A Highly ActiVe Urea-Based Organocatalyst
Synthesis of 26. A 1 mL reaction vessel equipped with a stir
bar charged with 6 (29.3 mg, 0.0688 mmol) and 5 Å molecular
sieves (40 mg) was fitted with a septum and placed under an
atmosphere of Ar (balloon). Compound 7 (200 mg, 1.37 mmol),
CH2Cl2 (40.4 µL), and 19 (78.5 µL, 0.688 mmol) were then added,
the septum was replaced with a cap, and the resulting solution was
stirred at ambient temperature for 26 h. Column chromatography
of the reaction mixture (CH2Cl2, Rf 0.5) yielded 26 (183 mg, 90%)
as a pale yellow oil. 1H NMR (DMSO-d6) δ 7.32-7.34 (dd, 2H, J
) 8.0 Hz), 7.23-7.26 (d, 2H, J ) 8.0 Hz), 6.98-7.02 (app. t, 1H,
J ) 7.5 Hz), 6.84-6.88 (app t, 1H, J ) 7.5 Hz), 6.79-6.81 (d,
2H, J ) 8.0 Hz), 4.68-4.70 (app t, 1H, J ) 5.5 Hz), 4.26-4.30
(app t, 1H, J ) 7.3 Hz), 4.17-4.23 (m, 1H), 3.93-3.98 (m, 1H),
3.69 (s, 3H), 3.63 (s, 3H), 2.36 (s, 3H) 13C NMR (DMSO-d6) δ:
157.1, 136.3, 135.4, 133.6, 128.9, 126.5, 119.7, 118.8, 118.2, 113.3,
111.6, 109.0, 64.0, 55.0, 44.1, 29.3, 10.4. IR (neat): 3399, 3048,
2933, 1610, 1511, 1034 cm-1. HRMS (ESI, m/z) calcd for C19H21-
NO2Na (M + Na)+ 318.1470, found 318.1461.
107.8, 64.2, 43.0, 29.5, 10.6. IR (neat): 3400, 2935, 1611, 1468,
1040, 741 cm-1. HRMS (ESI, m/z) calcd for C18H18NONaCl (M
+ Na)+ 322.0975, found 322.0984.
Synthesis of 30. A 1 mL reaction vessel equipped with a stir
bar charged with 6 (29.3 mg, 0.0688 mmol) and 5 Å molecular
sieves (40 mg) was fitted with a septum and placed under an
atmosphere of Ar (balloon). Compound 7 (200 mg, 1.37 mmol),
CH2Cl2 (66 µL), and 23 (137 mg, 0.688 mmol) were then added,
the septum was replaced with a cap, and the resulting solution was
stirred at ambient temperature for 163 h. Column chromatography
of the reaction mixture (CH2Cl2, Rf 0.3) yielded 30 (191 mg, 93%)
1
as a clear oil. H NMR (DMSO-d6) δ 7.28-7.37 (m, 6H), 6.99-
7.03 (app t, 1H, J ) 7.8 Hz), 6.85-6.89 (app t, 1H, J ) 7.5 Hz),
4.80-4.83 (app t, 1H, J ) 5.0 Hz), 4.32-4.35 (app t, 1H, J ) 7.0
Hz), 4.21-4.27 (m, 1H), 3.92-3.97 (m, 1H), 3.64 (s, 3H), 2.37 (s,
3H). 13C NMR (DMSO-d6) δ: 142.6, 136.3, 133.8, 130.0, 129.9,
127.8, 126.3, 119.9, 118.6, 118.4, 110.9, 109.1, 63.6, 44.3, 29.4,
10.4. IR (neat): 3434, 2250, 1661, 1056, 822, 759, cm-1. HRMS
(ESI, m/z) calcd for C18H19NOCl (M + H)+ 300.1155, found
300.1147.
