Synthesis of 1,4-amino alcohols by Grignard reagent addition to THF and N-tosyliminobenzyliodinane

Article abstract of DOI:10.1039/c5ob02302e

The synthesis of 1,4-amino alcohols from THF treated with N-tosyliminobenzyliodinane (PhINTs) followed by a Grignard reagent under mild reaction conditions at room temperature is described herein. Various Grignard reagents were shown to be compatible, furnishing the corresponding 4-substituted-N-1,4-tosylamino alcohols in good to excellent yields. A partial or full detosylation of the N-tosyl-1,4-amino alcohol was observed in instances involving a sterically bulky Grignard reagent, leading to the deprotected 1,4-amino alcohol product in moderate to good yields. The synthetic utility of this protocol was demonstrated by the synthesis of a 5-substituted-N-tosyl-1,5-amino alcohol from THP and the conversion of two examples to their corresponding γ-lactam and pyrrolidine adducts.

Full text of DOI:10.1039/c5ob02302e

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Page 1 of 5
Org aP nl ei ca s &e ꢀ dB oi oꢀ nmo to ꢀ al ed cj uu sl at ꢀrm Ca hr ge imn si sꢀ try
View Article Online
DOI: 10.1039/C5OB02302E
Organicꢀ&ꢀBiomolecularꢀChemistryꢀ
ꢀ
PAPERꢀ
Synthesisꢀofꢀ1,4-AminoꢀAlcoholsꢀbyꢀGrignardꢀReagentꢀAdditionꢀtoꢀ
THFꢀandꢀN-Tosyliminobenzyliodinane†ꢀ
Receivedꢀ00thꢀJanuaryꢀ20xx,ꢀ
Acceptedꢀ00thꢀJanuaryꢀ20xxꢀ
c
c
a
a,bꢀ
CiputraꢀTejo, ꢀYangꢀFengꢀAndersꢀSee, ꢀMitchꢀMathiew, ꢀandꢀPhilipꢀWaiꢀHongꢀChan
DOI:ꢀ10.1039/x0xx00000xꢀ
Theꢀsynthesisꢀofꢀ1,4-aminoꢀalcoholsꢀfromꢀTHFꢀtreatedꢀwithꢀN-tosyliminobenzyliodinaneꢀ(PhINTs)ꢀfollowedꢀbyꢀaꢀGrignardꢀ
reagentꢀunderꢀmildꢀreactionꢀconditionsꢀatꢀroomꢀtemperatureꢀisꢀdescribedꢀherein.ꢀVariousꢀGrignardꢀreagentsꢀwereꢀshownꢀ
toꢀ beꢀ compatible,ꢀ furnishingꢀ theꢀ correspondingꢀ 4-substituted-N-1,4-tosylaminoꢀ alcoholsꢀ inꢀ goodꢀ toꢀ excellentꢀ yields.ꢀ Aꢀ
partialꢀorꢀfullꢀdetosylationꢀofꢀtheꢀN-tosyl-1,4-aminoꢀalcoholꢀwasꢀobservedꢀinꢀinstancesꢀinvolvingꢀaꢀstericallyꢀbulkyꢀGrignardꢀ
reagent,ꢀleadingꢀtoꢀtheꢀdeprotectedꢀ1,4-aminoꢀalcoholꢀproductꢀinꢀmoderateꢀtoꢀgoodꢀyields.ꢀTheꢀsyntheticꢀutilityꢀofꢀthisꢀ
protocolꢀwasꢀdemonstratedꢀbyꢀtheꢀsynthesisꢀofꢀaꢀ5-substituted-N-tosyl-1,5-aminoꢀalcoholꢀfromꢀTHPꢀandꢀtheꢀconversionꢀofꢀ
twoꢀexamplesꢀtoꢀtheirꢀcorrespondingꢀγ-lactamꢀandꢀpyrrolidineꢀadducts.ꢀ
www.rsc.org/ꢀ
ꢀ
Introductionꢀ
O
O
R2
(
)n
R2
R3
Theꢀ developmentꢀ ofꢀ syntheticꢀ methodologyꢀ toꢀ accessꢀ 1,4-
aminoꢀalcoholsꢀfromꢀlowꢀcostꢀandꢀreadilyꢀaccessibleꢀsubstratesꢀ
1
isꢀ anꢀ importantꢀ pursuitꢀ inꢀ organicꢀ chemistry. ꢀ Thisꢀ isꢀ dueꢀ toꢀ
O
R1
(a)
O
DBU
ref 4l
previous study
R3
O
theirꢀpresenceꢀinꢀmanyꢀnaturalꢀproductsꢀandꢀpharmaceuticallyꢀ
interestingꢀ compoundsꢀ asꢀ wellꢀ asꢀ functionalꢀ materials.ꢀ Theꢀ
compoundꢀ classꢀ isꢀ alsoꢀ aꢀ usefulꢀ buildingꢀ blockꢀ inꢀ organicꢀ
synthesisꢀandꢀaꢀversatileꢀligandꢀforꢀnumerousꢀtypesꢀofꢀmetalꢀ
complexes.ꢀ
(
)n
PhINTs
R1
n = 1, 2
O
R1 = H, Me
5
