An efficient one-pot three-component process for the synthesis of highly substituted perfluoroalkylated cyclopentadienes

Article abstract of DOI:10.1016/j.tet.2013.03.093

A series of highly substituted perfluoroalkylated cyclopentadiene derivatives were efficiently synthesized in moderate to excellent yields by isocyanides, methyl 2-perfluoroalkynoates and electrophilic alkenes via a one-pot three-component reaction under

Full text of DOI:10.1016/j.tet.2013.03.093

Tetrahedron 69 (2013) 4205e4210
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
An efficient one-pot three-component process for the synthesis
of highly substituted perfluoroalkylated cyclopentadienes
You Lv a, Xufeng Yan a, Lijun Yan a, Zewei Wang a, Jie Chen a, Hongmei Deng d, Min Shao d,
,
a,b,c,
*
Hui Zhang a , Weiguo Cao
*
a Department of Chemistry, Shanghai University, Shanghai 200444, PR China
b State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, PR China
c Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, PR China
d Instrumental Analysis and Research Center of Shanghai University, Shanghai 200444, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
A series of highly substituted perfluoroalkylated cyclopentadiene derivatives were efficiently synthesized
in moderate to excellent yields by isocyanides, methyl 2-perfluoroalkynoates and electrophilic alkenes
via a one-pot three-component reaction under mild condition.
Received 24 January 2013
Received in revised form 18 March 2013
Accepted 25 March 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Available online 28 March 2013
Keywords:
Isocyanide
Methyl 2-perfluoroalkynoate
Electrophilic alkene
Highly substituted perfluoroalkylated
cyclopentadiene
1. Introduction
necessarily easy owing to the absence of general methods7 and also
to the facile migration of the endocyclic double bonds.8
In recent years, the development of new methods that provide
synthetic efficiencyandatom economy hasbeen an important goalof
synthetic chemistry.1 Multicomponent reactions (MCRs), by virtue of
their convergence, productivity, facile execution and generally high
yields of products, are good candidates for this target as theyembody
ideal synthesis.2 Among the MCRs, those with isocyanides (IMCRs)
have attracted enormous attention from organic chemists,3 and thus
isocyanides have proved themselves to be irreplaceable building
blocks in modern organic chemistry. From an organic view of point,
methods starting from isocyanides often have distinct advantages
including enhanced convergence, inherent atom economy and the
great variety of readily available isocyanides for use.
Cyclopentadienes are useful not only as a reactive diene com-
ponent in the DielseAlder reaction4 but also as a precursor for the
preparation of transition-metal complexes with Cp-type ligands.5
However, though the introduction of substituents into the cyclo-
pentadienyl (Cp) backbone is well-known to dramatically affect the
reactivity of transition metals containing these ligands,6 the prep-
aration of well-defined, highly substituted cyclopentadienes is not
Furthermore, due to the strong electronegativity, the small size
and low polarizability of fluorine atom, perfluoroalkyl (RF) moieties
exhibit properties of great interest (chemical and thermal stability,
low surface energy, self organization ability) for a wide variety of
applications.9
Therefore, there has been considerable interest in developing an
efficient method for the synthesis of highly substituted per-
fluoroalkylated cyclopentadiene derivatives.10
Zwitterionic species derived from isocyanides and DMAD can be
efficiently trapped by dipolarophiles, such as aryl aldehydes, N-tosy-
limines and activated alkenes, leading to a facile synthesis of furan,
pyrrole derivatives and highly substituted cyclopentadienes, re-
spectively.11 Against this background, we envisaged that the zwitter-
ions derived from isocyanides and methyl 2-perfluoroalkynoates
might undergo cycloaddition to activated alkenes, thus constituting
a synthesis of highly substituted perfluoroalkylated cyclopentadienes.
Ourpreliminaryresults validatingthisideaarepresentedinthis paper.
2. Results and discussion
Highly substituted perfluoroalkylated cyclopentadienes 4 were
obtained via a one-pot three-component reaction (MCR) by using
* Corresponding authors. Fax: þ86 21 66134856; e-mail addresses: wgcao@
staff.shu.edu.cn, yehao7171@shu.edu.cn (W. Cao).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.03.093

4206
Y. Lv et al. / Tetrahedron 69 (2013) 4205e4210
isocyanides 1, methyl 2-perfluoroalkynoates 2 and electrophilic
alkenes 3 (Scheme 1). The structures of products were confirmed by
IR, 1H NMR, 13C NMR, 19F NMR, MS and HRMS as well.
On the basis of the previous reports,5 the proposed mechanism
is shown in Scheme 2. First, isocyanide attacks methyl
2-perfluoroalkynoate 2 nucleophilically to generate the zwitterion
1
CO2Me
RF
DCM
r.t.
H
CN
CN
R1
N
C
RF
CO2Me
Ar
R1HN
NC
Ar
2
1
CN
3
4
1a
1b
: R1 = cyclohexyl;
2b: RF = C2F5;
: R1 = t-butyl;
2a: RF = CF3;
2c: RF = n-C3F7;
Scheme 1. Preparation of highly substituted perfluoroalkylated cyclopentadienes 4.
Table 2
Preparation of highly substituted perfluoroalkylated cyclopentadienes 4a
Initially, we carried out the reaction of tert-butyl isocyanide 1a
(1.2 equiv), methyl 4,4,4-trifluorobut-2-ynoate 2a (1.2 equiv) and
2-benzylidenemalononitrile 3a (1.0 mmol) in dry DCM (5 mL) at
room temperature for 8 h and the desired product 4a was obtained in
excellent yield (90%). Further screening of the reaction conditions
was carried out and the results were summarized in Table 1. The role
of the solvent in this reaction was studied by performing the same
reaction in other various solvents, such as tetrahydrofuran (THF),
chloroform, ethanol and toluene. It is worth mentioning that
dichloromethane (DCM) is the most suitable solvent for the synthesis
(Table 1, entries 1 vs 2e5). A lower yield was obtained when the
reaction was performed at 40 or 0 ꢀC (Table 1, entries 1 vs 6 or 7).
