Ketone Catalyst Probing for Asymmetric Epoxidation
J . Org. Chem., Vol. 63, No. 23, 1998 8483
CuSO4 (6.0 g) and concentrated H2SO4 (0.2 g). After being
stirred at room temperature overnight, the reaction mixture
was neutralized with concentrated NH4OH, concentrated, and
purified by flash chromatography (hexane:ether, 50:1 to 3:1,
v/v) to give alcohol 16c as a white solid (5.56 g, 43%); mp 85.5-
86.5 °C. [R]25D ) -127.0 (c 0.6, CHCl3); IR 3449 cm-1; 1H NMR
δ 4.24 (dd, J ) 6.2, 2.7 Hz, 1H), 4.18 (dd, J ) 6.3, 6.2 Hz, 1H),
4.05 (d, J ) 13.4 Hz, 1H), 4.04 (ddd, J ) 11.4, 11.4, 3.3 Hz,
1H), 3.91 (dd, J ) 13.4, 2.7 Hz, 1H), 3.85 (d, J ) 11.9 Hz, 1H),
3.78 (dd, J ) 11.7, 3.3 Hz, 1H), 3.69 (ddd, 11.7, 11.4, 2.7 Hz,
1H), 3.68 (d, J ) 11.9 Hz, 1H), 3.59 (dd, J ) 11.4, 2.7, Hz,
1H), 3.46 (dd, J ) 6.3, 5.9 Hz, 1H), 2.33 (br s, 1H), 1.31-1.73
PCC (4.0 g, 18.6 mmol) oxidation of alcohol 16e (2.79 g, 7.5
mmol) gave ketone 2e as a white solid (1.43 g, 51%); mp 193.5-
194.5 °C. IR 1752 cm-1; 1H NMR δ 7.2-7.6 (m, 10H), 4.79 (d,
J ) 6.6 Hz, 1H), 4.53 (dd, J ) 6.6, 2.1 Hz, 1H), 4.32 (d, J )
13.4 Hz, 1H), 4.18 (dd, J ) 13.4, 2.1 Hz, 1H), 4.07 (td, J )
11.2, 3.2 Hz, 1H), 3.85 (d, J ) 12.3 Hz, 1H), 3.78 (dd, J ) 12.0,
3.2 Hz, 1H), 3.70 (d, J ) 12.3 Hz, 1H), 3.68 (ddd, J ) 12.0,
11.4, 2.4 Hz, 1H), 3.59 (dd, J ) 11.4, 2.4 Hz, 1H); 13C NMR δ
197.8, 141.9, 140.9, 128.8, 128.5, 128.4, 128.2, 126.8, 126.5,
110.8, 94.17, 78.58, 75.63, 67.47, 65.60, 60.44, 59.55. Anal.
Calcd for C21H20O6: C, 68.47; H, 5.47. Found: C, 68.34; H,
5.85.
(m, 8H), 0.93 (t, J ) 7.2 Hz, 3H), 0.91 (t, J ) 7.2 Hz, 3H); 13
C
P r ep a r a tion of Keton e 2f. Alcohol 16f was prepared in
a way similar to that of alcohol 16b using cyclopentanone (5.04
g, 60 mmol), trimethyl orthoformate (4.4 mL, 4.24 g, 40 mmol),
methanol (20 mL), TsOH‚H2O (0.05 g), alcohol 15 (8.24 g, 40
mmol), THF (100 mL), and 4 drops of 70% perchloric acid.
Alcohol 16f was obtained as a solid (5.97 g, 52%); mp 131.0-
NMR δ 112.9, 94.77, 76.31, 73.32, 71.45, 69.46, 65.76, 60.49,
60.34, 40.45, 38.92, 17.82, 17.68, 14.61.
