F
P. Rajasekaran et al.
Letter
Synlett
was purified by column chromatography (silica gel, EtOAc–
hexane) to afford the Prins/Friedel–Crafts cyclized product 9
as the sole product.
115.32, 115.11, 81.56, 80.14, 73.65, 73.53, 73.34, 70.10, 68.31,
67.35, 45.19, 40.34. HRMS: m/z [M
34H37FNO4: 542.2707; found: 542.2706.
+
NH4]+ calcd for
C
(1S,2R,4R,4aS,10bR)-1,4-Bis[(benzyloxy)methyl]-2-(4-tolyl)-
1,2,4,4a,6,10b-hexahydropyrano[3,4-c]isochromene (9a)
Viscous liquid; yield: 83 mg (69%); Rf = 0.5 (hexane–EtOAc, 9:1);
[α]D25 +10.5 (c 0.62, CH2Cl2). IR (neat): 2922, 1453, 1063, 814,
(1S,2R,4R,4aS,10bR)-1,4-Bis[(benzyloxy)methyl]-2-(4-chloro-
phenyl)-1,2,4,4a,6,10b-hexahydropyrano[3,4-c]isochromene
(9e)
Viscous liquid; yield: 75 mg (58%); Rf = 0.5 (hexane–EtOAc, 9:1);
697 cm–1 1H NMR (400 MHz, CDCl3): δ = 7.45–7.02 (m, 18 H),
.
[α]D25 +9.4 (c 0.46, CH2Cl2). IR (neat): 2922, 1453, 1493, 1361,
4.86 (dd, J = 33.0, 14.0 Hz, 2 H), 4.69 (d, J = 10.2 Hz, 1 H), 4.58 (q,
J = 12.4 Hz, 2 H), 4.38–4.29 (m, 2 H), 3.85–3.70 (m, 4 H), 3.45–
3.32 (m, 2 H), 3.21 (t, J = 10.7 Hz, 1 H), 2.36 (s, 3 H), 2.28–2.21
(m, 1 H). 13C NMR (100 MHz, CDCl3): δ = 138.87, 138.25, 138.18,
137.85, 137.66, 136.20, 129.11, 128.40, 128.34, 127.82, 127.78,
127.75, 127.70, 127.44, 127.05, 126.29, 125.38, 124.73, 82.18,
80.16, 73.79, 73.57, 73.29, 70.18, 68.61, 67.39, 45.10, 40.38,
21.37. HRMS: m/z [M + NH4]+ calcd for C35H40NO4: 538.2957;
found: 538.2958.
1029, 735, 697 cm–1 1H NMR (500 MHz, CDCl3): δ = 7.47–7.01
.
(m, 18 H), 4.85 (dd, J = 34.4, 14.0 Hz, 2 H), 4.68 (d, J = 10.1 Hz, 1
H), 4.63–4.52 (m, 2 H), 4.38–4.28 (m, 2 H), 3.86–3.74 (m, 3 H),
3.70 (dd, J = 10.7, 5.4 Hz, 1 H), 3.41–3.30 (m, 2 H), 3.19 (t,
J = 10.6 Hz, 1 H), 2.19 (t, J = 10.6 Hz, 1 H). 13C NMR (100 MHz,
CDCl3): δ = 139.33, 138.74, 137.98, 137.90, 136.15, 133.69,
129.26, 128.57, 128.49, 128.37, 127.90, 127.72, 127.51, 127.12,
126.42, 125.46, 124.57, 81.59, 80.15, 73.62, 73.55, 73.35, 70.09,
68.29, 67.35, 45.12, 40.33. HRMS: m/z [M + H]+ calcd for C34H34
ClO4: 541.2146; found: 541.2147
-
(1S,2R,4R,4aS,10bR)-1,4-Bis[(benzyloxy)methyl]-2-phenyl-
1,2,4,4a,6,10b-hexahydropyrano[3,4-c]isochromene (9b)
Viscous liquid; yield: 74 mg (61%); Rf = 0.5 (hexane–EtOAc, 9:1);
[α]D25 +52.8 (c 0.14, CH2Cl2). IR (neat): 2923, 1453, 1064, 738,
(1S,2R,4R,4aS,10bR)-1,4-Bis[(Benzyloxy)methyl]-2-(4-bro-
mophenyl)-1,2,4,4a,6,10b-hexahydropyrano[3,4-c]iso-
chromene (9f)
698 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 7.58–6.92 (m, 19 H),
Viscous liquid; yield: 85 mg (61%); Rf = 0.5 (hexane–EtOAc, 9:1);
4.86 (dd, J = 40.6, 14.0 Hz, 2 H), 4.73 (d, J = 10.2 Hz, 1 H), 4.59 (q,
J = 12.4 Hz, 2 H), 4.33 (s, 2 H), 3.86–3.70 (m, 4 H), 3.46–3.36 (m,
1 H), 3.33 (dd, J = 9.9, 1.9 Hz, 1 H), 3.23 (t, J = 10.6 Hz, 1 H), 2.33–
2.19 (m, 1 H). 13C NMR (125 MHz, CDCl3): δ = 140.79, 138.82,
138.18, 138.10, 136.19, 128.43, 128.35, 128.04, 127.91, 127.82,
127.74, 127.46, 127.07, 126.32, 125.41, 124.69, 116.68, 82.29,
80.13, 73.74, 73.54, 73.30, 70.12, 68.43, 67.37, 45.12, 40.32.
