Fast and efficient preparation of Baylis-Hillman-derived (E)-allylic azides and related compounds in aqueous medium

Article abstract of DOI:10.1016/j.tet.2006.09.059

A practical access to alkyl- and aryl-substituted (E)-2-(azidomethyl)alkenoates and related azido compounds from the corresponding allylic bromides in aqueous acetone is described. An alternative method to obtain the starting bromides based on heterogeneo

Full text of DOI:10.1016/j.tet.2006.09.059

Tetrahedron 62 (2006) 11652–11656
Fast and efficient preparation of Baylis–Hillman-derived
(E)-allylic azides and related compounds in aqueous medium
*
Marcus M. Sa, Marcia D. Ramos and Luciano Fernandes
ꢀ
´
Departamento de Quımica, Universidade Federal de Santa Catarina, Florianopolis, SC 88040-900, Brazil
ꢀ
Received 24 July 2006; revised 14 September 2006; accepted 15 September 2006
Available online 16 October 2006
Abstract—A practical access to alkyl- and aryl-substituted (E)-2-(azidomethyl)alkenoates and related azido compounds from the corre-
sponding allylic bromides in aqueous acetone is described. An alternative method to obtain the starting bromides based on heterogeneous
catalysis under mild conditions was also investigated.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
or aqueous solutions10 can be viewed as very attractive
mediums for these transformations.11
While the enormous interest in the chemistry of azides and
azido-related compounds1 dates from the 19th century, only
recently have the synthesis and reactivity of multifunctional
allylic azides become an area of active research.2 Allylic
azides are versatile building blocks for the synthesis of nat-
ural products and nitrogen-containing heterocycles of phar-
macological relevance.3 However, the propensity of allylic
azides to undergo dynamic [3,3]-sigmatropic rearrange-
ment4 at ambient temperature must be taken into account,
because the thermodynamic ratio of the two equilibrating re-
gioisomeric azides is normally substrate-dependent.5 There-
fore, the development of simple and efficient methods to
selectively access allylic azides of structural complexity is
highly desirable. 3-Aryl-2-(azidomethyl)alkenoates 1 are a
class of stable allylic azides,6 which are not prone to rear-
rangement, making them attractive intermediates for synthe-
sis. Multifunctional allylic azides of structure 1 have been
prepared by a two-step sequence involving acetylation of
a-methylene-b-hydroxy esters 2 (Baylis–Hillman7 adducts)
followed by reaction of acetate 3 with NaN3 in a SN20-type
mechanism (Scheme 1).8 However, nucleophilic displace-
ments of this type involve long reaction times and the use
of a toxic and high-boiling solvent such as DMSO. These
shortcomings could be partially circumvented by the
introduction of 1 equiv of 1,4-diazabicyclo[2.2.2]octane
(DABCO) in aqueous THF to accelerate the substitution re-
action,9 although the required presence of an additive creates
further environmental and economic concerns. Indeed, water
AcO
R
O
Ac2O
Py
NaN3
DMSO
OCH3
OCH3
HO
O
O
3
R
OCH3
OCH3
R
O
2
1
N3
R
4
Br
Scheme 1.
In continuation of our studies on synthetic methodologies
involving allylic azides and Baylis–Hillman adducts,6,12,13
we envisaged that allylic bromides 4, readily obtained13,14
by direct bromination of Baylis–Hillman adducts 2, would
be the useful substrates15 for an easy introduction of azide,
as well as for other nucleophilic groups, onto the allylic
framework. In this paper we describe a practical and efficient
preparation of alkyl- and aryl-substituted (E)-2-(azido-
methyl)alkenoates and related azido compounds from the
corresponding allylic bromides in aqueous medium. We also
investigate an alternative method to obtain the starting
bromides based on heterogeneous catalysis under mild
conditions.
2. Results and discussion
Allylic bromides such as 4 have been routinely prepared by
treatment of Baylis–Hillman adducts 2 with a combination
of HBr and H2SO4 in CH2Cl2 at low temperature.13a,14a In
spite of the good yields commonly associated with this trans-
formation, the utilization of large quantities of strong
Keywords: Baylis–Hillman reaction; Allylic azides; Allylic bromides; [3,3]-
Sigmatropic rearrangement; Aqueous solvents; Heterogeneous catalysis.
