Lewis acids in dipolar diazo esters addition
Russ.Chem.Bull., Int.Ed., Vol. 59, No. 5, May, 2010
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EtAlCl2 in hexane (0.8 M, 100 mol.%) or GaCl3 in dichloroꢀ
methane (0.5—1 mL) (20—50 mol.%) to a stirred solution of
methyl diazoacetate (2 mmol) and unsaturated compound
(4 mmol) in dichloromethane (5 mL) under argon at 5—20 °C.
The reaction mixture was stirred over period of time indicated in
Tables 1 and 2, then treated with 5% aq. HCl at 0 °C to pH 3,
and extracted with dichloromethane (3×10 mL). The organic
extracts were combined, dried with anhydrous MgSO4, the
solvent was evaporated in vacuo, and the residue was analyzed
NH). 13C NMR, δ: 17.2 (Me); 43.2 (C(4)); 52.2 and 52.9
(2 OMe); 69.1 (C(5)); 146.4 (C(3)); 162.2 (COO at C(3)); 171.9
(COO at C(5)).
Methyl 5ꢀcyanoꢀ4,5ꢀdihydroꢀ1Hꢀpyrazoleꢀ3ꢀcarboxylate (7a)
and methyl 3ꢀcyanoꢀ4,5ꢀdihydroꢀ1Hꢀpyrazoleꢀ5ꢀcarboxylate (7b).
A mixture of pyrazolines 7a and 7b (0.25 g, 82%, the ratio ~4 : 1)
was obtained from methyl diazoacetate (0.20 g, 2 mmol),
acrylonitrile (0.21 g, 4 mmol), and Yb(OTf)3 (62 mg, 0.1 mmol)
as a colorless oil. Found (%): C, 47.35; H, 4.79; N, 27.27.
C6H7N3O2. Calculated (%): C, 47.06; H, 4.61; N, 27.44.
Isomer 7a. 1H NMR, δ: 3.30 (m, 2 H, H2C(4)); 3.87 (s, 3 H,
OMe); 4.72 (dd, 1 H, H(5), 3J = 8.9 Hz and 9.5 Hz); 6.99 (br.s,
1 H, NH). 13C NMR, δ: 36.7 (C(4)); 49.3 (C(5)); 52.5 (OMe);
117.9 (C≡N); 142.7 (C(3)); 161.6 (COO). Isomer 7b. 1H NMR,
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by H NMR spectroscopy. The reaction products were isolated
by column chromatography on silica gel using a mixture of
benzene and AcOEt with the gradient from 4 : 1 to 2 : 1 as an
eluent, unless otherwise is specified.
Dimethyl 4,5ꢀdihydroꢀ1Hꢀpyrazoleꢀ3,5ꢀdicarboxylate (1).
Methyl diazoacetate (0.20 g, 2 mmol), methyl acrylate (0.35 g,
4 mmol), and 0.8 M solution of EtAlCl2 in hexane (2.5 mL,
2 mmol), which was added over 1 min, yielded pyrazoline 1
(0.34 g, 91%) with the purity >95%. 1H NMR spectrum
agrees with that described earlier.14 Pyrazoline 1 (0.17 g, 90%)
was obtained similarly from methyl diazoacetate (0.10 g,
1 mmol), methyl acrylate (0.17 g, 2 mmol), and Yb(OTf)3
(36 mg, 0.06 mmol).
Dimethyl 1ꢀ(2ꢀmethoxyꢀ2ꢀoxoethyl)ꢀ4,5ꢀdihydroꢀ1Hꢀpyrazoleꢀ
3,5ꢀdicarboxylate (2). Methyl diazoacetate (0.20 g, 2 mmol),
methyl acrylate (0.26 g, 3.0 mmol), and GaCl3 (70 mg, 20 mol.%)
in CH2Cl2 (0.5 mL) yielded pyrazoline 1 (56 mg, 15%) and
pyrazoline 2 (195 mg, 76%). 1H NMR, δ: 3.30 (dd, 1 H, HaC(4),
2J = 17.8 Hz, 3J = 11.6 Hz); 3.40 (dd, 1 H, HbC(4), 2J = 17.8 Hz,
3J = 13.2 Hz); 3.71, 3.77, and 3.82 (all s, 3 H each, 3 OMe); 4.21
and 4.46 (both d, 1 H each, H2CN, 2J = 18.2 Hz); 4.66 (dd, 1 H,
H(5), 3J = 11.6 Hz and 13.2 Hz). 13C NMR, δ: 36.2 (C(4));
52.1, 52.3 and 52.8 (3 OMe); 52.5 (NCH2); 65.2 (C(5)); 139.7
(C(3)); 162.3 (COO at C(3)); 169.9 and 170.3 (2 COO). If the
reaction mixture before treatment with dilute HCl was passed
through a layer of silica gel, individual pyrazoline 2 was isolated
in 72% yield.
