Phosphine-catalyzed [4 + 2] annulation and vinylogous addition reactions between 1,4-dien-3-ones and 1,1-dicyanoalkenes

Article abstract of DOI:10.1039/c1ob06187a

Phosphine-catalyzed [4 + 2] annulation and vinylogous Michael addition reactions between 1,4-dien-3-ones and 1,1-dicyanoalkenes are presented. Under the catalysis of PBu₃ (20 mol %), 1,4-dien-3-ones like styryl ketones with 2-aryl 1,1-dicyanoal

Full text of DOI:10.1039/c1ob06187a

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PAPER
Phosphine-catalyzed [4 + 2] annulation and vinylogous addition reactions
between 1,4-dien-3-ones and 1,1-dicyanoalkenes†
Rong Zhou, Jianfang Wang, Junjun Tian and Zhengjie He*
Received 17th July 2011, Accepted 5th October 2011
DOI: 10.1039/c1ob06187a
Phosphine-catalyzed [4 + 2] annulation and vinylogous Michael addition reactions between
1,4-dien-3-ones and 1,1-dicyanoalkenes are presented. Under the catalysis of PBu3 (20 mol %),
1,4-dien-3-ones like styryl ketones with 2-aryl 1,1-dicyanoalkenes as doubly activated alkenes readily
undergo a formal [4 + 2] cycloaddition reaction, affording polysubstituted cyclohexanones in
satisfactory yield and good diastereoselectivity; with the doubly activated alkenes bearing an acidic
methyl or methylene at the 2-position, a vinylogous Michael addition of 1,4-dien-3-ones occurs under
the same reaction conditions, giving a non-cyclized multifunctional adduct in good yield. These two
phosphine-catalyzed transformations represent atom economical carbon–carbon bond forming
reactions capable of rapid construction of molecular complexity. Based on experimental results,
formation of the products has been mechanistically rationalized, and a phosphonium activation is
proposed.
achieved under the influence of a nucleophilic phosphine, as
Introduction
evidenced in the reported MBH reactions.3a However, a highly
The carbon–carbon bond forming reaction is fundamental to or-
chemo-controlled phosphine-catalyzed cross-coupling between
two different Michael acceptors remains a challenging goal,4
although encouraging progress has been made in recent years,
particularly with regard to intramolecular versions of the RC
reaction.3c
Recently, we have successfully developed a conjugated enone–
doubly activated alkene strategy to achieve highly chemoselective
cross-couplings between two different Michael acceptors (Scheme
1).5 Under the catalysis of a tertiary amine Lewis base, a highly
diastereoselective three-component cascade annulation reaction
has been realized in a Michael–Michael–Henry sequence from
ganic synthesis, with enormous research efforts engaged in improv-
ing reaction efficiency, stereoselectivity, and chemoselectivity.1
Over the past decade, nucleophilic phosphine organocatalysis,2 as
a powerful strategy for efficient C–C bond formation, has become
one of the hot research topics in the field of synthetic chemistry.
A number of phosphine-catalyzed reactions, typically including
the Morita–Baylis–Hillman (MBH) reaction,3a,3b the Rauhut–
Currier (RC) reaction,3c and many important annulation reactions
of electron-deficient allenes or alkynes,2c,2d have been actively
explored as efficient and atom economical synthetic methods.
In those reactions, carbonyl-activated alkenes, such as conju-
gated enones and enoates, are the most popular substrates, acting
as latent enolates (nucleophiles) and/or Michael acceptors (elec-
trophiles). A common phosphine-catalyzed reaction of carbonyl-
activated alkenes encompasses generation of a latent enolate via
nucleophilic addition of a catalyst phosphine and subsequent
coupling of the enolate with an electrophile, like aldehydes, imines,
or Michael acceptors, to fulfill a new C–C bond formation. The
chemoselective coupling between an activated alkene (acting as
a latent enolate) and an aldehyde (or imine) could be readily
The State Key Laboratory of Elemento-Organic Chemistry and Department
of Chemistry, Nankai University, 94 Weijin Road, Tianjin, 300071, China.
E-mail: zhengjiehe@nankai.edu.cn; Tel: +86 22-23501520
† Electronic supplementary information (ESI) available: experimental
details for Scheme 4; X-ray crystal structure data and ORTEP drawings
1
for (trans, E)-3b and 4b; copies of H and 13C NMR spectra for 3, 4, 5
and 6; copies of 2D-NMR spectra for representative compounds. CCDC
reference numbers 827159 and 827760. For ESI and crystallographic data
in CIF or other electronic format see DOI: 10.1039/c1ob06187a
Scheme 1 Lewis base-catalyzed cross-couplings between two different
activated alkenes.
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Table 1 Survey on the reaction conditionsa
enones, 1,1-dicyanoalkenes and nitromethane, providing an ef-
ficient synthetic method for densely functionalized cyclohexanes
and some bicyclic compounds (Scheme 1, a).5a Interestingly, under
the mediation of tertiary phosphines possessing different leaving
group abilities, highly chemoselective cascade [2 + 2 + 2] and [2
+ 2 + 1] annulation reactions occurred, respectively, between two
molecules of 1,1-dicyanoalkenes (or 2-cyanoacrylates) and one
molecule of enones, leading to highly diastereoselective syntheses
of polysubstituted cyclohexanes and cyclopentenes (Scheme 1,
b).5b The effectiveness of this strategy may be attributed to the
decent reactivity difference between enones and doubly activated
alkenes: an enone is a better latent enolate (nucleophile) under the
catalysis of a nucleophilic organic Lewis base; a doubly activated
alkene acts as a more reactive Michael acceptor (electrophile).
As a reasonable extension of our prior work, we further
investigated the feasibility of phosphine-catalyzed cross-couplings
between 1,4-dien-3-ones and 1,1-dicyano alkenes. As a group
of versatile multifunctional building blocks, 1,4-dien-3-ones are
widely used in many important organic transformations,6,7 like
the Nazarov cyclization6a and the Diels–Alder cycloaddition,6b,6c
to build molecular ring systems. A pioneering example of a
phosphine-mediated homo-coupling reaction of 1,4-dien-3-ones
was also disclosed by Schaus et al., leading to an efficient and
diastereoselective synthesis of bicyclo[3.2.1]octenones through a
tandem [4 + 2] cycloaddition–Wittig olefination process.8 En-
couragingly, our investigation unveiled that, under the catalysis
of nuleophilic phosphines, two cross-couplings of 1,4-dien-3-ones
and 1,1-dicyanoalkenes could be highly chemoselectively realized,
which was embodied in phosphine-catalyzed [4 + 2] annulation
and vinylogous Michael addition reactions, respectively. These
two reactions represent atom economical C–C forming reactions
capable of efficiently constructing molecular complexity. Herein
we wish to report the detail.
Entry
Catalyst
Solvent
Time (h)
Yield (%)b
drc
1
2
PPh3
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CHCl3
THF
toluene
CH3CN
ethanol
CHCl3
24
24
24
24
24
24
24
24
24
48
24
48
48
24
41(7)
46(9)
51(9)
14(15)
58(8)
60(9)
—
6 : 1
5 : 1
6 : 1
1 : 1
7 : 1
7 : 1
—
PPh2Me
PPhMe2
PTA
PBu3
PBu3
DABCO
DBU
PBu3
PBu3
PBu3
3
4d
5
6
7
8
9
10
11
12
13
14e
—
—
62(13)
60(15)
55(14)
20(14)
—
6 : 1
4 : 1
4 : 1
2 : 1
—
PBu3
PBu3
PBu3
69(10)
7 : 1
a Typical conditions: under N2 atmosphere, dienone 1a (for entries 1–5,
0.6 mmol; for entries 6–14, 0.5 mmol), activated alkene 2a (for entries 1–5,
0.5 mmol; for entries 6–14, 0.6 mmol) and catalyst (0.1 mmol) in solvent
(2 mL) were stirred at rt. b Isolated yield of the isomer (trans, E)-3a and
data in parentheses for the isomer (cis, E)-3a. c Determined by 1H NMR
assay of the crude product. d PTA = 1,3,5-triaza-7-phosphaadamantane.
e CHCl3 (5 mL) was used.
reaction (entry 4). Adjusting the molar ratio of 1a/2a to 1 : 1.2
resulted in a slight improvement of yield in the PBu3-catalyzed
reaction (entry 6). Common tertiary amine catalysts, like DABCO
and DBU, were completely ineffective for the transformation
(entries 7 and 8). Choosing PBu3 as the catalyst, several common
solvents other than CH2Cl2 were further surveyed (entries 9–13).
CHCl3 emerged as the best solvent with respect to the yield and
diastereoselectivity (entry 9), although THF and toluene also gave
comparable results (entries 10, 11). The polar solvent CH3CN and
protic solvent ethanol were detrimental to the reaction (entries 12,
13). A dilute substrate concentration was found to be good for the
reaction. When the reaction was run at 0.1 M concentration of 1a,
the yield of 3a was considerably improved (entry 14).
Under the optimized conditions, the generality of the reaction
was examined (Table 2). With dienone 1a employed, a variety of
1,1-dicyanoalkenes 2 were explored. Phenyl-substituted alkenes
2 bearing either electron-donating or -withdrawing groups on
the benzene ring readily afforded their corresponding [4 + 2]
annulation products 3 in moderate to good yields and good to
high diastereoselectivities (entries 1–10). Heteroaryl-substituted
alkenes 2k and 2l were also suitable substrates in the annulation
reaction with 1a, giving corresponding cyclohexanones 3 in
moderate yields and excellent diastereoselectivities (entries 11 and
12). E-styryl-substituted activated alkene 2m was also examined,
readily affording the annulation product 3m in 86% yield and high
diastereoselectivity (entry 13). However, ethyl-substituted alkene
2n was not an effective candidate for the annulation reaction with
1a (entry 14).
