Silver(I)-catalyzed tandem 1,3-acyloxy migration/Mannich-type addition/elimination of the sulfonyl group of N-sulfonylhydrazone-propargylic esters to 5,6-dihydropyridazin-4-one derivatives

Article abstract of DOI:10.1002/chem.201103404

The addition of nucleophiles to C=N bonds offers a highly efficient synthetic strategy for accessing nitrogen-containing molecules.1 Among the well-developed addition reactions, such as the highly efficient Mannich reaction, various C-H bond-activated compounds including carboxylic acid derivatives, nitroalkanes, and terminal alkynes have been applied as nucleophiles to achieve different classes of amines.2 However, employing new nucleophiles without activated C-H bonds, such as internal alkynes and allenic esters are limited when using metal catalysts.3 Herein, we wish to report a new addition of allenic esters to C=N bonds initiated by a silver-catalyzed 1,3-migration of propargylic esters. Copyright

Full text of DOI:10.1002/chem.201103404

DOI: 10.1002/chem.201103404
Silver(I)-Catalyzed Tandem 1,3-Acyloxy Migration/Mannich-type Addition/
Elimination of the Sulfonyl Group of N-Sulfonylhydrazone-propargylic
Esters to 5,6-Dihydropyridazin-4-one Derivatives
Zhen Zhang[a] and Min Shi*[a, b]
Abstract: The addition of nucleophiles
to C=N bonds offers a highly efficient
synthetic strategy for accessing nitro-
gen-containing molecules.[1] Among the
well-developed addition reactions, such
as the highly efficient Mannich reac-
kynes have been applied as nucleo-
philes to achieve different classes of
amines.[2] However, employing new nu-
bonds, such as internal alkynes and al-
lenic esters are limited when using
metal catalysts.[3] Herein, we wish to
report a new addition of allenic esters
to C=N bonds initiated by a silver-cata-
lyzed 1,3-migration of propargylic
esters.
À
cleophiles without activated C H
Keywords: Mannich reaction
·
À
tion, various C H bond-activated com-
propargylic esters · silver · sulfonyl-
hydrazones · tandem reaction
pounds including carboxylic acid deriv-
atives, nitroalkanes, and terminal al-
Introduction
In the context of gold or silver catalysis, propargylic esters
have highly valuable reactivity to undergo 1,2- or 1,3-acy-
loxy migration, leading to the formation of a metal–carbene
or an allenic intermediate.[4] In the case of further transfor-
mation arising from 1,3-migration, selective coordination of
the metal catalyst to the pendant functional group rather
than the allenic moiety is a challenge. In this aspect, Tosteꢀs
group explored a silver-catalyzed tandem 1,3-acyloxy migra-
tion/formal Myers–Saito cyclization of diynyl esters to form
aromatic ketones,[5] and Malacria and his co-workers report-
ed a gold-catalyzed cyclization of diynyl esters led to dike-
tones after 1,3-acyloxy migration/5-exo-dig cyclization/1,5-
acyl migration (Scheme 1a).[6] Our group has also developed
a gold(I)-catalyzed tandem Meyer–Schuster-like rearrange-
ment/5-endo-dig cycloaddition of diynyl esters to afford 2,3-
disubstituted 3-pyrrolines in good yields.[7] Although diynyl
esters are very efficient in this transformation, other sub-
strates bearing no diyne moiety are still not known until
Chanꢀs group recently reported a gold-catalyzed tandem 1,3-
Scheme 1. Distinct cyclization modes for various propargylic esters:
a) through alkyne activation; b) through alkene activation; c) through hy-
drazone activation. M=Au or Ag.
acyloxy migration/ACTHNUTRGNEUNG[2+2]-cycloaddition of 1,7-enyne ben-
[a] Z. Zhang, M. Shi
Laboratory for Advanced Materials & Institute
of Fine Chemicals, East China University of Science and Technology
130 Mei Long Road, Shanghai 200237 (P.R. China)
zoates (Scheme 1b).[8,9] In the light of these findings, an effi-
cient method for the preparation of 5,6-dihydropyridazin-4-
one derivatives, a class of new compounds that have been
seldom reported in the previous literature,[10–11] based on a
silver-catalyzed tandem 1,3-acyloxy migration/Mannich-type
addition/elimination of the sulfonyl group of N-sulfonylhy-
[b] M. Shi
State Key Laboratory of Organometallic Chemistry
Shanghai Institute of Organic Chemistry, Chinese Academy of Scien-
ces
354 Fenglin Road, Shanghai 200032 (P.R. China)
Fax : (+86)21-64166128
E-mail: Mshi@mail.sioc.ac.cn
drazone-propargylic
(Scheme 1c).[12]
Initially, we started the optimization of the reaction condi-
tions by using (E)-5-(2-benzylidene-1-tosylhydrazinyl)-2-
methylpent-3-yn-2-yl acetate (1a) and AgSbF6 (10 mol%) in
wet dichloromethane at room temperature; the desired
esters,
has
been
disclosed
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201103404. It contains experi-
mental procedures, compound characterization data, and X-ray crys-
tal data of 2a, 3c, and 5b.
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Chem. Eur. J. 2012, 18, 3654 – 3658

