Aza-Michael addition reactions of hydrazones with activated alkynes catalyzed by nitrogen-containing organic bases

Article abstract of DOI:10.1002/ejoc.201000365

Several highly efficient DABCO (1, 4-diazabicyclo[2.2.2]octane)-catalyzed Michael-type reactions of hydrazones with activated alkynes are described in this paper. This azaMichael addition reaction can be applied to different types of hydrazones, such as hydrazones 1 and hydroxy-bearing hydrazones 5. The corresponding adducts are achieved in high yields under mild reaction conditions. DABCO-promoted aza-Michael addition reactions were successfully applied to a serious of hydrazones with activated alkynes to afford the corresponding adducts in moderate to good yields.

Full text of DOI:10.1002/ejoc.201000365

FULL PAPER
DOI: 10.1002/ejoc.201000365
Aza-Michael Addition Reactions of Hydrazones with Activated Alkynes
Catalyzed by Nitrogen-Containing Organic Bases
Zhi-Liang Yuan,[a] Yin Wei,[b] and Min Shi*[a,b]
Keywords: Organocatalysis / Michael addition / Hydrazones / Alkynes
Several highly efficient DABCO (1,4-diazabicyclo[2.2.2]-
octane)-catalyzed Michael-type reactions of hydrazones with
activated alkynes are described in this paper. This aza-
Michael addition reaction can be applied to different types
of hydrazones, such as hydrazones 1 and hydroxy-bearing
hydrazones 5. The corresponding adducts are achieved in
high yields under mild reaction conditions. DABCO-pro-
moted aza-Michael addition reactions were successfully ap-
plied to a serious of hydrazones with activated alkynes to
afford the corresponding adducts in moderate to good yields.
and phenyl vinyl ketone (PVK),[13] affording the corre-
sponding adducts in good yields under mild conditions.
Since the activated alkynes, such as diethyl acetylenedi-
carboxylate, dimethyl acetylenedicarboxylate (DMAD) and
propiolate have been widely used as important building
blocks in organic synthesis[14] and have a similar nature as
activated olefins, we envisaged to utilize activated alkynes
as substrates in the reaction system described above instead
of activated olefins. During our ongoing investigation on
the development of this reaction, we were pleased to find
this nitrogen-containing organic-base-promoted Michael-
type reaction system can be applied to the reactions of dif-
ferent hydrazones 1 (R–CH=N–NH–Bz and R–CH=N–
NH–Ts) and hydroxy-containing hydrazones 5 with acti-
vated alkynes, such as diethyl acetylenedicarboxylate,
DMAD and propiolate. The reactions proceeded smoothly
and the corresponding adducts were achieved in moderate
to excellent yields. In this paper, we wish to report the de-
tails of this finding.
Introduction
The Michael addition reaction,[1] which is one of the
most important reactions in organic synthesis, has been well
studied thus far. In addition, the Morita–Baylis–Hillman
(MBH) reaction, which is also one of the most fundamental
reactions in organic chemistry consisting of a Michael ad-
dition, an aldol reaction and a proton transfer in the pres-
ence of catalytic amounts of nucleophilic Lewis bases, has
made great progress recently.[2] Furthermore, in the base-
catalyzed Michael addition,[3] many interesting findings
have been disclosed when using inorganic[4] or organic
bases[5,6] during recent years. It should also be noted that
besides classical Michael addition, oxo-[7] and aza-
Michael[8] additions, which are of great importance in both
pharmacology and biosynthesis,[9] have been well investi-
gated with regards to their developments in asymmetric in-
duction.[10] On the basis of these previously reported results,
it was found that, in some cases, nitrogen-containing or-
ganic bases can act as a Brønsted base instead of a Lewis
base. For example, Nemoto has reported a novel modified
MBH reaction of propiolate with different aldehydes pro-
moted by a catalytic amount of 1,4-diazabicyclo[2.2.2]-
octane (DABCO) in 2002.[11] Earlier, a DABCO-catalyzed
self- and cross-condensation of acetylenic ketones was re-
ported by Ramachandran and his co-workers.[12] In 2005,
Shi and co-workers reported DABCO-catalyzed Michael
additions of hydrazones with activated olefins, such as
methyl vinyl ketone (MVK), methyl acrylate, acrylonitrile
Results and Discussion
We initially examined the reaction of hydrazone 1a
(0.20 mmol) and diethyl acetylenedicarboxylate (2a)
(0.50 mmol) in the presence of various bases in CH2Cl2
(2.0 mL) at room temperature (25 °C) and the results of
these experiments are summarized in Table 1. It was found
that the reaction could not be promoted without the ad-
dition of base (Table 1, Entry 1), and none of the corre-
sponding aza-Michael addition product (Z)-3a was ob-
tained if using phosphorus-containing bases, such as PPh3
and PnBu3, as the catalysts (Table 1, Entries 11 and 12). In
the presence of 100, 50 or 10 mol-% of Et3N, the reaction
proceeded inefficiently to give the addition product (Z)-3a
[a] Laboratory for Advanced Materials & Institute of Fine
Chemicals, School of Chemistry & Molecular Engineering
130 Mei Long Lu, Shanghai 200237, China
Fax: +86-21-64166128
[b] State Key Laboratory of Organometallic Chemistry, Shanghai
Institute of Organic Chemistry, Chinese Academy of Sciences,
354 Fenglin Lu, Shanghai 200032, P. R. China
E-mail: Mshi@mail.sioc.ac.cn
1
in up to 36% yield after 24 h (Table 1, Entries 2–4). Its H
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201000365.
NMR spectrum has been indicated in Figure°S1 (Support-
4088
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 4088–4097

Aza-Michael Addition Reactions of Hydrazones with Activated Alkynes
ing Information). When we employed commonly used terti- tries 14, 15 and 18). It should also be noted that when using
ary amine catalyst DABCO, the reaction proceeded 10 mol-% of DABCO in THF, the starting materials disap-
smoothly to give the adduct (Z)-3a in 77% yield after only peared after stirring for 6 h at room temperature (the con-
6 h (Table 1, Entry 5). The use of 10 mol-% of DABCO in version of 1a Ͼ 99%), and the isolated yield of 3a can be
CH2Cl2 also promoted the reaction efficiently to give (Z)- improved to 93% (Table 1, Entry 14). The yields of (Z)-3a
3a in 71% yield, unless the lower catalyst loading was used decreased when we utilized toluene and MeCN as the sol-
(Table 1, Entries 6 and 7). Other nitrogen-containing bases, vents and no reaction occurred in H2O even after a pro-
for instance DBU (1,8-diazabicyclo[5.4.0]undec-7-ene), longed reaction time, presumably due to the very low solu-
DMAP [4-(N,N-dimethylamino)pyridine)] and pyridine, are bility of hydrazone 1a in toluene, MeCN and H2O since the
not as effective as DABCO under identical conditions starting materials 1a and 2a still remained in the reaction
(Table 1, Entries 8–10). It was found that when using system (Table 1, Entries 16, 17 and 19).
K2CO3, an inorganic base, as the catalyst the reaction could
Interestingly, when the reaction took place in EtOH, not
not be promoted even after a prolonged reaction time only the Michael addition product (Z)-3a was formed in
(Table 1, Entry 13).
39% yield, but the ethanol adduct 4 was also obtained in
32% yield. This is because the solvent EtOH could also
participate in a Michael addition with 2a in the presence of
DABCO (Table 1, Entry 20).
Table 1. Survey of base catalysts and solvent effects of the reaction
of hydrazone 1a (1.0 equiv.) with 2a (2.5 equiv.) at room tempera-
ture.[a]
When these aza-Michael reactions proceeded very well
and the isolated yields of the products were over 80%, all
of the starting materials disappeared and the conversions
were over 96%. When the reaction afforded the products in
poor isolated yields, the starting materials still remained in
the reaction system and the conversions were low. The re-
maining starting materials could be isolated as well and did
not decompose during the reaction.
With these optimized reaction conditions in hand, we
next turned our interest to the reaction scope by using a
variety of hydrazones 1 with diethyl acetylenedicarboxylate
(2a)under the standard conditions. As summarized in
Table 2, the corresponding adducts (Z)-3 were obtained in
high yields in the presence of 10 mol-% of DABCO
(Table 2, Entries 1–11). For aromatic hydrazones 1b–j, the
reaction proceeded smoothly to produce adducts (Z)-3b–j
in high yields in most cases whether electron-withdrawing
Table 2. Survey of hydrazone 1 (1.0 equiv.) with 2a (2.5 equiv.) in
the presence of DABCO (10 mol-%) at room temperature.[a]
[a] The reaction was carried out with 0.20 mmol of 1a, 0.50 mmol
of 2a and 10 mol-% of base catalysts in CH2Cl2 (2.0 mL) under an
ambient atmosphere. [b] Isolated yield. [c] 100 mol-% of Et3N was
used. [d] 50 mol-% of Et3N was used. [e] 20 mol-% of DABCO was
used. [f] 5 mol-% of DABCO was used. [g] 100 mol-% of K2CO3
was used. [h] Ethanol adduct (Z)-4 was obtained in 32% yield.
Subsequently, the solvent effects have been examined by
using DABCO (10 mol-%) as a catalyst. The reaction pro-
ceeded efficiently to give the corresponding adduct (Z)-3a
[a] The reaction was carried out with 0.20 mmol of 1, 0.50 mmol
of 2a and 10 mol-% of DABCO in THF (2.0 mL) under an ambient
in good yields in THF, EtOAc and DMF (Table 1, En- atmosphere. [b] Isolated yield.
Eur. J. Org. Chem. 2010, 4088–4097
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4089

Z.-L. Yuan, Y. Wei, M. Shi
FULL PAPER
or -donating groups were present on the benzene ring of 1H NMR spectra as shown in Figures°S2 and S3 (Support-
hydrazones 1 or not (Table 2, Entries 1 and 3–9), with the ing Information). From Figures°S2 and S3, it can be seen
1
exception of 3-chlorobenzaldehyde 1c. The use of this 3- that the exact chemical shifts of CH3 and OCH3 in the H
substituted hydrazone 1c as a reactant under the optimized NMR spectrum of major product (Z)-3n are at δ = 2.41,
reaction conditions afforded the corresponding product 3.61 and 3.72 ppm, which differ from its corresponding
(Z)-3c in 76% yield, a lower yield than with other aromatic minor product at δ = 2.45, 3.71 and 3.83 ppm. Moreover,
hydrazones (Table 2, Entry 2). With aliphatic hydrazones, the exact chemical shifts of the olefinic proton and CH=N
such as 1k and 1l, the reaction also proceeded smoothly to in the 1H NMR spectrum of (E)-3n at δ = 5.97 and
give the corresponding adducts (Z)-3k and (Z)-3l in high 8.46 ppm were completely different from those of (Z)-3n at
yields of up to 90% (Table 2, Entries 10 and 11).
