Free radical cyclization reactions of allylsulfonyl substituted N-aryl amide derivatives

Article abstract of DOI:10.1016/j.tet.2013.02.009

p-Toluenesulfonyl radical can be generated by the manganese(III) acetate oxidation of sodium p-toluenesulfinate. The corresponding alkyl radicals could be produced effectively by the p-toluenesulfonyl radical induced radical reaction of allylsulfonyl substituted N-aryl amides. These alkyl radicals undergo 5-exo-trig, 6-endo-trig, or 6-exo-trig cyclization onto the aromatic ring effectively. The product distribution is highly dependent on the substituent of aromatic ring and the stability of radical intermediate. This p-toluenesulfonyl radical induced reaction provides a synthetically useful method for the synthesis of dihydroquinolinones, azaspirocyclic cyclohexadienes, and spirodihydroquinolinones.

Full text of DOI:10.1016/j.tet.2013.02.009

Tetrahedron 69 (2013) 3293e3301
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Free radical cyclization reactions of allylsulfonyl substituted N-aryl
amide derivatives
*
Che-Ping Chuang , An-I Tsai, Ming-Yi Tsai
Department of Chemistry, National Cheng Kung University, Tainan 70101, Taiwan, ROC
a r t i c l e i n f o
a b s t r a c t
Article history:
p-Toluenesulfonyl radical can be generated by the manganese(III) acetate oxidation of sodium p-tolue-
nesulfinate. The corresponding alkyl radicals could be produced effectively by the p-toluenesulfonyl
radical induced radical reaction of allylsulfonyl substituted N-aryl amides. These alkyl radicals undergo 5-
exo-trig, 6-endo-trig, or 6-exo-trig cyclization onto the aromatic ring effectively. The product distribution
is highly dependent on the substituent of aromatic ring and the stability of radical intermediate. This p-
toluenesulfonyl radical induced reaction provides a synthetically useful method for the synthesis of
dihydroquinolinones, azaspirocyclic cyclohexadienes, and spirodihydroquinolinones.
Received 8 November 2012
Received in revised form 9 January 2013
Accepted 1 February 2013
Available online 8 February 2013
Keywords:
Free radical cyclization
Sulfonyl radical
Ó 2013 Elsevier Ltd. All rights reserved.
Sodium p-toluenesulfinate
Manganese(III) acetate
N-Aryl amide derivatives
1. Introduction
Free radical reactions have received considerable attention
during the last two decades and there is a tremendous de-
velopment of new radical reactions designed for organic synthe-
sis.1,2 Free radical reactions mediated by sulfonyl radicals have been
.
Ts
-
O
O
Ts
S
S
Ts
.
R
R
1
O
2
O
noted by several groups.3e5 The
a-scission of most alkylsulfonyl
radicals to generate alkyl radicals is an unfavorable process, but if
the alkyl group represents a stabilized radical, the extrusion of
sulfur dioxide occurs readily.6 p-Toluenesulfonyl radical can be
generated by the Mn(III) oxidation of sodium p-toluenesulfinate.7
The alkyl radicals generated from p-toluenesulfonyl radical in-
duced reaction of allylsulfones (Scheme 1) can undergo free radical
cyclization reactions effectively.5c,d
Quinolinones have long been targeted in synthetic in-
vestigations for their known biological activities and pharmaco-
logical properties, which include antiviral (HIV) activities,8aec
inotropic,8d 5HT3 receptor antagonists,8e farnesyl transferase
inhibitors,8f and maxi-K channel opening agents.8g The de-
velopment of new and efficient method for their synthesis repre-
sents a challenge in organic and medical chemistry. Alongside
classical Friedlander/FriedeleCrafts cyclization approaches,9 more
recent methods have been employed in the synthesis of quinoli-
nones including oxidative cyclization of 2-(3-hydroxypropyl)
R SO . .
R
4
2
3
Scheme 1.
anilines,10 radical cyclization of anilides,11 palladium-catalyzed
cyclocarbonylation of 2-alkenylanilines,12 rhodium catalyzed
addition-cyclization of aminophenylboronates.13 This report de-
scribes our results on the free radical cyclization reactions of
allylsulfonyl substituted N-aryl amide derivatives mediated by so-
dium p-toluenesulfinate/manganese(III) acetate.
2. Results and discussion
Our studies commenced with the readily available b-allylsulfo-
nylpropanamide 5a (R¼Me, PG¼Et, E¼CO2Et), which was prepared
by the alkylation of 2-bromo-N-ethyl-N-(4-methylphenyl)-etha-
namide with ethyl allylsulfonylacetate (see Supplementary data).
With this propanamide 5a in hand, we examined the reaction of 5a
* Corresponding author. Fax: þ886
6 2740552; e-mail address: cpchuang@
mail.ncku.edu.tw (C.-P. Chuang).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.02.009

3294
C.-P. Chuang et al. / Tetrahedron 69 (2013) 3293e3301
with sodium p-toluenesulfinate/manganese(III) acetate under var-
ious reaction conditions (Scheme 2). When the reaction of 5a with
sodium p-toluenesulfinate and manganese(III) acetate was carried
out in CF3CH2OH at room temperature, the expected dihy-
droquinolinone 6a was obtained in 89% yield (Table 1, entry 1).
Encouraged by this preliminary result, different solvents including
acetonitrile, methanol, DME, and DMSO were screened by using 5a
as substrate. As shown in Table 1, it was found that the best result
was accessed in CF3CH2OH (entry 1). In acetonitrile, 6a was ob-
tained in good yield (90%), however, it proceeded sluggishly and it
needs 4 h to complete the reaction (entry 2). When the reactions
were performed in methanol, DME, and DMSO, the desired product
6a was produced in lower yields (entries 3e5).
E
R
R
E
.
SO2Allyl
Ts
O
N
PG
O
N
5
syn-11 PG
.
E
E
Mn(III)
O
R
.
R
path a
6
.
N
O
N
anti-11 PG
PG
12
a: R = Me, PG = Et, E = CO2Et
E
path b
R
p: R = OMe, PG = Et, E = CO2Et
TsNa
SO2Allyl
R
OMe
Mn(OAc)3
N
PG
O
.
Mn(III)
O
5
7p
For 13p
E
E
E
PG
N
O
R
PG
N
O
+
E
PG
N
13
14p
N
PG
O
Scheme 3.
O 7
6
Scheme 2.
Table 2
Reactions of
b
-allylsulfonylpropanamides 5aema
Table 1
Optimization of reaction conditions
Entry
Amide
R
E
Product (yield (%))
1
2
3
4
5
6
7
8
5a
5b
5c
5d
5e
5f
5g
5h
5i
4-Me
4-Me
4-Me
3,5-diMe
3,5-diMe
d
CO2Et
p-ClC6H4CO
CH3CO
6a(89)
6b(86)
6c(95)
6d(98)
6e(92)
6f(87)
6g(89)
6h(80)
6i(81)
6j(76)
6k(83)
6l(64)
6m(74)
Entry
Solvent
Reaction time
Product (yield (%))
1
2
3
4
5
CF3CH2OH
CH3CN
CH3OH
DME
45 min
4 h
2 h
2 h
30 min
6a(89)
6a(90)
6a(64)
6a(49)
6a(55)
CO2Et
p-ClC6H4CO
p-ClC6H4CO
CH3CO
p-ClC6H4CO
CH3CO
p-ClC6H4CO
CH3CO
CO2Et
d
DMSO
4-Cl
4-Cl
4-Br
4-Br
4-CO2Et
4-CO2Et
9
10
11
12
13
5j
5k
5l
This dihydroquinolinone 6a was formed by the reaction mech-
anism outlined in Scheme 3. Radical 11a (R¼Me, PG¼Et, E¼CO2Et)
generated from 5a via a similar reaction route shown in Scheme 1
undergoes a 6-endo-trig ring cyclization (path a) to produce radical
intermediate 12a, which is subsequently oxidized by man-
ganese(III) acetate to give dihydroquinolinone 6a via deprotonation
and aromatization. The 5-exo-trig (ipso-type)14 cyclization of radi-
cal 11a (path b) may also occur to afford the cyclohexadienyl radical
intermediate 13a. This radical intermediate 13a is extremely un-
stable and would undergo fragmentation back to radical 11a.
Therefore, no product derived from 5-exo-trig cyclization of radical
11a was observed.
The scope of this transformation was next investigated accord-
ing to the optimized reaction conditions (Table 1, entry 1). As
shown in Table 2, a great variety of
5aem were converted to the corresponding dihydroquinolinones
6aem effectively. In all cases, -allylsulfonylpropanamides 5aem
bearing a radical stabilizing substituent (E) underwent this radical
reaction in excellent to good yields. This process was well tolerant
toward a variety of arylic substituents (R). However, an electron-
donating substituent favored product formation (entries 1e5),
whereas an electron-withdrawing substituent slightly hindered the
reaction (entries 8e13).
When N-4-methoxyphenyl substituted propanamide 5p
(R¼OMe, PG¼Et, E¼CO2Et) was treated with sodium p-toluene-
sulfinate and manganese(III) acetate in CF3CH2OH, in addition to the
5m
p-ClC6H4CO
a
PG¼Et.
expected dihydroquinolinone 6p (68%), a spirolactam 7p was also
produced in 31% yield (Table 3, entry 3). This spirolactam 7p was
formed via the reaction route outlined in Scheme 3 (path b).15
Radical 11p generated from 5p undergoes 5-exo-trig cyclization to
afford cyclohexadienyl radical intermediate 13p, which is then
Table 3
Reactions of N-4-methoxyphenyl substituted propanamidesa
Entry
Amide
E
PG
Product (yield (%))
1
2
3
4
5
6
7
8
5n
5o
5p
5q
5r
5s
5t
5u
5v
8a
8b
8c
p-ClC6H4CO
CH3CO
CO2Et
PhSO2
H
Et
Et
Et
Et
Et
Et
6n(86)
6o(89)
6p(68)
6q(16)
6r(0)
7n(0)
7o(0)
b-allylsulfonylpropanamides
7p(31)
7q(64)
7r(47)
7s(65)
7t(54)
7u(76)
7v(81)
10a(24)
10b(40)
b
Me
H
Me
6s(0)
6t(0)
TMBnb
TMBnb
TMBnb
Et
6u(0)
6v(0)
9a(70)
9b(46)
9c(62)
9
PhSO2
PhSO2
CO2Et
H
10
11
12
Et
Et
a
R¼OMe.
b
TMBn¼2,4,6-Trimethylbenzyl.

C.-P. Chuang et al. / Tetrahedron 69 (2013) 3293e3301
3295
oxidized by manganese(III) acetate to give oxonium ion 14p. This
oxonium ion 14p would then be transformed into the observed
spirolactam 7p by the attack of the solvent or water. In contrast to
the selective formation of 6aem shown in Table 2, spirolactam 7p
was also formed from 5p. This is likely to be attributed to the ioni-
zation potential of cyclohexadienyl radical 13p having a 4-methoxy
group must be lower than that of other cyclohexadienyl radicals
13aem. Therefore once radical 11p undergoes 5-exo cyclization to
produce the corresponding cyclohexadienyl radical 13p, which could
be immediately subjected to irreversible oxidation by man-
ganese(III) acetate followed by demethylation to give spirolactam 7p.
In order to scrutinize the effect of b-substituent (E) on the regiose-
lectivity for this radical cyclization reaction, we examined the radical
reaction of N-(4-methoxyphenyl)-propanamides 5nes. As shown in
Table 3, the 6/7 ratio is highly dependent on the stability of radical
intermediate 11. In particular, with 5n and 5o bearing a strong
electron-withdrawing substituent, dihydroquinolinones 6n and 6o
were produced exclusively (entries 1 and 2). On the contrary, with 5r
and 5s, spirolactams 7r and 7s are the only products (entries 5 and
6). Presumably, due to the strong electron-withdrawing keto groups,
the fragmentation of cyclohexadienyl radical intermediates 13n and
13o back to the stable radicals 11n and 11o proceeded much faster
than the manganese(III) oxidation to produce oxonium ions 14n and
14o. On the other hand, the fragmentation of cyclohexadienyl radical
intermediates 13r and 13s to produce the less stable radicals 11r and
11s proceeded much slower and the manganese(III) oxidation of 13r
and 13s to generate oxonium ions 14r and 14s became the only
route. With 5q bearing a benzenesulfonyl group, spirolactam 7q is
the major product (entry 4) and the 7/6 ratio could be increased by
changing the ethyl group (PG) with the bulkier 2,4,6-
trimethylbenzyl group (entry 9).16 Owing to the generation of the
less stable primary and secondary alkyl radicals by the sulfur dioxide
extrusion of alkylsulfonyl radicals is a less favorable process, the
radical cyclizations of 5r and 5s are less productive (entries 5 and 6).
