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Hz, 1H), 7.33 (d, J = 7.9 Hz, 3H), 7.29−7.20 (m, 2H), 7.01−6.87 (m,
1H), 5.91 (d, J = 15.7 Hz, 1H), 4.39 (d, J = 28.7 Hz, 2H), 3.74 (s, 3H),
2.48 (s, 3H). 13C NMR (75 MHz, CDCl3): δ 166.0 (C), 144.0 (C),
142.2 (CH), 137.6 (C), 136.6 (C), 134.1 (CH), 132.6 (CH), 130.2
(CH), 129.7 (CH), 128.2 (CH), 127.9 (CH), 125.2 (C), 124.0 (CH),
51.9 (CH2), 51.7 (CH3), 21.6 (CH3). HRMS (magnet-EI, 70 eV): m/z
calcd for C18H18O4NBrS [M]+ 423.0140, found 423.0145.
Synthesis of (E)-N-(2-Bromophenyl)-N-tosylbut-2-enamide (18).
(E)-But-2-enoyl chloride (0.18 mL, 1.84 mmol) was slowly added to a
mixture of Et3N (0.26 mL, 1.84 mmol) and N-(2-bromophenyl)-4-
methylbenzenesulfonamide (499 mg, 1.53 mmol) in CH2Cl2 (10 mL)
at 0 °C. The resulting solution was stirred at room temperature for 16
h. Then the mixture was diluted with CH2Cl2, washed with water, and
dried over anhydrous Na2SO4. The residue was submitted to flash
chromatography (SiO2, EtOAc/hexane, 2:8) to give 18 (410 mg, 68%)
Synthesis of (E)-Methyl 4-(N-(2-Iodobenzyl)-4-
methylphenylsulfonamido)but-2-enoate (12). (E)-Methyl 4-bromo-
but-2-enoate (278 mg, 1.55 mmol) was added to a mixture of N-(2-
iodobenzyl)-4-methylbenzenesulfonamide86 (400 mg, 1.03 mmol) and
NaH (60%) (62 mg, 1.54 mmol) in THF (12 mL) at 0 °C. The
resulting solution was stirred at room temperature for 16 h. Then the
mixture was diluted with EtOAc, washed with brine, and dried over
anhydrous Na2SO4. The residue was submitted to flash chromatog-
raphy (SiO2, EtOAc/hexane, 15:85) to give 12 (165 mg, 33%) as a
colorless oil. 1H NMR (400 MHz, CDCl3): δ 7.76 (d, J = 7.9 Hz, 1H),
7.73 (d, J = 8.3 Hz, 2H), 7.45 (d, J = 7.8 Hz, 1H), 7.33 (d, J = 8.3 Hz,
3H), 6.95 (t, J = 7.6 Hz, 1H), 6.61−6.51 (m, 1H), 5.71 (d, J = 15.7 Hz,
1H), 4.39 (s, 2H), 3.90 (d, J = 4.8 Hz, 2H), 3.65 (s, 3H), 2.44 (s,
3H).13C NMR (100 MHz, CDCl3): δ 165.9 (C), 144.0 (C), 142.0
(CH), 139.6 (CH), 137.8 (C), 136.5 (C), 130.0 (CH), 129.7 (CH),
129.6 (CH), 128.8 (CH), 127.3 (CH), 123.7 (CH), 98.8 (C), 56.3
(CH2), 51.7 (CH3), 48.8 (CH2), 21.6 (CH3). HRMS (magnet-EI, 70
eV): m/z calcd for C19H20O4NIS [M]+ 485.0158, found 485.0155.
Synthesis of (E)-Dimethyl 2-(2-Iodobenzyl)-2-(4-oxopent-2-en-1-
yl)malonate (14). Methyl vinyl ketone (0.70 mL, 8.49 mmol) was
added to a deoxygenated solution of Grubb’s second-generation
catalyst (25 mg, 0.029 mmol) and dimethyl 2-allylmalonate (0.47 mL,
2.90 mmol) in dry CH2Cl2 (8 mL), and the resulting mixture was
refluxed for 48 h. The solvent was removed, and the residue was
submitted to flash chromatography (SiO2, EtOAc/hexane, 2:8) to give
(E)-dimethyl 2-(4-oxopent-2-en-1-yl)malonate (275 mg, 45%) as a
yellowish oil. Its spectroscopic data were identical to the reported
compound.87
1-(Bromomethyl)-2-iodobenzene (578 mg, 1.95 mmol) was added
to a mixture of (E)-dimethyl 2-(4-oxopent-2-en-1-yl)malonate (275
mg, 1.30 mmol) and NaH (60%) (52 mg, 1.30 mmol) in THF (15
mL). The resulting solution was stirred at room temperature for 16 h.
