Asymmetric Synthesis of Cyclopentene-Fused Tetrahydroquinolines via N-Heterocyclic Carbene Catalyzed Domino Reactions

Article abstract of DOI:10.1055/s-0036-1591995

A new strategy for the N-heterocyclic carbene catalyzed asymmetric synthesis of cyclopentene-fused tetrahydroquinoline derivatives has been developed. The one-pot organocatalytic domino protocol allows a direct entry to the characteristic cyclopenta[ c ]tetrahydroquinoline core of many alkaloids and some potential drugs employing readily available quinolinone and enal substrates in good domino yields and stereoselectivities.

Full text of DOI:10.1055/s-0036-1591995

SYNTHESIS
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
© Georg Thieme Verlag Stuttgart · New York
2018, 50, A–J
paper
A
en
L. Zhao et al.
Paper
Synthesis
Asymmetric Synthesis of Cyclopentene-Fused Tetrahydroquino-
lines via N-Heterocyclic Carbene Catalyzed Domino Reactions
R2
Long Zhao
Sun Li
NHC (10 mol%)
Cs2CO3 (1.0 equiv)
toluene, rt
O
Lei Wang
R1
CHO
+
R2
H
R1
Shun Yu
N
N
NHC pre-catalyst
O
R
Gerhard Raabe
Dieter Enders*
Boc
R
Boc
0
0
0
0
0-
0
0
1
6-
9
5
6
7-
2
2
2
17 examples
up to 99.5:0.5 er
up to 20:1 dr
up to 72% yield
N
N
N
Institute of Organic Chemistry, RWTH Aachen University,
Landoltweg 1, 52074 Aachen, Germany
enders@rwth-aachen.de
Mes
BF4
Received: 23.03.2018
Accepted: 28.03.2018
Published online: 03.05.2018
DOI: 10.1055/s-0036-1591995; Art ID: ss-2018-z0203-op
col by the combination of Lewis acid and NHC catalysis and
obtained better enantioselectivities and a wider reaction
scope.6 Further elegant NHC-catalyzed asymmetric synthe-
ses of cyclopentene derivatives have recently been reported
by Studer et al.,7 Biju et al.,8 and Ye et al.9 Very recently Glori-
us et al. and our group successfully realized [3+2] cycloaddi-
tions of enals and C–C double bonds for the asymmetric syn-
thesis of cyclopentanes.10 Despite this progress, the applica-
tion of organocatalytic methods for the stereoselective
construction of more complex cyclopentene or cyclopentane
derivatives is still highly desirable.11 Inspired by vabicaserin
(A), a potent 5-hydroxytryptamine 2C receptor agonist,
which is under development for its antipsychotic proper-
ties,12a–c melodinine T (B),12d and calebassinine-1 (C),12e all
containing a characteristic cyclopenta[c]tetrahydroquinoline
central core, we now report an NHC-catalyzed domino reac-
tion for the asymmetric synthesis of cyclopenta[c]quinoline
derivatives (Scheme 1, b).
Initially, we investigated the reaction with tetrahydro-
quinolinone 1a and cinnamaldehyde (2a) as the substrates.
Using Cs2CO3 as the base and CH2Cl2 as the solvent, different
NHC precatalysts were screened at room temperature (Ta-
ble 1, entries 1–5). It turned out that the desired product 4a
was obtained in 52% yield with 82:18 er and 20:1 dr in the
presence of precatalyst 3e (entry 5). Solvent effects were
next investigated (entries 6–9); toluene gave the best result,
with product 4a obtained in 50% yield with 89.5:10.5 er
and 12:1 dr (entry 9).
Abstract A new strategy for the N-heterocyclic carbene catalyzed
asymmetric synthesis of cyclopentene-fused tetrahydroquinoline deriv-
atives has been developed. The one-pot organocatalytic domino proto-
col allows a direct entry to the characteristic cyclopenta[c]tetrahydro-
quinoline core of many alkaloids and some potential drugs employing
readily available quinolinone and enal substrates in good domino yields
and stereoselectivities.
Key words asymmetric synthesis, domino reaction, N-heterocyclic
carbene, organocatalysis, cyclopenta[c]quinoline
Over the last decades, N-heterocyclic carbenes (NHCs)
have emerged as a powerful tool in catalytic asymmetric or-
ganic synthesis.1 Beside the classical benzoin and Stetter re-
actions, the NHC-organocatalysis repertoire has recently
been dramatically extended by novel activation modes and a
variety of cycloaddition/annulation reactions are now at our
disposal. In 2004, Glorius and Burstein and Bode et al. inde-
pendently reported their pioneering NHC-catalyzed [3+2]-
cycloaddition reaction of enals and aldehydes.2 Since then a
series of NHC-catalyzed [3+n]-cycloaddition reactions of
enals have been developed for the synthesis of a variety of
carbocycles and heterocycles.3 However, compared to the
well-established NHC-catalyzed cycloaddition reactions via
homoenolate equivalents for the synthesis of heterocycles,
the corresponding cycloadditions for the synthesis carbocy-
cles have remained limited. In 2006, Nair et al. reported an
efficient protocol for the synthesis of trisubstituted cyclo-
pentenes through an NHC-catalyzed a3-d3 Umpolung/Mi-
chael/aldol/ lactonization/decarboxylation domino sequence
(Scheme 1, a).4 Later, the asymmetric version of this transfor-
mation was successfully realized by Bode and co-workers.5 In
2009, Scheidt and co-workers further developed this proto-
With the optimized reaction conditions in hand, we
then investigated the substrate scope (Scheme 2). Enals
with electron-donating or electron-withdrawing substitu-
ents all worked well, leading to the desired tricyclic hetero-
cycles 4a–f in good domino yields with moderate to excel-
lent stereoselectivities. Notably, the reaction of 2-methoxy-
cinnamaldehyde led to product 4c in 50% yield with 8:1 dr
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–J

B
L. Zhao et al.
Paper
Synthesis
and 99.5:0.5 er. In addition, hexa-2,4-dienal (2g) was also
tolerated. When the nitrogen protecting group was changed
from Boc to the benzyloxycarbonyl (Cbz) group, the domino
reactions also worked well and gave the desired cyclopen-
tene-fused tetrahydroquinoline products 4h and 4i in good
yields with good to high stereoselectivities. The reaction
scope of the tetrahydroquinolinone substrates 1 was then
investigated. Heteroaryl- and aryl-substituted quinolinones
could be successfully used in this domino reaction (4j,k).
Further variation of the substituent on the tetrahydroquin-
olinone phenyl ring of the substrates 1 revealed that both
electron-withdrawing (4-F) and electron-donating groups
(4-Me, 5-MeO) were well tolerated (4l–n). An important ex-
tension of the new domino protocol is the fact that the cor-
responding chromane (X = O), naphthalene, and indane (X =
C) derivatives also can be synthesized; products 4o–q were
obtained in moderate to good stereoselectivities, albeit in
lower yields.
a)
previous work
O
R3
R2
R1
NHC cat.
CHO
+
R1
R2
R3
R1
b) this work
O
N
R3
R3
NHC cat.
CHO
R1
+
N
R2
R2
Boc
Boc
X
H
Me
O
N
N
Me
H
Me
CO2Me
O
H
OH
N
N
H
O
N
H
HN
A
B
C
vabicaserin
melodinidine T
calebassinine-1
Scheme 1 NHC-catalyzed cyclopentene synthesis and typical mole-
cules containing the cyclopenta[c]tetrahydroquinoline core
The absolute configuration of 4i was established by
X-ray crystal structure analysis13 and the other product
configurations were assigned by analogy (Figure 1).
Table 1 Screening of the Optimal Reaction Conditionsa
Ph
O
Ph
cat 3 (10 mol%)
Cs2CO3 (1.0 equiv)
Ph
CHO
+
Ph
H
N
solvent, r.t., 24 h
N
Boc
Boc
1a
2a
4a
N
Ar
N
N
N
N
N
R
N
N
N
BF4
Ph
BF4
BF4
OTBDPS
Ph
O
3b R = Bn
3c R = C6F5
3d Ar = 2,4,6-Cl3C6H2
3e Ar = Mes
3a
Entry
Cat.
Solvent
Yield (%)b
erc
drd
nd
1
2
3
4
5
6
7
8
9
3a
3b
3c
3d
3e
3e
3e
3e
3e
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
Et2O
12
6
53.5:46.5
54:46
nd
9
57:43
nd
7
74.5:25.5
82:18
nd
52
33
55
40
50
20:1
8:1
8:1
12:1
12:1
85:15
MeCN
dioxane
toluene
74.5:25.5
88.5:11.5
89.5:10.5
a Reaction conditions: 1a (0.2 mmol, 1.0 equiv), 2a (0.6 mmol, 3.0 equiv), catalyst (0.02 mmol, 10 mol%), base (0.2 mmol, 1.0 equiv), solvent (1 mL), r.t., 24 h.
b Yield of 4a after column chromatography.
c The ee value was determined by HPLC on a chiral stationary phase.
d The dr was determined by 1H NMR; nd = not determined.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–J

C
L. Zhao et al.
Paper
Synthesis
R2
H
O
R1
cat. 3e (10 mol%)
Cs2CO3 (1.0 equiv)
CHO
R2
+
R1
X
toluene, rt, 24 h
X
X = NBoc, NCbz, O, CH2
1
2
4
Y
Me
4a, Y = H, 50%, 12:1 dr, 89.5:10.5 er
4b, Y = 4-MeO, 43%, 6:1 dr, 90:10 er
4c, Y = 2-MeO, 50%, 8:1 dr, 99.5:0.5 er
4d, Y = 4-Br, 38%, 8:1 dr, 76:24 er
4e, Y = 4-Cl, 43%, 7:1 dr, 86:14 er
4f, Y = 4-F, 49%, 5:1 dr, 84:16 er
Ph
Ph
H
H
N
N
Boc
Boc
4g, 33%, 4:1 dr, 80.5:19.5 er
Y
Ph
O
H
Ph
N
4h, Y = H, 72%, 8:1 dr, 87.5:12.5 er
4i, Y = Br, 52%, >20:1 dr, 85:15 er
H
Boc
N
4j, 23%, 4:1 dr, 82.5:17.5 er
Cbz
Ph
H
Ph
H
Ph
H
Ph
Ph
Me
OMe
MeO
N
Boc
N
N
Boc
Boc
4k, 45%, 8:1 dr, 81:19 er
4l, 67%, 5:1 dr, 83.5:16.5 er
4m, 51%, 5:1 dr, 99.5:0.5 er
Ph
Ph
Ph
Ph
Ph
F
H
H
n
H
N
O
Ph
Boc
4n, 43%, 4:1 dr, 81.5:18.5 er
4o, 40%, 4:1 dr, 86.5:13.5 er
4p, n = 1, 22%, 13:1 dr, 87.5:12.5 er
4q, n = 2, 24%, 7:1 dr, 95.5:4.5 er
Scheme 2 Reaction scope (yields of isolated compounds 4 after column chromatography; dr determined by 1H NMR; ee determined by HPLC on a
chiral stationary phase)
Ph
Ph
H
Ph
Ph
TFA, CH2Cl2
0 °C to r.t.
