nm): tR (major) = 10.7 min, tR (minor) = 13.5 min, ee = 95%; [a]D25
= +102.4 (c = 1.15 in CHCl3).
(125 MHz, CDCl3): d = 192.83, 169.13, 142.88, 140.83, 134.12,
128.94, 128.53, 127.31, 93.67, 63.01, 40.09, 38.29, 36.86, 27.81,
22.11, 13.93; HRMS (EI) calcd for C18H20O5 316.1311, found
316.1307; HPLC (Chiralpak IA, i-propanol/hexane = 10/90, flow
rate 1.0 mL min-1, l = 254 nm): tR (major) = 9.6 min, tR (minor) =
11.9 min, ee = 95%; [a]2D5 = +113.0 (c = 1.11 in CHCl3).
(2R,4S)-Ethyl 2-hydroxy-4-(4-nitrophenyl)-8-oxo-3,4,5,6,7,8-
hexahydro-2H-chromene-2-carboxylate (3g). (Table 3, entry 7).
84% yield; 1H NMR (500 MHz, CDCl3): d = 8.24 (d, J = 8.7 Hz,
2H), 7.44 (d, J = 8.7 Hz, 2H), 4.50 (br, 1H), 4.37–4.28 (m, 2H),
3.97 (dd, J = 12.4, 6.6 Hz, 1H), 2.61–2.43 (m, 2H), 2.31 (dd, J =
20.1, 7.7 Hz, 1H), 2.24 (dd, J = 13.5, 6.6 Hz, 1H), 2.07–1.87 (m,
4H), 1.33 (t, J = 7.1 Hz, 3H); 13C NMR (125 MHz, CDCl3): d =
192.48, 168.68, 148.57, 147.38, 143.28, 131.47, 129.46, 124.29,
93.40, 63.29, 40.09, 38.25, 36.63, 27.80, 22.11, 13.94; HRMS (EI)
calcd for C18H19O7N 361.1162, found 361.1160; HPLC (Chiralcel
OD-H, i-propanol/hexane = 10/90, flow rate 1.0 mL min-1, l =
254 nm): tR (major) = 17.8 min, tR (minor) = 29.3 min, ee = 93%;
[a]2D5 = +127.2 (c = 1.00 in CHCl3).
(2R,4R)-Ethyl 4-(2-chlorophenyl)-2-hydroxy-8-oxo-3,4,5,6,7,8-
hexahydro-2H-chromene-2-carboxylate (3b). (Table 3, entry 2).
1
92% yield; H NMR (500 MHz, CDCl3): d = 7.39 (dd, J = 11.8,
4.7 Hz, 1H), 7.32–7.17 (m, 3H), 4.54 (br, 1H), 4.38–4.23 (m, 2H),
2.59–2.43 (m, 2H), 2.35–2.03 (m, 4H), 2.00–1.93 (m, 2H), 1.32
(td, J = 7.1, 3.1 Hz, 3H); 13C NMR (125 MHz, CDCl3): d =
192.77, 168.96, 144.26, 138.11, 134.14, 133.59, 131.86, 129.83,
129.72, 128.50, 128.35, 127.49, 126.86, 94.51, 93.66, 63.04, 62.79,
38.41, 38.26, 35.55, 34.09, 34.04, 28.06, 27.59, 22.25, 22.10, 13.96,
13.92; HRMS (EI) calcd for C18H19O5Cl 350.0921, found 350.0916;
HPLC (Chiralpak IA, i-propanol/hexane = 10/90, flow rate
1.0 mL min-1, l = 254 nm): tR (major) = 9.8 min, tR (minor) =
11.9 min, ee = 96%; [a]2D5 = +75.3 (c = 0.98 in CHCl3).
