Cross Coupling of Bromo Sydnones
CDCl3) δ 167.2, 159.7, 134.6, 131.9, 130.0, 128.9, 124.8, 116.5,
we carried out the cycloaddition of simple terminal alkynes.
Specifically, 4-ethynyl-N,N-dimethylaniline 25 provided 26 in
65% yield as a single regioisomer, while ethylpropiolate 27
underwent a highly efficient cycloaddition that resulted in an
inseparable mixture of ethylcarboxylate pyrazole isomers 28
with no regiocontrol.
114.2, 108.1, 55.2. FTIR (CH2Cl2) 1731 (s), 1606 (m), 1528 (s),
1297 (s), 1245 (s), 1177 (s), 1000 (m), 966 (m) cm-1
.
4-(4-Nitrophenyl)-3-phenyl-1,2,3-oxadiazol-3-ium-5-olate (15).7a
15 was isolated as a yellow solid (97 mg, 86%), mp 166-168 °C
1
(lit.3 mp 167-170 °C). H (400 MHz, CDCl3) δ 7.47-7.54 (m, 4
H), 7.65-7.70 (m, 2 H), 7.74-7.79 (m, 1 H), 8.11-816 (m, 2 H);
13C NMR (100.6 MHz, CDCl3) δ 166.3, 146.7, 134.2, 132.9, 130.8,
130.7, 126.9, 124.8, 123.9, 105.7; FTIR (CH2Cl2) 1760 (s), 1739
(s), 1591 (m), 1512 (s), 1344 (s), 1331 (s), 1269 (s), 1004 (S), 964
Conclusion
(m), 852 (s) cm-1
.
In conclusion, we have demonstrated that boronic acids,
esters, and trifluoroborates readily participate in Pd-catalyzed
cross-coupling reactions with sydnone 2, thus providing a
convenient means for the generation of a diverse array of these
compounds, and ultimately, a range of pyrazole products.
Notably, these processes are extremely robust and simple to
perform. Indeed, these reactions were carried out with com-
mercial grade nondegassed solvents, using Pd-salts and ligands
directly as received.
3-Phenyl-4-o-tolyl-1,2,3-oxadiazol-3-ium-5-olate (16). 16 was
1
isolated as an off-white solid (69 mg, 69%), mp 165-167 °C. H
(400 MHz, CDCl3) δ 2.24 (s, 3 H), 6.95-7.00 (m, 1 H), 7.07-7.12
(m, 1 H), 7.22-7.30 (m, 2 H), 7.34-7.38 (m, 2 H), 7.43-7.48
(m, 2 H), 7.54 (m, 1 H); 13C NMR (100.6 MHz, CDCl3) δ 167.0,
138.7, 134.5, 131.7, 131.1, 130.8, 129.9, 129.8, 126.1, 123.9, 123.4,
107.9, 19.8. FTIR (CH2Cl2) 1733 (s), 1468 (m), 1275 (m), 1004
(m), 969 (m) cm-1; HRMS (EI) m/z [M]+ calcd for C15H13N2O2
253.0977, found 253.0978.
4-(3,4-Dichlorophenyl)-3-phenyl-1,2,3-oxadiazol-3-ium-5-
olate (17). 17 was isolated as an off-white solid (102 mg, 83%),
mp 115-117 °C. H (400 MHz, CDCl3) δ 7.01-7.08 (m, 1 H),
Experimental Section
1
7.32 (d, J ) 8.5 Hz, 1 H), 7.44-7.52 (m, 3 H), 7.61-7.68 (m, 2
H), 7.72-7.77 (m, 1 H); 13C NMR (100.6 MHz, CDCl3) δ 166.4,
134.1, 133.1, 132.7, 130.6, 130.4, 128.5, 128.4, 125.8, 124.7, 124.3,
105.6. FTIR (CH2Cl2) 1732 (s), 1509 (m), 1250 (m), 1027 (m),
1014 (s), 974 (w) cm-1; HRMS (EI) m/z [M]+ calcd for C14H9
35Cl2N2O2 307.0041, found 307.0038.
