Ca tP al el ya ss ies ꢀ dSo cꢀ ni eo nt ꢀca ed j&u sTt ꢀemc ha rn g oi nl os ꢀg y
Page 4 of 5
COMMUNICATIONꢀ
JournalꢀNameꢀ
O
5
aqueous
waste
OH
400 mg
NO2
OAc
check valve
Ar
(0.23 mmol)
liq-liq
sep.
DOI: 10.1039/C6CY00473C
+
6
0.2 mL/min
O
0.1 M
CH2Cl2/THF (9:1)
O
10 mL
O
CH2Cl2/THF (9:1)
NO2
NaHCO3 (sat)
O
Ar
8
0.45 mL/min
Ar =
Cl
O
O
S
OMe
O
8c
Cl
8
b
8d
8a
8e
8f
8g
8
dr: 85:15
7% ee
3% yield
74% yield
dr: 87:13
97% ee
80% yield
dr: 92:8
96% ee
71% yield
dr: 87:13
98% ee
62% yield
dr: 84:16
97% ee
65% yield
dr: 78:22
98% ee
81% yield*
dr: >99:1
98% ee
9
*
ꢀNewꢀresinꢀwasꢀused.ꢀ
Schemeꢀ2ꢀEnantioselectiveꢀcontinuousꢀflowꢀproductionꢀofꢀaꢀlibraryꢀofꢀpyranonaphthoquinones.ꢀꢀ
pyranonaphthoquinonesꢀ byꢀ meansꢀ ofꢀ aꢀ sequentialꢀ two-stepꢀ
synthesis.ꢀWeꢀbelieveꢀthisꢀworkꢀcouldꢀbeꢀofꢀinterestꢀinꢀtheꢀdrugꢀ
discoveryꢀ fieldꢀ asꢀ itꢀ providesꢀ easyꢀ accessꢀ toꢀ aꢀ varietyꢀ ofꢀ
structuresꢀwithꢀpotentialꢀbiologicalꢀactivity.ꢀ
1093-1123;ꢀ (g)ꢀ C.ꢀ Rodríguez-Escrich,ꢀ Chim.ꢀ Oggi,ꢀ 2015,ꢀ 33,ꢀ
12-15;ꢀ(h)ꢀS.ꢀB.ꢀÖtvös,ꢀA.ꢀSzloszár,ꢀI.ꢀM.ꢀMándityꢀandꢀF.ꢀFülöp,ꢀ
Adv.ꢀ Synth.ꢀ Catal.,ꢀ 2015,ꢀ 357,ꢀ 3671-3680;ꢀ (i)ꢀ C.ꢀ Rodríguez-
Escrichꢀ andꢀ M.ꢀ A.ꢀ Pericàs,ꢀ Eur.ꢀ J.ꢀ Org.ꢀ Chem.,ꢀ 2015,ꢀ 1173-
1
2
188;ꢀ(j)ꢀA.ꢀPuglisi,ꢀM.ꢀBenagliaꢀandꢀV.ꢀChiroli,ꢀGreenꢀChem.,ꢀ
013,ꢀ 15,ꢀ 1790-1813;ꢀ (k)ꢀ T.ꢀ Tsubogo,ꢀ T.ꢀ Ishiwataꢀ andꢀ S.ꢀ
Acknowledgmentsꢀ
Kobayashi,ꢀAngew.ꢀChem.,ꢀInt.ꢀEd.,ꢀ2013,ꢀ52,ꢀ6590-6604;ꢀ(l)ꢀ
G.ꢀKardosꢀandꢀT.ꢀSoós,ꢀEur.ꢀJ.ꢀOrg.ꢀChem.,ꢀ2013,ꢀ4490-4494.ꢀ
.ꢀ P.ꢀKasaplar,ꢀP.ꢀRiente,ꢀC.ꢀHartmannꢀandꢀM.ꢀA.ꢀPericàs,ꢀAdv.ꢀ
Synth.ꢀCatal.,ꢀ2012,ꢀ354,ꢀ2905-2910.ꢀ
ThisꢀworkꢀwasꢀfundedꢀbyꢀtheꢀInstituteꢀofꢀChemicalꢀResearchꢀofꢀ