The yields of spiro derivatives could be improved by replacing the
ethyl group (PG) with the bulkier 2,4,6-trimethylbenzyl group (en-
tries 7 and 8). This can be reasoned that the introduction of a large
PG group would shift the equilibrium in favor of the anti-11 con-
former, which then could cyclize (Scheme 3).17 We also conducted
this reaction with the naphthalene precursors 8a and 8b (entries 10
and 11). The reaction worked well, and spirolactams 9a,b and their
stereoisomers 10a,b were formed exclusively in excellent yields
(Scheme 4). The stereochemistry of 9a was confirmed by single
crystal X-ray analysis (Fig. 1).18 Similarly, spirolactam 9c was formed
as the only product from 8c in 62% yield (entry 12).
Fig. 1. The molecular structure of 9a.
formation shown in Table 3, we reasoned that it might be possible
to form spirodihydroquinolinone derivatives 17 through the so-
dium p-toluenesulfinate/manganese(III) acetate mediated radical
reaction of
a
-(allylsulfonyl)-N-(40-methoxybiphen-2-yl)-ethana-
mides 16 (Scheme 5).
O
OMe
R1
N
O
15
N
Bn
O
19
OMe Me
OMe
R2
TsNa
R1
O
Mn(OAc)3
SO2Allyl
N
Bn
O
O
E
16
R2
O
E
OMe
E
R2
MeO
SO2Allyl
E
E
PG
R1
N
O
PG
N
O
R1
E
N
O
PG
8
10
9
N
Bn
N
Bn
O
O
Scheme 4.
17
18
Spirodihydroquinolinone 15 is the key intermediate in the
preparation of aza-galanthamine19 and other indole alkaloids.20
Methods that have been employed for their syntheses are less
abundant, which include palladium-catalyzed Heck cyclization of
2-cyclohexenylacetanilides,20 oxidative cyclization of 2-(p-
hydroxyphenyl)-acetanilides,21 and radical cyclization of 2-(p-alk-
oxy or p-azido substituted phenyl)-acetanilides.15b,e The de-
velopment of efficient methods for their synthesis remains an area
of current interest. In view of the results on the spirolactam
Scheme 5.
Indeed, ethanamide 16a (R1¼R2¼E¼H) was transformed into
the desired spirodihydroquinolinone 17a (75%) by the reaction of
16a with sodium p-toluenesulfinate and manganese(III) acetate in
CF3CH2OH at room temperature (Table 4, entry 1). A possible re-
action mechanism for the formation of spirodihydroquinolinone
17a is shown in Scheme 6. Radical 20a generated from 16a

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C.-P. Chuang et al. / Tetrahedron 69 (2013) 3293e3301
Table 4
allylsulfonyl substituted N-aryl amides and the corresponding alkyl
radicals can be generated efficiently. These alkyl radicals undergo
5-exo-trig, 6-endo-trig, or 6-exo-trig cyclization onto the aromatic
Reactions of N-(40-methoxybiphen-2-yl) substituted ethanamides 16
Entry
Amide
R1
R2
E
Product (yield (%))
ring effectively. With b-allylsulfonylpropanamides 5, this reaction
1
2
3
4
5
6
7
8
9
16a
16b
16c
16d
16e
16f
16g
16h
16i
H
Me
Cl
H
Me
Cl
H
Me
Cl
H
H
H
Me
Me
Me
H
H
H
H
H
H
H
H
H
Me
Me
Me
17a(75)
17b(76)
17c(72)
17d(82)
17e(83)
17f(82)
17g(95)
17h(96)
17i(94)
18a(9)
18b(14)
18c(12)
18d(5)
18e(6)
18f(6)
18a(0)
18a(0)
18a(0)
provides a synthetically useful method for the synthesis of dihy-
droquinolinones and azaspirocyclic cyclohexadienes. The product
distributions are highly dependent on the substituent of aromatic
ring and the stability of radical intermediate 11. With a-allylsulfo-
nylethanamides 16, spirodihydroquinolinones 17 were obtained as
the exclusive or major products.
4. Experimental section
4.1. General
undergoes a 6-exo cyclization (path b) to afford cyclohexadienyl
radical 22a, which is then oxidized by manganese(III) acetate to
give oxonium ion 23a. This oxonium ion 23a would then be
attacked by the solvent or water to produce spirolactam 17a. In
addition to spirodihydroquinolinone 17a, a small amount (9%) of
dibenzoazepinone 18a formed by 7-exo cyclization of radical 20a
(path a) was also obtained. It is noteworthy to note that no products
derived from the five- or six-membered ring cyclization of radical
20a onto the other two benzene rings can be observed.
Melting points are uncorrected. The NMR spectra were recorded
on a Brucker AMX-400 or AVANCE 500 spectrometer. Chemical
shifts are reported in parts per million relative to TMS as internal
reference. Elemental analyses were performed with Heraeus CHN-
Rapid Analyzer. HRMS were recorded on a JEOL JMS-SX 102A mass
spectrometer. X-ray diffraction structure analyses were performed
with a Nonius Kappa CCD diffractometer. Structure analysis was
made by using SHELXTL program on a personal computer. Analyt-
ical thin-layer chromatography was performed with precoated
silica gel 60 F254 plates (0.25 mm thick) and visualized by UV light.
The reaction mixture was purified by column chromatography over
silica gel (70e230 mesh).
Typical procedure for the radical reaction: A mixture of 128 mg
(0.35 mmol) of 5a, 233 mg (0.87 mmol) of manganese(III) acetate,
and 373 mg (2.1 mmol) of sodium p-toluenesulfinate in 10 mL of
CF3CH2OH was stirred at room temperature for 45 min. The reaction
mixture was diluted with 100 mL of EtOAc, washed with saturated
aqueous bisulfite (2ꢀ50 mL), H2O (3ꢀ50 mL), dried (Na2SO4), and
concentrated in vacuo. The residue was chromatographed over 20 g
of silica gel (eluted with 8:1 hexaneeEtOAc) followed by re-
crystallization (hexaneeEtOAc) to give 81 mg (89%) of 6a.
OMe
OMe
.
path a
Mn(III)
18a
.
N
Bn
N
O
O
21a
20a
Bn
path b
OMe
OMe
.
4.1.1. 4-Ethoxycarbonyl-1-ethyl-6-methyl-3,4-dihydro-2(1H)-quinoli-
Mn(III)
17a
none 6a. White needles; mp 72e73 ꢁC; IR (CHCl3) 2920, 1730, 1665,
1615, 1590, 1505 cmꢂ1; 1H NMR (400 MHz, CDCl3)
d 1.15e1.30 (m, 6H,
CH3), 2.31 (s, 3H, CH3), 2.76 (dd, J¼16.0, 6.2 Hz, 1H, CH), 2.96 (dd,
J¼16.0, 4.4 Hz, 1H, CH), 3.77 (dd, J¼6.2, 4.4 Hz, 1H, CH), 3.88e4.07 (m,
2H, NCH2), 4.07e4.21 (m, 2H, OCH2), 6.93 (d, J¼8.3 Hz, 1H, ArH), 7.07
(s, 1H, ArH), 7.10 (d, J¼8.3 Hz, 1H, ArH); 13C NMR (100.6 MHz, CDCl3)
N
Bn
O
N
Bn
O
23a
22a
Scheme 6.
d
12.5 (q), 14.0 (q), 20.5 (q), 34.0 (t), 37.0 (t), 42.4 (d), 61.3 (t), 115.0 (d),
122.9 (s), 129.2 (d), 129.3 (d), 132.4 (s), 136.7 (s), 167.4 (s), 171.6 (s);
Anal. Calcd for C15H19NO3: C, 68.94; H, 7.33; N 5.36. Found: C, 68.70;
H, 7.29; N, 5.33.
To investigate the scope of this spirolactamization process,
a series of 16 was prepared and subjected to the optimized reaction
conditions shown in Table 1 (entry 1). As shown in Table 4, a great
variety of N-(40-methoxybiphen-2-yl) substituted amides 16 were
converted to the corresponding spirodihydroquinolinones 17 ef-
fectively. The expected spirodihydroquinolinones 17 were formed
predominantly and a small amount of dibenzoazepinones 18 was
also obtained. With ethanamides 16def, the steric hindrance of the
methyl group (R2) might contribute to the exclusive production of
dibenzoazepinones 18def and their isomeric products 19def can-
not be found (entries 4e6). Secondary allylsulfones 16gei can also
be used, in which cases spirodihydroquinolinones 17gei containing
4.1.2. 4-(4-Chlorobenzoyl)-1-ethyl-6-methyl-3,4-dihydro-2(1H)-qui-
nolinone 6b. White crystals; mp 138e139 ꢁC; IR (CHCl3) 3015, 1680,
1660, 1385, 1175 cmꢂ1; 1H NMR (400 MHz, CDCl3)
d
1.26 (t, J¼7.1 Hz,
3H, CH3), 2.21 (s, 3H, CH3), 2.83 (dd, J¼15.9, 6.1 Hz,1H, CH), 2.98 (dd,
J¼15.9, 6.1 Hz, 1H, CH), 3.91e4.07 (m, 2H, NCH2), 4.77 (t, J¼6.1 Hz,
1H, CH), 6.84 (s, 1H, ArH), 6.96 (d, J¼8.3 Hz, 1H, ArH), 7.07 (d,
J¼8.3 Hz, 1H, ArH), 7.47 (d, J¼8.6 Hz, 2H, ArH), 7.95 (d, J¼8.6 Hz, 2H,
ArH); 13C NMR (100.6 MHz, CDCl3)
d 12.5 (q), 20.5 (q), 34.5 (t), 37.2
(t), 43.1 (d), 115.3 (d), 123.6 (s), 128.9 (d), 129.1 (d), 129.2 (2ꢀ d),
130.1 (2ꢀ d), 132.4 (s), 134.2 (s), 137.4 (s), 140.1 (s), 167.8 (s), 197.2
(s); Anal. Calcd for C19H18ClNO2: C, 69.62; H, 5.53; N, 4.27. Found: C,
69.34; H, 5.60; N, 4.23.
a methyl substituent (E)
duced in better reaction yields (entries 7e9).
a to the lactam carbonyl group are pro-
3. Conclusions
4.1.3. 4-Acetyl-1-ethyl-6-methyl-3,4-dihydro-2(1H)-quinolinone
p-Toluenesulfonyl radical can be generated by the man-
ganese(III) acetate oxidation of sodium p-toluenesulfinate. This p-
toluenesulfonyl radical can induce the free radical reaction of
6c. White needles; mp 103e104 ꢁC; IR (CHCl3) 3010, 1715, 1665, 1380,
1135 cmꢂ1
;
1H NMR (400 MHz, CDCl3)
d
1.20 (t, J¼7.1 Hz, 3H, CH3),
2.16 (s, 3H, CH3), 2.34 (s, 3H, CH3), 2.68 (dd, J¼16.0, 6.2 Hz, 1H, CH),

C.-P. Chuang et al. / Tetrahedron 69 (2013) 3293e3301
3297
2.99 (dd, J¼16.0, 2.8 Hz, 1H, CH), 3.74 (dd, J¼6.2, 2.8 Hz, 1H, CH), 3.94
(q, J¼7.1 Hz, 2H, NCH2), 6.94 (d, J¼8.7 Hz, 1H, ArH), 7.10 (s, 1H, ArH),
Calcd for C18H15Cl2NO2: C, 62.08; H, 4.34; N, 4.02. Found: C, 62.05;
H, 4.36; N, 4.06.
7.11 (d, J¼8.7 Hz, 1H, ArH); 13C NMR (75.4 MHz, CDCl3)
d 12.4 (q), 20.5
(q), 27.6 (q), 33.2 (t), 37.0 (t), 50.0 (d), 115.2 (d), 122.9 (s), 129.3 (d),
129.8 (d), 132.6 (s), 136.9 (s), 167.8 (s), 205.4 (s); Anal. Calcd for
C14H17NO2: C, 72.70; H, 7.41; N, 6.06. Found: C, 72.54; H, 7.44; N, 6.06.
