Scandium-catalyzed cascade cyclization to produce cyclobutane-fused tetrahydroquinoline, chromane, thiochromane, and tetrahydronaphthalene derivatives

Article abstract of DOI:10.1002/adsc.201400020

We have succeeded in the highly diastereoselective synthesis of cyclobutane-fused multi-cyclic compounds using a scandium-catalyzed cascade cyclization. Using 3-10 mol% of scandium(III) triflate [Sc(OTf)₃], various cyclobutane-fused tetrahydroquinoline derivatives as well as its chromane, thiochromane, and tetrahydronaphthalene analogues were obtained in good to excellent yields. Derivatizations of the reaction products, as well as the plausible reaction mechanism, are also discussed.

Full text of DOI:10.1002/adsc.201400020

UPDATES
DOI: 10.1002/adsc.201400020
Scandium-Catalyzed Cascade Cyclization to Produce
Cyclobutane-Fused Tetrahydroquinoline, Chromane,
Thiochromane, and Tetrahydronaphthalene Derivatives
Shun-ichi Nakano,a Kazumi Kakugawa,a Tetsuhiro Nemoto,a
and Yasumasa Hamadaa,*
a
Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba 260-8675, Japan
Fax : (+81)-43-226-2920; e-mail: y-hamada@faculty.chiba-u.jp
Received: January 7, 2014; Revised: March 10, 2014; Published online: && &&, 0000
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201400020.
Abstract: We have succeeded in the highly diaste-
reoselective synthesis of cyclobutane-fused multi-
cyclic compounds using a scandium-catalyzed cas-
cade cyclization. Using 3–10 mol% of scandium
ACHTUNGTNER(NUNG III)
triflate [Sc(OTf)3], various cyclobutane-fused tetra-
ACHTUNGTRENNUNG
hydroquinoline derivatives as well as its chromane,
thiochromane, and tetrahydronaphthalene ana-
logues were obtained in good to excellent yields.
Derivatizations of the reaction products, as well as
the plausible reaction mechanism, are also dis-
cussed.
Keywords: cascade catalysis; cyclization; cyclobu-
tanes; scandium; tetrahydroquinolines
Scheme 1. Background and plan of this work.
The development of an efficient synthetic method to-
wards complex molecular frameworks is an important
challenge in synthetic organic chemistry and medici- sponding alcohol derivatives in the presence of Lewis
nal chemistry. One of the most straightforward ap- acid catalysts such as Sc(OTf)3 or B(C6F5)3. Subse-
A
ACHTUNGTRENNUNG
proaches to this end is cascade catalysis, which allows quent intramolecular Friedel–Crafts alkylation of in-
for the rapid construction of complex molecular doles with benzylic cations results in the formation of
frameworks from relatively simple starting materials a 5-membered ring skeleton. This background led us
in a single reaction operation, while reducing waste to hypothesize that the present reaction mode could
and cost. A wide variety of catalytic cascade reactions be extended to a diastereoselective synthesis of cyclo-
has been developed to date.[1]
butane-fused tetrahydroquinoline derivatives and its
As part of our ongoing studies aimed at developing chromane, thiochromane, and tetrahydronaphthalene
a novel synthetic method for fused-polycyclic mole- analogues by using benzylidenemalonates as electro-
cules,[2] we recently reported a Lewis acid-catalyzed philic partners. Moreover, the use of heteroatom-teth-
highly diastereoselective cascade cyclization to pro- ered alkylidenemalonate variants would provide
duce structurally diverse polycyclic cyclopenta[b]in- access to cyclobutane-fused heterocycles. In general,
dole derivatives.[2c] The developed process is based on activated alkenes such as enol ethers are utilized as
sequential C C bond forming events (Scheme 1). The nucleophiles in formal [2+2]cycloaddition reactions.[3]
À
reaction is initiated by an intramolecular ene-type ad- There are limited applications of unactivated alkenes
dition of a cinnamyl derivative unit to 3-alkylidenein- to this type of transformations.[4] In addition, hetero-
dolenium cations, which are generated from the corre- cyclic compounds bearing such cyclobutane-fused
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Shun-ichi Nakano et al.
product 2a in 84% yield as a diastereomerically pure
form (entry 7).[6] The relative configuration of 2a was
determined based on 2D-NMR and NOE analyses.
The reactivity increased when the reaction was per-
formed at a reflux temperature. Moreover, the reac-
tion proceeded smoothly even in the presence of
3 mol% of Sc catalyst, affording 2a in 94% yield after
48 h.
We next examined the scope and limitations of dif-
ferent substrates (Table 2). In addition to model sub-
strate 1a, substrates 1b–f, bearing an electron-donat-
ing group or an electron-withdrawing group on the ar-
omatic ring of the cinnamylamine unit, were reacted
under the optimized reaction conditions to provide
cyclobutane-fused tetrahydroquinoline derivatives 2a–
f in 69–97% yield (entries 1–6). Introduction of a tert-
butyldimethylsilyloxy, a nitro, or an ester substituent
on the aniline moiety was also tolerated in this reac-
tion, affording the corresponding products 2g–i in 78–
90% yield (entries 7–9). Substrates with a methanesul-
Figure 1. Examples of bioactive molecules with a cyclobu-
tane-fused heterocyclic core.
structures are present in various biologically active fonyl (Ms) group (1j), o-nitrobenzenesulfonyl (Ns)
natural products and pharmaceutical leads (Figure 1), group (1k), and benzyloxylcarbonyl (Cbz) group (1l)
indicating the potential utilities of the reaction prod- on the nitrogen tether, were also applicable to this re-
ucts for drug candidate screening.[5] Herein, we report action and the corresponding tetrahydroquinoline de-
an Sc-catalyzed cascade cyclization using benzylidene rivatives 2j–l were obtained in excellent yield (en-
or alkylidene malonate derivatives with a cinnamyl tries 10–12). Furthermore, tetrahydronaphthalene,
derivative unit as substrates that produces various cy- chromane, and thiochromane analogues 2m–o were
clobutane-fused multi-cyclic compounds in a highly
diastereoselective manner.
Table 2. Substrate scope.
We began our investigations with N-tosyl (Ts) teth-
ered substrate 1a (Table 1). We first examined the re-
action using 10 mol% of various Lewis acid catalysts
at room temperature. Although almost all of the trials
gave unsatisfactory results, the reaction using
ScACHTUNGTRENNUNG(OTf)3 successfully produced the cyclobutane-fused
Table 1. Optimization of the reaction conditions.
Entry
Lewis Acid
A
Temp.
[8C]
Time
[h]
Yield
[%][a]
1
2
3
4
5
6
7
8
9
10
BF3·OEt2 (10)
Mg(OTf)2 (10)
Zn(OTf)2 (10)
Cu(OTf)2 (10)
Yb(OTf)3 (10)
La(OTf)3 (10)
(OTf)3 (10)
(OTf)3 (10)
(OTf)3 (5)
(OTf)3 (3)
27
27
27
27
27
27
27
reflux
reflux
reflux
18
18
18
18
18
18
18
12
12
48
trace
no reaction
no reaction
no reaction
G
R
R
R
5
N
no reaction
Sc
Sc
Sc
Sc
U
84
92
91
94
[a]
Isolated yield.
10 mol% of ScACTHUNGTRENNUNG
[b]
[a]
[c]
Isolated yield.
2
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Scandium-Catalyzed Cascade Cyclization
accessible under the same reaction conditions, demon- substituents on the nitrogen atom. After acetylation
À
strating the broad substrate generality of this catalytic of 5 (89% yield, 2 steps), C H chlorination of the
cascade process (entries 13–15).
ortho position to the anilinic substituent proceeded in
Monoester variants of 2, such as compound 4, could the presence of 10 mol% of PdACTHNUTRGEN(UNG OAc)2, 2 equiv. of
not be synthesized from the corresponding methyl CuCl2, and 2 equiv. of CuACHTUNTRGNE(NUG OAc)2, affording 7 in 71%
cinnamate derivatives under the same reaction condi- yield.[8] In addition, when compound 2a was treated
À
tions. We thus developed an alternative two-step pro- with Pd(OH)2 C in CH3CN under a hydrogen atmos-
cess (Scheme 2). Compound 3, derived from allyl phere, hydrogenolysis of the C C bond between the
À
methyl malonate, was treated with 3 mol% of Sc cata- quaternary carbon and the benzylic carbon of the ani-
lyst to give the tetrahydroquinoline derivative in 82% linic benzene ring occurred selectively, affording
yield as a nearly 1:1 mixture of diastereomers. The linear compound 8 quantitatively. Furthermore, the
obtained product was then refluxed in toluene in the reaction using nosyl amide-tethered alkylidenemalo-
presence of 10 mol% of PdACHTNUTRGEN(UNG PPh3)4 and 20 equiv. of nate 9 proceeded in the presence of 10 mol% of
morpholine, providing tetrasubstituted cyclobutane ScACHTUNGTRENNUNG
derivative 4 in 78% yield as a single diastereomer.[7]
The synthetic utility of the developed reaction was in 90% yield.
further demonstrated (Scheme 3). Thioacetic acid effi-
To gain a mechanistic insight into the developed
ciently deprotected the Ns group in 2k under basic cascade process, we performed the reaction using
conditions, enabling divergent introduction of various a cis-type substrate (Scheme 4). When compound 1a’
(1:10 E/Z mixture) was reacted under the optimized
reaction conditions, 2a was obtained in 64% yield and
product 2a’ was not formed at all. Moreover,
1H NMR analyses of the reaction mixture revealed
that isomerization of (Z)-1a’ into (E)-1a did not occur
during the course of the reaction. These results led us
to propose a plausible reaction pathway of this cas-
À
cade process (Scheme 5). For the first C C bond for-
mation of 1a, two possible transition states A and B
Scheme 2. Synthesis of a tetrasubstituted cyclobutane deriv-
are postulated. The energetically more preferred tran-
sition state A gives zwitterionic intermediate C with
a gauche conformation, which is not suitable for the
cyclobutane ring formation. In contrast, zwitterionic
intermediate D, derived from transition state B, can
ative.
