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Pleaseꢀd Co hꢀ ne omt ꢀ Ca do j mu smt ꢀmarginsꢀ
JournalꢀNameꢀ
ꢀCOMMUNICATIONꢀ
Tableꢀ3.ꢀTheꢀscopeꢀofꢀsubstitutedꢀbenzoxazolesꢀinꢀtheꢀcopper-catalyzedꢀdecarboxylativeꢀ theꢀsameꢀreactionꢀconditionsꢀresultsꢀinꢀnoꢀreacti
/
C
T
5C
h
C
se
J
ꢀ
ꢀ
aꢀ
arylationꢀwithꢀ2-nitrobenzoicꢀacid.
theꢀcarboxylicꢀacidꢀstartingꢀmaterialꢀisꢀr
D Oc oI :
e
v
10
e
.
r
1
e
0
d
3 9. ꢀ
e
0
ꢀ
6
d
64 5t a
a
indicateꢀthatꢀtheꢀcoordinatingꢀsubstituentꢀinꢀtheꢀortho-positionꢀ
facilitatesꢀdecarboxylation,ꢀhoweverꢀtheꢀnitroꢀgroupꢀisꢀneededꢀ
toꢀfacilitateꢀcouplingꢀtoꢀgenerateꢀ3.ꢀWeꢀbelieveꢀthatꢀtheꢀortho-
O
CuCl (10 mol%), phen (10 mol%)
Ag2O (2 equiv), Cs2CO3 (1 equiv)
N
O
N
O
R
+
HO
R
O2N
2a
(0.6 mmol)
DMF, 4 Å MS, 110°C, 23 h
15
1
3
O2N
nitroꢀ groupꢀ mayꢀ playꢀ aꢀ keyꢀ roleꢀ inꢀ aꢀ transmetallationꢀ step ꢀ
andꢀcurrentꢀworkꢀisꢀexploringꢀthisꢀpossibility.ꢀ
(
0.9 mmol)
N
tBu
N
O
MeO
N
ꢀ
Inꢀ summary,ꢀ weꢀ haveꢀ identifiedꢀ aꢀ copper-catalyzedꢀ
decarboxylativeꢀ C-Hꢀ arylationꢀ ofꢀ benzoxazolesꢀ withꢀ
-nitrobenzoicꢀ acidsꢀ toꢀ generateꢀ substitutedꢀ heterobiarylꢀ
O
O
O2N
O2N
O2N
2
3
ba, 61%
3ca, 44%
3da, 62%
products.ꢀ Theseꢀ reactionsꢀ areꢀ theꢀ firstꢀ exampleꢀ ofꢀ aꢀ copper-
catalyzedꢀ decarboxylativeꢀ arylationꢀ andꢀ operateꢀ underꢀ
relativelyꢀmildꢀconditions.ꢀWeꢀareꢀcurrentlyꢀexploringꢀmethodsꢀ
toꢀ broadenꢀ theꢀ substrateꢀ scopeꢀ andꢀ mechanisticꢀ studiesꢀ areꢀ
underwayꢀtoꢀunderstandꢀtheꢀroleꢀofꢀtheꢀ2-nitroꢀsubstituentꢀinꢀ
