The Journal of Organic Chemistry
Article
C13H13F3N2 m/z = 254.1025 (found m/z = 254.1032). Mp: 83.4−85
°C.
EtOAc/hexanes) gave compounds 25a and 25b as white solids in 87%
combined yield (282 mg).
For 25a (240 mg, 74%). 1H NMR (400 MHz, CDCl3): δ 7.79 (d, J
= 7.9 Hz, 2H), 7.60 (t, J = 7.2 Hz, 1H), 7.50(t, J = 7.7 Hz, 2H), 7.26−
7.19(m, 5H), 4.09 (d, J = 13.3 Hz, 1H), 3.73−3.62 (m, 2H), 3.47−
3.54 (m, 1H), 3.07 (dd, J = 9.5, 7.4 Hz, 1H), 2.89 (t, J = 9.4 Hz, 1H),
2.52 (dt, J = 13.7, 9.4 Hz, 1H), 2.14−2.08 (m, 1H) ppm. 13C NMR
(100 MHz, CDCl3): δ 138.1, 137.7, 134.2, 129.5, 128.5, 128.4, 128.3,
127.5, 124.7, 63.3 (q, J = 30 Hz), 61.6, 59.2, 52.9, 27.2 ppm. 19F NMR
(376 MHz, CDCl3): δ −76.04 (s) ppm. IR (neat film): 3063 (w),
2877 (w), 1495 (w), 1447 (m), 1310 (m) 1285 (m), 1126 (s) cm−1.
HRMS (ESI+): [M + H]+ calcd for C18H18F3NO2S m/z = 370.1089
(found m/z = 370.1086). Mp: 89.9−90.7 °C.
For 21b (97 mg, 30%). 1H NMR (400 MHz, CDCl3): δ 7.30−7.20
(m, 5H), 4.11 (d, J = 13.7 Hz, 1H), 3.58 (d, J = 13.6 Hz, 1H), 3.39−
3.20 (m, 1H), 3.15 (dd, J = 10.2, 4.1 Hz, 1H), 2.96−2.90 (m, 1H),
2.74 (dd, J = 10.2, 6.4 Hz, 1H), 2.40 (dt, J = 14.2, 9.0 Hz, 1H), 2.25
(dt, J = 14.2, 4.8 Hz, 1H) ppm. 13C NMR (100 MHz, CDCl3): δ
137.2, 128.6, 128.5, 127.7, 126.0 (q, J = 281 Hz), 120.2, 62.5 (q, J = 30
Hz), 58.5, 56.2, 30.66, 26.7 ppm. 19F NMR (376 MHz, CDCl3): δ
−74.69 (s) ppm. IR (neat film): 3035 (w), 2848 (w), 2242 (w), 1722
(w), 1497 (w), 1457 (w), 1280 (s), 1142 (s) cm−1. HRMS (EI): [M]+
calcd for C13H13F3N2 m/z = 254.1025 (found m/z = 254.1030). Mp:
65.5−66.8 °C.
For 25b (42 mg, 13%). 1H NMR (400 MHz, CDCl3): δ 7.95 (d, J =
7.1 Hz, 3H), 7.73 (tt, J = 7.5, 1.5 Hz, 1H), 7.63 (t, J = 7.6 Hz, 2H),
7.38−7.24 (m, 5H), 8.21 (d, J = 13 Hz, 1H), 3.86 (qd, J = 7.0, 2.5 Hz,
1H), 3.78 (d, J = 13 Hz, 1H), 3.68 (dt, J = 8.8, 2.1 Hz, 1H), 3.00 (td, J
= 8.4, 1.7 Hz, 1H), 2.86 (td, J = 10.0, 6.3 Hz, 1H), 2.42 (broad dd, J =
14.2, 6.2 Hz, 1H), 2.22−2.15 (m, 1H) ppm. 13C NMR (100 MHz,
CDCl3): δ 138.3, 137.3, 134.3, 129.5, 128.7, 128.6, 128.4, 127.3, 125.4
(q, J = 281 Hz), 65.1, 64.8 (q, J = 30 Hz), 59.7, 52.6, 26.4 ppm. 19F
NMR (376 MHz, CDCl3): δ −75.88 (s) ppm. IR (neat film): 3063
(w), 3030 (w), 2847 (w), 1586 (w), 1496 (w), 1447 (m), 1310 (m),
1262 (m), 1148 (s) cm−1. HRMS(ESI+): [M + H]+ calcd for
C18H18F3NO2S m/z = 370.1089 (found m/z = 370.1079). Mp: 65.1−
66 °C.
