Poloukhtine et al.
JOCArticle
19.0, 10.1. HRMS calcd for C22H20INO3S (Mþ) 505.0209,
found 505.0207.
(q, J = 27.6, Hz, 2 H), 3.96 (t, J = 5.6 Hz, 2 H), 2.45 (s, 1 H), 2.23
(s, b, 1 H), 1.98-1.83 (m, 4 H), 1.78-1.66 (m, 1 H), 1.60-1.50 (m,
1 H). 13C NMR: 171.9, 145.2, 137.2, 136.7, 132.4, 131.0, 130.1
128.9, 128.0, 127.6, 123.0, 95.4, 84.0, 63.2, 46.7, 43.2, 36.1, 28.1,
21.9, 20.3. HRMS calcd for C22H23NO4SNa (M þ Naþ) 420.1246,
found 420.1194.
N-((2-Iodoethynylphenyl)ethynyl)-N-(4-oxohexyl)tosylamide
(10d). Yield 78%. 1H NMR: 9.76 (s, 1 H), 7.87 (d, J = 8 Hz, 2
H), 7.42-7.31 (m, 4 H), 7.26 (td, J = 7.6, 1.6 Hz, 1 H), 7.20 (td,
J = 7.6, 1.6 Hz, 1 H), 3.43 (t, J = 7.2 Hz, 2 H), 2.45 (s, 5 H),
1.83-1.75 (m, 2 H), 1.72-1.61 (m, 2 H), 1.49-1.37 (m, 2 H). 13
C
8-Hydroxy-N-tosyl-4,5-benzoazacyclotrideca-6-yne-2-one (21d).
A solution of enediyne 1d (0.25 g, 0.64 mmol) and TsOH (∼50 μg)
in 2-propanol (200 mL) was stirred for 4 days at 55 °C and cooled
to rt, the solvent was removed under reduced pressure, and the
residue was purified by chromatography (ethyl acetate/hexanes 1:5
to 1:1) to provide 0.139 g (0.34 mmol, 53%) of 21d as white
crystalline. NMR: 7.83 (d, J = 8.0 Hz, 2 H), 7.47-7.40 (m, 1 H),
7.34 (d, J = 8.0 Hz, 2 H) 7.25-7.21 (m, 2 H), 7.12-7.16 (m, 1 H),
4.65 (q, J = 6.4 Hz, 1 H), 4.09 (s, 2 H), 4.04 (t, J = 6.8, Hz, 1 H),
3.88-3.80 (m, 1 H), 2.45 (s, 1 H), 2.01 (d, J = 5.6 Hz, 1 H),
1.95-1.91 (m, 1 H), 1.90-1.81 (m, 1 H), 1.72-1.64 (m, 1 H),
1.60-1.50 (m, 3 H). 13C NMR: 171.0, 145.1, 136.8, 135.6, 132.5,
130.1, 129.9 128.9, 128.2, 127.6, 123.2, 94.9, 83.7, 63.1, 46.1, 42.5,
36.1, 28.0, 24.7, 23.7, 21.9. HRMS calcd for C23H26NO4S (M þ
Hþ) 412.1583, found 412.1594
1-Tosyl-2,3,4,5-tetrahydro-1H-naphtho[2,3-b]azepine-5,6-diol
(23b). A solution of enediyne 1b (0.25 g, 0.68 mmol) and TsOH
(∼5 μg) in 200 mL of THF/H2O (2:1) was stirred for 2 days at
60 °C, cooled to rt, and concentrated in vacuum. The residue was
purified by chromatography (ethyl acetate/hexanes 1:5 to 1:1) to
provide 0.12 g (0.31 mmol, 46%) of 23b as white crystalline. Mp
154-155 °C. 1H NMR: 10.55 (s, 1 H), 8.2 (dd, J = 8.0, 1.2 Hz,
1 H), 7.76 (d, J = 8.0 Hz, 2 H), 7.52 (m, 1 H), 7.45-7.41 (m, 2 H),
7.31 (d, J = 8.0 Hz, 2 H), 6.94 (s, 1 H), 5.45 (m, 1 H), 4.15 (m,
1 H), 3.91 (s, b, 1 H), 2.98 (t, b, 1 H), 2.44 (s, 3 H), 2.1-1.85 (m,
2 H), 1.84-1.8 (m, 1 H), 1.55 (m, 1 H). 13C NMR: 151.9, 143.6,
138.3, 135.0, 132.8, 129.8, 129.2, 127.3, 127.2, 126.7, 125.6, 125.4,
122.2, 117.7, 74.2, 50.3, 36.0, 26.3, 21.6. HRMS calcd for
C21H22NO4S (M þ Hþ) 384.1270, found 384.1276.
NMR: 202.6, 145.0, 134.8, 132.9, 130.9, 130.2, 128.8, 127.8,
127.2, 126.8, 124.7, 93.2, 86.7, 70.0, 51.7, 44.0, 28.0, 26.1, 21.9,
21.8, 14.4. MS calcd for C23H22INO3S (Mþ) 519.0, found 519.0.