(2R,4S)-Ethyl
2-hydroxy-4-(4-methoxyphenyl)-8-oxo-3,4,5,
6,7,8-hexahydro-2H-chromene-2-carboxylate (3h). (Table 3,
entry 8). 82% yield; 1H NMR (500 MHz, CDCl3): d = 7.15
(d, J = 8.6 Hz, 2H), 6.89 (d, J = 8.6 Hz, 2H), 4.52 (br, 1H),
4.39–4.22 (m, 2H), 3.81 (s, 3H), 3.77 (dd, J = 13.6, 7.6 Hz, 1H),
2.55–2.41 (m, 2H), 2.31 (t, J = 13.1 Hz, 1H), 2.20 (dd, J = 13.6,
6.5 Hz, 1H), 2.12–2.01 (m, 2H), 1.95–1.83 (m, 2H), 1.32 (t, J =
7.3 Hz, 3H); 13C NMR (125 MHz, CDCl3) d = 192.76, 169.16,
158.88, 142.77, 134.53, 132.69, 129.48, 114.39, 93.74, 62.94,
55.28, 39.22, 38.28, 36.90, 27.80, 22.11, 13.91; HRMS (EI) calcd
for C19H22O6 346.1416, found 346.1413; HPLC (Chiralpak IA,
i-propanol/hexane = 10/90, flow rate 1.0 mL min-1, l = 254 nm):
(2R,4S)-Ethyl 4-(3-chlorophenyl)-2-hydroxy-8-oxo-3,4,5,6,7,8-
hexahydro-2H-chromene-2-carboxylate (3c). (Table 3, entry 3).
1
95% yield; H NMR (500 MHz, CDCl3): d = 7.32–7.22 (m, 3H),
7.13 (dt, J = 7.0, 1.5 Hz, 1H), 4.71 (br, 1H), 4.38–4.24 (m, 2H),
3.81 (dd, J = 12.3, 6.7 Hz, 1H), 2.57–2.41 (m, 2H), 2.34–2.26
(m, 1H), 2.23 (dd, J = 13.6, 6.7 Hz, 1H), 2.14–1.99 (m, 2H),
1.94–1.89 (m, 2H), 1.33 (t, J = 7.1 Hz, 3H); 13C NMR (125 MHz,
CDCl3): d = 192.80, 168.93, 142.95, 142.90, 134.75, 132.98, 130.21,
128.59, 127.57, 126.72, 93.57, 63.04, 39.86, 38.18, 36.66, 27.69,
22.05, 13.90; HRMS (EI) calcd for C18H19O5Cl 350.0921, found
350.0918; HPLC (Chiralpak IA, i-propanol/hexane = 10/90, flow
rate 1.0 mL min-1, l = 254 nm): tR (major) = 9.0 min, tR (minor) =
11.4 min, ee = 92%; [a]2D5 = +104.2 (c = 0.96 in CHCl3).
tR (major) = 12.8 min, tR (minor) = 16.9 min, ee = 95%; [a]D25
+142.6 (c = 0.95 in CHCl3).
=
(2R,4S)-Ethyl 2-hydroxy-4-(4-(methylthio)phenyl)-8-oxo-3,4,
5,6,7,8-hexahydro-2H-chromene-2-carboxylate (3i). (Table 3,
entry 9). 82% yield; 1H NMR (500 MHz, CDCl3): d = 7.25 (d, J =
8.2 Hz, 2H), 7.16 (d, J = 8.2 Hz, 2H), 4.50 (br, 1H), 4.39–4.22 (m,
2H), 3.77 (dd, J = 12.5, 6.5 Hz, 1H), 2.56–2.41 (m, 5H), 2.31 (t,
J = 13.0 Hz, 1H), 2.20 (dd, J = 13.6, 6.5 Hz, 1H), 2.13–2.01 (m,
2H), 1.97–1.83 (m, 2H), 1.32 (t, J = 7.0 Hz, 3H); 13C NMR (125
MHz, CDCl3): d = 192.85, 169.07, 142.86, 137.57, 137.51, 133.98,
128.98, 127.07, 93.62, 63.05, 39.53, 38.26, 36.74, 27.79, 22.08,
15.80, 13.92; HRMS (EI) calcd for C19H22O5S 362.1188, found
362.1180; HPLC (Chiralpak IA, i-propanol/hexane = 10/90,
flow rate 1.0 mL min-1, l = 254 nm): tR (major) = 12.6 min, tR
(minor) = 17.2 min, ee = 95%; [a]2D5 = +140.8 (c = 0.97 in CHCl3).
(2R,4S)-Ethyl 4-(4-chlorophenyl)-2-hydroxy-8-oxo-3,4,5,6,7,8-
hexahydro-2H-chromene-2-carboxylate (3d). (Table 3, entry 4).
