Proline triflate catalysed Diels-Alder reaction in the synthesis of tetrahydroquinoline derivatives

Article abstract of DOI:10.3184/030823409X12474221035082

Proline triflate was found to catalyse efficiently the one-pot synthesis of 2H-pyranotetrahydroquinolines from aryl imines, and 3,4-dihydro-2H-pyran with high stereoselectivity. The aryl imines were formed in situ from aromatic amines and arylaldehydes.

Full text of DOI:10.3184/030823409X12474221035082

JOURNALꢀOFꢀCHEMICALꢀRESEARCHꢀ2009
AUGUST,ꢀ499–504ꢀ
RESEARCH PAPERꢀ 499
Proline triflate catalysed Diels–Alder reaction in the synthesis of
tetrahydroquinoline derivatives
Jianjun Li, Jia Li and Weike Su*
Key Laboratory of Pharmaceutical Engineering of Ministry of Education, College of Pharmaceutical Sciences,
Zhejiang University of Technology, Hangzhou 310014, P.R. China
Prolineꢀtriflateꢀwasꢀfoundꢀtoꢀcatalyseꢀefficientlyꢀtheꢀone-potꢀsynthesisꢀofꢀ2H-pyranotetrahydroquinolinesꢀfromꢀarylꢀ
imines,ꢀandꢀ3,4-dihydro-2H-pyranꢀwithꢀhighꢀstereoselectivity.ꢀTheꢀarylꢀiminesꢀwereꢀformedꢀin situꢀfromꢀaromaticꢀ
aminesꢀandꢀarylaldehydes.
Keywords: tetrahydroquinoline, aza-D-A reactions, proline triflate
Derivativesꢀ ofꢀ tetrahydroquinolinesꢀ haveꢀ attractedꢀ
considerableꢀ interestꢀ becauseꢀ ofꢀ theirꢀ pharmaceuticalꢀ andꢀ
synthesis.16-18ꢀ Asꢀ aꢀ partꢀ ofꢀ ourꢀ ongoingꢀ interestꢀ inꢀ greenꢀ
chemistry and triflate catalysed organic reactions, we report
here that proline triflate, obtained from L-proline and
trifluoromethanesulfonic acid, is totally a new catalyst. It is
cheapꢀtoꢀproduce,ꢀeasyꢀtoꢀhandleꢀandꢀrecyclable.
Hereꢀweꢀdescribeꢀtheꢀsynthesisꢀofꢀtetrahydroquinolinesꢀinꢀ
a one-pot process using a catalytic amount of proline triflate
underꢀ mildꢀ conditions.ꢀ Generally,ꢀ theꢀ syntheticꢀ procedureꢀ
involvesꢀimpregnatingꢀaꢀmixtureꢀofꢀ3,4-dihydro-2H-pyranꢀandꢀ
proline triflate with an acetonitrile solution of benzaldehyde
andꢀaniline,ꢀtoꢀgiveꢀtheꢀcorrespondingꢀtetrahydroquinolinesꢀ3aꢀ
andꢀ4aꢀinꢀ85%ꢀyieldꢀ(Schemeꢀ1).
1
2ꢀ
biochemicalꢀ properties, ꢀ includingꢀ anti-allergenic, anti-
3
4
inflammatory ꢀandꢀestrogenicꢀactivities. ꢀTheꢀaza-Diels–Alderꢀ
reactionsꢀ haveꢀ beenꢀ usedꢀ forꢀ theꢀ synthesisꢀ ofꢀ heterocyclesꢀ
5
andꢀ naturalꢀ products. ꢀAnꢀ easyꢀ routeꢀ toꢀ tetrahydroquinolineꢀ
derivativesꢀisꢀviaꢀtheꢀaza-Diels–Alderꢀreactionꢀbetweenꢀarylꢀ
iminesꢀasꢀheterodienesꢀandꢀvariousꢀdienophilesꢀinꢀtheꢀpresenceꢀ
ofꢀ acidꢀ catcalysts.6 Unfortunately,ꢀ someꢀ ofꢀ theꢀ iminesꢀ areꢀ
hygroscopic, thermally unstable, and difficult to isolate and
-8ꢀ
9
purifyꢀ byꢀ columnꢀ chromatographyꢀ orꢀ distillation. ꢀ Recentlyꢀ
one-potꢀ proceduresꢀ haveꢀ beenꢀ developedꢀ forꢀ thisꢀ reactionꢀ
10
using lanthanide triflates ꢀasꢀcatalysts.ꢀDifferentꢀLewisꢀacidsꢀ
Inꢀ orderꢀ toꢀ developꢀ suitableꢀ conditionsꢀ forꢀ theꢀ aboveꢀ
transformation,ꢀweꢀinvestigatedꢀtheꢀreactionꢀofꢀ3,4-dihydro-
1
1
12
13
suchꢀ asꢀ BF ·OEt , ꢀ GdCl , ꢀ ZrCl ꢀ haveꢀ alsoꢀ beenꢀ usedꢀ
inꢀ thisꢀ reaction.
3
2
3
4
1
4-15ꢀ
However,ꢀ excessꢀ traditionalꢀ Lewisꢀ acidꢀ
2
H-pyran,ꢀ benzaldehydeꢀ andꢀ anilineꢀ inꢀ variousꢀ solventsꢀ
catalystsꢀ areꢀ neededꢀ andꢀ someꢀ proceduresꢀ sufferꢀ fromꢀ longꢀ
reactionꢀtimes,ꢀcorrosionꢀandꢀsafetyꢀproblems.ꢀHence,ꢀthereꢀ
isꢀstillꢀroomꢀforꢀimprovementꢀtoꢀreduceꢀtheꢀreactionꢀtimeꢀandꢀ
improve yields. Consequently, development of an efficient and
versatileꢀmethodꢀforꢀtheꢀpreparationꢀofꢀtetrahydroquinolinesꢀisꢀ
anꢀimportantꢀareaꢀofꢀactiveꢀresearch.
suchꢀasꢀtetrahydrofuran,ꢀtoluene,ꢀether,ꢀdichloromethaneꢀandꢀ
acetonitrile.ꢀTheꢀreactionꢀwasꢀveryꢀslowꢀinꢀseveralꢀsolventsꢀorꢀ
underꢀsolvent-freeꢀconditions.ꢀComparedꢀwithꢀotherꢀcatalysts,ꢀ
proline triflate showed the best catalytic effect at 25ꢀ°Cꢀ inꢀ
CH3CN (Table 1, entry 1). Significantly, in the absence of
catalyst,ꢀtheꢀreactionsꢀdidꢀnotꢀproceedꢀevenꢀafterꢀlongꢀreactionꢀ
timesꢀ(24ꢀh,ꢀTableꢀ1,ꢀentryꢀ10).
Recently, our group has reported that metal triflates
areꢀ excellentꢀ catalystsꢀ withꢀ aꢀ wideꢀ applicationꢀ inꢀ organicꢀ
CHO
NH2
H
H
H
H
O
O
O
Proline triflate ( 5 mol%)
+
+
H
+
H
NH
NH
o
2
5 C, CH CN
3
1a
2a
3a cis-
4a trans-
Scheme 1
Table 1ꢀ Effectꢀofꢀsolventꢀonꢀtheꢀaza-Diels–Alderꢀreactionꢀofꢀbenzaldehydeꢀiminea
b
Entryꢀ
Catalystꢀ
Loading/mol%ꢀ
Solventꢀ
Time/hꢀ
Yield /%ꢀ
3a/4aꢀratio
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
1ꢀ
2ꢀ
3ꢀ
4ꢀ
5ꢀ
6ꢀ
7ꢀ
8ꢀ
9ꢀ
Prolineꢀtriflateꢀ
Prolineꢀtriflateꢀ
Prolineꢀtriflateꢀ
Prolineꢀtriflateꢀ
Prolineꢀtriflateꢀ
Prolineꢀtriflateꢀ
CF SO Hꢀ
5ꢀ
5ꢀ
CH CNꢀ
5ꢀ
5ꢀ
85ꢀ
10ꢀ
35ꢀ
41ꢀ
81ꢀ
57ꢀ
70ꢀ
–ꢀ
25:75
–
3
tolueneꢀ
5ꢀ
Et Oꢀ
5ꢀ
48:52
51:49
28:72
63:37
31:69
–
2
5ꢀ
CH Cl ꢀ
5ꢀ
2
2
5ꢀ
THFꢀ
–ꢀ
5ꢀ
5ꢀ
5ꢀ
5ꢀ
CH CNꢀ
5ꢀ
3
3
3
L-prolineꢀ
10ꢀ
5ꢀ
CH CNꢀ
10ꢀ
5ꢀ
3
p-CH PhSO Hꢀ
CH CNꢀ
62ꢀ
–ꢀ
33:67
–
3
3
3
ꢀ1 0ꢀ
Noneꢀ
0ꢀ
CH CNꢀ
24ꢀ
3
a
Reactionꢀconditions:ꢀ1ꢀmmolꢀbenzaldehyde,ꢀbenzaldehyde/aniline/dihydropyranꢀ=ꢀ1 ꢀ: ꢀ1 .1 ꢀ: ꢀ1 .4,ꢀ5-Åꢀmolecularꢀsieves,ꢀ25 ꢀ° C.
b
Yieldꢀrefersꢀtoꢀpureꢀproductꢀafterꢀcolumnꢀchromatography.
*
ꢀCorrespondent.ꢀE-mail:ꢀsuweike@zjut.edu.cn

5
00ꢀ JOURNALꢀOFꢀCHEMICALꢀRESEARCHꢀ2009
Toꢀinvestigateꢀtheꢀstereoselectivityꢀofꢀtheꢀmodelꢀreaction,ꢀ
Toꢀexploreꢀtheꢀscopeꢀandꢀlimitationꢀofꢀthisꢀreaction,ꢀweꢀhaveꢀ
carriedꢀoutꢀtheꢀreactionꢀofꢀ3,4-dihydro-2H-pyran withꢀaꢀrangeꢀofꢀ
aromaticꢀ aldehydesꢀ (1a–n) andꢀ aromaticꢀ aminesꢀ (2o–v)ꢀ underꢀ
we modified several conditions (Table 2). As a result, we
foundꢀthatꢀtheꢀcis- andꢀtrans- isomersꢀhadꢀaꢀdifferentꢀactivationꢀ
energy.ꢀ Theꢀ cis- productꢀ wasꢀ obtainedꢀ atꢀ higherꢀ substrateꢀ
concentrationꢀandꢀlowerꢀtemperature,ꢀandꢀtheꢀtrans-ꢀrequiredꢀaꢀ
lowerꢀsubstrateꢀconcentrationꢀandꢀhigherꢀtemperature.ꢀOnꢀtheꢀ
otherꢀhand,ꢀitꢀwasꢀfoundꢀthatꢀwhenꢀtheꢀreactionꢀtemperatureꢀ
wasꢀ raised,ꢀ theꢀ amountꢀ ofꢀ trans-ꢀ isomerꢀ increasedꢀ slowly.ꢀ
similarꢀconditionsꢀ(usingꢀCH CN and proline triflate). Most of
3
theꢀ reactionsꢀ proceededꢀ smoothlyꢀ underꢀ theꢀ essentiallyꢀ mildꢀ
basicꢀconditionsꢀtoꢀaffordꢀtheꢀcorrespondingꢀtetrahydroquinolinesꢀ
(3 and 4)ꢀinꢀ71–85%ꢀyieldsꢀ(Schemeꢀ2,ꢀTableꢀ3).
Fromꢀ Tableꢀ 3,ꢀ itꢀ canꢀ beꢀ seenꢀ thatꢀ theꢀ processꢀ toleratesꢀ
bothꢀ electron-withdrawingꢀ substituentsꢀ notꢀ onlyꢀ onꢀ theꢀ
benzaldehydeꢀbutꢀalsoꢀaniline.ꢀMostꢀcases,ꢀtheꢀproductꢀwasꢀ
obtainedꢀasꢀaꢀmixtureꢀofꢀ3ꢀcis-ꢀandꢀ4ꢀtrans-ꢀisomersꢀfavouringꢀ
theꢀ trans-ꢀ diastereomer.ꢀ Theꢀ twoꢀ diastereoisomersꢀ fromꢀ
thiophene-2-carbaldehyde,ꢀ aniline,ꢀ andꢀ dihydropyranꢀ wereꢀ
obtainedꢀ inꢀ aꢀ reasonableꢀ yield.ꢀ Itꢀ wasꢀ easyꢀ toꢀ separateꢀ theꢀ
diastereomersꢀ byꢀ columnꢀ chromatographyꢀ onꢀ silicaꢀ gelꢀ andꢀ
alsoꢀtoꢀcharacteriseꢀthemꢀbyꢀNMRꢀspectroscopy.
