
a,ꢀppꢀ44ꢀandꢀ1b,ꢀppꢀ15.ꢀ
ꢀ Referenceꢀ1b,ꢀppꢀ184.ꢀ
(B)
1
2
1
1
0
0
.00
.50
.00
.50
.00
4
OMe
5ꢀ Phenoxeniumꢀ ionsꢀ haveꢀ alsoꢀ beenꢀ implicatedꢀ inꢀ anodicꢀ
oxidationsꢀofꢀphenols.ꢀSee:ꢀJ.ꢀS.ꢀSwenton,ꢀK.ꢀCarpenter,ꢀY.ꢀChen.,ꢀ
M.ꢀL.ꢀKerns,ꢀandꢀG.ꢀW.ꢀMorrow,ꢀJ.ꢀOrg.ꢀChem.,ꢀ1993,ꢀ58,ꢀ3308.ꢀ
6ꢀ A.ꢀM.ꢀHarned,ꢀTetrahedronꢀLett.ꢀ2014,ꢀ55,ꢀ4681.ꢀ
CH3
F
sigma-p
◆
σ
p
-
-
-
-
-
-
0.50
1.00
1.50
2.00
2.50
7ꢀ Recentꢀ reviews:ꢀ (a)ꢀ A.ꢀ Parraꢀ andꢀ S.ꢀ Reboredo,ꢀ Chem.ꢀ Eur.ꢀ J.,ꢀ
sigma+
+
■
σ
2
013,ꢀ19,ꢀ17244;ꢀ(b)ꢀF.ꢀSinghꢀandꢀT.ꢀWirth,ꢀChem.ꢀAsianꢀJ.,ꢀ2014,ꢀ
y = -2.7934x - 0.4532
R² = 0.93397
sigma-
–
Br
̖ σ
9,ꢀ950;ꢀ(c)ꢀF.ꢀBerthiol,ꢀSynthesis,ꢀ2015,ꢀ47,ꢀ587.ꢀ
y = -3.6001x + 0.0703
CF3
8ꢀ Recentꢀ examples:ꢀ (a)ꢀ S.ꢀ J.ꢀ Murrayꢀ andꢀ H.ꢀ Ibrahim,ꢀ Chem.ꢀ
Commun.ꢀ2015,ꢀ51,ꢀ2376;ꢀ(b)ꢀD.-Y.ꢀZhang,ꢀL.ꢀXu,ꢀH.ꢀWu,ꢀandꢀL.-Z.ꢀ
Gong,ꢀ Chem.—Eur.ꢀ J.,ꢀ 2015,ꢀ 21,ꢀ 10314;ꢀ (c)ꢀ R.ꢀ Coffinier,ꢀ M.ꢀ Elꢀ
Assal,ꢀP.ꢀA.ꢀPeixoto,ꢀC.ꢀBosset,ꢀK.ꢀMiqueu,ꢀJ.-M.ꢀSotiropoulos,ꢀL.ꢀ
Pouységu,ꢀ andꢀ S.ꢀ Quideau,ꢀ Org.ꢀ Lett.,ꢀ 2016,ꢀ 18,ꢀ 1120;ꢀ (d)ꢀ K.ꢀ
Antien,ꢀ G.ꢀ Viault,ꢀ L.ꢀ Pouységu,ꢀ P.ꢀ A.ꢀ Peixoto,ꢀ andꢀ S.ꢀ Quideau,ꢀ
Tetrahedron,ꢀ2017,ꢀ73,ꢀ3684;ꢀ(e)ꢀM.ꢀOgasawara,ꢀH.ꢀSasa,ꢀH.ꢀHu,ꢀ
Y.ꢀ Amano,ꢀ H.ꢀ Nakajima,ꢀ N.ꢀ Takenaga,ꢀ K.ꢀ Nakajima,ꢀ Y.ꢀ Kita,ꢀ T.ꢀ
Takahashi,ꢀandꢀT.ꢀDohi,ꢀOrg.ꢀLett.,ꢀ2017,ꢀ19,ꢀ4102;ꢀ(f)ꢀM.ꢀUyanik,ꢀ
N.ꢀ Sasakura,ꢀ M.ꢀ Mizuno,ꢀ andꢀ K.ꢀ Ishihara,ꢀ ACSꢀ Catal.,ꢀ 2017,ꢀ 7,ꢀ