Entry
1
2
Ar
Time (h)
Product
Yieldb (%)
1
2
3
4
5
6
7
8
1a
1a
1a
1a
1a
1a
1a
1a
1a
1b
1b
1b
1b
1a
1a
1a
1a
1a
1a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2b
2b
2b
2b
2c
2c
Ph
8
13
24
7
10
12
24
15
13
15
6
6
6
15
8
8
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
4q
4r
4s
90
75
61
86
95
93
50
70
73
86
92
96
95
69
96
90
95
63
87
4-CH3C6H4
4-MeOC6H4
2-NO2C6H4
2-ClC6H4
2-BrC6H4
1-Naphthalene
2-CH3C6H4
3-CH3C6H4
2-CH3C6H4
2-ClC6H4
2-BrC6H4
2-NO2C6H4
2-CH3C6H4
2-ClC6H4
2-BrC6H4
2-NO2C6H4
2-CH3C6H4
2-ClC6H4
9
10
11
12
13
14
15
16
17
18
19
Table 1
Optimization of the reaction conditions
Entry
Solvent
Temp (ꢀC)
4a Yielda (%)
1
2
3
4
5
6
7
DCM
THF
rt
rt
rt
rt
rt
0
90
73
82
0
57
83
72
8
18
7
CHCl3
EtOH
Toluene
DCM
DCM
a
Reaction conditions: isocyanide 1 (1.2 equiv), methyl 2-perfluoroalkynoate 2
(1.2 equiv), electrophilic alkene 3 (1.0 mmol), dry DCM (5 mL), room temperature.
b
Isolated yield.
40
Bold signifies the best result under different reaction conditions.
a
Isolated yield.
After optimization of the reaction conditions, a variety of elec-
trophilic alkenes 3 containing electron donating or electron with-
drawing groups in the aromatic ring were reacted with various
2-perfluoroalkynoates 2 and isocyanides 1. In all cases, the corre-
sponding perfluoroalkylated cyclopentadiene derivatives were
obtained in good to excellent yields under similar reaction condi-
tions, which are summarized in Table 2. From these successful re-
sults, we concluded that alkenes 3 with electron withdrawing
groups on the Ar ring had a shorter reaction time as compared to
those with electron donating groups and provided a better yield
(Table 2, entries 2, 3 vs 4e6). Only 50% yield of product was obtained
when 2-(naphthalen-2-ylmethylene)malononitrile was used (Table
2, entry 7). This might be due to its steric hindrance in the reaction
process. However, interestingly, it was found that 3 with an ortho
substituent on benzene ring gave good yields of products (Table 2,
entries 4e6 and 8). Both tert-butyl isocyanide and cyclohexyl iso-
cyanide are suitable partners in this reaction. The variability of the
reaction with respect to the alkyne was also tested. C2F5- or n-C3F7
substituted 2-perfluoroalkynoates also worked well. The structure
of the final product was further confirmed by X-ray diffraction
analysis of 4c (Fig. 1).12 From the crystal structure, it is clear that C2
of methyl 2-perfluoroalkynoate is attached to C1 of isocyanide and
C3 of methyl 2-perfluoroalkynoate is attached to C4 of alkene. The
dihedral angle of benzene ring and plane C5C1C2C3 is 87.8ꢀ. The
dihedral angle of plane C5C1C2C3 and plane C3C4C5 is 20.9ꢀ, which
shows that the cyclopentadiene ring has an envelope conformation.
Fig. 1. X-ray diffraction of compound 4c.
A. Subsequent nucleophilic addition of A to alkene 3 occurs,
affording imine B as the pivotal intermediate, which then un-
dergoes cyclization to deliver the adduct C. The latter isomerizes to
give the final product 4 via a [1,5]-H shift.
3. Conclusion
We have developed a novel and efficient route for the prepa-
ration of highly substituted perfluoroalkylated cyclopentadienes

Y. Lv et al. / Tetrahedron 69 (2013) 4205e4210
4207
Scheme 2. Mechanism for the formation of product 4.
via a three-component reaction of isocyanide, methyl 2-perfluoro-
alkynoate and activated alkene. The generality of this three-
component reaction has been demonstrated. A possible reaction
mechanism is proposed. Further synthetic applications of highly
substituted perfluoroalkylated cyclopentadienes are in progress in
our laboratory.
4.2.5. 2-(2-Chlorobenzylidene)malononitrile 3e.14d Pale red solid;
yield: 89%. 1H NMR (CDCl3, 500 MHz, ppm):
7.44e7.47 (m, 1H),
7.55e7.56 (m, 2H), 8.18e8.19 (m, 1H), 8.27 (s, 1H).
d
4.2.6. 2-(2-Bromobenzylidene)malononitrile (3f).14e Pale yellow
solid; yield: 84%. 1H NMR (CDCl3, 500 MHz, ppm):
d
7.44e7.51
(m, 2H), 7.74e7.75 (m, 1H), 8.11e8.13 (m, 1H), 8.22 (s, 1H).
4. Experimental
4.2.7. 2-(Naphthalen-1-ylmethylene)malononitrile
3g.14f Yellow
7.60e7.71
solid; yield: 75%. 1H NMR (CDCl3, 500 MHz, ppm):
d
4.1. General information
(m, 3H), 7.95e7.97 (m, 2H), 8.11e8.12 (m, 1H), 8.27e8.29 (m, 1H),
8.66 (s, 1H).
All reagents were purchased from commercial sources and
used without further purification, except that methyl 2-
perfluoroalkynoates 213 and electrophilic alkenes 314 were pre-
pared according to the known literature. Melting points were
recorded on a WRS-1 instrument and uncorrected. 1H, 19F and 13C
NMR spectra were recorded on a Bruker DRX-500 MHz spectrom-
eter. All chemical shifts are reported in parts per million downfield
(positive) of the standard: C6F6 for 19F, TMS for 1H and 13C NMR
spectra. IR spectra were obtained on an AVATAR370 FT-IR spec-
trometer. LRMS (lower resolution mass spectra) and HRMS (high
resolution mass spectra) were obtained on LCMS 2020 and Bruker
Daltonics APEXIII 7.0 TESALA FTMS instrument, respectively. X-ray
analysis was performed on a Bruker Smart Apex2 CCD spectrom-
eter. All yields reported in this publication referred to isolated ones
of compounds and their purity was determined by 1H NMR.
4.2.8. 2-(2-Methylbenzylidene)malononitrile (3h).14g White solid;
yield: 68%. 1H NMR (CDCl3, 500 MHz, ppm):
d 2.45 (s, 3H), 7.32e7.37
(m, 2H), 7.48e7.51 (m, 1H), 8.08e8.09 (m, 1H), 8.10 (s, 1H).
4.2.9. 2-(3-Methylbenzylidene)malononitrile 3i.14h White solid;
yield: 72%. 1H NMR (CDCl3, 500 MHz, ppm):
d 2.43 (s, 3H), 7.41e7.45
(m, 2H), 7.69 (s, 1H), 7.72e7.74 (m, 2H).
4.3. General procedure for preparation of compound 4
To a solution of methyl 2-perfluoroalkynoate 2 (1.2 mmol) and
electrophilic alkene 3 (1.0 mmol) in dry DCM (5 mL) was added
isocyanide 1 (1.2 mmol) and the mixture was stirred at room
temperature. After the completion of the reaction (monitored by
TLC), the solvent was removed in vacuo to give the crude product,
which was purified by silica gel chromatography.