PCC (9.12 g, 42.3 mmol) oxidation of alcohol 16c (4.73 g,
15.7 mmol) gave ketone 2c as a syrup (3.89 g, 83%). [R]25
)
D
-65.0 (c 1.1, CHCl3); IR 1751 cm-1; 1H NMR δ 4.66 (d, J ) 6.3
Hz, 1H), 4.50 (ddd, J ) 6.3, 1.5, 1.5 Hz, 1H), 4.17 (d, J ) 1.5
Hz, 2H), 4.06 (td, J ) 11.1, 3.2 Hz, 1H), 3.92 (d, J ) 12.6 Hz,
1H), 3.80 (dd, J ) 11.7, 3.2 Hz, 1H), 3.75 (d, J ) 12.6 Hz, 1H),
3.70 (ddd, 11.7, 11.0, 2.7 Hz, 1H), 3.62 (dd, J ) 11.1, 2.7 Hz,
1H), 1.62 (m, 4H), 1.40 (m, 4H), 0.912 (t, J ) 7,3 Hz, 3H), 0.907
(t, J ) 7.2 Hz, 3H); 13C NMR δ 199.2, 114.1, 94.03, 78.09, 75.26,
67.42, 65.62, 60.44, 59.74, 39.89, 39.22, 17.65, 17.44, 14.55.
Anal. Calcd for C15H24O6: C, 59.98; H, 8.05. Found: C, 59.93;
H, 8.15.
132.5 °C. [R]25 ) -133.1 (c 0.5, CHCl3); IR 3444 cm-1 1H
;
D
NMR δ 4.08-4.14 (m, 3H), 4.02 (td, J ) 11.4, 3.2, 1H), 3.95
(dd J ) 13.5, 2.6, 1H), 3.90 (d, J ) 11.8, 1H), 3.77 (dd, J )
11.4, 3.2, 1H), 3.71 (dd, J ) 11.4, 2.6, 1H), 3.69 (td, J ) 11.8,
2.6, 1H), 3.65 (d, J ) 11.8 Hz, 1H), 3.59 (dd, 11.4, 2.6, Hz,
1H), 3.39 (m, 1H), 2.12 (br s, 1H), 1.96 (m, 2H), 1.74 (m, 6H);
13C NMR δ 119.2, 95.25, 76.33, 73.97, 71.36, 68.57, 65.56,
60.28, 59.59, 37.65, 37.59, 23.69, 23.43.
PCC (9.92 g, 46 mmol) oxidation of alcohol 16f (5.48 g, 20
mmol) gave ketone 2f as a white solid (4.29 g, 78%); mp 98.0-
100 °C. [R]25D ) - 88.5 (c, 1.1, CHCl3); IR 1751 cm-1; 1H NMR
δ 4.73 (d, J ) 5.8 Hz, 1H), 4.46 (ddd, J ) 5.8, 1.8, 0.6 Hz, 1H),
3.60-4.25 (m, 8H), 1.61-2.05 (m, 8H); 13C NMR δ 198.8, 120.3,
93.85, 78.97, 75.40, 67.16, 65.55, 60.45, 59.34, 37.47, 37.04,
23.71, 23.40. Anal. Calcd for C13H18O6: C, 57.77; H, 6.71.
Found: C, 57.62; H, 6.81.
P r ep a r a tion of Keton e 2d . Alcohol 16d was prepared in
a way similar to that of alcohol 16b using 1,3-diphenylacetone
(2.1 g, 10 mmol), trimethyl orthoformate (1.2 mL, 1.15 g, 11
mmol), methanol (10 mL), TsOH‚H2O (0.01 g), alcohol 15 (3.10
g, 15 mmol), THF (100 mL), and 3 drops of 70% perchloric
acid. Alcohol 16d was obtained as a solid (2.36 g, 59%); mp
180.0-181.0 °C. [R]25 ) -86.2 (c 0.5, CHCl3); IR 3419 cm-1
;
D
1H NMR δ 7.30 (m, 10H), 3.98 (d, J ) 13.2 Hz, 1H), 3.90 (dd,
J ) 6.9, 6.6 Hz, 1H), 3.84 (td, J ) 11.4, 3.2 Hz, 1H), 3.71 (dd,
J ) 6.6, 2.9 Hz, 1H), 3.67 (dd, J ) 11.7, 3.2 Hz, 1H), 3.64 (dd,
J ) 13.2, 2.9 Hz, 1H), 3.56 (ddd, J ) 11.7, 11.4, 2.7 Hz, 1H),
3.55 (d, J ) 12.0 Hz, 1H), 3.45 (dd, J ) 11.4, 2.7 Hz, 1H), 3.16
(d, J ) 12.0 Hz, 1H), 3.05 (d, J ) 13.8 Hz, 1H), 3.03 (d J )
13.8 Hz, 1H), 2.98 (d, J ) 13.8 Hz, 1H), 2.91 (d, J ) 13.8 Hz,
1H), 1.87 (dd, J ) 8.0, 6.9 Hz, 1H), 1.72 (d, J ) 8.0, Hz, 1H);
13C NMR δ 136.7, 136.3, 131.7, 130.8, 128.4, 128.1, 126.8,
111.5, 94.76, 77.47, 73.86, 70.51, 68.46, 65.54, 60.21, 59.49,
45.49, 44.53.