8-Hydroxy-N-tosyl-4,5-benzoazacycloundeca-2,6-diyne (1b).
A solution of iodo-aldehyde 10b (3.67 g, 7.49 mmol) in 10 mL
of THF was added dropwise to a suspension of CrCl2 (2.30 g,
18.73 mmol) and NiCl2 (0.21 g, 1.87 mmol) in degassed THF
(400 mL) at 0 °C, and the mixture was stirred for 30 min at 0 °C.
The reaction mixture was quenched by the addition of 50 mL of
brine and diluted with Et2O. The organic layer was separated,
washed twice with brine, dried over anhydrous MgSO4, and
concentrated. The residue was immediately purified by chroma-
tography (hexanes/ethyl acetate 2:1 f 1.5:1) to provide 1.68 g
(4.60 mmol, 61%) of 1b as slightly brownish oil. 1H NMR: 7.86
(d, J = 8.4 Hz, 2 H), 7.41-7.36 (m, 4 H), 7.28 (t,d, J = 7.6, 1.6
Hz, 1 H), 7.22 (t,d, J = 7.6, 1.6 Hz, 1 H), 4.66 (q, J = 3.6 Hz,
1 H), 3.51-3.38 (m, 2 H), 2.46 (s, 3 H), 2.22-2.13 (m, 1 H),
2.12-2.02 (m, 1 H), 1.90 (d, J = 5.2 Hz, 1 H), 1.84-1.78 (m, 2 H).
13C NMR: 144.9, 134.1, 129.9, 129.8, 129.3 128.4, 128.3 127.7,
127.2, 125.4, 95.7, 86.1, 85.2, 71.9, 63.2, 48.3, 34.1, 22.2, 21.7.
HRMS calcd for C21H19NO3S (Mþ) 365.1086, found 365.1091.
8-Hydroxy-N-tosyl-4,5-benzoazacyclododeca-2,6-diyne (1c).
Yield 72%. 1H NMR: 7.85 (d, J = 8 Hz, 2 H), 7.42-7.34 (m,
4 H), 7.25 (td, J = 7.6, 1.6 Hz, 1 H), 7.19 (td, J = 7.6, 1.6 Hz,
1 H), 4.70-4.61 (m, 1 H), 3.58-3.43 (m, 2 H), 2.45 (s, 3 H), 1.97-
1.62(m,7 H). 13C NMR: 145.0, 134.8, 131.1, 130.06, 130.02, 128.5,
127.9, 127.2, 127.1, 124.3, 93.6, 87.2, 84.8, 70.5, 63.0, 50.4, 35.6,
27.9, 21.9, 21.4. HRMS calcd for C22H22NO3S (M þ Hþ)
380.1320, found 380.1324.
1-Tosyl-5-phenyl-1,2-dihydrobenzo[g]quinoline (24b). A solu-
tion of enediyne (0.25 g), TsOH (∼25 μg) in C6H6 (100 mL) was
stirred for 20 h at 55 °C, cooled to room temperature, and
concentrated in vacuum. The residue was purified by chroma-
tography (ethyl acetate/hexanes 1:5 to 1:1) to give 24b in 21%
yield. Mp 146-148 °C. 1H NMR: 8.09 (s, 1 H), 7.84 (d, J = 8.0
Hz, 1 H) 7.75-7.39 (m, 6 H), 7.31 (d, J = 4.0 Hz, 2 H), 7.16 (dd,
J = 7.6, 1.2 Hz, 2 H), 7.10 (d, J = 8.0 Hz, 2 H), 5.81(d, J = 12.4
Hz, 1 H), 5.45 (dd, J = 12.4, 4.8 Hz, 1 H), 4.2-3.8 (s, b, 1 H),
2.59 (s, b, 2 H), 2.45 (s, 1 H). 13C NMR: 143.2, 141.2, 139.2,
138.3, 137.0, 132.4, 132.2, 131.2, 130.1, 130.1, 129.3, 128.6,
128.3, 127.6, 127.5 m 127.5, 127.1, 126.9, 126.7, 126.4, 51.2,
31.3, 21.9. MS calcd for C27H23NO2S (Mþ) 425.1, found 425.1.
7-Phenyl-1-tosyl-1,2,3,4-tetrahydronaphtho[2,3-b]azocine (24c).
Yield 28%. 1H NMR: 7.71-7.65 (m, 3 H), 7.51-7.41 (m, 6 H),
7.39-7.31 (m, 2 H) 7.30-7.24 (m, 4 H), 5.94 (d, J = 11.6 Hz, 1 H),
5.73 (dt J = 11.6, 6.4, Hz, 1 H), 2.45 (s, 1 H), 2.23-2.00 (m, 2 H),
1.78-1.65 (m, 2 H). 13C NMR: 143.3, 139.8, 138.9, 138.0, 136.9,
135.8, 133.1, 132.4, 131.9, 129.8, 129.5, 128.4, 128.02, 128.00,
127.96, 127.6, 127.0, 126.6, 126.3, 126.2, 53.0, 28.4, 25.1, 21.8. MS
calcd for C28H25NO2S (Mþ) 439.2, found 439.2.