FULL PAPER
Table 1. Optimization of the reaction conditions.[a]
Table 2. Silver-catalyzed tandem reaction of N-sulfonylhydrazone-prop-
argylic esters 1b–k.[a]
Entry Catalyst
Additive
[(equiv)]
Solvent
t
Yield[b]
[%]
Entry
Substrate
t
Product
Yield[b]
[%]
G
[h]
[h]
1
2
3
4
5
6
AgSbF6
AgOTf
AgBF4
AgOAc
AgSbF6
AgSbF6
–
–
–
–
–
–
–
–
–
–
–
–
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
ClCH2CH2Cl
toluene
CH2Cl2
CH2Cl2
CH2Cl2
2
2.5
79
38
64
1
2
3
4
5
6
7
8
9
1b, R1 =4-MeC6H4
1c, R1 =4-MeOC6H4
1d, R1 =4-BrC6H4
1e, R1 =4-ClC6H4
1 f, R1 =4-CF3C6H4
1g, R1 =2-FC6H4
1h, R1 =2-ClC6H4
1i, R1 =2,3-Cl2C6H3
1j, R1 =iPr
1
1
3
5
5
6
6
8
2b
2c
2d
2e
2 f
2g
2h
2i
60
30
81
65
80
74
73
70
0
2
24
2
2.5
3.5
24
24
24
24
3
n.r.[c]
61
42
19
7
Au
N
8
TfOH
n.r.[c]
n.r.[c]
n.r.[c]
n.r.[c]
9
BF3·Et2O
10
5
2j
2k
10
11
12
13
14
Sc
AlCl3
AgSbF6
AgSbF6
AgSbF6
(OTf)3
CH2Cl2
CH2Cl2
dry CH2Cl2
10
1k, R1 =2-furan
0[c]
[d]
–
[a] Conditions: 1, AgSbF6 (10 mol%), H2O (1.0 equiv), CH2Cl2, RT.
[b] Isolated product yield. [c] For details, see the Supporting Information.
H2O (1.0) dry CH2Cl2
H2O (1.0) dry CH2Cl2
1
1
84
84
[a] All reactions were performed on a 0.10 mmol scale. [b] Isolated prod-
uct yield. [d] n.r.=no reaction. [d] Trace.
ing groups (fluoride, chloride, bromide, or trifluoromethyl
group) on their benzene rings, the reactions proceeded
smoothly to give the desired products 2d–i in 65–81%
yields at room temperature (Table 2, entries 3–8). On the
basis of the results, it could be seen that the ortho- or para-
substitution on the aromatic ring did not significantly inter-
fere with the reaction outcomes. The hydrazone possessing
an alkyl group 1j was also tested, but none of the corre-
sponding product was observed with all the starting materi-
als recovered (Table 2, entry 9). For the 2-furan-substituted
hydrazone 1k, the corresponding product 2k was not ob-
tained and the 1,3-migration product was formed (Table 2,
entry 10, see the Supporting Information).
product 6-phenyl-5-(propan-2-ylidene)-5,6-dihydropyridazin-
4(1H)one (2a) was formed in 79% yield after 2 h (Table 1,
entry 1). The structure of 2a has been unequivocally con-
firmed by X-ray diffraction.[13] Other silver catalysts, such as
AgOTf, AgBF4, and AgOAc did not give better results than
AgSbF6 (Table 1, entries 2–4). Other solvents were also
tested in the reaction. The desired product 2a was formed
in 61 and 42% yields in 1,2-dichloroethane and toluene, re-
spectively (Table 1, entries 5 and 6). The combined catalyst
Au
ACHTUNGTRENNUNG
acid (TfOH), and Lewis acids, such as BF3·Et2O, Sc
G
Furthermore, to extend the scope of this reaction, we in-
vestigated a range of propargylic esters tethered with hydra-
zones 1l–v and the results of these experiments are summar-
ized in Table 3. For propargylic esters substituted with a sub-
cycloalkyl group (compounds 1l–n), the expected products
2l–n were obtained in 55–66% yields under the standard
conditions. When an alkylsulfonyl group was introduced to
the substrate instead of the tosyl group, the reactions also
proceeded smoothly to give the corresponding products in
good yields (substrates 1p–t). Introducing a methyl group to
propargylic hydrazone (substrates 1s and 1t), the corre-
sponding 3-substituted 5,6-dihydropyridazin-4-one 2s could
be also formed in 30 and 44% yields, respectively. For styr-
enyl hydrazone 1u, the pyrazole 3a was formed in 73%
yield without the formation of the 5,6-dihydropyridazin-4-
one product. As for substrate 1v, which contains a hydrogen
atom at the terminal of the alkyne moiety, 4,5-dihydropyra-
zole 3b was obtained in 41% yield.[14] Other substrates, such
as 1w tethered by an oxygen atom, gave no reaction under
the standard conditions (see the Supporting Information).
To verify the reaction pathway, the control experiment
has been performed upon treating 1a with the decreased
silver catalyst loading (5 mol%) and it was found that 2a
and AlCl3, have also been applied to the reaction, but no su-
perior results were obtained (Table 1, entries 7–11). To in-
vestigate the additive affect of water in this transformation,
dry dichloromethane was used in this reaction under the
standard conditions, giving 2a in trace amounts (Table 1,
entry 12). When using dry dichloromethane containing 1.0
or 2.0 equivalents of water, the reaction was accelerated and
an 84% yield of 2a was obtained after 1 h (Table 1, en-
tries 13 and 14). Thus, the use of AgSbF6 (10 mol%) as the
catalyst and 1.0 equivalent of water as the additive in dry di-
chloromethane at room temperature has been identified as
the optimal reaction conditions.
Under the optimized conditions, we next investigated the
tolerance of silver(I)-catalyzed tandem cyclization of various
hydrazones 1b–k and the results are shown in Table 2. As
for substrates 1b and 1c bearing electron-donating groups
(methyl or methoxy group) on their benzene rings, the cor-
responding products 2b and 2c were obtained in 60 and
30% yields, respectively (Table 2, entries 1 and 2). The poor
yield of 2c is presumably due to the electronic effect be-
cause many unidentified by-products were observed in the
reaction. As for substrates 1d–i bearing electron-withdraw-
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3655

