Access to N-cyanosulfoximines by transition metal-free iminations of sulfoxides

Article abstract of DOI:10.1039/c6ob02691e

A transition metal-free synthesis of N-cyanosulfoximines from sulfoxides using N-chlorosuccinimide (NCS) as oxidising agent and cyanamide as nucleophilic amine source is reported. The products are obtained in moderate to excellent yields. The protocol enables an easy access to N-cyanosulfoximines from readily available starting materials under inversion of configuration at a preexisting stereogenic center.

Full text of DOI:10.1039/c6ob02691e

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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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Organic & Biomolecular Chemistry
View Article Online
DOI: 10.1039/C6OB02691E
JournalꢀNameꢀ
COMMUNICATIONꢀ
ꢀ
AccessꢀtoꢀN-CyanosulfoximinesꢀbyꢀTransitionꢀMetal-Freeꢀ
IminationsꢀofꢀSulfoxidesꢀ
Receivedꢀ00thꢀJanuaryꢀ20xx,ꢀ
Acceptedꢀ00thꢀJanuaryꢀ20xxꢀ
C.ꢀA.ꢀDannenberg,ꢀL.ꢀFritze,ꢀF.ꢀKrauskopfꢀandꢀC.ꢀBolmꢀ*
DOI:ꢀ10.1039/x0xx00000xꢀ
www.rsc.org/ꢀ
Me
O
Aꢀ transitionꢀ metal-freeꢀ synthesisꢀ ofꢀ N-cyanosulfoximinesꢀ fromꢀ
sulfoxidesꢀusingꢀN-chlorosuccinimideꢀ(NCS)ꢀasꢀoxidisingꢀagentꢀandꢀ
cyanamideꢀasꢀnucleophilicꢀamineꢀsourceꢀisꢀreported.ꢀTheꢀproductsꢀ
areꢀobtainedꢀinꢀmoderateꢀtoꢀexcellentꢀyields.ꢀTheꢀprotocolꢀenablesꢀ
anꢀ easyꢀ accessꢀ toꢀ N-cyanosulfoximinesꢀ fromꢀ readilyꢀ availableꢀ
startingꢀmaterialsꢀunderꢀinversionꢀofꢀconfigurationꢀatꢀaꢀpreexistingꢀ
stereogenicꢀcenter.ꢀ
Me
N
O
NH
S
S
CO2H
CN
Me
F3C
N
NH2
MSO (1)
Sulfoxaflor (2)
O
N
Me
N
N
N
OMe
Sinceꢀ theirꢀ discoveryꢀ inꢀ theꢀ 1940s,ꢀ sulfoximinesꢀ representꢀ aꢀ
steadilyꢀ diversifyingꢀ classꢀ ofꢀ compoundsꢀ exhibitingꢀ highlyꢀ
HN
Me
O
N
S
HN
O
N
NH
S
H
1-4
N
Me
interestingꢀbioactivities. ꢀBeingꢀidentifiedꢀasꢀtheꢀresponsibleꢀ
biotoxicꢀ agentꢀ forꢀ canineꢀ hysteria,ꢀ methionineꢀ sulfoximineꢀ
F
N
BAY 1143572 (3)
AZD6738 (4)
(
reported. ꢀ Subsequently,ꢀ sulfoximinesꢀ haveꢀ mostlyꢀ beenꢀ
MSO,ꢀ1)ꢀwasꢀtheꢀfirstꢀrepresentativeꢀofꢀsuchꢀmoleculesꢀeverꢀ
5
ꢀ
6,7
employedꢀ inꢀ asymmetricꢀ synthesis. ꢀ Moreꢀ recently,ꢀ theirꢀ
potentialꢀ inꢀ pesticideꢀ researchꢀ andꢀ medicinalꢀ chemistryꢀ hasꢀ Fig.ꢀ1ꢀProminentꢀbioactiveꢀsulfoximines.ꢀ
1-4
beenꢀrecognised, ꢀwhereꢀsulfoximinesꢀofferꢀadvantagesꢀoverꢀ
theirꢀnon-azaꢀanalogues,ꢀsulfones,ꢀdueꢀtoꢀtheirꢀsolubilityꢀandꢀ trifluoroacetamide.ꢀ Subsequentꢀ oxidationꢀ andꢀ concurrentꢀ
ꢀ
11
theirꢀ potentialꢀ forꢀ structuralꢀ diversificationꢀ throughꢀ nitrogenꢀ deprotectionꢀwithꢀOxone
®
ꢀthenꢀprovidesꢀNH-sulfoximines. ꢀIfꢀ
N-methylsulfoximinesꢀ areꢀ targeted,ꢀ aꢀ one-potꢀ protocolꢀ byꢀ
Examplesꢀ ofꢀ bioactiveꢀ sulfoximinesꢀ areꢀ theꢀ insecticideꢀ sequentialꢀ imination/oxidationꢀ withꢀ methylamine,ꢀ bromineꢀ
6a,8
substitutionꢀ atꢀ theꢀ stableꢀ stereogenicꢀ sulfurꢀ center.
ꢀ
4
12ꢀ
Sulfoxaflorꢀ (2) ꢀ andꢀ theꢀ twoꢀ potentꢀ enzymeꢀ inhibitorsꢀ andꢀ potassiumꢀ permanganateꢀ canꢀ beꢀ applied. Theꢀ secondꢀ
1,2c
2d
BAYꢀ1143572ꢀ (3) ꢀ andꢀ AZD6738ꢀ (4) ,ꢀ whichꢀ haveꢀ beenꢀ routeꢀ towardsꢀ sulfoximinesꢀ (Schemeꢀ 1,ꢀ pathꢀ B)ꢀ reversesꢀ theꢀ
promotedꢀtoꢀclinicalꢀtrialsꢀ(Fig.ꢀ1).ꢀ
imination/oxidationꢀ order.ꢀ Alsoꢀ forꢀ thisꢀ pathway,ꢀ whichꢀ
Forꢀ accessingꢀ sulfoximinesꢀ fromꢀ theirꢀ correspondingꢀ sulfidesꢀ involvesꢀ aꢀ sulfoxideꢀ imination,ꢀ severalꢀ methodsꢀ haveꢀ beenꢀ
9
twoꢀgeneralꢀpathwaysꢀcanꢀbeꢀdistinguishedꢀ(Schemeꢀ1,ꢀpathꢀAꢀ described. ꢀMostꢀofꢀthemꢀrelyꢀonꢀtheꢀuseꢀofꢀaꢀtransitionꢀmetalꢀ
9
13
14
7b,15
16
ꢀrhodium, ꢀ
andꢀpathꢀB). ꢀTheꢀfirstꢀoneꢀproceedsꢀbyꢀsulfideꢀiminationꢀandꢀ catalystꢀ(basedꢀonꢀiron, ꢀcopper, ꢀruthenium,
17 18
subsequentꢀ oxidationꢀ ofꢀ theꢀ initiallyꢀ formedꢀ sulfilimineꢀ (pathꢀ silver ) ꢀandꢀutiliseꢀamineꢀsourcesꢀsuchꢀasꢀazidesꢀorꢀrelatedꢀ
A).ꢀ Alongꢀ thoseꢀ linesꢀ weꢀ haveꢀ reportedꢀ theꢀ useꢀ ofꢀ aꢀ nitrene-formingꢀagentsꢀinꢀcombinationꢀwithꢀhypervalentꢀiodineꢀ
19ꢀ
combinationꢀ ofꢀ N-bromosuccinimideꢀ (NBS),ꢀ potassiumꢀ tert- species.
