The Journal of Organic Chemistry
Note
CH2Cl2/benzene, Rf 0.34; HRMS calcd for C14H19DO4Na+
276.131657, found m/z = 276.131365, error = 1.1 ppm. IR (neat,
(3H, s) 3.34−3.22 (1H, m) 2.56 (1H, dd, J = 16.1, 3.7 Hz) 2.53−2.36
(2H, m) 2.33 (1H, dd, J = 16.1, 10.3 Hz) 1.79−1.59 (4H, m); 13C
NMR (100.57 MHz, CDCl3) δ 171.1, 165.0, 145.8, 119.5, 117.4, 52.6,
51.9, 37.5, 31.8, 29.6, 25.7, 17.3. Chiral HPLC analysis: CHIRALPAK
AS, flow rate 1 mL/min, 10% ethanol/hexanes. Retention times 38.9
min, 45.2 min.
Methyl 2-Cyano-5-(2-methoxy-2-oxoethyl)-4,4-dimethylcy-
clopent-1-enecarboxylate (2g). 1g (39 mg, 0.17 mmol) and
PBu3 (0.048 mmol) afforded 26 mg (59%) of 2g: colorless oil; TLC,
4:1 hexane/EtOAc, Rf 0.21; HRMS calcd for C13H17NO4Na+
274.104979, found m/z = 274.104797, error = 1.0 ppm. IR (neat,
cm−1) 2223, CN; 1736, CO; 1725, CO; 1628, CC; 1H
NMR (400 MHz, CDCl3) δ 3.83 (3H, s) 3.66 (3H, s) 3.17 (1H, m)
2.64−2.41 (4H, m) 1.12 (3H, s) 1.00 (3H, s); 13C NMR (100.53
MHz, CDCl3) δ 172.3, 162.5, 149.8, 121.0, 114.8, 52.4, 51.9, 51.5,
49.1, 41.8, 33.2, 29.1, 22.9.
1
cm−1) 2235, CC; 1716, CO; 1640, CC; H NMR (400 MHz,
CDCl3) δ 5.80 (1H, t, J = 2.1 Hz) 4.22 (2H, q, J = 7.1 Hz) 4.20 (2H,
q, J = 7.1 Hz) 2.39 (2H, s) 1.31 (3H, t, J = 7.1 Hz) 1.30 (3H, t, J = 7.1
Hz) 1.20 (6H, s); 13C NMR (100 MHz, CDCl3) δ 166.7, 154.5 (t,
JC‑D= 23.9 Hz), 153.6, 118.9, 85.5, 75.4, 61.9, 60.4, 36.7, 31.5, 26.1,
14.2, 14.0.
General Method for TMSCN Cyclizations. A flask containing 1
was purged with N2. CH3CN (0.1 M) and TMSCN (1.5 equiv) were
added, followed by the trialkylphosphine (0.1−0.5 equiv). The mixture
was stirred for 8−15 h or until the reaction was complete by TLC.
Alternatively, some reactions were performed using deuterated
solvents and monitored by NMR. When the reaction reached
completion, the solution was poured onto aqueous CsF (0.1 M
solution) and stirred for 2 h. The solution was extracted with CH2Cl2,
dried (MgSO4), and concentrated (aspirator) to yield an orange oil,
which was purified by flash chromatography.
Methyl 2-Cyano-5-(2-methoxy-2-oxoethyl)cyclopent-1-ene-
carboxylate (2a). 1a (26 mg, 0.13 mmol) and PBu3 (0.013 mmol)
afforded 18 mg (61%) of 2a: colorless oil; TLC, 1:1 hexane/Et2O, Rf
0.26; HRMS calcd for C11H13NO4Na+ 246.0742, found m/z =
246.0742, error = 0 ppm; IR (neat, cm−1) 2223, CN; 1722, CO;
1H NMR (500 MHz, CDCl3) δ 3.86 (3H, s) 3.68 (3H, s) 3.55−3.48
(1H, m) 2.86−2.67 (2H, m) 2.81 (1H, dd, J = 15.9, 3.7 Hz) 2.44 (1H,
dd, J = 15.9, 9.5 Hz) 2.33 (1H, dddd, J = 13.7, 9.3, 9.3, 6.3 Hz) 1.80
(1H, dddd, J = 13.8, 8.7, 5.3, 5.3 Hz); 13C NMR (100.57 MHz,
CDCl3) δ 171.9, 162.3, 149.7, 122.8, 114.7, 52.4, 51.8, 42.5, 37.0, 34.7,
28.8. Chiral HPLC analysis: CHIRALPAK AS, flow rate 1 mL/min,
5% isopropanol/hexanes. Retention times 13.3 min, 15.0 min.