* Corresponding author. Tel.: +55 48 33316844; fax: +55 48 33316850;
e-mail: msa@qmc.ufsc.br
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.09.059

M. M. Saꢀ et al. / Tetrahedron 62 (2006) 11652–11656
11653
mineral acids is a major drawback due to the safety proce-
dures required for the manipulation of hazardous reagents
and wastes. Also, substrates carrying acid-labile groups
such as electron-rich olefins and aromatics are incompatible
with the strongly acidic conditions, thus limiting the scope
of the method. Heterogeneous catalysis is amongst the
most efficient and environmentally friendly processes in
chemical synthesis, allowing the performance of operation-
ally-simple reactions without the use of toxic or corrosive
reagents.16 Alternative methods to access allylic bromides
4 employing inexpensive solid catalysts include the use of
remarkably dependent upon the substitution pattern. Very
slow conversions were observed for electron-deficient sub-
strates, even after a prolonged time under reflux (entries 7
and 8). The anticipated13,14 Z-stereochemistry assigned to
2-(bromomethyl)-2-alkenoates 4 was based on the character-
istic NMR shift of the b-olefinic hydrogen cis to the carboxyl
group and also on the X-ray crystallography of 4b.18
Next, the preparation of allylic azides 1 from bromides 4 was
investigated. Bromide 4a was selected as a model substrate
for reactions with NaN3 under different reaction parameters
in order to achieve optimal conversions to azide 1a (Table 2).
Reaction rates were strongly influenced by the nature of the
solvent (or solvent combination) used, slow conversions be-
ing a consequence of the low solubility of sodium azide (en-
tries 1–3) or 4a (entry 4) in the medium. DMSO (entry 5) and
DMF (entry 6), typically employed for azide displacement
of bromide,2c,19 enabled quantitative conversion to allylic
azide 1a in 10 min. However, both solvents are toxic, expen-
sive, and difficult to separate from the crude product by sim-
ple aqueous workup. In contrast, a combination of acetone/
water proved to be the best solvent system for the reaction
(entries 7–9). Allylic azide 1a was quantitatively obtained
with either 1.5 equiv of NaN3 in 10 min (entry 8) or
2.0 equiv in 5 min (entry 9). It is also noteworthy that accept-
able conversions to 1a could be performed using a nearly
equimolar amount of NaN3 in 5 min (entry 10).
17
montmorillonite KSF clay and silica-supported NaHSO4
in combination with a bromide source.14b,d In our hands,
however, attempts to react substrates 2a and 2b under these
conditions led to modest conversions to 4a and 4b (up to
˚
40%). Montmorillonite K10, zeolite ZSM-5, and 5 A molec-
ular sieves were also ineffective catalysts under similar
experimental procedure.
A smooth conversion of Baylis–Hillman adducts 2 to the
corresponding bromides 4 was achieved with Amberlist-
15Ò/LiBr (or NaBr) in acetonitrile at ambient temperature
(Table 1). High yields were obtained with alcohols bearing
alkyl or electron-rich aryl groups (entries 1–6 and 9).
Accordingly, piperonyl-substituted alcohol 2b reacted al-
most instantaneously under the stated conditions to give
bromide 4b in excellent yield (entries 2 and 3). Even reused
Amberlist-15Ò (which was readily recovered by filtration of
the reaction mixture and successive washings with 1 M HCl
and H2O) was suitable for another cycle, in spite of the par-
tially decreased catalytic activity (entry 4). Styryl-derived
substrate 2d is also very reactive toward Amberlist-15Ò/
LiBr, but the formation of the expected (E,E)-diene 4d was
accompanied by small amounts of an unstable by-product,
possibly a geometrical isomer, that could not be isolated.
Gratifyingly, a fractional crystallization of the crude reaction
mixture in ethanol gave bromide 4d in higher purity and
better yield than those obtained with the HBr–H2SO4 method
(entry 6). However, the relative reactivity of alcohols 2 was
Encouraged by the excellent results achieved with the NaN3/
acetone/water system, we further extended this procedure to
the azidation of representative allylic bromides 4 (Table 3).
