The Journal of Organic Chemistry
Article
hexane/ethyl acetate (80:20) as eluent. Rf 0.16 (20% EtOAc in
hexane). H NMR (250 MHz, C6D6): δ 0.84−0.90 (m, 6H); 1.22−
(m, 1H). 13C NMR (62.5 MHz, C6D6): δ 9.6; 19.8; 25.8; 29.6; 30.3;
34.3; 36.5; 46.0; 49.8; 66.1; 70.2; 74.7; 98.7; 209.8. IR (neat): 704,
739, 854, 876, 899, 924, 962, 1009, 1030, 1086, 1122, 1149, 1173,
1202, 1265, 1366, 1381, 1466, 1479, 1707, 2874, 2916, 2943, 2964,
3053, 3501. HRMS (ESI TOF-MS): calcd for C16H31O4, 287.2222;
found, 287.2250.
1
1.56 (m, 20H); 2.08 (dd, J = 4.5 and 16.0 Hz, 2H); 2.38−2.55 (m,
4H); 2.70 (dd, J = 9.2 and 16.9 Hz, 1H); (2.74 (dd, J = 9.2 and
16.7 Hz, 1H)); 3.34 (s, 6H); 3.49−3.61 (m, 4H); 4.21−4.35 (m, 2H);
5.15 (dd, J = 3.2 and 9.1 Hz, 2H); 6.81 (d, J = 8.8 Hz, 4H); 7.23−7.30
(m, 4H). 13C NMR (62.5 MHz, C6D6): δ 9.9; 24.7; 25.0; 29.1; 37.9;
49.3; (49.5); (52.7); 52.8; 54.8; 63.2; (63.4); 67.9; 69.6; (69.9); 100.5;
114.0; 127.2; (127.3); 136.3; (136.3); 159.4; (159.5); 208.1; (208.3).
IR (neat): 704, 739, 833, 899, 957, 991, 1036, 1080, 1136, 1175, 1227,
1250, 1265, 1304, 1381, 1443, 1464, 1514, 1587, 1612, 1709, 2839,
2880, 2937, 2964, 2988, 3053, 3472. HRMS (ESI TOF-MS): calcd for
C19H28O5Na, 359.1834; found, 359.1858.
(SR)-1-((4RS,6RS)-6-Ethyl-2,2-dimethyl-1,3-dioxan-4-yl)-4-hy-
droxy-5-methylhex-5-en-2-one (36d) and (RS)-1-((4RS,6RS)-6-
Ethyl-2,2-dimethyl-1,3-dioxan-4-yl)-4-hydroxy-5-methylhex-5-
en-2-one (37d). The mixture of aldol adducts 36d and 37d (89%,
60 mg, 0.222 mmol) was obtained as a yellow oil (92:08 diastereo-
selectivity), after purification by flash column chromatography (silica gel
200−400 mesh) using a mixture of hexane/ethyl acetate (70:30) as
eluent. Rf 0.53 (30% EtOAc in hexane). 1H NMR (500 MHz, C6D6): δ
0.86 (t, J = 7.5 Hz, 6H); 0.93−1.02 (m, 2H); 1.11 (dt, J = 2.6 and
12.7 Hz, 1H); (1.12−1.16 (m, 1H)); 1.25−1.33 (m, 2H); 1.30 (s, 6H);
1.45 (s, 6H); 1.45−1.56 (m, 2H); 1.60−1.61 (m, 3H); (1.62 (m,
3H)); 1.99 (dd, J = 4.6 and 15.9 Hz, 1H); (2.04 (dd, J = 4.8 and
15.9 Hz, 1H)); 2.32 (dd, J = 3.2 and 16.8 Hz, 1H); (2.30−2.34 (m, 1H));
2.39−2.50 (m, 4H); 2.84 (d, J = 2.8 Hz, 2H); 3.43−3.48 (m, 2H);
(4.14−4.17 (m, 1H)); 4.18−4.23 (m, 1H); 4.47−4.49 (m, 2H); 4.79−
4.80 (m, 2H); 5.06−5.07 (m, 2H). 13C NMR (62.5 MHz, C6D6): δ
9.6; 18.4; 19.7; 29.6; 30.3; 36.5; 49.4; 49.9; 65.9; 70.2; 71.1; 98.7;
110.7; 146.6; 208.4. IR (neat): 789, 874, 901, 964, 1030, 1078, 1122,
1171, 1202, 1261, 1381, 1437, 1458, 1655, 1711, 2878, 2939, 2964,
2991, 3074, 3454. HRMS (ESI TOF-MS): calcd for C15H27O4,
271.1909; found, 271.1885.
