The reaction of acyl cyanides with "huisgen zwitterion": An interesting rearrangement involving ester group migration between oxygen and nitrogen atoms

Article abstract of DOI:10.1039/b913196e

A novel rearrangement involving ester group migration was found in the reaction of acyl cyanides and Huisgen zwitterions, affording hydrazone derivatives at higher temperature (90 °C) and azine derivatives at lower temperature (20 °C), respectively. Inter

Full text of DOI:10.1039/b913196e

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The reaction of acyl cyanides with “Huisgen zwitterion”: an interesting
rearrangement involving ester group migration between oxygen and
nitrogen atoms†
Xu-Guang Liu,a Yin Wei*b and Min Shi*a,b
Received 2nd July 2009, Accepted 24th August 2009
First published as an Advance Article on the web 17th September 2009
DOI: 10.1039/b913196e
A novel rearrangement involving ester group migration was found in the reaction of acyl cyanides
and Huisgen zwitterions, affording hydrazone derivatives at higher temperature (90 ◦C) and azine
derivatives at lower temperature (20 ◦C), respectively. Interestingly, the reaction temperature is
identified as a critical factor to control the final products. Presumably, the rearrangement involving
ester group migration between oxygen and nitrogen atoms leads to the formation of different products.
Introduction
Nucleophilic phosphine organocatalysis has drawn remarkable
attention and become a highly dynamic chemical research area
due to its wide applicability in organic synthesis.1 Phosphines
Scheme 1 Huisgen zwitterions.
have proven to be particular versatile as catalysts or reagents
in many types of reactions.2 One of these reactions is the Mit-
zwitterions and as a part of our continuing interest on nucleophilic
sunobu reaction,3 in which the “Huisgen zwitterion”4 formed by
phosphine and amine mediated or catalyzed reactions,11 we sys-
phosphines and azodicarboxylates plays a crucial role (Scheme 1).
tematically investigated the reactions of Huisgen zwitterions with
Although the Huisgen zwitterions can be applied in preparation of
acyl cyanides. Herein, we are delighted to report our novel findings
synthetically useful compounds such as vinyl hydra-a-ketoesters,5
in these reactions. The results of our studies provide an alternative
and protected hydrazones from salicylaldehydes,6 the chemistry
way to synthesize medically and synthetically interesting azine and
hydrazone derivatives.12
of Huisgen zwitterions has received limited attention until re-
cent years. Recently, a number of interesting reactions including
the reaction of this zwitterion with various carbonyl compounds
have been explored. In 2005, Lee and co-workers have reported
the reaction of the zwitterions with aliphatic aldehydes and
a-ketoesters for the synthesis of bisadducts and oxadiazolines.7
The Huisgen zwitterions have also been systemically studied by
Nair’s group, which led to fruitful results for the synthesis of
N,N-dicarboethoxy monohydrazones, dihydro-1,2,3-benzoxa-
Results and discussion
On the basis of the previous investigation, it was known that
both steric and electronic properties of phosphines may affect
dramatically the outcome of the reaction.13 Therefore, we initiated
our investigation by seeking an optimal phosphine promoter for
the reaction between acyl cyanides 1a and diisopropyl azodicar-
boxylate (DIAD) 2a (Table 1, entries 1–5). The results revealed
that triphenylphosphine was the best promoter in this reaction,
yielding the product in 98% yield (Table 1, entry 1). However,
other phosphines gave poor results, with yields of less than 80%,
presumably due to the different nucleophilicity of the employed
phosphines (Table 1, entries 2-4). The structure of product 3a
was assigned based on spectroscopic data. Unambiguous evidence
for structure of 3c (Table 2, entry 3) was obtained from single-
crystal X-ray analysis (Fig. 1),14 which showed both of the
carboisopropoxy groups on the same nitrogen atom (Fig. 1).
Triphenylphosphine oxide was also isolated from the reaction
mixture, which indicated that triphenylphosphine participated in
the reaction and was oxidized into triphenylphosphine oxide.
During the optimization of reaction conditions, we were
surprised to find that reducing the reaction temperature to room
temperature (20 ◦C) led to totally different products. The 1H
NMR data implied that the two isopropyl groups were separated
far away from each other, which were different from the previously
observed chemical shifts of product 3. It was initially difficult to
diazoles, functional pyrazoles and pyrazolines, as well as pyra-
zolopyridazine derivatives through the reactions involving the
Huisgen zwitterions.8 Very recently, Wang and co-workers re-
ported the reaction of 2-acylaziridines with the Huisgen zwitte-
rions to furnish the 2-pyrazoline ring with excellent yields.9
Acyl cyanides have proven to be extremely useful reagents in
organic synthesis due to the electrophilicity of both functions in
acyl cyanides being enhanced by the proximity of the CO and CN
groups.10 Inspired by previous work on the chemistry of Huisgen
aSchool of Chemistry & Molecular Engineering, East China University of
Science and Technology130 Mei Long Road, Shanghai, 200237, China.
Fax: 86-21-64166128
bState Key Laboratory of Organometallic Chemistry, Shanghai Institute of
Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shang-
hai, 200032, China. E-mail: weiyin@mail.sioc.ac.cn, Mshi@mail.sioc.ac.cn
† Electronic supplementary information (ESI) available: 13C and 1H NMR
spectroscopic and analytic data for all new compounds shown in Tables 1–
3 and X-ray crystal data of 3c and 4g. CCDC reference numbers 713523
& 724590. For ESI and crystallographic data in CIF or other electronic
format see DOI: 10.1039/b913196e
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Table 1 Phosphine-mediated reaction of dialkyl azodicarboxylate with
Table 2 Triphenylphosphine-mediated reaction of dialkyl azodicarboxy-
acyl cyanidesa
late with acyl cyanides at 90 ◦Ca
entry
R1
R2
Product
yield/3b
Yield Yield
Temperature/◦C Time/h (3a)b
(4a)b
1
2
3
4
5
6
7
8
(1a) H
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
Et
3a
3b
3c
3d
3e
3f
3g
3h
3i
98
95
73
68
81
92
88
80
90
74
73
84
87
Entry PR3
(1b) 4-Br
c
(1c) 4-Cl
(1d) 3-CF3
(1e) 2-Cl
(1f) 4-CH3
(1g) 4-OCH3
(1h) 3,5-2CH3
(1i) 3,4,5-3OCH3
(1a) H
1
2
3
4
PPh3
90
90
90
90
90
20
1
3
3
3
3
1
1
1
1
1
1
1
98
81
46
53
68
—
—
—
—
—
—
—
—
PPh2Me
PPhMe2
PBu3
—
—
—
—
71
62
73
46
50
72
62
5
6
P(OEt)3
PPh3
9
7
8
9
P(4-OMeC6H4)3 20
P(4-FC6H4)3
PBu3
10
11
12
13
3j
3k
3l
20
20
20
20
20
(1b) 4-Br
(1g) 4-OCH3
(1j)
Et
Et
i-Pr
10
11
12
P(OEt)3
PPh2Me
PPhMe2
3m
a Reactions were carried out with 1a (0.3 mmol), 2a (0.3 mmol), phosphine
(0.3 mmol) in 2 mL of toluene. b Yield of isolated product. c Not detected.