Methyl 2-Cyano-5-(cyanomethyl)cyclopent-1-enecarboxy-
late (2b). 1b (80 mg, 0.49 mmol) and PMe3 (0.07 mmol) afforded
44 mg (47%) of 2b: crystalline solid. Pure material was obtained by
crystallization from Et2O: mp 59.2−60.1 °C; TLC, 1:2 hexane/Et2O,
Rf 0.22; HRMS calcd for C10H10N2O2Na+ 213.0640, found m/z =
213.0640, error = 0 ppm; IR (neat, cm−1) 2235, CN; 2225, CN;
1721, CO; 1H NMR (400 MHz, CDCl3) δ 3.89 (3H, s) 3.49−3.41
(1H, m) 3.05−2.94 (1H, m) 2.85−2.71 (3H, m) 2.49−2.36 (1H, m)
2.07−1.95 (1H, m); 13C NMR (125.7 MHz, CDCl3) δ 161.8, 146.7,
125.2, 117.5, 114.0, 52.7, 42.6, 35.1, 28.1, 21.7.
Ethyl 2-Cyano-5-(2-ethoxy-2-oxoethyl)-4,4-dimethylcyclo-
pent-1-enecarboxylate (2h). 1h (601 mg, 2.38 mmol) and PBu3
(0.72 mmol) afforded 365 mg (55%) of 2h: colorless oil; TLC, 4:1
hexanes/EtOAc, Rf 0.31; HRMS calcd for C15H21NO4Na+ 302.136279,
found m/z = 302.135945, error = 1.1 ppm. IR (neat, cm−1) 2223, C
1
C; 1735, CO; 1720, CO; 1625, CC; H NMR (400 MHz,
CDCl3) δ 4.28 (2H, m) 4.11 (2H, m) 3.17 (1H, m) 2.51 (4H, m) 1.34
(3H, t, J =7.2 Hz) 1.23 (3H, t, J =7.2 Hz) 1.12 (3H, s) 1.01 (3H, s);
13C (100.52 MHz NMR) (CDCl3) δ 171.9, 162.1, 150.1, 120.5, 114.9,
61.8, 60.7, 51.4, 49.1, 41.7, 33.4, 29.2, 23.0, 14.1, 13.9.
3-(Cyanomethyl)-5,5-dimethyl-2-(phenylsulfonyl)cyclopent-
1-enecarbonitrile (2i). 1i (26 mg, 0.095 mmol) and PBu3 (0.014
mmol) afforded 14 mg (50%) of 2i: yellow oil; TLC, 1:2 hexane/Et2O,
Rf 0.14; HRMS calcd for C16H16N2O2SNa+ 323.0831, found m/z =
323.0828, error = 1 ppm; IR (neat, cm−1) 2251, CN; 2226, CN;
1327, SO2 ss; 1157, SO2 as; 1H NMR (400 MHz, CDCl3) δ 8.05−7.99
(2H, m) 7.81−7.74 (1H, m) 7.70−7.62 (2H, m) 3.52−3.44 (1H, m)
3.00 (1H, dd, J = 16.8, 4.1 Hz) 2.79 (1H, dd, J = 16.8, 8.1 Hz) 2.31
(1H, dd, J = 13.6, 8.5 Hz) 1.86 (1H, dd, J = 13.6, 7.0 Hz) 1.37 (3H, s)
1.22 (3H, s); 13C NMR (100.57 MHz, CDCl3) δ 152.7, 138.1, 135.2,
134.2, 130.0, 128.4, 116.9, 111.3, 48.4, 43.6, 41.8, 27.4, 26.9, 22.4.
Ethyl 2-Cyano-5-(2-ethoxy-2-oxoethyl)-4,4-dimethylcyclo-
pent-1-enecarboxylate-(5-d1) (11). 10 (40 mg, 0.16 mmol) and
PBu3 (0.05 mmol) afforded 26 mg (59%) of 11: yellow oil; TLC, 4:1
hexanes/EtOAc, Rf 0.31; HRMS calcd for C15H20DNO4Na+
303.14256, found m/z = 303.142215, error = 1.1 ppm. IR (neat,
cm−1) 2224, CN; 1732, CO; 1721, CO; 1624, CC; 1H
NMR (400 MHz, CDCl3) δ 4.28 (2H, m) 4.11 (2H, m) 2.51 (2H, dd,
J = 63.0, 17.4 Hz) 2.48 (2H, dd, J = 40.0, 16.3 Hz) 1.34 (3H, t, J = 7.2
Hz) 1.23 (3H, t, J = 7.2 Hz) 1.12 (3H, s) 1.01 (3H, s); 13C NMR
(100.53 MHz, CDCl3) δ 171.9, 162.1, 150.1, 120.6, 114.9, 61.8, 60.7,
51.0 (JC‑D= 20.8 Hz), 49.1, 41.6, 33.3, 29.2, 23.0, 14.1, 13.9.