δ = 7.31 to 7.35 ppm. The stereochemical outcome of (Z)-
Furthermore, the reaction between hydrazone 1a with 3n has been unambiguously assigned by single-crystal X-
ethyl propiolate (2b) was investigated under the optimized ray diffraction (Figure 1).[15] Therefore, the major products
reaction conditions. To our delight, it did take place, afford- in Table 3 should have a Z configuration.
ing the corresponding adduct (E)-3m in 77% yield
(Scheme 1).
Scheme 1. The reaction of hydrazone 1a (1.0 equiv.) with propiolate
(2b) (2.5 equiv.) in the presence of DABCO (10 mol-%) at room
temperature in THF (2.0 mL).
The substrate scope of this reaction was examined fur-
ther with hydrazone 1n bearing a N-Tos protecting group
and DMAD (2c). The results are summarized in Table 3.
We observed that hydrazones bearing a N-Bz protecting
group produced the corresponding adduct as a single iso-
mer (Table 1), but hydrazones with a N-Tos protecting
group led to the adduct as mixtures of Z and E isomers,
presumably due to the fact that the N-Tos protecting group
is a sterically more bulky substituent than the N-Bz group
and this steric effect affects the stereochemical outcome.
Figure 1. X-ray crystal structure of (Z)-3n.
1
By comparison of the H NMR spectra of (Z)-3n and
3a, we could further confirm that adducts 3a–j in Tables 1
and 2 have a Z configuration (Figures°S1 and S2, Support-
ing Information).
The reaction of hydrazone 1n with 2c proceeded smoothly
under the optimized reaction conditions to give adduct 3n
as a couple of Z/E (2.5:1) isomers in 90% yield (Table 3,
Entry 1). The Z/E isomers of 3n can be separated by a pre-
parative TLC and the difference between the major (Z)-3n
and minor product (E)-3n can be clearly observed from the
Treatment of 1n with 2c in the presence of 10 mol-%
DMAP in THF for 24 h afforded 3n as a couple of Z/E
(1:1) isomers in only 49% yield (Table 3, Entry 2) and a
single isomer of adduct 3n (Z/E, 99:1) was obtained in 35%
yield with 10 mol-% DBU as a promoter (Table 3, Entry 3).
Hydrazones 1o and 1p, synthesized by ethyl glyoxalate and
trifluoroacetaldehyde ethyl hemiacetal, could also be ap-
plied in this reaction under the optimized conditions, giving
the corresponding Michael addition products 3o and 3p in
77 and 83% yield, respectively, as two isomers in a 10:1
(Z/E) ratio (Table 3, Entries 4 and 5).
Table 3. Survey of hydrazone 1 with 2a in the presence of base
catalyst at room temperature.[a]
After having established the aza-Michael addition cata-
lyzed by DABCO, we turned our attention to the investiga-
tion this Michael addition reaction with respect to hydra-
zone 5a,which bears a phenolic hydroxy group. We assumed
that the hydroxy group may also participate in the Michael
reaction with DMAD (2c) in the presence of DABCO and
we were pleased to find that hydrazone 5a indeed reacted
with 2c in the presence of 10 mol-% DABCO in THF for
6 h, giving the corresponding multi-addition product (Z)-
6a in 62% yield as a single isomer (Scheme 2).
[a] The reaction was carried out with 1.0 equiv. of 1, 2.5 equiv. of 2c
and 10 mol-% of base catalyst in THF (2.0 mL) under an ambient
atmosphere. [b] Isolated yield. [c] Determined by analysis of the
1
400 MHz H NMR spectra.
4090
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 4088–4097

Aza-Michael Addition Reactions of Hydrazones with Activated Alkynes
Table 4. Survey of hydrazone 5 (1.0 equiv.) with dimethyl acetylene-
dicarboxylate 2c (3.0 equiv.) in the presence of base catalyst
(10 mol-%) at room temperature.[a]
Scheme 2. Reaction of hydrazone 5a (1.0 equiv.) with 2c (2.5 equiv.)
in the presence of DABCO (10 mol-%) at room temperature in
THF (2.0 mL).
Moreover, the further survey of hydrazone 5 (1.0 equiv.)
with 2c (3.0 equiv.) was also performed and the results of
these experiments are summarized in Table 4 and Scheme 3.
Under the optimized reaction conditions and prolonged re-
action time (12 to 24 h), the reaction proceeded efficiently
to give the addition product 6 in up to 92% yield. But the
substituted groups on the benzene ring may exert steric ef-
fects and the corresponding multi-adduct was obtained as
a couple of Z/E isomers. When the benzene ring of 5 bears
a 3-methoxy group (R1 = OMe), the corresponding adduct
[a] The reaction was carried out with 0.20 mmol of 5, 0.60 mmol
of 2c and 10 mol-% of DABCO in THF (2.0 mL) under an ambient
atmosphere. [b] Isolated yield. [c] Determined by analysis of the
1
400 MHz H NMR spectra.
(Z)-6b was obtained in 73% yield and the ratio of isomers adduct (Z)-6e in 73% yield along with a high ratio of iso-
was 84:16 (Z/E) (Table 4, Entry 1).
mers (Z/E, 92:8) (Scheme 3, Equation°1). When using a 4-
By using 4-substituted hydrazone 5c (R2 = OMe) as a hydroxy-substituted hydrazone 5f, the corresponding ad-
reactant under the optimized reaction conditions product duct (Z)-6f was obtained in the highest yield (92%) and
(Z)-6c was formed in a higher yield (83%) and as a moder- the ratio of isomers was moderate (Z/E, 83:17; Scheme 3,
ate ratio of isomers (Z/E, 91:9; Table 4, Entry 2). When Equation°2).
bearing a strongly electron-withdrawing group, such as a 5-
It should be noted that unlike adduct (Z)-3n, Z and E
nitro group (R3 = NO2), however, the reaction proceeded isomers of multi-adduct 6b could not be separated by pre-
slowly to give the adduct (Z)-6d in 63% yield, even though parative TLC. The difference between multi-adduct 6a,
the reaction time was prolonged, with a 83:17 (Z/E) ratio which is obtained as a single isomer, and 6b, which is
of isomers (Table 4, Entry 3). Hydrazone 5e, containing a formed as a couple of Z/E isomers, was clear from their 1H
naphthalene group, could also react with 2c, affording the NMR spectra, as shown in Figures°S4 and S5 (Supporting
Scheme 3. Reaction of hydrazones 5e, 5f and 5g (1.0 equiv.) with 2c (3.0 equiv.) in the presence of DABCO (10 mol-%) at room temperature
in THF (2.0 mL).
Eur. J. Org. Chem. 2010, 4088–4097
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4091

Z.-L. Yuan, Y. Wei, M. Shi
FULL PAPER
Information). From Figure°S5, it can be seen that the sig-
1
nals of the methoxy group (OCH3) in the H NMR spec-
trum of the minor multi-adduct 6b appeared at δ = 3.62,
3.73, 3.74 and 3.84 ppm and the major multi-adduct 6b ap-
peared at δ = 3.63, 3.71, 3.81 and 3.95 ppm, respectively.
Moreover, the exact chemical shifts of the olefinic proton
and CH=N in the 1H NMR spectrum of the couple of
Z/E isomers were completely different. The olefinic proton
and CH=N signals of the minor multi-adduct 6b appeared
at δ = 6.22 and 7.92 ppm and these signals in the major
multi-adduct 6b appeared at δ = 7.37 to 7.66 ppm, respec-
tively. Since the stereochemical outcome of (Z)-6e has been
unambiguously assigned by single-crystal X-ray diffraction
Scheme 4. Reaction of hydrazones 5a (1.0 equiv.) with 2c
(3.0 equiv.) in the presence of base catalysts (10 mol-%) at room
temperature in THF (2.0 mL).
1
(Figure 2),[16] by comparison with the H NMR spectra of
6a, 6b and 6e (Figure°S6, Supporting Information), we con-
firmed that the stereochemical outcomes of major multi-
adducts 6a–g in Table 4 and Scheme 3 are Z isomers.
duct (Z)-3a in excellent yields (up to 99%) within 12 h and
none of the phenol addition product was formed (Table 5,
Entries 1 to 3). These results suggest that a substrate bear-
ing a hydroxy group is essential to form the corresponding
multi-addition products 6 during the reaction.
Table 5. Survey of hydrazone 1a (1.0 equiv.) with 2a (3.0 equiv.) in
the presence of DABCO (10 mol-%) and phenol (x°equiv.) at room
temperature.[a]
Figure 2. X-ray crystal structure of 6e.
[a] The reaction was carried out with 0.20 mmol of 1a, 0.60 mmol
of 2a, x°equiv. phenol and 10 mol-% of DABCO in THF (2.0 mL)
under an ambient atmosphere. [b] Isolated yield.
Under the same conditions, we next examined the reac-
tion of hydrazone 5g, bearing a 2,3-dihydroxybenzaldehyde,
with 2c (Scheme 3, Equation°3). The corresponding adduct
(Z)-6g, which was formed by using one equivalent of hydraz-
one 5g with three equivalents of 2c, was achieved in 63%
yield and the ratio of isomers 85:15 (Z/E).
Replacing base catalyst DABCO with other nitrogen-
containing organic bases, such as DMAP and DBU af-
forded different results in the reaction of hydroxy-bearing
substrate 5a with 2c under the optimized reaction condi-
tions (Scheme 4, Equations°1 and 2). Hydrazone 5a reacted
with only one equivalent of 2c, even with a prolonged reac-
tion time, with DMAP and DBU as the catalysts respec-
tively, to afford the corresponding adduct (Z)-6h in 38 and
48% yield as a single isomer.
A plausible mechanism for this reaction is shown in
Scheme 5. On the basis of the control experiments, we be-
lieve that DABCO acts as a Brønsted base in this reaction.