General Procedure for the Microwave-Promoted Suzuki
Coupling of Bromosydnone 2. To a microwave vial was added
base (1.2 mmol), bromosydnone 211 (0.4 mmol), and the boronic
acid derivative (0.6 mmol) followed by either palladium catalyst
(0.05 equiv) or palladium salt (0.05 equiv) with ligand (0.1 equiv).
To this mixture was added dimethoxyethane and water (1:1, 2 mL).
The vial was sealed after addition of a stirrer bar. The microwave
reactor was set for high absorption, 30 min at 130 °C with 60 s
prestirring and a fixed hold time. The crude reaction mixture was
poured straight into a round-bottomed flask and concentrated onto
silica gel, packed onto a dry loading cartridge, and purified by an
ISCO automated chromatography system (gradient running from
0 to 45% ethyl acetate in hexane over 30 min). The relevant
fractions were evaporated to dryness yielding the products.
Procedure for the Suzuki Coupling of Bromosydnone 2
under Thermal Conditions As Applied to the Synthesis of
3-Phenyl-4-p-tolyl-1,2,3-oxadiazol-3-ium-5-olate (3). To a 10 mL
round-bottomed flask was added bromosydnone 2 (0.4 mmol, 100
mg), p-tolylboronic acid (0.6 mmol, 82 mg), CsF (1.2 mmol, 182
mg), and PdCl2(PPh3)2 (0.02 mmol, 14 mg). The mixture was
dissolved in a 1:1 DME/H2O mixture (2 mL) and heated at reflux
for 1 h. The crude reaction mixture was dry loaded onto silica gel
and purified by flash chromatography (stepwise gradient; starting
with petroleum ether and finishing with 20% EtOAc in petroleum
ether).
(E)-3-Phenyl-4-styryl-1,2,3-oxadiazol-3-ium-5-olate (18).7a 18
was isolated as a yellow solid (83 mg, 79%), mp 177-179 °C (lit.3
1
mp 179-181 °C). H (400 MHz, CDCl3) δ 6.58 (d, J ) 16.0 Hz,
1 H), 7.22-7.32 (m, 3 H), 7.34-7.37 (m, 2 H), 7.58-7.63 (m, 2
H), 7.67-7.77 (m, 4 H); 13C NMR (100.6 MHz, CDCl3) δ 166.0,
136.2, 133.4, 132.3, 131.2, 130.2, 128.7, 128.5, 126.6, 125.0, 109.7,
108.6; FTIR (CH2Cl2) 1725 (s), 1475 (m), 1245 (S), 1073 (w), 954
(m) cm-1
.
3-Phenyl-4-(thiophen-3-yl)-1,2,3-oxadiazol-3-ium-5-olate (19).
19 was isolated as a biege solid (73 mg, 75%), mp 134-136 °C
dec. 1H (400 MHz, CDCl3) δ 5.94-5.98 (m, 1 H), 7.30-7.35 (m,
1 H), 7.55-7.59 (m, 2 H), 7.65-7.70 (m, 2 H), 7.73-7.78 (m, 2
H); 13C NMR (100.6 MHz, CDCl3) δ 166.7, 134.4, 132.4, 130.2,
126.2, 125.2, 124.5, 124.4, 123.3, 106.1; FTIR (CH2Cl2) 1720 (s),
1475 (m), 1388 (m), 1243 (s), 1213 (s), 1016 (m), 907 (m) cm-1
;
HRMS (EI) m/z [M]+ calcd for C12H9N2O2S 245.0385, found
245.0381.
3-Phenyl-4-(pyridin-3-yl)-1,2,3-oxadiazol-3-ium-5-olate (20).
20 was isolated as a orange solid (75 mg, 78%), mp 128-130 °C.
1H (400 MHz, CDCl3) δ 7.25-7.31 (m, 1 H), 7.49-7.54 (m, 2 H),
7.60-7.64 (m, 2 H), 7.68-7.74 (m, 1 H), 7.77-7.83 (m, 1 H),
8.36-8.40 (m, 1 H), 8.47-8.51 (m, 1 H); 13C NMR (100.6 MHz,
CDCl3) δ 166.6, 149.1, 147.5, 134.2, 134.0, 132.5, 130.5, 124.6,
123.4, 121.2, 104.9; FTIR (CH2Cl2) 1734 (s), 1512 (m), 1470 (m),
1265 (m), 1119 (w), 1028 (m), 968 (m) cm-1; HRMS (EI) m/z
[M]+ calcd for C13H9N3O2 240.0773, found 240.0777.