The corresponding aromatic-substituted (E)-allylic azides
1a–f were cleanly obtained in nearly quantitative yields after
purification in a short plug of silica gel. On the other hand,
when aliphatic-substituted allylic bromides 4g–i were sub-
jected to the present protocol, NMR analysis of the crude re-
action indicated the formation of the expected allylic azides
1g–i accompanied by a minor product (5–30%), which was
assigned as the rearranged regioisomers 5g–i (Scheme 2).
Table 1. Synthesis of (E)-allylic bromides 4 from alcohols 2a
Table 2. Conversion of bromide 4a to azide 1a under different reaction
conditionsa
O
OH
O
O
O
LiBr
Amberlist-15®
Acetonitrile
OCH3
R
OCH3
R
NaN3
OCH3
OCH3
2
4
solvent
Br
Br
N3
4a
1a
Entry Product
R
Yield (%) Yield (%)c
with HBr/ with LiBr/
H2SO4
Time
(h)
Solvent system
NaN3 (equiv)
Conversion to 1a (%)b
Amberlist-15Ò
b
1
2
3
4
5
6
7
8
9
10
THF
CH3CN
2.0
2.0
2.0
2.0
2.0
2.0
2.0
1.5
2.0
1.2
5
18
31
0
100
100
100
100
100
78
1
2
3
4
5
6
7
8
9
4a
4b
4b
4b
4c
4d
4e
4f
C6H5
85
64
91
90d
77e
85
75
45f
0
6
1
1
1
2
0.5
4
50
6
3,4-(OCH2O)C6H3 60
3,4-(OCH2O)C6H3
3,4-(OCH2O)C6H3
2-C10H7 85
(E)-C6H5CH]CH 64
2-ClC6H4
4-NO2C6H4
CH3
Me2CO
H2O
DMSOc
DMFc
Me2CO/H2O 3:1
Me2CO/H2O 3:1
Me2CO/H2O 3:1d
Me2CO/H2O 3:1d
80
65
70
4g
75
a
b
c
a
Isolated yields.
Data from Ref. 13a.
Allylic bromide 4a (1 mmol) and NaN3 (1.2–2.0 mmol) in 4 mL of a given
solvent were stirred at 25 ꢀC for 10 min (unless otherwise stated),
followed by quenching the reaction mixture with CH2Cl2 and H2O.
Determined by 1H NMR spectrum (400 MHz, CDCl3).
Solvent residue (10–20%) present in the crude reaction product after
aqueous workup.
Conditions: 1.0 mmol 2, 1.0 g Amberlist-15Ò, 2.0 mmol LiBr, acetonitrile
or acetone (3 mL) at 25 ꢀC.
b
c
Amberlist-15Ò (0.5 g/mmol 2b) was used.
d
e
f
The reaction was carried out with recycled Amberlist-15Ò.
The reaction was carried out at reflux temperature for 4 h.
d
Reaction was quenched (CH2Cl2/H2O) after 5 min.

11654
M. M. Saꢀ et al. / Tetrahedron 62 (2006) 11652–11656
Table 3. Synthesis of (E)-allylic azides 1 from bromides 4 in acetone/water
(3:1)
and a quantitative conversion to allylic azide 1a reached
completion after 2 min. In the case of methyl-substituted
allylic bromide 4g, however, conversion to both the allylic
azide 1g and the corresponding rearranged isomer 5g (ratio
1g:5gw3:1) was observed in the early stages, with the iso-
meric ratio being unaltered throughout the entire course of
the reaction (conversion higher than 95% was accomplished
after 2 min).
