5526
N. Kern et al. / Tetrahedron 70 (2014) 5519e5531
CDCl3)
d
0.87 (t, J¼6.8 Hz, 3H), 1.18e1.40 (m, 6H), 1.41e1.52 (m, 2H),
59.8, 85.6, 88.0, 120.2, 122.1, 124.7, 128.3, 128.7, 129.1, 131.8, 137.4,
168.8; HRMS 288.099 (C17H15NO2þNa, calcd 288.099).
2.19 (dt, J¼7.0, 1.9 Hz, 2H), 2.71 (dd, JAB¼15.6 Hz, J¼7.2 Hz, 1H), 2.79
(dd, JAB¼15.6 Hz, J¼4.3 Hz, 1H), 3.05 (b, 1H), 4.83 (dddt, J¼7.2, 4.5,
4.3, 1.9 Hz, 1H), 7.28 (d, J¼8.8 Hz, 2H), 7.47 (d, J¼8.8 Hz, 2H), 7.88 (b,
4.2.9. N-(4-Ethoxyphenyl)-3-hydroxy-5-(triisopropylsilyl)pent-4-
ynamide (3i). Yield: 81% (4.72 g); Pale yellow solid: mp 98e99 ꢁC;
TLC Rf 0.33 (Cyclohexane/EtOAc 40%); IR (neat) nmax 521, 660, 685,
796, 824, 884, 921, 996, 1035, 1242, 1511, 1543, 1635, 2863, 2965,
1H); 13C NMR (125.8 MHz, CDCl3)
d 14.3, 18.9, 22.7, 28.7, 28.7, 31.5,
45.0, 59.7, 79.3, 87.3, 121.5, 129.3, 129.7, 136.4, 169.0; HRMS 330.124
(C17H22ClNO2þNa, calcd 330.123).
3251; 1H NMR (300 MHz, CDCl3)
d 0.97e1.10 (m, 21H), 1.40
4.2.4. 3-Hydroxy-N-(3-methoxyphenyl)dec-4-ynamide (3d). Yield:
75% (1.75 g); Pale yellow solid: mp 99 ꢁC; TLC Rf 0.50 (Cyclohexane/
EtOAc 50%); IR (neat) nmax 456, 680, 783, 1034, 1056, 1156, 1408,
1492, 1549, 1606, 1666, 2237, 2959, 3244; 1H NMR (300 MHz,
(t, J¼7.0 Hz, 3H), 2.74 (dd, JAB¼15.3 Hz, J¼7.3 Hz, 1H), 2.82 (dd,
JAB¼15.3 Hz, J¼3.7 Hz, 1H), 3.49 (d, J¼5.2 Hz, 1H), 4.01 (q, J¼6.9 Hz,
2H), 4.81e4.90 (m,1H), 6.84 (d, J¼9.0 Hz, 2H), 7.37 (d, J¼9.0 Hz, 2H),
7.57 (s, 1H); 13C NMR (125.8 MHz, CDCl3)
d 11.1, 14.8, 18.6, 44.3, 59.9,
CDCl3)
d
0.87 (t, J¼7.0 Hz, 3H), 1.21e1.39 (m, 4H), 1.43e1.54 (m, 2H),
63.7, 86.6, 106.6, 114.8, 122.0, 130.3, 156.1, 168.5; HRMS 412.226
(C22H35NO3SiþNa, calcd 412.228).
2.19 (dt, J¼7.1, 2.0 Hz, 2H), 2.72 (dd, JAB¼15.5 Hz, J¼7.1 Hz, 1H), 2.79
(dd, JAB¼15.5, J¼4.3 Hz, 1H), 3.24 (b, 1H), 3.80 (s, 3H), 4.84 (dddt,
J¼7.1, 4.5, 4.3, 2.0 Hz, 1H), 6.67 (dd, J¼8.2, 2.2 Hz, 1H), 6.97 (dd,
J¼8.2, 1.8 Hz, 1H), 7.21 (dd, J¼8.2, 8.2 Hz, 1H), 7.28 (dd, J¼2.2, 1.8 Hz,
4.2.10. 3-Hydroxy-N-(4-methoxyphenyl)-6-((triisopropylsilyl)oxy)
hex-4-ynamide (3j). Yield: 83% (4.42 g); Pale yellow solid: mp 82 ꢁC;
TLC Rf 0.63 (Cyclohexane/EtOAc 50%); IR (neat) nmax 688, 792, 862,
990, 1060, 1240, 1510, 1655, 2953, 3270; 1H NMR (400 MHz, CDCl3)
1H), 7.78 (b, 1H); 13C NMR (125.8 MHz, CDCl3)
d 14.1, 18.9, 22.4, 28.4,
31.2, 45.0, 55.5, 59.7, 79.4, 87.0, 106.4, 110.6, 112.4, 129.9, 138.9,
160.4, 169.1; HRMS 312.156 (C17H23NO3þNa, calcd 312.157).
