The Journal of Organic Chemistry
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purification (10−60% EtOAc/hex), 7e was obtained as a colorless oil
(94 mg, 74%).
J = 7.8 Hz), 7.60 (td, 1 H, J = 7.1, 0.9 Hz), 7.67 (td, 1 H, J = 7.1, 1.3
Hz), 7.90 (d, 1 H, J = 7.8 Hz), 7.95 (d, 1 H, J = 8.1 Hz), 8.05 (dd, 1 H,
J = 7.3, 1.2 Hz), 8.59 (d, 1 H, J = 8.5 Hz); 13C NMR (CDCl3, 100
MHz) δ 21.7, 56.9, 124.2, 124.9, 126.3, 126.4 (2 C), 127.1 (3 C),
127.9, 128.2, 128.6 (3 C), 129.1, 129.6, 129.7, 130.1, 133.5, 134.2,
134.4, 135.7, 137.2, 138.8, 142.4, 143.7 (2 C); IR (KBr) 3467, 3059,
2868, 1595, 1493, 1451, 1330, 1162, 1135, 1052, 805, 772 cm−1;
HRMS (ESI) m/z for C28H25NO3S2 [M]+ calcd 487.1276, observed
487.1245. Anal. Calcd for C28H25NO3S2: C, 68.97; H, 5.17; N, 2.87; S,
13.15. Found: C, 68.75; H, 5.20; N, 2.65; S, 12.93.
Data for 7e: Rf 0.25 (40% EtOAc/hex); [α]20D +19.5 (c = 1.10); 1H
NMR (CDCl3, 500 MHz) δ 2.32 (s, 3 H), 5.49 (d, 1 H, J = 9.8 Hz),
5.53 (d, 1 H, J = 15.6 Hz), 5.84 (d, 1 H, J = 8.1 Hz), 6.64 (ddd, 1 H,
J = 15.7, 11.3, 9.8 Hz), 6.67 (d, 1 H, J = 10.8 Hz), 6.96 (d, 1 H, J = 8.3
Hz), 7.03−7.08 (m, 5 H), 7.14 (d, 2 H, J = 7.8 Hz), 7.32 (d, 2 H, J =
8.3 Hz), 7.55 (td, 1 H, J = 7.8, 1.2 Hz), 7.60 (td, 1 H, J = 7.6, 1.5 Hz),
7.78 (dd, 1 H, J = 7.8, 1.2 Hz), 7.81 (dd, 1 H, J = 7.8, 1.2 Hz); 13C
NMR (CDCl3, 100 MHz) δ 21.3, 56.1, 125.0, 125.3 (2 C), 126.8,
126.9 (2 C), 127.7, 128.4 (2 C), 129.6, 129.8 (2 C), 130.8, 132.5,
133.2, 134.2, 134.3, 137.4, 139.0, 141.8, 143.4, 147.4; IR (film) 3435,
1540, 1451, 1355, 1168, 1051, 742, 700, 591 cm−1; MS (ESI) 483 [M
+ 1]+ (100%), 987 [2M + Na]+; HRMS (ESI) m/z for C24H22N2O5S2
[M]+ calcd 482.0970, observed 482.0965.
4.6. Synthesis of (+)-N-[(1S,2E)-1-Phenyl-2-((S)-p-tolylsulfinyl)-
2,4-pentadien-1-yl]pyridine-2-sulfonamide, 7k. From amine 5c10a
(70 mg, 0.24 mmol, 1.0 equiv), 2-pyridinesulfonyl chloride (70 mg,
0.31 mmol, 1.3 equiv), and Et3N (67 μL, 0.48 mmol, 2.0 equiv),
following the standard procedure (20 h) and after chromatographic
purification (5−60% EtOAc/CH2Cl2), 7k was obtained as a white
solid (84 mg, 80%).
4.3. Synthesis of (+)-N-[(1S,2E)-1-Phenyl-2-((S)-p-tolylsulfinyl)-
2,4-pentadien-1-yl]-2,4,6-triisopropylbenzenesulfonamide, 7f. From
amine 5c10a (74 mg, 0.25 mmol, 1.0 equiv), 2,4,6-triisopro-
pylbenzenesulfonyl chloride (204 mg, 0.67 mmol, 2.7 equiv), and
Et3N (0.14 mL, 1.0 mmol, 4.0 equiv), following the standard
procedure (48 h) and after chromatographic purification (10−40%
EtOAc/hex), 7f was obtained as a colorless oil (72 mg, 51%).