À
exist in an eclipsed conformation. The second C C
bond formation proceeds smoothly in this conforma-
tion, affording cyclobutane-fused tricyclic compound
À
2a. Similarly, for the first C C bond formation of 1a’,
transition state A’ provides a non-productive inter-
mediate C’. Thus, the reaction proceeds from transi-
tion state B’ to give a zwitterionic intermediate D’,
which suffers severe steric repulsion. Intermediate D’
is, therefore, immediately transformed into intermedi-
ate D via s-bond rotation, resulting in the formation
of 2a. On the other hand, no reaction occurred when
2a and benzaldehyde were refluxed in CH2Cl2 in the
presence of the ScACTHNUTRGNEUNG(OTf)3 catalyst, suggesting that 2a
does not function as a donor-acceptor cyclobuta-
Scheme 3. Demonstration of the synthetic utility of the de-
veloped catalysis.
Scheme 4. Reaction using cis-type substrate 1a’.
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Shun-ichi Nakano et al.
Scheme 5. Plausible reaction pathway,
ne[4b–c,9] based on the retro-cycloaddition pathway
from 2a to D.
(2C), 127.6, 127.9 (2C), 128.4 (2C), 128.7, 128.7, 128.9, 129.7
(2C), 130.3, 130.7, 134.7, 134.8, 136.0, 136.1, 138.6, 140.6,
143.9, 163.9, 166.5; (+)-ESI-HR-MS: m/z=528.1453, calcd,
for C28H27NNaO6S+ (M+Na+): 528.1451.
In conclusion, we have succeeded in the highly dia-
stereoselective synthesis of cyclobutane-fused multi-
cyclic compounds using the Sc-catalyzed cascade cyc-
lization. Using 3–10 mol% of the catalyst, various tet-
rahydroquinoline derivatives and its chromane, thio-
chromane, and tetrahydronaphthalene analogues were
obtained in good to excellent yields. Derivatizations
of the reaction products, as well as the plausible reac-
tion mechanism, were also described.
(Z)-Dimethyl 2-[2-(N-cinnamyl-4-methylphenylsulfonami-
do)benzylidene]malonate (1a’): Pale yellow oil; IR (ATR):
n=1727, 1436, 1350, 1257, 1216, 1160, 1067, 907, 814,
1
726 cmÀ1; H NMR (CDCl3): d=2.42 (s, 3H), 3.69 (s, 3H),
3.82 (s, 3H), 4.30 (br-s, 1H), 4.49 (br-s, 1H), 5.60 (dt, J=
11.6 Hz, 6.8 Hz, 1H), 6.47 (d, J=11.6 Hz, 1H), 6.81 (dd, J=
1.2 Hz, 7.6 Hz, 1H), 6.96 (dd, J=1.2 Hz, 7.6 Hz, 1H), 7.20–
7.33 (m, 9H), 7.41 (dd, J=1.6 Hz, 8.0 Hz, 1H), 7.54 (dt, J=
8.8 Hz, 2.0 Hz, 2H), 8.01 (s, 1H); 13C NMR (CDCl3): d=
21.6, 49.6, 52.5, 52.6, 125.6, 127.2, 127.5, 128.0 (2C), 128.2
(2C), 128.5 (2C), 128.6, 128.8, 129.5, 129.6 (2C), 130.7,
133.0, 135.0, 135.3, 135.8, 138.7, 140.4, 143.9, 164.0, 166.5;
(+)-ESI-HR-MS: m/z=528.1469, calcd. for C28H27NNaO6S+
(M+Na+): 528.1451.
Experimental Section
General
(E)-Dimethyl
2-{2-[4-methyl-N-(3-{para-tolyl}allyl)phe-
IR spectra were recorded on a JASCO FT/IR 230 Fourier
transform infrared spectrophotometer, equipped with ATR
(Smiths Detection, DuraSample IR II). NMR spectra were
recorded on a JEOL ecs 400 spectrometer, operating at
400 MHz for 1H NMR, and 100 MHz for 13C NMR. ESI-
TOF mass spectra were measured on JEOL AccuTOF LC-
plus JMS-T100LP. Melting points were measured with
a SIBATA NEL-270 melting point apparatus. Reactions
were carried out in dry solvent under an argon atmosphere.
Other reagents were purified by the usual methods.
nylsulfonamido]benzylidene}malonate (1b): Colorless oil;
IR (ATR): n=1728, 1435, 1347, 1256, 1217, 1159, 1066, 971,
1
768, 693 cmÀ1; H NMR (CDCl3): d=2.30 (s, 3H), 2.44 (s,
3H), 3.60 (s, 3H), 3.80 (s, 3H), 4.25 (br-s, 1H), 4.32 (br-s,
1H), 6.04 (dt, J=16.0 Hz, 6.8 Hz, 1H), 6.23 (d, J=16.0 Hz,
1H), 6.98 (dd, J=1.6 Hz, 8.0 Hz, 1H), 7.05 (d, J=8.4 Hz,
2H), 7.11 (d, J=8.4 Hz, 2H), 7.25–7.32 (m, 4H), 7.36 (dd,
J=1.6 Hz, 8.0 Hz, 1H), 7.64 (d, J=8.0 Hz, 2H), 7.89 (s,
1H); 13C NMR (CDCl3): d=21.2, 21.6, 52.4, 52.6, 54.7,
122.1, 126.4 (2C), 127.6, 127.9 (2C), 128.6, 128.9, 129.1 (2C),
129.6 (2C), 130.5, 130.7, 133.4, 134.6, 134.7, 136.2, 137.8,
138.6, 140.6, 143.8, 163.9, 166.5; (+)-ESI-HR-MS: m/z=
542.1598, calcd. for C29H29NNaO6S+ (M+Na+): 542.1608.
(E)-Dimethyl 2-(2-{N-[3-(4-methoxyphenyl)allyl]-4-meth-
ylphenylsulfonamido}benzylidene)malonate (1c): White
solid; mp 74–768C; IR (ATR): n=1727, 1606, 1510, 1436,
Substrate Synthesis
Benzylidene malonates 1a–o were prepared from the corre-
sponding benzaldehyde derivatives and malonate deriva-
tives. For the detailed synthetic methods, see the Supporting
Information.
1
(E)-Dimethyl 2-[2-(N-cinnamyl-4-methylphenylsulfonami-
do)benzylidene]malonate (1a): Yellow solid; mp 82–848C;
IR (ATR): n=1727, 1435, 1345, 1215, 1158, 1065, 967, 815,
1345, 1250, 1158, 1065, 814, 732 cmÀ1; H NMR (CDCl3): d=
2.44 (s, 3H), 3.61 (s, 3H), 3.77 (s, 3H), 3.79 (s, 3H), 4.21 (br-
s, 1H), 4.33 (br-s, 1H), 5.96 (dt, J=16.0 Hz, 7.2 Hz, 1H),
6.21 (d, J=16.0 Hz, 1H), 6.78 (d, J=8.4 Hz, 2H), 6.97 (dd,
J=2.0 Hz, 7.6 Hz, 1H), 7.15 (d, J=8.4 Hz, 2H), 7.25–7.32
(m, 4H), 7.37 (dd, J=2.0 Hz, 7.6 Hz, 1H), 7.64 (d, J=
8.0 Hz, 2H), 7.90 (s, 1H); 13C NMR (CDCl3): d=21.5, 52.3,
52.5, 54.7, 55.2, 113.7 (2C), 120.7, 127.4, 127.7 (2C), 127.8
(2C), 128.6, 128.8, 128.9, 129.6 (2C), 130.3, 130.7, 134.2,
1
691, 655 cmÀ1; H NMR (CDCl3): d=2.44 (s, 3H), 3.59 (s,
3H), 3.79 (s, 3H), 4.25 (br-s, 1H), 4.34 (br-s, 1H), 6.10 (dt,
J=16.0 Hz, 7.2 Hz, 1H), 6.28 (d, J=16.0 Hz, 1H), 6.98 (dd,
J=1.6 Hz, 8.0 Hz, 1H), 7.20–7.33 (m, 9H), 7.37 (dd, J=
1.6 Hz, 8.0 Hz, 1H), 7.64 (d, J=8.4 Hz, 2H), 7.89 (s, 1H);
13C NMR (CDCl3): d=21.6, 52.4, 52.6, 54.6, 123.1, 126.5
4
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134.6, 136.0, 138.6, 140.5, 143.8, 159.3, 163.9, 166.4; (+)-ESI-
HR-MS: m/z=558.1547, calcd. for C29H29NNaO7S+ (M+
Na+): 558.1557.
(+)-ESI-HR-MS:
m/z=658.2298,
calcd.
for
C34H41NNaO7SSi+ (M+Na+): 658.2265.