d
1.01e1.15 (m, 21H), 2.71 (dd, JAB¼15.5 Hz, J¼6.9 Hz, 1H), 2.76 (dd,
JAB¼15.5 Hz, J¼4.8 Hz,1H), 3.76 (s, 3H), 4.00 (d, J¼5.0 Hz,1H), 4.39 (d,
J¼1.6 Hz, 2H), 4.87 (dddt, J¼6.9, 5.0, 4.8,1.6 Hz,1H), 6.82 (d, J¼9.0 Hz,
2H), 7.38 (d, J¼9.0 Hz, 2H), 8.00 (b, 1H); 13C NMR (125.8 MHz, CDCl3)
4.2.5. N-(3-Chlorophenyl)-3-hydroxydec-4-ynamide
(3e). Yield:
95% (2.24 g); Pale yellow solid: mp 92 ꢁC; TLC Rf 0.57 (Cyclohexane/
EtOAc 50%); IR (neat) nmax 420, 625, 668, 773, 871, 1051, 1298, 1412,
1481, 1537, 1590, 1667, 2229, 2928, 3234; 1H NMR (500 MHz, CDCl3)
d
12.1, 17.9, 44.0, 51.9, 55.4, 59.3, 84.0, 84.3, 114.3, 122.3, 130.7, 156.8,
169.0; HRMS 428.223 (C22H35NO4SiþNa, calcd 428.223).
d
0.87 (t, J¼7.2 Hz, 3H), 1.24e1.37 (m, 4H), 1.45e1.52 (m, 2H), 2.20
(dt, J¼7.2, 2.0 Hz, 2H), 2.73 (dd, JAB¼15.5 Hz, J¼7.3 Hz, 1H), 2.80 (dd,
JAB¼15.5, J¼3.8 Hz, 1H), 2.95 (d, J¼4.5 Hz, 1H), 4.83 (dddt, J¼7.3, 4.5,
3.8, 2.0 Hz, 1H), 7.09 (ddd, J¼8.1, 1.9, 0.9 Hz, 1H), 7.24 (dd, J¼8.1,
8.1 Hz, 1H), 7.35 (ddd, J¼8.1, 1.9, 0.9 Hz, 1H), 7.64 (dd, J¼1.9, 1.9 Hz,
4.2.11. 3-Hydroxy-N-phenylpent-4-enamide
(3k). Yield:
87%
(1.23 g); Colorless crystals: mp 126e127 ꢁC; TLC Rf 0.29 (Cyclohex-
ane/EtOAc 50%); IR (neat) nmax 505, 690, 755, 915, 1038, 1072, 1124,
1312, 1441, 1495, 1543, 1598, 1661, 1675, 3135, 3193, 3255, 3287; 1H
1H), 7.87 (b, 1H); 13C NMR (125.8 MHz, CDCl3)
d
14.1, 18.8, 22.4, 28.4,
NMR (500 MHz, CDCl3)
d
2.56 (dd, JAB¼15.5 Hz, J¼8.7 Hz, 1H), 2.64
31.2, 45.0, 59.7, 79.2, 87.4, 118.1, 120.3, 124.7, 130.2, 134.9, 138.9,
168.9; HRMS 316.107 (C16H20ClNO2þNa, calcd 316.107).