R MgBr
NHX
HO
( )
n
(b)
for R1 = H
R5
1, X = Ts
, X = H
Recently,ꢀ iminoiodane-basedꢀ reagentsꢀ haveꢀ beenꢀ
demonstratedꢀtoꢀpossessꢀanꢀintriguingꢀarrayꢀofꢀreactivitiesꢀinꢀaꢀ
numberꢀ ofꢀ transitionꢀ metal-ꢀ andꢀ transitionꢀ metal-free-
this study
2
ꢀ
2-5
mediatedꢀorganicꢀtransformations. ꢀInꢀtheꢀcaseꢀofꢀtheꢀlatter,ꢀ
forꢀ example,ꢀ weꢀ reportedꢀ theꢀ preparationꢀ ofꢀ 2-
tetrahydrofuranꢀ andꢀ -pyranꢀ substitutedꢀ 1,3-dicarbonylꢀ
compoundsꢀ fromꢀ iminoiodane-ꢀ andꢀ Brønstedꢀ base-mediatedꢀ
crossꢀdehydrativeꢀcouplingꢀofꢀtheꢀcorrespondingꢀcyclicꢀethersꢀ
Schemeꢀ1.ꢀReactivitiesꢀofꢀcyclicꢀethersꢀinꢀtheꢀpresenceꢀofꢀPhINTsꢀꢀ
wayꢀinvolvingꢀring-openingꢀunderꢀtheꢀbasicꢀconditionsꢀofferedꢀ
4f,i,l
byꢀ aꢀ Grignardꢀ reagent. ꢀ Subsequentꢀ additionꢀ ofꢀ aꢀ secondꢀ
moleculeꢀ ofꢀ theꢀ Grignardꢀ reagentꢀ toꢀ theꢀ ensuingꢀ 4-
tosyliminobutan-1-olꢀ wouldꢀ thenꢀ beꢀ expectedꢀ toꢀ giveꢀ theꢀ N-
tosyl-1,4-aminoꢀalcoholꢀproduct.ꢀHerein,ꢀweꢀreportꢀtheꢀdetailsꢀ
ofꢀthisꢀchemistryꢀthatꢀprovidesꢀanꢀexpedientꢀsyntheticꢀrouteꢀtoꢀ
4l
withꢀ1,3-dicarbonylꢀcompoundsꢀ(Schemeꢀ1a). ꢀBuildingꢀonꢀthisꢀ
initialꢀ workꢀ andꢀ theꢀ well-documentedꢀ reactionꢀ chemistryꢀ ofꢀ
cyclicꢀethersꢀtowardꢀorganometallicꢀreagents,ꢀweꢀenvisagedꢀaꢀ
syntheticꢀapproachꢀtoꢀ1,4-aminoꢀalcoholsꢀbyꢀGrignardꢀreagentꢀ
additionꢀtoꢀTHFꢀinꢀtheꢀpresenceꢀofꢀPhINTsꢀmightꢀbeꢀachievableꢀ
4
-substituted-4-tosyl-aminobutan-1-ols,ꢀandꢀoneꢀexampleꢀofꢀaꢀ
6
,7
N-tosyl-1,5-aminoꢀalcoholꢀanalogueꢀfromꢀTHP,ꢀinꢀmoderateꢀtoꢀ
excellentꢀyieldsꢀunderꢀmildꢀconditionsꢀatꢀroomꢀtemperature.ꢀAꢀ
concomitantꢀ detosylationꢀ inꢀ reactionsꢀ involvingꢀ aꢀ stericallyꢀ
bulkyꢀ Grignardꢀ reagentꢀ toꢀ affordꢀ theꢀ 4-substituted-4-
aminobutan-1-olꢀadductꢀandꢀsyntheticꢀutilityꢀofꢀtheꢀmethodꢀbyꢀ
convertingꢀtwoꢀexamplesꢀtoꢀtheirꢀcorrespondingꢀγ-lactamꢀandꢀ
pyrrolidineꢀderivativesꢀisꢀalsoꢀpresented.ꢀ
(
Schemeꢀ
1b). ꢀ
Itꢀ
wasꢀ
reasonedꢀ
thatꢀ
2-
tosylaminotetrahydrofuran,ꢀ generatedꢀ inꢀ situꢀ fromꢀ theꢀ
reactionꢀofꢀTHFꢀwithꢀPhINTs,ꢀmightꢀbeꢀsusceptibleꢀtoꢀaꢀpath-ꢀ
a.
SchoolꢀofꢀChemistry,ꢀMonashꢀUniversity,ꢀClayton,ꢀVictoriaꢀ3800,ꢀAustralia;ꢀEmail:ꢀ
b. phil.chan@monash.eduꢀꢀ
DepartmentꢀofꢀChemistry,ꢀUniversityꢀofꢀWarwick,ꢀCoventry,ꢀCV4ꢀ7AL,ꢀUK;ꢀEmail:ꢀ
P.W.H.Chan@warwick.ac.ukꢀꢀ
DivisionꢀofꢀChemistryꢀandꢀBiologicalꢀChemistry,ꢀSchoolꢀofꢀPhysicalꢀandꢀ
c.
MathematicalꢀSciences,ꢀNanyangꢀTechnologicalꢀUniversity,ꢀSingaporeꢀ637371,ꢀ
Singaporeꢀ
Electronicꢀ Supplementaryꢀ Informationꢀ (ESI)ꢀ available:ꢀ Experimentalꢀ detailsꢀ and
ResultsꢀandꢀDiscussionꢀ
†
Inꢀanꢀinitialꢀstudy,ꢀtheꢀtreatmentꢀofꢀTHFꢀ(2ꢀmL)ꢀwithꢀPhINTsꢀ
0.5ꢀ mmol)ꢀ atꢀ roomꢀ temperatureꢀ forꢀ 50ꢀ minꢀ followedꢀ byꢀ 3ꢀ
NMRꢀspectra.ꢀSeeꢀDOI:ꢀ10.1039/x0xx00000xꢀ
(
Thisꢀjournalꢀisꢀ©ꢀTheꢀRoyalꢀSocietyꢀofꢀChemistryꢀ2015ꢀ
Org.ꢀBiomol.ꢀChem.,ꢀ2015,ꢀ00,ꢀ1-4ꢀ|ꢀ1ꢀꢀ
Pleaseꢀdoꢀnotꢀadjustꢀmarginsꢀ

Org aP nl ei ca s &e ꢀ dB oi oꢀ nmo to ꢀ al ed cj uu sl at ꢀrm Ca hr ge imn si sꢀ try
Page 2 of 5
ARTICLEꢀ
JournalꢀNameꢀ