4.1.9. 4-Acetyl-6-chloro-1-ethyl-3,4-dihydro-2(1H)-quinolinone
6i. White crystals; mp 132e133 ꢁC; IR (CHCl3) 3015, 1715, 1675,
1375, 1135 cmꢂ1; 1H NMR (400 MHz, CDCl3)
d
1.19 (t, J¼7.1 Hz, 3H,
CH3), 2.19 (s, 3H, CH3), 2.69 (dd, J¼16.1, 6.1 Hz, 1H, CH), 3.01 (dd,
J¼16.1, 2.6 Hz, 1H, CH), 3.77 (dd, J¼6.1, 2.6 Hz, 1H, CH), 3.87e3.99
4.1.4. 4-Ethoxycarbonyl-1-ethyl-5,7-dimethyl-3,4-dihydro-2(1H)-
quinolinone 6d. White crystals; mp 71e72 ꢁC; IR (CHCl3) 2980,
(m, 2H, NCH2), 6.95e6.99 (m, 1H, ArH), 7.26e7.31 (m, 2H, ArH); 13
C
1725, 1660, 1320, 1275 cmꢂ1
;
1H NMR (400 MHz, CDCl3)
d
1.19 (t,
NMR (100.6 MHz, CDCl3) d 12.3 (q), 27.7 (q), 32.9 (t), 37.2 (t), 49.7
J¼7.2 Hz, 3H, CH3), 1.22 (t, J¼7.3 Hz, 3H, CH3), 2.33 (s, 3H, CH3), 2.37
(s, 3H, CH3), 2.68 (dd, J¼16.0, 6.5 Hz, 1H, CH), 2.99 (dd, J¼16.0,
1.4 Hz, 1H, CH), 3.94 (dd, J¼6.5, 1.4 Hz, 1H, CH), 3.98 (q, J¼7.2 Hz, 2H,
NCH2), 4.03e4.15 (m, 2H, OCH2), 6.73 (s, 1H, ArH), 6.75 (s, 1H, ArH);
(d), 116.5 (d), 124.7 (s), 128.0 (s), 128.7 (d), 129.0 (d), 138.0 (s), 167.4
(s), 204.4 (s); Anal. Calcd for C13H14ClNO2: C, 62.03; H, 5.61; N, 5.56.
Found: C, 62.09; H, 5.64; N, 5.55.
13C NMR (100.6 MHz, CDCl3)
d
12.7 (q), 14.0 (q), 19.6 (q), 21.5 (q),
4.1.10. 6-Bromo-4-(4-chlorobenzoyl)-1-ethyl-3,4-dihydro-2(1H)-
quinolinone 6j. Whitecrystals;mp145e146 ꢁC; IR (CHCl3)3010,1680,
34.1 (t), 37.4 (t), 38.5 (d), 61.2 (t), 114.1 (d), 119.2 (s), 126.0 (d), 136.9
(s), 138.2 (s), 139.5 (s), 167.7 (s), 171.6 (s); Anal. Calcd for C16H21NO3:
C, 69.79; H, 7.69; N, 5.09. Found: C, 69.60; H, 7.75; N, 5.08.
1665, 1375, 1135 cmꢂ1; 1H NMR (300 MHz, CDCl3)
d
1.25 (t, J¼7.0 Hz,
3H, CH3), 2.86 (dd, J¼16.0, 5.8 Hz,1H, CH), 2.98 (dd, J¼16.0, 5.8 Hz, 1H,
CH), 3.86e4.10 (m, 2H, NCH2), 4.78 (t, J¼5.8 Hz, 1H, CH), 6.94 (d,
J¼8.7 Hz,1H, ArH), 7.18 (d, J¼1.8 Hz,1H, ArH), 7.38 (dd, J¼8.7,1.8Hz,1H,
ArH), 7.49 (d, J¼8.5 Hz, 2H, ArH), 7.93 (d, J¼8.5 Hz, 2H, ArH); 13C NMR
4.1.5. 4-(4-Chlorobenzoyl)-1-ethyl-5,7-dimethyl-3,4-dihydro-2(1H)-
quinolinone 6e. White crystals; mp 199e200 ꢁC; IR (CHCl3) 3010,
1685, 1660, 1380, 1140 cmꢂ1
;
1H NMR (400 MHz, CDCl3)
d
1.27 (t,
(100.6 MHz, CDCl3) d 12.4 (q), 34.2 (t), 37.4 (t), 42.9 (d), 115.3 (s), 117.0
J¼7.1 Hz, 3H, CH3), 2.14 (s, 3H, CH3), 2.35 (s, 3H, CH3), 2.91 (dd,
J¼16.0, 2.0 Hz, 1H, CH), 3.00 (dd, J¼16.0, 7.7 Hz, 1H, CH), 4.00 (q,
J¼7.1 Hz, 2H, NCH2), 4.86 (dd, J¼7.7, 2.0 Hz, 1H, CH), 6.73 (s, 1H,
ArH), 6.81 (s, 1H, ArH), 7.47 (d, J¼8.6 Hz, 2H, ArH), 7.90 (d, J¼8.6 Hz,
(d), 125.6 (s), 129.4 (2ꢀ d), 130.0 (2ꢀ d), 131.1 (d), 131.5 (d), 133.6 (s),
139.1 (s),140.5 (s),167.3 (s),196.3 (s); Anal. Calcd for C18H15BrClNO2: C,
55.06; H, 3.85; N, 3.57. Found: C, 55.11; H, 3.86; N, 3.60.
2H, ArH); 13C NMR (100.6 MHz, CDCl3)
d
12.6 (q), 19.7 (q), 21.5 (q),
4.1.11. 4-Acetyl-6-bromo-1-ethyl-3,4-dihydro-2(1H)-quinolinone
34.9 (t), 37.5 (t), 40.5 (d), 114.4 (d), 119.7 (s), 125.9 (d), 129.2 (2ꢀ d),
129.8 (2ꢀ d), 133.7 (s), 135.5 (s), 138.3 (s), 140.0 (s), 140.4 (s), 166.3
(s), 197.0 (s); Anal. Calcd for C20H20ClNO2: C, 70.27; H, 5.90; N, 4.10.
Found: C, 70.27; H, 5.99; N, 4.08.
6k. White needles; mp 133e134 ꢁC; IR (CHCl3) 3015, 1715, 1675,
1370, 1135 cmꢂ1; 1H NMR (400 MHz, CDCl3)
d
1.19 (t, J¼7.1 Hz, 3H,
CH3), 2.19 (s, 3H, CH3), 2.69 (dd, J¼16.1, 6.1 Hz, 1H, CH), 3.00 (dd,
J¼16.1, 2.7 Hz, 1H, CH), 3.77 (dd, J¼6.1, 2.7 Hz, 1H, CH), 3.87e3.98
(m, 2H, NCH2), 6.90e6.94 (m, 1H, ArH), 7.41e7.44 (m, 1H, ArH), 7.44
4.1.6. 4-(4-Chlorobenzoyl)-1-ethyl-3,4-dihydro-2(1H)-quinolinone
6f. White needles; mp 109e110 ꢁC; IR (CHCl3) 2925, 1685, 1665,
(s,1H, ArH); 13C NMR (100.6 MHz, CDCl3)
d 12.3 (q), 27.7 (q), 32.9 (t),
37.1 (t), 49.6 (d), 115.4 (s), 116.9 (d), 125.1 (s), 131.7 (d), 131.8 (d),
138.5 (s), 167.4 (s), 204.4 (s); Anal. Calcd for C13H14BrNO2: C, 52.72;
H, 4.76; N, 4.73. Found: C, 52.89; H, 4.80; N, 4.69.
1385, 1260 cmꢂ1; 1H NMR (400 MHz, CDCl3)
d
1.28 (t, J¼7.1 Hz, 3H,
CH3), 2.85 (dd, J¼15.9, 6.1 Hz, 1H, CH), 3.01 (dd, J¼15.9, 6.1 Hz, 1H,
CH), 3.96e4.10 (m, 2H, NCH2), 4.80 (t, J¼6.1 Hz, 1H, CH), 6.94 (t,
J¼7.7 Hz, 1H, ArH), 7.04 (d, J¼7.7 Hz, 1H, ArH), 7.07 (d, J¼7.7 Hz, 1H,
ArH), 7.27 (t, J¼7.7 Hz, 1H, ArH), 7.47 (d, J¼8.6 Hz, 2H, ArH), 7.94 (d,
4.1.12. 4,6-Bis(ethoxycarbonyl)-1-ethyl-3,4-dihydro-2(1H)-quinoli-
none 6l. White powder; mp 90e91 ꢁC; IR (CHCl3) 2990, 1730, 1715,
J¼8.6 Hz, 2H, ArH); 13C NMR (100.6 MHz, CDCl3)
d
12.6 (q), 34.3 (t),
1680, 1615, 1375 cmꢂ1 1H NMR (400 MHz, CDCl3)
; d 1.20e1.28 (m,
37.3 (t), 43.2 (d), 115.4 (d), 122.8 (d), 123.7 (s), 128.3 (d), 128.7 (d),
129.2 (2ꢀ d), 130.1 (2ꢀ d), 134.3 (s), 139.9 (s), 140.2 (s), 167.9 (s),
197.0 (s); Anal. Calcd for C18H16ClNO2: C, 68.90; H, 5.14; N, 4.46.
Found: C, 68.93; H, 5.15; N, 4.47.
6H, CH3), 1.40 (t, J¼7.1 Hz, 3H, CH3), 2.80 (dd, J¼16.1, 6.3 Hz, 1H, CH),
3.04 (dd, J¼16.1, 3.9 Hz, 1H, CH), 3.89 (dd, J¼6.3, 3.9 Hz, 1H, CH),
3.97e4.09 (m, 2H, NCH2), 4.11e4.21 (m, 2H, OCH2), 4.33e4.43 (m,
2H, OCH2), 7.08 (d, J¼8.6 Hz, 1H, ArH), 7.96 (d, J¼1.9 Hz, 1H, ArH),
8.00 (dd, J¼8.6, 1.9 Hz, 1H, ArH); 13C NMR (100.6 MHz, CDCl3)
d 12.4
4.1.7. 4-Acetyl-1-ethyl-3,4-dihydro-2(1H)-quinolinone
needles; mp 99e100 ꢁC; IR (CHCl3) 3015, 1715, 1670, 1385,
1135 cmꢂ1; 1H NMR (400 MHz, CDCl3)
6g. White
(q), 14.0 (q), 14.3 (q), 33.6 (t), 37.3 (t), 42.1 (d), 60.9 (t), 61.5 (t), 114.7
(d), 122.7 (s), 124.7 (s), 130.2 (d), 130.5 (d), 142.9 (s), 165.7 (s), 167.5
(s), 171.1 (s); Anal. Calcd for C17H21NO5: C, 63.94; H, 6.63; N, 4.39.
Found: C, 63.89; H, 6.65; N, 4.39.
d
1.21 (t, J¼7.1 Hz, 3H, CH3),
2.16 (s, 3H, CH3), 2.70 (dd, J¼16.1, 6.1 Hz, 1H, CH), 3.01 (dd, J¼16.1,
2.7 Hz, 1H, CH), 3.80 (dd, J¼6.1, 2.7 Hz, 1H, CH), 3.87e4.04 (m, 2H,
NCH2), 7.02e7.10 (m, 2H, ArH), 7.28e7.34 (m, 2H, ArH); 13C NMR
4.1.13. 4-(4-Chlorobenzoyl)-6-ethoxycarbonyl-1-ethyl-3,4-dihydro-
(100.6 MHz, CDCl3)
d
12.5 (q), 27.6 (q), 33.1 (t), 37.1 (t), 49.9 (d),
2(1H)-quinolinone 6m. White needles; mp 184e185 ꢁC; IR (CHCl3)
115.3 (d), 122.9 (d), 128.9 (d), 129.2 (d), 139.4 (s), 167.9 (s), 205.2 (s);
Anal. Calcd for C13H15NO2: C, 71.87; H, 6.96; N, 6.45. Found: C,
71.86; H, 7.04; N, 6.41.
3010, 1710, 1685, 1375, 1265 cmꢂ1; 1H NMR (300 MHz, CDCl3)
d 1.27
(t, J¼7.0 Hz, 3H, CH3), 1.34 (t, J¼7.1 Hz, 3H, CH3), 2.91 (dd, J¼16.1,
5.2 Hz,1H, CH), 3.03 (dd, J¼16.1, 5.2 Hz,1H, CH), 4.05 (q, J¼7.0 Hz, 2H,
NCH2), 4.31 (q, J¼7.1 Hz, 2H, OCH2), 4.86 (t, J¼5.2 Hz, 1H, CH), 7.09 (d,
J¼8.6 Hz, 1H, ArH), 7.49 (d, J¼8.6 Hz, 2H, ArH), 7.78 (s, 1H, ArH), 7.96
4.1.8. 6-Chloro-4-(4-chlorobenzoyl)-1-ethyl-3,4-dihydro-2(1H)-qui-
nolinone 6h. White crystals; mp 145e146 ꢁC; IR (CHCl3) 3015, 1680,
(d, J¼8.6 Hz, 3H, ArH); 13C NMR (75.4 MHz, CDCl3)
d 12.4 (q),14.2 (q),
1670,1380, 1135 cmꢂ1; 1H NMR (400 MHz, CDCl3)
d
1.26 (t, J¼7.1 Hz,
34.1 (t), 37.4 (t), 43.1 (d), 60.9 (t), 115.0 (d), 123.0 (s), 124.6 (s), 129.3
(2ꢀ d), 139.98 (d), 130.09 (2ꢀ d), 130.4 (d), 133.5 (s), 140.4 (s), 143.7
(s), 165.6 (s), 167.7 (s), 196.4 (s); Anal. Calcd for C21H20ClNO4: C,
65.37; H, 5.22; N, 3.63. Found: C, 65.22; H, 5.22; N, 3.59.
