1344
P. Fries et al. / Tetrahedron 70 (2014) 1336e1347
HRMS (EIþ) m/z 252.1505 [Mþ]; calculated mass for C18H20Oþ:
252.1514.
(26) [Mþ], 215 (3), 200 (5), 180 (19), 131 (19), 118 (24), 111 (30), 104
(100), 91 (27), 77 (20). Anal. Calcd for C16H18OS (258.38): C 74.38; H
7.02; S 12.41. Found: C 74.33; H 7.01; S 12.19. HRMS (EIþ) m/z
258.1077 (Mþ); calculated mass for C16H18OSþ: 258.1078. rel-
(2S,4R,6R)-6-Methyl-4-phenyl-2-(thien-2-yl)-tetrahydropyran rel-(2S,
4.2.10. Oxidation of unlike-1,3-diphenylhex-5-en-1-ol rel-(1S,3R)-
(1i). A solution of alcohol rel-(1S,3R)-1i (137 mg, 544
mmol) and co-
balt complex 5 (28.5 mg, 54.3
m
mol) in toluene (1.2 mL) and CHD
4R,6R)-(3j). Yield: 46.4 mg (180 mmol, 32%), Rf 0.56 [SiO2, acetone/
(0.5 mL)was stirred at 70 ꢁC for 15 h while being exposed to laboratory
atmosphere. The reaction mixture was cooled to 20 ꢁC and purified by
column chromatography [SiO2, Et2O/acetone/pentane¼1:1:20 (v/v)].
pentane¼1:5 (v/v)], colorless oil. dH (400 MHz, CDCl3) 1.47 (3H, d, J
6.8), 1.72 (1H, ddt, Jd 13.2, 3.7, Jt 1.7), 1.85 (1H, td, Jt 12.6, Jd 11.5), 2.07
(1H, td, Jt 13.1, Jd 5.7), 2.17 (1H, dt, Jd 12.6, Jt 3.7), 3.16 (1H, tt, J 12.6,
3.7), 4.54 (1H, quin, J 6.5), 5.08 (1H, dd, J 11.5, 2.2), 6.93e6.98 (2H,
m), 7.19e7.27 (4H, m), 7.29e7.34 (4H, m). dC (100 MHz, CDCl3) 17.2,
36.0, 36.8, 41.6, 67.7, 70.0, 123.2, 124.3, 126.4, 126.8, 128.6, 145.2,
146.7. MS (EI) m/z 258 (44) [Mþ], 215 (3), 200 (3), 180 (13), 131 (17),
118 (22),111 (24),104 (100), 91 (25), 77 (12). Anal. Calcd for C16H18OS
(258.38): C 74.38; H 7.02; S 12.41. Found: C 74.12; H 6.85; S 12.46.
HRMS (EIþ) m/z 258.1077 [Mþ]; calculated mass for C16H18OSþ:
258.1078.
