5-exo-trig Diastereoselective Radical Cyclization on Acrylamides
J . Org. Chem., Vol. 64, No. 12, 1999 4287
1H NMR (CDCl3): δ 0.85-1.10 (m, 3H), 0.93 (d, 3H, J ) 6.6
Hz), 1.13 (d, 3H, J ) 7.4 Hz), 1.19 (s, 3H), 1.20-1.35 (m, 2H),
1.40-1.55 (m, 2H), 1.73 (s, 3H), 1.83 (ddd, 1H, J ) 6.2 Hz, J
) 6.6 Hz, J ) 13.7 Hz), 1.90-2.05 (m, 1H), 1.99 (ddd, 1H, J )
13.7 Hz, J ) 5.0 Hz, J ) 9.4 Hz), 2.55 (ddq, 1H, J ) 7.4 Hz,
J ) 6.6 Hz, J ) 9.4 Hz), 3.42 (dt, 1H, J ) 4.0 Hz, J ) 10.2
Hz), 5.02 (dd, 1H, J ) 6.2 Hz, J ) 5.0 Hz). 13C NMR (CDCl3):
δ 17.0; 18.9; 22.1; 24.0; 25.1; 31.2; 33.0; 34.1; 35.8; 41.0; 49.9;
57.0; 76.2; 84.1; 176.5. IR (neat, cm-1): 1680, 1270, 735. CIMS
(m/z, %): 252 (M + 1, 100), 137 (15), 139 (12). Anal. Calcd for
12.6; 19.2; 22.0; 24.1; 25.6; 31.2; 34.4; 40.7; 41.0; 47.5; 50.0;
57.3; 76.4; 87.8; 126.9; 128.2; 128.4; 137.4; 175.7. IR (neat,
cm-1): 1680, 695. CIMS (m/z, %): 328 (M + 1, 100), 211 (22),
172 (24), 137 (12).
La cta m (4d ). Colorless oil; [R]20D ) -53.8 (c 1.11, CH2Cl2).
1H NMR (CDCl3): δ 0.93 (t, 3H, J ) 7.5 Hz), 0.95 (d, 3H, J )
6.4 Hz), 0.95-1.15 (m, 3H), 1.17 (s, 3H), 1.20-1.35 (m, 1H),
1.35-1.50 (m, 3H), 1.65-1.80 (m, 2H), 1.72 (s, 3H), 1.83-2.05
(m, 2H), 2.10-2.25 (m, 1H), 2.30-2.45 (m, 1H), 3.40 (dt, 1H,
J ) 4.0 Hz, J ) 10.2 Hz), 4.88 (dd, 1H, J ) 6.4 Hz, J ) 7.3
Hz). 13C NMR (CDCl3): δ 10.9; 18.1; 22.2; 23.9; 24.1; 25.0; 30.9;
31.1; 33.9; 41.2; 42.1; 50.1; 56.7; 76.2; 84.0; 175.0. IR (neat,
cm-1 ): 1685, 1265. CIMS (m/z, %): 266 (M + 1, 100), 112
(16). Anal. Calcd for C16H27NO2: C, 72.41; H, 10.25; N, 5.28.
Found: C, 72.19; H, 9.98; N, 5.07.
C
15H25NO2: C, 71.67; H, 10.02; N, 5.57. Found: C, 71.57; H,
9.66; N, 5.21.
La cta m (4b). White solid, mp 68-69 °C (pentane), [R]20
D
) -54.5 (c 2.06, CH2Cl2). 1H NMR (CDCl3): δ 0.85-1.10 (m,
3H), 0.94 (d, 3H, J ) 6.5 Hz), 1.15 (d, 3H, J ) 6.7 Hz), 1.16 (s,
3H), 1.17 (d, 3H, J ) 7.3 Hz), 1.30 (m, 1H), 1.40-1.55 (m, 1H),
1.60-1.85 (m, 4H), 1.72 (s, 3H), 2.05 (m, 1H), 3.37 (dt, 1H, J
) 4.2 Hz, J ) 10.5 Hz), 4.42 (d, 1H, J ) 7.0 Hz). 13C NMR
(CDCl3): δ 14.0; 14.8; 17.9; 21.7; 23.6; 25.3; 30.9; 34.2; 40.8;
41.3; 43.5; 49.3; 56.3; 75.8; 89.3; 174.7. IR (neat, cm-1): 1690.
