Application of Nazarov cyclization to access [6-5-6] and [6-5-5]tricyclic core embedded new heterocycles: An easy entry to structures related to Taiwaniaquinoids

Article abstract of DOI:10.1039/b901632e

A concise and general route to synthesize a new class of [6-5-6] tricyclic core embedded polyheterocycles has been accomplished using diastereoselective Nazarov cyclization with an overall yield of 35-40%. Versatility of this synthetic route has also been

Full text of DOI:10.1039/b901632e

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www.rsc.org/obc | Organic & Biomolecular Chemistry
Application of Nazarov cyclization to access [6-5-6] and [6-5-5]tricyclic core
embedded new heterocycles: an easy entry to structures related to
Taiwaniaquinoids†
Ritesh Singh, Maloy Kumar Parai and Gautam Panda*
Received 26th January 2009, Accepted 3rd March 2009
First published as an Advance Article on the web 27th March 2009
DOI: 10.1039/b901632e
A concise and general route to synthesize a new class of [6-5-6] tricyclic core embedded
polyheterocycles has been accomplished using diastereoselective Nazarov cyclization with an overall
yield of 35–40%. Versatility of this synthetic route has also been demonstrated by accessing a variety of
[6-5-5] tricyclic core incorporated polycycles. It was observed that the efficiency of cyclization depends
upon the impact of polarization on the reacting systems. Amongst the various Lewis and Brønsted
acids screened for cyclization, triflic acid was found to be the most effective catalyst.
The Nazarov reaction6 is considered as one of the most
versatile reactions to construct cyclopentenone fused carbocy-
Introduction
cles. Although the concept of the polarized Nazarov substrate,7
i.e. divinyl ketone 1, has been exploited to construct simple
functionalized cyclopentenone 3 via intermediate 2 under mild
reaction conditions (Scheme 1), its utilization for the construc-
tion of [6-5-6] tricyclic skeleton fused heteropolycycles is rather
limited.8 Trauner et al. utilized the Nazarov chemistry efficiently
to synthesize several members of the Taiwaniaquinoid family
containing [6-5-6] tricyclic skeleton including Taiwaniaquinol B
using trimethylsilyl triflate(TMSOTf) in nitromethane.9 Fillion
et al. reported the synthesis of Taiwaniaquinol B, applying domino
acylation/alkylation as a key step.5a Approaches based on palla-
dium catalyzed alkylation5b and intramolecular Heck reactions5c–e
to assemble [6-5-6] tricyclic skeleton containing natural products
have also been well delineated by several groups. However, as
such, no general and efficient method to assemble heterocycles
with heteroatom impregnated [6-5-6] tricyclic skeleton has been
reported so far.
The [6-5-6]ABC tricyclic skeleton, which is rather uncommon,
has been found in several natural products, among which the
taiwaniaquinoids deserve a special mention (Fig 1).1a–c Taiwani-
aquinol B, isolated from Taiwanese pine tree Taiwania cryptome-
rioide, is one such 6-nor-5(6→7)abeo-abietane type diterpenoid
containing the uncommon fused [6-5-6] tricyclic carbon skeleton.2
Several members of the taiwaniaquinoids have shown activity as
aromatase inhibitors and are currently under evaluation for their
potential as drug leads in the treatment of estrogen-dependent
cancers.3,4 Thus, the distinctive [6-5-6] fused ring system has
received considerable attention from synthetic organic chemists,
and several total syntheses of such norditerpenoids have appeared
in the last few years.5
Fig. 1 Representative natural [6-5-6] tricyclic skeleton and our designed
novel ]6-5-6]/[6-5-5] skeleton embedded polycycles.
Medicinal and Process Chemistry Division, Central Drug Research Institute,
Lucknow-226001, UP, India. E-mail: gautam.panda@gmail.com, gautam_
panda@cdri.res.in; Fax: 91-522-2623405; Tel: 91-522-2612411-18
Scheme 1 A general polarized Nazarov reaction and our designed
polarized substrate 4.
† Electronic supplementary information (ESI) available: 1H and 13C NMR
spectra of compounds 9, 10, 13, 14, 15, 16, 19, 20, 21, 1H-1H COSY,
HSQC, HMBC spectra of 15k and scheme for synthesis of 16. See DOI:
10.1039/b901632e
Therefore, a mild and expedient method for the construction of
heteroatom embedded [6-5-6] tricyclic skeletons is highly desirable.
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Table 1 Catalyst optimization for Nazarov cyclization
In the quest for attaining novel molecules with interesting
properties, we envisaged to encompass the polarized Nazarov
concept to access diversified [6-5-6] tricyclic skeletons. Further
cognizing the fact that the cis ring fusion preferences in the cyclic
systems could direct the protonation in diastereoselective Nazarov
product,10,11 we endeavoured to design a new class of polarized
Nazarov substrate 4 by casting aromatics/heteroaromatics12 as
vinyl nucleophiles to access a variety of novel benzene annulated
[6-5-6]/[6-5-5] tricylic heteropolycycles 6 via intermediate 5.
Entry
Substrate
Catalyst
Conditions
Time/h
Yield
Results and discussion
1
2
3
4
5
6
7
8
10a
10a
10c
10b
10b
10c
10a
10c
CF3SO3H
H2SO4
CF3COOH
p-TsOH
AlCl3
DCM, rt
DCM, rt
DCM, rt
DCM, rt
DCM, rt
DCM, rt
DCM, rt
DCM, rt
1.5
3
91%
85%
82%
65%
62%
45%
47%
28%
The general retrosynthetic analysis of the target molecule depicted
that the Nazarov substrates D could be assembled by oxidizing
the alcohol C, which would be procured through the coupling
of suitable bromo substrates A with different aromatic and
heteroaromatic aldehydes B (Scheme 2).
2.5
12
10
16
14
48
FeCl3
BF3·Et2O
Sc(OTf)3
very good reactivity and remained low yielding even after an
increase in the catalyst loading (47–62%).
Use of milder Lewis acid like Sc(OTf)3 also did not improve
the reactivity significantly, as a substantial amount of substrate
was left unreacted even after 48 hrs (28% yield) (Table 1). The
syn stereochemistry established by NOESY experiments in the
products 12a-c reflects the greater stability of cis fused cyclopen-
tenone [6-5-6] tricyclic systems. This is due to the enol protonation
step of one of the intermediates c in the Nazarov cyclization
process (Scheme 4) during the aqueous workup, which gave
thermodynamically favourable cis fused products. However, it was
delightful to achieve products with excellent diastereoselectivity
(>99%) with no trace of other isomer detected even in the HPLC
analysis. Change of solvent from DCM to dry benzene did not
change the yields. With the best optimized reaction conditions
at hand, we set out to explore the generality of the synthetic
pathway to synthesize new molecular entities embedded with
[6-5-6] tricyclic systems. Thus 14a (eq 1) and 21 (eq 3) were
synthesized (Scheme 5) from bromo substrates 8b and 2214 with
benzaldehyde and veratraldehyde respectively, following similar
reaction conditions as given in Scheme 3. But to our dismay, 14a
failed to give the cyclized product under the optimized cyclization
reaction conditions indicating that activated aromatic rings are
required for cyclization of such a class of aromatic Nazarov
substrates (entry 2, Table 2). In order to achieve a [6-5-6] tricyclic
system with a quarternary stereocenter, our attempt to cyclize
21 was futile presumably due to the steric hindrance caused by
a substituted methyl group in the reaction intermediate (entry 3,
Table 2). Further increase in catalytic loading and temperature
only led to decomposition of the starting material.
Scheme 2 Retrosynthetic analysis of target molecule.
Towards the realization of our goal, we first embarked
upon the syntheses of benzo annulated [6-5-6]tricyclic skele-
ton embedded polyheterocycles. Syntheses of the Nazarov sub-
strates 10a-c were achieved as outlined in Scheme 2. Chro-
manones/thiochromanones 7 were treated with PBr3 in dry ben-
zene at 60 ◦C to furnish the bromo compounds 8a-c in good yields
(60–64%).13 8a-c were further treated with n-BuLi under an inert
atmosphere at -78 ◦C in dry THF and reacted with commercially
available veratraldehyde 11 to obtain the corresponding divinyl
alcohols 9a-c in reasonable yields (55–60%). MnO2 oxidation of
allylic alcohols 9a-c furnished the coveted Nazarov substrate 10a-c
in high yields (80–85%).
In an effort to optimize the best catalyst for the Nazarov
cyclization to obtain the [6-5-6] tricyclic core of 12a-c, substrates
10a-c were reacted with various catalytic Lewis and Brønsted acids
in dichloromethane at room temperature (Table 1). It was observed
that the Nazarov substrates 10a-c cyclized to furnish the [6-5-6]
tricyclic embedded heteropolycycles 12a-c in high yields (87–91%)
at room temperature with just one equivalent of triflic acid in a
very short reaction time. Besides triflic acid, other Brønsted acids
such as H2SO4, CF3COOH and p-TsOH also gave the cyclized
product albeit in low yields (65–85%) and longer reaction times.
Well known Lewis acids like AlCl3, FeCl3, BF3·Et2O did not show
Thereafter we turned our attention to further explore this
synthetic methodology to attain a varied class of heteroatom
impregnated [6-5-5]ABC tricycle skeleton. Towards this objective
various heteroaromatic Nazarov substrates 14b-m and 18 (Table 2)
were synthesized essentially following reaction conditions similar
to those depicted in eq. 1 and eq. 2 (Scheme 5). The intermediate
aldehyde 16 in eq. 2 which is required for the synthesis of substrate
18 was synthesized following standard reaction conditions (see
ESI for the scheme†).15,16 Synthesized substrates (14a-m, 18) were
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Table 2 Results of Nazarov reaction on aryl and heteroaryl polarized substratesa
Entry
Substrate
Time
Temperature
Product
drb (%)
Yield (%)
1
10a,b,10c
1.5 h
1 h
1.2 h
rt
rt
rt
12a,b,c
12a R = OMe, X = O
12b R = H, X = O
12c R = H, X = S
>99
>99
>99
90
91
87
2
14a
24 h
24 h
rt/60 ◦
rt/60 ◦
C
C
No reaction
No reaction
—
—
—
—
3
4
21
14b,c,d,e
1 min
1 min
1 min
1 min
rt
rt
rt
rt
15b,c,d,e
15b R = OMe,X = O
15c R = OMe, X = S
15d R = H, X = O
15e R = H, X = S
>99
>99
>99
>99
90
92
92
91
5
6
14f,g,h
14i,j,k
45 min
35 min
40 min
rt
rt
rt
15f,g,h
15i,j,k
15f R = OMe, X = O
15g R = OMe, X = S
15h R = H, X = O
>99
>99
>99
85
88
87
1.5 h
1 h
1.3 h
rt
rt
rt
15i R = OMe, X = O
15j R = H, X = S
>99
>99
>99
84
88
81
15k R = H, X = O
7
8
14l
24 h
24 h
rt/60 ◦
rt/60 ◦
C
C
No reaction
No reaction
—
—
14m
—
—
85
9
18
1.5 h
rt
19
>99
a
= DCM is used as solvent in all reactions. b = determined by NMR/HPLC.
then surveyed under one of the best optimized reaction conditions
(triflic acid in DCM) for the desired cyclized products.
reaction conditions. Increasing temperature and catalyst loading
gave only uncharacterizable products. In contrast, 2-substituted
pyrrole based substrates 14f, 14g, and 14h furnished 15f, 15g,
and 15h in good yields (85, 88, and 87% respectively). Indole
based Nazarov substrates 14b, 14c, 14d, 14e gave the desired
[6-5-5] tricycle skeleton embedded novel pentacyclic molecules
15b, 15c, 15d, 15e under similar reaction conditions in a minute
with very high yields (90, 92, 92, 91% respectively).
