3556
J.H. Kim et al. / Tetrahedron 67 (2011) 3553e3558
was extracted with CH2Cl2 (5 mLꢂ4). The combined extracts were
dried over anhydrous magnesium sulfate and filtered. The solvent
was removed under reduced pressure and the residue was purified
by flash column chromatography on silica gel using mixture of n-
hexane and EtOAc as an eluent to give the hydroxymethyl pyrrole
products 4.
4.52(s, 2H); 13C NMR (125 MHz, CDCl3)
135.9, 134.2, 128.6, 126.9, 126.1, 122.3, 120.9, 110.6, 109.9, 57.4, 48.4;
d 152.7, 148.9, 139.8, 136.6,
FT-IR:
n
3304 cmꢀ1 (br, OH); mp 73e75 ꢁC; HRMS m/z calcd for
C17H16N2O [MþNa]þ 287.1161, found 287.1160. TLC Rf(EtOAc/Hex-
ane 3:7)¼0.17, yellow solid.
4.2.8. (1-Benzyl-5-(1-methyl-1H-imidazol-5-yl)-1H-pyrrol-2-yl)
4.2.1. (1-Benzyl-5-phenyl-1H-pyrrol-2-yl)methanol (4a). 1H NMR
methanol (4h). 1H NMR (500 MHz, CDCl3):
d 7.36(s, 1H), 7.23e7.16
(500 MHz, CDCl3):
d
7.36e7.20(m, 8H), 6.91(d, J¼7.5 Hz, 2H), 6.27(d,
(m, 3H), 6.83(s, 1H), 6.79(d, J¼9.0 Hz, 2H), 6.27(d, J¼4 Hz, 1H), 6.19
J¼3.5 Hz, 1H), 6.24(d, J¼3.5 Hz, 1H), 5.31(s, 2H), 4.45(s, 2H); 13C
(d, J¼4.0 Hz, 1H), 5.16(s, 2H), 4.56(s, 2H), 3.19(s, 3H); 13C NMR
NMR (125 MHz, CDCl3)
d
139.3, 137.0, 133.4, 133.2, 129.1, 128.9,
(125 MHz, CDCl3) d 138.7, 138.4, 134.2, 129.7, 128.7, 127.3, 126.1,
128.6, 127.4, 127.3, 125.7, 109.9, 108.4, 57.5, 47.8; FT-IR:
n
3360 cmꢀ1
124.6, 122.1, 111.2, 109.2, 56.9, 47.7, 31.7; FT-IR: n
3336 cmꢀ1 (br,
(br, OH); HRMS m/z calcd for C18H17NO [MþNa]þ 286.1208, found
286.1206. TLC Rf(EtOAc/Hexane 3:7)¼0.31, yellow oil.
OH); HRMS m/z calcd for C16H17N3O [MþNa]þ 290.1270, found
290.1271. TLC Rf(MeOH/EtOAc 1:9)¼0.31, yellow oil.
4.2.2. (1-Benzyl-5-(2-methoxyphenyl)-1H-pyrrol-2-yl)methanol
4.2.9. (1-Benzyl-5-(phenanthren-9-yl)-1H-pyrrol-2-yl)methanol
(4b). 1H NMR (500 MHz, CDCl3):
d
7.36e7.13(m, 5H), 6.92e6.87(m,
4H), 6.28(d, J¼3.0 Hz, 1H), 6.14(d, J¼3.5 Hz, 1H), 5.10(s, 2H), 4.45(s,
2H), 3.68(s, 3H); 13C NMR (125 MHz, CDCl3)
157.5, 139.3, 133.2,
132.9, 132.6, 129.6, 128.6, 127.0, 126.2, 122.5, 120.7, 110.8, 109.7,
(4i). 1H NMR (500 MHz, CDCl3):
d
8.70(d, J¼8.0 Hz, 1H), 8.65(d,
J¼8.5 Hz, 1H), 7.81(d, J¼8.0 Hz, 1H), 7.73(d, J¼8.0 Hz, 1H), 7.65e7.43
(m, 5H), 7.14e7.07(m, 3H), 6.77(d, J¼7.5 Hz, 2H), 6.40(d, J¼3.5 Hz,
1H), 6.32(d, J¼3.0 Hz, 1H), 5.21(br, 1H), 4.92(br, 1H), 4.56(br, 2H);
d
108.6, 57.7, 55.4, 48.3; FT-IR:
n
3380 cmꢀ1 (br, OH); HRMS m/z calcd
13C NMR (125 MHz, CDCl3)
d 139.0, 134.2, 132.8, 132.4, 131.4, 130.6,
for C19H19NO2 [MþNa]þ 316.1314, found 286.1312. TLC Rf(EtOAc/
Hexane 3:7)¼0.13, yellow oil.
