Palladium-catalysed direct arylation of sydnones

Article abstract of DOI:10.1055/s-0028-1083344

Conditions for the palladium-catalysed direct arylation of sydnones with aryl iodides and bromides are revealed. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0028-1083344

650
PAPER
Palladium-Catalysed Direct Arylation of Sydnones
P
alladium-Catalys
r
ed Direc
a
t
A
rylation
nof Sydnonestxa Rodriguez, Wesley J. Moran*
Department of Chemical & Biological Sciences, University of Huddersfield, Queensgate, Huddersfield, HD1 3DH, UK
Fax +44(1484)472182; E-mail: w.j.moran@hud.ac.uk
Received 30 September 2008
An important consideration when developing this reaction
was the desire for simple conditions using readily avail-
able reaction components. Accordingly, we began our in-
vestigations by heating sydnone 1 with iodobenzene in the
presence of 5 mol% palladium(II) acetate, 10 mol% tri-
phenylphosphine, and potassium carbonate (2 equiv) in
wet N,N-dimethylformamide at 120 °C open to the air. We
were pleased to find that clean conversion into the cou-
pled product was observed in very good yield. Optimisa-
tion studies did not reveal any superior conditions to the
original ones, however it was found that high temperature
was very important for good conversion (Scheme 2).
Abstract: Conditions for the palladium-catalysed direct arylation
of sydnones with aryl iodides and bromides are revealed.
Key words: palladium, cross-coupling, heterocycles, catalysis,
arylations
Sydnones are five-membered heterocycles that are part of
an intriguing family of molecules termed mesoionic.1
Sydnones have been investigated for their potential uses
as therapeutic agents,2 as liquid crystals,3 and as electro-
lytic solvents.4 In synthesis, the principle reactions of
sydnones are metallation, electrophilic aromatic substitu-
tions, and 1,3-dipolar cycloadditions;5,6 however, little
new reactivity has been revealed over the last few de-
cades.7 It is known that butyllithium will deprotonate syd-
nones at the 4-position and that the resulting lithiosydnone
species are unstable, but react with various electrophiles
at low temperature.8 Unstable 4-lithio-3-phenylsydnone
has been shown to react with copper(I) bromide to gener-
ate a stable copper reagent and undergo palladium-
catalysed cross-coupling reactions with three different
aryl iodides and b-bromostyrene in excellent yields.9
Ph
Pd(OAc)2 (5 mol%)
Ph3P (10 mol%)
Ph
Ph
N
N
N
N
+
PhI
O
O
K2CO3 (2 equiv)
wet DMF
O
O
1
run 1 120 °C 81%
run 2 100 °C 77%
run 3 50 °C
0%
Scheme 2 Effect of temperature on cross-coupling efficiency
The scope of the cross-coupling process was investigated
and a range of aryl halides were found to be effective
(Table 1). Electron-poor 1-iodo-3-nitrobenzene and 1-
iodo-4-nitrobenzene coupled in very good yields (entries
2 and 3) and electron-rich 1-iodo-4-methoxybenzene (en-
try 4) provided a good yield of product 2d. Bromobenzene
was found to be somewhat less effective than iodobenzene
under these conditions, but generated the coupled product
2a in 62% yield (entry 5). 4-Bromotoluene led to a mod-
erate yield of 2e (entry 6), whereas N-(4-bromophenyl)acet-
amide (entry 7) led to an excellent yield of product 2f. 1-
Bromonaphthalene and 2-bromopyridine also coupled in
good yields (entries 8 and 9). However, chlorobenzene
was found to be ineffective under these conditions (entry
10).
The direct functionalisation of C–H bonds is emerging as
a powerful tool for organic synthesis.10 In a typical cross-
coupling process two activated compounds are required,
i.e., an organometallic reagent and a halide. Possible con-
cerns about these reactions include the generation and cost
of the starting materials and the waste generated from the
organometallic compounds. Therefore, replacing these
processes with direct coupling reactions of one or two un-
activated compounds is of interest. As part of a research
programme aimed at discovering new cross-coupling re-
actions of unactivated substrates, we were interested in
developing an arylation reaction of sydnones that did not
require the use of organometallic species (Scheme 1).
