RESEARCH FRONT
664
A. S. K. Hashmi, S. Wagner, and F. Rominger
δH (CDCl3, 500 MHz) 1.81 (s, 3H), 1.98 (s, 3H), 2.03 (s, 1H),
2.41 (s, 3H), 3.68 (s, 3H), 3.94 (dd, J 18.4, J 2.4, 2H), 5.86 (s,
1H), 6.01 (d, J 1.6, 1H), 6.04 (s, 1H), 6.42 (d, J 1.6, 1H), 7.25
(d, J 8.2, 2H), 7.78 (d, J 8.2, 2H). δC (CDCl3, 125 MHz) 9.71
(q), 11.20 (q), 21.48 (q), 34.78 (t), 52.06 (q), 55.87 (d), 71.96
(d), 78.91 (s), 113.59 (d), 114.73 (s), 127.87 (d, 2C), 127.92 (t),
129.12 (d, 2C), 136.78 (s), 137.45 (s), 143.31 (s), 146.13 (s),
147.71 (s), 166.01 (s).
148.21 (s), 165.76 (s). (Found: 402.1342 [M + H]+. Calcd for
C21H24NO5S: 402.1375.) λmax (0.055 mg mL−1 in CH2Cl2)/nm
(log ε) 270 (3.34), 280 (3.26).
Methyl 2-(4-hydroxy-5-phenyl-2-tosyl isoindolin-1-yl)
acrylate (2c):Yield: 557 mg (1.24 mmol, 86%). Rf 0.21 (PE/EE:
3/1), mp 58◦C. νmax (KBr)/cm−1 3442, 1718, 1629, 1599, 1462,
1437, 1345, 1307, 1292, 1230, 1196, 1163, 1097, 1072, 1054,
815, 760, 672, 597, 551. δH (CDCl3, 300 MHz) 2.39 (s, 3H), 3.74
(s, 3H), 4.72 (d, J 13.8, 1H), 4.84 (dd, J 13.8, J 2.4, 1H), 5.38 (s,
1H), 5.86 (d, J 2.4, 1H), 6.08 (s, 1H), 6.41 (s, 1H), 6.72 (d, J 7.8,
1H), 7.07 (d, J 7.8, 1H), 7.27 (d, J 8.3, 2H), 7.41 (m, 5H), 7.77
(d, J 8.3, 2H). δC (CDCl3, 75 MHz) 21.48 (q), 51.88 (q), 52.13
(t), 66.23 (d), 114.84 (d), 122.64 (s), 127.34 (t), 127.57 (d, 2C),
127.93 (s), 128.17 (d), 128.87 (d, 2C), 129.52 (d, 2C), 129.73 (d,
2C), 130.25 (d), 134.80 (s), 135.97 (s), 140.76 (s), 141.00 (s),
143.53 (s), 147.22 (s), 165.93 (s). (Found: 450.1359 [M + H]+.
Calcd for C25H24NO5S: 450.1375.) λmax (0.051 mg mL−1 in
CH2Cl2)/nm (log ε) 250 (4.14), 284 (3.62), 352 (2.94), 338
(3.39).
General Procedure C: Gold Catalysis
Exemplified for the Formation of Methyl 2-(4-hydroxy-5-
methyl-2-tosyl isoindolin-1-yl)acrylate (2a): Compound 1a
(100 mg, 258 µmol) was taken up in CDCl3 (0.5 mL) andAuCl3
(3.91 mg, 12.9 µmol) was added.The reaction was monitored by
NMR spectroscopy. When complete, the solvent was removed
under reduced pressure and the crude reaction mixture was sep-
arated on silica gel (eluent: PE/EE: 3/1) to afford 2a: Yield:
99.0 mg (256 µmol, 99%). Rf 0.18 (PE/EE: 3/1), mp 138◦C.
