The Journal of Organic Chemistry
Note
The reaction was completed in 2 h. The residue was purified using
silica gel chromatography (hexane/ethyl acetate, v/v, 5/1) (489 mg,
85%); 1H NMR (300 MHz; CDCl3; Me4Si) δ 1.17 (d, J = 6.3 Hz, 3H),
2.53 (m, 2H), 2.76 (t, J = 7.3 Hz, 2H), 2.89 (t, J = 7.3 Hz, 2H), 3.07
(br s, 1H), 4.22 (m, 1H), 7.24 (m, 5H); 13C NMR (75 MHz; CDCl3;
Me4Si) δ 22.4, 29.4, 44.9, 50.8, 63.8, 126.2, 128.2 (2C), 128.5 (2C),
140.7, 210.9; HRMS (ESI-Orbitrap) m/z [M + H]+ calcd for
C12H17O2 193.1228, found 193.1223.
General Jones Oxidation for the Synthesis of Methyl 3-Oxo-
3-phenylpropionate (7), tert-Butyl 3-Oxopent-4-enoate (8),
and 6-Phenylhexane-2,4-dione (15).44 A 1 mmol portion of the
corresponding hydroxy ester or hydroxy ketone (methyl 3-hydroxy-3-
phenylpropanoate, tert-butyl 3-hydroxy-pent-4-enoate, and 5-hydroxy-
1-phenylhexan-3-one, respectively) was dissolved in 5 mL of acetone.
The mixture was cooled in an ice bath and Jones reagent (1.08 mmol,
360 μL, dissolved in 1 mL acetone) was added dropwise. After the
addition of the Jones reagent, the reaction mixture was allowed to
warm slowly to room temperature. After the completion of the
reaction, which was observed by TLC analysis, 2-propanol (2.65
mmol, 200 μL) was added to quench the excess of Jones reagent. Then
a solution of sodium phosphate buffer pH 8 (6 mL, 200 mM) was
added and the mixture was extracted with diethyl ether (2 × 10 mL).
The combined organic layers were dried over anhydrous MgSO4 and
evaporated to dryness. No purification was needed.
dryness. (15 g, 60%); 1H NMR (300 MHz; CDCl3; Me4Si) δ 1.27 (t, J
= 7.1 Hz, 3H), 3.35 (s, 2H), 3.80 (d, JP−H = 24.9 Hz, 1H), 4.20 (q, 2H,
J = 7.1 Hz), 7.5 (m, 15H); 13C NMR (75 MHz; CDCl3; Me4Si) δ 14.2
(2C), 48.3, 48.5, 51.5, 53.0, 60.4 (2C), 126.0 (2C), 127.2 (2C), 128.7
(2C), 128.9 (2C), 132.1 (4C), 133.0 (2C), 133.2 (2C), 170.7 (2C),
184.00 (2C).
B. Wittig Olefination of Ethyl 3-Oxo-4-(triphenylphosphoranyli-
dene) Butanoate with Benzaldehyde. A 2 mmol portion of ethyl 3-
oxo-4-(triphenylphosphoranylidene) butanoate (780 mg) and 4 mmol
of benzaldehyde (407 μL) were added in dry THF (10 mL), and the
mixture was left overnight to reflux. After the completion of the
reaction, most of the solvent was evaporated, and hexane (3 mL) was
added to precipitate phosphine oxides, which were removed by
filtration through a silica pad. The silica pad was washed with hexane/
ethyl acetate (2/1) mixture (6 mL), and the organic layer was
evaporated to dryness. The residue was purified using silica gel flash
chromatography (hexane/ethyl acetate, v/v, 70/1). The product
appeared as a mixture of keto−enol forms in a 1.5/1 ratio. (196 mg,
45%). Keto form: 1H NMR (300 MHz; CDCl3; Me4Si) δ 1.26 (t, 3H),
3.70 (s, 2H), 4.22 (q, 2H), 6.81 (d, J = 15.9 Hz, 1H), 7.34 (m, 6H);
1
enol form: H NMR (300 MHz; CDCl3; Me4Si) δ 1.26 (t, 3H), 4.22
(q, 2H), 5.17 (s, 1H), 6.43 (d, J = 10.5 Hz, 1H), 7.34 (m, 6H), 12.00
(s, 1H); 13C NMR of keto−enol mixture (75 MHz; CDCl3; Me4Si) δ
14.1, 14.2, 47.6, 60.2, 61.4, 91.9, 121.9, 125.2, 127.5 (2C), 128.5 (2C),
128.8 (2C), 129.0 (2C), 129.3, 130.9, 134.1, 135.3, 136.7, 144.5, 167.3,
169.2, 172.8, 191.9; HRMS (ESI-Orbitrap) m/z [M + H]+ calcd for
C13H15O3 219.1021, found 219.1012.