After a proton has been abstracted by DABCO (NR3), the
hydrazone A is then transformed into a nucleophilic inter-
mediate B that subsequently reacts with activated alkyne C
To clarify whether a phenolic hydroxy-bearing substrate
is essential to react with more than one equivalent of 2a
resulting the multi-addition product, the control experi-
ments with the addition of one, two and three equivalents
of phenol into the reaction system of hydrazone 1a with 2a
were carried out under the standard conditions and the re-
sults are outlined in Table 5. It was found that the reactions
of hydrazone 1a with 2a proceeded smoothly to afford ad- Scheme 5. A plausible reaction mechanism.
4092 Eur. J. Org. Chem. 2010, 4088–4097
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Aza-Michael Addition Reactions of Hydrazones with Activated Alkynes
ArH), 7.68 (dd, J = 8.0, 2.0 Hz, 1 H, ArH), 7.85 (dd, J = 8.0,
1.6 Hz, 2 H, ArH), 7.94 (s, 1 H, CH) ppm. 13C NMR (100 MHz,
CDCl3, TMS): δ = 13.8, 13.9, 61.6, 62.7, 126.9, 127.2, 127.5, 129.6,
129.8, 130.8, 131.0, 131.1, 131.2, 134.0, 134.3, 136.1, 138.1, 161.5,
162.2, 170.3 ppm. MS (EI): m/z (%) = 428 (0.7) [M]+, 393 (1.6),
355 (1.7), 315 (1.5), 288 (6.9), 218 (7.1), 105 (100), 77 (22.0), 51
(2.1). HRMS (EI): calcd. for C22H21ClN2O5 [M + H]+ 428.1139;
found 428.1140.
and generates allenic enolate D. Then, deprotonation of all-
enic enolate D produces the corresponding product E and
regenerates DABCO to complete the catalytic cycle.
Conclusions
In conclusion, we have developed a Michael-type ad-
dition reaction of different hydrazones with activated
alkynes. Through this synthesis route, we can achieve the
corresponding interesting adducts in good to excellent
yields.[17] The advantages of this method are the use of sim-
ple and cheap starting materials and mild reaction condi-
tions. In addition, several interesting results were obtained
when using hydroxyl-substituted substrates, affording unex-
pected products in which both the NH and OH groups have
reacted with the acetylenic bond.
Diethyl 2-[(E)-1-Benzoyl-2-(3-chlorobenzylidene)hydrazinyl]fumar-
ate (3c): Pale-yellow oil (76%, 65 mg). IR (acetone): ν = 3065, 2983,
˜
2938, 2906, 1729, 1601, 1564, 1474, 1447, 1391, 1312, 1261, 1206,
1158, 1096, 1076, 1055, 1028, 915 cm–1. 1H NMR (400 MHz,
CDCl3, TMS): δ = 1.22 (t, J = 7.2 Hz, 3 H, CH3), 1.29 (t, J =
7.2 Hz, 3 H, CH3), 4.19 (q, J = 7.2 Hz, 2 H, CH2), 4.30 (q, J =
7.2 Hz, 2 H, CH2), 7.22–7.35 (m, 2 H, ArH), 7.36–7.39 (m, 2 H,
ArH and CH), 7.44–7.55 (m, 5 H, ArH and CH), 7.85 (dd, J =
8.4, 1.6 Hz, 2 H, ArH) ppm. 13C NMR (100 MHz, CDCl3, TMS):
δ = 13.9, 13.9, 61.6, 62.7, 125.4, 127.1, 127.5, 129.7, 129.8, 131.1,
131.3, 133.9, 134.6, 135.7, 135.9, 139.7, 161.6, 162.3, 170.2 ppm.
MS (EI): m/z (%) = 428 (0.8) [M]+, 383 (1.0), 355 (1.4), 288 (9.5),
218 (2.6), 105 (100), 89 (1.8), 77 (18.9), 51 (2.3). HRMS (EI): calcd.
for C22H21ClN2O5 [M + H]+ 428.1139; found 428.1133.
Experimental Section
1
General Remarks: H and 13C NMR spectra were recorded with a
Diethyl 2-[(E)-1-Benzoyl-2-(4-chlorobenzylidene)hydrazinyl]fumar-
Bruker AM-400 spectrometer for solutions in CDCl3 with tet-
ramethylsilane (TMS) as an internal standard. Mass spectra were
recorded by EI methods, and HRMS was measured with a Finni-
gan MA+ mass spectrometer. THF and toluene were distilled from
sodium (Na) under an argon atmosphere. CH3CN and dichloro-
methane were distilled from CaH2 under an argon atmosphere.
Commercially obtained reagents were used without further purifi-
cation. All reactions were monitored by TLC with Huanghai GF254
silica-gel coated plates. Flash column chromatography was carried
out by using 300–400 mesh silica gel at increased pressure.
ate (3d): Pale-yellow oil (87%, 75 mg). IR (acetone): ν = 3066,
˜
2983, 2938, 2906, 1728, 1673, 1610, 1491, 1447, 1395, 1322, 1263,
1206, 1159, 1088, 1070, 1054, 1028, 1014, 908 cm–1. 1H NMR
(400 MHz, CDCl3, TMS): δ = 1.21 (t, J = 7.2 Hz, 3 H, CH3), 1.28
(t, J = 7.2 Hz, 3 H, CH3), 4.18 (q, J = 7.2 Hz, 2 H, CH2), 4.30 (q,
J = 7.2 Hz, 2 H, CH2), 7.27–7.30 (m, 3 H, ArH), 7.39–7.53 (m, 6
H, ArH and CH), 7.87 (dd, J = 8.4, 1.2 Hz, 2 H, ArH) ppm. 13C
NMR (100 MHz, CDCl3, TMS): δ = 13.8, 13.9, 61.6, 62.7, 127.4,
128.5, 128.8, 129.8, 131.0, 131.3, 132.4, 134.0, 135.8, 136.0, 140.0,
161.6, 162.3, 170.2 ppm. MS (EI): m/z (%) = 428 (0.8) [M]+, 383
(0.8), 355 (1.3), 315 (1.5), 288 (7.6), 218 (3.4), 105 (100), 77 (22.8),
41 (0.6). HRMS (EI): calcd. for C22H21ClN2O5 [M + H]+ 428.1139;
found 428.1138.
General Procedure for the Reactions of Hydrazones with Activated
Alkynes Promoted by DABCO: Diethyl acetylenedicarboxylate (2a)
(85 mg, 0.5 mmol) was added dropwise into a reaction vessel con-
taining a solution of hydrazone 1a (45.4 mg, 0.20 mmol) and
DABCO (2.2 mg, 0.02 mmol) in THF (2.0 mL) at room tempera-
ture. After the resulting mixture had been stirred for 6 h, the corre-
sponding adduct 3a was purified by flash column chromatography
(SiO2).
Diethyl 2-[(E)-1-Benzoyl-2-(4-bromobenzylidene)hydrazinyl]fumar-
ate (3e): Pale-yellow solid (92%, 87 mg). M.p. 105–109 °C. IR (ace-
tone): ν = 3065, 2983, 2938, 2905, 1728, 1673, 16109, 1489, 1447,
˜
1393, 1368, 1321, 1259, 1206, 1158, 1097, 1070, 1055, 1028, 10140,
907 cm–1. 1H NMR (400 MHz, CDCl3, TMS): δ = 1.21 (t, J =
7.2 Hz, 3 H, CH3), 1.27 (t, J = 7.2 Hz, 3 H, CH3), 4.18 (q, J =
Diethyl 2-[(E)-1-Benzoyl-2-benzylidenehydrazinyl]fumarate (3a):
Pale-yellow oil (93%, 73 mg). IR (acetone): ν = 3065, 2983, 2938, 7.2 Hz, 2 H, CH2), 4.30 (q, J = 7.2 Hz, 2 H, CH2), 7.34–7.36 (m,
˜
2905, 1729, 1673, 1609, 1489, 1447, 1393, 1321, 1259, 1206, 1158,
2 H, ArH), 7.39 (s, 1 H, CH), 7.43 (s, 1 H, CH), 7.43–7.53 (m, 5
1097, 1070, 1055, 1028, 1010, 907 cm–1. 1H NMR (400 MHz, H, ArH), 7.84 (dd, J = 8.4, 1.6 Hz, 2 H, ArH) ppm. 13C NMR
CDCl3, TMS): δ = 1.21 (t, J = 6.8 Hz, 3 H, CH3), 1.28 (t, J =
6.8 Hz, 3 H, CH3), 4.18 (q, J = 6.8 Hz, 2 H, CH2), 4.30 (q, J =
(100 MHz, CDCl3, TMS): δ = 13.8, 13.9, 61.5, 62.6, 124.1, 125.4,
127.4, 128.6, 129.8, 130.9, 131.2, 131.7, 132.8, 134.0, 135.9, 140.0,
6.8 Hz, 2 H, CH2), 7.31–7.33 (m, 3 H, ArH), 7.39 (s, 1 H, CH), 161.6, 162.2, 170.1 ppm. MS (EI): m/z (%) = 474 (0.8) [M]+, 472
7.43–7.51 (m, 5 H, ArH), 7.53 (s, 1 H, CH), 7.87 (dd, J = 2.8,
(0.8) [M]+, 401 (1.4), 399 (1.4), 346 (18.7), 315 (24.7), 288 (11.1),
1.2 Hz, 2 H, ArH) ppm. 13C NMR (100 MHz, CDCl3, TMS): δ = 226 (4.7), 218 (4.2), 105 (100), 89 (3.8), 77 (23.2), 43 (4.3). HRMS
13.9, 13.9, 61.6, 62.6, 127.3, 127.4, 128.6, 129.9, 130.0, 130.9, 131.2,
133.9, 134.2, 136.1, 141.5, 161.8, 162.4, 170.2 ppm. MS (EI): m/z
(%) = 394 (1.4) [M]+, 349 (2.0), 321 (3.7), 288 (12.8), 218 (8.7), 105
(100), 77 (27.6). 51 (3.3). C22H22N2O5 (394.15): calcd. C 66.99, H
5.62, N 7.10; found C 66.91, H 5.56, N 7.06.
(EI): calcd. for C22H21BrN2O5 [M + H]+ 472.0634; found 472.0637.