Results and discussion
Our research was initiated with symmetric styryl ketone 1a and a
doubly activated alkene 2-(4-chlorophenylmethylidene) malonon-
itrile 2a. In the presence of PPh3 (20 mol%), a reaction mixture of
1a (0.6 mmol) and 2a (0.5 mmol) in CH2Cl2 (2.0 mL) was stirred at
room temperature for 24 h. To our delight, two separable isomeric
products (trans, E)-3a and (cis, E)-3a were collected from the
reaction mixture in 48% combined yield with the trans-isomer
being the major product after column chromatographic isolation
(Table 1, entry 1). Structural identification of 3a revealed that a
formal [4 + 2] cycloaddition reaction between dienone 1a and
doubly activated alkene 2a occurred. This reaction represents
a new phosphine-catalyzed reactivity pattern of dienones.8,9 It
also offers a convenient access to highly functionalized cyclo-
hexanones, which are common structural components in many
natural products and pharmaceutically interesting compounds.10
A brief survey on the reaction conditions was carried out by
using the reaction of 1a and 2a as a probe (Table 1). Among a series
of chosen tertiary phosphines (entries 1–5), electron-rich PBu3
gave the best result regarding the yield and diastereoselectivity,
although others were all effective for the reaction. Air-stable and
strongly nucleophilic 1,3,5-triaza-7-phosphaadamantane (PTA),
often used as a convenient alternative phosphine for the air-
sensitive PBu3,11 only brought about much inferior yields in this
Choosing activated alkenes 2a and 2e as two representative re-
actants, several differently substituted dienones 1 were also tested
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Table 2 Synthesis of cyclohexanones 3 from dienones 1 and 1,1-
dicyanoalkenes 2a
Scheme 2 Regioselective annulations of asymmetric 1,4-dien-3-ones 1f
and 1g.
Entry R1 in 1
R2 in 2
Yield (%)b
drc
7 : 1
aryl-substituted alkenes 2 bearing an acidic methyl or methylene
at the 2-position readily occurred, producing vinylogous Michael
addition products 4 as a single diastereomer in satisfactory
yields (Scheme 3). Recently, many amine-catalyzed vinylogous
Michael additions between 1,1-dicyanoalkenes like 2o–q and
various Michael acceptors were documented as an efficient C–C
bond forming protocol.12 In contrast, similar phosphine-catalyzed
vinylogous Michael additions were seldom reported.13 The PBu3-
catalyzed vinylogous Michael addition of dienones 1a and 1d
with activated alkenes 2o–q indeed represents a new example of
the phosphine-catalyzed reaction, as well as provides an efficient
method to construct molecular complexity.
1
2
3
4
5
6
7
8
Ph (1a)
4-ClC6H4 (2a)
4-MeOC6H4 (2b)
2-MeOC6H4 (2c)
4-MeC6H4 (2d)
Ph (2e)
2-ClC6H4 (2f)
2-BrC6H4 (2g)
2,4-ClC6H3 (2h)
4-FC6H4 (2i)
4-CF3C6H4 (2j)
2-furyl (2k)
2-thiofuryl (2l)
E-styryl (2m)
Et (2n)
4-ClC6H4 (2a)
Ph (2e)
4-ClC6H4 (2a)
Ph (2e)
4-ClC6H4 (2a)
Ph (2e)
Ph (2e)
3a, 69 (10)
3b, 81
3c, 84
3d, 86
3e, 70
3f, 70
3g, 69
3h, 58
3i, 48
3j, 51
3k, 55
3l, 62
3m, 86
trace
3n, 74
3o, 43
3p, 56
3q, 57 (11)
3r, 62
3s, 80
3t, 46
Ph (1a)
11 : 1
7 : 1
7 : 1
7 : 1
20 : 1
14 : 1
8 : 1
7 : 1
5 : 1
12 : 1
20 : 1
14 : 1
—
5 : 1
5 : 1
7 : 1
5 : 1
7 : 1
7 : 1
8 : 1
Ph (1a)
Ph (1a)
Ph (1a)
Ph (1a)
Ph (1a)
Ph (1a)
9
Ph (1a)
10
11
12
13
14
15
16
17
18
19
20
21
Ph (1a)
Ph (1a)
Ph (1a)
Ph (1a)
Ph (1a)
4-MeOC6H4 (1b)
4-MeOC6H4 (1b)
4-MeC6H4 (1c)
4-MeC6H4 (1c)
4-FC6H4 (1d)
4-FC6H4 (1d)
4-CF3C6H4 (1e)
a For a typical procedure, see Experimental section. b Isolated yield of the
major product (trans, E)-3 and data in parentheses for isolated minor
products (cis, E)-3. c Ratio of (trans, E)-3/(cis, E)-3, determined by 1H
NMR assay of the crude product.
(Table 2, entries 15–21). Under the standard conditions, phenyl-
substituted dienones 1b–1e bearing either electron-donating or
-withdrawing groups readily underwent the PBu3-catalyzed [4 +
2] annulations with activated alkenes 2a or 2e, affording their
corresponding cyclohexanones 3 in moderate to good yields and
good diastereoselectivities.
Scheme 3 Phosphine-catalyzed vinylogous Michael additions.
The structures of cyclohexanones 3 and Michael addition
products 4 were fully identified by spectrometric methods, in-
cluding IR, NMR (1H and 13C), and HRMS-ESI. The structural
assignments, including relative configuration determination, were
further confirmed by NOSEY and X-ray crystallographic analyses
for representative compounds. The crystal structures of (trans, E)-
3b (CCDC 827159) and 4b (CCDC 827760) are shown in the
Supplementary Information.†
In order to better interpret the mechanisms of the PBu3-
catalyzed [4 + 2] annulation and vinylogous Michael addition
reactions between dienones 1 and activated alkenes 2, the following
experiments were deliberately conducted (Scheme 4, for detail,
also see the Supplementary Information†). A H/D exchange
experiment was first carried out to probe the mechanism. In the
presence of PBu3 (20 mol%), the annulation product (trans, E)-3a
was stirred at room temperature for 24 h in a mixture of CHCl3–
D2O (5 : 1), giving a partially deuterated product (trans, E)-3a-d2
(Scheme 4, a). According to the reported work by Bergman, et
al.,14 the H/D exchange at the a-position of the carbonyl of 3a
most likely proceeded through an enolate intermediate generated
from the nucleophilic addition of PBu3 to the alkene unit. It
was also found that no isomerization was observed in the H/D
In all cases listed in Table 2, the [4 + 2] annulation reaction
furnished the cyclohexanone product 3 in a pair of diastereomers
1
with a varying ratio, as determined by H NMR measurement
of the crude product. However, in most of cases, only the major
products (trans, E)-3 were isolated as pure compounds by column
chromatography on silica gel. Except 3a and 3q (entries 1 and 18),
the minor products (cis, E)-3 were all obtained as impure fractions
in column chromatographic isolation.
Asymmetric 1,4-dien-3-ones were also examined (Scheme 2).
Under the standard conditions, the regioselective annulation
products (trans, E)-3u and (trans, E)-3v were successfully obtained
in modest yields from the respective reactions of asymmetric 1,4-
dien-3-ones 1f and 1g with doubly activated alkene 2f. Apparently,
the regioselectivity of the annulation reactions depends on the
electronic property difference between two aryl substituents of
asymmetric dienones 1.
Although monoalkyl-substituted activated alkene 2n was inef-
fective for the PBu3-catalyzed [4 + 2] annulation with dienone 1a
(Table 2, entry 14), however, under the catalysis of PBu3 (20 mol%),
a highly chemoselective cross-coupling between dienones 1 and
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chalcone do not possess enough reactivity to couple with the
activated alkene 2o or its corresponding allylic carbanion.
Based on the above results, a plausible mechanism to account
for the formation of 3 and 4 is depicted in Scheme 5. Initially,
nucleophilic addition of PBu3 to dienone 1 generates a phospho-
nium dienolate intermediate A. When the doubly activated alkene
2 does not possess an acidic group, intermediate A undergoes a
formal [4 + 2] cycloaddition with alkene 2 predominantly in an exo
fashion,15 producing intermediate B. Intermediate B interconverts
with intermediate C, which undertakes an elimination of PBu3 to
furnish the [4 + 2] annulation product 3. In another scenario,
when the alkene 2, like 2o, bears an acidic methyl group at
the 2-position, the dienolate intermediate A as a strong base is
readily protonated with the activated alkene 2, producing a b-
phosphonium-substituted monoenone D and an allylic carbanion.
Considering a possible activation effect of the phosphonium unit
on the monoenone moiety through a Coulombic interaction
between the phosphonium unit and the adjacent carbonyl in
intermediate D,16 we postulate that a Michael addition between
intermediate D and the allylic carbanion takes place, resulting
in the formation of intermediate E. Finally, E undergoes proton
transfer and elimination of PBu3 to give out the vinylogous
Michael addition product 4.
Scheme 4 Experiments for mechanistic investigation.
exchange of 3a, particularly with regard to the configuration of
the alkene unit, although addition of the phosphine PBu3 to the
alkene unit and subsequent elimination were presumably involved
in the H/D exchange process. This result implies that the reversible
addition of PBu3 to the alkene unit is a highly stereoselective
process.
The H/D exchange strategy was also applied in the case of
the vinylogous Michael addition. Under the standard conditions,
the PBu3-catalyzed vinylogous Michael addition reaction of styryl
ketone 1a and activated alkene 2o was run in a media of CHCl3–
D2O (5 : 1), producing a partially deuterated adduct 4a-d5 in
68% yield with substantial deuterium incorporations at the a-
and g-positions of the carbonyl (Scheme 4, b). In contrast,
the normal adduct 4a was treated under the same conditions,
giving a deuterated product 4a-d3 with comparable deuterium
incorporations only at the a-positions of the carbonyl (Scheme
4, c). This fact strongly supports a hypothesis that an allylic
carbanion intermediate is formed through deprotonation of the
acidic methyl of the activated alkene 2o in the vinylogous Michael
addition reaction.
