Total Synthesis of (()-Paulownin
a 33:1 mixture (1H NMR) after flash chromatography (2:1 hexanes/
ethyl acetate). The characterization of 19b was not possible due to
the small amount isolated. Diastereomer 19a was partially separated
by HPLC (2:1 hexanes/ethyl acetate) for analytical purposes, 19a
tR ) 22 min. Major diastereomer 19a (2R*,3R*,4S*,5R*): colorless
oil; 1H NMR (400 MHz, CDCl3) δ 7.48-7.29 (m, 5H), 6.99 (d, J
) 1.6 Hz, 1H), 6.91 (dd, J ) 7.8, 1.4 Hz, 1H), 6.82 (d, J ) 7.6
Hz, 1H), 5.98 (s, 2H), 4.93 (d, J ) 2.4 Hz, 1H), 4.63 (d, J ) 10.0
Hz, 1H), 4.21 (dd, J ) 6.0, 2.4 Hz, 1H), 2.16 (br. s, 1H), 2.12 (m,
1H), 1.00 (d, J ) 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ
147.8, 147.3, 141.0, 134.0, 128.4, 127.5, 125.8, 120.6, 108.1, 107.0,
101.0, 88.0, 86.0, 81.1, 45.7, 9.0; IR (CH2Cl2) 3425, 3060, 2966,
2895, 1503, 1444, 1250 cm-1; MS (DEI) m/z 298 (M+, 37), 192
(54), 135 (100), 91 (39), 77 (15); HRMS (EI) m/z 298.1210
(298.1205 calcd for C18H18O4, M+).
(s, 1H), 6.78 (s, 2H), 5.95 (s, 2H), 4.47 (d, J ) 10.3 Hz, 1H), 4.38
(br. s, 1H), 4.31 (dd, J ) 9.8, 4.1 Hz, 1H), 3.92 (d, J ) 10.2 Hz,
1H), 1.97 (m, 1H), 1.73 (br. s, 1H), 1.03 (d, J ) 6.6 Hz, 3H); 13
C
NMR (75 MHz, CDCl3) δ 147.7, 147.1, 135.1, 119.9, 108.0, 106.5,
100.9, 85.1, 75.9, 74.9, 47.8, 9.2; IR (neat) 3406, 2960, 2927, 1613,
1514, 1460, 1246 cm-1; MS (40 eV) m/z 222 (M+, 45), 151 (100),
135 (38), 123 (27), 93 (47), 77 (20); HRMS (EI) m/z 222.0893
(222.0892 calcd for C12H14O4, M+). Diastereomer 21c
1
(2R*,3R*,4S*): colorless oil; H NMR (300 MHz, CDCl3) δ 6.77
(m, 3H), 5.95 (s, 2H), 5.22 (d, J ) 5.1 Hz, 1H), 4.32 (dd, J )
10.3, 4.6 Hz, 1H), 4.24 (br. s, 1H), 3.82 (dd, J ) 9.8, 1.5 Hz, 1H),
2.30 (m, 1H), 1.82 (br. s, 1H), 0.59 (d, J ) 7.2 Hz, 3H); 13C NMR
(75 MHz, CDCl3) δ 147.4, 146.3, 133.4, 119.0, 107.9, 106.7, 100.8,
81.7, 78.7, 74.3, 47.0, 12.8; IR (neat) 3405, 2959, 2926, 1613, 1514,
1246 cm-1; MS (40 eV) m/z 222 (M+, 53), 151 (100), 135 (32),
123 (27), 93 (59), 77 (14); HRMS (EI) m/z 222.0893 (222.0892
calcd for C12H14O4, M+).