Diethyl 2-[(E)-1-Benzoyl-2-(4-methylbenzylidene)hydrazinyl]fumar-
ate (3f): Pale-yellow oil (90%, 73 mg). IR (acetone): ν = 3059, 2983,
˜
2938, 1729, 1668, 1613, 1579, 1493, 1447, 1397, 1324, 1259, 1206,
1178, 1155, 1095, 1054, 1029, 908 cm–1. 1H NMR (400 MHz,
CDCl3, TMS): δ = 1.19 (t, J = 7.2 Hz, 3 H, CH3), 1.26 (t, J =
7.2 Hz, 3 H, CH3), 2.31 (s, 3 H, CH3), 4.17 (q, J = 7.2 Hz, 2 H,
CH2), 4.28 (q, J = 7.2 Hz, 2 H, CH2), 7.12 (d, J = 6.8 Hz, 2 H,
ArH), 7.32–7.51 (m, 6 H, ArH and CH), 7.53 (s, 1 H, CH), 7.87 (d,
Diethyl 2-[(E)-1-Benzoyl-2-(2-chlorobenzylidene)hydrazinyl]fumar-
ate (3b): Pale-yellow oil (85%, 73 mg). IR (acetone): ν = 3066,
˜
2983, 2938, 1729, 1677, 1601, 1473, 1447, 1390, 1319, 1259, 1206,
1
1158, 1052, 1030, 907 cm–1. H NMR (400 MHz, CDCl3, TMS): δ
= 1.23 (t, J = 7.2 Hz, 3 H, CH3), 1.30 (t, J = 7.2 Hz, 3 H, CH3), J = 6.8 Hz, 2 H, ArH) ppm. 13C NMR (100 MHz, CDCl3, TMS): δ
4.20 (q, J = 7.2 Hz, 2 H, CH2), 4.32 (q, J = 7.2 Hz, 2 H, CH2),
7.15–7.33 (m, 3 H, ArH), 7.40 (s, 1 H, CH), 7.43–7.53 (m, 3 H,
= 13.8, 13.8, 21.2, 61.4, 62.5, 127.2, 127.3, 129.2, 129.8, 130.8,
131.0, 131.1, 134.2, 136.1, 140.2, 141.7, 161.8, 162.3, 170.0 ppm.
Eur. J. Org. Chem. 2010, 4088–4097
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4093

Z.-L. Yuan, Y. Wei, M. Shi
FULL PAPER
MS (EI): m/z (%) = 408 (0.8) [M]+, 363 (0.8), 335 (1.5), 288 (4.2),
218 (5.0), 105 (100), 91 (4.9), 77 (19.4), 51 (2.6). HRMS (EI): calcd.
for C23H24N2O5 [M + H]+ 408.1685; found 408.1686.
HRMS (EI): calcd. for C20H20N2O6 [M + H]+ 384.1321; found
384.1327.
Diethyl 2-[(E)-1-Benzoyl-2-(3-phenylpropylidene)hydrazinyl]fumar-
ate (3k): Pale-yellow oil (90%, 76 mg). IR (acetone): ν = 3061,
˜
Diethyl 2-[(E)-1-Benzoyl-2-(2-methoxybenzylidene)hydrazinyl]fum-
3027, 2983, 2983, 2937, 1729, 1671, 1602, 1579, 1495, 1448, 1399,
1368, 1322, 1259, 1206, 1095, 1054, 1029, 899 cm–1. 1H NMR
(400 MHz, CDCl3, TMS): δ = 1.22 (t, J = 7.2 Hz, 3 H, CH3), 1.26
(t, J = 7.2 Hz, 3 H, CH3), 2.56 (dt, J = 8.0, 5.6 Hz, 2 H, CH2),
2.77 (t, J = 8.0 Hz, 2 H, CH2), 4.17 (q, J = 7.2 Hz, 2 H, CH2), 4.25
(q, J = 7.2 Hz, 2 H, CH2), 6.95–6.98 (m, 1 H, ArH), 7.10 (dd, J =
6.8, 1.6 Hz, 2 H, ArH), 7.16–7.20 (m, 2 H, ArH and CH), 7.23–
7.27 (m, 2 H, ArH), 7.34–7.45 (m, 3 H, ArH and CH), 7.71 (dd, J =
8.0, 1.6 Hz, 2 H, ArH) ppm. 13C NMR (100 MHz, CDCl3, TMS): δ
= 13.9, 32.2, 33.9, 61.4, 62.4, 125.9, 127.3, 128.2, 128.2, 128.3,
129.6, 130.6, 130.7, 134.2, 136.3, 140.5, 145.1, 161.7, 162.4,
169.9 ppm. MS (EI): m/z (%) = 422 (1.0) [M]+, 349 (1.7), 317 (6.5),
218 (4.7), 117 (3.6), 105 (100), 91 (7.7), 77 (19.5), 51 (2.3). HRMS
(EI): calcd. for C24H26N2O5 [M + H]+ 422.1842; found 422.1839.
arate (3g): Pale-yellow oil (95%, 80 mg). IR (acetone): ν = 3072,
˜
2982, 2939, 2906, 2840, 1728, 1668, 1606, 1577, 1489, 1466, 1447,
1394, 1368, 1322, 1289, 1206, 1157, 1106, 1049, 1026, 909 cm–1. 1H
NMR (400 MHz, CDCl3, TMS): δ = 1.21 (t, J = 7.2 Hz, 3 H, CH3),
1.27 (t, J = 7.2 Hz, 3 H, CH3), 3.79 (s, 3 H, OCH3), 4.18 (q, J =
7.2 Hz, 2 H, CH2), 4.29 (q, J = 7.2 Hz, 2 H, CH2), 6.83–6.88 (m,
2 H, ArH), 7.26–7.31 (m, 1 H, ArH), 7.37 (s, 1 H, CH), 7.41–7.51
(m, 3 H, ArH), 7.62 (dd, J = 7.6, 2.0 Hz, 1 H, ArH), 7.86 (dd, J =
8.4, 2.0 Hz, 2 H, ArH), 7.95 (s, 1 H, CH) ppm. 13C NMR
(100 MHz, CDCl3, TMS): δ = 13.8, 13.8, 55.3, 61.4, 62.5, 110.8,
120.6, 122.2, 126.2, 127.3, 129.9, 130.7, 130.9, 131.2, 134.3, 136.4,
137.4, 158.0, 161.9, 162.4, 170.2 ppm. MS (EI): m/z (%) = 424 (1.2)
[M]+, 379 (1.2), 351 (1.5), 288 (4.4), 218 (14.8), 105 (100), 91 (3.9),
77 (24.7), 43 (14.3). HRMS (EI): calcd. for C23H24N2O6 [M + H]+
424.1634; found 424.1636.
Diethyl 2-[(E)-1-Benzoyl-2-butylidenehydrazinyl]fumarate (3l): Pale-
yellow oil (87%, 58 mg). IR (acetone): ν = 3052, 2958, 2874, 1732,
˜
Diethyl 2-[(E)-1-Benzoyl-2-(4-methoxybenzylidene)hydrazinyl]fum-
1667, 1602, 1448, 1436, 1400, 1326, 1266, 1213, 1173, 1147, 1059,
arate (3h): Pale-yellow oil (93%, 78 mg). IR (acetone): ν = 3066,
˜
1
1015, 909 cm–1. H NMR (400 MHz, CDCl3, TMS): δ = 0.89 (t, J
2982, 2938, 2839, 1729, 1667, 1607, 1578, 1514, 1447, 1400, 1368,
1325, 1299, 1254, 1205, 1170, 1110, 1054, 1029, 909 cm–1. 1H NMR
(400 MHz, CDCl3, TMS): δ = 1.20 (t, J = 7.2 Hz, 3 H, CH3), 1.27
(t, J = 7.2 Hz, 3 H, CH3), 3.77 (s, 3 H, OCH3), 4.17 (q, J = 7.2 Hz,
2 H, CH2), 4.28 (q, J = 7.2 Hz, 2 H, CH2), 6.84 (dd, J = 6.8, 2.0 Hz,
2 H, ArH), 7.36 (s, 1 H, CH), 7.42–7.51 (m, 6 H, ArH and CH),
7.86 (dd, J = 8.8, 2.0 Hz, 2 H, ArH) ppm. 13C NMR (100 MHz,
CDCl3, TMS): δ = 13.8, 13.9, 55.2, 61.4, 62.5, 113.9, 126.5, 127.3,
128.8, 129.8, 130.7, 130.9, 134.3, 136.2, 141.5, 161.1, 161.9, 162.4,
170.0 ppm. MS (EI): m/z (%) = 424 (2.9) [M]+, 379 (1.4), 351 (2.0),
288 (3.6), 218 (9.6), 105 (100), 91 (2.5), 77 (24.2), 51 (2.6). HRMS
(EI): calcd. for C23H24N2O6 [M + H]+ 424.1634; found 424.1636.
= 7.2 Hz, 3 H, CH3), 1.47 (dt, J = 14.8, 7.2 Hz, 2 H, CH3), 2.23
(dt, J = 7.2, 5.6 Hz, 2 H, CH2), 3.74 (s, 3 H, CH3), 3.82 (s, 3 H,
CH3), 6.94 (t, J = 5.2 Hz, 1 H, ArH), 7.25 (s, 1 H, CH), 7.37–7.48
(m, 3 H, ArH and CH), 7.77 (dd, J = 7.2, 1.6 Hz, 2 H, ArH) ppm.
13C NMR (100 MHz, CDCl3, TMS): δ = 13.3, 19.5, 34.2, 52.3,
53.2, 127.3, 129.6, 130.3, 130.7, 134.1, 136.6, 147.0, 162.4, 162.8,
170.0 ppm. MS (EI): m/z (%) = 332 (1.0) [M]+, 289 (5.8), 260 (1.9),
210 (1.9), 105 (100), 77 (37.3), 51 (4.7), 43 (3.3). HRMS (EI): calcd.
for C17H20N2O5 [M + H]+ 332.1372; found 332.1371.
