Bifunctional phosphine-catalyzed cross-Rauhut-Currier/Michael/aldol condensation triple domino reaction: Synthesis of functionalized cyclohexenes

Article abstract of DOI:10.1039/c1ob05693j

A novel bifunctional phosphine-catalyzed reaction was developed. Cross-Rauhut-Currier, Michael and aldol reactions were successfully combined into a domino process. This method offers a powerful approach to the construction of highly substituted cyclohexene skeletons.

Full text of DOI:10.1039/c1ob05693j

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PAPER
Bifunctional phosphine-catalyzed cross-Rauhut–Currier/Michael/aldol
condensation triple domino reaction: synthesis of functionalized cyclohexenes†
Peizhong Xie, You Huang,* Wenqing Lai, Xiangtai Meng and Ruyu Chen*
Received 2nd May 2011, Accepted 23rd June 2011
DOI: 10.1039/c1ob05693j
A novel bifunctional phosphine-catalyzed reaction was developed. Cross-Rauhut–Currier, Michael and
aldol reactions were successfully combined into a domino process. This method offers a powerful
approach to the construction of highly substituted cyclohexene skeletons.
rare,16,17 especially for the a,b-unsaturated aldehydes/ketones that
Introduction
will provide more functionality in the final products.4,7a,16 More
Combining different organocatalytic reactions into a domino
recently, great effort has been directed toward incorporating the
process1 has become a fruitful concept for the synthesis of func-
RC reaction into domino processes to construct diverse and
tionalized and diversified molecules,2 and is of great value in both
highly functionalized molecules with high atom efficiency, such
target-oriented and diversity-oriented synthesis.3 These methods
swiftly assemble complex molecules from simple starting materials
with minimal time, and waste as well as manipulation of reaction
intermediates.4 Significant progress has been made by applying this
strategy to the total synthesis of natural products and biologically
active molecules.5 The domino strategy fundamentally relies on
reaction compatibility and is often realized in organocatalysis.2
The phosphine-catalyzed dimerization of activated alkenes,
first discovered by Rauhut and Currier in 1963,6 and coined as
the Rauhut–Currier (RC) reaction,9a is a unique method that
creates a new C–C bond between the a-position of an activated
alkene and b-position of a second alkene.6,7 To date, a number of
intramolecular RC reactions, as well as enantioselective variants,
have been reported.7 In 1999, Moore revealed a unique example of
an intramolecular RC reaction in the synthesis of waihoensene.8
In 2002, Krische and Roush respectively presented detailed studies
of a phosphine-catalyzed intramolecular RC reaction,9 which was
successfully used in the construction of ring systems10 and for the
total synthesis of (-)-spinosyn A,11 (+)-harziphilone,12 antimitotic
agent FR182877,13 ( )-ricciocarpin A and ( )-quinine.14 Recently,
elegant studies on the catalysts, domino process, asymmetric
variants, and extensions of intramolecular RC reaction have been
reported.15 Despite the progress in the intramolecular manifolds,
intermolecular reactions suffer from anionic polymerization or
oligomerization and difficulty in controlling the selectivity of
the cross-coupling.7 Thus, effective methodologies for efficient
intermolecular cross-coupling of different activated olefins are
as the RC–Wittig18 and RC–aldol19,20 domino reactions. These
remarkable developments re-emphasize the advantages of domino
processes, as well as the compatibility of the RC reaction with other
reactions.
To the best of our knowledge, intermolecular RC-domino reac-
tions have so far been confined to two-components or two-steps.
Few triple domino17c reactions have been reported to date. Acrolein
is an interesting Michael reaction acceptor that is more active than
other vinyl ketones and acrylates.11a However, it has not been used
in the RC reaction, because of its propensity to form oligomers or
polymers in the presence of basic catalysts. Since Shibasaki et al.
described the concept of multifunctional catalysis, a variety of re-
actions have been addressed with multifunctional organocatalysts,
including the (aza)-Morita–Baylis–Hillman reaction.21 However,
efficient multifunctional organocatalysts for the RC reaction have
seldom been reported. Functionalized cyclohexenes can serve as
building blocks in organic synthesis and play a central role in many
natural product syntheses.22 Nevertheless, the intermolecular RC
reaction has not been utilized previously for the formation of
cyclohexenes. Intrigued by these elegant studies and our work con-
cerning phosphine-catalyzed domino reactions,23 herein, we report
the Lewis base–Brønsted acid (LBBA)-catalyzed triple domino
reaction for the synthesis of highly functionalized cyclohexenes
(Fig. 1).
This three-component domino reaction proceeds via a catalyzed
cross-RC/Michael/aldol condensation sequence in which three
new carbon–carbon bonds are formed.
State Key Laboratory and Institute of Elemento-organic Chemistry Nankai
University, Tianjin 300071, People’s Republic of China. E-mail: hyou@
nankai.edu.cn; Fax: (+86) 22-23503627; Tel: (+86) 22-23508857
Results and discussion
† Electronic supplementary information (ESI) available: 1H NMR, 13C
NMR, IR for all new compounds 3a–3t, chiral HPLC analyses 3a, crystal
structure of cis-3a and trans-3a. CCDC reference numbers 769828 and
769829. For ESI and crystallographic data in CIF or other electronic
format see DOI: 10.1039/c1ob05693j
We started our investigation by reacting (E)-ethyl-2-cyano-3-
(2,4-dichlorophenyl)acrylate (1a) with acrolein 2 in the presence
of LBBA-1 (20 mol%) (Table 1, entry 1) in CHCl3. To our
delight, 3a was isolated as two stereoisomers in 34% overall yield.
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Table 1 Screening catalysts and conditions for the domino reactiona
Entry
Solvent
Cat. (mol%)
V/ml
Yield (%)b
1
2
3
4
5
6
CHCl3
THF
DMF
LBBA-1 (20)
LBBA-1 (20)
LBBA-1 (20)
LBBA-1 (20)
LBBA-1 (20)
LBBA-1 (20)
LBBA-1 (20)
LBBA-1 (20)
LBBA-2 (20)
LBBA-3 (20)
LBBA-4 (20)
LBBA-5 (20)
LBBA-6 (20)
LBBA-1 (30)
LBBA-1 (50)
LBBA-1 (100)
LBBA-1 (30)
LBBA-1 (30)
PPh3 (30)
2
2
2
2
2
2
5
5
5
5
5
5
5
5
5
5
34
—
—
Trace
11
31
42
41
Trace
Trace
Trace
36
38
51
42
46
58
52
CH3CN
Toluene
CH2Cl2
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
7
8c
Fig. 1 Bifunctional phosphine-catalyzed triple domino reaction.
9
10
11
12
13
14
15
16
17d
18e
19d
20d
The structure and stereochemistry of 3a were determined by a
combination of NMR spectra, HRMS and single-crystal X-ray
analysis (Fig. 2).24 In attempt to improve the yield of the reaction,
other reaction conditions were screened. In solvents such as THF,
DMF, CH3CN and toluene, either none or only a trace amount
of product was obtained. The use of CH2Cl2, CHCl3 led to higher
yields. In addition, decreasing the concentration could further
improve the yields (Table 1, entries 1, 7, 17). Stronger or weaker
nucleophilic bifunctional phosphine catalysts led to lower yields
(Table 1, entries 9–13). PPh3 and PBu3 were inefficient for this
domino reaction (Table 1, entries 19 and 20).