Then the mixture was diluted with EtOAc, washed with water, and
dried over anhydrous Na2SO4. The residue was submitted to flash
chromatography (SiO2, EtOAc/hexane, 3:7) to give 14 (44 mg, 44%)
as a yellowish oil. 1H NMR (400 MHz, CDCl3): δ 7.84 (d, J = 7.9 Hz,
1H), 7.28−7.22 (m, 1H), 7.15 (d, J = 7.15 Hz, 1H), 6.91 (t, J = 7.9 Hz,
1H), 6.77−6.66 (m, 1H), 6.01 (d, J = 15.9 Hz, 1H), 3.74 (s, 6H), 3.57
(s, 2H), 2.79 (d, J = 8.6 Hz, 2H), 2.20 (s, 3H). 13C NMR (100 MHz,
CDCl3): δ 198.2 (C), 170.6 (C), 142.4 (CH), 140.1 (C), 139.0 (C),
134.1 (CH), 130.0 (CH), 129.0 (CH), 128.4 (CH), 103.1 (C), 59.1
(C), 52.8 (CH3), 43.1 (CH2), 36.5 (CH2), 26.8 (CH3). HRMS
(magnet-EI, 70 eV): m/z calcd for C17H19O5I [M]+ 430.0277, found
430.0275.
Synthesis of (E)-N-(2-Iodophenyl)-N-tosylbut-2-enamide (16).
(E)-But-2-enoyl chloride (0.24 mL, 2.52 mmol) was slowly added to
a mixture of Et3N (0.35 mL, 2.52 mmol) and N-(2-iodophenyl)-4-
methylbenzenesulfonamide (785 mg, 2.10 mmol) in CH2Cl2 (10 mL)
at 0 °C. The resulting solution was stirred at room temperature for 16
h. Then the mixture was diluted with CH2Cl2, washed with aqueous
NH4Cl, and dried over anhydrous Na2SO4. The residue was submitted
to flash chromatography (SiO2, EtOAc/hexane, 20:80) to give 16 (520
mg, 56%) as a vitreous solid. 1H NMR (400 MHz, CDCl3): δ 8.06 (d,
J = 8.4 Hz, 2H), 7.99 (dd, J = 7.7, 1.4 Hz, 1H), 7.47 (dt, J = 7.7, 1.4
Hz, 1H), 7.33 (d, J = 8.4 Hz, 2H), 7.37 - 7.30 (m, 1H), 7.18 (dt, J =
7.7, 1.4 Hz, 1H), 7.03 (dq, J = 15.0, 7.0 Hz, 1H), 5.41 (d, J = 15.0 Hz,
1H), 2.44 (s, 3H), 1.71 (d, J = 7.0 Hz, 3H). 13C NMR (100 MHz,
CDCl3): δ 164.4 (C), 147.1 (CH), 145.2 (C), 140.7 (CH), 139.2 (C),
136.4 (C), 131.6 (CH), 131.3 (CH), 130.1 (CH), 129.6 (CH), 129.3
(CH), 122.2 (CH), 102.5 (C), 21.8 (CH3), 18.4 (CH3). HRMS
(magnet-EI, 70 eV): m/z calcd for C17H17O3NIS [M + H]+ 441.9974,
found 441.9976.
1
as a white solid. Mp: 160−162 °C. H NMR (300 MHz, CDCl3): δ
8.05 (d, J = 8.3 Hz, 2H), 7.74 (d, J = 7.9 Hz, 1H), 7.51−7.36 (m, 3H),
7.33 (d, J = 8.3 Hz, 2H), 7.03 (dq, J = 15.0, 6.9 Hz, 1H), 5.43 (d, J =
15.0 Hz, 1H), 2.44 (s, 3H), 1.71 (d, J = 6.9 Hz, 3H). 13C NMR (75
MHz, CDCl3): δ 164.5 (C), 147.0 (CH), 145.1 (C), 136.4 (C), 135.6
(C), 134.1 (CH), 132.6 (CH), 131.4 (CH), 129.9 (CH), 129.3 (CH),
128.8 (CH), 125.8 (C), 21.8 (CH3), 18.4 (CH3). HRMS (magnet-EI,
70 eV): m/z calcd for C17H17O3NBrS [M + H]+ 394.0113, found
394.0111.
Representative Procedure for Intramolecular Protocol.
Rigorously deoxygenated dry THF (10 mL) was added to a
deoxygenated mixture of Cp2TiCl2 (0.7 mmol), Mn (8.0 mmol),
NiCl2 (0.2 mmol), and PPh3 (0.4 mmol) under Ar atmosphere, and
the suspension was stirred at room temperature until it turned green
(about 10 min). A solution of the previously synthesized
polyfunctionalized substrate (Table 4, starting material, 1.0 mmol)
in THF (2 mL) and Me3SiCl (4.0 mmol) were then added. The
reaction mixture was stirred at room temperature for 16 h and then
diluted with AcOEt, washed with HCl (10%), and dried over
anhydrous Na2SO4, and the solvent was removed. The residue was
submitted to flash column chromatography (SiO2, EtO Ac/hexane
mixture) to give the corresponding cyclic products (Table 4, product,
yield).