3H, CH3), 2.86 (dd, J¼16.0, 5.9 Hz, 1H, CH), 2.99 (dd, J¼16.0, 5.9 Hz,
1H, CH), 3.91e4.08 (m, 2H, NCH2), 4.77 (t, J¼5.9 Hz, 1H, CH), 6.99 (d,
J¼8.8 Hz, 1H, ArH), 7.03 (d, J¼2.4 Hz, 1H, ArH), 7.24 (dd, J¼8.8,
2.4 Hz, 1H, ArH), 7.50 (d, J¼8.6 Hz, 2H, ArH), 7.93 (d, J¼8.6 Hz, 2H,
ArH); 13C NMR (100.6 MHz, CDCl3)
d
12.4 (q), 34.2 (t), 37.4 (t), 42.9
4.1.14. 4-(4-Chlorobenzoyl)-1-ethyl-6-methoxyl-3,4-dihydro-2(1H)-
(d), 116.6 (d), 125.3 (s), 127.9 (s), 128.3 (d), 128.6 (d), 129.4 (2ꢀ d),
quinolinone 6n. White crystals; mp 119e120 ꢁC; IR (CHCl3) 3010,
130.0 (2ꢀ d), 133.7 (s), 138.6 (s), 140.6 (s), 167.4 (s), 196.4 (s); Anal.
1685, 1660, 1240, 1145 cmꢂ1 1H NMR (400 MHz, CDCl3)
; d 1.25 (t,

3298
C.-P. Chuang et al. / Tetrahedron 69 (2013) 3293e3301
J¼7.0 Hz, 3H, CH3), 2.83 (dd, J¼15.9, 6.0 Hz, 1H, CH), 2.98 (dd,
J¼15.9, 6.0 Hz, 1H, CH), 3.70 (s, 3H, OCH3), 3.91e4.08 (m, 2H, NCH2),
4.76 (t, J¼6.0 Hz,1H, CH), 6.60 (d, J¼2.0 Hz,1H, ArH), 6.80 (dd, J¼8.8,
2.0 Hz, 1H, ArH), 6.99 (d, J¼8.8 Hz, 1H, ArH), 7.47 (d, J¼8.3 Hz, 2H,
CH), 7.54 (t, J¼7.6 Hz, 2H, ArH), 7.69 (t, J¼7.6 Hz, 1H, ArH), 7.80 (d,
J¼7.6 Hz, 2H, ArH); 13C NMR (100.6 MHz, CDCl3)
d 14.9 (q), 30.5 (t),
35.9 (t), 62.3 (s), 64.9 (d), 128.6 (2ꢀ d), 129.7 (2ꢀ d), 131.3 (d), 131.8
(d), 134.8 (d), 137.7 (s), 143.2 (d), 145.8 (d), 169.7 (s), 183.7 (s); Anal.
Calcd for C17H17NO4S: C, 61.61; H, 5.17; N, 4.23. Found: C, 61.63; H,
5.20; N, 4.24.
ArH), 7.94 (d, J¼8.3 Hz, 2H, ArH); 13C NMR (100.6 MHz, CDCl3)
d 12.5
(q), 34.3 (t), 37.3 (t), 43.3 (d), 55.4 (q), 112.7 (d), 114.8 (d), 116.2 (d),
125.0 (s), 129.2 (2ꢀ d), 130.0 (2ꢀ d), 133.3 (s), 134.1 (s), 140.2 (s),
155.0 (s), 167.4 (s), 196.8 (s); Anal. Calcd for C19H18ClNO3: C, 66.38;
H, 5.28; N, 4.07. Found: C, 66.13; H, 5.31; N, 3.92.
4.1.20. 1-Ethyl-1-azaspiro[4.5]deca-6,9-diene-2,8-dione 7r. White
crystals; mp 98e99 ꢁC; IR (KBr) 2980, 1695, 1400, 1130, 865 cmꢂ1
;
1H NMR (400 MHz, CDCl3)
d
1.10 (t, J¼7.2 Hz, 3H, CH3), 2.17 (t,
4.1.15. 4-Acetyl-1-ethyl-6-methoxyl-3,4-dihydro-2(1H)-quinolinone
J¼8.1 Hz, 2H, CH2), 2.58 (t, J¼8.1 Hz, 2H, CH2), 3.15 (q, J¼7.2 Hz, 2H,
NCH2), 6.34 (d, J¼10.1 Hz, 2H, 2ꢀ CH), 6.78 (d, J¼10.1 Hz, 2H, 2ꢀ
6o. White needles; mp 90e91 ꢁC; IR (CHCl3) 2975, 1710,1655,1385,
1225 cmꢂ1; 1H NMR (400 MHz, CDCl3)
d
1.19 (t, J¼7.1 Hz, 3H, CH3),
CH); 13C NMR (100.6 MHz, CDCl3)
d 14.9 (q), 29.2 (t), 30.0 (t), 36.0
2.17 (s, 3H, CH3), 2.69 (dd, J¼16.0, 6.1 Hz, 1H, CH), 2.98 (dd, J¼16.0,
2.7 Hz, 1H, CH), 3.73 (dd, J¼6.1, 2.7 Hz, 1H, CH), 3.82 (s, 3H, OCH3),
3.89e3.98 (m, 2H, NCH2), 6.82e6.87 (m, 2H, ArH), 6.95e6.99 (m,
(t), 62.2 (s), 129.8 (2ꢀ d), 149.5 (2ꢀ d), 174.2 (s), 184.2 (s); Anal.
Calcd for C11H13NO2: C, 69.09; H, 6.85; N, 7.32. Found: C, 68.91; H,
6.86; N, 7.25.
1H, ArH); 13C NMR (100.6 MHz, CDCl3)
d 12.4 (q), 27.6 (q), 33.2 (t),
37.0 (t), 50.1 (d), 55.6 (q), 113.2 (d), 115.3 (d), 116.3 (d), 124.4 (s),
132.8 (s), 155.2 (s), 167.5 (s), 205.1 (s); Anal. Calcd for C14H17NO3: C,
68.00; H, 6.93; N, 5.66. Found: C, 67.97; H, 6.93; N, 5.63.
4.1.21. 1-Ethyl-4-methyl-1-azaspiro[4.5]deca-6,9-diene-2,8-dione
7s. White crystals; mp 102e103 ꢁC; IR (KBr) 2970, 1670, 1400, 1140,
890 cmꢂ1; 1H NMR (400 MHz, CDCl3)
d
0.96 (d, J¼7.0 Hz, 3H, CH3),
1.10 (t, J¼7.1 Hz, 3H, CH3), 2.24 (dd, J¼16.4, 11.5 Hz, 1H, CH),
2.42e2.53 (m, 1H, CH), 2.67 (dd, J¼16.4, 8.2 Hz, 1H, CH), 3.07 (dq,
J¼14.2, 7.1 Hz, 1H, NCH), 3.23 (dq, J¼14.2, 7.1 Hz, 1H, NCH),
6.39e6.44 (m, 2H, 2ꢀ CH), 6.66e6.72 (m, 2H, 2ꢀ CH); 13C NMR
4.1.16. 4-Ethoxycarbonyl-1-ethyl-6-methoxy-3,4-dihydro-2(1H)-qui-
nolinone 6p. White needles; mp 65e66 ꢁC; IR (CHCl3) 2990, 1730,
1670, 1505, 1385 cmꢂ1 1H NMR (400 MHz, CDCl3)
; d 1.18e1.26 (m,
6H, CH3), 2.76 (dd, J¼16.0, 6.2 Hz, 1H, CH), 2.97 (dd, J¼16.0, 4.3 Hz,
1H, CH), 3.74e3.84 (m, 1H, CH), 3.80 (s, 3H, CH3), 3.85e4.07 (m, 2H,
NCH2), 4.15 (q, J¼6.9 Hz, 2H, OCH2), 6.83 (s, 1H, ArH), 6.84 (d,
J¼8.8 Hz,1H, ArH), 6.97 (d, J¼8.8 Hz,1H, ArH); 13C NMR (100.6 MHz,
(100.6 MHz, CDCl3) d 13.6 (q), 14.7 (q), 36.2 (t), 37.2 (t), 37.6 (d), 65.9
(s), 131.0 (d), 131.2 (d), 146.8 (d), 149.0 (d), 173.7 (s), 184.4 (s); Anal.
Calcd for C12H15NO2: C, 70.22; H, 7.37; N, 6.82. Found: C, 70.01; H,
7.42; N, 6.71.
CDCl3) d 12.5 (q), 14.0 (q), 33.9 (t), 37.2 (t), 42.6 (d), 55.6 (q), 61.4 (t),
113.6 (d), 114.6 (d), 116.1 (d), 124.4 (s), 132.6 (s), 155.2 (s), 167.1 (s),
171.4 (s); Anal. Calcd for C15H19NO4: C, 64.97; H, 6.91; N, 5.05.
Found: C, 64.95; H, 6.90; N, 5.04.
4.1.22. 1-(2,4,6-Trimethylbenzyl)-1-aza-spiro[4,5]-deca-6,9-diene-
2,8-dione 7t. White crystals; mp 157e158 ꢁC; IR (KBr) 2985, 1695,
1395,1310,1150 cmꢂ1; 1H NMR (400 MHz, CDCl3)
d
2.04 (t, J¼8.1 Hz,
2H, CH2), 2.15 (s, 6H, 2ꢀ CH3), 2.23 (s, 3H, CH3), 2.64 (t, J¼8.1 Hz, 2H,
CH2), 4.51 (s, 2H, NCH2), 6.01 (d, J¼10.1 Hz, 2H, CH2), 6.44 (d,
J¼10.1 Hz, 2H, CH2), 6.73 (s, 2H, ArH); 13C NMR (100.6 MHz, CDCl3)
4.1.17. 4-Benzenesulfonyl-6-methoxyl-1-ethyl-3,4-dihydro-2(1H)-
quinolinone 6q. White crystals; mp 180e181 ꢁC; IR (KBr) 2935,
1660, 1515, 1305, 1040 cmꢂ1
;
1H NMR (400 MHz, CDCl3)
d
1.02 (t,
d
20.1 (2ꢀ q), 20.8 (q), 29.4 (t), 30.8 (t), 39.4 (t), 62.2 (s), 128.9 (2ꢀ
J¼7.1 Hz, 3H, CH3), 3.00 (dd, J¼17.7, 7.8 Hz, 1H, CH), 3.16 (dq, J¼14.3,
7.1 Hz, 1H, NCH), 3.33 (d, J¼17.7 Hz, 1H, CH), 3.56 (dq, J¼14.3, 7.1 Hz,
1H, NCH), 3.80 (s, 3H, OCH3), 4.26 (d, J¼7.8 Hz, 1H, SO2CH),
6.74e6.80 (m, 1H, ArH), 6.90e6.95 (m, 2H, ArH), 7.43 (t, J¼7.7 Hz,
2H, ArH), 7.57 (d, J¼7.7 Hz, 2H, ArH), 7.59 (t, J¼7.7 Hz, 1H, ArH); 13C
d), 129.2 (2ꢀ d), 129.9 (s), 137.62 (s), 137.67 (2ꢀ s), 149.5 (2ꢀ d),
174.0 (s), 184.4 (s); Anal. Calcd for C19H21NO2: C, 77.26; H, 7.17; N,
4.74. Found: C, 76.90; H, 7.17; N, 4.74.
4.1.23. 4-Methyl-1-(2,4,6-trimethylbenzyl)-1-aza-spiro[4,5]-deca-
NMR (100.6 MHz, CDCl3)
d
12.4 (q), 31.8 (t), 37.5 (t), 55.7 (q), 63.3
6,9-diene-2,8-dione 7u. White crystals; mp 127e128 ꢁC; IR (KBr)
(d), 116.0 (d), 116.5 (d), 116.6 (d), 117.1 (s), 128.8 (2ꢀ d), 129.5 (2ꢀ d),
133.6 (s), 134.1 (d), 136.0 (s), 155.0 (s), 164.1 (s); Anal. Calcd for
C18H19NO4S: C, 62.59; H, 5.54; N, 4.06. Found: C, 62.49; H, 5.54; N,
4.06.
