Allylic Oxidations Catalyzed by Dirhodium Caprolactamate
under atmospheric conditions. All reagents were obtained from
commercial sources. Dirhodium(II) caprolactamate [Rh2(cap)4 ·
2CH3CN] was prepared as previously described.40 Silica gel plates
(0.25 mm, 60 F254) were used for analytical thin-layer chromatog-
raphy, and spots were visualized using 254 nm ultraviolet light
before using potassium permanganate, vanillin, or anisaldehyde
stains as visualizing agents. Chromatographic purifications were
performed using silica gel (60 µm, 40-63 mesh) according to the
method of Still.41 Yields reported are for isolated compounds
according to their mass unless otherwise noted. All products were
characterized and in agreement with those that were previously
described. 1H NMR (400 MHz) and 13C NMR (100 MHz) spectra
were obtained on a 400 MHz spectrometer as solutions in CDCl3
unless otherwise noted. Chemical shifts are reported in parts per
1-(1-tert-Butylperoxy)cyclohex-2-enyl)ethanoate (10): Rf 0.69
(20% EtOAc/hexanes); H NMR (400 MHz, CDCl3) δ 6.12 (ddd,
1
J ) 3.2, 4.4, 10.0 Hz, 1 H), 5.66 (ddd, J ) 2.0, 2.0, 10.0 Hz, 1 H),
2.31 (s, 3 H), 2.07-2.02 (comp, 2 H), 1.97-1.91 (comp, 2 H),
1.73-1.65 (comp, 2 H), 1.23 (s, 9 H); 13C NMR (100 MHz, CDCl3)
δ 210.0, 135.6, 123.0, 85.2, 79.7, 26.9, 26.6, 25.3, 24.4, 18.2; FTIR
(thin film) 2979, 2935, 2871, 1720, 1363, 1197, 735 cm-1; exact
mass calcd for C12H20O3 + H (ES) 213.1490, found 213.1115.
4-(tert-Butylperoxy)-4-ethanoylcyclohex-2-enone (11): Rf 0.37
1
(20% EtOAc/hexanes); H NMR (400 MHz, CDCl3) δ 6.99 (d, J
) 10.4 Hz, 1 H), 6.17 (d, J ) 10.4 Hz, 1 H), 2.57 (m, 1 H)
2.46-2.44 (comp, 2 H), 2.38 (s, 3 H), 2.27-2.22 (comp, 3 H),
1.25 (s, 9 H); 13C NMR (100 MHz, CDCl3) δ 207.6, 198.0, 145.2,
131.8, 84.4, 81.06, 33.3, 28.7, 26.4, 24.6; FTIR (thin film) 3056,
2980, 2937, 1720, 1688, 1365, 1192, 874, 737 cm-1; exact mass
calcd for C12H18O4 + H (ES) 227.1283, found 227.1288.
1-(6-tert-Butylperoxy)cyclohex-1-enyl)ethanoate (12): Rf 0.58
(20% EtOAc/hexanes); 1H NMR (400 MHz, CDCl3) δ 7.08 (dd, J
) 4.8, 2.8 Hz, 1 H), 5.00 (bs, 1 H), 2.40-2.38 (comp, 2 H), 2.35
(m, 1 H), 2.32 (s, 3 H), 2.20-2.17 (m, 1 H), 1.75-1.78 (m, 1 H),
1.63-1.66 (m, 1 H), 1.26 (s, 9 H); 13C NMR (100 MHz, CDCl3)
δ 198.0, 146.1, 136.2, 80.1, 72.1, 26.5, 26.3, 26.0, 25.4, 15.7; FTIR
(thin film) 3060, 2928, 2977, 1674, 1362, 1258, 1240, 1196, 736
cm-1; exact mass calcd for C12H20O3 + H (ES) 213.1490, found
213.1481.
1
million (ppm, δ) relative to internal Me4Si (δ 0.00) for H and
relative to internal chloroform (δ 77.0) for 13C; coupling constants
are reported in hertz (Hz).