87%
N
N
H
Boc
4a
5
Scheme 3
A proposal for the reaction mechanism of this domino
process is given in Scheme 4. The catalytic cycle is initiated
by the formation of the Breslow intermediate I via addition
of the NHC to enal 2. The subsequent Michael addition of
the Breslow intermediate I to the diene-substituted tetra-
hydroquinolinone 1 leads to adduct II after a proton shift.
An intramolecular aldol reaction delivers III, which forms
Figure 1 X-ray crystal structure of 4i
To allow further reactions at the quinoline nitrogen, it
was shown that the Boc protecting group can be removed
by treatment with TFA in CH2Cl2, resulting in the N-un-
protected product 5 in 87% yield (Scheme 3).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–J

D
L. Zhao et al.
Paper
Synthesis
the β-lactone IV and returns the NHC catalyst for further
cycles. The final decarboxylation then generates the cyclo-
penta[c]quinoline product 4 (Scheme 4).
3a–e14 and quinolinones 115 were prepared according to literature
procedures. The racemic samples of the cyclopenta[c]quinoline deriv-
atives 4 were prepared by using the racemic precatalyst with Cs2CO3.
Cyclopenta[c]quinoline Derivatives 4; General Procedure
Ph
O
CO2
To an argon-filled and dried Schlenk vial were added dienone 1 (0.5
mmol, 1.0 equiv) and precatalyst 3e (21 mg, 0.05 mmol, 10 mol%) in
toluene (2.0 mL), followed by the addition of enal 2 (1.5 mmol, 3.0
equiv) and Cs2CO3 (163 mg, 0.5 mmol, 1.0 equiv). The mixture was
stirred at r.t. (36 h) until completion of the reaction (monitored by
TLC). After purification by column chromatography (silica gel) the de-
sired product was obtained as a pale yellow oil or foamy solid.
Ph
O
4
N
N
2
N
N
Boc
NHC
IV
OH
N
tert-Butyl (2R,3R,3aS)-2-Phenyl-3-[(E)-styryl]-2,3,3a,4-tetrahydro-
5H-cyclopenta[c]quinoline-5-carboxylate (4a)
R2
N
N
I
N
N
N
Compound 4a was isolated after flash chromatography (silica gel, sili-
ca gel, n-pentane/EtOAc, 20:1); yield: 112 mg (50%); pale yellow
foamy solid; [α]D27 +119 (c 0.5, CH2Cl2).
R2
O
R1
O
HPLC: Chiralpak OD, n-heptane/iPrOH (97:3), 0.5 mL/min, tR
(major) = 14.72 min, tR (minor) = 13.18 min; T = 30 °C; 89.5:10.5 er.
N
N
1
O
N
N
Boc
III
IR (ATR): 3388, 2947, 2329, 2076, 1697, 1465, 1353, 1154, 859, 737
R2
cm–1
.
O
1H NMR (600 MHz, CDCl3): δ (major) = 7.69–7.64 (m, 2 H, PhH), 7.36–
7.34 (m, 2 H, PhH) 7.33–7.30 (m, 4 H, PhH), 7.26–7.22 (m, 5 H, PhH),
7.11–7.08 (m, 1 H, PhH), 6.42 (dd, J = 15.8, 8.1 Hz, 1 H, CH=CHPh), 6.28
(d, J = 15.8 Hz, 1 H, CH=CHPh), 6.23–6.23 (m, 1 H, C=CH), 4.75 (dd, J =
12.4, 4.7 Hz, 1 H, NCHH), 3.95–3.92 (m, 1 H, NCHH), 3.11–3.05 (m, 1
H, PhCH), 2.92–2.88 (m, 1 H, CHCH=CHPh), 2.63–2.58 (m, 1 H, CH2CH),
1.53 (s, 9 H, Boc).
R1
N
Boc
II
Scheme 4 Proposed catalytic cycle for the NHC-catalyzed asymmetric
synthesis of cyclopenta[c]tetrahydroquinoline derivatives
13C NMR (151 MHz, CDCl3): δ (major) = 153.4, 143.4, 139.4, 137.4,
137.2, 131.7, 129.8, 128.5 (2 C), 128.4 (2 C), 127.9 (2 C), 127.5, 127.2,
126.6, 126.2 (2 C), 125.3, 125.2, 124.5, 124.0, 123.9, 81.2, 59.6, 57.1,
49.0, 48.3, 28.4 (3 C).
HRMS (ESI+): m/z [M + Na]+ calcd for C31H31NO2Na: 472.2247; found:
472.2241.
In conclusion, a new strategy for the asymmetric syn-
thesis of cyclopenta[c]quinoline derivatives has been devel-
oped via an NHC-catalyzed domino process between a
diene moiety bearing tetrahydroquinolinones and enals. The
organocatalytic one-pot protocol delivers the desired cyclo-
pentene-fused tetrahydroquinolines in moderate to good
yields and good stereoselectivities under mild conditions.
tert-Butyl (2R,3R,3aS)-2-(4-Methoxyphenyl)-3-[(E)-styryl]-
2,3,3a,4-tetrahydro-5H-cyclopenta[c]quinoline-5-carboxylate (4b)
Compound 4b was isolated after flash chromatography (silica gel, n-
pentane/EtOAc, 20:1); yield: 103 mg (43%); pale yellow foamy solid;
[α]D27 +169 (c 0.5, CH2Cl2).
Unless otherwise noted, all commercially available compounds were
used without further purification. Anhydrous toluene was purified by
distillation over Na. The products were purified by column chroma-
tography on Merck silica gel 60, particle size 0.040–0.063 mm (230–
240 mesh, flash). For TLC analysis, Merck precoated TLC plates (silica
gel 60 GF254 0.25 mm) were used. Visualization of the developed TLC
plates was performed with ultraviolet irradiation (254 nm). Optical
rotation values were measured on a PerkinElmer 241 polarimeter and
HPLC: Chiralpak IA, n-heptane/iPrOH (97:3), 0.5 mL/min, tR (major) =
13.66 min, tR (minor) = 19.11 min; T = 30 °C; 90:10 er.
IR (ATR): 2972, 2928, 2331, 2132, 2012, 1927, 1696, 1597, 1478, 1361,
1238, 1154, 1035, 965, 861, 749, 694 cm–1
.
1H NMR (600 MHz, CDCl3): δ (major) = 7.68–7.66 (m, 2 H, PhH), 7.38–
7.37 (m, 2 H, PhH), 7.34–7.31 (m, 2 H, PhH), 7.25–7.23 (m, 2 H, PhH),
7.18–7.17 (m, 2 H, PhH), 7.12–7.09 (m, 1 H, PhH), 6.89–6.87 (m, 2 H,
PhH), 6.43 (dd, J = 16.0, 8.3 Hz, 1 H, CH=CHPh), 6.30 (d, J = 16.0 Hz, 1
H, CH=CHPh), 6.22–6.21 (m, 1 H, C=CH), 4.74 (dd, J = 12.4, 4.7 Hz, 1 H,
NCHH), 3.91–3.90 (m, 1 H, NCHH), 3.81 (s, 3 H, OCH3), 3.10–3.05 (m, 1
H, PhCH), 2.93–2.89 (m, 1 H, CHCH=CHPh), 2.60–2.55 (m, 1 H, CH2CH),
1.55 (s, 9 H, Boc).
13C NMR (151 MHz, CDCl3): δ (major) = 158.3, 153.4, 139.2, 137.4,
137.3, 135.6, 131.6, 129.9, 128.8 (2 C), 128.5 (2 C), 127.5, 127.2, 126.2
(2 C), 125.7, 125.3, 124.5, 124.0 (2 C), 113.8 (2 C), 81.2, 59.7, 56.3,
55.3, 48.9, 48.3, 28.4 (3 C).
T
reported as follows: [α]D [c (g/100 mL), solvent]. High-resolution
mass spectra were acquired on a ThermoFisher Scientific LTQ-Or-
bitrap XL. IR spectra were recorded on a PerkinElmer Spectrum 100
FT-IR spectrophotometer. 1H NMR and 13C NMR spectra were record-
ed at r.t. on Inova 400 or Agilent VNMRS 600 spectrometers. Chemical
shifts (δ) are given in ppm relative to the solvent residual peak (CDCl3,
δ = 7.26) as external standard. Analytical HPLC was performed on a
Hewlett-Packard 1100 Series instrument using chiral stationary
phases (Daicel IA, IB, IC, IG, AD, OD, (s,s)-Whelk O1). Standard abbre-
viations are used to denote spin multiplicities. The melting points
were obtained with an LLG MPM-H2 apparatus. The carbene catalysts
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–J

E
L. Zhao et al.
Paper
Synthesis
HRMS (ESI+): m/z [M + Na]+ calcd for C32H33NO3Na: 502.2353; found:
502.2350.
IR (ATR): 3395, 3028, 2974, 2925, 2876, 2358, 2218, 2169, 2060, 2006,
1929, 1809, 1696, 1602, 1481, 1360, 1234, 1153, 1047, 1015, 966,
828, 747, 693 cm–1
.