Cataloniaꢀ (ICIQ)ꢀ Foundation,ꢀ MINECOꢀ (grantꢀ CTQ2015-69136-
R)ꢀandꢀDECꢀGeneralitatꢀdeꢀCatalunyaꢀ(Grantꢀ2014SGR827).ꢀWeꢀ
alsoꢀ thankꢀ MINECOꢀ forꢀ aꢀ Severoꢀ Ochoaꢀ Excellenceꢀ
Accreditationꢀ2014–2018ꢀ(SEV-2013-0319).ꢀ
3
4
5
.ꢀ P.ꢀ Kasaplar,ꢀ C.ꢀ Rodríguez-Escrichꢀ andꢀ M.ꢀ A.ꢀ Pericàs,ꢀ Org.ꢀ
Lett.,ꢀ2013,ꢀ15,ꢀ3498-3501.ꢀ
.ꢀ (a)ꢀA.ꢀBastero,ꢀD.ꢀFontꢀandꢀM.ꢀA.ꢀPericàs,ꢀJ.ꢀOrg.ꢀChem.,ꢀ2007,ꢀ
7
M.ꢀA.ꢀPericàs,ꢀChem.ꢀEur.ꢀJ.,ꢀ2014,ꢀ20,ꢀ2367-2372.ꢀ
2,ꢀ2460-2468;ꢀ(b)ꢀL.ꢀOsorio-Planes,ꢀC.ꢀRodríguez-Escrichꢀandꢀ
Notesꢀandꢀreferencesꢀ
6
.ꢀ (a)ꢀD.ꢀK.ꢀNair,ꢀR.ꢀF.ꢀS.ꢀMenna-Barreto,ꢀE.ꢀN.ꢀdaꢀSilvaꢀJúnior,ꢀS.ꢀ
M.ꢀMobinꢀandꢀI.ꢀN.ꢀN.ꢀNamboothiri,ꢀChem.ꢀCommun.,ꢀ2014,ꢀ
50,ꢀ6973-6976;ꢀ(b)ꢀG.ꢀA.ꢀM.ꢀJardim,ꢀT.ꢀT.ꢀGuimarães,ꢀM.ꢀC.ꢀF.ꢀ
R.ꢀ Pinto,ꢀ B.ꢀ C.ꢀ Cavalcanti,ꢀ K.ꢀ M.ꢀ deꢀ Farias,ꢀ C.ꢀ Pessoa,ꢀ C.ꢀ C.ꢀ
Gatto,ꢀ D.ꢀ K.ꢀ Nair,ꢀ I.ꢀ N.ꢀ N.ꢀ Namboothiriꢀ andꢀ E.ꢀ N.ꢀ daꢀ Silvaꢀ
Júnior,ꢀMedChemComm,ꢀ2015,ꢀ6,ꢀ120-130.ꢀ
†
ꢀNotꢀevenꢀtracesꢀofꢀtheꢀcyclizedꢀproductꢀhaveꢀbeenꢀobtainedꢀwithꢀ
anyꢀofꢀtheꢀcatalystsꢀtestedꢀinꢀthisꢀwork;ꢀadditionꢀofꢀanꢀexternalꢀbaseꢀ
wasꢀnecessaryꢀtoꢀobtainꢀ8.ꢀToꢀtheꢀbestꢀofꢀourꢀknowledge,ꢀthisꢀisꢀtheꢀ
firstꢀtimeꢀthatꢀ7aꢀhasꢀbeenꢀisolatedꢀandꢀcharacterized,ꢀincludingꢀanꢀ
‡
ꢀ
X-rayꢀstructureꢀ(CCDCꢀ1456999). ꢀ
‡
§
ꢀSeeꢀElectronicꢀSupportingꢀInformationꢀ(ESI)ꢀforꢀdetails.ꢀ
7
.ꢀ (a)ꢀA.ꢀFujiwara,ꢀT.ꢀMori,ꢀA.ꢀIida,ꢀS.ꢀUeda,ꢀY.ꢀHano,ꢀT.ꢀNomura,ꢀ
H.ꢀTokudaꢀandꢀH.ꢀNishino,ꢀJ.ꢀNat.ꢀProd.,ꢀ1998,ꢀ61,ꢀ629-632;ꢀ
ꢀSeeꢀsectionꢀ7ꢀofꢀtheꢀESIꢀforꢀaꢀproposedꢀstereochemicalꢀmodel.ꢀ
(
b)ꢀP.ꢀKrishnanꢀandꢀK.ꢀF.ꢀBastow,ꢀBiochem.ꢀPharmacol.,ꢀ2000,ꢀ
0,ꢀ1367-1379;ꢀ(c)ꢀA.ꢀJ.ꢀM.ꢀdaꢀSilva,ꢀC.ꢀD.ꢀNetto,ꢀW.ꢀPacienza-
§
§ꢀ Thisꢀ solutionꢀ hadꢀ toꢀ beꢀ dilutedꢀ withꢀ respectꢀ toꢀ theꢀ batchꢀ