(E)-Ethyl 3-[(E)-1-Benzoyl-2-benzylidenehydrazinyl]acrylate (3m):
Yellow solid (77%, 50 mg). M.p. 103–106 °C. IR (acetone): ν =
˜
3063, 2980, 2904, 1709, 1681, 1622, 1574, 1491, 1448, 1369, 1272,
1236, 1152, 1076, 1157, 1042, 1001, 965, 927 cm–1. 1H NMR
(400 MHz, CDCl3, TMS): δ = 1.26 (t, J = 7.2 Hz, 3 H, CH3), 4.17
(q, J = 7.2 Hz, 2 H, CH2), 5.73 (d, J = 13.6 Hz, 1 H, CH), 7.41–
7.52 (m, 5 H, ArH), 7.64 (dd, J = 6.8, 1.6 Hz, 2 H, ArH), 7.76 (dd,
J = 6.8, 1.2 Hz, 2 H, ArH), 8.19 (d, J = 13.6 Hz, 1 H, CH), 8.40
(s, 1 H, CH) ppm. 13C NMR (100 MHz, CDCl3, TMS): δ = 14.2,
60.1, 102.0, 128.4, 128.5, 128.8, 129.1, 131.7, 132.2, 132.3, 132.8,
140.6, 165.9, 167.1, 167.4 ppm. MS (EI): m/z (%) = 322 (2.6)
[M]+, 277 (1.9), 216 (4.4), 171 (1.1), 105 (100), 77 (32.5), 51 (6.1).
C19H18N2O3 (322.13): calcd. C 70.79, H 5.63, N 8.69; found C
70.56, H 5.59, N 8.66.
Diethyl 2-[(E)-1-Benzoyl-2-(naphthalen-1-ylmethylene)hydrazinyl]-
fumarate (3i): Pale-yellow oil (89%, 79 mg). IR (acetone): ν = 3058,
˜
2982, 2937, 1729, 1672, 1601, 1579, 1510, 1447, 1408, 1368, 1312,
1259, 1206, 1152, 1086, 1053, 1028, 911 cm–1. 1H NMR (400 MHz,
CDCl3, TMS): δ = 1.20 (t, J = 7.2 Hz, 3 H, CH3), 1.27 (t, J =
7.2 Hz, 3 H, CH3), 4.19 (q, J = 7.2 Hz, 2 H, CH2), 4.31 (q, J =
7.2 Hz, 2 H, CH2), 7.30–7.32 (m, 1 H, ArH), 7.34–7.56 (m, 6 H,
ArH and CH), 7.63 (d, J = 8.4 Hz, 1 H, ArH), 7.80–7.83 (m, 2 H,
ArH), 7.88 (dd, J = 8.4, 1.6 Hz, 2 H, ArH), 8.11 (s, 1 H, CH), 8.41
(d, J = 8.4 Hz, 1 H, ArH) ppm. 13C NMR (100 MHz, CDCl3,
TMS): δ = 13.9, 14.0, 61.6, 62.7, 124.6, 125.0, 126.0, 127.0, 127.6,
128.5, 129.0, 129.1, 129.4, 130.3, 130.6, 130.8, 131.6, 133.7, 134.6,
135.9, 142.1, 161.9, 162.5, 170.7 ppm. MS (EI): m/z (%) = 444 (1.6)
[M]+, 399 (1.2), 339 (0.8), 293 (1.6), 218 (18.6), 105 (100), 91 (1.0),
77 (20.1), 51 (2.3). HRMS (EI): calcd. for C26H24N2O5 [M + H]+
444.1685; found 444.1687.
Dimethyl 2-[(E)-2-Benzylidene-1-tosylhydrazinyl]fumarate (3n; Z/E,
2.5:1): Pale-yellow solid (90%, 101 mg). M.p. 109–112 °C. IR (ace-
tone): ν = 3074, 2952, 2830, 1746, 1725, 1602, 1573, 1492, 1449,
˜
1
1435, 1373, 1281, 1205, 1173, 1141, 1088, 1039, 844, 811 cm–1. H
NMR (400 MHz, CDCl3, TMS): δ = 2.41 (s, 3 H, CH3, Z), 2.45
(s, 1.2 H, CH3, E), 3.61 (s, 3 H, OCH3, Z), 3.71 (s, 1.2 H, CH3, E),
3.72 (s, 3 H, OCH3, Z), 3.83 (s, 1.2 H, CH3, E), 5.97 (s, 0.4 H, CH,
E), 7.31–7.35 (m, 7 H, ArH and CH, Z), 7.56–7.59 (m, 2 H, ArH,
Z), 7.91 (dd, J = 6.8, 2.0 Hz, 2 H, ArH, Z), 8.46 (s, 0.4 H, CH,
E) ppm. 13C NMR (100 MHz, CDCl3, TMS): δ = 21.5, 52.4, 53.1,
127.3, 128.5, 128.8, 129.0, 130.1, 133.0, 133.4, 134.3, 135.0, 142.9,
144.2, 162.4, 163.1 ppm. MS (EI): m/z (%) = 416 (7.5) [M]+, 385
(1.4), 352 (1.1), 261 (15.0), 245 (6.7), 229 (100), 201 (54.0), 133
(13.3), 104 (10.8), 91 (23.4), 77 (17.4), 65 (9.8), 51 (4.6). HRMS
(EI): calcd. for C20H20N2O6S [M + H]+ 416.1049; found 416.1038.
Diethyl 2-[(E)-1-Benzoyl-2-(furan-2-ylmethylene)hydrazinyl]fumar-
ate (3j): Yellow oil (87%, 67 mg). IR (acetone): ν = 3124, 3066,
˜
2984, 2939, 2906, 1729, 1668, 1601, 1579, 1484, 1448, 1400, 1368,
1320, 1260, 1207, 1170, 1095, 1075, 1053, 1026, 938 cm–1. 1H NMR
(400 MHz, CDCl3, TMS): δ = 1.22 (t, J = 7.2 Hz, 3 H, CH3), 1.27
(t, J = 7.2 Hz, 3 H, CH3), 4.19 (q, J = 7.2 Hz, 2 H, CH2), 4.29 (q,
J = 7.2 Hz, 2 H, CH2), 6.41 (dd, J = 3.6, 1.6 Hz, 1 H, ArH), 6.61
(d, J = 3.6 Hz, 1 H, ArH), 7.27 (s, 1 H, CH), 7.35–7.51 (m, 5 H,
ArH and CH), 7.87 (dd, J = 8.4, 1.6 Hz, 2 H, ArH) ppm. 13C NMR
(100 MHz, CDCl3, TMS): δ = 13.8, 13.9, 61.6, 62.6, 111.7, 112.3,
127.4, 130.1, 131.0, 131.2, 132.0, 133.7, 136.0, 144.2, 149.4, 161.7,
162.3, 169.8 ppm. MS (EI): m/z (%) = 384 (2.4) [M]+, 339 (1.6),
311 (2.2), 288 (5.3), 218 (2.1), 105 (100), 94 (3.6), 77 (21.2), 51 (2.9).
Dimethyl 2-[(E)-1-Benzoyl-2-(2-ethoxy-2-oxoethylidene)hydrazinyl]-
fumarate (3o; Z/E, 10:1): Colourless oil (93%, 68 mg). IR (acetone):
4094
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 4088–4097

Aza-Michael Addition Reactions of Hydrazones with Activated Alkynes
ν = 3074, 2978, 2956, 2896, 1736, 1687, 1595, 1448, 1438, 1382,
135.0, 135.9, 136.3, 140.0, 144.3, 149.6, 151.2, 152.0, 160.1, 161.7,
162.1, 162.4, 162.5, 162.7, 163.8, 165.4, 170.4 ppm. MS (EI): m/z
(%) = 554 (0.5) [M]+, 495 (5.6), 449 (2.5), 277 (4.3), 219 (2.3), 204
(4.4), 105 (100), 85 (6.7), 77 (28.8). 57 (10.1), 43 (6.5). HRMS (EI):
˜
1364, 1346, 1303, 1269, 1215, 1154, 1059, 1040, 908 cm–1. 1H NMR
(400 MHz, CDCl3, TMS): δ = 1.29 (t, J = 7.2 Hz, 3 H, CH3, Z),
3.75 (s, 3 H, CH3, Z), 3.79 (s, 0.3 H, CH3, E), 3.85 (s, 3 H, CH3,
Z), 3.90 (s, 0.3 H, CH3, E), 4.24 (q, J = 7.2 Hz, 2 H, CH2, Z), 6.52 calcd. for C27H26N2O11 [M + H]+ 554.1537; found 554.1540.
(s, 0.1 H, CH, E), 6.85 (s, 1 H, CH, Z), 7.28 (s, 0.1 H, CHH, E),
Dimethyl 2-[2-({2-Benzoyl-2-[(Z)-1,4-dimethoxy-1,4-dioxobut-2-en-
7.36 (s, 1 H, CH, Z), 7.42–7.46 (m, 2 H, ArH, Z), 7.51–7.55 (m, 1
2-yl]hydrazono}methyl)-5-methoxyphenoxy]maleate (6c; Z/E, 91:9):
H, ArH, Z), 7.91–7.93 (m, 2 H, ArH, Z) ppm. 13C NMR
Yellow oil (83%, 92 mg). IR (acetone): ν = 3067, 3005, 2955, 2845,
˜
(100 MHz, CDCl3, TMS): δ = 13.9, 52.6, 53.6, 61.5, 127.6, 130.7,
130.8, 131.3, 131.9, 132.2, 135.7, 161.3, 162.2, 162.6, 170.0 ppm.
MS (ESI): m/z (%) = 380 (100) [M + 1]+. HRMS (MALDI): calcd.
for C17H20N2O8 + 1 [M + 1]+ 380.1220; found 380.1215.