CIMS (m/z, %): 266 (M + 1, 100), 153 (4), 112 (18). Anal. Calcd
for C16H27NO2: C, 72.41; H, 10.25; N, 5.28. Found: C, 72.22;
H, 9.99; N, 5.41.
La cta m (5d ). Colorless oil, [R]20D ) -29.9 (c 0.85, CH2Cl2).
1H NMR (CDCl3): δ 0.90-1.10 (m, 3H), 0.93 (t, 3H, J ) 7.3
Hz), 0.95 (d, 3H, J ) 6.5 Hz), 1.19 (s, 3H), 1.25-1.55 (m, 4H),
1.65-1.80 (m, 2H), 1.74 (s, 3H), 1.90-2.00 (m, 3H), 2.45 (m,
1H), 3.43 (dt, 1H, J ) 4.0 Hz, J ) 10.2 Hz), 4.98 (t, 1H, J )
6.0 Hz). 13C NMR (CDCl3): δ 11.3; 18.9; 22.0; 24.1; 24.7; 25.3;
30.0; 30.7; 33.9; 41.1; 42.1; 50.1; 56.8; 76.2; 84.2; 176.1. IR
(neat, cm-1 ): 1685, 1265. CIMS (m/z, %): 266 (M + 1, 100),
112 (17).
La cta m epi-(4b). Colorless oil; [R]20D ) -36.0 (c 2.00, CH2-
1
Cl2). H NMR (CDCl3): δ 0.87 (d, 3H, J ) 7.0 Hz), 0.90-1.15
Cycliza tion of Am id e (3e). A solution of 3e (99 mg, 0.24
mmol) in refluxing benzene (12 mL) was treated with tribu-
tyltin hydride (0.1 mL, 0.35 mmol) and AIBN (3 mg) for 8 h.
After evaporation of the solvent under vacuum, the residue
was chromatographed on silica gel yielding the lactam 4e (51
(m, 3H), 0.95 (d, 3H, J ) 6.5 Hz), 1.10 (d, 3H, J ) 7.0 Hz),
1.16 (s, 3H), 1.20-1.35 (m, 1H), 1.40-1.55 (m, 1H), 1.60-1.80
(m, 2H), 1.70 (s, 3H), 2.05 (m, 1H), 2.30-2.50 (m, 2H), 3.39
(dt, 1H, J ) 4.2 Hz, J ) 10.5 Hz), 4.85 (d, 1H, J ) 7.0 Hz). 13
C
NMR (CDCl3): δ 8.2; 10.3; 18.0; 22.1; 23.9; 25.7; 31.2; 34.4;
34.5; 40.4; 41.0; 49.6; 56.4; 75.6; 85.6; 175.7. IR (neat, cm-1):
1690. CIMS (m/z, %): 266 (M + 1, 100), 153 (14), 112 (18).
Anal. Calcd for C16H27NO2: C, 72.41; H, 10.25; N, 5.28.
Found: C, 72.58; H, 10.08; N, 4.92.
mg, 81%) as a white solid, mp 58-59 °C (hexanes); [R]20
)
D
-39.1 (c 1.03, CH2Cl2). 1H NMR (CDCl3): δ 0.85-1.10 (m, 3H),
0.95 (d, 3H, J ) 6.5 Hz), 1.05 (s, 3H), 1.17 (s, 3H), 1.19 (s,
3H), 1.20-1.35 (m, 1H), 1.40-1.50 (m, 1H), 1.65 (dd, 1H, J )
13.0 Hz, J ) 6.8 Hz), 1.70-1.80 (m, 2H), 1.73 (s, 3H), 1.95 (m,
1H), 2.08 (dd, 1H, J ) 6.1 Hz, J ) 13.0 Hz), 3.40 (dt, 1H, J )
4.0 Hz, J ) 10.3 Hz), 4.93 (t, 1H, J ) 6.5 Hz). 13C NMR
(CDCl3): δ 18.1; 22.2; 24.0; 25.1; 25.4; 25.7; 31.1; 34.2; 40.1;
40.3; 41.0; 50.1; 55.8; 76.2; 83.2; 178.0. IR (neat, cm-1 ): 1685,
1275. CIMS (m/z, %): 266 (M + 1, 100), 153 (11), 112 (54).
Anal. Calcd for C16H27NO2: C, 72.41; H, 10.25; N, 5.28.