butoxideꢀ(KOtBu)ꢀandꢀcyanamideꢀforꢀtheꢀfirstꢀstepꢀfollowedꢀbyꢀ iminationsꢀ areꢀ alsoꢀ known,
sulfilimineꢀ oxidationꢀ withꢀ meta-chloroperbenzoicꢀ acidꢀ (m- theꢀ aforementionedꢀ criticalꢀ reagentsꢀ withꢀ respectꢀ toꢀ theꢀ
Transitionꢀ metal-freeꢀ methodsꢀ forꢀ sulfoxideꢀ
20-25
ꢀ howeverꢀ allꢀ ofꢀ themꢀ employꢀ
10
CPBA). ꢀAlternatively,ꢀtheꢀsulfideꢀiminationꢀcanꢀbeꢀperformedꢀ nitrogenꢀ sourceꢀ andꢀ theꢀ oxidantꢀ hamperingꢀ theirꢀ syntheticꢀ
ꢀ
24,25
withꢀ1,3-dibromo-5,5-dimethylhydantoinꢀ(DBDMH)ꢀandꢀ
applicability,ꢀ inꢀ particular,ꢀ onꢀ largeꢀ scale.
ꢀ Basedꢀ onꢀ thisꢀ
analysis,ꢀ weꢀ consideredꢀ findingꢀ aꢀ newꢀ sulfoxideꢀ iminationꢀ
processꢀwithꢀsimpleꢀ(harmless,ꢀnon-toxic,ꢀlow-cost)ꢀreagentsꢀasꢀ
topꢀ priority.ꢀ N-Cyanosulfoximinesꢀ appearedꢀ particularlyꢀ
a.
InstituteꢀofꢀOrganicꢀChemistry,ꢀRWTHꢀAachenꢀUniversity,ꢀLandoltwegꢀ1,ꢀ
ꢀD-52074ꢀAachen,ꢀGermany.ꢀE-mail:ꢀcarsten.bolm@oc.rwth-aachen.de;ꢀꢀ
ꢀFax:ꢀ+49ꢀ241ꢀ80ꢀ92ꢀ391;ꢀTel:ꢀ+49ꢀ24ꢀ80ꢀ94ꢀ675.ꢀ
3b,4
attractiveꢀ becauseꢀ ofꢀ theirꢀ occurrenceꢀ asꢀ bioactives ꢀ andꢀ
ꢀ
ꢀ
10
theirꢀ relevanceꢀ asꢀ intermediatesꢀ towardsꢀ NH-sulfoximines ꢀ
26
andꢀrelatedꢀderivatives. ꢀTheꢀresultsꢀofꢀourꢀsearchꢀandꢀ
†
ꢀFootnotesꢀrelatingꢀtoꢀtheꢀtitleꢀand/orꢀauthorsꢀshouldꢀappearꢀhere.ꢀꢀ
ElectronicꢀSupplementaryꢀInformationꢀ(ESI)ꢀavailable:ꢀ[detailsꢀofꢀanyꢀsupplementaryꢀ
informationꢀavailableꢀshouldꢀbeꢀincludedꢀhere].ꢀSeeꢀDOI:ꢀ10.1039/x0xx00000xꢀ
Thisꢀjournalꢀisꢀ©ꢀTheꢀRoyalꢀSocietyꢀofꢀChemistryꢀ20xxꢀ
J.ꢀName.,ꢀ2013,ꢀ00,ꢀ1-3ꢀ|ꢀ1ꢀꢀ
Pleaseꢀdoꢀnotꢀadjustꢀmarginsꢀ

Organic & Biomolecular Chemistry
Page 2 of 5
COMMUNICATIONꢀ
JournalꢀNameꢀ
aꢀ
ꢀ
ꢀ
Tableꢀ1ꢀScreeningꢀofꢀoxidantꢀandꢀbase
ꢀ
View Article Online
DOI: 10.1039/C6OB02691E
1
. sulfide to sulfilimine imination
. sulfilimine to sulfoximine oxidation
O
S
base (2.0 equiv.)
O
N
CN
O
O
Path A
S
S
H NCN (2.0 equiv.)
2
Me
2
Me
Me
O
N
R3
S
oxidant (4.0 equiv.)
MeOH, rt, 2 h
R1
R2
S
R1
R2
5
a
6a
7
1
. sulfide to sulfoxide oxidation
. sulfoxide to sulfoximine imination
ꢀ
Path B
2
ꢀ
Baseꢀ
bꢀ
This work For step 2 of path B (with R3 = CN):
Entryꢀ
Oxidantꢀ
Yieldꢀ(%)
use of H2NCN, NCS, KOtBu in H2O, rt, 2 h
1ꢀ
NCSꢀ
KOtBuꢀ
KOtBuꢀ
KOtBuꢀ
KOtBuꢀ
77ꢀ
ꢀ
2
ꢀ
DCDMHꢀ
NBSꢀ
55ꢀ
ꢀ
Schemeꢀ1ꢀSulfideꢀtoꢀsulfoximineꢀconversions.ꢀ
3ꢀ
4ꢀ
5ꢀ
6ꢀ
Traceꢀ
Traceꢀ
40ꢀ
ꢀ
ꢀ
DBDMHꢀ
Trichloroisocyanuricꢀacidꢀ KOtBuꢀ
developmentꢀ areꢀ reportedꢀ hereꢀ (Schemeꢀ 1,ꢀ pathꢀ B,ꢀ lowerꢀ
part).ꢀꢀ
NCSꢀ
NCSꢀ
NCSꢀ
NCSꢀ
NCSꢀ
NCSꢀ
NCSꢀ
NCSꢀ
NCSꢀ
NCSꢀ
-ꢀ
NaOAcꢀ
Cs CO
Et
n.r.ꢀ
n.r.ꢀ
n.r.ꢀ
60ꢀ
7
8
9
1
1
1
1
1
1
1
aꢀ
ꢀ
2
3
ꢀ
ꢀ
Forꢀ theꢀ initialꢀ reactivityꢀ screening,ꢀ methylphenylsulfoxideꢀ
5a)ꢀ wasꢀ selectedꢀ asꢀ startingꢀ material.ꢀ Targetingꢀ N-cyano-
ꢀ
3
Nꢀ
CO
PO
(
ꢀ
K
K
2
3
3
4
ꢀ
sulfoximineꢀ6aꢀasꢀproduct,ꢀcyanamideꢀwasꢀregardedꢀasꢀoptimalꢀ
nitrogenꢀsource.ꢀAlthoughꢀtheꢀstandardꢀproceduresꢀforꢀsulfideꢀ