1H NMR (600 MHz, CDCl3): δ (major) = 7.68–7.66 (m, 2 H, PhH), 7.37–
7.34 (m, 2 H, PhH), 7.34–7.31 (m, 2 H, PhH), 7.30–7.28 (m, 2 H, PhH),
7.27–7.23 (m, 2 H, PhH), 7.18–7.17 (m, 2 H, PhH), 7.21–7.09 (m, 1 H,
PhH), 6.40 (dd, J = 15.8, 8.3 Hz, 1 H, CH=CHPh), 6.27 (d, J = 15.8 Hz, 1
H, CH=CHPh), 6.19–6.18 (m, 1 H, C=CH), 4.74 (dd, J = 12.4, 4.7 Hz, 1 H,
NCHH), 3.92–3.90 (m, 1 H, NCHH), 3.11–3.05 (m, 1 H, PhCH), 2.92–
2.88 (m, 1 H, CHCH=CHPh), 2.56–2.52 (m, 1 H, CH2CH), 1.54 (s, 9 H,
Boc).
13C NMR (151 MHz, CDCl3): δ (major) = 153.4, 141.9, 139.9, 137.5,
137.0, 132.3, 132.1, 129.3, 129.2 (2 C), 128.6 (2 C), 128.5 (2 C), 127.7,
127.4, 126.2 (2 C), 125.3, 124.6, 124.5, 124.0, 123.7, 81.3, 59.9, 56.5,
49.0, 48.2, 28.4 (3 C).
tert-Butyl (2R,3R,3aS)-2-(2-Methoxyphenyl)-3-[(E)-styryl]-
2,3,3a,4-tetrahydro-5H-cyclopenta[c]quinoline-5-carboxylate (4c)
Compound 4c was isolated after flash chromatography (silica gel, n-
pentane/EtOAc, 20:1); yield: 120 mg (50%); pale yellow foamy solid;
[α]D27 +154 (c 0.5, CH2Cl2).
HPLC: Chiralpak IA, n-heptane/iPrOH (97:3), 0.5 mL/min, tR
(major) = 11.40 min, tR (minor) = 12.42 min; T = 30 °C; 99.5:0.5 er.
IR (ATR): 3374, 2932, 2316, 1698, 1471, 1350, 1149, 857, 739 cm–1
.
1H NMR (600 MHz, CDCl3): δ (major) = 7.66–7.64 (m, 2 H, PhH), 7.35–
7.34 (m, 2 H, PhH), 7.31–7.28 (m, 2 H, PhH), 7.25–7.23 (m, 1 H, PhH),
7.22–7.19 (m, 3 H, PhH), 7.09–7.07 (m, 1 H, PhH), 6.97–6.94 (m, 1 H,
PhH), 6.87–6.85 (m, 1 H, PhH), 6.47 (dd, J = 15.8, 8.1 Hz, 1 H,
CH=CHPh), 6.30 (d, J = 15.8 Hz, 1 H, CH=CHPh), 6.19–6.18 (m, 1 H,
C=CH), 4.74 (dd, J = 12.3, 4.7 Hz, 1 H, NCHH), 4.51–4.50 (m, 1 H,
NCHH), 3.76 (s, 3 H, OCH3), 3.08–3.03 (m, 1 H, PhCH), 2.92–2.88 (m, 1
H, CHCH=CHPh), 2.67–2.62 (m, 1 H, CH2CH), 1.53 (s, 9 H, Boc).
13C NMR (151 MHz, CDCl3): δ (major) = 157.2, 153.5, 138.6, 137.6,
137.2, 131.8, 130.9, 130.3, 128.4 (2 C), 128.1, 127.5, 127.2, 126.9,
126.2, 126.1 (2 C), 125.2, 124.4, 124.2, 123.9, 120.8, 110.6, 81.1, 58.9,
55.5, 49.0, 48.9, 48.2, 28.4 (3 C).
HRMS (ESI+): m/z [M + Na]+ calcd for C31H30NO2ClNa: 506.1857;
found: 506.1862.
tert-Butyl (2R,3R,3aS)-2-(4-Fluorophenyl)-3-[(E)-styryl]-2,3,3a,4-
tetrahydro-5H-cyclopenta[c]quinoline-5-carboxylate (4f)
Compound 4f was isolated after flash chromatography (silica gel, n-
27
pentane/EtOAc, 20:1); yield: 114 mg (49%); pale yellow oil; [α]D
+125 (c 0.5, CH2Cl2).
HPLC: (s,s)-Whelk O1, n-heptane/iPrOH (7:3), 0.5 mL/min, tR (major) =
12.19 min, tR (minor) = 10.16 min; T = 30 °C; 84:16 er.
HRMS (ESI+): m/z [M + Na]+ calcd for C32H33NO3Na: 502.2353; found:
502.2345.
IR (ATR): 2968, 2294, 1691, 1480, 1347, 1172, 860, 734 cm–1
.
1H NMR (400 MHz, CDCl3): δ (major) = 7.68–7.64 (m, 2 H, PhH), 7.37–
7.29 (m, 4 H, PhH), 7.26–7.17 (m, 4 H, PhH), 7.11–7.07 (m, 1 H, PhH),
7.02–6.98 (m, 2 H, PhH), 6.40 (dd, J = 15.8, 8.1 Hz, 1 H, CH=CHPh), 6.26
(d, J = 15.8 Hz, 1 H, CH=CHPh), 6.19–6.18 (m, 1 H, C=CH), 4.73 (dd,
J = 12.2, 4.4 Hz, 1 H, NCHH), 3.92–3.89 (m, 1 H, NCHH), 3.10–3.03 (m,
1 H, PhCH), 2.93–2.86 (m, 1 H, CHCH=CHPh), 2.57–2.50 (m, 1 H,
CH2CH), 1.53 (s, 9 H, Boc).
13C NMR (101 MHz, CDCl3): δ (major) = 162.9, 160.5, 153.4, 139.7,
137.5, 137.1, 132.0, 129.5, 129.3, 129.2, 128.5 (2 C), 127.6, 127.3,
126.2 (2 C), 125.3, 124.9, 124.5, 124.0, 123.8, 115.3, 115.1, 81.3, 59.9,
56.3, 49.0, 48.3, 28.4 (3 C).
tert-Butyl (2R,3R,3aS)-2-(4-Bromophenyl)-3-[(E)-styryl]-2,3,3a,4-
tetrahydro-5H-cyclopenta[c]quinoline-5-carboxylate (4d)
Compound 4d was isolated after flash chromatography (silica gel, n-
pentane/EtOAc, 20:1); yield: 100 mg (38%); pale yellow foamy solid;
[α]D27 +148 (c 0.5, CH2Cl2).
HPLC: Chiralpak IB, n-heptane/EtOH (9:1), 0.3 mL/min, tR (major) =
13.19 min, tR (minor) = 14.08 min; T = 30 °C; 76:24 er.
IR (ATR): 3734, 2935, 2644, 2324, 2210, 2051, 1695, 1472, 1356, 1153,
974, 840, 747 cm–1
.
1H NMR (600 MHz, CDCl3): δ (major) = 7.66–7.65 (m, 2 H, PhH), 7.44–
7.42 (m, 2 H, PhH), 7.36–7.34 (m, 2 H, PhH), 7.33–7.29 (m, 2 H, PhH),
7.25–7.22 (m, 2 H, PhH), 7.14–7.08 (m, 3 H, PhH), 6.38 (dd, J = 15.8, 8.2
Hz, 1 H, CH=CHPh), 6.26 (d, J = 15.8 Hz, 1 H, CH=CHPh), 6.17–6.17 (m,
1 H, C=CH), 4.72 (dd, J = 12.4, 4.7 Hz, 1 H, NCHH), 3.90–3.87 (m, 1 H,
NCHH), 3.09–3.04 (m, 1 H, PhCH), 2.90–2.86 (m, 1 H, CHCH=CHPh),
2.55–2.50 (m, 1 H, CH2CH), 1.52 (s, 9 H, Boc).
HRMS (ESI+): m/z [M + Na]+ calcd for C31H30NO2FNa: 490.2153; found:
490.2144.
tert-Butyl (2R,3R,3aS)-2-[(E)-Prop-1-en-1-yl]-3-[(E)-styryl]-
2,3,3a,4-tetrahydro-5H-cyclopenta[c]quinoline-5-carboxylate (4g)
Compound 4g was isolated after flash chromatography (silica gel, n-
pentane/EtOAc, 20:1); yield: 68 mg (33%); pale yellow oil; [α]D27 +112
(c 0.5, CH2Cl2).
13C NMR (151 MHz, CDCl3): δ (major) = 153.4, 142.4, 140.0, 137.5,
137.0, 132.1, 131.5 (2 C), 129.6 (2 C), 129.3, 128.5 (2 C), 127.7, 127.4,
126.2 (2 C), 125.2, 124.5, 124.5, 124.0, 123.7, 120.4, 81.3, 59.8, 56.5,
49.0, 48.2, 28.4 (3 C).
HPLC: Chiralpak IA, n-heptane/iPrOH (97:3), 0.5 mL/min, tR (major) =
8.03 min, tR (minor) = 8.58 min; T = 30 °C; 80.5:19.5 er.
HRMS (ESI+): m/z [M + Na]+ calcd for C31H30NO2BrNa: 550.1352;
found: 550.1348.
IR (ATR): 3386, 2938, 2290, 2087, 1697, 1461, 1355, 1156, 963, 865,
737 cm–1
.
1H NMR (400 MHz, CDCl3): δ (major) = 7.60–7.57 (m, 2 H, PhH), 7.40–
7.35 (m, 2 H, PhH), 7.33–7.29 (m, 2 H, PhH), 7.25–7.21 (m, 1 H, PhH),
7.20–7.15 (m, 1 H, PhH), 7.06–7.02 (m, 1 H, PhH), 6.47 (d, J = 15.9 Hz,
1 H, CH=CHPh), 6.34 (dd, J = 15.9, 7.8 Hz, 1 H, CH=CHPh), 6.06–6.05
(m, 1 H, C=CH), 5.58–5.51 (m, 1 H, CH3CH=CH), 5.45–5.38 (m, 1 H,
CH3CH=CH), 4.68 (dd, J = 12.2, 4.4 Hz, 1 H, NCHH), 3.34–3.30 (m, 1 H,
NCHH), 2.96–2.89 (m, 1 H, PhCH), 2.82–2.76 (m, 1 H, CHCH=CHPh),
2.40–2.33 (m, 1 H, CH2CH), 1.69–1.66 (m, 3 H, CH3), 1.49 (s, 9 H, Boc).
tert-Butyl (2R,3R,3aS)-2-(4-Chlorophenyl)-3-[(E)-styryl]-2,3,3a,4-
tetrahydro-5H-cyclopenta[c]quinoline-5-carboxylate (4e)
Compound 4e was isolated after flash chromatography (silica gel, n-
pentane/EtOAc, 20:1); yield: 104 mg (43%); pale yellow oil; [α]D27 +172
(c 0.5, CH2Cl2).