4.2. General procedure for preparation of compound 3
Malononitrile (10.0 mmol) was added to a stirred solution of
benzaldehyde (10.0 mmol) and piperidine (1.0 mmol) in ethanol
(10 mL). The reaction mixture was stirred at room temperature for
5 h. A precipitate was formed and collected by suction filtration,
washed with n-hexane/ethanol (v/v¼10:1), and then dried under
high vacuum.
4.3.1. Methyl
fluoromethyl)cyclopenta-1,4-dienecarboxylate 4a. White solid; mp:
133.3e134.5 ꢀC; yield: 90%. 1H NMR (CDCl3, 500 MHz, ppm):
1.57
(s, 9H), 3.72 (s, 3H), 5.06 (br s, 1H), 7.29e7.31 (m, 2H), 7.46e7.48 (m,
4-(tert-butylamino)-3,3-dicyano-2-phenyl-5-(tri-
d
3H). 13C NMR (CDCl3, 125 MHz, ppm):
d 30.1, 53.2, 60.2, 60.4, 111.3,
113.5, 119.3 (q, 1JCeF¼272.0 Hz, CF3), 128.8, 129.4, 130.4, 131.2, 132.9
4.2.1. 2-Benzylidenemalononitrile 3a.14b Pale yellow solid; yield:
(q, JCeF¼32.8 Hz, CCF3), 141.6, 148.7, 162.7. 19F NMR (CDCl3,
2
82%. 1H NMR (CDCl3, 500 MHz, ppm):
d
7.53e7.56 (m, 2H),
470 MHz, ppm):
d
ꢁ62.7 (s, CF3). IR (KBr, cmꢁ1):
n 2977, 2258, 1740,
7.62e7.65 (m, 1H), 7.78 (s, 1H), 7.90e7.92 (m, 2H).
1661, 1360, 1293, 1270, 1183, 1164, 1148, 1044, 705. MS (EI) m/z (%):
388 [(MꢁH)]þ. HRMS (ESI) calcd for C20H18F3N3O2 [(MꢁH)]þ:
388.1278, found: 388.1275.
4.2.2. 2-(4-Methylbenzylidene)malononitrile 3b.14b White solid;
yield: 64%. 1H NMR (CDCl3, 500 MHz, ppm):
d 2.46 (s, 3H), 7.34 (d,
J¼8.5 Hz, 2H), 7.72 (s, 1H), 7.81 (d, J¼8.5 Hz, 2H).
4.3.2. Methyl
fluoromethyl)cyclopenta-1,4-dienecarboxylate 4b. White solid; mp:
121.0e123.1 ꢀC; yield: 75%. 1H NMR (CDCl3, 500 MHz, ppm):
1.56
4-(tert-butylamino)-3,3-dicyano-2-(p-tolyl)-5-(tri-
4.2.3. 2-(4-Methoxybenzylidene)malononitrile 3c.14b Pale yellow
d
solid; yield: 71%. 1H NMR (CDCl3, 500 MHz, ppm):
d
3.91 (s, 3H),
(s, 9H), 2.38 (s, 3H), 3.72 (s, 3H), 5.02 (br s,1H), 7.17 (d, J¼7.5 Hz, 2H),
7.01 (d, J¼9.0 Hz, 2H), 7.65 (s, 1H), 7.91 (d, J¼9.0 Hz, 2H).
7.25 (d, J¼7.5 Hz, 2H). 13C NMR (CDCl3, 125 MHz, ppm):
d 21.2, 30.2,
1
53.2, 60.1, 60.4, 111.5, 113.6, 119.4 (q, JCeF¼272.0 Hz, CF3), 128.1,
4.2.4. 2-(2-Nitrobenzylidene)malononitrile 3d.14c Brown solid;
128.7, 130.2, 132.8 (q, 2JCeF¼32.8 Hz, CCF3), 140.6, 141.7, 148.9, 162.8.
yield: 86%. 1H NMR (CDCl3, 500 MHz, ppm):
d
7.79e7.83 (m, 2H),
19F NMR (CDCl3, 470 MHz, ppm):
2986, 2959, 2247, 1738, 1658, 1359, 1292, 1186, 1155, 1088, 828. MS
d
ꢁ62.7 (s, CF3). IR (KBr, cmꢁ1):
n
7.87e7.90 (m, 1H), 8.35e8.37 (m, 1H), 8.45 (s, 1H).

4208
Y. Lv et al. / Tetrahedron 69 (2013) 4205e4210
(EI) m/z (%): 402 [(MꢁH)]þ. HRMS (ESI) calcd for C21H20F3N3O2
[(MꢁH)]þ: 402.1435, found: 402.1422.
[(MþNa)]þ. HRMS (ESI) calcd for C24H20F3N3O2 [(MþNa)]þ:
462.1400, found: 462.1410.
4.3.3. Methyl 4-(tert-butylamino)-3,3-dicyano-2-(4-methoxy-
phenyl)-5-(trifluoromethyl)cyclopenta-1,4-dienecarboxylate
4c. White solid; mp: 111.9e113.1 ꢀC; yield: 61%. 1H NMR (CDCl3,
4.3.8. Methyl 4-(tert-butylamino)-3,3-dicyano-2-(o-tolyl)-5-(trifluoro-
methyl)cyclopenta-1,4-dienecarboxylate 4h. White solid; mp:
154.1e155.3 ꢀC; yield: 70%. 1H NMR (CDCl3, 500 MHz, ppm):
500 MHz, ppm):
d 1.56 (s, 9H), 3.72 (s, 3H), 3.83 (s, 3H), 5.01 (br s,
d
1.56 (s, 9H), 2.52 (s, 3H), 3.72 (s, 3H), 5.38 (br s, 1H), 7.06e7.08
1H), 6.96 (d, J¼8.7 Hz, 2H), 7.21 (d, J¼8.7 Hz, 2H). 13C NMR (CDCl3,
(m, 1H), 7.25e7.35 (m, 3H). 13C NMR (CDCl3, 125 MHz, ppm):
d
19.9, 30.2, 53.2, 56.2, 60.6, 111.4, 113.8, 119.4 (q, 1JCeF¼272.0 Hz,
125 MHz, ppm):
d 30.2, 53.3, 55.3, 60.0, 60.5, 111.5, 113.6, 114.9,
119.4 (q, 1JCeF¼272.0 Hz, CF3), 122.8, 130.2, 132.7 (q, 2JCeF¼32.8 Hz,
2
CF3), 126.9, 127.8, 130.2, 130.3, 131.5, 133.1 (q, JCeF¼32.8 Hz,
CCF3), 141.7, 148.9, 161.1, 162.9. 19F NMR (CDCl3, 470 MHz, ppm):
CCF3), 137.4, 141.6, 149.3, 162.9. 19F NMR (CDCl3, 470 MHz, ppm):
ꢁ62.7 (s, CF3). IR (KBr, cmꢁ1):
n 2976, 2960, 2250, 1739, 1661,
d
ꢁ62.6 (s, CF3). IR (KBr, cmꢁ1):
n 2975, 2248, 1738, 1671, 1363,
d
1294, 1192, 1152, 1082, 756. MS (ESI) m/z (%): 426 [(MþNa)]þ.