90% yield; 1H NMR (500 MHz, CDCl3): d = 7.34 (d, J = 8.3 Hz,
2H), 7.18 (d, J = 8.2 Hz, 2H), 4.54 (br, 1H), 4.38–4.21 (m, 2H), 3.80
(dd, J = 12.4, 6.6 Hz, 1H), 2.56–2.41 (m, 2H), 2.29 (t, J = 13.0 Hz,
1H), 2.21 (dd, J = 13.6, 6.6 Hz, 1H), 2.09–1.98 (m, 2H), 1.96–1.85
(m, 2H), 1.32 (t, J = 7.1 Hz, 3H); 13C NMR (125 MHz, CDCl3):
d = 192.70, 168.96, 153.86, 142.97, 139.32, 133.19, 129.85, 129.16,
93.58, 63.08, 39.53, 38.24, 36.77, 27.75, 22.08, 13.92; HRMS (EI)
calcd for C18H19O5Cl 350.0921, found 350.0910; HPLC (Chiralpak
IA, i-propanol/hexane = 10/90, flow rate 1.0 mL min-1, l = 254
(2R,4S)-Ethyl
4-(4-(allyloxy)phenyl)-2-hydroxy-8-oxo-3,4,5,
nm): tR (major) = 11.1 min, tR (minor) = 14.0 min, ee = 96%; [a]D25
+120.9 (c = 1.09 in CHCl3).
=
6,7,8-hexahydro-2H-chromene-2-carboxylate (3j). (Table 3,
1
entry 10). 87% yield; H NMR (500 MHz, CDCl3): d = 7.16–
(2R,4S)-Ethyl 4-(4-fluorophenyl)-2-hydroxy-8-oxo-3,4,5,6,7,8-
hexahydro-2H-chromene-2-carboxylate (3e). (Table 3, entry 5).
91% yield; H NMR (500 MHz, CDCl3): d = 7.20 (dd, J = 8.6,
7.11(m, 2H), 6.93–6.88 (m, 2H), 6.12–5.98 (m, 1H), 5.42 (ddd,
J = 17.3, 3.1, 1.6 Hz, 1H), 5.30 (ddd, J = 10.5, 2.7, 1.3 Hz, 1H),
4.55–4.53 (m, 3H), 4.39–4.22 (m, 2H), 3.76 (dd, J = 12.5, 6.6
Hz, 1H), 2.56–2.41 (m, 2H), 2.36–2.27 (m, 1H), 2.20 (dd, J =
13.6, 6.6 Hz, 1H), 2.13–1.98 (m, 2H), 1.97–1.83 (m, 2H), 1.32
(t, J = 7.1 Hz, 3H); 13C NMR (125 MHz, CDCl3): d = 193.02,
169.19, 157.85, 142.71, 134.73, 133.18, 132.77, 129.48, 117.71,
115.14, 93.71, 68.87, 63.01, 39.20, 38.25, 36.84, 27.80, 22.08,
13.93; HRMS (EI) calcd for C21H24O6 372.1573, found 372.1561;
HPLC (Chiralpak IA, i-propanol/hexane = 10/90, flow rate 1.0
mL min-1, l = 254 nm): tR (major) = 11.7 min, tR (minor) = 15.0
min, ee = 94%; [a]D25 = +144.6 (c = 0.83 in CHCl3).
1
5.3 Hz, 2H), 7.05 (t, J = 8.6 Hz, 2H), 4.50 (br, 1H), 4.36–4.27
(m, 2H), 3.81 (dd, J = 12.5, 6.6 Hz, 1H), 2.54–2.46 (m, 2H),
2.30 (t, J = 13.1 Hz, 1H), 2.21 (dd, J = 13.6, 6.6 Hz, 1H), 2.08–
2.02 (m, 2H), 1.93–1.88 (m, 2H), 1.33 (t, J = 7.1 Hz, 3H); 13C
NMR (125 MHz, CDCl3): d = 192.83, 169.01, 162.96, 161.00,
142.88, 136.45, 136.42, 133.68, 130.03, 129.96, 115.94, 115.78,
93.62, 63.10, 39.34, 38.24, 36.88, 27.77, 22.08, 13.93; HRMS (EI)
calcd for C18H19O5F 334.1217, found 334.1216; HPLC (Chiralpak
IA, i-propanol/hexane = 10/90, flow rate 1.0 mL min-1, l = 254
5300 | Org. Biomol. Chem., 2011, 9, 5297–5302
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