The Journal of Organic Chemistry
ARTICLE
(2b) (0.25 g, 1.48 mmol), K3PO4 (0.29g, 1.35 mmol), Pd2(dba)3 (0.0085
g, 9.3 μmol) and III (0.0094 g, 22 μmol) in t-AmOH (4.2 mL) was stirred
at 90 °C for 15 h. The crude product was purified via flash column
chromatography (0ꢀ20% EtOAc/heptanes) to provide the title com-
pound as a white solid (0.31 g, 91%). 1H NMR (400 MHz, CDCl3) δ
7.58ꢀ7.52 (m, 2H), 7.20 (app d, J = 8.0 Hz, 2H), 6.97ꢀ6.91 (m, 2H),
6.78ꢀ6.72 (m, 2H), 6.15 (s, 1H), 3.75 (s, 3H), 2.38 (s, 3H). 13C NMR
(101 MHz, CDCl3) δ 157.4 (C), 143.2 (C), 135.6 (C), 129.2 (CH),
128.6 (C), 127.0 (CH), 125.0 (CH), 114.1 (CH), 55.5 (CH3), 21.8
(CH3). HRMS (m/z): [M ꢀ H]ꢀ calcd for C14H14N1O3S1 276.0700;
found 276.0702. Mp 111.9ꢀ113.1 °C, lit. mp 112 °C.54
126.7 (CH), 126.2 (CH), 123.5 (CH), 21.0 (CH3). HRMS (m/z):
[M þ H]þ calcd for C12H13N2O2S1 249.0692; found 249.0696. Mp
191.5ꢀ193 °C, lit. mp 191ꢀ192 °C.56
4-Methyl-N-(quinolin-6-yl)benzenesulfonamide (3o).
(Table 2, entry 14). Following the general procedure, a mixture of
quinolin-6-yl nonaflate (1n) (0.50 g, 1.17 mmol), 4-tolylsulfonamide
(2b) (0.18 g, 1.05 mmol), K3PO4 (0.27 g, 1.29 mmol), Pd2(dba)3
(0.0054 g, 5.9 μmol) and III (0.0059 g, 14 μmol) in t-AmOH (4.0 mL)
was stirred at 80 °C for 15 h. The crude product was purified via flash
column chromatography (35ꢀ70% EtOAc/heptanes) to provide the
1
title compound as a white solid (0.30 g, 86%). H NMR (400 MHz,
tert-Butyl-4-(4-methylphenylsulfonamide)phenylcarba-
mate (3l). (Table 2, entry 11). Following the general procedure, a
mixture of 4-tert-butoxycarbonylaminophenyl nonaflate (1k) (0.50 g,
1.02 mmol), 4-tolylsulfonamide (2b) (0.21 g, 1.22 mmol), K3PO4 (0.24
g, 1.12 mmol), Pd2(dba)3 (0.0047 g, 5.1 μmol) and III (0.0052 g, 12
μmol) in t-AmOH (3.5 mL) was stirred at 80 °C for 15 h. The crude
product was purified via flash column chromatography (0ꢀ20% EtOAc/
heptanes) to provide the title compound as a white solid (0.34 g, 92%).
1H NMR (400 MHz, DMSO) δ 9.88 (s, 1H), 9.22 (s, 1H), 7.58ꢀ7.52
(m, 2H), 7.30 (d, J = 8.1 Hz, 2H), 7.24 (d, J = 8.8 Hz, 2H), 6.94ꢀ6.88
(m, 2H), 2.32 (s, 3H), 1.43 (s, 9H). 13C NMR (101 MHz, DMSO) δ
152.1 (C), 142.4 (C), 136.0 (C), 135.7 (C), 131.2 (C), 129.0 (CH),
126.2 (CH), 121.2 (CH), 118.3 (CH), 78.7 (C), 28.1 (CH3), 21.0
(CH3). HRMS (m/z): [M þ Na]þ calcd for C18H22N2O4S1Na
385.1193; found 385.1191. Mp 167ꢀ168 °C.