Observation of summarized results (Table 2) emphasized that
aryl and heteroaryls represented the electron donating vinyl
nucleophile in polarized Nazarov cyclization. It also provided
information about the extent of polarization in this relatively
new class of aromatic/heteroaromatic Nazarov substrates as the
2-substituted thiophene and furan substrates 14l and 14m failed
to cyclize whereas 3-substituted thiophene substrates 14i, 14j,
14k and 18 gave cyclized products 15i, 15j, 15k and 19 in
varying yields (84, 88, 81 and 85% respectively) under similar
The structure and stereochemistry of the synthesized cyclic
1
molecules were determined through incisive analysis of H, 13C
NMR, 1H-1H COSY, HSQC spectra. The cis relationship between
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a
Scheme 3 Synthesis of Nazarov substrates 10a-c. Reagents and condi-
tions: (a) PBr3, dry benzene, 60 ◦C, 24 h, 60–64%. (b) (i) n-BuLi, dry THF,
-78 ◦C, N2, 5–10 min. (ii) 11, -78 ◦C to r.t, 2 h, 55–60%. (c) MnO2, dry
ether, rt, 1 h, 80–85%.
Scheme 5 Synthesis of new aromatic/heteroaromatic Nazarov substrates
following similar reaction conditions as Scheme 3.
bioevaluation and the asymmetric version of the Nazarov reaction
on this system are currently underway in our lab and will be
reported in due course.
Experimental
General methods
All dry reactions were carried out under argon or nitrogen.
Commercial reagents were used without further purification
unless otherwise stated. Reactions were monitored on silica
gel TLC plates (coated with TLC grade silica gel, obtained
from Merck). The detecting agent used (for TLC) was iodine
vapors. Column chromatography was performed over silica gel
(100–200 mesh) procured from Qualigens (India). Mass spectra
were recorded using electron spray ionization (ESI-MS) or fast
atom bombardment spectra (FAB-MS) on a JEOL SX 102
spectrometer using Argon/xenon as the FAB gas. Melting points
were determined on COMPLAB melting point apparatus and
are uncorrected. IR spectra were recorded on a Perkin-Elmer
Scheme 4 Aromatic Nazarov cyclization process.
two vicinal protons in the final products was first revealed
by the coupling constant (J = 6–7 Hz) from 1H NMR. This
stereochemical assignment was further reinforced by NOESY
experiments.
In conclusion we have reported an easy, general and expedient
route to access a variety of uncommon hetero [6-5-6]ABC tricyclic
cores analogous to Taiwaniaquinoids as well as several hetero
[6-5-5] tricyclic systems via diastereoselective Nazarov cyclization.
This is the first aromatic Nazarov system to show excellent
diastereo and regioselectivity under very mild reaction conditions,
providing high yielding functionalized scaffolds that could serve
as valuable building blocks for diversity oriented synthesis. Their
1
FT-IR RXI spectrometer. H NMR and 13C NMR spectra were
recorded on Bruker DPX-200 (operating at 200 MHz for 1H and
50 MHz for 13C) or DPX-300 (operating at 300 MHz for 1H and
75 MHz for 13C) spectrometer using CDCl3 and CCl4 as solvent.
Tetramethylsilane (0.00 ppm) served as an internal standard in 1H
NMR and CDCl3 (77.0 ppm) in 13C NMR. Coupling constants (J
values) are given in hertz (Hz). Chemical shifts are expressed in
parts per million.
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THF (20 ml), n-BuLi (1.2 ml, 1.85 mmol), N-benzylpyrrole 2-
carboxaldehyde (308 mg, 1.67 mmol) in THF (2 mL) furnished 13f
(339 mg, 53%) as viscous colorless oil, Rf = 0.45 (AcOEt/hexane,
20:80); IR (Neat): 3419, 3021, 2360, 1211, 761, 670 cm-1; 1H NMR
(300 MHz, CDCl3): d 7.33–7.23 (m, 3H), 7.12–7.10 (m, 2H), 7.03–
6.97 (m, 1H), 6.76–6.74 (m, 2H), 6.57–6.52 (m, 1H), 6.40 (dd, 1H,
J1 = 1.4, J2 = 7.7), 6.07–6.01 (m, 2H), 5.82 (d, 1H, J = 1.2), 5.48
(s, 1H), 5.35 (d, 1H, J = 16.0), 5.17 (d, 1H, J = 16.0), 1.83 (s, br,
1H), 1.44 (s, 3H), 1.42 (s, 3H); MS (ESI): m/z 328 [M - OH]+;
Anal. Calcd. for C23H23 NO2: C, 79.97; H, 6.71; N, 4.05. Found:
C, 79.88; H, 6.79; N, 3.93.
Experimental procedures and characterization data
Typical procedure to prepare allyl alcohols
(1-Benzyl-1H-indol-2-yl)(7-methoxy-2,2-dimethyl-2H-chromen-
4-yl) methanol (13b). To a stirred solution of bromo substrate
8a (500 mg, 1.85 mmol) in anhydrous THF (20 mL) at -78 ◦C
and under N2, n- BuLi (1.6 M in hexane, 1.2 ml, 1.85 mmol)
was added. The resulting yellow solution was stirred at -78 ◦C
for 5–10 minutes after which N-benzyl indole 2-carboxaldehyde
(393 mg, 1.66 mmol) in THF (2 mL) were added at the same
temperature and stirred at room temperature for 1 h. After
quenching with water, THF was removed in vacuo. The mixture
was extracted with ethyl acetate (3 ¥ 20 ml), washed with brine
and dried over Na2SO4. The concentrated extract was subjected to
column chromatography on silica gel and elution with 20% ethyl
acetate in hexane furnished alcohol 13b (418 mg, 54%) as viscous
green oil, Rf = 0.51 (AcOEt/hexane, 20:80); IR (Neat): 3417,
3010, 2330, 1211, 759, 670 cm-1; 1H NMR (200 MHz, CDCl3): d
7.57 (d, 1H, J = 7.5), 7.33–7.02 (m, 8H), 6.47 (d, 2H, J = 7.7),
6.37 (d, 1H, J = 2.5), 6.14–6.10 (m, 1H), 5.71 (s, 1H), 5.67 (s, 1H),
5.54 (s, 2H), 3.71 (s, 3H), 2.00 (s, 1H), 1.46 (s, 3H), 1.43 (s, 3H);
MS (FAB): m/z 410 [M - OH]+; Anal. Calcd. for C28H27NO3: C,
79.03; H, 6.40; N, 3.29. Found: C, 78.95; H, 6.34; N, 3.35.
(3,4-Dimethoxyphenyl)(7-methoxy-2,2-dimethyl-2H-chromen-4-
yl)methanol (9a). As described for 13b, 8a (500 mg, 1.85 mmol)
in THF (20 ml), n-BuLi (1.2 ml, 1.85 mmol), veratraldehyde
(276 mg, 1.66 mmol) in THF (2mL) furnished 9a (364 mg, 55%)
as viscous colorless oil, Rf = 0.61 (AcOEt/hexane, 20:80); IR
(Neat): 3431, 2360, 1560, 1217,761, 670 cm-1; 1H NMR (300 MHz,
CDCl3+CCl4): d 6.95–6.91 (m, 2H), 6.87 (d, 1H, J = 8.6), 6.80
(d, 1H, J = 7.9), 6.36 (d, 1H, J = 2.5), 6.26 (dd, 1H, J1 = 2.6,
J2 = 8.6), 5.68 (s, 1H), 5.53 (s, 1H), 3.85 (s, 3H), 3.84 (s, 3H),
3.72 (s, 3H), 2.03 (s, br,1H), 1.47 (s, 6H); 13C NMR (75 MHz,
CDCl3+CCl4): d 160.4, 154.5, 149.2, 148.8, 134.4, 133.3, 124.8,
124.8, 119.5, 113.4, 111.2, 110.3, 106.5, 102.2, 76.0, 72.6, 55.8,
5.7, 55.0, 27.9; MS (ESI): m/z 339 [M - OH]+; Anal. Calcd. for
C21H24O5: C, 70.77; H, 6.79. Found: C, 70.65; H, 6.85.
(1-Benzyl-1H-indol-2-yl)(7-methoxy-2,
2-dimethyl-2H-thio-
chromen-4-yl) methanol (13c). As described for 13b, 8d (500 mg,
1.75 mmol) in THF (20 ml), n-BuLi (1.1 ml, 1.75 mmol), N-benzyl
indole 2-carboxaldehyde (372 mg, 1.57 mmol) in THF (2 mL)
furnished 13c (410 mg, 53%) as viscous colorless oil, Rf = 0.53
(AcOEt/hexane, 20:80); IR (Neat): 3409, 3020, 2360, 1216, 762,
(3,4-Dimethoxyphenyl)(2,2-dimethyl-2H-chromen-4-yl)me-
thanol (9b). As described for 13b, 8b (500 mg, 2.09 mmol) in
THF (20 ml), n-BuLi (1.3 ml, 2.09 mmol), veratraldehyde (312 mg,
1.88 mmol) in THF (2mL) furnished 9b (409 mg, 60%) as viscous
colorless oil, Rf = 0.59 (AcOEt/hexane, 20:80); IR (Neat): 3414,
3021, 2358, 1591, 1216, 758, 668 cm-1; 1H NMR (300 MHz,
CDCl3+CCl4): d 7.00–6.94 (m, 1H), 6.91–6.85 (m, 3H), 6.75–6.60
(m, 3H), 5.70 (s, 1H), 5.52 (s, 1H), 3.78 (s, 3H), 3.77 (s, 3H), 1.86 (s,
br,1H), 1.40 (s, 6H); 13C NMR (75 MHz, CDCl3+CCl4): d 153.1,
149.2, 148.9, 134.2, 133.4, 129.0, 127.5, 123.9, 120.5, 120.2, 119.5,
116.8, 111.1, 110.2, 75.7, 72.5, 55.8, 55.7, 27.9; MS (ESI): m/z 309
[M - OH]+; Anal. Calcd. for C20H22O4: C, 73.60; H, 6.79. Found:
C, 73.71; H, 6.90.