14
15
(1k)
(1l)
i-Pr
i-Pr
3n
3o
68
82
16
(1m)
i-Pr
3p
88
a Reactions were carried out with 1 (0.3 mmol); 2 (0.3 mmol), PPh3
(0.3 mmol) in toluene (2 mL) at 90 ◦C. b Isolated yield.
Fig. 1 Single-crystal X-ray structure of 3c.
assign the structures of the new products until the single-crystal
X-ray analysis of the product 4g (Table 3, entry 7) was obtained
from the product of the reaction between the 3,4,5-trimetho-
xybenzoyl cyanide and 2a (Fig. 2).15 From the X-ray analysis, we
can see that one of the isopropyl carboxy groups was isomerized,
and another isopropyl carboxy group was connected to the
oxygen atom of the isomerized isopropyl carboxy group (Fig. 2).
Similarly, several commonly used phosphines were investigated
to this reaction at room temperature, and the results were
also summarized in Table 1 (entries 6–12). Triphenylphosphine
was still better than other phosphines, such as PBu3, P(OEt)3,
to give the product 4a in 71% yield (Table 1, entries 9–12).
Further examination revealed that the triphenylphosphines with
different substituents influenced the yield slightly (Table 1, entries
6–8). The electron-withdrawing substituent on the benzene ring
of triphenylphosphine led to increasing the yield of 4a slightly
(Table 1, entry 8). Compromise the yield on the experimental cost,
Fig. 2 Single-crystal X-ray structure of 4g.
the cheaper triphenylphosphine was chosen as the best promoter
at room temperature (20 ◦C) for this reaction.
Having identified the optimal phosphine promoter for the
efficient syntheses of the products at two different temperatures
prompted us to probe the scope of the reaction using various
acyl cyanides (Table 2 and 3). First, the generality of the reaction
was investigated at 90 ◦C (Table 2, entries 1–16). In the pres-
ence of triphenylphosphine, the diazoester 2a reacted with both
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Table 3 Phosphine-mediated reaction of dialkyl azodicarboxylate with
acyl cyanides at room temperature (20 ◦C)a
Scheme 2 Reaction of the Huisgen zwittern obtained from DIAD and
triethyl phosphite with 1-(4-chlorophenyl)-2,2,2-trifluoroethanone 5.
We have examined the performance of aliphatic cyanides for this
reaction. Unfortunately, the aliphatic cyanides were not suitable
for this reaction under the identified optimal reaction conditions.
Although we attempted many times to improve the reactions of
pivaloyl cyanide with DIAD or DEAD, only small amounts of
the mono(alkoxycarbony)hydrazones as those obtained in Nair’s
system8e were isolated (Scheme 3).
Entry
R1
R2
Product
Yield (4)b
1
2
3
4
5
6
7
8
H
4-Br
4-Cl
4-CH3
4-OCH3
3,5-2CH3
3,4,5-3OCH3
3,4,5-3OCH3
4-OCH3
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
Et
4a
4b
4c
4d
4e
4f
71
68
69
87
99
86
87
79
70
73
4g
4h
4i
9
10
Et
i-Pr
4j
11
i-Pr
4k
60
Scheme 3 The reaction between pivaloyl cyanide and DEAD/DIAD.
a Reactions were carried out with 1 (0.3 mmol), 2 (0.3 mmol), PPh3
(0.3 mmol) in toluene (2 mL) at room temperature (20 ◦C). b Isolated
yield.
In 2007, Nair’s group has reported that the Huisgen zwitterions
with simple electron-deficient alkenes could afford pyrazolines in
moderate to good yields. Inspired by this work, we investigated fur-
ther the scope of reaction. The (E)-3-(furan-2-yl)acryloyl cyanide
1n was synthesized and employed as the substrate to examine
its reaction with Huisgen zwitterion in the presence of P(OEt)3
(Scheme 4). The reaction afford a product that was subsequently
characterized as the pyrazoline derivative 9 (Scheme 4, 50% yield).
This demonstrated that the a,b-unsaturated acyl cyanides do not
undergo the rearrangement, the reactions proceeding as found by
Nair’s group.
electron-deficient and electron-rich acyl cyanides to provide the
dialkyl monohydrazones in good to excellent isolated yields
(Table 2, entries 1–9). Similar results were obtained with respect
to DEAD (Table 2, entries 10–12). Notably, the heteroaryl
cyanides and 1-naphthoyl cyanide also proceeded smoothly to
give high yields under the optimal reaction conditions (Table 2,
entries 13–16).
Furthermore, the scope of the reaction was examined again at
room temperature (20 ◦C) using various acyl cyanides (Table 3,
entries 1–11). In general, the electron-rich acyl cyanides gave the
products in high yields, while the electron-deficient acyl cyanides
produced the products in slightly lower yields (Table 3, entries 1–7).
Instead of DIAD, diethyl azocarboxylate (DEAD) also displayed
good reactivity with acyl cyanides in this reaction (Table 3, entries 8
and 9). It should be noted that 1-naphthoyl cyanide and thiophene-
3-carbonyl cyanide also worked very well under the optimized
reaction conditions (Table 3, entries 10 and 11).
Further, we investigated whether this reaction could proceed
using other analogues, for instance, using analogues replaced
the CN group of acyl cyanides by another strong electron-
withdrawing group CF3.16 Thus, we conducted the reaction
of 1-(4-chlorophenyl)-2,2,2-trifluoroethanone with the DIAD
in the presence of phosphine. Fortunately, the corresponding
bis(alkoxycarboxy)hydrazone 6 was obtained in the reaction
between the 1-(4-chlorophenyl)-2,2,2-trifluoroethanone (5) and
the DIAD (2a) in the presence of P(OEt)3, although the yield
was moderate (Scheme 2). It should be mentioned that triflu-
oromethylated compounds have received considerable attention,
and they have diverse applications in the area of materials science,
agrochemistry and biomedical chemistry due to their unique
chemical, physical, and biological properties.17
Scheme 4 The reaction between DIAD and a,b-unsaturated acyl
cyanides 1n.
We also found that the products 4 could be transformed to
products 3 very slowly if we prolonged the reaction time at room
temperature. Based on our observations, we hypothesized that
the products 4 might be the intermediate in the formation of
the products 3 and could be converted to the products 3 upon
heating. Thus, we heated 4a at 90 ◦C in toluene without phosphine.
As expected, 4a was easily converted to 3a in toluene at 90 ◦C
only within 1 h, furnishing the product 3a in 80% isolated yield
(Scheme 5).