6
conditionsꢀandꢀaꢀsmallꢀportionꢀofꢀTHFꢀhadꢀtoꢀbeꢀaddedꢀinꢀorderꢀ
toꢀfullyꢀsolubilizeꢀtheꢀhydroxynaphthoquinone.ꢀ
Lima,ꢀ E.ꢀ C.ꢀ Torres-Santos,ꢀ B.ꢀ Rossi-Bergmann,ꢀ S.ꢀ Maurel,ꢀ A.ꢀ
Valentinꢀ andꢀ P.ꢀ R.ꢀ R.ꢀ Costa,ꢀ J.ꢀ Braz.ꢀ Chem.ꢀ Soc.,ꢀ 2009,ꢀ 20,ꢀ
176-182;ꢀ(d)ꢀR.ꢀL.ꢀFabri,ꢀR.ꢀM.ꢀGrazul,ꢀL.ꢀO.ꢀdeꢀCarvalho,ꢀE.ꢀS.ꢀ
Coimbra,ꢀG.ꢀM.ꢀM.ꢀCardoso,ꢀE.ꢀM.ꢀdeꢀSouza-Fagundes,ꢀA.ꢀD.ꢀ
daꢀSilvaꢀandꢀE.ꢀScio,ꢀAn.ꢀAcad.ꢀBras.ꢀCienc.,ꢀ2012,ꢀ84,ꢀ1081-
1090.ꢀ
1
2
.ꢀ F.ꢀDarvas,ꢀV.ꢀHesselꢀandꢀG.ꢀDormanꢀ(Eds.),ꢀFlowꢀChemistry,ꢀ
Volumeꢀ1ꢀFundamentals,ꢀDeꢀGruyter,ꢀBerlin,ꢀ2014.ꢀ
.ꢀ (a)ꢀJ.ꢀIzquierdoꢀandꢀM.ꢀA.ꢀPericàs,ꢀACSꢀCatalysis,ꢀ2016,ꢀ6,ꢀ348-
3
56;ꢀ(b)ꢀR.ꢀPorta,ꢀM.ꢀBenagliaꢀandꢀA.ꢀPuglisi,ꢀOrg.ꢀProcessꢀRes.ꢀ
Dev.,ꢀ2016,ꢀ20,ꢀ2-25;ꢀ(c)ꢀI.ꢀSagamanova,ꢀC.ꢀRodríguez-Escrich,ꢀ 8.ꢀ T.ꢀT.ꢀGuimarães,ꢀM.ꢀC.ꢀF.ꢀR.ꢀPinto,ꢀJ.ꢀS.ꢀLanza,ꢀM.ꢀN.ꢀMelo,ꢀR.ꢀ
I.ꢀG.ꢀMolnár,ꢀS.ꢀSayalero,ꢀR.ꢀGilmourꢀandꢀM.ꢀA.ꢀPericàs,ꢀACSꢀ
Catalysis,ꢀ 2015,ꢀ 5,ꢀ 6241-6248;ꢀ (d)ꢀ P.ꢀ Kasaplar,ꢀ E.ꢀ Ozkal,ꢀ C.ꢀ
Rodríguez-EscrichꢀandꢀM.ꢀA.ꢀPericàs,ꢀGreenꢀChem.,ꢀ2015,ꢀ17,ꢀ
L.ꢀ doꢀ Monte-Neto,ꢀ I.ꢀ M.ꢀ M.ꢀ deꢀ Melo,ꢀ E.ꢀ B.ꢀ T.ꢀ Diogo,ꢀ V.ꢀ F.ꢀ
Ferreira,ꢀ C.ꢀ A.ꢀ Camara,ꢀ W.ꢀ O.ꢀ Valenca,ꢀ R.ꢀ N.ꢀ deꢀ Oliveira,ꢀ F.ꢀ
FrezardꢀandꢀE.ꢀN.ꢀdaꢀSilvaꢀJúnior,ꢀEur.ꢀJ.ꢀMed.ꢀChem.,ꢀ2013,ꢀ
63,ꢀ523-530.ꢀ
3
122-3129;ꢀ (e)ꢀ I.ꢀ Atodiresei,ꢀ C.ꢀ Vilaꢀ andꢀ M.ꢀ Rueping,ꢀ ACSꢀ
Catalysis,ꢀ 2015,ꢀ 5,ꢀ 1972-1985;ꢀ (f)ꢀ R.ꢀ Munirathinam,ꢀ J.ꢀ 9.ꢀ M.ꢀA.ꢀBrimble,ꢀM.ꢀR.ꢀNairnꢀandꢀH.ꢀPrabaharan,ꢀTetrahedron,ꢀ
Huskensꢀ andꢀ W.ꢀ Verboom,ꢀ Adv.ꢀ Synth.ꢀ Catal.,ꢀ 2015,ꢀ 357,ꢀ
2000,ꢀ56,ꢀ1937-1992.ꢀ
4
ꢀ|ꢀJ.ꢀName.,ꢀ2012,ꢀ00,ꢀ1-3ꢀ
Thisꢀjournalꢀisꢀ©ꢀTheꢀRoyalꢀSocietyꢀofꢀChemistryꢀ20xxꢀ
Pleaseꢀdoꢀnotꢀadjustꢀmarginsꢀ