Cyclic Enamides from Acetylenic Amides
J . Org. Chem., Vol. 61, No. 15, 1996 5019
128.8, 138.3, 171.0. Anal. Calcd for C12H13NO: C, 76.98; H,
7.00; N, 7.48. Found: C, 76.92; H, 7.05; N, 7.41.
N-(4-Meth oxyben zyl)-3,3-dim eth yl-4-pen tyn am ide (24c).
This material was prepared in 86% yield from 176 mg (1.39
mmol) of acid 17c and 0.22 mL (1.67 mmol, 1.2 equiv) of
p-methoxybenzylamine using method A described above. Pu-
rification by chromatography (silica gel, 30% EtOAc/hexanes,
Rf 0.22) gave 296 mg of 24c as a colorless, crystalline solid:
N-Ben zyl-2,2-d im eth yl-4-p en tyn a m id e (23b). This ma-
terial was prepared in 70% yield from 625 mg (4.95 mmol) of
acid 17b and 0.65 mL (5.94 mmol, 1.2 equiv) of benzylamine
using method A described above. Purification by chromatog-
raphy (silica gel, 20% EtOAc/hexanes, Rf 0.33) gave 746 mg of
23b as a white solid: mp 69-71 °C (EtOAc/hexanes); IR
(CDCl3) 3296, 2964, 1638, 1533; 1H NMR (300 MHz, CDCl3)
1.31 (s, 6H), 2.04 (t, J ) 2 Hz, 1H), 2.48 (d, J ) 2 Hz, 2H),
mp 55-57 °C; IR (CDCl3) 3295, 2929, 1648, 1543, 1513 cm-1
;
1H NMR (300 MHz, CDCl3) 1.34 (s, 6H), 2.19 (s,1H), 2.38 (s,
2H), 3.81 (s, 3H), 4.42 (d, J ) 5.5 Hz, 2H), 6.32 (br, 1H), 6.87
(d, J ) 8.0 Hz, 2H), 7.25 (d, J ) 8.0 Hz, 2H); 13C NMR (75
MHz, CDCl3) 29.2, 30.0, 43.1, 49.5, 55.3, 69.7, 91.0, 114.0,
129.1, 130.6, 159.0, 169.9. Anal. Calcd for C15H19NO2: C,
73.44; H, 7.81; N, 5.71. Found: C, 73.16; H, 7.75; N, 5.59.
4.48 (d, J ) 5.7 Hz, 2H), 6.12 (br, 1H), 7.27-7.40 (m, 5H); 13
C
NMR (75 MHz, CDCl3) 25.2, 30.2, 42.0, 43.9, 71.2, 81.6,
127.6, 127.9, 128.9, 138.6, 176.3. Anal. Calcd for C14H17NO:
C, 78.10; H, 7.96; N, 6.51. Found: C, 78.08; H, 7.94; N, 6.48.
N-(4-Met h oxyb en zyl-2,3,3-t r im et h yl-4-p en t yn a m id e
(24d ). This material was prepared in 71% yield from 305 mg
(2.18 mmol) of acid 17d and 1.4 mL (10.9 mmol, 5 equiv) of
p-methoxybenzylamine using method B described above. Pu-
rification by chromatography (silica gel, 30% EtOAc/hexanes,
Rf 0.34) gave 399 mg of 24d as a colorless solid: mp 70-72
N-Ben zyl-3,3-d im eth yl-4-p en tyn a m id e (23c). This ma-
terial was prepared in 87% yield from 338 mg (2.68 mmol) of
acid 17c and 0.35 mL (3.22 mmol, 1.2 equiv) of benzylamine
using method A described above. Purification by chromatog-
raphy (silica gel, 30% EtOAc/hexanes, Rf 0.27) gave 503 mg of
1
°C; IR (CDCl3) 3293, 2970, 1644, 1512, 1247 cm-1; H NMR
23c as a colorless oil: IR (CDCl3) 3295, 2966, 1643, 1543 cm-1
;
1H NMR (300 MHz, CDCl3) 1.35 (s, 6H), 2.19 (s,1H), 2.39 (s,
2H), 4.49 (d, J ) 5.6 Hz, 2H), 6.39 (br, 1H), 7.28-7.38 (m, 5H);
13C NMR (75 MHz, CDCl3) 29.3, 30.0, 43.7, 49.6, 69.8, 91.0,
(300 MHz, CDCl3) 1.28 (d, J ) 7.2 Hz, 3H), 1.28 (s, 3H),
1.30 (s, 3H), 2.19 (s, 1H), 2.26 (q, J ) 7.2 Hz, 1H), 3.81 (s,
3H), 4.40 (d, J ) 5.5 Hz, 2H), 6.30 (br, 1H), 6.87 (d, J ) 8.6
Hz, 2H), 7.23 (d, J ) 8.6 Hz, 2H); 13C NMR (75 MHz, CDCl3)
13.9, 26.8, 27.6, 33.4, 42.7, 50.5, 55.1, 70.2, 90.1, 113.9, 129.0,
130.6, 158.8, 173.9. Anal. Calcd for C16H21NO2: C, 74.10; H,
8.16; N, 5.40. Found: C, 74.19; H, 8.20; N, 5.43.