M. Shi and Z. Zhang
Table 3. Scope of the silver-catalyzed tandem reaction of N-sulfonylhydra-
zone-propargylic esters.[a]
Substrate
Product[b]
Substrate
Product[b]
1l, n=1, R1 =4-
ClC6H4
2l (1 h, 55%)
1o, R=Ts
2o (4 h, 80%)
2o (2 h, 88%)
1m, n=2, R1 =C6H5 2m (1 h, 66%) 1p, R=Ms
1n, n=3, R1 =C6H5 2n (4 h, 64%)
1q, R1 =C6H5
2a (3 h, 70%)
2e (3 h, 62%)
1s, R=Ms
1t, R=EtSO2
2s (5 h, 44%)
2s (3 h, 30%)
1r, R1 =4-ClC6H5
Scheme 2. Isotopic labeling experiments.
1u
3a (4 h, 73%)
1v
3b (24 h, 41%)
[D]2b was formed in 47% yield along with 100% D content
in the nitrogen proton. However, treating 2b with 5.0 equiv-
alents of D2O in dichloromethane did not afford [D]2b, sup-
porting the hydrogen transfer from water to the final prod-
uct 2.
[a] Conditions: 1, AgSbF6 (10 mol%), H2O (1.0 equiv), CH2Cl2, RT. [b] Reac-
tion time and isolated product yield.
could be obtained in 28% yield along with the formation of
3,3-sigmatropic rearrangement product 4a in 49% yield
after 1 h (see reaction (1)). Subjecting 4a to the reaction
under the standard conditions, 2a was formed in 76% yield,
which indicated that compound 4a might be the intermedi-
ate of this reaction (see reaction (2)).
On the basis of above experiments, a plausible reaction
mechanism is outlined in Scheme 3. The cationic silver(I)
first coordinates to the alkyne moiety of 1 to afford inter-
mediate A, which undergoes a 3,3-sigmatropic rearrange-
ment to give carboxyallene intermediate 4.[16] Activation of
the hydrazone sp2 nitrogen atom of 4 by silver(I) produces
intermediate B,[17] which induces a Mannich-type addition of
the allenic acetate to the C=N bond to give intermediate C.
Moreover, isotope labeling experiments have been also
performed (Scheme 2). By using 1a as the substrate with ad-
dition of 1.0 equivalent H2O18 to the reaction mixture, it was
found that 2a was formed in 67% yield along with 0% of
18O content (determined by EI-MS analysis, see the Sup-
porting Information), which indicated that the oxygen atom
of product 2a is derived from substrate 1a and no Meyer–
Schuster rearrangement occurred in the cyclization.[15] The
deuterium-labeling experiment was carried out by using 1b
as the substrate in the presence of 1.0 equivalent of D2O
under the standard conditions. The corresponding product
Scheme 3. Plausible reaction mechanism.
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Chem. Eur. J. 2012, 18, 3654 – 3658