HRMS: m/z [M + NH4]+calcd for C34H38NO4: 524.2801; found:
524.2809.
[α]D25 +50.6 (c 0.32, CH2Cl2). IR (neat): 2923, 1486, 1071, 745,
697 cm–1 1H NMR (400 MHz, CDCl3): δ = 7.55–6.98 (m, 18 H),
.
4.85 (dd, J = 34.7, 14.0 Hz, 2 H), 4.67 (d, J = 10.2 Hz, 1 H), 4.62–
4.53 (m, 2 H), 4.39–4.27 (m, 2 H), 3.87–3.65 (m, 4 H), 3.42–3.28
(m, 2 H), 3.19 (t, J = 10.7 Hz, 1 H), 2.19 (t, J = 10.7 Hz, 1 H). 13C
NMR (125 MHz, CDCl3): δ = 139.85, 138.74, 137.97, 137.89,
136.14, 131.52, 129.62, 128.50, 128.37, 127.90, 127.72, 127.51,
127.13, 126.42, 125.46, 124.56, 121.88, 81.65, 80.16, 73.61,
73.56, 73.36, 70.10, 68.30, 67.35, 45.08, 40.34. HRMS: m/z [M +
H]+ calcd for C34H37BrNO4: 602.1906; found: 602.1906.
(1S,2R,4R,4aS,10bR)-1,4-Bis[(benzyloxy)methyl]-2-(2-naph-
thyl)-1,2,4,4a,6,10b-hexahydropyrano[3,4-c]isochromene
(9g)
(1S,2R,4R,4aS,10bR)-1,4-Bis[(benzyloxy)methyl]-2-(4-nitro-
phenyl)-1,2,4,4a,6,10b-hexahydropyrano[3,4-c]isochromene
(9c)
Viscous liquid; yield: 85.6 mg (65%); Rf = 0.4 (hexane–EtOAc,
8:2); [α]D25 +59.1 (c 0.12, CH2Cl2). IR (neat): 2922, 1605, 1520,
Viscous liquid; yield: 69 mg (52%); Rf = 0.5 (hexane–EtOAc, 9:1);
1347, 1072, 697 cm–1 1H NMR (500 MHz, CDCl3): δ = 8.13 (d,
.
[α]D25 +49.3 (c 0.32, CH2Cl2). IR (neat): 3028, 2861, 1495, 1453,
J = 8.6 Hz, 2 H), 7.48 (d, J = 8.6 Hz, 2 H), 7.37–7.11 (m, 14 H),
4.96–4.77 (m, 3 H), 4.63–4.54 (m, 2 H), 4.35 (dd, J = 40.1, 11.9
Hz, 2 H), 3.88–3.77 (m, 3 H), 3.69 (dd, J = 10.9, 5.7 Hz, 1 H), 3.36
(t, J = 9.8 Hz, 1 H), 3.31 (dd, J = 10.0, 1.8 Hz, 1 H), 3.20 (t, J = 10.6
Hz, 1 H), 2.21 (t, J = 10.6 Hz, 1 H). 13C NMR (125 MHz, CDCl3):
δ = 148.10, 147.67, 138.58, 137.68, 137.57, 136.11, 128.67,
128.55, 128.40, 128.06, 127.80, 127.71, 127.60, 127.21, 126.57,
125.58, 124.32, 123.57, 81.17, 80.15, 73.59, 73.43, 70.05, 67.86,
1064, 744, 697 cm–1 1H NMR (500 MHz, CDCl3): δ = 7.86–7.77
.