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3
δ: 3.18 (dd, 1 H, Ha(4), J = 17.3 Hz, J = 12.0 Hz); 3.25 (dd,
1 H, Hb(4), 2J = 17.3 Hz, 3J = 6.3 Hz); 3.81 (s, 3 H, OMe); 4.52
(dd, 1 H, H(5), 3J = 6.3 Hz and 12.0 Hz); 7.00 (br.s, 1 H, NH).
13C NMR, δ: 36.5 (C(4)); 53.1 (OMe); 60.8 (C(5)); 113.7 (C≡N);
123.8 (C(3)); 170.9 (COO). 1H NMR spectrum of ethyl
5ꢀcyanoꢀ4,5ꢀdihydroꢀ1Hꢀpyrazoleꢀ3ꢀcarboxylate, a homologue
of pyrazoline 7a, is given in Ref. 4.
Methyl 3ꢀcyanoꢀ5ꢀ(2ꢀmethoxyꢀ2ꢀoxoethyl)ꢀ4,5ꢀdihydroꢀ
1Hꢀpyrazoleꢀ5ꢀcarboxylate (8). A. Methyl diazoacetate (0.20 g,
2 mmol), acrylonitrile (0.21 g, 4 mmol), and GaCl3 (0.17 g,
1 mmol) dissolved in dichloromethane (4 mL) yielded colorless
oily liquid (0.19 g), from which pyrazoline 7b (115 mg, 37%)
(Rf 0.4) and pyrazoline 8 (80 mg, 35%) (Rf 0.7) were isolated
by preparative TLC on SiO2 (eluent: CH2Cl2—MeOH, 10 : 1).
Found (%): C, 48.21; H, 5.02; N, 18.50. C9H11N3O4. Calculꢀ
ated (%): C, 48.00; H, 4.92; N, 18.66. MS, m/z (Irel (%)): 225
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(16) [M]+, 193 (3), 166 (86), 138 (10), 106 (100). H NMR, δ:
3.34 (d, 2 H, H2C(4), 3J = 12.4 Hz); 3.75 and 3.81 (both s,
3 H each, 2 OMe); 4.23 and 4.43 (both d, 1 H each, CH2N,
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2J = 18.1 Hz); 4.69 (t, 1 H, H(5), J = 12.4 Hz). 13C NMR, δ:
37.7 (C(4)); 52.1 and 53.0 (2 OMe); 52.2 (CH2N); 64.3 (C(5));
113.7 (C≡N); 120.9 (C(3)); 169.2 and 169.4 (2 COO).
Dimethyl 5ꢀmethylꢀ4,5ꢀdihydroꢀ1Hꢀpyrazoleꢀ3,5ꢀdicarbꢀ
oxylate (5). A. Methyl diazoacetate (0.20 g, 2 mmol), methyl
methacrylate (0.40 g, 4 mmol), and 0.8 M solution of EtAlCl2 in
hexane (2.5 mL, 2 mmol) yielded pyrazoline 5 (0.35 g, 85%) as
a colorless oil. 1H NMR, δ: 1.53 (s, 3 H, Me); 2.80 and 3.49
(both d, 1 H each, H2C(4), 2J = 17.8 Hz); 3.75 and 3.81 (both s,
3 H each, 2 CO2Me); 6.70 (br.s, 1 H, NH). 13C NMR, δ: 24.1
(Me); 41.3 (C(4)); 52.2 and 53.0 (2 OMe); 69.9 (C(5)); 142.2
(C(3)); 162.5 (COO at C(3)); 174.2 (COO at C(5)).