However,ꢀwhenꢀtheꢀamountꢀofꢀCH CNꢀwasꢀincreasedꢀfromꢀ0ꢀ
3
toꢀ3ꢀmLꢀinꢀtheꢀmodelꢀreaction,ꢀtheꢀproportionꢀofꢀtrans-ꢀisomerꢀ
increased.ꢀ Hence,ꢀ toꢀ themꢀ theꢀ trans-ꢀ isomer,ꢀ theꢀ substrateꢀ
concentration had a stronger influence than temperature. Most
19
recently,ꢀ Z.Q.ꢀ Zhou ꢀ alsoꢀ reportedꢀ aꢀ similarꢀ result.ꢀ Sinceꢀ
theꢀconditionꢀCꢀgaveꢀtheꢀtrans-ꢀisomerꢀasꢀtheꢀmajorꢀproductꢀ
underꢀ mildꢀ conditions,ꢀ weꢀ performedꢀ theꢀ reactionꢀ atꢀ roomꢀ
temperatureꢀandꢀwithꢀaꢀlowerꢀsubstrateꢀconcentration.
a
Table 2ꢀ One-potꢀsynthesisꢀofꢀpyrano[3,2-c]quinolinesꢀfromꢀaldehydesꢀcatalysedꢀbyꢀprolineꢀtriflate ꢀunderꢀdifferentꢀconditions
b
c
b
b
Temp.ꢀ/ ꢀ° C(time/h)ꢀ
3a/4aꢀyield/% ConditionꢀA ꢀ
3a/4aꢀyield/% ConditionꢀBꢀ
3a/4aꢀyield/% ConditionꢀC
0
2
5
ꢀ(24)ꢀ
5ꢀ(5)ꢀ
0ꢀ(3)ꢀ
65:35(32)ꢀ
63:37(57)ꢀ
55:45(60)ꢀ
49:51(53)ꢀ
30:70(72)ꢀ
20:80(78)ꢀ
43:57(61)
25:75(85)
12:88(86)
aReactionꢀconditions:ꢀ1ꢀmmolꢀbenzaldehyde,ꢀbenzaldehyde/aniline/dihydropyranꢀ=ꢀ1/1.1/1.4,ꢀ5ꢀmol-%ꢀprolineꢀtriflateꢀrelativeꢀtoꢀ
aldehyde,ꢀ5-Åꢀmolecularꢀsieves,ꢀ25 ꢀ° Cꢀforꢀ5ꢀh.
b
Yieldꢀrefersꢀtoꢀpureꢀproductꢀafterꢀcolumnꢀchromatography.
c
ConditionsꢀA:ꢀ1ꢀmmolꢀPhCHO,ꢀsolvent-free;ꢀconditionꢀB:ꢀ1ꢀmmolꢀPhCHO,ꢀ1ꢀmLꢀCH CN;ꢀconditionꢀC:ꢀ1ꢀmmolꢀPhCHO,ꢀ3ꢀmLꢀCH CN.
3
3
NH2
H
H
O
O
O
Proline triflate ( 5 mol%)
5°C, CH CN
1
R2
R CHO
+
+
+
R2
H
H
NH
NH
2
3
R2
2a-w
H
H
R1
R1
1a-w
3a-w cis-
4a-w trans-
Scheme 2
Table 3ꢀ One-potꢀsynthesisꢀofꢀpyrano[3,2-c]quinolinesꢀfromꢀaldehydesꢀcatalysedꢀbyꢀprolineꢀtriflatea,b
1
2
Entryꢀ
R ꢀ
R ꢀ
Time/hꢀ
Yield/%ꢀ
3/4ꢀratio
aꢀ
bꢀ
cꢀ
dꢀ
eꢀ
fꢀ
C ꢀH ꢀ
Hꢀ
Hꢀ
Hꢀ
Hꢀ
Hꢀ
Hꢀ
Hꢀ
5ꢀ
4ꢀ
4ꢀ
5ꢀ
4ꢀ
4ꢀ
5ꢀ
85ꢀ
83ꢀ
82ꢀ
76ꢀ
80ꢀ
82ꢀ
81ꢀ
25:75
30:70
27:73
31:69
33:67
31:69
32:68
6
5
p-Cl-C H ꢀ
6
4
p-Br-C H ꢀ
6
4
m-F-C H ꢀ
6
4
m-Br-C H ꢀ
6
4
m-Cl-C H ꢀ
6
4
gꢀ
2,4-(OCH ) C H ꢀ
3 2 6 3
CHO
hꢀ
ꢀ
Hꢀ
5ꢀ
80ꢀ
31:69
O
O
iꢀ
jꢀ
o-OCH -C H ꢀ
Hꢀ
Hꢀ
5ꢀ
5ꢀ
76ꢀ
77ꢀ
33:67
26:74
3
6
4
S
ꢀ
CHO
kꢀ
lꢀ
o-OH-C H ꢀ
Hꢀ
Hꢀ
5ꢀ
5ꢀ
81ꢀ
75ꢀ
78ꢀ
80ꢀ
84ꢀ
82ꢀ
80ꢀ
79ꢀ
78ꢀ
80ꢀ
71ꢀ
–ꢀ
100:0
100:0
0:100
0:100
27:73
28:72
32:68
30:70
31:69
34:66
31:69
–
6
4
m-OCH -C H ꢀ
3
6
4
mꢀ
nꢀ
oꢀ
pꢀ
qꢀ
rꢀ
sꢀ
tꢀ
uꢀ
vꢀ
wꢀ
m-NO -C H ꢀ
Hꢀ
8ꢀ
2
6
4
p-OCH -C H ꢀ
Hꢀ
p-Clꢀ
7ꢀ
3
6
4
C ꢀH ꢀ
4ꢀ
6
5
C ꢀH ꢀ
p-OCH3ꢀ
p-Meꢀ
m-Clꢀ
2-Me,3-Clꢀ
2,5-(Me)2ꢀ
3,4-2Fꢀ
p-NO2ꢀ
Hꢀ
4ꢀ
6
5
C ꢀH ꢀ
5ꢀ
6
5
C ꢀH ꢀ
4ꢀ
6
5
C ꢀH ꢀ
5ꢀ
6
5
C ꢀH ꢀ
6ꢀ
6
5
C ꢀH ꢀ
8ꢀ
6
5
C ꢀH ꢀ
12ꢀ
12ꢀ
6
5
p-OH-C H ꢀ
–ꢀ
–
6
4
aReactionꢀ conditions:ꢀ 1ꢀ mmolꢀ benzaldehyde,ꢀ benzaldehyde/aniline/dihydropyranꢀ =ꢀ 1:1.1:1.4,ꢀ 5ꢀ mol%ꢀ prolineꢀ triflateꢀ relativeꢀ toꢀ
aldehyde,ꢀ5-Åꢀmolecularꢀsieves.ꢀ25 ꢀ° C.
b
TheꢀreactionꢀwasꢀmonitoredꢀbyꢀTLC.

JOURNALꢀOFꢀCHEMICALꢀRESEARCHꢀ2009ꢀ 501
CHO
R
NH2
H
O
O
Proline triflate ( 5 mol%)
H
+
+
NH
o
H
25 C, CH CN
3
R= o-OH or m-OCH3
R
cis- 100%
Scheme 3
H
CHO
R
NH2
O
O
Proline triflate ( 5 mol%)
H
NH
+
+
o
2
5 C, CH CN
H
3
R= m-NO or p-OCH
2
3
R
trans- 100%
Scheme 4
Interestingly,ꢀ whenꢀ theꢀ substratesꢀ wereꢀ 2-hydroxy-
benzaldehydeꢀ andꢀ 3-methoxybenzaldehyde,ꢀ 100%ꢀ yieldꢀ ofꢀ
cis-ꢀ isomerꢀ wereꢀ given.ꢀ Inꢀ contrast,ꢀ 3-nitrobenzaldehydeꢀ
andꢀ 4-methoxybenzaldehydeꢀ gaveꢀ theꢀ correspondingꢀ trans-ꢀ
isomersꢀtotallyꢀ(Schemeꢀ4).ꢀTheꢀreasonꢀforꢀthisꢀphenomenonꢀ
isꢀtheꢀsubjectꢀofꢀfurtherꢀstudy.
added,ꢀ andꢀ theꢀ productꢀ wasꢀ extractedꢀ withꢀ EtOAc.ꢀ Theꢀ organicꢀ
layerꢀ wasꢀ driedꢀ withꢀ anhydrousꢀ Na SO andꢀ concentratedꢀ underꢀ
vacuum. The crude product was purified by column chromatography
onꢀ silicaꢀ gelꢀ (2%ꢀ ethylꢀ acetateꢀ inꢀ petroleumꢀ ether)ꢀ toꢀ giveꢀ pureꢀ
tetrahydropyranoquinolinesꢀ3ꢀandꢀ4ꢀ(85%).
2
4ꢀ
Spectralꢀdataꢀofꢀtetrahydropyranoquinolines:
Disappointingly,ꢀ4-hydroxybenzaldehydeꢀdidꢀnotꢀreactꢀevenꢀ
whenꢀtheꢀtemperatureꢀwasꢀraisedꢀtoꢀ80ꢀ°Cꢀandꢀtheꢀreactionꢀtimeꢀ
(4aS,5S,10bS)-5-phenyl-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]
9
quinoline (3a):ꢀ Solid,ꢀ m.p.ꢀ 129–130ꢀ°Cꢀ (Lit. ꢀ m.p.ꢀ 129–130ꢀ°C).ꢀ
1
HꢀNMRꢀd:ꢀ7.42–7.28ꢀ(m,ꢀ6H),ꢀ7.08ꢀ(t,ꢀ1H,ꢀJ =ꢀ8.0ꢀHz),ꢀ6.78ꢀ(t,ꢀ1H,ꢀ
(Tableꢀ 3,ꢀ entryꢀ w)ꢀ wasꢀ prolonged.ꢀ Similarly,ꢀ 4-nitroanilineꢀ
J =ꢀ7.2ꢀHz),ꢀ6.57ꢀ(d,ꢀ1H,ꢀJꢀ=ꢀ8.0ꢀHz),ꢀ5.31ꢀ(d,ꢀ1H,ꢀJꢀ=ꢀ5.6ꢀHz),ꢀ4.65ꢀ(s,ꢀ
didꢀ notꢀ reactꢀ underꢀ similarꢀ conditionsꢀ (Tableꢀ 3,ꢀ entryꢀ v).ꢀ
Theꢀreasonꢀthatꢀ4-nitroanilineꢀdidꢀnotꢀreactꢀmayꢀbeꢀattributedꢀ
toꢀtheꢀstrongꢀelectron-withdrawingꢀeffectꢀofꢀtheꢀnitroꢀgroup.
Toꢀ ourꢀ disappointment,ꢀ thisꢀ reactionꢀ wasꢀ notꢀ successfulꢀ
whenꢀaliphaticꢀaldehydesꢀwereꢀusedꢀasꢀaꢀstartingꢀmaterialꢀunderꢀ
theꢀsameꢀconditions,.ꢀWhenꢀaliphaticꢀaldehydesꢀwereꢀusedꢀasꢀ
substrates,ꢀtheꢀproductsꢀwereꢀcomplexꢀandꢀinseparable.
Inꢀconclusion,ꢀweꢀhaveꢀprovidedꢀaꢀnewꢀcatalystꢀthatꢀcanꢀactꢀ
inꢀeco-friendlyꢀmannerꢀforꢀtheꢀaza-Diels–Alderꢀreaction.ꢀItꢀisꢀ
non-volatile,ꢀreadilyꢀavailable,ꢀrecyclableꢀandꢀeasyꢀtoꢀhandle.ꢀ
Thisꢀmethodꢀnotꢀonlyꢀaffordsꢀtheꢀproductsꢀinꢀgoodꢀyieldsꢀbutꢀ
alsoꢀavoidsꢀtheꢀproblemsꢀassociatedꢀwithꢀcomplicatedꢀworkupꢀ
andꢀenviromentalꢀpollution.
1
H),ꢀ3.88ꢀ(brs,ꢀ1H,ꢀNH),ꢀ3.58–3.55ꢀ(m,ꢀ1H),ꢀ3.42ꢀ(t,ꢀ1H,ꢀJ =ꢀ11.6ꢀHz),ꢀ
2.14ꢀ(s,ꢀ1H),ꢀ1.55–1.42ꢀ(m,ꢀ4H).ꢀm/z(ESI):ꢀ265ꢀ(M+).
(4aS,5R,10bS)-5-phenyl-3,4,4a,5,6,10b-hexahydro-2H-
1
pyrano[3,2-c]quinoline (4a):ꢀPaleꢀyellowꢀoil.ꢀ HꢀNMRꢀd:ꢀ7.36–7.24ꢀ
(
m,ꢀ5H),ꢀ7.17ꢀ(d,ꢀ1H,ꢀJ =ꢀ8.0ꢀHz),ꢀ7.01ꢀ(t,ꢀ1H,ꢀJ =ꢀ8.0ꢀHz),ꢀ6.64ꢀ(t,ꢀ
H,ꢀJ =ꢀ8.0ꢀHz),ꢀ6.40ꢀ(d,ꢀ1H,ꢀJ =ꢀ8.0ꢀHz),ꢀ4.60ꢀ(d,ꢀ1H,ꢀJ =ꢀ10.4ꢀHz),ꢀ
.31ꢀ(d,ꢀ1H,ꢀJ =ꢀ2.4ꢀHz),ꢀ4.03ꢀ(d,ꢀ2H,ꢀJ =ꢀ8.8ꢀHz),ꢀ3.67–3.62ꢀ(m,ꢀ1H),ꢀ
.01–1.96ꢀ(m,ꢀ1H),ꢀ1.82–1.72ꢀ(m,ꢀ1H),ꢀ1.61–1.52ꢀ(m,ꢀ1H),ꢀ1.43–1.40ꢀ
1
4
2
+
(m,ꢀ1H),ꢀ1.27–1.22ꢀ(m,ꢀ1H).ꢀm/z(ESI):ꢀ265ꢀ(M ).
