The Journal of Organic Chemistry
Article
mmol) following the standard α-fluorination procedure. The
diastereoselectivity (dr 98:2) was determined by 1H NMR of the
crude reaction mixture. The residue was purified by column
chromatography (silica, 15% ethyl acetate in hexanes−25% ethyl
acetate in hexanes) to afford the product as a white solid (84 mg, 0.34
(ESI+TOF) m/z calcd for C17H22FNO3Na [M + Na]+ 330.1481,
found 330.1485.
Table 3, Entry 3i. The title compound was prepared from (S)-3-(3-
(2-chlorophenyl)propanoyl)-4-isopropyl-5,5-dimethyloxazolidin-2-one
(0.162 g, 0.50 mmol) following the standard α-fluorination procedure.
1
mmol, 67%, single diastereomer): [α]2D6 +38.40 (c 0.7, CHCl3); H
1
The diastereoselectivity (dr 96:4) was determined by H NMR of the
crude reaction mixture. The residue was purified by column
chromatography (silica, 12% diethyl ether in toluene−15% diethyl
ether in toluene) to afford the product as a colorless oil (0.133 g, 0.39
NMR (600 MHz, CDCl3) δ 7.45 (d, J = 51.6 Hz, 1H), 4.08 (d, J = 3.0
Hz, 1H), 2.24−2.18 (m, 1H), 1.56 (s, 3H), 1.45 (s, 3H), 1.09 (d, J =
7.0 Hz, 3H), 0.98 (d, J = 6.8 Hz, 3H); 13C NMR (126 MHz, CDCl3) δ
163.9 (d, J = 26.3 Hz), 152.6 (s), 90.3 (d, J = 248.8 Hz), 85.2 (s), 67.7
(s), 29.5 (s), 28.9 (s), 21.5 (s), 21.3 (s), 16.9 (s); 19F NMR (564
MHz, CDCl3) δ −149.72 (dd, J = 51.6, 3.6 Hz, 1F); HRMS (ESI
+TOF) m/z Calcd for C10H15FClNO3Na [M + Na]+ 274.0622, found
274.0610.
mmol, 78%, single diastereomer): [α]2D5 +26.92 (c 0.1, CHCl3); H
1
NMR (600 MHz, CDCl3) δ 7.43 (d, J = 7.3 Hz, 1H), 7.36 (d, J = 7.6
Hz, 1H), 7.25−7.18 (m, 2H), 6.32 (ddd, J = 48.7, 8.2, 4.2 Hz, 1H),
4.13 (d, J = 3.1 Hz, 1H), 3.46 (ddd, J = 18.6, 14.7, 8.1 Hz, 1H), 3.30
(ddd, J = 30.1, 14.6, 4.1 Hz, 1H), 2.21 (dddd, J = 13.8, 5.1 Hz, 1H),
1.53 (s, 3H), 1.35 (s, 3H), 1.07 (d, J = 7.0 Hz, 3H), 0.99 (d, J = 6.8
Hz, 3H); 13C NMR (126 MHz, CDCl3) δ 169.3 (d, J = 22.6 Hz),
152.8 (s), 134.5 (s), 132.8 (d, J = 2.9 Hz), 131.6 (d, J = 1.3 Hz), 129.6
(s), 128.6 (s), 126.9 (s), 87.7 (d, J = 181.0 Hz), 83.9 (s), 66.9 (s), 35.2
(d, J = 22.7 Hz), 29.5 (s), 28.9 (s), 21.5 (s), 21.3 (s), 16.9 (s). 19F
NMR (564 MHz, CDCl3) δ −187.68 to −187.87 (m, 1F); HRMS
(ESI+TOF) m/z calcd for C17H21FClNO3Na [M + Na]+ 364.109,
found 364.1102.
Table 3, Entry 3f. The title compound was prepared from (S)-4-
benzyl-3-(2-cyclohexylacetyl)-5,5-dimethyloxazolidin-2-one (0.165 g,
0.50 mmol) following the standard α-fluorination procedure. The
diastereoselectivity (dr 96:4) was determined by 1H NMR of the crude
reaction mixture. The residue was purified by column chromatography
(silica, 20% ethyl acetate in hexanes−25% ethyl acetate in hexanes) to
afford the product as a white solid (0.160 g, 0.46 mmol, 92%, single
diastereomer): [α]2D6 +19.05 (c 0.42, CHCl3); H NMR (600 MHz,
1
Table 3, Entry 3j. The title compound was prepared from (S)-4-
isopropyl-5,5-dimethyl-3-(3-(3-(trifluoromethyl)phenyl)propanoyl)-
oxazolidin-2-one (0.179 g, 0.50 mmol) following the standard α-
fluorination procedure. The diastereoselectivity (dr 98:2) was
CDCl3) δ 7.33−7.27 (m, 4H), 7.24 (dd, J = 7.1 Hz, 1H), 5.83 (dd, J =
49.6, 3.6 Hz, 1H), 4.46 (dd, J = 9.9, 3.0 Hz, 1H), 3.25 (dd, J = 14.5, 2.8
Hz, 1H), 2.93 (dd, J = 14.5, 9.9 Hz, 1H), 1.84 (dddd, J = 58.1, 34.1,
16.5, 8.1 Hz, 4H), 1.65 (dd, J = 21.0, 12.8 Hz, 2H), 1.44−1.35 (m,
7H), 1.35−1.27 (m, 2H), 1.23−1.11 (m, 2H); 13C NMR (201 MHz,
CDCl3) δ 169.54 (d, J = 23.5 Hz), 152.1 (s), 136.6 (s), 129.0 (s),
128.8 (s), 126.9 (s), 92.1 (d, J = 180.8 Hz), 83.5 (s), 64.1 (s), 40.3 (d,
J = 20.8 Hz), 35.0 (s), 28.6 (d, J = 3.3 Hz), 28.5 (s), 26.1 (d, J = 4.3
Hz), 26.0 (s), 25.8 (s), 25.8 (s), 22.2 (s); 19F NMR (564 MHz,
CDCl3) δ −201.83 (dd, J = 50.1, 26.9 Hz, 1F); HRMS (ESI+TOF) m/
z calcd for C20H26FNO3Na [M + Na]+ 370.1794, found 370.1800.
