D. H. Huh et al. / Tetrahedron 58 (2002) 9925–9932
9929
(EI) calcd for C10H8Br2O2 319.8870 (Mþþ2), found
133.7, 136.7, 169.4; HRMS (EI) calcd for C13H17NO
203.1310, found 203.1315.
319.8878.
4.3. General procedure for the substitution reactions
with amine
4.3.5. Pyrrolidine 2-phenylacetamide. Yield (88 mg,
1
93%); colorless oil; Rf 0.23; H NMR d 1.79–1.97 (m,
4H), 3.42 (t, 2H, J¼6.8 Hz), 3.49 (t, 2H, J¼6.8 Hz), 3.66 (s,
2H), 7.20–7.35 (m, 5H); 13C NMR d 24.2, 26.0, 42.2, 45.8,
46.8, 126.6, 128.5, 129.9, 134.8, 169.4; HRMS (EI) calcd
for C12H15NO 189.1153, found 189.1159.
Method A: Use of amine as a reaction solvent. To a solution
of amine (5 mL) and water (0.5 mL) was added dibromo-
alkene (0.50 mmol) at room temperature. After stirring for
the indicated time, the resulting mixture was concentrated
under reduced pressure to remove excess amine. An aq. HCl
(3N, 20 mL) solution was added to the residue, and the
resulting mixture was extracted with chloroform
(3£10 mL). The combined organic layers were washed
with an aq. saturated NaHCO3 solution (2£10 mL) and then
water (2£10 mL), dried over anhydrous MgSO4, filtered,
and concentrated under reduced pressure. The crude product
was purified with column chromatography to give the pure
product, amide.
4.3.6. Pyrrolidine 2-(4-chlorophenyl)acetamide. Yield
(102 mg, 91%); pale yellowish solid, mp 106–1078C; Rf
0.22; 1H NMR d 1.80–1.98 (m, 4H), 3.42 (t, 2H, J¼6.8 Hz),
3.48 (t, 2H, J¼6.8 Hz), 3.61 (s, 2H), 7.20–7.30 (m, 4H); 13C
NMR d 24.3, 26.1, 41.4, 45.9, 46.8, 128.6, 130.4, 132.6,
133.4, 168.9; HRMS (EI) calcd for C12H14ClNO 223.0764,
found 223.0754.
4.3.7. Pyrrolidine 2-(2-chlorophenyl)acetamide. Yield
(108 mg, 96%); pale yellowish solid, mp 73–748C; Rf
0.21; 1H NMR d 1.83–2.01 (m, 4H), 3.48 (t, 2H, J¼6.8 Hz),
3.52 (t, 2H, J¼6.8 Hz), 3.76 (s, 2H), 7.17–7.25 (m, 2H),
7.32–7.39 (m, 2H); 13C NMR d 24.4, 26.2, 39.4, 46.0, 46.8,
127.0, 128.3, 129.3, 131.0, 133.5, 134.2, 168.5; HRMS (CI)
calcd for C12H15ClNO 224.0842 (Mþþ1), found 224.0848.
Method B: The optimum conditions with KOH and amine.
To a solution of 1,1-dibromo-2-(4-nitrophenyl)ethene
(154 mg, 0.50 mmol) in THF (2.0 mL) and H2O (1.5 mL)
were added amine (0.85 mmol) and KOH (114 mg,
2.0 mmol) at room temperature. After stirring for the
indicated time, an aq. HCl (3N, 20 mL) was added to the
reaction mixture and the resulting mixture was extracted
with chloroform (3£10 mL). The combined organic layers
were washed with an aq. saturated NaHCO3 solution
(2£10 mL) and then water (2£10 mL), dried over anhy-
drous MgSO4, filtered, and concentrated under reduced
pressure. The crude product was purified with column
chromatography to give the pure product, amide.
4.3.8. Pyrrolidine 2-(4-trifluoromethylphenyl)acetamide.
Yield (122 mg, 95%); white solid, mp 98–998C; Rf 0.22; 1H
NMR d 1.81–2.00 (m, 4H), 3.45 (t, 2H, J¼6.8 Hz), 3.50 (t,
2H, J¼6.8 Hz), 3.71 (s, 2H), 7.40 (d, 2H, J¼8.0 Hz), 7.58
(d, 2H, J¼8.0 Hz); 13C NMR d 24.2, 26.1, 41.7, 45.9, 46.8,
124.1 (q, J¼272 Hz), 125.3, 128.9 (q, J¼32.6 Hz), 129.4,
139.0, 168.4; HRMS (EI) calcd for C13H14F3NO 257.1028,
found 257.1023.