(E)-Dimethyl 2-[2-(N-cinnamyl-4-methylphenylsulfonami-
do)-5-nitrobenzylidene]malonate (1h): White solid; mp 109–
1108C; IR (ATR): n=1735, 1527, 1437, 1348, 1259, 1219,
(E)-Dimethyl 2-(2-{N-[3-(4-chlorophenyl)allyl]-4-methyl-
phenylsulfonamido}benzylidene)malonate (1d): Pale yellow
oil; IR (ATR): n=1727, 1491, 1435, 1345, 1216, 1158, 1065,
1163, 1068, 824, 663 cmÀ1 1H NMR (CDCl3): d=2.47 (s,
;
1
815, 767, 734 cmÀ1; H NMR (CDCl3): d=2.44 (s, 3H), 3.62
3H), 3.73 (s, 3H), 3.83 (s, 3H), 4.31 (d, J=7.2 Hz, 2H), 6.07
(dt, J=16.0 Hz, 7.2 Hz, 1H), 6.30 (d, J=16.0 Hz, 1H), 7.18
(d, J=8.8 Hz, 1H), 7.20–7.28 (m, 5H), 7.34 (d, J=8.0 Hz,
2H), 7.64 (d, J=8.0 Hz, 2H), 7.78 (s, 1H), 8.14 (dd, J=
2.0 Hz, 8.8 Hz, 1H), 8.28 (d, J=2.0 Hz, 1H); 13C NMR
(CDCl3): d=21.6, 52.7, 52.9, 54.6, 122.0, 124.1, 125.0, 126.6
(2C), 127.8 (2C), 128.3, 128.5 (2C), 129.9, 130.0 (2C), 131.3,
135.2, 135.6, 135.7, 136.1, 137.8, 143.7, 144.2, 144.6, 163.4,
165.4; (+)-ESI-HR-MS: m/z=573.1327, calcd. for
C28H26N2NaO8S+ (M+Na+): 573.1302.
(s, 3H), 3.79 (s, 3H), 4.20 (br-s, 1H), 4.35 (br-s, 1H), 6.09
(dt, J=13.6 Hz, 7.2 Hz, 1H), 6.25 (d, J=13.6 Hz, 1H), 6.97
(dd, J=1.6 Hz, 7.2 Hz, 1H), 7.15 (d, J=8.8 Hz, 2H), 7.22 (d,
J=8.8 Hz, 2H), 7.28–7.38 (m, 5H), 7.63 (d, J=8.4 Hz, 2H),
7.88 (s, 1H); 13C NMR (CDCl3): d=21.6, 52.4, 52.6, 54.5,
123.9, 127.6, 127.7 (2C), 127.8 (2C), 128.6 (2C), 128.8, 128.9,
129.7 (2C), 130.3, 130.8, 133.4, 133.5, 134.6, 134.7, 135.9,
138.6, 140.5, 143.9, 163.8, 166.4; (+)-ESI-HR-MS: m/z=
562.1043, calcd. for C28H26ClNNaO6S+ (M+Na+): 562.1062.
(E)-Dimethyl 2-(2-[4-methyl-N-[3-(meta-tolyl)allyl]phe-
nylsulfonamido}benzylidene)malonate (1e): Colorless oil;
IR (ATR): n=1727, 1435, 1346, 1214, 1158, 1065, 967, 816,
(E)-Dimethyl 2-[2-(N-cinnamyl-4-methylphenylsulfonami-
do)-5-(methoxycarbonyl)benzylidene]malonate (1i): White
solid; mp 66–688C; IR (ATR): n=1725, 1436, 1350, 1298,
1256, 1162, 1068, 816, 694, 662 cmÀ1; H NMR (CDCl3): d=
1
1
766, 688 cmÀ1; H NMR (CDCl3): d=2.29 (s, 3H), 2.44 (s,
2.45 (s, 3H), 3.68 (s, 3H), 3.81 (s, 3H), 3.90 (s, 3H), 4.31 (br-
s, 2H), 6.08 (dt, J=16.0 Hz, 7.2 Hz, 1H), 6.28 (d, J=
16.0 Hz, 1H), 7.06 (d, J=8.0 Hz, 1H), 7.19–7.27 (m, 5H),
7.31 (d, J=7.6 Hz, 2H), 7.62 (d, J=7.6 Hz, 2H), 7.85 (s,
1H), 7.96 (dd, J=2.4 Hz, 8.0 Hz, 1H), 8.06 (d, J=2.4 Hz,
1H); 13C NMR (CDCl3): d=21.6, 52.4, 52.5, 52.7, 54.5,
122.6, 126.5 (2C), 127.8 (2C), 128.0, 128.5 (2C), 129.8 (2C),
130.2, 130.4, 130.7, 131.5, 134.7, 135.2, 135.2, 135.5, 135.8,
139.3, 142.6, 144.2, 163.7, 165.6, 166.0; (+)-ESI-HR-MS:
m/z=586.1500, calcd. for C30H29NNaO8S+ (M+Na+):
586.1506.
3H), 3.60 (s, 3H), 3.79 (s, 3H), 4.25 (br-s, 1H), 4.32 (br-s,
1H), 6.09 (dt, J=15.6 Hz, 6.8 Hz, 1H), 6.24 (d, J=15.6 Hz,
1H), 6.99 (dd, J=1.2 Hz, 7.6 Hz, 2H), 7.03 (d, J=8.0 Hz,
2H), 7.14 (t, J=7.6 Hz, 1H), 7.25–7.33 (m, 4H), 7.37 (dd,
J=2.4 Hz, 8.0 Hz, 1H), 7.64 (d, J=8.0 Hz, 2H), 7.89 (s,
1H); 13C NMR (CDCl3): d=21.2, 21.5, 52.3, 52.5, 54.6,
122.9, 123.7, 127.2, 127.6, 127.9 (2C), 128.3, 128.6, 128.6,
128.9, 129.6 (2C), 130.4, 130.7, 134.6, 134.9, 136.1, 136.2,
138.0, 138.6, 140.5, 143.8, 163.9, 166.4; (+)-ESI-HR-MS:
m/z=542.1608, calcd. for C29H29NNaO6S+ (M+Na+):
542.1608.
(E)-Dimethyl 2-[2-(N-cinnamylmethylsulfonamido)benzy-
lidene]malonate (1j): Yellow oil; IR (ATR): n=1725, 1436,
(E)-Dimethyl 2-(2-{N-[3-(2-fluorophenyl)allyl]-4-methyl-
phenylsulfonamido}benzylidene)malonate (1f): Pale yellow
oil; IR (ATR): n=1727, 1486, 1435, 1346, 1215, 1158, 1065,
1
1336, 1256, 1216, 1149, 1066, 960, 733, 695 cmÀ1; H NMR
(CDCl3): d=3.64 (s, 3H), 3.78 (s, 3H), 4.35 (d, J=7.6 Hz,
2H), 6.20 (dt, J=16.0 Hz, 7.6 Hz, 1H), 6.40 (d, J=16.0 Hz,
1H), 7.20–7.28 (m, 5H), 7.33 (t, J=7.6 Hz, 1H), 7.41 (t, J=
7.6 Hz, 1H), 7.44 (d, J=8.0 Hz, 2H), 8.14 (s, 1H); 13C NMR
(CDCl3): d=39.5, 52.4, 52.6, 54.2, 122.7, 126.4 (2C), 127.9,
127.9, 128.4 (2C), 128.8, 129.0, 129.9, 131.1, 134.3, 135.1,
135.8, 138.6, 140.3, 163.8, 166.1; (+)-ESI-HR-MS: m/z=
452.1157, calcd. for C22H23NNaO6S+ (M+Na+): 452.1138.
(E)-Dimethyl 2-[2-(N-cinnamyl-2-nitrophenylsulfonami-
do)benzylidene]malonate (1k): White solid; mp 136–1378C;
IR (ATR): n=1727, 1542, 1436, 1365, 1216, 1164, 1065, 969,
1
816, 756, 693 cmÀ1; H NMR (CDCl3): d=2.44 (s, 3H), 3.58
(s, 3H), 3.80 (s, 3H), 4.24 (br-s, 1H), 4.38 (br-s, 1H), 6.19
(ddt, J=16.0 Hz, 1.2 Hz, 6.8 Hz, 1H), 6.42 (d, J=16.0 Hz,
1H), 6.94 (t, J=8.4 Hz, 1H), 6.97 (t, J=7.2 Hz, 1H), 7.03 (t,
J=7.2 Hz, 1H), 7.17 (dt, J=7.2 Hz, 7.2 Hz, 1H), 7.27–7.33
(m, 5H), 7.36 (dd, J=1.6 Hz, 6.0 Hz, 1H), 7.64 (d, J=
7.2 Hz, 2H), 7.90 (s, 1H); 13C NMR (CDCl3): d=21.5, 52.3,
52.5, 54.7, 115.5 (d, J=22.0 Hz), 123.9 (d, J=12.4 Hz), 124.0
(d, J=3.8 Hz), 125.8 (d, J=4.8 Hz), 127.0 (d, J=3.8 Hz),
127.4 (d, J=3.8 Hz), 127.7, 127.8 (2C), 128.7, 128.9, 129.2
(d, J=7.7 Hz), 129.7 (2C), 130.3, 130.7, 134.7, 136.0, 138.5,
140.5, 143.9, 160.1 (d, J=248.9 Hz), 163.9, 166.4; (+)-ESI-
HR-MS: m/z=546.1328, calcd. for C28H26FNNaO6S+ (M+
Na+): 546.1357.
1
890, 732 cmÀ1; H NMR (CDCl3): d=3.67 (s, 3H), 3.72 (s,
3H), 4.37 (br-s, 1H), 4.72 (br-s, 1H), 6.26 (dt, J=16.4 Hz,
7.2 Hz, 1H), 6.33 (d, J=16.4 Hz, 1H), 7.23–7.28 (m, 5H),
7.32–7.42 (m, 4H), 7.51 (dt, J=7.2 Hz, 1.2 Hz, 1H), 7.59 (d,
J=7.2 Hz, 1H), 7.64 (dd, J=1.2 Hz, 7.2 Hz, 1H), 7.65 (s,
1H), 7.68 (dt, J=1.2 Hz, 7.2 Hz, 1H); 13C NMR (CDCl3):
d=52.5, 52.5, 55.9, 123.2, 124.2, 126.6 (2C), 127.5, 128.0,
128.5 (2C), 128.7, 129.3, 131.2, 131.9, 131.9, 132.7, 133.3,
133.6, 133.7, 135.6, 136.1, 136.9, 139.1, 147.5, 163.5, 166.1;
(+)-ESI-HR-MS: m/z=559.1127, calcd. for C27H24N2NaO8S+
(M+Na+): 559.1146.