A reaction mechanism for the reaction of acyl cyanides with
Huisgen zwitterions is proposed in Scheme 6. Presumably, the
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For thin-layer chromatography (TLC), silica gel plates (Huanghai
GF254) were used. Elementary analysis was taken on a Carlo-
Erba 1106 analyzer. Mass spectra were recorded by EI, ESI, and
HRMS were measured on a HP-5989 instrument. All reactions
were performed under argon. The starting materials 1a–m were
synthesized according to the previous literature.18
Scheme 5 Product 4a can be converted to 3a upon heating.
Typical reaction procedure for the preparation of 3
Diisopropyl azodicarboxylate/diethyl azodicarboxylate
2
(0.3 mmol) was added to a stirred solution of acyl cyanide 1
(0.3 mmol) and Ph3P (0.3 mmol) in anhydrous toluene (2.0 mL)
under argon at 90 ◦C, and the mixture was maintained at 90 ◦C to
stir for the required time. The solvent was removed under reduced
pressure on a rotary evaporator. The residue was subjected to
column chromatography on silica gel (300–400 mesh) to afford
the products 3.
(Z)-Diisopropyl-2-(cyano(phenyl)methylene)hydrazine-1,1-di-
carboxylate (3a). Oil. IR (CH2Cl2) n 2985, 2940, 2228, 1791,
1763, 1358, 1304, 1231, 1094, 910 cm-1; 1H NMR (CDCl3,
300 MHz, TMS): d 1.38 (12H, d, J = 6.3 Hz, CH3), 5.12–5.21
(2H, m, CH), 7.51 (2H, t, J = 6.9 Hz, Ar), 7.61 (1H, t, J = 7.8 Hz,
Ar), 8.04 (2H, d, J = 7.5 Hz, Ar). 13C NMR (CDCl3, 75 MHz): d
21.6, 73.0, 109.8, 127.9, 129.1, 130.4, 133.2, 146.0, 150.4. MS (ESI)
m/z 318.2 (M++1). HRMS (ESI) calcd for C16H19N3O4 requires
(M++1) 318.1376, found 318.14538.
Scheme 6 Plausible reaction mechanism for the reaction.
combination of PPh3 and diisopropyl azodicarboxylate 2a gen-
erates the Huisgen zwitterion A, which undergoes addition to
the carbonyl group of the acyl cyanide to form B. Subsequently
B undergoes cyclization to form five-membered intermediate C
which then decomposes to triphenylphosphine oxide and the in-
termediate D. Then, the intermediate D rearranges to the product
4a by a nitrogen-to-oxygen migration of the alkoxycarbonyl group
(the first migration at room temperature. The carbon-oxygen bond
of 4a is cleaved upon heating, which is followed by an oxygen-
to-nitrogen migration of the alkoxycarbonyl group affording
the bis(alkoxycarbonyl)hydrazone product 3a via intermediate E
(Scheme 6) (the second migration).
(Z)-Diisopropyl-2-((4-bromophenyl)(cyano)methylene)hydrazine-
1,1-dicarboxylate (3b). mp. 94–96 ◦C; IR (CH2Cl2) n 2985, 2938,
2228, 1798, 1764, 1376, 1300, 1094, 910 cm-1; 1H NMR (CDCl3,
300 MHz, TMS): d 1.38 (12H, d, J = 6.3 Hz, CH3), 5.13–5.22
(2H, m, CH), 7.65 (2H, d, J = 8.7 Hz, Ar), 7.89 (2H, d, J =
8.7 Hz, Ar). 13C NMR (CDCl3, 75 MHz): d 21.6, 73.3, 109.5,
128.2, 129.1, 129.4, 132.3, 143.6, 150.4. MS (EI) m/z 309 (M+-86,
2.43), 269 (6.13), 267 (7.11), 223 (5.91), 195 (7.81), 114 (10.90), 44
(5.86), 43 (100.00), 41 (17.73). Anal. calcd for C16H18BrN3O4 (%)
(395.05): C, 48.50; H, 4.58; Br, 20.17; N, 10.60; O, 16.15 found: C,
48.39; H, 4.57; N, 10.58.
Conclusions
In conclusion, we have discovered a novel reaction between acyl
cyanides and Huisgen zwitterions under mild reaction conditions,
giving azine and hydrazone derivatives. The reaction temperature
is identified as a critical factor to control final products, presum-
ably due to a nitrogen-to-oxygen migration and an oxygen-to-
nitrogen remigration of the alkoxycarbonyl group occurring at
different temperatures. Efforts are in progress to elucidate further
mechanistic details of these reactions and to understand their
scope and limitations.
(Z)-Diisopropyl-2-((4-chlorophenyl)(cyano)methylene)hydrazine-
1,1-dicarboxylate (3c). mp. 81–83 ◦C; IR (CH2Cl2) n 2985,
2939, 2228, 1798, 1764, 1300, 1094, 837 cm-1; 1H NMR (CDCl3,
300 MHz, TMS): d 1.38 (12H, d, J = 6.3 Hz, CH3), 5.12–5.22
(2H, m, CH), 7.49 (2H, d, J = 8.4 Hz, Ar), 7.97 (2H, d, J =
8.4 Hz, Ar). 13C NMR (CDCl3, 75 MHz): d 21.6, 73.3, 109.6,
129.0, 129.4, 139.6, 143.7, 150.4. MS (EI) m/z 265 (M+-86, 3.49),
223 (9.16), 179 (7.16), 151 (8.82), 43 (100.00), 42 (4.60). Anal.
calcd for C16H18ClN3O4 (%) (351.09): C, 54.63; H, 5.16; Cl, 10.08;
N, 11.94; O, 18.19 found: C, 54.73; H, 5.28; N, 12.01.
Experimental
(Z)-Diisopropyl-2-(cyano(3-(trifluoromethyl)phenyl)methylene)-
hydrazine-1,1-dicarboxylate (3d). Oil. IR (CH2Cl2) n 2987, 2941,
2228, 1799, 1767, 1377, 1232, 1097 cm-1; 1H NMR (CDCl3,
300 MHz, TMS): d 1.41 (12H, d, J = 6.6 Hz, CH3), 5.15–5.24
(2H, m, CH), 7.68 (1H, dd, J1 = 7.8 Hz, J2 = 8.1 Hz, Ar), 7.85
(1H, d, J = 7.8 Hz, Ar), 8.20 (1H, d, J = 8.1 Hz, Ar), 8.29 (1H, s,
Ar). 19F NMR (CDCl3, 282 MHz): d -68.6. 13C NMR (CDCl3,
75 MHz): d 21.6, 73.6, 109.4, 123.3 (q, J = 271.4 Hz), 124.2 (q,
J = 3.7 Hz), 129.6 (q, J = 3.2 Hz), 129.8, 130.9, 131.4, 131.7 (q,
J = 33.2 Hz), 141.8, 150.4. MS (ESI) m/z 386.2 (M++1). HRMS
General
Toluene was distilled from sodium (Na) under argon (Ar) at-
mosphere. Melting points were determined on a digital melting
point apparatus and temperatures were uncorrected. H NMR
and 13C NMR spectra were recorded on a Bruker AM-300 or 400
spectrophotometer. Infrared spectra were recorded on a Perkin-
Elmer PE-983 spectrometer with absorption in cm-1. Flash column
chromatography was performed using 300–400 mesh silica gel.