Found: C, 72.14; H, 10.04; N, 4.93.
La cta m (5b). Colorless oil; [R]20 ) -80.8 (c 3.50, CH2Cl2).
D
1H NMR (CDCl3): δ 0.85-1.15 (m, 3H), 0.94 (d, 3H, J ) 6.6
Hz), 1.01 (d, 3H, J ) 7.7 Hz), 1.05 (d, 3H, J ) 7.1 Hz), 1.16 (s,
3H), 1.30 (m, 1H), 1.40-1.55 (m, 1H), 1.70-1.80 (m, 2H), 1.72
(s, 3H), 2.05 (m, 1H), 2.17 (m, 1H), 2.51 (dq, 1H, J ) 8.7 Hz,
J ) 7.7 Hz), 3.38 (dt, 1H, J ) 4.2 Hz, J ) 10.5 Hz), 4.52 (d,
1H, J ) 6.3 Hz). 13C NMR (CDCl3): δ 11.4; 11.8; 18.5; 21.9;
23.9; 25.4; 31.1; 34.3; 36.0; 39.7; 40.9; 49.7; 56.5; 76.1; 90.0;
176.3. IR (neat, cm-1): 1690. CIMS (m/z, %): 266 (M + 1, 100),
153 (7), 112 (8). Anal. Calcd for C16H27NO2: C, 72.41; H, 10.25;
N, 5.28. Found: C, 72.60; H, 10.42; N, 5.14.
Red u ctive Clea va ge of La cta m s (4-5). Gen er a l P r o-
ced u r e: To a mixture of LiAlH4 (0.5 g, 13.1 mmol) and AlCl3
(713 mg, 5.34 mmol) in anhydrous THF (30 mL) at 0 °C was
slowly injected a solution of the corresponding lactams 4 or 5
(2.7 mmol). The solution was stirred for 10 min at 0 °C, and
then the mixture was carefully quenched with water (40 mL)
and extracted with chloroform (3 × 50 mL). The organic layer
was washed with brine, dried over anhydrous Na2SO4, and the
solvent evaporated under vacuum giving pure pyrrolidinyl-
mentols 6a ,9 6d ,9 8a ,9 8d ,9 9b, 9c, 11b, 11c, and 13b.
La cta m epi-(5b). Colorless oil; [R]20 ) -81.5 (c 0.52 CH2-
D
1
Cl2). H NMR (CDCl3): δ 0.85-1.05 (m, 3H), 0.93 (d, 3H, J )
6.6 Hz), 1.04 (d, 3H, J ) 7.0 Hz), 1.11 (d, 3H, J ) 7.3 Hz),
1.20 (s, 3H), 1.20-1.35 (m, 1H), 1.35-1.55 (m, 1H), 1.65-1.75
(m, 2H), 1.72 (s, 3H), 1.80-1.95 (m, 2H), 2.14 (quintuplet, 1H,
J ) 7.3 Hz), 3.43 (dt, 1H, J ) 4.2 Hz, J ) 10.5 Hz), 4.91 (d,
1H, J ) 6.0 Hz). 13C NMR (CDCl3): δ 12.6; 14.8; 20.1; 22.0;
24.2; 25.5; 31.2; 34.5; 38.0; 41.0; 44.1; 50.5; 57.3; 76.1; 85.3;
177.0. IR (neat, cm-1): 1690. CIMS (m/z, %): 266 (M + 1, 100),
153 (6), 112 (15). Anal. Calcd for C16H27NO2: C, 72.41; H,
10.25; N, 5.28. Found: C, 72.63; H, 10.38; N, 5.09.
(3′R,4′R)-8-(3′,4′-Dim et h ylp yr r olid in yl)-m en t h ol (9b ).
1
Yield: 96%. Colorless oil, [R]20 ) -0.55 (c 2.00, CH2Cl2). H
D
NMR (CDCl3): δ 0.90-1.05 (m, 15H), 1.14 (s, 3H), 1.45-1.70
(m, 7H), 1.95 (m, 1H), 2.20 (m, 1H), 2.65 (m, 1H), 2.95 (m,
2H), 3.50-3.60 (m, 1H). 13C NMR (CDCl3): δ 15.9; 16.3; 17.5;
21.3; 22.0; 25.4; 30.9; 35.0; 40.0; 40.1; 44.2; 48.4; 52.6; 54.1;
59.0; 72.7. IR (neat, cm-1 ): 3100, 1450. CIMS (m/z, %): 254
(M + 1, 100), 238 (8), 140 (90). Anal. Calcd for C16H31NO: C,
75.83; H, 12.33; N, 5.53. Found: C, 75.68; H, 12.21; N, 5.65.