HRMS (ESI) calcd for C21H20F3N3O2 [(MþNa)]þ: 426.1400, found:
426.1405.
1515, 1360, 1293, 1184, 1157, 1029, 840. MS (ESI) m/z (%): 418
[(MꢁH)]þ. HRMS (ESI) calcd for C21H20F3N3O3 [(MꢁH)]þ: 418.1384,
found: 418.1373.
4.3.4. Methyl 4-(tert-butylamino)-3,3-dicyano-2-(2-nitrophenyl)-5-
(trifluoromethyl)cyclopenta-1,4-dienecarboxylate 4d. White solid;
mp: 177.7e178.1 ꢀC; yield: 86%. 1H NMR (CDCl3, 500 MHz, ppm):
4.3.9. Methyl 4-(tert-butylamino)-3,3-dicyano-2-(m-tolyl)-5-(trifluo-
romethyl)cyclopenta-1,4-dienecarboxylate 4i. White solid; mp:
106.5e108.0 ꢀC; yield: 73%. 1H NMR (CDCl3, 500 MHz, ppm):
d
1.57 (s, 9H), 3.75 (s, 3H), 5.66 (br s, 1H), 7.34e7.36 (m, 1H),
d
1.58 (s, 9H), 2.40 (s, 3H), 3.72 (s, 3H), 5.03 (br s, 1H), 7.07e7.11
7.67e7.71 (m, 1H), 7.75e7.79 (m, 1H), 8.22e8.24 (m, 1H). 13C NMR
(m, 2H), 7.27e7.36 (m, 2H). 13C NMR (CDCl3, 125 MHz, ppm):
(CDCl3, 125 MHz, ppm): d 30.2, 53.6, 55.5, 61.0, 111.8, 112.9, 119.2 (q,
d
21.4, 30.3, 53.3, 60.4, 60.6, 111.5, 113.7, 119.5 (q, 1JCeF¼272.0 Hz,
1JCeF¼272.0 Hz, CF3), 126.4, 127.6, 129.8, 131.7, 134.4, 135.1 (q,
2
CF3), 125.7, 129.4, 129.7, 131.2, 131.3, 133.0 (q, JCeF¼32.8 Hz,
2JCeF¼32.8 Hz, CCF3), 140.9, 147.4, 148.6, 162.4. 19F NMR (CDCl3,
CCF3), 139.5, 141.7, 148.9, 162.9. 19F NMR (CDCl3, 470 MHz, ppm):
470 MHz, ppm):
d
ꢁ62.5 (s, CF3). IR (KBr, cmꢁ1):
n 2979, 2253, 1743,
d
ꢁ62.7 (s, CF3). IR (KBr, cmꢁ1):
n 2978, 2250, 1739, 1663, 1361,
1668, 1527, 1365, 1352, 1283, 1190, 1143, 1033, 762. MS (ESI) m/z (%):
433 [(MꢁH)]þ. HRMS (ESI) calcd for C20H17F3N4O4 [(MꢁH)]þ:
433.1129, found: 433.1114.
1293, 1189, 1157, 1043, 760, 713. MS (ESI) m/z (%): 426 [(MþNa)]þ.
HRMS (ESI) calcd for C21H20F3N3O2 [(MþNa)]þ: 426.1400, found:
462.1408.
4.3.5. Methyl 4-(tert-butylamino)-2-(2-chlorophenyl)-3,3-dicyano-5-
(trifluoromethyl)cyclopenta-1,4-dienecarboxylate 4e. White solid;
mp: 169.8e170.4 ꢀC; yield: 90%. 1H NMR (CDCl3, 500 MHz, ppm):
4.3.10. Methyl 3,3-dicyano-4-(cyclohexylamino)-2-(o-tolyl)-5-(trifluo-
romethyl)cyclopenta-1,4-dienecarboxylate 4j. White solid; mp:
122.7e123.9 ꢀC; yield: 86%. 1H NMR (CDCl3, 500 MHz, ppm):
d
1.56 (s, 9H), 3.76 (s, 3H), 5.70 (br s, 1H), 7.19e7.21 (m, 1H),
d
1.34e1.86 (m, 10H), 2.53 (s, 3H), 3.73 (s, 3H), 4.02e4.06 (m, 1H),
7.34e7.43 (m, 2H), 7.55e7.57 (m, 1H). 13C NMR (CDCl3, 125 MHz,
5.33 (br s,1H), 7.07e7.08 (m,1H), 7.26e7.34 (m, 3H).13C NMR (CDCl3,
ppm):
d
30.2, 53.5, 56.4, 60.9, 111.3, 113.3, 119.3 (q, 1JCeF¼272.2 Hz,
125 MHz, ppm):
d 19.9, 23.4, 25.3, 31.9, 32.2, 37.3, 53.3, 54.9, 64.1,
2
CF3), 127.7, 129.3, 130.3, 130.6, 131.7, 134.1 (q, JCeF¼32.8 Hz,
109.6, 112.4, 119.2 (q, 1JCeF¼272.2 Hz, CF3), 126.9, 127.9, 130.2, 130.3,
CCF3), 135.4, 141.2, 148.3, 162.7. 19F NMR (CDCl3, 470 MHz, ppm):
2
131.5, 131.6 (q, JCeF¼32.8 Hz, CCF3), 137.2, 148.4, 151.0, 162.6. 19F
d
ꢁ62.6 (s, CF3). IR (KBr, cmꢁ1):
n 2976, 2250, 1740, 1672, 1364,
NMR (CDCl3, 470 MHz, ppm):
d
ꢁ62.1 (s, CF3). IR (KBr, cmꢁ1):
n 2934,
1293, 1191, 1157, 1145, 1085, 768. MS (ESI) m/z (%): 422 [(MꢁH)]þ.
HRMS (ESI) calcd for C20H17ClF3N3O2 [(MꢁH)]þ: 422.0889, found:
422.0879.
2251, 1736, 1664, 1375, 1294, 1201, 1160, 1076, 740. MS (ESI) m/z (%):
452 [(MþNa)]þ. HRMS (ESI) calcd for C23H22F3N3O2 [(MþNa)]þ:
452.1556, found: 452.1557.
