The Journal of Organic Chemistry
Article
MHz, CDCl3) δ 8.12 (d, J = 9.8 Hz, 1H; minor diastereomer), 7.89−
7.84 (m, 2H), 7.78 (dd, J = 8.4, 2.1 Hz, 2H), 7.74 (d, J = 9.6 Hz, 1H;
major diastereomer), 7.33 (d, J = 8.2 Hz, 2H), 6.97 (d, J = 8.8 Hz,
2H), 5.60−5.51 (m, 1H), 3.87 (s, 3H), 3.62 (qd, J = 7.2, 4.0 Hz, 1H;
major diastereomer), 3.43−3.37 (m, 1H; minor diastereomer), 3.33
(s, 3H; minor diastereomer), 3.23 (s, 3H; major diastereomer), 2.44
(s, 3H), 1.42 (d, J = 7.2 Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3;
major diastereomer) δ 167.2, 163.0, 144.8, 137.2, 129.6, 129.3, 128.9,
125.5, 114.1, 81.3, 62.6, 55.9, 55.6, 21.8, 11.0. 13C{1H} NMR (101
MHz, CDCl3; minor diastereomer) δ 166.8, 162.9, 145.1, 135.5,
129.7, 129.6, 129.3, 128.9, 125.6, 114.1, 81.3, 64.6, 56.4, 55.6, 13.0,
8.5. MS (ESI): m/z calcd for C19H23NO5SNa+ 400.1 [M + Na]+,
found 400.0 [M + Na]+. HRMS (EI) m/z calcd for C18H19NO4S
345.1035 [M − MeOH]+, found 345.1035 [M − MeOH]+. IR (ATR,
ν in cm−1): 2931 (w), 1650 (m), 1605 (m), 1527 (m), 1493 (m),
1351 (w), 1288 (m), 1251 (s), 1177 (m), 1135 (s), 1073 (s), 1025
(m), 952 (m), 843 (m), 814 (m), 767 (m), 733 (m), 666 (w).
Synthesis of 4-Fluoro-N-(1-methoxy-2-tosylpropyl)benzamide
4i. It was prepared according to TP1 from (E/Z)-enamide derivative
1e (36 mg, 1.0 equiv, 0.2 mmol, E/Z = 75:25) and sulfinate salt 2a
(71 mg, 2.0 equiv, 0.4 mmol) in methanol (2 mL). The reaction was
stirred at room temperature for 2 h. Purification by flash column
chromatography (n-hexane/EtOAc + 0.2 vol % NEt3) afforded the
analytically pure sulfone 4i as a colorless foam (45 mg, 0.123 mmol,
62%, isolated dr 80:20; dr of the crude mixture 81:19 as determined
by 1H NMR analysis of the unpurified product after aqueous workup).
1111 (s), 1064 (s), 1014 (m), 966 (m), 860 (m), 850 (m), 816 (m),
774 (m), 738 (m), 682 (m), 665 (m).
Synthesis of N-(1-Methoxy-2-tosylpropyl)thiophene-2-carboxa-
mide 4k. It was prepared according to TP1 from (E/Z)-enamide
derivative 1g (33 mg, 1.0 equiv, 0.2 mmol, E/Z = 69:31) and sulfinate
salt 2a (71 mg, 2.0 equiv, 0.4 mmol) in methanol (2 mL). The
reaction was stirred at room temperature for 2 h. Purification by flash
column chromatography (n-hexane/EtOAc + 0.2 vol % NEt3)
afforded the analytically pure sulfone 4k as a colorless foam (48
mg, 0.136 mmol, 68%, isolated dr 83:17; dr of the crude mixture
1
83:17 as determined by H NMR analysis of the unpurified product
after aqueous workup). Mp 145−148 °C. Rf (n-hexane/EtOAc = 7:3)
0.19. 1H NMR (400 MHz, CDCl3) δ 8.05 (d, J = 9.8 Hz, 1H; minor
diastereomer), 7.81−7.74 (m, 2H), 7.66 (d, J = 9.6 Hz, 1H; major
diastereomer), 7.61 (dd, J = 4.7, 1.9 Hz, 1H), 7.55 (dd, J = 4.9, 0.8
Hz, 1H), 7.32 (d, J = 8.1 Hz, 2H), 7.11 (dd, J = 4.9, 3.8 Hz, 1H),
5.56−5.45 (m, 1H), 3.59 (qd, J = 7.2, 4.1 Hz, 1H; major
diastereomer), 3.39 (dd, J = 7.2, 2.6 Hz, 1H; minor diastereomer),
3.33 (s, 3H; major diastereomer), 3.24 (s, 3H; major diastereomer),
2.43 (s, 3H), 1.41 (dd, J = 7.2, 3.9 Hz, 3H). 13C{1H} NMR (101
MHz, CDCl3; major diastereomer) δ 162.3, 144.9, 138.1, 137.0,
131.4, 129.6, 128.9, 128.0, 81.2, 62.5, 56.0, 21.8, 10.8. 13C{1H} NMR
(101 MHz, CDCl3; minor diastereomer) δ 161.9, 145.1, 138.3, 135.4,
131.4, 129.5, 128.9, 128.0, 81.2, 64.4, 56.5, 21.8, 12.9. MS (ESI): m/z
calcd for C16H19NO4S2Na+ 376.1 [M + Na]+, found 376.0 [M + Na]+.