Data for 7f: Rf 0.28 (30% EtOAc/hex); [α]20D +14.1 (c = 0.59); 1H
NMR (CDCl3, 500 MHz) δ 1.13 (t, 12 H, J = 6.8 Hz), 1.22 (d, 6 H,
J = 6.8 Hz), 2.36 (s, 3 H), 2.85 (m, 1 H), 3.95 (m, 2 H), 5.40 (dd, 1 H,
J = 10.0, 1.0 Hz), 5.44 (dd, 1 H, J = 16.6, 1.0 Hz), 5.85 (d, 1 H, J = 7.3
Hz), 6.14 (d, 1 H, J = 7.3 Hz), 6.43 (d, 1 H, J = 11.2 Hz), 6.55 (ddd,
1 H, J = 16.4, 11.0, 10.0 Hz), 6.99 (d, 2 H, J = 7.1 Hz), 7.05−7.12
(m, 5 H), 7.20 (d, 2 H, J = 7.8 Hz), 7.40 (d, 2 H, J = 8.1 Hz); 13C
NMR (CDCl3, 100 MHz) δ 21.4, 23.6 (2 C), 24.7 (2 C), 24.8 (2 C),
29.8 (2 C), 34.1, 56.1, 123.5 (2 C), 125.9, 126.3 (2 C), 127.0 (2 C),
127.7, 128.4 (2 C), 129.5, 129.9 (2 C), 132.8, 133.9, 138.0, 139.2,
142.1, 144.4, 149.7, 152.6; IR (film) 3435, 2959, 2927, 1629, 1455,
1324, 1153, 1040, 667 cm−1; MS (ESI) 564 [M + 1]+ (100%), 1149
[2M + Na]+; HRMS (ESI) m/z for C33H41NO3S2 [M]+ calcd
563.2528, observed 563.2502.
Data for 7k: Rf 0.22 (60% EtOAc/hex); mp 139−141 °C; [α]20
D
+107.4 (c = 3.80); 1H NMR (CDCl3, 300 MHz) δ 2.35 (s, 3 H), 5.48
(d, 1 H, J = 16.8 Hz), 5.50 (m, 1 H, J = 9.5 Hz), 5.95 (d, 1 H, J = 8.5
Hz), 6.48 (d, 1 H, J = 11.7 Hz), 6.63 (d, 1 H, J = 10.0 Hz), 6.68 (ddd,
1 H, J = 16.3, 11.0, 10.0 Hz), 7.13−7.20 (m, 7 H), 7.33 (d, 2 H, J = 8.1
Hz), 7.60 (m, 1 H), 7.77 (m, 2 H), 8.54 (ddd, 1 H, J = 4.6, 2.3, 1.0
Hz); 13C NMR (CDCl3, 75 MHz) δ 21.6, 56.6, 121.9, 125.9 (2 C),
126.2, 126.5, 127.0 (2 C), 127.8, 128.6 (2 C), 130.0 (2 C), 133.4,
133.5, 137.7, 138.1, 139.5, 142.0, 144.0, 150.0, 157.9; IR (KBr) 3436,
3233, 2975, 1577, 1492, 1428, 1344, 1172, 1121, 1011, 954, 808, 782
cm−1; HRMS (ESI) m/z for C23H22N2O3S2 [M]+ calcd 438.1072,
observed 438.1059.
4.7. Synthesis of (+)-N-[(1S,2E)-1-(3,4-Dimethoxyphenyl)-2-((S)-p-
tolylsulfinyl)-2,4-pentadien-1-yl]quinoline-8-sulfonamide, 7h.
From amine 5f (1100 mg, 3.08 mmol, 1.0 equiv), 8-quinolinesulfonyl
chloride (1050 mg, 4.62 mmol, 1.5 equiv), and Et3N (1.50 mL, 10.78
mmol, 3.5 equiv), following the general procedure (20 h) and after
chromatographic purification (25−40% EtOAc/hex), 7h was obtained
as a white solid (1569 mg, 93%).
