3658
S. Gosling et al.
PAPER
Liebeskind–Srogl Coupling Reaction; General Procedure E
IR (neat): 1737.9 (C=O ring), 1507.5–1595.0 (N=CS), 1304.3–
1260.8 cm–1 (C–N).
1H NMR (CDCl3): d = 3.86 (s, 3 H, OCH3), 4.48 (s, 2 H, CH2Ph),
5.40 (s, 2 H, CH2OCO), 6.94 (d, J = 8.8 Hz, 2 Harom), 6.98 (s, 1 H,
H-6), 7.36 (m, 10 H, 2 × C6H5), 8.11 (d, J = 8.8 Hz, 2 Harom).
13C NMR (CDCl3): d = 36.0 (SCH2), 55.4 (CH3, OCH3), 69.2
(CH2OCO), 114.3 (CHaryl), 126.2 (C-6), 126.9 (Caryl), 127.7, 128.2,
128.6, 128.6, 128.7, 129.2 (CHphenyl), 134.0 (CHaryl), 134.3 (C-4),
134.6, 135.8 (Cphenyl), 149.5 (OCO), 159.4 (4-MeOCaryl), 161.5 (C-
5), 165.2 (C-2).
To the N-3 protected imidazolinone (1 mmol, 1 equiv), dissolved in
anhyd THF (10 mL) under argon were added Pd(PPh3)4 (0.1 mmol,
0.1 equiv), copper(I) thiophene-2-carboxylate (CuTC) (3 mmol, 3
equiv), and 4-methoxyphenylboronic acid (1.2 mmol, 1.2 equiv) at
r.t. The mixture was stirred for 24 h at 70 °C, after which the solu-
tion was diluted with EtOAc (20 mL), and washed with sat. aq
NaHCO3 (3 × 50 mL). The combined organic layers were filtered
over Celite and concentrated in vacuo. The crude product was puri-
fied by flash silica gel column chromatography (Table 3).
MS (IS): m/z = 459.5 [M + H]+.
(4Z)-4-(4-Methoxybenzylidene)-2-(4-methoxyphenyl)-4,5-dihy-
dro-1H-imidazol-5-one (16a)
HRMS-ES: m/z [M – CO2 + H]+ calcd for C25H23N2O2S: 415.14748;
found: 415.14734; [M + H]+ calcd for C26H23N2O4S: 459.13730;
found: 459.13724; [M + Na]+ calcd for C26H22N2O4S + Na:
481.11925; found: 481.11927.
The hydantoin 9 (21 mg, 0.18 mmol, 1 equiv), Pd(PPh3)4 (9.24
mmol, 0.05 equiv), CuTC (0.56 mmol, 3 equiv), and 4-methoxyphe-
nylboronic acid (0.22 mmol, 1.2 equiv) were introduced in DMF (3
mL) in a vial under argon at r.t. The vial was sealed and the mixture
was stirred and irradiated (300 W) at 130 °C, for 1 h, after which the
solution was diluted with EtOAc (10 mL) and washed with sat. aq
of NaHCO3 (3 × 100mL). The combined organic layers were fil-
tered over Celiteand concentrated in vacuo. Flash chromatographic
purification (PE–EtOAc, 1:1) of the crude product afforded com-
pound 16a as a yellow solid; yield: 20 mg (36%); mp 264–266 °C;
Rf = 0.25 (CH2Cl2–MeOH, 19:1).
(4Z)-1-Benzyl-2-(benzylsulfanyl)-4-(4-methoxybenzylidene)-
4,5-dihydro-1H-imidazol-5-one (14)
The thiohydantoin 19 (2.00 g, 6.17 mmol, 1 equiv) was S-alkylated
according to general procedure B. Flash chromatographic purifica-
tion (PE–EtOAc, 7:3) afforded compound 14 as a yellow solid;
yield: 2.23 g (87%); mp 146–149 °C; Rf = 0.55 (PE–EtOAc, 7:3).
IR (neat): 1699.6 (C=O ring), 1496.3–1597.6 (N=CS), 1252.2–
1172.6 cm–1 (C–N).
1H NMR (CDCl3): d = 3.85 (s, 3 H, OCH3), 4.55 (s, 2 H, SCH2),
4.76 (s, 2 H, NCH2), 6.94 (d, J9,10 = 8.8 Hz, 2 Harom), 7.00 (s, 1 H,
H-6), 7.32 (m, 10 H, 2 × C6H5), 8.15 (d, J10,9 = 8.8 Hz, 2 Harom).
13C NMR (CDCl3): d = 35.1 (SCH2), 44.2 (NCH2), 55.3 (OCH3),
114.2 (CHaryl), 124.6 (C-6), 127.4 (Caryl), 127.7, 127.8, 128.6, 128.7,
129.2 (CHphenyl), 133.8 (CHaryl), 135.7 (C-4), 136.0, 136.5 (Cphenyl),
161.1 (4-MeOCaryl), 162.6 (C-5), 169.8 (C-2).
IR (neat): 2955.8 (NH), 1698.9 (C=O ring), 1595.7–1503.7
(N=CS), 1251.5–1170.6 cm–1 (C–N).
1H NMR (DMSO-d6): d = 3.83, 3.86 (2 s, 6 H, OCH3), 6.92 (s, 1 H,
H-6), 7.05 (d, J = 8.8 Hz, 2 Harom), 7.14 (d, J = 8.8 Hz, 2 Harom), 8.11
(d, J = 8.8 Hz, 2 Harom), 8.28 (d, J = 8.8 Hz, 2 Harom), 11.91 (br, 1 H,
NH).