Methyl 3-Oxo-3-phenylpropionate (7). Methyl 3-hydroxy-3-
phenylpropanoate (1 mmol, 178 mg) and Jones reagent (360 μL)
were used according to the general procedure. The reaction was
completed in 1 h. The product appeared as a mixture of keto−enol
forms in a 4/1 ratio. (175 mg, 98%); keto form: 1H NMR (300 MHz;
CDCl3; Me4Si) δ 3.74 (s, 3H), 4.00 (s, 2H), 7.45 (m, 2H), 7.59 (dd, J
= 8.4, 7.3 Hz, 1H), 7.92 (d, J = 8.4 Hz, 2H); 13C NMR (75 MHz;
CDCl3; Me4Si) δ 45.7, 52.5, 128.50 (2C), 128.53, 128.79 (2C), 131.3,
tert-Butyl 3-(Oxiran-2-yl)-3-oxopropanoate (10).47 tert-Butyl-
3-oxo-pentenoate (1 mmol, 170 mg), hydrogen peroxide (3 mmol,
830 μL 30% solution), and L-arginine (0.2 mmol, 35 mg) were
dissolved in 2 mL of absolute MeOH, and 2 mL of distilled water was
added. The reaction mixture was stirred for 5 h at rt. After the
reaction’s completion brine solution and diethyl ether were added.
The mixture was stirred vigorously for 30 min. The aqueous layer was
extracted with diethyl ether, and the combined organic phases were
evaporated to dryness. The residue was purified using silica gel
chromatography (hexane/ethyl acetate, v/v, 15/1). The product
appeared as a mixture of keto−enol forms in a 4/1 ratio (120 mg,
65%). Keto form: 1H NMR (300 MHz; CDCl3; Me4Si) δ 1.47 (s, 9H),
2.95 (m, 1H), 3.02−3.06 (m, 1H), 3.30 (s, 2H), 3.51 (m, 1H); enol
1
167.9, 192.4; enol form: H NMR (300 MHz; CDCl3; Me4Si) δ 3,79
(s, 3H), 5.67 (s, 1H), 7.45 (m, 2H), 7.59 (dd, J = 8.4, 7.3 Hz, 1H),
7.76 (d, J = 8.2 Hz, 2H), 12.50 (s, 1H); 13C NMR (75 MHz; CDCl3;
Me4Si) δ 51.4, 87.0, 126.1 (2C), 130.1, 133.8 (2C), 135.9, 171.5,
173.5; HRMS (ESI-Orbitrap) m/z [M + H]+ calcd for C10H11O3
179.0703, found 179.0700.
tert-Butyl 3-Oxopent-4-enoate (8). tert-Butyl 3-hydroxy-pent-4-
enoate (1 mmol, 172 mg) and Jones reagent (360 μL) were used
according to the general procedure. The reaction was completed in 1
h. The product appeared as a mixture of keto−enol forms in a 1/1
ratio. (165 mg, 97%); keto form: 1H NMR (300 MHz; CDCl3; Me4Si)
δ 1.44 (s, 9H), 3.51 (s, 2H), 5.90 (d, J = 11.2 Hz, 1H), 6.23 (d, J =
17.6 Hz, 1H), 6.37 (dd, J = 17.6, 11.2 Hz, 1H); 13C NMR (75 MHz;
CDCl3; Me4Si) δ 28.2, 47.8, 81.1, 121.8, 135.8, 168.1, 193.0; enol
form: 1H NMR (300 MHz; CDCl3; Me4Si): 1.47 (s, 9H), 4.96 (s, 1H),
5.47 (dd, J = 6.1, 5.9 Hz, 1H), 6.04 (d, J = 5.9 Hz, 2H), 11.91 (s, 1H);
13C NMR (75 MHz; CDCl3; Me4Si) 27.9 (3C), 81.9, 93.4, 129.7,
131.4, 166.3, 172.5; HRMS (ESI-Orbitrap) m/z [M + H]+ calcd for
C9H15O3 171.1021, found 171.1012.
