References and Notes
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General reviews:
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Oestreich M. In Modern Arylation Methods
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de Meijere A. In
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For the synthesis of azepino[4,5-b]indoles by Heck reactions of
2- and 3-haloindoles, see:
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Cherney RJ.
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<A NAME="RG00410ST-12">12</A>
Tetrahydropyridine
3a
¹H NMR (300 MHz, CDCl3): δ = 2.25
(m, 2 H), 2.63 (m, 2 H), 2.71 (t, J = 5.7
Hz, 2 H), 3.01 (m, 2 H), 3.14 (m, 2 H), 3.73 (s, 3 H), 5.71 (dm, J = 9.9 Hz,
1 H), 5.79 (dm, J = 9.9 Hz,
1 H), 7.07 (ddd, J = 7.8,
7.2, 1.2 Hz, 1 H), 7.15 (ddd, J = 8.1,
7.2, 1.2 Hz, 1 H), 7.28 (dd, J = 8.1,
1.2 Hz, 1 H), 7.56 (dd, J = 7.8,
1.2 Hz, 1 H). ¹³C NMR (75.5 MHz, CDCl3): δ = 25.4
(CH2), 26.2 (CH2), 34.1 (Me), 50.0 (CH2), 52.6
(CH2), 58.5 (CH2), 87.4 (C), 109.6 (CH), 118.1
(CH), 119.0 (C), 119.2 (CH), 121.8 (CH), 125.2 (CH), 125.3 (CH), 127.6
(C), 138.5 (C). ESI-HRMS: m/z calcd
for C16H20IN2 [M + H]+:
367.0666; found: 367.0664.
<A NAME="RG00410ST-13">13</A>
Tetrahydropyridine
3b
¹H NMR (300 MHz, CDCl3): δ = 2.22
(m, 2 H), 2.52 (m, 2 H), 2.65 (t, J = 5.7
Hz, 2 H), 2.93 (m, 2 H), 3.08 (m, 2 H), 5.68 (dm, J = 9.9
Hz, 1 H), 5.77 (dm, J = 9.9
Hz, 1 H), 7.20-7.31 (m, 2 H), 7.36-7.55 (m, 4
H), 7.84 (m, 2 H), 8.30 (m, 1 H). ¹³C
NMR (75.5 MHz, CDCl3): δ = 25.8
(CH2), 26.1 (CH2), 49.9 (CH2),
52.5 (CH2), 56.8 (CH2), 79.4 (C), 115.9 (CH),
118.5 (CH), 123.7 (CH), 125.0 (CH), 125.2 (CH), 127.0 (CH), 129.0
(2 CH), 130.4 (C), 130.7 (C), 133.8 (CH), 138.0 (C), 139.2 (C).
ESI-HRMS: m/z calcd for C21H22IN2O2S [M + H]+:
493.0441; found: 493.0439.
<A NAME="RG00410ST-14">14</A>
It should be noted that in the reduction
of 2b with NaBH4 (MeOH, 0 ˚C)
the hydrodehalogenated product 5b was also obtained
(13%). This side product was formed even when the reduction
was carried out at -10 ˚C.
<A NAME="RG00410ST-15">15</A> For a review on the bite angle effects
of diphosphines in C-C coupling reactons, see:
Birkholz M.-N.
Freixa Z.
van Leeuwen PWNM.
Chem.
Soc. Rev.
2009,
38:
1099
<A NAME="RG00410ST-16">16</A>
Heck Cyclization
of 3a (Table 1, Entry 6)
Pd2(dba)3 (17
mg, 0.019 mmol), dppp (24 mg, 0.058 mmol), and K2CO3 (79
mg, 0.57 mmol) were successively added to a solution of iodoindole 3a (70 mg, 0.19 mmol) in toluene (10 mL),
and the resulting mixture was heated at 80 ˚C for 18 h.
The reaction mixture was poured into H2O and extracted
with Et2O (3 × 50 mL). The
organic extracts were washed with brine, dried, and concentrated.