Data for 7h: Rf 0.20 (80% Et2O/CH2Cl2); mp 68−70 °C; [α]20
4.4. Synthesis of (+)-N-[(1S,2E)-1-Phenyl-2-((S)-p-tolylsulfinyl)-
2,4-pentadien-1-yl]-8-quinolinesulfonamide, 7g. From amine 5c10a
(97 mg, 0.33 mmol, 1.0 equiv), 8-quinolinesulfonyl chloride (96 mg,
0.42 mmol, 1.3 equiv), and Et3N (0.09 mL, 0.65 mmol, 2.0 equiv),
following the standard procedure (4 h) and after chromatographic
purification (5−40% EtOAc/CH2Cl2), 7g was obtained as a white
solid (104 mg, 65%).
D
+58.5 (c = 0.53); 1H NMR (CDCl3, 300 MHz)-COSY δ 2.29 (s, 3 H,
Me p-Tol), 3.40 (s, 3 H, OMe), 3.68 (s, 3 H, OMe), 5.34 (d, 1 H, J =
9.8 Hz, H-5 trans), 5.38 (d, 1 H, J = 16.6 Hz, H-5 cis), 5.63 (d, 1 H, J =
8.1 Hz, H-1 HMBC(H−N)), 6.18 (s, 1 H, ArH), 6.28 (d, 1 H, J = 8.3
Hz, ArH), 6.39 (d, 1 H, J = 8.3 Hz, ArH), 6.55 (m, 1 H, H-4), 6.63 (d,
1 H, J = 11.2 Hz, H-3), 7.04 (d, 2 H, J = 8.1, ArH), 7.19 (d, 2 H, J =
8.1, ArH), 7.38 (br d, 1 H, J = 8.6 Hz, NH HMBC(H−N)), 7.46 (dd,
1 H, J = 8.1, 4.2 Hz, ArH), 7.49 (dd, 1 H, J = 7.3, 8.1 Hz, ArH), 7.93
(d, 1 H, J = 8.3 Hz, ArH), 8.16 (d, 1 H, J = 8.3 Hz, ArH), 8.21 (d, 1 H,
J = 7.3 Hz, ArH), 8.90 (d, 1 H, J = 4.2 Hz, CH=N HMBC(H−N)); 13C
NMR (CDCl3, 75 MHz)-HSQC δ 21.3, 55.4, 55.8, 56.2, 110.2, 110.4,
119.5, 122.0, 125.3, 125.5 (2 C), 128.6, 129.5 (2 C), 129.8, 130.0, 130.4
132.4, 132.9, 136.6, 137.0, 140.3, 141.4, 143.0, 144.8, 148.3, 148.6,
151.0 (2 C); IR (KBr) 3259, 2931, 1595, 1515, 1492, 1335, 1246, 1165,
1144, 1029, 911, 839, 810, 790, 762, 732 cm−1; HRMS (ESI) m/z for
C29H28N2O5S2 [M]+ calcd 548.1440, observed 548.1434.
Data for 7g: Rf 0.22 (60% EtOAc/hex); mp 195 °C; [α]20 +94.4
D
1
(c = 0.75); H NMR (CDCl3, 500 MHz) δ 2.28 (s, 3 H), 5.35 (m,
1 H), 5.40 (m, 1 H), 5.68 (d, 1 H, J = 8.1 Hz), 6.57 (m, 1 H), 6.60 (d,
1 H, J = 11.0 Hz), 6.80−6.84 (m, 4 H), 6.88−6.91 (m, 1 H), 7.00 (d,
2 H, J = 8.1 Hz), 7.13 (d, 2 H, J = 8.1 Hz), 7.45 (d, 1 H, J = 9.5 Hz),
7.47 (dd, 1 H, J = 8.3, 4.4 Hz), 7.51 (dd, 1 H, J = 8.1, 7.51 Hz), 7.93
(dd, 1 H, J = 8.3, 1.5 Hz), 8.17 (dd, 1 H, J = 8.3, 1.7 Hz), 8.22 (dd, 1
H, J = 7.3, 1.5 Hz), 8.90 (dd, 1 H, J = 4.4, 1.7 Hz); 13C NMR (CDCl3,
100 MHz) δ 21.3, 56.1, 122.1, 125.3, 125.5 (2 C), 126.8 (2 C), 127.3,
127.9 (2 C), 128.6, 129.5 (2 C), 129.9, 130.4, 132.4, 133.1, 136.6,
136.7, 137.6, 139.8, 141.4, 142.9, 144.5, 151.0 (2 C); IR (KBr) 3435,
1493, 1333, 1166, 1146, 1082, 1049, 790, 701 cm−1; MS (ESI) 489
[M + 1]+ (100%), 511 [M + Na]+. Anal. Calcd for C27H24N2O3S2: C,
66.37; H, 4.95; N, 5.73; S, 13.12. Found: C, 66.09; H, 5.20; N, 5.65; S,
12.98.