Additional experiments provide more clues about the mech-
anism of the vinylogous Michael addition (Scheme 4, d and
e). Under the standard conditions, chalcone, as a monoenone
that is structurally in close proximity to the dienone 1a, did not
undergo any similar vinylogous Michael addition reaction with the
activated alkene 2o; meanwhile, in the presence of the equivalent
chalcone, only the adduct 4a from dienone 1a and alkene 2o was
formed in 75% yield. These results indicate that monoenones like
Scheme 5 A plausible mechanism for the formation of 3 and 4.
To illustrate the synthetic application of the cross-coupling
products, the following chemical transformations were performed
(Scheme 6). Starting from the [4 + 2] cycloaddition prod-
uct (trans, E)-3a, a complex bicyclic substructure 3-imino-2-
oxabicyclo[2.2.2]octane17 in 6 could be readily accessed in high
yields.
Conclusions
In summary, two kinds of PBu3-catalyzed cross-couplings between
1,4-dien-3-ones and 1,1-dicyanoalkenes have been realized, which
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3-Benzylidene-2-(4-chlorophenyl)-4-oxo-6-phenyl cyclohexane-
1,1-dicarbonitrile (3a). Prepared from 1a (117 mg, 0.5 mmol)
and 2a (113 mg, 0.6 mmol) and isolated as two pure diastereom◦ers.
(trans, E)-3a: yellow solid; yield 145 mg, 69%; m.p. 198–200 C;
IR (KBr): n 3062, 1687, 1597, 1492, 1410, 1263, 1175, 1094, 823,
738, 699 cm-1; 1H NMR (400 MHz, CDCl3): d 7.91 (s, 1H), 7.50
(d, J = 8.4 Hz, 2H), 7.45–7.26 (m, 10H), 7.13 (d, J = 6.9 Hz, 2H),
4.95 (s, 1H), 3.57 (dd, J = 13.2, 5.2 Hz, 1H), 3.31 (dd, J = 18.6,
13.2 Hz, 1H), 3.13 (dd, J = 18.6, 5.2 Hz, 1H); 13C NMR (100
MHz, CDCl3): d 195.7, 143.7, 135.9, 134.9, 134.3, 133.3, 131.4,
131.3, 130.4, 129.9, 129.8, 129.6, 129.3, 128.9, 128.2, 113.7, 113.1,
49.9, 45.2, 42.1, 42.0; Anal. Calcd for C27H19ClN2O: C 76.68, H
4.53, N 6.62; found: C 76.26, H 4.36, N 6.51. (cis, E)-3a: yellow
◦
Scheme 6 The construction of a bicyclic substructure from 3a (R2
4-ClC6H4).
=
solid; yield 21 mg, 10%; m.p. 95–98 C; IR (KBr): n 3061, 2917,
1
1703, 1594, 1493, 1264, 1093, 831, 749, 698 cm-1; H NMR (400
MHz, CDCl3): d 7.86 (s, 1H), 7.54–7.42 (m, 5H), 7.35–7.18 (m,
7H), 7.11 (d, J = 7.5 Hz, 2H), 5.00 (s, 1H), 3.74 (dd, J = 13.6,
4.5 Hz, 1H), 3.45 (dd, J = 19.4, 13.8 Hz, 1H), 3.04 (dd, J = 19.5,
4.5 Hz, 1H); 13C NMR (100 MHz, CDCl3): d 196.2, 144.2, 135.15,
135.12, 134.7, 133.3, 132.4, 130.5, 129.97, 129.91, 129.7, 129.5,
129.2, 128.5, 128.1, 114.4, 112.3, 52.3, 47.9, 45.6, 40.7; HRMS-
ESI Calcd for C27H19ClN2O [M + Na]+ 445.1078, found 445.1075.
consist of a formal [4 + 2] cycloaddition reaction and a vinylogous
Michael addition reaction, respectively. These two reactions
represent atom economical C–C forming reactions that are capable
of efficiently constructing multifunctional cyclohexanones and
acyclic carbonyl compounds. On the basis of the experimental
results in this study, the reactions are supposed to proceed through
a key intermediate phosphonium dienolate, and an activation
effect of the phosphonium unit presumably plays a key role in
the vinylogous Michael addition reaction. Future efforts in our
laboratory will be directed toward the potential application in
organic synthesis and detailed mechanism of these two reactions.
(E)-3-Benzylidene-2-(4-methoxyphenyl)-4-oxo-6-phenyl cyclo-
hexane-1,1-dicarbonitrile ((trans, E)-3b). Prepared from 1a (117
mg, 0.5 mmol) and 2b (110 mg, 0.6 mmol). Yellow solid; yield
169 mg, 81%; m.p. 143–144 ◦C; IR (KBr): n 3062, 2934, 1687,
1608, 1512, 1254, 1182, 1031, 829, 700 cm-1; 1H NMR (400 MHz,
CDCl3): d 7.88 (s, 1H), 7.46–7.26 (m, 10H), 7.17 (d, J = 6.9 Hz,
2H), 7.02 (d, J = 8.6 Hz, 2H), 4.94 (s, 1H), 3.86 (s, 3H), 3.65 (dd,
J = 13.2, 5.2 Hz, 1H), 3.29 (dd, J = 18.5, 13.2 Hz, 1H), 3.12 (dd,
J = 18.6, 5.2 Hz, 1H); 13C NMR (100 MHz, CDCl3): d 196.0,
160.3, 142.9, 135.3, 133.6, 132.0, 131.3, 130.2, 130.0, 129.5, 129.2,
128.8, 128.2, 127.6, 114.9, 114.0, 113.4, 55.4, 50.0, 45.5, 42.1,
41.9; elemental analysis: C28H22N2O2 requires C, 80.36; H, 5.30;
N, 6.69; found: C, 79.92; H, 4.98; N 6.52.
Experimental section
General information
Unless otherwise noted, all reactions were carried out in a nitrogen
atmosphere under anhydrous conditions. Solvents were purified
according to standard procedures. 1H and 13C NMR spectra
were recorded in CDCl3 on a Bruker AV 400 spectrometer with
tetramethylsilane as an internal standard. NOESY spectra were
obtained on a Varian 300 spectrometer in CDCl3. High resolution
ESI mass spectra were acquired with an IonSpec QFT-ESI
instrument. Infrared spectra were recorded on a JASCO FT/IR-
480 spectrophotometer. Elemental analyses were performed on
a Yanaco CHN Corder MT-3 automatic analyzer. X-ray crys-
tal diffraction data were collected on a Nonius Kappa CCD
(E)-3-Benzylidene-2-(2-methoxyphenyl)-4-oxo-6-phenyl cyclo-
hexane-1,1-dicarbonitrile ((trans, E)-3c). Prepared from 1a (117
mg, 0.5 mmol) and 2c (110 mg, 0.6 mmol). Yellow solid; yield 176
◦
mg, 84%; m.p. 178–179 C; IR (KBr): n 3062, 2840, 1690, 1600,
1492, 1457, 1250, 1025, 763, 737, 700 cm-1; 1H NMR (400 MHz,
CDCl3): d 7.82 (s, 1H), 7.47 (t, J = 7.7 Hz, 1H), 7.43–7.30 (m,
8H), 7.24 (d, J = 10.7 Hz, 1H), 7.17 (d, J = 7.1 Hz, 2H), 7.09 (dd,
J = 16.7, 8.0 Hz, 2H), 5.26 (s, 1H), 3.82 (s, 3H), 3.78 (dd, J = 13.0,
5.1 Hz, 1H), 3.26 (dd, J = 18.3, 13.1 Hz, 1H), 3.10 (dd, J = 18.4,
5.1 Hz, 1H); 13C NMR (100 MHz, CDCl3): d 195.3, 157.4, 141.7,
135.7, 133.7, 132.1, 131.8, 131.2, 130.1, 129.9, 129.4, 129.1, 128.6,
128.3, 124.3, 121.6, 114.1, 113.2, 112.5, 55.2, 45.1, 43.1, 42.2;
HRMS-ESI Calcd for C28H22N2O2 [M + Na]+ 441.1574, found
441.1575.
˚
diffractometer with Mo-Ka radiation (l = 0.7107 A) at room
temperature. Column chromatography was performed on silica gel
(200–300 mesh) using a mixture of petroleum ether/ethyl acetate
as eluant.
General procedure for PBu3-catalyzed [4 + 2] annulation reaction
between dienone 1 and activated alkene 2 (Table 2 and Scheme 2)
Under a N2 atmosphere, to a solution of dienone 1 (0.5 mmol) and
activated alkene 2 (0.6 mmol) in chloroform (5 mL) was added
PBu3 (25 uL, 0.1 mmol). The resulting mixture was stirred at
room temperature for a specified time (Table 2) till dienone 1
was completely consumed, as monitored by TLC. The solvent
was removed on a rotary evaporator under reduced pressure and
the residue was subjected to column chromatographic isolation
(E)-3-Benzylidene-4-oxo-6-phenyl-2-p-tolylcyclohexane-1,1-di-
carbonitrile ((trans, E)-3d). Prepared from 1a (117 mg, 0.5 mmol)
and 2d (100 mg, 0.6 mmol). Yellow solid; yield 172 mg, 86%;
m.p. 100–101 ◦C; IR (KBr): n 3060, 1687, 1597, 1264, 1117, 750,
1
699 cm-1; H NMR (400 MHz, CDCl3): d 7.89 (s, 1H), 7.41–
7.27 (m, 11H), 7.21–7.13 (m, 2H), 4.93 (s, 1H), 3.66 (dd, J =
13.1, 5.3 Hz, 1H), 3.30 (dd, J = 18.6, 13.2 Hz, 1H), 3.14 (dd, J =
18.6, 5.4 Hz, 1H), 2.43 (s, 3H); 13C NMR (100 MHz, CDCl3): d
o
on silica gel (gradient elution, petroleum ether (60–90 C)/ethyl
acetate 20 : 1–10 : 1) to give the annulation product 3.