O
O
NaN3
acetone:H2O (3:1)
25 °C, 10 min
OCH3
OCH3
R
R
4
1
Br
N3
Product
R
Yield (%)a
1a
1b
1c
1d
1e
1f
1g
1h
1i
C6H5
3,4-(OCH2O)C6H3
2-C10H7
97
93
95
96
96
97
92
95
93
These results indicate that alkyl-substituted azides 1g–i
might co-exist with their rearranged isomers 5g–i in a fast
equilibrium shifted to the thermodynamically more stable
olefins20 1g–i. The absence of rearranged products for the
aryl series 1a–f might have been due to a stronger stabiliza-
tion of the double bond by an extensive conjugation through
the carboxyl and the aromatic ring, precluding isomerization
to the less stable 5a–f. From a mechanistic view, nucleophilic
attack of azide anion on an allylic bromide system would
lead to the formation21 of either SN2- or SN20-type products
1 or 5, respectively (Scheme 2). While the direct SN2 attack
leading to the more stable 1 (path a) seems to be the exclu-
sive (or at least preferential) pathway for aryl-substituted
bromides 4a–f, the SN20 mechanism (path b) or even an ad-
dition-elimination process via intermediate 6 (path c) could
not be excluded at this moment to account for the formation
of alkyl-substituted azides 1g–i. The DABCO salt concept
has been successfully applied for the introduction of nucleo-
philes at the secondary position of Baylis–Hillman adducts
by SN20-type process.22 In order to tentatively obtain the
elusive azide 5a, we treated bromide 4a with DABCO fol-
lowed by the addition of NaN3, but the only product formed
in the reaction was, again, the SN2-type 1a. Whether the
mechanism is a direct SN2 (path a) or SN20 (path b) still re-
mains to be determined, because in both the cases the prod-
uct distribution (1:5) must be regarded as a thermodynamic
rather than a kinetic control due to the fast equilibration be-
tween the regioisomeric allylic azides.
(E)-C6H5CH]CH
2-ClC6H4
4-NO2C6H4
b
c
CH3
CH3CH2CH2
c
CH3CH2(CH3)CHc
a
Isolated yields.
b
c
A higher acetone/water ratio (6:1) was used due to the low solubility of
nitro-derivative 4f in aqueous acetone.
Obtained as inseparable mixture of regioisomers 1 and 5.
Unfortunately, all attempts to isolate any compound by chro-
matography led to extensive decomposition to an intractable
mixture of products.
-
N3
R
O
O
c
a
OCH3
OCH3
R
SN2
b
Br
N3
4a-i
1a-i
fast
N3
b
c
[3,3]
SN2'
N3 O-
O
R
OCH3
R
OCH3
Br
6
5g-i
Scheme 2.
In order to monitor these transformations by 1H NMR
(400 MHz), reactions of phenyl- (4a) and methyl- (4g)
substituted bromides were also performed in standard NMR
tubes, using (CD3)2CO/D2O as the solvent system under the
present conditions. For phenyl-substituted allylic bromide
4a, products arising from rearrangement were not detected
The superior reactivity of allylic bromides 4 over the ace-
tates 3 was demonstrated by control experiments performed
in acetone/water and in DMSO under equivalent conditions.
The results summarized in Table 4 clearly show that allylic
bromides 4 are much more reactive than acetates 3 (and
Table 4. Conversion (%)a of allylic acetates 3 and bromides 4 to allylic azides 1
AcO
R
O
O
O
O
NaN3
NaN3
OCH3
OCH3
OCH3
OCH3
R
R
R
4
1
3
3'
Br
N3
OAc
Entry
Compound
R
Solvent system
Conversion (%)
10 min
2 h
1
2
3
4
4a
3a
4a
3a
4g
3gb
4g
3gb
C6H5
C6H5
C6H5
C6H5
CH3
CH3
CH3
CH3
DMSO
DMSO
Acetone/H2O (3:1)
Acetone/H2O (3:1)
DMSO
DMSO
Acetone/H2O (3:1)
Acetone/H2O (3:1)
100
65
100
18
100
47
100
5
100
59
78
58
a
Conversions to azide 1 were performed by adding NaN3 (2 mmol) to a stirring solution of acetate 3 or bromide 4 (1 mmol) in 4 mL of acetone/H2O (3:1) or
DMSO, then quenching the reaction with CH2Cl2/H2O after 10 min or 2 h. After aqueous workup the conversion (%) was determined by 1H NMR integration
(400 MHz, CDCl3) of the crude mixture (w95% purity).
b
Pure 3 or a mixture of 3:30 (3:1) was employed, leading to similar results.

M. M. Saꢀ et al. / Tetrahedron 62 (2006) 11652–11656
11655
30) toward azide anion under any given conditions and this
difference in reactivity is remarkably enhanced in acetone/
water medium (entries 2 and 4).
2.0 mmol of LiBr and 1.0 g of Amberlist-15Ò (Merck) and
stirring was continued for the time presented in Table 1.