R² = 0.96014
y = -4.3712x + 0.0394
CO2Et
0.40 0.60
R² = 0.94601
3.00
-
1.00
-0.80
-0.60
-0.40
-0.20
0.00
0.20
0.80
1.00
sigma
ꢀ
Figureꢀ3.ꢀ(A)ꢀρꢀvaluesꢀofꢀtheꢀHammettꢀplotsꢀ(seeꢀESI)ꢀforꢀtheꢀ
conversionꢀofꢀphenolsꢀintoꢀphenoxeniumꢀionsꢀusingꢀcalculatedꢀfreeꢀ
energyꢀchanges.ꢀ(B)ꢀHammettꢀplotsꢀusingꢀcalculatedꢀtransitionꢀstateꢀ
energiesꢀ(ΔG‡).ꢀ
8
72.ꢀ
ꢀ A.ꢀM.ꢀHarned,ꢀOrg.ꢀBiomol.ꢀChem.,ꢀ2018,ꢀ16,ꢀ2324.ꢀ
analysisꢀ ofꢀ iodine(III)-mediatedꢀ oxidativeꢀ dearomatizationsꢀ ofꢀ 10ꢀ I.ꢀColomer,ꢀC.ꢀBatchelor-McAuley,ꢀB.ꢀOdell,ꢀT.ꢀJ.ꢀDonohoe,ꢀandꢀR.ꢀ
phenols.ꢀ Ourꢀ analysisꢀ indicatesꢀ theꢀ reactionꢀ likelyꢀ proceedsꢀ
G.ꢀCompton,ꢀJ.ꢀAm.ꢀChem.ꢀSoc.ꢀ2016,ꢀ138,ꢀ8855.
throughꢀaꢀmechanismꢀinꢀwhichꢀaꢀpositiveꢀchargeꢀdevelopsꢀonꢀ 11ꢀ Additionalꢀ computationalꢀ resultsꢀ usingꢀ alternativeꢀ functionals,ꢀ
ꢀ
Inꢀ conclusion,ꢀ weꢀ haveꢀ performedꢀ aꢀ detailedꢀ Hammettꢀ
9
basisꢀsets,ꢀandꢀsolvationꢀmodelꢀthatꢀsupportꢀthisꢀconclusionꢀcanꢀ
beꢀfoundꢀinꢀtheꢀESI.ꢀ
2ꢀ (a)ꢀC.ꢀD.ꢀJohnsonꢀTheꢀHammettꢀEquation,ꢀCambridgeꢀUniversityꢀ
Press,ꢀ London,ꢀ 1973;ꢀ (b)ꢀ E.ꢀ V.ꢀ Anslynꢀ andꢀ D.ꢀ A.ꢀ Dougherty,ꢀ
Modernꢀ Physicalꢀ Organicꢀ Chemistry,ꢀ Universityꢀ Scienceꢀ Books,ꢀ
Sausalito,ꢀCA,ꢀ2006,ꢀppꢀ445–453.ꢀ
theꢀphenolꢀduringꢀtheꢀrateꢀdeterminingꢀstep.ꢀThisꢀisꢀconsistentꢀ
withꢀaꢀunimolecularꢀredoxꢀdecompositionꢀpathwayꢀ(Figureꢀ1,ꢀ
pathꢀ B)ꢀ andꢀ isꢀ notꢀ consistentꢀ aꢀ bimolecularꢀ redoxꢀ