HPLC: Chiralpak IB, n-heptane/iPrOH (97:3), 0.5 mL/min, tR (major) =
9.90 min, tR (minor) = 11.74 min; T = 30 °C; 86:14 er.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–J

F
L. Zhao et al.
Paper
Synthesis
13C NMR (101 MHz, CDCl3): δ (major) = 153.4, 138.3, 137.4, 137.3,
132.3, 131.2, 130.5, 128.5 (2 C), 127.3, 127.1, 126.3, 126.2 (2 C), 125.4,
125.1, 124.3, 124.1, 123.9, 81.1, 56.2, 54.0, 48.7, 48.3, 28.3 (3 C), 18.0.
HRMS (ESI+): m/z [M + Na]+ calcd for C28H31NO2Na: 436.2247; found:
436.2238.
tert-Butyl (2R,3R,3aS)-3-[(E)-2-(Furan-2-yl)vinyl]-2-phenyl-
2,3,3a,4-tetrahydro-5H-cyclopenta[c]quinoline-5-carboxylate (4j)
Compound 4j was isolated after flash chromatography (silica gel, n-
pentane/EtOAc, 20:1); yield: 50 mg (23%); pale yellow oil; [α]D27 +140
(c 0.5, CH2Cl2).
HPLC: Chiralpak IA, n-heptane/EtOH (97:3), 0.5 mL/min, tR (major) =
9.71 min, tR (minor) = 10.63 min; T = 30 °C; 82.5:17.5 er.
Benzyl (2R,3R,3aS)-2-Phenyl-3-[(E)-styryl]-2,3,3a,4-tetrahydro-
5H-cyclopenta[c]quinoline-5-carboxylate (4h)
IR (ATR): 2971, 2926, 2873, 2293, 2089, 1834, 1696, 1604, 1468, 1360,
1235, 1152, 1046, 961, 861, 747, 700 cm–1
.
Compound 4h was isolated after flash chromatography (silica gel, n-
pentane/EtOAc, 20:1); yield: 174 mg (72%); pale yellow foamy solid;
[α]D27 +140 (c 0.5, CH2Cl2).
1H NMR (400 MHz, CDCl3): δ (major) = 7.65–7.62 (m, 2 H, PhH), 7.32–
7.29 (m, 3 H, PhH), 7.24–7.19 (m, 4 H, PhH), 7.09–7.05 (m, 1 H, fura-
nH), 6.38–6.30 (m, 2 H, furanH and CH=CHfuran), 6.21–6.17 (m, 1 H,
furanH), 6.12–6.07 (m, 2 H, CH=CHfuran and C=CH), 4.70 (dd, J = 12.3,
4.6 Hz, 1 H, NCHH), 3.92–3.89 (m, 1 H, NCHH), 3.09–3.00 (m, 1 H,
PhCH), 2.89–2.83 (m, 1 H, CHCH=CHPh), 2.57–2.50 (m, 1 H, CH2CH),
1.52 (s, 9 H, Boc).
13C NMR (101 MHz, CDCl3): δ (major) = 153.4, 152.6, 143.4, 141.5,
139.3, 137.4, 128.5, 128.4 (2 C), 127.8 (2 C), 127.5, 126.6, 125.3, 125.2,
124.5, 123.9 (2 C), 120.1, 111.1, 107.0, 81.2, 59.3, 57.0, 49.0, 48.2, 28.3
(3 C).
HPLC: Chiralpak AD, n-heptane/iPrOH (92:8), 0.7 mL/min, tR (major) =
15.32 min, tR (minor) = 17.84 min; T = 30 °C; 87.5:12.5 er.
IR (ATR): 3339, 3031, 2933, 2739, 2322, 2088, 1954, 1762, 1678, 1488,
1454, 1393, 1345, 1301, 1210, 1126, 1062, 972, 846, 748, 695 cm–1
.
1H NMR (400 MHz, CDCl3): δ (major) = 7.76–7.74 (m, 1 H, PhH), 7.70–
7.68 (m, 1 H, PhH), 7.60–7.45 (m, 1 H, PhH), 7.41–7.38 (m, 2 H, PhH),
7.36–7.30 (m, 8 H, PhH), 7.28–7.24 (m, 5 H, PhH), 7.16–7.12 (m, 1 H,
PhH), 6.43 (dd, J = 15.9, 8.0 Hz, 1 H, CH=CHPh), 6.29 (d, J = 15.9 Hz,
1 H, CH=CHPh), 6.26–6.25 (m, 1 H, C=CH), 5.35 (d, J = 12.4 Hz, 1 H,
PhCHH), 5.21 (d, J = 12.4 Hz, 1 H, PhCHH), 4.84 (dd, J = 12.0, 4.3 Hz,
1 H, NCHH), 3.98–3.94 (m, 1 H, NCHH), 3.15–3.08 (m, 1 H, PhCH),
3.04–2.98 (m, 1 H, CHCH=CHPh), 2.66–2.60 (m, 1 H, CH2CH).
HRMS (ESI+): m/z [M + Na]+ calcd for C29H29NO3Na: 462.2040; found:
462.2043.
13C NMR (101 MHz, CDCl3): δ (major) = 154.3, 143.3, 139.1, 137.1,
136.9, 136.3, 131.8, 129.7, 128.6 (2 C), 128.5 (4 C), 128.1, 127.9 (4 C),
127.8, 127.3, 126.7, 126.3 (2 C), 125.6, 125.0, 124.6, 124.4, 124.1, 67.7,
59.5, 57.1, 49.1, 48.6.
tert-Butyl (2R,3R,3aS)-3-[(E)-4-Methoxystyryl]-2-phenyl-2,3,3a,4-
tetrahydro-5H-cyclopenta[c]quinoline-5-carboxylate (4k)
Compound 4k was isolated after flash chromatography (silica gel, n-
pentane/EtOAc, 20:1); yield: 108 mg (45%); pale yellow oil; [α]D27 +142
(c 0.5, CH2Cl2).
HRMS (ESI+): m/z [M + Na]+ calcd for C34H29NO2Na: 506.2091; found:
506.2087.
HPLC: Chiralpak IG, n-heptane/iPrOH (9:1), 0.5 mL/min, tR (major) =
6.88 min, tR (minor) = 7.76 min; T = 30 °C; 81:19 er.
Benzyl (2R,3R,3aS)-2-(4-Bromophenyl)-3-[(E)-styryl]-2,3,3a,4-tet-
rahydro-5H-cyclopenta[c]quinoline-5-carboxylate (4i)
IR (ATR): 3029, 2974, 2928, 2645, 2179, 2112, 1999, 1885, 1829, 1769,
1695, 1605, 1510, 1480, 1456, 1362, 1301, 1243, 1157, 1032, 967,
857, 822, 754, 699 cm–1
.
Compound 4i was isolated after flash chromatography (silica gel, n-
pentane/EtOAc, 20:1); yield: 146 mg (52%); pale yellow solid; mp 71–
73 °C ; [α]D27 +105 (c 0.5, CH2Cl2).
1H NMR (600 MHz, CDCl3): δ (major) = 7.68–7.66 (m, 2 H, PhH), 7.34–
7.29 (m, 4 H, PhH), 7.26–7.23 (m, 4 H, PhH), 7.11–7.09 (m, 1 H, PhH),
6.87–6.85 (m, 2 H, PhH), 6.29 (dd, J = 15.8, 7.6 Hz, 1 H, CH=CHPh),
6.24–6.22 (m, 2 H, CH=CHPh and C=CH), 4.75 (dd, J = 12.3, 4.7 Hz, 1 H,
NCHH), 3.94–3.91 (m, 1 H, NCHH), 3.82 (s, 3 H, OCH3), 3.10–3.05 (m, 1
H, PhCH), 2.92–2.88 (m, 1 H, CHCH=CHPh), 2.61–2.57 (m, 1 H, CH2CH),
1.54 (s, 9 H, Boc).
HPLC: Chiralpak AD, n-heptane/iPrOH (92:8), 0.7 mL/min, tR (major) =
22.62 min, tR (minor) = 32.45 min; T = 30 °C; 85:15 er.
IR (ATR): 3020, 2924, 2878, 2328, 2162, 2078, 1999, 1887, 1768, 1703,
1600, 1484, 1455, 1389, 1348, 1296, 1259, 1195, 1135, 1052, 1007,
966, 905, 861, 823, 748, 693 cm–1
.
13C NMR (151 MHz, CDCl3): δ (major) = 158.9, 153.5, 143.5, 139.4,
137.4, 131.0, 130.1, 128.4 (2 C), 127.9 (2 C), 127.6, 127.5, 127.3 (2 C),
126.6, 125.4, 125.2, 124.5, 124.0, 123.9, 113.9 (2 C), 81.2, 59.6, 57.1,
55.3, 49.0, 48.3, 28.4 (3 C).
HRMS (ESI+): m/z [M + Na]+ calcd for C32H33NO3Na: 502.2353; found:
502.2351.