DMSO) δ 10.62 (br s, 1H), 8.74 (dd, J = 4.2, 1.6 Hz, 1H), 8.23 (d, J = 7.5
Hz, 1H), 7.88 (d, J = 9.0 Hz, 1H), 7.73ꢀ7.68 (m, 2H), 7.61 (d, J = 2.4
Hz, 1H), 7.50 (dd, J = 9.0, 2.5 Hz, 1H), 7.43 (dd, J = 8.3, 4.2 Hz, 1H),
7.30 (d, J = 8.0 Hz, 2H), 2.28 (s, 3H). 13C NMR (101 MHz, DMSO) δ
148.8 (CH), 144.2 (C), 142.9 (C), 135.9 (C), 135.3 (C), 134.8 (CH),
129.6 (CH), 129.2 (CH), 127.7 (C), 126.3 (CH), 123.0 (CH), 121.5
(CH), 114.8 (CH), 21.0 (CH3). HRMS (m/z): [M ꢀ H]ꢀ calcd for
C16H13N2O2S1 297.0703; found 297.0707. Mp 194ꢀ197 °C, lit. mp
196ꢀ197 °C.57
Ethyl 1-Benzyl-2-methyl-5-(4-methylphenylsulfonamido)-
1H-indole-3-carboxylate (3p). (Table 2, entry 15). Following the
general procedure, a mixture of ethyl 1-benzyl-2-methyl-5-(perfluoro-
butylsulfonyloxy)-1H-indole-3-carboxylate (1o) (0.50 g, 0.85 mmol),
4-tolylsulfonamide (2b) (0.17 g, 1.01 mmol), K3PO4 (0.20 g, 0.93
mmol), Pd2(dba)3 (0.0075 g, 8.2 μmol) and III (0.0086 g, 20 μmol) in
t-AmOH (2.9 mL) was stirred at 90 °C for 15 h. The crude product was
purified via flash column chromatography (0ꢀ3% MeOH/CH2Cl2).
The white solid obtained was stirred in a mixture of EtOAc (5 mL) and
hexanes (15 mL) at room temperature for 30 min, filtered through a
Buchner funnel, and washed with hexanes (5 mL) to obtain the title
compound as a white solid (0.34 g, 88%). 1H NMR (400 MHz, DMSO)
δ 9.94 (s, 1H), 7.74 (d, J = 2.1 Hz, 1H), 7.62ꢀ7.55 (m, 2H), 7.35 (d, J =
8.8 Hz, 1H), 7.32ꢀ7.19 (m, 5H), 7.00ꢀ6.93 (m, 2H), 6.88 (dd, J = 8.7,
2.1 Hz, 1H), 5.43 (s, 2H), 4.24 (q, J = 7.1 Hz, 2H), 2.63 (s, 3H), 2.30 (s,
3H), 1.33 (t, J = 7.1 Hz, 3H). 13C NMR (101 MHz, DMSO) δ 163.9 (C),
145.3 (C), 142.2 (C), 136.4 (C), 132.9 (C), 131.3 (C), 128.9 (CH), 128.2
(CH), 126.8 (CH), 126.2 (CH), 125.7 (C), 125.6 (CH), 116.6 (CH),
113.2 (CH), 110.2 (CH), 102.9 (C), 58.8 (CH2), 45.8 (CH2), 20.9 (CH3),
14.4 (CH3), 11.8 (CH3). HRMS (m/z): [M ꢀ H]ꢀ calcd for C26H25-
N2O4S1 461.1541; found 461.1537. Mp 216.5ꢀ220.0 °C.
4-Methyl-N-(naphthalene-1-yl)benzenesulfonamide (3m).
(Table 2, entry 12). Following the general procedure, a mixture of
naphthalene-1-yl nonaflate (1l) (0.50 g, 1.17 mmol), 4-tolylsulfonamide
(2b) (0.24 g, 1.41 mmol), K3PO4 (0.27g, 1.29 mmol), Pd2(dba)3 (0.0054
g, 5.9 μmol) and III (0.0060 g, 14 μmol) in t-AmOH (4.0 mL) was stirred
at 80 °C for 15 h. The crude product was purified via flash column
chromatography (0ꢀ10% EtOAc/hexanes) to provide the title com-
pound as a white solid (0.34 g, 95%).1H NMR (400 MHz, DMSO) δ
10.14 (s, 1H), 8.02 (dd, J = 8.3, 0.9 Hz, 1H), 7.86 (dd, J = 8.3, 1.0 Hz, 1H),
7.74 (d, J = 8.3 Hz, 1H), 7.60ꢀ7.53 (m, 2H), 7.48ꢀ7.40 (m, 2H), 7.37
(dd, J = 8.3, 7.5 Hz, 1H), 7.28 (app d, J = 8.3 Hz, 2H), 7.12 (dd, J = 7.4, 1.1
Hz, 1H), 2.31 (s, 3H). 13C NMR (101 MHz, DMSO) δ 142.4 (C), 136.7
(C), 133.3 (C), 132.0 (C), 129.0 (CH), 128.8 (C), 127.4 (CH), 126.2
(CH), 126.0 (CH), 125.7 (CH), 125.5 (CH), 125.0 (CH), 122.7 (CH),
122.3 (CH), 21.1 (CH3). HRMS (m/z): [M þ Na]þ calcd for
C17H15N1O2S1Na 320.0716; found 320.0726. Mp 156.3ꢀ158.2 °C, lit.
mp 157ꢀ158 °C.55
N-(4-Chlorophenyl)-4-methylbenzenesulfonamide (3q).