4-(1H-Indol-5-yl)-3-phenyl-1,2,3-oxadiazol-3-ium-5-olate (21).
21 was isolated as a yellow solid (91 mg, 82%), mp 135-137 °C.
1H (400 MHz, CDCl3) δ 6.41-6.45 (m, 1 H), 6.92-6.96 (m, 1 H),
7.17-7.25 (m, 2 H), 7.45-7.53 (m, 4 H), 7.57-7.65 (m, 2 H),
8.66 (br s, 1 H); 13C NMR (100.6 MHz, CDCl3) δ 167.8, 135.7,
134.9, 131.7, 129.9, 127.9, 125.5, 124.8, 121.7, 121.0, 115.5, 111.6,
109.7, 103.1; FTIR (CH2Cl2) 3356 (m) 1709 (s), 1465 (w), 1233
(m), 1012 (m), 890 (m) cm-1; HRMS (EI) m/z [M]+ calcd for
C16H12N3O2 278.0930, found 278.0926.
3-Phenyl-4-p-tolyl-1,2,3-oxadiazol-3-ium-5-olate (3). 3 was
1
isolated as an off-white solid (94 mg, 93%), mp 144-146 °C. H
(400 MHz, CDCl3) δ 2.31 (s, 3 H), 7.07-7.11 (m, 2 H),7.15-7.19
(m, 2 H), 7.46-7.50 (m, 2 H), 7.55-7.60 (m, 2 H), 7.63-7.68
(m, 1 H); 13C NMR (100.6 MHz, CDCl3) δ 167.1, 138.9, 134.7,
132.0, 130.1, 129.4, 127.2, 124.8, 121.4, 108.0, 21.2; FTIR (CH2Cl2)
1741 (s), 1533 (m), 1471 (w), 1262 (s), 1006 (s), 968 (m) cm-1
;
HRMS (EI) m/z [M]+ calcd for C15H13N2O2 253.0977, found
253.0989.
3,4-Diphenyl-1,2,3-oxadiazol-3-ium-5-olate (4).7a 4 was isolated
as a dark brown solid (79 mg, 81%), mp 189-191 °C (lit.3 mp
189-192 °C). 1H (400 MHz, CDCl3) δ 7.45-7.50 (m, 4 H),
7.53-7.61 (m, 4 H), 7.67-7.72 (m, 2 H); 13C NMR (100.6 MHz,
CDCl3) δ 167.1, 134.5, 132.1, 130.1, 128.7 (2C), 127.3, 124.7,
124.3, 107.8; FTIR (CH2Cl2) 1751 (s), 1735 (s), 1598 (w), 1516
(m), 1454 (w), 1265 (s), 1006 (m), 965 (m), cm-1
.
4-(4-Methoxyphenyl)-3-phenyl-1,2,3-oxadiazol-3-ium-5-olate
(14).7a 14 was isolated as a brown solid (76 mg, 71%), mp 146-148
°C dec (lit.3 mp 146-148 °C). 1H (400 MHz, CDCl3) δ 3.78 (s, 3
H), 6.79-6.84 (m, 2 H), 7.19-7.25 (m, 2 H), 7.46-7.51 (m, 2 H),
7.56-7.61 (m, 2 H), 7.63-7.66 (m, 1 H); 13C NMR (100.6 MHz,
Synthesis of 1-Phenyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaboro-
lan-2-yl)-5-p-tolyl-3-(trimethylsilyl)-1H-pyrazole (23). Sydnone
3 (126 mg, 0.5 mmol), alkynyl boronate 19 (224 mg, 1 mmol),
and o-dichlorobenzene (0.5 mL) where heated at reflux for 48 h
under nitrogen. The crude reaction mixture was purified by flash
J. Org. Chem. Vol. 74, No. 1, 2009 399