1H NMR (600 MHz, CDCl3): δ (major) = 7.75–7.73 (m, 1 H, PhH), 7.69–
7.67 (m, 1 H, PhH), 7.45–7.44 (m, 2 H, PhH), 7.39–7.38 (m, 2 H, PhH),
7.36–7.33 (m, 4 H, PhH), 7.33–7.31 (m, 3 H, PhH), 7.28–7.25 (m, 2 H,
PhH), 7.15–7.11 (m, 3 H, PhH), 6.39 (dd, J = 15.8, 8.3 Hz, 1 H,
CH=CHPh), 6.27 (d, J = 15.8 Hz, 1 H, CH=CHPh), 6.20–6.19 (m, 1 H,
C=CH), 5.33 (d, J = 12.4 Hz, 1 H, PhCHH), 5.21 (d, J = 12.4 Hz, 1 H,
PhCHH), 4.82 (dd, J = 12.3, 4.6 Hz, 1 H, NCHH), 3.92–3.89 (m, 1 H,
NCHH), 3.12–3.08 (m, 1 H, PhCH), 3.01–2.97 (m, 1 H, CHCH=CHPh),
2.57–2.52 (m, 1 H, CH2CH).
tert-Butyl (2R,3R,3aS)-8-Methyl-2-phenyl-3-[(E)-styryl]-2,3,3a,4-
tetrahydro-5H-cyclopenta[c]quinoline-5-carboxylate (4l)
13C NMR (151 MHz, CDCl3): δ (major) = 154.2, 142.4, 139.6, 137.0,
136.9, 136.2, 132.2, 131.6 (2 C), 129.6 (2 C), 129.2, 128.6 (4 C), 128.1,
128.0, 127.9 (2 C), 127.5, 126.3 (2 C), 125.0, 124.8, 124.6, 124.5, 123.8,
120.5, 67.8, 59.7, 56.5, 49.1, 48.5.
HRMS (ESI+): m/z [M + Na]+ calcd for C34H28NO2BrNa: 584.1196;
found: 584.1193.
Compound 4l was isolated after flash chromatography (silica gel, n-
pentane/EtOAc, 20:1); yield: 155 mg (67%); pale yellow foamy solid;
[α]D27 +103 (c 0.5, CH2Cl2).
HPLC: Chiralpak IA, n-heptane/iPrOH (97:3), 0.5 mL/min, tR (major) =
8.73 min, tR (minor) = 9.23 min; T = 30 °C; 83.5:16.5 er.
IR (ATR): 2929, 2316, 1696, 1473, 1356, 1156, 988, 843, 730 cm–1
.
1H NMR (400 MHz, CDCl3): δ (major) = 7.55–7.53 (m, 1 H, PhH), 7.47
(s, 1 H, PhH), 7.35–7.28 (m, 6 H, PhH), 7.25–7.19 (m, 4 H, PhH), 7.06–
7.04 (m, 1 H, PhH), 6.42 (dd, J = 15.8, 8.0 Hz, 1 H, CH=CHPh), 6.27 (d,
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–J

G
L. Zhao et al.
Paper
Synthesis
J = 15.8 Hz, 1 H, CH=CHPh), 6.22–6.20 (m, 1 H, C=CH), 4.72 (dd,
J = 12.2, 4.6 Hz, 1 H, NCHH), 3.95–3.91 (m, 1 H, NCHH), 3.10–3.03 (m,
1 H, PhCH), 2.90–2.84 (m, 1 H, CHCH=CHPh), 2.62–2.55 (m, 1 H,
CH2CH), 2.34 (s, 3 H, CH3), 1.53 (s, 9 H, Boc).
(2R,3R,3aS)-2-Phenyl-3-[(E)-styryl]-2,3,3a,4-tetrahydrocyclopen-
ta[c]chromene (4o)
Compound 4o was isolated after flash chromatography (silica gel, n-
27
pentane/EtOAc, 20:1); yield: 70 mg (40%); pale yellow oil; [α]D +67
13C NMR (101 MHz, CDCl3): δ (major) = 153.5, 143.5, 139.5, 137.2,
135.0, 133.4, 131.6, 129.8, 128.5, 128.4 (4 C), 127.9 (2 C), 127.2, 126.6,
126.2 (2 C), 125.1, 125.0, 124.6, 123.7, 81.0, 59.6, 57.1, 49.0, 48.4, 28.4
(3 C), 20.8.
HRMS (ESI+): m/z [M + Na]+ calcd for C32H33NO2Na: 486.2404; found:
486.2400.
(c 0.5, CH2Cl2).
HPLC: Chiralpak IB, n-heptane/iPrOH (97:3), 0.5 mL/min, tR (major) =
16.93 min, tR (minor) = 13.54 min; T = 30 °C; 86.5:13.5 er.
IR (ATR): 3439, 3028, 2924, 2873, 2318, 2079, 1946, 1877, 1805, 1722,
1603, 1575, 1478, 1453, 1377, 1310, 1223, 1153, 1115, 1073, 1034,
999, 968, 911, 862, 833, 749, 695, 542 cm–1
.
1H NMR (600 MHz, CDCl3): δ (major) = 7.61–7.60 (m, 1 H, PhH), 7.40–
7.34 (m, 6 H, PhH), 7.30–7.27 (m, 4 H, PhH), 7.25–7.23 (m, 1 H, PhH),
7.00–6.98 (m, 2 H, PhH), 6.45 (dd, J = 15.8, 8.4 Hz, 1 H, CH=CHPh), 6.27
(d, J = 15.8 Hz, 1 H, CH=CHPh), 6.17–6.13 (m, 1 H, C=CH), 4.60 (dd,
J = 10.0, 4.8 Hz, 1 H, OCHH), 4.01–3.99 (m, 1 H, OCHH), 3.88–3.82 (m,
1 H, PhCH), 3.26–3.20 (m, 1 H, CHCH=CHPh), 2.64–2.60 (m, 1 H,
CH2CH).
13C NMR (151 MHz, CDCl3): δ (major) =154.4, 143.6, 137.1, 136.8,
131.6, 130.0, 129.5, 128.6 (2 C), 128.5 (2 C), 127.9 (2 C), 127.4, 127.3,
126.7, 126.2 (2 C), 125.3, 123.2, 121.0, 117.5, 71.2, 58.4, 57.6, 47.3.
tert-Butyl (2R,3R,3aS)-7-Methoxy-2-phenyl-3-[(E)-styryl]-2,3,3a,4-
tetrahydro-5H-cyclopenta[c]quinoline-5-carboxylate (4m)
Compound 4m was isolated after flash chromatography (silica gel, n-
pentane/EtOAc, 20:1); yield: 122 mg (51%); pale yellow foamy solid;
[α]D27 +178 (c 0.5, CH2Cl2).
HPLC: Chiralpak IA, n-heptane/iPrOH (97:3), 0.5 mL/min, tR (major) =
11.95 min, tR (minor) = 15.19 min; T = 30 °C; 99.5:0.5 er.
IR (ATR): 2930, 2333, 2084, 1697, 1608, 1469, 1356, 1156, 1054, 843,
736 cm–1
.
HRMS (ESI+): m/z [M + Na]+ calcd for C26H22ONa: 373.1563; found:
373.1557.
1H NMR (400 MHz, CDCl3): δ (major) = 7.57–7.55 (m, 1 H, PhH), 7.35–
7.27 (m, 6 H, PhH), 7.26–7.18 (m, 5 H, PhH), 6.70–6.68 (m, 1 H, PhH),
6.40 (dd, J = 15.9, 8.0 Hz, 1 H, CH=CHPh), 6.26 (d, J = 15.9 Hz, 1 H,
CH=CHPh), 6.04–6.03 (m, 1 H, C=CH), 4.72 (dd, J = 12.2, 4.5 Hz, 1 H,
NCHH), 3.92–3.88 (m, 1 H, NCHH), 3.82 (s, 3 H, OCH3), 3.07–2.99 (m, 1
H, PhCH), 2.89–2.83 (m, 1 H, CHCH=CHPh), 2.59–2.52 (m, 1 H, CH2CH),
1.53 (s, 9 H, Boc).
13C NMR (101 MHz, CDCl3): δ (major) = 159.0, 153.3, 143.7, 139.1,
138.6, 137.3, 131.6, 130.0, 128.4 (4 C), 127.8 (2 C), 127.2, 126.5, 126.2
(2 C), 125.5, 122.7, 117.1, 111.5, 109.5, 81.3, 59.4, 57.0, 55.4, 48.9,
48.5, 28.4 (3 C).
(2R,3S,3aS)-2-Phenyl-3-[(E)-styryl]-3,3a,4,5-tetrahydro-2H-cyclo-
penta[a]naphthalene (4p)
Compound 4p was isolated after flash chromatography (silica gel, n-
pentane/EtOAc, 20:1); yield: 38 mg (22%); pale yellow oil; [α]D27 +192
(c 0.5, CH2Cl2).
HPLC: Chiralpak IA, n-heptane/EtOH (97:3), 0.5 mL/min, tR (major) =
8.42 min, tR (minor) = 8.80 min; T = 30 °C; 87.5:12.5 er.
IR (ATR): 3456, 3020, 2931, 1740, 1602, 1451, 1367, 1215, 962, 729
HRMS (ESI+): m/z [M + Na]+ calcd for C32H33NO3Na: 502.2353; found:
502.2348.
cm–1
.
1H NMR (600 MHz, CDCl3): δ (major) = 7.70–6.68 (m, 1 H, PhH), 7.39–
3.38 (m, 2 H, PhH), 7.34–7.31 (m, 4 H, PhH), 7.29–7.28 (m, 2 H, PhH),
7.26–7.23 (m, 2 H, PhH), 7.22–7.20 (m, 3 H, PhH), 6.45 (dd, J = 15.8, 8.6
Hz, 1 H, CH=CHPh), 6.27 (d, J = 15.8 Hz, 1 H, CH=CHPh), 6.20–6.19 (m,
1 H, C=CH), 3.98–3.96 (m, 1 H, PhCH), 2.99–2.88 (m, 3 H, ArCHH,
ArCHH and PhCH=CHCH), 2.63–2.58 (m, 1 H, CH2CH2CH), 2.23–2.19
(m, 1 H, ArCH2CHH), 1.62–1.56 (m, 1 H, ArCH2CHH).
tert-Butyl (2R,3R,3aS)-8-Fluoro-2-phenyl-3-[(E)-styryl]-2,3,3a,4-
tetrahydro-5H-cyclopenta[c]quinoline-5-carboxylate (4n)
Compound 4n was isolated after flash chromatography (silica gel, n-
pentane/EtOAc, 20:1); yield: 100 mg (43%); pale yellow foamy solid;
[α]D27 +137 (c 0.5, CH2Cl2).