(RS)-1-((4RS,6RS)-6-Ethyl-2,2-dimethyl-1,3-dioxan-4-yl)-4-hy-
droxyhexan-2-one (36a) and (SR)-1-((4RS,6RS)-6-Ethyl-2,2-
dimethyl-1,3-dioxan-4-yl)-4-hydroxyhexan-2-one (37a). The
mixture of aldol adducts 36a and 37a (92%, 60 mg, 0.23 mmol)
was obtained as a yellow oil (88:12 diastereoselectivity), after
purification by flash column chromatography (silica gel 200−
400 mesh) using a mixture of hexane/ethyl acetate (80:20) as eluent.
Rf 0.44 (20% EtOAc in hexane). 1H NMR (500 MHz, C6D6): δ 0.85 (t,
J = 7.4 Hz, 6H); 0.88 (t, J = 7.4 Hz, 3H); (0.89 (t, J = 7.4 Hz, 3H));
0.94−1.03 (m, 2H); 1.14 (dt, J = 2.5 and 12.6 Hz, 1H); (1.16−1.19
(m, 1H)); 1.23−1.33 (m, 4H); 1.30 (s, 6H); 1.37−1.53 (m, 4H); 1.44
(s, 6H); 2.01 (dd, J = 4.7 and 15.6 Hz, 1H); (2.07 (dd, J = 4.8 and 16.0
Hz, 1H)); (2.18 (dd, J = 2.8 and 16.6 Hz, 1H)); 2.20 (dd, J = 3.3 and
16.8 Hz, 1H); 2.26 (dd, J = 8.8 and 16.8 Hz, 1H); (2.31 (dd, J = 9.0
and 16.6 Hz, 1H)); 2.44 (dd, J = 7.8 and 15.6 Hz, 1H); (2.46 (dd, J =
7.6 and 15.8 Hz, 1H)); 3.10 (br s, 2H); 3.44−3.49 (m, 2H); 3.87−
3.93 (m, 2H); (4.16−4.20 (m, 1H)); 4.20−4.25 (m, 1H). 13C NMR
(62.5 MHz, C6D6): δ 9.6; 10.0; 19.8; 29.6; 29.8; (30.0); 30.3; 36.5;
49.7; (50.0); (50.3); 50.7; 66.0; 68.8; (69.2); 70.2; 98.7; 209.1;
(209.3). IR (neat): 704, 739, 787, 854, 876, 901, 924, 962, 1041, 1107,
1124, 1171, 1202, 1265, 1381, 1466, 1709, 2880, 2939, 2964, 2993,
3053, 3472. HRMS (ESI TOF-MS): calcd for C14H26O4Na, 281.1729;
found, 281.1716.
(SR)-1-((4RS,6RS)-6-Ethyl-2,2-dimethyl-1,3-dioxan-4-yl)-4-hy-
droxy-5-methylhexan-2-one (36b) and (RS)-1-((4RS,6RS)-6-
Ethyl-2,2-dimethyl-1,3-dioxan-4-yl)-4-hydroxy-5-methylhex-
an-2-one (37b). The mixture of aldol adducts 36b and 37b (96%,
65 mg, 0.24 mmol) was obtained as a yellow oil (95:05 diastereo-
selectivity), after purification by flash column chromatography (silica
gel 200−400 mesh) using a mixture of dichloromethane/ethyl acetate
(80:20) as eluent. Rf 0.70 (20% EtOAc in CH2Cl2). 1H NMR
(500 MHz, C6D6): δ 0.84 (d, J = 6.9 Hz, 6H); 0.86 (t, J = 7.5 Hz, 6H);
0.91 (d, J = 6.9 Hz, 6H); 0.95−1.02 (m, 2H); 1.13 (dt, J = 2.5 and
12.7 Hz, 2H); 1.25−1.35 (m, 2H); 1.30 (s, 6H); 1.44 (s, 6H); 1.47−
1.58 (m, 4H); 2.01 (dd, J = 4.5 and 15.7 Hz, 1H); (2.07 (dd, J =
4.8 and 15.7 Hz, 1H)); (2.22 (dd, J = 2.8 and 16.6 Hz, 1H)); 2.24 (dd,
J = 3.1 and 16.8 Hz, 1H); 2.30 (dd, J = 9.2 and 16.8 Hz, 1H); (2.34
(dd, J = 9.7 and 16.6 Hz, 1H)); 2.44 (dd, J = 7.8 and 15.6 Hz, 1H);
(2.46 (dd, J = 7.6 and 15.6 Hz, 1H)); 3.04 (br s, 2H); 3.44−3.49 (m,
2H); 3.78−3.82 (m, 2H); (4.15−4.19 (m, 1H)); 4.19−4.24 (m, 1H).