(E)-Dimethyl 2-{5-[(tert-butyldimethylsilyl)oxy]-2-(N-cin-
namyl-4-methylphenylsulfonamido)benzylidene}malonate
(1g): Colorless oil; IR (ATR): n=1733, 1488, 1349, 1235,
1
1161, 1068, 839, 784, 684, 661 cmÀ1; H NMR (CDCl3): d=
0.17 (s, 6H), 0.94 (s, 9H), 2.43 (s, 3H), 3.63 (s, 3H), 3.77 (s,
3H), 4.20 (d, J=6.8 Hz, 1H), 4.32 (d, J=6.8 Hz, 1H), 6.10
(dt, J=16.0 Hz, 6.8 Hz, 1H), 6.29 (d, J=16.0 Hz, 1H), 6.74
(dd, J=2.4 Hz, 8.4 Hz, 1H), 6.82 (d, J=8.4 Hz, 1H), 6.84 (d,
J=2.4 Hz, 1H), 7.18–7.29 (m, 7H), 7.63 (d, J=7.6 Hz, 2H),
7.78 (s, 1H); 13C NMR (CDCl3): d=À4.5 (2C), 18.1, 21.6,
25.5 (3C), 52.4, 52.5, 54.6, 119.7, 122.2, 123.3, 126.5 (2C),
127.4, 127.8, 127.9 (2C), 128.4 (2C), 129.6 (2C), 131.5, 131.7,
134.7, 135.5, 136.0, 136.2, 140.0, 143.7, 155.5, 163.9, 166.3;
(E)-Dimethyl
2-{2-[(benzyloxycarbonyl)-
AHCTUNGTREG(NNUN cinnamyl)amino]benzylidene}malonate (1l): Yellow oil; IR
(ATR): n=1730, 1701, 1435, 1398, 1257, 1216, 1066, 967,
1
732, 694 cmÀ1; H NMR (CDCl3): d=3.67 (s, 3H), 3.71 (s,
3H), 4.24 (br-s, 1H), 4.43 (br-s, 1H), 5.12 (br-s, 2H), 6.27
(br-s, 1H), 6.38 (d, J=15.6 Hz, 1H), 7.18–7.29 (m, 11H),
Adv. Synth. Catal. 0000, 000, 0 – 0
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asc.wiley-vch.de
5
ÞÞ
These are not the final page numbers!

UPDATES
Shun-ichi Nakano et al.
7.38 (t, J=7.6 Hz, 1H), 7.41 (d, J=8.0 Hz, 2H), 7.79 (br-s,
1H); 13C NMR (CDCl3): d=52.4, 52.5, 53.0, 67.4, 123.5,
126.4 (2C), 127.4, 127.5, 127.6, 127.7 (2C), 127.8, 128.2, 128.3
(2C), 128.4, 129.2 (2C), 131.0, 131.8, 134.0, 136.2, 136.3,
139.5, 140.8, 154.9, 163.8, 166.3; (+)-ESI-HR-MS: m/z=
1.2 Hz, 6.4 Hz, 1H), 7.62 (d, 8.0 Hz, 1H), 7.66 (dt, 8.0 Hz,
2.0 Hz, 2H); 13C NMR (CDCl3): d=21.5, 34.7, 37.7, 44.3,
46.7, 52.1, 52.1, 63.5, 122.7, 124.3, 126.4, 127.0 (2C), 127.3,
127.6, 127.9 (2C), 128.2 (2C), 129.8 (2C), 131.3, 137.7, 137.9,
138.3, 143.6, 168.5, 169.5; (+)-ESI-HR-MS: m/z=528.1451,
calcd. for C28H27NNaO6S+ (M+Na+): 528.1451.
+
486.1891, calcd. for C29H28NO6 (M+H+): 486.1911.
(E)-Dimethyl 2-[2-(4-phenylbut-3-en-1-yl)benzylidene]-
malonate (1m): Yellow oil; IR (ATR): n=1726, 1625, 1435,
Dimethyl 2-(para-tolyl)-4-tosyl-2,2a,3,4-tetrahydrocyclo-
buta[c]quinoline-1,1ACTHNUTRGNE(NUG 8bH)-dicarboxylate (2b): White solid;
1365, 1258, 1213, 1068, 966, 745, 693 cmÀ1
;
1H NMR
mp 145–1468C; IR (ATR): n=1727, 1434, 1349, 1265, 1160,
1
1090, 1020, 814, 758, 671 cmÀ1; H NMR (CDCl3): d=2.32
(CDCl3): d=2.49 (dt, J=7.2 Hz, 7.6 Hz, 2H), 2.87 (t, J=
7.6 Hz, 2H), 3.70 (s, 3H), 3.83 (s, 3H), 6.21 (dt, J=15.6 Hz,
7.2 Hz, 1H), 6.38 (d, J=15.6 Hz, 1H), 7.19 (dt, 2.0 Hz,
7.6 Hz, 1H), 7.20 (d, J=7.6 Hz, 1H), 7.24–7.34 (m, 7H),
8.09 (s, 1H); 13C NMR (CDCl3): d=33.6, 34.3, 52.5, 52.7,
126.0 (2C), 126.4, 127.0, 127.3, 127.9, 128.4 (2C), 129.1,
129.8, 130.2, 130.8, 132.2, 137.4, 141.3, 142.6, 164.3, 166.7;
(s, 3H), 2.42 (s, 3H), 3.16 (dddd, J=4.4 Hz, 5.2 Hz, 7.6 Hz,
10.0 Hz, 1H), 3.20 (s, 3H), 3.34 (s, 3H), 3.60 (dd, J=4.4 Hz,
13.6 Hz, 1H), 4.14 (dd, J=5.2 Hz, 13.6 Hz, 1H), 4.21 (d, J=
10.0 Hz, 1H), 4.27 (d, J=7.6 Hz, 1H), 7.01 (d, J=8.0 Hz,
2H), 7.03–7.11 (m, 4H), 7.19 (dt, J=8.8 Hz, 1.2 Hz, 1H),
7.25 (d, J=8.4 Hz, 2H), 7.62 (d, J=8.8 Hz, 1H), 7.65 (d, J=
8.4 Hz, 2H); 13C NMR (CDCl3): d=21.1, 21.5, 34.9, 37.6,
44.1, 46.7, 52.0, 52.1, 63.5, 122.8, 124.3, 126.6, 127.0 (2C),
127.5, 127.8 (2C), 128.8 (2C), 129.8 (2C), 131.2, 134.6, 136.9,
137.9, 138.3, 143.6, 168.6, 169.6; (+)-ESI-HR-MS: m/z=
542.1638, calcd. for C29H29NNaO6S+ (M+Na+): 542.1608.
+
(+)-ESI-HR-MS: m/z=373.1396, calcd. for C22H22NaO4
(M+Na+): 373.1410.
(E)-Dimethyl
2-[2-(cinnamyloxy)benzylidene]malonate
(1n): White solid; mp 46–488C; IR (ATR): n=1728, 1599,
1
1487, 1436, 1371, 1216, 1116, 1068, 968, 750 cmÀ1; H NMR
(CDCl3): d=3.79 (s, 3H), 3.85 (s, 3H), 4.77 (dd, J=1.2 Hz,
5.6 Hz, 2H), 6.31 (dt, J=16.0 Hz, 5.6 Hz, 1H), 6.72 (d, J=
16.0 Hz, 1H), 6.92 (d, J=7.2 Hz, 1H), 6.96 (d, J=8.0 Hz,
1H), 7.27 (tt, J=1.2 Hz, 7.2 Hz, 1H), 7.32–7.38 (m, 4H),
7.42 (dd, J=1.2 Hz, 7.2 Hz, 2H), 8.20 (s, 1H); 13C NMR
(CDCl3): d=52.5, 52.6, 69.2, 112.4, 120.8, 122.5, 123.9, 125.3,
126.6 (2C), 128.0, 128.6 (2C), 129.0, 132.1, 133.1, 136.2,
139.1, 157.1, 164.7, 167.3; (+)-ESI-HR-MS: m/z=375.1207,
Dimethyl
drocyclobuta[c]quinoline-1,1
White solid; mp 1708C (decomp.); IR (ATR): n=1726,
1514, 1490, 1434, 1348, 1251, 1160, 1090, 1021, 671 cmÀ1
2-(4-methoxyphenyl)-4-tosyl-2,2a,3,4-tetrahy-
AHCTUNGTRENNUNG
;
1H NMR (CDCl3): d=2.42 (s, 3H), 3.17 (dddd, J=4.4 Hz,
5.2 Hz, 8.4 Hz, 9.6 Hz, 1H), 3.23 (s, 3H), 3.34 (s, 3H), 3.57
(dd, J=4.4 Hz, 13.6 Hz, 1H), 3.80 (s, 3H), 4.14 (dd, J=
5.2 Hz, 13.6 Hz, 1H), 4.21 (d, J=9.6 Hz, 1H), 4.29 (d, J=
8.4 Hz, 1H), 6.82 (dt, J=8.8 Hz, 2.8 Hz, 2H), 7.03–7.11 (m,
4H), 7.19 (dt, J=8.4 Hz, 2.0 Hz, 1H), 7.26 (d, J=8.0 Hz,
2H), 7.60 (d, J=8.4 Hz, 1H), 7.67 (d, J=8.0 Hz, 2H);
13C NMR (CDCl3): d=21.5, 35.2, 37.6, 43.8, 46.7, 52.0, 52.2,
55.3, 63.6, 113.6 (2C), 122.7, 124.2, 126.5, 127.0 (2C), 127.5,
129.1 (2C), 129.7, 129.8 (2C), 131.3, 138.0, 138.3, 143.6,
158.8, 168.6, 169.7; (+)-ESI-HR-MS: m/z=558.1562, calcd.
for C29H29NNaO7S+ (M+Na+): 558.1557.