(4aS,5S,10bS)-5-(4-chlorophenyl)-3,4,4a,5,6,10b-hexahydro-2H-
9
pyrano[3,2-c]quinoline (3b):ꢀSolid,ꢀm.p.ꢀ168–169ꢀ°Cꢀ(Lit. ꢀm.p.ꢀ169–
1
1
70ꢀ°C). HꢀNMRꢀd:ꢀ7.41–7.33ꢀ(m,ꢀ5H),ꢀ7.08ꢀ(t,ꢀ1H,ꢀJ =ꢀ8.0ꢀHz),ꢀ6.79ꢀ
(t,ꢀ1H,ꢀJ =ꢀ8.0ꢀHz),ꢀ6.59ꢀ(d,ꢀ1H,ꢀJ =ꢀ8.0ꢀHz),ꢀ5.28ꢀ(d,ꢀ1H,ꢀJ =ꢀ5.2ꢀHz),ꢀ
4
.62ꢀ(s,ꢀ1H),ꢀ3.86ꢀ(brs,ꢀ1H,ꢀNH),ꢀ3.57ꢀ(d,ꢀ1H,ꢀJ =ꢀ11.2ꢀHz),ꢀ3.43–3.38ꢀ
(m,ꢀ1H),ꢀ2.09ꢀ(s,ꢀ1H),ꢀ1.53–1.24ꢀ(m,ꢀ4H).ꢀ13CꢀNMRꢀd:ꢀ144.8,ꢀ139.6,ꢀ
1
2
33.0,ꢀ128.4,ꢀ128.1,ꢀ127.5,ꢀ119.8,ꢀ118.5,ꢀ114.5,ꢀ72.5,ꢀ60.5,ꢀ58.7,ꢀ38.8,ꢀ
5.3,ꢀ17.8.ꢀm/z(ESI):ꢀ299ꢀ(M ).
+
Experimental
(
4aS,5R,10bS)-5-(4-chlorophenyl)-3,4,4a,5,6,10b-hexahydro-2H-
MeltingꢀpointsꢀwereꢀrecordedꢀonꢀaꢀBuchiꢀR-535ꢀapparatusꢀandꢀareꢀ
uncorrected.ꢀIRꢀspectraꢀwereꢀrecordedꢀusingꢀKBrꢀpelletsꢀonꢀaꢀNicoletꢀ
Aviatar-370ꢀ instrument.ꢀ Theꢀ NMRꢀ spectraꢀ wereꢀ measuredꢀ withꢀ aꢀ
BrukerꢀAdvanceꢀIIIꢀ500ꢀorꢀVarianꢀMercuryꢀPlus-400ꢀinstrumentꢀusingꢀ
9
pyrano[3,2-c]quinoline (4b):ꢀSolid,ꢀm.p.ꢀ124–126 ꢀ° Cꢀ(Lit. ꢀm.p.ꢀ122–
ꢀ1
1
23 ꢀ° C). HꢀNMRꢀd:ꢀ7.33ꢀ(s,ꢀ4H),ꢀ7.21ꢀ(d,ꢀ1H,ꢀJ =ꢀ7.6ꢀHz),ꢀ7.08ꢀ(t,ꢀ1H,ꢀ
J =ꢀ7.2ꢀHz),ꢀ6.70ꢀ(t,ꢀ1H,ꢀJ =ꢀ7.2ꢀHz),ꢀ6.51ꢀ(d,ꢀ1H,ꢀJ =ꢀ7.6ꢀHz),ꢀ4.65ꢀ(t,ꢀ1H,ꢀ
J =ꢀ5.6ꢀHz),ꢀ4.36ꢀ(s,ꢀ1H),ꢀ4.09–4.06ꢀ(m,ꢀ2H),ꢀ3.71ꢀ(t,ꢀ1H,ꢀJ =ꢀ11.6ꢀHz),ꢀ
CDCl ꢀasꢀtheꢀsolventꢀwithꢀTMSꢀasꢀinternalꢀstandard.ꢀMassꢀspectraꢀ
13
3
2.03–1.98ꢀ(m,ꢀ1H),ꢀ1.81–1.61ꢀ(m,ꢀ2H),ꢀ1.45–1.32ꢀ(m,ꢀ2H).ꢀ CꢀNMRꢀ
wereꢀmeasuredꢀwithꢀThermoꢀFinniganꢀLCQ-Advantage.
d:ꢀ144.5,ꢀ140.8,ꢀ133.4,ꢀ130.8,ꢀ129.3,ꢀ129.1,ꢀ128.7,ꢀ120.7,ꢀ117.7,ꢀ114.2,ꢀ
+
74.3,ꢀ68.5,ꢀ54.2,ꢀ38.9,ꢀ24.0,ꢀ21.9.ꢀm/z(ESI):ꢀ299ꢀ(M ).
General procedure
Prolineꢀ(20ꢀmmol)ꢀwasꢀdissolvedꢀinꢀwaterꢀ(10ꢀmL)ꢀcooledꢀinꢀice–
salt bath. Then trifluoromethanesulfonic acid in aqueous solutionꢀ
(
4aS,5S,10bS)-5-(4-bromophenyl)-3,4,4a,5,6,10b-hexahydro-2H-
pyrano[3,2-c]quinoline (3c):ꢀPaleꢀredꢀoilꢀ(Lit.20ꢀm.p.ꢀ124–126ꢀ°C).
1HꢀNMRꢀd:ꢀ7.50ꢀ(d,ꢀ2H,ꢀJ =ꢀ8.4ꢀHz),ꢀ7.42ꢀ(d,ꢀ1H,ꢀJ =ꢀ7.6ꢀHz),ꢀ7.30ꢀ
(20ꢀmmolꢀmL)ꢀwasꢀaddedꢀdropwise.ꢀTheꢀmixtureꢀwasꢀstirredꢀforꢀ2ꢀhꢀ
(d,ꢀ2H,ꢀJ =ꢀ8.4ꢀHz),ꢀ7.12–7.08ꢀ(m,ꢀ1H),ꢀ6.83–6.79ꢀ(m,ꢀ1H),ꢀ6.61ꢀ(d,ꢀ
1H,ꢀJ =ꢀ7.6ꢀHz),ꢀ5.31ꢀ(d,ꢀ1H,ꢀJ =ꢀ5.6ꢀHz),ꢀ4.65ꢀ(d,ꢀ1H,ꢀJ =ꢀ2.0ꢀHz),ꢀ
3.83ꢀ(brs,ꢀ1H,ꢀNH),ꢀ3.61–3.57ꢀ(m,ꢀ1H),ꢀ3.45–3.36ꢀ(m,ꢀ1H),ꢀ2.12–2.11ꢀ
atꢀ0ꢀ°C.ꢀTheꢀresidueꢀwasꢀextractedꢀwithꢀpetroleumꢀetherꢀthreeꢀtimes.ꢀ
Theꢀcombinedꢀorganicꢀlayerꢀwasꢀevaporatedꢀunderꢀreducedꢀpressureꢀ
to afford the pure proline triflate.
Molecularꢀsievesꢀwere addedꢀaꢀmixtureꢀofꢀbenzaldehydeꢀ(1.0ꢀmmol),ꢀ
anilineꢀ(1.0ꢀmmol)ꢀinꢀacetonitrileꢀ(3ꢀmL)ꢀatꢀ25ꢀ°C.ꢀTheꢀmixtureꢀwasꢀ
stirredꢀforꢀ10ꢀminꢀatꢀ25ꢀ°C.ꢀToꢀthisꢀmixture,ꢀdihydropyranꢀ(1.4ꢀmmol)ꢀ
and proline triflate (0.05 mmol) was added and the reaction stirred
forꢀtheꢀappropriateꢀtimeꢀ(Tableꢀ1).ꢀTheꢀprogressꢀofꢀtheꢀreactionꢀwasꢀ
monitoredꢀ byꢀ TLC.ꢀ Afterꢀ theꢀ reactionꢀ wasꢀ complete,ꢀ waterꢀ wasꢀ
1
3
(m,ꢀ1H),ꢀ1.55–1.25ꢀ(m,ꢀ4H).ꢀ CꢀNMRꢀd:ꢀ144.9,ꢀ140.2,ꢀ131.5,ꢀ128.5,ꢀ
127.6,ꢀ127.0,ꢀ121.2,ꢀ119.9,ꢀ118.6,ꢀ114.5,ꢀ72.6,ꢀ60.6,ꢀ58.9,ꢀ38.9,ꢀ25.3,ꢀ
18.0. m/z(ESI):ꢀ343ꢀ(M ).
+
(4aS,5R,10bS)-5-(4-bromophenyl)-3,4,4a,5,6,10b-hexahydro-2H-
2
0
pyrano[3,2-c]quinoline (4c):ꢀ Solid,ꢀ m.p.ꢀ 131–133ꢀ°Cꢀ (Lit. ꢀ m.p.ꢀ
127–129ꢀ°C). HꢀNMRꢀd:ꢀ7.51–7.48ꢀ(m,ꢀ2H),ꢀ7.31ꢀ(d,ꢀ2H,ꢀJ =ꢀ8.4ꢀHz),ꢀ
7.25–7.21ꢀ (m,ꢀ 1H),ꢀ 7.12–7.07ꢀ (m,ꢀ 1H),ꢀ 7.20ꢀ (t,ꢀ 1H,ꢀ J =ꢀ 7.6ꢀ Hz),ꢀ
1

5
02ꢀ JOURNALꢀOFꢀCHEMICALꢀRESEARCHꢀ2009
6
.53ꢀ(d,ꢀ1H,ꢀJ =ꢀ8.0ꢀHz),ꢀ4.69ꢀ(d,ꢀ1H,ꢀJ =ꢀ10.8ꢀHz),ꢀ4.38ꢀ(d,ꢀ1H,ꢀ
(4aS,5S,10bS)-5-(benzo[d][1,3]dioxol-5-yl)-3,4,4a,5,6,10b-
hexahydro-2H-pyrano[3,2-c]quinoline (3h):ꢀSolid,ꢀm.p.ꢀ162–163ꢀ°Cꢀ
J =ꢀ2.8ꢀHz),ꢀ4.11–4.07ꢀ(m,ꢀ2H),ꢀ3.72ꢀ(td,ꢀ1H,ꢀJ =ꢀ2.4,ꢀJ ꢀ=ꢀ11.2ꢀHz),ꢀ
1
ꢀ
2
2
3
1
2
(
.06–2.02ꢀ(m,ꢀ1H),ꢀ1.83–1.76ꢀ(m,ꢀ1H),ꢀ1.71–1.63ꢀ(m,ꢀ1H),ꢀ1.47–1.43ꢀ
(Lit. ꢀm.p.ꢀ158–160ꢀ°C). HꢀNMRꢀd:ꢀ7.41ꢀ(d,ꢀ1H,ꢀJ =ꢀ7.6ꢀHz),ꢀ7.08ꢀ
(t,ꢀ1H,ꢀJ =ꢀ7.6ꢀHz),ꢀ6.92–6.86ꢀ(m,ꢀ2H),ꢀ6.82–6.77ꢀ(m,ꢀ2H),ꢀ6.58ꢀ(d,ꢀ
1H,ꢀJ =ꢀ8.0ꢀHz),ꢀ5.96ꢀ(s,ꢀ2H),ꢀ5.30ꢀ(d,ꢀ1H,ꢀJ =ꢀ5.6ꢀHz),ꢀ4.59ꢀ(d,ꢀ1H,ꢀ
J =ꢀ2.0ꢀHz),ꢀ3.81ꢀ(brs,ꢀ1H,ꢀNH),ꢀ3.61–3.57ꢀ(m,ꢀ1H),ꢀ3.42ꢀ(t,ꢀ1H,ꢀJ =ꢀ
11.6ꢀHz),ꢀ2.11–2.09ꢀ(m,ꢀ1H),ꢀ1.57–1.36ꢀ(m,ꢀ4H).ꢀ CꢀNMRꢀd:ꢀ147.6,ꢀ
146.8,ꢀ145.1,ꢀ135.1,ꢀ128.1,ꢀ127.6,ꢀ120.0,ꢀ119.8,ꢀ118.3,ꢀ114.4,ꢀ108.1,ꢀ
m,ꢀ1H),ꢀ1.36–1.33ꢀ(m,ꢀ1H).ꢀ13CꢀNMRꢀd:ꢀ144.4,ꢀ141.4,ꢀ131.8,ꢀ130.9,ꢀ
1
2
29.5,ꢀ129.4,ꢀ121.6,ꢀ120.7,ꢀ117.8,ꢀ114.3,ꢀ74.3,ꢀ68.6,ꢀ54.4,ꢀ38.9,ꢀ24.1,ꢀ
+
2.0. m/z(ESI):ꢀ343ꢀ(M ).
13
(
4aS,5S,10bS)-5-(3-fluorophenyl)-3,4,4a,5,6,10b-hexahydro-2H-
-1
pyrano[3,2-c]quinoline (3d):ꢀ Solid,ꢀ m.p.ꢀ 153–154ꢀ°C.ꢀ IRꢀ (cm ):ꢀ
3
1
+
302ꢀ(NH).ꢀ HꢀNMRꢀd:ꢀ7.44–7.31ꢀ(m,ꢀ2H),ꢀ7.19–7.09ꢀ(m,ꢀ3H),ꢀ7.02–
107.4,ꢀ101.0,ꢀ72.7,ꢀ60.6,ꢀ59.1,ꢀ39.1,ꢀ25.4,ꢀ18.1. m/z(ESI):ꢀ309ꢀ(M ).