13C NMR (62.5 MHz, C6D6): δ 9.6; 17.8; 18.6; 19.8; 29.6; 30.3; 33.5;
(SR)-1-((4RS,6RS)-6-Ethyl-2,2-dimethyl-1,3-dioxan-4-yl)-4-hy-
droxy-4-phenylbutan-2-one (36e) and (RS)-1-((4RS,6RS)-6-
Ethyl-2,2-dimethyl-1,3-dioxan-4-yl)-4-hydroxy-4-phenylbutan-
2-one (37e). The mixture of aldol adducts 36e and 37e (96%, 73 mg,
0.24 mmol) was obtained as a yellow oil (94:06 diastereoselectivity),
after purification by flash column chromatography (silica gel 200−
400 mesh) using a mixture of hexane/ethyl acetate (80:20) as eluent.
Rf 0.29 (20% EtOAc in hexane). 1H NMR (500 MHz, C6D6): δ 0.82 (t,
J = 7.4 Hz, 6H); 0.88−0.95 (m, 2H); 1.06 (dt, J = 2.0 and 12.7 Hz,
1H); (1.07−1.11 (m, 1H)); 1.21−1.32 (m, 2H); 1.26 (s, 6H); 1.40 (s,
6H); 1.40−1.50 (m, 2H); 1.96 (dd, J = 4.6 and 15.8 Hz, 1H); (1.97−
2.01 (m, 1H)); 2.37 (dd, J = 7.7 and 16.1 Hz, 2H); 2.43 (dd, J = 2.9
and 17.2 Hz, 2H); 2.56 (dd, J = 9.2 and 16.9 Hz, 1H); (2.64 (dd, J =
9.2 and 16.6 Hz, 1H)); 3.35 (br s, 2H); 3.39−3.44 (m, 2H); (4.10−
4.13 (m, 1H)); 4.13−4.18 (m, 1H); 5.09−5.11 (m, 2H); 7.04−
7.07 (m, 2H); 7.13−7.15 (m, 4H); 7.26−7.30 (m, 4H). 13C NMR
(62.5 MHz, C6D6): δ 9.6; 19.7; 29.6; 30.3; 36.5; 49.8; 53.0; 65.9; 69.8;
70.2; 98.7; 126.0; 127.5; 128.5; 144.1; 208.2. IR (neat): 702, 739, 874,
897, 920, 960, 1030, 1067, 1109, 1122, 1149, 1173, 1202, 1265, 1381,
1452, 1495, 1605, 1707, 2880, 2939, 2966, 2993, 3053, 3456. HRMS
(ESI TOF-MS): calcd for C18H27O4, 307.1909; found, 307.1877.