iminationsꢀ provedꢀ largelyꢀ unsuitableꢀ forꢀ convertingꢀ sulfoxideꢀ
0ꢀ
1ꢀ
2ꢀ
3ꢀ
ꢀ
56ꢀ
NaOMeꢀ
NaOtBuꢀ
KOHꢀ
34ꢀ
38ꢀ
5
a,ꢀsmallꢀquantitiesꢀofꢀ6aꢀwereꢀdetectedꢀwhenꢀNBS,ꢀDBDMH,ꢀ
75ꢀ
orꢀ trichloroisocyanuricꢀ acidꢀ wereꢀ usedꢀ asꢀ oxidants.ꢀ Theꢀ
subsequentꢀ optimisationꢀ studiesꢀ includedꢀ variationsꢀ ofꢀ theꢀ
base,ꢀ theꢀ solvent,ꢀ andꢀ theꢀ temperatureꢀ andꢀ additionalꢀ
applicationsꢀ ofꢀ theꢀ chlorine-basedꢀ oxidantsꢀ NCSꢀ andꢀ 1,3-
cꢀ
4
KOtBuꢀ
-ꢀ
37ꢀ
5ꢀ
6ꢀ
n.r.ꢀ
n.r.ꢀ
KOtBuꢀ
27
dichloro-5,5-dimethylhydantoinꢀ (DCDMH). ꢀ Theꢀ resultsꢀ
obtainedꢀfromꢀreactionsꢀperformedꢀinꢀmethanolꢀasꢀsolventꢀatꢀ
ambientꢀtemperatureꢀforꢀ2ꢀhꢀareꢀsummarisedꢀinꢀTableꢀ1.ꢀ
Reactionsꢀ wereꢀ performedꢀ withꢀ 5aꢀ (0.20ꢀ mmol),ꢀ baseꢀ (0.40ꢀmmol),ꢀ
b
cyanamideꢀ (0.40ꢀmmol),ꢀ oxidantꢀ (0.80ꢀmmol),ꢀ MeOHꢀ (1ꢀmL).ꢀ ꢀ n.r.ꢀ =ꢀ noꢀ
cꢀ
reaction.ꢀ AdditionꢀofꢀNCSꢀ10ꢀminꢀbeforeꢀadditionꢀofꢀbaseꢀandꢀcyanamide.ꢀꢀ
ꢀ
Toꢀourꢀdelight,ꢀtheꢀiminationꢀprotocolꢀcouldꢀsignificantlyꢀbeꢀ
ꢀ
improved,ꢀandꢀaꢀmajorꢀadvanceꢀwasꢀachievedꢀwhenꢀNCSꢀwasꢀ
usedꢀasꢀoxidant,ꢀwhichꢀprovedꢀsuperiorꢀtoꢀallꢀotherꢀoxidisingꢀ
concurrentꢀ presenceꢀ ofꢀ allꢀ reagentsꢀ andꢀ theirꢀ inꢀ situꢀ
selfsorting.ꢀꢀ
28
agentsꢀ(Tableꢀ1,ꢀentriesꢀ1-5). ꢀInꢀthisꢀmannerꢀandꢀwithꢀKOtBuꢀ
asꢀbase,ꢀsulfoximineꢀ6aꢀwasꢀobtainedꢀinꢀ77%ꢀyield.ꢀ
ꢀ
Realisingꢀ thatꢀ theꢀ counterionꢀ ofꢀ theꢀ baseꢀ playedꢀ suchꢀ aꢀ
majorꢀ role,ꢀ weꢀ wonderedꢀ aboutꢀ solvationꢀ effects.ꢀ Hence,ꢀ aꢀ
rangeꢀ ofꢀ solventsꢀ wasꢀ testedꢀ nextꢀ (Tableꢀ 2).ꢀ Whileꢀ noꢀ
conversionꢀ ofꢀ 5aꢀ wasꢀ observedꢀ inꢀ reactionsꢀ performedꢀ inꢀ
toluene,ꢀ DCM,ꢀ DCE,ꢀ diethylꢀ ether,ꢀ andꢀ trifluoroethanol,ꢀ theꢀ
previouslyꢀ appliedꢀ methanolꢀ couldꢀ beꢀ substitutedꢀ byꢀ severalꢀ
otherꢀ polarꢀ solvents.ꢀ Thus,ꢀ formationꢀ ofꢀ 6aꢀ wasꢀ observedꢀ inꢀ
ethylꢀacetateꢀandꢀTHF,ꢀbutꢀdueꢀtoꢀincompleteꢀconversionꢀofꢀ5aꢀ
andꢀ theꢀ generationꢀ ofꢀ sideꢀ productsꢀ theꢀ resultsꢀ wereꢀ
unsatisfyingꢀ(Tableꢀ2,ꢀentriesꢀ1ꢀandꢀ2).ꢀReactionsꢀinꢀacetonitrileꢀ
andꢀethanolꢀwereꢀalmostꢀasꢀgoodꢀasꢀinꢀmethanolꢀ(77%ꢀyield),ꢀ
providingꢀ 6aꢀ inꢀ 66%ꢀ andꢀ 62%ꢀ yield,ꢀ respectivelyꢀ (Tableꢀ 2,ꢀ
entriesꢀ3-5).ꢀWaterꢀprovedꢀtoꢀbeꢀsuperiorꢀtoꢀallꢀotherꢀsolventsꢀ
leadingꢀtoꢀ6aꢀinꢀ89%ꢀyieldꢀ(Tableꢀ2,ꢀentryꢀ6).ꢀFinally,ꢀadjustingꢀ
theꢀ reagentꢀ amountsꢀ (Tableꢀ 2,ꢀ entriesꢀ 6-9)ꢀ andꢀ applyingꢀ
equimolarꢀ quantitiesꢀ ofꢀ base,ꢀ amineꢀ andꢀ oxidantꢀ (2.0ꢀ equiv.ꢀ
each)ꢀallowedꢀisolatingꢀsulfoximineꢀ6aꢀinꢀ93%ꢀyield.ꢀUsingꢀKOHꢀ
insteadꢀ ofꢀ KOtBuꢀ wasꢀ possibleꢀ too,ꢀ givingꢀ 6aꢀ inꢀ 85%ꢀ yieldꢀ
ꢀ
Twoꢀmoreꢀfactorsꢀprovedꢀcritical:ꢀTheꢀtypeꢀofꢀbaseꢀandꢀtheꢀ
orderꢀofꢀreagentꢀformationꢀandꢀaddition.ꢀThusꢀcombinationsꢀofꢀ
NCSꢀwithꢀsodiumꢀacetate,ꢀcesiumꢀcarbonate,ꢀorꢀtriethylamineꢀ
wereꢀunsuitableꢀandꢀdidꢀnotꢀleadꢀtoꢀproductꢀformationꢀ(Tableꢀ
1
,ꢀentriesꢀ6-8).ꢀInꢀcontrast,ꢀwithꢀK2CO3,ꢀK3PO4,ꢀNaOMe,ꢀNaOtBuꢀ