(m, 4 H), 7.56–7.44 (m, 3 H), 7.34–7.10 (m, 14 H), 4.89 (dt,
J = 38.7, 14.1 Hz, 3 H), 4.60 (q, J = 12.5 Hz, 2 H), 4.31 (s, 2 H),
3.90–3.79 (m, 3 H), 3.76 (dd, J = 11.2, 5.6 Hz, 1 H), 3.46 (t, J = 9.8
Hz, 1 H), 3.38–3.33 (m, 1 H), 3.27 (t, J = 10.6 Hz, 1 H), 2.38 (t,
J = 10.6 Hz, 1 H). 13C NMR (125 MHz, CDCl3): δ = 138.80, 138.16,
138.05, 136.19, 133.42, 133.36, 128.40, 128.36, 128.26, 128.22,
127.78, 127.74, 127.46, 127.22, 127.10, 126.36, 126.10, 126.03,
125.68, 125.43, 124.72, 82.49, 80.22, 73.77, 73.55, 73.34, 70.12,
68.57, 67.41, 44.98, 40.41. HRMS: m/z [M + NH4]+ calcd for
67.30, 45.11, 40.25. HRMS: m/z [M
34H37N2O6: 569.2652; found: 569.2652.
+
NH4]+ calcd for
C
(1S,2R,4R,4aS,10bR)-1,4-Bis[(benzyloxy)methyl]-2-(4-fluoro-
phenyl)-1,2,4,4a,6,10b-hexahydropyrano[3,4-c]isochromene
(9d)
C38H40NO4: 574.2957; found: 574.2954.
(1S,2S,4R,4aS,10bR)-1,4-Bis[(benzyloxy)methyl]-2-methyl-
1,2,4,4a,6,10b-hexahydropyrano[3,4-c]isochromene (9h)
Viscous liquid; yield: 80 mg (78%); Rf = 0.6 (hexane–EtOAc, 9:1).
1H NMR (500 MHz, CDCl3): δ = 7.42–6.97 (m, 14 H), 4.80 (dd,
J = 52.1, 14.0 Hz, 2 H), 4.60 (s, 2 H), 4.51 (dd, J = 36.6, 12.0 Hz, 2
H), 3.82 (dd, J = 9.4, 5.1 Hz, 1 H), 3.76 (d, J = 9.9 Hz, 1 H), 3.71–
3.63 (m, 1 H), 3.63–3.56 (m, 3 H), 3.15 (t, J = 10.9 Hz, 1 H), 2.74
(t, J = 10.7 Hz, 1 H), 2.03–1.94 (m, 1 H), 1.39 (d, J = 6.2 Hz, 3 H).
13C NMR (125 MHz, CDCl3): δ = 142.25, 138.74, 138.39, 138.14,
135.95, 128.54, 128.39, 127.91, 127.89, 127.85, 127.54, 127.13,
126.35, 125.25, 124.07, 79.59, 73.61, 73.54, 73.21, 70.66, 70.29,
Viscous liquid; yield: 78 mg (62%); Rf = 0.5 (hexane–EtOAc, 9:1);
[α]D25 +16.7 (c 0.32, CH2Cl2). IR (neat): 2924, 2868, 1129, 1101,
853 cm–1 1H NMR (500 MHz, CDCl3): δ = 7.44–6.74 (m, 18 H),
.
4.86 (dd, J = 34.3, 14.0 Hz, 2 H), 4.70 (d, J = 10.2 Hz, 1 H), 4.63–
4.54 (m, 2 H), 4.33 (q, J = 12.0 Hz, 2 H), 3.88–3.67 (m, 4 H), 3.42–
3.30 (m, 2 H), 3.20 (t, J = 10.6 Hz, 1 H), 2.21 (t, J = 10.7 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 163.78, 161.31, 138.75, 138.04,
137.94, 136.62, 136.16, 129.54, 129.46, 128.46, 128.35, 128.00,
127.88, 127.83, 127.71, 127.49, 127.10, 126.38, 125.44, 124.60,
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–G