I
E. T. Ledingham et al.
Paper
Synthesis
HRMS (ESI): m/z [M + H]+ calcd for C18H21O5: 317.1384; found:
HRMS (ESI): m/z [M + H]+ calcd for C17H17O7: 333.0969; found:
317.1388.
333.0974.
Ethyl (1S,2S,3S,4S,6R)-4-(4-Methoxyphenyl)-5-oxo-7,9-dioxatri-
tert-Butyl (1S,2S,3S,4S,6R)-4-(1,3-Benzodioxol-5-yl)-5-oxo-7,9-di-
cyclo[4.2.1.02,4]nonane-3-carboxylate (16b)
oxatricyclo[4.2.1.02,4]nonane-3-carboxylate (17c)
Purified via flash column chromatography (EtOAc/PhMe, 1:19) to af-
ford an amber oil (104 mg, 76%); Rf = 0.25 (EtOAc/PhMe, 1:19); [α]D
–141 (c 5.65, CHCl3).
Purified via repeated flash column chromatography (EtOAc/PhMe,
1:19 then EtOAc/hexanes, 3:7) to afford an amber oil (110 mg, 71%);
Rf = 0.25 (EtOAc/PhMe, 1:19); [α]D20 –103 (c 3.1, CHCl3).
20
FT-IR (neat): 2975, 2904, 2846, 1721, 1610, 1581, 1514, 1442, 1368,
FT-IR (neat): 2967, 2921, 2853, 1720, 1504, 1490, 1442, 1367, 1245,
1343, 1293, 1268, 1244, 1223, 1176, 1152, 1111, 1032 cm–1
.
1221, 1151, 1116, 1035, 800 cm–1
.
1H NMR (500 MHz, CDCl3, 25 °C): δ = 7.17–7.16 (m, 2 H), 6.84–6.82
(m, 2 H), 5.12 (s, 1 H), 5.01 (br s, 1 H), 4.28 (d, J = 7.2 Hz, 1 H), 4.00 (dd,
J = 7.2, 4.4 Hz, 1 H), 3.97–3.89 (m, 2 H), 3.77 (s, 3 H), 2.80 (d, J = 4.8 Hz,
1 H), 2.57 (br dd, J = 4.8, 1.8 Hz, 1 H), 1.06 (t, J = 7.1 Hz, 3 H).
1H NMR (500 MHz, CDCl3, 25 °C): δ = 6.76–6.72 (m, 3 H), 5.93–5.92
(m, 2 H), 5.10 (s, 1 H), 4.99 (br dd, J = 4.4, 1.6 Hz, 1 H), 4.24 (d, J = 7.1
Hz, 1 H), 3.98 (dd, J = 7.1, 4.4 Hz, 1 H), 2.69 (d, J = 4.9 Hz, 1 H), 2.46
(dd, J = 4.9, 1.6 Hz, 1 H), 1.28 (s, 9 H).
13C NMR (125 MHz, CDCl3, 25 °C): δ = 192.6, 167.6, 159.4, 131.2,
124.5, 113.7, 99.9, 71.2, 68.9, 61.3, 55.2, 40.0, 28.5, 25.3, 14.0.
MS (EI): m/z (%) = 318.1 (24) [M]+, 231.1 (100), 203 (88), 199 (23),
187.1 (20), 172.1 (21), 171.1 (64), 135 (28), 128 (26), 115 (24).
13C NMR (125 MHz, CDCl3, 25 °C): δ = 192.5, 166.5, 147.4, 147.3,
126.1, 123.7, 111.0, 107.9, 101.1, 99.9, 81.9, 71.2, 68.9, 40.3, 29.5,
27.8, 25.4.
MS (EI): m/z (%) = 304 (42) [M – C(CH3)3]+, 230 (94), 217 (100), 186
(27), 185 (66), 115.1 (30), 57.1 (68), 56.1 (39), 41.1 (79), 39 (33).