H
Ar
Next, we turned our attention to 3-methylsydnone 3 to see
if our cross-coupling conditions were effective for 3-
alkyl- as well as 3-arylsydnones. Notably, there is much
less information about the reactivity of 3-alkylsydnones in
the literature compared to 3-arylsydnones. Under our
cross-coupling conditions no desired product was ob-
served, but 3 was completely consumed. Lowering the re-
action temperature to 80 °C resulted in the desired
products 4 being isolated, but in slightly diminished yields
compared to those with 1. Nonetheless, a range of aryl
iodides and bromides were successfully coupled with
sydnone 3 (Table 2). Iodobenzene furnished the expected
R
R
conditions
N
N
N
N
ArX
+
O
O
O
O
X = I, Br
R = aryl, alkyl
Scheme 1 General equation for cross-coupling of sydnones and aryl
halides
SYNTHESIS 2009, No. 4, pp 0650–0654
Advanced online publication: 27.01.2009
DOI: 10.1055/s-0028-1083344; Art ID: P10908SS
© Georg Thieme Verlag Stuttgart · New York
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PAPER
Palladium-Catalysed Direct Arylation of Sydnones
651
product 4a in 60% yield (entry 1). 1-Iodo-3-nitrobenzene ring was observed. Running the reaction again with io-
led to a poor yield of product 4b (entry 2) whereas the iso- domethane in place of acetone-d6 led to no alkylation of
meric 1-iodo-4-nitrobenzene provided 4c in a more rea- the sydnone. These results suggest that the coupling does
sonable 57% yield (entry 3); the reason for this difference not proceed through deprotonation of the sydnone ring
remains unclear. 1-Iodo-4-methoxybenzene worked mod- followed by transmetallation, which has been proposed in
erately well (entry 4), as did 1-bromonaphthalene (entry other systems.12
5).
An alternative mechanism is electrophilic palladation
which is considered likely based on previous studies of
sydnones. Therefore the mechanism of this transforma-
tion is proposed to be a Pd(0)/Pd(II) catalytic manifold in-
volving oxidative addition to the aryl halide, electrophilic
addition to the sydnone, followed by rearomatisation, and
reductive elimination to furnish the product and regener-
ate the Pd(0) catalyst (Scheme 3).
Table 1 Scope of Cross-Coupling Reaction with Sydnone 1
Ar
Pd(OAc)2 (5 mol%)
Ph3P (10 mol%)
Ph
Ph
N
N
N
N
ArX
+
O
O
K2CO3 (2 equiv)
wet DMF
O
O
2
120 °C, air
1
Entry
ArX
Ph
X
I
Product
Yielda (%)
Ar
1
2a
2b
2c
2d
2a
2e
2f
81
79
85
77
62
53
92
73
61
0
R
N
N
Pd(0)
O
ArX
2
3-O2NC6H4
4-O2NC6H4
4-MeOC6H4
Ph
I
O
3
I
Ar
Pd
4
I
ArPdX
R
N
N
O
5
Br
Br
Br
Br
Br
Cl
O
Ar
Pd
H
R
6
4-MeC6H4
4-AcNHC6H4
1-naphthyl
2-pyridyl
Ph
N
N
R
H
O
N
7
K2CO3
O
O
N
O
8
2g
2h
2a
Scheme 3 Postulated cross-coupling mechanism
9
10
The reactivity of 4-substituted sydnones in 1,3-dipolar cy-
cloaddition reactions has not been investigated in detail.
Our studies show that a significant affect on rate is evident
depending on the electronics of the 4-substituent with an
electron-donating group leading to a markedly faster
cycloaddition than an electron-withdrawing group
(Table 3).13
a Isolated yields.
Table 2 Scope of Cross-Coupling Reaction with Sydnone 3
Ar
Pd(OAc)2 (5 mol%)
Ph3P (10 mol%)
Me
Me
N
N
N
N
ArX
+
O
O
K2CO3 (2 equiv)
wet DMF
80 °C, air
O
O
Table 3 1,3-Dipolar Cycloadditions
3
4
Ar
Ar
CO2Me
CO2Me
Ph
Ph
Entry
ArX
Ph
X
I
Product
4a
Yielda (%)
toluene
111 °C
N
N
N
N
+
O
CO2Me
CO2Me
1
2
3
4
5
60
19
57
53
55
O
2
5
3-O2NC6H4
4-O2NC6H4
4-MeOC6H4
1-naphthyl
I
4b
Entry Sydnone Ar
Time (h) Product Yielda (%)
I
4c
1
2
3
2a
2c
2d
Ph
4-O2NC6H4 60
4-MeOC6H4
16
5a
5b
5c
99
87
82
I
4d
Br
4e
5
a Isolated yields.
a Isolated yields.