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form: H NMR (300 MHz; CDCl3; Me4Si) δ 1.49 (s, 9H), 2.95 (m,
1H), 3.02−3.06 (m, 1H), 3.30 (m, 1H), 5.18 (s, 1H,), 12.08 (s, 1H);
13C NMR of keto−enol mixture (75 MHz; CDCl3; Me4Si) δ 27.9,
28.2, 29.7, 44.5, 46.0, 47.5, 49.6, 53.5, 82.4, 91.6, 165.6, 200.4; HRMS
(ESI-Orbitrap) m/z [M + H]+ calcd for C9H15O4 187.0965, found
187.0969.
General Procedure for the Oxidative Cleavage of the
Corresponding 1,3-Diketones and β-Keto Esters. A 1 mmol
portion (except in the case of compound 10 where 0.56 mmol was
used) of the corresponding 1,3-diketone or β-keto ester (20 mM) was
dissolved in 50 mL of distilled water. Oxone (2.1−4.6 equiv) and
AlCl3 (1.0−6.4 equiv) were added, and the mixture was stirred at room
temperature for 5 min to 24 h. The reaction was monitored by TLC.
After completion of the reaction, a saturated solution of Rochelle salt
(5 mL) was added. The mixture was extracted with diethyl ether. The
combined organic layers were dried over anhydrous MgSO4 and
evaporated to dryness. Further purification was achieved using flash
column chromatography (silica gel, hexane/ethyl acetate, v/v, 15:1).
tert-Butyl 2-Oxopropanoate (1a). tert-Butyl acetoacetate (1
mmol, 144 mg, 20 mM), Oxone (2.1 mmol, 1.291 g), and AlCl3 (2.3
mmol, 306 mg) were used according to the general procedure. The
6-Phenylhexane-2,4-dione (15). 5-Hydroxy-1-phenylhexan-3-
one (1 mmol, 192 mg) and Jones reagent (360 μL) were used. The
1
reaction was completed in 1 h. (185 mg, 97%); H NMR (300 MHz;
CDCl3; Me4Si) δ 2.05 (s, 3H), 2.62 (dd, J = 7.9, 7.4 Hz, 2H), 2.95 (dd,
J = 7.9, 7.4 Hz, 2H), 5.49 (s, 1H), 7.25 (m, 5H); 13C NMR (75 MHz;
CDCl3; Me4Si) δ 24.6, 31.3, 39.8, 99.8, 126.0, 128.1 (2C), 128.3 (2C),
140.5, 190.8, 193.1; HRMS (ESI-Orbitrap) m/z [M + H]+ calcd for
C12H15O2 191.1072, found 191.1064.
Ethyl 3-Oxo-5-phenylpent-4-enoate (9).45,46 A. Preparation of
Ylide Ethyl 3-Oxo-4-(triphenylphosphoranylidene) Butanoate. For
the synthesis of the stabilized ylide ethyl 3-oxo-4-(triphenylphosphor-
anylidene) butanoate, triphenyl phosphine (63.6 mmol, 16.7 g) and
ethyl 4-chloro-3-oxobutanoate (70 mmol, 9.46 mL) in 50 mL toluene
were stirred for 24 h at 50 °C. The solid product was washed with
toluene and then distilled water was added until the solid is dissolved.
The mixture was extracted with two portions of diethyl ether.
Saturated NaHCO3 was added to the aqueous phase until pH 8. The
solid product was filtrated through a Buchner funnel, washed twice
with distilled water and twice with diethyl ether and evaporated to
1
reaction was completed in 10 min (139 mg, 93%); H NMR (300
MHz; CDCl3; Me4Si) δ 1.51 (s, 9H), 2.44 (s, 3H); 13C NMR (75
MHz; CDCl3; Me4Si) δ 23.6, 27.5 (3C), 86.4, 161.8, 191.3; HRMS
(ESI-Orbitrap) m/z [M + H]+ calcd for C7H13O3 145.0864, found
145.0857.
Ethyl 2-Oxopropanoate (2a). Ethyl acetoacetate (1 mmol, 130
mg, 20 mM), Oxone (2.1 mmol, 1.291 g), and AlCl3 (2.3 mmol, 306
mg) were used according to the general procedure. The reaction was
1
completed in 10 min (114 mg, 98%); H NMR (300 MHz; CDCl3;
D
dx.doi.org/10.1021/jo4009047 | J. Org. Chem. XXXX, XXX, XXX−XXX