4.3.6. Methyl 2-(2-bromophenyl)-4-(tert-butylamino)-3,3-dicyano-5-
(trifluoromethyl)cyclopenta-1,4-dienecarboxylate 4f. White solid;
mp: 178.4e179.3 ꢀC; yield: 93%. 1H NMR (CDCl3, 500 MHz, ppm):
4.3.11. Methyl 2-(2-chlorophenyl)-3,3-dicyano-4-(cyclohexylamino)-
5-(trifluoromethyl)cyclopenta-1,4-diene carboxylate 4k. White solid;
mp: 132.3e133.5 ꢀC; yield: 92%. 1H NMR (CDCl3, 500 MHz, ppm):
d
1.56 (s, 9H), 3.76 (s, 3H), 5.72 (br s, 1H), 7.17e7.19 (m, 1H),
7.31e7.42 (m, 2H), 7.73e7.74 (m, 1H). 13C NMR (CDCl3, 125 MHz,
d
1.33e1.86 (m, 10H), 3.78 (s, 3H), 4.03e4.06 (m, 1H), 5.62 (br s, 1H),
7.20e7.21 (m, 1H), 7.34e7.44 (m, 2H), 7.56e7.58 (m, 1H). 13C NMR
ppm):
d
30.1, 53.4, 58.7, 60.7, 111.2, 113.1, 119.3 (q, 1JCeF¼272.2 Hz,
CF3), 126.0, 128.2, 129.4, 131.7, 132.0, 133.8, 133.9 (q, 2JCeF¼32.8 Hz,
(CDCl3, 125 MHz, ppm): d 23.5, 25.4, 32.0, 32.2, 37.2, 53.6, 55.0, 64.3,
109.5, 111.9, 119.3 (q, 1JCeF¼272.5 Hz, CF3), 127.8, 129.3, 130.4, 130.6,
CCF3), 141.2, 148.3, 162.5. 19F NMR (CDCl3, 470 MHz, ppm):
d
ꢁ62.6
2
131.7, 132.6 (q, JCeF¼34.4 Hz, CCF3), 135.2, 148.2, 149.9, 162.4. 19F
(s, CF3). IR (KBr, cmꢁ1):
n 2969, 2250, 1739, 1672, 1363, 1293, 1192,
NMR (CDCl3, 470 MHz, ppm):
d
ꢁ62.1 (s, CF3). IR (KBr, cmꢁ1):
n
1156, 1144, 1084, 761, 594. MS (ESI) m/z (%): 466 [(MꢁH)]þ. HRMS
(ESI) calcd for C20H17BrF3N3O2 [(MꢁH)]þ: 466.0384, found:
466.0385.
2939, 2251, 1742, 1657, 1294, 1199, 1163, 1078, 757. MS (ESI) m/z (%):
472 [(MþNa)]þ. HRMS (ESI) calcd for C22H19ClF3N3O2 [(MþNa)]þ:
472.1010, found: 472.1024.
4.3.7. Methyl 4-(tert-butylamino)-3,3-dicyano-2-(naphthalen-1-yl)-
5-(trifluoromethyl)cyclopenta-1,4-dienecarboxylate 4g. White solid;
mp: 120.1e121.5 ꢀC; yield: 50%. 1H NMR (CDCl3, 500 MHz, ppm):
4.3.12. Methyl 2-(2-bromophenyl)-3,3-dicyano-4-(cyclohexylamino)-
5-(trifluoromethyl)cyclopenta-1,4-diene carboxylate 4l. White solid;
mp: 139.3e140.5 ꢀC; yield: 96%. 1H NMR (CDCl3, 500 MHz, ppm):
d
1.56 (s, 9H), 3.70 (s, 3H), 5.98 (br s, 1H), 7.37e7.38 (m, 1H),
d
1.36e1.86 (m, 10H), 3.77 (s, 3H), 4.03e4.07 (m, 1H), 5.64 (br s, 1H),
7.18e7.20 (m, 1H), 7.31e7.35 (m, 1H), 7.39e7.42 (m, 1H), 7.73e7.75
(m, 1H). 13C NMR (CDCl3, 125 MHz, ppm):
23.5, 25.4, 32.0, 32.2,
7.51e7.54 (m, 1H), 7.61e7.64 (m, 1H), 7.71e7.74 (m, 1H), 7.95e7.97
(m, 1H), 8.12e8.14 (m, 1H). 13C NMR (CDCl3, 125 MHz, ppm):
d
30.2,
1
d
53.4, 55.4, 60.8, 111.3, 114.0, 119.4 (q, JCeF¼272.2 Hz, CF3), 122.0,
125.1, 126.8, 127.0, 128.1, 128.2, 129.5, 131.1, 131.6, 133.6 (q,
2JCeF¼32.8 Hz, CCF3), 134.1, 141.5, 149.3, 163.0. 19F NMR (CDCl3,
1
37.2, 53.6, 57.4, 64.3, 109.5, 111.9, 119.3 (q, JCeF¼272.5 Hz, CF3),
125.9, 128.4, 129.5,131.9,132.2,132.6 (q, 2JCeF¼34.4 Hz, CCF3),133.9,
148.2, 150.1, 162.3. 19F NMR (CDCl3, 470 MHz, ppm):
d
ꢁ62.1 (s, CF3).
470 MHz, ppm):
d
ꢁ62.5 (s, CF3). IR (KBr, cmꢁ1):
n 2980, 2249, 1732,
IR (KBr, cmꢁ1):
n 2938, 2252, 1741, 1656, 1294, 1198, 1162, 1078, 736,
1666, 1359, 1290, 1192, 1152, 1086, 779. MS (ESI) m/z (%): 462

Y. Lv et al. / Tetrahedron 69 (2013) 4205e4210
4209
605. MS (ESI) m/z (%): 516 [(MþNa)]þ. HRMS (ESI) calcd for
C22H19BrF3N3O2 [(MþNa)]þ: 516.0505, found: 516.0515.
1174, 1130, 1054, 761. MS (ESI) m/z (%): 507 [(MþNa)]þ. HRMS (ESI)
calcd for C21H17F5N4O4 [(MþNa)]þ: 507.1062, found: 507.1054.