HRMS (ESI): m/z [M – H]– calcd for C19H19O7: 359.1136; found:
HRMS (ESI): m/z [M + H]+ calcd for C17H19O6: 319.1176; found:
319.1192.
359.1123.
tert-Butyl (1S,2S,3S,4S,6R)-4-(4-Methoxyphenyl)-5-oxo-7,9-dioxa-
tricyclo[4.2.1.02,4]nonane-3-carboxylate (17b)
tert-Butyl (1S,2S,3S,4S,6R)-4-(2-Fluorophenyl)-5-oxo-7,9-dioxatri-
cyclo[4.2.1.02,4]nonane-3-carboxylate (17d)
Purified via repeated flash column chromatography (EtOAc/PhMe,
1:19 then EtOAc/hexanes, 3:7) and recrystallized (i-Pr2O) to give co-
lourless crystals (125 mg, 84%); Rf = 0.58 (EtOAc/hexanes, 3:7); mp
148–149 °C; [α]D20 –148 (c 0.66, CHCl3).
Purified via flash column chromatography (EtOAc/hexanes, 1:4) then
recrystallized (EtOH) to afford colourless crystals (122 mg, 85%); Rf =
23
0.61 (EtOAc/hexanes, 1:9); mp 145–148 °C; [α]D –137 (c 0.93, CH-
Cl3).
FT-IR (neat): 2959, 1722, 1703, 1609, 1513, 1475, 1458, 1393, 1368,
1333, 1300, 1260, 1240, 1179, 1157, 1109, 1064, 1022, 976 cm–1
.
FT-IR (neat): 2976, 2905, 1719, 1494, 1453, 1368, 1278, 1245, 1221,
1144, 1117, 755 cm–1
.
1H NMR (500 MHz, CDCl3, 25 °C): δ = 7.20–7.19 (m, 2 H), 6.84–6.83
(m, 2 H), 5.11 (s, 1 H), 5.00 (dd, J = 4.4, 1.7 Hz, 1 H), 4.26 (d, J = 7.1 Hz,
1 H), 3.99 (dd, J = 7.1, 4.4 Hz, 1 H), 3.77 (s, 3 H), 2.71 (d, J = 4.9 Hz, 1 H),
2.50 (dd, J = 4.9, 1.7 Hz, 1 H), 1.23 (s, 9 H).
13C NMR (125 MHz, CDCl3, 25 °C): δ = 192.8, 166.6, 159.3, 131.4,
124.5, 113.6, 99.9, 81.7, 71.3, 68.9, 55.2, 40.0, 29.5, 27.8, 25.1.
1H NMR (500 MHz, CDCl3, 25 °C): δ = 7.30–7.22 (m, 2 H), 7.11–7.08
(m, 1 H), 7.05–7.01 (m, 1 H), 5.13 (s, 1 H), 5.01 (br d, J = 4.3 Hz, 1 H),
4.39 (br d, J = 6.7 Hz, 1 H), 3.97 (dd, J = 6.7, 4.3 Hz, 1 H), 2.84 (br d, J =
4.9 Hz, 1 H), 2.52 (br d, J = 4.3 Hz, 1 H), 1.27 (s, 9 H).
13C NMR (125 MHz, CDCl3, 25 °C): δ = 191.7, 166.9, 162.8, 160.8,
132.9, 129.9 (d, J = 8.5 Hz), 123.8 (d, J = 3.5 Hz), 120.2 (d, J = 13.8 Hz),
115.5 (d, J = 21.8 Hz), 99.7, 81.9, 71.2, 68.3, 28.9, 27.7, 26.0.
MS (EI): m/z (%) = 290.1 (22), 216.1 (14), 204.1 (14), 203 (100), 172.1
(14), 171 (22), 135 (14), 57.1 (27), 56.1 (16), 41.1 (31).
MS (EI): m/z (%) = 250.1 (11), 204.1 (7), 192.1 (12), 191.1 (100), 160.1
(7), 159.1 (11), 146.1 (6), 133.1 (10), 57.1 (27), 41.1 (9).