orꢀKOHꢀasꢀbase,ꢀNCSꢀprovidedꢀ6a,ꢀalbeitꢀinꢀlowerꢀyieldsꢀasꢀwithꢀ
KOtBuꢀ (Tableꢀ 1,ꢀ entriesꢀ 1,ꢀ 9-13).ꢀ Asꢀ theꢀ detailsꢀ inꢀ theꢀ seriesꢀ
reveal,ꢀ theꢀ strengthꢀ ofꢀ theꢀ baseꢀ asꢀ wellꢀ asꢀ theꢀ cationꢀ typeꢀ
+
+
(
with,ꢀ forꢀ example,ꢀ K ꢀ beingꢀ superiorꢀ overꢀ Na )ꢀ playedꢀ aꢀ
significantꢀ role.ꢀ Theꢀ importanceꢀ ofꢀ reagentꢀ formationꢀ andꢀ
additionꢀ sequenceꢀ wasꢀ indicatedꢀ byꢀ theꢀ followingꢀ
observations:ꢀ Ifꢀ NCSꢀ wasꢀ addedꢀ toꢀ theꢀ sulfoxideꢀ beforeꢀ
cyanamideꢀandꢀKOtBu,ꢀtheꢀyieldꢀofꢀ6aꢀwasꢀsignificantlyꢀlowerꢀ
andꢀsubstantialꢀamountsꢀofꢀsulfoneꢀ7ꢀwereꢀdetectedꢀ(Tableꢀ1,ꢀ
entryꢀ14).ꢀBothꢀNCSꢀandꢀKOtBuꢀwereꢀcrucialꢀforꢀtheꢀiminationꢀ
ofꢀ 5a,ꢀ andꢀ inꢀ theꢀ absenceꢀ ofꢀ eitherꢀ ofꢀ theseꢀ reagents,ꢀ noꢀ
productꢀwasꢀformedꢀ(Tableꢀ1,ꢀentriesꢀ15ꢀandꢀ16).ꢀFromꢀtheseꢀ
resultsꢀ weꢀ concludeꢀ thatꢀ theꢀ iminationꢀ proceedsꢀ viaꢀ
deprotonatedꢀcyanamide,ꢀwhichꢀreactsꢀwithꢀanꢀNCS-activatedꢀ
sulfoxide.ꢀThus,ꢀtheꢀsuccessꢀofꢀtheꢀreactionꢀdependsꢀonꢀtheꢀ
ꢀ
(Tableꢀ 2,ꢀ entryꢀ 10).ꢀ Higherꢀ temperaturesꢀ ledꢀ toꢀ lowerꢀ yields,ꢀ
performingꢀtheꢀiminationꢀatꢀ0ꢀ°Cꢀincreasedꢀtheꢀyieldꢀofꢀ6aꢀonlyꢀ
insignificantlyꢀ(toꢀ95%;ꢀTableꢀ2,ꢀentriesꢀ11-13).ꢀꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
2
ꢀ|ꢀJ.ꢀName.,ꢀ2012,ꢀ00,ꢀ1-3ꢀ
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Organic & Biomolecular Chemistry
JournalꢀNameꢀ
Tableꢀ 2ꢀ Optimisationꢀ ofꢀ solvent,ꢀ stoichiometryꢀ andꢀ Tableꢀ3ꢀEvaluationꢀofꢀtheꢀsubstrateꢀscope ꢀ
ꢀCOMMUNICATIONꢀ
a
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aꢀ
DOI: 10.1039/C6OB02691E
temperature
ꢀ
ꢀ
2
H NCN (2.0 equiv.)
O
S
O
S
KOtBu (2.0 equiv.)
O
N
CN
O
N CN
S
KOtBu, H NCN
2
S
R
1
R
2
R
1
R
2
Me
Me
NCS (2.0 equiv.)
NCS, solvent
Temp., 2 h
5
2
H O, rt, 2 h
6
ꢀ
5
a
6a
ꢀ
ꢀ
O
NCN
Me
O
NCN
Me
O
NCN
Me
O
NCN
Me
Equiv.ꢀofꢀbase/ꢀ
bꢀ
S
S
S
S
Entryꢀ
Solventꢀ
Temp.ꢀ(°C)ꢀ
Yieldꢀ(%)
amine/oxidantꢀ
1
2
3
4
5
6
7
8
9
1
1
1
1
aꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ethylꢀacetateꢀ 2.0/2.0/4.0ꢀ
rtꢀ
rtꢀ
rtꢀ
rtꢀ
rtꢀ
rtꢀ
rtꢀ
rtꢀ
rtꢀ
rtꢀ
100ꢀ
50ꢀ
0ꢀ
n.d.ꢀ
n.d.ꢀ
66ꢀ
62ꢀ
77ꢀ
89ꢀ
39ꢀ
79ꢀ
93ꢀ
85ꢀ
59ꢀ
75ꢀ
95ꢀ
Me
MeO
Cl
6
a, 93% (86%)b
6b, 98%
6c, 98%
6d, 88%
THFꢀ
2.0/2.0/4.0ꢀ
2.0/2.0/4.0ꢀ
2.0/2.0/4.0ꢀ
2.0/2.0/4.0ꢀ
2.0/2.0/4.0ꢀ
1.0/2.0/2.0ꢀ
1.5/1.5/1.5ꢀ
2.0/2.0/2.0ꢀ
2.0/2.0/2.0ꢀ
2.0/2.0/2.0ꢀ
2.0/2.0/2.0ꢀ
2.0/2.0/2.0ꢀ
MeCNꢀ
EtOHꢀ
MeOHꢀ
Br
O
F
O
NCN
Me
O
NCN
Me
NCN
O
NCN
S
Br
S
S
S
Me
Me
6h 54%c
NCN
Br
H
2
H
2
H
2
H
2
H
2
H
2
H
2
H
2
Oꢀ
Oꢀ
Oꢀ
Oꢀ
Oꢀ
Oꢀ
Oꢀ
Oꢀ
6e, 85%
6f, 71%
6g, n.r.
O
NCN
Me
O
NCN
Me
O
O
S
NCN
Me
S
S
S
Me
Me
N
c
OHC
0 ꢀ
1ꢀ
2ꢀ
3ꢀ
2
O N
i, 31%c
O
6
6j, 67%
6k, 54%
6l, 69%
O
NCN
O
NCN
O
NCN
O
NCN
S
S
S
S
Reactionsꢀ wereꢀ performedꢀ withꢀ 5aꢀ (0.20ꢀ mmol),ꢀ base,ꢀ cyanamide,ꢀ oxidant,ꢀ
b
solventꢀ(1ꢀmL).ꢀ ꢀn.d.ꢀ=ꢀnotꢀdetermined.ꢀ ꢀUseꢀofꢀKOHꢀinsteadꢀofꢀKOtBuꢀasꢀbase.ꢀ
c
6n, 55%c
6p, 15%c
6m, 78%
6o, n.r.