1
670 cm-1; H NMR (300 MHz, CDCl3): d 7.60 (d, 1H, J = 7.8),
7.52 (d, 1H, J = 8.8), 7.30–7.24 (m, 4H), 7.15–7.04 (m, 6H),
6.81 (d, 1H, J = 1.1), 6.64 (dd, 1H, J1 = 2.5, J2 = 8.7), 6.72
(d, 1H, J = 2.5), 5.39 (s, 2H), 3.78 (s, 3H), 1.26 (s, 3H), 0.98 (s,
3H); 13C NMR (75 MHz, CDCl3): d 158.8, 150.1, 149.1, 140.6,
137.3, 134.8, 128.8, 127.5, 126.5, 126.2, 124.8, 123.0, 120.1,
120.0, 118.8, 17.5, 112.9, 112.3, 110.3, 55.3, 55.1, 48.9, 48.3,
29.6, 22.8; MS (ESI): m/z 424 [M-OH]+; Anal. Calcd. for C28H27
NO2 S: C, 76.16; H, 6.16; N, 3.17. Found: C, 76.09; H, 6.24;
N, 3.28.
(3,4-Dimethoxyphenyl)(2,2-dimethyl-2H-thiochromen-4-yl)me-
thanol (9c). As described for 13b, 8c (500 mg, 1.96 mmol) in
THF (20 ml), n-BuLi (1.2 ml, 1.96 mmol), veratraldehyde (293 mg,
1.76 mmol) in THF (2 mL) furnished 9c (395 mg, 59%) as viscous
colorless oil, Rf = 0.48 (AcOEt/hexane, 20:80); IR (Neat): 3430,
3020, 2331, 1571, 1212, 760, 660 cm-1; 1H NMR (300 MHz,
CDCl3+CCl4): d 7.30–7.27 (m, 1H), 7.19 (dd, 1H, J1 = 1.0, J2 =
7.8), 7.09–7.03 (m, 1H), 6.99–6.91 (m, 3H), 6.81–6.79 (m, 1H),
6.12 (s, 1H), 5.66 (s, 1H), 3.86 (s, 3H), 3.83 (s, 3H), 2.10 (s, br, 1H),
1.49 (s, 3H), 1.47 (s, 3H); 13C NMR (75 MHz, CDCl3+CCl4): d
149.1, 148.6, 137.0, 134.8, 133.1, 132.8, 130.8, 127.9, 127.4, 127.3,
125.4, 119.4, 111.1, 110.2, 55.7, 55.6, 40.2, 28.9. MS (ESI): m/z
325 [M - OH]+; Anal. Calcd. for C20H22O3S: C, 70.15; H, 6.48.
Found: C, 70.22; H, 6.57.
(1-Benzyl-1H-indol-2-yl)(2,2-dimethyl-2H-chromen-4-yl)metha-
nol (13d). As described for 13b, 8b (500 mg, 2.09 mmol) in
THF (20 ml), n-BuLi (1.3 ml, 2.09 mmol), N-benzyl indole
2-carboxaldehyde (594 mg, 1.88 mmol) in THF (2 mL)
furnished 13d (471 mg, 57%) as viscous colorless oil, Rf = 0.54
(AcOEt/hexane, 20:80); IR (Neat): 3429, 3021, 2359, 1620, 1218,
1
765 cm-1; H NMR (300 MHz, CDCl3): d 7.59 (d, 2H, J = 7.7),
7.35–7.20 (m, 5H), 7.16–7.03 (m, 4H), 6.58 (d, 2H, J = 4.1),
6.49 (s, 1H), 5.89 (d, 1H, J = 1.1), 5.74 (s, 1H), 5.61 (d, 1H,
J = 16.9), 5.53 (d, 1H, J = 16.8), 2.02 (s, br,1H), 1.51 (s, 3H),
1.47 (s, 3H); 13C NMR (75 MHz, CDCl3): d,152.7, 139.5, 138.2,
137.8, 129.0, 128.8, 127.6, 127.5, 127.2, 126.2, 123.5, 122.4, 121.1,
120.4, 120.2, 119.8, 116.6, 109.6,102.6, 75.9, 65.3, 46.9, 27.7, 27.6;
MS (ESI): m/z 396 [M + 1]+, 378 [M- OH]+; Anal. Calcd. for
C27H25 NO2: C, 82.00; H, 6.37; N, 3.54. Found: C, 81.92; H, 6.45;
N, 3.61.
(7-Methoxy-2,2-dimethyl-2H-chromen-4-yl)(thiophen-3-yl)me-
thanone (13i). As described for 13b, 8a (500 mg, 1.85 mmol)
in THF (20 ml), n-BuLi (1.2 ml, 1.85 mmol), thiophene 3-car-
boxaldehyde (186 mg, 1.66 mmol) in THF (2 mL) furnished 13i
(320 mg, 57%) as viscous colorless oil, Rf = 0.50 (AcOEt/hexane,
(1-Benzyl-1H-pyrrol-2-yl)(2,2-dimethyl-2H-chromen-4-yl)me-
thanol (13f). As described for 13b, 8a (500 mg, 1.85 mmol) in
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20:80); IR (Neat): 3434, 3020, 1217, 760 cm-1; 1H NMR (300 MHz,
CDCl3): d 7.29–7.24 (m, 2H), 7.06 (dd, 1H, J1 = 1.3, J2 = 4.9),
6.96 (d, 1H, J = 8.6), 6.39 (d, 1H, J = 2.5), 6.31 (dd, 1H, J1 = 2.5,
J2 = 8.5), 5.65 (s, 2H), 3.74 (s, 3H), 2.26 (s, br, 1H), 1.47 (s, 3H),
1.47 (s, 3H); 13C NMR (75 MHz, CDCl3): d 160.5, 154.5, 143.4,
133.4, 126.6, 124.8, 124.7, 122.4, 113.3, 106.5, 102.3, 76.1, 69.3,
55.0, 27.9, 27.8; MS (ESI): m/z 285 [M - OH]+; Anal. Calcd. for
C17H18O3S: C, 67.52; H, 6.00. Found: C, 67.42; H, 5.91.
1.76 mmol) in THF (20 ml), n-BuLi (1.1 ml, 1.76 mmol),
veratraldehyde (263 mg, 1.58 mmol) in THF (2 mL) furnished 20
(379 mg, 58%) as viscous colorless oil, Rf = 0.44 (AcOEt/hexane,
20:80); IR (Neat): 3430, 3021, 2323, 1213, 759, 661 cm-1; 1H
NMR (300 MHz, CDCl3): d 7.04 (s, 1H), 6.96 (d, 1H, J = 8.6),
6.86–6.77 (m, 3H), 6.36 (d, 1H, J = 2.2), 6.24 (dd, 1H, J1 = 2.0,
J2 = 8.5), 5.96 (s, 1H), 3.85 (s, 6H), 3.72 (s, 3H), 1.86 (s, 3H), 1.48
(s, 3H), 1.41 (s, 3H); MS (ESI): m/z 353 [M - OH]+; Anal. Calcd.
for C22H26 O5: C, 71.33; H, 7.07; Found: C, 71.45; H, 6.96.
(2,2-Dimethyl-2H-thiochromen-4-yl)thiophen-3-ylmethanol (13j).
As described for 13b, 8c (500 mg, 1.96 mmol) in THF (20 ml), n-
BuLi (1.2 ml, 1.96 mmol), thiophene 3-carboxaldehyde (197 mg,
1.76 mmol) in THF (2 mL) furnished 13j (305 mg, 54%) as viscous
colorless oil, Rf = 0.52 (AcOEt/hexane, 20:80); IR (Neat): 3443,
(1-Benzyl-2,2-dimethyl-1,2-dihydroquinolin-4-yl)thiophen-3-yl-
methanol (17). As described for 13b, 15 (500 mg, 3.06 mmol) in
THF (20 ml), n-BuLi (1.9 ml, 3.06 mmol), 16 (762 mg, 2.75 mmol)
in THF (2 mL) furnished 17 (631 mg, 57%) as viscous colorless oil,
Rf = 0.49 (AcOEt/hexane, 20:80); IR (Neat): 3433, 3021, 2359,
1210, 760, 671 cm-1; 1H NMR (300 MHz, CDCl3): d 7.24–7.10 (m,
7H), 7.07–7.05 (m, 1H), 6.93 (d, 1H, J = 6.8), 6.82–6.76 (m, 1H),
6.39 (t, 1H, J = 7.3), 6.22 (d, 1H, J = 8.2), 5.70 (s, 1H), 5.64 (s,
1H), 4.51–4.38 (m, 2H), 1.99 (s, br, 1H), 1.35 (s, 3H), 1.33 (s, 3H);
MS (ESI): m/z 344 [M - OH]+; Anal. Calcd. for C23H23 NOS: C,
76.42; H, 6.41; N, 3.87. Found: C, 76.33; H, 6.56; N, 3.75.
1
3020, 2330, 1211, 759 cm-1; H NMR (300 MHz, CDCl3+CCl4):
d 7.22–7.16 (m, 3H), 7.12–7.11 (m, 1H), 7.02–6.88 (m, 3H), 5.98
(s, 1H), 5.68 (s, 1H), 1.96 (s, br, 1H), 1.39 (s, 3H), 1.37 (s, 3H); 13
C
NMR (75 MHz, CDCl3+CCl4): d 144.0, 137.3, 133.3, 132.8, 130.7,
128.0, 127.5, 126.7, 125.3, 125.1, 122.4, 71.1, 40.2, 29.1, 29.0; MS
(ESI): m/z 271 [M - OH]+; Anal. Calcd. for C16H16OS2: C, 66.63;
H, 5.59. Found: C, 66.54; H, 5.51.
(2,2-Dimethyl-2H-chromen-4-yl)(thiophen-3-yl)methanol (13k).
As described for 13b, 8b (500 mg, 2.09 mmol) in THF (20 ml),
n-BuLi (1.3 ml, 2.09 mmol), thiophene 3-carboxaldehyde (210 mg,
1.88 mmol) in THF (2 mL) furnished 13k (313 mg, 55%) as viscous
colorless oil, Rf = 0.53 (AcOEt/hexane, 20:80); IR (Neat): 3404,
3021, 2359, 1216, 760 cm-1; 1H NMR (300 MHz, CDCl3): d 7.30–
7.26 (m, 2H), 7.14–7.06 (m, 3H), 6.85–6.73 (m, 2H), 5.81 (s, 1H),
5.72 (s, 1H), 2.38 (s, br, 1H), 1.47 (s, 6H); 13C NMR (75 MHz,
CDCl3): d 153.0, 143.2, 133.4, 129.0, 127.4, 126.5, 126.1, 123.7,
122.6, 120.4, 120.1, 116.7, 75.7, 68.9, 27.7, 27.6; MS (ESI): m/z
255 [M - OH]+; Anal. Calcd. for C16H16O2S: C, 70.56; H, 5.92.