decompositionꢀpathwayꢀ(Figureꢀ1,ꢀpathꢀA).ꢀTheseꢀfindingsꢀhaveꢀ
significantꢀimplicationsꢀwithꢀregardꢀtoꢀtheꢀdesignꢀofꢀfutureꢀarylꢀ
iodideꢀ catalystsꢀ andꢀ reagents,ꢀ asꢀ wellꢀ asꢀ newꢀ iodine(III)-
mediatedꢀreactionsꢀinvolvingꢀphenols.ꢀꢀ
1
1
3ꢀ (a)ꢀA.ꢀS.ꢀMitchellꢀandꢀR.ꢀA.ꢀRussell,ꢀTetrahedron,ꢀ1997,ꢀ53,ꢀ4387;ꢀ
(
b)ꢀ Y.ꢀ Sawama,ꢀ M.ꢀ Masuda,ꢀ R.ꢀ Nakatani,ꢀ H.ꢀ Yokoyama,ꢀ Y.ꢀ
Monguchi,ꢀT.ꢀDohi,ꢀY.ꢀKita,ꢀandꢀH.ꢀSajiki,ꢀAdv.ꢀSynth.ꢀCatal.,ꢀ2016,ꢀ
58,ꢀ3683.ꢀ
4ꢀ (a)ꢀ H.ꢀ M.ꢀ Yau,ꢀ A.ꢀ K.ꢀ Croft,ꢀ andꢀ J.ꢀ B.ꢀ Harper,ꢀ Chem.ꢀ Commun.ꢀ
012,ꢀ48,ꢀ8937;ꢀ(b)ꢀH.ꢀM.ꢀYau,ꢀR.ꢀS.ꢀRaines,ꢀandꢀJ.ꢀB.ꢀHarper,ꢀJ.ꢀ
3
1
1
Acknowledgementsꢀ
2
FinancialꢀsupportꢀforꢀthisꢀworkꢀprovidedꢀbyꢀTexasꢀTechꢀ
UniversityꢀandꢀtheꢀNationalꢀScienceꢀFoundationꢀ(CHE-
1541685).ꢀWeꢀareꢀgratefulꢀtoꢀProf.ꢀDavidꢀBirneyꢀ(TexasꢀTech)ꢀ
forꢀhelpfulꢀdiscussionsꢀandꢀsuggestions.ꢀ
Chem.ꢀEduc.ꢀ2015,ꢀ92,ꢀ538.ꢀ
5ꢀ OtherꢀexamplesꢀofꢀHammettꢀstudiesꢀusingꢀcompetitiveꢀrates:ꢀ(a)ꢀ
J.ꢀH.ꢀSchauble,ꢀG.ꢀJ.ꢀWalter,ꢀandꢀJ.ꢀG.ꢀMorin,ꢀJ.ꢀOrg.ꢀChem.,ꢀ1974,ꢀ
39,ꢀ755;ꢀ(b)ꢀH.ꢀYamataka,ꢀT.ꢀMatsuyama,ꢀandꢀT.ꢀHanafusa,ꢀJ.ꢀAm.ꢀ
ꢀ
Thisꢀjournalꢀisꢀ©ꢀTheꢀRoyalꢀSocietyꢀofꢀChemistryꢀ20xxꢀ
J.ꢀName.,ꢀ2013,ꢀ00,ꢀ1-3ꢀ|ꢀ3ꢀ
Pleaseꢀdoꢀnotꢀadjustꢀmarginsꢀ

O rP gl ea na is ce &ꢀ d Bo i ꢀon mo to ꢀ lae dc juu l sa tr ꢀ mC h ae r mg i ins ts rꢀ y
Page 4 of 4
COMMUNICATIONꢀ
JournalꢀNameꢀ
ꢀ
View Article Online
DOI: 10.1039/C8OB01652F
