The Journal of Organic Chemistry
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chromatography were unsuccessful, in part due to further decom-
position. A slightly higher yield of 69% of a similar mixture of the two
products was obtained when the procedure was repeated with 10 mol
% of catalyst 4a.
Preparation of Dimeric Hemiaminal 18. Hemiaminal 18 was
prepared as described above from 1-morpholinocyclohexene, except
that after the oxidation and removal of the solvent, the crude mixture
was flash chromatographed over silica gel (ethyl acetate/hexanes, 2:1)
and the product was isolated as a white solid, consisting of two isomers
in the ratio of 70:30 in a combined yield of 91%: IR (KBr) 2965, 2933,
The other epoxides listed in Table 5 were prepared similarly, except
that the yields are reported on products that were isolated by flash
chromatography over silica gel (ethyl acetate−hexanes). Their NMR
spectra are provided in the Supporting Information. All of the epoxides
are known compounds with spectra matching those reported in the
literature.
1
2849, 1202, 1121, 1020 cm−1; H NMR (300 MHz, CDCl3) major
isomer: δ 4.11 (s, 2 H), 3.67 (t, J = 4.9 Hz, 8 H), 2.90−2.70 (m, 8 H),
2.39−2.26 (m, 2 H), 1.90−1.65 (m, 2 H), 1.60−1.33 (m, 12 H);
minor isomer: δ 4.36 (s, 2 H); 13C NMR (100 MHz, CDCl3) major
isomer: δ 87.4, 67.8, 66.9, 44.8, 28.6, 25.0, 22.5, 20.6; minor isomer: δ
89.6, 67.6, 66.1, 45.2, 30.6, 27.2, 22.1, 20.3; mass spectrum, m/z (ESI)
389.2 (M+ + Na); exact mass calcd for C20H35N2O4 367.2591 (M+ +
H), found 367.2586. Recrystallization from THF afforded the major
isomer 18a, mp 180−182 °C (dec), which was subjected to X-ray
diffraction (see the Supporting Information).
1,2-Epoxycyclohexane (12b).49 1H NMR (400 MHz, CDCl3) δ
3.12 (m, 2 H), 1.98−1.92 (m, 2 H), 1.85−1.78 (m, 2 H), 1.47−1.41
(m, 2 H), 1.27−1.19 (m, 2 H); 13C NMR (100 MHz, CDCl3) δ 52.1,
24.4, 19.4.
1,2-Epoxyoctane (12c).49 1H NMR (400 MHz, CDCl3) δ 2.94−
2.89 (m, 1 H), 2.75 (dd, J = 5.0, 4.4 Hz, 1 H), 2.47 (dd, J = 5.0, 2.8 Hz,
1 H), 1.55−1.29 (m, 10 H), 0.90 (t, J = 6.8 Hz, 3 H); 13C NMR (100
MHz, CDCl3) δ 52.4, 47.1, 32.5, 31.8, 29.1, 25.9, 22.6, 14.0.
5,6-Epoxyhexan-1-ol (12d).50 1H NMR (400 MHz, CDCl3) δ
4.03−4.00 (m, 1 H), 3.59−3.43 (m, 4 H), 2.25 (br s, 1 H), 1.88−1.83
(m, 1 H), 1.57−1.40 (m, 1 H), 1.45−1.25 (m, 1 H); 13C NMR (100
MHz, CDCl3) δ 78.2, 68.3, 66.4, 27.4, 26.0, 22.9.
α-Hydroxycycloheptanone (22).56 1H NMR (300 MHz,
CDCl3) δ 4.29 (dd, J = 9.6, 3.6 Hz, 1 H), 3.78 (br s, 1 H), 2.60−
2.75 (m, 1 H), 2.45 (ddd, J = 17.4, 11.0, 3.5 Hz, 1 H), 1.96−2.09 (m, 1
H), 1.48−1.94 (m, 5 H), 1.18−1.40 (m, 2 H); 13C NMR (100 MHz,
CDCl3) δ 213.9, 77.2, 40.2, 34.0, 29.7, 26.8, 23.6.