B. Methyl diazoacetate (0.15 g, 1.5 mmol) in dioxane
(2 mL) was added to a boiling solution of pyrazoline 7b (0.23 g,
1.5 mmol) and Rh2(OAc)4 (3.5 mg, 0.008 mmol) in dioxane
(5 mL) over 1 h with stirring and the mixture was refluxed for
another 4 h. Then dioxane was evaporated in vacuo and the
residue was subjected to chromatography on silica gel with
CH2Cl2 as an eluent to obtain pyrazoline 8 (0.51 g, 70%), which
was identical to the sample obtained in method A.
Dimethyl
E,Zꢀ3,5ꢀdimethylꢀ4,5ꢀdihydroꢀ3Hꢀpyrazoleꢀ
B. Pyrazoline 5 (131—136 mg, 82—85%) was obtained
from methyl diazopropionate (115 mg, 2 mmol), methyl acrylate
(0.35 g, 4 mmol), and 0.8 M solution of EtAlCl2 in hexane
(2.5 mL, 2 mmol) or GaCl3 (35 mg, 0.2 mmol) in dichloroꢀ
methane (0.5 mL), which was identical to the sample obtained
in method A.
3,5ꢀdicarboxylate (10). Stereoisomeric pyrazolines 10
(E/Z = 3.7 : 1) (146 mg, 85%) were obtained from methyl
diazopropionate (91 mg, 0.8 mmol), methyl metacrylate
(200 mg, 2 mmol), and Yb(OTf)3 (24 mg, 0.04 mmol). Found
(%): C, 50.74; H, 6.77; N, 12.95. C9H14N2O6. Calculated (%):
C, 50.46; H 6.59; N, 13.08. 1H NMR, δ, Eꢀisomer: 1.66 (s, 6 H,
2 Me); 2.01 (s, 2 H, H2C(4)); 3.80 (s, 6 H, 2 CO2Me); Zꢀisomer:
1.72 (s, 6 H, 2 Me); 1.32 and 2.77 (both d, 1 H each, H2C(4),
2J = 13.5 Hz); 3.76 (s, 6 H, 2 CO2Me). 13C NMR, δ, Eꢀisomer:
22.8 (2 Me); 38.5 (C(4)); 53.0 (2 OMe); 98.1 (C(3), C(5));
170.6 (2 COO); Zꢀisomer: 24.0 (2 Me); 39.0 (C(4)); 52.4
(2 OMe); 97.3 (C(3), C(5)); 170.8 (2 COO).
Dimethyl transꢀ4ꢀmethylꢀ4,5ꢀdihydroꢀ1Hꢀpyrazoleꢀ3,5ꢀdicarbꢀ
oxylate (6). Pyrazoline 6 (0.22 g, 55%) was obtained from methyl
diazoacetate (0.20 g, 2 mmol), methyl (E)ꢀcrotonate (0.40 g,
4 mmol), and a 0.8 M solution of EtAlCl2 (2.5 mL, 2 mmol) at
10 °C as a colorless oil. Found (%): C, 48.22; H, 6.19; N, 13.77.
C8H12N2O4. Calculated (%): C, 48.00; H, 6.04; N, 13.99.
MS, m/z (Irel (%)): 200 (14) [M]+, 169 (10), 141 (100), 109 (54),
Trimethyl 1,1,2ꢀcyclopropanetricarboxylate (11). Cycloꢀ
propane 11 (65 mg, 30%) was obtained as a colorless oil from
dimethyl diazomalonate (0.16 g, 1 mmol), methyl acrylate
(0.17 g, 2 mmol), and GaCl3 (88 mg, 0.5 mmol), which was
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59 (34). H NMR, δ: 1.36 (d, 3 H, Me, J = 7.2 Hz); 3.59 (dq,
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1 H, H(4), J = 4.1 Hz and 7.2 Hz); 3.76 and 3.84 (both s, 3 H
each, 2 OMe); 4.04 (d, 1 H, H(5), 3J = 4.1 Hz); 6.66 (br.s, 1 H,