The final mixture was filtered, the catalyst was rinsed with
CH2Cl2, and the filtrate was washed with H2O, satd
NaHCO3, and brine, dried over Na2SO4, filtered, and con-
centrated under reduced pressure. The resulting residue
was purified by chromatography on a short plug of silica
gel (hexane/ethyl acetate 9:1) to give the corresponding
methyl 2-(bromomethyl)-2-alkenoates 4 in the yields pre-
sented in Table 1 (not optimized). Solid products were puri-
fied by recrystallization with ethanol.
Finally, simple azido compounds 7–10 (Fig. 1) were also pre-
pared in high yields and short reaction times (10–30 min)
from the corresponding bromides and NaN3 under aqueous
acetone as outlined here.
N3
O
N3
N3
N3
O
10
4.2.1. Methyl (2E,4E)-2-(bromomethyl)-5-phenyl-2,4-
pentadienoate (4d). Yellow solid; mp 86.1–86.6 ꢀC; IR
OEt
O
7
8
9
1
(KBr): nmax 3017, 2942, 1711, 1604, 1236, 742 cmꢁ1; H
Figure 1.
NMR: d 3.85 (s, 3H), 4.47 (s, 2H), 7.03 (d, J¼15.5 Hz,
1H), 7.13 (dd, J¼15.5, 11.0 Hz, 1H), 7.36–7.41 (m, 3H),
7.51 (d, J¼11.0 Hz, 1H), 7.53–7.56 (m, 2H); 13C NMR:
d 24.7, 52.2, 122.4, 126.8, 127.5 (2ꢂCAr), 128.9 (2ꢂCAr),
129.6, 135.8, 142.7, 142.8, 166.3. Anal. Calcd for
C13H13BrO2 (%): C, 55.54; H, 4.66. Found: C, 55.93;
H, 5.01.
3. Conclusion
The alternative access to 2-(bromomethyl)-2-alkenoates 4
by Amberlist-15Ò-mediated bromination of Baylis–Hillman
adducts 2 is a synthetically useful transformation, particu-
larly for substrates bearing electron-rich groups. The simple
protocol for conversion of allylic bromides 4 to the corre-
sponding azides 1 in acetone/H2O is straightforward and
superior to conventional methods, leading to fast reactions,
reproducible conditions, easy workup, and excellent yields,
avoiding the use of potential contaminants such as high-
boiling solvents or organic additives. The mechanistic
aspects involved in these nucleophilic displacements and
the application of this simple methodology to more complex
systems are currently being investigated.
4.3. Typical procedure for the synthesis of
2-(azidomethyl)-2-alkenoates (1)
To a stirred solution of the allylic bromides 4 (1.0 mmol) in
4.0 mL of acetone/H2O (3:1) at 25 ꢀC was added 2.0 mmol
of NaN3 and stirring was continued for a further 10 min.
The final mixture was diluted with CH2Cl2, washed with
H2O, and brine, dried over Na2SO4, filtered, and concen-
trated under reduced pressure. The resulting residue was
purified by chromatography on a short plug of silica gel
(hexane/ethyl acetate 9:1) to give the corresponding methyl
2-(azidomethyl)-2-alkenoates 1 quantitatively.
4. Experimental
4.1. General
4.3.1. Methyl (E)-2-(azidomethyl)-3-(2-naphthyl)-2-pro-
penoate (1c). Clear yellow oil; IR (neat): nmax 3065, 2998,
All chemicals were of reagent grade and were used as
received. Melting points were determined using a Micro-
2951, 2926, 2850, 2109, 1709, 1626 cmꢁ1 1H NMR:
;
´
quımica MQPF301 apparatus and are uncorrected. Infrared
d 3.90 (s, 3H), 4.24 (s, 2H), 7.46–7.50 (m, 3H), 7.80–7.91
(m, 4H), 8.09 (s, 1H); 13C NMR: d 47.1, 52.4, 126.3, 126.6,
127.3, 127.6, 127.8, 128.4, 128.6, 129.8, 131.5, 133.0,
133.5, 144.5, 167.4. Anal. Calcd for C15H13N3O2 (%): C,
67.40; H, 4.90; N, 15.72. Found: C, 67.11; H, 4.88; N, 15.80.