(2S*,3R*,4S*)-, (2S*,3R*,4R*)-, and (2R*,3R*,4S*)-2-(4-
Methoxyphenyl)-3-methyltetrahydrofuran-4-ol (20a, 20b, and
20c). Following the general procedure, aldehyde 11 (0.035 g, 0.20
mmol) gave tetrahydrofurans 20a, 20b, and 20c (0.033 g, 79%) as
an 8:5:1 mixture of three diastereomers (1H NMR) after flash
chromatography (2:1 hexanes/ethyl acetate). Analytical samples of
each diastereomer were obtained by using HPLC (1:2 hexanes/
ethyl acetate), 20a tR ) 24 min, 20b tR ) 26 min, 20c tR ) 22
min. Major diastereomer 20a (2S*,3R*,4S*): colorless oil; 1H NMR
(300 MHz, CDCl3) δ 7.31 (d, J ) 8.7 Hz, 2H), 6.89 (d, J ) 8.7
Hz, 2H), 4.31 (d, J ) 8.2 Hz, 1H), 4.11 (m, 1H), 4.04 (dd, J )
9.6, 5.7 Hz, 1H), 3.93 (dd, J ) 9.2, 4.1 Hz, 1H), 3.81 (s, 3H), 2.04
(m, 1H), 1.95 (d, J ) 4.7 Hz, 1H), 1.10 (d, J ) 6.7 Hz, 3H); 13C
NMR (75 MHz, CDCl3) δ 159.2, 133.0, 127.4, 113.8, 87.4, 79.2,
74.1, 55.3, 51.1, 15.0; IR (CH2Cl2) 3431, 3054, 2963, 1612, 1514,
1462, 1265 cm-1; MS (40 eV) m/z 208 (M+, 20), 137 (100), 121
(27), 109 (29); HRMS (EI) m/z 208.1106 (208.1099 calcd for
C12H16O3, M+). Diastereomer 20b (2S*,3R*,4R*): colorless oil; 1H
NMR (300 MHz, CDCl3) δ 7.26 (d, J ) 8.2 Hz, 2H), 6.89 (d, J )
8.2 Hz, 2H), 4.51 (d, J ) 10.3 Hz, 1H), 4.40 (apparent t, J ) 4.1
Hz, 1H), 4.32 (dd, J ) 10.3, 4.1 Hz, 1H), 3.92 (d, J ) 10.3 Hz,
1H), 3.81 (s, 3H), 2.01 (m, 1H), 1.73 (br. s, 1H), 1.03 (d, J ) 6.6
Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 159.2, 133.1, 127.5, 113.8,
84.9, 75.8, 75.0, 55.3, 47.7, 9.2; IR (CH2Cl2) 3417, 2960, 1612,
1586, 1458, 1248 cm-1; MS (40 eV) m/z 208 (M+, 21), 137 (100),
121 (31), 109 (29), 77 (23); HRMS (EI) m/z 208.1096 (208.1099
calcd for C12H16O3, M+). Diastereomer 20c (2R*,3R*,4S*): colorless
oil; 1H NMR (300 MHz, CDCl3) δ 7.21 (d, J ) 8.7 Hz, 2H), 6.88
(d, J ) 8.7 Hz, 2H), 5.25 (d, J ) 5.6 Hz, 1H), 4.34 (dd, J ) 9.8,
4.7 Hz, 1H), 4.25 (br. s, 1H), 3.82 (m, 1H), 3.81 (s, 3H), 2.31 (m,
1H), 1.89 (br. s, 1H), 0.58 (d, J ) 7.2 Hz, 3H); 13C NMR (75
MHz, CDCl3) δ 158.5, 131.4, 127.0, 113.4, 81.6, 78.8, 74.3, 55.3,
46.9, 12.9; IR (CH2Cl2) 3405, 2965, 2934, 1514, 1247 cm-1; MS
(40 eV) m/z 208 (M+, 26), 137 (100), 121 (24), 109 (24), 77 (16);
HRMS (EI) m/z 208.1098 (208.1099 calcd for C12H16O3, M+).
(2S*,3R*,4S*)-, (2S*,3R*,4R*)-, and (2R*,3R*,4S*)-2-(3,4-
Methylendioxyphenyl)-3-methyltetrahydrofuran-4-ol (21a, 21b,
and 21c). Following the general procedure, aldehyde 11 (0.047 g,
0.27 mmol) gave tetrahydrofurans 21a, 21b, and 21c (0.038 g, 64%)
as a 6.5:5:1 mixture of three diastereomers (1H NMR) after flash
chromatography (2:1 hexanes/ethyl acetate). Analytical samples of
each diastereomer were obtained by HPLC (1:2 hexanes/ethyl
acetate), 21a tR ) 21 min, 21b tR ) 24 min, 21c tR ) 20 min.
Major diastereomer 21a (2S*,3R*,4S*): colorless oil; 1H NMR (400
MHz, CDCl3) δ 6.92 (d, J ) 1.6 Hz, 1H), 6.82 (dd, J ) 7.8, 1.4
Hz, 1H), 6.77 (dd, J ) 8.0 Hz, 1H), 5.95 (s, 2H), 4.27 (d, J ) 8.0
Hz, 1H), 4.10 (m, 1H), 4.03 (dd, J ) 9.6, 5.6 Hz, 1H), 3.92 (dd, J
) 9.8, 4.2 Hz, 1H), 2.01 (m, 1H), 1.89 (br s, 1H), 1.11 (d, J ) 7.2
Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 147.7, 147.1, 135.0, 119.6,
107.9, 106.6, 100.9, 87.5, 79.0, 74.1, 51.1, 15.0; IR (neat) 3403,
2948, 2925, 1514, 1245 cm-1; MS (40 eV) m/z 222 (M+, 57), 151
(100), 135 (30), 123 (31), 93 (62), 77 (22); HRMS (EI) m/z
222.0892 (222.0892 calcd for C12H14O4, M+). Diastereomer 21b
(2S*,3S*,4R*,5S*)-, (2S*,3S*,4S*,5S*)-, (2R*,3S*,4R*,5S*)-
3,5-Dimethyl-2-(4-methoxyphenyl)tetrahydrofuran-4-ol (23a, 23b,
and 23c). Following the general procedure, aldehyde 22 (0.041 g,
0.22 mmol) gave a 17.1:9:1 mixture (1H NMR) of tetrahyrdofurans
23a, 23b, and 23c (0.027 g, 56%) which was not separable by flash
chromatography (2:1 hexanes/ethyl acetate). An analytical sample
of 23a was obtained by HPLC (1:1 hexanes/ethyl acetate). A 3.3:1
mixture (1H NMR) of 23b/23c, white solid, was used for analytical
purposes (23a, tR ) 25 min, a 3.3:1 mixture of 23b and 23c, tR )
22 min). Major diastereomer 23a (2S*,3S*,4R*,5S*): white solid;
1
mp ) 93-94 °C; [R]D –0.45 (c 0.0088, CH2Cl2); H NMR (300
MHz, CDCl3) δ 7.27 (m, 2H), 6.90 (m, 2H), 4.50 (d, J ) 10.2 Hz,
1H), 4.07 (dq, J ) 2.1, 6.3 Hz, 1H), 3.94 (dd, J ) 6.3, 2.1 Hz,
1H), 3.81 (s, 3H), 2.04 (m, 1H), 1.81 (br. s, 1H), 1.37 (d, J ) 6.3
Hz, 3H), 0.97 (d, J ) 7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ
159.1, 132.9, 127.6, 113.7, 85.7, 82.5, 80.0, 55.3, 45.9, 20.4, 9.1;
IR (CH2Cl2) 3398, 3005, 2959, 1612, 1513, 1460, 1244 cm-1; MS
(DEI) m/z 222 (M+, 55), 137 (100), 121 (73), 109 (14), 77 (13);
HRMS (EI) m/z 222.1258 (222.1256 calcd for C13H18O3, M+).