+
calcd. for C21H20NaO5 (M+Na+): 375.1203.
(E)-Dimethyl 2-[2-(cinnamylthio)benzylidene]malonate
(1o): Yellow solid; mp 100–1018C; IR (ATR): n=1724,
1624, 1434, 1363, 1253, 1216, 1066, 963, 750, 693 cmÀ1
;
1H NMR (CDCl3): d=3.65 (d, J=7.2 Hz, 2H), 3.70 (s, 3H),
3.85 (s, 3H), 6.19 (dt, J=16.0 Hz, 7.2 Hz, 1H), 6.33 (d, J=
16.0 Hz, 1H), 7.21 (dd, J=3.2 Hz, 8.0 Hz, 1H), 7.22 (d, J=
7.6 Hz, 1H), 7.24–7.29 (m, 4H), 7.31 (t, J=7.6 Hz, 1H), 7.34
(d, J=8.0 Hz, 1H), 7.48 (d, J=7.6 Hz, 1H), 8.29 (s,1H);
13C NMR (CDCl3): d=37.8, 52.4, 52.6, 124.3, 126.2 (2C),
127.1, 127.2, 127.5, 128.3, 128.4 (2C), 130.2, 132.4, 133.1,
135.3, 136.3, 136.5, 142.1, 164.2, 166.5; (+)-ESI-HR-MS:
m/z=391.0968, calcd. for C21H20NaO4S+ (M+Na+):
391.0975.
Dimethyl 2-(4-chlorophenyl)-4-tosyl-2,2a,3,4-tetrahydrocy-
clobuta[c]quinoline-1,1ACTHNURGTNE(NUG 8bH)-dicarboxylate (2d): White
solid; mp 110–1118C; IR (ATR): n=1726, 1490, 1348, 1266,
1
1159, 1089, 1015, 813, 735, 666 cmÀ1; H NMR (CDCl3): d=
2.42 (s, 3H), 32.4 (dddd, J=4.0 Hz, 4.4 Hz, 8.4 Hz, 9.6 Hz,
1H), 3.26 (s, 3H), 3.36 (s, 3H), 3.49 (dd, J=4.0 Hz, 13.6 Hz,
1H), 4.16 (dd, J=4.4 Hz, 13.6 Hz, 1H), 4.23 (d, J=9.6 Hz,
1H), 4.37 (d, J=8.4 Hz, 1H), 7.05 (dt, J=8.0 Hz, 1.2 Hz,
1H), 7.08 (dd, J=1.2 Hz, 8.0 Hz, 1H), 7.10 (d, J=8.0 Hz,
2H), 7.19 (dt, J=8.0 Hz, 1.2 Hz, 1H), 7.26 (d, J=8.0 Hz,
2H), 7.26 (d, J=8.4 Hz, 2H), 7.59 (d, J=8.0 Hz, 1H), 7.68
(d, J=8.4 Hz, 2H); 13C NMR (CDCl3): d=21.5, 35.1, 37.9,
43.4, 46.5, 52.1, 52.3, 63.3, 122.4, 124.2, 126.0, 126.9 (2C),
127.7, 128.3 (2C), 129.3 (2C), 129.8 (2C), 131.5, 133.2, 136.1,
138.0, 138.3, 143.7, 168.3, 169.4; (+)-ESI-HR-MS: m/z=
562.1089, calcd. for C28H26ClNNaO6S+ (M+Na+): 562.1062.
Dimethyl 2-(meta-tolyl)-4-tosyl-2,2a,3,4-tetrahydrocyclo-
ScACHTUNGTRENNUNG(OTf)3-Catalyzed Cascade Cyclization; Typical
Procedure
1a (30.0 mg, 0.0593 mmol) and ScACTHNUTRGENUN(G OTf)3 (0.87 mg,
1.78 mmol) were dissolved in CH2Cl (0.59 mL), and the re-
sulting solution was refluxed for 48 h. After the reaction
mixture was concentrated under vacuum, the obtained resi-
due was purified by flash column chromatography (SiO2,
hexane/AcOEt=5/1) to give dimethyl 2-phenyl-4-tosyl-
2,2a,3,4-tetrahydrocyclobuta[c]quinoline-1,1ACHTUNTRGNEU(GN 8bH)-dicarbox-
buta[c]quinoline-1,1ACTHNUTRGNE(NUG 8bH)-dicarboxylate (2e): White solid;
ylate 2a as a white solid; yield: 28.2 mg (94%); mp 126–
1288C; IR (ATR): n=1726, 1489, 1347, 1266, 1160, 1089,
mp 118–1198C; IR (ATR): n=1726, 1489, 1434, 1348, 1264,
1
1160, 1090, 1020, 700, 662 cmÀ1; H NMR (CDCl3): d=2.33
1
814, 735, 699, 661 cmÀ1; H NMR (CDCl3): d=2.42 (s, 3H),
(s, 3H), 2.42 (s, 3H), 3.18 (dddd, J=4.4 Hz, 5.2 Hz, 8.0 Hz,
9.6 Hz, 1H), 3.19 (s, 3H), 3.34 (s, 3H), 3.59 (dd, J=4.4 Hz,
13.6 Hz, 1H), 4.14 (dd, J=5.2 Hz, 13.6 Hz, 1H), 4.22 (d, J=
9.6 Hz, 1), 4.29 (d, J=8.0 Hz, 1H), 6.93 (d, J=7.2 Hz, 2H),
7.06 (dt, J=8.0 Hz, 2.4 Hz, 2H), 7.10 (dd, 2.4 Hz, 8.0 Hz,
3.17 (s, 3H), 3.22 (dddd, J=4.0 Hz, 5.6 Hz, 8.4 Hz, 9.6 Hz,
1H) 3.35 (s, 3H), 3.59 (dd, J=4.0 Hz, 14.0 Hz, 1H), 4.15
(dd, J=5.6 Hz, 14.0 Hz, 1H), 4.23 (d, J=9.6 Hz, 1H), 4.33
(d, J=8.4 Hz, 1H), 7.06 (dt, J=1.2 Hz, 8.0 Hz, 1H), 7.10
(dd, J=2.0 Hz, 8.0 Hz, 2H), 7.18–7.26 (m, 5H), 7.29 (dt, J=
6
asc.wiley-vch.de
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Adv. Synth. Catal. 0000, 000, 0 – 0
ÝÝ
These are not the final page numbers!

UPDATES
Scandium-Catalyzed Cascade Cyclization
1H), 7.16 (d, J=8.4 Hz, 1H), 7.19 (dt, J=8.4 Hz, 2.4 Hz,
1H), 7.26 (d, J=8.0 Hz, 2H), 7.61 (d, J=8.4 Hz, 1H), 7.66
(d, J=8.4 Hz, 2H); 13C NMR (CDCl3): d=21.4, 21.5, 34.8,
37.7, 44.4, 46.8, 52.1, 52.1, 63.5, 122.8, 124.3, 124.9, 126.6,
127.0, 127.0, 127.6, 128.0 (2C), 128.8, 129.8 (2C), 131.2,
137.6, 137.7, 137.9, 138.3, 143.6, 168.6, 169.6; (+)-ESI-HR-
MS: m/z=542.1630, calcd. for C29H29NNaO6S+ (M+Na+):
542.1608.
4.22 (dd, J=4.0 Hz, 13.6 Hz, 1H), 4.28 (d, J=9.2 Hz, 2H),
7.13 (d, J=8.4 Hz, 2H), 7.22–7.31 (m, 5H), 7.70 (d, 8.4 Hz,
2H), 7.78 (d, J=8.8 Hz, 1H), 7.82 (d, J=1.6 Hz, 1H), 7.86
(dd, J=1.6 Hz, 8.8 Hz, 1H); 13C NMR (CDCl3): d=21.5,
34.5, 37.8, 43.8, 46.5, 52.1, 52.1, 52.2, 63.4, 121.7, 125.4, 125.9,
127.0 (2C), 127.4, 127.8 (2C), 128.2 (2C), 128.8, 129.9 (2C),
133.2, 137.1, 137.2, 142.5, 144.1, 166.3, 168.2, 169.2; (+)-ESI-
HR-MS; m/z=586.1527, calcd. for C30H29NNaO8S+ (M+
Na+): 586.1506.
Dimethyl 2-(2-fluorophenyl)-4-tosyl-2,2a,3,4-tetrahydrocy-
clobuta[c]quinoline-1,1
G
Dimethyl 4-(methylsulfonyl)-2-phenyl-2,2a,3,4-tetrahydro-
solid; mp 114–1158C; IR (ATR): n=1727, 1491, 1455, 1348,
cyclobuta[c]quinoline-1,1ACTHNGUTERNNU(G 8bH)-dicarboxylate (2j): White
1
1265, 1160, 1090, 813, 757, 674 cmÀ1; H NMR (CDCl3): d=
solid; mp 159–1608C; IR (ATR): n=1725, 1491, 1434, 1343,
1
2.42 (s, 3H), 3.16 (dddd, J=4.4 Hz, 5.6 Hz, 7.6 Hz, 9.6 Hz,
1H), 3.24 (s, 3H), 3.32 (s, 3H), 3.74 (dd, J=4.4 Hz, 13.6 Hz,
1H), 4.12 (dd, J=5.6 Hz, 13.6 Hz, 1H), 4.26 (d, J=9.6 Hz,
1H) 4.55 (d, J=7.6 Hz, 1H), 7.01 (t, J=8.0 Hz, 1H), 7.05–
7.13 (m, 4H), 7.17–7.26 (m, 3H), 7.62 (d, J=9.2 Hz, 1H),
7.64 (d, J=8.0 Hz, 2H); 13C NMR (CDCl3): d=21.5, 34.1,
37.5, 38.5, 46.9, 52.1, 52.2, 62.9, 115.2 (d, J=2.2 Hz), 123.3,
123.9 (d, J=3.9 Hz), 124.6, 125.2 (d, J=15.3 Hz), 126.8,
127.0, 127.6 (2C), 128.7 (d, J=3.7 Hz), 129.1 (d, J=8.6 Hz),
129.7 (2C), 130.5, 137.6, 138.2, 143.7, 160.0 (d, J=246.0 Hz),
168.2, 169.5; (+)-ESI-HR-MS: m/z=546.1333, calcd. for
C28H26FNNaO6S+ (M+Na+): 546.1357.