6
.97ꢀ(m,ꢀ1H),ꢀ6.81ꢀ(t,ꢀ1H,ꢀJ =ꢀ7.6ꢀHz),ꢀ6.62ꢀ(d,ꢀ1H,ꢀJ =ꢀ8.0ꢀHz),ꢀ5.32ꢀ
(4aS,5R,10bS)-5-(benzo[d][1,3]dioxol-5-yl)-3,4,4a,5,6,10b-
(d,ꢀ1H,ꢀJ =ꢀ5.6ꢀHz),ꢀ4.69ꢀ(d,ꢀ1H,ꢀJ =ꢀ2.0ꢀHz),ꢀ3.85ꢀ(brs,ꢀ1H,ꢀNH),ꢀ
hexahydro-2H-pyrano[3,2-c]quinoline (4h):ꢀ Solid,ꢀ m.p.ꢀ 143–145 ꢀ° Cꢀ
3
.61–3.40ꢀ(m,ꢀ2H),ꢀ2.17–2.16ꢀ(m,ꢀ1H),ꢀ1.56–1.44ꢀ(m,ꢀ3H),ꢀ1.29–1.28ꢀ
(Lit.23ꢀm.p.ꢀ150–152 ꢀ° C).ꢀ1HꢀNMRꢀd:ꢀ7.21ꢀ(d,ꢀ1H,ꢀJ =ꢀ7.6ꢀHz),ꢀ7.10–
13
(m,ꢀ1H).ꢀ CꢀNMRꢀd:ꢀ164.1,ꢀ161.7,ꢀ144.8,ꢀ144.0,ꢀ143.9,ꢀ129.9,ꢀ129.8,ꢀ
7.06ꢀ(m,ꢀ1H), 6.92–6.85ꢀ(m,ꢀ2H),ꢀ6.79ꢀ(d,ꢀ1H,ꢀJ =ꢀ8.0ꢀHz),ꢀ6.70ꢀ(t,ꢀ1H,ꢀ
J=ꢀ7.6ꢀHz),ꢀ6.51ꢀ(d,ꢀ1H,ꢀJ=ꢀ8.4ꢀHz),ꢀ5.96ꢀ(s,ꢀ2H),ꢀ4.63ꢀ(d,ꢀ1H,ꢀJ=ꢀ10.8ꢀHz),ꢀ
1
28.1,ꢀ127.6,ꢀ122.4,ꢀ120.2,ꢀ119.9,ꢀ118.6,ꢀ114.6,ꢀ114.4,ꢀ114.2,ꢀ113.9,ꢀ
+
113.6,ꢀ72.6,ꢀ60.1,ꢀ58.9,ꢀ38.9,ꢀ25.3,ꢀ18.0.ꢀm/z(ESI):ꢀ283ꢀ(M ).ꢀHRMS-
ESI:ꢀCalcdꢀforꢀC H FNO:ꢀ283.1372.ꢀFound:ꢀ283.1389.
4
.37ꢀ(d,ꢀ1H,ꢀJ =ꢀ2.4ꢀHz),ꢀ4.11–4.04ꢀ(m,ꢀ2H),ꢀ3.72ꢀ(td,ꢀ1H,ꢀJ =ꢀ2.4,ꢀ
1ꢀ
18
18
J =ꢀ11.6ꢀHz),ꢀ2.03–1.09ꢀ(m,ꢀ1H),ꢀ1.84–1.76ꢀ(m,ꢀ1H),ꢀ1.70–1.61ꢀ(m,ꢀ
2ꢀ
(
4aS,5R,10bS)-5-(3-fluorophenyl)-3,4,4a,5,6,10b-hexahydro-2H-
ꢀ13
1
1
1
H),ꢀ1.54–1.50ꢀ(m,ꢀ1H),ꢀ1.35–1.32ꢀ(m,ꢀ1H). CꢀNMRꢀd:ꢀ148.0,ꢀ147.2,ꢀ
-1
pyrano[3,2-c]quinolineꢀ(4d):ꢀPaleꢀyellowꢀoil.ꢀIRꢀ(cm ):ꢀ3364ꢀ(NH).ꢀ
44.7,ꢀ136.2,ꢀ130.9,ꢀ129.3,ꢀ121.3,ꢀ120.7,ꢀ117.5,ꢀ114.2,ꢀ108.1,ꢀ107.7,ꢀ
1
HꢀNMRꢀd:ꢀ7.36–7.30ꢀ(m,ꢀ1H),ꢀ7.26–7.08ꢀ(m,ꢀ4H),ꢀ7.04–6.99ꢀ(m,ꢀ
+
01.0,ꢀ74.6,ꢀ68.7,ꢀ54.5,ꢀ39.0,ꢀ24.1,ꢀ22.0.ꢀm/z(ESI):ꢀ309ꢀ(M ).
1
4
1
1
H),ꢀ6.72ꢀ(td,ꢀ1H,ꢀJ =ꢀ1.2,ꢀJ =ꢀ7.6ꢀHz),ꢀ6.55ꢀ(d,ꢀ1H,ꢀJ =ꢀ8.0ꢀHz),ꢀ
1ꢀ 2ꢀ
(4aS,5S,10bS)-5-(2-methoxyphenyl)-3,4,4a,5,6,10b-hexahydro-
.72ꢀ(d,ꢀ1H,ꢀJ =ꢀ10.8ꢀHz),ꢀ4.39ꢀ(d,ꢀ1H,ꢀJ =ꢀ2.8ꢀHz),ꢀ4.12–4.08ꢀ(m,ꢀ
H),ꢀ 3.76–3.68ꢀ (m,ꢀ 2H),ꢀ 2.09–2.03ꢀ (m,ꢀ 1H),ꢀ 1.86–1.78ꢀ (m,ꢀ 1H),ꢀ
.72–1.63ꢀ(m,ꢀ1H),ꢀ1.49–1.46ꢀ(m,ꢀ1H),ꢀ1.39–1.33ꢀ(m,ꢀ1H).ꢀ CꢀNMRꢀ
-1
2
3
7
H-pyrano[3,2-c]quinolineꢀ(3i):ꢀSolid,ꢀm.p.ꢀ133–134ꢀ°C.ꢀIRꢀ(cm ):ꢀ
1
323ꢀ(NH).ꢀ HꢀNMRꢀd:ꢀ7.55ꢀ(d,ꢀ1H,ꢀJ=ꢀ7.6ꢀHz),ꢀ7.43ꢀ(d,ꢀ1H,ꢀJ=ꢀ7.6ꢀHz),ꢀ
1
3
.30–7.25ꢀ(m,ꢀ1H),ꢀ7.08ꢀ(t,ꢀ1H,ꢀJ =ꢀ7.6ꢀHz),ꢀ6.98ꢀ(t,ꢀ1H,ꢀJ =ꢀ7.2ꢀHz),ꢀ6.90ꢀ
d:ꢀ164.3,ꢀ161.9,ꢀ145.1ꢀ¥ꢀ2,ꢀ144.4,ꢀ130.8,ꢀ130.1,ꢀ130.0,ꢀ129.4,ꢀ123.5,ꢀ
(
d,ꢀ1H,ꢀJ =ꢀ8.0ꢀHz),ꢀ6.78ꢀ(t,ꢀ1H,ꢀJ =ꢀ7.2ꢀHz),ꢀ6.60ꢀ(d,ꢀ1H,ꢀJ =ꢀ8.0ꢀHz),ꢀ
.32ꢀ(d,ꢀ1H,ꢀJ =ꢀ5.6ꢀHz),ꢀ5.03ꢀ(s,ꢀ1H),ꢀ3.84ꢀ(s,ꢀ3H),ꢀ3.68ꢀ(brs,ꢀ1H,ꢀ
NH),ꢀ3.60–3.57ꢀ(m,ꢀ1H),ꢀ3.42ꢀ(t,ꢀ1H,ꢀJ =ꢀ11.2ꢀHz),ꢀ2.33–2.31ꢀ(m,ꢀ1H),ꢀ
1
2
2
20.6,ꢀ120.1,ꢀ117.7,ꢀ114.9,ꢀ114.6,ꢀ114.4,ꢀ114.2,ꢀ74.3,ꢀ68.5,ꢀ54.5,ꢀ39.0,ꢀ
5
+
4.1,ꢀ22.0.ꢀm/z(ESI):ꢀ283ꢀ(M ).ꢀHRMS-ESI:ꢀCalcdꢀforꢀC H FNO:ꢀ
1
8
18
83.1372.ꢀFound:ꢀ283.1378.
4aS,5S,10bS)-5-(3-bromophenyl)-3,4,4a,5,6,10b-hexahydro-
13
1
1
2
2
.56–1.25ꢀ(m,ꢀ4H).ꢀ CꢀNMRꢀd:ꢀ156.4,ꢀ145.7,ꢀ128.1,ꢀ127.9,ꢀ127.1,ꢀ
(
20.3,ꢀ120.2,ꢀ120.1,ꢀ118.0,ꢀ114.5,ꢀ110.3,ꢀ72.7,ꢀ60.6,ꢀ55.3,ꢀ52.6,ꢀ35.2,ꢀ
5.6,ꢀ18.5.ꢀm/z(ESI):ꢀ295ꢀ(M ).ꢀHRMS-ESI:ꢀCalcdꢀforꢀC H NO :ꢀ
95.1572.ꢀFound:ꢀ295.1583.
4aS,5R,10bS)-5-(2-methoxyphenyl)-3,4,4a,5,6,10b-hexahydro-
H-pyrano[3,2-c]quinolineꢀ(4i):ꢀSolid,ꢀm.p.ꢀ136–138ꢀ°C.ꢀIRꢀ(cm ):ꢀ
-1
ꢀ
2
H-pyrano[3,2-c]quinolineꢀ(3e):ꢀPaleꢀredꢀoil.ꢀIRꢀ(cm ):ꢀ3372ꢀ(NH).
+
1
9
21
2
1
HꢀNMRꢀd:ꢀ7.59ꢀ(s,ꢀ1H),ꢀ7.45–7.41ꢀ(m,ꢀ2H),ꢀ7.33ꢀ(d,ꢀ1H,ꢀJ =ꢀ7.6ꢀHz),ꢀ
7.27–7.23ꢀ(m,ꢀ1H),ꢀ7.10ꢀ(t,ꢀ1H,ꢀJ =ꢀ7.6ꢀHz),ꢀ6.81ꢀ(t,ꢀ1H,ꢀJ =ꢀ7.6ꢀHz),ꢀ6.62ꢀ
(
(
3
d,ꢀ1H,ꢀJ =ꢀ8.0ꢀHz),ꢀ5.31ꢀ(d,ꢀ1H,ꢀJ =ꢀ5.6ꢀHz),ꢀ4.65ꢀ(d,ꢀ1H,ꢀJ =ꢀ2.8ꢀHz),ꢀ
.83ꢀ(brs,ꢀ1H,ꢀNH),ꢀ3.61–3.57ꢀ(m,ꢀ1H),ꢀ3.46–3.39ꢀ(m,ꢀ1H),ꢀ2.19–2.13ꢀ
-1
2
3
7
1
1
2
(
1
5
1
389ꢀ(NH).ꢀ HꢀNMRꢀd:ꢀ7.43ꢀ(dd,ꢀ1H,ꢀJ ꢀ=ꢀ1.6,ꢀJ ꢀ=ꢀ7.6ꢀHz),ꢀ7.27–
ꢀ
13
1
2
(
1
m,ꢀ1H),ꢀ1.59–1.44ꢀ(m,ꢀ3H),ꢀ1.29–1.27ꢀ(m,ꢀ1H). CꢀNMRꢀd:ꢀ144.4,ꢀ
.21ꢀ(m,ꢀ2H),ꢀ7.08–7.04ꢀ(m,ꢀ1H),ꢀ6.97–6.88ꢀ(m,ꢀ2H),ꢀ6.69–6.66ꢀ(m,ꢀ
H),ꢀ6.50ꢀ(d,ꢀ1H,ꢀJ =ꢀ8.0ꢀHz),ꢀ5.18ꢀ(d,ꢀ1H,ꢀJ =ꢀ10.0ꢀHz),ꢀ4.41ꢀ(d,ꢀ
H,ꢀJ =ꢀ2.8ꢀHz),ꢀ4.01–3.99ꢀ(m,ꢀ1H),ꢀ3.83ꢀ(s,ꢀ3H),ꢀ3.70–3.63ꢀ(m,ꢀ2H),ꢀ
.13–2.12ꢀ(m,ꢀ1H),ꢀ1.94–1.90ꢀ(m,ꢀ1H),ꢀ1.66–1.61ꢀ(m,ꢀ1H),ꢀ1.51–1.46ꢀ
43.2,ꢀ130.3,ꢀ129.6,ꢀ129.5,ꢀ127.8,ꢀ127.3,ꢀ125.2,ꢀ122.3,ꢀ119.6,ꢀ118.3,ꢀ
+
114.3,ꢀ72.2,ꢀ60.3,ꢀ58.5,ꢀ38.5,ꢀ25.0,ꢀ17.6. m/z(ESI):ꢀ343ꢀ(M ).ꢀHRMS-
ESI:ꢀCalcdꢀforꢀC H BrNO:ꢀ343.0572.ꢀFound:ꢀ343.0580.