thisꢀdecarboxylativeꢀarylationꢀreaction.ꢀ
Ph
N
O
Cl
N
O
Br
N
O
O2N
O2N
O2N
3
ea, 70%
3fa, 48%
3ga, 69%
N
N
N
O
O
O
MeO
O2N
O2N
O2N
ꢀ
Weꢀ areꢀ gratefulꢀ toꢀ theꢀ NSFꢀ (CHE-1454879)ꢀ andꢀ Westꢀ
3
ha, 47%
3ia, 46%
3ja, 60%
Virginiaꢀ Universityꢀ forꢀ financialꢀ supportꢀ ofꢀ thisꢀ work.ꢀ NMRꢀ
spectroscopyꢀ facilitiesꢀ wereꢀ partiallyꢀ supportedꢀ byꢀ theꢀ NSFꢀ
N
O
N
O
N
O
Ph
Cl
Br
(
CHE-1228336).ꢀWeꢀthankꢀProf.ꢀStevenꢀValentineꢀandꢀGregoryꢀ
O2N
O2N
O2N
3
ka, 9%
3la, 48%
3ma, 42%
DonohueꢀforꢀHRMSꢀanalyses.ꢀ
ꢀ
a
ꢀ
Yieldsꢀgivenꢀareꢀisolatedꢀyields.ꢀAllꢀreactionsꢀwereꢀcarriedꢀoutꢀusingꢀ0.9ꢀmmolꢀ
benzoxazoleꢀandꢀ0.6ꢀmmolꢀ2-nitrobenzoicꢀacidꢀinꢀ6ꢀmLꢀDMFꢀforꢀ23ꢀhꢀatꢀ110°C.ꢀ
Notesꢀandꢀreferencesꢀ
§
(0.6ꢀ mmol),ꢀ CuClꢀ (0.06ꢀ mmol),ꢀ phenꢀ (0.06ꢀ mmol),ꢀ Cs CO ꢀ (0.6ꢀ
ꢀGeneralꢀprocedureꢀforꢀcatalyticꢀreactions:ꢀ2-nitrobenzoicꢀacidꢀ
2
Tableꢀ 4.ꢀ Theꢀ scopeꢀ ofꢀ theꢀ copper-catalyzedꢀ decarboxylativeꢀ arylationꢀ ofꢀ substitutedꢀ
aꢀ
benzoxazolesꢀwithꢀsubstitutedꢀ2-nitrobenzoicꢀacids.
3
mmol),ꢀAg
combinedꢀinꢀaꢀ50ꢀmLꢀSchlenkꢀtubeꢀfittedꢀwithꢀaꢀstirꢀbar.ꢀTheꢀtubeꢀ
wasꢀ evacuatedꢀ andꢀ backfilledꢀ withꢀ N ꢀ threeꢀ timesꢀ beforeꢀ aꢀ
solutionꢀofꢀbenzoxazoleꢀ(0.9ꢀmmol)ꢀinꢀdryꢀDMFꢀ(6.0ꢀmL,ꢀ0.15ꢀM)ꢀ
wasꢀadded.ꢀTheꢀreactionꢀmixtureꢀwasꢀstirredꢀunderꢀN ꢀatꢀ110°Cꢀ
forꢀ 23ꢀ h.ꢀ Uponꢀ completion,ꢀ theꢀ mixtureꢀ wasꢀ cooledꢀ toꢀ roomꢀ
temperatureꢀ andꢀ dilutedꢀ withꢀ ethylꢀ acetateꢀ (40ꢀ mL),ꢀ filteredꢀ
throughꢀceliteꢀandꢀtheꢀsolventꢀremoved.ꢀTheꢀcrudeꢀproductꢀwasꢀ