rel-(2S,4R,6S)-6-Methyl-2,4-diphenyltetrahydropyran
rel-(2S,4R,6S)-
(3i). Yield: 47.6 mg (189
mmol, 35%), Rf 0.57 [SiO2, acetone/
pentane¼1:5 (v/v)], colorless oil. dH (400 MHz, CDCl3) 1.33 (3H, d, J
6.2), 1.51 (1H, td, Jt 12.7, Jd 11.1), 1.69 (1H, td, Jt 12.7, Jd 11.3), 1.89 (1H,
ddt, Jd 13.2, 3.8, Jt 2.0), 2.05 (1H, ddt, Jd 13.2, 3.7, Jt 2.0), 2.97 (1H, tt, J
12.3, 3.7), 3.80 (1H, dqd, Jd 11.0, Jq 6.2, Jd 2.0), 4.53 (1H, dd, J 11.2, 2.0),
7.17e7.26 (4H, m), 7.27e7.35 (4H, m), 7.38e7.42 (2H, m). dC (150 MHz,
CDCl3) 22.1, 40.7, 40.9, 42.1, 74.1, 79.5, 125.9, 126.3, 126.7, 127.3, 128.3,
128.5, 142.9, 145.5. MS (EI) m/z 252 (8) [Mþ], 209 (8), 174 (27), 147 (3),
131 (8), 117 (17), 104 (100), 91 (22), 77 (21). HRMS (EIþ) m/z 252.1509
[Mþ]; calculated mass for C18H20Oþ: 252.1514. rel-(2S,4R,6R)-6-
Methyl-2,4-diphenyltetrahydropyran rel-(2S,4R,6R)-(3i). Yield: 46.0
4.2.13. Oxidation of like-1-(2,4-difluorophenyl)-3-phenylhex-5-en-1-
ol rel-(1R,3R)-(1k). A solution of alcohol rel-(1R,3R)-1k (146 mg,
507 mmol) and cobalt complex 5 (13.0 mg, 24.7 mmol) in toluene
mg (182
m
mol, 34%), Rf 0.55 [SiO2, acetone/pentane¼1:5 (v/v)], col-
(2.0 mL) and CHD (1.0 mL) was stirred at 70 ꢁC for 4 h while being
exposed to laboratory atmosphere. The reaction mixture was cooled
to 20 ꢁC and purified by column chromatography [SiO2, Et2O/ace-
tone/pentane¼1:1:20 (v/v)]. rel-(2R,4R,6S)-6-Methyl-4-phenyl-2-
(2,4-difluorophenyl)tetrahydropyran rel-(2R,4R,6S)-(3k). Yield: 116
orless oil. dH (400 MHz, CDCl3) 1.48 (3H, d, J 6.8), 1.69e1.78 (2H, m),
2.00e2.10 (2H, m), 3.19 (1H, tt, J 12.6, 3.7), 4.54 (1H, quin, J 6.5), 4.82
(1H, dd, J 11.5, 2.1), 7.17e7.35 (8H, m), 7.37e7.42 (2H, m). dC (150 MHz,
CDCl3) 17.2, 36.2, 37.1, 41.5, 69.7, 71.4, 125.9, 126.3, 126.8, 127.3, 128.3,
128.5,143.1,145.6. MS (EI) m/z 252 (3) [Mþ], 234 (3),194 (10),174 (19),
147 (15), 131 (10), 117 (18), 104 (100), 91 (24), 77 (24). HRMS (EIþ) m/z
252.1512 [Mþ]; calculated mass for C18H20Oþ: 252.1514.
mg (402
mmol, 79%), Rf 0.60 [SiO2, acetone/pentane¼1:5 (v/v)], col-
orless oil. dH (400 MHz, CDCl3) 1.25 (3H, d, J 6.2),1.59 (1H, td, Jt 13.0, Jd
10.7), 1.80e1.87 (1H, m), 2.17 (1H, td, Jt 13.3, Jd 6.0), 2.50e2.57 (1H,
m), 2.94 (1H, tt, J 12.4, 3.6), 3.76 (1H, dqd, Jd 11.0, Jq 6.2, Jd 1.9), 5.32
(1H, d, J 5.9), 6.83 (1H, ddd, J 11.3, 8.8, 2.5), 6.92 (1H, td, Jt 8.3, Jd 2.6),
7.22e7.27 (3H, m), 7.52 (1H, td, Jt 8.9, Jd 6.4). dC (100 MHz, CDCl3) 22.0,
34.9, 37.2 (d, J 4.5), 37.2, 40.6, 67.4, 70.4, 104.5 (dd, J 27.2, 25.3), 110.9
(dd, J 20.7, 3.6),123.9 (dd, J 12.7, 3.6),126.4,126.7,130.1 (dd, J 9.1, 6.4),
145.5, 160.3 (dd, J 134, 11.8), 162.7 (dd, 131, 12.7). MS (EI) m/z 288 (2)
[Mþ], 270 (2), 210 (41), 141 (19), 127 (10), 117 (18), 104 (100), 91 (19),
78 (15). HRMS (EIþ) m/z 288.1328 [Mþ]; calculated mass for
4.2.11. Oxidation of like-1-(thien-2-yl)-3-phenyl-hex-5-en-1-ol rel-
(1R,3R)-(1j). A solution of alcohol rel-(1R,3R)-1j (158 mg, 610
and cobalt complex 5 (14.8 mg, 28.2 mol) in toluene (2.0 mL) and
mmol)
m
CHD (1.0 mL) was stirred at 70 ꢁC for 4 h while being exposed to
laboratory atmosphere. The reaction mixture was cooled to 20 ꢁC
and purified by column chromatography [SiO2, Et2O/acetone/
pentane¼1:1:20 (v/v)]. rel-(2R,4R,6S)-6-Methyl-4-phenyl-2-(thien-
2-yl)-tetrahydropyran rel-(2R,4R,6S)-(3j). Yield: 124 mg (479
mmol,
C
18H18OF2þ: 288.1328.