18
18
(
4aS,5R,10bS)-5-(3-bromophenyl)-3,4,4a,5,6,10b-hexahydro-
1
3
m,ꢀ1H),ꢀ1.37–1.32ꢀ(m,ꢀ1H).ꢀ CꢀNMRꢀd:ꢀ157.4,ꢀ145.0,ꢀ130.9,ꢀ130.4,ꢀ
29.0,ꢀ 128.3,ꢀ 128.1,ꢀ 120.8,ꢀ 120.3,ꢀ 117.0,ꢀ 113.9,ꢀ 110.4,ꢀ 74.0,ꢀ 67.6,ꢀ
5.3,ꢀ38.2,ꢀ24.4,ꢀ22.6,ꢀ18.3.ꢀm/z(ESI):ꢀ295ꢀ(M ).ꢀHRMS-ESI:ꢀCalcdꢀ
-1
2
H-pyrano[3,2-c]quinoline (4e):ꢀSolid,ꢀm.p.ꢀ143–145ꢀ°C.ꢀIRꢀ(cm ):ꢀ
1
3
363ꢀ(NH).ꢀ HꢀNMRꢀd:ꢀ7.59ꢀ(s,ꢀ1H),ꢀ7.47–7.44ꢀ(m,ꢀ1H),ꢀ7.34ꢀ(d,ꢀ1H,ꢀ
+
J =ꢀ7.2ꢀHz),ꢀ7.26–7.21ꢀ(m,ꢀ2H),ꢀ7.10ꢀ(t,ꢀ1H,ꢀJ =ꢀ7.6ꢀHz),ꢀ6.72ꢀ(t,ꢀ1H,ꢀ
J =ꢀ7.6ꢀHz),ꢀ6.54ꢀ(d,ꢀ1H,ꢀJ =ꢀ8.0ꢀHz),ꢀ4.68ꢀ(d,ꢀ1H,ꢀJ =ꢀ10.8ꢀHz),ꢀ4.38ꢀ
forꢀC H NO :ꢀ295.1572.ꢀFound:ꢀ295.1581.
1
9
21
2
(
4aS,5S,10bS)-5-(thiophen-2-yl)-3,4,4a,5,6,10b-hexahydro-
(
d,ꢀ2H,ꢀJ =ꢀ2.8ꢀHz),ꢀ4.12–4.08ꢀ(m,ꢀ2H),ꢀ3.76–3.69ꢀ(m,ꢀ1H),ꢀ2.08–2.04ꢀ
24
2
H-pyrano[3,2-c]quinoline (3j):ꢀ Solid,ꢀ m.p.ꢀ 162–164ꢀ°Cꢀ (Lit. ꢀ
ꢀ
13
(m,ꢀ1H),ꢀ1.88–1.76ꢀ(m,ꢀ1H),ꢀ1.72–1.35ꢀ(m,ꢀ3H). CꢀNMRꢀd:ꢀ144.8,ꢀ
1
m.p.ꢀ155–156ꢀ°C). HꢀNMRꢀd:ꢀ7.42ꢀ(d,ꢀ1H,ꢀJ =ꢀ7.2ꢀHz),ꢀ7.25–7.23ꢀ
(m,ꢀ1H),ꢀ7.11–7.02ꢀ(m,ꢀ3H),ꢀ6.81ꢀ(t,ꢀ1H,ꢀJ =ꢀ7.2ꢀHz),ꢀ6.60ꢀ(d,ꢀ1H,ꢀ
J =ꢀ8.0ꢀHz),ꢀ5.28ꢀ(d,ꢀ1H,ꢀJ =ꢀ5.6ꢀHz),ꢀ4.96ꢀ(d,ꢀ1H,ꢀJ =ꢀ2.4ꢀHz),ꢀ4.01ꢀ
1
44.4,ꢀ131.0,ꢀ130.9,ꢀ130.8,ꢀ130.2,ꢀ129.4,ꢀ126.6,ꢀ122.8,ꢀ120.6,ꢀ117.8,ꢀ
+
114.2,ꢀ74.3,ꢀ68.6,ꢀ54.5,ꢀ38.9,ꢀ24.1,ꢀ22.0. m/z(ESI):ꢀ343ꢀ(M ).ꢀHRMS-
ESI:ꢀCalcdꢀforꢀC H BrNO:ꢀ343.0572.ꢀFound:ꢀ343.0575.
18
18
(
brs,ꢀ 1H,ꢀ NH),ꢀ 3.61–3.58ꢀ (m,ꢀ 1H),ꢀ 3.45–3.39ꢀ (m,ꢀ 1H),ꢀ 2.24–2.19ꢀ
(
4aS,5S,10bS)-5-(3-chlorophenyl)-3,4,4a,5,6,10b-hexahydro-2H-
ꢀ
13
2
1
ꢀ1
(m,ꢀ1H),ꢀ1.63–1.47ꢀ(m,ꢀ4H). CꢀNMRꢀd:ꢀ144.7,ꢀ144.6,ꢀ128.1,ꢀ127.6,ꢀ
1
1
pyrano[3,2-c]quinoline (3f): ꢀPaleꢀyellowꢀoil. HꢀNMRꢀd:ꢀ7.42ꢀ(d,ꢀ
H,ꢀJ =ꢀ8.0ꢀHz),ꢀ7.31–7.26ꢀ(m,ꢀ3H),ꢀ7.12–7.08ꢀ(m,ꢀ1H),ꢀ6.81ꢀ(t,ꢀ1H,ꢀ
J =ꢀ7.6ꢀHz),ꢀ6.62ꢀ(d,ꢀ1H,ꢀJ =ꢀ8.0ꢀHz),ꢀ5.31ꢀ(d,ꢀ1H,ꢀJ =ꢀ5.6ꢀHz),ꢀ4.66ꢀ
26.7,ꢀ123.9,ꢀ123.8,ꢀ120.2,ꢀ118.8,ꢀ114.6,ꢀ72.2,ꢀ60.6,ꢀ55.6,ꢀ39.6,ꢀ25.3,ꢀ
2
+
8.4.ꢀm/z(ESI):ꢀ271ꢀ(M ).
(
4aS,5R,10bS)-5-(thiophen-2-yl)-3,4,4a,5,6,10b-hexahydro-2H-
(
(
d,ꢀ1H,ꢀJ =ꢀ2.4ꢀHz),ꢀ3.61–3.57ꢀ(m,ꢀ1H),ꢀ3.46–3.39ꢀ(m,ꢀ1H),ꢀ2.17–2.15ꢀ
m,ꢀ1H),ꢀ1.56–1.44ꢀ(m,ꢀ4H). m/z(ESI):ꢀ299ꢀ(M ).
2
4
+
pyrano[3,2-c]quinoline (4j):ꢀSolid,ꢀm.p.ꢀ137–138ꢀ°Cꢀ(Lit. ꢀm.p.ꢀ135–ꢀ
37ꢀ°C). Hꢀ NMRꢀ d:ꢀ 7.29–7.20ꢀ (m,ꢀ 2H),ꢀ 7.11–7.06ꢀ (m,ꢀ 2H),ꢀ 6.99ꢀ
(t,ꢀ1H,ꢀJ =ꢀ4.4ꢀHz),ꢀ6.72ꢀ(t,ꢀ1H,ꢀJ =ꢀ7.6ꢀHz),ꢀ6.54ꢀ(d,ꢀ1H,ꢀJ =ꢀ7.6ꢀHz),ꢀ
1
1
(
4aS,5R,10bS)-5-(3-chlorophenyl)-3,4,4a,5,6,10b-hexahydro-2H-
2
1
ꢀ 1
pyrano[3,2-c]quinoline (4f): ꢀ Solid,ꢀ m.p.ꢀ 91–93ꢀ°C. Hꢀ NMRꢀ d:ꢀ
.43–7.36ꢀ(m,ꢀ3H),ꢀ7.05–6.97ꢀ(m,ꢀ2H),ꢀ6.59ꢀ(d,ꢀ1H,ꢀJ =ꢀ7.6ꢀHz),ꢀ6.52ꢀ
t,ꢀ1H,ꢀJ =ꢀ7.6ꢀHz),ꢀ6.18ꢀ(s,ꢀ1H),ꢀ4.55ꢀ(d,ꢀ1H,ꢀJ =ꢀ10.4ꢀHz),ꢀ4.28ꢀ(d,ꢀ1H,ꢀ
J =ꢀ3.2ꢀHz),ꢀ3.89–3.87ꢀ(m,ꢀ1H),ꢀ3.59ꢀ(dt,ꢀ1H,ꢀJ =ꢀ2.0,ꢀJ =ꢀ10.8ꢀHz),ꢀ
5
.05ꢀ(d,ꢀ1H,ꢀJ =ꢀ10.4ꢀHz),ꢀ4.39ꢀ(s,ꢀ1H),ꢀ4.24ꢀ(brs,ꢀ1H,ꢀNH),ꢀ4.09ꢀ(d,ꢀ
7
(
1
H,ꢀJ =ꢀ11.2ꢀHz),ꢀ3.75–3.69ꢀ(m,ꢀ1H),ꢀ2.06–2.03ꢀ(m,ꢀ1H),ꢀ1.86–1.60ꢀ
13
(
m,ꢀ3H),ꢀ1.37–1.35ꢀ(m,ꢀ1H).ꢀ CꢀNMRꢀd:ꢀ146.2,ꢀ144.1,ꢀ130.8,ꢀ129.3,ꢀ
1
ꢀ
2ꢀ
ꢀ
13
126.4,ꢀ125.4,ꢀ125.0,ꢀ120.8,ꢀ117.9,ꢀ114.3,ꢀ74.4,ꢀ68.6,ꢀ50.7,ꢀ40.2,ꢀ24.1,ꢀ
1
.95–1.92ꢀ(m,ꢀ1H),ꢀ1.78–1.60ꢀ(m,ꢀ2H),ꢀ1.30–1.24ꢀ(m,ꢀ2H). CꢀNMRꢀ
+
2
1.9. m/z(ESI):ꢀ271ꢀ(M ).
d:ꢀ 144.5,ꢀ 144.4,ꢀ 134.6,ꢀ 130.9,ꢀ 129.9,ꢀ 128.1,ꢀ 127.9,ꢀ 126.1,ꢀ 120.6,ꢀ
+
2-((4aS,5S,10bS)-3,4,4a,5,6,10b-hexahydro-2H-pyrano[3,2-c]
117.8,ꢀ114.2,ꢀ74.3,ꢀ68.6,ꢀ54.5,ꢀ38.9,ꢀ24.1,ꢀ22.0. m/z(ESI):ꢀ299ꢀ(M ).
-1
quinolin-5-yl)phenol (3k):ꢀSolid,ꢀm.p.ꢀ120–121ꢀ°C.ꢀIRꢀ(cm ):ꢀ3342ꢀ
(
4aS,5S,10bS)-5-(2,4-dimethoxyphenyl)-3,4,4a,5,6,10b-
1
2
2
(NH).ꢀ HꢀNMRꢀd:ꢀ7.42ꢀ(d,ꢀ1H,ꢀJ =ꢀ7.6ꢀHz),ꢀ7.25–7.19ꢀ(m,ꢀ3H),ꢀ6.94–
hexahydro-2H-pyrano[3,2-c]quinoline (3g): ꢀ Solid,ꢀ m.p.ꢀ 162–
1
6.90ꢀ(m,ꢀ2H),ꢀ6.79–6.71ꢀ(m,ꢀ3H),ꢀ5.57ꢀ(d,ꢀ1H,ꢀJ =ꢀ2.0ꢀHz),ꢀ5.01ꢀ(d,ꢀ
1
63ꢀ°C. HꢀNMRꢀd:ꢀ7.44–7.41ꢀ(m,ꢀ2H),ꢀ7.07ꢀ(t,ꢀ1H,ꢀJ =ꢀ7.2ꢀHz),ꢀ6.77ꢀ
1
2
H,ꢀJ =ꢀ5.2ꢀHz),ꢀ4.02ꢀ(td,ꢀ1H,ꢀJ =ꢀ2.8,ꢀJ =ꢀ11.6ꢀHz),ꢀ3.81–3.74ꢀ(m,ꢀ
H),ꢀ2.54–2.48ꢀ(m,ꢀ1H),ꢀ1.72–1.60ꢀ(m,ꢀ3H),ꢀ1.38–1.32ꢀ(m,ꢀ1H).ꢀ Cꢀ
(t,ꢀ1H,ꢀJ =ꢀ7.6ꢀHz),ꢀ6.59ꢀ(d,ꢀ1H,ꢀJ =ꢀ8.0ꢀHz),ꢀ6.51–6.49ꢀ(m,ꢀ2H),ꢀ5.30ꢀ
d,ꢀ1H,ꢀJ =ꢀ5.6ꢀHz),ꢀ4.95ꢀ(d,ꢀ1H,ꢀJ =ꢀ2.0ꢀHz),ꢀ3.82ꢀ(d,ꢀ6H,ꢀJ =ꢀ3.6ꢀHz),ꢀ
1ꢀ 2ꢀ
13
(
3
1
1
7
.64–3.57ꢀ (m,ꢀ2H),ꢀ 3.42ꢀ(t,ꢀ1H,ꢀJ =ꢀ11.6ꢀHz),ꢀ 2.28–2.26ꢀ (m,ꢀ1H),ꢀ
NMRꢀd:ꢀ153.1,ꢀ146.9,ꢀ129.6,ꢀ129.0,ꢀ126.7,ꢀ121.9,ꢀ121.1,ꢀ118.1,ꢀ116.4,ꢀ
1
3
113.2,ꢀ96.4,ꢀ60.9,ꢀ51.0,ꢀ34.8,ꢀ24.2,ꢀ17.1.ꢀm/z(ESI):ꢀ281ꢀ(M+).ꢀHRMS-
.60–1.41ꢀ(m,ꢀ3H),ꢀ1.28–1.23ꢀ(m,ꢀ1H).ꢀ CꢀNMRꢀd:ꢀ160.0,ꢀ157.4,ꢀ
45.8,ꢀ127.8,ꢀ127.7,ꢀ127.6,ꢀ121.5,ꢀ120.2,ꢀ118.0,ꢀ114.0,ꢀ103.5,ꢀ98.5,ꢀ
ESI:ꢀCalcdꢀforꢀC18H19NO2:ꢀ281.1416.ꢀFound:ꢀ281.1423.