4.3.13. Methyl 3,3-dicyano-4-(cyclohexylamino)-2-(2-nitrophenyl)-
5-(trifluoromethyl)cyclopenta-1,4-dienecar boxylate 4m. Pale yellow
solid; mp: 158.5e159.7 ꢀC; yield: 95%. 1H NMR (CDCl3, 500 MHz,
4.3.18. Methyl 4-(tert-butylamino)-3,3-dicyano-5-(heptafluoro-pro-
pyl)-2-(o-tolyl)cyclopenta-1,4-dienecarboxylate 4r. White solid; mp:
122.3e123.7 ꢀC; yield: 63%. 1H NMR (CDCl3, 500 MHz, ppm):
d
1.54
(s, 9H), 2.52 (s, 3H), 3.70 (s, 3H), 5.40 (br s, 1H), 7.03e7.04 (m, 1H),
7.28e7.35 (m, 3H). 13C NMR (CDCl3, 125 MHz, ppm):
20.0, 30.1,
ppm):
d 1.34e1.91 (m, 10H), 3.75 (s, 3H), 4.08e4.11 (m, 1H), 5.56
(s, 1H), 7.35e7.37 (m, 1H), 7.68e7.71 (m, 1H), 7.76e7.79
d
(m, 1H), 8.22e8.24 (m, 1H). 13C NMR (CDCl3, 125 MHz, ppm):
53.2, 56.6, 60.8, 108.9 (m, CF2), 111.4, 113.2 (m, CF2), 113.9, 117.8 (qt,
d
23.5, 25.3, 31.9, 32.1, 38.5, 53.7, 54.2, 64.3, 110.0, 111.6, 119.2
1JCeF¼287.8 Hz, 2JCeF¼34.0 Hz, CF3), 127.0, 127.9, 130.3, 130.4, 131.6,
1
2
(q, JCeF¼272.5 Hz, CF3), 126.3, 127.5, 130.1, 131.7, 133.5
132.8 (t, JCeF¼23.2 Hz, CCF2), 137.5, 141.9, 152.6, 163.0. 19F NMR
(q, JCeF¼34.4 Hz, CCF3), 134.5, 148.0, 148.6, 149.1, 162.1. 19F NMR
(CDCl3, 470 MHz, ppm):
d
ꢁ80.7 (t, J¼9.4 Hz, CF3), ꢁ108.0 (m, CF2),
2
(CDCl3, 470 MHz, ppm):
d
ꢁ62.0 (s, CF3). IR (KBr, cmꢁ1):
n
2937,
ꢁ122.7 (m, CF2). IR (KBr, cmꢁ1):
n 2983, 2254,1750,1363,1253,1208,
2252, 1736, 1660, 1532, 1354, 1288, 1203, 1150, 1072, 724. MS (ESI)
m/z (%): 483 [(MþNa)]þ. HRMS (ESI) calcd for C22H19F3N4O4
[(MþH)]þ: 461.1431, found: 461.1436.
1187, 1124, 1016, 751. MS (ESI) m/z (%): 526 [(MþNa)]þ. HRMS (ESI)
calcd for C23H20F7N3O2 [(MþNa)]þ: 526.1336, found: 526.1355.
4.3.19. Methyl 4-(tert-butylamino)-2-(2-chlorophenyl)-3,3-dicyano-
4.3.14. Methyl 4-(tert-butylamino)-3,3-dicyano-5-(pentafluoroethyl)-
2-(o-tolyl)cyclopenta-1,4-dienecarboxylate 4n. White solid; mp:
5-(heptafluoropropyl)cyclopenta-1,4-dienecarboxylate
solid; mp: 143.0e143.8 ꢀC; yield: 92%. 1H NMR (CDCl3, 500 MHz,
ppm): 1.56 (s, 9H), 3.74 (s, 3H), 5.75 (br s, 1H), 7.18e7.19 (m, 1H),
7.35e7.43 (m, 2H), 7.55e7.57 (m, 1H). 13C NMR (CDCl3, 125 MHz,
ppm): 30.1, 53.4, 56.6, 60.9, 108.8 (m, CF2), 111.3, 113.1 (m, CF2),
4s. White
120.5e121.3 ꢀC; yield: 64%. 1H NMR (CDCl3, 500 MHz, ppm):
d
1.54
(s, 9H), 2.52 (s, 3H), 3.70 (s, 3H), 5.39 (br s, 1H), 7.01e7.03 (m, 1H),
7.26e7.35 (m, 3H). 13C NMR (CDCl3, 125 MHz, ppm):
20.0,
30.2, 53.3, 56.5, 60.8, 111.0 (m, CF2), 111.4, 113.9, 118.5
d
d
d
1
2
113.3, 117.6 (qt, JCeF¼287.5 Hz, JCeF¼34.1 Hz, CF3), 127.8, 129.3,
1
2
(qt, JCeF¼287.8 Hz, JCeF¼36.3 Hz, CF3), 127.0, 127.9, 130.3, 130.4,
130.3, 130.6, 131.7, 133.7 (t, 2JCeF¼23.1 Hz, CCF2), 135.4, 141.5, 151.5,
131.6,132.5 (t, 2JCeF¼23.0 Hz, CCF2),137.5,141.7,152.5,163.1. 19F NMR
162.6. 19F NMR (CDCl3, 470 MHz, ppm):
d
ꢁ80.7 (t, J¼9.4 Hz,
(CDCl3, 470 MHz, ppm):
cmꢁ1):
d
ꢁ81.2 (s, CF3), ꢁ111.0 (m, CF2). IR (KBr,
CF3), ꢁ108.1 (m, CF2), ꢁ122.8 (m, CF2). IR (KBr, cmꢁ1):
n 2983, 2254,
n
2983, 2251, 1750, 1657, 1256, 1221, 1174,1129, 1055, 754. MS
1748, 1356, 1255, 1233, 1208, 1189, 1122, 1016, 755. MS (ESI) m/z (%):
546 [(MþNa)]þ. HRMS (ESI) calcd for C22H17ClF7N3O2 [(MþNa)]þ:
546.0790, found: 546.0797.
(ESI) m/z (%): 476 [(MþNa)]þ. HRMS (ESI) calcd for C22H20F5N3O2
[(MþNa)]þ: 476.1368, found: 476.1385.
4.3.15. Methyl 4-(tert-butylamino)-2-(2-chlorophenyl)-3,3-dicyano-5-
(pentafluoroethyl)cyclopenta-1,4-dienecarboxylate 4o. White solid;
mp: 137.2e137.9 ꢀC; yield: 96%. 1H NMR (CDCl3, 500 MHz, ppm):
Acknowledgements
The authors are grateful to the National Natural Science Foun-
dation of China (Grant No. 21072126, 21272152) and Leading
Academic Discipline Projects of Shanghai Municipal Education
Commission (Grant No. J50102) for their financial support.
d
1.54 (s, 9H), 3.75 (s, 3H), 5.70 (br s,1H), 7.14e7.15 (m,1H), 7.35e7.43
(m, 2H), 7.55e7.57 (m, 1H). 13C NMR (CDCl3, 125 MHz, ppm):
d 30.1,
53.4, 56.6, 60.9, 111.0 (m, CF2), 111.3, 113.3, 118.4 (qt, 1JCeF¼288.0 Hz,
2JCeF¼36.2 Hz, CF3), 127.8, 129.3, 130.3, 130.5, 131.7, 133.4
(t, JCeF¼23.0 Hz, CCF2), 135.4, 141.4, 151.5, 162.7. 19F NMR (CDCl3,
2
Supplementary data
470 MHz, ppm):
n
d
ꢁ81.2 (s, CF3), ꢁ111.1 (m, CF2). IR (KBr, cmꢁ1):
2983, 2253, 1748,1657, 1257, 1221, 1175, 1046, 751. MS (ESI) m/z (%):
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2013.03.093. These data include MOL files
and InChiKeys of the most important compounds described in this
article.