Found: C, 70.67; H, 6.05.
Typical procedure for the oxidation of allylic alcohols
2H-Chromen (1-benzyl-1H-indol-2-yl) (7-methoxy-2, 2-dimeth-
yl-4-yl) methanone (14b). To a stirred solution of substrate 13b
(300 mg, 0.70 mmol) in dry ether (50 ml) at room temperature,
was added activated MnO2 (613 mg, 7.05 mmol) and the reaction
was stirred for 2 h. It was filtered through celite, concentrated in
vacuo and was subjected to column chromatography on silica gel
and elution with 10% ethyl acetate in hexane furnished the desired
product 14b (229 mg, 77%) as colorless semi solid, Rf = 0.61
(AcOEt/hexane, 10:90); IR (KBr): 3018, 2920, 1614, 1276, 1142,
1
757 cm-1; H NMR (300 MHz, CDCl3): d 7.69 (d, 1H, J = 8.0),
7.42–7.32 (m, 2H), 7.24–7.08 (m, 8H), 6.44–6.36 (m, 2H), 5.88 (s,
1H), 5.87 (s, 2H), 3.76 (s, 3H), 1.50 (s, 6H); 13C NMR (75 MHz,
CDCl3): d 187.4, 161.1, 154.0, 140.5, 138.2, 134.9, 133.4, 132.6,
128.5, 127.2, 126.6, 126.5, 126.3, 125.8, 123.2, 121.1, 115.8, 112.3,
110.9, 107.0, 102.3, 75.7, 55.2, 48.0, 27.2. MS (ESI): m/z 424 [M +
1]+, 91 [C6H5CH2]+; Anal. Calcd. for C28H25 NO3: C, 79.41; H,
5.95; N, 3.31. Found: C, 79.49; H, 5.88; N, 3.40.
(2,2-Dimethyl-2H-chromen-4-yl)(phenyl) methanol (13a). As
described for 13b, 8b (500 mg, 1.85 mmol) in THF (20 ml), n-
BuLi (1.2 ml, 1.85 mmol), benzaldehyde (176 mg, 1.66 mmol) in
THF (2 mL) furnished 13a (322 mg, 58%) as viscous colorless oil,
Rf = 0.56 (AcOEt/hexane, 20:80); IR (Neat): 3430, 3019, 2360,
1210, 759, 669 cm-1; 1H NMR (300 MHz, CDCl3): d 7.48 (d, 1H,
J = 1.6), 7.45 (d, 1H, J = 1.0), 7.41–7.29 (m, 3H), 7.12–7.03 (m,
2H), 6.83 (dd, 1H, J1 = 1.0, J2 = 8.0), 6.75 (m, 1H), 5.84 (d, 1H,
J = 1.2), 5.69 (d, 1H, J = 2.5), 2.17 (d, 1H, J = 3.8), 1.50 (s,
3H), 1.50 (s, 3H); MS (ESI): m/z 249 [M - OH]+; Anal. Calcd. for
C18H18 O2: C, 81.17; H, 6.81; Found: C, 81.19; H, 6.91.
(1-Benzyl-1H-indol-2-yl)(7-methoxy-2,2-dimethyl-2H-thiochro-
men-4-yl) methanone (14c). As described for 14b, 13c (300 mg,
0.68 mmol) in dry ether (50 ml), MnO2 (591 mg, 6.80 mmol)
furnished 14c (236 mg, 79%) as colorless semi solid, Rf = 0.64
(AcOEt/hexane, 10:90); IR (KBr): 2925, 2358, 1710, 1594, 1210,
1
757 cm-1; H NMR (300 MHz, CDCl3): d 7.69 (d, 1H, J = 7.7),
(7-Methoxy-2, 2-dimethyl-2H-chromen-4-yl)(5-methylfuran-2-
yl) methanol (13m). As described for 13b, 8a (500 mg, 1.85 mmol)
in THF (20 ml), n-BuLi (1.2 ml, 1.85 mmol), 5-methyl furfural
(183 mg, 1.66 mmol) in THF (2 mL) furnished 13m (312 mg, 56%)
as viscous colorless oil, Rf = 0.52 (AcOEt/hexane, 20:80); IR
7.46–7.24 (m, 5H), 7.20–7.05 (m, 5H), 6.90 (d, 1H, J = 3.6 Hz),
6.56 (dd, 1H, J1 = 2.6, J2 = 3.6), 6.06 (s, 1H), 5.92 (s, 2H), 3.80
(s, 3H), 1.52 (s, 6H); 13C NMR (75 MHz, CDCl3): d 189.3, 159.2,
140.5, 138.3, 137.8, 135.7, 135.1, 133.9, 128.5, 128.1, 127.2, 126.6,
126.4, 125.9, 123.3, 123.2, 121.0, 116.2, 112.6, 111.6, 110.8, 55.2,
48.0, 40.8, 28.5; MS (ESI): m/z 440 [M + 1]+; Anal. Calcd. for
C28H25 NO2S: C, 76.51; H, 5.73; N, 3.19. Found: C, 76.59; H, 5.82;
N, 3.25.
1
(Neat): 3432, 3023, 2360, 1213, 760, cm-1; H NMR (300 MHz,
CDCl3): d 6.98 (d, 1H, J = 8.4), 6.43 (d, 1H, J = 2.5), 6.36 (dd,
1H, J1 = 2.5, J2 = 8.5), 6.07 (d, 1H, J = 2.8), 5.89 (d, 1H, J =
2.1), 5.77 (d, 1H, J = 0.8), 5.65 (s, 1H), 3.77 (s, 3H), 2.31 (s, 3H),
2.17 (s, br, 1H), 1.47 (s, 6H); MS (ESI): m/z 283 [M - OH]+; Anal.
Calcd. for C18H20 O4: C, 71.98; H, 6.71; Found: C, 72.90; H, 6.59.
(1-Benzyl-1H-indol-2-yl)(2,2-dimethyl-2H-chromen-4-yl)meth-
anone (14d). As described for 14b, 13d (300 mg, 0.76 mmol) in dry
ether (50 ml), MnO2 (659 mg, 7.59 mmol) furnished 14d (241 mg,
81%) as colorless semi solid, Rf = 0.62 (AcOEt/hexane, 10:90);
(3,4-Dimethoxyphenyl)(7-methoxy-2,
2,3-trimethyl-2H-chro-
men-4-yl) methanol (20). As described for 13b, 22 (500 mg,
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1
IR (KBr): 3020, 2360, 1730, 1637, 1260, 1216, 761, 669 cm-1; H
112.4, 111.2, 109.7, 106.9, 102.3, 75.7, 55.9, 55.8, 55.1; MS (ESI):
m/z 355 [M + 1]+; Anal. Calcd. for C21H22O5: C, 71.17; H, 6.26.
Found: C, 71.29; H, 6.17.
NMR (300 MHz, CDCl3): d 7.72 (d, 1H, J = 8.0), 7.43–7.39 (m,
2H), 7.28–7.12 (m, 9H), 6.90–6.81 (m, 2H), 6.02 (s, 1H), 5.92 (s,
2H), 1.55 (s, 6H); 13C NMR (75 MHz, CDCl3): d 187.3, 152.6,
140.6, 138.2, 134.9, 133.7, 129.9, 128.5, 127.2, 126.6, 125.9, 125.4,
123.2, 121.1, 120.9, 119.1, 117.0, 116.0, 110.9, 75.3, 48.1, 27.2; MS
(ESI): m/z 394 [M + 1]+; Anal. Calcd. for C27H23 NO2: C, 82.42;
H, 5.89; N, 3.56. Found: C, 82.35; H, 5.97; N, 3.65.
(3,4-Dimethoxyphenyl)(2,2-dimethyl-2H-chromen-4-yl)meth-
anone (10b). As described for 14b, 9b (300 mg, 0.92 mmol) in dry
ether (50 ml), MnO2 (800 mg, 6.80 mmol) furnished 10b (253 mg,
85%) as colorless semi solid, Rf = 0.72 (AcOEt/hexane, 10:90);
IR (KBr): 3020, 2361, 1724, 1591, 1216, 760, 668 cm-1; 1H NMR
(300 MHz, CDCl3): d 7.55 (d, 1H, J = 1.9), 7.50 (dd, 1H, J1 = 2.0,
J2 = 8.3), 7.20–7.14 (m, 2H), 6.88–6.80 (m, 3H), 5.87 (s, 1H), 3.94
(s, 3H), 3.93 (s, 3H), 1.52 (s, 6H); 13C NMR (75 MHz, CDCl3): d
193.9, 153.7, 152.5, 149.09, 133.7, 132.9, 130.0, 129.9, 125.5, 125.4,
121.0, 119.3, 117.0, 111.3, 109.9, 75.4, 56.1, 55.9, 27.3. MS(ESI):
m/z 325 [M + 1]+. Anal. Calcd. for C20H20O4: C, 74.06; H, 6.21.
Found: C, 74.17; H, 6.15.
(1-Benzyl-1H-indol-2-yl)(2,2-dimethyl-2H-thiochromen-4-
yl)methanone (14e). As described for 14b, 13e (300 mg,
0.73 mmol) in dry ether (50 ml), MnO2 (633 mg, 7.29 mmol)
furnished 14e (250 mg, 84%) as colorless semi solid, Rf = 0.67
(AcOEt/hexane, 10:90); IR (KBr): 3020, 2925, 2360, 1726, 1638,
1216, 761, 670 cm-1; 1H NMR (300 MHz, CDCl3): d 7.68 (d, 1H,
J = 7.8 Hz), 7.43–7.34 (m, 3H), 7.29–7.27 (m, 3H), 7.19–7.09 (m,
6H), 7.01–6.99 (m, 1H), 6.17 (s, 1H), 5.92 (s, 2H), 1.51 (s, 6H); 13
C
(3,4-Dimethoxyphenyl)-(2,2-dimethyl-2H-thiochromen-4-yl)-
methanone (10c). As described for 14b, 9c (300 mg, 0.87 mmol)
in dry ether (50 ml), MnO2 (762 mg, 8.77 mmol) furnished 10c
(235 mg, 79%) as colorless semi solid, Rf = 0.75 (AcOEt/hexane,
10:90); IR (KBr): 3021, 2361, 1732, 1268, 1217, 758, 668 cm-1; 1H
NMR (300 MHz, CDCl3+CCl4): d 7.45 (d, 1H, J = 1.8), 7.34–7.30
(m, 2H), 7.16–7.11 (m, 2H), 7.03–6.98 (m, 1H), 6.78 (d, 1H, J=
8.4), 6.01 (s, 1H), 3.90 (s, 3H), 3.88 (s, 3H), 1.49 (s, 6H); 13C NMR
(75 MHz, CDCl3+CCl4): d 195.1, 153.6, 149.1, 137.9, 136.5, 132.1,
130.2, 130.0, 128.3, 128.0, 126.9, 125.6, 125.5, 111.6, 110.0, 55.9,
55.8, 40.5, 28.6; MS (ESI): m/z 341 [M + 1]+; Anal. Calcd. for
C20H20O3 S: C, 70.56; H, 5.92. Found: C, 70.65; H, 6.02.