N-Tosyl-4,5-benzoazacyclododeca-6-yn-8-en-2-one (25c). Yield
18%. 1H NMR: 7.89 (d, J = 8.0 Hz, 2 H), 7.48-7.44 (m, 1 H),
7.35 (d, J = 8.0 Hz, 2 H) 7.28-7.24 (m, 2 H), 7.22-7.18 (m, 1 H),
6.23 (dt, J = 10.4, 7.6 Hz, 1 H), 5.72 (d, J = 10.4 Hz, 1 H), 4.28 (s,
2 H), 3.76 (t, J = 6.0 Hz, 2 H), 2.45 (s, 1 H), 2.33-2.24 (m, 2 H),
1.94-1.85 (m, 2 H). 13C NMR: 172.9, 145.1, 143.3, 136.8, 132.6,
131.2, 130.2 128.5, 127.9, 127.6, 124.1, 111.6, 94.4, 91.5, 45.7, 44.9,
27.0, 26.3, 21.9. MS calcd for C22H21NO3S (Mþ) 379.1, found
379.1.
8-Hydroxy-N-tosyl-4,5-benzoazacyclotrideca-2,6-diyne (1d).
Yield 70%. 1H NMR: 7.87 (d, J = 8 Hz, 2 H), 7.41-7.33 (m,
4 H), 7.27-7.18 (m, 2 H), 4.62 (m, 1 H), 3.61-3.45, 2.45 (s, 3 H),
2.18 (m, 1 H), 1.86-1.61 (m, 6 H), 1.59-1.44 (m, 2 H). 13C
NMR: 145.0, 135.0, 131.91, 131.87, 130.0, 128.3, 127.9, 127.6,
126.0, 124.9, 93.7, 87.4, 84.5, 69.1, 63.2, 52.1, 36.8, 29.0, 25.2,
24.1, 21.9. HRMS calcd for C23H24NO3S (M þ Hþ) 394.1477,
found 394.1492.
6-Isopropoxy-1-[(4-methylphenyl)sulfonyl]-2,3,4,5-tetrahydro-
1H-naphtho[2,3-b]azepin-5-ol (2b). A solution of enediyne 1b
(0.25 g, 0.68 mmol) and TsOH (∼5 μg) in 2-propanol (100 mL)
was stirred for 12 h at 60 °C, cooled to rt, and concentrated in
vacuum. The residue was purified by chromatography (ethyl
acetate/hexanes 1:5) to provide 0.15 g of 2b (0.36 mmol, 52%) as
a colorless oil that slowly crystallized upon standing in the
freezer. 1H NMR: 8.08 (dd, J = 8.0, 0.8 Hz, 1 H), 7.76 (d, J =
8.0 Hz, 2 H), 7.50-7.41 (m, 3 H), 7.33 (d, J = 8.0 Hz, 2 H), 6.98
(s, b, 1 H), 5.62 (s, b, 1 H), 4.53 (p, J = 6.0 Hz, 1 H), 4.38 (s, b,
1 H), 3.12 (s, b, 1 H), 2.53 (s, b, 1 H), 2.48 (s, 3 H), 2.35 (s, b, 1 H),
1.79-1.60 (m, 2 H), 1.45 (d, J = 6.4 Hz, 3 H), 1.34(d, J = 6.0 Hz,
3 H). 13C NMR: 152.4, 143.8, 138.2, 137.2, 133.2, 132.2, 129.7,
128.8, 127.7, 127.6, 126.9, 126.4, 123.60, 123.55, 78.3, 65.8, 52.3,
33.4, 25.4, 22.70, 22.57, 21.6. HRMS calcd for C24H27NO4SNa
(M þ Naþ) 448.1558, found 448.1549
8-Hydroxy-N-tosyl-4,5-benzoazacyclododeca-6-yne-2-one (21c).
A solution of enediyne 1c (0.25 g, 0.66 mmol) and TsOH (∼25 μg)
in 2-propanol (200 mL) was stirred for 4 days at 55 °C, cooled to rt,
and concentrated in vacuum. The residue was purified by chro-
matography (ethyl acetate/hexanes 1:5) to provide 0.112 g (0.28
mmol, 43%) of 21c as white crystalline. NMR: 7.81 (d, J = 8.0 Hz,
2 H), 7.43 (dd, J = 7.2, 1.6 Hz, 1 H), 7.34 (d, J = 8.0 Hz,
2 H) 7.28-7.20 (m, 2 H), 7.19-7.15 (m, 1 H), 4.63 (m, 1 H), 4.11
N-Tosyl-4,5-benzoazacyclotrideca-6-yn-8-en-2-one (25d). Yield
41%. 1H NMR (400 MHz, CDCl3) δ 7.83 (d, J = 8.0 Hz, 2 H),
7.46-7.41 (m, 1 H), 7.32 (d, J = 8.0 Hz, 2 H) 7.25-7.20 (m, 2 H),
J. Org. Chem. Vol. 75, No. 17, 2010 5961