1
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(ESI) calcd for C17H18F3N3O4 requires (M++1) 386.1249 found
386.13197.
(M++Na). HRMS (ESI) calcd for C14H15N3O4 requires (M++1)
290.1063 found 290.11353.
(Z)-Diisopropyl-2-((2-chlorophenyl)(cyano)methylene)hydrazine-
1,1-dicarboxylate (3e). Oil. IR (CH2Cl2) n 2986, 2939, 2225,
1799, 1766, 1590, 1377, 1311, 1093 cm-1; 1H NMR (CDCl3,
400 MHz, TMS): d 1.40 (12H, d, J = 6.4 Hz, CH3), 5.15–5.22
(2H, m, CH), 7.39–7.43 (1H, m, Ar), 7.50–7.52 (2H, m, Ar),
7.70 (1H, d, J = 7.6 Hz, Ar). 13C NMR (CDCl3, 100 MHz): d
21.6, 73.2, 109.6, 127.4, 129.9, 130.7, 131.4, 133.1, 133.4, 144.0,
149.9. MS (ESI) m/z 352.2 (M++1). HRMS (ESI) calcd for
C16H18ClN3O4 requires (M++1) 352.0986 found 352.10558.
(Z)-Diethyl-2-((4-bromophenyl)(cyano)methylene)hydrazine-
1,1-dicarboxylate (3k). mp. 82–84 ◦C; IR (CH2Cl2) n 2984,
1937, 2228, 1802, 1767, 1588, 1310,1006 cm-1; 1H NMR (CDCl3,
400 MHz, TMS): d 1.38 (6H, t, J = 7.2 Hz, CH3), 4.41 (4H, q,
J = 7.2 Hz, CH2), 7.66 (2H, d, J = 8.8 Hz, Ar), 7.90 (2H, d, J =
8.8 Hz, Ar). 13C NMR (CDCl3, 100 MHz): d 14.0, 64.6, 109.3,
128.5, 129.2, 132.4, 145.2, 150.5. MS (ESI) m/z 368.0 (M++1).
HRMS (ESI) calcd for C14H14BrN3O4 requires (M++1) 368.0168
found 368.02421.
(Z)-Diisopropyl-2-(cyano(p-tolyl)methylene)hydrazine-1,1-di-
carboxylate (3f). Oil. IR (CH2Cl2) n 2985, 2939, 2229, 1797,
1762, 1305, 1094, 910 cm-1; 1H NMR (CDCl3, 400 MHz, TMS): d
1.37 (12H, d, J = 6.0 Hz, CH3), 2.44 (3H, s, CH3), 5.12–5.19 (2H,
m, CH), 7.31 (2H, d, J = 8.0 Hz, Ar), 7.93 (2H, d, J = 8.0 Hz, Ar).
13C NMR (CDCl3, 100 MHz): d 21.6, 72.8, 109.9, 127.8, 127.9,
144.4, 147.0, 150.4. MS (ESI) m/z 332.0 (M++1), 354.0 (M++Na).
HRMS (ESI) calcd for C17H21N3O4 requires (M++Na) 354.1430,
found 354.14226.
(Z)-Diethyl-2-(cyano(4-methoxyphenyl)methylene)hydrazine-
1,1-dicarboxylate (3l). Oil. IR (CH2Cl2) n 2984, 2939, 2229, 1799,
1761, 1605, 1176, 1103 cm-1; 1H NMR (CDCl3, 400 MHz, TMS):
d 1.36 (6H, t, J = 7.2 Hz, CH3), 3.89 (3H, s, OCH3), 4.38 (4H,
q, J = 7.2 Hz, CH2), 7.01 (2H, d, J = 9.2 Hz, Ar), 8.01 (2H,
d, J = 9.2 Hz, Ar). 13C NMR (CDCl3, 75 MHz): d 14.1, 55.6,
64.3, 109.8, 114.7, 122.9, 130.3, 148.7, 150.7, 164.2. MS (ESI)
m/z 320.2 (M++1). HRMS (ESI) calcd for C15H17N3O5 requires
(M++1) 320.1168 found 320.12407.
(Z)-Diisopropyl-2-(cyano(4-methoxyphenyl)methylene)hydra-
zine-1,1-dicarboxylate (3g). Oil. IR (CH2Cl2) n 2985, 2939, 2228,
(E)-Diisopropyl-2-(cyano(furan-2-yl)methylene)hydrazine-1,1-
dicarboxylate (3m). Oil. IR (CH2Cl2) n 3131, 2986, 2940, 2234,
1791, 1794, 1095 cm-1; 1H NMR (CDCl3, 400 MHz, TMS): d 1.37
(12H, d, J = 6.0 Hz, CH3), 5.12–5.19 (2H, m, CH), 6.65 (1H, dd,
J1 = 1.6 Hz, J2 = 3.6 Hz, Ar), 7.25 (1H, dd, J1 = 0.8 Hz, J2 =
3.6 Hz, Ar), 7.72 (1H, dd, J1 = 0.8 Hz, J2 = 1.6 Hz, Ar). 13C NMR
(CDCl3, 100 MHz): d 21.6, 73.1, 108.8, 113.0, 119.1, 135.6, 145.9,
147.9, 150.3. MS (ESI) m/z 308.2 (M++1). HRMS (ESI) calcd for
C14H17N3O5 requires (M++1) 308.1168 found 308.12402.
1
1795, 1764, 1606, 1308, 1095 cm-1; H NMR (CDCl3, 300 MHz,
TMS): d 1.36 (12H, d, J = 6.3 Hz, CH3), 3.89 (3H, s, OCH3),
5.10–5.19 (2H, m, CH), 7.01 (2H, d, J = 9.0 Hz, Ar), 8.00 (2H,
d, J = 9.0 Hz, Ar). 13C NMR (CDCl3, 75 MHz): d 21.6, 55.5,
72.7, 109.9, 114.5, 122.8, 130.0, 147.5, 150.4, 163.9. MS (ESI)
m/z 348.2 (M++1). HRMS (ESI) calcd for C17H21N3O5 requires
(M++1) 348.1481, found 348.15603.