10
20
10
10
Trace
—
PBu3 (30)
a All reactions were performed on a 0.5 mmol scale and carried out for 24 h.
The ratio of 1a/2 is 1 : 3.0. b Product isolated by flash chromatography.
c The ratio of the 1a/2 is 1 : 5.0. d Acrolein (1.50 mmol) in CHCl3 (5 ml)
was added to a mixture of catalyst LBBA or PR3 (R = Ph, Bu) (0.15 mmol,
30 mol%), 1a (0.5 mmol) in CHCl3 (5 ml). e Acrolein (1.50 mmol) in CHCl3
(10 ml) was added to a mixture of catalyst LBBA (0.15 mmol, 30 mol%),
1a (0.5 mmol) in CHCl3 (10 ml).
A variety of activated alkenes 1 were tolerated under the
optimized reaction conditions (Table 2). The electronic charac-
teristics of the substituent on the phenyl ring have little effect
on the yields and the diastereoselectivities. Furyl- and naphthyl-
substituted activated alkenes 1 were also successfully employed
in this reaction. Although the domino process afforded the final
products in moderate overall yield (30–66%), this corresponded
to an average yield of 67–87% per bond formed. Under optimized
conditions, the reaction can be performed on a 20 mmol scale
to obtain a 42% yield of 3a (Scheme 1). Although activated
allenes7a,17c and silyloxyallenes17a have been investigated in place
of alkenes in Rauhut–Currier reactions, conjugated dienes have
seldom been employed in a similar capacity.17b We questioned
whether it would be possible to extend the present multicom-
ponent triple domino transformation to conjugated diene com-
pounds under the same conditions. As outlined in Fig. 3, the
Fig. 2 X-Ray crystal structure of cis- and trans-3a.
6708 | Org. Biomol. Chem., 2011, 9, 6707–6714
Scheme 1 The reaction on a 20 mmol scale.
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Table 2 Scope of the domino reactions in the presence of LBBA-1a
Entry
R1
R2
Time/h
Yield (%)b
cis/transc
1
2
3
4
2,4-ClC6H3
2,4-ClC6H3
2,4-ClC6H3
2-Cl-C6H4
3-Cl-C6H4
4-Cl-C6H4
2-Br-C6H4
4-Br-C6H4
4-F-C6H4
3-Me-C6H4
C6H5
4-OMe-C6H4
2-Me-C6H4
4-Me-C6H4
2-Naphthyl
2-Furyl
Et
24
24
72
28
24
48
24
24
25
72
40
72
72
72
72
72
58(3a)
51(3b)
45(3c)
45(3d)
53(3e)
43(3f)
42(3g)
48(3h)
52(3i)
54(3j)
65(3k)
35(3l)
41(3m)
59(3n)
66(3o)
30(3p)
1.5/1
1.4/1
1.7/1
1.2/1
4/1
5/1
2/1
2.9/1
7/1
3/1
5/1
5/1
Me
Bu-t
Et
Et
Et
Et
Et
Et
Et
Et
Et
Me
Et
Et
5
6c
7
Scheme 2 The comparison of catalytic reactivity between LBBA-1 and
LB-OMe.
8
9
10
11
12d
13
14
15
16
1.2/1
3/1
2.5/1
>20/1
Et
a See experimental procedure for reaction conditions. b Isolated yield.
c Determined through NMR spectroscopic analysis and comparison with
the NMR spectra of cis-3a and trans-3a. d 45 mol% catalyst was used.
Scheme 3 The reaction carried out by combination of PPh3 and phenol.
Preliminary studies on the asymmetric variant of this reaction
tested with the optically pure bifunctional catalyst LB.21a We
obtained a promising 32% and 4% enantiomeric excess for trans-
and cis-3a, respectively (Scheme 4).
Scheme 4 Asymmetric annulation.
Fig. 3 Triple domino reaction of conjugated dienes 1 with acrolein 2.
The detailed mechanism of this triple domino reaction has
not been clarified. A possible mechanism for the formation of
cyclohex-1-ene-carbaldehyde derivatives 3 is presented in Scheme
5. In the first step, 2 reacts with catalyst LBBA to give the
zwitterionic phosphonium intermediate A. The phenolic OH
serves as a Brønsted acid to stabilize intermediate A through
an intramolecular hydrogen bond. The RC reaction then occurs,
producing intermediate B. Subsequent Michael addition of inter-
mediate B to another molecular of acrolein gives intermediate C
(C1 or C2). Intramolecular aldol condensation then takes place
(C1–D), producing 3 via dehydration, and regenerating LBBA to
complete the catalytic cycle. As shown in the Newman projection,
the steric repulsions between R1 and acrolein suggest that the
generation of intermediate C1 is favoured and hence 3 with a
diastereoselectivity for the cis-isomer is obtained.
domino reactions proceeded well for both aliphatic and aromatic
conjugated dienes and provided the corresponding products with
high diastereoselectivity, albeit with a slightly lower yield.
Notably, the phenolic hydroxyl group on the LBBA is im-
portant, because when the O-methylated catalyst (LB-OMe) was
employed, the rate of the reaction decreased, giving the 3o only in
7% yield (Scheme 2).
In addition, the reaction was also carried out by combination
of PPh3 and phenol. 3a could also be obtained in 12% yield with
lower diastereoselectivity (cis/trans: 1.2 : 1) after 20 h (Scheme 3).
This indicated that not only are the phenolic and phosphine
groups both necessary, but also that being at an appropriate
distance from each other and on the same molecule facilitates the
catalysis.
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Preparation of the catalyst LB-OMe
LBBA-1 (717 mg, 2.00 mmol) in CHCl3 (10 ml) was added 30%
hydrogen peroxide (3.0 ml) at 0 ◦C, and stirred for 2 h. The
organic phase was washed with 3 ¥ 10 ml of water and dried
(MgSO4), and finally concentrated, without further purification
giving 2¢-(diphenylphosphoryl)biphenyl-2-ol 740 mg (99%). To a
mixture of 2¢-(diphenylphosphoryl)biphenyl-2-ol (708.67 mg, 2.00
mmol) and K2CO3 (1014 mg, 8.00 mmol) in acetone (12 ml), was
added MeI (140 mg, 8.00 mmol), and the mixture was refluxed
for 5 h. After being cooled to room temperature, the mixture
was filtered though Celite, and the solid was washed with Et2O,
without further purification, to give 2-(diphenylphosphinyl)- 2¢-
methoxyl-1,1¢-biphenyl 760 mg (99%). Then to a mixture of 2-
(diphenylphosphinyl)- 2¢-methoxyl-1,1¢-biphenyl (768 mg, 2.00
mmol) and Et3N (4040 mg, 40.00 mmol) in xylene (50 ml) was
added HSiCl3 (1350 mg, 10.00 mmol) at 0 ◦C. The reaction
mixture was stirred at 120 ◦C for 5 h. After being cooled to room
temperature, the mixture was diluted with Et2O and quenched with
a small amount of saturated NaHCO3. The resulting suspension
was filtered through Celite, and the solid was washed with
Et2O. The combined organic layer was dried over MgSO4 and
concentrated under reduced pressure. The crude phosphine was
purified by silica gel column chromatography, giving LB-OMe
382 mg (52%). White solid, 1H NMR (400 MHz, CDCl3) d = 7.30
(t, J = 6.3, 1H), 7.18 (s, 11H), 7.11 – 6.96 (m, 4H), 6.81 (td, J = 7.3,
3.1, 1H), 6.72 (dd, J = 8.0, 2.3, 1H), 6.71 (s, 1H), 3.41 – 3.06 (m,
1H). 13C NMR (101 MHz, CDCl3) d = 155.5, 144.1, 143.8, 137.4,
137.3, 136.6, 136.5, 136.0, 135.9, 133.1, 132.7, 132.5, 130.2, 129.3,
129.3, 127.9, 127.7, 127.2, 127.1, 127.1, 127.0, 126.3, 118.8, 109.1,
53.7. 31P NMR (162 MHz, CDCl3) d = -13.04. mp = 175–176 ◦C.