It is known that the pKa value of the N-arylsydnone C4
proton is about 18–20 at room temperature.11 To see if
deprotonation of the sydnone was occurring under the re-
action conditions, sydnone 1 was heated at 120 °C in N,N-
dimethylformamide with two equivalents of potassium
carbonate and acetone-d6 for 15 hours. Upon cooling,
about 40% incorporation of deuterium into the sydnone
In summary, an operationally simple cross-coupling reac-
tion between unactivated sydnones and aryl halides has
been demonstrated. These direct coupling conditions ren-
der the pre-formation of copper species unnecessary, thus
reducing chemical waste and time. These sydnones can be
utilised in 1,3-dipolar cycloadditions to obtain further het-
Synthesis 2009, No. 4, 650–654 © Thieme Stuttgart · New York

652
A. Rodriguez, W. J. Moran
PAPER
1H NMR (400 MHz, CDCl3): d = 3.77 (s, 3 H), 6.83 (d, J = 8.7 Hz,
2 H), 7.23 (d, J = 8.7 Hz, 2 H), 7.44–7.50 (m, 2 H), 7.54–7.60 (m, 2
H), 7.62–7.67 (m, 1 H).
13C NMR (100 MHz, CDCl3): d = 55.3, 108.1, 114.3 (2 C), 116.6,
124.9 (2 C), 129.0 (2 C), 130.1 (2 C), 132.0, 134.7, 159.8, 167.3.
erocycles of potential interest. Further new reactivity of
sydnones and the properties of these molecules are being
investigated and will be reported in due course.
NMR spectra were recorded on a Bruker Avance DPX400 spec-
trometer. Mass spectra were performed on a Bruker MicroTOF LC
operating in ESI mode, with only molecular ions reported. IR spec-
tra were recorded on a Thermo Nicolet 380. Flash chromatography
was performed on silica gel 60 from Merck KGaA. TLC was per-
formed on Polygram SIL G/UV254 pre-coated plastic sheets from
Macherey-Nagel. Visualisation was achieved by UV radiation and
basic KMnO4 soln, followed by heating. Petroleum ether (PE) used
was the fraction boiling at 40–60 °C.
HRMS: m/z [M + Na]+ calcd for C15H12N2NaO3: 291.0740; found:
291.0731.
4-(4-Methylphenyl)-3-phenylsydnone (2e)
Tan crystalline solid; mp 141–143 °C (PE–EtOAc).
IR (neat): 1005 (s), 1260 (s), 1737 (s), 2922 cm–1 (w).
1H NMR (400 MHz, CDCl3): d = 2.30 (s, 3 H), 7.08 (d, J = 8.1 Hz,
2 H), 7.16 (d, J = 8.3 Hz, 2 H), 7.44–7.50 (m, 2 H), 7.53–7.60 (m, 2
H), 7.62–7.68 (m, 1 H).
13C NMR (100 MHz, CDCl3): d = 21.3, 108.1, 121.4, 124.9 (2 C),
127.3 (2 C), 128.8, 129.5 (2 C), 130.1 (2 C), 132.0, 134.7, 167.2.
3,4-Diphenylsydnone (2a); Typical Procedure
A flask was charged with 3-phenylsydnone (1, 47 mg, 0.29 mmol,
1 equiv), Pd(OAc)2 (3 mg, 0.0145 mmol, 0.05 equiv), K2CO3 (80
mg, 0.58 mmol, 2 equiv), Ph3P (8 mg, 0.029 mmol, 0.1 equiv), PhI
(49 mL, 0.435 mmol, 1.5 equiv), and wet DMF (1 mL) and heated at
reflux for 12 h open to the air. Upon cooling, H2O (30 mL) was add-
ed to the mixture, which was extracted with EtOAc (3 × 15 mL).