13C NMR (151 MHz, CDCl3): δ (major) = 144.4, 142.4, 137.5, 137.2,
131.3, 131.2, 129.2, 128.5 (2 C), 128.3 (2 C), 127.8 (2 C), 127.6, 127.1,
126.4, 126.1 (4 C), 124.6, 123.8, 62.1, 57.4, 50.5, 30.6, 28.6.
HPLC: Chiralpak IG, n-heptane/iPrOH (9:1), 0.5 mL/min, tR (major) =
5.16 min, tR (minor) = 5.88 min; T = 30 °C; 81.5:18.5 er.
IR (ATR): 3850, 3432, 2928, 2551, 2451, 2186, 2067, 1978, 1958, 1698,
1480, 1359, 1154, 1035, 966, 854, 741 cm–1
.
HRMS (ESI+): m/z [M + Na]+ calcd for C27H24Na: 371.1770; found:
1H NMR (400 MHz, CDCl3): δ (major) = 7.62–7.58 (m, 1 H, PhH), 7.34–
7.27 (m, 7 H, PhH), 7.26–9.19 (m, 4 H, PhH), 6.95–6.90 (m, 1 H, PhH),
6.39 (dd, J = 15.9, 7.9 Hz, 1 H, CH=CHPh), 6.26 (d, J = 15.9 Hz, 1 H,
CH=CHPh), 6.21–6.20 (m, 1 H, C=CH), 4.69 (dd, J = 12.3, 4.6 Hz, 1 H,
NCHH), 3.94–3.90 (m, 1 H, NCHH), 3.08–3.00 (m, 1 H, PhCH), 2.88–
2.82 (m, 1 H, CHCH=CHPh), 2.63–2.56 (m, 1 H, CH2CH), 1.51 (s, 9 H,
Boc).
371.1771.
(1S,2R,8aS)-2-Phenyl-1-[(E)-styryl]-1,2,8,8a-tetrahydrocyclopen-
ta[a]indene (4q)
Compound 4q was isolated after flash chromatography (silica gel, n-
pentane/EtOAc, 20:1); yield: 40 mg (24%); pale yellow oil; [α]D +62
(c 0.5, CH2Cl2).
27
13C NMR (101 MHz, CDCl3): δ(major) = 160.4, 158.0, 153.4, 143.0,
138.9, 137.1, 133.5 (2 C), 131.8, 129.5, 128.5 (2 C), 127.8, 127.3, 127.0
(2 C), 126.8, 126.7, 126.2, 114.8, 114.6, 110.2, 110.0, 81.3, 59.5, 57.0,
48.7, 48.2, 28.3 (3 C).
HRMS (ESI+): m/z [M + Na]+ calcd for C31H30NO2FNa: 490.2153; found:
490.2152.
HPLC: Chiralpak IB, n-heptane/iPrOH (99:1), 0.5 mL/min, tR (major) =
15.62 min, tR (minor) = 12.29 min; T = 30 °C; 95.5:4.5 er.
IR (ATR): 3456, 3018, 2331, 1740, 1602, 1367, 1214, 963, 729 cm–1
.
1H NMR (600 MHz, CDCl3): δ (major) = 7.55–7.53 (m, 1 H, PhH), 7.43–
7.37 (m, 3 H, PhH), 7.36–7.32 (m, 6 H, PhH), 7.31–7.24 (m, 4 H, PhH),
6.49 (dd, J = 15.9, 7.7 Hz, 1 H, CH=CHPh), 6.32 (d, J = 15.9 Hz, 1 H, CH=
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–J

H
L. Zhao et al.
Paper
Synthesis
CHPh), 5.89–5.88 (m, 1 H, C=CH), 4.24–4.22 (m, 1 H, PhCH), 3.63–3.57
(m, 1 H, CHCH=CHPh), 3.16 (dd, J = 15.8, 8.4 Hz, 1 H, CHH), 2.86–2.81
(m, 1 H, ArCH2CH), 2.76 (dd, J = 15.8, 8.4 Hz, 1 H, CHH).
13C NMR (151 MHz, CDCl3): δ (major) = 152.8, 149.7, 143.6, 137.5,
136.3, 130.8, 130.7, 128.5 (2 C), 128.4 (2 C), 128.3, 128.0 (2 C), 127.1,
126.9, 126.5, 126.2 (2 C), 126.0, 122.1, 120.1, 63.4, 63.0, 56.7, 35.7.
dissolved in CH2Cl2 (20 mL) and then triethylamine (1.03 mL, 7.4
mmol) and DMAP (0.9 g, 7.4 mmol) were added. To the solution di-
tert-butyl dicarbonate (3.3 g, 14.8 mmol) was added portionwise. The
reaction was stirred at r.t. for 2 h, then concentrated on a rotary evap-
orator to an oil. The oil was chromatographed (silica gel, EtOAc/n-hex-
ane, 1:9) to give a clear colorless oil; yield: 1.35 g (74%). Step 5: A mix-
ture of tert-butyl 4-oxo-3,4-dihydroquinoline-1(2H)-carboxylate
(1.35 g, 5.5 mmol), cinnamaldehyde (0.87 mL, 6.6 mmol), 10% KOH
(12 mL), and EtOH (35 mL) was stirred at r.t. for 3 h, then poured into
crushed ice. The precipitate was separated by filtration, washed free
of base, and recrystallized from MeOH; this gave product 1a; yield:
1.01 g (51%); yellow solid; mp 150–152 °C.
HRMS (ESI+): m/z [M + Na]+ calcd for C26H22Na: 357.1614; found:
357.1615.
(E)-2-Phenyl-3-styryl-3,3a,4,5-tetrahydro-2H-cyclopenta[c]quino-
line (5)
To a solution of the Boc-protected quinoline 4a (0.1 mmol) in anhyd
CH2Cl2 (1 mL) at 0 °C was added trifluoroacetic acid (0.11 mL) over 1
min. The reaction mixture was stirred for 1 h during which time the
mixture warmed to r.t. The mixture was concentrated under reduced
pressure. The residue was dissolved in CH2Cl2 (10 mL) and washed
with sat. aq NaHCO3 solution (10 mL). The aqueous phase was ex-
tracted with CH2Cl2 (10 mL) and the organic extracts were dried (Na2-
SO4) and concentrated under reduced pressure. After purification by
column chromatography (silica gel, n-pentane/EtOAc, 20:1), the de-
sired product 5 was obtained as a colorless solid; mp 68–70 °C; yield:
31 mg (87%); [α]D27 +105 (c 0.5, CH2Cl2).
tert-Butyl (E)-4-Oxo-3-[(E)-3-phenylallylidene]-3,4-dihydroquino-
line-1(2H)-carboxylate (1a)
Yellow solid; mp 150–152 °C; yield: 1.01 g (14%).
IR (ATR): 3077, 2986, 2644, 2328, 2112, 2044, 1881, 1694, 1582, 1467,
1361, 1315, 1231, 1148, 1017, 952, 853, 745, 683 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.05–8.02 (m, 1 H, PhH), 7.64–7.62 (m,
1 H, PhH), 7.55–7.48 (m, 4 H, CHCH=CHPh and PhH), 7.41–7.34 (m,
3 H, PhH), 7.23–7.18 (m, 1 H, PhH), 7.15–7.08 (m, 2 H, CHCH=CHPh),
4.92 (d, J = 1.5 Hz, 2 H, NCH2), 1.54 (s, 9 H, Boc).
IR (ATR): 3398, 3345, 3013, 2927, 2855, 2324, 2165, 2109, 1993, 1940,
1866, 1740, 1622, 1587, 1494, 1459, 1365, 1301, 1238, 1168, 1141,
13C NMR (101 MHz, CDCl3): δ = 184.2, 152.6, 143.2, 143.1, 136.1,
135.9, 133.2, 130.8, 129.4, 128.9 (2 C), 127.9, 127.4 (2 C), 127.3, 124.5,
124.3, 122.3, 82.1, 45.0, 28.3 (3 C).
1103, 1052, 1023, 967, 932, 862, 839, 807, 747, 689 cm–1
.
1H NMR (600 MHz, CDCl3): δ (major) = 7.53–7.51 (m, 1 H, PhH), 7.37–
7.35 (m, 2 H, PhH), 7.34–7.31 (m, 4 H, PhH), 7.27–7.22 (m, 4 H, PhH),
7.10–7.07 (m, 1 H, PhH), 6.74–6.72 (m, 1 H, PhH), 6.63–6.61 (m, 1 H,
PhH), 6.44 (dd, J = 15.8, 8.6 Hz, 1 H, CH=CHPh), 6.23 (d, J = 15.8 Hz, 1
H, CH=CHPh), 6.04–6.03 (m, 1 H, C=CH), 4.08 (br, 1 H, NH), 3.98–3.96
(m, 1 H, PhCH), 3.57 (dd, J = 9.9, 4.6 Hz, 1 H, NCHH), 3.13–3.08 (m, 1 H,
NCHH), 3.07–3.03 (m, 1 H, CHCH=CHPh), 2.60–2.56 (m, 1 H, CH2CH).
13C NMR (151 MHz, CDCl3): δ (major) = 144.5, 144.3, 139.2, 137.3,
131.2, 130.8, 128.9, 128.5 (2 C), 128.4 (2 C), 127.8 (2 C), 127.2, 126.4,
126.1 (2 C), 125.4, 121.6, 117.9, 115.1, 60.0, 57.5, 48.4, 47.3, 28.4.
HRMS (ESI+): m/z [M + Na]+ calcd for C23H23NO3Na: 384.1570; found:
384.1570.
Benzyl (E)-4-Oxo-3-[(E)-3-phenylallylidene]-3,4-dihydroquino-
line-1(2H)-carboxylate (1b)
Yellow solid; mp 155–157 °C; yield: 1.26 g (16%).
