The Journal of Organic Chemistry
NOTE
spectra were obtained using neat films on a sodium chloride window.
High-resolution mass spectra were obtained in ESI (cation mode). All
other reagents were used as received from commercial sources. Nitrones
were prepared according to literature reports.4c,5a
Compound 4c was obtained as a yellow solid in 77% yield. 1H NMR
(500 MHz, CDCl3): δ 8.63 (d, J = 7.5 Hz, 1H), 7.83 (d, J = 8.0 Hz, 1H),
7.56À7.53 (m, 1H), 7.48À7.45 (m, 1H), 2.96 (t, J = 7.5 Hz, 2H), 1.66À
1.60 (m, 2H), 1.44 (s, 9H), 1.42À1.39 (m, 2H), 0.96 (t, J = 7.0 Hz, 3H).
13C NMR (125 MHz, CDCl3): δ 150.2, 147.4, 134.9, 133.3, 130.6,
129.6, 123.8, 123.4, 79.6, 54.3, 39.7, 31.3, 30.2, 21.7, 14.0. IR (cmÀ1):
1774, 1684, 1385, 1146, 999, 760. HRMS (ESI): calcd for [C17H22I-
NO + H]+ 384.0824, found 384.0827.
Synthesis and Characterization of Compound 2. NitroneÀ
alkyne 1a (50 mg, 0.249 mmol), IPrAuCl (7.7 mg, 5 mol %), and AgOTf
(3.2 mg, 5 mol %) were weighed into a pressure tube, to which was
added dichloromethane (5 mL). After being purged with nitrogen, the
mixture was stirred at 70 °C for 12 h. The mixture was then diluted with
CH2Cl2 and filtered through Celite. All volatiles were removed under
reduced pressure, and the residue obtained was purified by silica gel
column chromatography (10% EtOAc in petroleum ether) to give 2
Compound 4d was obtained as a yellow solid in 66% yield. 1H NMR
(500 MHz, CDCl3): δ 8.50 (d, J = 9.0 Hz, 1H), 7.25 (d, J = 3.0 Hz, 1H),
7.09 (dd, J = 8.5, 2.0 Hz, 1H), 3.89 (s, 3H), 2.90 (t, J = 7.5 Hz, 2H),
1.69À1.62 (m, 2H), 1.44 (s, 9H), 0.97 (t, J = 7.5 Hz, 3H). 13C NMR
(125 MHz, CDCl3): δ 161.2, 150.4, 147.5, 135.3, 128.0, 125.1, 119.6,
105.4, 55.8, 54.3, 41.4, 30.2, 29.9, 22.4, 13.0. IR (cmÀ1): 1701, 1487,
1294, 1211, 1078, 1032, 822. HRMS (ESI): calcd for [C17H22INO2 + H]+
400.0773, found 400.0775.
1
(24.4 mg, 0.169 mmol, 68%). H NMR (500 MHz, benzene-d6): δ
7.67À7.64 (m, 1H), 6.86À6.85 (m, 1H), 6.78À6.72 (m, 2H), 4.59
(d, J = 2.5 Hz, 1H), 4.38 (d, J = 2.5 Hz, 1H), 1.41 (s, 9H). 13C NMR
(100 MHz, benzene-d6): δ 155.9, 150.8, 135.9, 132.7, 131.1, 129.9,
123.6, 120.1, 84.5, 54.8, 30.8. HRMS (ESI): calcd for [C13H15NO + H]+
202.1232, found 202.1235.
Compound 4e was obtained as a yellow solid in 60% yield. 1H NMR
(500 MHz, CDCl3): δ 8.62 (dd, J = 9.0, 4.5 Hz, 1H), 7.49 (dd, J = 8.0,
2.5 Hz, 1H), 7.26À7.22 (m, 1H), 2.91 (t, J = 7.5 Hz, 2H), 1.70À1.63
(m, 2H), 1.42 (s, 9H), 0.98 (t, J = 7.0 Hz, 3 H). 13C NMR (125 MHz,
Representative Procedure for the Synthesis of Com-
pounds 3. Nitrone 1b (50 mg, 0.206 mmol), IPrAuCl (6.4 mg, 5
mol %), and AgOTf (2.6 mg, 5 mol %) were weight into a 10 mL
pressure tube, to which was added THF (5 mL). After being purged with
nitrogen, the mixture was stirred at 70 °C for 12 h. The mixture was then
diluted with CH2Cl2 and filtered through Celite. The solvent was
evaporated under reduced pressure, and the crude product was purified
by flash column chromatography on silica gel (10% EtOAc in petroleum
ether) to give 3b as a yellow oil (21.3 mg, 0.113 mmol, 55%). 1H NMR
(400 MHz, CDCl3): δ 10.04 (s, 1H), 7.91À7.89 (m, 1H), 7.59À7.56
(m, 2H), 7.49À7.47 (m, 1H), 6.71 (td, J = 15.8, 6.2 Hz, 1H), 6.51 (td, J =
15.8, 1.6 Hz, 1H), 2.27À2.23 (m, 2H), 1.04 (t, J = 7.4 Hz, 3H). 13C
NMR (100 MHz, CDCl3): δ 194.9, 191.0, 154.3, 141.8, 135.4, 133.1,
130.7, 129.5, 129.4, 128.4, 25.9, 12.0. HRMS (ESI): calcd for [C12H12O2 +
H]+ 189.0916, found 189.0919.