The combined organic layers were dried (MgSO4) and filtered. The
volatiles were removed in vacuo and the mixture was purified by
flash chromatography (silica gel, PE–EtOAc, 9:1) to give 2a (56
mg, 81%) as a light orange crystalline solid; mp 183–186 °C (PE–
EtOAc).
IR (neat): 1006 (m), 1265 (s), 1734 (s), 2360 (w), 2921 cm–1 (w).
1H NMR (400 MHz, CDCl3): d = 7.26–7.30 (m, 5 H), 7.45–7.50 (m,
2 H), 7.54–7.61 (m, 2 H), 7.63–7.69 (m, 1 H).
13C NMR (100 MHz, CDCl3): d = 107.9, 124.4, 124.9 (2 C), 127.4
(2 C), 128.7, 128.8 (2 C), 130.2 (2 C), 132.2, 134.7, 167.1.
HRMS: m/z [M + Na]+ calcd for C14H10N2NaO2: 261.0634; found:
HRMS: m/z [M + Na]+ calcd for C15H12N2NaO2: 275.0791; found:
275.0796.
4-[4-(Acetylamino)phenyl]-3-phenylsydnone (2f)
Tan crystalline solid; mp 129–131 °C (PE–EtOAc).
IR (neat): 1072 (m), 1255 (s), 1533 (s), 1665 (s), 1736 (m), 2360
(w), 3293 cm–1 (w).
1H NMR (400 MHz, CDCl3): d = 2.14 (s, 3 H), 7.35–7.70 (m, 9 H),
7.80 (br, 1 H).
13C NMR (100 MHz, CDCl3): d = 24.5, 108.0, 116.7, 119.8 (2 C),
124.8 (2 C), 128.1 (2 C), 130.3 (2 C), 132.0, 134.5, 137.1, 168.7,
169.0.
HRMS: m/z [M + Na]+ calcd for C16H13N3NaO3: 318.0849; found:
318.0844.
261.0640.
4-(1-Naphthyl)-3-phenylsydnone (2g)
Brown oil.
4-(3-Nitrophenyl)-3-phenylsydnone (2b)
IR (neat): 1050 (m), 1250 (m), 1270 (m), 1483 (m), 1731 (s), 3057
cm–1 (w).
1H NMR (400 MHz, CDCl3): d = 7.19–7.23 (m, 1 H), 7.30–7.38 (m,
5 H), 7.41–7.53 (m, 3 H), 7.76–7.81 (m, 1 H), 7.83–7.89 (m, 2 H).
13C NMR (100 MHz, CDCl3): d = 107.2, 121.5, 123.9 (2 C), 124.7,
125.2, 126.7, 127.4, 128.7, 129.8 (2 C), 130.2, 130.7, 131.6, 131.8,
133.8, 134.5, 167.6.
HRMS: m/z [M + Na]+ calcd for C18H12N2NaO2: 311.0791; found:
311.0792.
Yellow crystalline solid; mp 159–160 °C (PE–EtOAc).
IR (neat): 1016 (m), 1256 (s), 1342 (s), 1525 (s), 1721 (s), 2921
cm–1 (w).
1H NMR (400 MHz, CDCl3): d = 7.46–7.55 (m, 3 H), 7.61–7.81 (m,
4 H), 7.94–7.99 (m, 1 H), 8.05–8.12 (m, 1 H).
13C NMR (100 MHz, CDCl3): d = 105.6, 121.3, 123.0, 124.8 (2 C),
126.3, 130.0, 130.7 (2 C), 132.2, 132.9, 134.1, 148.2, 166.5.
HRMS: m/z [M + Na]+ calcd for C14H9N3NaO4: 306.0485; found:
306.0484.
3-Phenyl-4-(2-pyridyl)sydnone (2h)
Brown crystalline solid; mp 142–143 °C (PE–EtOAc).
4-(4-Nitrophenyl)-3-phenylsydnone (2c)
Light yellow crystalline solid; mp 162–163 °C (PE–EtOAc).
IR (neat): 1015 (m), 1275 (s), 1506 (m), 1581 (m), 1737 (s), 1755
(s), 2924 cm–1 (w).
1H NMR (400 MHz, CDCl3): d = 7.06–7.12 (m, 1 H), 7.42–7.57 (m,
4 H), 7.57–7.65 (m, 1 H), 7.67–7.76 (m, 1 H), 8.05 (d, J = 8.0 Hz, 1
H), 8.19–8.22 (m, 1 H).