(dd, JAB¼15.5 Hz, J¼3.2 Hz, 1H), 3.19 (d, J¼3.2 Hz, 1H), 4.60e4.70
(m, 1H), 5.20 (dt, J¼10.5, 1.1 Hz, 1H), 5.36 (dt, J¼17.2, 1.1 Hz, 1H), 5.94
(ddd, J¼17.2, 10.5, 5.7 Hz, 1H), 7.12 (tt, J¼7.5, 0.9 Hz,, 1H), 7.33 (dd,
J¼8.4, 7.5 Hz, 2H), 7.50 (dd, J¼8.4, 0.9 Hz, 2H), 7.83 (b, 1H); 13C NMR
4.2.6. 3-Hydroxy-N-(3-isopropylphenyl)dec-4-ynamide (3f). Yield:
71% (2.57 g); Pale yellow solid: mp 79 ꢁC; TLC Rf 0.30 (Cyclohexane/
EtOAc 30%); IR (neat) nmax 696, 788, 1057, 1267, 1300, 1486, 1552,
(125.8 MHz, CDCl3) d 43.7, 69.7, 115.8, 120.1, 124.6, 129.1, 137.5, 138.9,
169.7; HRMS 214.0832 (C11H13NO2þNa, calcd 214.0838).
1608, 1666, 2927, 3283; 1H NMR (400 MHz, CDCl3);
d 0.87
(t, J¼7.1 Hz, 3H), 1.24 (d, J¼6.9 Hz, 6H) 1.26e1.38 (m, 4H), 1.45e1.54
(m, 2H), 2.20 (dt, J¼7.1, 1.6 Hz, 2H), 2.72 (dd, JAB¼15.5 Hz, J¼7.4 Hz,
1H), 2.78 (dd, JAB¼15.5 Hz, J¼4.0 Hz, 1H), 2.89 (qq, J¼6.9, 6.9 Hz,
1H), 3.26 (b, 1H), 4.84 (m, 1H), 7.00 (d, J¼7.7 Hz, 1H), 7.24 (dd, J¼8.5,
7.7 Hz, 1H), 7.37 (d, J¼8.5 Hz, 1H), 7.37 (s, 1H), 7.65 (b, 1H); 13C NMR
4.2.12. 3-Hydroxy-5-methyl-N-phenylhex-4-enamide
(3l). Yield:
80% (1.29 g); Colorless needles: mp 136 ꢁC; TLC Rf 0.29 (Cyclohex-
ane/EtOAc 50%); IR (neat) nmax 510, 691, 757, 848, 1009, 1067, 1154,
1251, 1313, 1413, 1440, 1485, 1496, 1549, 1597, 1667, 2910, 2971,
2991, 3043, 3079, 3131, 3188, 3247; 1H NMR (500 MHz, CDCl3)
(125.8 MHz, CDCl3)
d
14.1, 18.9, 22.4, 24.1, 28.4, 31.2, 34.3, 44.9, 59.8,
d
1.72 (d, J¼1.0 Hz, 3H), 1.73 (d, J¼1.0 Hz, 3H), 2.52 (dd, JAB¼15.6 Hz,
79.5, 86.9, 117.8, 118.5, 122.9, 129.2, 137.7, 150.3, 169.0; HRMS
324.191 (C19H27NO2þNa, calcd 324.193).
J¼3.5 Hz, 1H), 2.58 (dd, JAB¼15.4 Hz, J¼8.5 Hz, 1H), 2.78e2.92 (b,
1H), 4.85 (dt, J¼8.5, 3.5 Hz, 1H), 5.23e5.28 (m, 1H), 7.11 (tt, J¼7.5,
1.0 Hz, 1H), 7.32 (dd, J¼8.5, 7.5 Hz, 2H), 7.52 (dd, J¼8.5, 1.0 Hz, 2H),
4.2.7. 5-Cyclohexyl-3-hydroxy-N-phenylpent-4-ynamide
(3g).
8.12 (b, 1H); 13C NMR (125.8 MHz, CDCl3)
d 18.3, 25.8, 44.2, 65.8,
Yield: 74% (0.746 g); Pale yellow solid: mp 130 ꢁC; TLC Rf 0.53
(Cyclohexane/EtOAc 50%); IR (neat) nmax 513, 696, 756, 1074, 1247,
1400, 1440, 1488, 1547, 1599, 1657, 2221, 2852, 2923, 3301; 1H NMR
120.0, 124.4, 125.7, 129.0, 136.6, 137.8, 170.1; HRMS 242.123
(C13H17NO2þNa, calcd 242.115).