P r ep a r a tion of Keton e 2g. Alcohol 16g was prepared in
a way similar to that of alcohol 16b using cyclohexanone (5.88
g, 61 mmol), trimethyl orthoformate (4.4 mL, 4.24 mmol),
methanol (20 mL), TsOH‚H2O (0.05 g), alcohol 15 (8.24 g, 40
mmol), THF (100 mL), and 4 drops of 70% perchloric acid.
Alcohol 16g was obtained as a solid (7.64 g, 66%); mp 138.0-
139.5 °C. [R]25 ) -128.6 (c 0.5, CHCl3), IR 3452 cm-1 1H
;
D
NMR δ 4.23 (ddd, J ) 5.7, 2.4, 0.6 Hz, 1H), 4.17 (dd, J ) 6.9,
5.7 Hz, 1H), 4.10 (d, J ) 13.2 Hz, 1H), 4.02 (ddd, J ) 11.4,
11.1, 3.6 Hz, 1H), 3.92 (dd, J ) 13.2, 2.4 Hz, 1H), 3.88 (d, J )
11.9 Hz, 1H), 3.78 (dd, J ) 11.7, 3.6 Hz, 1H), 3.71 (ddd, J )
11.7, 11.4, 2.4 Hz, 1H), 3.65 (d, J ) 11.9 Hz, 1H), 3.59 (dd, J
) 11.1, 2.4 Hz, 1H), 3.43 (dd, J ) 7.2, 6.9 Hz, 1H), 2.53 (d, J
) 7.2 Hz, 1H), 1.76-1.58 (m, 8H), 1.43-1.38 (m, 2H); 13C NMR
δ 110.2, 95.05, 76.24, 73.21, 71.81, 68.95, 65.64, 60.34, 59.96,
37.93, 35.41, 25.11, 24.14, 23.78.
PCC (2.34 g, 10.4 mmol) oxidation of alcohol 16d (1.8 g, 4.5
mmol) gave ketone 2d as a solid (1.68 g, 93%); mp 131.0-131.5
°C. [R]25 ) -6.3 (c 0.7, CHCl3); IR 1749 cm-1 1H NMR δ
;
D
7.20-7.45 (m, 10H), 4.45 (d, J ) 6.3 Hz, 1H), 4.05 (d, J ) 13.2
Hz, 1H), 3.97 (ddd, J ) 11.4, 11.1, 3.0 Hz, 1H), 3.90 (dd, J )
13.2, 2.4 Hz, 1H), 3.87 (d, J ) 12.4 Hz, 1H), 3.76 (dd, J ) 11.7,
3.0 Hz, 1H), 3.66 (ddd, J ) 11.7, 11.4, 2.4 Hz, 1H), 3.65 (d, J
) 12.4 Hz, 1H), 3.62 (dd, J ) 6.3, 2.4 Hz, 1H), 3.54 (dd, J )
11.1, 2.4 Hz, 1H), 2.98 (d, J ) 13.8 Hz, 1H), 2.93 (d, J ) 13.8
Hz, 1H), 2.91 (d, J ) 13.9 Hz, 1H), 2.82 (d, J ) 13.9 Hz, 1H);
13C NMR δ 198.9, 136.2, 136.0, 131.0, 130.9, 128.2, 128.1,
126.7, 112.5, 93.63, 79.03, 75.45, 66.99, 65.39, 60.22, 59.23,
46.13, 43.63. Anal. Calcd for C23H24O6: C, 69.68; H, 6.10.