2960, 1700, 1670, 1380 cmꢂ1 1H NMR (400 MHz, CDCl3)
; d 2.15 (s,
6H, 2ꢀ CH3), 2.23 (s, 3H, CH3), 2.23e2.39 (m, 4H, CHþCH3),
2.68e2.83 (m, 2H, CH2), 4.10 (d, J¼15.1 Hz, 1H, NCH), 4.91 (d,
J¼15.1 Hz, 1H, NCH), 5.88 (dd, J¼10.2, 2.0 Hz, 1H, CH), 6.02 (dd,
J¼10.2, 3.0 Hz, 1H, CH), 6.32 (dd, J¼10.2, 2.0 Hz, 1H, CH), 6.61 (dd,
J¼10.2, 3.0 Hz, 1H, CH), 6.73 (s, 2H, ArH); 13C NMR (100.6 MHz,
4.1.18. 1-Ethyl-4-ethoxycarbonyl-1-azaspiro[4,5]deca-6,9-diene-2,8-
dione 7p. White crystals; mp 91e92 ꢁC; IR (KBr) 2930, 1730, 1695,
CDCl3)
d
13.6 (q), 20.0 (2ꢀ q), 20.8 (q), 37.6 (t), 37.7 (t), 39.5 (t), 66.2
1670, 1225 cmꢂ1; 1H NMR (400 MHz, CDCl3)
d
1.11 (t, J¼7.2 Hz, 3H,
(s), 128.9 (d), 129.2 (2ꢀ d), 130.1 (s), 132.0 (d), 137.6 (s), 137.7 (2ꢀ s),
146.7 (d), 149.2 (d), 173.7 (s), 184.7 (s); Anal. Calcd for C20H23NO2: C,
77.64; H, 7.49; N, 4.53. Found: C, 77.70; H, 7.52; N, 4.48.
CH3), 1.14 (t, J¼7.1 Hz, 3H, CH3), 2.67 (dd, J¼17.2, 9.1 Hz, 1H, CH),
2.98e3.12 (m, 2H, 2ꢀ CH), 3.17e3.33 (m, 2H, NCH2), 4.00e4.15 (m,
2H, OCH2), 6.34 (dd, J¼10.1, 1.9 Hz, 1H, CH), 6.45 (dd, J¼10.0, 1.9 Hz,
1H, CH), 6.69 (dd, J¼10.1, 3.0 Hz, 1H, CH), 6.76 (dd, J¼10.0, 3.0 Hz,
4.1.24. 4-Benzenesulfonyl-1-(2,4,6-trimethylbenzyl)-1-aza-spiro[4,5]-
deca-6,9-diene-2,8-dione 7v. White crystals; mp 210e211 ꢁC; IR
(KBr) 2985, 1695, 1395, 1310, 1150 cmꢂ1; 1H NMR (400 MHz, CDCl3)
1H, CH); 13C NMR (100.6 MHz, CDCl3)
d 14.0 (q), 15.0 (q), 31.7 (t),
36.4 (t), 47.2 (d), 61.9 (t), 63.5 (s), 131.35 (d), 131.39 (d), 145.4 (d),
148.7 (d), 168.7 (s), 172.4 (s), 184.1 (s); Anal. Calcd for C14H17NO4: C,
63.87; H, 6.51; N, 5.32. Found: C, 63.60; H, 6.54; N, 5.25.
d
2.08 (s, 6H, 2ꢀ CH3), 2.20 (s, 3H, CH3), 2.88 (dd, J¼17.1, 8.8 Hz, 1H,
CH), 3.26 (dd, J¼17.1, 11.2 Hz, 1H, CH), 3.79 (dd, J¼11.2, 8.8 Hz, 1H,
SO2CH), 4.11 (d, J¼15.3 Hz, 1H, NCH), 4.83 (d, J¼15.3 Hz, 1H, NCH),
5.52 (dd, J¼10.1, 1.9 Hz,1H, CH), 5.78 (dd, J¼10.1, 3.1 Hz,1H, CH), 6.36
(dd, J¼10.2, 1.9 Hz, 1H, CH), 6.69 (s, 2H, ArH), 6.90 (dd, J¼10.2, 3.1 Hz,
1H, CH), 7.49 (t, J¼7.7 Hz, 2H, ArH), 7.63 (t, J¼7.7 Hz,1H, ArH), 7.72 (d,
4.1.19. 4-Benzenesulfonyl-1-ethyl-1-aza-spiro[4,5]-deca-6,9-diene-
2,8-dione 7q. White crystals; mp 187e188 ꢁC; IR (KBr) 2985, 1695,
1395, 1310, 1150 cmꢂ1; 1H NMR (400 MHz, CDCl3)
d
1.05 (t, J¼7.1 Hz,
3H, CH3), 2.78 (dd, J¼16.8, 8.8 Hz, 1H, CH), 2.85 (dq, J¼14.2, 7.1 Hz,
1H, NCH), 3.13e3.25 (m, 2H, NCHþCH), 3.95 (dd, J¼11.6, 8.8 Hz, 1H,
SO2CH), 6.09 (dd, J¼10.1, 1.8 Hz, 1H, CH), 6.39 (dd, J¼10.1, 3.1 Hz, 1H,
CH), 6.46 (dd, J¼10.1, 1.8 Hz, 1H, CH), 7.01 (dd, J¼10.1, 3.1 Hz, 1H,
J¼7.7 Hz, 2H, ArH); 13C NMR (100.6 MHz, CDCl3)
d
20.1 (2ꢀ q), 20.8
(q), 30.6 (t), 39.2 (t), 62.3 (s), 64.2 (d), 128.5 (2ꢀ d), 129.33 (2ꢀ d),
129.37 (s), 129.6 (3ꢀ d), 132.0 (d), 134.7 (d), 137.5 (2ꢀ s), 137.7 (s),
137.8 (s), 142.9 (d), 145.5 (d), 169.4 (s), 183.8 (s); Anal. Calcd for

C.-P. Chuang et al. / Tetrahedron 69 (2013) 3293e3301
3299
C25H25NO4S: C, 68.94; H, 5.79; N, 3.22. Found: C, 68.97; H, 5.72; N,
3.23.
3.63e3.72 (m, 1H, OCH), 6.62 (d, J¼10.1 Hz, 1H, CH), 6.93 (d,
J¼10.1 Hz, 1H, CH), 7.21 (d, J¼7.7 Hz, 1H, ArH), 7.50 (t, J¼7.7 Hz, 1H,
ArH), 7.58 (t, J¼7.7 Hz, 1H, ArH), 8.16 (d, J¼7.7 Hz, 1H, ArH); 13C
4.1.25. rel-(1R,30S)-30-(Benzenesulfonyl)-10-ethyl-4H-spiro[naphtha-
NMR (100.6 MHz, CDCl3) d 13.3 (q), 14.5 (q), 31.5 (t), 37.0 (t), 47.9 (d),
lene-1,20-pyrrolidin]-4,50-dione 9a. White needles; mp 164e165 ꢁC;
61.5 (t), 65.5 (s), 126.1 (d), 126.9 (d), 129.2 (d), 130.3 (d), 132.0 (s),
132.9 (d), 139.9 (s), 150.2 (d), 168.4 (s), 173.1 (s), 183.4 (s); Anal.
Calcd for C18H19NO4: C, 68.99: H, 6.11; N, 4.47. Found: C, 68.73; H,
6.10; N, 4.46.
IR (KBr) 1700, 1300, 1155, 1085, 590 cmꢂ1 1H NMR (400 MHz,
;
CDCl3)
d
0.89 (t, J¼7.1 Hz, 3H, CH3), 2.77 (dq, J¼14.2, 7.1 Hz, 1H,
NCH), 2.95 (dq, J¼14.2, 7.1 Hz, 1H, NCH), 3.02 (dd, J¼17.0, 8.7 Hz, 1H,
CH), 3.37 (dd, J¼17.0, 11.0 Hz, 1H, CH), 4.36 (dd, J¼11.4, 8.7 Hz, 1H,
CH), 6.60 (d, J¼10.3 Hz, 1H, CH), 7.07 (d, J¼10.3 Hz, 1H, CH), 7.24 (t,
J¼7.7 Hz, 2H, ArH), 7.36 (d, J¼7.7 Hz, 1H, ArH), 7.40 (t, J¼7.7 Hz, 1H,
ArH), 7.465 (t, J¼7.7 Hz, 1H, ArH), 7.473 (d, J¼7.7 Hz, 2H, ArH), 7.60
(t, J¼7.7 Hz, 1H, ArH), 7.85 (d, J¼7.7 Hz, 1H, ArH); 13C NMR
4.1.30. 10-Benzyl-10H,4H-spiro[cyclohexa-2,5-diene-1,40quinoline]-
20,4(30H)-dione 17a. White crystals; mp 139e140 ꢁC; IR (KBr) 1665,
1630,1380,1295, 850 cmꢂ1; 1H NMR (400 MHz, CDCl3)
d 2.92 (s, 2H,
CH2), 5.26 (s, 2H, NCH2), 6.39 (d, J¼10.3 Hz, 2H, CH), 6.97 (d,
J¼10.3 Hz, 2H, CH), 7.03 (t, J¼7.8 Hz, 1H, ArH), 7.04 (t, J¼7.8 Hz, 1H,
ArH), 7.08 (dd, J¼7.8, 1.5 Hz, 1H, ArH), 7.23 (td, J¼7.8, 1.5 Hz, 1H,
ArH), 7.25e7.30 (m, 3H, ArH), 7.31e7.37 (m, 2H, ArH); 13C NMR
(100.6 MHz, CDCl3)
d 13.8 (q), 30.1 (t), 36.6 (t), 63.7 (s), 68.2 (d),
126.0 (d), 127.0 (d), 128.0 (2ꢀ d), 129.1 (d), 129.2 (2ꢀ d), 131.2 (d),
131.6 (s), 133.3 (d), 134.1 (d), 137.1 (s), 140.7 (s), 143.7 (d), 170.2 (s),
182.2 (s); Anal. Calcd for C21H19NO4S: C, 66.12; H, 5.02; N, 3.67.
Found: C, 65.76; H, 4.92; N, 3.58.
(100.6 MHz, CDCl3)
d 40.7 (t), 43.1 (s), 46.3 (t), 116.5 (d), 124.0 (s),
124.4 (s), 126.5 (2ꢀ d), 126.6 (d), 127.4 (d), 128.8 (2ꢀ d), 129.3 (d),
129.5 (2ꢀ d), 136.2 (s), 139.0 (s), 149.1 (2ꢀ d), 166.7 (s), 184.8 (s);
Anal. Calcd for C21H17NO2: C, 79.98; H, 5.43; N, 4.44. Found: C,
79.65; H, 5.31; N, 4.36.
4.1.26. rel-(1R,30S)-30-Ethoxycarbonyl-10-ethyl-4H-spiro[naphtha-
lene-1,20-pyrrolidin]-4,50-dione 9b. White crystals; mp 136e137 ꢁC;
IR (KBr) 1730,1695,1600,1235, 770 cmꢂ1; 1H NMR (400 MHz, CDCl3)
d
0.98 (t, J¼7.1 Hz, 6H, 2ꢀ CH3), 2.78 (dd, J¼17.4, 9.4 Hz,1H, CH), 2.84
4.1.31. 10-Benzyl-60-methyl-10H,4H-spiro[cyclohexa-2,5-diene-
(dq, J¼14.3, 7.1 Hz, 1H, NCH), 3.17 (dd, J¼17.4, 11.0 Hz, 1H, CH), 3.24
(dq, J¼14.3, 7.1 Hz, 1H, NCH), 3.54 (dd, J¼11.0, 9.4 Hz, 1H, CH),
3.87e4.04 (m, 2H, OCH2), 6.52 (d, J¼10.3 Hz, 1H, CH), 6.83 (d,
J¼10.3 Hz, 1H, CH), 7.51 (d, J¼7.7 Hz, 1H, ArH), 7.55 (t, J¼7.7 Hz, 1H,
ArH), 7.71 (t, J¼7.7 Hz,1H, ArH), 8.20 (d, J¼7.7 Hz,1H, ArH); 13C NMR
1,40quinoline]-20,4(30H)-dione 17b. White crystals; mp 185e186 ꢁC;
IR (KBr) 1665, 1500, 1375, 1220, 860 cmꢂ1 1H NMR (400 MHz,
;
CDCl3) d 2.23 (s, 3H, CH3), 2.90 (s, 2H, CH2), 5.24 (s, 2H, NCH2), 6.40
(d, J¼10.1 Hz, 2H, CH), 6.86 (d, J¼1.6 Hz, 1H, ArH), 6.93 (d, J¼8.3 Hz,
1H, ArH), 6.96 (d, J¼10.1 Hz, 2H, CH), 7.02 (dd, J¼8.3, 1.6 Hz, 1H,
ArH), 7.24e7.29 (m, 3H, ArH), 7.31e7.37 (m, 2H, ArH); 13C NMR
(100.6 MHz, CDCl3) d 13.7 (q), 13.9 (q), 31.9 (t), 36.7 (t), 52.4 (d), 61.6
(t), 65.0 (s),126.3 (d),126.8 (d),128.9 (d),131.0 (d),132.0 (s),133.6 (d),
142.9 (s), 146.2 (d), 168.9 (s), 173.0 (s), 183.0 (s); Anal. Calcd for
C18H19NO4: C, 68.99: H, 6.11; N, 4.47. Found: C, 68.80; H, 6.14; N, 4.43.