13C NMR (100 MHz, CDCl3): d = 107.0, 121.8, 122.6, 125.0 (2 C),
129.3 (2 C), 131.5, 135.9, 136.7, 144.8, 149.1, 167.0.
IR (neat): 1120 (m), 1330 (s), 1512 (s), 1590 (s), 1760 (s), 3087
cm–1 (w).
1H NMR (400 MHz, CDCl3): d = 7.42 (d, J = 8.8 Hz, 2 H), 7.52 (d,
J = 7.7 Hz, 2 H), 7.62–7.70 (m, 2 H), 7.72–7.80 (m, 1 H), 8.11 (d,
J = 8.7 Hz, 2 H).
13C NMR (100 MHz, CDCl3): d = 105.7, 124.0 (2 C), 124.8 (2 C),
127.0 (2 C), 130.7 (2 C), 130.9, 132.9, 134.3, 146.8, 166.3.
HRMS: m/z [M + Na]+ calcd for C13H9N3NaO2: 262.0587; found:
262.0595.
HRMS: m/z [M + Na]+ calcd for C14H9N3NaO4: 306.0485; found:
306.0483.
3-Methyl-4-phenylsydnone (4a)
Cream crystalline solid; mp 133–134 °C (PE–EtOAc).
IR (neat): 1091 (m), 1312 (m), 1448 (m), 1718 (s), 3013 cm–1 (w).
1H NMR (400 MHz, CDCl3): d = 4.13 (s, 3 H), 7.35–7.43 (m, 1 H),
7.45–7.51 (m, 2 H), 7.53–7.58 (m, 2 H).
4-(4-Methoxyphenyl)-3-phenylsydnone (2d)
Brown crystalline solid; mp 121–123 °C (PE–EtOAc).
IR (neat): 1001 (m), 1248 (s), 1529 (m), 1731 (s), 2924 cm–1 (w).
Synthesis 2009, No. 4, 650–654 © Thieme Stuttgart · New York

PAPER
Palladium-Catalysed Direct Arylation of Sydnones
653
13C NMR (100 MHz, CDCl3): d = 39.0, 108.0, 124.3, 127.7 (2 C),
129.2, 129.3 (2 C), 167.2.
1H NMR (400 MHz, CDCl3): d = 3.78 (s, 3 H), 4.00 (s, 3 H), 7.22–
7.42 (m, 10 H).
HRMS: m/z [M + Na]+ calcd for C9H8N2NaO2: 199.0478; found:
199.0486.
13C NMR (100 MHz, CDCl3): d = 52.3, 52.6, 115.6, 125.6 (2 C),
127.8, 128.4 (2 C), 129.0, 129.3 (2 C), 129.7, 130.2 (2 C), 138.6,
143.2, 144.9, 162.3, 163.5.
3-Methyl-4-(3-nitrophenyl)sydnone (4b)
Yellow crystalline solid; mp 133–136 °C (PE–EtOAc).
HRMS: m/z [M + Na]+ calcd for C19H16N2NaO4:359.1002; found:
359.0990.
IR (neat): 1064 (m), 1347 (s), 1433 (m), 1530 (s), 1721 (s), 2960
(w), 3089 cm–1 (w).
1H NMR (400 MHz, CDCl3): d = 4.28 (s, 3 H), 7.68–7.74 (m, 1 H),
8.06–8.10 (m, 1 H), 8.23–8.28 (m, 1 H), 8.40–8.44 (m, 1 H).
Dimethyl 5-(4-Nitrophenyl)-1-phenyl-1H-pyrazole-3,4-dicar-
boxylate (5b)
Orange crystalline solid; mp 137–140 °C (PE–EtOAc).
IR (neat): 1074 (m), 1218 (s), 1346 (s), 1470 (m), 1524 (s), 1719 (s),
2946 cm–1 (w).
1H NMR (400 MHz, CDCl3): d = 3.77 (s, 3 H), 3.98 (s, 3 H), 7.18–
7.25 (m, 2 H), 7.29–7.37 (m, 3 H), 7.48–7.61 (m, 2 H), 8.15–8.25
(m, 2 H).