1267, 1152, 1020, 977, 749, 700 cmÀ1; H NMR (CDCl3): d=
3.20 (s, 3H), 3.22 (s, 3H), 3.28 (dd, J=3.2 Hz, 13.2 Hz, 1H),
3.34 (s, 3H), 3.50 (dddd, J=2.4 Hz, 3.2 Hz, 9.2 Hz, 10.0 Hz,
1H), 4.24 (dd, J=2.4 Hz, 13.2 Hz, 1H), 4.44 (d, J=10.0 Hz,
1H), 4.47 (d, J=9.2 Hz, 1H), 7.08 (t, J=7.2 Hz, 1H), 7.17
(d, J=7.2 Hz, 1H), 7.18–7.33 (m, 6H), 7.72 (d, J=8.4 Hz,
1H); 13C NMR (CDCl3): d=35.4, 38.1, 39.8, 43.9, 45.5, 52.0,
52.2, 63.5, 120.6, 123.9, 126.0, 127.5, 127.9 (2C), 128.0, 128.3
(2C), 132.1, 137.1, 138.4, 168.5, 169.3; (+)-ESI-HR-MS:
mz=452.1141, calcd. for C22H23NNaO6S+ (M+Na+):
452.1138.
Dimethyl
tetrahydrocyclobuta[c]quinoline-1,1
(2k): White solid; mp 2008C (decomp.); IR (ATR): n=
1726, 1542, 1490, 1435, 1358, 1267, 1164, 1021, 737, 700 cmÀ1
4-[(2-nitrophenyl)sulfonyl]-2-phenyl-2,2a,3,4-
Dimethyl
tosyl-2,2a,3,4-tetrahydrocyclobuta[c]quinoline-1,1
carboxylate (2g): White solid; mp 143–1448C; IR (ATR):
n=1728, 1492, 1260, 1160, 1089, 986, 882, 837, 782, 687 cmÀ1
7-[(tert-butyldimethylsilyl)oxy]-2-phenyl-4-
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
;
;
1H NMR (CDCl3): d=3.22 (s, 3H), 3.40 (s, 3H), 3.48 (dddd,
J=3.6 Hz, 4.0 Hz, 8.8 Hz, 10.0 Hz, 1H), 3.56 (dd, J=4.0 Hz,
14.0 Hz, 1H), 4.25 (dd, J=3.6 Hz, 14.0 Hz, 1H), 4.37 (d, J=
10.0 Hz, 1H), 4.46 (d, J=8.8 Hz, 1H), 7.10–7.30 (m, 9H),
7.65 (dt, J=7.6 Hz, 1.6 Hz, 1H), 7.71 (dt, J=7.6 Hz, 1.6 Hz,
1H), 7.76 (dd, J=1.6 Hz, 7.6 Hz, 1H), 8.01 (dd, J=1.6 Hz,
7.6 Hz, 1H); 13C NMR (CDCl3): d=35.0, 38.0, 44.1, 47.6,
52.1, 52.2, 63.5, 122.5, 124.9, 125.0, 126.9, 127.4, 127.7, 127.9
(2C), 128.2 (2C), 129.8, 132.0, 132.4, 133.7, 135.5, 137.1,
138.1, 147.7, 168.3, 169.5; (+)-ESI-HR-MS: m/z=559.1144,
calcd. for C27H24N2NaO8S+ (M+Na+): 559.1146.
1H NMR (CDCl3): d=0.19 (s, 6H), 0.97 (s, 9H), 2.43 (s,
3H), 3.07 (dddd, J=4.8 Hz, 6.8 Hz, 7.2 Hz, 9.6 Hz, 1H), 3.15
(s, 3H), 3.41 (s, 3H), 3.69 (dd, J=4.8 Hz, 14.0 Hz, 1H), 4.07
(dd, J=6.8 Hz, 14.0 Hz, 1H), 4.09 (d, J=9.6 Hz, 1H), 4.22
(d, J=7.2 Hz, 1H), 6.57 (d, J=2.8 Hz, 1H), 6.69 (dd, J=
2.8 Hz, 9.2 Hz, 1H), 7.09 (d, J=7.2 Hz, 2H), 7.22–7.29 (m,
5H), 7.48 (d, J=9.2 Hz, 1H), 7.58 (d, J=8.0 Hz, 2H);
13C NMR (CDCl3): d=À4.4 (2C), 18.1, 21.5, 25.6 (3C), 34.2,
37.5, 44.8, 46.9, 52.1, 52.3, 63.4, 119.2, 121.5, 124.6, 127.0
(2C), 127.3, 127.9 (2C), 128.1, 128.2 (2C), 129.7 (2C), 131.5,
137.8, 137.8, 143.5, 152.5, 168.6, 169.5; (+)-ESI-HR-MS:
m/z=658.2290, calcd. for C34H41NNaO7SSi+ (M+Na+):
658.2265.
4-Benzyl 1,1-dimethyl 2-phenyl-2a,3-dihydrocyclobuta[c]-
quinoline-1,1,4
98–1008C; IR (ATR): n=1727, 1698, 1492, 1396, 1255, 1198,
1100, 1048, 734, 696 cmÀ1 1H NMR (CDCl3): d=3.05 (dd,
ACHTUNGTREN(NUNG 2H,8bH)-tricarboxylate (2l): White solid; mp
Dimethyl 7-nitro-2-phenyl-4-tosyl-2,2a,3,4-tetrahydrocy-
;
clobuta[c]quinoline-1,1
solid; mp 101–1028C; IR (ATR): n=1728, 1519, 1342, 1268,
1163, 1089, 906, 738, 686, 663 cmÀ1 1H NMR (CDCl3): d
G
J=3.2 Hz, 13.6 Hz, 1H), 3.19 (s, 3H), 3.25 (s, 3H), 3.46
(ddd, J=3.2 Hz, 8.8 Hz, 10.0 Hz, 1H), 4.33 (d, J=8.8 Hz,
1H), 4.41 (d, J=10.0 Hz, 1H), 4.44 (d, J=13.6 Hz, 1H),
5.21 (d, J=12.0 Hz, 1H), 5.37 (d, J=12.0 Hz, 1H), 7.07 (t,
J=7.6 Hz, 1H), 7.14 (d, J=7.6 Hz, 1H), 7.19 (d, J=8.0 Hz,
2H), 7.20–7.34 (m, 10H), 7.61 (br-s, 1H); 13C NMR
(CDCl3): d=36.2, 38.4, 43.6, 44.5, 52.0, 52.1, 63.5, 67.6,
124.3, 125.0, 127.2, 127.3, 127.5, 127.8 (2C), 127.9, 128.0
(2C), 128.2 (2C), 128.4 (2C), 131.3, 136.4, 137.6, 139.4,
155.0, 168.2, 169.5; (+)-ESI-HR-MS: m/z=486.1889, calcd.
2.42 (s 3H), 3.21 (s, 3H), 3.40 (ddt, J=3.2 Hz, 4.4 Hz,
9.2 Hz, 1H), 3.40 (s, 3H), 3.50 (dd, J=3.2 Hz, 13.6 Hz, 1H),
4.22 (d, J=9.2 Hz, 1H), 4.24 (dd, J=4.4 Hz, 13.6 Hz, 1H),
4.32 (d, J=9.2 Hz, 1H), 7.12 (d, J=8.4 Hz, 2H), 7.23–7.32
(m, 5H), 7.71 (d, J=8.4 Hz, 2H), 7.91 (d, J=8.8 Hz, 1H),
8.04 (d, J=2.4 Hz, 1H), 8.07 (dd, J=2.4 Hz, 8.8 Hz, 1H);
13C NMR (CDCl3): d=21.6, 34.3, 37.8, 43.8, 46.5, 52.3, 52.4,
63.2, 122.3, 122.8, 126.9, 127.0, 127.1 (2C), 127.6, 127.7 (2C),
128.2 (2C), 130.1 (2C), 136.6, 136.6, 143.2, 144.2, 144.7,
168.0, 168.9; (+)-ESI-HR-MS: m/z=573.1326, calcd. for
C28H26N2NaO8S+ (M+Na+): 573.1302.
+
for C29H28NO6 (M+H+): 486.1911.