purifiedꢀ byꢀ silicaꢀ gelꢀ columnꢀ chromatographyꢀ (ethylꢀ acetateꢀ inꢀ
hexanes)ꢀtoꢀyieldꢀtheꢀdecarboxylativeꢀarylationꢀproduct.ꢀ
ꢀ
2
Oꢀ(1.2ꢀmmol),ꢀandꢀ4Åꢀmolecularꢀsievesꢀ(600ꢀmg)ꢀwereꢀ
O
2
CuCl (10 mol%), phen (10 mol%)
Ag O (2 equiv), Cs CO (1 equiv)
N
O
HO
N
O
R
1
(
+
2
2
3
R
1
O
2
N
R
R2
2
2
DMF, 4 Å MS, 110°C, 23 h
O
2
N
1
2
3
0.9 mmol)
(0.6 mmol)
Ph
N
N
MeO
N
O
Cl
Cl
O
O
O
2
N
O
2
N
O
2
N
3
bb, 51%
3bj, 60%
3db, 77%
1
D.ꢀ K.ꢀ Dalvie,ꢀ A.ꢀ S.ꢀ Kalgutkar,ꢀ S.ꢀ C.ꢀ Khojasteh-Bakht,ꢀ R.ꢀ S.ꢀ
Obachꢀ andꢀ J.ꢀ P.ꢀ O’Donnell,ꢀ Chem.ꢀ Res.ꢀ Toxicol.,ꢀ 2002,ꢀ 15,ꢀ
Ph
MeO
N
O
MeO
N
O
Ph
N
O
2
69.ꢀ
N.ꢀ Rodríguezꢀ andꢀ L.ꢀ J.ꢀ Goossen,ꢀ Chem.ꢀ Soc.ꢀ Rev.,ꢀ 2011,ꢀ 40,ꢀ
030.ꢀ
Br
Cl
2
3
O
2
N
O
2
N
2
O N
5
3
dc, 52%
3dj, 50%
3eb, 50%
(a)ꢀL.ꢀJ.ꢀGoossen,ꢀG.ꢀDengꢀandꢀL.ꢀM.ꢀLevy,ꢀScience,ꢀ2006,ꢀ313,ꢀ
662;ꢀ(b)ꢀL.ꢀJ.ꢀGoossen,ꢀN.ꢀRodríguez,ꢀB.ꢀMelzer,ꢀC.ꢀLinder,ꢀG.ꢀ
DengꢀandꢀL.ꢀM.ꢀLevy,ꢀJ.ꢀAm.ꢀChem.ꢀSoc.,ꢀ2007,ꢀ129,ꢀ4824;ꢀ(c)ꢀ
L.ꢀJ.ꢀGoossen,ꢀN.ꢀRodríguezꢀandꢀC.ꢀLinder,ꢀJ.ꢀAm.ꢀChem.ꢀSoc.,ꢀ
Ph
Ph
Ph
N
O
Ph
N
O
N
O
Br
MeO
O
2
N
O
2
N
2
O N
2008,ꢀ130,ꢀ15248.ꢀꢀ
(a)ꢀC.ꢀWang,ꢀI.ꢀPielꢀandꢀF.ꢀGlorius,ꢀJ.ꢀAm.ꢀChem.ꢀSoc.,ꢀ2009,ꢀ
3
ec, 41%
3ej, 48%
3jj, 90%
4
1
2
31,ꢀ 4194;ꢀ (b)ꢀ J.ꢀ Cornella,ꢀ P.ꢀ Luꢀ andꢀ I.ꢀ Larrosa,ꢀ Org.ꢀ Lett.,ꢀ
009,ꢀ11,ꢀ5506;ꢀ(c)ꢀK.ꢀXie,ꢀZ.ꢀYang,ꢀX.ꢀZhou,ꢀX.ꢀLi,ꢀS.ꢀWang,ꢀZ.ꢀ
a
ꢀ
Yieldsꢀgivenꢀareꢀisolatedꢀyields.ꢀAllꢀreactionsꢀwereꢀcarriedꢀoutꢀusingꢀ0.9ꢀmmolꢀ
benzoxazoleꢀandꢀ0.6ꢀmmolꢀ2-nitrobenzoicꢀacidꢀinꢀ6ꢀmLꢀDMFꢀforꢀ23ꢀhꢀatꢀ110°C.ꢀ