spectra were acquired with a Perkin–Elmer FTIR 1600
spectrometer using KBr for solids and film for liquid
samples (range 4000–400 cmꢁ1). H NMR (400 MHz) and
1
13C NMR (100 MHz, fully decoupled) spectra were re-
corded with a Varian AS-400 spectrometer. Samples were
prepared in CDCl3 solution containing 1–2% tetramethyl-
silane (TMS) as internal standard. Chemical shifts are re-
ported in parts per million (d) relative to TMS. Coupling
constants (J) are measured in hertz (Hz). Elemental analyses
were conducted in a Carlo Erba CHN equipment by UFSC-
4.3.2. Methyl (2E,4E)-2-(azidomethyl)-5-phenyl-2,4-pen-
tadienoate (1d). White solid; mp 59.2–59.6 ꢀC; IR (KBr):
nmax 2946, 2105, 1705, 1615, 1283 cmꢁ1; 1H NMR: d 3.84
(s, 3H), 4.24 (s, 2H), 7.00 (d, J¼15.0 Hz, 1H), 7.07 (dd,
J¼15.0, 10.5 Hz, 1H), 7.33–7.39 (m, 3H), 7.49–7.51 (m,
2H), 7.61 (d, J¼10.5 Hz, 1H); 13C NMR: d 46.2, 52.5,
122.4, 124.7, 127.8 (2ꢂCAr), 129.1 (2ꢂCAr), 129.8, 135.9,
143.2, 143.8, 167.5. Anal. Calcd for C13H13N3O2 (%): C,
64.19; H, 5.39; N, 17.27. Found: C, 64.53; H, 5.74; N, 16.91.
´
´
ꢀ
Central Analıtica, Departamento de Quımica, Florianopolis,
SC, Brazil. Purifications by column chromatography were
performed with silica gel (Aldrich, 100–200 mesh particle
size). Compounds 1a,b6,8a and 4a–c,e–i13,14 were fully char-
acterized spectroscopically (IR, 1H NMR, CHN) and showed
physical and spectral data in accordance with their expected
structure and by comparison with spectral data in literature.
4.3.3. Methyl (E)-2-(azidomethyl)-3-(2-chlorophenyl)-2-
propenoate (1e). Clear yellow oil; IR (neat): nmax 3063,
2999, 2952, 2847, 2099, 1716, 1638 cmꢁ1 1H NMR:
;
4.2. Typical procedure for the synthesis of
2-(bromomethyl)-2-alkenoates (4)
d 3.90 (s, 3H), 4.09 (s, 2H), 7.32–7.45 (m, 4H), 8.04
(s, 1H); 13C NMR: d 46.9, 52.3, 126.7, 128.4, 129.5,
130.2, 130.4, 132.5, 134.1, 140.9, 166.7. Anal. Calcd for
C11H10ClN3O2 (%): C, 52.50; H, 4.01; N, 16.70. Found:
C, 52.34; H, 3.81; N, 16.58.
To a stirred solution of a Baylis–Hillman adduct 2
(1.0 mmol) in 3.0 mL of acetonitrile at 25 ꢀC were added

11656
M. M. Saꢀ et al. / Tetrahedron 62 (2006) 11652–11656
3. (a) Trost, B. M.; Pulley, S. R. Tetrahedron Lett. 1995, 36, 8737–
8740; (b) Trost, B. M.; Cook, G. R. Tetrahedron Lett. 1996, 37,
7485–7488; (c) Capaccio, C. A. I.; Varela, O. Tetrahedron:
Asymmetry 2000, 11, 4945–4954; (d) Cleophax, J.; Olesker,
A.; Rolland, A.; Gero, S. D.; Forchioni, A. Tetrahedron 1977,
33, 1303–1308; (e) Hu, T.; Panek, J. S. J. Am. Chem. Soc.
2002, 124, 11368–11378; (f) Askin, D.; Angst, C.;
Danishefsky, S. J. J. Org. Chem. 1985, 50, 5005–5007.
4. Gagneux, A.; Winstein, S.; Young, W. G. J. Am. Chem. Soc.
1960, 82, 5956–5958.