(Table 2, entry 16). Following the general procedure, a mixture of
4-chlorophenyl nonaflate (1p) (0.58 g, 1.41 mmol), 4-tolylsulfonamide
(2b) (0.22 g, 1.28 mmol), K3PO4 (0.30 g, 1.34 mmol), Pd2(dba)3
(0.0059 g, 6.4 μmol) and III (0.0065 g, 15 μmol) in t-AmOH (4.2 mL)
was stirred at 80 °C for 15 h. The crude product was purified via flash
column chromatography (20ꢀ50% EtOAc/hexanes) to provide the title
compound as a white solid (0.31 g, 86%). 1H NMR (400 MHz, CDCl3)
δ 7.66ꢀ7.60 (m, 2H), 7.23 (d, J = 8.0 Hz, 2H), 7.21ꢀ7.16 (m, 2H),
7.02ꢀ6.97 (m, 2H), 6.66 (s, 1H), 2.41 (s, 3H). 13C NMR (101 MHz,
CDCl3) δ 143.8 (C), 135.3 (C), 134.7 (C), 130.6 (C), 129.5 (CH),
129.1 (CH), 126.9 (CH), 122.7 (CH), 21.8 (CH3). HRMS (m/z):
[M ꢀ H]ꢀ calcd for C13H11N1O2S1Cl1 280.0205; found 280.0206. Mp
115ꢀ118 °C, lit. mp 118ꢀ119 °C.58
4-Methyl-N-(pyridine-3-yl)benzenesulfonamide (3n).
(Table 2, entry 13). Following the general procedure, a mixture of
pyridine-3-yl nonaflate (1m) (1.0 g, 2.65 mmol), 4-tolylsulfonamide
(2b) (0.50 g, 2.92 mmol), Cs2CO3 (1.04 g, 3.18 mmol), Pd2(dba)3
(0.049 g, 54 μmol) and III (0.054 g, 127 μmol) in t-AmOH (8.5 mL)
was stirred at 90 °C for 20 h. The unpurified mixture was diluted with
40 mL of THF and 5 mL of saturated sodium chloride solution, and the
pH of the aqueous solution was adjusted to neutral with 3.2 mL of 1 M
HCl solution. After separation, the organic solution was concentrated to
dryness in vacuo. Heptane was added and removed in vacuo. The residue
was dissolved in THF and absorbed onto silica gel. The desired product
was purified by flash column chromatography using a gradient elution
(50ꢀ100% EtOAc/hexanes). Product-containing fractions were com-
bined and concentrated in vacuo to give a white solid. This solid was
slurried with 25% EtOAc/heptane (10 mL), filtered and dried in a
vacuum oven at 50 °C to obtain the title compound as a white solid
(0.53 g, 80%). 1H NMR (400 MHz, DMSO) δ 10.46 (br s, 1H), 8.25
(dd, J = 2.6, 0.6 Hz, 1H), 8.22 (dd, J = 4.7, 1.4 Hz, 1H), 7.66ꢀ7.59 (m,
2H), 7.47 (ddd, J = 8.3, 2.7, 1.5 Hz, 1H), 7.36ꢀ7.32 (m, 2H), 7.26 (ddd,
J = 8.3, 4.7, 0.7 Hz, 1H), 2.33 (s, 3H). 13C NMR (101 MHz, DMSO) δ
144.6 (CH), 143.0 (C), 141.1 (CH), 135.6 (C), 133.9 (C), 129.3 (CH),
N-p-Tolylmethanesulfonamide (3a). (Table 3, entry 1). Fol-
lowing the general procedure, a mixture of 4-methylphenyl nonaflate
(1a) (0.50 g, 1.28 mmol), methanesulfonamide (2a) (0.15 g, 1.54
mmol), K3PO4 (0.41 g, 1.92 mmol), Pd2(dba)3 (0.0059 g, 6.4 μmol) and
III (0.0065 g, 15 μmol) in t-AmOH (4.4 mL) was stirred at 80 °C for
15 h. The crude product was purified via flash column chromatography
(0ꢀ25% EtOAc/hexanes) to provide the title compound as a white solid
1
(0.22 g, 94%). H NMR (400 MHz, CDlL3) δ 7.22ꢀ7.15 (m, 4H),
7.03ꢀ6.89 (br s, 1H), 3.02 (s, 3H), 2.37 (s, 3H). 13C NMR (101 MHz,
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dx.doi.org/10.1021/jo200443u |J. Org. Chem. 2011, 76, 4552–4563