NMR (75 MHz, CDCl3): d 189.1, 140.6, 138.3, 137.8, 135.1, 132.2,
130.1, 128.5, 128.3, 127.9, 127.2, 126.9, 126.7, 126.6, 125.9, 125.4,
123.3, 121.1, 116.4, 48.0, 40.4, 28.5; MS (ESI): m/z 410 [M + 1]+;
Anal. Calcd. for C27H23 NOS: C, 79.18; H, 5.66; N, 3.42. Found:
C, 79.27; H, 5.71; N, 3.33.
(1-Benzyl-1H-pyrrol-2-yl)(7-methoxy-2,2-dimethyl-2H-chro-
men-4-yl)methanone (14f). As described for 14b, 13f (300 mg,
0.80 mmol) in dry ether (50 ml), MnO2 (695 mg, 8.00 mmol)
furnished 14f (244 mg, 81%) as colorless semi solid, Rf = 0.67
(AcOEt/hexane, 10:90); IR (KBr): 3021, 2361,1730, 1606, 1216,
1045, 761 cm-1; 1H NMR (300 MHz, CDCl3): d 7.36–7.17 (m, 5H),
7.11 (d, 1H, J = 8.4), 7.03–7.01 (m, 2H), 6.92 (dd, 1H, J1 = 1.5,
J2 = 3.9), 6.45–6.36 (m, 2H), 6.20–6.17 (m, 1H), 5.77 (s, 1H), 5.67
(s, 2H), 3.76 (s, 3H), 1.50 (s, 6H); 13C NMR (75 MHz, CDCl3): d
184.8, 160.9, 154.0, 138.0, 133.3, 131.6, 130.4, 130.2, 128.5, 127.5,
127.2, 126.1, 123.5, 112.6, 198.6, 106.8, 102.2, 75.6, 55.2, 52.5,
27.3; MS (ESI): m/z 374 [M + 1]+; Anal. Calcd. for C24H23 NO3:
C, 77.19; H, 6.21; N, 3.75. Found: C, 77.10; H, 6.31; N, 3.81.
(7-Methoxy-2,2-dimethyl-2H-chromen-4-yl)thiophen-3-yl-
methanone (14i). As described for 14b, 13i (300 mg, 0.99 mmol)
in dry ether (50 ml), MnO2 (863 mg, 9.93 mmol) furnished 14i
(223 mg, 75%) as colorless semi solid, Rf = 0.68 (AcOEt/hexane,
10:90); IR (KBr): 3020, 236, 1731, 1651, 1614, 1218, 764 cm-1; 1H
NMR (300 MHz, CDCl3): d 7.95 (dd, 1H, J1 = 1.1, J2 = 2.9),
7.55 (dd, 1H, J1 = 1.1, J2 = 5.0), 7.33–7.30 (m,1H), 7.26–7.23 (m,
1H), 6.41–6.37 (m, 2H), 5.86 (s, 1H), 3.77 (s, 3H), 1.50 (s, 6H);
13C NMR (75 MHz, CDCl3): d 188.2, 161.4, 154.2, 142.0, 134.2,
133.5, 131.9, 128.2, 126.5, 126.2, 112.0, 107.1, 102.6, 75.6, 55.2,
27.4; MS (ESI): m/z 301 [M + 1]+; Anal. Calcd. for C17H16O3 S:
C, 67.98; H, 5.37. Found: C, 68.06; H, 5.48.
(1-Benzyl-1H-pyrrol-2-yl)(7-methoxy-2,2-dimethyl-2H-thio-
chromen-4-yl)methanone (14g). As described for 14b, 13g
(300 mg, 0.76 mmol) in dry ether (50 ml), MnO2 (667 mg,
7.67 mmol) furnished 14g (253 mg, 85%) as colorless semi solid,
Rf = 0.66 (AcOEt/hexane, 10:90); IR (KBr) :3020, 2359,1681,
1220, 759, 670 cm-1; 1H NMR (300 MHz, CDCl3): d 7.35–7.14 (m,
5H), 7.01–6.96 (m, 2H), 6.82 (d, 1H, J = 2.4), 6.77–6.75 (m, 1H),
6.55–6.49 (m, 1H), 6.14–6.11 (m, 1H), 5.89 (s, 1H), 5.64 (s, 2H),
3.75 (s, 3H), 1.45 (s, 6H); 13C NMR (75 MHz, CDCl3): d 186.5,
159.0, 138.0, 137.5, 133.7, 133.6, 131.4, 130.6, 128.5, 127.9, 127.2,
123.9, 123.4, 112.3, 111.5, 108.6, 55.2, 52.5, 40.6, 28.6; MS (ESI):
m/z 390 [M + 1]+; Anal. Calcd. for C24H23 NO2S: C, 74.00; H,
5.95; N, 3.60. Found: C, 74.07; H, 5.88; N, 3.52.
(2,2-Dimethyl-2H-thiochromen-4-yl) thiophen-3-ylmethanone
(14j). As described for 14b, 13j (300 mg, 1.04 mmol) in dry
ether (50 ml), MnO2 (905 mg, 10.4 mmol) furnished 14j (229 mg,
77%) as colorless semi solid, Rf = 0.65 (AcOEt/hexane, 10:90);
1H NMR (300 MHz, CDCl3): d 7.78–7.77 (m, 1H), 7.42–7.41
(m, 1H), 7.28–7.25 (m, 1H), 7.22–7.18 (m, 2H), 7.12–7.06 (m,
1H), 7.00–6.95 (m, 1H), 6.07 (s, 1H), 1.42 (s, 6H); MS (ESI): m/z
303 [M + NH4]+; Anal. Calcd. for C16H14OS2: C, 67.10; H, 4.93.
Found: C, 67.16; H, 5.03.
(3,4-Dimethoxyphenyl)(7-methoxy-2,2-dimethyl-2H-chro-
men-4-yl)methanone (10a). As described for 14b, 9a (300 mg,
0.84 mmol) in dry ether (50 ml), MnO2 (732 mg, 8.42 mmol)
furnished 10a (244 mg, 82%) as colorless semi solid, Rf = 0.71
(AcOEt/hexane, 10:90); IR (KBr): n 3021, 2361, 1730, 1217,761,
670 cm-1; 1H NMR (300 MHz, CDCl3): d 7.54 (d, 1H, J = 1.8z),
7.48 (dd, 1H, J1 = 1.8, J2 = 8.3), 7.12 (d, 1H, J = 8.4), 6.85 (d,
1H, J = 8.3), 6.44–6.37 (m, 2H), 5.70 (s, 1H), 3.96 (s, 3H), 3.95
(s, 3H), 3.79 (s, 3H), 1.53 (s, 6H); 13C NMR (75 MHz, CDCl3): d
193.9, 161.0, 153.9, 153.4, 148.9, 132.5, 131.2, 129.9, 126.3, 125.3,
(2,2-Dimethyl-2H-chromen-4-yl)(thiophen-3-yl)methanone (14k).
As described for 14b, 13k (300 mg, 1.10 mmol) in dry ether (50
ml), MnO2 (958 mg, 11.0 mmol) furnished 14k (232 mg, 77%) as
colorless semi solid, Rf = 0.63 (AcOEt/hexane, 10:90); 1H NMR
(300 MHz, CDCl3): d 7.90–7.89 (m, 1H), 7.51–7.49 (m, 1H), 7.28–
7.25 (m, 1H), 7.22–7.18 (m, 2H), 7.12–7.06 (m, 1H), 7.00–6.95 (m,
1H), 5.92 (s, 1H), 1.45 (s, 6H); 13C NMR (75 MHz, CDCl3): d
193.9, 161.0, 153.9, 153.4, 148.9, 132.5, 131.2, 129.9, 126.3, 125.3,
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112.4, 111.2, 109.7, 106.9, 102.3, 75.7, 55.9, 55.8, 55.1, 27.2; MS
(ESI): m/z 271 [M + 1]+; Anal. Calcd. for C16H14O2S: C, 71.08; H,
5.22. Found: C, 71.16; H, 5.13.
J1 = 2.5, J2 = 8.5), 3.94 (s, 3H), 3.91 (s, 3H), 3.74 (s, 3H), 1.67
(s, 3H), 1.49 (s, 6H); 13C NMR (75 MHz, CDCl3): d 195.9, 160.3,
153.8, 152.7, 149.3, 131.2, 129.9, 129.5, 125.4, 125.2, 114.5, 110.2,
107.0, 78.4, 55.9, 55.8, 55.0, 25.4, 15.6; MS (ESI): m/z 369 [M +
1]+; Anal. Calcd. for C22H24O5: C, 71.72; H, 6.57. Found: C, 71.63;
H, 6.68.
1-Benzyl-2,2-dimethyl-1,2-dihydroquinoline-4-carbaldehyde (16).
To
a
stirred solution of N-benzyl-2,2,4-trimethyl-1,2-
dihydroquinoline (580 mg, 2.196 mmol) in anhydrous dioxane
(44 ml) was added SeO2 (365.66 mg, 3.295 mmol). It was then
heated to reflux and stirred for 2 h. The mixture was filtered
through celite, concentrated in vacuo and was subjected to column
chromatography on silica gel and elution with 10% ethyl acetate
in hexane furnished the desired product 16 (250 mg, 41–45%) as
Typical procedure for the aromatic Nazarov cyclization
11-Benzyl-3-methoxy-6,6-dimethyl-6a,11-dihydro-6H,12aH-5-
oxa-11-azabenzo[5,6]pentaleno[2,1-b]naphthalen-12-one(15b). To
a stirred solution of substrate 14b (200 mg, 0.47 mmol) in
anhydrous DCM (20 ml) at room temperature, was added triflic
acid (CF3SO3H, 0.04 ml, 0.47 mmol) at the same temperature and
the solution was stirred vigorously till the completion of reaction.