ꢀ
ꢀ
O
NCN
O
NCN
O
NCN
O
NCN
Me
S
S
S
Takingꢀ allꢀ resultsꢀ intoꢀ account,ꢀ theꢀ subsequentꢀ substrateꢀ
screeningꢀ wasꢀ performedꢀ withꢀ anꢀ equimolarꢀ amountꢀ ofꢀ
cyanamide,ꢀKOtBu,ꢀandꢀNCSꢀ(2.0ꢀequiv.ꢀeach)ꢀinꢀwaterꢀatꢀroomꢀ
temperatureꢀ forꢀ 2ꢀ h.ꢀ Underꢀ theseꢀ optimisedꢀ reactionꢀ
conditions,ꢀ variousꢀ sulfoxidesꢀ 5a-tꢀ wereꢀ appliedꢀ (Tableꢀ 3).ꢀ S-
Me
S
Me
N
6q, 17%
6r, 48%c
6s, 50%
6t, 23%d
ꢀ
ꢀ
aꢀ
Reactionsꢀ wereꢀ performedꢀ onꢀ aꢀ 0.20ꢀ mmolꢀ scaleꢀ inꢀ H Oꢀ (1ꢀmL).ꢀ n.r.ꢀ =ꢀ noꢀ
2
b
Aryl-S-methylꢀ derivativesꢀ withꢀ electron-donatingꢀ substituentsꢀ reaction.ꢀ ꢀInꢀparentheses,ꢀyieldꢀofꢀ6aꢀobtainedꢀinꢀaꢀreactionꢀonꢀaꢀ50ꢀmmolꢀscale.ꢀ
c
onꢀ theꢀ areneꢀ gaveꢀ veryꢀ goodꢀ toꢀ excellentꢀ yieldsꢀ ofꢀ theꢀ ꢀIsolatedꢀproductꢀcontainsꢀsmallꢀamountsꢀ(<5%)ꢀofꢀimpuritiesꢀ(suchꢀasꢀsolvents).ꢀ
d
correspondingꢀ N-cyanosulfoximinesꢀ 6a-f.ꢀ Presumablyꢀ dueꢀ toꢀ ꢀYieldꢀofꢀ6tꢀobtainedꢀinꢀaꢀreactionꢀonꢀaꢀ5ꢀmmolꢀscale.ꢀ
stericꢀ reasons,ꢀ noꢀ reactionꢀ wasꢀ observedꢀ withꢀ ortho-bromo-
substitutedꢀ sulfoxideꢀ 5g.ꢀ Inꢀ contrast,ꢀ theꢀ analogousꢀ ortho-
ꢀ
desiredꢀproductꢀ6aꢀinꢀ86%ꢀyield.ꢀFinally,ꢀaꢀone-potꢀprocedureꢀ
fluoroꢀ derivativeꢀ gaveꢀ sulfoximineꢀ 6hꢀ inꢀ 54%ꢀ yield.ꢀ S-Methylꢀ
forꢀdirectꢀconversionsꢀofꢀsulfidesꢀtoꢀN-cyanosulfoximinesꢀ6ꢀviaꢀ
sulfoxidesꢀ5i-kꢀwithꢀelectron-withdrawingꢀarylꢀsubstituentsꢀledꢀ
sulfoxidesꢀ 5ꢀ wasꢀ developedꢀ (Schemeꢀ 2,ꢀ top,ꢀ andꢀ ESI).ꢀ Asꢀ
toꢀtheꢀcorrespondingꢀproductsꢀ6i-kꢀinꢀmoderateꢀtoꢀgoodꢀyields.ꢀ
demonstratedꢀforꢀtheꢀreactionꢀofꢀmethylphenylsulfideꢀ(8),ꢀtheꢀ
S-Methyl-S-2-pyridinyl-substitutedꢀ sulfoximineꢀ 6lꢀ wasꢀ formedꢀ
oxidationꢀ ofꢀ 8ꢀ withꢀ NaIO4ꢀ followedꢀ byꢀ iminationꢀ ofꢀ theꢀ
inꢀ69%ꢀyield.ꢀChangingꢀtheꢀS-methylꢀgroupꢀtoꢀanotherꢀalkylꢀorꢀ
resultingꢀsulfoxideꢀ5aꢀunderꢀtheꢀoptimisedꢀconditionsꢀaffordedꢀ
arylꢀ groupꢀ significantlyꢀ affectedꢀ theꢀ yieldꢀ ofꢀ theꢀ resultingꢀ
sulfoximineꢀdependingꢀonꢀtheꢀindividualꢀsubstituent.ꢀWhereasꢀ
N-cyanosulfoximineꢀ6aꢀinꢀ85%ꢀoverꢀtwoꢀsteps.ꢀ
ꢀ
O
N
CN
S-cyclopropyl-S-phenylsulfoximineꢀ 6mꢀ andꢀ S-allyl-S-phenyl-
sulfoximineꢀ 6nꢀ wereꢀ formedꢀ inꢀ 78%ꢀ andꢀ 55%ꢀ yield,ꢀ
respectively,ꢀ theꢀ yieldsꢀ forꢀ S,S-diphenylsulfoximineꢀ 6pꢀ andꢀ S-
phenyl-S-(2-pyridinyl)sulfoximineꢀ6qꢀwereꢀonlyꢀ15%ꢀandꢀ17%.ꢀ
Theꢀlowꢀyieldsꢀinꢀtheꢀlatterꢀtwoꢀcasesꢀwereꢀattributedꢀtoꢀpoorꢀ
substrateꢀsolubilitiesꢀinꢀtheꢀsolventꢀ(H2O)ꢀandꢀtheꢀformationꢀofꢀ
theꢀcorrespondingꢀsulfonesꢀasꢀfavouredꢀproducts.ꢀS-Phenyl-S-
vinylsulfoximineꢀ 6oꢀ remainedꢀ inaccessible.ꢀ Theꢀ yieldsꢀ ofꢀ S,S-
dialkyl-substitutedꢀ sulfoximinesꢀ 6r-tꢀ wereꢀ lowꢀ toꢀ moderateꢀ
presumablyꢀdueꢀtoꢀtheirꢀhighꢀwaterꢀsolubilityꢀwhichꢀhamperedꢀ
theirꢀisolation.ꢀꢀ
S
4 2
first: NaIO , H O, rt, 16 h
S
Me
Me
2