Tan,ꢀ X.ꢀ Anꢀ andꢀ C.-C.ꢀ Guo,ꢀ Org.ꢀ Lett.,ꢀ 2010,ꢀ 12,ꢀ 1564;ꢀ (d)ꢀ J.ꢀ
Zhou,ꢀP.ꢀHu,ꢀM.ꢀZhang,ꢀS.ꢀHuang,ꢀM.ꢀWang,ꢀW.ꢀSu,ꢀChem.ꢀEur.ꢀ
J.ꢀ2010,ꢀ16,ꢀ5876;ꢀ(e)ꢀH.ꢀZhao,ꢀY.ꢀWei,ꢀJ.ꢀXu,ꢀJ.ꢀKan,ꢀW.ꢀSuꢀandꢀ
M.ꢀHong,ꢀJ.ꢀOrg.ꢀChem.,ꢀ2011,ꢀ76,ꢀ882;ꢀ(f)ꢀP.ꢀHu,ꢀM.ꢀZhang,ꢀX.ꢀ
JieꢀandꢀW.ꢀSu,ꢀAngew.ꢀChem.ꢀInt.ꢀEd.,ꢀ2012,ꢀ51,ꢀ227;ꢀ(g)ꢀS.ꢀ
Seo,ꢀM.ꢀSlaterꢀandꢀM.ꢀF.ꢀGreaney,ꢀOrg.ꢀLett.,ꢀ2012,ꢀ14,ꢀ2650;ꢀ
ꢀ
Underꢀ ourꢀ reactionꢀ conditions,ꢀ benzoicꢀ acidsꢀ lackingꢀ theꢀ
ortho-nitroꢀ groupꢀ doꢀ notꢀ undergoꢀ decarboxylativeꢀ cross-
couplingꢀtoꢀgenerateꢀproductꢀ3ꢀ(ChartꢀS1).ꢀToꢀgainꢀsomeꢀinsightꢀ
intoꢀtheꢀrequirementꢀforꢀtheꢀ2-nitroꢀsubstituent,ꢀtheꢀproductꢀ
distributionꢀ forꢀ unreactiveꢀ benzoicꢀ acidsꢀ wasꢀ evaluated.ꢀ
Treatingꢀ 2-methoxybenzoicꢀ acidꢀ andꢀ 2-fluorobenzoicꢀ acidꢀ
underꢀ ourꢀ standardꢀ reactionꢀ conditionsꢀ inꢀ theꢀ presenceꢀ ofꢀ
benzoxazoleꢀ 1aꢀ generatesꢀ onlyꢀ anisoleꢀ andꢀ fluorobenzene,ꢀ
respectively.ꢀ Alternatively,ꢀ subjectingꢀ 4-nitrobenzoicꢀ acidꢀ toꢀ
(
h)ꢀK.ꢀYang,ꢀC.ꢀZhang,ꢀP.ꢀWang,ꢀY.ꢀZhangꢀandꢀH.ꢀGe,ꢀChem.-
Eur.ꢀJ.,ꢀ2014,ꢀ20,ꢀ7241;ꢀ(i)ꢀG.ꢀShi,ꢀC.ꢀShao,ꢀS.ꢀPan,ꢀJ.ꢀYuꢀandꢀY.ꢀ
Zhang,ꢀOrg.ꢀLett.,ꢀ2015,ꢀ17,ꢀ38;ꢀ(j)ꢀJ.ꢀKan,ꢀS.ꢀHuang,ꢀJ.ꢀLin,ꢀM.ꢀ
ZhangꢀandꢀW.ꢀSu,ꢀAngew.ꢀChem.ꢀInt.ꢀEd.,ꢀ2015,ꢀ54,ꢀ2199;ꢀ(k)ꢀ
Y.ꢀZhang,ꢀH.ꢀZhao,ꢀM.ꢀZhangꢀandꢀW.ꢀSu,ꢀAngew.ꢀChem.ꢀInt.ꢀ
Ed.,ꢀ2015,ꢀ54,ꢀ3817.ꢀ
Thisꢀjournalꢀisꢀ©ꢀTheꢀRoyalꢀSocietyꢀofꢀChemistryꢀ20xxꢀ
J.ꢀName.,ꢀ2013,ꢀ00,ꢀ1-3ꢀ|ꢀ3ꢀ
Pleaseꢀdoꢀnotꢀadjustꢀmarginsꢀ
Chen, Lijun