νmax (KBr)/cm−1 3448, 1711, 1597, 1487, 1439, 1348, 1310,
1294, 1265, 1218, 1194, 1166, 1093, 1051, 821, 814, 671, 658,
593, 549. δH (CDCl3, 300 MHz) 2.14 (s, 3H), 2.37 (s, 3H), 3.67
(s, 3H), 4.67 (d, J 13.4, 1H), 4.80 (dd, J 13.4, J 2.8, 1H), 5.75 (m,
1H), 6.00 (s, 1H), 6.35 (s, 1H), 6.54 (d, J 7.7, 1H), 6.93 (d, J 7.7,
1H), 7.26 (d, J 8.1, 2H), 7.73 (d, J 8.1, 2H). δC (CDCl3, 75 MHz)
15.19 (q), 21.42 (q), 51.82 (d), 52.02 (q), 66.29 (d), 114.42 (d),
122.10 (s), 122.71 (s), 127.44 (d, 2C), 127.81 (t), 129.71 (d,
2C), 130.79 (d), 134.64 (s), 138.90 (s), 140.68 (s), 143.55 (s),
148.80 (s), 165.87 (s). (Found: 388.1273 [M + H]+. Calcd for
C20H22NO5S: 388.1219.) λmax (0.074 mg mL−1 in CH2Cl2)/nm
(log ε) 270 (3.27).
Methyl 2-(4-hydroxy-5,6-dimethyl-2-tosylisoindolin-1-yl)
acrylate (2d): Compound 1d (473 mg, 1.18 mmol) was dissolved
in CH3CN (4 mL) and AuCl3 (17.8 mg, 58.9 µmol) was added.
The reaction was monitored by thin layer chromatography. After
16 h the solvent was removed under reduced pressure and the
residue was separated on silica gel (eluent: PE/EE: 3/1) to afford
2d: Yield: 453 mg (1.13 mmol, 96%). Rf 0.21 (PE/EE: 3/1),
mp 176◦C. νmax (KBr)/cm−1 3438, 1717, 1630, 1597, 1465,
1440, 1336, 1306, 1235, 1194, 1163, 1092, 1058, 816, 670,
608, 595 cm−1. δH ((D6)DMSO, 300 MHz) 1.96 (s, 3H), 2.06
(s, 3H), 2.34 (s, 3H), 3.62 (s, 3H), 4.53 (d, J 13.8, 1H), 4.63
(d, J 13.8, 1H), 5.58 (s, 1H), 6.07 (s, 1H), 6.23 (s, 1H), 6.30 (s,
1H), 7.40 (d, J 8.1, 2H), 7.69 (d, J 8.1, 2H), 8.88 (s, 1H). δC
((D6)DMSO, 75 MHz) 11.42 (q), 19.99 (q), 20.85 (q), 51.68
(q), 52.42 (t), 66.19 (d), 114.27 (d), 119.69 (s), 122.52 (s),
127.02 (d, 2C), 127.65 (t), 129.88 (d, 2C), 133.99 (s), 136.65 (s),
137.38 (s), 140.28 (s), 143.55 (s), 149.03 (s), 164.90 (s). (Found:
402.1397 [M + H]+. Calcd for C21H24O5NS: 402.1375.) λmax
(0046 mg mL−1 in CH2Cl2)/nm (log ε) 264 (3.20), 270 (3.14).
Methyl 2-methyl-3-(5-methylfuran-2-yl)-3-(4-methylphenyl
sulfonamido)propanoate (5): In a flame dried flask, com-
pound 4a (349 mg, 100 µmol) was dissolved in 8 mL of dry
dichloromethane. Crabtree’s Catalyst (8.04 mg, 10.0 µmol) was
then added to the solution and the mixture was flooded with
hydrogen gas. The crude reaction mixture was stirred for 10 h
under a hydrogen atmosphere. The solvent was removed under
reduced pressure and the residue was separated on silica gel (elu-
ent: PE/EE/DCM: 6/1/1) to afford 5: Yield: 328 mg (934 µmol,
93%). Rf 0.27 (PE/EE/DCM: 6/1/1). δH (CDCl3, 300 MHz) 1.15
(d, J 7.2, 3H), 1.17 (d, J 7.2, 3H), 2.03 (s, 3H), 2.36 (s, 3H), 2.82–
2.96 (m, 1H), 3.59 (s, 3H), 3.63 (s, 3H), 4.50–4.57 (m, 1H), 5.47
(d, J 9.8, 1H), 5.60 (d, J 9.8, 1H), 5.63 (m, 1H), 5.78 (t, J 3.4,
1H), 7.16 (d, J 8.3, 2H), 7.59 (d, J 8.3, 2H). δC (CDCl3, 75 MHz)
13.13 (q), 13.17 (q), 14.16 (q), 14.55 (q), 21.40 (q), 43.64 (d),
44.05 (d), 51.88 (q), 51.92 (q), 53.84 (d), 54.01 (d), 105.85 (d),
105.88 (d), 108.43 (d), 108.71 (d), 126.94 (d, 2C), 126.98 (d, 2C),
129.12 (d, 2C), 129.17 (d, 2C), 137.55 (s), 137.83 (s), 142.83 (s),
142.94 (s), 148.73 (s), 149.29 (s), 151.53 (s), 151.59 (s), 173.63
(s), 174.51 (s). m/z (GC-MS: EI+) Rt 21.869 min: 351 [M]+,
320 [M − CH3O]+, 196 [M − C7H7O2S]+. Rt 22.143 min: 351
[M]+, 320 [M − CH3O]+, 196 [M − C7H7O2S]+.