α-Hydroxycyclooctanone (23).56 1H NMR (400 MHz, CDCl3)
δ 4.18 (d, J = 6.4 Hz, 1 H), 3.72 (br s, 1 H), 2.71 (td, J = 12.2, 3.8 Hz,
1 H), 2.44−2.29 (m, 2 H), 2.08−1.91 (m, 2 H), 1.87−1.62 (m, 4 H),
1.45−1.32 (m, 2 H), 0.98−0.84 (m, 1 H); 13C NMR (100 MHz,
CDCl3) δ 217.4, 76.2, 37.3, 29.2, 28.7, 25.5, 24.5, 22.1.
trans-2,3-Epoxyhexan-1-ol (12e).51 1H NMR (400 MHz,
CDCl3) δ 3.92 (d, J = 12.4 Hz, 1 H), 3.63 (dt, J = 12.5, 5.0 Hz, 1
H), 2.99−2.92 (m, 2 H), 1.79 (br s, 1 H), 1.60−1.40 (m, 4 H), 0.97 (t,
J = 7.2 Hz, 3 H); 13C NMR (100 MHz, CDCl3) δ 61.7, 58.4, 55.8,
33.6, 19.2, 13.7.
α-Hydroxyacetophenone (24).57 1H NMR (300 MHz, CDCl3)
δ 7.96 (d, J = 8.6 Hz, 2 H), 7.67 (t, J = 7.5 Hz, 1 H), 7.54 (t, J = 7.5
Hz, 2 H), 4.91 (d, J = 4.7 Hz, 2 H), 3.53 (t, J = 4.7 Hz, 1 H); 13C
NMR (100 MHz, CDCl3) δ 198.4, 134.3, 133.4, 129.0, 127.7, 65.5.
2-Hydroxy-1-phenyl-1-propanone (25).58 1H NMR (400 MHz,
CDCl3) δ 7.96−7.93 (m, 2 H), 7.64 (tt, J = 7.4, 1.3 Hz, 1 H), 7.52 (m,
2 H), 5.21−5.13 (m, 1 H), 3.78 (d, J = 6.3 Hz, 1 H), 1.47 (d, J = 7.1
Hz, 3 H); 13C NMR (100 MHz, CDCl3) δ 202.4, 134.0, 133.4, 128.9,
128.7, 69.3, 22.3.
cis-2,3-Epoxyhexan-1-ol (12f).51 1H NMR (400 MHz, CDCl3) δ
3.87 (dd, J = 12.1, 4.0 Hz, 1 H), 3.69 (dd, J = 12.1, 7.0 Hz, 1 H), 3.17
(dt, J = 6.9, 4.3, 1 H), 3.07−3.05 (m, 1 H), 1.75 (br s, 1 H), 1.57−1.45
(m, 4 H), 0.95 (t, J = 7.0 Hz, 3 H); 13C NMR (100 MHz, CDCl3) δ
61.0, 57.2, 56.7, 29.9, 19.9, 13.9.
6,7-Epoxycitronellyl Acetate (12g).52 1H NMR (400 MHz,
CDCl3) δ 4.04−4.17 (m, 2 H), 2.69 (t, J = 6.2 Hz, 1 H), 2.04 (s, 3 H),
1.34−1.75 (m, 7 H), 1.31 (s, 3 H), 1.26 (s, 3 H), 0.93 (d, J = 4.9 Hz, 3
H); 13C NMR (100 MHz, CDCl3) δ 171.0, 64.4, 64.3, 62.70, 62.67,
58.2, 58.1, 35.4, 35.2, 33.5, 33.4, 29.7, 29.6, 26.3, 26.2, 24.8, 20.9, 19.3,
19.2, 18.6, 18.6.
Preparation of α-Morpholinocyclopentanone (32).59 The
oxidation of 1-morpholinocyclopentene was carried out as in the
preparation of 19, except that after the oxidation was complete, the
solvent was evaporated and the crude mixture was chromatographed
1,2-Epoxyindane53 (12h) and 2-Indanone.54 Ratio of epox-
1
ide:ketone = 74:26. 1,2-Epoxyindane: H NMR (400 MHz, CDCl3) δ
7.53 (d, J = 7.4 Hz, 1 H), 7.35−7.15 (m, 3 H), 4.28 (dd, J = 2.8, 1.2
Hz, 1 H), 4.15 (t, J = 2.9 Hz, 1 H), 3.23 (d, J = 17.6 Hz, 1 H), 3.00
(dd, J = 17.6, 2.8 Hz); 13C NMR (100 MHz, CDCl3) δ 143.5, 140.9,
128.5, 126.2, 126.1, 125.0, 59.1, 57.6, 34.6. 2-Indanone: 1H NMR (400
MHz, CDCl3) δ 7.35−7.15 (m, 4 H), 3.52 (s, 4 H); 13C NMR (100
MHz, CDCl3) δ 212.9, 137.8, 127.4, 125.2, 44.1.