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196.0, 142.9, 139.7, 135.3, 133.5, 132.7, 131.9, 130.3, 130.2, 129.98,
129.92, 129.5, 129.2, 128.8, 128.2, 114.0, 113.3, 50.3, 45.4, 42.2,
42.0, 21.2; elemental analysis: C28H22N2O requires C, 83.56; H,
5.51; N, 6.96; found: C, 83.75; H, 5.37; N 6.79.
1238, 832, 738, 700 cm-1; 1H NMR (400 MHz, CDCl3): d 7.91 (s,
1H), 7.46–7.27 (m, 10H), 7.27–7.19 (m, 2H), 7.13 (d, J = 6.9 Hz,
2H), 4.97 (s, 1H), 3.59 (dd, J = 13.2, 5.2 Hz, 1H), 3.31 (dd, J =
18.6, 13.2 Hz, 1H), 3.13 (dd, J = 18.6, 5.3 Hz, 1H); 13C NMR
(100 MHz, CDCl3): d 195.7, 163.2 (d, J = 250.9 Hz), 143.5, 135.0,
133.4, 131.9 (d, J = 8.3 Hz), 131.7 (d, J = 3.2 Hz), 131.6, 130.3,
129.8, 129.6, 129.3, 128.9, 128.2, 116.8 (d, J = 21.8 Hz), 113.8,
113.1, 49.9, 45.3, 42.0; elemental analysis: C27H19FN2O requires
C, 79.79; H, 4.71; N, 6.89; found: C, 80.07; H, 4.57; N 7.19.
(E)-3-Benzylidene-4-oxo-2,6-diphenylcyclohexane-1,1-dicar-
bonitrile ((trans, E)-3e). Prepared from 1a (117 mg, 0.5 mmol)
and 2e (93 mg, 0.6 mmol). Yellow solid; yield 135 mg, 70%; m.p.
208–209 ◦C; IR (KBr): n 3005, 2838, 1679, 1583, 1511, 1260, 1173,
1030, 831, 758, 702 cm-1; 1H NMR (400 MHz, CDCl3): d 7.91 (s,
1H), 7.61–7.45 (m, 3H), 7.45–7.25 (m, 10H), 7.15 (d, J = 6.7 Hz,
2H), 4.98 (s, 1H), 3.65 (dd, J = 13.1, 5.3 Hz, 1H), 3.31 (dd, J = 18.6,
13.1 Hz, 1H), 3.14 (dd, J = 18.6, 5.3 Hz, 1H); 13C NMR (100 MHz,
CDCl3): d 195.9, 143.2, 135.9, 135.2, 133.5, 131.7, 130.2, 130.1,
129.9, 129.8, 129.6, 129.5, 129.2, 128.9, 128.2, 113.9, 113.2, 50.6,
45.3, 42.1; HRMS-ESI Calcd for C27H20N2O [M + Na]+ 411.1468,
found 411.1468.
(E)-3-Benzylidene-4-oxo-6-phenyl-2-(4-(trifluoromethyl)
phe-
nyl)cyclohexane-1,1-dicarbonitrile ((trans, E)-3j). Prepared from
1a (117 mg, 0.5 mmol) and 2j (133 mg, 0.6 mmol). Yellow solid;
yield 116 mg, 51%; m.p. 189–190 ◦C; IR (KBr): n 3064, 1688,
1598, 1326, 1124, 832, 740, 700 cm-1; 1H NMR (400 MHz,
CDCl3): d 7.95 (s, 1H), 7.80 (d, J = 8.2 Hz, 2H), 7.54 (d, J =
8.1 Hz, 2H), 7.46–7.34 (m, 6H), 7.34–7.27 (m, 2H), 7.11 (d, J =
7.0 Hz, 2H), 5.02 (s, 1H), 3.56 (dd, J = 13.1, 5.2 Hz, 1H), 3.34 (dd,
J = 18.6, 13.1 Hz, 1H), 3.17 (dd, J = 18.5, 5.3 Hz, 1H); 13C NMR
(100 MHz, CDCl3): d 195.4, 144.1, 139.8, 134.7, 133.2, 131.9 (q,
J = 32.9 Hz), 130.9, 130.6, 130.5, 129.7, 129.3, 128.9, 128.1, 126.6
(q, J = 3.7 Hz), 123.6 (q, J = 272.5), 113.5, 112.9, 50.2, 45.1, 42.2,
42.0; elemental analysis: C28H19F3N2O requires C, 73.68; H, 4.20;
N, 6.14; found: C, 73.82; H, 4.34; N, 6.13.
(E)-3-Benzylidene-2-(2-chlorophenyl)-4-oxo-6-phenyl cyclohe-
xane-1,1-dicarbonitrile ((trans, E)-3f). Prepared from 1a (117
mg, 0.5 mmol) and 2f (113 mg, 0.6 mmol). Yellow solid; yield 148
mg, 70%; m.p. 93–95 ◦C; IR (KBr): n 3063, 1688, 1593, 1262,
761, 699 cm-1; 1H NMR (400 MHz, CDCl3): d 7.90 (s, 1H), 7.60
(dd, J = 7.7, 1.7 Hz, 1H), 7.48–7.29 (m, 10H), 7.22–7.11 (m,
3H), 5.64 (s, 1H), 3.82 (dd, J = 13.4, 5.0 Hz, 1H), 3.36 (dd, J =
18.4, 13.4 Hz, 1H), 3.18 (dd, J = 18.4, 5.0 Hz, 1H); 13C NMR
(100 MHz, CDCl3): d 195.7, 144.2, 135.6, 134.9, 133.6, 133.2,
131.6, 131.5, 131.3, 130.9, 130.2, 129.7, 129.6, 129.2, 128.9, 128.4,
127.6, 113.8, 112.4, 46.7, 43.7, 42.6, 42.1; HRMS-ESI Calcd for
C27H19ClN2O [M + Na]+ 445.1078, found 445.1069.
(E)-3-Benzylidene-2-(2-furyl)-4-oxo-6-phenylcyclohexane-1,1 -
dicarbonitrile ((trans, E)-3k). Prepared from 1a (117 mg,
0.5 mmol) and 2k (86 mg, 0.6 mmol). Yellow solid; yield 103
mg, 55%; m.p. 79–80 ◦C; IR (KBr): n 3062, 1692, 1609, 1496,
1
1245, 1016, 740, 700 cm-1; H NMR (400 MHz, CDCl3): d 7.86
(s, 1H), 7.59 (s, 1H), 7.49–7.30 (m, 9H), 7.28–7.18 (m, 2H), 6.55
(dd, J = 12.9, 2.4 Hz, 2H), 5.10 (s, 1H), 3.59 (dd, J = 12.8, 5.5 Hz,
1H), 3.23 (dd, J = 18.3, 12.9 Hz, 1H), 3.10 (dd, J = 18.3, 5.5 Hz,
1H);13C NMR (100 MHz, CDCl3): d 195.1, 148.1, 144.6, 142.7,
135.2, 133.3, 130.2, 129.9, 129.7, 129.6, 129.3, 129.0, 128.2, 113.14,
113.13, 112.2, 111.4, 45.2, 44.7, 43.6, 41.9; HRMS-ESI Calcd for
C25H18N2O [M + Na]+ 401.1261, found 401.1260.
(E)-3-Benzylidene-2-(2-bromophenyl)-4-oxo-6-phenyl cyclohe-
xane-1,1-dicarbonitrile ((trans, E)-3g). Prepared from 1a (117
mg, 0.5 mmol) and 2g (140 mg, 0.6 mmol). Yellow solid; yield
160 mg, 69%; m.p. 74–76 ◦C; IR (KBr): n 3062, 1689, 1596, 1259,
1
1179, 1025, 761, 699 cm-1; H NMR (400 MHz, CDCl3): d 7.91
(s, 1H), 7.80 (d, J = 8.0 Hz, 1H), 7.51–7.30 (m, 10H), 7.23–7.09
(m, 3H), 5.61 (s, 1H), 3.82 (dd, J = 13.4, 5.0 Hz, 1H), 3.36 (dd, J =
18.3, 13.4 Hz, 1H), 3.19 (dd, J = 18.3, 5.0 Hz, 1H);13C NMR (100
MHz, CDCl3): d 195.8, 144.4, 135.0, 134.8, 133.1, 131.7, 131.4,
131.0, 130.2, 129.7, 129.6, 129.2, 129.0, 128.4, 128.2, 126.6, 113.8,
112.4, 48.9, 43.6, 42.6, 42.0; HRMS-ESI Calcd for C27H19BrN2O
[M + Na]+ 489.0573, found 489.0566.