It was then neutralized by saturated Na2CO3 solution at 0 ◦C,
extracted with DCM (3 ¥ 10 ml), dried over anhydrous Na2SO4.
After the evaporation, the residue was subjected to column
chromatography on silica gel and elution with 10% ethyl acetate
in hexane furnished the cyclized product 15b (180 mg, 90%) as
colorless semi solid, Rf = 0.51 (AcOEt/hexane, 10:90); IR (KBr):
1716, 1217, 1027, 766 cm-1; 1H NMR (300 MHz, CDCl3): d 7.81
(d, 1H, J = 8.2), 7.73 (dd, 1H, J1 = 0.5, J2 = 8.6), 7.42–7.33 (m,
2H), 7.26–7.18 (m, 6H), 6.64 (dd, 1H, J1 = 2.5, J2 = 8.5), 6.48 (d,
1H, J = 2.5), 5.62 (d, 1H, J = 15.7), 5.52 (d, 1H, J = 15.6), 4.03
(d, 1H, J = 5.9), 3.91 (d, 1H, J = 5.9), 3.77 (s, 3H), 1.78 (s, 3H),
0.71 (s, 3H); 13C NMR (75 MHz, CDCl3): d 191.8, 159.6, 153.3,
144.0, 141.8, 138.4, 137.1, 129.9, 128.7, 127.6, 127.1, 126.8, 123.2,
122.5, 120.9, 113.1, 112.0, 107.8, 102.5, 77.9, 55.2, 50.7, 47.5,
43.6, 29.0, 21.7. MS (ESI): m/z 424 [M + 1]+, 91 [C6H5CH2]+;
Anal. Calcd. for C28H25 NO3: C, 79.41; H, 5.95; N, 3.31. Found:
C, 79.37; H, 5.88; N, 3.39.
1
a viscous yellow oil. Rf = 0.55; H NMR (300 MHz, CDCl3): d
9.70 (s, 1H), 8.14 (dd, 1H, J1 = 1.2, J2 = 7.7), 7.23–7.13 (m, 5H),
6.95–6.90 (m, 1H), 6.62–6.57 (m, 1H), 6.29 (d, 1H, J = 8.3), 6.20
(s, 1H), 4.45 (s, 2H), 1.41 (s, 6H); 13C NMR (75 MHz, CDCl3): d
192.2, 151.6, 143.7, 138.9, 132.4, 130.0, 128.6, 126.7, 126.0, 125.7,
116.9, 116.7, 112.9, 57.4, 47.8, 27.3; MS (ESI): m/z 278 [M + 1]+;
Anal. Calcd. for C19H19 NO: C, 82.28; H, 6.90; N, 5.05. Found: C,
82.19; H, 6.81; N, 4.95.
(2,2-Dimethyl-2H-chromen-4-yl)(phenyl)methanone (14a). As
described for 14b, 13a (300 mg, 1.18 mmol) in dry ether (50 ml),
MnO2 (1.03 g, 11.8 mmol) furnished 14a (235 mg, 79%) as colorless
semi solid, Rf = 0.65 (AcOEt/hexane, 10:90); 1H NMR (300 MHz,
CDCl3+CCl4): d 7.92–7.90(m, 2H), 7.63–7.58 (m, 1H), 7.50–7.45
(m, 2H), 7.30 (dd, 1H, J1 = 1.5, J2 = 7.6), 7.23–7.14 (m, 1H),
6.91–6.83 (m, 2H), 5.95 (s, 1H), 1.53 (s, 6H); 13C NMR (75 MHz,
CDCl3): d 195.1, 152.6, 137.2, 135.6, 133.2, 132.8, 130.0, 129.9,
128.5, 125.7, 121.0, 119.1, 117.0, 75.4, 27.3; MS (ESI): m/z 252
[M + 1]+; Anal. Calcd. for C17H15O2: C, 81.25; H, 6.02. Found: C,
81.16; H, 5.93.
(7-Methoxy-2,2-dimethyl-2H-chromen-4-yl)(thiophen-2-yl) me-
thanone (14l). As described for 14b, 13l (300 mg, 0.99 mmol)
in dry ether (50 ml), MnO2 (863 mg, 9.93 mmol) furnished 14l
(235 mg, 79%) as colorless semi solid, Rf = 0.65 (AcOEt/hexane,
10:90); 1H NMR (300 MHz, CDCl3): d 7.72–7.68 (m, 2H), 7.30 (d,
1H, J = 7.9), 7.15–7.12 (m, 1H), 6.46–6.42 (m, 2H), 5.96 (s, 1H),
3.79 (s, 3H), 1.53 (s, 6H); 13C NMR (75 MHz, CDCl3): d 186.9,
161.3, 154.1, 144.0, 134.8, 134.6, 132.6, 132.0, 128.0, 126.3, 111.8,
107.1, 102.5, 75.7, 55.3, 27.2; MS (ESI): m/z 301 [M + 1]+; Anal.
Calcd. for C17H16O3S: C, 67.98; H, 5.37. Found: C, 68.10; H, 5.29.
11-Benzyl-3-methoxy-6,6-dimethyl-6a,11-dihydro-6H,12aH-5-
thia-11-azabenzo[5,6]pentaleno[2,1-b]naphthalen-12-one
(15c).
As described for 15b, 14c (200 mg, 0.45 mmol) in anhydrous
DCM (20 ml), triflic acid (0.04 ml, 0.45 mmol) furnished 15c
(184 mg, 92%) as colorless white solid, m.p. 165–170 ◦C; Rf =
0.53 (AcOEt/hexane, 10:90); IR (KBr): 2926, 2361, 1692, 1594,
1216, 759 cm-1; 1H NMR (300 MHz, CDCl3): d 7.78 (d, 1H, J =
8.0), 7.63 (d, 1H, J = 9.2), 7.41–7.32 (m, 2H), 7.27–7.17 (m, 6H),
6.82–6.78 (m, 2H), 5.63 (d, 1H, J = 15.8), 5.53 (d, 1H, J = 15.9),
4.19 (d, 1H, J = 5.9), 4.08 (d, 1H, J = 6.0), 3.79 (s, 3H), 1.58 (s,
3H), 1.17 (s, 3H); 13C NMR (75 MHz, CDCl3): d 191.4, 158.4,
143.9, 141.5, 138.9, 137.1, 134.4, 131.2, 128.6, 127.6, 127.2, 126.6,
125.2, 124.2, 123.1, 120.9, 113.4, 111.9, 111.8, 57.2, 55.2, 49.2,
47.6, 47.5, 26.0; MS (ESI): m/z 440 [M + 1]+; Anal. Calcd. for
C28H25 NO2S: C, 76.51; H, 5.73; N, 3.19. Found: C, 76.59; H,
5.81; N, 3.11.
(7-Methoxy-2,2-dimethyl-2H-chromen-4-yl)(5-methylfuran-2-
yl)methanone (14m). As described for 14b, 13m (300 mg,
1.0 mmol) in dry ether (50 ml), MnO2 (869 mg, 10.0 mmol)
furnished 14m (238 mg, 80%) as colorless semi solid, Rf = 0.69
(AcOEt/hexane, 10:90); 1H NMR (300 MHz, CDCl3): d 7.31 (d,
1H, J = 9.0), 7.04 (d, 1H, J = 3.4), 6.44–6.40 (m, 2H), 6.15 (d,
1H, J = 3.0), 5.94 (s, 1H), 3.76 (s, 3H), 2.42 (s, 3H), 1.50 (s, 6H);
MS (ESI): m/z 299 [M + 1]+; Anal. Calcd. for C18H18O4: C, 72.47;
H, 6.08. Found: C, 72.36; H, 5.93.
11-Benzyl-6,6-dimethyl-6a,11-dihydro-6H,12aH-5-oxa-11-aza-
benzo[5,6]pentaleno[2,1-b]naphthalene (15d). As described for
15b, 14d (200 mg, 0.50 mmol) in anhydrous DCM (20 ml), triflic
acid (0.045 ml, 0.50 mmol) furnished 15d (183 mg, 92%) as
colorless white solid, m.p. 160–165 ◦C; Rf = 0.56 (AcOEt/hexane,
10:90); IR (KBr): 2923, 2855, 2361, 1692, 1461, 1217, 759, cm-1;
1H NMR (300 MHz, CDCl3): d 7.86–7.80 (m, 2H), 7.42–7.34 (m,
2H), 7.26–7.15 (m, 7H), 7.06–7.01 (m, 1H), 6.90 (dd, 1H, J1 =
0.9, J2 = 8.0), 5.63 (d, 1H, J = 15.6), 5.53 (d, 1H, J = 15.7), 4.09
(d, 1H, J = 5.8), 3.93 (d, 1H, J = 6.0), 1.79 (s, 3H), 0.70 (s, 3H);
(3,4-Dimethoxyphenyl)(7-methoxy-2,2,3-trimethyl-2H-chro-
men-4-yl)methanone (21). As described for 14b, 20 (300 mg,
0.81 mmol) in dry ether (50 ml), MnO2 (705 mg, 8.10 mmol)
furnished 14m (226 mg, 76%) as colorless semi solid, Rf = 0.71
(AcOEt/hexane, 10:90); 1H NMR (300 MHz, CDCl3): d 7.58 (d,
1H, J = 1.58), 7.44 (dd, 1H, J1 = 1.7, J2 = 8.3), 6.80 (d, 1H, J =
8.4), 6.59 (d, 1H, J = 8.4), 6.40 (d, 1H, J = 2.4), 6.27 (dd, 1H,
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13C NMR (75 MHz, CDCl3): d 191.3, 152.4, 144.1, 141.9, 138.3,
137.0, 129.3, 128.7, 127.9, 127.6, 127.1, 126.8, 123.2, 122.5, 121.1,
121.0, 122.0, 77.6, 51.1, 47.5, 43.7, 29.0, 21.6; MS (ESI): m/z 394
[M + 1]+; Anal. Calcd. for C27H23 NO2: C, 82.42; H, 5.89; N, 3.56.
Found: C, 82.38; 5.95; N, 3.63
14.7), 3.99 (d, 1H, J = 6.2), 3.52 (d, 1H, J = 6.2), 1.51 (s,
3H), 1.00 (s, 3H). MS (ESI): m/z 344 [M + 1]+; Anal. Calcd for
C23H21 NO2: C, 80.44; H, 6.16; N, 4.08. Found: C, 80.56; H, 6.28;
N, 3.98.