Synthesis of 27. A 1 mL reaction vessel equipped with a stir
bar charged with 6 (29.3 mg, 0.0688 mmol) and 5 Å molecular
sieves (40 mg) was fitted with a septum and placed under an
atmosphere of Ar (balloon). Compound 7 (200 mg, 1.37 mmol),
CH2Cl2 (78 µL), and 20 (92.3 mg, 0.688 mmol) were then added,
the septum was replaced with a cap, and the resulting solution was
stirred at ambient temperature for 48 h. Column chromatography
of the reaction mixture (CH2Cl2, Rf 0.45) yielded 27 (188 mg, 98%)
Synthesis of 31. A 1 mL reaction vessel equipped with a stir
bar charged with 6 (29.3 mg, 0.0688 mmol) and 5 Å molecular
sieves (40 mg) was fitted with a septum and placed under an
atmosphere of Ar (balloon). Compound 7 (200 mg, 1.37 mmol),
CH2Cl2 (66 µL), and 24 (137 mgs, 0.688 mmol) were then added,
the septum was replaced with a cap, and the resulting solution was
stirred at ambient temperature for 77 h. Column chromatography
of the reaction mixture (CH2Cl2, Rf 0.3) yielded 31 (218 mg, 92%)
1
as a pale yellow oil. H NMR (DMSO-d6) δ 7.57-7.59 (d, 1H, J
) 7.8 Hz), 7.28-7.32 (app t, 2H, J ) 7.8 Hz), 7.18-7.21 (m,
1H), 7.06 (m, 2H), 6.96-7.00 (app t, 1H, J ) 7.8 Hz), 6.80-6.83
(app t, 1H, J ) 7.3 Hz), 4.68-4.70 (app t, 1H, J ) 5.4 Hz), 4.37-
4.40 (app t, 1H, J ) 7.3 Hz), 4.12-4.18 (m, 1H), 3.91-3.97 (m,
1H), 3.62 (s, 3H), 2.33 (s, 3H), 2.13 (s, 3H). 13C NMR (DMSO-
d6) δ: 140.8, 136.6, 136.3, 134.0, 130.1, 127.3, 126.7, 125.6, 125.3,
119.6, 118.4, 118.1, 109.6, 108.9, 63.5, 41.7, 29.3, 19.3, 10.4. IR
(neat): 3410, 3049, 2251, 1657, 1470, 1008 cm-1. HRMS (ESI,
m/z) calcd for C19H21NONa (M + Na)+ 302.1521, found 302.1511.
Synthesis of 28. A 1 mL reaction vessel equipped with a stir
bar charged with 6 (29.3 mg, 0.0688 mmol) and 5 Å molecular
sieves (40 mg) was fitted with a septum and placed under an
atmosphere of Ar (balloon). Compound 7 (200 mg, 1.37 mmol),
CH2Cl2 (78 µL), and 21 (92.3 mg, 0.688 mmol) were then added,
the septum was replaced with a cap, and the resulting solution was
stirred at ambient temperature for 48 h. Column chromatography
of the reaction mixture (4:1 hexane/ethyl acetate, Rf 0.3) yielded
1
as a pale yellow oil. H NMR (DMSO-d6) δ 7.42-7.44 (d, 2H, J
) 8.0 Hz), 7.30-7.35 (m, 4H), 6.99-7.03 (app t, 1H, J ) 7.5
Hz), 6.86-6.89 (app t, 1H, J ) 7.5 Hz), 4.80-4.83 (m, 1H), 4.30-
4.34 (m, 1H), 4.21-4.27 (m, 1H), 3.92-3.97 (m, 1H), 3.64 (s,
3H), 2.37 (s, 3H). 13C NMR (DMSO-d6) δ: 143.0, 136.3, 133.9,
130.7, 130.4, 126.3, 119.9, 118.6, 118.5, 118.4, 110.8, 109.1, 63.6,
44.3, 29.4, 10.4. IR (neat): 3435, 2251, 2125, 1661, 1055, 822,
760 cm-1. HRMS (ESI, m/z) calcd for C18H18NONaBr (M + Na)+
366.0469, found 366.0461.
Synthesis of 34. A 1 mL reaction vessel equipped with a stir
bar charged with 6 (33.3 mg, 0.0782 mmol) and 5 Å molecular
sieves (40 mg) was fitted with a septum and placed under an
atmosphere of Ar (balloon). Compound 32 (200 µL, 1.56 mmol),
CH2Cl2 (424 µL), and 24 (155.7 mg, 0.782 mmol) were then added,
the septum was replaced with a cap, and the resulting solution was
stirred at ambient temperature for 7.8 days. Column chromatography
of the reaction mixture (3:1 hexane/ethyl acetate, Rf 0.5) yielded
1
28 (181 mg, 94%) as a pale yellow oil. H NMR (DMSO-d6) δ
1
7.31-7.35 (app t, 2H, J ) 6.8 Hz), 7.20-7.22 (d, 2H, J ) 8.0
Hz), 6.98-7.04 (m, 3H), 6.84-6.87 (app t, 1H, J ) 7.3 Hz), 4.67-
4.69 (app t, 1H, J ) 5.0 Hz), 4.26-4.30 (app t, 1H, J ) 7.3 Hz),
4.18-4.24 (m, 1H), 3.93-3.98 (m, 1H), 3.63 (s, 3H), 2.36 (s, 3H),
2.22 (s, 3H). 13C NMR (DMSO-d6) δ: 140.5, 136.3, 134.3, 133.6,
128.5, 127.9, 126.5, 119.7, 118.8, 118.2, 111.5, 108.9, 63.8, 44.6,
29.3, 20.6, 10.4. IR (neat): 3392, 3047, 2923, 1470, 1036, 739
cm-1. HRMS (ESI, m/z) calcd for C19H21NONa (M + Na)+
302.1521, found 302.1516.