8
equivꢀ ofꢀ phenylmagnesiumꢀ bromideꢀ furnishedꢀ theꢀ N- takeꢀplace. ꢀSuppressionꢀofꢀthisꢀcompetingꢀside-reactionꢀbyꢀtheꢀ
View Article Online
tosylamino-1,4-aminoꢀalcoholꢀproductꢀ1aꢀinꢀ43%ꢀyieldꢀ(Schemeꢀ introductionꢀ ofꢀ 5ꢀ molꢀ %ꢀ ofꢀ copper(I)ꢀ t rDi fOl aI :t 1e0 ꢀ. 1t 0o 3ꢀ 9t /hC e5 ꢀ Or Be 0a 2c 3t 0i o2 nE ꢀ
2
equivꢀwasꢀfoundꢀtoꢀgiveꢀtheꢀdesiredꢀproductꢀinꢀ86%ꢀyield.ꢀꢀ
).ꢀIncreasingꢀtheꢀamountꢀofꢀtheꢀGrignardꢀreagentꢀfromꢀ3ꢀtoꢀ5ꢀ conditionsꢀgaveꢀtheꢀdesiredꢀN-tosyl-1,4-aminoꢀalcoholꢀproductꢀ
inꢀ anꢀ improvedꢀ yieldꢀ ofꢀ 82%.ꢀ Similarly,ꢀ theꢀ respectiveꢀ
transformationsꢀ withꢀ n-pentyl-ꢀ andꢀ cyclopentylmagnesiumꢀ
bromideꢀ wereꢀ foundꢀ toꢀ requireꢀ theꢀ copper(I)ꢀ saltꢀ soꢀ thatꢀ 1gꢀ
andꢀ 1hꢀ couldꢀ beꢀ obtainedꢀinꢀ yieldsꢀ ofꢀ 71%ꢀ andꢀ 72%.ꢀ Severalꢀ
alkenylꢀ andꢀ alkynylꢀ Grignardꢀ reagentsꢀ wereꢀ alsoꢀ testedꢀ andꢀ
foundꢀ toꢀ giveꢀ theꢀ correspondingꢀ N-tosyl-1,4-aminoꢀ alcoholꢀ
productsꢀ1i-kꢀinꢀ66–72%ꢀyield.ꢀ
1
. PhINTs (0.5 mmol)
rt, 50 min
NHTs
HO
O
2. PhMgBr (1.5–2.5 mmol)
rt, 18 h
Ph
1a
4
8
3% yield (3 equiv)
6% yield (5 equiv)
ꢀ
Inꢀ ourꢀ hands,ꢀ theꢀ additionꢀ ofꢀ cyclopropylmagnesiumꢀ
bromideꢀ toꢀ THFꢀ andꢀ PHI=NTsꢀ wasꢀ foundꢀ toꢀ resultꢀ inꢀ theꢀ
formationꢀ ofꢀ N-tosylꢀ protectedꢀ 1,4-aminoꢀ alcoholꢀ 1lꢀ andꢀ 4-
amino-4-cyclopropylbutan-1-olꢀ 2lꢀ inꢀ 29ꢀ andꢀ 33%ꢀ yield,ꢀ
respectively.ꢀ Aꢀ similarꢀ outcomeꢀ wasꢀ observedꢀ forꢀ reactionsꢀ
withꢀ theꢀ Grignardꢀ reagentsꢀ p-methoxyphenyl-ꢀ andꢀ p-
chlorophenylmagnesiumꢀ bromide.ꢀ Inꢀ theseꢀ experiments,ꢀ theꢀ
correspondingꢀ N-tosylꢀ protectedꢀ andꢀ secondaryꢀ aminoꢀ
alcoholsꢀwereꢀobtainedꢀinꢀrespectiveꢀyieldsꢀofꢀ62ꢀandꢀ37%ꢀforꢀ
Schemeꢀ2.ꢀReactionsꢀofꢀTHFꢀwithꢀPhINTsꢀandꢀPhMgBrꢀ
Withꢀ theseꢀ conditionsꢀ inꢀ hand,ꢀ theꢀ presentꢀ methodꢀ wasꢀ
nextꢀassessedꢀwithꢀaꢀseriesꢀofꢀGrignardꢀreagentsꢀ(Schemeꢀ3).ꢀ
Whenꢀ theꢀ reactionꢀ wasꢀ repeatedꢀ withꢀ o-tolylmagnesiumꢀ
bromideꢀ inꢀ placeꢀ ofꢀ phenylmagnesiumꢀ bromide,ꢀ theꢀ
anticipatedꢀ o-tolylꢀ substitutedꢀ N-tosyl-1,4-aminoꢀ alcoholꢀ 1bꢀ
wasꢀobtainedꢀinꢀ72%ꢀyield.ꢀLikewise,ꢀtheꢀanalogousꢀreactionsꢀ
withꢀ alkylꢀ Grignardꢀ reagentsꢀ suchꢀ asꢀ methyl-,ꢀ ethyl-,ꢀ andꢀ
allylmagnesiumꢀbromideꢀwereꢀfoundꢀtoꢀbeꢀwellꢀtoleratedꢀandꢀ
affordedꢀ theꢀ correspondingꢀ 4-substituted-1,4-aminoꢀ alcoholsꢀ
1
mꢀandꢀ2m,ꢀandꢀ29ꢀandꢀ59%ꢀforꢀ1nꢀandꢀ2n.ꢀOnꢀtheꢀotherꢀhand,ꢀ
theꢀanalogousꢀtransformationsꢀwithꢀtheꢀmeta-substitutedꢀarylꢀ
Grignardꢀ reagentsꢀ m-trifluoromethylphenyl-ꢀ andꢀ 3,5-
dimethylphenylmagnesiumꢀ bromideꢀ gaveꢀ theꢀ correspondingꢀ
1
c–eꢀ inꢀ goodꢀ toꢀ excellentꢀ yieldsꢀ ofꢀ 68–88%.ꢀ Theꢀ useꢀ ofꢀ theꢀ
Grignardꢀ reagentꢀ isobutylmagnesiumꢀ bromideꢀ bearingꢀ aꢀ β-
hydrogenꢀonꢀtheꢀalkylꢀgroup,ꢀwasꢀfoundꢀtoꢀgiveꢀ1fꢀinꢀ42%ꢀyield.ꢀ
1
Basedꢀonꢀ HꢀNMRꢀanalysisꢀofꢀtheꢀcrudeꢀmixture,ꢀthisꢀcouldꢀbeꢀ
1
,4-aminoꢀ alcoholsꢀ 2oꢀ andꢀ 2pꢀ asꢀ theꢀ onlyꢀ productꢀ inꢀ 44ꢀ andꢀ
62%ꢀyield,ꢀrespectively.ꢀLikewise,ꢀrepeatingꢀtheꢀreactionꢀwithꢀ