(E)-3-Benzylidene-4-oxo-6-phenyl-2-(2-thiofuryl)cyclohexane-1,
1-dicarbonitrile ((trans, E)-3l). Prepared from 1a (117 mg,
0.5 mmol) and 2l (96 mg, 0.6 mmol). Yellow solid; yield 122
mg, 62%; m.p. 74–76 ◦C; IR (KBr): n 3062, 1689, 1600, 1244,
1199, 737, 699 cm-1; 1H NMR (400 MHz, CDCl3): d 7.90 (s, 1H),
7.49 (dd, J = 5.1, 0.8 Hz, 1H), 7.46–7.32 (m, 8H), 7.31 (d, J =
3.6 Hz, 1H), 7.25–7.21 (m, 2H), 7.19 (dd, J = 5.1, 3.7 Hz, 1H),
5.27 (s, 1H), 3.72 (dd, J = 12.9, 5.5 Hz, 1H), 3.26 (dd, J = 18.6,
12.9 Hz, 1H), 3.10 (dd, J = 18.6, 5.5 Hz, 1H); 13C NMR (100
MHz, CDCl3): d 195.0, 143.4, 137.9, 135.2, 133.3, 132.1, 130.4,
129.9, 129.6, 129.5, 129.3, 129.0, 128.22, 128.17, 127.9, 113.6,
113.5, 46.1, 45.7, 42.5, 41.8; HRMS-ESI Calcd for C25H18N2OS
[M + Na]+ 417.1032, found 417.1036.
(E)-3-Benzylidene-2-(2,4-dichlorophenyl)-4-oxo-6-phenyl cyclo-
hexane-1,1-dicarbonitrile ((trans, E)-3h). Prepared from 1a (117
mg, 0.5 mmol) and 2h (112 mg, 0.6 mmol). Yellow solid; yield 132
mg, 58%; m.p. 90–91 ◦C; IR (KBr): n 3064, 1689, 1587, 1471, 1257,
766, 750, 699 cm-1; 1H NMR (400 MHz, CDCl3): d 7.91 (s, 1H),
7.63 (d, J = 1.8 Hz, 1H), 7.51–7.30 (m, 9H), 7.19–7.06 (m, 3H),
5.57 (s, 1H), 3.74 (dd, J = 13.3, 4.9 Hz, 1H), 3.36 (dd, J = 18.4,
13.4 Hz, 1H), 3.18 (dd, J = 18.4, 4.9 Hz, 1H); 13C NMR (100 MHz,
CDCl3): d 195.5, 144.6, 136.5, 136.4, 134.6, 133.0, 132.2, 131.9,
131.3, 131.2, 130.4, 129.7, 129.5, 129.3, 129.0, 128.4, 128.0, 113.6,
112.2, 46.3, 43.6, 42.6, 41.9; HRMS-ESI Calcd for C27H18Cl2N2O
[M + Na]+ 479.0688, found 479.0684.
(E)-3-Benzylidene-4-oxo-6-phenyl-2-styrylcyclohexane-1,1-di-
carbonitrile ((trans, E)-3m). Prepared from 1a (117 mg,
0.5 mmol) and 2m (108 mg, 0.6 mmol). Yellow semi-solid; yield
178 mg, 86%; IR (KBr): n 3061, 1689, 1604, 1448, 1200, 769, 698
1
cm-1; H NMR (400 MHz, CDCl3) d 7.95 (s, 1H), 7.51 (d, J =
(E)-3-Benzylidene-2-(4-fluorophenyl)-4-oxo-6-phenyl cyclohe-
xane-1,1-dicarbonitrile ((trans, E)-3i). Prepared from 1a (117
mg, 0.5 mmol) and 2i (1◦03 mg, 0.6 mmol). Yellow solid; yield 97
mg, 48%; m.p. 199–200 C; IR (KBr): n 3063, 1687, 1604, 1509,
6.8 Hz, 2H), 7.48–7.36 (m, 13H), 6.70 (d, J = 16.3 Hz, 1H), 6.65
(d, J = 16.2 Hz, 1H), 4.68 (d, J = 1.9 Hz, 1H), 3.75 (dd, J =
13.1, 5.2 Hz, 1H), 3.20 (dd, J = 18.3, 13.2 Hz, 1H), 3.00 (dd, J =
18.3, 5.2 Hz, 1H); 13C NMR (100 MHz, CDCl3): d 195.9, 143.5,
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138.7, 135.2, 135.0, 133.3, 130.43, 130.37, 129.65, 129.62, 129.4,
129.3, 129.1, 128.9, 128.1, 127.1, 122.4, 113.48, 113.45, 47.7, 44.2,
43.1, 42.1; HRMS-ESI Calcd for C29H22N2O [M + Na]+ 437.1624,
found 437.1617.
114.0, 113.3, 50.6, 45.5, 42.1, 41.7, 21.5, 21.2; Anal. Calcd for
C29H24N2O: C 83.63, H 5.81, N 6.73; found: C 83.19, H 5.70, N
6.52. (cis, E)-3q: yellow solid; yield 23 mg, 11%; H NMR (400
1
MHz, CDCl3): d 7.75 (s, 1H), 7.43–7.34 (m, 4H), 7.34–7.21 (m,
5H), 7.08 (d, J = 7.6 Hz, 2H), 7.01 (d, J = 7.7 Hz, 2H), 5.02 (s,
1H), 3.67 (dd, J = 13.7, 3.7 Hz, 1H), 3.41 (dd, J = 19.3, 13.9 Hz,
(E)-2-(4-Chlorophenyl)-3-(4-methoxybenzylidene)-6-(4-meth-
oxyphenyl)-4-oxocyclohexane-1,1-dicarbonitrile ((trans, E)-3n).
Prepared from 1b (147 mg, 0.5 mmol) and 2a (113 mg, 0.6 mmol).
1H), 2.96 (dd, J = 19.2, 3.9 Hz, 1H), 2.37 (s, 3H), 2.27 (s, 3H); 13
C
NMR (100 MHz, CDCl3): d 197.3, 143.3, 140.6, 139.5, 136.9,
132.3, 131.9, 130.7, 130.4, 130.0, 129.2, 129.13, 129.08, 128.9,
128.1, 115.1, 112.4, 52.7, 48.3, 45.2, 40.7, 21.4, 21.2; HRMS-ESI
Calcd for C29H24N2O [M + Na]+ 439.1781, found 439.1781.
◦
Yellow solid; yield 179 mg, 74%; m.p. 188–190 C; IR (KBr): n
3004, 2838, 1681, 1585, 1512, 1260, 1173, 830 cm-1; 1H NMR (400
MHz, CDCl3): d 7.89 (s, 1H), 7.50 (d, J = 8.5 Hz, 2H), 7.37 (d, J =
8.5 Hz, 2H), 7.22 (d, J = 8.8 Hz, 2H), 7.14 (d, J = 8.7 Hz, 2H), 6.88
(dd, J = 8.7, 6.4 Hz, 4H), 4.95 (s, 1H), 3.83 (s, 3H), 3.80 (s, 3H), 3.52
(dd, J = 13.1, 5.4 Hz, 1H), 3.26 (dd, J = 18.7, 13.1 Hz, 1H), 3.10
(dd, J = 18.7, 5.4 Hz, 1H); 13C NMR (100 MHz, CDCl3): d 195.5,
161.5, 160.3, 143.7, 135.9, 134.4, 132.4, 131.5, 129.8, 129.3, 128.7,
127.0, 125.8, 114.6, 114.5, 113.9, 113.3, 55.4, 55.3, 49.9, 45.6, 41.9,
41.3; elemental analysis: C29H23ClN2O3 requires C, 72.12; H, 4.80;
N, 5.80; found: C, 71.85; H, 4.48; N, 5.34.
(E)-2-(4-Chlorophenyl)-3-(4-fluorobenzylidene)-6-(4-fluoro phe-
nyl)-4-oxocyclohexane-1,1-dicarbonitrile ((trans, E)-3r). Pre-
pared from 1d (135 mg, 0.5 mmol) and 2a (113 mg, 0.6 mmol).
Yellow solid; yield 142 mg, 62%; m.p. 188–190 ◦C; IR (KBr):
1
n 3057, 1688, 1602, 1510, 1410, 1243, 1069, 1014, 835 cm-1; H
NMR (400 MHz, CDCl3): d 7.87 (s, 1H), 7.51 (d, J = 8.5 Hz, 2H),
7.37–7.28 (m, 4H), 7.19–7.01 (m, 6H), 4.90 (s, 1H), 3.57 (dd, J =
13.0, 5.4 Hz, 1H), 3.26 (dd, J = 18.6, 13.1 Hz, 1H), 3.13 (dd, J =
18.6, 5.5 Hz, 1H); 13C NMR (100 MHz, CDCl3): d 195.1, 163.7
(d, J = 253.3 Hz), 163.3 (d, J = 149.5 Hz), 142.7, 136.2, 133.9,
132.1 (d, J = 8.6 Hz), 131.3, 130.9, 130.6 (d, J = 3.2 Hz), 130.0,
129.99 (d, J = 8.6 Hz), 129.3 (d, J = 3.2 Hz), 116.4 (d, J = 21.7
Hz), 116.3 (d, J = 21.9 Hz), 113.5, 112.9, 49.8, 45.3, 41.9, 41.4;
elemental analysis: C27H17ClF2N2O requires C, 70.67; H, 3.73; N,
6.10; found: C, 70.43; H, 3.59; N, 6.04.
(E)-3-(4-Methoxybenzylidene)-6-(4-methoxyphenyl)-4-oxo-2-
phenylcyclohexane-1,1-dicarbonitrile ((trans, E)-3o). Prepared
from 1b (147 mg, 0.5 mmol) and 2e (93 mg, 0.6 mmol). Yellow
solid; yield 96 mg, 43%; m.p. 202–203 ◦C; IR (KBr): n 3030, 2922,
1685, 1594, 1511, 1175, 816, 756, 702 cm-1; 1H NMR (400 MHz,
CDCl3): d 7.89 (s, 1H), 7.56–7.45 (m, 3H), 7.43–7.37 (m, 2H),
7.21–7.12 (m, 6H), 7.07 (d, J = 8.1 Hz, 2H), 4.98 (s, 1H), 3.61 (dd,
J = 13.1, 5.4 Hz, 1H), 3.28 (dd, J = 18.6, 13.1 Hz, 1H), 3.11 (dd,
J = 18.6, 5.4 Hz, 1H), 2.35 (s, 3H), 2.33 (s, 3H); 13C NMR (100
MHz, CDCl3): d 195.8, 161.4, 160.3, 143.2, 135.9, 132.4, 130.2,
129.6, 129.5, 129.4, 129.3, 127.3, 126.0, 114.5, 114.4, 114.1, 113.4,
55.4, 55.3, 50.5, 45.7, 42.0, 41.3; elemental analysis: C29H24N2O
requires C, 83.63; H, 5.81; N, 6.73; found: C, 83.19; H, 5.70; N,
6.52.