then: H NCN, KOtBu, NCS, rt, 2 h
8
6a
+
O
•
Cl
O
O
N
CN
•
S
NCS
S
S
Me
Me
Me
– HCl
succinimide–
(
S)-5a
–
H
(R)-6a
N
K+
H
2
NCN + KOtBu
CN
– HOtBu
ꢀ
ꢀ
ꢀ
Theꢀ scalabilityꢀ ofꢀ theꢀ processꢀ wasꢀ provenꢀ byꢀ performingꢀ Schemeꢀ 2ꢀ Top:ꢀ One-potꢀ sulfide-to-sulfoximineꢀ conversion;ꢀ
theꢀreactionꢀstartingꢀfromꢀ5aꢀonꢀaꢀ50ꢀmmolꢀscaleꢀprovidingꢀtheꢀꢀ bottom:ꢀmechanisticꢀproposal.ꢀ
Thisꢀjournalꢀisꢀ©ꢀTheꢀRoyalꢀSocietyꢀofꢀChemistryꢀ20xxꢀ
J.ꢀName.,ꢀ2013,ꢀ00,ꢀ1-3ꢀ|ꢀ3ꢀ

Organic & Biomolecular Chemistry
Page 4 of 5
COMMUNICATIONꢀ
JournalꢀNameꢀ
(a)ꢀY.ꢀZhu,ꢀM.ꢀR.ꢀLoso,ꢀG.ꢀB.ꢀWatson,ꢀT.ꢀC.ꢀSparks,ꢀR.ꢀB.ꢀ
ꢀ
4
View Article Online
DOI: 10.1039 6OB0269
Rogers,ꢀJ.ꢀX.ꢀHuang,ꢀB.ꢀC.ꢀGerwick,ꢀJ.ꢀM.ꢀBabcock,ꢀ D/ C.ꢀKelley,ꢀ V1 E. ꢀ
ꢀ
Theꢀ stereochemicalꢀ pathꢀ ofꢀ thisꢀ processꢀ wasꢀ investigatedꢀ
byꢀsubjectingꢀaꢀsampleꢀofꢀenantiomericallyꢀenrichedꢀsulfoxideꢀ
aꢀ toꢀ theꢀ iminationꢀ conditionsꢀ (Schemeꢀ 2,ꢀ bottom).ꢀ Forꢀ theꢀ
B.ꢀHegde,ꢀB.ꢀM.ꢀNugent,ꢀJ.ꢀM.ꢀRenga,ꢀI.ꢀDenholm,ꢀK.ꢀGorman,ꢀ
G.ꢀJ.ꢀDeBoer,ꢀJ.ꢀHasler,ꢀT.ꢀMeadeꢀandꢀJ.ꢀD.ꢀThomas,ꢀJ.ꢀAgric.ꢀ
FoodꢀChem.,ꢀ2011,ꢀ59,ꢀ2950;ꢀ(b)ꢀJ.ꢀM.ꢀBabcock,ꢀC.ꢀB.ꢀGerwick,ꢀ
J.ꢀX.ꢀHuang,ꢀM.ꢀR.ꢀLoso,ꢀG.ꢀNakamura,ꢀS.ꢀP.ꢀNolting,ꢀR.ꢀB.ꢀ
Rogers,ꢀT.ꢀC.ꢀSparks,ꢀJ.ꢀThomas,ꢀG.ꢀB.ꢀWatsonꢀandꢀY.ꢀZhu,ꢀPestꢀ
Manag.ꢀSci.,ꢀ2011,ꢀ67,ꢀ328;ꢀ(c)ꢀG.ꢀB.ꢀWatson,ꢀM.ꢀR.ꢀLoso,ꢀJ.ꢀM.ꢀ
Babcock,ꢀJ.ꢀM.ꢀHasler,ꢀT.ꢀJ.ꢀLetherer,ꢀC.ꢀD.ꢀYoung,ꢀY.ꢀZhu,ꢀJ.ꢀE.ꢀ
CasidaꢀandꢀT.ꢀC.ꢀSparks,ꢀInsect.ꢀBiochem.ꢀMol.ꢀBiol.,ꢀ2011,ꢀ41,ꢀ
432;ꢀ(d)ꢀK.ꢀE.ꢀArndt,ꢀD.ꢀC.ꢀBland,ꢀN.ꢀM.ꢀIrvine,ꢀS.ꢀL.ꢀPowers,ꢀT.ꢀ
P.ꢀMartin,ꢀJ.ꢀR.ꢀꢀMcConnell,ꢀD.ꢀE.ꢀꢀPodhorez,ꢀJ.ꢀM.ꢀRenga,ꢀR.ꢀ
Ross,ꢀG.ꢀA.ꢀRoth,ꢀB.ꢀD.ꢀScherzerꢀandꢀT.ꢀW.ꢀToyzan,ꢀOrg.ꢀ
ProcessꢀRes.ꢀDev.,ꢀ2015,ꢀ19,ꢀ454.ꢀ
5
subsequentꢀanalysis,ꢀtheꢀobtainedꢀN-cyanosulfoximineꢀ6aꢀwasꢀ
convertedꢀ toꢀ itsꢀ NH-analogueꢀ 9ꢀ withoutꢀ affectingꢀ theꢀ
10
stereogenicꢀ center. ꢀ Analysingꢀ compoundꢀ 9ꢀ byꢀ chiralꢀ HPLCꢀ
andꢀcomparingꢀtheꢀretentionꢀtimesꢀwithꢀknownꢀdataꢀrevealedꢀ
thatꢀ theꢀ iminationꢀ wasꢀ stereospecificꢀ convertingꢀ 5aꢀ toꢀ 6aꢀ
underꢀ inversionꢀ ofꢀ configurationꢀ (forꢀ details,ꢀ seeꢀ ESI).ꢀ Thisꢀ
resultꢀcouldꢀbeꢀexplainedꢀbyꢀaꢀretentiveꢀoxidativeꢀchlorinationꢀ
ofꢀtheꢀsulfoxideꢀfollowedꢀbyꢀinvertiveꢀnucleophilicꢀsubstitutionꢀ
byꢀtheꢀdeprotonatedꢀcyanamide.ꢀ
5
6
(a)ꢀH.ꢀR.ꢀBentley,ꢀE.ꢀE.ꢀMcDermottꢀandꢀJ.ꢀK.ꢀWhitehead,ꢀ
Nature,ꢀ1950,ꢀ165,ꢀ735;ꢀ(b)ꢀH.ꢀR.ꢀBentley,ꢀE.ꢀE.ꢀMcDermott,ꢀ
J.ꢀPace,ꢀJ.ꢀK.ꢀWhiteheadꢀandꢀT.ꢀMoran,ꢀNature,ꢀ1950,ꢀ
Conclusionsꢀ
1
65,ꢀ150;ꢀ(c)ꢀH.ꢀR.ꢀBentley,ꢀE.ꢀE.ꢀMcDermott,ꢀJ.ꢀ
Pace,ꢀJ.ꢀK.ꢀWhiteheadꢀandꢀT.ꢀMoran,ꢀNature,ꢀ1949,ꢀ163,ꢀ675.ꢀ
Forꢀreviewsꢀonꢀsulfoximines,ꢀsee:ꢀ(a)ꢀM.ꢀReggelinꢀandꢀC.ꢀZur,ꢀ
Synthesis,ꢀ2000,ꢀ1;ꢀ(b)ꢀM.ꢀHarmata,ꢀChemtracts,ꢀ2003,ꢀ16,ꢀ
Weꢀdiscoveredꢀanꢀunprecedentedꢀiminationꢀofꢀsulfoxidesꢀthatꢀ