4.8. Synthesis of (+)-N-[(1S,2E)-1-Isopropyl-2-((S)-p-tolylsulfinyl)-
2,4-pentadien-1-yl]quinoline-8-sulfonamide, 7i. From amine 5h10a
(125 mg, 0.48 mmol, 1.0 equiv), 8-quinolinesulfonyl chloride (141 mg,
0.62 mmol, 1.3 equiv), and Et3N (1.34 mL, 0.96 mmol, 2.0 equiv),
following the standard procedure (4 h) and after chromatographic
purification (1−30% EtOH/CH2Cl2), 7i was obtained as a solid (159 mg,
73%).
4.5. Synthesis of (−)-N-[(1S,2E)-1-Phenyl-2-((S)-p-tolylsulfinyl)-
2,4-pentadien-1-yl]naphthalene-1-sulfonamide, 7j. From amine
5c10a (70 mg, 0.24 mmol, 1.0 equiv), 1-naphthalenesulfonyl chloride
(70 mg, 0.31 mmol, 1.3 equiv), and Et3N (67 μL, 0.48 mmol, 2.0
equiv), following the standard procedure (24 h) and after chromato-
graphic purification (5−40% EtOAc/CH2Cl2), 7j was obtained as a
white solid (101 mg, 87%).
Data for 7i: Rf 0.20 (5% EtOH/CH2Cl2); mp 49−51 °C; [α]20
D
+239 (c = 0.53); 1H NMR (CDCl3, 300 MHz) δ 0.45 (d, 3 H, J = 6.6
Hz), 1.01 (d, 3 H, J = 6.6 Hz), 1.72 (m, 1 H), 2.28 (s, 3 H), 4.24 (t, 1
H, J = 8.8 Hz), 5.28 (d, 1 H, J = 16.6 Hz), 5.31 (d, 1 H, J = 9.8 Hz),
6.25 (d, 1 H, J = 11.5 Hz), 6.59 (ddd, 1 H, J = 16.6, 11.0, 10.0 Hz),
6.95 (d, 1 H, J = 8.8 Hz), 7.00 (d, 2 H, J = 8.1 Hz), 7.13 (d, 2 H, J =
8.1 Hz), 7.46 (dd, 1 H, J = 8.3, 7.3 Hz), 7.51 (dd, 1 H, J = 8.3, 4.2 Hz),
7.94 (dd, 1 H, J = 8.3, 1.5 Hz), 8.13 (dd, 1 H, J = 7.3, 1.5 Hz,), 8.21
(dd, 1 H, J = 8.3, 1.7 Hz), 9.02 (dd, 1 H, J = 8.3, 1.7 Hz); 13C NMR
(CDCl3, 75 MHz) δ 19.2, 19.8, 21.4, 32.6, 59.2, 122.3, 124.3, 125.3,
Data for 7j: Rf 0.22 (40% EtOAc/hex); mp 76−78 °C; [α]20D −9.60
(c = 1.60); 1H NMR (CDCl3, 300 MHz) δ 2.36 (s, 3 H), 5.30 (d, 1 H,
J = 16.6 Hz), 5.36 (m, 1 H, J = 10.0 Hz), 5.80 (d, 1 H, J = 8.1 Hz),
6.04 (dd, 1 H, J = 11.0, 0.9 Hz), 6.52 (ddd, 1 H, J = 16.5, 11.0, 10.0
Hz), 6.88 (d, 1 H, J = 8.0 Hz), 7.03−7.14 (m, 9 H), 7.35 (t, 1 H,
534
dx.doi.org/10.1021/jo202144k | J. Org. Chem. 2012, 77, 525−542