13C NMR (DMSO-d6): d = 55.3, 55.6 (OCH3), 114.4 (CHarom),
114.5 (CHarom), 120.4 (Carom), 123.9 (C-6), 127.3 (Carom), 129.1
(CHarom), 133.8 (C-4), 159.9 (C-2), 160.6 (4-MeOCarom), 162.5 (4-
MeOCarom), 172.1 (C-5).
MS (IS): m/z = 415.0 [M + H]+, 437.5 [M + Na]+.
HRMS-ES: m/z [M + H]+ calcd for C25H23N2O2S: 415.14748;
found: 415.14765; [M + Na]+ calcd for C25H22N2O2S + Na:
437.12942; found: 437.12932.
MS (IS): m/z = 309.5 [M + H]+.
HRMS-ES: m/z [M + H]+ calcd for C18H17N2O3: 309.12337; found:
309.12349.
(4Z)-2-(Benzylsulfanyl)-1-(4-methoxybenzyl)-4-(4-methoxy-
benzylidene)-4,5-dihydro-1H-imidazol-5-one (15)
(4Z)-1-Benzyloxycarbonyl-4-(4-methoxybenzylidene)-2-(4-
methoxyphenyl)-4,5-dihydro-1H-imidazol-5-one (16c)
Compound 13 (100 mg, 0.22 mmol, 1 equiv) was submitted to the
coupling reaction according to general procedure E. Flash chro-
matographic purification (PE–EtOAc, 8:2) afforded the imidazolo-
ne 16c as a yellow solid; yield: 67 mg (69%); mp 126–128 °C;
Rf = 0.34 (PE–EtOAc, 7:3).
Compound 9 (500 mg, 1.54 mmol, 1 equiv) dissolved in THF (7.5
mL) under argon in a 50 mL round-bottom flask was cooled to 0 °C.
Bu4NI (57.0 mg, 0.154 mmol, 0.1 equiv), NaH (60% in oil; 203 mg,
8.47 mmol, 5.5 equiv), and 4-methoxybenzyl chloride (0.65 mL,
4.93 mmol, 3.2 equiv) were added and the mixture was stirred 4 h
at r.t. After quenching with ice and extraction with EtOAc (3 × 20
mL), the combined organic layers were dried (MgSO4), and concen-
trated in vacuo. Flash chromatographic purification (PE–EtOAc,
9:1) of the crude product afforded compound 15 as a yellow solid;
yield: 301 mg (44%); mp 86–88 °C; Rf = 0.47 (PE–EtOAc, 7:3).
IR (neat): 1735.9 (C=O), 1597.0–1502.9 (C=C), 1250.8–1170.3
cm–1 (C–N).
1H NMR (CDCl3): d = 3.85, 3.86 (2 s, 6 H, OCH3), 5.33 (s, 2 H,
CH2OCO), 6.89 (d, J = 8.8 Hz, 2 Harom), 6.96 (d, J = 8.8 Hz, 2
H
arom), 7.23 (s, 1 H, H-6), 7.59 (d, J = 8.8 Hz, 2 Harom), 7.34 (s, 5 H,
IR (neat): 1700.0 (C=O ring), 1510.0–1594.1 (N=CS), 1260.8–
1171.1 cm–1 (C–N).
C6H5), 8.19 (d, J = 8.8 Hz, 2 Harom).
13C NMR (CDCl3): d = 55.4 (2 × OCH3), 69.6 (CH2OCO), 113.6
(CHaryl), 114.4 (CHaryl), 122.1 (Caryl), 126.8 (Caryl), 128.5, 128.6
(CHphenyl), 130.0 (C-6), 130.0 (CHaryl), 134.1 (Cphenyl), 134.7
(CHaryl), 135.0 (C-4), 149.5 (OC=O), 156.8 (C-2), 162.0 (4-MeO-
Carom), 161.8 (4-MeOCarom), 167.07 (C-5).
1H NMR (CDCl3): d = 3.76, 3.84 (2 s, 6 H, OCH3), 4.55 (s, 2 H,
SCH2), 4,69 (s, 2 H, NCH2), 6.82 (d, J = 8.5 Hz, 2 Harom), 6.94 (d,
J0 = 8.8 Hz, 2 Harom), 6.98 (s, 1 H, H-6), 7.24 (d, J = 8.5 Hz, 2 Harom),
7.37 (m, 5 H, C6H5), 8.14 (d, J = 8.8 Hz, 2 Harom).
13C NMR (CDCl3): d = 35.1 (SCH2), 43.7 (NCH2), 55.2, 55.3
(OCH3), 114.0 (CHaryl), 114.2 (CHaryl), 124.4 (C-6), 127.4 (Caryl),
127.9 (Caryl), 127.8, 128.7, 129.2 (CHphenyl), 129.3 (CHaryl), 133.7
(CHaryl), 136.0 (C-4, Cphenyl), 136.6 (Cphenyl), 159.2 (4-MeOCaryl),
161.0 (4-MeOCaryl), 162.6 (C-5), 169.8 (C-2).
MS (IS): m/z = 399.0 [M – CO2 + H]+, 443.5 [M + H]+, 465.0 [M +
Na]+.
HRMS-ES: m/z [M – CO2 + H]+ calcd for C25H23N2O3: 399.17032;
found: 399.17032; [M + H]+ calcd for C26H23N2O5: 443.16015;
found: 443.16031; [M + Na]+ calcd for C26H22N2O5 + Na:
465.14209; found: 465.14207.
MS (IS): m/z = 445.5 [M + H]+, 467.5 [M + Na].
HRMS-ES: m/z [M + H]+ calcd for C26H25N2O3S: 445.15804;
found: 445.15819.
Synthesis 2011, No. 22, 3649–3660 © Thieme Stuttgart · New York