(E)-3-(4-Fluorobenzylidene)-6-(4-fluorophenyl)-4-oxo-2-pheny-
lcyclohexane-1,1-dicarbonitrile ((trans, E)-3s). Prepared from 1d
(135 mg, 0.5 mmol) and 2e (93 mg, 0.6 mmol). Yellow solid; yield
170 mg, 80%; m.p. 179–180 ◦C; IR (KBr): n 3062, 1687, 1601, 1510,
1
1239, 1161, 836, 738, 702 cm-1; H NMR (400 MHz, CDCl3): d
7.87 (s, 1H), 7.59–7.48 (m, 3H), 7.42–7.34 (m, 2H), 7.32–7.23 (m,
2H), 7.16 (dd, J = 8.6, 5.4 Hz, 2H), 7.06 (dd, J = 15.5, 8.6 Hz,
4H), 4.92 (s, 1H), 3.65 (dd, J = 13.0, 5.5 Hz, 1H), 3.26 (dd, J =
18.6, 13.0 Hz, 1H), 3.14 (dd, J = 18.6, 5.6 Hz, 1H); 13C NMR (100
MHz, CDCl3): d 195.3, 163.6 (d, J = 252.9 Hz), 163.2 (d, J = 249.2
Hz), 142.2, 135.5, 132.1 (d, J = 8.6 Hz), 131.3, 130.9 (d, J = 3.3
Hz), 130.01, 130.00 (d, J = 8.3 Hz), 129.9, 129.8, 129.5 (d, J = 3.1
Hz), 116.3 (d, J = 21.7 Hz), 116.2 (d, J = 21.8 Hz), 113.7, 113.0,
50.4, 45.4, 42.0, 41.3; elemental analysis: C27H18F2N2O requires C,
76.40; H, 4.27; N, 6.60; found: C, 76.28; H, 4.46; N, 6.44.
(E)-2-(4-Chlorophenyl)-3-(4-methylbenzylidene)-4-oxo-6-p-tol-
ylcyclohexane-1,1-dicarbonitrile ((trans, E)-3p). Prepared from
1c (131 mg, 0.5 mmol) and 2a (113 mg, 0.6 mmol). Yellow solid;
yield 126 mg, 56%; m.p. 179–180 ◦C; IR (KBr): n 3030, 2922, 1685,
1594, 1492, 1409, 1174, 1095, 819, 738 cm-1; 1H NMR (400 MHz,
CDCl3): d 7.89 (s, 1H), 7.50 (d, J = 8.4 Hz, 2H), 7.34 (d, J = 8.4 Hz,
2H), 7.17 (d, J = 8.7 Hz, 6H), 7.05 (d, J = 8.0 Hz, 2H), 4.95 (s,
1H), 3.54 (dd, J = 13.1, 5.2 Hz, 1H), 3.28 (dd, J = 18.6, 13.2 Hz,
1H), 3.11 (dd, J = 18.6, 5.3 Hz, 1H), 2.37 (s, 3H), 2.34 (s, 3H);
13C NMR (100 MHz, CDCl3): d 195.8, 143.9, 141.1, 139.6, 135.8,
134.4, 131.9, 131.4, 130.5, 130.3, 130.1, 129.9, 129.8, 129.7, 128.0,
113.8, 113.2, 49.9, 45.4, 41.9, 41.7, 21.5, 21.2; elemental analysis:
C29H23ClN2O requires C, 77.24; H, 5.14; N, 6.21; found: C, 76.87;
H, 5.20; N, 6.09.
(E)-4-Oxo-2-phenyl-3-(4-(trifluoromethyl)benzylidene)-6-(4-
(trifluoromethyl)phenyl)cyclohexane-1,1-dicarbonitrile ((trans, E)-
3t). Prepared from 1e (185 mg, 0.5 mmol) and 2e (93 mg,
0.6 mmol). Yellow solid; yield 120 mg, 46%; m.p. 90–92 ◦C; IR
(KBr): n 2925, 1693, 1610, 1325, 1170, 1129, 1070, 908, 735, 702
3-(4-Methylbenzylidene)-4-oxo-2-phenyl-6-p-tolyl cyclohexane-
1,1-dicarbonitrile (3q). Prepared from 1c (131 mg, 0.5 mmol)
and 2e (93 mg, 0.6 mmol) and isolated as two pure diastereomers.
(trans, E)-3q: yellow solid; yield 119 mg, 57%; m.p. 202–203 ◦C; IR
(KBr): n 3030, 2922, 1685, 1594, 1511, 1175, 816, 756, 702 cm-1;
1H NMR (400 MHz, CDCl3): d 7.89 (s, 1H), 7.56–7.45 (m, 3H),
7.43–7.37 (m, 2H), 7.21–7.12 (m, 6H), 7.07 (d, J = 8.1 Hz, 2H), 4.98
(s, 1H), 3.61 (dd, J = 13.1, 5.4 Hz, 1H), 3.28 (dd, J = 18.6, 13.1 Hz,
1
cm-1; H NMR (400 MHz, CDCl3): d 7.91 (s, 1H), 7.64 (t, J =
9.0 Hz, 4H), 7.56 (d, J = 5.7 Hz, 3H), 7.44 (d, J = 8.0 Hz, 2H), 7.37
(d, J = 7.5 Hz, 2H), 7.30–7.20 (m, 2H), 4.88 (s, 1H), 3.73 (dd, J =
13.0, 5.3 Hz, 1H), 3.32 (dd, J = 18.5, 13.1 Hz, 1H), 3.19 (dd, J =
18.5, 5.3 Hz, 1H); 13C NMR (100 MHz, CDCl3): d 194.7, 141.5,
138.7, 136.8, 135.2, 133.4, 131.88 (q, J = 32.9 Hz), 131.85 (q, J =
32.9 Hz), 130.1, 129.9, 129.87, 129.81, 128.7, 126.3 (q, J = 3.6 Hz),
125.8 (q, J = 3.7 Hz), 123.6 (q, J = 272.3 Hz), 113.5, 112.6, 50.5,
44.8, 41.86, 41.78; HRMS-ESI Calcd for C29H18F6N2O [M + Na]+
547.1216, found 547.1210.
1H), 3.11 (dd, J = 18.6, 5.4 Hz, 1H), 2.35 (s, 3H), 2.33 (s, 3H); 13
C
NMR (100 MHz, CDCl3): d 196.0, 143.4, 140.9, 139.4, 135.9,
132.3, 130.8, 130.7, 130.21, 130.17, 129.9, 129.6, 129.5, 128.0,
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(E)-2-(2-Chlorophenyl)-3-(2,4-dichlorobenzylidene)-4-oxo-6-ph-
enylcyclohexane-1,1-dicarbonitrile ((trans, E)-3u). Prepared from
1f (151 mg, 0.5 mmol) and 2f (113 mg, 0.6 mmol). Yellow solid;
yield 98 mg, 40%; m.p. 182–184 ◦C; IR (KBr): n 3064, 1688,
1590, 1474, 1260, 1178, 1052, 756, 657 cm-1; 1H NMR (400 MHz,
CDCl3): d 7.95 (s, 1H), 7.64 (dd, J = 16.8, 8.3 Hz, 2H), 7.48–7.34
(m, 7H), 7.23–7.13 (m, 3H), 5.64 (s, 1H), 4.77 (dd, J = 12.7, 5.6 Hz,
1H), 3.18 (dd, J = 18.3, 13.3 Hz, 1H), 3.10 (dd, J = 18.3, 5.6 Hz,
1H); 13C NMR (100 MHz, CDCl3): d 194.4, 144.9, 135.9, 135.6,
135.5, 133.2, 133.1, 131.7, 131.5, 131.4, 131.1, 131.0, 130.4, 130.3,
129.8, 129.0, 128.5, 128.4, 127.6, 113.8, 111.6, 47.0, 42.4, 41.8,
36.5; HRMS-ESI Calcd for C27H17Cl3N2O [M + Na]+ 513.0299,
found 513.0297.
MHz, CDCl3): d 8.05 (d, J = 8.0 Hz, 1H), 7.56 (t, J = 7.5 Hz, 1H),
7.46 (dd, J = 8.4, 5.5 Hz, 2H), 7.42–7.24 (m, 5H), 7.11–6.99 (m,
4H), 6.46 (d, J = 16.1 Hz, 1H), 3.57 (dt, J = 11.2, 3.2 Hz, 1H),
3.31 (td, J = 10.6, 4.2 Hz, 1H), 3.15 (dd, J = 16.4, 9.9 Hz, 1H),
3.03 (ddd, J = 18.0, 11.8, 6.0 Hz, 1H), 2.85 (dd, J = 18.4, 6.2 Hz,
1H), 2.74 (dd, J = 16.4, 4.2 Hz, 1H), 2.02–1.89 (m, 1H), 1.75 (d,
J = 14.3 Hz, 1H); 13C NMR (100 MHz, CDCl3): d 196.6, 176.9,
164.2 (d, J = 252.6 Hz), 161.9 (d, J = 246.3 Hz), 142.1, 139.9,
136.5 (d, J = 3.1 Hz), 134.2, 130.3 (d, J = 8.6 Hz), 130.2 (d, J = 3.4
Hz), 129.9, 129.4 (d, J = 7.9 Hz), 128.7, 128.4, 127.1, 125.3, 116.2
(d, J = 22.0 Hz), 115.9 (d, J = 21.2 Hz), 113.8, 113.5, 80.5, 47.3,
45.6, 40.9, 25.6, 24.3; elemental analysis: C30H22F2N2O requires C,
77.57; H, 4.77; N, 6.03; found: C, 77.47; H, 4.74; N, 5.96.