HRMS (EI) m/z calcd for C15H15NO3S2 321.0493 [M − MeOH]+,
found 321.0512 [M − MeOH]+. IR (ATR, ν in cm−1): 3228 (w),
3091 (w), 2931 (w), 2836 (w), 1616 (m), 1532 (m), 1509 (m), 1451
(m), 1420 (m), 1361 (m), 1285 (s),1251 (m), 1197 (w), 1119 (s),
1131 (s), 1074 (s), 1038 (m), 945 (m), 863 (w), 801 (m), 729 (s),
665 (m).
1
Mp 109−127 °C. Rf (n-hexane/EtOAc = 7:3) 0.19. H NMR (400
MHz, CDCl3) δ 8.19 (d, J = 9.8 Hz, 1H), 7.90 (ddd, J = 5.2, 4.2, 2.7
Hz, 2H), 7.81 (d, J = 9.7 Hz, 1H), 7.79−7.73 (m, 2H), 7.32 (d, J =
8.1 Hz, 2H), 7.15 (t, J = 8.6 Hz, 2H), 5.58−5.48 (m, 1H), 3.61 (qd, J
= 7.2, 4.1 Hz, 1H), 3.44−3.37 (m, 1H), 3.33 (s, 3H), 3.23 (s, 3H),
2.43 (s, 3H), 1.41 (d, J = 7.2 Hz, 3H). 13C{1H} NMR (101 MHz,
CDCl3) δ 166.6, 165.3 (d, J = 253.1 Hz), 144.9, 137.0, 129.80 (d, J =
9.1 Hz), 129.6, 129.6, 128.9, 116.0 (d, J = 21.9 Hz), 81.4, 62.5, 56.0,
21.8, 11.0. 13C{1H} NMR (101 MHz, CDCl3; minor diastereomer) δ
166.2, 165.3 (d, J = 253.0 Hz), 145.1, 135.3, 129.7, 129.6, 129.5 (d, J
= 3.1 Hz), 128.9, 116.0 (d, J = 21.7 Hz), 81.3, 64.4, 56.5, 21.8, 12.9.
19F{1H} NMR (376 MHz, CDCl3) δ −106.90 (tt, J = 8.4, 5.3 Hz;
Synthesis of N-(1-Methoxy-2-tosylpropyl)pivalamide 4l. It was
prepared according to TP1 from (E/Z)-enamide derivative 1h (28
mg, 1.0 equiv, 0.2 mmol, E/Z = 91:9) and sulfinate salt 2a (71 mg, 2.0
equiv, 0.4 mmol) in methanol (2 mL). The reaction was stirred at
room temperature for 2 h. Purification by flash column chromatog-
raphy (n-hexane/EtOAc + 0.2 vol % NEt3) afforded the analytically
pure sulfone 4l as a colorless oil (47 mg, 0.144 mmol, 72%, isolated dr
1
89:11; dr of the crude mixture 88:12 as determined by H NMR
major diastereomer), −107.00 (tt, J = 8.4, 5.2 Hz; minor
diastereomer). MS (ESI): m/z calcd for C18H20NO4SFNa+ 388.1
[M + Na]+, found 388.0 [M + Na]+. HRMS (EI) m/z calcd for
C17H16NO3SF 333.0835 [M − MeOH]+, found 333.0849 [M −
MeOH]+. IR (ATR, ν in cm−1): 2939 (w), 1650 (m), 1602 (m), 1526
(m), 1493 (s), 1350 (m), 1286 (m), 1229 (m), 1133 (s), 1073 (s),
1014 (m), 962 (m), 851 (m), 815 (m), 764 (m), 732 (m), 665 (m).
Synthesis of N-(1-Methoxy-2-tosylpropyl)-4-(trifluoromethyl)-
benzamide 4j. It was prepared according to TP1 from (E/Z)-
enamide derivative 1f (50 mg, 1.0 equiv, 0.2 mmol, E/Z = 55:45) and
sulfinate salt 2a (71 mg, 2.0 equiv, 0.4 mmol) in methanol (2 mL).
The reaction was stirred at room temperature for 2 h. Purification by
flash column chromatography (n-hexane/EtOAc + 0.2 vol % NEt3)
afforded the analytically pure sulfone 4j as a colorless foam (51 mg,
0.123 mmol, 61%, isolated dr 80:20; dr of the crude mixture 80:20 as
determined by 1H NMR analysis of the unpurified product after
aqueous workup). Mp 129−141 °C. Rf (n-hexane/EtOAc = 7:3) 0.24.