130.5, 130.3, 129.6, 129.0, 128.7, 127.2, 127.1, 127.0, 126.92, 126.89,
126.76, 126.0, 122.9, 122.6, 109.9, 109.7, 57.6, 48.3; FT-IR:
n
3356 cmꢀ1 (br, OH); mp 53e55 ꢁC; HRMS m/z calcd for C26H21NO
[MþNa]þ 386.1521, found 386.1522. TLC Rf(EtOAc/Hexane 3:7)¼
0.31, yellow solid.
4.2.3. (1-Benzyl-5-o-tolyl-1H-pyrrol-2-yl)methanol (4c). 1H NMR
(500 MHz, CDCl3):
J¼3.5 Hz, 1H), 6.08(d, J¼3.0 Hz), 5.05(s, 2H), 4.50(d, J¼4.0 Hz, 2H),
2.13(s, 3H); 13C NMR (125 MHz, CDCl3)
139.0, 138.4, 135.4, 133.1,
132.1, 131.4, 130.2, 128.7, 128.3, 127.2, 126.2, 125.6, 109.3, 108.3, 57.6,
d
7.25e7.10(m, 7H), 6.80(d, J¼7.0 Hz, 2H), 6.28(d,
d
4.3. General procedure for the Ag(I)-catalyzed synthesis of 2-
azidomethyl pyrroles 5
47.8, 20.3; FT-IR:
n
3337 cmꢀ1 (br, OH); mp 51e53 ꢁC; HRMS m/z
calcd for C19H19NO [MþNa]þ 300.1365, found 286.1367. TLC Rf(E-
tOAc/Hexane 3:7)¼0.38, yellow solid.
To a solution of propargylic alcohol 3 (0.3 mmol) in acetonitrile
(1.2 mL) were added azidotrimethylsilane (0.39 mmol, 50
mL) and
TMEDA (20 mol %, 9.1 L). The mixture was stirred at room tem-
m
4.2.4. (1-Benzyl-5-(4-(trifluoromethyl)phenyl)-1H-pyrrol-2-yl)meth-
perature and the progress of the reaction was monitored by TLC.
After consumption of the starting material, the mixture was treated
with AgOAc (5 mol %, 2.5 mg). The resulting mixture was stirred for
30 min and then quenched with water. The aqueous layer was
extracted with CH2Cl2 (5 mLꢂ4). The combined extracts were dried
over anhydrous magnesium sulfate and filtered. The solvent was
removed under reduced pressure and the reside was purified by
flash column chromatography on silica gel using mixture of n-
hexane and EtOAc as an eluent to give the azidomethyl pyrrole
products 5.
anol (4d). 1H NMR (500 MHz, CDCl3):
d
7.54(d, J¼8.5 Hz, 2H), 7.39
(d, J¼8.0 Hz, 2H), 7.30e7.21(m, 3H), 6.90(d, J¼7.5 Hz, 2H), 6.31e6.29
(m, 2H), 5.31(s, 2H), 4.46(s, 2H); 13C NMR (125 MHz, CDCl3)
138.8,
136.82, 136.81, 135.3, 134.3, 129.0, 128.9, 125.61, 125.58, 125.56,
d
125.53, 110.2, 109.5, 57.3, 47.9; FT-IR:
n
3339 cmꢀ1 (br, OH); HRMS
m/z calcd for C19H16F3NO [MþNa]þ 354.1082, found 354.1084. TLC
Rf(EtOAc/Hexane 3:7)¼0.23, yellow oil.