IR (KBr): 3051, 2962, 2832, 1968, 1896, 1583, 1433, 1249, 1090,
1027, 743, 697, 508 cm-1. HRMS (ESI/[M + Na]+) Cacld. for:
C25H21OPNa 369.1403, found 369.1399.
Scheme 5 Possible mechanism for the formation of 3.
Conclusions
In conclusion, we have developed a bifunctional phosphine-
catalyzed cross-Rauhut–Currier/Michael/aldol condensation
domino reaction to provide highly functionalized cyclohexene
carbaldehydes from simple, inexpensive starting materials. The
possibility to perform the developed cascade in gram-scale reac-
tions has also been demonstrated. This work could open up new
opportunities to develop domino reactions. Experiments designed
to explore the scope, limitations and applications in organic
synthesis are ongoing and will be reported in due course.
General procedure for the synthesis of cyclohexene carbaldehydes
(3a)
Acrolein (84 mg, 1.50 mmol) in CHCl3 (5 ml) was added dropwise
to a solution of (E)-ethyl-2-cyano-3-(2,4-dichlorophenyl) acrylate
(135 mg, 0.50 mmol) and catalyst LBBA-1 (53 mg, 0.15 mmol) in
CHCl3 (5 ml). The stirring was maintained at room temperature
until completion of the reaction (the reaction was monitored by
TLC). The solvent was removed under reduced pressure to give a
residue. The residue was purified by flash column chromatography
(petroleum ether/EtOAc 10 : 1) to yield 3a: 105 mg, 58%; colorless
solid; cis-3a/trans-3a = 1.5/1. 3b–3t were produced under the same
conditions.
Experimental
General
All solvents were purified according to standard procedures. The
1H NMR spectra were recorded at 400 MHz, 13C NMR spectra
were was recorded at 100 MHz. 1H and 13C NMR chemical shifts
are reported in ppm calibrated to tetramethylsilane as an external
reference. The data with an asterisk (*) indicate peaks of the
minor diastereomer (trans). Coupling constants are given in Hz.
The following abbreviations are used to indicate the multiplicity:
s, singlet; d, doublet: t, triplet; q, quartet; m, multiplet. HRMS
were recorded on an IonSpec FT-ICR mass spectrometer with
ESI resource. Melting points were measured on a RY-I apparatus
and are reported uncorrected. Catalysts LBBA,23 (R)-LB21 and
activated alkenes and conjugated dienes were prepared according
to known methods.25
The reaction can be performed in 20 mmol scale
Acrolein (4.5 g, 80.00 mmol) in CHCl3 (50 ml) was added dropwise
to a solution of (E)-ethyl-2-cyano-3-(2,4-dichlorophenyl) acrylate
(5.5 g, 20.00 mmol) and catalyst LBBA-1 (2.1 g, 12.00 mmol) in
CHCl3 (50 ml) over 2 h. The stirring was maintained at room
temperature for 30 h. The solvent was removed under reduced
pressure to give a residue. The residue was purified by flash column
chromatography (petroleum ether/EtOAc 10 : 1) to yield 3a: 3.0 g,
42%; colorless solid; cis/trans = 1.5 : 1.
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The procedure for the asymmetric synthesis of cyclohexene
carbaldehydes (3a)
CDCl3) d = 191.6, 166.1, 145.7, 140.1, 135.4, 135.0, 134.7, 133.3,
129.9, 129.5, 128.2, 128.0, 118.3, 53.9, 46.3, 46.1, 29.7, 25.6. m.p.
120–122 ◦C; IR (KBr): 2955, 2923, 27178, 2244, 1749, 1682, 1435,
1257 cm-1; HRMS (ESI/[M + Na]+) Calcd. for: C17H13Cl2NO3Na
372.0165, found 372.0171.
Acrolein (84 mg, 1.50 mmol) in CHCl3 (5 ml) was added dropwise
to a solution of (E)-ethyl-2-cyano-3-(2,4-dichlorophenyl) acrylate
(135 mg, 0.50 mmol) and catalyst LB (68 mg, 0.15 mmol) in
CHCl3 (5 ml). The stirring was maintained at room temperature
until completion of the reaction (the reaction was monitored by
TLC). The solvent was removed under reduced pressure to give a
residue. The residue was purified by flash column chromatography
(petroleum ether/EtOAc 10 : 1) to yield 3a. Yield: 35%, cis/trans:
1.5/1. trans-3a: 32% ee, [a]2D0 = 22 (c = 0.1 in CHCl3); cis-3a: 4%
ee, [a]2D0 = 11 (c = 0.2 in CHCl3).
trans-tert-Butyl-1-cyano-6-(2,4-dichlorophenyl)-3-formyl-5-
methylenecyclohex-3-enecarboxylate (trans-3c). 1H NMR (400
MHz, CDCl3) d = 9.59 (s, 1H), 7.72 (d, J = 8.4 Hz, 1H), 7.42
(s, 1H), 7.28 (d, J = 8.3 Hz, 1H), 7.20 (s, 1H), 5.64 (s, 1H), 4.88 (s,
1H), 4.59 (s, 1H), 3.15 (d, J = 17.7 Hz, 1H), 2.94 (d, J = 17.8 Hz,
1H), 1.17 (s, 9H). 13C NMR (101 MHz, CDCl3) d = 190.8, 164.3,
144.9, 138.9, 135.3, 134.1, 133.9, 131.2, 129.0, 128.6, 126.8, 125.4,
116.9, 84.0, 48.0, 45.7, 31.3, 26.3. oil; IR (KBr): 3157, 3055, 2928,
2716, 2241, 1744, 1683, 1478, 1253, 1160 cm-1; HRMS (ESI/[M +
Na]+) Calcd. for: C20H19NO3Cl2Na 414.0634, found 414.0629.