1H NMR (400 MHz, CDCl3) δ 8.33 (d, J = 9.8 Hz, 1H), 8.01 (d, J =
8.2 Hz, 2H), 7.94 (d, J = 9.5 Hz, 1H), 7.77 (t, J = 8.3 Hz, 4H), 7.34
(d, J = 8.1 Hz, 2H), 5.56 (dt, J = 9.7, 3.4 Hz, 1H), 3.63 (qd, J = 7.2,
4.1 Hz, 1H), 3.42 (td, J = 6.8, 4.5 Hz, 1H), 3.35 (s, 3H), 3.25 (s, 2H),
2.45 (s, 3H), 1.43 (d, J = 7.2 Hz, 3H). 13C{1H} NMR (101 MHz,
CDCl3) δ 166.5, 166.0, 145.3, 145.0, 137.0, 136.7, 136.6, 136.6, 135.2,
134.2, 134.1 (q, J = 32.8 Hz), 133.8, 129.7, 129.7, 129.6, 128.9, 127.9,
127.8, 126.0 (dd, J = 7.4, 3.6 Hz), 123.7 (d, J = 272.6 Hz), 81.6, 81.4,
64.4, 62.4, 56.7, 56.1, 21.8, 13.0, 11.2. 19F{1H} NMR (376 MHz,
CDCl3) δ −63.0 (s; minor diastereomer), −63.0 (s; major
diastereomer). MS (ESI): m/z calcd for C19H20NO4SF3Na+ 438.1
[M + Na]+, found 338.0 [M + Na]+. HRMS (EI) m/z calcd for
C18H16NO3S F3383.0803 [M − MeOH]+, found 383.0820 [M −
MeOH]+. IR (ATR, ν in cm−1): 3323 (w), 2933 (w), 1659 (m), 1533
(m), 1510 (m), 1451 (m), 1364 (w), 1325 (m), 1298 (s), 1140 (m),
analysis of the unpurified product after aqueous workup). Rf (n-
hexane/EtOAc = 7:3) 0.25. 1H NMR (400 MHz, CDCl3) δ 7.78 (t, J
= 16.0 Hz, 2H), 7.33 (d, J = 8.1 Hz, 2H), 7.25 (d, J = 7.4 Hz, 1H),
5.37 (dd, J = 9.7, 3.9 Hz, 1H; major diastereomer), 5.33 (dd, J = 9.8,
2.7 Hz, 1H; minor diastereomer), 3.52 (qd, J = 7.2, 3.9 Hz, 1H; major
diastereomer), 3.33−3.25 (m, 1H; minor diastereomer), 3.24 (s, 3H;
minor diastereomer), 3.14 (s, 3H; major diastereomer), 2.44 (s, 3H;
minor diastereomer), 1.33 (dd, J = 7.3, Hz, 3H), 1.29−1.24 (m, 9H).
13C{1H} NMR (101 MHz, CDCl3; major diastereomer) δ 179.6,
144.8, 137.2, 129.6, 128.9, 80.8, 62.4, 55.6, 39.3, 27.6, 21.8, 10.8. MS
(ESI): m/z calcd for C16H25NO4SNa+ 350.1 [M + Na]+, found 350.1
[M + Na]+. HRMS (EI) m/z calcd for C15H21NO3S 295.1242 [M −
MeOH]+, found 295.1234 [M − MeOH]+. IR (ATR, ν in cm−1):
3364 (w), 2957 (w), 1658 (m), 1598 (w), 1502 (m), 1454 (m), 1366
(w), 1302 (m), 1287 (m), 1239 (m), 1183 (m), 1136 (s),1074 (s),
955 (w), 879 (m), 814 (m), 744 (m), 714 (m), 680 (w), 665 (w).
Synthesis of N-(1-Methoxy-2-tosylpropyl)-2-phenylacetamide
4m. It was prepared according to TP1 from (E/Z)-enamide derivative
1i (35 mg, 1.0 equiv, 0.2 mmol, E/Z = 60:40) and sulfinate salt 2a (71
mg, 2.0 equiv, 0.4 mmol) in methanol (2 mL). The reaction was
stirred at room temperature for 2 h. Purification by flash column
chromatography (n-hexane/EtOAc + 0.2 vol % NEt3) afforded the
analytically pure sulfone 4m as a colorless oil (51 mg, 0.141 mmol,
70%, isolated dr 63:37; dr of the crude mixture 62:38 as determined
by 1H NMR analysis of the unpurified product after aqueous workup).
Rf (n-hexane/EtOAc = 7:3) 0.1. 1H NMR (400 MHz, CDCl3) δ 7.66
(dd, J = 8.3, 2.2 Hz, 2H), 7.43−7.28 (m, 7H), 7.00 (d, J = 9.8 Hz, 1H;
minor diastereomer), 6.70 (d, J = 9.4 Hz, 1H; major diastereomer),
5.35 (dd, J = 9.7, 4.0 Hz, 1H; major diastereomer), 5.31 (dd, J = 10.0,
3.0 Hz, 1H; minor diastereomer), 3.64 (s, 2H), 3.40 (qd, J = 7.2, 4.0
Hz, 1H; major diastereomer), 3.23−3.16 (m, 4H; minor diaster-
3628
J. Org. Chem. 2020, 85, 3617−3637