1735, 1671, 1640, 1612, 1567, 1503, 1438, 1400, 1364, 1267, 1211,
1153, 1129, 1098, 1055, 1028, 951 cm–1. 1H NMR (400 MHz,
CDCl3, TMS): δ = 3.65 (s, 3 H, CH3, Z), 3.68 (s, 0.3 H, CH3, E),
3.71 (s, 3 H, CH3, Z), 3.75 (s, 0.3 H, CH3, E), 3.79 (s, 3 H, CH3,
Dimethyl 2-[(E)-1-Benzoyl-2-(2,2,2-trifluoroethylidene)hydrazinyl]- Z), 3.82 (s, 3 H, CH3, Z), 3.85 (s, 0.3 H, CH3, minor), 3.91 (s, 0.3
fumarate (3p; Z/E, 10:1): Yellow oil (83%, 59 mg). IR (acetone): ν
H, CH3, minor), 3.95 (s, 3 H, CH3, Z), 4.95 (s, 1 H, CH, Z), 6.59
(s, 0.1 H, CH, E), 6.59 (d, J = 2.8 Hz, 1 H, ArH, Z), 6.79 (dd, J =
˜
= 3072, 3007, 2958, 1737, 1692, 1633, 1601, 1581, 1493, 1449, 1438,
1402, 1308, 1274, 1222, 1146, 1059, 1013, 916 cm–1. 1H NMR 8.8, 2.8 Hz, 1 H, ArH, Z), 7.42 (s, 1 H, CH, Z), 7.44–7.54 (m, 3
(400 MHz, CDCl3, TMS): δ = 3.77 (s, 3 H, CH3, Z), 3.81 (s, 0.3
H, CH3, E), 3.86 (s, 3.3 H, CH3, Z and E), 6.54 (br., 0.1 H, CH,
E), 6.80 (q, JH,F = 3.2 Hz, 1 H, CH, Z), 7.24 (q, JH,F = 3.2 Hz, 0.1
H, CH, E), 7.35 (s, 1 H, CH, Z), 7.44 (t, J = 7.2 Hz, 2 H, ArH,
H, ArH, Z), 7.58 (s, 1 H, CH, Z), 7.68 (d, J = 8.0 Hz, 1 H, ArH,
Z), 7.85 (dd, J = 8.0, 1.6 Hz, 1 H, ArH, Z), 8.01 (s, 0.1 H, CH,
E) ppm. 13C NMR (100 MHz, CDCl3, TMS): δ = 51.6, 52.3, 53.0,
55.6, 98.8, 106.4, 113.7, 118.4, 127.4, 128.1, 130.0, 131.2, 134.0,
Z), 7.50–7.54 (m, 1 H, ArH, Z), 7.80 (dd, J = 7.2, 1.2 Hz, 2 H, 135.2, 136.1, 152.3, 160.8, 161.9, 162.2, 162.5, 162.8, 165.3,
ArH, Z) ppm. 13C NMR (100 MHz, CDCl3, TMS): δ = 52.7, 53.6, 170.3 ppm. MS (EI): m/z (%) = 554 (0.6) [M]+, 495 (6.6), 417 (1.3),
119.5 (q, JC,F = 270.3 Hz), 127.7, 127.8 (q, JC,F = 40.1 Hz), 129.0
(q, JC,F = 244.5 Hz), 130.1, 131.7, 131.9, 132.2, 135.2, 161.3, 162.2,
170.1 ppm. 19F NMR (376 MHz, CDCl3, TMS): δ = –67.0 (d, J =
3.2 Hz, 0.1 F, minor), –66.8 (d, J = 3.2 Hz, 1 F, major) ppm. MS
(EI): m/z (%) = 358 (0.4) [M]+, 289 (1.8), 105 (100), 91 (0.5), 77
(29.6), 58 (2.8), 43 (9.6). HRMS (EI): calcd. for C15H13N2O5F3 [M
+ H]+ 358.0777; found 358.0773.
277 (6.0), 204 (9.3), 105 (100), 85 (12.9), 77 (31.3), 57 (20.2), 43
(12.8). HRMS (EI): calcd. for C27H26N2O11 [M + H]+ 554.1537;
found 554.1542.
Dimethyl 2-[2-({2-Benzoyl-2-[(Z)-1,4-dimethoxy-1,4-dioxobut-2-en-
2-yl]hydrazono}methyl)-4-nitrophenoxy]maleate (6d; Z/E, 83:17):
Yellow oil (63%, 71 mg). IR (acetone): ν = 3080, 3007, 2956, 1732,
˜
1681, 1643, 1607, 1574, 1532, 1475, 1437, 1349, 1298, 1269, 1233,
1160, 1128, 1074, 1056, 1016, 961 cm–1. 1H NMR (400 MHz,
CDCl3, TMS): δ = 3.70 (s, 3 H, CH3, Z), 3.73 (s, 0.6 H, CH3, E),
3.75 (s, 3 H, CH3, Z), 3.83 (s, 0.6 H, CH3, E,), 3.85 (s, 0.6 H, CH3,
E), 3.88 (s, 3 H, CH3, Z), 3.89 (s, 0.6 H, CH3, E), 3.92 (s, 3 H,
Dimethyl 2-[2-({2-Benzoyl-2-[(Z)-1,4-dimethoxy-1,4-dioxobut-2-en-
2-yl]hydrazono}methyl)phenoxy]maleate (6a): Yellow oil (62%,
65 mg). IR (acetone): ν = 3067, 2985, 2954, 2844, 1732, 1672, 1638,
˜
1605, 1571, 1438, 1365, 1324, 1268, 1215, 1163, 1129, 1056, 1029,
913 cm–1. 1H NMR (400 MHz, CDCl3, TMS): δ = 3.64 (s, 3 H, CH3, Z), 5.16 (s, 1 H, CH, Z), 6.49 (s, 0.2 H, CH, E), 7.23 (d, J =
CH3), 3.72 (s, 3 H, CH3), 3.83 (s, 3 H, CH3), 3.95 (s, 3 H, CH3), 8.8 Hz, 1 H, ArH, Z), 7.45 (s, 1 H, CH, Z), 7.51–7.61 (m, 3 H,
4.90 (s, 1 H, CH), 7.08 (dd, J = 8.0, 0.8 Hz, 1 H, ArH), 7.23 (dt, J ArH, Z), 7.64 (s, 1 H, CH, Z), 7.84 (d, J = 8.0 Hz, 0.3 H, ArH,
= 8.0, 0.4 Hz, 1 H, ArH), 7.37–7.41 (m, 1 H, ArH), 7.44 (s, 1 H,
CH), 7.45–7.54 (m, 3 H, ArH), 7.65 (s, 1 H, CH), 7.75 (dd, J =
E), 7.87 (dd, J = 8.0, 1.2 Hz, 2 H, ArH, Z), 8.09 (s, 0.2 H, CH, E),
8.21 (dd, J = 8.0, 2.8 Hz, 1 H, ArH, Z), 8.60 (d, J = 2.8 Hz, 1 H,
8.0, 1.6 Hz, 1 H, ArH), 7.86 (dd, J = 8.4, 1.6 Hz, 2 H, ArH) ppm. ArH, Z) ppm. 13C NMR (100 MHz, CDCl3, TMS): δ = 52.0, 52.2,
13C NMR (100 MHz, CDCl3, TMS): δ = 51.6, 52.3, 53.1, 53.3, 52.5, 53.2, 53.3,53.5, 103.0, 105.2, 121.8, 123.1, 125.7, 127.7, 127.9,
98.8, 121.5, 126.4, 127.1, 127.2, 127.5, 130.0, 131.1, 131.3, 131.4,
129.9, 131.5, 131.6, 132.4, 132.8, 133.4, 135.7, 145.9, 155.3, 157.9,
133.9, 134.9, 136.0, 151.3, 161.1, 161.8, 162.5, 162.9, 165.3, 161.7, 162.1, 162.5, 164.4, 164.6, 170.5 ppm. MS (EI): m/z (%) =
170.5 ppm. MS (EI): m/z (%) = 524 (0.2) [M]+, 493 (0.3), 416 (2.5),
261 (5.0), 229 (34.3), 201 (21.6), 105 (100), 91 (49.0), 77 (30.0). 65
(12.0), 51 (10.8). HRMS (EI): calcd. for C26H24N2O10 [M + H]+
524.1431; found 524.1432.
569 (0.1) [M]+, 510 (1.7), 448 (1.6), 260 (2.8), 204 (2.2), 201 (21.6),
105 (100), 85 (4.1), 77 (26.1). 57 (6.5), 53 (4.3). HRMS (EI): calcd.
for C26H23N3O12 [M + H]+ 569.1282; found 569.1286.
Dimethyl 2-[1-Benzoyl-2-({2-[(E)-1,4-dimethoxy-1,4-dioxobut-2-en-
2-yloxy]naphthalen-1-yl}methylene)hydrazinyl]fumarate (6e; Z/E,
Dimethyl 2-[2-({2-Benzoyl-2-[(Z)-1,4-dimethoxy-1,4-dioxobut-2-en-
2-yl]hydrazono}methyl)-6-methoxyphenoxy]maleate
(6b;
Z/E, 92:8): Yellow oil (72%, 81 mg). IR (acetone): ν = 3066, 2954, 2845,
˜
84:16): Yellow oil (77%, 85 mg). IR (acetone): ν = 3072, 3006,
1735, 1679, 1638, 1601, 1578, 1509, 1437, 1411, 1365, 1314, 1267,
1217, 1129, 1057, 1028, 909 cm–1. 1H NMR (400 MHz, CDCl3,
TMS): δ = 3.63 (s, 3 H, CH3, Z), 3.65 (s, 0.3 H, CH3, E), 3.73 (s,
3 H, CH3, Z), 3.80 (s, 0.3 H, CH3, E), 3.85 (s, 3 H, CH3, Z), 3.88
˜
2955, 2845, 1735, 1676, 1641, 1610, 1577, 1479, 1460, 1438, 1396,
1364, 1302, 1267, 1215, 1163, 1128, 1068, 1028, 938 cm–1. 1H NMR
(400 MHz, CDCl3, TMS): δ = 3.62 (s, 0.6 H, CH3, E), 3.63 (s, 3
H, CH3, Z), 3.71 (s, 3 H, CH3, Z), 3.73 (s, 0.6 H, CH3, E), 3.74 (s, (s, 0.3 H, CH3, E), 3.92 (s, 0.3 H, CH3, E), 3.98 (s, 3 H, CH3, Z),
0.6 H, CH3, E), 3.81 (s, 3 H, CH3, Z), 3.82 (s, 3.6 H, CH3, Z and 4.90 (s, 1 H, CH, Z), 6.45 (s, 0.1 H, CH, E), 7.16–7.23 (m, 1 H,
E), 3.84 (s, 0.6 H, CH3, E), 3.95 (s, 3 H, CH3, Z), 4.85 (s, 1 H, CH,
ArH, Z), 7.43–7.58 (m, 4 H, ArH, Z + CH), 7.77 (d, J = 8.0 Hz,
Z), 6.22 (s, 0.2 H, CH, E), 6.97 (dd, J = 8.0, 1.2 Hz, 1 H, ArH, Z), 1 H, ArH, Z), 7.85–7.88 (m, 3 H, ArH, Z), 8.05 (s, 1 H, CH, Z),
7.16 (t, J = 8.0 Hz, 1 H, ArH, Z), 7.29–7.34 (m, 1 H, ArH, Z), 8.72 (d, J = 8.0 Hz, 1 H, ArH, Z) ppm. 13C NMR (100 MHz,
7.44 (s, 1 H, CH, Z), 7.46–7.53 (m, 4 H, ArH), 7.65 (s, 1 H, CH, CDCl3, TMS): δ = 51.6, 52.3, 53.1, 53.3, 98.8, 119.5, 120.1, 126.4,
Z), 7.86 (dd, J = 8.4, 1.6 Hz, 2 H, ArH, Z), 7.92 (s, 0.2 H, CH, 127.1, 127.7, 128.0, 128.3, 129.0, 130.4, 130.5, 132.0, 132.1, 133.0,
E) ppm. 13C NMR (100 MHz, CDCl3, TMS): δ = 51.5, 52.2, 52.3,
52.7, 52.9, 53.2, 53.3, 55.9, 56.1, 97.5, 108.0, 113.6, 113.9, 117.9,
118.1, 124.4, 126.2, 127.3, 129.9, 130.9, 131.0, 131.2, 133.8, 134.1,
134.7, 135.7, 137.1, 150.9, 160.8, 161.9, 162.5, 162.8, 165.3,
171.3 ppm. MS (EI): m/z (%) = 574 (0.3) [M]+, 515 (2.8), 469 (1.2),
280 (3.9), 252 (5.4), 204 (12.9), 105 (100), 85 (5.9), 77 (33.9). 57
Eur. J. Org. Chem. 2010, 4088–4097
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4095

Z.-L. Yuan, Y. Wei, M. Shi
FULL PAPER
(12.0), 43 (8.8). HRMS (EI): calcd. for C30H26N2O10 [M + H]+
574.1587; found 574.1587.
