The Journal of Organic Chemistry
Note
δ C 208.0, 196.3, 150.2, 141.1; CH 129.4, 123.8, 59.2; CH2 42.4, 29.5,
27.2, 23.3; HRMS (CI) calcd for C13H14NO4 [M + H] 248.0923,
found 248.0927.
EXPERIMENTAL SECTION
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Swern Oxidation General Procedure (Entry 2, Table 1). To a
solution of DMSO (341 μL, 2.29 mmol) in CH2Cl2 (6.0 mL) at −78
°C was added (COCl)2 (99 μL, 1.15 mmol) dropwise. After 15 min, a
solution of β-hydroxyketone (216 mg, 0.956 mmol) in CH2Cl2 (0.37
mL) was added, and the mixture was stirred for 30 min. Et3N (718 μL,
5.16 mmol) was added, and the mixture was allowed to warm to rt.
The reaction mixture was diluted with hexanes (10 mL) and poured
into a separatory funnel containing saturated aqueous NaHCO3 (10
mL). The layers were separated, and the organic layer was washed with
additional NaHCO3 solution (3 × 10 mL). The combined aqueous
layers were extracted with EtOAc (3 × 10 mL). The combined organic
layers were washed with saturated aqueous NaCl, dried over MgSO4,
filtered, and concentrated to give the crude reaction mixture. This
mixture was purified by flash column chromatography (4:1 hexanes/
EtOAc) to give 2b (112 mg, 0.497 mmol, 52%).
Dess−Martin Oxidation General Procedure (Entry 2, Table
1). To a solution of β-hydroxyketone (23.5 mg, 0.104 mmol) in
CH2Cl2 (1.04 mL) at rt were sequentially added NaHCO3 (34.9 mg,
0.416 mmol) and the Dess−Martin periodinane (88.2 mg, 0.208
mmol). The reaction mixture was stirred until complete consumption
of the starting material was observed (TLC). The reaction mixture was
diluted with CH2Cl2 (5 mL) and poured into a separatory funnel
containing a 1:1 mixture of saturated aqueous NaHCO3 and saturated
aqueous Na2S2O3 (10 mL). The aqueous phase was extracted with
EtOAc (3 × 10 mL). The combined organic layers were washed with
saturated aqueous NaCl, dried over MgSO4, filtered, and concentrated
to give the crude reaction mixture. This mixture was purified by flash
column chromatography (4:1 hexanes/EtOAc) to give 2b (10 mg,
0.045 mmol, 42%).
5-Methyl-1-phenylhexane-1,3-dione. 2e: Rf 0.73 (4:1 hexanes/
EtOAc); IR (thin film) 3063, 2954, 1604 cm−1; (exists as the enol
tautomer) 1H NMR (400 MHz, CDCl3) δ 16.3 (br s, 1 H), 7.89 (d, J
= 8 Hz, 2 H), 7.51 (t, J = 7 Hz, 1 H), 7.44 (t, J = 8 Hz, 2 H), 6.16 (s, 1
H), 2.29 (d, J = 7 Hz, 2 H), 2.17 (sept, J = 6 Hz, 1 H), 1.00 (d, J = 6
Hz, 6 H); 13C NMR (175 MHz, CDCl3, HSQC) δ C 195.6, 184.2,
135.2; CH 132.2, 128.6, 127.0, 96.8, 26.5; CH2 48.2; CH3 22.6; HRMS
(CI) calcd for C13H17O2 [M + H] 205.1229, found 205.1226.
2-Chloro-1-phenylhexane-1,3-dione. 2f: Rf 0.50 (4:1 hexanes/
EtOAc); IR (thin film) 2965, 1723, 1686, 1596, 1449, 1288 cm−1
;
(exists as a 2.6:1 ratio of keto/enol tautomers; data is for the keto
1
tautomer) H NMR (400 MHz, CDCl3) δ 7.96 (d, J = 7 Hz, 2 H),
7.60 (t, J = 7 Hz, 1 H), 7.48 (m, 2 H), 5.61 (s, 1 H), 2.73 (m, 2 H),
1.61 (pent, J = 7 Hz, 2 H), 0.89 (t, J = 7 Hz, 3 H); 13C NMR (175
MHz, CDCl3, HSQC) δ C 200.8, 189.9, 133.7; CH 134.5, 129.4, 129.0,
64.4; CH2 40.9, 16.9; CH3 13.4; HRMS (CI) calcd for C12H14ClO2 [M
+ H] 225.0682, found 225.0679.