127.5, 127.9, 128.7, 138.4, 170.1; exact mass calcd for C14H17
NO 215.1310, found 215.1311.
-
N-Ben zyl-2,3,3-tr im eth yl-4-p en tyn a m id e (23d ). This
material was prepared in 83% yield from 267 mg (1.9 mmol)
of acid 17d and 1.04 mL (9.5 mmol, 5 equiv) of benzylamine
using method B described above. Purification by chromatog-
raphy (silica gel, 30% EtOAc/hexanes, Rf 0.33) gave 364 mg of
23d as a colorless solid: mp 83-84 °C (EtOAc/hexanes); IR
(CH2Cl2) 3287, 1635, 1535 cm-1; 1H NMR (300 MHz, CDCl3)
1.29 (s, 3H), 1.30 (d, J ) 7.2 Hz, 3H), 1.32 (s, 3H), 2.21 (s,
1H), 2.29 (q, J ) 7.2 Hz, 1H), 4.48 (d, J ) 5.5 Hz, 2H), 6.30
(br, 1H), 7.29-7.39 (m, 5H); 13C NMR (75 MHz, CDCl3) 14.2,
27.6, 27.9, 33.6, 43.7, 51.5, 70.8, 90.2, 127.6, 128.0, 128.8, 138.6,
174.2. Anal. Calcd for C15H19NO: C, 78.56; H, 8.35; N, 6.11.
Found: C, 78.40; H, 8.31; N, 6.02.
N -(3,4-D im e t h o x y b e n zy l)-2,2-d im e t h y l-4-p e n t y n -
a m id e (25b). This material was prepared in 60% yield from
186 mg (1.47 mmol) of acid 17b and 0.27 mL (1.76 mmol, 1.2
equiv) of 3,4-dimethoxybenzylamine using method A described
above. Purification by chromatography (silica gel, 40% EtOAc/
hexanes, Rf 0.27) gave 242 mg of 25b as an off-white solid:
mp 98-99 °C (EtOAc/hexanes); IR (CDCl3) 3290, 2964, 1641,
1
1516, 1264 cm-1; H NMR (300 MHz, CDCl3) 1.30 (s, 6H),
2.03 (t, J ) 2.6 Hz, 1H), 2.47 (d, J ) 2.6 Hz, 2H), 3.87 (s, 3H),
3.88 (s, 3H), 4.40 (d, J ) 5.6 Hz, 2H), 6.07 (br, 1H), 6.80-6.88
(m, 3H); 13C NMR (75 MHz, CDCl3) 25.2, 30.2, 42.0, 43.8,
56.1, 56.2, 71.2, 81.7, 111.4, 111.5, 120.2, 131.3, 148.7, 149.4,
176.3. Anal. Calcd for C16H21NO3: C, 69.79; H, 7.67; N, 5.09.
Found: C, 69.71; H, 7.70; N, 5.06.
N-Ben zyl-2(R),3(R)-dim eth yl-4-pen tyn am ide (23e). This
material was prepared in 81% yield from 287 mg (2.27 mmol)
of acid 17e and 0.30 mL (2.72 mmol, 1.2 equiv) of benzylamine
using method A described above. Purification by chromatog-
raphy (silica gel, 20% EtOAc/hexanes, Rf 0.25) gave 394 mg of
23f as a colorless, crystalline solid: mp 64-65 °C (EtOAc/
N -(3,4-D im e t h o x y b e n zy l)-3,3-d im e t h y l-4-p e n t y n -
a m id e (25c). This material was prepared in 67% yield from
211 mg (1.67 mmol) of acid 17c and 0.30 mL (2.00 mmol, 1.2
equiv) of 3,4-dimethoxybenzylamine using method A described
above. Purification by chromatography (silica gel, 40% EtOAc/
hexanes, Rf 0.14 in 30% EtOAc/hexanes) gave 310 mg of 25c
as a white solid: mp 75-77 °C; IR (CDCl3) 3291, 2968, 1646,
hexanes); IR (CDCl3) 3288, 1643, 1549 cm-1 1H NMR (300
;
MHz, CDCl3) 1.23 (d, J ) 6.9 Hz, 3H), 1.25 (d, J ) 6.9 Hz,
3H), 2.10 (d, J ) 2.4 Hz, 1H), 2.35 (m, 1H), 2.78 (m, 1H), 4.40-
4.56 (m, 2H), 6.06 (br, 1H), 7.24-7.40 (m, 5H); 13C NMR (75
MHz, CDCl3) 15.4, 18.2, 29.3, 43.8, 46.7, 70.6, 87.2, 127.7,
1
1516, 1264 cm-1; H NMR (300 MHz, CDCl3) 1.34 (s, 6H),
2.19 (s, 1H), 2.38 (s, 2H), 3.87 (s, 6H), 4.42 (d, J ) 5.6 Hz,
2H), 6.35 (br, 1H), 6.80-6.90 (m, 3H); 13C NMR (75 MHz,
CDCl3) 29.1, 29.9, 43.2, 49.3, 55.76, 55.81, 69.5, 90.8, 111.1,
119.9, 131.0, 148.2, 149.0, 169.9. Anal. Calcd for C16H21NO3:
C, 69.79; H, 7.69; N, 5.09. Found: C, 69.72; H, 7.73; N, 5.04.