-naphthylmagnesiumꢀ bromideꢀ gaveꢀ 4-amino-4(naphta-1-
1
dueꢀtoꢀaꢀpossibleꢀcompetitiveꢀreductionꢀofꢀtheꢀputativeꢀring-
openingꢀ adductꢀ ofꢀ 2-tosylaminotetrahydrofuranꢀ beforeꢀ
additionꢀofꢀaꢀsecondꢀmoleculeꢀofꢀtheꢀGrignardꢀreagentꢀcouldꢀ
yl)butan-1-olꢀ asꢀ theꢀ onlyꢀ adductꢀ inꢀ 85%ꢀ yield.ꢀ Replacingꢀ THFꢀ
withꢀTHPꢀandꢀsubjectingꢀtheꢀhexacyclicꢀetherꢀtoꢀPhINTsꢀ
1
. PhINTs (0.5 mmol)
rt, 50 min
(
)n
NHX
HO
( )
n
O
2. RMgBr (2.5 mmol)
rt, 18 h
Ph
1, X = Ts
, X = H
2
NHTs
NH2
NHTs
HO
HO
HO
HO
R
1
1
1
1
1
1
1
1
1
1
b, R = o-Tol (72%)
c, R = Me (88%)
1l (29%)
2l (33%)
NHTs
NH2
d, R = Et (68%)
HO
e, R = Allyl (86%)
f, R = i-Bu (82%)a
g, R = Pent (71%)a
h, R = c-Pent (72%)a
i, R = i-Propenyl (66%)
j, R = i-Butenyl (72%)
k, R = Propynyl (66%)
R
R
1m, R = OMe (62%)
1n, R = Cl (28%)
2m, R = OMe (37%)
2n, R = Cl (59%)
NH2
NH2
HO
NHTs
Me
HO
HO
Et
Me
Y
HO
NHTs
R1
R2
o, R1 = CF , R2 = H (44%)
2q (85%)
1r (-)b
2
2
1s, Y = CH (24%)
3
2
p, R1 = R2 = Me (62%)
1t, Y = O (-)b
ꢀ
Schemeꢀ3.ꢀReactionsꢀofꢀTHFꢀandꢀPhINTsꢀwithꢀaꢀvarietyꢀofꢀGrignardꢀreagents.ꢀAllꢀreactionsꢀwereꢀcarriedꢀoutꢀunderꢀN
2
ꢀatmosphereꢀwithꢀ0.5ꢀmmolꢀofꢀPhINTsꢀandꢀTHFꢀ
a
b
1
(
2ꢀmL).ꢀValuesꢀinꢀparenthesesꢀrepresentꢀisolatedꢀproductꢀyield.ꢀ ReactionꢀperformedꢀinꢀtheꢀpresenceꢀofꢀCuOTfꢀ(5ꢀmolꢀ%)ꢀasꢀcatalyst.ꢀ NoꢀreactionꢀbasedꢀonꢀTLCꢀandꢀ Hꢀ
NMRꢀanalysisꢀofꢀtheꢀcrudeꢀmixture.ꢀ
2
ꢀ|ꢀThisꢀjournalꢀisꢀ©ꢀTheꢀRoyalꢀSocietyꢀofꢀChemistryꢀ2015ꢀ
Org.ꢀBiomol.ꢀChem.,ꢀ2015,ꢀ00,ꢀ1-4ꢀ
Pleaseꢀdoꢀnotꢀadjustꢀmarginsꢀ

Page 3 of 5
Org aP nl ei ca s &e ꢀ dB oi oꢀ nmo to ꢀ al ed cj uu sl at ꢀrm Ca hr ge imn si sꢀ try
Organicꢀ&ꢀBiomolecularꢀChemistryꢀ
ꢀPaperꢀ
followedꢀbyꢀethylmagnesiumꢀbromideꢀgaveꢀtheꢀcorrespondingꢀ
N-tosyl-1,5-aminoꢀ alcoholꢀ 1sꢀ inꢀ 24%ꢀ yield.ꢀ Theꢀ treatmentꢀ ofꢀ
THFꢀandꢀPhINTsꢀwithꢀ2,6-dimethylphenylmagnesiumꢀbromide,ꢀ
andꢀ 1,4-dioxaneꢀ andꢀ PhINTsꢀ withꢀ ethylmagnesiumꢀ bromideꢀ
wereꢀ theꢀ onlyꢀ instancesꢀ inꢀ whichꢀ noꢀ reactionꢀ wasꢀ observedꢀ
Ts
N
View Article Online
DOI: 10.1039/C5OB02302E
PhINTs
path a
H
O
O
IPh
A
−
PhI
path b
NHTs
O
D
1
basedꢀ onꢀ TLCꢀ andꢀ Hꢀ NMRꢀ analysisꢀ ofꢀ theꢀ crudeꢀ reactionꢀ
mixtures.ꢀ
O
O
−PhI
I
NTs
Next,ꢀ theꢀ syntheticꢀ utilityꢀ ofꢀ theꢀ 1,4-aminoꢀ alcoholsꢀ Ph
obtainedꢀbyꢀtheꢀpresentꢀprocedureꢀwasꢀexaminedꢀ(Schemeꢀ4).ꢀ
First,ꢀ oxidativeꢀ cyclizationꢀ ofꢀ N-tosyl-1,4-aminoꢀ alcoholꢀ 1aꢀ inꢀ
theꢀ presenceꢀ ofꢀ 5ꢀ equivꢀ ofꢀ pyridiniumꢀ dichromateꢀ (PDC)ꢀ inꢀ
dimethylformamideꢀ atꢀ roomꢀ temperatureꢀ wasꢀ demonstratedꢀ
toꢀgiveꢀtheꢀγ-lactamꢀ3aꢀinꢀ75%ꢀyieldꢀ(Schemeꢀ4a).ꢀTheꢀsynthesisꢀ
ofꢀ theꢀ N-tosylpyrrolidineꢀ 4fꢀ wasꢀ realizedꢀ inꢀ 89%ꢀ yieldꢀ byꢀ
subjectingꢀ N-tosyl-1,4-aminoꢀ alcoholꢀ 1fꢀ toꢀ theꢀ Mitsunobuꢀ
reactionꢀ conditionsꢀ ofꢀ 1.2ꢀ equivꢀ ofꢀ diisopropylꢀ
azodicarboxylateꢀandꢀtriphenylphosphineꢀ(Schemeꢀ4b).ꢀ
NHTs
NTs
B
C
BrMgO
H
E
path d
for R = n-alkyl)
path c
(
RMgBr
Br
Mg
TsN MgBr
R
N
R
BrMgO
BrMgO
MgBr
R
G
F
H+
−MgBrOH
NTsMgBr
NHX
NHTs
PDC (5 equiv)
DMF, rt, 18 h