IR (ATR): 3407, 3035, 2645, 2330, 2088, 1953, 1825, 1708, 1665, 1587,
1467, 1399, 1328, 1227, 1148, 1031, 964, 849, 741, 687 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.07–8.05 (m, 1 H, PhH), 7.71–7.69 (m,
1 H, PhH), 7.54–7.47 (m, 4 H, CHCH=CHPh and PhH), 7.41–7.32 (m,
8 H, PhH), 7.27–7.23 (m, 1 H, PhH), 7.10–7.08 (m, 2 H, CHCH=CHPh),
5.27 (s, 2 H, COCH2Ph), 4.98 (d, J = 1.5 Hz, 2 H, NCH2).
HRMS (ESI+): m/z [M + Na]+ calcd for C26H23NNa: 372.1723; found:
372.1719.
13C NMR (101 MHz, CDCl3): 183.9, 153.6, 143.4, 142.6, 136.3, 136.0,
135.7, 133.5, 130.2, 129.5, 128.8 (2 C), 128.6 (2 C), 128.4, 128.1 (2 C),
128.0, 127.5 (2 C), 127.3, 125.0, 124.0, 122.2, 68.3, 45.4.
HRMS (ESI+): m/z [M + Na]+ calcd for C26H21NO3Na: 418.1414; found:
418.1418.
Dihydroquinolinone 1a; Typical Procedure
Steps 1 and 2: To a suspension of aniline (1.8 mL, 20 mmol) and K2CO3
(3.3 g, 24 mmol) in CH2Cl2 (20 mL) at 0 °C was added dropwise 3-bro-
mopropanoyl chloride (2.5 mL, 24 mmol). The mixture was stirred at
0 °C for 5 min and allowed to warm to r.t. for another 3 h. The reaction
was quenched with H2O and extracted with EtOAc (3 × 15 mL). The
combined organic layers were evaporated, and the residue was re-
crystallized from a hot solution of petroleum ether/EtOAc (1:1) to af-
ford 3.42 g (15 mmol, 75%) of crude 3-bromo-N-phenylpropanamide
as colorless crystals. This solid was then dissolved in DMF (20 mL) and
cooled to 0 °C. To this solution was added sodium tert-butoxide (1.57
g, 16.5 mmol) in one portion, and the mixture was gradually allowed
to warm to r.t. The reaction was quenched with H2O after 3 h and ex-
tracted with EtOAc (30 mL). The combined organic layers were evapo-
rated, and the residue was recrystallized from a hot solution of petro-
leum ether/EtOAc (1:1) to afford 1-phenylazetidin-2-one as a red sol-
id; yield: 1.32 g (60%). Step 3: To a solution of 1-phenylazetidin-2-one
(1.32 g, 9 mmol) in DCE (30 mL) at 0 °C was added trifluoromethane-
sulfonic acid (1.06 mL, 12 mmol). The solution was stirred at r.t. for 60
min, quenched with sat. aq NaHCO3, extracted with EtOAc, dried over
anhyd Na2SO4, and concentrated in vacuo to yield a clear oil; yield:
1.08 g (82%). Step 4: The 4-azachromanone (1.08 g, 7.4 mmol) was
tert-Butyl (E)-3-[(E)-3-(Furan-2-yl)allylidene]-4-oxo-3,4-dihydro-
quinoline-1(2H)-carboxylate (1c)
Yellow solid; mp 158–160 °C; yield: 0.84 g (12%).
IR (ATR): 3816, 3458, 2979, 2642, 2327, 2217, 2103, 1992, 1911, 1738,
1692, 1576, 1467, 1363, 1225, 1148, 1059, 1014, 956, 860, 746 cm–1
.
1H NMR (600 MHz, CDCl3): δ = 8.03–8.01 (m, 1 H, PhH), 7.64–7.62 (m,
1 H, PhH), 7.50–7.46 (m, 2 H, PhH), 7.42 (d, J = 12.2 Hz, 1 H,
CHCH=CHPh), 7.21–7.18 (m, 1 H, furanH), 7.03 (dd, J = 15.1, 12.2 Hz,
1 H, CHCH=CHPh), 6.84 (d, J = 15.1 Hz, 1 H, CHCH=CHPh), 6.52–6.46
(m, 2 H, furanH), 4.88 (d, J = 1.6 Hz, 2 H, NCH2), 1.53 (s, 9 H, Boc).
13C NMR (151 MHz, CDCl3): δ = 184.1, 152.7, 152.4, 144.1, 143.3,
135.5, 133.2, 130.8, 129.1, 127.9, 127.4, 124.5, 124.3, 120.8, 112.8,
112.4, 82.1, 45.0, 28.3 (3 C).
HRMS (ESI+): m/z [M + Na]+ calcd for C21H21NO4Na: 374.1363; found:
374.1363.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–J

I
L. Zhao et al.
Paper
Synthesis
tert-Butyl (E)-3-[(E)-3-(4-Methoxyphenyl)allylidene]-4-oxo-3,4-
dihydroquinoline-1(2H)-carboxylate (1d)
13C NMR (151 MHz, CDCl3): δ = 183.3, 160.2, 158.6, 152.6, 143.7,
139.4, 136.7, 136.0, 130.2, 129.6, 128.9 (2 C), 127.5 (2 C), 126.4, 122.2,
120.6 and 120.4 (1 C), 113.5 and 113.4 (1 C), 82.3, 45.0, 28.3 (3 C).
HRMS (ESI+): m/z [M + Na]+ calcd for C23H22NO3FNa: 402.1476; found:
402.1478.
Yellow solid; mp 155–157 °C; yield: 1.28 g (16%).
IR (ATR): 2980, 2928, 2845, 2331, 2182, 2105, 1995, 1890, 1696, 1662,
1570, 1462, 1356, 1315, 1239, 1157, 1014, 954, 822, 749 cm–1
.
1H NMR (600 MHz, CDCl3): δ = 8.04–8.02 (m, 1 H, PhH), 7.63–7.71 (m,
1 H, PhH), 7.51–7.47 (m, 4 H, CHCH=CHPh and PhH), 7.21–7.19 (m,
1 H, PhH), 7.05 (d, J = 15.2 Hz, 1 H, CHCH=CHPh), 7.00 (dd, J = 15.2,
11.0 Hz, 1 H, CHCH=CHPh), 6.91–6.90 (m, 2 H, PhH), 4.89 (d, J = 1.5 Hz,
2 H, NCH2), 3.84 (s, 3 H, OCH3), 1.53 (s, 9 H, Boc).
Acknowledgment
L. Zhao thanks the China Scholarship Council for a fellowship.
13C NMR (151 MHz, CDCl3): δ = 184.2, 160.8, 152.7, 143.2, 143.0,
136.6, 133.1, 129.6, 129.0 (3 C), 127.9, 127.5, 124.5, 124.3, 120.3,
114.4 (2 C), 82.0, 55.4, 44.9, 28.3 (3 C).
Supporting Information
Supporting information for this article is available online at
HRMS (ESI+): m/z [M + Na]+ calcd for C24H25NO4Na: 414.1676; found:
414.1682.
https://doi.org/10.1055/s-0036-1591995.
S
u
p
p
o
nrtogI
f
rmoaitn
S
u
p
p
ortiInfogrmoaitn
tert-Butyl (E)-6-Methyl-4-oxo-3-[(E)-3-phenylallylidene]-3,4-di-
hydroquinoline-1(2H)-carboxylate (1e)
References
Yellow solid; mp 159–161 °C; yield: 0.68 g (9%).
(1) For selected reviews, see: (a) Enders, D.; Balensiefer, T. Acc.
Chem. Res. 2004, 37, 534. (b) Zeitler, K. Angew. Chem. Int. Ed.
2005, 44, 7506. (c) Enders, D.; Niemeier, O.; Henseler, A. Chem.
Rev. 2007, 107, 5606. (d) Moore, J. L.; Rovis, T. Top. Curr. Chem.
2010, 291, 77. (e) Nair, V.; Menon, R. S.; Biju, A. T.; Sinu, C. R.;
Paul, R. R.; Jose, A.; Sreekumar, V. Chem. Soc. Rev. 2011, 40, 5336.
(f) Douglas, J.; Churchill, G.; Smith, A. D. Synthesis 2012, 44,
2295. (g) Bugaut, X.; Glorius, F. Chem. Soc. Rev. 2012, 41, 3511.
(h) Grossmann, A.; Enders, D. Angew. Chem. Int. Ed. 2012, 51,
314. (i) Izquierdo, J.; Hutson, G. E.; Cohen, D. T.; Scheidt, K. A.
Angew. Chem. Int. Ed. 2012, 51, 11686. (j) De Sarkar, S.; Biswas,
A.; Samanta, R. C.; Studer, A. Chem. Eur. J. 2013, 19, 4664.
(k) Ryan, S. J.; Candish, L.; Lupton, D. W. Chem. Soc. Rev. 2013,
42, 4906. (l) Mahatthananchai, J.; Bode, J. W. Acc. Chem. Res.
2014, 47, 696. (m) Hopkinson, M. N.; Richter, C.; Schedler, M.;
Glorius, F. Nature 2014, 510, 485. (n) Flanigan, D. M.; Romanov-
Michailidid, F.; White, N. A.; Rovis, T. Chem. Rev. 2015, 115,
9307. (o) Menon, R. S.; Biju, A. T.; Nair, V. Chem. Soc. Rev. 2015,
44, 5040. (p) Yetra, S. R.; Patra, A.; Biju, A. T. Synthesis 2015, 47,
1357. (q) Reyes, E.; Uria, U.; Carrillo, L.; Vicario, J. L. Synthesis
2017, 49, 451. For selected papers, see: (r) Huang, X.-L.; He, L.;
Shao, P.-L.; Ye, S. Angew. Chem. Int. Ed. 2009, 48, 192. (s) Hao, L.;
Du, Y.; Lv, H.; Chen, X.; Jiang, H.; Shao, Y.; Chi, Y. R. Org. Lett.
2012, 14, 2154. (t) Chen, X. Y.; Sun, L.-H.; Ye, S. Chem. Eur. J.
2013, 19, 4441. (u) Lee, A.; Scheidt, K. A. Chem. Commun. 2015,
51, 3407. (v) Chen, X.-Y.; Liu, Q.; Chauhan, P.; Li, S.; Peuronen,
A.; Rissanen, K.; Jafari, E.; Enders, D. Angew. Chem. Int. Ed. 2017,
56, 6241.