Found: C, 69.46; H, 5.88.
PCC (9.92 g, 46 mmol) oxidation of alcohol 16g (5.76 g, 20
mmol) gave ketone 2g as a white solid (4.98 g, 86%); mp 136.0-
137.0 °C. [R]25 ) -75.9 (c 1, CHCl3); IR 1750 cm-1; 1H NMR
D
δ 4.73 (d, J ) 5.6 Hz, 1H), 4.59 (dt, J ) 5.6, 1.5 Hz, 1H), 4.19
(d, J ) 1.5 Hz, 2H), 4.07 (td, J ) 11.2, 3.2 Hz, 1H), 3.90 (d, J
) 12.6 Hz, 1H), 3.60-3.84 (m, 3H), 3.76 (d, J ) 12.6 Hz, 1H),
1.62 (m, 8H), 1.40 (m, 2H); 13C NMR δ 199.5, 111.3, 93.93,
78.26, 75.28, 67.25, 65.55, 60.42, 59.53, 36.91, 35.61, 25.07,
24.05, 23.90. Anal. Calcd for C14H20O6: C, 59.14; H, 7.09.
Found: C, 59.21; H, 7.03.
P r ep a r a tion of Keton e 2e. Alcohol 16e was prepared in
a way similar to that of alcohol 16b using benzophenone (4.86
g, 27 mmol), trimethyl orthoformate (3.1 mL, 3.0 g, 28 mmol),
methanol (20 mL), TsOH‚H2O (0.02 g), alcohol 15 (6.18 g, 30
mmol), THF (150 mL), and 3 drops of 70% perchloric acid.
P r ep a r a tion of Keton e 3a . tert-Butyldimethylsilyl chlo-
ride (22.61 g, 150 mmol) was added to a mixture of alcohol 14
(36.32 g, 150 mmol), dimethylaminopropylamine (DMAP) (1.0
g), and imidazole (10.8 g, 150 mmol) in DMF (200 mL) at room
temperature. After being stirred overnight, the reaction
mixture was concentrated to give a residue which was treated
with ethyl acetate (400 mL). After filtration, the filtrate was
dried (Na2SO4) and concentrated to give alcohol 17 as a syrup.
The syrup was mixed with acetone (800 mL), 2,2-dimethoxy-
propane (70 mL, 57 mmol), CuSO4 (180 g), and concentrated
H2SO4 (2.8 g). After being stirred at room temperature for 40
min, the reaction mixture was neutralized with Et3N, filtered,
and concentrated. The resulting residue was dissolved in ethyl
acetate (300 mL), washed with brine, dried (Na2SO4), concen-
trated, and purified by flash chromatography (hexane:ether,
Alcohol 16e was obtained as a syrup (7.24 g, 67%). [R]25
)
D
-48.6 (c 1.2, CHCl3); IR 3445 cm-1; 1H NMR δ 7.50-7.56 (m,
4H), 7.20-7.36 (m, 6H), 4.35 (dd, J ) 6.9, 6.3 Hz, 1H), 4.23(d,
J ) 13.2 Hz, 1H), 4.15 (dd, J ) 6.3, 2.9 Hz, 1H), 4.02 (ddd, J
) 11.4, 11.4, 3.3 Hz, 1H), 3.92 (dd, J ) 13.2, 2.9 Hz, 1H), 3.80
(d, J ) 12.0 Hz, 1H), 3.75 (dd, J ) 11.4. 3.3 Hz, 1H), 3.66
(ddd, J ) 11.4, 11.4, 2.7 Hz, 1H), 3.58 (d, J ) 12.0 Hz, 1H),
3.57 (dd, J ) 11.4, 2.7 Hz, 1H), 3.43 (dd, J ) 7.2, 6.9 Hz, 1H),
2.37 (d, J ) 7.2 Hz, 1 H); 13C NMR δ 143.3, 142.7, 128.3, 128.2,
126.3, 126.2, 126.1, 109.6, 95.02, 77.42, 74.10, 71.01, 69.08,
65.68, 60.44, 59.78.