HO
R
+
BrMgO
HO
O
Ph
(a)
R
N
Ph
Ts
H
1, R = Ts
, R = H
R
2
1
a
3a
7
5% yield
H+ −MgBrOH
DIAD (1.2 equiv)
NTsMgBr
R
NHTs
PPh
3
(1.2 equiv)
BrMgO
HO
i-Bu
(b)
N
i-Bu
I
ꢀ
THF, rt, 12 h
Ts
1
f
4f
9% yield
Schemeꢀ5.ꢀProposedꢀmechanismꢀforꢀtheꢀsynthesisꢀofꢀ1,4-ꢀandꢀ1,5-aminoꢀalcoholsꢀ
8
ꢀ
fromꢀTHFꢀorꢀTHP,ꢀrespectively,ꢀPhINTsꢀandꢀRMgBrꢀ
Schemeꢀ4.ꢀSelectiveꢀtransformationsꢀofꢀN-tosyl-1,4-aminoꢀalcoholsꢀ1aꢀandꢀ1fꢀ
deliverꢀtheꢀ1,4-aminoꢀalcoholꢀ2.ꢀTheꢀproposedꢀinvolvementꢀofꢀ
theꢀ radicalꢀ sourceꢀ generatedꢀ fromꢀ theꢀ Grignardꢀ reagentꢀ
initiatingꢀ detosylationꢀ wasꢀ furtherꢀ corroboratedꢀ byꢀ ourꢀ
findingsꢀforꢀtheꢀcontrolꢀreactionsꢀdepictedꢀinꢀSchemeꢀ6.ꢀFirstly,ꢀ
subjectingꢀ THFꢀ andꢀ PhINTsꢀ toꢀ 7ꢀ equivꢀ ofꢀ phenylmagnesiumꢀ
bromideꢀ atꢀ roomꢀ temperatureꢀ forꢀ 18ꢀ hꢀ gaveꢀ theꢀ N-tosylꢀ
productꢀ 1ꢀ andꢀ 1,4-aminoꢀ alcoholꢀ 2ꢀ inꢀ 40ꢀ andꢀ 49%ꢀ yield,ꢀ
respectivelyꢀ (Schemeꢀ 6a).ꢀ Inꢀ aꢀ secondꢀ setꢀ ofꢀ experiments,ꢀ
treatmentꢀ ofꢀ 1fꢀ toꢀ 4ꢀ equivꢀ ofꢀ phenylmagnesiumꢀ bromideꢀ inꢀ
THFꢀ atꢀ roomꢀ temperatureꢀ forꢀ 18ꢀ hꢀ affordedꢀ 1aꢀ inꢀ 35%ꢀ yieldꢀ
Aꢀ plausibleꢀ mechanismꢀ forꢀ theꢀ presentꢀ N-tosyl-1,4-aminoꢀ
alcoholꢀformingꢀreactionꢀisꢀillustratedꢀinꢀSchemeꢀ5.ꢀThisꢀcouldꢀ
involveꢀtheꢀdirectꢀinsertionꢀofꢀtheꢀputativeꢀnitrenoidꢀgroupꢀinꢀ
PhINTsꢀintoꢀtheꢀC–Hꢀbondꢀofꢀtheꢀcyclicꢀetherꢀviaꢀtheꢀconcertedꢀ
4f,i
asynchronousꢀ transitionꢀ stateꢀ Aꢀ (Schemeꢀ 5,ꢀ pathꢀ a). ꢀ
Alternatively,ꢀ theꢀ directꢀ C–Hꢀ insertionꢀ ofꢀ THFꢀ withꢀ PhINTsꢀ
mightꢀ occurꢀ inꢀ aꢀ stepwiseꢀ mannerꢀ throughꢀ theꢀ sequentialꢀ
oxoniumꢀylideꢀintermediaciesꢀBꢀandꢀCꢀ(Schemeꢀ5,ꢀpathꢀb).ꢀInꢀ
bothꢀinstances,ꢀtheꢀeliminationꢀofꢀiodobenzeneꢀmightꢀaffordꢀ2-
tosylaminotetrahydrofuranꢀ D.ꢀ Underꢀ theꢀ basicꢀ conditionsꢀ
providedꢀ byꢀ theꢀ Grignardꢀ reagent,ꢀ deprotonationꢀ ofꢀ theꢀ
sulfonamideꢀ moietyꢀ ofꢀ theꢀ inꢀ situꢀ formedꢀ aminatedꢀ cyclicꢀ
adductꢀ mightꢀ resultꢀ inꢀ itsꢀ ring-openingꢀ toꢀ giveꢀ theꢀ 1,4-iminoꢀ
alcoholꢀ E.ꢀ Subsequentꢀ additionꢀ ofꢀ aꢀ secondꢀ moleculeꢀ ofꢀ theꢀ
Grignardꢀ reagentꢀ toꢀ theꢀ imineꢀ moietyꢀ ofꢀ thisꢀ newlyꢀ formedꢀ
putativeꢀintermediateꢀviaꢀtheꢀMg-coordinatedꢀspeciesꢀFꢀandꢀitsꢀ
aqueousꢀ work-upꢀ wouldꢀ provideꢀ theꢀ 4-substituted-4-
tosylamino-1-olꢀ productꢀ (Schemeꢀ 5,ꢀ pathꢀ c).ꢀ Forꢀ reactionsꢀ
leadingꢀtoꢀtheꢀformationꢀofꢀtheꢀ1,4-aminoꢀalcoholꢀ2,ꢀthisꢀcouldꢀ
beꢀ dueꢀ toꢀ aꢀ competingꢀ pathwayꢀ involvingꢀ singleꢀ electronꢀ
transferꢀ onꢀ exposingꢀ theꢀ Grignardꢀ reagentꢀ toꢀ intermediateꢀ Eꢀ
11
(
Schemeꢀ6b). ꢀInꢀmarkedꢀcontrast,ꢀrepeatingꢀtheꢀreactionꢀofꢀ1fꢀ
withꢀ ethylmagnesiumꢀ bromideꢀ wasꢀ foundꢀ toꢀ leadꢀ toꢀ theꢀ
recoveryꢀofꢀtheꢀN-tosyl-1,4-aminoꢀalcoholꢀinꢀnearꢀquantitativeꢀ
yieldꢀ(Schemeꢀ6c).ꢀ
1. PhINTs (0.5 mmol)
rt, 50 min
NHTs
NH2
HO
HO
+
(a)
O
2. PhMgBr (3.5 mmol)
rt, 18 h
Ph
1a
0% yield
Ph
2a
49% yield
4
NHTs PhMgBr (4 equiv)
NH2
HO
HO
HO
(
b)
c)
i-Bu
THF, rt, 18 h
Ph
1
f
2a
9
,10
(
Schemeꢀ5,ꢀpathꢀd). ꢀCollapseꢀofꢀtheꢀensuingꢀradical-amine-