IR (ATR): 2975, 2924, 2326, 2105, 1991, 1905, 1697, 1597, 1490, 1360,
1299, 1234, 1146, 1026, 969, 823, 752, 689 cm–1
.
1H NMR (600 MHz, CDCl3): δ = 7.83–7.83 (m, 1 H, PhH), 7.54–7.48 (m,
4 H, PhH and CHCH=CHPh), 7.39–7.37 (m, 2 H, PhH), 7.35–7.30 (m, 2
H, PhH), 7.14 (dd, J = 15.3, 11.1 Hz, 1 H, CHCH=CHPh), 7.09 (d, J = 15.3
Hz, 1 H, CHCH=CHPh), 4.89 (d, J = 1.6 Hz, 2 H, NCH2), 2.37 (s, 3 H, CH3),
1.53 (s, 9 H, Boc).
13C NMR (151 MHz, CDCl3): δ = 184.4, 152.8, 143.0, 140.9, 136.1,
135.9, 134.3, 134.2, 131.0, 129.4, 128.9 (2 C), 127.8, 127.4 (2 C), 127.1,
124.2, 122.4, 81.9, 44.9, 28.3 (3 C), 20.7.
HRMS (ESI+): m/z [M + Na]+ calcd for C24H25NO3Na: 398.1727; found:
398.1726.
tert-Butyl (E)-7-Methoxy-4-oxo-3-[(E)-3-phenylallylidene]-3,4-di-
hydroquinoline-1(2H)-carboxylate (1f)
Yellow solid; mp 162–165 °C; yield: 0.86 g (11%).
IR (ATR): 2975, 2324, 2107, 1996, 1916, 1701, 1659, 1593, 1452, 1359,
1238, 1143, 1024, 957, 857, 745, 685 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.99–7.97 (m, 1 H, PhH), 7.52–7.47 (m,
3 H, CHCH=CHPh and PhH), 7.38–7.31 (m, 3 H, PhH), 7.17–7.16 (m,
1 H, PhH), 7.12–7.03 (m, 2 H, CHCH=CHPh), 6.75–6.73 (m, 1 H, PhH),
4.88 (d, J = 1.5 Hz, 2 H, NCH2), 3.86 (s, 3 H, CH3O), 1.53 (s, 9 H, Boc).
13C NMR (101 MHz, CDCl3): δ = 183.2, 163.7, 152.5, 145.1, 142.5,
136.2, 135.3, 130.7, 129.9, 129.3, 128.8 (2 C), 127.3 (2 C), 122.4, 120.9,
111.7, 108.4, 82.2, 55.5, 45.2, 28.3 (3 C).
(2) (a) Burstein, C.; Glorius, F. Angew. Chem. Int. Ed. 2004, 43, 6205.
(b) Sohn, S. S.; Rosen, E. L.; Bode, J. W. J. Am. Chem. Soc. 2004,
126, 14370.
HRMS (ESI+): m/z [M + Na]+ calcd for C24H25NO4Na: 414.1676; found:
414.1680.
(3) (a) Nair, V.; Vellalath, S.; Poonoth, M.; Mohan, R.; Suresh, E. Org.
Lett. 2006, 8, 507. (b) Nair, V.; Poonoth, M.; Vellalath, S.; Suresh,
E.; Thirumalai, R. J. Org. Chem. 2006, 71, 8964. (c) Li, Y.; Zhao, Z.-
A.; He, H.; You, S.-L. Adv. Synth. Catal. 2008, 350, 1885. (d) Sun,
L.-H.; Shen, L.-T.; Ye, S. Chem. Commun. 2011, 47, 10136.
(e) Cohen, D. T.; Scheidt, K. A. Chem. Sci. 2012, 3, 53. (f) Dugal-
Tessier, J.; O’Bryan, E. A.; Schroeder, T. B. H.; Cohen, D. T.;
Scheidt, K. A. Angew. Chem. Int. Ed. 2012, 51, 4963. (g) Nawaz, F.;
Zaghouani, M.; Bonne, D.; Chuzel, O.; Rodriguez, J.; Coquerel, Y.
Eur. J. Org. Chem. 2013, 8253. (h) Lv, H.; Jia, W.-Q.; Sun, L.-H.; Ye,
S. Angew. Chem. Int. Ed. 2013, 52, 8607. (i) Jang, K.-P.; Hutson, G.
E.; Johnston, R. C.; McCusker, E. O.; Cheong, P. H.-Y.; Scheidt, K.
tert-Butyl (E)-6-Fluoro-4-oxo-3-[(E)-3-phenylallylidene]-3,4-dihy-
droquinoline-1(2H)-carboxylate (1g)
Yellow solid; mp 175–177 °C; yield: 0.45 g (6%).
IR (ATR): 2972, 2925, 2317, 2109, 1913, 1700, 1666, 1593, 1484, 1441,
1361, 1304, 1241, 1146, 1025, 975, 884, 838, 758, 715 cm–1
.
1H NMR (600 MHz, CDCl3): δ = 7.69–7.67 (m, 1 H, PhH), 7.63–7.61 (m,
1 H, PhH), 7.55–7.50 (m, 3 H, PhH and CHCH=CHPh), 7.40–7.33 (m,
3 H, PhH), 7.22–7.19 (m, 1 H, PhH), 7.16–7.09 (m, 2 H, CHCH=CHPh),
4.89 (d, J = 1.6 Hz, 2 H, NCH2), 1.53 (s, 9 H, Boc).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–J

J
L. Zhao et al.
Paper
Synthesis
A. J. Am. Chem. Soc. 2014, 136, 76. (j) Guo, C.; Sahoo, B.; Daniliuc,
C. G.; Glorius, F. J. Am. Chem. Soc. 2014, 136, 17402. (k) Guo, C.;
Fleige, M.; Janssen-Müller, D.; Daniliuc, C. G.; Glorius, F. Nature
Chem. 2015, 7, 842. (l) Wang, L.; Li, S.; Blümel, M.; Philipps, A.
R.; Wang, A.; Peuronen, A.; Rissanen, K.; Raabe, G.; Enders, D.
Angew. Chem. Int. Ed. 2016, 55, 11110. (m) Guo, C.; Fleige, M.;
Janssen-Müller, D.; Daniliuc, C. G.; Glorius, F. J. Am. Chem. Soc.
2016, 138, 7840.
(12) (a) Rosenzweig-Lipson, S.; Dunlop, J.; Marquis, K. L. Drug News
Perspect. 2005, 9, 565. (b) Dunlop, J.; Watts, S. W.; Barrett, J. E.;
Coupet, J.; Harrison, B.; Mazandarani, H.; Nawoschik, S.;
Pangalos, M. N.; Ramamoorthy, S.; Schechter, L.; Smith, D.;
Stack, G.; Zhang, J.; Zhang, G.; Rosenzweig-Lipson, S. J. Pharm.
Exp. Tech. 2011, 337, 673. (c) Dragan, V.; McWilliams, J. C.;
Miller, R.; Sutherland, K.; Dillon, J. L.; O’Brien, M. A. Org. Lett.
2013, 15, 2942. (d) Liu, Y.-P.; Li, Y.; Cai, X.-H.; Li, X.-Y.; Kong, L.-
M.; Cheng, G.-G.; Luo, X.-D. J. Nat. Prod. 2012, 75, 220.
(e) Palmisano, G.; Danieli, B.; Lesma, G.; Mauro, M. J. Chem. Soc.,
Chem. Commun. 1986, 1564.
(4) Nair, V.; Vellalath, S.; Poonoth, M.; Sureth, E. J. Am. Chem. Soc.
2006, 128, 8736.
(5) Chiang, P. C.; Kaeobamrung, J.; Bode, J. W. J. Am. Chem. Soc.
2007, 129, 3520.
(6) Cardinal-David, B.; Raup, D. E. A.; Scheidt, K. A. J. Am. Chem. Soc.
2010, 132, 5345.
(13) CCDC 1587958 contains the supplementary crystallographic
data of 4i. These data can be obtained free of charge from The
Cambridge
Crystallographic
Data
Centre
via
(7) Bera, S.; Samanta, R. C.; Daniliuc, C. G.; Studer, A. Angew. Chem.
Int. Ed. 2014, 53, 9622.
(8) Mondal, S.; Yetra, S. R.; Patra, A.; Kunte, S. S.; Gonnade, R. G.;
Biju, A. T. Chem. Commun. 2014, 50, 14539.
(9) Zhang, Z.-F.; Chen, K.-Q.; Zhang, C.-L.; Ye, S. Chem. Commun.
2017, 53, 4327.
(10) (a) Guo, C.; Schedler, M.; Daniliuc, C. G.; Glorius, F. Angew.
Chem. Int. Ed. 2014, 53, 10232. (b) Wang, L.; Li, S.; Chauhan, P.;
Hack, D.; Philipps, A. R.; Peuronen, A.; Rissanen, K.; Raabe, G.;
Enders, D. Chem. Eur. J. 2016, 22, 5123.
www.ccdc.cam.ac.uk/getstructures.
(14) Kerr, M. S.; Read de Alaniz, J.; Rovis, T. J. Org. Chem. 2005, 70,
5725.
(15) (a) Schmidt, R. G.; Bayburt, E. K.; Latshow, S. P.; Koenig, J. R.;
Daanen, J. F.; McDonald, H. A.; Bianchi, B. R.; Zhong, C. M.; Joshi,
S.; Honore, P.; Marsh, K. C.; Lee, C. H.; Faltynek, C. R.; Gomtsyan,
A. Bioorg. Med. Chem. Lett. 2011, 21, 1338. (b) Harland, A. A.;
Yeomans, L.; Grigge, N. W.; Anand, J. P.; Pogozheva, I. D.;
Jutkiewicz, E. M.; Traynor, J. R.; Mosberg, H. I. J. Med. Chem.
2015, 58, 8952. (c) Levai, A.; Simon, A.; Jenei, A.; Kalman, G.;
Jeko, J.; Toth, G. ARKIVOC 2009, (xii), 161.
(11) For a recent organocatalytic synthesis of fully substituted cyclo-
pentanes, see: Zou, L.-H.; Philipps, A. R.; Raabe, G.; Enders, D.
Chem. Eur. J. 2015, 21, 1004.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–J