(Z)Diisopropyl-2-(cyano(3,5-dimethylphenyl)methylene)hydra-
zine-1,1-dicarboxylate (3h). Oil. IR (CH2Cl2) n 2985, 2939, 2229,
(E)-Diisopropyl-2-(cyano(thiophen-2-yl)methylene)hydrazine-
1,1-dicarboxylate (3n). Oil. IR (CH2Cl2) n 3107, 2984, 2938,
1
1789, 1763, 1609, 1233, 1095 cm-1; H NMR (CDCl3, 400 MHz,
1
2230, 1795, 1763, 1309,1093 cm-1; H NMR (CDCl3, 400 MHz,
TMS): d 1.37 (12H, d, J = 6.4 Hz, CH3), 2.39 (6H, s, CH3),
5.12–5.19 (2H, m, CH), 7.23 (1H, s, Ar), 7.65 (2H, s, Ar). 13C
NMR (CDCl3, 100 MHz): d 21.1, 21.7, 72.9, 110.0, 125.7, 130.2,
135.2, 138.9, 147.5, 150.4. MS (ESI) m/z 346.2 (M++1). HRMS
(MALDI) calcd for C18H23N3O4 requires (M++Na) 368.1588,
found 368.15808.
TMS): d 1.37 (12H, d, J = 6.0 Hz, CH3), 5.11–5.18 (2H, m, CH),
7.20 (1H, dd, J1 = 4.4 Hz, J2 = 5.2 Hz, Ar), 7.64 (1H, dd, J1 =
1.2 Hz, J2 = 5.2 Hz, Ar), 7.75 (1H, dd, J1 = 1.2 Hz, J2 = 4.4 Hz,
Ar). 13C NMR (CDCl3, 100 MHz): d 21.6, 72.9, 109.2, 128.2,
133.3, 134.3, 135.2, 141.6, 150.3. MS (ESI) m/z 324.2 (M++1).
HRMS (ESI) calcd for C14H17N3O4S requires (M++1) 324.0940
found 324.10089.
(Z)-Diisopropyl
(Z)-Diisopropyl-2-(cyano(naphthalen-1-yl)methylene)hydraz-
ine-1,1-dicarboxylate (3o). Oil. IR (CH2Cl2) n 2985, 2939, 2226,
1798, 1761, 1511, 1093 cm-1; 1H NMR (CDCl3, 400 MHz, TMS):
d 1.42 (12H, d, J = 6.0 Hz, CH3), 5.18–5.25 (2H, m, CH), 7.55–
7.67 (3H, m, Ar), 7.91–7.93 (1H, m, Ar), 8.00–8.03 (1H, m, Ar),
8.05 (1H, d, J = 8.0 Hz, Ar), 8.99 (1H, d, J = 8.4 Hz, Ar).
13C NMR (CDCl3, 100 MHz): d 21.7, 73.0, 110.7, 124.7, 125.5,
127.0, 127.3, 128.5, 128.8, 130.0, 131.1, 133.9, 148.7, 150.1. MS
(ESI) m/z 368.0 (M++1), 389.9 (M++Na). HRMS (ESI) calcd for
C20H21N3O4 requires (M++Na) 390.1424 found 390.14222.
2-(Cyano(3,4,5-trimethoxyphenyl)methylene)hydrazine-1,1-di-
carboxylate (3i). Oil. IR (CH2Cl2) n 2985, 2941, 1842, 2229,
1798, 1762, 1504, 1351, 1130 cm-1; H NMR (CDCl3, 400 MHz,
1
TMS): d 1.38 (12H, d, J = 6.0 Hz, CH3), 3.93 (6H, s, OCH3),
3.94 (3H, s, OCH3), 5.13–5.20 (2H, m, CH), 7.28 (2H, s, Ar). 13
C
NMR (CDCl3, 100 MHz): d 21.7, 56.3, 61.0, 73.0, 105.3, 110.0,
125.5, 142.8, 146.7, 150.4, 153.5. MS (ESI) m/z 408.0 (M++1).
HRMS (ESI) calcd for C19H25N3O7 requires (M++Na) 430.1585
found 430.15769.
(Z) - Diethyl - 2 - (cyano(phenyl)methylene)hydrazine - 1,1 - dicar-
boxylate (3j). Oil. IR (CH2Cl2) n 2985, 2938, 2228, 1802, 1768,
1102 cm-1; 1H NMR (CDCl3, 400 MHz, TMS): d 1.37 (6H, t, J =
7.6 Hz, CH3), 4.40 (4H, q, J = 7.6 Hz, CH2), 7.52 (2H, t, J = 8.0 Hz,
Ar), 7.62 (1H, t, J = 7.6 Hz, Ar), 8.05 (2H, d, J = 7.2 Hz, Ar).
13C NMR (CDCl3, 100 MHz): d 14.0, 64.4, 109.6, 128.0, 129.1,
130.2, 133.5, 147.4, 150.5. MS (ESI) m/z 290.2 (M++1), 312.2
(Z)-Diisopropyl-2-(cyano(thiophen-3-yl)methylene)hydrazine-
1,1-dicarboxylate (3p). Oil. IR (CH2Cl2) n 3107, 2984, 1938,
1
2230, 1795, 1763, 1561, 1093 cm-1; H NMR (CDCl3, 400 MHz,
TMS): d 1.37 (12H, d, J = 6.4 Hz, CH3), 5.12–5.19 (2H, m, CH),
7.44 (1H, dd, J1 = 2.8 Hz, J2 = 5.2 Hz, Ar), 7.68 (1H, dd, J1 =
1.2 Hz, J2 = 5.2 Hz, Ar), 8.08 (1H, dd, J1 = 1.2 Hz, J2 = 2.8 Hz,
Ar). 13C NMR (CDCl3, 100 MHz): d 21.7, 73.0, 110.1, 125.3,
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128.0, 132.1, 133.9, 141.8, 150.4. MS (ESI) m/z 323.9 (M++1).
HRMS (ESI) calcd for C14H17N3O4S requires (M++Na) 346.0832
found 346.08304.
7.55 (2H, s, Ar). 13C NMR (CDCl3, 75 MHz): d 21.1, 21.2, 21.4,
74.8, 76.4, 111.1, 125.0, 131.2, 133.6, 138.5, 138.7, 148.6, 155.3.
MS (ESI) m/z 346.0 (M++1), 368.0 (M++Na). HRMS (ESI) calcd
for C18H23N3O4 requires (M++Na) 368.1581 found 368.15692.
(4g) Oil. IR (CH2Cl2) n 2986, 2942, 2842, 2226, 1784, 1628, 1590,
1212, 1096 cm-1; 1H NMR (CDCl3, 400 MHz, TMS): d 1.31 (6H,
d, J = 6.4 Hz, CH3), 1.48 (6H, d, J = 6.0 Hz, CH3), 3.92 (9H, s,
OCH3), 4.90–4.97 (1H, m, CH), 5.30–5.37 (1H, m, CH), 7.19
(2H, s, Ar). 13C NMR (CDCl3, 100 MHz): d 21.2, 21.4, 56.2, 61.0,
74.9, 76.5, 104.4, 110.9, 126.6, 138.0, 141.4, 148.4, 153.4, 155.2.