35% yield
radicalꢀ cationꢀ pairꢀ Gꢀ couldꢀ giveꢀ theꢀ radicalꢀ speciesꢀ Hꢀ andꢀ R·,ꢀ
whichꢀonꢀrecombinationꢀwouldꢀprovideꢀtheꢀsubstitutedꢀadductꢀ
I;ꢀ onꢀ aqueousꢀ work-up,ꢀ thisꢀ intermediateꢀ wouldꢀ thenꢀ deliverꢀ
theꢀproductꢀ1.ꢀTheꢀpresenceꢀofꢀanꢀexcessꢀamountꢀofꢀtheꢀradicalꢀ
speciesꢀEꢀmightꢀresultꢀinꢀtheꢀ4-substituted-4-tosylamino-1-olꢀtoꢀ
undergoꢀaꢀsingleꢀelectronꢀtriggeredꢀN–Sꢀbondꢀcleavageꢀtoꢀ
NHTs
i-Bu
EtMgBr (4 equiv)
THF, rt, 18 h
NH2
HO
(
Et
1f
2d
0
% yield
ꢀ
Schemeꢀ6.ꢀControlꢀexperimentsꢀwithꢀTHFꢀandꢀ1fꢀ
Thisꢀjournalꢀisꢀ©ꢀTheꢀRoyalꢀSocietyꢀofꢀChemistryꢀ2015ꢀ
Org.ꢀBiomol.ꢀChem.,ꢀ2015,ꢀ00,ꢀ1-4ꢀ|ꢀ3ꢀꢀ
Pleaseꢀdoꢀnotꢀadjustꢀmarginsꢀ

Org aP nl ei ca s &e ꢀ dB oi oꢀ nmo to ꢀ al ed cj uu sl at ꢀrm Ca hr ge imn si sꢀ try
Page 4 of 5
ARTICLEꢀ
JournalꢀNameꢀ
5
N.ꢀRavasio,ꢀCatal.ꢀCommun.ꢀ2013,ꢀ40,ꢀ63-66;ꢀ(l)ꢀJ.ꢀWang,ꢀM.ꢀ
2,ꢀ5309-5313;ꢀꢀ(k)ꢀR.ꢀGava,ꢀA.ꢀBiffis,ꢀC.ꢀTubaro,VꢀiFew.ꢀZAartcicclehOenrliinae,ꢀ
DOI: 10.1039/C5OB02302E
Fringsꢀ andꢀ C.ꢀ Bolm,ꢀ Angew.ꢀ Chem.ꢀ Int.ꢀ Ed.ꢀ 2013,ꢀ 52,ꢀ 8661-
Conclusionsꢀ
Inꢀsummary,ꢀweꢀhaveꢀdevelopedꢀaꢀprotocolꢀtoꢀprepareꢀN-
tosyl-1,4-aminoꢀ alcoholsꢀ fromꢀ THF,ꢀ PhINTsꢀ andꢀ aꢀ Grignardꢀ
reagent.ꢀAccomplishedꢀinꢀgoodꢀtoꢀexcellentꢀproductꢀyields,ꢀtheꢀ
syntheticꢀmethodꢀwasꢀshownꢀtoꢀbeꢀapplicableꢀtoꢀaꢀwideꢀvarietyꢀ
ofꢀGrignardꢀreagentsꢀandꢀtheꢀsynthesisꢀofꢀ1,5-aminoꢀalcoholsꢀ
fromꢀTHP.ꢀTheꢀformationꢀofꢀtheꢀdetosylatedꢀ1,4-aminoꢀalcoholꢀ
adductꢀ alsoꢀ providedꢀ experimentalꢀ evidenceꢀ ofꢀ aꢀ competingꢀ
electronꢀtransferꢀpathwayꢀinꢀreactionsꢀinvolvingꢀtheꢀadditionꢀofꢀ
aꢀstericallyꢀbulkyꢀGrignardꢀreagent.ꢀFurtherꢀexplorationꢀonꢀtheꢀ
syntheticꢀ utilityꢀ ofꢀ theꢀ presentꢀ transformationꢀ isꢀ currentlyꢀ
underwayꢀandꢀwillꢀbeꢀreportedꢀinꢀdueꢀcourse.ꢀ
8665;ꢀ (m)ꢀ J.ꢀ Buendia,ꢀ B.ꢀ Darsesꢀ andꢀ P.ꢀ Dauban,ꢀ Angew.ꢀ
Chem.ꢀInt.ꢀEd.ꢀ2015,ꢀ54,ꢀ5697-5701.ꢀ
Selectedꢀ examplesꢀ ofꢀ transitionꢀ metal-free-mediatedꢀ
reactions:ꢀ (a)ꢀ B.-W.ꢀ Limꢀ andꢀ K.-H.ꢀ Ahn,ꢀ Synth.ꢀ Commun.ꢀ
4
1
996,ꢀ26,ꢀ3407-3412;ꢀ(b)ꢀJ.ꢀLi,ꢀP.ꢀW.ꢀH.ꢀChanꢀandꢀC.-M.ꢀChe,ꢀ
Org.ꢀLett.ꢀ2005,ꢀ7,ꢀ5801-5804;ꢀ(c)ꢀM.ꢀOchiai,ꢀT.ꢀKaneaki,ꢀN.ꢀ
Tada,ꢀK.ꢀMiyamoto,ꢀH.ꢀChuman,ꢀM.ꢀShiro,ꢀS.ꢀHayashiꢀandꢀW.ꢀ
Nakanishi,ꢀJ.ꢀAm.ꢀChem.ꢀSoc.,ꢀ2007,ꢀ129,ꢀ12938-12939;ꢀ(d)ꢀC.ꢀ
Fang,ꢀW.ꢀQianꢀandꢀW.ꢀBao,ꢀSynlettꢀ2008,ꢀ2529;ꢀ(e)ꢀM.ꢀOchiai,ꢀ
K.ꢀMiyamoto,ꢀS.ꢀHayashiꢀandꢀW.ꢀNakanishi,ꢀChem.ꢀCommun.,ꢀ
2
010,ꢀ46,ꢀ511-521;ꢀ(f)ꢀM.ꢀOchiai,ꢀK.ꢀMiyamoto,ꢀT.ꢀKaneaki,ꢀS.ꢀ
HayashiꢀandꢀW.ꢀNakanishi,ꢀScience,ꢀ2011,ꢀ332,ꢀ448-451;ꢀ(g)ꢀR.ꢀ
Kowalczyk,ꢀA.ꢀJ.ꢀF.ꢀEdmunds,ꢀR.ꢀG.ꢀHallꢀandꢀC.ꢀBolm,ꢀOrg.ꢀLett.ꢀ
2
011,ꢀ13,ꢀ768-771;ꢀ(h)ꢀD.-H.ꢀZhang,ꢀY.ꢀWeiꢀandꢀM.ꢀShi,ꢀEur.ꢀJ.ꢀ
Org.ꢀChem.ꢀ2011,ꢀ4940-4944;ꢀ(i)ꢀM.ꢀOchiai,ꢀS.ꢀYamane,ꢀM.ꢀM.ꢀ
Hoque,ꢀ M.ꢀ Saitoꢀ andꢀ K.ꢀ Miyamoto,ꢀ Chem.ꢀ Commun.,ꢀ 2012,ꢀ
48,ꢀ 5280-5282;ꢀ (j)ꢀ K.ꢀ Kiyokawa,ꢀ T.ꢀ Kosakaꢀ andꢀ S.ꢀ Minakata,ꢀ
Org.ꢀLett.ꢀ2013,ꢀ15,ꢀ4858-4861;ꢀ(k)ꢀC.ꢀTejo,ꢀH.ꢀQ.ꢀYeoꢀandꢀP.ꢀ
W.ꢀH.ꢀChan,ꢀSynlett,ꢀ2014,ꢀ25,ꢀ201-204;ꢀ(l)ꢀC.ꢀTejo,ꢀX.ꢀR.ꢀSim,ꢀ
