Cycloalkenyl nonaflates as electrophilic cross-coupling substrates for palladium catalyzed C-N bond forming reactions with enolizable heterocycles under microwave enhanced conditions

Article abstract of DOI:10.1039/c3nj01355c

Microwave-mediated, palladium catalyzed C-N bond forming reactions with activated cycloalkenyl nonaflates and enolizable heterocycles using cesium carbonate as a base and a catalytic system employing Pd(OAc)₂/ Xantphos or Pd(OAc)₂/dp

Full text of DOI:10.1039/c3nj01355c

NJC
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Cycloalkenyl nonaflates as electrophilic
cross-coupling substrates for palladium catalyzed
C–N bond forming reactions with enolizable
heterocycles under microwave enhanced
conditions†
Cite this: New J. Chem., 2014,
3
8, 1294
a
bc
a
K. K. Abdul Khader, Ayyiliath. M. Sajith,* bcM. Syed Ali Padusha,*
d
H. P. Nagaswarupa and A. Muralidharan
Microwave-mediated, palladium catalyzed C–N bond forming reactions with activated cycloalkenyl non-
aflates and enolizable heterocycles using cesium carbonate as a base and a catalytic system employing
2 2
Pd(OAc) /Xantphos or Pd(OAc) /dppp were found to be effective in driving the reactions to completion.
Received (in Porto Alegre, Brazil)
rd November 2013,
Accepted 29th November 2013
3
This method resulted in good to excellent yields of the coupled products (22 examples, 25–90%) in
short reaction time (30–60 min). Under optimum conditions, cycloalkenyl nonaflates were found to be
an effective alternative to analogous triflates in C–N bond forming processes due to their increased
DOI: 10.1039/c3nj01355c
4
stability under the reaction conditions. The use of tetrabutylammonium bromide (Bu NBr) as an additive
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in these transformations proved to be effective and resulted in better yields of the coupled products.
The use of perfluoroalkene sulfonates as electrophilic cross-
coupling substrates in Buchwald–Hartwig cross-coupling
Introduction
The palladium catalyzed amination of aryl, vinyl, heteroaryl reaction has also been explored and studied in detail by various
2
,3
halides and pseudo halides has become a common method in the researchers.
Among these perfluoroalkene sulfonates tri-
O ) are the most popular derivatives and have
1
4
À
field of organic synthesis. Recently, the use of arenediazonium flates (CF
3
SO
2
salts as electrophilic cross-coupling partners in various palladium been studied in countless applications. While aryl and alkenyl
mediated cross-couplings has been explored by various triflates were found to be suitable cross-coupling substrates
1
b
5
researchers. Also research on palladium(II) catalyzed oxidative in many palladium catalyzed cross-coupling reactions, base
amination
1
e–j
with olefins is gaining tremendous potential in promoted nucleophilic cleavage of the triflate moiety can occur
recent years. Guosheng Liu et al. reported a highly efficient with competitive rates lowering the yields of the coupled
protocol for palladium-catalyzed intermolecular aerobic oxida- product. Many improved conditions were explored through
tive amination of terminal alkenes for the synthesis of allylamine the use of weaker bases or by the slow addition of the triflate;
derivatives. All these protocols have gained much importance however, this protocol is not always successful or practical.
in the synthesis and functionalization of heterocyclic analogues. An effective alternative to aryl/alkenyl triflates are aryl/alkenyl
6
As a part of our research program we were interested in the direct nonaflates, which can be prepared from the corresponding
7
,8
9,10
amination reactions of cycloalkenyl nonaflates with enolizable alcohols or ketones. Nonaflates are stable to chromatography
heterocycles.
9
and can be stored at room temperature. Nonaflates as electro-
philes have been shown to have reactivity similar to triflates in
11
metal catalyzed cross-coupling reactions (Suzuki–Miyuara,
a
Post Graduate and Research Department of Chemistry, Jamal Mohamed College,
12
13
14
Negishi and Heck ) and are less prone to hydrolysis. Buchwald
Bharathidasan University, Tiruchirapalli, India. E-mail: m.padusha@gmail.com;
et al. have done extensive optimization studies of palladium-
Fax: +91 4672331435; Tel: +91 9865447289
b
15
Postgraduate and Research Department of Chemistry, Kasaragod Govt. College,
catalyzed amination of aryl nonaflates. Many useful applications
À
Kannur University, Kasaragod, India. E-mail: sajithmeleveetil@gmail.com
of nonaflates (nonafluorobutane sulfonates, NfO ), which are the
c
Organic Chemistry Division, School of Chemical Sciences, Nehru Arts and Science
16
C4 homologues of triflates have been published emphasizing
College, Kannur University, Kannur, India
17,18
d
their tremendous synthetic advantages.
From a synthetic point
East West Institute of Technology, off Magadi Road, Bangalore, India
of view the transformation of a carbonyl function into an alkenyl
sulfonate is of great interest since these intermediates are very
†
Electronic supplementary information (ESI) available. See DOI: 10.1039/
c3nj01355c
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The introduction of halogen substituents can however be
tedious and unselective during a complex synthetic process.
The conversion of a carbonyl compound into an alkenyl sulfo-
nate, however, can be achieved with fairly simple and highly
2
1–23
selective methods.
The presence of substituted pyrid-2-ones in biologically relevant
analogues (Fig. 1) has attracted synthetic organic chemists and
hence an efficient protocol to access these compounds is of high
relevance. The presence of these N-alkylated heterocycles in both
natural products and pharmacologically relevant molecules renders
them as useful synthons in the field of medicinal chemistry.
24
24c
Moreover, enolizable heterocycles, such as 2-hydroxypyridine,
-hydroxypyrimidine, 2-hydroxybenzimidazole, 3-hydroxypyridazine
etc. have provoked great interest in biological and chemical fields as
4
2
5
a result of their ability to serve as models for hydrogen bonding
25
25
tautomerization, and proton shuttling in both chemical and
biological processes. These data stimulated our studies on the
20a,b,24c
synthesis of 2,3 substituted cycloalkenes
which can be useful
Fig. 1 Pharmacologically relevant pyridones.
synthons in the field of medicinal chemistry during the lead
optimization processes. Herein, we report highly efficient protocol
for palladium catalysed cross-coupling reactions of cycloalkenyl
Although nonaflates with enolizable heterocycles. Fig. 2 shows the synthetic
1
9,20
frequently employed in metal-catalyzed reactions.
2
0
20b
alkenyl bromides and iodides
are commonly used in utility of the central core moiety which allows a diversity oriented
metal-promoted reactions they are not always easily available. synthesis of novel analogues based on this core moiety.
Fig. 2 Synthetic utility of the core moiety.
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Results and discussion
Table 1 Effect of catalyst on cross-coupling of 2a with 4a
a,b
Entry
Catalytic system
Yield (%)
The synthesis of the electrophilic cross-coupling partners
(
2a, 2b, 3a and 3b) employed for the Buchwald–Hartwig coupling
1
2
3
4
5
Pd
Pd
Pd
Pd
Pd
2
2
2
2
2
(dba)
(OAc)
3
/PPh
/X-phos
/BINAP
/Xantphos
/dppp
3
0
0
2
reaction were accomplished according to the conditions shown
in Fig. 3. Mariano et al. reported a general approach for the
synthesis of 1-substituted-vinyl-2-pyridones via a nucleophilic
displacement of cycloalkenyl chlorides with 2-hydroxy pyridine.