13C NMR (100 MHz, CDCl3): d = 38.9, 105.0, 120.7, 122.8, 125.6,
129.9, 132.1, 147.9, 166.0.
HRMS: m/z [M + Na]+ calcd for C9H7N3NaO4: 244.0329; found:
244.0335.
3-Methyl-4-(4-nitrophenyl)sydnone (4c)
Bright yellow crystalline solid; mp 150–151 °C (PE–EtOAc).
13C NMR (100 MHz, CDCl3): d = 52.4, 52.8, 115.7, 124.4, 125.3,
125.8 (2 C), 129.3, 129.4 (2 C), 129.5, 130.7, 136.1, 137.9, 142.6,
143.9, 147.9, 162.1, 162.8.
IR (neat): 1067 (m), 1315 (s), 1331 (s), 1513 (m), 1591 (m), 1726
(s), 2923 cm–1 (w).
HRMS: m/z [M + Na]+ calcd for C19H15N3NaO6: 404.0853; found:
404.0853.
1H NMR (400 MHz, CDCl3): d = 4.29 (s, 3 H), 7.87 (d, J = 9.0 Hz,
2 H), 8.34 (d, J = 9.0 Hz, 2 H).
Dimethyl 5-(4-Methoxyphenyl)-1-phenyl-1H-pyrazole-3,4-di-
carboxylate (5c)
Yellow crystalline solid; mp 120–122 °C (PE–EtOAc).
13C NMR (100 MHz, CDCl3): d = 39.4, 105.1, 123.8 (2 C), 126.4 (2
C), 130.2, 146.4, 165.8.
HRMS: m/z [M + Na]+ calcd for C9H7N3NaO4: 244.0329; found:
244.0336.
IR (neat): 1073 (s), 1172 (s), 1213 (s), 1435 (s), 1722 (s), 2952
cm–1 (w).
1H NMR (400 MHz, CDCl3): d = 3.77 (s, 3 H), 3.78 (s, 3 H), 3.97
(s, 3 H), 6.83 (d, J = 8.7 Hz, 2 H), 7.18 (d, J = 8.7 Hz, 2 H), 7.20–
7.25 (m, 2 H), 7.29–7.3 (m, 3 H).
13C NMR (100 MHz, CDCl3): d = 52.3, 52.6, 55.3, 113.9 (2 C),
115.2, 119.8, 125.7 (2 C), 128.5, 129.0 (2 C), 131.5 (2 C), 138.7,
143.2, 144.9, 160.4, 162.4, 163.7.
4-(4-Methoxyphenyl)-3-methylsydnone (4d)
Brown crystalline solid; mp 126–129 °C (PE–EtOAc).
IR (neat): 1026 (m), 1190 (m), 1252 (s), 1536 (m), 1721 (s), 2921
cm–1 (w).
1H NMR (400 MHz, CDCl3): d = 3.84 (s, 3 H), 4.08 (s, 3 H), 6.99
(d, J = 9 Hz, 2 H), 7.47 (d, J = 9 H, 2 H).
13C NMR (100 MHz, CDCl3): d = 38.7, 55.4, 108.1, 114.8 (2 C),
116.5, 129.3 (2 C), 160.2, 167.4.
HRMS: m/z [M + Na]+ calcd for C20H18N2NaO5: 389.1108; found:
389.1099.
HRMS: m/z [M + Na]+ calcd for C10H10N2NaO3: 229.0584; found:
229.0587.
Acknowledgment
We thank the University of Huddersfield for funding.
3-Methyl-4-(1-naphthyl)sydnone (4e)
Light yellow crystalline solid; mp 153–154 °C (PE–EtOAc).
References
IR (neat): 1028 (m), 1317 (m), 1448 (m), 1500 (m), 1715 (s), 2922
(w), 3028 cm–1 (w).
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A. Adv. Heterocycl. Chem. 1976, 19, 1.
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7.52–7.59 (m, 3 H), 7.61–7.66 (m, 1 H), 7.90–7.95 (m, 1 H), 7.99
(d, J = 8.0 Hz, 1 H).
(2) (a) Wagner, H. A.; Hill, J. B. J. Med. Chem. 1974, 17, 1337.
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Biensan, Ph. ITE Lett. Batter., New Technol. Med. 2000, 1,
20. (b) Chan, W.; Zhang, W.; Szeto, Y. Mater. Lett. 2000,
42, 280. (c) Tien, H.; Hwang, Y.; Wen, T. J. Chin. Chem.