trans-Ethyl-1-cyano-6-(2,4-dichlorophenyl)-3-formyl-5-
methylenecyclohex-3-enecarboxylate (trans-3a)
1H NMR (400 MHz, CDCl3) d 9.66 (s, 1H), 7.74 (dd, J = 8.5, 2.9
Hz, 1H), 7.56 – 7.42 (m, 1H), 7.34 (d, J = 8.5 Hz, 1H), 7.27 (d, J =
1.4 Hz, 1H), 5.73 (s, 1H), 4.99 (s, 1H), 4.73 (d, J = 1.4 Hz, 1H),
4.19 – 3.99 (m, 2H), 3.23 (dd, J = 17.8, 3.5 Hz, 1H), 3.05 (d, J =
17.8 Hz, 1H), 1.06 (td, J = 7.1 Hz, 3.5, 3H).
cis-tert-Butyl-1-cyano-6-(2,4-dichlorophenyl)-3-formyl-5-
methylenecyclohex-3-enecarboxylate (cis-3c)
13C NMR (101 MHz, CDCl3) d = 191.6, 166.5, 145.8, 139.8,
136.2, 135.1, 134.9, 132.2, 130.0, 129.8, 128.0, 126.7, 117.5, 63.4,
48.3, 46.6, 32.2, 13.6. m.p. 156–158 ◦C; IR (KBr): 2983, 2926, 2720,
2244, 1744, 1681, 1587, 1474, 1253, 1164 cm-1; HRMS (ESI/[M +
Na]+) Cacld. for: C18H15Cl2NO3Na 386.0321, found 386.0324.
1H NMR (400 MHz, CDCl3) d = 9.62 (s, 1H), 7.38 (d, J = 1.8
Hz, 1H), 7.22 (s, 1H), 7.11 (dd, J = 8.5, 1.9 Hz, 1H), 6.83 (d, J =
8.5 Hz, 1H), 5.67 (s, 1H), 5.50 (s, 1H), 5.00 (s, 1H), 3.03 (d, J =
19.1 Hz, 1H), 2.92 (d, J = 18.8 Hz, 1H), 1.31 (s, 9H). 13C NMR
(101 MHz, CDCl3) d = 190.9, 163.3, 144.7, 139.3, 134.1, 134.0,
133.7, 133.0, 128.8, 128.5, 126.9, 126.4, 117.8, 84.3, 45.9, 44.5,
26.4, 26.3, 25.4. oil; IR (KBr): 3158, 3055, 2928, 2718, 2243, 1745,
1686, 1475, 1244, 1167 cm-1; HRMS (ESI/[M + Na]+) Calcd. for:
C20H19NO3Cl2Na 414.0634, found 414.0630.
cis-Ethyl-1-cyano-6-(2,4-dichlorophenyl)-3-formyl-5-
methylenecyclohex-3-enecarboxylate (cis-3a)
1H NMR (400 MHz, CDCl3) d = 9.70 (s, 1H), 7.42 (d, J = 2.0 Hz,
1H), 7.34 (s, 1H), 7.17 (dd, J = 8.5, 2.0 Hz, 1H), 6.88 (d, J = 8.5
Hz, 1H), 5.79 (s, 1H), 5.58 (s, 1H), 5.03 (s, 1H), 4.33 – 3.97 (m,
2H), 3.10 (d, J = 19.0 Hz, 1H), 2.90 (d, J = 19.0 Hz, 1H), 1.27 (t,
J = 7.1 Hz, 3H).13C NMR (101 MHz, CDCl3) d = 191.6, 165.6,
145.7, 140.3, 135.4, 134.9, 134.8, 133.6, 129.9, 129.6, 127.9, 118.3,
63.5, 46.4, 46.2, 25.9, 13.7. m.p. 117–119 ◦C. IR (KBr): 2982, 2928,
2718, 2243, 1744, 1680, 1475, 1249, 1164 cm-1; HRMS (ESI/[M +
Na]+) Cacld. for: C18H15Cl2NO3Na 386.0321, found 386.0322.
trans-Ethyl-6-(2-chlorophenyl)-1-cyano-3-formyl-5-
methylenecyclohex-3-enecarboxylate (trans-3d)
1H NMR (400 MHz, CDCl3) d = 9.66 (s, 1H), 7.80 (dd, J = 7.6, 1.7
Hz, 1H), 7.45 (dd, J = 7.7, 1.6 Hz, 1H), 7.40 – 7.28 (m, 3H), 5.72
(d, J = 2.1 Hz, 1H), 5.01 (d, J = 1.7 Hz, 1H), 4.79 (s, 1H), 4.06 (qq,
J = 10.7, 7.1 Hz, 2H), 3.24 (d, J = 17.7 Hz, 1H), 3.08 (d, J = 17.8
Hz, 1H), 1.00 (t, J = 7.1 Hz, 3H).13C NMR (101 MHz, CDCl3)
d = 191.7, 166.7, 146.1, 140.1, 135.4, 134.9, 133.5, 130.0, 129.7,
129.2, 127.6, 126.7, 117.8, 63.2, 48.4, 47.1, 32.3, 13.5. m.p. 161–
162 ◦C; IR (KBr): 2982, 2926, 2719, 2243, 1743, 1681, 1435, 1252,
1162 cm-1; HRMS (ESI/[M + Na]+) Cacld. for: C18H16ClNO3Na
352.0711, found 352.0715.
trans-Methyl-1-cyano-6-(2,4-dichlorophenyl)-3-formyl-5-
methylenecyclohex-3-enecarboxylate (trans-3b)
1H NMR (400 MHz, CDCl3) d = 9.66 (s, 1H), 7.71 (d, J = 8.5 Hz,
1H), 7.49 (s, 1H), 7.34 (d, J = 8.5 Hz, 1H), 7.28 (s, 1H), 5.74 (s,
1H), 5.01 (s, 1H), 4.75 (s, 1H), 3.65 (s, 3H), 3.25 (d, J = 17.7 Hz,
1H), 3.06 (d, J = 17.8 Hz, 1H). 13C NMR (101 MHz, CDCl3) d =
191.6, 167.1, 145.9, 139.7, 136.1, 135.1, 134.8, 132.1, 129.9, 129.9,
128.1, 127.0, 117.4, 54.0, 48.2, 46.5, 32.1. m.p. 170–172 ◦C; IR
(KBr): 2924, 2850, 2722, 2354, 2245, 1748, 1680, 1630, 1475, 1255,
1164 cm-1; HRMS (ESI/[M + Na]+) Calcd. for: C17H13Cl2NO3Na
372.0165, found 372.0170.
cis-Ethyl-6-(2-chlorophenyl)-1-cyano-3-formyl-5-
methylenecyclohex-3-enecarboxylate (cis-3d)
1H NMR (400 MHz, CDCl3) d = 9.64 (s, 1H), 7.37 – 7.30 (m, 1H),
7.28 (d, J = 1.5 Hz, 1H), 7.23 – 7.05 (m, 2H), 6.86 (dd, J = 7.7, 1.5
Hz, 1H), 5.71 (s, 1H), 5.53 (s, 1H), 5.04 (s, 1H), 4.19 – 3.96 (m, 2H),
3.02 (d, J = 18.7 Hz, 1H), 2.88 (d, J = 18.7 Hz, 1H), 1.17 (t, J =
7.2 Hz, 3H).13C NMR (101 MHz, CDCl3) d = 190.8, 164.7, 144.9,
139.6, 134.5, 133.9, 133.0, 129.0, 128.6, 127.7, 126.8, 126.5, 117.6,
62.4, 45.6, 45.5, 24.7, 12.6. m.p. 146–148 ◦C; IR (KBr): 2981, 2927,
2720, 2243, 1743, 1681, 1435, 1251, 1162 cm-1; HRMS (ESI/[M +
Na]+) Calcd. for: C18H16ClNO3Na 352.0711, found 352.0713.