Table 3, Entry 3g. The title compound was prepared from (S)-4-
isopropyl-5,5-dimethyl-3-(4-phenoxybutanoyl)oxazolidin-2-one (0.160
g, 0.50 mmol) following the standard α-fluorination procedure. The
diastereoselectivity (dr 98:2) was determined by 1H NMR of the crude
reaction mixture. The residue was purified by column chromatography
(silica, 1.5% diethyl ether in toluene) to afford the product as a white
solid (0.155 g, 0.46 mmol, 92%, single diastereomer): [α]2D6 +31.81 (c
1.0, CHCl3); 1H NMR (600 MHz, CDCl3) δ 7.27 (d, J = 7.6 Hz, 1H),
7.25 (s, 1H), 6.95 (dd, J = 7.3 Hz, 1H), 6.89 (d, J = 8.3 Hz, 2H), 6.21
(ddd, J = 49.0, 5.3 Hz, 1H), 4.22−4.14 (m, 2H), 4.13 (d, J = 3.0 Hz,
1H), 2.41 (ddd, J = 5.9 Hz, 1H), 2.37 (ddd, J = 5.9 Hz, 1H), 2.21
(ddd, J = 13.8, 8.4, 5.0 Hz, 1H), 1.53 (s, 3H), 1.41 (s, 3H), 1.08 (d, J =
7.0 Hz, 3H), 0.99 (d, J = 6.8 Hz, 3H); 13C NMR (126 MHz, CDCl3) δ
169.5 (d, J = 22.6 Hz), 158.4 (s), 153.0 (s), 129.4 (s), 121.1 (s), 114.8
(d, J = 0.7 Hz), 86.3 (d, J = 178.7 Hz), 84.2 (s), 66.9 (s), 62.9 (d, J =
3.3 Hz), 32.0 (d, J = 21.8 Hz), 29.4 (s), 28.9 (s), 21.4 (s), 21.3 (s),
16.9 (s); 19F NMR (564 MHz, CDCl3) δ −192.47 to −192.69 (m,
1F); HRMS (ESI+TOF) m/z calcd for C18H24FNO4Na [M + Na]+
360.1587, found 360.1594.
1
determined by H NMR of the crude reaction mixture. The residue
was purified by column chromatography (silica, 1.5% diethyl ether in
toluene) to afford the product as a white solid (0.115 g, 0.31 mmol,
61%, 98:2 dr): [α]2D6 +25.27 (c 1.0, CHCl3); H NMR (600 MHz,
1
CDCl3) δ 7.57 (s, 1H), 7.56−7.51 (m, 2H), 7.45 (dd, J = 7.7 Hz, 1H),
6.18 (ddd, J = 49.4, 8.7, 2.5 Hz, 1H), 4.12 (d, J = 2.9 Hz, 1H), 3.19
(dddd, J = 34.6, 23.1, 14.5, 5.7 Hz, 2H), 2.21 (dddd, J = 13.7, 6.9, 3.2
Hz, 1H), 1.54 (s, 3H), 1.35 (s, 3H), 1.07 (d, J = 7.0 Hz, 3H), 0.98 (d, J
= 6.8 Hz, 3H); 13C NMR (126 MHz, CDCl3) δ 169.2 (d, J = 22.5 Hz),
153.1 (s), 136.2 (d, J = 1.0 Hz), 133.0 (s), 130.9 (q, J = 32.2 Hz),
129.0 (s), 126.3 (q, J = 3.7 Hz), 124.1 (q, J = 3.8 Hz), 124.0 (d, J =
273.42 Hz), 89.0 (d, J = 181.9 Hz), 84.3 (s), 66.9 (s), 38.2 (d, J = 22.5
Hz), 29.5 (s), 28.9 (s), 21.4 (s), 21.3 (s), 16.9 (s); 19F NMR (564
MHz, CDCl3) δ −62.65 (s, 3F), −189.13 (ddd, J = 49.5, 34.0, 20.1 Hz,
1F); HRMS (ESI+TOF) m/z calcd for C18H21F4NO3Na [M + Na]+
398.1355, found 398.1356.