proceedsꢀ underꢀ mildꢀ reactionꢀ conditionsꢀ leadingꢀ toꢀ N-
cyanosulfoximinesꢀ inꢀ moderateꢀ toꢀ excellentꢀ yields.ꢀ Theꢀ
protocolꢀ isꢀ scalable,ꢀ avoidsꢀ theꢀ useꢀ ofꢀ transitionꢀ metalꢀ andꢀ
thermallyꢀ labileꢀ reagents.ꢀ Chiralꢀ sulfoxidesꢀ canꢀ stereo-
specificallyꢀbeꢀconvertedꢀwithꢀinversionꢀofꢀconfiguration.ꢀꢀ
6
(
60;ꢀ(c)ꢀH.ꢀOkamuraꢀandꢀC.ꢀBolm,ꢀChem.ꢀLett.,ꢀ2004,ꢀ33,ꢀ482;ꢀ
d)ꢀH.-J.ꢀGais,ꢀHeteroat.ꢀChem.,ꢀ2007,ꢀ18,ꢀ472;ꢀ(e)ꢀV.ꢀBizet,ꢀR.ꢀ
KowalczykꢀandꢀC.ꢀBolm,ꢀChem.ꢀSoc.ꢀRev.,ꢀ2014,ꢀ43,ꢀ2426;ꢀ(f)ꢀ
X.ꢀShenꢀandꢀJ.ꢀHu,ꢀEur.ꢀJ.ꢀOrg.ꢀChem.,ꢀ2014,ꢀ4437.ꢀ
7
Forꢀselectedꢀrecentꢀarticlesꢀdealingꢀwithꢀsulfoximineꢀ
syntheses,ꢀsee:ꢀ(a)ꢀJ.ꢀWang,ꢀM.ꢀFringsꢀandꢀC.ꢀBolm,ꢀAngew.ꢀ
Chem.ꢀInt.ꢀEd.,ꢀ2013,ꢀ52,ꢀ8661;ꢀ(b)ꢀV.ꢀBizet,ꢀL.ꢀBuglioniꢀandꢀC.ꢀ
Bolm,ꢀAngew.ꢀChem.ꢀInt.ꢀEd.,ꢀ2014,ꢀ53,ꢀ5639;ꢀ(c)ꢀJ.ꢀMiao,ꢀN.ꢀ
G.ꢀJ.ꢀRichards,ꢀH.ꢀGe,ꢀChem.ꢀCommun.,ꢀ2014,ꢀ50,ꢀ9687;ꢀ(d)ꢀM.ꢀ
Zenzola,ꢀR.ꢀDoran,ꢀL.ꢀDegennaro,ꢀR.ꢀLuisiꢀandꢀJ.ꢀA.ꢀBull,ꢀ
Angew.ꢀChem.ꢀInt.ꢀEd.,ꢀ2016,ꢀ55,ꢀ7203;ꢀ(e)ꢀA.ꢀTota,ꢀM.ꢀ
Zenzola,ꢀS.ꢀJ.ꢀChawner,ꢀS.ꢀSt.ꢀJohn-Campbell,ꢀC.ꢀCarlucci,ꢀG.ꢀ
Romanazzi,ꢀL.ꢀDegennaro,ꢀJ.ꢀA.ꢀBullꢀandꢀR.ꢀLuisi,ꢀChem.ꢀ
Commun.,ꢀ2017,ꢀ53,ꢀ348;ꢀ(f)ꢀH.ꢀWang,ꢀY.ꢀCheng,ꢀP.ꢀBecker,ꢀG.ꢀ
RaabeꢀandꢀC.ꢀBolm,ꢀAngew.ꢀChem.ꢀInt.ꢀEd.,ꢀ2016,ꢀ55,ꢀ12655ꢀ
andꢀreferencesꢀcitedꢀtherein.ꢀ
Acknowledgementsꢀ
WeꢀthankꢀS.ꢀGrünebaumꢀandꢀP.ꢀWinandyꢀforꢀtheꢀpreparationꢀofꢀ
severalꢀ sulfoxides.ꢀ B.ꢀ Schulte,ꢀ V.ꢀ Bizetꢀ andꢀ J.ꢀ Mottweilerꢀ areꢀ
acknowledgedꢀforꢀproofreadingꢀtheꢀmanuscript.ꢀ
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Turner,ꢀAstraZenecaꢀPatentꢀWOꢀ2011/154737ꢀA1,ꢀ2011.ꢀ
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3
1 J.ꢀGriesꢀandꢀJ.ꢀKrüger,ꢀSynlett,ꢀ2014,ꢀ25,ꢀ1831.ꢀ
809.ꢀ
1
1
ꢀ
ꢀ
2 C.ꢀA.ꢀDannenberg,ꢀV.ꢀBizetꢀandꢀC.ꢀBolm,ꢀSynthesis,ꢀ2015,ꢀ47,ꢀ
1
951.ꢀ
1
3 (a)ꢀT.ꢀBachꢀandꢀC.ꢀKörber,ꢀEur.ꢀJ.ꢀOrg.ꢀChem.,ꢀ1999,ꢀ1033;ꢀ(b)ꢀ
O.ꢀGarcíaꢀMacheñoꢀandꢀC.ꢀBolm,ꢀOrg.ꢀLett.,ꢀ2006,ꢀ8,ꢀ2349;ꢀ(c)ꢀ
O.ꢀGarcíaꢀMacheño,ꢀJ.ꢀDallimore,ꢀA.ꢀPlantꢀandꢀC.ꢀBolm,ꢀOrg.ꢀ
Lett.,ꢀ2009,ꢀ11,ꢀ2429.ꢀ
4 (a)ꢀJ.ꢀNakayama,ꢀT.ꢀOtani,ꢀY.ꢀSugihara,ꢀY.ꢀSano,ꢀA.ꢀIshiiꢀandꢀA.ꢀ
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Kinahan,ꢀC.ꢀL.ꢀSkinnerꢀandꢀH.ꢀTye,ꢀTetrahedronꢀLett.,ꢀ2002,ꢀ
ꢀ
1
4
3,ꢀ2749;ꢀ(c)ꢀE.ꢀLacote,ꢀM.ꢀAmatore,ꢀL.ꢀFensterbankꢀandꢀM.ꢀ
Malacria,ꢀSynlett,ꢀ2002,ꢀ116.ꢀ
15 V.ꢀBizetꢀandꢀC.ꢀBolm,ꢀEur.ꢀJ.ꢀOrg.ꢀChem.,ꢀ2015,ꢀ2854.ꢀ
3
Walker,ꢀM.ꢀP.ꢀZawistoski,ꢀM.ꢀA.ꢀMcGlynn,ꢀJ.-C.ꢀLi,ꢀD.ꢀW.ꢀKung,ꢀ 16 (a)ꢀH.ꢀOkamuraꢀandꢀC.ꢀBolm,ꢀOrg.ꢀLett.,ꢀ2004,ꢀ6,ꢀ1305;ꢀ(b)ꢀF.ꢀ
P.ꢀC.ꢀBonnette,ꢀA.ꢀBaumann,ꢀL.ꢀBuckbinder,ꢀJ.ꢀA.ꢀHouser,ꢀJ.ꢀ
Boer,ꢀA.ꢀMistry,ꢀS.ꢀHan,ꢀL.ꢀXingꢀandꢀA.ꢀGuzman-Perez,ꢀBioorg.ꢀ
Med.ꢀChem.ꢀLett.,ꢀ2009,ꢀ19,ꢀ3253;ꢀ(b)ꢀS.ꢀJ.ꢀPark,ꢀH.ꢀBaars,ꢀS.ꢀ