Crystal data and structure refinement for 2a: colourless crys-
tal (polyhedron), dimensions 0.24 × 0.18 × 0.16 mm3, crystal
system monoclinic, space group P21/c, Z 4, a 15.1057(13) Å,
b 8.1047(7) Å, c 15.6102(13) Å, α 90◦, β 105.728(2)◦, γ 90◦,
V 1839.6(3) Å3, ρ 1.399 g cm−3, t 200(2) K, θmax 28.31◦, radia-
tion MoKα, λ 0.71073 Å, 0.3◦ ꢀ-scans with CCD area detector,
covering a whole sphere in reciprocal space, 18 710 reflec-
tions measured, 4575 unique (R(int) 0.0282), 4123 observed
(I > 2σ(I)), intensities were corrected for Lorentz and polar-
ization effects, an empirical absorption correction was applied
using SADABS[8] based on the Laue symmetry of the reciprocal
space, µ 0.21 mm−1, Tmin 0.95, Tmax 0.97, structure solved by
direct methods and refined against F2 with a full-matrix least-
squares algorithm using the SHELXTL-PLUS (6.10) software
package,[9] 251 parameters refined, hydrogen atoms were treated
using appropriate riding models, except of H16 of the hydroxyl
group, which was refined isotropically, goodness of fit 1.16 for
observed reflections, final residual values R1(F) 0.051, wR(F2)
0.122 for observed reflections, residual electron density −0.35
to 0.49 e Å−3
.
Methyl2-(5-ethyl-4-hydroxy-2-tosylisoindolin-1-yl)acrylate
(2b): Yield: 70.0 mg (174 µmol, 99%). Rf 0.26 (PE/EE: 3/1).
νmax (KBr)/cm−1 3447, 2966, 1718, 1628, 1597, 1493, 1430,
1306, 1292, 1198, 1163, 1095, 1093, 1060, 1018, 814, 671, 593,
549. δH (CDCl3, 300 MHz) 1.14 (t, J 7.5, 3H), 2.36 (s, 3H),
2.52 (q, J 7.5, 2H), 3.68 (s, 3H), 4.69 (d, J 13.4, 1H), 4.83
(dd, J 13.4, J 2.5, 1H), 5.55 (s, 1H), 5.77 (d, J 2.5, 1H), 6.01
(s, 1H), 6.35 (s, 1H), 6.58 (d, J 7.7, 1H), 6.95 (d, J 7.7, 1H),
7.25 (d, J 8.1, 2H), 7.73 (d, J 8.1, 2H). δC (CDCl3, 75 MHz)
13.77 (q), 21.23 (q), 22.10 (t), 51.64 (q), 51.86 (t), 65.99 (d),
114.38 (d), 122.03 (s), 127.29 (d, 2C), 127.61 (t), 128.92 (d,
2C), 129.52 (d, 2C), 134.34 (s), 138.54 (s), 140.65 (s), 143.37 (s),
Methyl-2-methyl-3-(5-methylfuran-2-yl)-3-{[(4-methyl-
phenyl)sulfonyl](prop-2-in-1-yl)amino}propanoate (6): Yield:
351 mg (909 µmol, 90%), Rf 0.36 (PE/EE/DCM: 6/1/1).