Based on these results we were interested in exploring the (3 equiv.), Bu NBr (1.5 equiv.), 2a (1 equiv.), 4a (1.2 equiv.), microwave,
use of other electrophilic substrates for palladium mediated
cross-coupling reactions. Our initial attempts to cross-couple
cycloalkenyl triflate 2a and 2b with pyridone 4a using various
palladium catalyst and ligand combinations as described in
Table 1 under microwave conditions did not yield any product. Entry
Different bases (Cs CO , K CO , Na CO , NaOtBu etc.) were
2 3 2 3 2 3
explored to optimize the reaction condition of 2a with 4a. None
of the conditions gave any promising results. The cycloalkenyl
triflate being an activated triflate was more prone to decom-
position under the chosen conditions. The use of soluble
organic bases like DBU and DABCO did not lead to any product
formation (Table 2). The sluggish reactivity of triflates under
these conditions may be due to the enhanced rate of triflate
cleavage which competes with the cross-coupling reaction. The
use of coordinating solvents such as THF and DMF were also not
(dba)
(OAc)
(OAc)
3
Traces
25
25
2
2
24c
a
2 3
Method A: Pd catalyst (0.04 equiv.), ligand (0.08 equiv.), Cs CO
4
b
1
20 1C, 30–60 min, 1,4-dioxane (10 vol). Isolated yields.
Table 2 Effect of base on cross-coupling of 2a with 4a
a,b
Base (3 equiv.)
Na CO
Yield (%)
1
2
3
4
5
6
7
2
3
0
0
0
15
25
20
25
NaOtBu
CO
CsOAc
Cs CO
DBU
DABCO
K
2
3
2
3
a
Method A: Pd (OAc)2 (0.04 equiv.), Xantphos (0.08 equiv.), Cs CO
3
NBr (1.5 equiv.), 2a (1 equiv.), 4a (1.2 equiv.), microwave,
20 1C, 30–60 min, 1,4-dioxane (10 vol). Isolated yields.
2
2
(3 equiv.), Bu
4
b
1
1j
found to be successful. However, in the presence of Bu NBr as resulted in the formation of coupled products in reasonable
4
additive in these reactions resulted in product formation, though yields when compared to triflates. Conventional heating con-
the yields were not promising (Table 1).
ditions were also tried to access these compounds. We found
Failure of the aforementioned conditions led us to pursue a that longer reaction times were required for driving the reac-
more robust and stable electrophilic cross-coupling substrate. tions to completion and the yields were not promising. On the
Our subsequent efforts were to use cycloalkenyl nonaflates as basis of these observations, we speculate that exposing the
the coupling partner as they are found to be much more stable electrophilic cross-coupling substrate for a onger period of time
than the corresponding triflate. To our delight, the coupling of under heating conditions resulted in its decomposition. Under
3
a with 4a using the catalyst system comprised of (Pd (OAc) )/ microwave condition the yields were better which indicates that
2 2
2
5,26
Xantphos
and Cs CO in 1,4-dioxane yielded 50% of pro- the rate of this reaction is much faster compared to conventional
2 3
2
5,29c
duct (Table 3) under microwave assisted conditions. From the heating. The development of efficient phosphine ligands
above results we observed that the use of nonaflates (3a, 3b) (Fig. 5) for Buchwald–Hartwig amination
2
6,27
reaction provided a
Fig. 3 Synthetic route for N-substituted pyridone.
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Table 3 Effect of catalyst on cross-coupling of 3a with 4a
2b, 3a and 3b with enolizable heterocycles improved drastically
c
4
by the use of Bu NBr as an additive (Table 3).
Entry
Catalytic system
Yield (%)
Various inorganic bases were explored to find an optimum
base that would improve the coupling yield of 3a with 4a.
Cesium acetate and cesium carbonate were found to be very
effective for these transformations. The unique effect of cesium
salts in palladium catalyzed cross-coupling reactions arise from
b
1
2
3
4
5
6
7
Pd
Pd
Pd
Pd
2
2
2
2
(dba)
(OAc)
3
/PPh
/X-phos
/BINAP
3
0
b
2
15
b
(dba)
(OAc)
3
25
b
2
/Xantphos
/dppp
50
b
Pd(OAc)
Pd (OAc)
Pd(OAc) /dppp/Bu
2
55
a
2
2
/Xantphos/Bu
NBr
4
NBr
80
a
2
4
90
a
Method A: catalyst (0.04 equiv.), ligand (0.08 equiv.), Cs
2 3
CO
Table 4 Effect of bases on cross-coupling of 3a with 4a
(
3 equiv.), Bu
20 1C, 30–60 min, 1,4-dioxane (10 vol). Method C: catalyst (0.04 equiv.),
ligand (0.08 equiv.), Cs CO (3 equiv.), 3a (1 equiv.), 4a (1.2 equiv.),
4
NBr (1.5 equiv.), 3a (1 equiv.), 4a (1.2 equiv.), microwave,
b
c
1
Entry
Base
Na CO
NaOtBu
CsOAc
Yield (%)
2
3
c
microwave, 120 1C, 30–60 min, 1,4-dioxane (10 vol). Isolated yields.
1
2
3
4
5
6
7
8
2
3
0
0
55
30
30
35
K
3
PO
DBU
DABCO
4
reliable extension in using triflates or nonaflates as effective
electrophilic cross-coupling substrates. The use of these
ligands in these types of reactions typically produces the
coupled products at higher rates and better yields than the
first generation of catalysts.
that the use of chelating diphosphines (dppp and Xantphos)
results in better conversions of the coupled products. It is worth
b
Cs
Cs
2
CO
CO
3
55
a
2
3
90
1
5b,28
a
In this work we also found
2 2 2 3
Method A: Pd (OAc) (0.04 equiv.), Xantphos (0.08 equiv.), Cs CO
(
1
3 equiv.), Bu
20 1C, 30–60 min, 1,4-dioxane (10 vol). Method C: Pd
Xantphos (0.08 equiv.), Cs CO (3 equiv.), 3a (1 equiv.), 4a (1.2 equiv.),
4
NBr (1.5 equiv.), 3a (1 equiv.), 4a (1.2 equiv.), microwave,
b
2 2
(OAc) (0.04 equiv.),
2
3
c
emphasizing that the efficiency of the coupling reactions of 2a, microwave, 120 1C, 30–60 min, 1,4-dioxane (10 vol). Isolated yields.
Fig. 4 Synthetic route for N-substituted pyridine using bromo intermediate.
Fig. 5 Ligands used during optimization.
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the special properties of cesium cation like very large ionic coupled products were obtained. The electron withdrawing
radius, low charge density and high polarizability. The use of groups on pyridone reduces the nucleophilicity of the nitrogen
bases like NaOtBu and KOtBu did not lead to any product thereby making the reactions very sluggish. To extend the scope
formation. Organic bases like DBU and DABCO were also of this methodology, we screened a variety of heterocycles
explored (Table 4, entry 5 and 6). A series of solvents were also containing more than one nitrogen atom (4h, 4j, 4k and 4m).
explored to enhance the cross-coupling process as shown in Our initial attempts to cross couple 2-hydroxy benzimidazole
Table 5. Applying these optimized reaction conditions to a led to the formation of bis coupled products (5h and 5q). The
series of differentially substituted 2-hydroxypyridines, allowed mono N-alkylated product was obtained in reasonable yields by
2
8,29
the rapid synthesis of a variety of N-alkylated pyridones
in employing higher equivalents of 2-hydroxy benzimidazole
excellent yields (Table 7). For substrates bearing electron- (5i and 5r). The reaction of phthalimide also yielded the
withdrawing groups (5b, 5f, 5g and 5p), longer reaction times coupled product in excellent yields (5j). The formation of the
(
1 h compared to 45 min) were required and low yields of the products under these optimised conditions was confirmed by
1
13
H NMR, IR, LCMS and C NMR spectrum analysis. The
structural assignment was supported by IR and NMR spectro-
Table 5 Effect of solvents on cross-coupling of 3a with 4a
scopy. The final coupled product shows characteristic IR
a,b
À1
Entry
Solvent
Yield (%) absorption bands of pyridone at 1670 and 1619 cm
.