1-(4-Nitrophenyl)butane-1,3-dione. 2g: Rf 0.85 (2:1 hexanes/
EtOAc); IR (thin film) 3107, 1734, 1696, 1587, 1527, 1342; (exists as
1
the enol tautomer) H NMR (400 MHz, CDCl3) δ 15.9 (br s, 1 H),
8.29 (d, J = 9 Hz, 2 H), 8.02 (d, J = 9 Hz, 2 H), 6.23 (s, 1 H), 2.26 (s,
3 H); 13C NMR (175 MHz, CDCl3, HSQC) δ C 196.3, 179.0, 149.7,
140.3; CH 127.8, 123.8, 98.0; CH3 26.5; HRMS (CI) calcd for
C10H10NO4 [M + H] 208.0610, found 208.0608.
2-(4-Chlorobenzoyl)cyclohexanone. 2h: Rf 0.65 (2:1 hexanes/
EtOAc); IR (thin film) 2938, 1713, 1680, 1593, 1081; (exists as a 1.3:1
1
ratio of keto/enol tautomers; data is for the keto tautomer) H NMR
IBX Oxidation General Procedure (Entry 2, Table 1). To a
solution of β-hydroxyketone (100 mg, 0.442 mmol) in EtOAc (3.2
mL) at rt was added IBX (371 mg, 1.33 mmol). The reaction mixture
was heated to 77 °C until complete consumption of the starting
material was observed (TLC, approximately 3−12 h). The reaction
mixture was allowed to cool to rt, filtered through a small pad (1−2
cm) of silica, and concentrated to give pure 2b (98 mg, 0.438 mmol,
99%).
(700 MHz, CDCl3) δ 7.82 (d, J = 6 Hz, 2 H), 7.41 (d, J = 6 Hz, 2 H),
4.31 (ddd, J = 9, 6, 1 Hz, 1 H), 2.54−1.25 (m, 8 H); (data is for the
keto/enol mixture) 13C NMR (175 MHz, CDCl3, HSQC) δ C 208.5,
196.3, 189.94, 189.88, 139.7, 136.5, 135.7, 134.8, 107.02; CH 129.9,
129.1, 128.9,128.4, 58.8; CH2 42.3, 32.7, 29.8, 27.2, 26.4, 23.3, 23.1,
21.7; HRMS (CI) calcd for C13H14ClO2 [M + H] 237.0682, found
237.0680.
1-(2-Chlorophenyl)butane-1,3-dione. 2i: Rf 0.53 (4:1 hexanes/
EtOAc); IR (thin film) 3063, 1729, 1609, 1424, 1293; (exists as the
1-(4-(Benzyloxy)phenyl)-7-(3-bromo-4-methoxyphenyl)-
heptane-3,5-dione. 2a: Rf 0.45 (3:1 hexanes/EtOAc); IR (thin
film) 3025, 2921, 1728, 1717, 1603, 1249 cm−1; (exists as a 2:1 ratio of
1
enol tautomer) H NMR (700 MHz, CDCl3) δ 15.7 (br s, 1 H), 7.58
(dd, J = 8, 2 Hz, 1 H), 7.43 (dd, J = 8, 1 Hz, 1 H), 7.37 (td, J = 8, 2 Hz,
1 H), 7.33 (td, J = 8, 1 Hz, 1 H), 6.05 (s, 1 H), 2.19 (s, 3 H); 13C
NMR (175 MHz, CDCl3, HSQC, DEPT) δ C 192.8, 184.6, 135.5,
131.7; CH 131.6, 130.6, 130.0, 126.9, 101.9; CH3 25.5; HRMS (CI)
calcd for C10H10ClO2 [M + H] 197.0369, found 197.0364.
1
enol/keto tautomers; data is for the enol tautomer) H NMR (400
MHz, CDCl3) δ 15.4 (br s, 1H), 7.45−6.80 (m, 12 H), 5.42 (s, 1 H),
5.04 (s, 2 H), 3.86 (s, 3 H), 2.85 (m, 4 H), 2.56 (m, 4 H); (data is for
the keto/enol mixture) 13C NMR (100 MHz, CDCl3) δ C 203.2,
202.8, 193.0, 192.8, 157.2, 154.3, 137.1, 134.3, 134.1, 132.9, 132.7,
111.5; CH 133.0, 129.24, 129.20, 128.5, 128.3, 128.2, 127.9, 127.4,
114.9, 111.9, 99.7; CH2 69.9, 57.5, 45.3, 45.0, 40.1, 39.9, 30.7, 30.2,
28.5, 28.0; CH3 56.2; HRMS (CI) calcd for C27H27BrO4 [M+]
494.1093, found 494.1100.