(E)-2-(2-Chlorophenyl)-3-(4-nitrobenzylidene)-4-oxo-6-pheny-
lcyclohexane-1,1-dicarbonitrile ((trans, E)-3v). Prepared from 1g
(139 mg, 0.5 mmol) and 2f (113 mg, 0.6 mmol). Yellow solid; yield
126 mg, 54%; m.p. 132–134 ◦C; IR (KBr): n 3081, 2922, 1691, 1599,
2-(3-((E)-3-Oxo-1,5-diphenylpent-4-enyl)chroman-4-ylidene)
malononitrile (4c). Prepared from 1a (117 mg, 0.5 mmol) and 2q
(118 mg, 0.6 mmol). Yellow solid; yield 141 mg, 66%; m.p. 161–
162 ◦C; IR (KBr): n 3060, 2925, 2223, 1691, 1607, 1450, 1327,
1258, 765, 749, 697 cm-1; 1H NMR (400 MHz, CDCl3): d 8.21 (d,
J = 8.1 Hz, 1H), 7.56 (t, J = 7.8 Hz, 1H), 7.51–7.32 (m, 10H),
7.31–7.22 (m, 1H), 7.10 (t, J = 7.7 Hz, 1H), 7.03 (d, J = 8.4 Hz,
1H), 6.58 (d, J = 16.2 Hz, 1H), 4.14–3.99 (m, 2H), 3.57 (td, J =
10.4, 5.0 Hz, 1H), 3.36–3.21 (m, 2H), 2.88 (dd, J = 16.5, 5.0 Hz,
1H); 13C NMR (100 MHz, CDCl3): d 196.5, 167.9, 156.4, 143.4,
140.2, 137.1, 134.1, 130.8, 129.1, 128.9, 128.4, 128.2, 128.0, 127.8,
125.7, 121.9, 118.4, 115.5, 113.8, 113.3, 78.4, 66.8, 45.4, 44.2, 40.9;
HRMS-ESI Calcd for C29H22N2O2 [M + Na]+ 453.1574, found
453.1579.
1
1525, 1347, 855, 758, 699 cm-1; H NMR (400 MHz, CDCl3): d
8.25 (d, J = 8.6 Hz, 2H), 7.93 (s, 1H), 7.64 (d, J = 7.6 Hz, 1H), 7.56
(d, J = 8.6 Hz, 2H), 7.50–7.32 (m, 6H), 7.16 (t, J = 5.3 Hz, 3H), 5.67
(s, 1H), 3.96 (dd, J = 13.2, 5.0 Hz, 1H), 3.35 (dd, J = 18.3, 13.4 Hz,
1H), 3.21 (dd, J = 18.3, 5.1 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d 194.2, 148.6, 144.9, 141.7, 135.6, 133.2, 132.9, 131.7, 131.2,
130.9, 130.5, 129.75, 129.66, 129.1, 127.8, 124.4, 113.3, 112.0, 46.7,
43.0, 42.4, 41.5; HRMS-ESI Calcd for C27H18ClN3O3 [M + Na]+
490.0929, found 490.0925.
General procedure for PBu3-catalyzed vinylogous Michael addition
reaction between dienone 1 and activated alkene 2 (Scheme 3)
3-Benzylidene-2-(4-chlorophenyl)-4-hydroxy-6-phenyl cyclo-
hexane-1,1-dicarbonitrile (5a). To a stirred solution of 3a
(235 mg, 0.56 mmol) in methanol (9 mL) at 0 ◦C were added
CeCl3·7H2O (238 mg, 0.64 mmol) and NaBH4 (39 mg, 1.03 mmol).
After the resulting mixture was stirred for 20 min, the reaction
was quenched by addition of water (5 mL) and the solvent was
removed on a rotary evaporator under reduced pressure. The
residue was extracted with dichloromethane (3 ¥ 8 mL), and the
combined extracts were washed with brine (8 mL), and dried
over anhydrous Na2SO4. After filtration and concentration on
a rotary evaporator under reduced pressure, the crude product
was subjected to column chromatography isolation on silica gel
(gradient elution, petroleum ether–ethyl acetate 10 : 1–3 : 1) to give
5a as a si◦ngle diastereomer. White Solid; yield 188 mg, 80%; m.p.
202–203 C; IR (KBr): n 3060, 2932, 1493, 1265, 1098, 741, 700
Under a N2 atmosphere, to a solution of dienone 1 (0.5 mmol) and
activated alkene 2 (0.6 mmol) in chloroform (5 mL) was added
PBu3 (25 uL, 0.1 mmol). The resulting mixture was stirred at
room temperature until the dienone was completely consumed as
monitored by TLC. The solvent was removed on a rotary evap-
orator under reduced pressure, and the residue was subjected to
column chromatographic isolation on silica gel (gradient elution,
petroleum ether–ethyl acetate 20 : 1–10 : 1) to yield vinylogous
Michael addition product 4 as a single diastereomer.
(E)-2-(5-Oxo-1,3,7-triphenylhept-6-enylidene)malononitrile
(4a). Prepared from 1a (117 mg, 0.5 mmol) and 2o (101 mg,
0.6 mmol). White solid; yield 152 mg, 76%; m.p. 127–128 ◦C; IR
(KBr): n 3061, 3029, 2958, 2229, 1688, 1660, 1603, 1494, 1449,
1
cm-1; H NMR (400 MHz, CDCl3): d 7.46–7.28 (m, 13H), 7.12
1
1332, 1177, 977, 760, 700 cm-1; H NMR (400 MHz, CDCl3): d
(d, J = 7.0 Hz, 2H), 4.97 (dd, J = 10.5, 5.0 Hz, 1H), 4.82 (s, 1H),
3.53 (dd, J = 13.2, 3.0 Hz, 1H), 2.55 (ddd, J = 13.0, 5.3, 3.3 Hz,
1H), 2.42 (dd, J = 24.9, 13.0 Hz, 1H), 2.16 (s, 1H); 13C NMR (100
MHz, CDCl3): d 135.9, 135.6, 135.3, 135.0, 134.7, 130.9, 130.3,
129.5, 129.3, 129.1, 128.7, 128.4, 128.3, 127.9, 113.9, 113.7, 68.6,
50.2, 46.2, 43.4, 37.9; HRMS-ESI Calcd for C27H21ClN2ONa [M
+ Na]+ 447.1235, found 447.1234.
7.61–7.45 (m, 6H), 7.44–7.34 (m, 5H), 7.33–7.21 (m, 3H), 7.04–
6.96 (m, 2H), 6.65 (d, J = 16.2 Hz, 1H), 3.56 (dd, J = 13.5, 4.5 Hz,
1H), 3.32 (dd, J = 13.4, 10.5 Hz, 1H), 3.28–3.20 (m, 1H), 3.07 (dd,
J = 17.4, 8.3 Hz, 1H), 2.99 (dd, J = 17.3, 5.2 Hz, 1H); 13C NMR
(100 MHz, CDCl3): d 197.7, 178.1, 143.4, 140.8, 134.1, 133.9,
132.3, 130.8, 129.1, 129.0, 128.9, 128.4, 128.0, 127.6, 127.4, 125.8,
112.8, 112.6, 85.7, 47.0, 42.7, 40.0; elemental analysis: C28H22N2O
requires C, 83.56; H, 5.51; N, 6.96; found: C, 83.29; H, 5.73; N,
7.00.
6-Benzylidene-5-(4-chlorophenyl)-3-imino-8-phenyl-2-oxabi-
cyclo[2.2.2]octane-4-carbonitrile (6a). To a stirred solution of 5a
(42 mg, 0.1 mmol) in absolute methanol (1 mL) at 0 ◦C was
dropwise added a freshly prepared MeONa solution (0.3 mmol,
0.15 mL) through a microsyringe. After stirred at rt for 2 h, the
reaction was quenched by addition of water (3 mL). The resulting
solution was extracted with dichloromethane (3 ¥ 5 mL), and the
2-(2-((E)-1,5-Bis(4-fluorophenyl)-3-oxopent-4-enyl)-3,4-dihy-
dro-2H-naphthalen-1-ylidene)malononitrile (4b). Prepared from
1d (135 mg, 0.5 mmol) and 2p (116 mg, 0.6 mmol). White solid;
yield 140 mg, 60%; m.p. 208–209 ◦C; IR (KBr): n 3070, 2935, 2226,
1689, 1659, 1599, 1509, 1231, 1159, 765, 749 cm-1; 1H NMR (400
780 | Org. Biomol. Chem., 2012, 10, 773–781
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combined extracts were washed with brine (5 mL) and dried over
anhydrous Na2SO4. After filtration, the solvent was evaporated
on a rotary evaporator under reduced pressure and the residue
was subjected to column chromatography isolation on silica gel
(gradient elution, petroleum ether–ethyl acetate 10 : 1–3 : 1) to give
6a as a white solid. White solid; yield 42 mg, 99%; m.p. 210–214 ◦C;
1H NMR (400 MHz, CDCl3): d 7.51–7.20 (m, 8H), 7.21–7.05 (m,
5H), 7.00 (s, 2H), 6.79 (s, 1H), 5.09 (s, 1H), 4.75 (s, 1H), 3.38–
3.21 (m, 1H), 2.79–2.55 (m, 2H); 13C NMR (100 MHz, CDCl3): d
162.4, 138.9, 134.5, 133.9, 133.0, 130.8, 129.0, 128.9, 128.7, 128.2,
128.1, 116.2, 80.9, 51.0, 49.4, 39.5, 33.7; HRMS-ESI Calcd for
C27H22ClN2O [M + H]+ 425.1415, found 425.1409.