3,8,9-Trimethoxy-6,6-dimethyl-6a,11a-dihydro-6H-indeno[1,2-
c]chromen-11-one (12a). As described for 15b, 10a (200 mg,
0.56 mmol) in anhydrous DCM (20 ml), triflic acid (0.05 ml,
0.56 mmol) furnished 12a (180 mg, 90%) as colorless semi solid,
Rf = 0.64 (AcOEt/hexane, 10:90); IR (KBr): 3018, 2925, 2360,
11-Benzyl-6,6-dimethyl-6a,11-dihydro-6H,12aH-5-thia-11-aza-
benzo[5,6]pentaleno[2,1-b]naphthalen-12-one (15e). As described
for 15b, 14e (200 mg, 0.48 mmol) in anhydrous DCM (20 ml),
triflic acid (0.04 ml, 0.48 mmol) furnished 15e (182 mg, 91%) as
colorless semi solid, Rf = 0.58 (AcOEt/hexane, 10:90); IR (KBr):
3020, 2360, 1691, 1595, 1216, 761, 670 cm-1; 1H NMR (300 MHz,
CDCl3): d 7.80 (d, 1H, J = 8.0), 7.71 (d, 1H, J = 6.8), 7.42–
7.33 (m, 2H), 7.24–7.18 (m, 9H), 5.63 (d, 1H, J = 15.6), 5.54
(d, 1H, J = 15.6), 4.24 (d, 1H, J = 6.0), 4.11 (d, 1H, J = 6.0),
1.57 (s, 3H), 1.18 (s, 3H); 13C NMR (75 MHz, CDCl3): d 190.9,
143.9, 141.6, 139.0, 137.1, 133.4, 133.1, 130.4, 128.7, 128.5, 127.6,
127.2, 127.1, 126.7, 125.5, 124.2, 123.1, 120.9, 111.9, 57.9, 49.4,
47.5, 29.6, 26.0; MS (ESI): m/z 410 [M + 1]+; Anal. Calcd. for
C27H23 NOS: C, 79.18; H, 5.66; N, 3.42. Found: C, 79.30; H, 5.75;
N, 3.35.
1
1708, 1591, 1462, 1219, 1035, 762 cm-1; H NMR (300 MHz,
CDCl3+CCl4): d 7.65 (d, 1H, J = 8.5), 7.24 (s, 1H), 6.98 (s, 1H),
6.61 (dd, 1H, J1 = 2.5, J2 = 8.5), 6.41 (d, 1H, J = 2.5), 4.00 (s, 3H),
3.94 (s, 3H), 3.77 (s, 3H), 3.66 (d, 1H, J = 5.9), 3.59 (d, 1H, J = 5.9),
1.67 (s, 3H), 0.55 (s, 3H); 13C NMR (75 MHz, CDCl3+CCl4): d
201.2, 159.6, 154.9, 153.1, 150.2, 147.0, 130.4, 129.8, 112.4, 107.9,
107.8, 105.0, 102.3, 56.2, 56.1, 55.1, 47.3, 46.7, 28.4, 20.6; MS
(ESI): m/z 355 [M + 1]+; Anal. Calcd. for C21H22O5: C, 71.17; H,
6.26. Found: C, 71.25; H, 6.34.
8,9-Dimethoxy-6,6-dimethyl-6a,11a-dihydro-6H-indeno[1,2-c]-
chromen-11-one (12b). As described for 15b, 10b (200 mg,
0.61 mmol) in anhydrous DCM (20 ml), triflic acid (0.05 ml,
0.61mmol) furnished 12b (182 mg, 91%) as colorless semi solid,
Rf = 0.65 (AcOEt/hexane, 10:90); IR (KBr): 3020, 2360, 1710,
1591, 1219, 1032, 759 cm-1; 1H NMR (300 MHz, CDCl3): d 7.80
(dd, 1H, J1 = 1.1, J2 = 7.6), 7.28 (s, 1H), 7.21–7.15 (m, 1H), 7.05
(dd, 1H, J1 = 1.1, J2 = 7.4), 7.01 (s, 1H), 6.90–6.87 (m, 1H), 4.01
(s, 3H), 3.94 (s, 3H), 3.72 (d, 1H, J = 5.9), 3.67 (d, 1H, J = 5.9),
1.70 (s, 3H), 0.56 (s, 3H); 13C NMR (75 MHz, CDCl3): d 201.0,
154.8, 152.2, 150.0, 147.1, 129.8, 129.5, 127.8, 121.1, 120.2, 117.1,
107.8, 104.9, 77.2, 56.3, 56.1, 47.2, 47.1, 28.3, 20.4; MS (ESI): m/z
325[M + 1]+; Anal. Calcd. for C20H20O4: C, 74.06; H, 6.21. Found:
C, 73.95; H, 6.13.
(9-Benzyl-3-methoxy-6,6-dimethyl-6a,9-dihydro-6H,10aH-5-
oxa-9-azapentaleno[2,1-a]naphthalen-10-one (15f). As described
for 15b, 14f (200 mg, 0.53 mmol) in anhydrous DCM (20 ml),
triflic acid (0.045 ml, 0.53 mmol) furnished 15f (170 mg, 85%) as
colorless semi solid, Rf = 0.49 (AcOEt/hexane, 10:90); IR (KBr):
1
3020, 2361, 1709, 1216, 1104, 761 cm-1; H NMR (300 MHz,
CDCl3): d 7.66 (d, 1H, J = 8.6), 7.30–7.21 (m, 5H), 7.01 (d, 1H,
J = 2.4), 6.58 (dd, 1H, J1 = 2.5, J2 = 8.4), 6.40 (d, 1H, J = 2.4),
6.17 (d, 1H, J = 2.3), 5.30 (d, 1H, J = 14.7), 5.20 (d, 1H, J = 14.6),
3.93 (d, 1H, J = 6.2), 3.77 (s, 3H), 3.49 (d, 1H, J = 6.2 Hz), 1.50
(s, 3H), 1.01 (s, 3H); MS (ESI): m/z 374 [M + 1]+; Anal. Calcd. for
C24H23 NO3: C, 77.19; H, 6.21; N, 3.75. Found: C, 77.26; H, 6.14;
N, 3.86.
8,9-Dimethoxy-6,6-dimethyl-6a,11a-dihydro-6H-5-thiabenzo-
[a]fluoren-11-one (12c). As described for 15b, 10c (200 mg,
0.58 mmol) in anhydrous DCM (20 ml), triflic acid (0.046 ml,
0.58 mmol) furnished 12c (173 mg, 87%) as colorless semi solid,
Rf = 0.67 (AcOEt/hexane, 10:90); IR (KBr): 3021, 2360, 1730,
9-Benzyl-3-methoxy-6,6-dimethyl-6a,9-dihydro-6H,10aH-5-
thia-9-azapentaleno[2,1-a]naphthalen-10-one (15g). As described
for 15b, 14g (200 mg, 0.51 mmol) in anhydrous DCM (20 ml),
triflic acid (0.045 ml, 0.51 mmol) furnished 15g (175 mg, 88%) as
colorless semi solid, Rf = 0.53 (AcOEt/hexane, 10:90); IR(KBr)
3021, 2360, 1731, 1218, 763, 670 cm-1; 1H NMR (300 MHz,
CDCl3): d 7.80 (d, 1H), 7.33–7.25 (m, 5H), 7.05 (d, 1H, J = 2.4),
6.81–6.74 (m, 2H), 6.20 (d, 1H, J = 2.4), 5.32 (d, 1H, J = 14.8),
5.18 (d, 1H, J = 14.7), 4.09 (d, 1H, J = 6.7), 3.78 (s, 3H), 3.65
(d, 1H, J = 6.3), 1.46 (s, 3H), 1.38 (s, 3H); 13C NMR (75 MHz,
CDCl3): d 187.8, 158.2, 150.3, 137.0, 134.4, 133.9, 133.9, 131.2,
128.8, 127.9, 124.8, 113.5, 111.9, 107.3, 56.8, 55.2, 50.9, 48.7, 46.1,
29.0, 25.9; MS (ESI): m/z 390 [M + 1]+; Anal. Calcd. for C24H23
NO2S: C, 74.00; H, 5.95; N, 3.60. Found: C, 74.08; H, 6.02; N,
3.53.
1
1217, 1044, 764 cm-1; H NMR (300 MHz,CDCl3+CCl4): d 7.75
(d, 1H, J = 7.5), 7.25–7.12 (m, 4H), 6.97 (s, 1H), 4.00 (s, 3H),
3.94 (s, 3H), 3.89 (d, 1H, J = 5.9), 3.86 (d, 1H, J = 5.9), 1.54
(s, 3H), 0.88 (s, 3H); 13C NMR (75 MHz, CDCl3+CCl4): d 200.2,
154.4, 150.2, 146.2, 132.7, 131.5, 131.0, 129.8, 127.8, 125.3, 109.0,
104.7, 56.2, 56.0, 53.1, 52.1, 45.7, 28.58, 24.0; MS (ESI): m/z 341
[M + 1]+; Anal. Calcd. for C20H20O3S: C, 70.56; H, 5.92. Found:
C, 70.44; H, 6.01.
3-Methoxy-6,6-dimethyl-6a,10a-dihydro-6H-5-oxa-7-thiapent-
aleno[2,1-a]naphthalen-10-one (15i). As described for 15b, 14i
(200 mg, 0.67 mmol) in anhydrous DCM (20 ml), triflic acid
(0.06 ml, 0.67 mmol) furnished 15i (168 mg, 84%) as colorless semi
solid, Rf = 0.48 (AcOEt/hexane, 10:90); IR (KBr): 3019, 2360,
1714, 1584, 1215, 760, 669 cm-1; 1H NMR (300 MHz, CDCl3): d
7.55 (dd, 1H, J1 = 0.6, J2 = 8.5), 7.29 (d, 1H, J = 5.0), 7.13 (d,
1H, J = 5.2), 6.51 (dd, 1H, J1 = 2.5, J2 = 8.5), 6.30 (d, 1H, J =
2.5), 3.93 (d, 1H, J = 6.5), 3.71 (d, 1H, J = 6.6), 3.68 (s, 3H),
1.51 (s, 3H), 0.91 (s, 3H); 13C NMR (75 MHz, CDCl3): d 194.5,
166.7, 159.7, 152.9, 146.1, 131.0, 129.8, 120.3, 111.7, 108.3, 102.6,
76.0, 55.1, 51.2, 47.2, 27.2, 22.5; MS (ESI): m/z 301 [M + 1]+.
9-Benzyl-6,6-dimethyl-6a,9-dihydro-6H,10aH-5-oxa-9-azapen-
taleno[2,1-a]naphthalen-10-one (15h). As described for 15b, 14h
(200 mg, 0.58 mmol) in anhydrous DCM (20 ml), triflic acid
(0.046 ml, 0.58 mmol) furnished 15h (174 mg, 87%) as colorless
semi solid, Rf = 0.45 (AcOEt/hexane, 10:90); IR (KBr): 3021,
2361, 1667, 1595, 1216, 763, 670 cm-1; 1H NMR (300 MHz,
CDCl3): d 7.77 (d, 1H, J = 7.6), 7.30–7.21 (m, 5H), 7.16–7.11
(m, 1H), 7.03–6.96 (m, 2H), 6.83 (dd, 1H, J1 = 1.0, J2 = 8.1),
6.18 (d, 1H, J = 2.4), 5.31 (d, 1H, J = 14.8), 5.21 (d, 1H, J =
1866 | Org. Biomol. Chem., 2009, 7, 1858–1867
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Anal. Calcd. for C17H16O3 S:C, 67.98; H, 5.37. Found: C, 68.07; H,
5.31.