(100.6 MHz, CDCl3) d 20.5 (q), 40.9 (t), 43.2 (s), 46.3 (t), 116.5 (d),
124.2 (s),126.6 (2ꢀ d),127.2 (d),127.4 (d),128.8 (2ꢀ d),129.5 (2ꢀ d),
129.8 (d), 133.8 (s), 136.4 (s), 136.6 (s), 149.4 (2ꢀ d), 166.7 (s), 184.9
(s); Anal. Calcd for C22H19NO2: C, 80.22; H, 5.81; N, 4.25. Found: C,
80.27; H, 5.79; N, 4.16.
4.1.27. 10-Ethyl-4H-spiro[naphthalene-1,20-pyrrolidin]-4,50-dione
9c. White powder; mp 123e124 ꢁC; IR (KBr) 2980, 1675, 1455,
1300, 775 cmꢂ1; 1H NMR (400 MHz, CDCl3)
d
0.97 (t, J¼7.1 Hz, 3H,
4.1.32. 10-Benzyl-60-chloro-10H,4H-spiro[cyclohexa-2,5-diene-
1,40quinoline]-20,4(30H)-dione 17c. White crystals; mp 208e209 ꢁC;
IR (KBr) 1680,1490,1370,1225, 860 cmꢂ1; 1H NMR (400 MHz, CDCl3)
CH3), 2.25e2.40 (m, 2H, CH2), 2.63e2.81 (m, 2H, CH2), 2.84 (dq,
J¼14.3, 7.1 Hz, 1H, NCH), 3.27 (dq, J¼14.3, 7.1 Hz, 1H, NCH), 6.50 (d,
J¼10.2 Hz, 1H, CH), 6.94 (d, J¼10.2 Hz, 1H, CH), 7.39 (d, J¼7.8 Hz, 1H,
ArH), 7.50 (dt, J¼7.8,1.2 Hz,1H, ArH), 7.64 (dt, J¼7.8,1.2 Hz,1H, ArH),
d
2.92 (s, 2H, CH2), 5.24 (s, 2H, NCH2), 6.43 (d, J¼10.1 Hz, 2H, CH), 6.93
(d, J¼10.1 Hz, 2H, CH), 6.96 (d, J¼8.8 Hz, 1H, ArH), 7.04 (d, J¼2.6 Hz,
1H, ArH), 7.19 (dd, J¼8.8, 2.6 Hz, 1H, ArH), 7.22e7.31 (m, 3H, ArH),
8.19 (dd, J¼7.8, 1.2 Hz, 1H, ArH); 13C NMR (100.6 MHz, CDCl3)
d 14.2
(q), 29.5 (t), 34.3 (t), 36.4 (t), 63.6 (s), 126.0 (d), 127.0 (d), 128.5 (d),
128.8 (d), 131.0 (s), 133.5 (d), 144.5 (s), 150.8 (d), 174.9 (s), 183.3 (s);
Anal. Calcd for C15H15NO2: C, 74.67; H, 6.27; N, 5.81. Found: C, 74.35;
H, 6.33; N, 5.65.
7.32e7.38 (m, 2H, ArH); 13C NMR (100.6 MHz, CDCl3)
d 40.5 (t), 42.9
(s), 46.3 (t),117.8 (d),126.2 (s),126.5 (2ꢀ d),126.6 (d),127.6 (d),129.0
(2ꢀ d),129.2 (s),129.3 (d),130.0 (2ꢀ d),135.8 (s),137.6 (s),148.2 (2ꢀ
d), 166.4 (s), 184.4 (s); Anal. Calcd for C21H16ClNO2: C, 72.10; H, 4.61;
N, 4.00. Found: C, 72.00; H, 4.67; N, 4.00.
4.1.28. rel-(1S,30S)-30-(Benzenesulfonyl)-10-ethyl-4H-spiro[naphtha-
lene-1,20-pyrrolidine]-4,50-dione 10a. White needles; mp 167e168 ꢁC;
IR (KBr) 1685, 1295, 1150, 1085, 585 cmꢂ1; 1H NMR (400 MHz, CDCl3)
4.1.33. 10-Benzyl-3-methyl-10H,4H-spiro[cyclohexa-2,5-diene-
1,40quinoline]-20,4(30H)-dione 17d. White crystals; mp 162e163 ꢁC;
d
1.00 (t, J¼7.2 Hz, 3H, CH3), 2.69 (dq, J¼14.3, 7.2 Hz, 1H, NCH), 2.84
IR (KBr) 1665, 1635, 1495, 1380, 765 cmꢂ1 1H NMR (400 MHz,
;
(dd, J¼16.9, 9.3 Hz, 1H, CH), 3.29 (dq, J¼14.3, 7.2 Hz, 1H, NCH), 3.36
(dd, J¼16.9, 11.5 Hz, 1H, CH), 4.04 (dd, J¼11.5, 9.3 Hz, 1H, CH), 6.47 (d,
J¼10.1 Hz, 1H, CH), 6.72 (d, J¼10.1 Hz, 1H, ArH), 7.24e7.30 (m, 1H,
ArH), 7.40e7.47 (m, 4H, ArH), 7.55e7.64 (m, 3H, ArH), 8.16e8.22 (m,
CDCl3)
d
1.94 (d, J¼1.4 Hz, 3H, CH3), 2.86 (d, J¼15.4 Hz, 1H, CH), 2.93
(d, J¼15.4 Hz, 1H, CH), 5.22 (d, J¼16 Hz, 1H, NCH), 5.32 (d, J¼16 Hz,
1H, NCH), 6.41 (d, J¼9.9 Hz, 1H, CH), 6.71e6.75 (m, 1H, CH), 6.94
(dd, J¼9.9, 3.0 Hz, 1H, CH), 7.01 (t, J¼7.8 Hz, 1H, ArH), 7.03 (d,
J¼7.8 Hz, 1H, ArH), 7.07 (dd, J¼7.8, 1.6 Hz, 1H, ArH), 7.22 (td, J¼7.8,
1.6 Hz,1H, ArH), 7.27e7.31 (m, 3H, ArH), 7.32e7.38 (m, 2H, ArH); 13C
1H, ArH); 13C NMR (100.6 MHz, CDCl3)
d 14.5 (q), 31.5 (t), 36.7 (t), 64.3
(d), 64.5 (s), 127.1 (d), 128.0 (d), 128.2 (2ꢀ d), 129.4 (2ꢀ d), 129.9 (d),
131.4 (d), 132.4 (d), 132.7 (s), 134.3 (d), 136.7 (s), 138.0 (s), 147.8 (d),
170.3 (s), 182.6 (s); Anal. Calcd for C21H19NO4S: C, 66.12; H, 5.02; N,
3.67. Found C, 65.88; H, 4.97; N, 3.62.
NMR (100.6 MHz, CDCl3)
d 16.0 (q), 41.0 (t), 43.2 (s), 46.3 (t), 116.5
(d), 123.9 (d), 125.1 (s), 126.4 (d), 126.5 (2ꢀ d), 127.4 (d), 128.8 (2ꢀ
d), 129.1 (d), 129.4 (d), 135.8 (s), 136.4 (s), 139.0 (s), 144.4 (d), 149.0
(d), 167.1 (s), 185.5 (s); Anal. Calcd for C22H19NO2: C, 80.22; H, 5.81;
N, 4.25. Found: C, 80.28; H, 5.78; N, 4.18.
4.1.29. rel-(1S,30S)-30-Ethoxycarbonyl-10-ethyl-4H-spiro[naphthalene-
1,20-pyrrolidin]-4,50-dione 10b. White needles; mp 140e141 ꢁC; IR
(KBr) 1735, 1695, 1600, 1215, 770 cmꢂ1
;
1H NMR (400 MHz, CDCl3)
4.1.34. 10-Benzyl-3,60-dimethyl-10H,4H-spiro[cyclohexa-2,5-diene-
d
0.80 (t, J¼7.2 Hz, 3H, CH3), 1.03 (t, J¼7.2 Hz, 3H, CH3),
1,40quinoline]-20,4(30H)-dione 17e. White powder; mp 125e126 ꢁC;
2.74 (dd, J¼17.2, 9.8 Hz, 1H, CH), 2.84 (dq, J¼14.3, 7.2 Hz, 1H,
NCH), 3.27e3.40 (m, 2H, NCHþCH), 3.40e3.51 (m, 2H, OCHþCH),
IR (KBr) 1665, 1640, 1500, 1380, 725 cmꢂ1 1H NMR (400 MHz,
;
CDCl3)
d
1.94 (d, J¼1.2 Hz, 3H, CH3), 2.23 (s, 3H, CH3), 2.83 (d,

3300
C.-P. Chuang et al. / Tetrahedron 69 (2013) 3293e3301
J¼15.5 Hz, 1H, CH), 2.90 (d, J¼15.5 Hz, 1H, CH), 5.19 (d, J¼15.9 Hz,
1H, NCH), 5.29 (d, J¼15.9 Hz, 1H, NCH), 6.41 (d, J¼9.6 Hz, 1H, CH),
6.69e6.73 (m, 1H, CH), 6.84 (d, J¼1.3 Hz, 1H, ArH), 6.92 (d, J¼8.3 Hz,
1H, ArH), 6.93 (dd, J¼9.6, 3.7 Hz, 1H, CH), 7.01 (dd, J¼8.3, 1.3 Hz, 1H,
ArH), 7.25e7.29 (m, 3H, ArH), 7.31e7.37 (m, 2H, ArH); 13C NMR
(d), 126.5 (2ꢀ d), 126.7 (d), 126.8 (s), 127.6 (d), 128.9 (2ꢀ d), 129.12
(s), 129.19 (d), 130.7 (d), 132.1 (d), 136.1 (s), 137.6 (s) 145.6 (d), 149.5
(d), 169.5 (s), 184.9 (s); Anal. Calcd for C22H18ClNO2: C, 72.62; H,
4.99; N, 3.85. Found: C, 72.48; H, 4.88; N, 3.81.
(100.6 MHz, CDCl3)
d
16.0 (q), 20.5 (q), 41.1 (t), 43.2 (s), 46.3 (t),
4.1.39. N-Benzyl-9-methoxy-5H-dibenzo[b,d]azepin-6(7H)-one
116.5 (d), 125.0 (s), 126.6 (2ꢀ d), 127.0 (d), 127.4 (d), 128.8 (2ꢀ d),
129.4 (d), 129.6 (d), 133.7 (s), 135.8 (s), 136.5 (s), 136.7 (s), 144.6 (d),
149.3 (d), 167.1 (s), 185.7 (s); HRMS (EI) calcd for C23H21NO2Na m/e
366.1470, found: 366.1472.
18a. White powder; mp 180e181 ꢁC; IR (KBr) 1665, 1485, 1375,
1255, 855 cmꢂ1; 1H NMR (400 MHz, CDCl3)
d
3.51 (d, J¼12.1 Hz, 1H,
CH), 3.59 (d, J¼12.1 Hz, 1H, CH), 3.88 (s, 3H, OCH3), 4.92 (d,
J¼15.6 Hz, 1H, NCH), 5.17 (d, J¼15.6 Hz, 1H, NCH), 6.89e6.93 (m, 2H,
ArH), 6.95 (s, 1H, ArH), 6.97e6.98 (m, 1H, ArH), 7.10e7.15 (m, 3H,
ArH), 7.22 (td, J¼7.7, 1.6 Hz, 1H, ArH), 7.27 (td, J¼7.7, 1.6 Hz, 1H, ArH),
7.32 (dd, J¼7.7, 1.6 Hz, 1H, ArH), 7.43 (d, J¼8.2 Hz, 1H, ArH), 7.47 (dd,
4.1.35. 10-Benzyl-60-chloro-3-methyl-10H,4H-spiro[cyclohexa-2,5-
diene-1,40quinoline]-20,4(30H)-dione 17f. White crystals; mp
185e186 ꢁC; IR (KBr) 1665, 1640, 1420, 1375, 720 cmꢂ1
;
1H NMR
J¼7.7, 1.6 Hz, 1H, ArH); 13C NMR (100.6 MHz, CDCl3)
d 42.4 (t), 51.8
(400 MHz, CDCl3)
d
1.95 (d, J¼1.4 Hz, 3H, CH3), 2.86 (d, J¼15.6 Hz,
(t), 55.4 (q), 112.3 (d), 114.1 (d), 123.1 (d), 125.6 (d), 126.78 (d),
126.80 (2ꢀ d), 127.7 (d), 128.3 (2ꢀ d), 129.06 (d), 129.09 (s), 129.7
(d), 134.6 (s), 136.5 (s), 137.4 (s), 140.2 (s), 160.3 (s), 170.8 (s);
HMRS(EI) calcd for C22H19NO2 m/e 329.1416, found m/e 329.1411.