Cycloaddition Using Methyl Vinyl Ketone (26). Methyl vinyl
ketone (55 μL, 0.727 mmol) and compound 3 (320 mg, 1.046 mmol)
were reacted together according to the general procedure. Purification
by flash chromatography (1:25 EtOAc/hexanes to 1:15 EtOAc/
hexanes) gave compounds 27a and 27b as colorless oils in 39%
combined yield (178 mg).
1
For 21c (27 mg, 9%). H NMR (400 MHz, CDCl3): δ 7.45−7.21
(m, 5H), 4.14 (d, J = 13.2 Hz, 1H), 3.67 (d, J = 13.2 Hz, 1H), 3.57
(qd, J = 6.8, 2.6 Hz, 1H), 3.13−3.11 (m, 1H), 3.00 (broad t, J = 7.9
Hz, 1H), 2.71 (td, J = 9.8, 6.3 Hz, 1H), 2.21−2.09 (m, 2H) ppm. 13C
NMR (100 MHz, CDCl3): δ 137.7, 128.5, 128.5, 127.6, 125.1 (q, J =
280 Hz), 120.1, 67.7 (q, J = 30 Hz), 59.6, 52.2, 30.1, 29.5 ppm. 19F
NMR (376 MHz, CDCl3): δ −76.07 (s) ppm. IR (neat film, cm−1):
3030 (w), 2816 (w), 2246 (w), 1497 (w), 1455 (m), 1277 (s), 1124
(s) cm−1. HRMS (ESI+): [M + H]+ calcd for C13H14F3N2 m/z =
255.1104 (found m/z = 255.1099).
Cycloaddition Using Nitroethylene (22). Nitroethylene (97 mg,
1.31 mmol) and compound 3 (400 mg, 1.31 mmol) were reacted
together in toluene (1.2 mL) according to the general procedure.
Purification was attempted by flash chromatography, which resulted in
almost total epimerization of the stereogenic center α to the nitro
moiety (later confirmed by subjection of a pure isomer to treatment
with silica gel). Three of the four possible isomers could be isolated;
however, the initial ratio had to be determined from the crude NMR.
Ratio of compounds 23a/23b/23c from the crude NMR: 70:15:15.
Combined yield after column: 96% (348 mg).
For 27a (160 mg, 35%). 1H NMR (500 MHz, CDCl3): δ 7.38−7.26
(m, 5H), 4.21 (d, J = 13.2 Hz, 1H), 3.63 (d, J = 13.2 Hz, 1H), 3.45
(dqd, J = 10.1, 7.3, 2.9 Hz, 1H), 3.32−3.16 (m, 2H), 2.50 (t, J = 9.3
Hz, 1H), 2.33 (m, 1H), 2.16 (s, 3H), 2.13 (ddd, J = 2.9, 7.9, 13.8 Hz,
1H) ppm. 13C NMR (125 MHz, CDCl3): δ 207.2, 138.3, 128.6, 128.4,
127.3, 126.6 (q, J = 280 Hz), 64.3 (q, J = 29 Hz), 59.6, 55.6, 50.1, 29.6,
28.1 ppm. 19F NMR (376 MHz, CDCl3): δ −76.49 (s) ppm. IR (neat
film): 3032 (w), 2925 (w), 2853 (w), 2810 (w), 1714 (m), 1496 (w),
1455 (m), 1357 (m), 1281 (m), 1167 (s), 1137 (s), 1112 (s) cm−1.