General Procedure for the Oxidation of r,ꢀ-Unsaturated
Carbonyl Compounds. A 10 mL vial equipped with a stirbar was
charged with substrate (1.36 mmol) and Rh2(cap)4 (5 mg, 0.007
mmol). Solvent (2.5 mL) was added followed by the addition of
TBHP (0.75 mL, 5.5 mmol, 4 equiv). The vial was loosely capped
and stirred for 16 h, and then the second portion of Rh2(cap)4 (5
mg, 0.007 mmol) and TBHP (0.75 mL, 5.5 mmol, 4 equiv) was
added. After an additional 24 h, the solution was concentrated and
purified by column chromatography to obtain analytically pure
compounds whose spectral characteristics were identical to those
previously reported: trans-3-nonen-2,5-dione (1)11 and ethyl (E)-
4-oxo-2-decenoate (2).42 (E)-4-Oxo-2-pentenamide (5),43 4-andros-
ten-17ꢀ-3,6-dione (25),44 17ꢀ-acetoxyandrost-4-en-3,6-dione (26),45
4-androstene-3,6,17-trione (27),46 4-cholesten-3,6-dione (28),47 and
acids were purified by recrystallization in ethyl acetate and matched
with those in the literature: (E)-4-oxo-2-nonenoic acid (3),25a (E)-
4-oxo-2-pentenoic acid (4),48 2-cyclohexenone-1-carboxylic acid
(7),49 and fumaric acid monomethyl ester (8).50
1-(3-tert-Butylperoxy)cyclohex-1-enyl)ethanoate (13): Rf 0.62
(20% EtOAc/hexanes); 1H NMR (400 MHz, CDCl3) δ 6.86 (t, J )
1.5 Hz, 1 H), 4.63 (bs, 1 H), 2.34 (s, 3 H), 2.25-2.19 (comp, 2 H),
1.87-1.70 (comp, 3 H), 1.63-1.61 (m, 1 H), 1.28 (s, 9 H); 13C
NMR (100 MHz, CDCl3) d 199.7, 142.3, 136.3, 80.4, 77.4, 26.4,
26.3, 25.6, 23.3, 18.9; FTIR (thin film) 3055, 2980, 2930, 1672,
1265, 1235, 734 cm-1; exact mass calcd for C12H20O3 (CI)
214.1412, found 214.1481.
4-(tert-Butylperoxy)-3-ethanoylcyclohex-2-enone (18): Rf 0.33
1
(20% EtOAc/hexanes); H NMR (400 MHz, CDCl3) δ 6.53 (s, 1
Oxidation of 1-Acetylcyclohexene: Isolation and Character-
ization of 10-13 and 18. 1-Acetylcyclohexene (0.750 g, 6.04
mmol) and Rh2(cap)4 (22 mg, 0.030 mmol) were dissolved in 22
mL of 1,2-dichloroethane in a 100 mL round-bottom flask.
T-HYDRO (3.31 mL, 24.1 mmol) was slowly added (1 mL/min),
and the color of the reaction solution turned from purple to brown-
red in color. The flask was capped with a rubber septum, vented
with a 18-gauge needle, and heated at 40 °C in an oil bath. After
17.5 h, the reaction was concentrated under reduced pressure to
yield 2.11 g of a red-brown oil. The oil was purified via silica gel
column chromatography (100% hexanes to 2:1 hexanes/ethyl
acetate, gradient). Only the purest fractions were used for full
characterization: 55 mg of 10, 20 mg of 11, 18 mg of 12, 32 mg
of 13, 20 mg of 16, and 312 mg of 3-acetyl-2-cyclohexenone (9).
H), 5.16 (t, J ) 3.2 Hz, 1 H), 2.81 (ddd, J ) 5.2, 12.8, 17.6 Hz, 1
H), 2.62-2.60 (m, 1 H), 2.47-2.45 (m, 1 H), 2.44 (s, 3 H), 2.00
(m, 1 H), 1.23 (s, 9 H); 13C NMR (100 MHz, CDCl3) δ 200.7,
198.9, 149.4, 133.6, 81.0, 71.41, 32.9, 26.8, 26.3, 25.7; FTIR (thin
film) 2982, 2937, 2253, 1685, 1365, 1222, 1191, 907, 736 cm-1
;
exact mass calcd for C12H18O4 + H (ES) 227.1283, found 227.1259.