Dimethyl 2-phenyl-2,2a,3,4-tetrahydrocyclobuta[a]naph-
thalene-1,1
1108C; IR (ATR): n=1728, 1495, 1434, 1365, 1266, 1203,
1103, 1070, 748, 700 cmÀ1 1H NMR (CDCl3): d=1.65 (m,
ACHTUNGTREN(NUNG 8bH)-dicarboxylate (2m): White solid; mp 109–
Trimethyl
ta[c]quinoline-1,1,7
2-phenyl-4-tosyl-2,2a,3,4-tetrahydrocyclobu-
(8bH)-tricarboxylate (2i): White solid;
;
U
1H), 1.86 (m, 1H), 2.75 (m, 1H), 3.07 (m, 1H), 3.20 (s, 3H),
3.33 (s, 3H), 4.36 (d, J=9.2 Hz, 1H), 4.40 (d, J=9.6 Hz,
1H), 7.09–7.15 (m, 4H), 7.21–7.26 (m, 1H), 7.30 (d, J=
4.4 Hz, 4H); 13C NMR (CDCl3): d=22.7, 25.8, 32.1, 39.4,
43.5, 51.8, 51.9, 65.0, 125.7, 126.6, 127.1, 128.0 (2C), 128.1
mp 109–1108C; IR (ATR): n=1723, 1435, 1268, 1162, 1089,
1
1020, 769, 737, 686, 663 cmÀ1; H NMR (CDCl3): d=2.41 (s,
3H), 3.20 (s, 3H), 3.35 (s, 3H), 3.36 (ddd, J=3.6 Hz, 4.0 Hz,
9.2 Hz, 1H), 3.48 (dd, J=3.6 Hz, 13.6 Hz, 1H), 3.88 (s, 3H),
Adv. Synth. Catal. 0000, 000, 0 – 0
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UPDATES
Shun-ichi Nakano et al.
(2C), 129.0, 131.2, 133.2, 138.3, 138.4, 169.1, 169.8; (+)-ESI-
(8 mL, 0.112 mmol) and LiOH·H2O (9.38 mg, 0.224 mmol),
and the reaction mixture was stirred for 5 h at the same tem-
perature. The reaction mixture was poured into AcOEt, and
the organic layer was washed with saturated aqueous
NaHCO3, water and brine, dried over Na2SO4, and then con-
centrated under vacuum. The obtained crude product was
directly used for the next reaction without further purifica-
tion.
+
HR-MS: m/z=373.1414, calcd. for C22H22NaO4 (M+Na+):
373.1410.
Dimethyl
2-phenyl-2a,3-dihydro-1H-cyclobuta[c]chro-
mene-1,1(2H,8bH)-dicarboxylate (2n): White solid; mp 120–
ACHTUNGTRENNUNG
1228C; IR (ATR): n=1726, 1488, 1434, 1246, 1200, 1108,
1
1048, 992, 759, 698 cmÀ1; H NMR (CDCl3): d=3.24 (s, 3H),
3.42 (s, 3H), 3.50 (dddd, J=1.2 Hz, 2.4 Hz, 9.2 Hz, 10.4 Hz,
1H), 3.81 (dd, J=2.4 Hz, 12.0 Hz, 1H), 4.11 (dd, J=1.2 Hz,
12.0 Hz, 1H), 4.23 (d, J=9.2 Hz, 1H), 4.62 (d, J=10.4 Hz,
1H), 6.92 (dt, J=8.0 Hz, 1.6 Hz, 1H), 6.95 (d, J=8.4 Hz,
1H), 7.08 (dd, J=1.6 Hz, 8.0 Hz, 1H), 7.18 (dt, J=8.0 Hz,
1.6 Hz, 1H), 7.23–7.33 (m, 5H); 13C NMR (CDCl3): d=34.3,
36.1, 42.4, 51.9, 52.0, 64.2, 64.9, 117.9, 120.6, 121.2, 127.3,
127.9 (2C), 128.2 (2C), 128.3, 131.5, 137.2, 156.0, 168.6,
169.5; (+)-ESI-HR-MS: m/z=375.1199, calcd. for
To a stirred solution of the crude product in CH2Cl2
(0.56 mL) was added acetic anhydride (16 mL, 0.168 mmol)
at 08C, and the reaction was stirred for 14 h at room tem-
perature. The reaction mixture was concentrated under
vacuum and the obtained residue was purified by flash
column chromatography (SiO2, hexane/AcOEt=3/1 to 2/1)
to give 6 as a white solid; yield: 21.3 mg (89% over 2 steps);
mp 163–1648C; IR (ATR): n=1726, 1656, 1492, 1434, 1379,
+
1
C21H20NaO5 (M+Na+): 375.1203.
1262, 1203, 1107, 749, 700 cmÀ1; H NMR (CDCl3): d=2.36
Dimethyl 2-phenyl-2a,3-dihydro-1H-cyclobuta[c]thiochro-
mene-1,1ACHTUNGTRENNUNG(2H,8bH)-dicarboxylate (2o): White solid; mp 119–
(s, 3H), 2.80 (d, J=8.0 Hz, 1H), 3.20 (s, 3H), 3.31 (s, 3H),
3.49 (m, 1H), 4.22 (dd, J=8.8 Hz, 1H), 4.45 (d, J=10.0,
1H), 4.87 (d, J=12.0 Hz, 1H), 7.14–7.31 (m, 9H); 13C NMR
(CDCl3): d=22.7, 35.9, 38.5, 42.5, 43.6, 52.0, 52.2, 63.1,
124.9, 125.4, 127.3, 127.4, 128.1 (2C), 128.2 (2C), 128.9,
131.7, 137.4, 140.6, 168.5, 169.4, 170.8; (+)-ESI-HR-MS:
1208C; IR (ATR): n=1725, 1433, 1257, 1201, 1105, 1050,
1
942, 790, 746, 697 cmÀ1; H NMR (CDCl3): d 2.77 (dd, J=
3.6 Hz, 14.0 Hz, 1H), 2.97 (dd, J=3.6 Hz, 14.0 Hz, 1H), 3.21
(s, 3H), 3.31 (s, 3H), 3.74 (tt, J=3.6 Hz, 9.2 Hz, 1H), 4.43
(d, J=9.2 Hz, 1H), 5.01 (d, J=9.2 Hz, 1H), 7.04–7.13 (m,
3H), 7.22–7.32 (m, 6H); 13C NMR (CDCl3): d=28.8, 34.4,
39.7, 43.6, 51.8, 52.1, 65.2, 124.7, 127.0, 127.3, 128.0 (2C),
128.3 (2C), 128.6, 131.6, 132.8, 134.2, 137.5, 168.4, 169.5;
(+)-ESI-HR-MS: m/z=391.0974, calcd. for C21H20NaO4S+
(M+Na+): 391.0975.
+
m/z=394.1658, calcd. for C23H24NO5 (M+H+): 394.1649.
Synthesis of Compound 7
Compound 6 (19.5 mg, 0.0496 mmol), Cu
ACHTUNGTRENNUNG
0.0991 mmol), CuCl2 (13.3 mg, 0.0991 mmol) and PdACHTUNGTRENNUNG
(1.11 mg, 4.96 mmol) were dissolved in (CH2Cl)2 (0.50 mL),
and the resulting solution was refluxed for 45 h. After the
reaction mixture had been concentrated under vacuum, the
obtained residue was purified by flash column chromatogra-
phy (SiO2, hexane/AcOEt=4/1 to 3/1) to give 7 as a white
solid; yield: 15.1 mg (71%); mp 152–1538C; IR (ATR): n=
Synthesis of Compound 4
Compound 3 (45.0 mg, 0.0846 mmol) and ScACTHNURTGNENG(U OTf)3 (1.25 mg,
2.54 mmol) were dissolved in CH2Cl (0.85 mL), and the re-
sulting solution was refluxed for 48 h. After the reaction
mixture had been concentrated under vacuum, the obtained
residue was purified by flash column chromatography (SiO2,
hexane/AcOEt=5/1) to give the corresponding cyclobutane-
fused tetrahydroquinoline derivative as nearly 1:1 mixture
of diastereomers, white solid; yield: 36.9 mg (82%).
To a stirred solution of the obtained product (10.0 mg,
0.0188 mmol) and morpholine (33 mL, 0.376 mmol) in anhy-
drous toluene (1 mL) was added PdACHTNUTRGNE(UNG PPh3)4 (2.17 mg,
1728, 1663, 1460, 1369, 1269, 1203, 1053, 805, 748, 669 cmÀ1
;
1H NMR (CDCl3): d=2.26 (s, 3H), 2.76 (dd, J=3.2 Hz,
13.2 Hz, 1H), 3.21 (s, 3H), 3.38 (s, 3H), 3.45 (m, 1H), 4.23
(d, J=9.2 Hz, 1H), 4.48 (d, J=9.2 Hz, 1H), 4.90 (d, J=
13.2 Hz, 1H), 7.11–7.19 (m, 2H), 7.21–7.33 (m, 6H), 7.39
(dd, J=2.8 Hz, 7.2 Hz, 1H); 13C NMR (CDCl3): d=22.3,
35.9, 39.0, 43.4, 43.9, 52.1, 52.3, 62.7, 126.6, 127.5, 128.1
(2C), 128.2 (2C), 129.6, 130.1, 130.5, 132.5, 137.1, 138.6,
168.4, 169.2, 172.1; (+)-ESI-HR-MS: m/z=428.1242, calcd.
1.88 mmol), and the resulting solution was refluxed for 48 h.
After the reaction mixture had been concentrated under
vacuum, the obtained residue was purified by flash column
chromatography (SiO2, hexane/AcOEt=5/1) to give 4 as
a white solid; yield: 6.6 mg (78%); mp 50–528C; IR (ATR):
n=1728, 1487, 1454, 1347, 1159, 1089, 815, 740, 699,
+
for C23H23ClNO5 (M+H+): 428.1259.