MS (ESI) m/z 407.9 (M++1), 429.9 (M++Na). HRMS (ESI) calcd
for C19H25N3O7 requires (M++Na) 430.1585 found 430.15792.
(4h) Oil. IR (CH2Cl2) n 2985, 2942, 2842, 2227, 1789, 1633, 1590,
1206 cm-1; 1H NMR (CDCl3, 400 MHz, TMS): d 1.33 (3H, t, J =
7.2 Hz, CH3), 1.48 (3H, t, J = 7.2 Hz, CH3), 3.91 (3H, s, OCH3),
3.92 (6H, s, OCH3), 4.31 (2H, q, J = 7.2 Hz, CH2), 4.57 (2H, q,
J = 7.2 Hz, CH), 7.19 (2H, s, Ar). 13C NMR (CDCl3, 100 MHz,
TMS): d 13.8, 14.0, 56.2, 61.0, 66.2, 68.0, 104.4, 110.8, 126.5,
138.4, 141.5, 148.9, 153.4, 155.9. MS (ESI) m/z 380.0 (M++1).
HRMS (ESI) calcd for C17H21N3O7 requires (M++Na) 402.1272
found 402.12674.
Typical reaction procedure for the preparation of 4
To a stirred solution of acyl cyanide 1 (0.3 mmol) and Ph3P
(0.3 mmol) in anhydrous toluene (2.0 mL) under argon was
added diisopropyl azodicarboxylate/diethyl azodicarboxylate 2
(0.3 mmol) at 20 ◦C, the mixture was maintained at 20 ◦C to
stir for the time needed. The solvent was removed under reduced
pressure on a rotary evaporator. The residue was subjected to
column chromatography on silica gel (300–400 mesh) to afford
the products 4.
(4a) Oil. IR (CH2Cl2) n 2986, 2940, 1783, 1626, 1214, 1095 cm-1;
1H NMR (CDCl3, 400 MHz, TMS): d 1.34 (6H, d, J = 6.0 Hz,
CH3), 1.48 (6H, d, J = 6.0 Hz, CH3), 4.91–4.99 (1H, m, CH),
5.31–5.38 (1H, m, CH), 7.42–7.52 (3H, m, Ar), 7.92–7.95 (2H,
m, Ar). 13C NMR (CDCl3, 100 MHz): d 21.2, 21.4, 74.9, 76.6,
110.9, 127.2, 128.8, 131.4, 131.8, 138.4, 148.6, 155.7. MS (ESI) m/z
318.0 (M++1), 340.1 (M++Na). HRMS (ESI) calcd for C16H19N3O4
requires (M++Na) 340.1268 found 340.12676.
(4i) Oil. IR (CH2Cl2) n 2985, 2940, 2842, 2225, 1785, 1630, 1604,
1261, 1205 cm-1; 1H NMR (CDCl3, 400 MHz, TMS): d 1.35 (3H,
t, J = 7.2 Hz, CH3), 1.46 (3H, t, J = 7.2 Hz, CH3), 3.86 (3H, s,
OCH3), 4.32 (2H, q, J = 7.2 Hz, CH2), 4.55 (2H, q, J = 7.2 Hz,
CH), 6.95 (2H, d, J = 9.2 Hz, Ar), 7.87 (2H, d, J = 9.2 Hz,
Ar). 13C NMR (CDCl3, 100 MHz, TMS): d 13.7, 14.0, 55.5, 66.2,
67.7, 111.0, 114.3, 124.0, 129.0, 138.5, 149.1, 155.4, 162.7. MS
(ESI) m/z 320.0 (M++1), 341.9 (M++Na). HRMS (ESI) calcd for
C15H17N3O5 requires (M++Na) 342.1060 found 342.10585.
(4j) Oil. IR (CH2Cl2) n 3051, 2985, 2939, 2223, 1778, 1628, 1217,
1093 cm-1; 1H NMR (benzene-d6, 300 MHz, TMS): d 0.79 (6H, d,
J = 6.3 Hz, CH3), 1.17 (6H, d, J = 6.3 Hz, CH3), 4.56–4.65 (1H,
m, CH), 5.24–5.33 (1H, m, CH), 7.00 (1H, t, J = 7.8 Hz, Ar), 7.24
(1H, t, J = 7.8 Hz, Ar), 7.42 (1H, t, J = 8.4 Hz, Ar), 7.49 (1H, d,
J = 8.1 Hz, Ar), 7.54 (1H, d, J = 8.1 Hz, Ar), 7.95 (1H, d, J =
8.1 Hz, Ar), 9.20 (1H, d, J = 8.4 Hz, Ar). 13C NMR (benzene-d6,
75 MHz, TMS): d 21.0, 21.2, 74.8, 76.8, 112.4, 125.1, 126.4, 126.7,
128.2, 128.5, 129.0, 130.7, 131.1, 132.5, 134.4, 140.4, 149.2, 156.4.
MS (ESI) m/z 368.0 (M++1). HRMS (ESI) calcd for C20H21N3O4
requires (M++Na) 390.1424 found 390.14189.
(4k) Oil. IR (CH2Cl2) n 3105, 2986, 2940, 2227, 1783, 1626,
1218, 1095 cm-1; 1H NMR (CDCl3, 400 MHz, TMS): d 1.34 (6H,
d, J = 6.4 Hz, CH3), 1.46 (6H, d, J = 6.0 Hz, CH3), 4.91–4.98 (1H,
m, CH), 5.28–5.35 (1H, m, CH), 7.36 (1H, dd, J1 = 2.8 Hz, J2 =
4.8 Hz, Ar), 7.52 (1H, dd, J1 = 1.2 Hz, J2 = 4.8 Hz, Ar), 7.90 (1H,
dd, J1 = 1.2 Hz, J2 = 2.8 Hz, Ar). 13C NMR (CDCl3, 100 MHz,
TMS): d 21.2, 21.4, 74.9, 76.4, 111.2, 124.9, 127.4, 129.2, 133.8,
134.9, 148.5, 155.2. MS (ESI) m/z 323.9 (M++1), 345.9 (M++Na).
HRMS (ESI) calcd for C14H17N3O4S requires (M++Na) 346.0832
found 346.08309.
(4b) Oil. IR (CH2Cl2) n 2986, 1939, 2225, 1783, 1622, 1213,
1095 cm-1; 1H NMR (CDCl3, 300 MHz, TMS): d 1.35 (6H, d, J =
6.3 Hz, CH3), 1.48 (6H, d, J = 6.3 Hz, CH3), 4.90–4.99 (1H, m,
CH), 5.30–5.39 (1H, m, CH), 7.58 (2H, d, J = 8.7 Hz, Ar), 7.80
(2H, d, J = 8.7 Hz, Ar). 13C NMR (CDCl3, 75 MHz): d 21.2, 21.4,
75.0, 76.8, 110.6, 126.5, 128.5, 130.3, 132.1, 137.3, 148.5, 155.9.