B.ꢀR.ꢀLee,ꢀB.ꢀJ.ꢀAyers,ꢀC.-H.ꢀLeung,ꢀD.-L.ꢀMaꢀandꢀP.ꢀW.ꢀH.ꢀChan,ꢀ
Molecules,ꢀ2015,ꢀ20,ꢀ13336-13353.ꢀ
Acknowledgementsꢀ
Thisꢀworkꢀwasꢀsupportedꢀbyꢀstart-upꢀgrantsꢀfromꢀtheꢀSchoolꢀofꢀ
Chemistry,ꢀMonashꢀUniversity,ꢀandꢀDepartmentꢀofꢀChemistry,ꢀ
UniversityꢀofꢀWarwick,ꢀandꢀaꢀTierꢀ1ꢀ grantꢀ(MOE2013-T1-002-
0
35)ꢀfromꢀtheꢀMinistryꢀofꢀEducationꢀofꢀSingapore.ꢀ
5
Selectedꢀexamplesꢀfromꢀourꢀgroup:ꢀrefsꢀ4k,ꢀ4lꢀandꢀ(a)ꢀJ.ꢀW.ꢀ
W.ꢀChangꢀandꢀP.ꢀW.ꢀH.ꢀChan,ꢀAngew.ꢀChem.ꢀInt.ꢀEd.,ꢀ2008,ꢀ
47,ꢀ1138-1140;ꢀ(b)ꢀJ.ꢀW.ꢀW.ꢀChang,ꢀT.ꢀM.ꢀU.ꢀTon,ꢀS.ꢀTania,ꢀP.ꢀ
C.ꢀTaylorꢀandꢀP.ꢀW.ꢀH.ꢀChan,ꢀChem.ꢀCommun.,ꢀ2010,ꢀ46,ꢀ922-
Notesꢀandꢀreferencesꢀ
1
2
3
Selectedꢀreviews:ꢀ(a)ꢀT.ꢀHudlicky,ꢀD.ꢀA.ꢀEntwistle,ꢀK.ꢀK.ꢀPitzer,ꢀ
A.ꢀ J.ꢀ Thorpe,ꢀ Chem.ꢀ Rev.ꢀ 1996,ꢀ 96,ꢀ 1195-1220;ꢀ (b)ꢀ Y.ꢀ
Chapleur,ꢀ Carbohydrateꢀ Mimics–Conceptsꢀ andꢀ Methods,ꢀ
Wiley-VCH,ꢀWeinheim,ꢀ1998;ꢀ(c)ꢀE.ꢀS.ꢀelꢀAshry,ꢀN.ꢀRashed,ꢀA.ꢀ
H.ꢀ Shobier,ꢀ Pharmazie,ꢀ 2000,ꢀ 55,ꢀ 251-262;ꢀ (d)ꢀ F.ꢀ Velazquezꢀ
andꢀ H.ꢀ Olivo,ꢀ Curr.ꢀ Org.ꢀ Chem.,ꢀ 2002,ꢀ 6,ꢀ 303-340;ꢀ (e)ꢀ Z.ꢀ
Rappoport,ꢀ Theꢀ Chemistryꢀ ofꢀ Organozincꢀ Compounds,ꢀ Johnꢀ
WileyꢀandꢀSons,ꢀLtd,ꢀ2006;ꢀ(f)ꢀA.ꢀDelgado,ꢀEur.ꢀJ.ꢀOrg.ꢀChem.ꢀ
9
24;ꢀ(c)ꢀT.ꢀM.ꢀU.ꢀTon,ꢀC.ꢀTejo,ꢀS.ꢀTania,ꢀJ.ꢀW.ꢀW.ꢀChangꢀandꢀP.ꢀ
W.ꢀH.ꢀChan,ꢀJ.ꢀOrg.ꢀChem.,ꢀ2011,ꢀ76,ꢀ4894-4904;ꢀ(d)ꢀT.ꢀM.ꢀU.ꢀ
Ton,ꢀC.ꢀTejo,ꢀD.ꢀL.ꢀY.ꢀTiongꢀandꢀP.ꢀW.ꢀH.ꢀChan,ꢀJ.ꢀAm.ꢀChem.ꢀ
Soc.,ꢀ2012,ꢀ134,ꢀ7344-7350;ꢀ(e)ꢀT.ꢀM.ꢀU.ꢀTon,ꢀF.ꢀHimawan,ꢀJ.ꢀ
W.ꢀ W.ꢀ Changꢀ andꢀ P.ꢀ W.ꢀ H.ꢀ Chan,ꢀ Chem—Eur.ꢀ J.,ꢀ 2012,ꢀ 18,ꢀ
1
2020-12027.ꢀ
6
7
Selectedꢀ reviews:ꢀ (a)ꢀ V.ꢀ Capriati,ꢀ S.ꢀ Florioꢀ andꢀ R.ꢀ Luisi,ꢀ
Synlett,ꢀ 2005,ꢀ 1359-1369;ꢀ (b)ꢀ V.ꢀ Capriati,ꢀ S.ꢀ Florioꢀ andꢀ R.ꢀ
Luisi,ꢀChem.ꢀRev.,ꢀ2008,ꢀ108,ꢀ1918-1942;ꢀ(c)ꢀD.ꢀLeonoriꢀandꢀV.ꢀ
K.ꢀAggarwal,ꢀAcc.ꢀChem.ꢀRes.,ꢀ2014,ꢀ47,ꢀ3174-3183.ꢀ
Selectedꢀ recentꢀ examples:ꢀ (a)ꢀ P.ꢀ P.ꢀ Singh,ꢀ S.ꢀ Gudup,ꢀ S.ꢀ
Ambala,ꢀU.ꢀSingh,ꢀS.ꢀDadhwal,ꢀB.ꢀSingh,ꢀS.ꢀD.ꢀSawantꢀandꢀR.ꢀ
A.ꢀVishwakarma,ꢀChem.ꢀCommun.,ꢀ2011,ꢀ47,ꢀ5852-5854;ꢀ(b)ꢀ
P.ꢀP.ꢀSingh,ꢀS.ꢀGudup,ꢀH.ꢀAruri,ꢀU.ꢀSingh,ꢀS.ꢀAmbala,ꢀM.ꢀYadav,ꢀ
S.ꢀ D.ꢀ Sawantꢀ andꢀ R.ꢀ A.ꢀ Vishwakarma,ꢀ Org.ꢀ Biomol.ꢀ Chem.,ꢀ
2
008,ꢀ 3893-3906;ꢀ (g)ꢀ E.ꢀ J.ꢀ Corey;ꢀ L.ꢀ Kurtis,ꢀ Enantioselectiveꢀ
ChemicalꢀSynthesis:ꢀMethods,ꢀLogicꢀandꢀPractice,ꢀDirectꢀBookꢀ
Publishing,ꢀ2010;ꢀ(h)ꢀT.ꢀJ.ꢀDonohoe,ꢀC.ꢀK.ꢀA.ꢀCallens,ꢀA.ꢀR.ꢀLacyꢀ
andꢀC.ꢀWinter,ꢀEur.ꢀJ.ꢀOrg.ꢀChem.ꢀ2012,ꢀ655-663.ꢀ
Selectedꢀ reviews:ꢀ (a)ꢀ P.ꢀ Müllerꢀ andꢀ C.ꢀ Fruit,ꢀ Chem.ꢀ Rev.,ꢀ
2
Ed.,ꢀ 2006,ꢀ 45,ꢀ 6422-6425; (c)ꢀ H.ꢀ M.ꢀ L.ꢀ Daviesꢀ andꢀ J.ꢀ R.ꢀ
003,ꢀ103,ꢀ2905-2920;ꢀ(b)ꢀH.ꢀM.ꢀL.ꢀDavies,ꢀAngew.ꢀChem.ꢀInt.ꢀ
ꢀ
Manning,ꢀ Nature,ꢀ 2008,ꢀ 451,ꢀ 417-424;ꢀ (d)ꢀ M.ꢀ M.ꢀ Díaz-
RequejoꢀandꢀP.ꢀJ.ꢀPérez,ꢀChem.ꢀRev.,ꢀ2008,ꢀ108,ꢀ3379-3394;ꢀ
2
012,ꢀ 10,ꢀ 1587-1597;ꢀ (c)ꢀ R.ꢀ Mansueto,ꢀ V.ꢀ Mallardo,ꢀ F.ꢀ M.ꢀ
Perna,ꢀA.ꢀSalomoneꢀandꢀV.ꢀCapriati,ꢀChem.ꢀCommun.,ꢀ2013,ꢀ
9,ꢀ10160-10162;ꢀ(d)ꢀH.ꢀChristensen,ꢀT.ꢀHolmꢀandꢀR.ꢀMadsen,ꢀ
(
2
e)ꢀ F.ꢀ Collet,ꢀ R.ꢀ H.ꢀ Doddꢀ andꢀ P.ꢀ Dauban,ꢀ Chem.ꢀ Commun.,ꢀ
009,ꢀ5061-5074;ꢀ(f)ꢀJ.ꢀW.ꢀW.ꢀChang,ꢀT.ꢀM.ꢀU.ꢀTonꢀandꢀP.ꢀW.ꢀ