79%), Rf 0.58 [SiO2, acetone/pentane¼1:5 (v/v)], colorless oil. dH
(400 MHz, CDCl3) 1.14 (3H, d, J 6.1), 1.44 (1H, td, J 12.5, 11.5), 1.67
(1H, ddt, Jd 12.9, 3.5, Jt 1.8), 2.09 (1H, ddd, J 14.2, 12.5, 5.7), 2.28 (1H,
ddt, Jd 13.9, 3.5, Jt 1.7), 2.98 (1H, tt, J 12.5, 3.5), 3.82 (1H, dqd, Jd 11.5,
Jq 6.1, Jd 1.7), 5.32 (1H, d, J 5.5), 6.88e6.91 (1H, m), 6.94 (dd, J 4.9,
3.5), 7.11e7.18 (3H, m), 7.21e7.27 (3H, m). dC (100 MHz, CDCl3) 21.8,
35.5, 36.8, 40.7, 67.0, 71.8, 124.5, 125.1, 126.4, 126.8, 127.0, 128.6,
145.5, 146.2. MS (EI) m/z 258 (55) (Mþ), 215 (4), 200 (4), 180 (21),
131 (22), 118 (25), 111 (32), 104 (100), 91 (28), 77 (23). Anal. Calcd
for C16H18OS (258.38): C 74.38; H 7.02; S 12.41. Found: C 74.31; H
7.02; S 12.19. HRMS (EIþ) m/z 258.1086 [Mþ]; calculated mass for
4.2.14. Oxidation of unlike-1-(2,4-difluorophenyl)-3-phenylhex-5-
en-1-ol rel-(1S,3R)-(1k). A solution of alcohol rel-(1S,3R)-1k
(147 mg, 509 mmol) and cobalt complex 5 (13.1 mg, 24.9 mmol) in
toluene (2.0 mL) and CHD (1.0 mL) was stirred at 70 ꢁC for 15 h while
being exposed to laboratory atmosphere. The reaction mixture was
cooled to 20 ꢁC and purified by column chromatography [SiO2, Et2O/
acetone/pentane¼1:1:20 (v/v)]. rel-(2S,4R,6S)-6-Methyl-4-phenyl-2-
(2,4-difluorophenyl)-tetrahydropyran rel-(2S,4R,6S)-(3k). Yield: 50.2
mg (174
mmol, 34%), Rf 0.58 [SiO2, acetone/pentane¼1:5 (v/v)], col-
orless crystalline solid. dH (400 MHz, CDCl3) 1.35 (3H, d, J 6.2), 1.54
(1H, td, Jt 12.7, Jd 11.1), 1.93 (1H, ddt, Jd 13.1, 3.8, Jt 1.9), 2.06e2.10 (1H,
m), 3.02 (1H, tt, J 12.3, 3.7), 3.84 (1H, dqd, Jd 10.9, Jq 6.2, Jd 2.0), 4.84
(1H, dd, J 11.1,1.3), 6.78 (1H, ddd, J 10.5, 9.0, 2.5), 6.90 (1H, tdd, Jt 8.4, Jd
2.5, 1.2), 7.20e7.27 (3H, m), 7.30e7.36 (2H, m), 7.57 (1H, td, Jt 8.6, Jd
6.4). dC (100 MHz, CDCl3) 22.0, 40.0, 40.5, 41.9, 72.8, 74.3, 103.4 (t, J
25.4), 111.3 (dd, J 19.7, 3.6), 126.2 (dd, J 13.6, 3.6), 126.4, 126.7, 128.3
(dd, J 9.2, 6.4), 128.5, 145.2, 159.4 (dd, J 248, 11.8), 162.0 (dd, J 248,
11.8). MS (EI) m/z 288 (5) [Mþ], 270 (2), 210 (20),140 (14),127 (9),117
(16), 104 (100), 91 (16), 78 (13). HRMS (EIþ) m/z 288.1333 [Mþ];
calculated mass for C18H18OF2þ: 288.1326. rel-(2S,4R,6R)-6-Methyl-
4-phenyl-2-(2,4-difluorophenyl)-tetrahydropyran rel-(2S,4R,6R)-(3k).