+
(4aS,5S,10bS)-5-(3-methoxyphenyl)-3,4,4a,5,6,10b-hexahydro-
2.7,ꢀ60.7,ꢀ55.4,ꢀ55.3,ꢀ52.2,ꢀ35.5,ꢀ25.6,ꢀ18.4. m/z (ESI):ꢀ325ꢀ(M ).ꢀ
4aS,5R,10bS)-5-(2,4-dimethoxyphenyl)-3,4,4a,5,6,10b-hexahydro-
-1
(
2H-pyrano[3,2-c]quinolineꢀ(3l):ꢀSolid,ꢀm.p.ꢀ119–120ꢀ°C.ꢀIRꢀ(cm ):ꢀ
22
ꢀ1
1
2
H-pyrano[3,2-c]quinoline (4g): ꢀSolid,ꢀm.p.ꢀ144–146 ꢀ° C. HꢀNMRꢀd:
3300ꢀ(NH).ꢀ HꢀNMRꢀd:ꢀ7.42ꢀ(d,ꢀ1H,ꢀJ=ꢀ7.6ꢀHz),ꢀ7.28ꢀ(q,ꢀ1H,ꢀJ=ꢀ8.0ꢀHz),ꢀ
7.34ꢀ(d,ꢀ1H,ꢀJ =ꢀ8.4ꢀHz),ꢀ7.24ꢀ(t,ꢀ1H,ꢀJ =ꢀ7.2ꢀHz),ꢀ7.06ꢀ(t,ꢀ1H,ꢀJ =ꢀ7.6ꢀ
7.09ꢀ(t,ꢀ1H,ꢀJ =ꢀ7.6ꢀHz),ꢀ7.00–6.98ꢀ(m,ꢀ2H),ꢀ6.86–6.77ꢀ(m,ꢀ2H),ꢀ6.60ꢀ
(d,ꢀ1H,ꢀJ =ꢀ8.0ꢀHz),ꢀ5.32ꢀ(d,ꢀ1H,ꢀJ =ꢀ5.2ꢀHz),ꢀ4.66ꢀ(d,ꢀ1H,ꢀJ =ꢀ2.0ꢀHz),ꢀ
3.86–3.83ꢀ(m,ꢀ4H),ꢀ3.58ꢀ(dd,ꢀ1H,ꢀJ1ꢀ=ꢀ3.6,ꢀJ2ꢀ=ꢀ11.2ꢀHz),ꢀ3.45–3.40ꢀ
Hz),ꢀ6.68ꢀ(t,ꢀ1H,ꢀJ =ꢀ7.2ꢀHz),ꢀ6.52–6.47ꢀ(m,ꢀ3H),ꢀ5.12ꢀ(d,ꢀ1H,ꢀJ =ꢀ10.0ꢀ
Hz),ꢀ4.40ꢀ(d,ꢀ1H,ꢀJ =ꢀ2.8ꢀHz),ꢀ4.04–3.99ꢀ(m,ꢀ1H),ꢀ3.81ꢀ(s,ꢀ6H),ꢀ3.68ꢀ(td,ꢀ
1
3
1
H,ꢀJ =ꢀ2.8,ꢀJ =ꢀ11.2ꢀHz),ꢀ2.10ꢀ(s,ꢀ1H),ꢀ1.92–1.89ꢀ(m,ꢀ1H),ꢀ1.68–1.62ꢀ
(m,ꢀ1H),ꢀ2.17ꢀ(s,ꢀ1H),ꢀ1.56–1.25ꢀ(m,ꢀ4H).ꢀ CꢀNMRꢀd:ꢀ159.7,ꢀ145.1,ꢀ
1ꢀ
2ꢀ
ꢀ
13
(
m,ꢀ1H),ꢀ1.53–1.49ꢀ(m,ꢀ1H),ꢀ1.34–1.31ꢀ(m,ꢀ1H). CꢀNMRꢀd:ꢀ160.1,ꢀ
142.9,ꢀ129.4,ꢀ128.1,ꢀ127.6,ꢀ120.2,ꢀ119.9,ꢀ119.1,ꢀ118.3,ꢀ114.4,ꢀ112.6,ꢀ
+
1
58.6,ꢀ145.1,ꢀ130.6,ꢀ129.0,ꢀ128.2,ꢀ123.2,ꢀ120.5,ꢀ117.1,ꢀ114.0,ꢀ104.7,ꢀ
72.7,ꢀ60.6,ꢀ59.3,ꢀ55.3,ꢀ38.9,ꢀ25.4,ꢀ18.1.ꢀm/z(ESI):ꢀ295ꢀ(M ).ꢀHRMS-
+
98.2,ꢀ74.3,ꢀ68.0,ꢀ55.3,ꢀ47.2,ꢀ38.3,ꢀ24.5,ꢀ22.5. m/z(ESI):ꢀ325ꢀ(M ).
ESI:ꢀCalcdꢀforꢀC H NO :ꢀ295.1572.ꢀFound:ꢀ295.1574.
1
9
21
2

JOURNALꢀOFꢀCHEMICALꢀRESEARCHꢀ2009ꢀ 503
(
4aS,5R,10bS)-5-(3-nitrophenyl)-3,4,4a,5,6,10b-hexahydro-2H-
140.5,ꢀ 133.5,ꢀ 128.9,ꢀ 128.4,ꢀ 127.7,ꢀ 126.7,ꢀ 118.2,ꢀ 113.8,ꢀ 72.3,ꢀ 60.6,ꢀ
59.3,ꢀ38.6,ꢀ25.3,ꢀ18.0. m/z(ESI):ꢀ299ꢀ(M ).
2
3
+
pyrano[3,2-c]quinoline (4m):ꢀ Solid,ꢀ m.p.ꢀ 175–176ꢀ°Cꢀ (Lit. ꢀ m.p.ꢀ
1
1
(
7
60–162ꢀ°C). HꢀNMRꢀd:ꢀ8.29ꢀ(s,ꢀ1H),ꢀ8.17ꢀ(d,ꢀ1H,ꢀJ =ꢀ8.0ꢀHz),ꢀ7.75ꢀ
d,ꢀ1H,ꢀJ =ꢀ7.6ꢀHz),ꢀ7.54ꢀ(t,ꢀ1H,ꢀJ =ꢀ8.0ꢀHz),ꢀ7.22ꢀ(d,ꢀ1H,ꢀJ =ꢀ7.6ꢀHz),ꢀ
.11ꢀ(t,ꢀ1H,ꢀJ =ꢀ7.6ꢀHz),ꢀ6.74ꢀ(d,ꢀ1H,ꢀJ =ꢀ7.2ꢀHz),ꢀ6.56ꢀ(d,ꢀ1H,ꢀJ =ꢀ8.0ꢀ
Hz),ꢀ4.80ꢀ(d,ꢀ1H,ꢀJ =ꢀ10.8ꢀHz),ꢀ4.38ꢀ(d,ꢀ1H,ꢀJ =ꢀ2.4ꢀHz),ꢀ4.15–4.09ꢀ
(4aS,5R,10bS)-8-chloro-5-phenyl-3,4,4a,5,6,10b-hexahydro-2H-
2
5
1
pyrano[3,2-c]quinoline (4r): ꢀSolid,ꢀm.p.ꢀ104–106ꢀ°C.ꢀ HꢀNMRꢀd:ꢀ
7.39–7.31ꢀ(m,ꢀ5H),ꢀ7.13ꢀ(d,ꢀ1H,ꢀJ =ꢀ8.0ꢀHz),ꢀ6.65ꢀ(dd,ꢀ1H,ꢀJ =ꢀ2.0,ꢀ
1ꢀ
J =ꢀ8.0ꢀHz),ꢀ6.51ꢀ(d,ꢀ1H,ꢀJ =ꢀ2.0ꢀHz),ꢀ4.68ꢀ(d,ꢀ1H,ꢀJ =ꢀ10.8ꢀHz),ꢀ4.35ꢀ
2
ꢀ
(
m,ꢀ2H),ꢀ3.73ꢀ(t,ꢀ1H,ꢀJ =ꢀ10.8ꢀHz),ꢀ2.10–2.07ꢀ(m,ꢀ1H),ꢀ1.87–1.66ꢀ
(d,ꢀ1H,ꢀJ =ꢀ2.8ꢀHz),ꢀ4.07ꢀ(dt,ꢀ1H,ꢀJ =ꢀ2.8,ꢀJ =ꢀ11.6ꢀHz),ꢀ3.70ꢀ(td,ꢀ1H,ꢀ
1ꢀ 2ꢀ
1
3
(m,ꢀ2H),ꢀ1.40–1.38ꢀ(m,ꢀ2H).ꢀ CꢀNMRꢀd:ꢀ148.5,ꢀ144.7,ꢀ144.1,ꢀ133.9,ꢀ
J =ꢀ2.8,ꢀJ =ꢀ11.6ꢀHz),ꢀ2.08–2.02ꢀ(m,ꢀ1H),ꢀ1.88–1.79ꢀ(m,ꢀ1H),ꢀ1.69–
1ꢀ 2ꢀ
ꢀ
13
1
5
30.8,ꢀ 129.5,ꢀ 129.4,ꢀ 122.9,ꢀ 122.6,ꢀ 120.6,ꢀ 118.0,ꢀ 114.3,ꢀ 74.0,ꢀ 68.4,ꢀ
1.60ꢀ(m,ꢀ1H),ꢀ1.49–1.45ꢀ(m,ꢀ1H),ꢀ1.37–1.33ꢀ(m,ꢀ1H). CꢀNMRꢀd:ꢀ
+
4.4,ꢀ38.9,ꢀ24.0,ꢀ22.0.ꢀm/z(ESI):ꢀ310ꢀ(M ).
145.6,ꢀ141.8,ꢀ134.7,ꢀ132.0,ꢀ128.7,ꢀ128.0,ꢀ127.7,ꢀ119.1,ꢀ117.4,ꢀ113.6,ꢀ
+
(
4aS,5R,10bS)-5-(4-methoxyphenyl)-3,4,4a,5,6,10b-hexahydro-
73.8,ꢀ68.4,ꢀ54.7,ꢀ38.7,ꢀ24.0,ꢀ22.0. m/z(ESI):ꢀ299ꢀ(M ).
2
3
2
H-pyrano[3,2-c]quinoline (4n):ꢀ Solid,ꢀ m.p.ꢀ 136–138ꢀ°Cꢀ (Lit. ꢀ
(4aS,5S,10bS)-8-chloro-7-methyl-5-phenyl-3,4,4a,5,6,10b-
hexahydro-2H-pyrano[3,2-c]quinolineꢀ(3s):ꢀSolid,ꢀm.p.ꢀ137–139ꢀ°C.ꢀ
1
m.p.ꢀ148–150ꢀ°C). HꢀNMRꢀd:ꢀ7.33ꢀ(d,ꢀ2H,ꢀJ =ꢀ8.4ꢀHz),ꢀ7.22ꢀ(d,ꢀ1H,ꢀ
J =ꢀ7.6ꢀHz),ꢀ7.08ꢀ(t,ꢀ1H,ꢀJ =ꢀ7.2ꢀHz),ꢀ6.91ꢀ(d,ꢀ1H,ꢀJ =ꢀ8.8ꢀHz),ꢀ6.70ꢀ(t,ꢀ
-1
1
IRꢀ(cm ):ꢀ3362ꢀ(NH).ꢀ HꢀNMRꢀd:ꢀ7.46–7.33ꢀ(m,ꢀ5H),ꢀ7.24ꢀ(d,ꢀ1H,ꢀ
J =ꢀ8.8ꢀHz),ꢀ6.84ꢀ(d,ꢀ1H,ꢀJ =ꢀ8.4ꢀHz),ꢀ5.30ꢀ(d,ꢀ1H,ꢀJ =ꢀ5.2ꢀHz),ꢀ4.70ꢀ
(s,ꢀ1H),ꢀ3.82ꢀ(brs,ꢀ1H,ꢀNH),ꢀ3.59–3.56ꢀ(m,ꢀ1H),ꢀ3.38ꢀ(t,ꢀ1H,ꢀJ =ꢀ11.2ꢀ
1
4
1
1
H,ꢀJ =ꢀ7.6ꢀHz),ꢀ6.51ꢀ(d,ꢀ1H,ꢀJ =ꢀ8.0ꢀHz),ꢀ4.68ꢀ(d,ꢀ1H,ꢀJ =ꢀ10.8ꢀHz),ꢀ
.39ꢀ(d,ꢀ1H,ꢀJ =ꢀ2.4ꢀHz),ꢀ4.11–4.08ꢀ(m,ꢀ2H),ꢀ3.82ꢀ(s,ꢀ3H),ꢀ3.72ꢀ(td,ꢀ
H,ꢀJ =ꢀ2.4,ꢀJ =ꢀ12.0ꢀHz),ꢀ2.06–2.04ꢀ(m,ꢀ1H),ꢀ1.84–1.81ꢀ(m,ꢀ1H),ꢀ
1
3
Hz),ꢀ 2.22–2.16ꢀ (m,ꢀ 4H),ꢀ 1.55–1.30ꢀ (m,ꢀ 4H).ꢀ Cꢀ NMRꢀ d:ꢀ 144.3,ꢀ
1
ꢀ
2ꢀ
ꢀ
13
.68–1.61ꢀ(m,ꢀ1H),ꢀ1.51–1.47ꢀ(m,ꢀ1H),ꢀ1.34–1.30ꢀ(m,ꢀ1H). CꢀNMRꢀ
140.9,ꢀ133.4,ꢀ128.5,ꢀ127.7,ꢀ126.8,ꢀ125.8,ꢀ119.0,ꢀ118.7,ꢀ118.0,ꢀ72.6,ꢀ
+
d:ꢀ 159.3,ꢀ 144.8,ꢀ 134.2,ꢀ 130.9,ꢀ 129.3,ꢀ 128.8,ꢀ 120.7,ꢀ 117.4,ꢀ 114.1,ꢀ
1
60.6,ꢀ59.3,ꢀ38.3,ꢀ25.3,ꢀ18.0,ꢀ13.6.ꢀm/z(ESI):ꢀ313ꢀ(M ).ꢀHRMS-ESI:ꢀ
+
14.0,ꢀ74.7,ꢀ68.7,ꢀ55.3,ꢀ54.1,ꢀ38.9,ꢀ24.1,ꢀ22.0.ꢀm/z(ESI):ꢀ295ꢀ(M ).