1H, CH), 2.92 (d, J¼15.6 Hz, 1H, CH), 5.20 (d, J¼16 Hz, 1H, NCH), 5.29
(d, J¼16 Hz, 1H, NCH), 6.43 (d, J¼9.9 Hz, 1H, CH), 6.67e6.70 (m, 1H,
CH), 6.90 (dd, J¼9.9, 3.1 Hz, 1H, CH), 6.96 (d, J¼8.8 Hz, 1H, ArH), 7.03
(d, J¼2.4 Hz,1H, ArH), 7.17 (dd, J¼8.8, 2.4 Hz,1H, ArH), 7.23e7.31 (m,
3H, ArH), 7.32e7.38 (m, 2H, ArH); 13C NMR (100.6 MHz, CDCl3)
4.1.40. N-Benzyl-9-methoxy-2-methyl-5H-dibenzo[b,d]azepin-
d
16.0 (q), 40.8 (t), 43.0 (s), 46.3 (t), 117.8 (d), 126.49 (d), 126.57 (2ꢀ
6(7H)-one 18b. White powder; mp 146e147 ꢁC; IR (KBr) 1660,
d), 127.0 (s), 127.6 (d), 128.92 (2ꢀ d), 128.96 (d), 129.2 (s), 129.9 (d),
136.0 (s), 136.5 (s), 137.7 (s), 143.3 (d), 148.0 (d), 166.8 (s), 185.2 (s);
Anal. Calcd for C22H18ClNO2: C, 72.62; H, 4.99; N, 3.85. Found: C,
72.33; H, 5.09; N, 3.83.
1605, 1380,1235, 845 cmꢂ1; 1H NMR (400 MHz, CDCl3)
d 2.35 (s, 3H,
CH3), 3.51 (d, J¼12.2 Hz, 1H, CH), 3.57 (d, J¼12.2 Hz, 1H, CH), 3.87 (s,
3H, OCH3), 4.88 (d, J¼15.7 Hz, 1H, NCH), 5.16 (d, J¼15.7 Hz, 1H,
NCH), 6.87e6.92 (m, 2H, ArH), 6.94 (s, 1H, ArH), 6.95e6.97 (m, 1H,
ArH), 7.07 (dd, J¼8.3, 1.7 Hz, 1H, ArH), 7.10e7.15 (m, 3H, ArH), 7.20
(d, J¼8.3 Hz, 1H, ArH), 7.25 (s, 1H, ArH), 7.42 (d, J¼8.3 Hz, 1H, ArH);
4.1.36. 10-Benzyl-30-methyl-10H,4H-spiro[cyclohexa-2,5-diene-
1,40quinoline]-20,4(30H)-dione 17g. White crystals; mp 139e140 ꢁC;
13C NMR (100.6 MHz, CDCl3)
d 20.9 (q), 42.5 (t), 51.7 (t), 55.4 (q),
IR (KBr) 1665, 1490, 1450, 1375, 850 cmꢂ1
;
1H NMR (400 MHz,
112.3 (d), 114.1 (d), 122.9 (d), 126.7 (d), 126.8 (2ꢀ d), 128.2 (2ꢀ d),
128.5 (d), 129.0 (d), 129.2 (s), 130.2 (d), 134.3 (s), 135.2 (s), 136.5 (s),
137.5 (s), 137.8 (s), 160.2 (s), 170.8 (s); Anal. Calcd for C23H21NO2: C,
80.44; H, 6.16 N, 4.08. Found: C, 80.07; H, 6.19; N, 3.98.
CDCl3)
d
1.24 (d, J¼7.0 Hz, 3H, CH3), 3.04 (q, J¼7.0 Hz, 1H, CH), 5.02
(d, J¼16.1 Hz, 1H, NCH), 5.49 (d, J¼16.1 Hz, 1H, NCH), 6.32 (dd,
J¼10.1, 1.7 Hz, 1H, CH), 6.62 (dd, J¼10.1, 1.7 Hz, 1H, CH), 6.80 (dd,
J¼10.1, 3.1 Hz, 1H, CH), 6.94 (dd, J¼10.1, 3.1 Hz, 1H, CH), 6.98e7.06
(m, 2H, ArH), 7.09 (dd, J¼7.6, 1.3 Hz, 1H, ArH), 7.20e7.30 (m, 4H,
4.1.41. N-Benzyl-2-chloro-9-methoxy-5H-dibenzo[b,d]azepin-6(7H)-
one 18c. White powder; mp 161e162 ꢁC; IR (KBr) 1670, 1605, 1310,
ArH), 7.32e7.37 (m, 2H, ArH); 13C NMR (100.6 MHz, CDCl3)
d
10.6
(q), 42.4 (d), 46.9 (t), 47.6 (s), 116.5 (d), 123.9 (d), 125.0 (s), 126.5 (2ꢀ
d), 126.7 (d), 127.4 (d), 128.8 (2ꢀ d), 129.4 (d), 130.2 (d), 131.6 (d),
136.5 (s), 139.0 (s), 146.6 (d), 150.6 (d), 169.8 (s), 185.3 (s); Anal.
Calcd for C22H19NO2: C, 80.22; H, 5.87; N, 4.25. Found: C, 80.29; H,
5.74; N, 4.14.
1245, 810 cmꢂ1; 1H NMR (400 MHz, CDCl3)
d
3.48 (d, J¼12.5 Hz, 1H,
CH), 3.60 (d, J¼12.5 Hz, 1H, CH), 3.88 (s, 3H, OCH3), 4.85 (d,
J¼15.6 Hz, 1H, NCH), 5.18 (d, J¼15.6 Hz, 1H, NCH), 6.86e6.90 (m, 2H,
ArH), 6.93e6.99 (m, 2H, ArH), 7.11e7.16 (m, 3H, ArH), 7.22 (dd,
J¼8.5, 2.3 Hz, 1H, ArH), 7.26 (d, J¼8.5 Hz, 1H, ArH), 7.40 (d, J¼8.5 Hz,
1H, ArH), 7.44 (d, J¼2.3 Hz, 1H, ArH); 13C NMR (100.6 MHz, CDCl3)
4.1.37. 10-Benzyl-30,60-dimethyl-10H,4H-spiro[cyclohexa-2,5-diene-
1,40quinoline]-20,4(30H)-dione 17h. White crystals; mp 184e185 ꢁC;
IR (KBr) 1670,1500,1375,1215, 815 cmꢂ1; 1H NMR (400 MHz, CDCl3)
d
42.3 (t), 51.7 (t), 55.5 (q),112.6 (d),114.3 (d),124.6 (d),126.8 (2ꢀ d),
127.0 (d), 127.6 (d), 127.9 (s), 128.4 (2ꢀ d), 129.0 (d), 129.4 (d), 130.8
(s), 136.2 (s), 136.5 (s), 137.0 (s), 138.6 (s), 160.7 (s), 170.5 (s); HMRS
(EI) calcd for C22H18ClNO2 m/e 363.1026, found m/e 363.1021.
d
1.23 (d, J¼7.1 Hz, 3H, CH3), 2.23 (s, 3H, CH3), 3.01 (q, J¼7.1 Hz, 1H,
CH), 5.03 (d, J¼16.1 Hz, 1H, NCH), 5.44 (d, J¼16.1 Hz, 1H, NCH), 6.31
(dd, J¼10.2,1.8 Hz,1H, CH), 6.61 (dd, J¼10.2,1.8 Hz,1H, CH), 6.78 (dd,
J¼10.2, 3.1 Hz, 1H, CH), 6.87 (d, J¼1.3 Hz, 1H, ArH), 6.92 (d, J¼8.3 Hz,
1H, ArH), 6.93 (dd, J¼10.2, 3.1 Hz,1H, CH), 7.03 (dd, J¼8.3,1.3 Hz,1H,
ArH), 7.24e7.29 (m, 3H, ArH), 7.31e7.37 (m, 2H, ArH); 13C NMR
4.1.42. N-Benzyl-9-methoxy-10-methyl-5H-dibenzo[b,d]azepin-
6(7H)-one 18d. White powder; mp 126e127 ꢁC; IR (KBr) 1665,
1605, 1380, 1270, 705 cmꢂ1; 1H NMR (400 MHz, CDCl3)
d 2.29 (s, 3H,
CH3), 3.48 (d, J¼12.1 Hz, 1H, CH), 3.58 (d, J¼12.1 Hz, 1H, CH), 3.91 (s,
3H, OCH3), 4.96 (d, J¼15.8 Hz, 1H, NCH), 5.09 (d, J¼15.8 Hz, 1H,
NCH), 6.86 (s, 1H, ArH), 6.91e6.96 (m, 2H, ArH), 7.12e7.17 (m, 3H,
ArH), 7.23 (td, J¼7.4, 1.9 Hz, 1H, ArH), 7.24e7.27 (m, 1H, ArH),
7.28e7.32 (m, 2H, ArH), 7.49 (dd, J¼7.2, 2.0 Hz, 1H, ArH); 13C NMR
(100.6 MHz, CDCl3) d 10.6 (q), 20.5 (q) 42.5 (d), 46.9 (t), 47.6 (s),116.4
(d),124.9 (s),126.6 (2ꢀ d),127.3 (d),127.4 (d),128.8 (2ꢀ d),129.8 (d),
130.2 (d), 131.6 (d), 133.7 (s), 136.6 (s), 136.7 (s), 146.8 (d), 150.8 (d),
169.7 (s), 185.4 (s); Anal. Calcd for C23H21NO2: C, 80.44; H, 6.16; N,
4.08. Found: C, 80.44; H, 6.18; N, 3.99.
(100.6 MHz, CDCl3)
d 16.1 (q), 42.2 (t), 51.9 (t), 55.5 (q), 109.1 (d),
123.1 (d), 125.5 (d), 126.1 (s), 126.8 (2ꢀ d), 127.5 (2ꢀ d), 128.28 (2ꢀ
d), 128.34 (s), 129.7 (d), 130.0 (d), 133.8 (s), 134.7 (s), 137.6 (s), 140.3
(s), 158.5 (s), 171.1 (s); HMRS (EI) calcd for C23H22NO2 m/e 344.1649,
found m/e 344.1650.
4.1.38. 10-Benzyl-60-chloro-30-methyl-10H,4H-spiro[cyclohexa-
2,5-diene-1,40quinoline]-20,4(30H)-dione 17i. White crystals; mp
163e164 ꢁC; IR (KBr) 1665, 1630, 1370, 1255, 820 cmꢂ1 1H NMR
;
(400 MHz, CDCl3)
d
1.23 (d, J¼7.0 Hz, 3H, CH3), 3.02 (q, J¼7.0 Hz, 1H,
CH), 5.04 (d, J¼16.1 Hz, 1H, NCH), 5.43 (d, J¼16.1 Hz, 1H, NCH), 6.34
(dd, J¼10.1,1.7 Hz,1H, CH), 6.63 (dd, J¼10.1,1.7 Hz,1H, CH), 6.75 (dd,
J¼10.1, 3.2 Hz, 1H, CH), 6.90 (dd, J¼10.1, 3.2 Hz, 1H, CH), 6.96 (d,
J¼8.6 Hz, 1H, ArH), 7.05 (d, J¼2.5 Hz, 1H, ArH), 7.19 (dd, J¼8.6,
2.5 Hz,1H, ArH), 7.21e7.31 (m, 3H, ArH), 7.32e7.38 (m, 2H, ArH); 13C
4.1.43. N-Benzyl-9-methoxy-2,10-dimethyl-5H-dibenzo[b,d]azepin-
6(7H)-one 18e. White powder; mp 117e118 ꢁC; IR (KBr) 1665, 1605,
1375, 1235, 875 cmꢂ1; 1H NMR (400 MHz, CDCl3)
d 2.29 (s, 3H, CH3),
2.36 (s, 3H, CH3), 3.48 (d, J¼12.3 Hz, 1H, CH), 3.55 (d, J¼12.3 Hz, 1H,
CH), 3.90 (s, 3H, OCH3), 4.92 (d, J¼15.8 Hz, 1H, NCH), 5.09 (d,
J¼15.8 Hz, 1H, NCH), 6.85 (s, 1H, ArH), 6.90e6.94 (m, 2H, ArH),
NMR (100.6 MHz, CDCl3)
d 10.6 (q), 42.3 (d), 46.9 (t), 47.3 (s), 117.7

C.-P. Chuang et al. / Tetrahedron 69 (2013) 3293e3301
3301
Lee, W.-H. Tetrahedron 1999, 55, 6109e6118; (d) Wu, Y. L.; Chuang, C.-P.; Lin, P.-Y.
Tetrahedron 2000, 56, 6209e6217.