The resulting residue was chromatographed (SiO2, flash,
from CH2Cl2 to CH2Cl2-MeOH
8%) to give tetracycle 4a; 31
mg (68%). ¹H NMR (300 MHz, CDCl3): δ = 2.81
(ddd, J = 15.6,
4.2, 3.3 Hz, 1 H), 3.10 (dq, J = 15.6,
6.9 Hz, 1 H), 3.25 (m, 2 H), 3.31 (dm, J = 18.0
Hz, 1 H), 3.39 (br, 1 H), 3.50 (m, 2 H), 3.71 (s, 3 H), 3.82 (dm, J = 18.0 Hz,
1 H), 5.84 (m, 2 H), 7.07 (ddd, J = 7.5,
6.9, 1.2 Hz, 1 H), 7.15 (ddd, J = 8.1,
6.9, 1.2 Hz, 1 H), 7.24 (dd, J = 8.1,
1.2 Hz, 1 H), 7.45 (dd, J = 7.5,
1.2 Hz, 1 H). ¹³C NMR (75.5 MHz, CDCl3): δ = 22.9
(CH2), 29.5 (Me), 31.2 (CH), 49.7 (CH2), 51.0
(CH2), 56.2 (CH2), 109.0 (CH), 112.7 (C),
117.5 (CH), 119.0 (CH), 120.6 (CH), 125.2 (CH), 126.1 (CH), 127.5
(C), 135.9 (C), 139.0 (C). ESI-HRMS: m/z calcd
for C16H19N2 [M + H]+:
239.1543; found: 239.1545.
<A NAME="RG00410ST-17">17</A>
Tetracycle 4b
¹H
NMR (300 MHz, CDCl3): δ = 2.65
(ddd, J = 15.6,
3.9, 1.8 Hz, 1 H), 2.95-3.27 (m, 5 H), 3.37 (dd, J = 14.1,
4.8 Hz, 1 H), 3.74 (dm, J = 18.3
Hz, 1 H), 4.16 (m, 1 H), 5.64 (dm, J = 9.9
Hz, 1 H), 5.82 (dm, J = 9.9
Hz, 1 H), 7.21-7.47 (m, 5 H), 7.55 (tt, J = 7.5,
1.2 Hz, 1 H), 7.71 (m, 2 H), 8.23 (dm, J = 8.1
Hz, 1 H). ¹³C NMR (75.5 MHz, CDCl3): δ = 22.7 (CH2),
31.4 (CH), 49.6 (CH2), 50.7 (CH2), 54.6 (CH2),
115.1 (CH), 117.8 (CH), 122.7 (C), 123.4 (CH), 124.3 (CH), 125.1 (CH),
125.8 (CH), 126.1 (CH), 129.3 (CH), 130.3 (C), 133.7 (CH), 136.2
(C), 138.4 (C), 139.4 (C). ESI-HRMS: m/z calcd for
C21H21N2O2S [M + H]+:
365.1318; found: 365.1319.
<A NAME="RG00410ST-18">18</A>
Tetracycle 4c
¹H
NMR (400 MHz, CDCl3): δ = 2.75
(ddd, J = 15.6,
4.0, 2.4 Hz, 1 H), 3.08 (ddd, J = 15.6,
12.0, 3.2 Hz, 1 H), 3.14 (br s, 1 H), 3.22 (ddd, J = 13.6,
12.0, 2.0 Hz, 1 H), 3.29-3.40 (m, 2 H), 3.48 (m, 2 H),
3.83 (dm, J = 18.8
Hz, 1 H), 5.83 (dm, J = 10.0
Hz, 1 H), 5.89 (dm, J = 10.0
Hz, 1 H), 7.06-7.13 (m, 2 H), 7.28 (m, 1 H), 7.45 (dd, J = 6.0, 2.0
Hz, 1 H), 7.89 (br, 1 H). ¹³C NMR (100.5
MHz, CDCl3): δ = 23.0
(CH2), 34.7 (CH), 49.3 (CH2), 51.3 (CH2),
56.3 (CH2), 110.5 (CH), 112.8 (C), 117.5 (CH), 119.4
(CH), 120.8 (CH), 125.4 (CH), 126.0 (CH), 129.0 (C), 134.3 (C),
137.8 (C). ESI-HRMS:
m/z calcd
for C15H17N2 [M + H]+:
225.1386; found: 225.1384.