496 [(MþNa)]þ. HRMS (ESI) calcd for C21H17ClF5N3O2 [(MþNa)]þ:
496.0822, found: 496.0825.
4.3.16. Methyl 2-(2-bromophenyl)-4-(tert-butylamino)-3,3-dicyano-
5-(pentafluoroethyl)cyclopenta-1,4-dienecarboxylate 4p. White solid;
References and notes
1
mp: 148.5e149.7 ꢀC; yield: 90%. H NMR (CDCl3, 500 MHz, ppm):
1. Trost, B. M. Science 1991, 254, 1471.
d
1.54 (s, 9H), 3.74 (s, 3H), 5.72 (br s, 1H), 7.11e7.13 (m, 1H), 7.31e7.34
(m, 1H), 7.39e7.43 (m, 1H), 7.73e7.74 (m, 1H). 13C NMR (CDCl3,
125 MHz, ppm): 30.1, 53.5, 59.1, 61.0, 111.0 (m, CF2), 111.3, 113.3,
2. (a) Isonitrile Chemistry; Ugi, I., Ed.; Academic: New York, NY, 1971; (b) Ugi, I.;
€
DOmling, A.; Horl, W. Endeavour 1994, 18, 115; (c) Multicomponent Reactions;
d
ꢀ
Zhu, J., Bienayme, H., Eds.; Wiley-VCH: Weinheim, Germany, 2005; (d)
1
2
€
118.4 (qt, JCeF¼287.8 Hz, JCeF¼36.4 Hz, CF3), 126.1, 128.4, 129.4,
DOmling, A. Chem. Rev. 2006, 106, 17; (e) Toure, B. B.; Hall, D. G. Chem. Rev. 2009,
131.9, 132.1, 133.3 (t, 2JCeF¼23.0 Hz, CCF2),133.9,141.3,151.6,162.7.19
F
109, 4439; (f) Sunderhaus, J. D.; Martin, S. F. Chem.dEur. J. 2009, 15, 1300; (g)
Isambert, N.; Lavilla, R. Chem.dEur. J. 2008, 14, 8444; (h) Ganem, B. Acc. Chem.
Res. 2009, 42, 463.
NMR (CDCl3, 470 MHz, ppm):
d
ꢁ81.1 (s, CF3), ꢁ111.1 (m, CF2). IR (KBr,
cmꢁ1):
n 2985, 2251, 1739, 1658, 1274, 1205, 1173, 1128, 1050, 766,
3. For recent examples on isocyanide chemistry, see: (a) Kim, J.; Schneekloth, J.
S.; Sorensen, E. J. Chem. Sci. 2012, 3, 2849; (b) Bhojgude, S. S.; Biju, A. T.
Angew. Chem., Int. Ed. 2012, 51, 1520; (c) Khoury, K.; Sinha, M. K.; Nagashima,
598. MS (ESI) m/z (%): 540 [(MþNa)]þ. HRMS (ESI) calcd for
C21H17BrF5N3O2 [(MþNa)]þ: 540.0317, found: 540.0339.
€
T.; Herdtweck, E.; DOmling, A. Angew. Chem., Int. Ed. 2012, 51, 10280; (d)
€
Huang, Y. J.; Khoury, K.; Chanas, T.; DOmling, A. Org. Lett. 2012, 14, 5916; (e)
Spisa, F. L.; Feo, A.; Mossetti, R.; Tron, G. C. Org. Lett. 2012, 14, 6044; (f)
Castellano, T. G.; Neo, A. G.; Marcaccini, S.; Marcos, C. F. Org. Lett. 2012, 14,
6218; (g) Moliner, F. D.; Hulme, C. Org. Lett. 2012, 14, 1354; (h) Masui, H.; Fuse,
S.; Takahashi, T. Org. Lett. 2012, 14, 4090; (i) Sha, F.; Wu, L. L.; Huang, X. J. Org.
Chem. 2012, 77, 3754; (j) Perez-Labrada, K.; Brouard, I.; Mendez, I.; Rivera, D. G.
J. Org. Chem. 2012, 77, 4660; (k) Terzidis, M. A.; Zarganes-Tzitzikas, T.; Tsime-
nidis, C.; Stephanidou-Stephanatou, J.; Tsoleridis, C. A.; Kostakis, G. E. J. Org.
Chem. 2012, 77, 9018; (l) Sun, H. P.; Zhou, H. Y.; Khorev, O.; Jiang, R. W.; Yu, T.;
Wang, X.; Du, Y. L.; Ma, Y.; Meng, T.; Shen, J. K. J. Org. Chem. 2012, 77, 10745;
(m) Qiu, G.; Liu, G.; Pu, S. Z.; Wu, J. Chem. Commun. 2012, 2903; (n) Li, J.; Liu, Y. J.;
Li, C. J.; Jie, H. H.; Jia, X. S. Green Chem. 2012, 14, 1314; (o) Khan, A. T.; Basha, R. S.;
Lal, M.; Mir, M. H. RSC Adv. 2012, 2, 5506; (p) Li, J.; Wang, N.; Li, C. J.; Jia, X. S.
Chem.dEur. J. 2012, 18, 9645.
4.3.17. Methyl 4-(tert-butylamino)-3,3-dicyano-2-(2-nitrophenyl)-5-
(pentafluoroethyl)cyclopenta-1,4-dienecarboxylate 4q. White solid;
mp: 154.1e155.3 ꢀC; yield: 95%. 1H NMR (CDCl3, 500 MHz, ppm):
ꢀ
ꢀ
d
1.55 (s, 9H), 3.74 (s, 3H), 5.66 (br s, 1H), 7.28e7.30 (m, 1H),
7.67e7.71 (m, 1H), 7.76e7.79 (m, 1H), 8.22e8.24 (m, 1H). 13C NMR
(CDCl3, 125 MHz, ppm): 30.1, 53.6, 55.8, 61.1, 110.9 (m, CF2), 111.9,
d
1
2
112.9, 118.4 (qt, JCeF¼287.8 Hz, JCeF¼36.1 Hz, CF3), 126.4, 127.6,
129.8, 131.8, 134.4 (t, 2JCeF¼23.0 Hz, CCF2), 134.6, 141.1, 148.7, 150.6,
162.6. 19F NMR (CDCl3, 470 MHz, ppm):
d
ꢁ80.9 (s, CF3), ꢁ111.1 (m,
CF2). IR (KBr, cmꢁ1):
n 2985, 2253,1739,1657,1533,1348,1272,1207,

4210
Y. Lv et al. / Tetrahedron 69 (2013) 4205e4210
4. (a) Rajakumar, P.; Kannan, A.; Sujatha, R. Synth. Commun. 1994, 24, 1847; (b)
Kumar, P. R. J. Chem. Soc., Chem. Commun. 1989, 509; (c) Mori, M.; Nojima, M.;
Kusabayashi, S. J. Am. Chem. Soc. 1987, 109, 4407; (d) The DielseAlder Reaction:
Selected Practical Methods; Fringuelli, F., Taticchi, A., Eds.; Wiley: New York, NY,
2002.