Silver(I)-Catalyzed Tandem 1,3-Acyloxy Migration
FULL PAPER
Commercially obtained reagents were used without further purification.
Dichloromethane was distilled from calcium hydride under argon. All re-
actions 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.
In the presence of water, intermediate C undergoes hydroly-
sis to give intermediate D and regenerates the silver(I) cata-
lyst. Then the carbonyl group of intermediate D is activated
by cationic silver(I), affording intermediate E, which under-
goes a soft enolization to give intermediate F.[18] Release of
the tosyl moiety of F produces the product 2.[19]
The transformation of the product 5,6-dihydropyridazin-4-
one 2 to other pyridazin derivatives was briefly examined
(Scheme 4). Compound 2e was readily converted into the
General procedure for the preparation of compounds 2: Substrate 1
(0.15 mmol) and AgSbF6 (5.1 mg, 0.015 mmol) were added to a flame-
dried Schlenk flask. Then water (3 mL, 0.15 mmol) and dry CH2Cl2
(1.5 mL) were added sequentially. The reaction mixture was stirred at
room temperature under argon. When the reaction was completed, the
yellow mixture was evaporated under reduced pressure and the residue
was purified by silica gel flash column chromatography eluting with pe-
troleum and ethyl acetate (v/v, 5:1). Compound 2 could be afforded as a
yellow solid or oil.
6-Phenyl-5-(propan-2-ylidene)-5,6-dihydropyridazin-4(1H)one
(2a):
Yellow solid; m.p. 125–1278C; 1H NMR (CDCl3, 400 MHz, TMS): d=
1.97 (3H, s), 2.33 (3H, s), 5.64 (1H, s), 6.67 (1H, s), 7.21–7.23 (2H, m),
7.26–7.34 ppm (4H, m); 13C NMR (CDCl3, 100 MHz, TMS): d=22.6,
23.9, 59.8, 125.6, 126.3, 128.0, 128.9, 134.8, 138.8, 151.7, 179.3 ppm; IR
(neat): n˜ =3294, 2926, 2854, 1740, 1656, 1610, 1492, 1458, 1363, 1267,
1169, 1089, 1020 cmÀ1; MS (%): m/z: 214 (10.33) [M]+, 173 (3.21), 137
(100.00), 83 (9.93); HRMS (EI): m/z: calcd for C13H14N2O: 214.1106 [M+
]; found: 214.1109.
CCDC-805834 (2a), -800969 (3c), and -845690 (5b) contain the supple-
mentary crystallographic 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.
Scheme 4. The transformation of 2 to pyridazin derivatives 5 and 6.
DMAP=4-dimethylaminopyridine.
N-acetylated product 5a in the presence of acetic anhydride
when pyridine was used as the base. However, when trie-
thylamine was used instead of pyridine, the base could de-
Acknowledgements
We thank the Shanghai Municipal Committee of Science and Technology
(08dj1400100-2), National Basic Research Program of China
2009CB825300), the Fundamental Research Funds for the Central Uni-
versities, and the National Natural Science Foundation of China for fi-
nancial support (21072206, 20472096, 20872162, 20672127, 20821002, and
20732008) and Mr. J. Sun for performing the X-ray diffraction.
À
protonate the C H bond of the methyl group to promote
(ACHTUNGTRENNUNG(973)-
enolization, which was followed by acetylation to form the
product 5b. The structure of 5b has been ascertained by X-
ray diffraction.[13] By a conventional O3 oxidation procedure,
compound 5a could be readily converted to 5-hydroxypyri-
dazin-4-one 6a and compound 5b could be easily trans-
formed to 1,6-dihydropyridazin 6b, respectively.
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Experimental Section
General information: Melting points were obtained with a Yanagimoto
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in CDCl3 with tetramethylsilane (TMS) as internal standard; J values are
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compounds reported in this paper gave satisfactory HRMS analytic data.
Chem. Eur. J. 2012, 18, 3654 – 3658
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3657

M. Shi and Z. Zhang
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Received: September 9, 2011
Published online: February 22, 2012
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