Characterization Data of Cyclic Compounds 2, 7, 10, 13, 15,
and 17. Dimethyl 4-(2-Methoxy-2-oxoethyl)-3,4-dihydronaphtha-
lene-2,2(1H)-dicarboxylate (2). Colorless oil, 63−72% yield. NMR
spectra were identical to the reported data.83
Dimethyl 4-(2-tert-Butoxy-2-oxoethyl)-3,4-dihydronaphthalene-
2,2(1H)-dicarboxylate (7). Colorless oil, 56−58% yield. NMR spectra
were identical to the reported data.83
Methyl 2-(1-Tosylindolin-3-yl)acetate (10). Vitreous solid, 34−
1
73% yield. H NMR (400 MHz, CDCl3): δ 7.68 (d, J = 8.2 Hz, 2H),
7.65 (d, J = 8.5 Hz, 1H), 7.23 (d, J = 8.2 Hz, 2H), 7.12−6.95 (m, 3H),
4.15−4.05 (m, 1H), 3.69 (s, 3H), 3.68−3.62 (m, 1H), 3.60−3.49 (m,
1H), 2.53 (dd, J = 16.5, 5.1 Hz, 1H), 2.37 (s, 3H), 2.23 (dd, J = 16.5,
9.7 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ 172.0 (C), 144.3 (C),
141.8 (C), 133.9 (C), 133.8 (C), 129.8 (CH), 129.4 (CH), 128.7
(CH), 127.4 (CH), 124.5 (CH), 124.0 (CH), 55.8 (CH2), 52.0
(CH3), 39.4 (CH2), 36.5 (CH), 21.7 (CH3). HRMS (magnet-EI, 70
eV): m/z calcd for C18H19O4NS [M]+ 345.1035, found 345.1035.
Methyl 2-(2-Tosyl-1,2,3,4-tetrahydroisoquinolin-4-yl)acetate (13).
Colorless oil, 58% yield. Compound 13 was isolated as a 5:1 mixture
w i t h r e d u c e d c o m p o u n d m e t h y l 4 - ( N - b e n z y l - 4 -
methylphenylsulfonamido)butanoate. See the corresponding 1H
NMR spectra in the Supporting Information. Spectroscopic data for
1
compound 13: H NMR (400 MHz, CDCl3): δ 7.73 (d, J = 8.1 Hz,
2H), 7.34 (d, J = 8.1 Hz, 2H), 7.31−7.26 (m, 1H), 7.18−7.12 (m,
2H), 7.06−6.99 (m, 1H), 4.61 (d, J = 15.0 Hz, 1H), 3.88−3.82 (m,
1H), 3.82 (d, J = 15.0 Hz, 1H), 3.72 (s, 3H), 3.44−3.37 (m, 1H), 2.91
(dd, J = 16.8, 9.6 Hz, 1H), 2.81 (dd, J = 12.0, 3.0 Hz, 1H), 2.59 (dd, J
= 16.8, 4.3 Hz, 1H), 2.42 (s, 3H). 13C NMR (100 MHz, CDCl3): δ
172.8 (C), 143.9 (C), 136.2 (C), 133.2 (C), 131.6 (C), 129.9 (CH),
128.7 (CH), 127.9 (CH), 127.2 (CH), 127.1 (CH), 126.6 (CH), 51.9
(CH3), 47.8 (CH2), 47.5 (CH2), 39.6 (CH2), 35.1 (CH), 21.7 (CH3).
MS (EI, 70 eV): m/z calcd for C19H21O4NS [M]+ 359.12, found
359.12.
Dimethyl 4-(2-Oxopropyl)-3,4-dihydronaphthalene-2,2(1H)-di-
carboxylate (15). Yellowish oil, 51% yield. 1H NMR (500 MHz,
CDCl3): δ 7.22−7.01 (m, 4H), 3.73 (s, 3H), 3.67 (s, 3H), 3.51−3.45
(m, 1H), 3.34 (d, J = 16.0 Hz, 1H), 3.20 (d, J = 16.0 Hz, 1H), 2.97
(dd, J = 17.2, 4.7 Hz, 1H), 2.68 (dd, J = 17.2, 8.3 Hz, 1H), 2.67−2.62
(m, 1H), 2.20 (s, 3H), 1.86 (dd, J = 13.6, 10.2 Hz, 1H). 13C NMR
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dx.doi.org/10.1021/jo402626u | J. Org. Chem. 2014, 79, 1529−1541