CalcdꢀforꢀC H ClNO:ꢀ313.1312.ꢀFound:ꢀ313.1318.
1
9
20
(
4aS,5S,10bS)-9-chloro-5-phenyl-3,4,4a,5,6,10b-hexahydro-2H-
(4aS,5R,10bS)-8-chloro-7-methyl-5-phenyl-3,4,4a,5,6,10b-
hexahydro-2H-pyrano[3,2-c]quinoline (4s):ꢀSolid,ꢀm.p.ꢀ142–143ꢀ°C.ꢀ
9
pyrano[3,2-c]quinoline (3o):ꢀ Solid,ꢀ m.p.ꢀ 169–170ꢀ°Cꢀ (Lit. ꢀ m.p.ꢀ
70–171ꢀ°C).ꢀ HꢀNMRꢀd:ꢀ7.39–7.26ꢀ(m,ꢀ6H),ꢀ7.05–7.02ꢀ(m,ꢀ1H),ꢀ6.53ꢀ
d,ꢀ1H,ꢀJ =ꢀ8.4ꢀHz),ꢀ5.27ꢀ(d,ꢀ1H,ꢀJ =ꢀ5.2ꢀHz),ꢀ4.66ꢀ(s,ꢀ1H),ꢀ3.89ꢀ(brs,ꢀ
H,ꢀNH),ꢀ3.62–3.60ꢀ(m,ꢀ1H),ꢀ3.41ꢀ(t,ꢀ1H,ꢀJ =ꢀ7.2ꢀHz),ꢀ2.15ꢀ(s,ꢀ1H),ꢀ
.56–1.33ꢀ(m,ꢀ4H). CꢀNMRꢀd:ꢀ143.7,ꢀ140.7,ꢀ128.4,ꢀ128.0,ꢀ127.7,ꢀ
27.3,ꢀ126.8,ꢀ123.1,ꢀ121.6,ꢀ115.6,ꢀ72.4,ꢀ60.8,ꢀ59.3,ꢀ38.6,ꢀ25.3,ꢀ18.0.
1
-1
1
1
(
1
1
1
IRꢀ(cm ):ꢀ3401ꢀ(NH).ꢀ HꢀNMRꢀd:ꢀ7.45–7.35ꢀ(m,ꢀ5H),ꢀ7.04ꢀ(d,ꢀ1H,ꢀJ
=ꢀ8.0ꢀHz),ꢀ6.75ꢀ(d,ꢀ1H,ꢀJ =ꢀ8.4ꢀHz),ꢀ4.74ꢀ(d,ꢀ1H,ꢀJ =ꢀ11.2ꢀHz),ꢀ4.37ꢀ(d,ꢀ
1H,ꢀJ =ꢀ2.8ꢀHz),ꢀ4.11–4.07ꢀ(m,ꢀ1H)ꢀ3.71ꢀ(td,ꢀ1H,ꢀJ =ꢀ2.4,ꢀJ =ꢀ11.6ꢀ
1
ꢀ
2ꢀ
ꢀ
13
Hz),ꢀ2.12ꢀ(s,ꢀ3H),ꢀ2.07–2.03ꢀ(m,ꢀ1H),ꢀ1.90–1.81ꢀ(m,ꢀ1H),ꢀ1.70–1.61ꢀ
1
3
(m,ꢀ1H),ꢀ1.48–1.45ꢀ(m,ꢀ1H),ꢀ1.37–1.33ꢀ(m,ꢀ1H).ꢀ CꢀNMRꢀd:ꢀ143.8,ꢀ
+
m/z (ESI):ꢀ299ꢀ(M ).
(
142.2,ꢀ134.6,ꢀ129.0,ꢀ128.8,ꢀ128.1ꢀ¥ꢀ2,ꢀ127.8,ꢀ118.7,ꢀ117.8,ꢀ77.3,ꢀ77.0,ꢀ
+
4aS,5R,10bS)-9-chloro-5-phenyl-3,4,4a,5,6,10b-hexahydro-2H-
76.7,ꢀ 74.4,ꢀ 68.6,ꢀ 54.9,ꢀ 38.4,ꢀ 24.0,ꢀ 21.9,ꢀ 13.4.ꢀ m/z(ESI):ꢀ 313ꢀ (M ).ꢀ
9
pyrano[3,2-c]quinolineꢀ(4o):ꢀSolid,ꢀm.p.ꢀ124–125 ꢀ° Cꢀ(Lit. ꢀm.p.ꢀ124–
HRMS-ESI:ꢀCalcdꢀforꢀC H ClNO:ꢀ313.1312.ꢀFound:ꢀ313.1320.
1
9
20
ꢀ
1
1
(
26 ꢀ° C). HꢀNMRꢀd:ꢀ7.40–7.25ꢀ(m,ꢀ5H),ꢀ7.21ꢀ(d,ꢀ1H,ꢀJ =ꢀ2.4ꢀHz),ꢀ7.03ꢀ
(4aS,5S,10bS)-7,10-dimethyl-5-phenyl-3,4,4a,5,6,10b-hexahydro-
6
1
dd,ꢀ1H,ꢀJ =ꢀ2.4,ꢀJ =ꢀ8.4ꢀHz),ꢀ6.45ꢀ(d,ꢀ1H,ꢀJ =ꢀ8.8ꢀHz),ꢀ4.67ꢀ(d,ꢀ1H,ꢀ
2H-pyrano[3,2-c]quinoline (3t): ꢀSolid,ꢀm.p.ꢀ112–113ꢀ°C.ꢀ HꢀNMRꢀd:ꢀ
7.45ꢀ(d,ꢀ2H,ꢀJ =ꢀ7.6ꢀHz),ꢀ7.39–7.35ꢀ(m,ꢀ2H),ꢀ7.32–7.28ꢀ(m,ꢀ1H),ꢀ6.92ꢀ
(d,ꢀ1H,ꢀJ =ꢀ7.6ꢀHz),ꢀ6.53ꢀ(d,ꢀ1H,ꢀJ =ꢀ7.6ꢀHz),ꢀ5.32ꢀ(d,ꢀ1H,ꢀJ =ꢀ5.6ꢀHz),ꢀ
4.60ꢀ(d,ꢀ1H,ꢀJ =ꢀ2.8ꢀHz),ꢀ3.74ꢀ(brs,ꢀ1H,ꢀNH),ꢀ3.55–3.52ꢀ(m,ꢀ1H),ꢀ3.27ꢀ
(td,ꢀ1H,ꢀJ =ꢀ2.4,ꢀJ =ꢀ10.8ꢀHz),ꢀ2.37ꢀ(s,ꢀ3H),ꢀ2.12ꢀ(s,ꢀ3H),ꢀ1.84–1.74ꢀ
1ꢀ
2ꢀ
J=ꢀ10.4ꢀHz),ꢀ4.34ꢀ(d,ꢀ1H,ꢀJ=ꢀ2.8ꢀHz),ꢀ4.07ꢀ(dd,ꢀ1H,ꢀJ =ꢀ2.4,ꢀJ =ꢀ10.8ꢀHz),ꢀ
.07ꢀ(td,ꢀ1H,ꢀJ =ꢀ2.4,ꢀJ =ꢀ10.8ꢀHz),ꢀ2.07–2.04ꢀ(m,ꢀ1H),ꢀ1.85–1.78ꢀ(m,ꢀ
H),ꢀ1.70–1.61ꢀ(m,ꢀ1H),ꢀ1.48–1.45ꢀ(m,ꢀ1H),ꢀ1.37–1.33ꢀ(m,ꢀ1H). Cꢀ
NMRꢀd:ꢀ143.3,ꢀ142.0,ꢀ130.4,ꢀ129.2,ꢀ128.7,ꢀ128.0,ꢀ127.7,ꢀ121.9,ꢀ121.8,ꢀ
15.3,ꢀ73.9,ꢀ68.5,ꢀ54.9,ꢀ38.6,ꢀ24.0,ꢀ22.0. m/z(ESI):ꢀ299ꢀ(M ).
(
pyrano[3,2-c]quinoline (3p):ꢀSolid,ꢀm.p.ꢀ143–145ꢀ°Cꢀ(Lit. ꢀm.p.ꢀ145–
46ꢀ°C).ꢀ HꢀNMRꢀd:ꢀ7.43–7.35ꢀ(m,ꢀ4H), 7.32–7.28ꢀ(m,ꢀ1H),ꢀ7.04–7.03ꢀ
m,ꢀ1H),ꢀ6.72ꢀ(dd,ꢀ1H,ꢀJ =ꢀ3.2,ꢀJ =ꢀ8.8ꢀHz),ꢀ6.57ꢀ(d,ꢀ1H,ꢀJ =ꢀ8.8ꢀHz),ꢀ
1ꢀ
2ꢀ
3
1
1ꢀ 2ꢀ
ꢀ
13
1
ꢀ
2ꢀ
+
ꢀ13
1
(m,ꢀ1H),ꢀ1.47–1.28ꢀ(m,ꢀ4H). CꢀNMRꢀd:ꢀ144.1,ꢀ142.0,ꢀ137.3,ꢀ129.1,ꢀ
128.3,ꢀ127.4,ꢀ127.1,ꢀ120.3,ꢀ119.1,ꢀ118.3,ꢀ73.3,ꢀ61.6,ꢀ59.1,ꢀ38.6,ꢀ24.3,ꢀ
21.3,ꢀ19.3,ꢀ17.4. m/z(ESI):ꢀ293ꢀ(M ).
4aS,5S,10bS)-9-methoxy-5-phenyl-3,4,4a,5,6,10b-hexahydro-2H-
9
+
1
ꢀ
1
(
5
3
(
1
2
(4aS,5R,10bS)-7,10-dimethyl-5-phenyl-3,4,4a,5,6,10b-hexahydro-
6
1
1
ꢀ
2ꢀ
2H-pyrano[3,2-c]quinoline (4t): ꢀSolid,ꢀm.p.ꢀ109–111ꢀ°C.ꢀ HꢀNMRꢀ
d:ꢀ7.50–7.48ꢀ(m,ꢀ2H),ꢀ7.42–7.35ꢀ(m,ꢀ3H),ꢀ6.90ꢀ(d,ꢀ1H,ꢀJ =ꢀ7.6ꢀHz),ꢀ
6.51ꢀ(d,ꢀ1H,ꢀJ =ꢀ7.6ꢀHz),ꢀ4.75ꢀ(d,ꢀ1H,ꢀJ =ꢀ11.6ꢀHz),ꢀ4.50ꢀ(d,ꢀ1H,ꢀ
J =ꢀ 2.4ꢀ Hz),ꢀ 4.14–4.10ꢀ (m,ꢀ 1H),ꢀ 3.73–3.66ꢀ (m,ꢀ 1H),ꢀ 2.35ꢀ (s,ꢀ 3H),ꢀ
2.05–2.02ꢀ(m,ꢀ4H),ꢀ1.92–1.87ꢀ(m,ꢀ1H),ꢀ1.70–1.63ꢀ(m,ꢀ1H),ꢀ1.50–1.45ꢀ
.31ꢀ (d,ꢀ 1H,ꢀ J =ꢀ 5.6ꢀ Hz),ꢀ 4.62ꢀ (d,ꢀ 1H,ꢀ J =ꢀ 2.0ꢀ Hz),ꢀ 3.78ꢀ (s,ꢀ 3H),ꢀ
.66–3.58ꢀ(m,ꢀ2H),ꢀ3.46–3.40ꢀ(m,ꢀ1H),ꢀ2.17–2.14ꢀ(m,ꢀ1H),ꢀ1.58–1.42ꢀ
m,ꢀ3H),ꢀ1.33–1.25ꢀ(m,ꢀ1H).ꢀ13CꢀNMRꢀd:ꢀ152.9,ꢀ144.3,ꢀ139.1,ꢀ128.3,ꢀ
27.4,ꢀ126.8,ꢀ121.1,ꢀ115.7,ꢀ115.0,ꢀ111.9,ꢀ72.9,ꢀ60.8,ꢀ59.6,ꢀ55.8,ꢀ39.1,ꢀ
5.3,ꢀ17.9. m/z(ESI):ꢀ295ꢀ(M ).