1
over silica gel (ethyl acetate/hexanes, 3:1), affording 79% of 32: H
NMR (300 MHz, CDCl3) δ 3.74 (t, J = 4.7 Hz, 4 H,), 3.71−3.58 (m, 1
H), 3.03−2.94 (m, 1 H), 2.84−2.73 (m, 2 H), 2.56−2.46 (m, 2 H),
2.39−1.65 (m, 5 H); 13C NMR (100 MHz, CDCl3) δ 216.4, 71.1,
67.1, 50.6, 37.3, 24.4, 18.2; mass spectrum (CI), m/z (relative
intensity) 170 (M+ + H, 20), 168 (100), 133 (10), 119 (10).
Preparation of Dimeric Hemiaminal 33. The oxidation of 1-
morpholino-2-phenylethylene was carried out as described for the
preparation of 18, except that after the oxidation and removal of the
solvent, the crude mixture was recrystallized from ethyl acetate,
affording a 91% yield of the product as a white solid, mp 197−199 °C
(dec) in the form of a single diastereomer: IR (KBr) 2968, 2880, 2849,
1450, 1118, 1055 cm−1; 1H NMR (300 MHz, CDCl3) δ 7.46 (dd, J =
7.9, 1.5 Hz, 4 H), 7.42−7.32 (m, 6 H), 4.81 (d, J = 8.7 Hz, 2 H), 4.06
(d, J = 8.7 Hz, 2 H), 3.60 (m, 8 H), 3.03 (m, 4 H), 2.70 (m, 4 H); 13C
NMR (100 MHz, CDCl3) δ 138.7, 127.9, 127.8, 127.2, 95.2, 77.0, 67.1,
48.7; mass spectrum (ESI), m/z (relative intensity) 449 (M+ + K, 5),
433 (M+ + Na, 50), 411 (M+ + H, 5); exact mass calcd for
C24H31N2O4 (M+ + H) 411.2278, found 411.2274.
trans-Stilbene Oxide (12i).48 1H NMR (400 MHz, CDCl3) δ
7.43−7.38 (m, 10 H), 3.92 (s, 2 H); 13C NMR (100 MHz, CDCl3) δ
137.2, 128.6, 128.4, 125.6, 62.9.
Typical Procedure for the Oxidation of Enamines (Table 6,
entry 1). Preparation of α-Hydroxycyclohexanone (19).55
Catalyst 4a (3.0 mg, 0.015 mmol) was dissolved in 10 mL of 4:1
dichloromethane/methanol containing 500 mg of crushed anhydrous
CaSO4 (500 mg) and 20 mg of K2CO3. Hydrogen peroxide (30%, 0.36
mmol) was added, and the mixture was stirred for 30 min. 1-
Morpholinocyclohexene (50 mg, 0.30 mmol) was added, and stirring
was continued for 4 h, after which the mixture was filtered and the
solvent removed in vacuo. The crude residue was stirred for 2 h at
room temperature in 5 mL of 1 M HCl prior to extraction with
dichloromethane and purification by flash chromatography over silica
1
gel (ethyl acetate−hexanes) to afford 32 mg (94%) of 19: H NMR
(300 MHz, CDCl3) δ 4.13 (ddd, J = 12.5, 6.9, 1.3 Hz, 1 H), 3.25 (br s,
1 H,), 2.61−2.31 (m, 3 H); 2.17−2.07 (m, 1 H), 1.95−1.85 (m, 1 H),
1.81−1.43 (3 H); 13C NMR (100 MHz, CDCl3) δ 211.4, 75.3, 39.5,
36.7, 27.6, 23.4.
The yields of the other α-hydroxy ketones that were prepared in this
manner are listed in Table 6, and their NMR spectra are provided in
the Supporting Information. All of the products are known
compounds with spectra matching those reported in the literature.
ASSOCIATED CONTENT
■
S
* Supporting Information
1H and 13C NMR spectra of final products; 77Se NMR spectra
of 4a with H2O2 and/or TFA; X-ray crystallographic data for
18a in CIF format. This material is available free of charge via
3515
dx.doi.org/10.1021/jo300313v | J. Org. Chem. 2012, 77, 3508−3517