CDCl3): δ 163.6 (d, JFÀC = 250.3 Hz), 148.9, 147.1, 135.8 (d, JFÀC
9.8Hz), 131.0(d, JFÀC = 3.0 Hz), 125.7 (d, JFÀC = 9.4 Hz), 118.5 (d, JFÀC
=
=
23.6 Hz), 109.8 (d, JFÀC = 24.9 Hz), 79.0, 54.5, 41.6, 30.2, 22.3, 13.0. IR
(cmÀ1): 1711, 1479, 1285, 1217, 1078, 995, 947, 880, 816, 683, 629. HRMS
(ESI): calcd for [C16H19FINO + H]+ 388.0574, found 388.0577.
Compound 4f was obtained as a yellow solid in 58% yield. 1H NMR
(500 MHz, CDCl3): δ 8.08 (s, 1H), 7.17 (s, 1H), 6.07 (s, 2H), 2.89
(t, J = 7.5 Hz, 2H), 1.68À1.61 (m, 2H), 1.41 (s, 9H), 0.97 (t, J = 7.5 Hz,
3H). 13C NMR (125 MHz, CDCl3): δ 150.5, 149.9, 149.7, 147.3, 130.2,
128.6, 103.6, 102.6, 102.3, 77.9, 54.2, 41.6, 30.3, 22.4, 13.0. IR (cmÀ1):
1676, 1474, 1387, 1341, 1308, 1032, 988, 930, 876. HRMS (ESI): calcd
for [C17H20INO3 + H]+ 414.0566, found 414.0565.
Compound 4g was obtained as a yellow solid in 61% yield. 1H NMR
(500 MHz, CDCl3): δ 8.72 (d, J = 8.0 Hz, 1H), 7.84 (d, J = 7.5 Hz, 1H),
7.58 (td, J = 7.5, 1.0 Hz, 1H), 7.52 (td, J = 7.5, 1.0 Hz, 1H), 4.62 (s, 2H),
3.37 (s, 3H), 1.44 (s, 9H). 13C NMR (125 MHz, CDCl3): δ 149.9, 149.3,
134.5, 133.6, 131.0, 130.6, 124.3, 123.5, 74.4, 74.2, 57.2, 54.6, 30.3. IR
(cmÀ1): 1705, 1628, 1460, 1356, 1283, 1086, 1026, 982, 772, 643.
HRMS (ESI): calcd for [C15H18INO2 + H]+ 372.0460, found 372.0462.
Compound 4h was obtained as a yellow solid in 80% yield. 1H NMR
(500 MHz, CDCl3): δ 8.43 (s, 1H), 7.70 (d, J = 8.0 Hz, 1H), 7.27 (d, J =
8.0 Hz, 1H), 2.93 (t, J = 7.0 Hz, 2H), 2.47 (s, 3H), 1.70À1.63 (m, 2H),
1.44 (s, 9H), 0.98 (t, J = 7.5 Hz, 3H). 13C NMR (125 MHz, CDCl3): δ
150.4, 147.6, 141.3, 135.2, 130.9, 130.8, 124.0, 123.1, 79.1, 54.2, 41.8,
30.3, 22.3, 22.1, 12.9. IR (cmÀ1): 1707, 1636, 1458, 1360, 1275, 1213,
1011, 934, 826, 675. HRMS (ESI): calcd for [C17H22INO + H]+
384.0824, found 384.0826.
1
Compound 3c was obtained as a yellow oil in 48% yield. H NMR
(400 MHz, acetone-d6): δ 10.08 (s, 1H), 7.95 (dd, J = 7.2, 2.0 Hz, 1H),
7.79À7.67 (m, 3H), 6.77À6.70 (m, 1H), 6.63 (d, J = 17.2 Hz, 1H),
2.32À2.26 (m, 2H), 1.56À1.47 (m, 2H), 0.93 (t, J = 7.2 Hz, 3H). 13C
NMR (100 MHz, acetone-d6): δ 194.8, 191.9, 152.4, 142.6, 136.8, 134.0,
131.7, 131.0, 130.2, 129.4, 35.2, 21.9, 13.9. HRMS (ESI): calcd for
[C13H14O2 + H]+ 203.1072, found 203.1076.