(300 MHz, CDCl3)
d
1.18e1.55 (m, 6H), 1.58e1.82 (m, 4H), 2.33e2.44
4.2.13. (E)-3-Hydroxy-N,5-diphenylpent-4-enamide
(3m). Yield:
(m, 1H), 2.73 (dd, JAB¼15.3 Hz, J¼7.0 Hz, 1H), 2.80 (dd, JAB¼15.3 Hz,
J¼4.2 Hz, 1H), 3.25 (d, J¼4.5 Hz, 1H), 4.85 (dddd, J¼7.0, 4.6, 4.2,
2.0 Hz, 1H), 7.11 (t, J¼7.4 Hz, 1H), 7.32 (dd, J¼8.1, 7.4 Hz, 2H), 7.50 (d,
86% (3.12 g); Yellowish needles: mp 170 ꢁC; TLC Rf 0.18 (Cyclohex-
ane/EtOAc 40%); IR (neat) nmax 462, 507, 689, 732, 756, 962, 1071,
1111, 1180, 1245, 1312, 1405, 1442, 1486, 1547, 1598, 1657, 3133, 3190,
J¼8.1 Hz, 2H), 7.82 (b, 1H); 13C NMR (125.8 MHz, CDCl3)
d
25.0, 26.0,
3249, 3280; 1H NMR (500 MHz, acetone-d6)
d
2.66 (dd, JAB¼14.6 Hz,
29.1, 32.7, 45.1, 59.8, 79.5, 91.0, 120.3, 124.7, 129.2, 137.7, 169.1;
J¼7.9 Hz, 1H), 2.71 (dd, JAB¼14.6 Hz, J¼4.7 Hz, 1H), 4.83 (dddd, J¼7.9,
5.4, 4.7, 4.2 Hz, 1H), 6.44 (dd, J¼15.9, 5.4 Hz, 1H), 6.73 (d, J¼15.9 Hz,
1H), 7.08 (tt, J¼7.4, 1.1 Hz, 1H), 7.26 (tt, J¼7.4, 1.0 Hz, 1H), 7.32 (t,
J¼7.6 Hz, 2H), 7.35 (t, J¼7.5 Hz, 2H), 7.46 (d, J¼7.6 Hz, 2H), 7.71 (d,
HRMS 294.146 (C17H21NO2þNa, calcd 294.141).
4.2.8. 3-Hydroxy-N,5-diphenylpent-4-ynamide (3h). Yield: 70%
(2.75 g); Pale yellow solid: mp 134e135 ꢁC; TLC Rf 0.27 (Cyclo-
hexane/EtOAc 40%); IR (neat) nmax 506, 688, 750, 1068, 1140, 1247,
1317, 1441, 1484, 1545, 1596, 1639, 3297, 3409; 1H NMR (300 MHz,
J¼7.6 Hz, 2H), 9.39 (b, 1H); 13C NMR (125.8 MHz, acetone-d6)
d 44.6,
69.0, 119.3, 123.3, 126.4, 127.4, 128.5, 128.6, 129.1, 132.3, 137.2, 139.4,
169.5; HRMS 290.114 (C17H17NO2þNa, calcd 290.115).
CDCl3)
d
2.82e2.94 (m, 2H), 3.60 (d, J¼4.9 Hz, 1H), 5.06e5.12 (m,
1H), 7.13 (t, J¼7.3 Hz,1H), 7.26e7.36 (m, 5H), 7.38e7.43 (m, 2H), 7.52
4.2.14. 3-Hydroxy-N-phenylpentanamide (3n). Yield: 89% (1.27 g);
Colorless needles: mp 142 ꢁC; TLC Rf 0.12 (Cyclohexane/EtOAc 40%);
(d, J¼7.8 Hz, 2H), 7.79 (b, 1H); 13C NMR (125.8 MHz, CDCl3)
d 44.3,