4
During the study we observed that Bu NBr is required as an
1
2
3
4
5
Toluene
NMP
DMF
THF
1,4-Dioxane
65
NR
Traces
NR
90
additive for improving the yields of the coupling reaction.
Based on the above observation, we tried to figure out the
effectiveness of the corresponding cycloalkenyl bromides (6),
(
Fig. 4) for these transformations. Unfortunately, the yields
a
Method A: Pd
2 2 2 3
(OAc) (0.04 equiv.), Xantphos (0.08 equiv.), Cs CO
of the coupled products were not promising (Table 6). We
speculate that this might be due to the prolonged exposure of
(3 equiv.), Bu
4
NBr (1.5 equiv.), 3a (1 equiv.), 4a (1.2 equiv.), microwave,
b
1
20 1C, 30–60 min, solvents (10 vol). Isolated yields.
Table 6 Cross-coupling of 6 with 4c
a,b
Entry
SM1 (6)
SM2 (4)
Catalytic system
Product
Yield (%)
1
Pd
2
(OAc)
2
/Xantphos
30
2
3
Pd
2
(OAc)
2
/Xantphos
/Xantphos
28
48
Pd
2
(OAc)
2
4
Pd
2
(OAc)
2
/Xantphos
/Xantphos
30
35
5
Pd
2
(OAc)
2
a
Method C: catalyst (0.04 equiv.), ligand (0.08 equiv.), Cs
2
CO
3
(3 equiv.), 6 (1 equiv.), 4a (1.2 equiv.), microwave, 120 1C, 30–60 min, 1,4-dioxane
b
(10 vol). Isolated yields.
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Table 7 Cross-coupling of 3 with pyridones 4a–4m
Table 7 (continued)
b
b
Entry SM1
SM2 (3)
Product
Yield 5 (%) Entry SM1
SM2 (3)
Product
Yield 5 (%)
a
1
90
a
15
78
c
c
2
3
4
78
80
82
16
17
32
a
a
c
58
c
18
78
a
c
c
5
6
7
83
25
34
c
1
2
9
0
82
c
90
a
c
8
9
68
88
21
88
a
c
22
86
a
c
1
1
0
1
72
a
Method A: Pd
2 2 2 3
(OAc) (0.04 equiv.), Xantphos (0.08 equiv.), Cs CO
(
3 equiv.), Bu
20 1C, 30–60 min, 1,4-dioxane (10 vol). Isolated yields. Method C:
Pd (OAc) (0.04 equiv.), dppp (0.08 equiv.), Cs CO (3 equiv.), Bu NBr
1.5 equiv.), 3 (1 equiv.), 4 (1.2 equiv.), microwave, 120 1C, 30–60 min,
,4-dioxane (10 vol).
4
NBr (1.5 equiv.), 3 (1 equiv.), 4 (1.2 equiv.), microwave,
b
c
1
2
2
2
3
4
(
1
82
bromo intermediate (6) under thermal conditions which
resulted in its degradation. Hence our optimal conditions
c
1
1
2
3
55
were 1 equiv. of 3, 1.2 equiv. of 4, 3 equiv. of Cs
2 3
CO , 10 vol
1
,4-dioxane as solvent, 0.04 equiv. of Pd (OAc) , 0.08 equiv.% of
2
2
a
Xantphos, 1.5 equiv. of Bu NBr, microwave treatment at 120 1C
4
85
for 30–60 min in a sealed vial. From Table 3 it is very clear that
2
the use of Pd(OAc) along with Xantphos gave 55% of the
product. 1,3-Bis(diphenylphosphino)propane (dppp) was also
found to be an efficient ligand in these transformations as the
yields are comparable.
a
1
4
83
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Fig. 6 Mechanism of coupling reaction.
2
9
A plausible catalytic cycle for the amination of cycloalkenyl Experimental section
nonaflates is shown in (Fig. 6). The mixture of palladium acetate
and bis-(phosphine) (P–P) reacts to form (P–P) Pd(OAc) which
2
All anhydrous solvents and reagents were obtained from com-
mercial suppliers and used without any further purification
unless otherwise noted. All the reactions were carried out under
an inert atmosphere of argon. A Biotage Initiator 60 instrument
was used for all microwave-assisted reactions, using sealed
reaction vessels with the temperature measured by an external
IR sensor. Analytical TLC was performed on pre-coated aluminum
sheets of silica (60 F254 nm) and visualized by short-wave UV light
at l 254. Flash column chromatography was carried out on
silica gel (230–400 mm) and semi-automated purification was
carried out on a Biotage SP1 purification system, using SNAP
cartridges, or SINGLE STEP flash column cartridges. Solvent
systems are reported by column volume (CV) with the solvent
flow rate as stated. Melting points were determined on an
is then reduced under reaction conditions to a zero valent Pd
species [(P–P)Pd], (1). Tetrabutylammonium bromide then dis-
places the nonaflates to give the corresponding bromides, (2).
Oxidative addition to these species results in the formation
of (3). Coordination of the enolizable heterocycles follows to
give (4) which are deprotonated by cesium carbonate to afford
complex (5). Reductive elimination from (5) yields the cross-
coupled product (6) and regenerates the true palladium(0)
catalytic species.
Conclusion
In summary, we have reported a highly efficient method for the EZ-Melt automated melting point apparatus. IR spectra were
construction of N-alkylated heterocycles using palladium recorded on a Bruker Alpha P FT-IR spectrometer. Absorption
À1
1
mediated cross-coupling reactions under microwave enhanced maxima (nmax) are quoted in wave numbers (cm ). H NMR
conditions from cycloalkenyl nonaflates. The use of ligands spectra were recorded at 400 MHz and 300 MHz using an
Xantphos or 1,3-bis(diphenylphosphino)propane was found to internal deuterium lock. Chemical shifts were measured in
be effective in these transformations, which led to complete parts per million (ppm) using the following internal references
conversions to the coupled products in a very short time. The for residual protons in the solvent: CDCl (d H: 7.26), CD OD
3
3
compounds thus synthesized using this methodology can be (d H: 3.32) and DMSO-d
6
(d H: 2.50). Data is presented as
useful as amine synthons in the field of medicinal chemistry follows: chemical shift, multiplicity, coupling constant ( J) in
during the lead optimization process.
Hz, and integration. The following abbreviations are used for
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the splitting patterns: s for singlet, d for doublet, t for triplet, passed through a celite bed, washed with ethyl acetate (10 mL),
1
3
4
m for multiplet and br for broad. C NMR spectra were recorded bi-phased with saturated NH Cl solution (10 mL), washed with
at 100 MHz using an internal deuterium lock. The following water (10 mL), brine solution (10 mL), the organic layer was
internal references were used: CDCl (d C: 77.0), CD OD (d C: 49.0) dried over Na SO and concentrated. The crude compound was
3
3
2
4
1
9
and DMSO-d (d C: 39.5). F NMR spectra were recorded at purified by column chromatography packed with 230–400 silica
6
376.5 MHz using an internal deuterium lock. LCMS analyses gel, eluted with 25–50% ethyl acetate in petroleum ether which
were performed using ESI/APCI, with an ATLANTIS C18 (50 Â yielded pure compounds (25–90%).