Table 3, Entry 3k. The title compound was prepared from (S)-3-(5-
(benzyloxy)pentanoyl)-4-isopropyl-5,5-dimethyloxazolidin-2-one
(0.174 g, 0.50 mmol) following the standard α-fluorination procedure.
1
The diastereoselectivity (dr 98:2) was determined by H NMR of the
crude reaction mixture. The residue was purified by column
chromatography (silica, 15% ethyl acetate in hexanes hexanes−25%
ethyl acetate in hexanes) to afford the product as a colorless oil (0.124
g, 0.34 mmol, 68%, single diastereomer): [α]2D5 +30.86 (c 1.0, CHCl3);
1H NMR (600 MHz, CDCl3) δ 7.35−7.30 (m, 4H), 7.29−7.26 (m,
1H), 6.10−5.99 (m, 1H), 4.49 (d, J = 2.8 Hz, 2H), 4.10 (d, J = 3.0 Hz,
1H), 3.57−3.49 (m, 2H), 2.20 (dddd, J = 13.9, 7.0, 3.2 Hz, 1H), 2.02−
1.91 (m, 2H), 1.90−1.79 (m, 2H), 1.53 (s, 3H), 1.36 (s, 3H), 1.07 (d,
J = 7.0 Hz, 3H), 0.98 (d, J = 6.8 Hz, 3H); 13C NMR (201 MHz,
CDCl3) δ 171.9 (d, J = 22.7 Hz), 154.9 (s), 140.2 (s), 130.1 (s), 129.4
(s), 129.3 (s), 90.7 (d, J = 178.8 Hz), 85.9 (s), 74.6 (s), 70.9 (s), 68.7
(s), 31.3 (s), 31.0 (d, J = 22.1 Hz), 30.7 (s), 26.8 (d, J = 2.0 Hz), 23.2
(s), 23.1 (s), 18.8 (s); 19F NMR (564 MHz, CDCl3) δ −192.32 (ddd, J
= 50.1, 30.1, 24.4 Hz, 1F); HRMS (ESI+TOF) m/z Calcd for
C20H28FNO4Na [M + Na]+ 388.1900, found 388.1901.
Table 3, Entry 3h. The title compound was prepared from (S)-4-
isopropyl-5,5-dimethyl-3-(3-phenylpropanoyl)oxazolidin-2-one (0.145
g, 0.50 mmol) following the standard α-fluorination procedure. The
diastereoselectivity (dr 98:2) was determined by 1H NMR of the crude
reaction mixture. The residue was purified by column chromatography
(silica, 12% ethyl acetate in hexanes−15% ethyl acetate in hexanes) to
afford the product as a colorless oil after purification (0.136 g, 0.44
mmol, 88%, single diastereomer): [α]2D6 +37.73 (c 1.0, CHCl3); H
1
NMR (600 MHz, CDCl3) δ 7.34−7.29 (m, 4H), 7.25 (dd, J = 8.4, 2.4
Hz, 1H), 6.22 (ddd, J = 49.5, 8.6, 3.3 Hz, 1H), 4.10 (d, J = 3.0 Hz,
1H), 3.14 (dddd, J = 22.9, 19.4, 14.3, 6.0 Hz, 2H), 2.19 (dddd, J =
13.7, 6.9, 3.2 Hz, 1H), 1.51 (s, 3H), 1.30 (s, 3H), 1.07 (d, J = 7.0 Hz,
3H), 0.97 (d, J = 6.8 Hz, 3H); 13C NMR (126 MHz, CDCl3) δ 169.5
(d, J = 22.5 Hz), 152.9 (s), 135.1 (d, J = 1.9 Hz), 129.4 (s), 128.5 (s),
127.1 (s), 89.2 (d, J = 181.1 Hz), 84.0 (s), 66.7 (s), 38.5 (d, J = 22.5
Hz), 29.4 (s), 28.7 (s), 21.3 (s), 21.2 (s), 16.9 (s); 19F NMR (564
MHz, CDCl3) δ −188.75 (ddd, J = 49.6, 33.6, 19.4 Hz, 1F); HRMS
Table 3, Entry 3l. The title compound was prepared from (S,E)-3-
(but-2-enoyl)-4-isopropyl-5,5-dimethyloxazolidin-2-one (0.113 g, 0.50
mmol) following the standard α-fluorination procedure. The
1
diastereoselectivity (dr >98:2) was determined by H NMR of the
crude reaction mixture. The residue was purified by column
chromatography (silica, 15% ethyl acetate in hexanes−25% ethyl
acetate in hexanes) to afford the product as a clear oil (56 mg, 0.23
mmol, 46%, single diastereomer): [α]2D5 +36.44 (c 1.0, CHCl3); H
1
NMR (600 MHz, CDCl3) δ 6.46 (dd, J = 48.7, 6.2 Hz, 1H), 6.07−5.97
J
dx.doi.org/10.1021/jo500957d | J. Org. Chem. XXXX, XXX, XXX−XXX