Chem.ꢀSoc.,ꢀ1989,ꢀ111,ꢀ4912;ꢀ(c)ꢀR.ꢀJ.ꢀMullins,ꢀA.ꢀVedernikov,ꢀandꢀ
R.ꢀViswanathan,ꢀJ.ꢀChem.ꢀEduc.,ꢀ2004,ꢀ81,ꢀ1357;ꢀ(d)ꢀP.ꢀFristrup,ꢀS.ꢀ
Leꢀ Quement,ꢀ D.ꢀ Tanner,ꢀ andꢀ P.-O.ꢀ Norrby,ꢀ Organometallics,ꢀ
2
004,ꢀ23,ꢀ6160;ꢀ(e)ꢀK.ꢀK.ꢀW.ꢀMak,ꢀW.-F.ꢀChan,ꢀK.-Y.ꢀLung,ꢀW.-Y.ꢀ
Lam,ꢀW.-C.ꢀNg,ꢀandꢀS.-F.ꢀLee,ꢀJ.ꢀChem.ꢀEduc.,ꢀ2007,ꢀ84,ꢀ1819;ꢀ(f)ꢀ
L.ꢀV.ꢀDesai,ꢀK.ꢀJ.ꢀStowers,ꢀandꢀM.ꢀS.ꢀSanford,ꢀJ.ꢀAm.ꢀChem.ꢀSoc.,ꢀ
2
008,ꢀ 130,ꢀ 13285;ꢀ (g)ꢀ A.ꢀ Bartoszewicz,ꢀ G.ꢀ Gonzálezꢀ Miera,ꢀ R.ꢀ
Marcos,ꢀP.-O.ꢀNorrby,ꢀandꢀB.ꢀMartín-Matute,ꢀACSꢀCatal.,ꢀ2015,ꢀ
,ꢀ3704;ꢀ(h)ꢀA.ꢀL.ꢀNash,ꢀR.ꢀHertzberg,ꢀY.-Q.ꢀWen,ꢀB.ꢀDahlgren,ꢀT.ꢀ
5
Brinck,ꢀandꢀC.ꢀMoberg,ꢀChem.ꢀEur.ꢀJ.,ꢀ2016,ꢀ22,ꢀ3821.ꢀ
1
1
6ꢀ SeeꢀESIꢀforꢀdetails.ꢀ
+
–
7ꢀ Valuesꢀforꢀσ
andꢀR.ꢀW.ꢀTaft,ꢀChem.ꢀRev.,ꢀ1991,ꢀ91,ꢀ165.ꢀValuesꢀforꢀσ
wereꢀobtainedꢀfromꢀM.ꢀCharton,ꢀProg.ꢀPhys.ꢀOrg.ꢀChem.,ꢀ1981,ꢀ
3,ꢀ119.ꢀ
p
,ꢀσ ,ꢀandꢀσ ꢀwereꢀobtainedꢀfromꢀC.ꢀHansch,ꢀA.ꢀLeo,ꢀ
I
ꢀandꢀσ
R
ꢀ
1
1
1
2
8ꢀ H.ꢀH.ꢀJaffé,ꢀChem.ꢀRev.,ꢀ1953,ꢀ53,ꢀ191.ꢀ
9ꢀ K.ꢀH.ꢀPausacker,ꢀJ.ꢀChem.ꢀSoc.,ꢀ1953,ꢀ107.ꢀ
0ꢀ J.ꢀ March,ꢀ Advancedꢀ Organicꢀ Chemistry,ꢀ 4thꢀ Ed.,ꢀ Wiley,ꢀ Newꢀ
York,ꢀ1992,ꢀppꢀ281.ꢀ
2
1ꢀ Similarꢀcurvatureꢀwasꢀalsoꢀseenꢀwhenꢀplottingꢀtheꢀfreeꢀenergyꢀ
changeꢀ forꢀ theꢀ formationꢀ ofꢀ theꢀ phenoxeniumꢀ ion.ꢀ Seeꢀ
supportingꢀinformation.ꢀ
4
ꢀ|ꢀJ.ꢀName.,ꢀ2012,ꢀ00,ꢀ1-3ꢀ
Thisꢀjournalꢀisꢀ©ꢀTheꢀRoyalꢀSocietyꢀofꢀChemistryꢀ20xxꢀ
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