À1
4.6 mm–5 mm), column and a flow rate of 1.2 mL min
.
5-Methyl-1-(3-oxocyclopent-1-enyl)pyridin-2(1H)-one, 5a. Yielded
UV detection was at 215 nm.
product as a light brown gummy solid, (90%).
1
6
H NMR (400 MHz, DMSO-d ): d = 7.61 (s, 1H), 7.40–7.37
General procedure for the preparation of 2
(
dd, J = 2.3 Hz, J = 9.4 Hz, 1H), 6.94–6.93 (d, J = 1.4 Hz, 1H),
1 2
To a solution of 1,3-cyclopentanone (3.0 g, 30.6 mmol) in DCM 6.49–6.47 (d, J = 9.4 Hz, 1H), 3.13–3.11 (m, 2H), 2.43–2.41
(
30 mL) was added triethylamine (9.3 g, 91.8 mmol) at À10 1C, (m, 2H), 2.08 (s, 3H).
13
followed by drop wise addition of triflic anhydride (8.6 g,
6
C NMR (100 MHz, DMSO-d ): d = 207.97, 168.87, 161.09,
30.6 mmol), the reaction mixture was warm up to 0 1C and 143.52, 130.95, 121.85, 121.73, 116.10, 33.79, 29.48, 17.11 ppm.
stirred for about 1 h. The reaction mixture was diluted with
IR (KBr) 3354.4, 2941.7, 2925.3, 2361.4, 2332.8, 1707.9,
DCM (100 mL), bi-phased with water (100 mL), washed with 1670.8, 1619.8, 1574.4, 1523.7, 1341.1, 1242.7, 1184.2, 1139.8,
À1
NaHCO
3
(100 mL), brine solution (100 mL), the organic layer 988.9, 819.4, 628.4, 467.0, 403.0 cm
LCMS: 190.2 (M + H).
Anal. calcd for C H N O : C, 69.83; H, 5.86; N, 7.40%,
.
was dried over Na SO and concentrated to get the crude
material. The crude compound thus obtained was purified by
column chromatography packed with 60–120 silica gel, eluted found: C, 69.73; H, 5.99; N, 7.35%.
2
4
2
2
22 2 4
with 10–12% ethyl acetate in petroleum ether to obtain the pure
4-Methyl-3-nitro-1-(3-oxocyclopent-1-enyl)pyridin-2(1H)-one, 5b.
Yielded product as a brown solid, (78%), Mp (145.6–146.7 1C).
compound (6.5 g, 94%) as a colorless oil.
1
1
H NMR (400 MHz, CDCl
3
): d = 6.13–6.12 (t, J = 1.7 Hz, 1H),
3
H NMR (400 MHz, CDCl ): d = 7.48 (d, J = 7.5 Hz, 1H),
2
.91–2.88 (m, 2H), 2.65–2.62 (m, 2H).
6.93–6.92 (t, J = 1.6 Hz, 1H), 6.28 (d, J = 7.4 Hz, 1H), 3.20–3.17
1
9
F NMR (376.5 MHz, CDCl
3
): d = À73.11.
(m, 2H), 2.65–2.63 (m, 2H), 2.33 (s, 3H).
1
3
13
C NMR (100 MHz, CDCl ): d = 204.8, 183.5, 118.7, 113.1,
C NMR (100 MHz, CD OD): d = 207.97, 155.8, 152.4, 151.2,
3
3
3
4.2, 28.6 ppm.
135.85, 128.73, 112.10, 99.40, 34.79, 30.48, 13.55 ppm.
LCMS: 233.2 (M + H).
General procedure for the preparation of 3
IR (KBr) 3784.0, 3096.3, 3064.6, 2920.1, 2361.4, 1978.7,
To a solution of 1,3-cyclopentanone (5.0 g, 51.0 mmol) in DCM 1672.1, 1582.3, 1523.4, 1432.7, 1404.6, 1370.4, 1272.4, 1241.8
(
100 mL) triethylamine (15.2 g, 153.0 mmol) was added at 1165.2, 1087.4, 1023.8, 991.7, 898.8, 862.8, 828.2, 798.6, 773.8,
À1
À10 1C, followed by the drop wise addition of nonafluoro- 751.2, 623.1, 571.3, 544.9, 513.4, 403.6 cm
butane sulfonic anhydride (29.6 g, 51.0 mmol), the reaction Anal. calcd for C11
mixture was warm up to 0 1C and stirred for about 1 h. The found: C, 56.60; H, 4.30; N, 11.86%.
.
10 2 4
H N O : C, 56.41; H, 4.30; N, 11.96%,
reaction mixture was diluted with DCM (200 mL), bi-phased
1-(3-Oxocyclopent-1-enyl)pyridin-2(1H)-one, 5c. Yielded pro-
with water (200 mL), washed with NaHCO3 (250 mL), brine duct as a off-white solid, (80%), Mp (138.6–140.7 1C).
1
solution (250 mL), the organic layer was dried over Na
2
SO
4
and
3
H NMR (400 MHz, CDCl ): d = 7.43–7.44 (m, 2H), 6.96–6.95
concentrated. The crude compound was purified by column (t, J = 1.6 Hz, 1H), 6.66–6.64 (d, J = 8.6 Hz, 1H), 6.33–6.29
chromatography packed with 60–120 silica gel, eluted with 15 (m, 1H), 2.62–2.60 (m, 2H).
1
3
to 20% ethyl acetate in petroleum ether to obtain the pure
3
C NMR (100 MHz, CD OD): d = 206.67, 167.77, 162.02,
compound (16.5 g, 87%) as a colorless oil.
142.00, 129.05, 122.75, 122.63, 116.76, 33.75, 29.76 ppm.
LCMS: 176.2 (M + H).
1
H NMR (400 MHz, CDCl ): d = 5.76–5.75 (t, J = 1.5 Hz, 1H),
3
2
.84–2.81 (m, 2H), 2.59–2.56 (m, 2H).
IR (KBr) 3358.4, 3134.4, 2996.9, 2856.1, 2856.1, 2364.4,
1
9
F NMR (376.5 MHz, CDCl ): d = À127.32 to À127.22 (m), 2332.4, 1674.4, 1619.8, 1588.9, 1471.2, 1428.4, 1437.4, 1371.2,
3
À122.78 to À122.68 (m), À115.97 to À115.88 (m), À82.60 to 1341.1, 1328.4, 1306.4, 1184.2, 1139.8, 1040.2, 988.9, 963.7,
À82.53 (m).
850.6, 846.4, 819.4, 765.2, 628.4, 562.4, 525.0, 497.8, 467.0,
1
3
À1
C NMR (100 MHz, CDCl
3
): d = 205.05, 183.45, 140.45, 416.9 cm
.
120.58, 113.05, 110.38, 107.92, 34.27, 28.97 ppm.
9 2
Anal. calcd for C10H NO : C, 68.56; H, 5.18; N, 8.00%, found:
C, 68.43; H, 5.25; N, 8.03%.
-Methyl-1-(3-oxocyclopent-1-enyl)pyridin-2(1H)-one, 5d. Yielded
To a degassed solution of 3 (1.0 equiv.) and 4 (1.2 equiv.) in product as a off-white solid, (82%), Mp (152.4–153.1 1C).
General procedure for the preparation of 5
3
1
1
,4-dioxane (10 vol), Cs CO (3.0 equiv.), Bu NBr (1.5 equiv.),
H NMR (400 MHz, DMSO-d ): d = 8.20–8.19 (dd, J = 1.2 Hz,
2
3
4
6
1
Pd(OAc)
2
(0.04 equiv.) and Xantphos (0.08 equiv.) were added.