Notes and references
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M. Iwamoto, H. Ohishi, S. Matsunaga and R. Tanaka, Tetrahedron
Lett., 1999, 40, 6419.
2 (a) W. H. Lin, J. M. Fang and Y. S. Cheng, Phytochemistry, 1996, 42,
1657; (b) C. I. Chang, S. C. Chien, S. M. Lee and Y. H. Kuo, Chem.
Pharm. Bull., 2003, 51, 1420.
3 C. I. Chang, J. Y. Chang, C. C. Kuo, W. Y. Pan and W. Y. Kuo, Planta
Med., 2005, 71, 72.
4 (a) M. Iwamoto, H. Ohtsu, H. Tokuda, H. Nishino, S. Matsunaga
and R. Tanaka, Bioorg. Med. Chem., 2001, 9, 1911; (b) T. Minami, M.
Wamoto, H. Ohtsu, H. Ohishi, R. Tanaka and A. Yoshitake, Planta
Med., 2002, 68, 742.
5 (a) E. Fillion and D. Fishlock, J. Am. Chem. Soc., 2005, 127, 13144;
(b) R. M. McFadden and B. M. Stoltz, J. Am. Chem. Soc., 2006,
128, 7738; (c) M. Banerjee, R. Mukhopadhyay, B. Achari and A. K.
Banerjee, Org. Lett., 2003, 5, 3931; (d) L. Planas, M. Mogi, H. Takita, T.
Kajimoto and M. Node, J. Org. Chem., 2006, 71, 2896; (e) M. Banerjee,
R. Mukhopadhyay, B. Achari and A. K. Banerjee, J. Org. Chem., 2006,
71, 2787.
6 For recent reviews on Nazarov chemistry, see: (a) M. Harmata,
Chemtracts, 2004, 17, 416; (b) M. A. Tius, Eur. J. Org. Chem., 2005, 11,
2193; (c) A. J. Frontier and C. Collison, Tetrahedron, 2005, 61, 7577;
(d) H. Pellissier, Tetrahedron, 2005, 61, 6479.
7 (a) V. Aggarwal and A. Belfield, Org. Lett., 2003, 5, 5075; (b) E.
Occhiato, C. Prandi, A. Ferrali, A. Guarna and P. Venturello, J. Org.
Chem., 2003, 68, 9728; (c) C. Bee, E. Leclerc and M. A. Tius, Org. Lett.,
2003, 5, 4927; (d) D. Trauner, S. Gradl and G. Liang, Org. Lett., 2003,
5, 4913.
8 (a) S. E. Denmark, M. A. Wallace and C. B. Walker, J. Org. Chem.,
1990, 55, 5543; (b) S. E. Denmark and R. C. Klix, Tetrahedron, 1988,
44, 4043; (c) J. A. Bender, A. M. Arif and F. G. West, J. Am. Chem.
Soc., 1999, 121, 7443; (d) C. C. Browder, F. P. Marmsater and F. G.
West, Org. Lett., 2001, 3, 3033.
6,6-Dimethyl-6a,11a-dihydro-6H,7H-5,8-dithiacyclopenta[b]-
phenanthren-11-one (15j). As described for 15b, 14j (200 mg,
0.70 mmol) in anhydrous DCM (20 ml), triflic acid (0.062 ml,
0.70 mmol) f◦urnished 15j (176 mg, 88%) as colorless semi solid,
m.p. 95–100 C; Yield: 88%, Rf = 0.47 (AcOEt/hexane, 10:90);
IR (KBr): 3015, 2351, 1704, 1586, 1219, 760, 669 cm-1; 1H NMR
(300 MHz, CDCl3): d 7.64 (d, 1H, J = 7.5), 7.27 (d, 1H, J =
5.0), 7.17–7.04 (m, 4H), 4.13 (d, 1H, J = 6.6), 3.87 (d, 1H, J =
6.6), 1.44 (s, 3H), 1.24 (s, 3H); 13C NMR (75 MHz, CDCl3): d
193.2, 167.1, 146.7, 132.1, 131.0, 130.8, 130.3, 128.4, 127.0, 125.7,
120.1, 57.1, 52.3, 44.5, 28.3, 25.4; MS (ESI): m/z 303 [M + NH4]+;
Anal. Calcd. for C16H14OS2: C, 67.10; H, 4.93. Found: C, 67.02;
H, 5.01.
6,6-Dimethyl-6a,10a-dihydro-6H-5-oxa-7-thiapentaleno[2,1-a]-
naphthalen-10-one (15k). As described for 15b, 14k (200 mg,
0.74 mmol) in anhydrous DCM (20 ml), triflic acid (0.065 ml,
0.74 mmol) furnished 15k (162 mg, 81%) as colorless white solid,
◦
1
m.p. 170–175 C; Rf = 0.46 (AcOEt/hexane, 10:90); H NMR
(300 MHz, CDCl3): d 7.78 (d, 1H, J = 7.6), 7.38 (d, 1H, J = 5.7),
7.21 (d, 1H, J = 5.0), 7.17–7.12 (m, 1H), 7.06–6.98 (m, 1H), 6.88
(dd, 1H, J1 = 1.1, J2 = 8.0), 4.09 (d, 1H, J = 6.5), 3.83 (d, 1H,
J = 6.5), 1.60 (s, 3H), 0.98 (s, 3H); 13C NMR (75 MHz, CDCl3): d
194.4, 167.1, 152.1, 145.9, 131.3, 129.2, 128.1, 121.5, 120.1, 119.8,
117.5, 75.9, 51.58, 47.23, 27.1, 22.4; MS (ESI): m/z 271 [M + 1]+;
Anal. Calcd. for C16H14O2S: C, 71.08; H, 5.22. Found: C, 70.95;
H, 5.11.
9 G. Liang, Y. Xu, I. B. Seiple and D. Trauner, J. Am. Chem. Soc., 2006,
128, 11022.
5-Benzyl-6,6-dimethyl-5,6,6a,10a-tetrahydro-7-thia-5-azapent-
aleno[2,1-a]naphthalen-10-one (19). As described for 15b, 18
(200 mg, 0.56 mmol) in anhydrous DCM (20 ml), triflic acid
(0.05 ml, 0.56 mmol) furnished 19 (170 mg, 85%) as dark solid, m.p.
100–105 ◦C; Rf = 0.49 (AcOEt/hexane, 10:90); IR (Neat): 3021,
10 (a) G. Mehta and N. Krishnamurthy, J. Chem. Soc., Chem. Commun.,
1986, 1319; (b) S. E. Denmark, K. L. Habermas and G. A. Hite, Helv.
Chim. Acta, 1988, 71, 168; (c) S. E. Denmark, M. A. Wallace, Jr. and
C. B. Walker, J. Org. Chem., 1990, 55, 5543; (d) C. Prandi, A. Ferrali,
A. Guarna, P. Venturello and E. G. Occhiato, J. Org. Chem., 2004, 69,
7705.
1
2360, 1731, 1216, 761, 670 cm-1; H NMR (300 MHz, CDCl3):
11 R. D. Mazzola, Jr., T. D. White, H. R. Vollmer-Snarr and F. G. West,
Org. Lett., 2005, 7, 2799.
12 (a) K. F. Cheng, K. P. Chan and T. F. Lai, J. Chem. Soc., Perkin Trans.
1, 1991, 2461; (b) C. Song, D. Knight and M. Whatton, Org. Lett.,
2006, 8, 163; (c) J. A. Malona, J. M. Colbourne and A. J. Frontier, Org.
Lett., 2006, 8, 5661.
13 (a) Shagufta, M. K. Parai and G. Panda, Tetrahedron Lett., 2005,
46, 8849; (b) Shagufta, A. K. Srivastava and G. Panda, Tetrahedron
Lett., 2006, 47, 1065; (c) M. K. Parai, Shagufta, A. K. Srivastava, M.
Kassack and G. Panda, Tetrahedron, 2008, 64, 9962; (d) Shagufta, R.
Raghunandan, P. R. Moulik and G. Panda, Tetrahedron Lett., 2005, 46,
5337; (e) C. D. Gabbutt, D. J. Hartley, J. D. Hepworth, B. M. Heron,
M. Kanjia and M. M. Rahman, Tetrahedron, 1994, 50, 2507; (f) C. D.
Gabbutt, J. D. Hepworth and B. M. Heron, J. Chem. Soc., Perkin Trans.
1, 1994, 653.
d 7.69 (d, 1H, J = 7.4), 7.37 (d, 1H, J = 5.1), 7.28–7.16 (m,
6H), 7.02–6.97 (m, 1H), 6.83–6.78 (m, 1H), 6.45 (d, 1H, J = 8.2),
4.59 (d, 1H, J = 17.5), 4.37 (d, 1H, J = 17.5), 4.24 (d, 1H, J =
6.5), 3.82 (d, 1H, J = 6.5), 1.43 (s, 6H); 13C NMR (75 MHz,
CDCl3): d 195.2, 168.2, 146.8, 144.2, 140.2, 131.0, 129.2, 128.5,
127.7, 126.6, 126.0, 120.3, 118.6, 118.1, 114.3, 56.4, 53.8, 51.4,
49.4, 25.0, 24.2; MS (ESI): m/z 360 [M + 1]+; Anal. Calcd. for
C23H21 NOS: C, 76.84; H, 5.89; N, 3.90. Found: C, 76.93; H, 5.97;
N, 4.01.
Acknowledgements
14 R. K. Akuamoah, P. E. Brown, W. Y. Marcus and J. E. Steele, J. Chem.
Soc., Perkin Trans. 1, 1995, 197.
15 (a) M. A. Weaver, D. J. Wallace, and J. M. Straley, U. S. Patent 3 247,
211, 1996; (b) M. A. Marsini, K. M. Gowin and T. R. R. Pettus, Org.
Lett., 2006, 8, 3481.
This research project was supported by the Department of Science
and Technology (SR/S1/OC-23/2005), New Delhi, India in
the form of grant. Ritesh and Maloy thank DST and CSIR
respectively for fellowships. This has CDRI communication num-
ber 7345.
16 I. Fleming, Frontier Orbitals and Organic Chemical Reactions, John
Wiley & Sons, Ltd., New York, NY, 1976, Chapter 3, p. 57.
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