Soc. 1998, 45, 209.
(4) Sasaki, Y.; Hirobomi, O.; Handa, M. Nippon Kagaku Kaishi
1993, 11, 1217; Chem. Abstr. 1994, 120, 34459t.
(5) (a) Huisgen, R.; Grashey, R. Angew. Chem. 1962, 74, 29.
(b) Vasil’eva, V. F.; Yashunskii, V. G.; Shchukina, M. N.
Zh. Obshch. Khim. 1960, 30, 698.
13C NMR (100 MHz, CDCl3): d = 38.3, 107.1, 120.9, 124.3, 125.4,
126.9, 127.7, 128.9, 130.0, 131.1, 132.0, 133.9, 167.6.
HRMS: m/z [M + Na]+ calcd for C13H10N2NaO2: 249.0634; found:
249.0639.
Dimethyl 1,5-Diphenyl-1H-pyrazole-3,4-dicarboxylate (5a);
Typical Procedure
A flask was charged with 3,4-diphenylsydnone (2a, 50 mg, 0.21
mmol, 1 equiv), DMAD (26 mL, 0.21 mmol, 1 equiv), and toluene
(1 mL) and heated at reflux for 16 h open to air. The volatiles were
removed in vacuo and the mixture was purified by flash chromatog-
raphy (silica gel, PE–EtOAc, 1:1) to furnish 5a (70 mg, 99%) as an
orange solid; mp 92–93 °C (PE–EtOAc).
IR (neat): 1073 (m), 1218 (s), 1475 (m), 1715 (s), 1739 (m), 2923
(w), 2952 cm–1 (w).
Synthesis 2009, No. 4, 650–654 © Thieme Stuttgart · New York

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A. Rodriguez, W. J. Moran
PAPER
(6) For a recent example of this reactivity, see: Browne, D. L.;
Helm, M. D.; Plant, A.; Harrity, J. P. A. Angew. Chem. Int.
Ed. 2007, 46, 8656.
(7) For the transformation of sydnones into oxadiazolinones
with bromine in acetic anhydride, see: Mallur, S. G.;
Badami, B. V. Farmaco 2000, 55, 65.
(8) (a) Greco, C. V.; Pesce, M.; Franco, J. M. J. Heterocycl.
Chem. 1966, 3, 391. (b) Kato, H.; Ohta, M. Bull. Chem. Soc.
Jpn. 1959, 32, 282.
(9) Kalinin, V. N.; Min, S. F. J. Organomet. Chem. 1988, 352,
C34.
(10) For representative examples, see: (a) Pivsa-Art, S.; Satoh,
T.; Kawamura, Y.; Miura, M.; Nomura, M. Bull. Chem. Soc.
Jpn. 1998, 71, 467. (b) Bellina, F.; Calandri, C.;
Cauteruccio, S.; Rossi, R. Tetrahedron 2007, 63, 1970.
(c) Flegeau, E. F.; Popkin, M. E.; Greaney, M. F. Org. Lett.
2008, 10, 2717. (d) For reviews, see: Martin, T.; Verrier, C.;
Hoarau, C.; Marsais, F. Org. Lett. 2008, 10, 2909.
(e) Campeau, L.-C.; Fagnou, K. Chem. Commun. 2006,
1253. (f) Seregin, I. V.; Gevorgyan, V. Chem. Soc. Rev.
2007, 36, 1173. (g) Alberico, D.; Scott, M. E.; Lautens, M.
Chem. Rev. 2007, 107, 174.
(11) Greco, C. V.; O’Reilly, B. P. J. Heterocycl. Chem. 1970, 7,
1433.
(12) This mechanism was reported for the Pd-catalysed direct
cross-coupling reactions of adenosines with aryl iodides:
Storr, T. E.; Firth, A. G.; Wilson, K.; Darley, K.; Baumann,
C. G.; Fairlamb, I. J. S. Tetrahedron 2008, 64, 6125.
(13) These results suggest that this is a ‘Type 1’ cycloaddition:
Sustmann, R. Pure Appl. Chem. 1974, 40, 569.
Synthesis 2009, No. 4, 650–654 © Thieme Stuttgart · New York