34 (235 mg, 91%) as a white solid, mp 141-143 °C. H NMR
(CDCl3) δ 7.43-7.45 (m, 3H), 7.32-7.34 (d, 1H, J ) 8.3 Hz),
7.23-7.26 (m, 3H), 7.06-7.09 (app. t, 1H, J ) 6.8 Hz), 6.97 (s,
1H), 4.45-4.47 (app. t, 1H, J ) 6.8 Hz), 4.23-4.26 (dd, 1H, J )
6.7, 10.9 Hz), 4.15-4.18 (dd, 1H, J ) 6.8, 10.9 Hz), 3.80 (s, 3H).
13C NMR (CDCl3) δ: 141.0, 137.3, 131.6, 130.0, 127.2, 126.7,
122.0, 120.5, 119.3, 119.2, 113.9, 109.4, 66.2, 45.0, 32.8. IR
(Nujol): 3302, 2923, 1377, 1053, 1007, 731 cm-1. HRMS (ESI,
m/z) calcd for C17H17NOBr (M + H)+ 330.0494, found 330.0495.
Synthesis of 35. A 1 mL reaction vessel equipped with a stir
bar charged with 6 (32.5 mg, 0.0762 mmol) and 5 Å molecular
sieves (40 mg) was fitted with a septum and placed under an
atmosphere of Ar (balloon). Compound 33 (200 mg, 1.52 mmol),
CH2Cl2 (261 µL), and 24 (151.7 mg, 0.762 mmol) were then added,
the septum was replaced with a cap, and the resulting solution was
stirred at ambient temperature for 7.2 days. Column chromatography
of the reaction mixture (CH2Cl2, Rf 0.5) yielded 35 (221 mg, 89%)
Synthesis of 29. A 1 mL reaction vessel equipped with a stir
bar charged with 6 (29.3 mg, 0.0688 mmol) and 5 Å molecular
sieves (40 mg) was fitted with a septum and placed under an
atmosphere of Ar (balloon). Compound 7 (200 mg, 1.37 mmol),
CH2Cl2 (64 µL), and 22 (106.4 mg, 0.688 mmol) were then added,
the septum was replaced with a cap, and the resulting solution was
stirred at ambient temperature for 621 h. Column chromatography
of the reaction mixture (4:1 hexane/ethyl acetate, Rf 0.3) yielded
29 (165 mg, 80%) as a pale yellow oil. 1H NMR (CDCl3) δ 7.62-
7.65 (d, 1H, J ) 8.0 Hz), 7.57-7.59 (d, 1H, J ) 7.5 Hz), 7.35-
7.37 (d, 1H, J ) 8.0 Hz), 7.29-7.32 (d, 1H, J ) 8.5 Hz), 7.14-
7.24 (m, 3H), 7.04-7.08 (app t, 1H, J ) 7.5 Hz), 4.86-4.89 (dd,
1H, J ) 6.5, 9.0 Hz), 4.37-4.42 (m, 1H), 4.27-4.31 (m, 1H), 3.70
(s, 3H), 2.44 (s, 3H). 13C NMR (CDCl3) δ: 139.3, 136.8, 135.5,
134.1, 129.7, 129.1, 127.5, 126.7, 126.6, 120.5, 119.2, 118.8, 108.9,
1
as a yellow wax. H NMR (DMSO-d6) δ 10.80 (br s, 1H), 7.42-
7.44 (d, 2H, J ) 8.5 Hz), 7.28-7.31 (m, 3H), 7.20-7.22 (d, 1H,
J ) 8.0 Hz), 6.91-6.95 (app t, 1H, J ) 7.5 Hz), 6.80-6.84 (app
t, 1H, J ) 7.5 Hz), 4.78-4.81 (app t, 1H, J ) 5.0 Hz), 4.17-4.28
(m, 2H), 3.91-3.96 (m, 1H), 2.34 (s, 3H). 13C NMR (DMSO-d6)
δ: 143.2, 135.2, 132.2, 130.7, 130.4, 127.3, 119.8, 118.5, 118.4,
118.2, 110.7, 110.5, 63.6, 44.2, 12.0. IR (neat): 3399, 3325, 2926,
J. Org. Chem, Vol. 73, No. 3, 2008 955