C
16H18OSþ: 258.1078.
4.2.12. Oxidation of unlike-1-(thien-2-yl)-3-phenyl-hex-5-en-1-ol
rel-(1S,3R)-(1j). A solution of alcohol rel-(1S,3R)-1j (145 mg,
560 mmol) and cobalt complex 5 (14.7 mg, 28.0 mmol) in toluene
(2.0 mL) and CHD (1.0 mL) was stirred at 70 ꢁC for 15 h while being
exposed to laboratory atmosphere. The reaction mixture was cooled
to 20 ꢁC and purified by column chromatography [SiO2, Et2O/ace-
tone/pentane¼1:1:20 (v/v)]. rel-(2S,4R,6S)-6-Methyl-4-phenyl-2-
(thien-2-yl)-tetrahydropyran rel-(2S,4R,6S)-(3j). Yield: 61.4 mg
(238
m
mol, 42%), Rf 0.58 [SiO2, acetone/pentane¼1:5 (v/v)], colorless
oil. dH (400 MHz, CDCl3) 1.32 (3H, d, J 6.1), 1.53 (1H, td, Jt 12.7, Jd 11.1),
1.79e1.92 (2H, m), 2.19 (1H, ddt, Jd 13.1, 3.8, Jt 1.9), 2.96 (1H, tt, J 12.3,
3.7), 3.82 (1H, dqd, Jd 11.2, Jq 6.1, Jd 1.7), 4.79 (1H, dd, J 11.1, 1.7),
6.94e6.97 (1H, m), 7.00 (1H, dd, J 3.4, 1.0), 7.20e7.27 (4H, m),
7.30e7.35 (2H, m). dC (100 MHz, CDCl3) 22.0, 40.4, 40.6, 41.9, 74.3,
75.4, 123.4, 124.4, 126.4, 126.8, 128.6, 145.2, 146.0. MS (EI) m/z 258
Yield: 52.7 mg (183
m
mol, 36%), Rf 0.56 [SiO2, acetone/pentane¼1:5
(v/v)], colorless oil. dH (400 MHz, CDCl3) 1.50 (3H, d, J 6.8), 1.64 (1H,
td, Jt 12.7, Jd 11.4), 1.76 (1H, ddt, Jd 13.2, 3.6, Jt 1.8), 2.02e2.12 (2H, m),
3.22 (1H, tt, J 12.6, 3.6), 4.55 (1H, quin, J 6.5), 5.13 (1H, dd, J 11.3, 1.9),
6.77 (1H, ddd, J 10.5, 8.8, 2.5), 6.89 (1H, tdd, Jt 8.4, Jd 2.6,1.3), 7.21e7.28
(3H, m), 7.29e7.35 (2H, m), 7.54 (1H, td, Jt 8.5, Jd 6.5). dC (100 MHz,