Compound 3d was obtained as a yellow oil in 66% yield. 1H NMR
(400 MHz, acetone-d6): δ 10.11 (s, 1H), 7.84 (d, J = 8.8 Hz, 1H), 7.37
(d, J = 2.8 Hz, 1H), 7.26 (dd, J = 8.4, 2.8 Hz, 1H), 6.97À6.90 (m, 1H),
6.78 (d, J = 16.0 Hz, 1H), 3.95 (s, 3H), 2.38À2.31 (m, 2H), 1.11 (t, J =
7.2 Hz, 3H). 13C NMR (125 MHz, acetone-d6): δ 192.0, 191.7, 162.7,
152.6, 139.9, 134.4, 131.9, 128.3, 118.5, 113.6, 56.0, 26.0, 12.2. HRMS
(ESI): calcd for [C13H14O3 + H]+ 219.1021, found 219.1024.
Representative Synthesis of Compounds 4. Nitrone 1b
(50 mg, 0.206 mmol), NaHCO3 (34.6 mg, 0.412 mmol, 2.0 equiv),
and dichloromethane (3 mL) were placed in a flask, to which was added
dropwise a solution of iodine (104.4 mg, 0.412 mmol, 2.0 equiv) in
DCM (2 mL) at 0 °C. The mixture was stirred at room temperature for
8 h. The reaction mixture was diluted with CH2Cl2 (25 mL) and washed
(3Â) with saturated aq Na2S2O3. The combined organic extracts were
dried with Na2SO4. The solvent was evaporated under reduced pressure,
and the crude product was purified by flash column chromatography on
silica gel (5% EtOAc in petroleum ether) to give 4b as a yellow oil (49.9
Compound 4i was obtained as a yellow solid in 74% yield. 1H NMR
(500 MHz, CDCl3): δ 8.70 (d, J = 8.0 Hz, 1H), 7.86 (t, J = 8.0 Hz, 1H),
7.59À7.51 (m, 2H), 7.29À7.26 (m, 2H), 7.03À7.01 (m, 2H), 6.99À
6.96 (m, 1H), 5.20 (s, 2H), 1.45 (s, 9H). 13C NMR (125 MHz, CDCl3):
δ 157.8, 149.8, 148.9, 134.4, 133.5, 131.0, 130.7, 129.5, 124.4, 123.6,
121.4, 115.4, 72.3, 70.0, 54.7, 30.4. IR (cmÀ1): 1707, 1597, 1497, 1460,
1271, 1215, 1003, 976, 750, 669. HRMS (ESI): calcd for [C20H20INO2 +
H]+ 434.0617, found 434.0620.
Compound 4j was obtained as a yellow solid in 66% yield. 1H NMR
(400 MHz, CDCl3): δ 8.64 (d, J = 7.6 Hz, 1H), 7.86 (d, J = 7.6 Hz, 1H),
7.57À7.47 (m, 2H), 7.34À7.25 (m, 5H), 4.34 (s, 2H), 1.45 (s, 9H). 13C
NMR (100 MHz, CDCl3): δ 149.9, 147.8, 138.7, 134.8, 133.4, 130.9,
130.0, 129.0, 128.5, 126.8, 124.0, 123.4, 77.3, 54.5, 45.6, 30.3. IR (cmÀ1):
1705, 1560, 1460, 1269, 993, 760, 702, 671. HRMS (ESI): calcd for
[C20H20INO + H]+ 418.0668, found 418.0670.
1
mg, 0.152 mmol, 74%). H NMR (500 MHz, CDCl3): δ 8.64 (d, J =
8.0 Hz, 1H), 7.83 (d, J = 7.5 Hz, 1H), 7.54 (t, J = 7.0 Hz, 1H), 7.46 (t, J =
8.0 Hz, 1H), 2.94 (t, J = 7.0 Hz, 2H), 1.71À1.64 (m, 2H), 1.44 (s, 9H),
0.98 (t, J = 7.5 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 150.4, 147.6,
134.9, 133.2, 130.8, 129.7, 123.8, 123.4, 79.5, 54.3, 41.7, 30.2, 22.3, 13.0.
IR (cmÀ1): 1778, 1672, 1397, 1156, 1097, 997, 743. HRMS (ESI): calcd
for [C16H20INO + H]+ 370.0668, found 370.0671.
Compound 4k was obtained as a yellow solid in 62% yield. 1H NMR
(400 MHz, CDCl3): δ 8.64 (d, J = 7.6 Hz, 1H), 7.84 (d, J = 7.6 Hz, 1H),
8492
dx.doi.org/10.1021/jo201347r |J. Org. Chem. 2011, 76, 8488–8494