4-Methyldodecane-3,5-dione. 2j: Rf 0.58 (6:1 hexanes/
EtOAc); IR (thin film) 2922, 1723, 1702, 1598, 1457; (exists as a
1
4.2:1 ratio of keto/enol tautomers; data is for the keto tautomer) H
NMR (700 MHz, CDCl3) δ 3.68 (q, J = 7 Hz, 1 H), 2.53−2.42 (m, 4
H), 1.30 (d, J = 7 Hz, 3 H), 1.29−1.21 (m, 10 H), 1.04 (t, J = 7 Hz, 3
H), 0.87 (m, 3 H); 13C NMR (175 MHz, CDCl3, HSQC) δ C 207.9,
207.5; CH 60.62; CH2 41.5, 34.7, 31.6, 29.0, 23.4, 22.6; CH3 14.1, 12.8,
7.6; HRMS (CI) calcd for C13H25O2 [M + H] 213.1855, found
213.1848.
1,3-Diphenylpropane-1,3-dione. 2b: Rf 0.71 (3:1 hexanes/
EtOAc); IR (thin film) 3058, 2922, 1593, 1527, 1478, 1299 cm−1
;
(exists as the enol tautomer) 1H NMR (700 MHz, CDCl3) δ 16.9 (br
s, 1 H), 8.00 (m, 4 H), 7.57 (t, J = 7 Hz, 2 H), 7.50 (t, J = 8 Hz, 4 H),
6.91 (s, 1 H); 13C NMR (175 MHz, CDCl3, HSQC) δ C 185.7, 135.4;
CH 132.4, 128.6, 127.1, 93.0; HRMS (CI) calcd for C15H13O2 [M +
H] 225.0916, found 225.0911.
5-Ethylnonane-4,6-dione. 2k: Rf 0.64 (4:1 hexanes/EtOAc); IR
(thin film) 2965, 1723, 1696, 1462 cm−1; (exists as a 10:1 ratio of
1
keto/enol tautomers; data is for the keto tautomer) H NMR (700
1-Phenylbutane-1,3-dione. 2c: Rf 0.65 (3:1 hexanes/EtOAc);
IR (thin film) 1602, 1276 cm−1; (exists as the enol tautomer) 1H
NMR (400 MHz, CDCl3) δ 16.2 (br s, 1 H), 7.86 (d, J = 8 Hz, 2 H),
7.49 (t, J = 7 Hz, 1 H), 7.42 (t, J = 7 Hz, 2 H), 6.16 (s, 1 H), 2.17 (s, 3
H); 13C NMR (175 MHz, CDCl3, HSQC) δ C 193.8, 183.3, 134.8;
CH 132.3, 128.6, 127.0, 96.7; CH3 25.9; HRMS (CI) calcd for
C10H11O2 [M + H] 163.0759, found 163.0755.
MHz, CDCl3) δ 3.55 (t, J = 7 Hz, 1 H), 2.42 (m, 4 H), 1.86 (pent, J =
7 Hz, 2 H), 1.57 (sext, J = 7 Hz, 4 H), 0.88 (t, J = 7 Hz, 6 H), 0.87 (t, J
= 7 Hz, 3 H); 13C NMR (175 MHz, CDCl3, HSQC) δ C 206.6; CH
69.6; CH2 43.8, 21.7, 16.8; CH3 13.6, 12.2; HRMS (CI) calcd for
C11H21O2 [M + H] 185.1542, found 185.1545.
2-Methyl-1-phenylhexane-1,3-dione. 2l: Rf 0.56 (4:1 hexanes/
EtOAc); IR (thin film) 3058, 2960, 1712, 1669, 1440 cm−1; (exists as
the keto tautomer) 1H NMR (400 MHz, CDCl3) δ 7.93 (d, J = 7 Hz, 2
H), 7.55 (t, J = 8 Hz, 1 H), 7.44 (t, J = 8 Hz, 2 H), 4.47 (q, J = 7 Hz, 1
H), 2.46 (dt, J = 17, 7 Hz, 1 H), 2.34 (dt, J = 17, 7 Hz, 1 H), 1.52 (m,
2 H), 1.40 (d, J = 7 Hz, 3 H), 0.80 (t, J = 7 Hz, 3 H); 13C NMR (100
MHz, CDCl3, HSQC) δ C 206.9, 197.3, 136.0; CH 133.5, 128.7, 128.5,
2-(4-Nitrobenzoyl)cyclohexanone. 2d: Rf 0.71 (2:1 hexanes/
EtOAc); IR (thin film) 3107, 2933, 2867, 1696, 1674, 1603, 1516,
1
1397, 1342 cm−1; (exists as the keto tautomer) H NMR (400 MHz,
CDCl3) δ 8.26 (d, J = 9 Hz, 2 H), 8.00 (d, J = 8 Hz, 2 H), 4.36 (dd, J =
10, 6 Hz, 1 H), 2.51 (app t, J = 6 Hz, 2 H), 2.34−2.14 (m, 2 H), 2.04
(m, 2 H), 1.91−1.71 (m, 2 H); 13C NMR (100 MHz, CDCl3, HSQC)
9854
dx.doi.org/10.1021/jo201810c|J. Org. Chem. 2011, 76, 9852−9855