4
Tetrahedron,ꢀ2014,ꢀ70,ꢀ4942-4946;ꢀ(e)ꢀV.ꢀMallardo,ꢀR.ꢀRizzi,ꢀF.ꢀ
C.ꢀ Sassone,ꢀ R.ꢀ Mansueto,ꢀ F.ꢀ M.ꢀ Perna,ꢀ A.ꢀ Salomoneꢀ andꢀ V.ꢀ
Capriati,ꢀ Chem.ꢀ Commun.ꢀ 2014,ꢀ 50,ꢀ 8655-8658;ꢀ (f)ꢀ F.ꢀ C.ꢀ
Sassone,ꢀF.ꢀM.ꢀPerna,ꢀA.ꢀSalomone,ꢀS.ꢀFlorioꢀandꢀV.ꢀCapriatiꢀ
Chem.ꢀCommun.ꢀ2015,ꢀ51,ꢀ9459-9462.ꢀ
(a)ꢀM.ꢀHatanoꢀandꢀK.ꢀIshihara,ꢀSynthesis,ꢀ2008,ꢀ1647;ꢀ(b)ꢀA.ꢀV.ꢀ
R.ꢀ Madduri,ꢀ A.ꢀ J.ꢀ Minnaardꢀ andꢀ S.ꢀ R.ꢀ Harutyunyan,ꢀ Chem.ꢀ
Commun.,ꢀ2012,ꢀ48,ꢀ1478.ꢀ
(a)ꢀ C.ꢀ Walling,ꢀ Acc.ꢀ Chem.ꢀ Res.,ꢀ 1991,ꢀ 24,ꢀ 255-256;ꢀ (b)ꢀ N.ꢀ
Zhang,ꢀS.ꢀR.ꢀSamanta,ꢀB.ꢀM.ꢀRosenꢀandꢀV.ꢀPercec,ꢀChem.ꢀRev.,ꢀ
2
0 Selectedꢀ examples:ꢀ (a)ꢀ E.ꢀ C.ꢀ Ashbyꢀ andꢀ A.ꢀ B.ꢀ Goel,ꢀ J.ꢀ Am.ꢀ
Chem.ꢀSoc.,ꢀ1981,ꢀ103,ꢀ4983-4985;ꢀ(b) K.ꢀMaruyamaꢀandꢀT.ꢀ
Katagiri,ꢀ J.ꢀ Am.ꢀ Chem.ꢀ Soc.,ꢀ 1986,ꢀ 108,ꢀ 6263-6270;ꢀ (d)ꢀ H.ꢀ
Yamataka,ꢀM.ꢀShimizuꢀandꢀM.ꢀMishima,ꢀBull.ꢀChem.ꢀSoc.ꢀJpn.,ꢀ
H.ꢀ Chan,ꢀ Chem.ꢀ Rec.,ꢀ 2011,ꢀ 11,ꢀ 331-357;ꢀ (g)ꢀ F.ꢀ Collet,ꢀ C.ꢀ
LescotꢀandꢀP.ꢀDauban,ꢀChem.ꢀSoc.ꢀRev.,ꢀ2011,ꢀ40,ꢀ1926-1936;ꢀ
(
2
h)ꢀJ.ꢀL.ꢀRoizen,ꢀM.ꢀE.ꢀHarveyꢀandꢀJ.ꢀDuꢀBois,ꢀAcc.ꢀChem.ꢀRes.,ꢀ
012,ꢀ45,ꢀ911-922;ꢀ(i)ꢀG.ꢀDequirez,ꢀV.ꢀPonsꢀandꢀP.ꢀDauban,ꢀ
Angew.ꢀChem.ꢀInt.ꢀEd.ꢀ2012,ꢀ51,ꢀ7384-7395.ꢀ
8
9
1
Selectedꢀ examplesꢀ ofꢀ reactionsꢀ mediatedꢀ byꢀ aꢀ transitionꢀ
metalꢀcatalyst:ꢀ(a)ꢀL.ꢀHe,ꢀP.ꢀW.ꢀH.ꢀChan,ꢀW.-M.ꢀTsui,ꢀW.-Y.ꢀYu,ꢀ
andꢀ C.-M.ꢀ Che,ꢀ Org.ꢀ Lett.ꢀ 2004,ꢀ 6,ꢀ 2405-2408;ꢀ (b)ꢀ M.ꢀ R.ꢀ
Fructos,ꢀS.ꢀTrofimenko,ꢀM.ꢀM.ꢀDíaz-RequejoꢀandꢀP.ꢀJ.ꢀPérez,ꢀJ.ꢀ
Am.ꢀChem.ꢀSoc.ꢀ 2006,ꢀ128,ꢀ11784-11791;ꢀ(c)ꢀM.ꢀAnada,ꢀM.ꢀ
Tanaka,ꢀT.ꢀWashio,ꢀM.ꢀYamawaki,ꢀT.ꢀAbeꢀandꢀS.ꢀHashimoto,ꢀ
Org.ꢀLett.ꢀ2007,ꢀ9,ꢀ4559-4562;ꢀ(d)ꢀL.ꢀHe,ꢀJ.ꢀYu,ꢀJ.ꢀZhangꢀandꢀX.-
Q.ꢀYu,ꢀOrg.ꢀLett.,ꢀ2007,ꢀ9,ꢀ2277-2280;ꢀ(e)ꢀM.ꢀNakanishi,ꢀA.-F.ꢀ
SalitꢀandꢀC.ꢀBolm,ꢀAdv.ꢀSynth.ꢀCatal.ꢀ2008,ꢀ350,ꢀ1835-1840;ꢀ
014,ꢀ114,ꢀ5848-5958.ꢀ
(
(
f)ꢀY.ꢀLiuꢀandꢀC.-M.ꢀChe,ꢀChem.ꢀEur.ꢀJ.ꢀ2010,ꢀ16,ꢀ10494-10501;ꢀ
g)ꢀA.ꢀYoshimura,ꢀV.ꢀN.ꢀNemykinꢀandꢀV.ꢀV.ꢀZhdankin,ꢀChem.ꢀ
2
002,ꢀ 75,ꢀ 127-129;ꢀ (e)ꢀ T.ꢀ Ramnial,ꢀ S.ꢀ A.ꢀ Taylor,ꢀ J.ꢀ A.ꢀ C.ꢀ
Clyburneꢀ andꢀ C.ꢀ J.ꢀ Walsby,ꢀ Chem.ꢀ Commun.,ꢀ 2007,ꢀ 2066-
068.ꢀ
Eur.ꢀ J.ꢀ 2011,ꢀ 17,ꢀ 10538-10541;ꢀ (h)ꢀ L.ꢀ Maestre,ꢀ W.ꢀ M.ꢀ C.ꢀ
Sameera,ꢀM.ꢀM.ꢀDíaz-Requejo,ꢀF.ꢀMaserasꢀandꢀP.ꢀJ.ꢀPérez,ꢀJ.ꢀ
Am.ꢀ Chem.ꢀ Soc.ꢀ 2012,ꢀ 135,ꢀ 1338-1348;ꢀ (i)ꢀ Á.ꢀ Beltrán,ꢀ C.ꢀ
Lescot,ꢀ M.ꢀ M.ꢀ Díaz-Requejo,ꢀ P.ꢀ J.ꢀ Pérezꢀ andꢀ P.ꢀ Dauban,ꢀ
Tetrahedronꢀ2013,ꢀ69,ꢀ4488-4492;ꢀ(j)ꢀL.-M.ꢀJin,ꢀX.ꢀXu,ꢀH.ꢀLu,ꢀX.ꢀ
Cui,ꢀL.ꢀWojtasꢀandꢀX.ꢀP.ꢀZhang,ꢀAngew.ꢀChem.ꢀInt.ꢀEd.ꢀ2013,ꢀ
2
1
1 Selectedꢀexamples:ꢀ(a)ꢀR.ꢀM.ꢀRoberts,ꢀE.ꢀK.ꢀBaylisꢀandꢀG.ꢀJ.ꢀ
Fonken,ꢀ J.ꢀ Am.ꢀ Chem.ꢀ Soc.,ꢀ 1963,ꢀ 85,ꢀ 3454-3458;ꢀ (b)ꢀ S.ꢀ
Fukuzumi,ꢀJ.ꢀK.ꢀKochi,ꢀJ.ꢀOrg.ꢀChem.,ꢀ1980,ꢀ45,ꢀ2654-2662;ꢀ(c)ꢀ
4
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ꢀARTICLEꢀ
D.ꢀA.ꢀRobaugh,ꢀB.ꢀD.ꢀBartonꢀandꢀS.ꢀE.ꢀStein,ꢀJ.ꢀPhys.ꢀChem.,ꢀ
981,ꢀ85,ꢀ2378-2383.ꢀ
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DOI: 10.1039/C5OB02302E
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