4.2.5. (1-Benzyl-5-(3,5-difluorophenyl)-1H-pyrrol-2-yl)methanol
(4e). 1H NMR (500 MHz, CDCl3):
d 7.55e7.45(m, 1H), 7.30e7.21(m,
2H), 6.88(d, J¼7.5 Hz, 2H), 6.83e6.80(m, 2H), 6.71e6.67(m, 1H),
4.3.1. 2-(Azidomethyl)-1-benzyl-5-phenyl-1H-pyrrole (5a). 1H NMR
6.27(s, 2H), 5.33(s, 2H), 4.47(s, 2H); 13C NMR (125 MHz, CDCl3)
(500 MHz, CDCl3):
d
7.32e7.22(m, 8H), 6.91(d, J¼7.5 Hz, 2H), 6.35(d,
d
164.0, 163.9, 162.1, 162.0, 138.6, 136.4, 136.34, 136.26, 134.5, 134.4,
J¼3.0 Hz, 1H), 6.27(d, J¼3.0 Hz, 1H), 5.23(s, 2H), 4.14(s, 2H); 13C
134.3, 132.1, 129.4, 129.4, 129.1, 127.6, 125.6, 111.64, 111.59, 111.48,
NMR (125 MHz, CDCl3)
d 138.7, 133.1, 129.05, 128.98, 128.6, 127.5,
111.43, 110.1, 109.6, 102.8, 102.6, 102.4, 57.4, 47.9; FT-IR:
n
3395 cmꢀ1
127.4, 127.2, 125.6, 111.4, 108.5, 47.9, 47.4; FT-IR: n
2102 cmꢀ1 (N3);
(br, OH); HRMS m/z calcd for C18H15F2NO [MþNa]þ 322.1020, found
322.1022. TLC Rf(EtOAc/Hexane 3:7)¼0.33, yellow oil.
HRMS m/z calcd for C18H16N4 [MþNa]þ 311.1273, found 311.1275.
TLC Rf(EtOAc/Hexane 3:7)¼0.69, yellow oil.
4.2.6. (1-Benzyl-5-(thiophen-3-yl)-1H-pyrrol-2-yl)methanol (4f). 1H
4.3.2. 2-(Azidomethyl)-1-benzyl-5-(2-methoxyphenyl)-1H-pyrrole
NMR (500 MHz, CDCl3):
d
8.49e8.48(m, 1H), 7.60(td, J¼8 Hz, 1.5 Hz,
(5b). 1H NMR (500 MHz, CDCl3):
d
7.32e7.15(m, 5H), 6.94e6.86(m,
4H), 6.35(d, J¼3.5 Hz, 1H), 6.16(d, J¼3.5 Hz, 1H), 5.03(s, 2H), 4.15(s,
2H), 3.67(s, 3H); 13C NMR (125 MHz, CDCl3)
157.5, 138.8, 132.9,
129.8, 128.6, 127.1, 126.6, 126.1, 122.3, 120.8, 111.2, 111.0, 108.7, 55.4,
1H), 7.51e7.36(m, 2H), 7.27e7.13(m, 3H), 7.05e7.02(m, 1H), 6.92(d,
J¼7.5 Hz, 2H), 6.55(d, J¼4 Hz, 1H), 6.26(d, J¼4 Hz, 1H), 5.94(s, 2H),
d
4.52(s, 2H); 13C NMR (125 MHz, CDCl3)
d 152.7, 148.9, 139.8, 136.6,
135.9, 134.2, 128.6, 126.9, 126.1, 122.3, 120.9, 110.6, 109.9, 57.4, 48.4;
48.4, 47.5; FT-IR: n
2097 cmꢀ1 (N3); mp 98e100 ꢁC; HRMS m/z calcd
FT-IR:
n
3350 cmꢀ1 (br, OH); HRMS m/z calcd for C17H16N2O
for C19H18N4O [MþNa]þ 341.1379, found 341.1376. TLC Rf(EtOAc/
Hexane 3:7)¼0.68, white solid.
[MþNa]þ 287.1161, found 287.1160. TLC Rf(EtOAc/Hexane 3:7)¼
0.33, yellow oil.
4.3.3. 2-(Azidomethyl)-1-benzyl-5-o-tolyl-1H-pyrrole (5c). 1H NMR
4.2.7. (1-Benzyl-5-(pyridin-2-yl)-1H-pyrrol-2-yl)methanol (4g). 1H
(500 MHz, CDCl3):
J¼3.5 Hz, 1H), 6.11(d, J¼3.5 Hz, 1H), 4.96(s, 2H), 4.17(s, 2H), 2.14(s,
3H); 13C NMR (125 MHz, CDCl3)
138.5, 138.4, 136.1, 132.8, 131.4,
130.2, 128.7, 128.5, 127.4, 126.0, 125.9, 125.7, 111.2, 108.4, 47.8, 47.4;
d
7.26e7.10(m, 7H), 6.78(d, J¼7.5 Hz, 2H), 6.35(d,
NMR (500 MHz, CDCl3):
1H), 7.51e7.36(m, 2H), 7.27e7.13(m, 3H), 7.05e7.02(m, 1H), 6.92(d,
J¼7.5 Hz, 2H), 6.55(d, J¼4 Hz, 1H), 6.26(d, J¼4 Hz, 1H), 5.94(s, 2H),
d
8.49e8.48(m, 1H), 7.60(td, J¼8 Hz, 1.5 Hz,
d