Acknowledgments
We thank the Shanghai Municipal Committee of Science and Tech-
nology (08dj1400100-2), National Basic Research Program of
China (973-2009CB825300) and the National Natural Science
Foundation of China (20872162, 20672127, 20821002, 20732008)
for financial support and Mr. Jie Sun for performing X-ray diffrac-
tion.
Dimethyl 2-[4-({2-Benzoyl-2-[(Z)-1,4-dimethoxy-1,4-dioxobut-2-en-
2-yl]hydrazono}methyl)phenoxy]maleate (6f; Z/E, 83:17): Yellow oil
(92%, 93 mg). IR (acetone): ν = 3066, 3004, 2955, 2847, 1730, 1671,
˜
1601, 1579, 1504, 1437, 1497, 1363, 1324, 1268, 1211, 1162, 1130,
1057, 1015, 912 cm–1. 1H NMR (400 MHz, CDCl3, TMS): δ = 3.67
(s, 3 H, CH3, Z), 3.69 (s, 0.6 H, CH3, E), 3.73 (s, 0.6 H, CH3, E),
3.75 (s, 3 H, CH3, Z), 3.84 (s, 0.6 H, CH3, E), 3.86 (s, 3 H, CH3,
Z), 3.89 (s, 3 H, CH3, Z), 5.20 (s, 1 H, CH, Z), 5.28 (s, 0.2 H, CH,
E), 6.65 (s, 0.2 H, ArH, E), 6.91 (d, J = 7.2 Hz, 0.4 H, ArH, E),
7.08 (dd, J = 7.2, 2.0 Hz, 2 H, ArH, Z), 7.41 (s, 1 H, CH, Z), 7.45–
7.56 (m, 6 H, ArH and CH, Z), 7.85 (dd, J = 7.2, 0.8 Hz, 1 H,
ArH, Z) ppm. 13C NMR (100 MHz, CDCl3, TMS): δ = 51.6, 51.7,
52.3, 52.4, 52.8, 52.9, 53.3, 53.4, 100.1, 100.2, 115.8, 116.0, 120.7,
127.4, 127.7, 128.9, 129.2, 129.6, 129.7, 129.8, 131.0, 131.1, 131.9,
133.8, 134.0, 136.0, 136.2, 139.8, 149.0, 154.1, 157.9, 159.9, 162.1,
162.2, 162.6, 162.8, 163.4, 165.4, 169.4, 170.29 ppm. MS (EI): m/z
(%) = 524 (1.2) [M]+, 493 (1.3), 380 (1.1), 260 (3.7), 204 (6.9), 105
(100), 85 (2.5), 77 (26.7). 57 (4.7), 43 (2.9). HRMS (EI): calcd. for
C26H24N2O10 [M + H]+ 524.1431; found 524.1432.
[1] The addition was first discovered by Hantzsch, Komnenos,
Crismer and Claisen. Later on, it was summarized by Michael
in 1887: a) T. Purdie, Ber. Dtsch. Chem. Ges. 1881, 14, 2238–
2286; b) A. Hantzsch, Justus Liebigs Ann. Chem. 1882, 215, 1–
82; c) T. Komnenos, Justus Liebigs Ann. Chem. 1883, 218, 145–
169; d) L. Claisen, Justus Liebigs Ann. Chem. 1883, 218, 121–
129; e) L. Claisen, L. Crismer, Justus Liebigs Ann. Chem. 1883,
218, 129–144; f) L. Claisen, J. Prakt. Chem. 1886, 35, 413–415;
g) A. Michael, J. Prakt. Chem. 1886, 35, 349–352.
[2] The MBH reaction was first reported by Morita in 1968 and by
Baylis and Hillman in 1972: a) A. B. Baylis, M. E. D. Hillman,
German Patent 2155113, 1972; b) K. Morita, Z. Suzuki, H.
Hirose, Bull. Chem. Soc. Jpn. 1968, 41, 2815–2819; for reviews
of the Morita-Baylis–Hillman reaction, see: c) D. Basavaiah,
P. D. Rao, R. S. Hyma, Tetrahedron 1996, 52, 8001–8063; d) D.
Basavaiah, A. J. Rao, T. Satyanarayana, Chem. Rev. 2003, 103,
811–892; e) V. Declerck, J. Martinez, F. Lamaty, Chem. Rev.
2009, 109, 1–48.
(2ЈE)-Tetramethyl 2,2Ј-[3-({2-Benzoyl-2-[(Z)-1,4-dimethoxy-1,4-di-
oxobut-2-en-2-yl]hydrazono}methyl)-1,2-phenylene]bis(oxy)di-
maleate (6g; Z/E, 85:15): Yellow oil (61%, 78 mg). IR (acetone): ν
˜
= 3067, 3005, 2955, 2845, 1735, 1671, 1640, 1612, 1579, 1504, 1437,
1497, 1363, 1267, 1211, 1153, 1129, 1098, 1055, 1028, 951 cm–1. 1H
NMR (400 MHz, CDCl3, TMS): δ = 3.62 (s, 0.6 H, CH3, E), 3.65
(s, 3 H, CH3, Z), 3.69 (s, 0.6 H, CH3, E), 3.73 (s, 3 H, CH3, Z),
3.76 (s, 3.5 H, CH3, Z and E), 3.84 (s, 0.6 H, CH3, E), 3.87 (s, 3.6
H, CH3, Z and E), 3.88 (s, 3 H, CH3, Z), 3.90 (s, 0.6 H, CH3, E),
3.93 (s, 3 H, CH3, Z), 4.92 (s, 1 H, CH, Z), 5.10 (s, 0.2 H, CH, E),
5.23 (s, 1 H, CH, Z), 6.36 (s, 0.2 H, CH, E), 7.19 (dd, J = 8.0,
1.6 Hz, 1 H, ArH, Z), 7.27 (dt, J = 8.0, 2.0 Hz, 2 H, ArH, Z), 7.28
(s, 1 H, CH, Z), 7.45 (s, 1 H, CH, Z), 7.46–7.54 (m, 3 H, ArH, Z),
7.63 (s, 1 H, CH, Z), 7.64 (dd, J = 7.6, 1.6 Hz, 1 H, ArH, Z), 7.85
(dd, J = 8.0, 1.6 Hz, 1 H, ArH, Z) ppm. 13C NMR (100 MHz,
CDCl3, TMS): δ = 51.6, 51.7, 51.8, 52.3, 52.4, 52.9, 53.0, 53.1, 53.4,
99.3, 101.4, 110.9, 123.3, 124.5, 127.5, 127.8, 129.1, 129.9, 130.0,
131.0, 131.2, 131.6, 133.8, 135.8, 142.4, 145.0, 158.1, 159.4, 161.7,
162.2, 162.5, 165.0, 165.1, 170.5 ppm. MS (EI): m/z (%) = 682 (0.3)
[M]+, 623 (3.1), 577 (2.1), 440 (90.2), 397 (65.1), 328 (93.2), 203
(41.8), 105 (100), 77 (27.4), 57 (87.8), 43 (73.2). HRMS (EI): calcd.
for C32H30N2O15 [M + H]+ 682.1646; found 682.1643.
[3] For recent accounts of catalytic Michael addition reactions,
see: a) J. Rodriguez, Synlett 1999, 505–518; b) N. Krause, A.
Hoffmann-Röder, Synthesis 2001, 0171–0196; c) J. Christoffers,
G. Koripelly, A. Rosiak, M. Rössle, Synthesis 2007, 1279–1300.
[4] For recent examples of Michael addition reactions catalyzed
by inorganic base: a) S.-M. Ma, S.-H. Yin, L.-T. Li, F.-G. Tao,
Org. Lett. 2002, 4, 505–507; b) D. Y. Khim, K. H. Suh, S. C.
Huh, K. Lee, Synth. Commun. 2001, 31, 3315–3322.
[5] For Michael addition reactions catalyzed by nucleophilic phos-
phane Lewis base, see: D. Bhuniya, S. Mohan, S. Narayanan,
Synthesis 2003, 1018–1024.
[6] Phosphane-catalyzed hydration and hydroalkoxylation of acti-
vated olefins have been reported: a) I. C. Stewart, R. G.
Bergman, F. D. Toste, J. Am. Chem. Soc. 2003, 125, 8696–8697
and references cited therein; b) L.-C. Wang, A. L. Luis, K.