(3′R,4′S)-8-(3′-Met h yl-4′-p h en ylp yr r olid in yl)-m en t h ol
La cta m (4c). White solid, mp 111-112 °C (hexanes), [R]20
D
) -63.3 (c 1.00, CH2Cl2). 1H NMR (CDCl3): δ 0.85-1.10 (m,
3H), 0.92 (d, 3H, J ) 6.5 Hz), 1.21 (s, 3H), 1.22 (d, 3H, J ) 7.0
Hz), 1.30-1.50 (m, 2H), 1.65-1.75 (m, 2H), 1.78 (s, 3H), 1.95
(m, 1H), 2.44 (dq, 1H, J ) 10.8 Hz, J ) 7.0 Hz), 2.80 (dd, 1H,
J ) 10.8 Hz, J ) 7.2 Hz), 3.33 (dt, 1H, J ) 4.3 Hz, J ) 10.5
Hz), 4.84 (d, 1H, J ) 7.2 Hz), 7.30-7.40 (m, 5H). 13C NMR
(CDCl3): δ 14.8; 18.4; 22.0; 23.9; 25.6; 31.2; 34.4; 41.0; 43.3;
49.6; 52.8; 57.0; 76.3; 89.1; 127.3; 127.9; 128.7; 138.8; 174.1.
IR (neat, cm-1): 1700, 690. CIMS (m/z, %): 328 (M + 1, 100),
282 (19). Anal. Calcd for C21H29NO2: C, 77.02; H, 8.92; N, 4.27.
Found: C, 77.24; H, 8.73; N, 4.31.
(9c). Yield: 99%. Colorless oil, [R]20 ) -11.5 (c 1.06, CH2-
D
1
Cl2). H NMR (CDCl3): δ 0.85-1.10 (m, 4H), 0.90 (d, 3H, J )
6.4 Hz), 0.91 (s., 6H), 1.18 (s, 3H), 1.35-1.50 (m, 2H), 1.55-
1.70 (m, 2H), 1.95-2.25 (m, 2H), 2.30-2.95 (m, 3H), 3.05-
3.25 (m, 2H), 3.66 (dt, 1H, J ) 4.2 Hz, J ) 10.5 Hz), 7.20-
7.40 (m, 5H). 13C NMR (CDCl3): δ 16.5; 18.0; 21.5; 22.1; 25.5;
31.0; 35.1; 44.3; 48.5; 52.4; 52.8; 53.7; 54.5; 59.4; 72.9; 126.3;
127.6; 128.4. IR (neat, cm-1 ): 3100, 1490, 700. CIMS (m/z,
%): 316 (M + 1, 100), 202 (24). Anal. Calcd for C21H33NO: C,
79.95; H, 10.54; N, 4.44. Found: C, 80.11; H, 10.68; N, 4.29.
8-(3′,4′-cis-Dim eth ylp yr r olid in yl)-m en th ol (11b). The
general cleavage-reduction protocol was followed starting from
La cta m (5c). White solid, mp 94-95 °C (hexanes), [R]20
D
1
) -172 (c 0.74, CH2Cl2). H NMR (CDCl3): δ 0.76 (d, 3H, J )
7.5 Hz), 0.85-1.10 (m, 3H), 0.92 (d, 3H, J ) 6.5 Hz), 1.28 (s,
3H), 1.30-1.55 (m, 2H), 1.70-1.90 (m, 2H), 1.80 (s, 3H), 1.95
(m, 1H), 2.86 (dq, 1H, J ) 9.2 Hz, J ) 7.5 Hz), 3.39 (dd, 1H,
J ) 9.2 Hz, J ) 5.3 Hz), 3.49 (dt, 1H, J ) 4.1, J ) 10.7), 5.22
(d, 1H, J ) 5.3 Hz), 7.10-7.40 (m, 5H). 13C NMR (CDCl3): δ
lactam 5c. Yield: 99%. Oil, [R]20 ) -17.1 (c 1.70, CH2Cl2).
D
1H NMR (CDCl3): δ 0.80-1.10 (m, 15H), 1.15 (s, 3H), 1.20 (s,