J
2
= 4.7 Hz, 1H), 7.87–7.85 (dd, J
1
= 0.9 Hz, J
2
= 7.4 Hz, 1H),
The reaction mixture was heated at 120 1C under microwave 7.32–7.29 (dd, J
1 2
= 4.8 Hz, J = 2.5 Hz, 1H), 5.42 (d, J = 1.08 Hz,
condition for about 30 min. The reaction mixture was cooled to RT, 1H), 2.85–2.82 (m, 2H), 2.44–2.41 (m, 2H), 2.25 (s, 3H).
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Paper
1
3
13
C NMR (100 MHz, CD
3
OD): d = 206.67, 169.99, 162.02,
C NMR (100 MHz, CD
3
OD): 207.7, 158.2, 146.3, 129.5,
143.92, 136.99, 134.45, 120.73, 116.16, 33.65, 29.73, 16.16 ppm. 127.8, 123.4, 121.8, 112. 2, 32.6, 29.8 ppm.
LCMS: 190.2 (M + H).
IR (KBr): 3051.4, 2944.7, 2896.0, 1704.1, 1659.5, 1619.3,
IR (KBr) 3334.2, 2944.6, 2927.5, 2363.6, 2335.2, 1711.2, 1595.8, 1477.1, 1417.9, 1381.2, 1345.0, 1307.7, 1286.8, 1248.3,
672.2, 1623.1, 1572.2, 1524.1, 1342.3, 1240.1, 1184.9, 1138.7, 1221.5, 1157.2, 1101.2, 1032.7, 966.9, 931.8, 898.8, 847.3, 808.2,
1
9
À1
À1
89.9, 818.7, 629.7, 468.9, 406.4 cm
LCMS: 190.2 (M + H).
.
775.6, 746.1, 727.0, 690.5, 654.3, 604.8, 539.6 cm
LCMS: 215.2 (M + H).
.
Anal. calcd for C11
found: C, 69.79; H, 5.88; N, 7.38%.
-Methyl-1-(3-oxocyclopent-1-enyl)pyridin-2(1H)-one, 5e. Yielded
H
11NO
2
: C, 69.83; H, 5.86; N, 7.40%,
9 2 2
Anal. calcd for C11H N O : C, 65.66; H, 4.51; N, 13.92%,
found: C, 65.75; H, 4.53; N, 13.85%.
4
1,3-Bis(3-oxocyclopent-1-enyl)-1H-benzo[d]imidazol-2(3H)-one, 5i.
Yielded product as a white solid, (88%), Mp (195.5–196.3 1C).
product as a off-white solid, (83%), Mp (150.1–151.1 1C).
1
1
H NMR (400 MHz, DMSO-d ): d = 7.71 (d, J = 7.2 Hz, 1H),
H NMR (400 MHz, DMSO-d ): d = 7.75–7.73 (dd, J = 3.3 Hz,
6
6
1
6.97 (s, 1H), 6.39 (d, J = 6.5 Hz, 1H), 6.35–6.31 (t, J = 6.8 Hz, 1H), J = 6.1 Hz, 2H), 7.33–7.31 (dd, J = 3.2 Hz, J = 6.1 Hz, 2H),
2 1 2
3
.13–3.11 (m, 2H), 2.45–2.43 (m, 2H), 2.05 (s, 3H).
3.44–3.41 (m, 4H), 2.49–2.47 (m, 4H).
1
3
13
C NMR (100 MHz, CD
3
OD): d = 205.66, 170.54, 159.91,
3
C NMR (100 MHz, CDCl ): d = 206.49, 165.66, 149.61,
148.57, 140.16, 128.01, 114.51, 108.41, 36.45, 25.86, 17.39 ppm. 127.87, 124.71, 119.15, 112.23, 33.94, 29.65 ppm.
LCMS: 190.2 (M + H).
LCMS: 295.2 (M + H).
IR (KBr) 3058.6, 2948.3, 1657.8, 1615.4, 1588.0, 1464.4,
IR (KBr): 3084.4, 1732.6, 1695.6, 1611.8, 1576.5, 1471.7, 1411.8,
1
9
5
427.7, 1368.4, 1327.2, 1250.6, 1212.6, 1158.4, 1128.8, 1046.7, 1377.5, 1281.2, 1244.7, 1220.9, 1161.7, 1091.8, 995.5, 906.4, 865.7,
À1
92.9, 968.2, 908.7, 867.5, 831.3, 788.4, 741.2, 620.3, 589.2, 842.6, 748.5, 685.9, 626.2, 553.3, 515.0, 488.6, 424.9 cm
.
À1
15.6, 414.2 cm
.
Anal. calcd for C H N O : C, 72.32; H, 6.43; N, 9.92%,
17 18 2 2
Anal. calcd for C11
9.95; H, 5.78; N, 7.46%.
-Nitro-1-(3-oxocyclopent-1-enyl)pyridin-2(1H)-one, 5f. Yielded product as a brown solid, (72%), Mp (172.5–173.1 1C).
H
11NO
2
: 69.83; H, 5.86; N, 7.40%, found: found: C, 72.40; H, 6.38; N, 9.95%.
6
2-(3-Oxocyclopent-1-enyl)isoindoline-1,3-dione, 5j. Yielded
5
1
product as a brown solid, (25%), Mp (183.1–184.3 1C).
H NMR (400 MHz, DMSO-d
): d = 8.54 (s, 1H), 7.75–7.69 7.94–7.92 (dd, J = 1.0 Hz, J
dd, J = 2.8 Hz, J = 10 Hz, 1H), 7.40 (d, J = 6.48 Hz, 1H), 6.35 (t, J = 1.4 Hz, 1H), 3.31–3.29 (m, 2H), 2.36–2.38 (m, 2H).
6
): d = 8.0–7.98 (m, 2H),
= 3.4 Hz, 2H), 6.58–6.57
1
H NMR (400 MHz, DMSO-d
6
1
2
(
(
1
2
1
3
d, J = 7.0 Hz, 1H), 3.13–3.12 (m, 2H), 2.45–2.43 (m, 2H).
C NMR (100 MHz, CDCl ): d = 207.5, 165.6, 150.6, 133.8,
3
1
3
C NMR (100 MHz, CD OD): d = 205.57, 170.05, 160.59, 127.7, 112.2, 33.9, 29.6 ppm.
3
1
50.55, 143.52, 136.59, 122.73, 116.16, 33.69, 29.42 ppm.
LCMS: 221.2 (M + H).
IR (KBr): 3048.4, 2946.7, 2898.2, 1714.1, 1655.2, 1618.3, 1610.5,
1595.8, 1477.1, 1417.9, 1381.2, 1368.2, 1345.0, 1307.7, 1286.8,
IR (KBr) 3781.3, 3091.3, 3064.6, 2920.1, 2361.3, 2301.3, 1248.3, 1221.5, 1157.2, 1101.2, 1032.7, 966.9, 931.8, 898.8, 847.3,
À1
1
1
1
6
978.7, 1672.1, 1582.3, 1523.4, 1432.7, 1404.6, 1370.4, 1343.2, 808.2, 775.6, 746.1, 727.0, 690.5, 654.3, 614.8, 519.6 cm
304.6, 1370.4, 1343.2, 1304.3, 1272.4, 1250.6, 1212.6, 1158.4,
.
LCMS: 228.2 (M + H).
Anal. calcd for C H NO : C, 68.72; H, 3.99; N, 6.16%, found:
128.8, 991.7, 932.0, 898.8, 862.8, 828.2, 773.8, 751.2, 696.3,
1
3
9
3
À1
23.1, 571.3, 544.9, 513.4, 403.6 cm
.