4.3.4. Methyl (E)-2-(azidomethyl)-3-(4-nitrophenyl)-2-
propenoate (1f). Yellow solid; mp 102.5–103.5 ꢀC; IR
(KBr): nmax 3107, 3082, 3006, 2955, 2110, 1722, 1633,
1
1514, 1263 cmꢁ1; H NMR: d 3.92 (s, 3H), 4.14 (s, 2H),
7.59 (d, J¼8.0 Hz, 2H), 7.96 (s, 1H), 8.29 (d, J¼8.0 Hz,
2H); 13C NMR: d 46.5, 52.6, 123.7 (2ꢂCAr), 129.8, 130.1
(2ꢂCAr), 140.2, 141.3, 147.8, 166.5. Anal. Calcd for
C11H10N4O4 (%): C, 50.38; H, 3.84; N, 21.36. Found: C,
50.43; H, 4.04; N, 21.31.
5. (a) Fava, C.; Galeazzi, R.; Mobbili, G.; Orena, M. Tetrahedron:
Asymmetry 2001, 12, 2731–2741; (b) Kawabata, H.; Kubo, S.;
4.3.5. Methyl (E)-2-(azidomethyl)-2-butenoate (1g) and
methyl 3-azido-2-methylenebutanoate (5g). Unstable oil,
obtained as a mixture with the corresponding isomer 5g in
90–95% purity (ratio 1g/5g w4:1); IR (neat): nmax 2993,
2954, 2853, 2107, 1717, 1652 cmꢁ1; major isomer (1g)
exhibited the following spectral properties: 1H NMR:
d 1.93 (d, J¼7.0 Hz, 3H), 3.79 (s, 3H), 4.08 (s, 2H), 7.19
(q, J¼7.0 Hz, 1H); 13C NMR: d 14.9, 45.6, 52.0, 127.4,
143.9, 166.6. Data for minor isomer (5g): 1H NMR: d 1.36
(d, J¼6.5 Hz, 3H), 3.74 (s, 3H), 4.44 (q, J¼6.5 Hz, 1H),
5.81 (s, 1H), 6.30 (s, 1H); 13C NMR: d 19.3, 51.7, 56.6,
125.5, 139.8, 165.7.
€
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Spino, C. Org. Lett. 2005, 7, 4769–4771.
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4.3.6. Methyl (E)-2-(azidomethyl)-4-methyl-2-hexenoate
(1i). Unstable oil, obtained as a mixture with the correspond-
ing isomer 5i in 90–95% purity (ratio 1g/5gw9:1); IR (neat):
1
nmax 2962, 2930, 2875, 2105, 1719, 1646 cmꢁ1; H NMR:
9. Patra, A.; Roy, A. K.; Batra, S.; Bhaduri, A. P. Synlett 2002,
1819–1822.
d 0.96 (t, J¼7.5 Hz, 3H), 1.06 (d, J¼3.5 Hz, 3H); 1.35–
1.52 (m, 2H), 2.41–2.51 (m, 1H), 3.83 (s, 3H), 4.05 (s,
2H), 6.85 (d, J¼10.5 Hz, 1H); 13C NMR: d 11.7, 20.0,
29.4, 35.2, 45.9, 52.4, 125.3, 154.0, 167.5.
ꢀ
10. Lubineau, A.; Auge, J. Topics in Current Chemistry; Springer:
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Acknowledgements
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13. (a) Fernandes, L.; Bortoluzzi, A. J.; Sa, M. M. Tetrahedron
The authors wish to thank Mr. Angelo Ruzza, Mr. Fabio
ꢀ
2004, 60, 9983–9989; (b) Nascimento, M. G.; Zanotto, S. P.;
ꢀ
´
Roehrs, and Central de Analises (Departamento de Quımica,
UFSC, Florianopolis) for spectroscopic analysis. L.F. and
ꢀ
ꢀ
Melegari, S. P.; Fernandes, L.; Sa, M. M. Tetrahedron:
Asymmetry 2003, 14, 3111–3115.
M.D.R. are grateful to CAPES and CNPq (Brazil) for fellow-
ships. Financial support by MCT/CNPq (Brazilian Research
Council) and FAPESC (Santa Catarina State Research
Council, Brazil) is also gratefully acknowledged.
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