Synthesis of Compound 8
A
suspension of 2a (30.0 mg, 0.0593 mmol) and 20%
1
668 cmÀ1; H NMR (CDCl3): d=2.45 (s, 3H), 2.85–2.92 (m,
Pd(OH)2-C (9 mg) in CH3CN (1.0 mL) was stirred under an
H2 atmosphere. After 24 h, the reaction mixture was filtered
through a short pad of celite. The reaction mixture was con-
centrated under vacuum and the obtained residue was puri-
fied by flash column chromatography (SiO2, hexane/
AcOEt=3/1) to give 8 as a colorless oil; yield: 30.0 mg
(quant.); IR (ATR): n=1734, 1489, 1434, 1351, 1162, 1090,
1H), 3.23 (s, 3H), 3.23 (s, 3H), 3.40 (dd, J=7.2 Hz, 10.8 Hz,
1H), 3.63 (dd, J=4.4 Hz, 10.8 Hz, 1H), 3.76–3.82 (m, 2H),
4.01 (dd, J=5.6 Hz, 14.4 Hz, 1H), 7.10–7.30 (m, 7H), 7.59
(d, J=8.4 Hz, 2H); 13C NMR (CDCl3): d=21.6, 33.3, 36.9,
44.2, 49.3, 49.8, 51.4, 124.6, 126.0, 127.0, 127.0 (2C), 127.0,
127.6 (2C), 128.3 (2C), 128.6, 129.8 (2C), 133.0, 137.5, 137.7,
139.4, 143.8, 172.3; (+)-ESI-HR-MS: m/z=470.1425, calcd.
for C26H25NNaO4S+ (M+Na+): 470.1397.
1
813, 735, 701, 661 cmÀ1; H NMR (CDCl3): d=2.09–2.21 (m,
2H), 2.34 (s, 3H), 2.67 (dd, J=2.8 Hz, 12.4 Hz, 1H), 3.31 (s,
3H), 3.40 (d, J=9.2 Hz, 1H), 3.50–3.58 (m, 2H), 3.77 (s,
3H), 3.86 (dd, J=5.6 Hz, 12.4 Hz, 1H), 6.98–7.00 (m, 2H),
7.03 (d, J=6.8 Hz, 2H), 7.19–7.30 (m, 6H), 7.49 (d, J=
8.4 Hz, 2H), 7.85 (d, J=8.4 Hz, 1H); 13C NMR (CDCl3):
d=21.5, 36.2, 39.3, 41.0, 47.1, 52.3, 52.4, 52.9, 122.8, 123.9,
Synthesis of Compound 6
To a stirred solution of 2k (30.0 mg, 0.0559 mmol) in DMF
(0.28 mL) at room temperature were added thioacetic acid
8
asc.wiley-vch.de
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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UPDATES
Scandium-Catalyzed Cascade Cyclization
126.6, 127.0 (2C), 128.0, 128.3, 128.6 (2C), 128.8 (2C), 129.6
(2C), 129.9, 135.6, 136.1, 138.5, 143.7, 168.0, 168.8; (+)-ESI-
HR-MS: m/z=508.1805, calcd. for C28H30NO6S+ (M+H+):
508.1788.
Chem. 2004, 69, 517; c) K. Inanaga, K. Takasu, M. Ihara,
J. Am. Chem. Soc. 2005, 127, 3668; d) E. Canales, E. J.
Corey, J. Am. Chem. Soc. 2007, 129, 12686; e) J. Burꢁs,
A. Armstrong, D. G. Blackmond, J. Am. Chem. Soc.
2011, 133, 8822; f) L. Albrecht, G. Dickmeiss, F. Cruz-
Acosta, C. Rodrꢂgues-Escrich, R. L. Davis, K. A. Jørgen-
sen, J. Am. Chem. Soc. 2012, 134, 2543; g) G. Talavera,
E. Reyes, J. L. Vicario, L. Carrillo, Angew. Chem. 2012,
124, 4180; Angew. Chem. Int. Ed. 2012, 51, 4104; h) G.-J.
Duan, J.-B. Ling, W.-P. Wang, Y.-C. Luo, P.-F. Xu, Chem.
Commun. 2013, 49, 4625.
Compound 9: Yellow oil; IR (ATR): n=1712, 1542, 1508,
1437, 1355, 1223, 1160, 922, 851, 752 cmÀ1
;
1H NMR
(CDCl3): d=3.70 (s, 3H), 3.74 (s, 3H), 4.07 (d, J=7.2 Hz,
2H), 4.28 (d, J=6.4 Hz, 2H), 5.96 (dt, J=16.0 Hz, 7.2 Hz,
1H), 6.46 (d, J=16.0 Hz, 1H), 6.96 (t, J=6.4 Hz, 1H), 6.99
(d, J=8.4 Hz, 2H), 7.26–7.30 (m, 2H), 7.68–7.76 (m, 3H),
8.07–8.10 (m, 1H); 13C NMR (CDCl3): d=45.6, 50.5, 52.5,
52.6, 115.5 (d, J=21.0 Hz) (2C), 122.3 (d, J=1.9 Hz), 124.5,
128.2 (d, J=8.6 Hz) (2C), 129.4, 131.2, 131.9, 132.0, 133.1,
133.9, 134.4, 145.9, 147.8, 162.5 (d, J=246.9 Hz), 163.3,
164.5; (+)-ESI-HR-MS: m/z=515.0911, calcd. for
C22H21FN2NaO8S+ (M+Na+): 515.0895.
[4] a) K. Ishihara, K. Nakano, J. Am. Chem. Soc. 2007, 129,
8930; b) A. T. Parsons, J. S. Johnson, J. Am. Chem. Soc.
2009, 131, 14202; c) M. M. Abd Rabo Moustafa, B. L.
Pagenkopf, Org. Lett. 2010, 12, 4732; d) J. Deng, R. P.
Hsung, C. Ko, Org. Lett. 2012, 14, 5562; e) H.-S. Yeom,
H. Li, Y. Tang, R. P. Hsung, Org. Lett. 2013, 15, 3130.
[5] Synthesis of the target tricyclic frameworks using
a [2+2]photocycloaddition, see: a) S. Brandes, P. Selig,
T. Bach, Synlett 2004, 2588; b) P. Selig, T. Bach, Angew.
Chem. 2008, 120, 5160; Angew. Chem. Int. Ed. 2008, 47,
5082; c) C. Mꢃller, A. Bauer, M. M. Maturi, M. C. Cu-
querella, M. A. Miranda, T. Bach, J. Am. Chem. Soc.
2011, 133, 16689; d) S. C. Coote, T. Bach, J. Am. Chem.
Soc. 2013, 135, 14948; e) F. Yagishita, M. Sakamoto, T.
Mino, T. Fujita, Org. Lett. 2011, 13, 6186; f) F. Yagishita,
T. Mino, T. Fujita, M. Sakamoto, Org. Lett. 2012, 14,
2638.
Compound 10: White solid; mp 88–898C, IR (ATR): n=
1731, 1545, 1511, 1436, 1360, 1275, 1170, 1127, 1019,
1
847 cmÀ1, H NMR (CDCl3): d=3.18–3.26 (m, 1H), 3.22 (s,
3H), 3.31–3.39 (m, 2H), 3.62–3.74 (m, 3H), 3.79 (s, 3H),
4.21 (d, J=7.2 Hz, 1H), 6.99 (t, J=8.4 Hz, 2H), 7.22 (dd,
J=5.6 Hz, 8.4 Hz, 2H), 7.65–7.77 (m, 3H), 8.12 (dd, J=
2.0 Hz, 7.2 Hz, 1H); 13C NMR (CDCl3): d=38.3, 40.5, 46.4,
49.6, 52.3, 52.9, 53.3, 60.0, 115.1 (d, J=20.7 Hz) (2C), 124.2,
129.5 (d, J=7.4 Hz) (2C), 130.9, 130.9, 131.5, 133.0 (d, J=
3.1 Hz), 133.8, 148.6, 162.1 (d, J=244.7 Hz), 169.0, 169.2;
(+)-ESI-HR.MS; m/z=493.1057, calcd. for C22H22FN2O8S+
(M+H+): 493.1075.
[6] Solvent effects were also examined under the same reac-
tion conditions [ScACHTUNTRGNEUNG(OTf)3 (10 mol%), solvent (0.1M),
278C, 18 h]. Toluene: 57% yield. CH3NO2: 54% yield.
THF: no reaction. CH3CN: the desired product 2a was
not formed.
Acknowledgements
This work was supported by a Grant-in Aid for Scientific Re-
search from the Ministry of Educationx, Culture, Sports, Sci-
ence, and Technology, Japan, Chiba University, and the
Uehara Memorial Foundation.
[7] Although selective decarboxylation of 2a was examined
using the Krapchoꢄs conditions (LiCl, DMSO, 1508C),
the reaction gave the product in low yield, accompanied
by the formation of some by-products. For selective de-
carboxylation reactions using related substrates, see:
a) M. D. Varney, W. H. Romines III, T. Boritzki, S. A.
Margosiak, C. Bartlett, E. J. Howland, J. Heterocycl.
Chem. 1995, 32, 1493; b) P. D. Pohlhaus, J. S. Johnson, J.
Am. Chem. Soc. 2005, 127, 16014.
References
[1] For a general review, see: P.-F. Xu, W. Wang, Catalytic
Cascade Reactions, Wiley, New Jersey, 2013.
[2] a) T. Yokosaka, T. Nemoto, Y. Hamada, Chem.
Commun. 2012, 48, 5431; b) T. Yokosaka, T. Nemoto, Y.
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ka, H. Nakayama, T. Nemoto, Y. Hamada, Org. Lett.
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UPDATES
10 Scandium-Catalyzed Cascade Cyclization to Produce
Cyclobutane-Fused Tetrahydroquinoline, Chromane,
Thiochromane, and Tetrahydronaphthalene Derivatives
Adv. Synth. Catal. 2014, 356, 1 – 10
Shun-ichi Nakano, Kazumi Kakugawa, Tetsuhiro Nemoto,
Yasumasa Hamada*
10
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