C, 68.66; H, 3.92; N, 6.23%.
Anal. calcd for C H N O : C, 54.55; H, 3.66; N, 12.72%,
found: C, 54.45; H, 3.78; N, 12.67%.
3-Chloro-7-(3-oxocyclopent-1-enyl)-1,7-naphthyridin-8(7H)-
one, 5k. Yielded product as a light brown solid, (82%),
1
0
8 2 4
4
-(Trifluoromethyl)-1-(3-oxocyclopent-1-enyl)pyridin-2(1H)-one, Mp (189.5–191.1 1C).
1
5
g. Yielded product as a off-white solid, (34%), Mp (132.7–133.9 1C).
H NMR (400 MHz, DMSO-d
): d = 7.83 (d, J = 3.7 Hz, 1H), 8.40 (d, J = 3.0 Hz, I H), 7.83 (d, J = 10.4 Hz, 1H), 6.9 (s, 1H),
= 1.6 Hz, J = 7.4 Hz, 1H), 6.13 (s, 6.7 (d, J = 10.4 Hz, 1H), 3.17–3.16 (t, J = 3.9 Hz, 2H), 2.49–2.48
H), 2.71–2.69 (t, J = 5.6 Hz, 2H), 2.44–2.41 (t, J = 6.6 Hz, 2H). (t, J = 4.0 Hz 2H).
6
): d = 8.82 (d, J = 3.0 Hz, 1H),
1
H NMR (400 MHz, DMSO-d
.87 (s, 1H), 6.58–6.56 (dd, J
6
6
1
1
2
1
3
13
C NMR (100 MHz, CD OD): d = 207.2, 168.12, 162.71,
C NMR (100 MHz, CDCl ): d = 203.43, 163.36, 161.22,
3
3
158.21, 151.31, 142.76, 138.60, 122.05, 114.32, 32.62, 29.88 ppm. 160.05, 143.09, 137.21, 135.60, 134.92, 133.63, 127.31, 121.10,
IR (KBr) 3356.1, 2945.1, 2929.7, 2364.9, 1717.0, 1672.8, 114.63, 109.74, 37.58, 29.71 ppm.
1
8
618.1, 1576.6, 1525.5, 1342.2, 1243.9, 1186.7, 1139.0, 983.6,
IR (KBr): 3059.5, 2937.2, 2859.2, 1659.3, 1627.2, 1591.1,
1479.0, 1457.3, 1417.6, 1345.6, 1309.3, 1227.3, 1171.2, 1133.1,
À1
19.4, 624.6, 467.9, 404.9 cm
LCMS: 244.2 (M + H).
.
1109.7, 1063.7, 1038.9, 1011.1, 961.4, 895.3, 849.3, 808.2, 782.7,
À1
Anal. calcd for C11
found: C, 54.45; H, 3.26; N, 5.70%.
-(3-Oxocyclopent-1-enyl)-1H-benzo[d]imidazol-2(3H)-one, 5h.
Yielded product as a white solid, (68%), Mp (167.1–168.4 1C).
H
8
F
3
NO
2
: C, 54.33; H, 3.32; N, 5.76%, 756.8, 734.0, 691.1, 620.3, 532.1, 502.2, 440.3 cm
LCMS: 261.2 (M + H).
Anal. calcd for C H ClN O : C, 59.90; H, 3.48; N, 10.75%,
.
1
1
3
9
2 2
found: C, 59.94; H, 3.55; N, 10.66%.
1
H NMR (400 MHz, DMSO-d
6
): d = 11.29 (s, 1H), 7.21
6-(3-Oxocyclopent-1-enyloxy)-2-(3-oxocyclopent-1-enyl)pyridazin-
(d, J = 10.8 Hz, 2H), 7.03 (d, J = 6.8 Hz, 2H), 6.18 (d, J = 9.6 1H), 3(2H)-one, 5l. Yielded product as a dark brown solid, (55%),
2.97–2.90 (m, 2H), 2.45–2.39 (m, 2H).
Mp (173.5–174.7 1C).
1302 | New J. Chem., 2014, 38, 1294--1305
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1
13
H NMR (400 MHz, DMSO-d
6
): d = 7.63–7.61 (dd, J
1
= 1.2 Hz,
3
C NMR (100 MHz, CDCl ): d = 198.66, 175.54, 159.91, 148.57,
J
2
= 10.0 Hz, 1H), 7.3–7.27 (dd, J
1
= 1.6 Hz, J = 10.0 Hz, 1H), 140.16, 129.0, 128.02, 114.54, 108.41, 36.45, 26.86, 22.39 ppm.
2
6
2
.89 (s, 1H), 5.94 (s, 1H), 3.05–3.01 (m, 2H), 2.86–2.84 (m, 2H),
.40–2.38 (m, 2H), 2.33–2.35 (m, 2H).
LCMS: 273.2 (M + H).
LCMS: 256.2 (M + H).
Anal. calcd for C H F NO : C, 56.04; H, 3.92; N, 5.45%,
1
2
10
3
2
found: C, 55.94; H, 3.92; N, 5.43%.
Anal. calcd for C14
found: C, 61.80; H, 4.46; N, 10.20%.
-(3-Oxocyclohex-1-enyl)pyridin-2(1H)-one, 5m. Yielded pro-
H
12
N
2
O
4
: C, 61.76; H, 4.44; N, 10.29%,
1-(3-Oxocyclohex-1-enyl)-1H-benzo[d]imidazol-2(3H)-one, 5q.
Yielded product as a white solid, (58%), Mp (163.1–164.9 1C).
1
1
6
H NMR (400 MHz, DMSO-d ): d = 11.29 (s, 1H), 7.21 (d, J =
duct as a dark brown gummy solid, (85%).
10.8 Hz, 2H), 7.11–7.08 (m, 2H), 2.97–2.90 (m, 2H), 6.18 (d, J =
1
H NMR (400 MHz, DMSO-d ): d = 8.37–8.36 (dd, J = 1.8 Hz, 9.6 1H), 2.45–2.39 (t, J = 8.6 Hz, 2H), 2.08–1.97 (m, 2H).
6 1
1
3
J = 4.8 Hz, 1H), 7.99–7.95 (m, 1H), 7.36–7.33 (dd, J = 5.2 Hz,
2
C NMR (100 MHz, CD OD): 207.7, 158.2, 146.3, 129.5,
3
1
J2 = 7.2 Hz, 1H), 7.19 (d, J = 8.0 Hz, 1H), 5.16 (s, 1H), 2.63–2.60 127.8, 123.4, 121.8, 112.2, 32.6, 29.8, 22.39 ppm.
(
(
t, J = 6.2 Hz, 2H), 2.30–2.27 (t, J = 6.6 Hz, 2H), 1.94–2.05
LCMS: 229.2 (M + H).
IR (KBr): 3051.4, 2944.7, 2896.0, 1704.1, 1659.5, 1619.3,
m, 2H).
1
3
C NMR (100 MHz, CDCl
3
): d = 199.66, 175.53, 159.92, 1595.8, 1477.1, 1417.9, 1381.2, 1345.0, 1307.7, 1286.8, 1248.3,
1
48.57, 140.16, 121.53, 114.93, 108.97, 36.62, 25.86, 21.14 ppm. 1221.5, 1157.2, 1101.2, 1032.7, 966.9, 931.8, 898.8, 847.3, 808.2,
À1
LCMS: 190.2 (M + H).