5. (a) Kanthak, M.; Aniol, A.; Nestola, M.; Merz, K.; Oppel, I. M.; Dyker, G.
Organometallics 2011, 30, 215; (b) Schumann, H.; Stenz, S.; Grigsdies, F.; Muhle,
S. H. Z. Naturforsch., B: J. Chem. Sci. 2002, 57,1017; (c) Xu, S. S.; Yuan, F.; Zhuang, Y.;
Wang, B. Q.; Li, Y. F.; Zhou, X. Z. Inorg. Chem. Commun. 2002, 5, 102; (d)
Legzdins, P.; Reina, R.; Shaw, M. J.; Batchelor, R. J.; Einstein, F. W. B.
Organometallics 1993, 12, 1029.
6. (a) King, R. B. Coord. Chem. Rev. 1976, 20, 155; (b) Macomber, D. W.; Hart, W. P.;
Rausch, M. D. Adv. Organomet. Chem. 1982, 21, 1; (c) Gassman, P. G.;
Macomber, D. W.; Hershberger, J. W. Organometallics 1983, 2, 1470 and
references therein.
7. (a) Quindt, V.; Saurenz,D.; Schmitt, O.;SchFr, M.; Dezember, T.;WolmershFuser, G.;
Sitzmann, H. J. Organomet. Chem. 1999, 579, 376 and references therein; (b)
Rausch, B. J.; Gleiter, R.; Rominger, F. J. Organomet. Chem. 2002, 658, 242.
8. (a) Venier, C. G.; Casserly, E. W. J. Am. Chem. Soc. 1990, 112, 2808; (b) Duan, Z.;
Sun, W. H.; Liu, Y.; Takahashi, T. Tetrahedron Lett. 2000, 41, 7471; (c) Fang, H.;
Zhao, C.; Li, G.; Xi, Z. Tetrahedron 2003, 59, 3779 and references therein; (d)
Zhou, S.; Yan, B.; Liu, Y. J. Org. Chem. 2005, 70, 4006; (e) Datta, S.; Odedra, A.;
Liu, R. S. J. Am. Chem. Soc. 2005, 127, 11606.
10. (a) Chambers, R. D.; Mullins, S. J.; Roche, A. J.; Vaughan, J. F. S. J. Chem. Soc.,
Chem. Commun. 1995, 841; (b) Laganis, E. D.; Lemal, D. M. J. Am. Chem. Soc. 1980,
102, 6633; (c) Burk, M. J.; Arduengo, A. J., III; Calabrese, J. C.; Harlow, R. L. J. Am.
Chem. Soc. 1989, 111, 8938.
11. (a) Nair, V.; Vinod, A. U. Chem. Commun. 2000, 1019; (b) Nair, V.; Vinod, A. U.;
Rajesh, C. J. Org. Chem. 2001, 66, 4427; (c) Nair, V.; Vinod, A. U.; Abhilash, N.;
Menon, R. S.; Santhi, V.; Varma, L. R.; Viji, S.; Mathew, S.; Srinivas, R. Tetrahedron
2003, 59, 10279; (d) Nair, V.; Menon, R. S.; Beneesh, P. B.; Sreekumar, V.; Bindu,
S. Org. Lett. 2004, 6, 767.
12. CCDC 890131 (4c) contains all crystallographic details of this publication and is
available free of charge at www.ccdc.cam.ac.uk/consts/retrieving.html or can
be ordered from the following address: Cambridge Crystallographic Data
Centre, 12 Union Road, GB-Cambridge CB21EZ; fax: þ44 1223 336 033; or
ꢁ
deposit@ccdc.cam.ac.uk. Unit cell parameters (4c): a: 20.349(14) A; b: 9.
195(7) A; c: 23.382(16) A;
: 90ꢀ; : 90ꢀ; : 90ꢀ; space group: Pbca.
b g
ꢁ
ꢁ
a
ꢀ
13. (a) Hamper, B. C. Org. Synth. 1992, 70, 246; (b) Jeannin, O.; Fourmigue, M.
Chem.dEur. J. 2006, 12, 2994.
14. (a) Guo, K.; Thompson, M. J.; Chen, B. J. Org. Chem. 2009, 74, 6999; (b) Dieskau, A. P.;
Holzwarth, M. S.; Plietker, B. Chem.dEur. J. 2012,18, 2423; (c) Wang, X. S.; Zeng, Z. S.;
Li, Y. L.; Shi, D. Q.; Tu, S. J.; Wei, X. Y.; Zong, Z. M. Synth. Commun. 2005, 35,1915; (d)
Shi, D. Q.; Wang, X. S.; Yao, C. S.; Mu, L. L. J. Chem. Res., Synop. 2002, 344; (e)
Song, Y. Y.; Jing, H. W.; Li, B.; Bai, D. S. Chem.dEur. J. 2011, 17, 8731; (f) Yang, X. H.;
Fox, T.; Berke, H. Org. Biomol. Chem. 2012, 10, 852; (g) Curini, M.; Epifano, F.;
Marcotullio, M. C.; Rosati, O.; Tsadjout, A. Synth. Commun. 2002, 32, 355; (h)
9. (a) O’Neal, K. L.; Zhang, H.; Yang, Y.; Hong, L.; Lu, D.; Weber, S. G. J.
Chromatogr., A 2010, 1217, 2287; (b) Zhang, W. Chem. Rev. 2009, 109, 749;
(c) Zhang, W. Green Chem. 2009, 11, 911; (d) Thayer, A. M. Chem. Eng. News
2006, 84, 15.
€
€
€
Mantri, M.; Graaf, O. D.; Veldhoven, J. V.; GOblyOs, A.; KUnzel, J. K. V. F. D.;
Mulder-Krieger, T.; Link, R.; Vries, H. D.; Beukers, M. W.; Brussee, J.; IJzerman, A. P.
J. Med. Chem. 2008, 51, 4449.