Oxidation of Cholesterol (19): Isolation of 22-24. Cholesterol
(0.525 g; 1.36 mmol) and Rh2(cap)4 (10 mg; 0.013 mmol) were
dissolved in 5 mL of 1,2-dichloroethane in a 6 dram vial equipped
with a stirbar. T-HYDRO (0.74 mL, 5.43 mmol) was added, and
the color of the reaction solution turned from purple to brown-red
in color. The vial was loosely capped and stirred at room
temperature. After 15 h, the reaction was concentrated under
reduced pressure to 1.01 g of a red-brown semisolid. The crude
material was purified via silica gel column chromatography (100%
hexanes to 1:1 hexanes/ethyl acetate, gradient) to afford 164 mg
of 22, 62 mg of R-23, 13 mg of ꢀ-23, 57 mg of R-24, 25 mg of
ꢀ-24, and 106 mg of starting material (21). The full characterization
of 22-24 has been reported.10,38a
Oxidation of 17ꢀ-Acetoxyandrost-4-en-3-one in Water. 17ꢀ-
Acetoxyandrost-4-en-3-one51 (1.32 g, 4.0 mmol) was stirred
vigorously in 12 mL of water at room temperature in a 50 mL
flask. Then Rh2(cap)4 (29.5 mg, 0.040 mmol) was added, followed
by addition of T-HYDRO (4.6 mL, 32 mmol). The reaction became
dark purple-red in color. The flask was closed with a rubber septum
with a balloon and stirred for 24 h in a 40 °C oil bath. At that
time, additional portions of Rh2(cap)4 (15 mg, 0.02 mmol) and
T-HYDRO (2.3 mL, 16 mmol) were added, and the reaction
solution was stirred for another 24 h. The reaction was extracted
into diethyl ether (3 × 20 mL). The organic extracts were combined,
dried over anhydrous MgSO4, filtered, and then concentrated under
(36) (a) Arsenou, E. S.; Koutsourea, A. I.; Fousteris, M. A.; Nikolaropoulos,
S. S. Steroids 2003, 68, 407.
(37) Schenck, G. O.; Neumu¨ller, O. A.; Eisfeld, W. Justus Liebigs Ann. Chem.
1958, 618, 202.
(38) (a) Beckwith, A. L. J.; Davies, A. G.; Davison, I. G. E.; Maccoll, A.;
Mruzek, M. H. J. Chem. Soc., Perkin Trans. 2 1989, 815. (b) Dang, H.; Davies,
A. G.; Davison, I. G. E.; Schiesser, C. H. J. Org. Chem. 1990, 55, 1432. (c)
Ponce, M. A.; Ramirez, J. A.; Galagovsky, L. R.; Gros, E. G.; Erra-Balsells, R.
J. Chem. Soc., Perkin Trans. 2 2000, 2351.
(39) Miyamoto, S.; Martinez, G. R.; Medeiros, M. H. G.; Di Mascio, P. J. Am.
Chem. Soc. 2003, 125, 6172.
(40) Doyle, M. P.; Westrum, L. J.; Wolthuis, W. N. E.; See, M. M.; Boone,
W. P.; Bagheri, V.; Pearson, M. M. J. Am. Chem. Soc. 1993, 115, 958.
(41) Still, W. C.; Kahn, M.; Mitra, A. J. J. Org. Chem. 1978, 43, 2923.
(42) Manfredini, S.; Simoni, D.; Zanirato, V.; Casolari, A. Tetrahedron Lett.
1988, 29, 3997.
(43) Scheffold, R.; Dulos, P. HelV. Chim. Acta 1967, 50, 798–807.
(44) Jasiczak, J. J. Chem. Soc., Perkin Trans. 1 1988, 10, 2687.
(45) Marwah, P.; Marwah, A.; Lardy, H. A. Green Chem. 2004, 570.
(46) Kiran, I. J. Chem. Res. 2004, 3, 208.
(47) Hunter, C. A.; Priest, S.-M. Steroids 2006, 71, 30.
(48) Lu¨o¨nd, R. M.; Walker, J.; Neier, R. W. J. Org. Chem. 1992, 57, 5005.
(49) Webster, F. X.; Silverstein, R. M. Synthesis 1987, 10, 922.
(50) Davis, R. A. J. Nat. Prod. 2005, 68, 769.
(51) 17ꢀ-Acetoxyandrost-4-en-3-one was prepared according to: Krauser,
J. A.; Guengerich, F. P. J. Biol. Chem. 2005, 280, 19496.
J. Org. Chem. Vol. 74, No. 2, 2009 737