128.1, 128.9, 138.6, 174.4; [R]26 ) +12.69° (c ) 0.26, CH2-
D
Cl2). Anal. Calcd for C14H17NO: C, 78.10; H, 7.96; N, 6.51.
Found: C, 78.22; H, 7.98; N, 6.45.
N-Ben zyl-2(S),3(S)-d im eth yl-4-p en tyn a m id e (23f). This
material was prepared in 65% yield from 372 mg (2.95 mmol)
of acid 17f and 0.39 mL (3.54 mmol, 1.2 equiv) of benzylamine
using method A described above. Purification by chromatog-
raphy (silica gel, 20% EtOAc/hexanes, Rf 0.25) gave 410 mg of
23f as a colorless solid: mp 64-65 °C (EtOAc/hexanes);
N -(3,4-Dim e t h oxyb e n zyl)-2,3,3-t r im e t h yl-4-p e n t yn -
a m id e (25d ). This material was prepared in 77% yield from
252 mg (1.80 mmol) of acid 17d and 1.4 mL (9.0 mmol, 5 equiv)
of 3,4-dimethoxybenzylamine using method B described above.
Purification by chromatography (silica gel, 40% EtOAc/hex-
anes, Rf 0.21 in 30% EtOAc/hexanes) gave 400 mg of 25d as a
white solid: mp 104-105 °C (EtOAc/hexanes); IR (CDCl3)
3294, 2972, 1646, 1514, 1461 cm-1; 1H NMR (300 MHz, CDCl3)
1.28 (s, 3H), 1.29 (d, J ) 7.1 Hz, 3H), 1.34 (s, 3H), 2.20 (s,
1H), 2.28 (q, J ) 7.1 Hz, 1H), 3.87 (s, 6H), 4.39-4.43 (m, 2H),
6.28 (br, 1H), 6.80-6.90 (m, 3H); 13C NMR (75 MHz, CDCl3)
14.2, 27.4, 27.8, 33.6, 43.4, 51.3, 56.0, 56.1, 70.7, 90.2, 111.4,
120.1, 131.3, 148.5, 149.3, 174.0. Anal. Calcd for C17H23NO3:
C, 70.56; H, 8.01; N, 4.84. Found: C, 70.66; H, 8.07; N, 4.89.
spectral data identical to that of 23e; [R]26 ) -12.44° (c )
D
0.45, CH2Cl2). Anal. Calcd for C14H17NO: C, 78.10; H, 7.96;
N, 6.51. Found: C, 78.17; H, 8.00; N, 6.46.
N-(4-Meth oxyben zyl)-2,2-dim eth yl-4-pen tyn am ide (24b).
This material was prepared in 62% yield from 213 mg (1.68
mmol) of acid 17b and 0.26 mL (2.02 mmol, 1.2 equiv) of
p-methoxybenzylamine using method A described above. Pu-
rification by chromatography (silica gel, 30% EtOAc/hexanes,
Rf 0.27) gave 257 mg of 24b as a white solid: mp 75-77 °C
(EtOAc/hexanes); IR (CDCl3) 3300, 2964, 1641, 1512, 1247
3,3-Dim eth yl-4-p en tyn oic Acid , N ′-Meth yl-N ′-(m eth -
oxyca r bon yl)h yd r a zid e (26c). This material was prepared
in 79% yield from 369 mg (2.92 mmol) of acid 17c and a
solution of 366 mg (3.51 mmol, 1.2 equiv) of 1-(methoxycar-
bonyl)-1-methylhydrazine25 in 2 mL of anhydrous THF using
1
cm-1; H NMR (300 MHz, CDCl3) 1.29 (s, 6H), 2.03 (t, J )
2.7 Hz, 1H), 2.46 (d, J ) 2.7 Hz, 2H), 3.80 (s, 3H), 4.40 (d, J
) 5.5 Hz, 2H), 6.05 (br, 1H), 6.87 (d, J ) 8.6 Hz, 2H), 7.22 (d,
J ) 8.6 Hz, 2H); 13C NMR (75 MHz, CDCl3) 25.2, 30.2, 41.9,
43.4, 55.5, 71.2, 81.6, 114.3, 129.3, 130.7, 159.2, 176.3. Anal.
Calcd for C15H19NO2: C, 73.44; H, 7.81; N, 5.71. Found: C,
73.36; H, 7.83; N, 5.65.
(25) Wadsworth, W. S. J . Org. Chem. 1969, 34, 2994.