775.6, 746.1, 727.0, 690.5, 654.3, 604.8, 539.6 cm
Anal. calcd for C13
.
IR (KBr) 3058.6, 2948.3, 1657.8, 1615.4, 1588.0, 1464.4, 1427.7,
H
12
N
2
O
2
: C, 68.41; H, 5.30; N, 12.27%,
1
368.4, 1250.6, 1212.6, 1158.4, 1128.8, 1046.7, 992.9, 968.2, 908.7, found: C, 68.58; H, 5.23; N, 12.32%.
À1
867.5, 831.3, 788.4, 741.2, 620.3, 589.2, 515.6, 414.2 cm
.
1,3-Bis(3-oxocyclohex-1-enyl)-1H-benzo[d]imidazol-2(3H)-one, 5r.
Anal. calcd for C H NO : C, 69.83; H, 5.86; N, 7.40%, Yielded product as a white solid, (78%), Mp (203.3–204.8 1C).
1
1
11
2
1
found: C, 69.90; H, 5.90; N, 7.48%.
6
H NMR (400 MHz, DMSO-d ): d = 7.22–7.17 (m, 2H),
6-Methyl-1-(3-oxocyclohex-1-enyl)pyridin-2(1H)-one, 5n. Yielded 7.11–7.04 (m, 2H), 6.19 (s, 2H), 2.97–2.90 (m, 2H), 2.45–2.39
product as a light brown thick liquid, (83%).
(m, 4H), 2.08–1.97 (m, 4H).
1
13
H NMR (400 MHz, DMSO-d
2
.80–7.77 (dd, J = 2.4 Hz, J = 8.0 Hz, 1H), 7.08 (d, J = 8.0 Hz, 1H), 127.72, 123.72, 118.25, 114.38, 36.94, 29.65, 23.11 ppm.
.07 (s, 1H), 2.61–2.58 (t, J = 6.0 Hz, 2H), 2.28–2.25 (t, J =
6
): d = 8.19–8.18 (t, J = 1.6 Hz, 1H),
3
C NMR (100 MHz, CDCl ): d = 207.50, 169.42, 150.82,
7
5
6
1
LCMS: 323.2 (M + H).
IR (KBr): 3084.4, 1732.6, 1695.6, 1611.8, 1576.5, 1471.7,
.8 Hz, 2H), 2.30 (s, 3H), 1.94–1.97 (m, 2H).
1
3
C NMR (100 MHz, CDCl ): d = 200.5, 176.5, 158.1, 149.7, 1411.8, 1377.5, 1281.2, 1244.7, 1220.9, 1161.7, 1091.8, 995.5,
3
1
41.2, 127.8, 113.3, 109.3, 36.6, 26.6, 21.9, 18.1 ppm.
LCMS: 204.2 (M + H).
906.4, 865.7, 842.6, 748.5, 685.9, 626.2, 553.3, 515.0, 488.6,
À1
424.9 cm
.
IR (KBr) 3353.1, 2946.3, 2368.0, 2340.1, 1715.2, 1675.1,
18 2 3
Anal. calcd for C19H N O : C, 70.79; H, 5.63; N, 8.69%,
1
8
625.1, 1569.1, 1533.9, 1348.2, 1266.2, 1189.1, 1145.2, 988.2, found: C, 70.89; H, 5.73; N, 8.54%.
À1
16.8, 620.3, 460.5, 414.1 cm
.
3-Methoxy-7-(3-oxocyclohex-1-enyl)-1,7-naphthyridin-8(7H)-
Anal. calcd for C H NO : C, 70.92; H, 6.45; N, 6.89%, one, 5s. Yielded product as a pale brown solid, (82%),
1
2
13
2
found: C, 70.74; H, 6.55; N, 6.93%.
-Methyl-1-(3-oxocyclohex-1-enyl)pyridin-2(1H)-one, 5o. Yielded
product as a off-white solid, (78%), Mp (135.6–136.7 1C).
Mp (203.9–204.2 1C).
H NMR (400 MHz, DMSO-d ): d = 7.49 (d, J = 2.4 Hz, 1H), 7.2
(d, J = 2.4 Hz, 1H), 7.5 (d, J = 7.6 Hz, 1H), 6.64 (d, J = 7.2 Hz, 1H),
1
5
6
1
H NMR (400 MHz, DMSO-d
.80–7.77 (dd, J = 2.4 Hz, J = 8.0 Hz, 1H), 7.9 (d, J = 8.0 Hz, 1H), (t, J = 6.4 Hz, 2H), 2.07–2.04 (t, J = 6.4 Hz 2H).
3
.07 (s, 1H), 2.61–2.59 (t, J = 6.0 Hz, 2H), 2.30 (s, 3H), 2.29–2.25 OD): d = 201.46, 164.36, 164.36,
6
): d = 8.19 (d, J = 1.6 Hz, 1H), 6.1 (s, 1H), 3.94 (s, 3H), 2.81–2.78 (t, J = 6.0 Hz, 2H), 2.45–2.42
7
5
1
2
1
3
C NMR (100 MHz, CD
161.22, 160.04, 143.10, 143.10, 137.01, 133.63, 127.30, 127.10,
C NMR (100 MHz, CDCl ): d = 199.66, 175.54, 159.91, 114.65, 106.78, 56.74, 37.98, 29.75, 23.11 ppm.
(
t, J = 6.8 Hz, 2H), 1.98–1.95 (t, J = 6.4, 2H).
1
3
3
1
1
48.57, 140.16, 128.02, 114.54, 108.41, 36.45, 25.86, 21.39,
7.74 ppm.
LCMS: 271.2 (M + H).
IR (KBr): 3059.5, 2937.2, 1660.3, 1617.2, 1591.1, 1479.0,
IR (KBr) 3352.8, 2945.1, 2928.3, 2363.6, 2335.2, 1709.5, 1453.3, 1417.6, 1345.6, 1309.3, 1227.3, 1171.2, 1133.1, 1109.7,
672.5, 1615.3, 1577.6, 1526.4, 1345.3, 1246.2, 1183.2, 1135.8, 1063.7, 1038.9, 1011.1, 961.4, 895.3, 849.3, 808.2, 782.7, 756.8,
1
9
À1
À1
84.9, 815.2, 626.1, 465.2, 404.4 cm
Anal. calcd for C12 : C, 70.92; H, 6.45; N, 6.89%,
found: C, 70.76; H, 6.45; N, 6.91%.
-(Trifluoromethyl)-1-(3-oxocyclohex-1-enyl)pyridin-2(1H)-one, 5p.
.
734.0, 691.1, 620.3, 532.1, 502.2, 440.3 cm
.
H
13NO
2
Anal. calcd for C15 : C, 66.63; H, 5.22; N, 10.36%,
14 2 3
H N O
found: C, 66.66; H, 5.32; N, 10.39%.
4
1-(5,5-Dimethyl-3-oxocyclohex-1-enyl)pyridin-2(1H)-one, 5t.
Yielded product as a off-white solid, (90%), Mp (105.3–107.0 1C).
Yielded product as a off-white solid, (32%), Mp (145.6–146.9 1C).
1
1
H NMR (400 MHz, DMSO-d ): d = 7.83 (d, J = 7.2 Hz, 1H),
H NMR (400 MHz, CDCl ): d = 8.35–8.33 (dd, J = 1.8 Hz, J =
6
3
1
2
6
(
2
.87 (s, 1H), 6.58–6.56 (dd, J
s, 1H), 2.71–2.69 (t, J = 5.6 Hz, 2H), 2.44–2.41 (t, J = 6.6 Hz, 2H), 7.2 Hz, 1H), 7.03–7.00 (dd, J
.10–2.07 (m, 2H). (s, 1H), 2.78 (s, 2H), 2.36 (d, J = 6.6 Hz, 2H), 1.20 (s, 6H).