cis-Methyl-1-cyano-6-(2,4-dichlorophenyl)-3-formyl-5-
methylenecyclohex-3-enecarboxylate (cis-3b)
1H NMR (400 MHz, CDCl3) d = 9.71 (s, 1H), 7.42 (d, J = 2.1 Hz,
1H), 7.36 (s, 1H), 7.17 (dd, J = 8.5, 2.1 Hz, 1H), 6.86 (d, J = 8.5 Hz,
1H), 5.81 (s, 1H), 5.59 (s, 1H), 5.01 (s, 1H), 3.78 (s, 3H), 3.09 (d,
J = 18.8 Hz, 1H), 2.87 (d, J = 18.8 Hz, 1H). 13C NMR (101 MHz,
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cis-Ethyl-6-(3-chlorophenyl)-1-cyano-3-formyl-5-
methylenecyclohex-3-enecarboxylate (cis-3e)
cis-Ethyl-6-(4-bromophenyl)-1-cyano-3-formyl-5-
methylenecyclohex-3-enecarboxylate. (cis-3h)
1H NMR (400 MHz, CDCl3) d = 9.71 (s, 1H), 9.65* (s, 1H), 7.37
(d, J = 2.0 Hz, 2H), 7.27 (s, 1H), 7.00 – 6.91 (m, 1H), 6.88 (d,
J = 7.6 Hz, 1H), 5.84 (s, 1H), 5.79* (s, 1H), 5.62 (s, 1H), 5.30* (s,
1H), 5.23* (s, 1H), 4.40 (s, 1H), 4.20 (q, J = 7.2 Hz, 2H), 4.09 –
4.02* (m, 2H), 3.17* (d, J = 17.7 Hz, 1H), 3.09 (d, J = 18.6 Hz,
1H), 3.00* (d, J = 17.9 Hz, 1H), 2.70 (d, J = 18.6 Hz, 1H), 1.27 (t,
J = 7.2 Hz, 3H), 1.01* (t, J = 7.1 Hz, 3H).13C NMR (101 MHz,
CDCl3) d = 191.8, 191.6*, 167.0*, 165.6, 146.0*, 145.8, 140.1*,
139.9, 138.5, 137.3*, 135.6, 134.8, 134.6*, 130.2, 130.1*, 128.9*,
128.8, 128.4, 128.0, 127.5*, 126.1, 118.4, 117.3*, 63.4, 63.3*, 51.7*,
51.6, 49.1*, 47.1, 31.2*, 24.3, 13.9, 13.6*; IR (KBr): 2983, 2936,
2722, 2243, 1746, 1683, 1431, 1242, 1162 cm-1; HRMS (ESI/[M +
Na]+) Calcd. for: C18H16ClNO3Na 352.0711, found 352.0715.
1H NMR (400 MHz, CDCl3) d = 9.70 (s, 1H), 9.65* (s, 1H), 7.52*
(d, J = 8.0 Hz, 2H), 7.41 (d, J = 8.1 Hz, 2H), 7.36 (s, 1H), 6.89
(d, J = 8.0 Hz, 2H), 5.82 (s, 1H), 5.60 (s, 1H), 4.39 (s, 1H), 4.23 –
4.12 (m, 2H), 3.16* (d, J = 17.7 Hz, 1H), 3.08 (d, J = 18.6 Hz,
1H), 2.98* (d, J = 17.7 Hz, 1H), 2.70 (d, J = 18.6 Hz, 1H), 1.27
(t, J = 7.4 Hz, 3H), 1.02* (t, J = 7.2 Hz, 3H).NMR (101 MHz,
CDCl3) d = 191.8, 191.7*, 167.1*, 165.6, 146.0*, 145.8, 140.3*,
1402, 135.6*, 135.6, 134.8, 132.1, 132.0*, 129.8, 127.8, 127.4*,
122.9*, 122.8, 118.4, 117.4*, 63.3, 51.5*, 51.5, 49.1, 47.0, 29.7*,
24.4, 13.9, 13.6*. oil; IR (KBr): 2982, 2932, 2850, 2722, 2243,
1745, 1683, 1488, 1244, 1162, 1011 cm-1; HRMS (ESI/[M + Na]+)
Calcd. for: C18H16BrNO3Na 396.0206, found 396.0201.
cis-Ethyl-1-cyano-6-(4-fluorophenyl)-3-formyl-5-
methylenecyclohex-3-enecarboxylate (cis-3i)
cis-Ethyl-6-(4-chlorophenyl)-1-cyano-3-formyl-5-
methylenecyclohex-3-enecarboxylate (cis-3f)
1H NMR (400 MHz, CDCl3) d = 9.71 (s, 1H), 9.65* (s, 1H), 7.36
(d, J = 2.1 Hz, 1H), 7.01 – 6.95 (m, 3H), 5.82 (s, 1H), 5.78 (d, J =
2.0 Hz, 1H), 5.60 (s, 1H), 5.30* (s, 1H), 5.21* (d, J = 1.5 Hz, 1H),
4.42 (s, 1H), 4.17 (qd, J = 7.1, 1.3 Hz, 2H), 4.03* (t, J = 7.3 Hz,
2H), 3.17* (d, J = 17.7 Hz, 1H), 3.08 (d, J = 18.6 Hz, 1H), 2.99* (d,
J = 16.7 Hz, 1H), 2.71 (d, J = 20.1 Hz, 1H), 1.26 (t, J = 7.2 Hz, 3H),
1.00* (t, J = 7.1 Hz, 3H).13C NMR (101 MHz, CDCl3) d = 191.8,
191.7*, 165.7, 161.4*, 146.1*, 145.9, 140.7*, 140.5, 135.6, 134.8*,
132.5, 132.5*, 129.9, 129.8, 127.7, 127.3*, 118.5, 116.1, 115.9*,
115.8, 115.7*, 63.2, 63.2*, 51.4*, 51.3, 47.2, 24.3, 13.9, 13.6*. m.p.
118–123 ◦C, IR (KBr): 2985, 2931, 2850, 2722, 2243, 1748, 1681,
1427, 1244, 1163, 845 cm-1; HRMS (ESI/[M + Na]+) Cacld. for:
C18H16FNO3Na 336.1006, found 336.1004.