Mersmann,ꢀH.ꢀBuschmann,ꢀJ.ꢀM.ꢀBaron,ꢀP.ꢀM.ꢀAmann,ꢀK.ꢀ
Czaja,ꢀH.ꢀHollert,ꢀK.ꢀBluhm,ꢀR.ꢀRedelsteinꢀandꢀC.ꢀBolm,ꢀ
ChemMedChem,ꢀ2013,ꢀ8,ꢀ217;ꢀ(c)ꢀS.ꢀJ.ꢀPark,ꢀH.ꢀBuschmannꢀ
andꢀC.ꢀBolm,ꢀBioorg.ꢀMed.ꢀChem.ꢀLett.,ꢀ2011,ꢀ21,ꢀ4888.ꢀ
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8 Forꢀstudiesꢀcomparingꢀvariousꢀmetalꢀcatalystsꢀinꢀsulfurꢀ
iminations,ꢀsee:ꢀ(a)ꢀO.ꢀGarcíaꢀMacheñoꢀandꢀC.ꢀBolm,ꢀChem.ꢀ
Eur.ꢀJ.,ꢀ2007,ꢀ13,ꢀ6674;ꢀ(b)ꢀN.ꢀBarry,ꢀN.ꢀBrondel,ꢀS.ꢀE.ꢀ
LawrenceꢀandꢀA.ꢀR.ꢀMaguire,ꢀTetrahedron,ꢀ2009,ꢀ65,ꢀ10660.ꢀ
1
1
4
ꢀ|ꢀJ.ꢀName.,ꢀ2012,ꢀ00,ꢀ1-3ꢀ
Thisꢀjournalꢀisꢀ©ꢀTheꢀRoyalꢀSocietyꢀofꢀChemistryꢀ20xxꢀ

Page 5 of 5
Organic & Biomolecular Chemistry
JournalꢀNameꢀ
ꢀCOMMUNICATIONꢀ
1
9 Aꢀnoteworthyꢀexceptionꢀisꢀtheꢀlight-inducedꢀrutheniumꢀ
View Article Online
catalysisꢀdescribedꢀinꢀrefs.ꢀ7bꢀandꢀ15,ꢀwhichꢀinvolvesꢀratherꢀ
stableꢀ3-substitutedꢀ1,4,2-dioxazol-5-onesꢀasꢀacylꢀnitreneꢀ
source.ꢀForꢀanꢀinvestigationꢀofꢀtheꢀthermalꢀproperties,ꢀsee:ꢀY.ꢀ
Park,ꢀS.ꢀJee,ꢀJ.ꢀG.ꢀKimꢀandꢀS.ꢀChang,ꢀOrg.ꢀProcessꢀRes.ꢀDev.,ꢀ
DOI: 10.1039/C6OB02691E
2
015,ꢀ19,ꢀ1024.ꢀ
0 ForꢀsulfoxideꢀiminationsꢀwithꢀcombinationsꢀofꢀNaN
see:ꢀH.ꢀR.ꢀBentleyꢀandꢀJ.ꢀK.ꢀWhitehead,ꢀJ.ꢀChem.ꢀSoc.,ꢀ1952,ꢀ
572.ꢀ
1 ForꢀsulfoxideꢀiminationsꢀwithꢀO-mesitylsulfonyl-
hydroxylamineꢀ(MSH),ꢀsee:ꢀY.ꢀTamura,ꢀK.ꢀSumoto,ꢀJ.ꢀ
MinamikawaꢀandꢀM.ꢀIkeda,ꢀTetrahedronꢀLett.,ꢀ1972,ꢀ13,ꢀ
2
2
3
ꢀandꢀacid,ꢀ
1
4
137.ꢀ
2
2 Forꢀiminationsꢀwithꢀcombinationsꢀofꢀuncriticalꢀnitreneꢀ
sourcesꢀandꢀhypervalentꢀiodineꢀreagents,ꢀsee:ꢀ(a)ꢀG.ꢀY.ꢀChoꢀ
andꢀC.ꢀBolm,ꢀTetrahedronꢀLett.,ꢀ2005,ꢀ46,ꢀ8007;ꢀ(b)ꢀref.ꢀ7d.ꢀ
3 Forꢀelectrochemicalꢀiminations,ꢀsee:ꢀT.ꢀSiuꢀandꢀA.ꢀK.ꢀYudin,ꢀ
Org.ꢀLett.,ꢀ2002,ꢀ4,ꢀ1839.ꢀ
4 J.ꢀMendiola,ꢀJ.ꢀA.ꢀRincón,ꢀC.ꢀMateos,ꢀJ.ꢀF.ꢀSoriano,ꢀO.ꢀdeꢀ
Frutos,ꢀJ.ꢀK.ꢀNiemeierꢀandꢀE.ꢀM.ꢀDavis,ꢀOrg.ꢀProcessꢀRes.ꢀ
Dev.,ꢀ2009,ꢀ13,ꢀ263.ꢀ
2
2
2
5 Forꢀtheꢀazideꢀchemistry,ꢀflowꢀsynthesisꢀhasꢀrecentlyꢀbeenꢀ
suggestedꢀasꢀaꢀpossibleꢀsolution.ꢀSee:ꢀ(a)ꢀB.ꢀGutmann,ꢀP.ꢀ
Elsner,ꢀA.ꢀO’Kearney-McMullan,ꢀW.ꢀGoundry,ꢀD.ꢀM.ꢀRobergeꢀ
andꢀC.ꢀO.ꢀKappe,ꢀOrg.ꢀProcessꢀRes.ꢀDev.,ꢀ2015,ꢀ19,ꢀ1062;ꢀ(b)ꢀ
H.ꢀLebel,ꢀH.ꢀPirasꢀandꢀM.ꢀBorduy,ꢀACSꢀCat.ꢀ2016,ꢀ6,ꢀ1109.ꢀ
6 O.ꢀGarcíaꢀMacheñoꢀandꢀC.ꢀBolm,ꢀOrg.ꢀLett.,ꢀ2007,ꢀ9,ꢀ2951.ꢀ
7 Theꢀprogressꢀofꢀtheꢀreactionsꢀwasꢀmonitoredꢀbyꢀthinꢀlayerꢀ
chromatography.ꢀTwoꢀhoursꢀwereꢀfoundꢀtoꢀbeꢀsufficientꢀforꢀ
completeꢀconversion.ꢀ
2
2
2
8 Thisꢀresultꢀwasꢀinꢀlineꢀwithꢀearlierꢀobservationsꢀmadeꢀinꢀ
synthesesꢀofꢀsulfonimidamidesꢀandꢀsulfondiimines.ꢀForꢀ
respectiveꢀreferences,ꢀsee:ꢀ(a)ꢀO.ꢀGarcíaꢀMacheñoꢀandꢀC.ꢀ
Bolm,ꢀBeilsteinꢀJ.ꢀOrg.ꢀChem.,ꢀ2007,ꢀ3,ꢀ1;ꢀ(b)ꢀM.ꢀCandy,ꢀC.ꢀ
Guyon,ꢀS.ꢀMersmann,ꢀJ.-R.ꢀChenꢀandꢀC.ꢀBolm,ꢀAngew.ꢀChem.ꢀ
Int.ꢀEd.,ꢀ2012,ꢀ51,ꢀ4440.ꢀ
Thisꢀjournalꢀisꢀ©ꢀTheꢀRoyalꢀSocietyꢀofꢀChemistryꢀ20xxꢀ
J.ꢀName.,ꢀ2013,ꢀ00,ꢀ1-3ꢀ|ꢀ5ꢀ