6. (a) Chatgiliaoglu, C.; Lunazzi, L.; Ingold, K. U. J. Org. Chem. 1983, 48, 3588e3589;
7.03e7.07 (m, 1H, ArH), 7.11e7.15 (m, 2H, ArH), 7.18 (d, J¼8.6 Hz, 1H,
ArH), 7.25e7.29 (m, 3H, ArH); 13C NMR (100.6 MHz, CDCl3)
16.1
d
(q), 20.9 (q), 42.3 (t), 51.8 (t), 55.5 (q), 109.1 (d), 122.9 (d), 126.0 (s),
126.7 (d), 126.8 (2ꢀ d), 128.26 (2ꢀ d), 128.33 (d), 128.5 (s), 129.9 (d),
130.1 (d), 133.8 (s), 134.4 (s), 135.1 (s), 137.7 (s), 137.9 (s), 158.4 (s),
171.1 (s); HMRS (EI) calcd for C24H23NO2 m/e 357.1729, found m/e
357.1727.
(b) Kang, Y.-H.; Kice, J. L. J. Org. Chem. 1984, 49, 1507e1511.
7. Narasaka, K.; Mochizuki, T.; Hayakawa, S. Chem. Lett. 1994, 1705e1708.
8. (a) Patel, M.; McHugh, R. J., Jr.; Cordova, B. C.; Klabe, R. M.; Bacheler, L. T.;
Erickson-Viitanen, S.; Rodgers, J. D. Bioorg. Med. Chem. Lett. 2001, 11,
1943e1945; (b) Yong, S. R.; Ung, A. T.; Pyne, S. G.; Skelton, B. W.; White, A. H.
Tetrahedron 2007, 1191e1199; (c) Ellis, D.; Kuhen, K. L.; Anaclerio, B.; Wu, B.;
Wolff, K.; Yin, H.; Bursulaya, B.; Caldwell, J.; Karanewsky, D.; He, Y. Bioorg. Med.
Chem. Lett. 2006, 16, 4246e4251; (d) Fujioka, T.; Teramoto, S.; Mori, T.;
Hosokawa, T.; Sumida, T.; Tominaga, M.; Yabuuchi, Y. J. Med. Chem. 1992, 35,
3607e3612; (e) Hayashi, H.; Miwa, Y.; Miki, I.; Ichikawa, S.; Yoda, N.; Ishii, A.;
Kono, M.; Suzuki, F. J. Med. Chem. 1992, 35, 4893e4902; (f) Angibaud, P. R.;
Venet, M. G.; Filliers, W.; Broeckx, R.; Ligny, Y. A.; Muller, P.; Poncelet, V. S.; End,
D. W. Eur. J. Org. Chem. 2004, 479e486; (g) Boy, K. M.; Guernon, J. M.; Sit, S.-Y.;
Xie, K.; Hewawasam, P.; Boissard, C. G.; Dworetzky, S. I.; Natale, J.; Gribkoff, V.
K.; Lodge, N.; Starret, J. E. Bioorg. Med. Chem. Lett. 2004, 14, 5089e5093.
9. (a) Jones, G. In Comprehensive Heterocyclic Chemistry; Boulton, A. J., Ed.Mckillop,
A., Ed.; Pergamon: Oxford, 1984; Vol. 2, Chapter 8; (b) Li, K.; Foresee, L. N.;
Tunge, J. A. J. Org. Chem. 2005, 70, 2881e2883.
4.1.44. N-Benzyl-2-chloro-9-methoxy-10-methyl-5H-dibenzo[b,d]
azepin-6(7H)-one 18f. White powder; mp 129e130 ꢁC; IR (KBr)
1672, 1483, 1376, 1260, 872 cmꢂ1; 1H NMR (400 MHz, CDCl3)
d 2.28
(s, 3H, CH3), 3.45 (d, J¼12.5 Hz, 1H, CH), 3.58 (d, J¼12.5 Hz, 1H, CH),
3.91 (s, 3H, OCH3), 4.89 (d, J¼15.6 Hz, 1H, NCH), 5.10 (d, J¼15.6 Hz,
1H, NCH), 6.85 (s, 1H, ArH), 6.88e6.92 (m, 2H, ArH), 7.12e7.17 (m,
4H, ArH), 7.19 (dd, J¼8.5, 2.2 Hz, 1H, ArH), 7.23 (d, J¼8.5 Hz, 1H,
ArH), 7.46 (d, J¼2.2 Hz, 1H, ArH); 13C NMR (100.6 MHz, CDCl3)
d 16.1
10. Fujita, K.-i.; Takahashi, Y.; Owaki, M.; Yamamoto, K.; Yamaguchi, R. Org. Lett.
(q), 42.1 (t), 51.8 (t), 55.5 (q), 109.2 (d), 124.5 (d), 126.4 (s), 126.8 (2ꢀ
d), 127.0 (d), 127.1 (s), 127.4 (d), 128.4 (2ꢀ d), 129.3 (d), 129.9 (d),
130.8 (s), 133.8 (s), 136.3 (s), 137.2 (s), 138.6 (s), 158.9 (s), 170.8 (s);
HMRS (EI) calcd for C23H20ClNO2 m/e 377.1183, found m/e 377.1185.
2004, 6, 2785e2788.
11. (a) Clark, A. J.; Jones, K.; McCarthy, C.; Storey, J. M. D. Tetrahedron Lett. 1991, 32,
2829e2832; (b) Binot, G.; Zard, S. Z. Tetrahedron Lett. 2005, 46, 7503e7506.
12. Okuro, K.; Kai, H.; Alper, H. Tetrahedron: Asymmetry 1997, 8, 2307e2309.
13. Horn, J.; Li, H. Y.; Marsden, S. P.; Nelson, A.; Shearer, R. J.; Campbell, A. J.; House,
D.; Weingarten, G. G. Tetrahedron 2009, 65, 9002e9007.
14. For references on ipso-type free radical cyclization, see: (a) Studer, A.; Bossart,
M. Tetrahedron 2001, 57, 9649e9667; (b) Harrowven, D. C.; Sutton, B. J.;
Coulton, S. Tetrahedron Lett. 2001, 42, 9061e9064; (c) Zhang, W.; Pugh, G.
Tetrahedron 2003, 59, 3009e3018; (d) Ganguly, A. K.; Wang, C. H.; Chan, T. M.;
Ing, Y. H.; Buevich, A. V. Tetrahedron Lett. 2004, 45, 883e886; (e) Kaim, L. E.;
Grimaud, L.; Vieu, E. Org. Lett. 2007, 9, 4171e4173; (f) Robertson, J.; Palframan,
M. J.; Shea, S. A.; Tchabanenko, K.; Unsworth, W. P.; Winters, C. Tetrahedron
2008, 64, 11896e11907.
Acknowledgements
We are grateful to the National Science Council of ROC for
financial support. (Grant No. NSC-100-2113-M-006-009-MY2).
Supplementary data
15. Similar free radical cyclization approach to spirocyclohexadienones, see: (a)
Citterio, A.; Sebastiano, R.; Maronati, A.; Santi, R.; Bergamini, F. J. Chem. Soc.,
Chem. Commun. 1994, 1517e1518; (b) Gonzalez-Lopez de Turiso, F.; Curran, D. P.
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2013.02.009.
ꢀ
~
Org. Lett. 2005, 7, 151e154; (c) Ibarra-Rivera, T. R.; Gamez-Montano, R.;
Miranda, L. D. Chem. Commun. 2007, 3485e3487; (d) Tsubusaki, T.; Nishino, H.
Tetrahedron 2009, 65, 9448e9459; (e) Lanza, T.; Leardini, R.; Minozzi, M.;
Nanni, D.; Spagnolo, P.; Zanardi, G. Angew. Chem., Int. Ed. 2008, 47, 9439e9442.
16. (a) Boivin, J.; Yousfi, M.; Zard, S. Z. Tetrahedron Lett. 1997, 38, 5985e5988; (b)
References and notes
ꢀ
Bacque, E.; El Qacemi, M.; Zard, S. Z. Org. Lett. 2005, 7, 3817e3820.
17. (a) Stork, G.; Mah, R. Heterocycles 1989, 28, 723e727; (b) Curran, D. P.; Tamine, J.
1. (a) Neumann, W. P. Synthesis 1987, 665e682; (b) Curran, D. P. Synthesis 1988,
417e439 and 489e513; (c) Giese, B.; Kopping, B.; Gobel, T.; Dickhaut, J.; Thoma,
G.; Kulicke, K. J.; Trach, F. In Organic Reactions; John Wiley & Sons: New York,
NY, 1996; Vol. 48; Chapter 2, pp 301e855; (d) Bowman, W. R.; Bridge, C. F.;
Brookes, P. J. Chem. Soc., Perkin Trans. 1 2000, 1e14; (e) Zheng, W. Tetrahedron
2001, 57, 7237e7262.
2. (a) Melikyan, G. G. Synthesis 1993, 833e850; (b) Iqbal, J.; Bhatia, B.; Nayyar, N. K.
Chem. Rev. 1994, 94, 519e564; (c) Snider, B. B. Chem. Rev. 1996, 96, 339e363; (d)
Nair, V.; Panicker, S. B.; Nair, L. G.; George, T. G.; Augustine, S. Synlett 2003,156e165;
(e) Nair, V.; Balagopal, L.; Rajan, R.; Mathew, J. Acc. Chem. Res. 2004, 37, 21e30.
3. (a) Cristol, S. J.; Reeder, J. A. J. Org. Chem. 1961, 26, 2182e2185; (b) Orochov, A.;
Asscher, M.; Vofsi, D. J. Chem. Soc. B 1969, 255e259; (c) Sinnerich, J.; Asscher, M.
J. Chem. Soc., Perkin Trans. 1 1972, 1543e1545; (d) Fong, J.-M.; Chen, M.-Y.;
Cheng, M.-C. Tetrahedron Lett. 1987, 28, 2853e2856.
J. Org. Chem. 1991, 56, 2746e2750; (c) Bryans, J. S.; Large, J. M.; Parsons, A. F.
Tetrahedron Lett. 1999, 40, 3487e3490.
ꢁ
ꢁ
18. Crystal data for 9a: C21H19NO4S, M¼381.44, T¼200 (2) K,
l
¼0.71073 A,
ꢁ
ꢁ
monoclinic, space group C 2/c, a¼29.5819(9) A, b¼8.8805(3) A, c¼14.8685(4) A,
3
ꢁ
a
m
¼90ꢁ,
b
¼100.0250(10)ꢁ,
g
¼90 , V¼3751.1(2) A , Z¼4, Dcalcd¼1.381 mg/m3,
ꢁ
¼0.203 mmꢂ1, F (000)¼1636, crystal size 0.54ꢀ0.45ꢀ0.11 mm3, reflections
collected 12,729, independent reflections 3300 [R (int)¼0.0302], refinement
method, full-matrix least-squares on F2, goodness-of-fit on F2 1.032, final R
indices [I>2
s
(I)] R1¼0.0381, wR2¼0.0914,
R
indices (all data) R1¼0.0462,
ꢁꢂ3
wR2¼0.0964, largest diff. peak and hole 0.378 and ꢂ0.321 e A . Crystallo-
graphic data for the structure in this paper have been deposited with the
Cambridge Crystallographic Data Centre as supplementary publication no.
CCDC 890808. Copies of the data can be obtained, free of charge, on application
to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK, (fax: þ44-(0)1223-336033 or
e-mail: deposit@ccdc.cam.ac.uk).
4. (a) De Riggi, I.; Surzur, J.-M.; Bertrand, M. P. Tetrahedron 1988, 44, 7119e7125;
(b) Chuang, C.-P.; Ngoi, T. H. J. Tetrahedron Lett. 1989, 30, 6369e6370; (c) De
Riggi, I.; Surzur, J.-M.; Bertrand, M. P. Tetrahedron 1990, 46, 5285e5294; (d)
Chuang, C.-P. Synlett 1990, 527e528; (e) Chuang, C.-P. Tetrahedron 1991, 47,
5425e5436.
19. Thal, C.; Guillou, C.; Beunard, J. C.; Gras, E.; Potier, P. E. U. Fr 2,826,005-A1 Chem.
Abstr. 2003, 138, 39446.
20. Pereira, J.; Barlier, M.; Guillou, C. Org. Lett. 2007, 9, 3101e3103.
21. (a) Moisan, L.; Wagner, M.; Comesse, S.; Doris, E. Tetrahedron Lett. 2006, 47,
9093e9094; (b) Yu, Z.; Ju, X.; Wang, J.; Yu, W. Synthesis 2011, 860e866.
5. (a) Chuang, C.-P.; Wang, S.-F. Synlett 1995, 763e764; (b) Wang, S.-F.; Chuang, C.-P.;
Lee, J.-H.;Liu, S.-T. Tetrahedron 1999, 55, 2273e2288; (c)Wang, S.-F.;Chuang, C.-P.;