MS (ESI) m/z 395.9 (M++1), 418.9 (M++Na). HRMS (ESI) calcd
for C16H18BrN3O4 requires (M++Na) 418.0373 found 418.03621.
(4c) Oil. IR (CH2Cl2) n 2987, 2940, 2225, 1783, 1622, 1214,
1094 cm-1; 1H NMR (CDCl3, 400 MHz, TMS): d 1.35 (6H, d, J =
6.0 Hz, CH3), 1.48 (6H, d, J = 6.0 Hz, CH3), 4.91–4.98 (1H, m,
CH), 5.31–5.38 (1H, m, CH), 7.42 (2H, d, J = 8.4 Hz, Ar), 7.87
(2H, d, J = 8.4 Hz, Ar). 13C NMR (CDCl3, 100 MHz): d 21.2, 21.5,
75.1, 76.8, 110.7, 128.4, 129.2, 129.9, 137.2, 138.0, 148.5, 155.9.
MS (ESI) m/z 352.0 (M++1), 373.9 (M++Na). HRMS (ESI) calcd
for C16H18ClN3O4 requires (M++Na) 374.0878 found 374.08694.
(4d) Oil. IR (CH2Cl2) n 2987, 2940, 2225, 1783, 1622, 1214,
1094 cm-1; 1H NMR (CDCl3, 400 MHz, TMS): d 1.35 (6H, d, J =
6.0 Hz, CH3), 1.48 (6H, d, J = 6.0 Hz, CH3), 4.91–4.98 (1H, m,
CH), 5.31–5.38 (1H, m, CH), 7.42 (2H, d, J = 8.4 Hz, Ar), 7.87
(2H, d, J = 8.4 Hz, Ar). 13C NMR (CDCl3, 100 MHz): d 21.2, 21.5,
75.1, 76.8, 110.7, 128.4, 129.2, 129.9, 137.2, 138.0, 148.5, 155.9.
MS (ESI) m/z 352.0 (M++1), 373.9 (M++Na). HRMS (ESI) calcd
for C16H18ClN3O4 requires (M++Na) 374.0878 found 374.08694.
(4e) mp. 75–77 ◦C; IR (CH2Cl2) n 2986, 1939, 2225, 1783, 1627,
1214, 1095 cm-1; 1H NMR (benzene-d6, 400 MHz, TMS): d 0.96
(6H, d, J = 6.0 Hz, CH3), 1.14 (6H, d, J = 6.0 Hz, CH3), 3.23
(3H, s, OCH3), 4.67–4.74 (1H, m, CH), 5.16–5.23 (1H, m, CH),
6.61 (2H, d, J = 8.8 Hz, Ar), 7.94 (2H, d, J = 8.8 Hz, Ar). 13C
NMR (benzene-d6, 100 MHz): d 21.0, 21.2, 54.9, 74.6, 76.4, 111.6,
114.6, 124.7, 129.3, 138.7, 149.2, 155.8, 162.9. MS (ESI) m/z 348.1
(M++1). HRMS (ESI) calcd for C17H21N3O5 requires (M++Na)
370.1373 found 370.13749.
The products 6–9 were prepared using a procedure similar to that
for the preparation of 3
(4f) Oil. IR (CH2Cl2) n 2986, 2939, 2225, 1782, 1627, 1207,
1086 cm-1; 1H NMR (CDCl3, 300 MHz, TMS): d 1.36 (6H, d, J =
6.0 Hz, CH3), 1.48 (6H, d, J = 6.0 Hz, CH3), 2.35 (6H, s, CH3),
4.92–5.01 (1H, m, CH), 5.29–5.39 (1H, m, CH), 7.12 (1H, s, Ar),
(Z)-Diisopropyl-2-(1-(4-chlorophenyl)-2,2,2-trifluoroethyli-
dene)hydrazine-1,1-dicarboxylate (6). Oil. IR (CH2Cl2) n 2986,
1
2941, 1752, 1594, 1281, 1147 cm-1; H NMR (CDCl3, 300 MHz,
TMS): d 1.21 (12H, d, J = 6.0 Hz, CH3), 4.84–4.93 (2H, m,
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CH), 7.31 (2H, d, J = 8.7 Hz, Ar), 7.44 (2H, d, J = 8.7 Hz,
Ar). 13C NMR (CDCl3, 100 MHz): d 21.4, 72.7, 119.7 (q, J =
3 For reviews, see: (a) O. Mitsunobu, Synthesis, 1981, 1–28; (b) D. L.
Hughes, Org. Prep. Proced. Int., 1996, 28, 127–164. For selected papers
see: (c) T. Watanabe, I. Gridnev and T. Imamoto, Chirality, 2000, 12,
346–351; (d) G. K. S. Prakash, S. Chacko, S. Alconcel, T. Stewart,
T. Mathew and G. A. Olah, Angew. Chem., Int. Ed., 2007, 46, 4933–
4936; (e) C. Ahn, R. Correia and P. DeShong, J. Org. Chem., 2002,
67, 1751–1753; (f) J. M. Keith and L. Gomez, J. Org. Chem., 2006, 71,
7113–7116.
275.8 Hz), 126.7, 129.1, 137.4, 150.3, 158.0 (q, J = 33.5 Hz). 19
F
NMR (CDCl3, 282 MHz): d -73.94. MS (ESI) m/z 395.2 (M++1).
HRMS (MALDI) calcd for C16H18ClF3N2O4 requires (M++Na)
417.0811 found 417.07994.
4 (a) E. Brunn and R. Huisgen, Angew. Chem., 1969, 81, 534–536; E.
Brunn and R. Huisgen, Angew. Chem., Int. Ed. Engl., 1969, 8, 513–515;
(b) R. Huisgen, in The Adventure Playground of Mechanisms and Novel
Reactions, Profiles, Pathways and Dreams ed. J. I. Seeman, American
Chemical Society, Washington DC, 1994, p. 62.
5 (a) Y. X. Liu, C. F. Xu and L. Z. Liu, Synthesis, 2003, 1335–1338;
(b) D. C. Morrison, J. Org. Chem., 1958, 23, 1072–1074.
6 M. Girard, P. Murphy and N. N. Tsou, Tetrahedron Lett., 2005, 46,
2449–2452.