1
= 1.6 Hz, J
2
= 7.4 Hz, 1H), 6.14 4.8 Hz, 1H), 7.98–7.95 (m, 1H), 7.23–7.21 (dd, J
1 2
= 5.2 Hz, J =
1
= 1.8 Hz, J = 4.8 Hz, 1H), 5.18
2
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1
3
C NMR (100 MHz, CDCl
3
): d = 201.66, 174.30, 159.92,
1910–1923; (g) S. Yosuke, O. Yasushi and I. Yasutaka, Org.
Lett., 2010, 12, 1372–1374; (h) G. Liu, G. Yin and L. Wu,
Angew. Chem., Int. Ed., 2008, 47, 4733–4736; (i) L. Wu, S. Qiu
and G. Liu, Org. Lett., 2009, 11, 2707–2710; ( j) G. Liu and
S. S. Stahl, J. Am. Chem. Soc., 2007, 129, 6328–6335;
(k) G. Abbiati, E. Beccalli, G. Broggini, M. Martinelli and
G. Paladino, Synlett, 2006, 73–76.
2 J. P. Wolfe, H. Tomori, J. P. Sadighi, J. Yin and S. L.
Buchwald, J. Org. Chem., 2000, 65, 1158–1174.
3 R. A. Singer and S. L. Buchwald, Tetrahedron Lett., 1999, 40,
1095–1098.
1
2
46.22, 140.16, 121.53, 114.93, 108.97, 46.62, 37.62, 29.40,
5.86 ppm.
LCMS: 218.2 (M + H).
IR (KBr) 3045.5, 2938.2, 1647.8, 1625.4, 1580.0, 1520.3,
464.4, 1427.7, 1368.4, 1250.6, 1212.6, 1158.4, 1128.8, 1046.7,
92.9, 968.2, 908.7, 877.5, 831.3, 768.4, 741.2, 620.3, 589.2,
1
9
5
À1
13.6, 410.2 cm
.
Anal. calcd for C13
found: C, 71.86; H, 6.92; N, 6.43%.
-(3-Oxo-5-phenylcyclohex-1-enyl)pyridin-2(1H)-one, 5u. Yielded
2
H15NO : C, 71.87; H, 6.96; N, 6.45%,
1
product as a off-white solid, (88%), Mp (125.6–126.7 1C).
4 (a) J. Ahman and S. L. Buchwald, Tetrahedron Lett., 1997, 38,
6363–6366; (b) J. Louie, M. S. Driver, B. C. Hamann and
J. F. Hartwig, J. Org. Chem., 1997, 62(5), 1268–1273.
5 J. Loule, M. S. Driver, B. C. Hamann and J. F. Hartwig, J. Org.
Chem., 1997, 1262–1268.
6 (a) L. R. Subramanian, H. Bentz and M. Hnack, Synthesis,
1973, 293–294; (b) J. H o¨ germeier and H.-U. Reissig,
Adv. Synth. Catal., 2009, 351, 2747–2763, DOI: 10.1002/
adsc.200900566.
1
H NMR (400 MHz, DMSO-d ): d = 8.24–8.23 (dd, J = 1.8 Hz,
6
1
J
J
(
2
2
1
= 4.8 Hz, 1H), 7.92–7.88 (m, 1H), 7.28–7.27 (dd, J = 5.2 Hz,
= 7.2 Hz, 1H), 7.23–7.08 (m, 6H), 5.25 (s, 1H), 3.38–3.12
m, 2H), 2.90–2.67 (m, 1H), 2.36–2.10 (m, 2H).
1
3
C NMR (100 MHz, CDCl
3
): d = 200.11, 174.30, 160.12,
1
4
46.22, 141.06, 138.5, 136.20, 135.10, 123.31, 116.3, 109.71,
8.2, 37.60, 30.12 ppm.
LCMS: 266.2 (M + H).
Anal. calcd for C H NO : C, 76.96; H, 5.70; N, 5.28%,
7 J. Zhu, A. Bigot and M. E. Tran Huu Dau, Tetrahedron Lett.,
1997, 38, 1181–1185.
8 S. Boisnard, J. Chastanet and J. Zhu, Tetrahedron Lett., 1999,
40, 7469–7472.
9 P. J. Stang, M. Hnaack and L. R. Subramanian, Synthesis,
1982, 85–126.
1
7
15
2
found: C, 76.82; H, 5.58; N, 5.08%.
-(5-(4-Chlorophenyl)-3-oxocyclohex-1-enyl)pyridin-2(1H)-one, 5v.
Yielded product as a off-white solid, (86%), Mp (137.4–138.7 1C).
1
1
H NMR (400 MHz, DMSO-d = 1.8 Hz,
1
= 4.8 Hz, 1H), 7.90–7.88 (m, 1H), 7.28–7.27 (dd, J = 5.2 Hz,
6
): d = 8.14–8.13 (dd, J
1
J
2
J2 = 7.2 Hz, 1H), 7.23–7.08 (m, 5H), 5.45 (s, 1H), 3.36–3.12 10 K. Ritter, Synthesis, 1993, 735–762.
(
m, 2H), 2.92–2.77 (m, 1H), 2.42–2.08 (m, 2H).
11 C. G. Blettner, W. A. Konig, W. Stenzel and T. Schotten,
1
3
C NMR (100 MHz, CDCl ): d = 201.70, 175.32, 161.22,
J. Org. Chem., 1999, 64, 3885–3890.
3
1
4
46.02, 140.06, 139.15, 138.02, 135.11, 124.13, 118.33, 109.11, 12 M. Rottlander and P. Knochel, J. Org. Chem., 1998, 63,
9.34, 36.43, 31.52 ppm.
LCMS: 301.2 (M + H).
203–208.
13 A. E. Jensen, W. Dohle and P. Knochel, Tetrahedron, 2000,
56, 4197–4201.
2
Anal. calcd for C17H14ClNO : C, 68.12; H, 4.71; N, 4.67%,
found: C, 68.20; H, 4.54; N, 4.75%.
14 X. Zhang and Z. Sui, Tetrahedron Lett., 2003, 44,
3
071–3073.
1
5 (a) R. E. Tundel, K. W. Anderson and S. L. Buchwald,
J. Org. Chem., 2006, 71, 430–433; (b) K. W. Anderson,
M. Mendez-Perez, J. Priego and S. L. Buchwald, J. Org.
Chem., 2003, 68, 9563–9573; (c) J. D. Hicks, A. M. Hyde,
A. M. Cuezva and S. L. Buchwald, J. Am. Chem. Soc., 2009,
Acknowledgements
The authors are thankful to the Indian Institutes of Technology
Chennai and the Indian Institute of Science Bangalore for
providing analytical support. They are also grateful to Post
Graduate and Research Department of Chemistry, Jamal Mohamed
College, Bharathidasan University, Tiruchirapalli and Head of
Chemistry Department, Govt. College Kasaragod for providing
support and facilities for conducting the research.
1
31, 5766–5768.
6 J. H o¨ germeier and H.-U. Reissig, Adv. Synth. Catal., 2009,
51, 2747–2763.
1
1
1
1
3
7 M. A. K. Vogel, C. B. W. Stark and I. M. Lyapkalo, Adv. Synth.
Catal., 2007, 349(7), 1019–1024.
8 S. Wagaw, R. A. Rennels and S. L. Buchwald, J. Am. Chem.
Soc., 1997, 119, 8451–8458.
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