Diastereomer 23b (2S*,3S*,4S*,5S*) 3.3:1 mixture of 23b/23c: 1H
NMR (300 MHz, CDCl3) δ 7.31 (m, 2H), 6.88 (m, 2H), 4.24 (d, J
) 7.8 Hz, 1H), 4.07 (m, 1H), 3.88 (apparent t, J ) 4.7 Hz, 1H),
3.80 (s, overlaps with diastereomer, 3H), 2.05 (m, 1H), 1.81 (br. s,
overlaps with diastereomer, 1H), 1.35 (d, J ) 6.6 Hz, 3H), 1.12
(d, J ) 6.9 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 159.2, 133.3,
127.6, 113.8, 86.2, 80.5, 76.9, 55.3, 51.1, 15.6, 14.6. Diastereomer
1
23c (2R*,3S*,4R*,5S*) 3.3:1 mixture of 23b/23c: H NMR (300
MHz, CDCl3) δ 7.17 (m, 2H), 6.88 (m, overlaps with diastereomer,
2H), 5.13 (d, J ) 6.9 Hz, 1H), 3.84 (m, overlaps with diastereomer,
1H), 3.80 (s, overlaps with diastereomer, 3H), 3.56 (apparent t, J
) 5.1 Hz, 1H), 2.28 (m, 1H), 1.81 (br. s, overlaps with diastereomer,
1H), 1.43 (d, J ) 6.3 Hz, 3H), 0.63 (d, J ) 7.2 Hz, 3H); 13C NMR
(100 MHz, CDCl3) δ 158.6, 130.7, 127.5, 113.4, 84.0, 81.7, 80.9,
55.2, 46.7, 19.9, 13.8. Mixture of 23b and 23c (3.3:1): IR (CDCl3)
3407, 2961, 2929, 2971, 1613, 1514, 1457, 1247.
(2S*,3S*,4R*,5S*)-, (2S*,3S*,4S*,5S*)-, and (2R*,3S*,4R*,5S*)-
2-(3,4-Methylendioxyphenyl)-3,5-dimethyltetrahydrofuran-4-
ol (24a, 24b, and 24c). Following the general procedure, aldehyde
22 (0.036 g, 0.19 mmol) gave tetrahydrofurans 24a, 24b, and 24c
(0.022 g, 0.093 mmol, 49%) as a 12:5:1 mixture (1H NMR) which
was not separable by flash chromatography (2:1 hexanes/ethyl
acetate). Diastereomers 24a and 24b were separated by HPLC (2:1
hexanes/ethyl acetate) for analytical purposes. Diastereomer 24c
was mixed with other two diastereomers after HPLC, and charac-
terization was not possible, 24a tR ) 25 min, 24b tR ) 22 min.
Major diastereomer 24a (2S*,3S*,4R*,5S*): pale yellow oil; [R]D
+22.3 (c 0.0090, CH2Cl2); 1H NMR (400 MHz, CDCl3) δ 6.86 (s,
1H), 6.78 (s, 2H), 5.95 (s, 2H), 4.46 (d, J ) 10.0 Hz, 1H), 4.07
(dq, J ) 2.4, 6.4 Hz, 1H), 3.94 (dd, J ) 5.6, 2.4 Hz, 1H), 2.00 (m,
1H), 1.79 (br. s, 1H), 1.36 (d, J ) 6.8 Hz, 3H), 0.97 (d, J ) 7.2
Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 147.8, 147.1, 134.9, 120.2,
108.0, 106.7, 101.9, 85.9, 82.5, 79.9, 45.9, 20.3, 9.0; IR (CH2Cl2)
1
(2S*,3R*,4R*): colorless oil; H NMR (300 MHz, CDCl3) δ 6.85
J. Org. Chem. Vol. 73, No. 16, 2008 6275