(SR)-1-((4RS,6RS)-6-Ethyl-2,2-dimethyl-1,3-dioxan-4-yl)-4-hy-
droxy-4-(4-nitrophenyl)butan-2-one (36f) and (RS)-1-
((4RS,6RS)-6-Ethyl-2,2-dimethyl-1,3-dioxan-4-yl)-4-hydroxy-4-
(4-nitrophenyl)butan-2-one (37f). The mixture of aldol adducts
36f and 37f (82%, 72.5 mg, 0.206 mmol) was obtained as a yellow oil
(95:05 diastereoselectivity), after purification by flash column
chromatography (silica gel 200−400 mesh) using a mixture of
hexane/ethyl acetate (70:30) as eluent. Rf 0.36 (30% EtOAc in
36.5; 48.1; 49.8; 66.1; 70.2; 72.1; 98.7; 209.4. IR (neat): 704, 739, 856,
874, 899, 922, 962, 1007, 1030, 1063, 1107, 1124, 1171, 1202, 1265,
1381, 1466, 1709, 2878, 2939, 2964, 2991, 3485. HRMS (ESI TOF-
MS): calcd for C15H29O4, 273.2066; found, 273.2073.
1
hexane). H NMR (500 MHz, C6D6): δ 0.87 (t, J = 7.4 Hz, 6H);
0.93−1.00 (m, 2H); 1.05 (dt, J = 2.6 and 12.7 Hz, 1H); (1.09 (dt, J =
2.6 and 12.7 Hz, 1H)); 1.26−1.37 (m, 2H); 1.30 (s, 6H); 1.44 (s, 6H);
1.44−1.57 (m, 2H); 1.91 (dd, J = 4.1 and 15.6 Hz, 1H); (1.97 (dd, J =
4.4 and 15.4 Hz, 1H)); 2.24 (dd, J = 3.4 and 17.3 Hz, 2H); 2.32 (dd,
J = 9.2 and 17.6 Hz, 1H); 2.34 (dd, J = 8.2 and 15.8 Hz, 1H); (2.34−
2.43 (m, 2H)); 3.20 (d, J = 3.2 Hz, 1H); (3.25 (d, J = 2.8 Hz, 1H));
3.43−3.48 (m, 2H); (4.09−4.15 (m, 1H)); 4.15−4.20 (m, 1H); 4.88−
4.90 (m, 2H); 6.95−7.00 (m, 4H); 7.88 (dt, J = 2.2 and 9.0 Hz, 4H).
13C NMR (62.5 MHz, C6D6): δ 9.5; 19.7; 29.6; 30.3; 36.4; 49.6; 52.4;
66.0; 68.8; 70.2; 98.8; 123.6; 126.4; 147.4; 150.7; 207.8; (208.1). IR
(neat): 702, 739, 856, 874, 899, 924, 960, 1014, 1045, 1080, 1109,
1173, 1202, 1265, 1348, 1381, 1466, 1522, 1605, 1709, 2880, 2939,
2966, 2993, 3057, 3433. HRMS (ESI TOF-MS): calcd for C18H26NO6,
352.1760; found, 352.1746.
(SR)-1-((4RS,6RS)-6-Ethyl-2,2-dimethyl-1,3-dioxan-4-yl)-4-hy-
droxy-5,5-dimethylhexan-2-one (36c) and (RS)-1-((4RS,6RS)-6-
Ethyl-2,2-dimethyl-1,3-dioxan-4-yl)-4-hydroxy-5,5-dimethyl-
hexan-2-one (37c). The mixture of aldol adducts 36c and 37c (89%,
64 mg, 0.223 mmol) was obtained as a yellow solid (>95:05
diastereoselectivity), after purification by flash column chromatog-
raphy (silica gel 200−400 mesh) using a mixture of hexane/ethyl
acetate (80:20) as eluent. Rf 0.42 (20% EtOAc in hexane). mp: 39−
1
41 °C. H NMR (250 MHz, C6D6): δ 0.86 (t, J = 7.4 Hz, 3H); 0.88
(s, 9H); 0.95−1.05 (m, 1H); 1.09−1.16 (m, 1H); 1.23−1.38 (m, 1H);
1.30 (s, 3H); 1.41−1.58 (m, 1H); 1.44 (s, 3H); 2.01 (dd, J = 4.4 and
15.6 Hz, 1H); 2.23−2.35 (m, 2H); 2.44 (dd, J = 8.1 and 15.6 Hz, 1H);
3.19 (br s, 1H); 3.41−3.51 (m, 1H); 3.74−3.77 (m, 1H); 4.15−4.26
3786
dx.doi.org/10.1021/jo300125d | J. Org. Chem. 2012, 77, 3766−3792