HRMS (ESI+): [M + H]+ calcd for C14H16F3NO m/z = 272.1257
(found m/z = 272.1248).
For 23a. 1H NMR (400 MHz, CDCl3): δ 7.20−7.09 (m, 5H),
4.81−4.87 (m, 1H), 4.00 (d, J = 13.4 Hz, 1H), 3.65−3.56 (m, 2H),
3.30 (dd, J = 11.4, 6.4 Hz, 1H), 3.00 (dd, J = 11.4, 5 Hz, 1H), 2.68
(ddd, J = 14.3, 8.9, 5.3 Hz, 1H), 2.30 (ddd, J = 14.5, 7.5, 5.7 Hz, 1H)
ppm. 13C NMR (100 MHz, CDCl3): δ 137.3, 128.2, 128.9, 127.3,
125.8 (q, J = 279 Hz), 82.7, 63.0 (q, J = 30 Hz), 58.6, 56.6, 31.0 (q, J =
2 Hz) ppm. 19F NMR (376 MHz, CDCl3): δ −75.58 (s) ppm. IR
(neat film): 3032 (w), 2845 (w), 2310 (w), 1551 (s), 1497 (w), 1451
(w), 1375 (m), 1279 (s), 1120 (br, s) cm−1. HRMS (ESI+): [M +
Na]+ calcd for C12H13F3N2O2 m/z = 297.0827 (found m/z =
297.0828).
1
For 27b (18 mg, 5%). H NMR (500 MHz, CDCl3): δ 7.29−7.14
(m, 5H), 4.12 (d, J = 13.2 Hz, 1H), 3.69 (qd, J = 7.6, 2.6 Hz, 1H), 3.59
(d, J = 13.1 Hz, 1H), 3.19 (dt, J = 9.1, 2.5 Hz, 1H), 2.83 (m, 1H), 2.27
(td, J = 10.1, 9.3 Hz, 1H), 2.19 (s, 3H), 2.13(m, 1H), 1.85 (dd, J =
12.7, 7.5 Hz, 1H) ppm. 13C NMR (125 MHz, CDCl3): δ 206.3, 139.0,
128.5, 128.3, 127.1, 126.7 (q, J = 280 Hz), 64.6 (q, J = 29 Hz), 59.8,
52.3, 52.1, 28.4, 28.2 ppm. 19F NMR (376 MHz, CDCl3): δ −75.61 (s)
ppm. IR (neat film): 3032 (w), 2948 (w), 2820 (w), 1717 (m), 1496
(w), 1454 (m), 1360 (m), 1278 (m), 1152 (s), 1118 (s) cm−1. HRMS
(ESI+): [M + H]+ calcd for C14H16F3NO m/z = 272.1257 (found m/z
= 272.1249).
For 23b. 1H NMR (400 MHz, CDCl3): δ 7.31−7.19 (m, 5H),
4.64−4.68 (m, 1H), 4.17 (d, J = 13.8 Hz, 1H), 3.72 (d, J = 11.7 Hz,
1H), 3.54 (d, J = 13.8 Hz, 1H), 3.37−3.29 (m, 1H), 2.96−2.90 (m,
1H), 2.76 (dd, J = 11.7, 5.7 Hz, 1H), 2.56 (ddd, J = 15.7, 9.7, 8.5 Hz,
1H) ppm. 13C NMR (100 MHz, CDCl3): δ 136.8, 128.63, 128.4,
127.65, 125.8 (q, J = 279 Hz), 81.9, 62.0 (q, J = 30 Hz), 58.0, 56.3,
30.6 (q, J = 2 Hz) ppm. 19F NMR (376 MHz, CDCl3): δ −74.43 (s)
ppm. IR (neat film) 3031 (w), 2985 (w), 1547 (s), 1495 (m), 1451
(m), 1378 (m), 1275 (m), 1171 (s), 1147 (s), 1115 (s) cm−1. HRMS
(ESI+): [M + H]+ calcd for C12H13F3N2O2 m/z = 275.1007 (found
m/z = 275.1009). Mp: 65.6−67.3 °C.