(Z)-isopropyl-2-(1-cyano-2,2-dimethylpropylidene)hydrazine-
carboxylate (7). Oil. IR (CH2Cl2) n 3226, 2979, 2211, 1760, 1513,
1222, 1108 cm-1; 1H NMR (CDCl3, 400 MHz, TMS): d 1.27 (9H, s,
CH3), 1.32 (6H, d, J = 6.0 Hz, CH3), 5.04–5.11 (1H, m, CH), 8.52
(1H, s, NH). 13C NMR (CDCl3, 100 MHz): d 21.9, 27.4, 36.7, 70.8,
109.5, 132.1, 151.7. MS (ESI) m/z 212.1 (M++1). HRMS (EI)
calcd for C10H17N3O2 requires (M+) 211.1321, found 211.1321.
7 R. D. Otte, T. Sakata, I. A. Guzei and D. Lee, Org. Lett., 2005, 7,
495–498.
8 For reviews see ref. 2c; for selected papers, see: (a) V. Nair, S. C. Mathew,
A. T. Biju and E. Suresh, Angew. Chem., Int. Ed., 2007, 46, 2070–2073;
(b) V. Nair, A. T. Biju, K. Mohanan and E. Suresh, Org. Lett., 2006,
8, 2213–2216; (c) V. Nair, A. T. Biju, A. U. Vinod and E. Suresh, Org.
Lett., 2005, 7, 5139–5142; (d) V. Nair, A. T. Biju, K. G. Abhilash, R. S.
Menon and E. Suresh, Org. Lett., 2005, 7, 2121–2123; (e) V. Nair, S. C.
Mathew, A. T. Biju and E. Suresh, Synthesis, 2008, 1078–1084; (f) V.
Nair, A. T. Biju and S. C. Mathew, Synthesis, 2007, 0697–0704; (g) V.
Nair, S. C. Mathew, A. T. Biju and E. Suresh, Tetrahedron Lett., 2007,
48, 9018–9020.
(Z)-Ethyl-2-(1-cyano-2,2-dimethylpropylidene)hydrazinecar-
boxylate (8). Oil. IR (CH2Cl2) n 3239, 2971, 2211, 1766, 1514,
1216, 1031 cm-1; 1H NMR (CDCl3, 400 MHz, TMS): d 1.27 (9H, s,
CH3), 1.34 (3H, t, J = 7.2 Hz, CH3), 4.31 (2H, q, J = 7.2 Hz, CH),
8.54 (1H, s, NH). 13C NMR (CDCl3, 100 MHz): d 14.4, 27.4, 36.8,
62.7, 109.4, 132.3, 152.2. MS (ESI) m/z 198.1 (M++1). HRMS (EI)
calcd for C9H15N3O2 requires (M+) 197.1164, found 197.1168.
9 S. L. Cui, J. Wang and Y. G. Wang, Org. Lett., 2008, 10, 13–
16.
Diisopropyl-5-cyano-3-(furan-2-yl)-3H -pyrazole-1,2-dicar-
boxylate (9). Oil. IR (CH2Cl2) n 3113, 2985, 2939, 2240, 1736,
10 For reviews, see: S. Hu¨nig and R. Schaller, Angew. Chem., Int. Ed. Engl.,
1982, 21, 36–49.
11 (a) W. Zhang and M. Shi, Chem. Commun., 2006, 1218–1220; (b) G. L.
Zhao and M. Shi, Tetrahedron, 2005, 61, 7277–7288; (c) X. G. Liu and
M. Shi, Eur. J. Org. Chem., 2008, 6168–6174; (d) C. Q. Li and M. Shi,
Org. Lett., 2003, 5, 4273–4276; (e) Y. W. Guo, Y. L. Shi, H. B. Li and
M. Shi, Tetrahedron, 2006, 62, 5875–5882; (f) X. Y. Guan and M. Shi,
J. Org. Chem., 2009, 74, 1977–1981; (g) Y. L. Shi and M. Shi, Org. Lett.,
2005, 7, 3057–3060; (h) G. L. Zhao, Y. L. Shi and M. Shi, Org. Lett.,
2005, 7, 4527–4530; (i) X. Y. Guan and M. Shi, Org. Biomol. Chem.,
2008, 6, 3616–3620.
12 (a) A. I. Khodair, Tetrahedron, 1998, 54, 4859–4872; (b) R. Cohen,
B. Rybtchinski, M. Gandelman, L. J. W. Shimon, J. M. L. Martin
and D. Milsterin, Angew. Chem., Int. Ed., 2003, 42, 1949–1952; (c) C.
Bournaud, F. Chung, A. P. Luna, M. Pasco, G. Errasti, T. Lecourt
and L. Micouin, Synthesis, 2009, 0869–0887; (d) A. Bredihhin and U.
Maeorg, Tetrahedron, 2008, 64, 6788–6793; (e) L. Ling, L. Urichuk,
B. D. Sloley, R. T. Coutts, G. B. Baker, J. J. Shan and P. K. T. Pang,
Bioorg. Med. Chem. Lett., 2001, 11, 2715–2717.
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14 CCDC file No. 713523 contains the supplementary crystallographic
data for the compound. See the ESI†for details.
15 CCDC file No. 724590 contains the supplementary crystallographic
data for the compound. See the ESI†for details.
16 (a) M. Shi, X. G. Liu, Y. W. Guo and W. Zhang, Tetrahedron, 2007,
63, 12731–12734; (b) W. Zhang and M. Shi, Tetrahedron, 2006, 62,
8715–8719.
17 (a) Organofluorine Compounds: Chemistry Applications, ed. T. Hiyama,
Springer, New York, 2000; (b) P. Kirsch, Modern Fluoroorganic Chem-
istry, Wiley-VCH, Weinheim, Germany, 2004; (c) R. D. Chambers,
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1
1366, 1105 cm-1; H NMR (CDCl3, 300 MHz, TMS): d 1.26–
1.38 (12H, m, CH3), 5.00–5.11 (2H, m, CH), 6.04 (1H, d, J =
3.3 Hz, CH), 6.31 (1H, d, J = 3.3 Hz, CH), 6.34 (2H, m,
Ar), 7.37–7.39 (1H, m, Ar). 13C NMR (CDCl3, 75 MHz): d
21.5, 21.6, 21.7, 21.8, 60.5, 71.7, 72.5, 108.4, 110.5, 110.6, 116.9,
125.2, 143.5, 148.7, 153.8, 156.3. MS (ESI) m/z 334.2 (M++1),
356.2 (M++Na). HRMS (MALDI) calcd for C16H19N3O5 requires
(M++Na) 356.1219 found 356.12169.
Acknowledgements
We thank the Shanghai Municipal Committee of Science and
Technology (06XD14005, 08dj1400100-2), National Basic Re-
search Program of China (973)-2009CB825300, and the National
Natural Science Foundation of China for financial support
(20872162, 20672127, 20821002 and 20732008) and also thank
Mr Jie Sun for X-ray diffraction.
Notes and references
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4714 | Org. Biomol. Chem., 2009, 7, 4708–4714
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