4.3.1. Pyrrolidine 2-(4-methoxyphenyl)acetamide. Yield
(102 mg, 93%); colorless oil; Rf 0.22; 1H NMR d 1.79–1.96
(m, 4H), 3.42 (t, 2H, J¼6.8 Hz), 3.48 (t, 2H, J¼6.8 Hz),
3.59 (s, 2H), 3.79 (s, 3H), 6.86 (d, 2H, J¼8.8 Hz), 7.20 (d,
2H, J¼8.8 Hz); 13C NMR d 24.3, 26.1, 41.3, 45.9, 46.8,
55.2, 114.0, 127.0, 130.0, 158.4, 169.8; HRMS (EI) calcd
for C13H17NO2 219.1260, found 219.1251.
4.3.9. Pyrrolidine 2-(2-trifluoromethylphenyl)acetamide.
1
Yield (125 mg, 97%); colorless oil; Rf 0.24; H NMR d
1.83–2.01 (m, 4H), 3.43 (t, 2H, J¼6.7 Hz), 3.52 (t, 2H,
J¼6.7 Hz), 3.82 (s, 2H), 7.33–7.43 (m, 2H), 7.49–7.54 (m,
1H), 7.64–7.66 (m, 1H); 13C NMR d 24.4, 26.1, 38.5, 46.0,
46.7, 124.5 (q, J¼272 Hz), 125.9 (q, J¼5.6 Hz), 126.9,
128.6 (q, J¼30.0 Hz), 131.8, 131.9, 133.7, 168.4; HRMS
(EI) calcd for C13H14F3NO 257.1028, found 257.1036.
4.3.2. Pyrrolidine 2-(2-methoxyphenyl)acetamide. Yield
(108 mg, 99%); colorless oil; Rf 0.22; 1H NMR d 1.81–1.97
(m, 4H), 3.45 (t, 2H, J¼6.8 Hz), 3.50 (t, 2H, J¼6.8 Hz),
3.64 (s, 2H), 3.82 (s, 3H), 6.85–6.94 (m, 2H), 7.20–7.25
(m, 2H); 13C NMR d 24.2, 26.0, 35.7, 45.6, 46.5, 55.2,
110.1, 120.4, 123.7, 127.8, 130.1, 156.9, 169.7; HRMS (EI)
calcd for C13H17NO2 219.1260, found 219.1266.
4.3.10. Pyrrolidine 2-(4-cyanophenyl)acetamide. Yield
(96 mg, 90%); white solid, mp 72–748C; Rf 0.23; 1H NMR
d 1.82–2.02 (m, 4H), 3.45 (t, 2H, J¼6.6 Hz), 3.49 (t, 2H,
J¼6.6 Hz), 3.70 (s, 2H), 7.40 (d, 2H, J¼8.4 Hz), 7.62 (d,
2H, J¼8.4 Hz); 13C NMR d 23.7, 25.5, 41.1, 45.4, 46.3,
109.8, 118.3, 129.6, 131.5, 140.2, 167.4; HRMS (EI) calcd
for C13H14N2O 214.1106, found 214.1103.
4.3.3. Pyrrolidine 2-(4-methylphenyl)acetamide. Yield
(96 mg, 95%); colorless oil; Rf 0.21; 1H NMR d 1.78–1.95
(m, 4H), 2.32 (s, 3H), 3.41 (t, 2H, J¼6.6 Hz), 3.48 (t, 2H,
J¼6.6 Hz), 3.61 (s, 2H), 7.12 (d, 2H, J¼8.1 Hz), 7.18 (d,
2H, J¼8.1 Hz); 13C NMR d 21.0, 24.3, 26.1, 41.9, 45.9,
46.8, 128.8, 129.2, 131.8, 136.2, 169.7; HRMS (EI) calcd
for C13H17NO 203.1310, found 203.1307.
4.3.11. Pyrrolidine 2-(2-cyanophenyl)acetamide. Yield
(88 mg, 81%); pale yellowish solid, mp 98–1008C; Rf 0.23;
1H NMR d 1.83–1.93 (m, 2H), 1.96–2.05 (m, 2H), 3.51 (t,
2H, J¼6.9 Hz), 3.57 (t, 2H, J¼6.9 Hz), 3.87 (s, 2H), 7.33–
7.39 (m, 1H), 7.50–7.66 (m, 3H); 13C NMR d 23.7, 25.4,
39.1, 45.3, 46.2, 112.4, 117.3, 126.7, 130.2, 131.8, 132.1,
138.7, 166.6; HRMS (EI) calcd for C13H14N2O 214.1106,
found 214.1104.
4.3.4. Pyrrolidine 2-(2-methylphenyl)acetamide. Yield
(101 mg, 99%); colorless oil; Rf 0.23; 1H NMR d 1.81–1.98
(m, 4H), 2.30 (s, 3H), 3.41 (t, 2H, J¼6.7 Hz), 3.53 (t, 2H,
J¼6.7 Hz), 3.62 (s, 2H), 7.14–7.17 (m, 4H); 13C NMR d
19.7, 24.4, 26.2, 39.9, 45.9, 46.8, 126.1, 126.8, 129.0, 130.2,
4.3.12. Pyrrolidine 2-(4-nitrophenyl)acetamide. Yield
(116 mg, 99%); pale yellowish solid, mp 106–1078C; Rf