Methyl 2-Cyano-5-(2-methoxy-2-oxoethyl)-3,3-dimethylcy-
clopent-1-enecarboxylate (2c). 1c (49 mg, 0.22 mmol) and PBu3
(0.11 mmol) afforded 34 mg (61%) of 2c: colorless oil; TLC, 2:1
hexane/Et2O, Rf 0.23; HRMS calcd for C13H17NO4Na+ 274.1055,
found m/z = 274.1049, error = 2 ppm; IR (neat, cm−1) 2223, CN;
1
1728, CO; H NMR (500 MHz, CDCl3) δ 3.85 (3H, s) 3.68 (3H,
s) 3.55 (1H, dddd, J = 9.3, 8.3, 6.9, 3.9 Hz) 2.92 (1H, dd, J = 16.1, 3.9
Hz) 2.43 (1H, dd, J = 16.1, 9.3 Hz) 2.23 (1H, dd, J = 13.1, 8.3 Hz)
1.60 (1H, dd, J = 13.1, 6.9 Hz) 1.29 (3H, s) 1.23 (3H, s); 13C NMR
(100.57 MHz, CDCl3) δ 172.0, 162.6, 146.7, 132.5, 113.9, 52.4, 51.7,
47.5, 44.2, 41.1, 37.8, 27.8, 26.9.
(2-Benzenesulfonyl-3-methoxy-4,4-dimethylcyclopent-2-
enyl)acetonitrile (8). Alkynyl sulfone 1i (29 mg, 0.11 mmol) was
added to an N2-purged flask with CH3CN (2.2 mL). Methanol (4.7
μL, 0.12 mmol) was added followed by PBu3 (6.6 μL, 0.03 mmol), and
the reaction was stirred for 3 h. Ethyl iodide (10 μL) was added to
quench the catalyst. The solution was concentrated (aspirator) to
afford a 4:1 ratio of products 8 and 9. Purification by flash
chromatography (2 × 16 cm), 1:1 hexane/Et2O, afforded 24.4 mg
of pure 8 (73%): amorphous solid; TLC, 1:1 hexane/Et2O, Rf 0.29;
HRMS calcd for C16H19NO3SNa+ 328.0984, found m/z = 328.0978,
error = 2 ppm; IR (neat, cm−1) 2246, CN; 1602, CO; 1304,
Methyl 2-Cyano-5-(cyanomethyl)-3,3-dimethylcyclopent-1-
enecarboxylate (2d). 1d (50 mg, 0.26 mmol) and PBu3 (0.04
mmol) afforded 21 mg (37%) of 2d: colorless oil; TLC, 1:2 hexane/
Et2O, Rf 0.29; HRMS calcd for C12H14N2O2Na+ 241.0953, found m/z
= 241.0957, error = 2 ppm; IR (neat, cm−1) 2248, CN; 2224, C
1
N; 1723, CO; H NMR (400 MHz, CDCl3) δ 3.90 (3H, s) 3.47
(1H, dddd, J = 8.1, 8.1, 8.1, 4.4 Hz) 2.87 (1H, dd, J = 16.8, 4.4 Hz)
2.79 (1H, dd, J = 16.8, 8.1 Hz) 2.30 (1H, dd, J = 13.6, 8.1 Hz) 1.81
(1H, dd, J = 13.6, 8.1 Hz) 1.39 (3H, s) 1.27 (3H, s); 13C NMR
(100.57 MHz, CDCl3) δ 162.1, 143.5, 135.0, 117.5, 113.3, 52.7, 47.8,
43.3, 41.1, 27.6, 27.0, 21.9. Chiral HPLC analysis: CHIRALPAK AS,
flow rate 1 mL/min, 20% ethanol/hexanes. Retention times 6.4 min,
9.9 min.
1
SO2; H NMR (400 MHz, CDCl3) δ 7.95−7.88 (2H, m) 7.65−7.58
(1H, m) 7.58−7.49 (2H, m) 3.92 (3H, s) 3.22 (1H, dddd, J = 8.1, 8.1,
5.9, 3.7 Hz) 3.00 (1H, dd, J = 16.8, 3.7 Hz) 2.70 (1H, dd, J = 16.8, 8.1
Hz) 2.10 (1H, dd, J = 13.1, 8.8 Hz) 1.68 (1H, dd, J = 13.1, 5.9 Hz)
1.28 (3H, s) 1.15 (3H, s); 13C NMR (125.7 MHz, CDCl3) δ 175.0,
142.2, 129.0, 127.0, 118.3, 115.1, 61.6, 45.0, 42.8, 37.3, 33.7, 26.9, 26.9,
24.0.
Methyl 2-Cyano-6-(2-methoxy-2-oxoethyl)cyclohex-1-ene-
carboxylate (2f). 1f (80 mg, 0.38 mmol) and PMe3 (0.06 mmol)
afforded 57 mg (63%) of 2f: yellow oil; TLC, 1:1 hexane/Et2O, Rf
0.25; HRMS calcd for C12H15NO4Na+ 260.0898, found m/z=
260.0894, error = 2 ppm; IR (neat, cm−1) 2215, CN; 1725, C
1
O; 1625, CO; H NMR (400 MHz, CDCl3) δ 3.87 (3H, s) 3.69
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dx.doi.org/10.1021/jo3015769 | J. Org. Chem. 2012, 77, 7768−7774