HRMS (ESI): m/z [M – H]– calcd for C18H18O5F: 333.1144; found:
HRMS (ESI): m/z [M – H]– calcd for C19H21O6: 345.1344; found:
345.1326.
333.1136.
Ethyl (1S,2S,3S,4S,6R)-4-(1,3-Benzodioxol-5-yl)-5-oxo-7,9-dioxatri-
cyclo[4.2.1.02,4]nonane-3-carboxylate (16c)
tert-Butyl (1S,2S,3S,4S,6R)-5-Oxo-4-(2,3,4-trifluorophenyl)-7,9-di-
Purified via flash column chromatography (EtOAc/PhMe, 3:7) to
afford a yellow oil (92 mg, 64%); Rf = 0.25 (EtOAc/PhMe, 3:7); [α]D
oxatricyclo[4.2.1.02,4]nonane-3-carboxylate (17e)
20
–107 (c 1.6, CHCl3).
Purified via repeated flash column chromatography (EtOAc/PhMe,
1:19 then EtOAc/hexanes, 1:9) to afford a yellow oil (141 mg, 89%);
Rf = 0.68 (EtOAc/hexanes, 3:7); [α]D20 –111 (c 3.2, CHCl3).
FT-IR (neat): 2976, 2916, 2853, 1776, 1720, 1490, 1442, 1373, 1332,
1242, 121, 1181, 1116, 1034 cm–1
.
FT-IR (neat): 2978, 2916, 1719, 1613, 1513, 1482, 1394, 1368, 1277,
1H NMR (500 MHz, CDCl3, 25 °C): δ = 6.75–6.69 (m, 3 H), 5.93 (s, 2 H),
5.12 (s, 1 H), 4.99 (dd, J = 4.4, 1.7 Hz, 1 H), 4.26 (d, J = 7.1 Hz, 1 H),
4.03–3.93 (m, 3 H), 2.78 (d, J = 4.9 Hz, 1 H), 2.54 (dd, J = 4.9, 1.7 Hz, 1
H), 1.11 (t, J = 7.1 Hz, 3 H).
13C NMR (125 MHz, CDCl3, 25 °C): δ = 192.3, 167.6, 147.5, 147.4,
126.0, 123.6, 110.6, 108.1, 101.2, 99.9, 71.2, 68.9, 61.4, 40.4, 28.5,
25.6, 14.0.
1245, 1205, 1157, 1141, 1117, 1085, 1040, 1005, 731 cm–1
.
1H NMR (500 MHz, CDCl3, 25 °C): δ = 6.96–6.89 (m, 2 H), 5.13 (s, 1 H),
5.01 (br dd, J = 4.5, 1.6 Hz, 1 H), 4.33 (d, J = 7.1 Hz, 1 H), 3.98 (dd, J =
7.1, 4.5 Hz, 1 H), 2.84 (br dd, J = 4.6, 1.6 Hz, 1 H), 2.49 (br d, J = 4.6 Hz,
1 H), 1.32 (s, 9 H).
13C NMR (125 MHz, CDCl3, 25 °C): δ = 190.9, 166.7, 152.0 (ddd, JCF
=
249.8, 9.8, 9.8 Hz), 150.9 (ddd, JCF = 249.5, 9.7, 9.7 Hz),, 139.9 (ddd,
JCF = 250.3, 15.4, 15.4 Hz), 126.1, 118.1 (d, JCF = 12.2 Hz), 111.7 (dd,
JCF = 17.5, 3.7 Hz), 99.6, 82.4, 71.0, 68.3, 35.4, 28.7, 27.7, 26.0.
MS (EI): m/z (%) = 332.1 (82) [M]+, 258.1 (31), 245.1 (66), 217 (100),
213 (34), 199 (33), 186.1 (34), 185.1 (82), 149 (29), 115.1 (39).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–K