(
H-pyrano[3,2-c]quinoline (4p):ꢀPaleꢀredꢀoilꢀ(Lit. ꢀSolid,ꢀm.p.ꢀ99–
00ꢀ°C). HꢀNMRꢀd:ꢀ7.43–7.30ꢀ(m,ꢀ5H),ꢀ6.82ꢀ(d,ꢀ1H,ꢀJ =ꢀ2.8ꢀHz),ꢀ
.75ꢀ(dd,ꢀ1H,ꢀJ =ꢀ2.8,ꢀJ =ꢀ8.8ꢀHz),ꢀ6.50ꢀ(d,ꢀ1H,ꢀJ =ꢀ8.8ꢀHz),ꢀ4.67ꢀ(d,ꢀ
+
ꢀ13
(m,ꢀ1H),ꢀ1.35–1.31ꢀ(m,ꢀ1H). CꢀNMRꢀd:ꢀ142.7,ꢀ142.6,ꢀ136.4,ꢀ129.9,ꢀ
4aS,5R,10bS)-9-methoxy-5-phenyl-3,4,4a,5,6,10b-hexahydro-
128.6,ꢀ128.0,ꢀ120.1,ꢀ119.0,ꢀ118.8,ꢀ118.5,ꢀ72.3,ꢀ68.8,ꢀ54.3,ꢀ39.2,ꢀ24.2,ꢀ
9
+
2
1
6
1
3
(
1
5
21.9,ꢀ18.1,ꢀ17.1. m/z(ESI):ꢀ293ꢀ(M ).
ꢀ
1
(5S)-8,9-difluoro-5-phenyl-3,4,4a,5,6,10b-hexahydro-2H-
-1
1
ꢀ
2ꢀ
pyrano[3,2-c]quinolineꢀ(3u):ꢀSolid,ꢀm.p.ꢀ151–152ꢀ°C.ꢀIRꢀ(cm ):ꢀ3371ꢀ
1
H,ꢀJ =ꢀ10.4ꢀHz),ꢀ4.38ꢀ(d,ꢀ1H,ꢀJ =ꢀ2.8ꢀHz),ꢀ4.10ꢀ(d,ꢀ1H,ꢀJ =ꢀ11.2ꢀHz),ꢀ
(NH).ꢀ HꢀNMRꢀd:ꢀ7.39–7.31ꢀ(m,ꢀ5H),ꢀ7.24–7.19ꢀ(m,ꢀ1H),ꢀ6.41–6.36ꢀ
.76–3.69ꢀ(m,ꢀ4H),ꢀ2.11–2.09ꢀ(m,ꢀ1H),ꢀ1.84–1.81ꢀ(m,ꢀ1H),ꢀ1.68–1.60ꢀ
(m,ꢀ1H),ꢀ5.23ꢀ(d,ꢀ1H,ꢀJ =ꢀ5.2ꢀHz),ꢀ4.65ꢀ(s,ꢀ1H),ꢀ3.82ꢀ(brs,ꢀ1H,ꢀNH),ꢀ
3.60ꢀ(dd,ꢀ1H,ꢀJ =ꢀ2.0,ꢀJ =ꢀ11.2ꢀHz),ꢀ3.40–3.34ꢀ(m,ꢀ1H),ꢀ2.17–2.14ꢀ
m,ꢀ1H),ꢀ1.49–1.46ꢀ(m,ꢀ1H),ꢀ1.35–1.32ꢀ(m,ꢀ1H).ꢀ13CꢀNMRꢀd:ꢀ152.0,ꢀ
1
ꢀ
2ꢀ
1
3
42.3,ꢀ 138.9,ꢀ 128.5,ꢀ 127.8,ꢀ 121.3,ꢀ 116.8,ꢀ 115.5,ꢀ 114.8,ꢀ 74.5,ꢀ 68.5,ꢀ
5.9,ꢀ55.2,ꢀ38.9,ꢀ24.1,ꢀ22.0. m/z(ESI):ꢀ295ꢀ(M ).
(
pyrano[3,2-c]quinoline (3q):ꢀ Solid,ꢀ m.p.ꢀ 129–130ꢀ°Cꢀ (Lit. ꢀ m.p.ꢀ
29–130ꢀ°C).ꢀ HꢀNMRꢀd:ꢀ7.42–7.24ꢀ(m,ꢀ6H),ꢀ6.91ꢀ(d,ꢀ1H,ꢀJ =ꢀ8.4ꢀHz),ꢀ
.52ꢀ(d,ꢀ1H,ꢀJ =ꢀ7.6ꢀHz),ꢀ5.30ꢀ(d,ꢀ1H,ꢀJ =ꢀ5.6ꢀHz),ꢀ4.63ꢀ(s,ꢀ1H),ꢀ3.76ꢀ
(m,ꢀ1H),ꢀ1.54–1.44ꢀ(m,ꢀ3H),ꢀ1.33–1.32ꢀ(m,ꢀ1H).ꢀ CꢀNMRꢀd:ꢀ151.3,ꢀ
151.1,ꢀ148.9,ꢀ148.7,ꢀ145.2,ꢀ145.0,ꢀ142.8,ꢀ142.7,ꢀ141.7,ꢀ141.6,ꢀ140.5,ꢀ
128.5,ꢀ 127.7,ꢀ 126.7,ꢀ 120.2,ꢀ 115.9,ꢀ 115.8,ꢀ 102.8,ꢀ 102.6,ꢀ 72.1,ꢀ 60.7,ꢀ
+
4aS,5S,10bS)-9-methyl-5-phenyl-3,4,4a,5,6,10b-hexahydro-2H-
9
+
59.5,ꢀ 38.5,ꢀ 25.2,ꢀ 17.9.ꢀ m/z(ESI):ꢀ 301ꢀ (M ).ꢀ HRMS-ESI:ꢀ Calcdꢀ forꢀ
1
1
6
(
(
1
3
C H F NO:ꢀ301.1356.ꢀFound:ꢀ301.1365.
1
8
17 2
(5R)-8,9-difluoro-5-phenyl-3,4,4a,5,6,10b-hexahydro-2H-
-1
brs,ꢀ1H,ꢀNH),ꢀ3.58ꢀ(d,ꢀ1H,ꢀJ =ꢀ11.2ꢀHz),ꢀ3.47–3.36ꢀ(m,ꢀ1H),ꢀ2.27ꢀ
pyrano[3,2-c]quinolineꢀ (4u):ꢀ Solid,ꢀ m.p.ꢀ 156–157ꢀ°C.ꢀ IRꢀ (cm ):ꢀ
s,ꢀ3H),ꢀ2.16ꢀ(s,ꢀ1H),ꢀ1.57–1.29ꢀ(m,ꢀ4H).ꢀ13CꢀNMRꢀd:ꢀ142.8,ꢀ141.3,ꢀ
1
3344ꢀ(NH).ꢀ HꢀNMRꢀd:ꢀ7.40–7.33ꢀ(m,ꢀ5H),ꢀ7.04ꢀ(dd,ꢀ1H,ꢀJ =ꢀ8.8,ꢀ
1ꢀ
28.7,ꢀ128.3,ꢀ127.7,ꢀ127.4ꢀ¥ꢀ2,,ꢀ126.8,ꢀ119.8,ꢀ114.5,ꢀ72.8,ꢀ60.6,ꢀ59.4,ꢀ
9.0,ꢀ25.4,ꢀ20.6,ꢀ17.9. m/z(ESI):ꢀ279ꢀ(M ).
(
pyrano[3,2-c]quinoline (4q):ꢀ Paleꢀ redꢀ oil. Hꢀ NMRꢀ d:ꢀ 7.35–7.22ꢀ
m,ꢀ5H),ꢀ7.07–6.99ꢀ(m,ꢀ1H),ꢀ6.83ꢀ(d,ꢀ1H,ꢀJ =ꢀ8.0ꢀHz),ꢀ6.32ꢀ(d,ꢀ1H,ꢀ
J =ꢀ8.0ꢀHz),ꢀ4.55ꢀ(d,ꢀ1H,ꢀJ =ꢀ10.4ꢀHz),ꢀ4.26ꢀ(s,ꢀ1H),ꢀ4.04–4.01ꢀ(m,ꢀ
J =ꢀ10.4ꢀHz),ꢀ6.31ꢀ(dd,ꢀ1H,ꢀJ =ꢀ6.8,ꢀJ =ꢀ12.0ꢀHz),ꢀ4.65ꢀ(d,ꢀ1H,ꢀ
2ꢀ 1ꢀ 2ꢀ
+
J =ꢀ10.4ꢀHz),ꢀ4.31ꢀ(d,ꢀ1H,ꢀJ =ꢀ2.4ꢀHz),ꢀ4.09–4.05ꢀ(m,ꢀ1H),ꢀ3.69ꢀ(td,ꢀ
1H,ꢀJ =ꢀ2.4,ꢀJ =ꢀ11.6ꢀHz),ꢀ2.07–2.04ꢀ(m,ꢀ1H),ꢀ1.84–1.77ꢀ(m,ꢀ1H),ꢀ
4aS,5R,10bS)-9-methyl-5-phenyl-3,4,4a,5,6,10b-hexahydro-2H-
1
ꢀ
2ꢀ
1
13
1.69–1.60ꢀ(m,ꢀ1H),ꢀ1.45–1.36ꢀ(m,ꢀ1H),ꢀ1.36–1.33ꢀ(m,ꢀ1H).ꢀ CꢀNMRꢀ
d:ꢀ21.9,ꢀ23.9,ꢀ38.6,ꢀ54.8,ꢀ68.5,ꢀ73.6,ꢀ102.4,ꢀ118.7,ꢀ118.8,ꢀ127.7,ꢀ128.1,ꢀ
128.8,ꢀ141.5,ꢀ149.8,ꢀ141.5,ꢀ128.8,ꢀ128.1,ꢀ127.7,ꢀ118.8,ꢀ118.7,ꢀ102.4,ꢀ
(
+
1
1
(
1
H),ꢀ 3.86ꢀ (brs,ꢀ 1H,ꢀ NH),ꢀ 3.62ꢀ (t,ꢀ 1H,ꢀ J =ꢀ 11.2ꢀ Hz),ꢀ 2.19ꢀ (s,ꢀ 3H),ꢀ
73.6,ꢀ68.5,ꢀ54.8,ꢀ38.6,ꢀ23.9,ꢀ21.9.ꢀm/z(ESI):ꢀ301ꢀ(M ).ꢀHRMS-ESI:ꢀ
.98–1.95ꢀ(m,ꢀ1H),ꢀ1.80–1.71ꢀ(m,ꢀ1H),ꢀ1.58–1.49ꢀ(m,ꢀ1H),ꢀ1.41–1.37ꢀ
CalcdꢀforꢀC H F NO:ꢀ301.1356.ꢀFound:ꢀ301.1354.
1
8
17 2
m,ꢀ1H),ꢀ1.26–1.22ꢀ(m,ꢀ1H).ꢀ13CꢀNMRꢀd:ꢀ142.2,ꢀ130.7,ꢀ129.7,ꢀ129.3,ꢀ
28.2,ꢀ127.5,ꢀ127.4,ꢀ126.0,ꢀ120.3,ꢀ114.0,ꢀ74.1,ꢀ68.1,ꢀ54.5,ꢀ38.7,ꢀ23.8,ꢀ
1.7,ꢀ20.1. m/z(ESI):ꢀ279ꢀ(M ).
(
pyrano[3,2-c]quinoline (3r): ꢀSolid,ꢀm.p.ꢀ165–167ꢀ°C.ꢀ HꢀNMRꢀd:ꢀ
.39–7.25ꢀ(m,ꢀ6H),ꢀ6.74ꢀ(dd,ꢀ1H,ꢀJ =ꢀ2.0,ꢀJ =ꢀ8.4ꢀHz),ꢀ6.59ꢀ(d,ꢀ1H,ꢀ
J =ꢀ2.0ꢀHz),ꢀ5.25ꢀ(d,ꢀ1H,ꢀJ =ꢀ5.6ꢀHz),ꢀ4.68ꢀ(d,ꢀ1H,ꢀJ =ꢀ2.4ꢀHz),ꢀ3.93ꢀ
Weꢀ thankꢀ theꢀ Nationalꢀ Scienceꢀ Foundationꢀ ofꢀ Chinaꢀ
No.ꢀ20806073]ꢀandꢀScienceꢀ&ꢀTechnologyꢀProjectsꢀofꢀZhejiangꢀ
+
2
[
4aS,5S,10bS)-8-chloro-5-phenyl-3,4,4a,5,6,10b-hexahydro-2H-
2
5
1
[2007C21111 and 2008C11046] for financial support.
7
1
ꢀ
2ꢀ
Received 3 July 2009; accepted 10 July 2009
Paper 09/0675 doi: 10.3184/030823409X12474221035082
Published online: 10 August 2009
(
(
brs,ꢀ 1H,ꢀ NH),ꢀ 3.60–3.57ꢀ (m,ꢀ 1H),ꢀ 3.41–3.36ꢀ (m,ꢀ 1H),ꢀ 2.17–2.12ꢀ
m,ꢀ1H),ꢀ1.60–1.42ꢀ(m,ꢀ3H),ꢀ1.31–1.29ꢀ(m,ꢀ1H).ꢀ13CꢀNMRꢀd:ꢀ146.1,

5
04ꢀ JOURNALꢀOFꢀCHEMICALꢀRESEARCHꢀ2009
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14ꢀ G.ꢀMaitiꢀandꢀP.ꢀKundu,ꢀTetrahedron Lett.,ꢀ2006,ꢀ47,ꢀ5733.
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