1H NMR (400 MHz, CDCl3) d = 9.70 (s, 1H), 7.36 (d, J = 2.2 Hz,
1H), 7.28 – 7.20 (m, 1H), 6.94 (d, J = 8.5 Hz, 1H), 5.82 (s, 1H),
5.60 (s, 1H), 4.41 (s, 1H), 4.25 – 3.99 (m, 1H), 3.08 (d, J = 18.8 Hz,
1H), 2.70 (dd, J = 18.8, 1.9 Hz, 1H), 1.26 (t, J = 7.2 Hz, 3H).13C
NMR (101 MHz, CDCl3) d = 191.8, 165.6, 145.9, 140.2, 135.6,
135.1, 134.7, 129.4, 129.1, 127.8, 118.4, 63.3, 51.4, 47.1, 24.3, 13.9.
oil, IR (KBr): 2981, 2927, 2719, 2242, 1748, 1682, 1492, 1243,
1161 cm-1; HRMS (ESI/[M + Na]+) Cacld. for: C18H16ClNO3Na
352.0711, found 352.0710.
trans-Ethyl-6-(2-bromophenyl)-1-cyano-3-formyl-5-
methylenecyclohex-3-enecarboxylate (trans-3g)
cis-Ethyl-2-cyano-4-formyl-3¢-methyl-6-methylene-1,2,3,6-
tetrahydro-[1,1¢-biphenyl]-2-carboxylate (cis-3j)
1H NMR (400 MHz, CDCl3) d = 9.59 (s, 1H), 7.74 (d, J = 7.8
Hz, 1H), 7.57 (d, J = 7.8 Hz, 1H), 7.32 (t, J = 7.6 Hz, 1H), 7.16
(t, J = 7.6 Hz, 1H), 5.66 (s, 1H), 4.92 (s, 1H), 4.70 (s, 1H), 4.11 –
3.77 (m, 2H), 3.18 (d, J = 17.8 Hz, 1H), 3.02 (d, J = 17.8 Hz,
1H), 0.92 (t, J = 7.1 Hz, 3H).13C NMR (101 MHz, CDCl3) d =
190.7, 165.6, 145.1, 139.0, 134.1, 133.9, 132.4, 129.0, 128.1, 127.2,
125.8, 125.4, 116.8, 62.2, 49.0, 47.4, 31.3, 12.5. m.p. 152–154 ◦C;
IR (KBr): 2963, 2927, 2720, 2244, 1743, 1681, 1431, 1252, 1162,
1054 cm-1; HRMS (ESI/[M + Na]+) Calcd. for: C18H16BrNO3Na
396.0206, found 396.0198.
1H NMR (400 MHz, CDCl3) d = 9.63 (s, 1H), 9.57* (s, 1H), 7.32 –
7.28 (m, 1H), 7.20 (s, 1H), 7.11 – 7.05 (m, 1H), 7.02 (d, J = 7.5
Hz, 1H), 6.72 (s, 1H), 5.73 (s, 1H), 5.69* (s, 1H), 5.53 (s, 1H),
5.19* (s, 1H), 4.32 (s, 1H), 4.08 (q, J = 7.1 Hz, 2H), 3.08* (d, J =
17.5 Hz, 1H), 2.99 (d, J = 18.8 Hz, 1H), 2.66 (d, J = 18.4 Hz,
1H), 2.28* (s, 3H), 2.20 (s, 3H), 1.17 (t, J = 7.1 Hz, 3H), 0.88* (t,
J = 7.1 Hz, 3H). 13C NMR (101 MHz, CDCl3) d = 191.0, 190.9*,
166.3*, 164.8, 145.4*, 145.3, 139.7*, 139.7, 137.6, 137.4*, 135.5*,
134.6, 134.1*, 133.7*, 128.3, 127.8, 127.7, 127.6*, 126.6, 126.4*,
124.0*, 123.9, 117.8, 116.63*, 62.0, 62.0*, 51.1, 46.2, 23.2, 23.0*,
20.4, 12.8, 12.5*. oil; IR (KBr): 2983, 2928, 2871, 2724, 2242, 1745,
1686, 1445, 1246, 1162 cm-1; HRMS (ESI/[M + Na]+) Calcd. for:
C19H19NO3Na 332.1257, found 332.1251.
cis-Ethyl-6-(2-bromophenyl)-1-cyano-3-formyl-5-
methylenecyclohex-3-enecarboxylate (cis-3g)
1H NMR (400 MHz, CDCl3) d = 9.64 (s, 1H), 7.52 (d, J = 7.9
Hz, 1H), 7.15 (t, J = 7.5 Hz, 1H), 7.08 (t, J = 7.7 Hz, 1H), 6.85
(d, J = 7.7 Hz, 1H), 5.71 (s, 1H), 5.55 (s, 1H), 5.05 (s, 1H), 4.20 –
3.95 (m, 2H), 3.04 (d, J = 18.7 Hz, 1H), 2.92 (d, J = 18.7 Hz,
1H), 1.17 (t, J = 7.1 Hz, 3H).13C NMR (101 MHz, CDCl3) d =
190.8, 164.6, 144.9, 139.5, 135.7, 134.3, 132.5, 128.8, 127.6, 127.2,
126.8, 123.9, 117.6, 62.4, 48.1, 45.4, 24.9, 12.6. m.p. 157–159 ◦C;
IR (KBr): 2983, 2928, 2721, 2244, 1744, 1680, 1470, 1242, 1164,
1022 cm-1; HRMS (ESI/[M + Na]+) Calcd. for: C18H16BrNO3Na
396.0206, found 396.0201.
cis-Ethyl-1-cyano-3-formyl-5-methylene-6-phenylcyclohex-3-
enecarboxylate (cis-3k)
1H NMR (400 MHz, CDCl3) d = 9.71 (s, 1H), 9.65* (s, 1H), 7.37
(d, J = 2.3 Hz, 1H), 7.29 – 7.25 (m, 3H), 7.04 – 6.92 (m, 2H), 5.81
(s, 1H), 5.77* (d, J = 1.9 Hz, 1H), 5.61 (s, 1H), 5.24* (s, 1H), 4.43 (s,
1H), 4.15 (q, J = 7.1 Hz, 2H), 3.99* (qd, J = 7.1, 2.3 Hz, 2H), 3.16*
(d, J = 17.7 Hz, 1H), 3.07 (d, J = 18.6 Hz, 1H), 2.74 (dd, J = 18.5,
1.5 Hz, 1H), 1.23 (t, J = 7.2 Hz, 3H), 0.94* (t, J = 7.1 Hz, 3H).
13C NMR (101 MHz, CDCl3) d = 191.9, 191.8*, 167.3*, 165.8,
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146.3*, 146.2, 140.8*, 140.7, 136.6, 135.7, 135.2*, 134.8*, 128.9,
128.8, 128.7*, 128.6*, 128.1, 127.6*, 127.4, 118.7, 117.6*, 63.1,
63.0*, 52.3*, 52.1, 49.3*, 47.3, 24.3, 13.8, 13.6*. m.p. 157–160 ◦C,
IR (KBr): 2984, 2930, 2827, 2720, 2242, 1747, 1679, 1427, 1246,
1164 cm-1; HRMS (ESI/[M + Na]+) Calcd. for: C18H17NO3Na
318.1101, found 318.1108.