Cycloaddition Using Ethyl Acrylate (28). Ethyl acrylate (80 μL,
0.727 mmol) and compound 3 (320 mg, 1.046 mmol) were reacted
together according to the general procedure. Purification by flash
chromatography (1:35 EtOAc/hexanes to 1:25 EtOAc/hexanes) gave
compounds 29a, 29b, 29c, and 29d as colorless oils in 81% combined
yield (178 mg).
For 23c. 1H NMR (400 MHz, CDCl3): δ 7.33−7.25 (m, 5H), 5.02
(dt, J = 7.2, 1.3 Hz, 1H), 4.25 (d, J = 13.1, 1H), 4.08 (q, J = 7.3 Hz,
1H), 3.78 (d, J = 13.1 Hz, 1H), 3.07 (t, J = 8.3 Hz, 1H), 2.73 (ddd, J =
11.3, 9.5, 5.9 Hz, 2H), 2.47 (dd, J = 14.4, 5.8 Hz, 1H), 2.41−2.31 (m,
1H) ppm. 13C NMR (100 MHz, CDCl3): δ 137.9, 128.5, 128.4, 127.5,
124.9 (q, J = 280 Hz), 86.0, 68.1 (q, J = 30.0 Hz), 59.6, 51.5, 31.6 ppm.
19F NMR (376 MHz, CDCl3): δ −75.33 (s) ppm. IR (neat film): 3033
(w), 2843 (w), 1557 (s), 1497 (m), 1455 (m), 1375 (m), 1273 (s),
1165 (s), 1124 (s) cm−1. HRMS (ESI+): [M + H]+ calcd for
C12H13F3N2O2 m/z = no mass found.
For 29a (128 mg, 58%). 1H NMR (400 MHz, CDCl3): δ 7.25−7.17
(m, 5H), 4.12 (d, J = 13.2 Hz, 1H), 4.04 (qd, J = 7.1, 2.2 Hz, 2H), 3.57
(d, J = 13.2 Hz, 1H), 3.36 (dqd, J = 10.3, 7.2, 3.2 Hz 1H), 3.15−2.98
(m, 2H), 2.52 (t, J = 9.3 Hz, 1H), 2.27 (dt, J = 13.7, 10.1 Hz, 1H), 2.14
(ddd, J = 13.5, 7.6, 3.1 Hz, 1H), 1.16 (t, J = 7.1 Hz, 3H) ppm. 13C
NMR (100 MHz, CDCl3): δ 173.0, 138.3, 128.6, 128.4, 127.3, 126.6
(q, J = 281 Hz), 63.2 (q, J = 29 Hz), 60.9, 59.5, 56.1, 42.2, 29.4, 14.2
ppm. 19F NMR (376 MHz, CDCl3): δ −76.45 (s) ppm. IR (neat film):
3036 (w), 2983 (w), 2813 (w), 1732 (s), 1497 (w), 1455 (m), 1372
(m), 1339 (m), 1281 (s), 1173 (s), 1138 (s), 1111 (s), 1030 (m)
Cycloaddition Using Phenyl Vinyl Sulfone (24). Phenyl vinyl
sulfone (148 mg, 0.880 mmol) and compound 3 (430 mg, 1.408
mmol) were reacted together according to the general procedure.
Purification by flash chromatography (1:9 EtOAc/hexanes to 1:5
F
dx.doi.org/10.1021/jo302052m | J. Org. Chem. XXXX, XXX, XXX−XXX