Ye, J. Zhou and Y. Tang, Chem. Soc. Rev., 2008, 37, 1140; (d) B. J. Cowen
and S. J. Miller, Chem. Soc. Rev., 2009, 38, 3102; (e) A. Marinetti and
A. Voituriez, Synlett, 2010, 174.
3 (a) D. Basavaiah, A. J. Rao and T. Satyanarayana, Chem. Rev., 2003,
103, 811; (b) Y. Wei and M. Shi, Acc. Chem. Res., 2010, 43, 1005;
(c) C. E. Aroyan, A. Dermenci and S. J. Miller, Tetrahedron, 2009, 65,
4069.
4 (a) X. Sun, S. Sengupta, J. L. Petersen, H. Wang, J. P. Lewis and X.
Shi, Org. Lett., 2007, 9, 4495; (b) C. Zhong, Y. Chen, J. L. Petersen,
N. G. Akhmedov and X. Shi, Angew. Chem., Int. Ed., 2009, 48,
1279.
5 (a) B. Zhang, L. Cai, H. Song, Z. Wang and Z. He, Adv. Synth. Catal.,
2010, 352, 97; (b) L. Cai, B. Zhang, G. Wu, H. Song and Z. He, Chem.
Commun., 2011, 47, 1045.
6 (a) K. L. Habermas, S. E. Denmark and T. K. Jones, Org. React., 1994,
45, 1; (b) M. E. Jung, C. A. McCombs, Y. Takeda and Y.-G. Pan, J.
Am. Chem. Soc., 1981, 103, 6677; (c) J. D. Winkler, H. S. Kim, S. Kim,
K. Ando and K. N. Houk, J. Org. Chem., 1997, 62, 2957.
7 For recent examples, see: (a) P. J. Dunn, A. B. Graham, R. Grigg, P.
Higginson and M. Thornton-Pett, Tetrahedron, 2002, 58, 7727; (b) J.
Tan, X.-X. Xu, L.-J. Zhang, Y.-F. Li and Q. Liu, Angew. Chem., Int.
Ed., 2009, 48, 2868; (c) A. C. Silvanus, B. J. Groombridge, B. I. Andrew,
G. Kociok-Kohn and D. R. Carbery, J. Org. Chem., 2010, 75, 7491;
(d) X.-M. Li, B. Wang, J.-M. Zhang and M. Yan, Org. Lett., 2011, 13,
374.
6-Benzylidene-5-(4-chlorophenyl)-3-imino-1-methoxy-8-phenyl-
2-oxabicyclo[2.2.2]octane-4-carbonitrile (6b) and its diastereomer
(6c). To a stirred solution of 3a (42 mg, 0.1 mmol) in absolute
methanol (1 mL) at 0 ◦C was dropwise added a freshly prepared
MeONa solution (0.3 mmol, 0.15 mL) through a microsyringe.
After stirred at rt for 2 h, the reaction was quenched by
addition of water (3 mL). The resulting solution was extracted
with dichloromethane (3 ¥ 5 mL). The combined extracts were
washed with brine (5 mL), dried over anhydrous Na2SO4. After
filtration, the solvent was evaporated on a rotary evaporator
under reduced pressure and the residue was subjected to column
chromatography isolation on silica gel (gradient eluant, petroleum
ether–ethyl acetate 10 : 1–3 : 1) to yield 6b and 6c as two separable
8 N. T. McDougal and S. E. Schaus, Angew. Chem., Int. Ed., 2006, 45,
3117.
9 (a) J. E. Wilson and G. C. Fu, Angew. Chem., Int. Ed., 2006, 45,
1426; (b) N. Pinto, M. Neel, A. Panossian, P. Retailleau, G. Frison,
A. Voituriez and A. Marinetti, Chem.–Eur. J., 2010, 16, 1033; (c) V.
Nair, B. P. Babu, S. Vellalath and E. Suresh, Chem. Commun., 2008,
747.
10 (a) J. Jiang, J. L. Bunda, G. A. Doss, G. G. Chichi, M. M. Kurtz, K.-L.
C. Tsao, X. Tong, S. Zheng, A. Upthagrove, K. Samuel, R. Tschirret-
Guth, S. Kumar, A. Wheeldon, E. J. Carlson, R. Hargreaves, S. Burns,
T. Hamill, C. Ryan, S. M. Krause, W. Eng, R. J. Devita and S. G. Mills,
J. Med. Chem., 2009, 52, 3039; (b) T. Bui and C. F. Barbas, Tetrahedron
Lett., 2000, 41, 6951.
11 (a) Z. He, X. Tang, Y. Chen and Z. He, Adv. Synth. Catal., 2006, 348,
413; (b) X. Tang, B. Zhang, Z. He, R. Gao and Z. He, Adv. Synth.
Catal., 2007, 349, 2007.
12 H.-L. Cui and Y.-C. Chen, Chem. Commun., 2009, 4479.
13 (a) Z. Lu, S. Zheng, X. Zhang and X. Lu, Org. Lett., 2008, 10, 3267;
(b) S. Zheng and X. Lu, Tetrahedron Lett., 2009, 50, 4532.
14 I. C. Stewart, R. G. Bergman and F. D. Toste, J. Am. Chem. Soc., 2003,
125, 8696.
15 The stereochemistry outcome in the formation of cyclohexanones 3
(trans-isomers as the major product) favors a pathway of [4 + 2]
cycloaddition between intermediate A and alkene 2. A similar [4 +
2] cycloaddition pathway is also proposed by Schaus et al. for a
phosphine-mediated homo-coupling reaction of 1,4-dien-3-ones. See
ref. 8.
16 A similar phosphonium effect of the phosphine–enone Michael adduct
in controlling the regiochemistry of the intramolecular Aldol reactions
of unsaturated 1,5-diketones was also observed. R. K. Thalji and W.
R. Roush, J. Am. Chem. Soc., 2005, 127, 16778.
1
diastereomers. For 6b, semi-solid; yield 26 mg, 57%; H NMR
(400 MHz, CDCl3): d 7.51–7.35 (m, 5H), 7.26 (d, J = 6.8 Hz, 1H),
7.17–6.96 (m, 7H), 6.89 (d, J = 8.5 Hz, 2H), 4.26 (d, J = 1.4 Hz,
1H), 3.76 (s, 3H), 3.54 (dd, J = 10.7, 5.3 Hz, 1H), 2.49–2.33 (m,
2H); 13C NMR (100 MHz, CDCl3): d 162.0, 138.6, 136.2, 135.3,
135.1, 133.8, 130.5, 129.4, 128.9, 128.6, 128.4, 128.4, 128.2, 127.4,
125.3, 116.1, 88.0, 54.5, 50.0, 45.7, 43.7, 41.2; HRMS-ESI Calcd
for C28H23ClN2O2Na [M + Na]+ 477.1340, found 477.1345. For
1
6c, semi-solid; yield 19 mg, 42%; H NMR (400 MHz, CDCl3):
d 7.39–7.16 (m, J = 8.6 Hz, 8H), 7.11 (d, J = 2.3 Hz, 1H), 7.09–
6.91 (m, 7H), 4.44 (d, J = 2.2 Hz, 1H), 3.92 (s, 3H), 3.21 (dd, J =
10.4, 5.2 Hz, 1H), 2.67 (dd, J = 13.5, 10.5 Hz, 1H), 2.31 (dd, J =
13.5, 5.2 Hz, 1H); 13C NMR (100 MHz, CDCl3): d 162.4, 139.3,
137.3, 134.9, 134.2, 132.2, 128.8, 128.7, 128.3, 128.2, 127.9, 127.3,
124.2, 115.9, 87.3, 54.6, 49.7, 49.1, 41.3, 40.1; HRMS-ESI Calcd
for C28H23ClN2O2Na [M + Na]+ 477.1340, found 477.1345.
Acknowledgements
17 The bicyclic core structure and its corresponding lactone analogue
are important structural components or key synthetic intermediates of
many bioactive compounds. The 3-imino bicyclic structure could be
readily converted into its 3-oxo bicyclic lactone analogue by a well-
established procedure (ref. 17d) (a) T. A. Magee, R. D. Battershell, L.
E. Limpel, A. W. W. Ho, A. J. Friedman, H. G. Corkins, W. W. Brand,
R. Buchman, L. Storace and E. R. Osgood, Eur. Pat. Appl., 51 990,
1982; (b) T. P. O’Sullivan, H. Zhang and L. N. Mander, Org. Biomol.
Chem., 2007, 5, 2627; (c) L. N. Mander and T. P. O’Sullivan, Synlett,
2003, 1367; (d) A. T. Rowland and B. C. Gill, J. Org. Chem., 1988, 53,
434.
Financial support from National Natural Science Foundation
of China (grant nos. 20872063; 21072100) is gratefully acknowl-
edged.
Notes and references
1 (a) P. I. Dalko and L. Moisan, Angew. Chem., Int. Ed., 2004, 43, 5138;
(b) P. I. Dalko and L. Moisan, Angew. Chem., Int. Ed., 2001, 40, 3726.
2 (a) X. Lu, C. Zhang and Z. Xu, Acc. Chem. Res., 2001, 34, 535; (b) J. L.
Methot and W. R. Roush, Adv. Synth. Catal., 2004, 346, 1035; (c) L.-W.
This journal is
The Royal Society of Chemistry 2012
Org. Biomol. Chem., 2012, 10, 773–781 | 781
©