126.8, 126.4, 126.3*, 117.8, 116.7*, 62.0, 50.8, 48.74*, 46.2, 30.1*,
23.3, 20.1*, 20.0, 12.8, 12.5*. oil; IR (KBr): 2984, 2927, 2859, 2722,
2242, 1746, 1682, 1513, 1244, 1162 cm-1; HRMS (ESI/[M + Na]+)
Calcd. for: C19H19NO3Na 332.1257, found 332.1257.
cis-Ethyl-1-cyano-3-formyl-5-methylene-6-(naphthalen-2-
yl)cyclohex-3-enecarboxylate (cis-3o)
cis-Ethyl-1-cyano-3-formyl-6-(4-methoxyphenyl)-5-
methylenecyclohex-3-enecarboxylate (cis-3l)
1H NMR (400 MHz, CDCl3) d = 9.67 (s, 1H), 9.59* (s, 1H), 7.82 –
7.69 (m, 2H), 7.66 (t, J = 7.5 Hz, 1H), 7.46 – 7.37 (m, 3H), 7.35
(d, J = 1.8 Hz, 1H), 6.99 (dd, J = 8.5 Hz, 1.2, 1H), 5.76 (s, 1H),
5.70* (s, 1H), 5.56 (s, 1H), 5.21* (s, 1H), 5.16* (s, 1H), 4.53 (s,
1H), 4.10 – 4.00 (m, 2H), 3.83* (q, J = 7.0 Hz, 2H), 3.14* (d, J =
17.7 Hz, 1H), 3.03 (d, J = 18.6 Hz, 1H), 2.97* (d, J = 18.9 Hz,
1H), 2.73 (d, J = 18.5 Hz, 1H), 1.10 (t, J = 7.2 Hz, 3H), 0.69* (t,
J = 7.1 Hz, 3H).13C NMR (101 MHz, CDCl3) d = 191.0, 190.8*,
166.3*, 164.8, 145.3*, 145.3, 139.8*, 139.6, 134.7, 133.8*, 133.0,
132.2*, 132.1*, 132.1, 131.9, 131.6*, 127.8, 127.5, 127.0*, 126.9,
126.8, 126.6, 126.53*, 125.7, 125.6, 125.4*, 124.2, 117.7, 116.7*,
62.1, 62.0*, 51.3*, 51.2, 48.3*, 46.4, 28.7*, 23.5, 12.8, 12.4*. oil;
IR (KBr): 3058, 2983, 2917, 2721, 2245, 1782, 1600, 1250, 1244,
1162, 749 cm-1; HRMS (ESI/[M + Na]+) Calcd. for: C22H19NO3Na
368.1257, found 363.1253.
NMR (400 MHz) d = 9.70 (s, 1H), 9.64* (s, 1H), 7.35 (d, J =
2.1 Hz, 1H), 6.91 (d, J = 8.8 Hz, 2H), 6.78 (d, J = 8.8 Hz, 2H),
5.79 (s, 1H), 5.76* (s, 1H), 5.60 (s, 1H), 5.30* (s, 1H), 5.26* (s,
1H), 4.39 (s, 1H), 4.17 (qd, J = 7.1 Hz, 1.5, 2H), 4.05 – 3.98*
(m, 2H), 3.81* (s, 3H), 3.76 (s, 3H), 3.15* (d, J = 17.6 Hz, 1H),
3.06 (d, J = 18.5 Hz, 1H), 2.99* (d, J = 17.6 Hz, 1H), 2.72 (dd,
J = 18.5, 1.6 Hz, 1H), 1.26 (t, J = 7.2 Hz, 3H). 13C NMR (101
MHz) d = 192.0, 191.8*, 167.4*, 165.9, 159.8*, 159.6, 146.4*,
146.2, 141.1*, 141.0, 135.6, 129.2, 128.9, 127.4, 127.3*, 118.8,
114.2, 114.1*, 63.1, 63.0*, 55.3*, 55.2, 51.5*,51.5, 47.3, 24.3, 13.9,
13.7*. oil, IR (KBr): 2959, 2928, 2840, 2718, 2242, 1748, 1686,
1513, 1252, 1181, 1031 cm-1; HRMS (ESI/[M + Na]+) Calcd. for:
C18H17NO3Na 348.1206, found 348.1207.
trans-Methyl-1-cyano-3-formyl-5-methylene-6-o-tolylcyclohex-3-
enecarboxylate (trans-3m)
cis-Ethyl-1-cyano-3-formyl-6-(furan-2-yl)-5-methylenecyclohex-3-
enecarboxylate (cis-3p)
1H NMR (400 MHz, CDCl3) d = 9.59 (s, 1H), 7.66 – 7.52 (m, 1H),
7.20 – 7.09 (m, 3H), 5.64 (s, 1H), 4.98 (s, 1H), 4.28 (s, 1H), 3.47 (s,
3H), 3.16 (d, J = 17.7 Hz, 1H), 2.97 (d, J = 17.6 Hz, 1H), 2.25 (s,
3H). 13C NMR (101 MHz, CDCl3) d = 190.8, 167.0, 145.6, 139.7,
136.4, 133.7, 132.8, 129.8, 127.3, 126.3, 126.1, 125.8, 117.0, 52.7,
47.4, 45.8, 31.5, 18.6. m.p. 138–139 ◦C; IR (KBr): 2957, 2922, 2851,
2719, 2244, 1745, 1679, 1435, 1259, 1162 cm-1;HRMS (ESI/[M +
Na]+) Calcd. for: C18H17NO3Na 348.1101, found 318.1109.
1H NMR (400 MHz, CDCl3) d = 9.64 (s, 1H), 7.28 (d, J = 0.7 Hz,
1H), 7.24 (d, J = 2.1 Hz, 1H), 6.32 – 6.23 (m, 1H), 6.04 (d, J =
3.2 Hz, 1H), 5.83 (s, 1H), 5.68 (s, 1H), 4.58 (s, 1H), 4.42 – 4.15
(m, 2H), 3.06 (d, J = 18.4 Hz, 1H), 2.65 (d, J = 18.4 Hz, 1H),
1.35 (t, J = 7.2 Hz, 3H). 13C NMR (101 MHz, CDCl3) d = 192.1,
165.8, 149.6, 144.7, 143.0, 138.2, 135.6, 127.2, 118.1, 110.6, 109.3,
63.4, 46.2, 46.1, 25.1, 13.9. oil, IR (KBr): 2984, 2938, 2835, 2723,
2243, 1749, 1680, 1426, 1251, 1165 cm-1; HRMS (ESI/[M + Na]+)
Calcd. for: C16H15FO4Na 308.0893, found 303.0898.
cis-Methyl-1-cyano-3-formyl-5-methylene-6-o-tolylcyclohex-3-
enecarboxylate. (cis-3m)
cis-Ethyl-1-cyano-3-formyl-5-methylene-6-(2-
methylstyryl)cyclohex-3-enecarboxylate (cis-3q)
1H NMR (400 MHz, CDCl3) d = 9.71 (s, 1H), 7.34 (s, 1H), 7.21 –
7.16 (m, J = 5.5, 1.7 Hz, 2H), 7.14 – 7.06 (m, 1H), 6.81 (d, J =
7.7 Hz, 1H), 5.75 (s, 1H), 5.49 (s, 1H), 4.74 (s, 1H), 3.65 (s, 3H),
3.08 (s, 2H), 2.43 (s, 3H). 13C NMR (101 MHz, CDCl3) d = 191.0,
165.4, 145.4, 140.2, 134.8, 134.5, 134.1, 130.2, 127.3, 126.2, 126.1,
1H NMR (400 MHz, CDCl3) d 9.55 (s, 1H), 7.21 – 7.17 (m, 1H),
7.14 – 7.02 (m, 4H), 6.66 (d, J = 15.5 Hz, 1H), 5.73 – 5.65 (m, 2H),
5.61 (s, 1H), 4.23 (q, J = 7.1 Hz, 2H), 3.89 (d, J = 8.2 Hz, 1H),
2.99 (d, J = 18.6 Hz, 1H), 2.84 (d, J = 18.5 Hz, 1H), 2.21 (s, 3H),
1.26 (t, J = 7.1 Hz, 3H). 13C NMR (101 MHz, CDCl3) d = 191.0,
164.9, 143.6, 138.8, 134.5, 134.0, 133.9, 132.4, 129.3, 127.2, 125.3,
125.2, 124.9, 123.4, 117.2, 62.2, 49.4, 45.4, 24.4, 18.7, 13.0. oil.