Apapiou, H.-Y. Jang, M. J. Krische, J. Am. Chem. Soc. 2002,
124, 2402–2403; c) S. A. Frank, D. J. Mergott, W. R. Roush, J.
Am. Chem. Soc. 2002, 124, 2404–2405; for some representative
reviews in nitrogen-containing base-catalyzed Michael addition
reactions, see: d) A. Alexakis, S. Sulzer-Mossé, Chem. Com-
mun. 2007, 3123–3135; e) D. Almasi, D. A. Alonso, C. Najera,
Tetrahedron: Asymmetry 2007, 18, 299–365; f) S. B. Tsogoeva,
Eur. J. Org. Chem. 2007, 1701–1716; g) J. L. Vicario, D. Badía,
L. Carrillo, Synthesis 2007, 2065–2092.
[7] Oxa-Michael addition was first reported by Loydl in 1878: a)
F. Loydl, Justus Liebigs Ann. Chem. 1878, 192, 80–89; for some
recent reviews on the oxa-Michael reaction, see: b) C. F. Nis-
ing, S. Bräse, Chem. Soc. Rev. 2008, 37, 1218–1228 and the
references cited therein; c) see ref.[6g] and the references cited
therein.
[8] Aza-Michael addition was first reported in the reaction of am-
monia with acetone or mesityloxide to form diacetoneamine in
1874: a) N. Sokoloff, P. Latschinoff, Ber. Dtsch. Chem. Ges.
1874, 7, 1384–1387; b) W. Heintz, N. Sokoloff, P. Latschinoff,
Ber. Dtsch. Chem. Ges. 1874, 7, 1518–1520; c) P. R. Haeseler,
Org. Synth. 1926, 6, 28–30; for some recent reviews on the aza-
Michael reaction, see: d) D. Enders, C. Wang, J. X. Liebich,
Chem. Eur. J. 2009, 15, 11058–11076 and the references cited
therein; e) see ref.[6g] and the references cited therein.
Dimethyl 2-[(E)-1-Benzoyl-2-(2-hydroxybenzylidene)hydrazinyl]-
fumarate (6h): Red solid (48%, 38 mg). M.p. 118–120 °C. IR (ace-
tone): ν = 3185, 3065, 2954, 1732, 1678, 1618, 1572, 1489, 1447,
˜
1436, 1403, 1327, 1306, 1268, 1217, 1157, 1058, 1013, 919 cm–1. 1H
NMR (400 MHz, CDCl3, TMS): δ = 3.77 (s, 3 H, CH3), 3.86 (s, 3
H, CH3), 6.85 (t, J = 6.8 Hz, 2 H, ArH), 7.13 (dd, J = 8.0, 1.6 Hz,
1 H, ArH), 7.23 (dt, J = 6.8, 1.6 Hz, 1 H, ArH), 7.45 (s, 1 H, CH),
7.48–7.58 (m, 4 H, ArH), 7.61 (s, 1 H, CH), 7.73 (d, J = 6.8 Hz, 2
H, ArH), 9.61 (br., 1 H, OH) ppm. 13C NMR (100 MHz, CDCl3,
TMS): δ = 52.6, 53.6, 116.9, 117.1, 119.4, 128.2, 128.3, 128.4, 128.5,
128.7, 131.3, 131.4, 131.8, 133.7, 145.0, 157.3, 161.9, 162.5,
170.1 ppm. MS (EI): m/z (%) = 382 (3.1) [M]+, 217 (0.3), 132 (0.3),
105 (100), 91 (1.0), 77 (25.1), 65 (2.6), 51 (4.3). 43 (0.4). HRMS
(EI): calcd. for C20H18N2O6 [M + H]+ 382.1165; found 382.1169.
Supporting Information (see footnote on the first page of this arti-
cle): 1H and 13C NMR spectroscopic data, X-ray crystal data of 3a
and 6e, and detailed descriptions of experimental procedures.
[9] P. A. Magriotis, Angew. Chem. Int. Ed. 2001, 40, 4377–4379.
[10] a) D. Enders, W. Bettray, G. Raabe, J. Runsink, Synthesis 1994,
1322–1326; b) D. Enders, H. Wahl, W. Bettray, Angew. Chem.
4096
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 4088–4097

Aza-Michael Addition Reactions of Hydrazones with Activated Alkynes
Int. Ed. Engl. 1995, 34, 455–457; c) D. Enders, J. Wiedemann,
W. Bettray, Synlett 1995, 369–371; d) D. Enders, J. Wiedemann,
Synthesis 1996, 1443–1450; e) D. Enders, S. F. Müller, G.
Raabe, Angew. Chem. Int. Ed. 1999, 38, 1195–1197; f) D. En-
ders, S. E. Muller, G. Raabe, Angew. Chem. Int. Ed. 1999, 38,
195–197; g) D. Enders, S. F. Muller, G. Raabe, J. Runsink, Eur.
J. Org. Chem. 2000, 879–892; h) G. Cardillo, L. Gentilucci, V.
De Matteis, J. Org. Chem. 2002, 67, 5957–5962; i) D. Enders,
S. Wallert, Synlett 2002, 304–306; j) M. Liu, M. P. Sibi, Tetra-
hedron 2002, 58, 7991–8035; k) A. G. Moglioni, E. Muray, J. A.
Castillo, A. Alvarez-Larena, G. Y. Moltrasio, V. Branchadell,
R. M. Ortuno, J. Org. Chem. 2002, 67, 2402–2410; l) G. V. M.
Sharma, V. G. Reddy, A. S. Chander, K. R. Reddy, Tetrahe-
dron: Asymmetry 2002, 13, 21–24; m) D. Enders, S. Wallert, J.
Runsink, Synthesis 2003, 1856–1868; n) M. Sani, L. Bruch, G.
Chiva, S. Fustero, J. Piera, A. Volonterio, M. Zanda, Angew.
Chem. Int. Ed. 2003, 42, 2060–2063; o) J. Etxebarria, J. L. Vic-
ario, D. Badia, L. Carrillo, J. Org. Chem. 2004, 69, 2588–2590;
p) S. G. Davies, A. D. Smith, P. D. Price, Tetrahedron: Asym-
metry 2005, 16, 2833–2891; q) J. Turconi, L. Lebeau, J.-M.
Paris, C. Mioskowski, Tetrahedron 2006, 62, 8109–8114; r) M.
Koutsaplis, P. C. Andrews, S. D. Bull, P. J. Duggan, B. H. Fra-
ser, P. Jensen, Chem. Commun. 2007, 3580–3582; s) L.-J. Chen,
D.-R. Hou, Tetrahedron: Asymmetry 2008, 19, 715–720; t) G.
Pandey, M. Balakrishnan, P. S. Swaroop, Eur. J. Org. Chem.
2008, 5839–5847; u) S. Fustero, G. Chiva, J. Piera, J. F. Sanz-
Cervera, A. Volonterio, M. Zanda, C. R. de Arellano, J. Org.
Chem. 2009, 74, 3122–3132.
vated alkynes, see: d) Z.-M. Chen, M. L. Trudell, Chem. Rev.
1996, 96, 1179–1193 and the references cited therein; e) V. Nair,
C. Rajesh, A. U. Vinod, S. Bindu, A. R. Sreekanth, J. S.
Mathen, L. Balagopal, Acc. Chem. Res. 2003, 36, 899–907 and
the references cited therein.
[15] CCDC-750942 (for 3n) contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif. Empirical formula:
C20H20N2O6S; Fw: 416.44; crystal color/habit: colorless/pris-
matic; crystal dimensions: 0.375ϫ0.301ϫ0.269 mm; crystal
system: monoclinic; lattice type: primitive; lattice parameters:
a = 15.5206(16) Å, b = 9.8874(11) Å, c = 13.4767(14) Å; α =
90°, β = 98.125(2)°, γ = 90°; V = 2047.4(4) Å3; space group:
P21/c; Z = 4; Dcalcd = 1.351 g/cm3; F(000) = 872; dif-
fractometer: Rigaku AFC7R; residuals: R/Rw 0.0504/0.1328.
[16] CCDC-768442 (for 6e) contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif. Empirical formula:
C30H26N2O10; Fw: 574.53; crystal color/habit: colorless/pris-
matic; crystal dimensions: 0.428ϫ0.360ϫ0.295 mm; crystal
system: monoclinic; lattice type: primitive; lattice parameters:
a = 11.3843(10) Å, b = 28.932(3) Å, c = 8.7987(8) Å, α = 90°,
β = 95.226(2)°, γ = 90°, V = 2886.0(4) Å3; space group: P21/c;
Z = 4; Dcalcd = 1.322 g/cm3; F(000) = 1200; diffractometer: Ri-
gaku AFC7R; residuals: R/Rw 0.0626/0.1637.
[17] For the synthetic utility of these aza-Michael adducts, see: a)
M. K. Saxena, M. N. Gudi, M. V. George, Tetrahedron 1973,
29, 101–105; b) C. Djerassi, E. Lund, E. Bunnenberg, B. Sjo-
berg, J. Am. Chem. Soc. 1961, 83, 2307–2312; c) A. Khalik, M.
Mohammed, A. S. Michel, E. M. Hilmy, Synthesis 2001, 12,
1861–1865; d) M. Masahiro, I. Naoki, M. Tomoya, Chem. Lett.
2007, 36, 476–477; e) A. A. Mohammad, G. Fatemeh, A. A.
Hossein, Synth. Commun. 2009, 39, 544–551.
[11] Y. Matsuya, K. Hayashi, H. Nemoto, J. Am. Chem. Soc. 2003,
125, 646–647.
[12] P. V. Ramachandran, M. T. Rudd, M. V. R. Reddy, Tetrahedron
Lett. 1999, 40, 3819–3822.
[13] G.-L. Zhao, M. Shi, Tetrahedron 2005, 61, 7277–7288.
[14] a) V. Nair, A. R. Ramachandran, A. U. Vinod, Org. Lett. 2001,
3, 3495–3497; b) C.-Q. Li, M. Shi, Org. Lett. 2003, 5, 4273–
4276; c) J.-L. Jiang, J. Ju, R.-M. Hua, Org. Biomol. Chem. 2007,
5, 1854–1857; for some recent reviews on the reactions of acti-
Received: March 17, 2010
Published Online: May 31, 2010
Eur. J. Org. Chem. 2010, 4088–4097
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4097