IR (KBr): 2961, 2928, 2851, 2321, 2241, 1745, 1684, 1449, 1252,
1016 cm-1; HRMS (ESI/[M + Na]+) Calcd. for: C21H21NO3Na
358.1414, found 358.1417.
◦
125.8, 117.9, 52.4, 45.6, 45.4, 28.7, 24.8, 18.8. m.p. 135–137 C;
IR (KBr): 2955, 2922, 2851, 2719, 2243, 1752, 1678, 1435, 1249,
1164 cm-1; HRMS (ESI/[M + Na]+) Cacld. for: C18H17NO3Na
318.1101, found 318.1109.
cis-Ethyl-1-cyano-3-formyl-5-methylene-6-p-tolylcyclohex-3-
enecarboxylate (cis-3n)
cis-Ethyl-1-cyano-3-formyl-5-methylene-6-((E)-prop-1-
enyl)cyclohex-3-enecarboxylate (cis-3r)
1H NMR (400 MHz, CDCl3) d = 9.62 (s, 1H), 9.57* (s, 1H), 7.28
(s, 1H), 7.10* (d, J = 8.1 Hz, 2H), 6.99 (d, J = 7.9 Hz, 2H), 6.80 (d,
J = 8.1 Hz, 2H), 5.72 (s, 1H), 5.68* (d, J = 1.6 Hz, 1H), 5.52 (s, 1H),
5.18* (s, 1H), 4.33 (s, 1H), 4.16 – 4.01 (m, 2H), 3.97 – 3.89* (m, 2H),
2.98 (d, J = 19.0 Hz, 1H), 2.65 (d, J = 18.5 Hz, 1H), 2.28* (s, 3H),
2.22 (s, 3H), 1.18 (t, J = 7.2 Hz, 3H), 0.90* (t, J = 7.1 Hz, 3H).13C
NMR (101 MHz, CDCl3) d = 190.9, 190.8*, 166.3*, 164.8, 145.4,
145.2*, 139.8, 137.5, 134.7, 133.8*, 132.6, 131.1*, 128.6, 128.4*,
1H NMR (400 MHz, CDCl3) d = 9.52 (s, 1H), 7.04 (s, 1H), 5.61 –
5.51 (m, 1H), 5.11 (ddd, J = 14.9, 7.9, 1.3 Hz, 1H), 4.29 – 4.19 (m,
1H), 3.66 (d, J = 7.9 Hz, 1H), 2.92 (d, J = 18.3 Hz, 1H), 2.73 (d,
J = 18.0 Hz, 1H), 1.59 (d, J = 6.4 Hz, 3H), 1.27 (t, J = 7.1 Hz,
3H). 13C NMR (101 MHz, CDCl3) d = 191.1, 165.0, 149.5, 143.8,
139.0, 130.8, 124.9, 123.6, 117.4, 62.1, 49.0, 24.0, 21.1, 17.0, 13.0.
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oil IR (KBr): 2966, 2928, 2854, 2320, 2245, 1743, 1687, 1443, 1252,
1029 cm-1; HRMS (ESI/[M + Na]+) Calcd. for: C20H18ClNO3Na
282.1101, found 282.1107.
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3157; (b) J. L. Methot and W. R. Roush, Org. Lett., 2003, 5, 4223.
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A., 2004, 101, 12064.
cis-Ethyl-6-(2-chlorostyryl)-1-cyano-3-formyl-5-
methylenecyclohex-3-enecarboxylate (cis-3s)
1H NMR (400 MHz, CDCl3) d = 9.55 (s, 1H), 7.30 (dd, J = 6.0,
3.3, 1H), 7.26 (dd, J = 6.0, 3.3 Hz, 1H), 7.12 (dd, J = 6.0, 3.3,
3H), 6.83 (d, J = 15.6 Hz, 1H), 5.78 (dd, J = 15.6, 8.5 Hz, 1H),
5.72 (s, 1H), 5.62 (s, 1H), 4.30 – 4.19 (m, 2H), 3.94 (d, J = 8.4 Hz,
1H), 2.99 (d, J = 18.6 Hz, 1H), 2.81 (d, J = 18.9 Hz, 1H), 1.27 (t,
J = 7.1 Hz, 3H). 13C NMR (101 MHz, CDCl3) d = 191.0, 164.8,
143.4, 138.3, 133.9, 132.9, 132.1, 130.5, 128.7, 128.4, 126.0, 126.0,
125.7, 124.7, 117.1, 62.4, 49.4, 45.3, 24.2, 13.0. oil. IR (KBr): 2984,
2936, 2836, 2724, 2350, 2243, 1746, 1684, 1572, 1242, 1162 cm-1;
HRMS (ESI/[M + Na]+) Calcd. for: C20H18ClNO3Na 378.0867,
found 378.0863.
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2977; (k) C. E. Aroyan and S. J. Miller, J. Am. Chem. Soc., 2007, 129,
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cis-Ethyl-1-cyano-3-formyl-5-methylene-6-styrylcyclohex-3-
enecarboxylate (cis-3t)
1H NMR (400 MHz, CDCl3) d = 9.56 (s, 1H), 7.27 – 7.17 (m, 1H),
7.10 (s, 1H), 6.42 (d, J = 15.6 Hz, 1H), 5.82 (dd, J = 15.4, 8.1
Hz, 1H), 5.70 (s, 1H), 5.59 (s, 1H), 4.30 – 4.17 (m, 1H), 3.87 (d,
J = 7.9 Hz, 1H), 2.99 (d, J = 18.6 Hz, 1H), 2.81 (d, J = 18.6 Hz,
1H), 1.25 (t, J = 6.5 Hz, 1H). 13C NMR (101 MHz, CDCl3) d =
191.1, 164.9, 143.6, 138.6, 134.6, 134.2, 133.9, 127.7, 127.7, 127.4,
125.6, 125.5, 125.5, 121.7, 117.2, 62.3, 49.3, 45.3, 24.3, 13.1. oil. IR
(KBr): 2981, 2928, 2851, 2728, 2375, 2243, 1745, 1684, 1447, 1249,
1164 cm-1; HRMS (ESI/[M + Na]+) Calcd. for: C20H19NO3Na
344.1257, found 344.1260.
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Acknowledgements
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3117.
We thank the National Natural Science Foundation of China
(20972076, 20772061) and the Natural Science Foundation of
Tianjin (10JCYBJC04000) for financial support.
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Notes and references
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6714 | Org. Biomol. Chem., 2011, 9, 6707–6714
This journal is
The Royal Society of Chemistry 2011
©