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DOI: 10.1055/s-0030-1260965
Palladium-Mediated Intramolecular C-O and C-C Coupling Reactions: An Efficient Synthesis of Benzannulated Oxazepino- and Pyranocarbazoles
Publication History
Publication Date:
21 July 2011 (online)
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Abstract
An efficient route towards the synthesis of benzannulated oxazepino- and pyranocarbazoles has been accomplished via palladium-catalyzed intramolecular C-O and C-C cross-coupling reactions, respectively.
Key words
C-O and C-C coupling - intramolecular arylation - palladium catalysis - oxazepinocarbazoles - pyranocarbazoles.
- Supporting Information for this article is available online:
- Supporting Information
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References and Notes
General Procedure
for the Preparation of 4 and 5
To 2-halobenzoic acid
(2.5 mmol) was added SOCl2 (2 mL). The solution was refluxed
for 2 h, after which the excess of SOCl2 was removed
under reduced pressure, and the residual traces were then removed
by coevaporation with dry toluene. The acid chloride was then added
to a solution of 1-hydroxy-carbazole (2.5 mmol) and Et3N
(2 mL) in dry THF (10 mL) at 0 ˚C. After the addition
of the acid chloride, the mixture was allowed to warm up to r.t.
while stirring under a nitrogen atmosphere. After stirring overnight,
the mixture was diluted with H2O and neutralized with
4% HCl to pH 7. The precipitated amide was then filtered
off and washed with 4% HCl and copious amounts of H2O.
The crude product was purified by chromatography using 1% EtOAc
and afforded 4 and 5.
1-Hydroxy-9-(2-bromobenzoyl)-6-methylcarbazole
(4a)
White solid; mp 126 ˚C; yield
0.682 g, 72%. IR (KBr): ν = 3432 (OH),
1646 (C=O) cm-¹. ¹H
NMR (500 MHz, CDCl3): δ = 2.42
(s, 3 H, CH3), 6.86 (t, 1 H, J = 8.0
Hz, H-3), 7.13 (dd, 1 H, J
m
= 2.0
Hz, J
o
= 8.0
Hz, H-7), 7.21 (dd, 1 H, J
m
= 2.0
Hz, J
o
= 8.0
Hz, H-2), 7.58-7.62 (m, 2 H, Harom), 7.67-7.71
(m, 2 H, Harom), 7.75 (d, 1 H, J = 8.0
Hz, H-8), 7.85 (s, 1 H, H-5), 7.94 (dd, 1 H, J
m
= 2.0
Hz, J
o
= 7.5
Hz,
H-3′), 12.76 (s, 1 H, OH). ¹³C
NMR (125 MHz, CDCl3): δ = 21.6
(CH3), 111.0, 111.6, 116.8, 119.1, 120.2, 122.3, 122.9,
126.1, 126.5, 127.5, 128.3, 129.9, 131.8, 132.2, 132.8, 138.4, 139.3,
148.5, 165.7 (CO). LC-MS: m/z = 380 [M + H+].
Anal. Calcd (%) for C20H14BrNO2:
C, 63.32; H, 3.69; N, 3.69. Found: C, 63.34; H, 3.67; N, 3.72.
General Procedure
for the Preparation of 6 and 7
To a solution of 1-hydroxycarbazole
(3a-d,
2.5 mmol) in
dry CH2Cl2, 2-bromobenzoyl
chloride, or 2-iodobenzoyl chloride (prepared as before) in dry
CH2Cl2 solution (10 mL) was added, and the
reaction mixture was heated to reflux for 12 h. The mixture was
then washed with H2O and brine solution and dried (Na2SO4).
Evaporation of the CH2Cl2 gave a crude product
which was purified by chromatography with PE-EtOAc (98:2)
to afford 6 and 7.
6-Methyl-9
H
-carbazol-1-yl 2-Bromobenzoate (6a)
White solid; mp 147 ˚C;
yield 0.682 g, 72%. IR (KBr): ν = 3389
(NH), 1741 (OC=O) cm-¹. ¹H
NMR (500 MHz, CDCl3): δ = 2.55
(s, 3 H, CH3), 7.24-7.28 (m, 2 H, Harom), 7.35
(d, 1 H, J = 8.0
Hz, H-8), 7.39 (dd, 1 H, J
m
= 1.0
Hz, J
o
= 8.0
Hz, H-4), 7.46-7.53 (m, 2 H, Harom), 7.81 (dd,
1 H, J
m
= 1.5
Hz, J
o
= 7.7
Hz, H-2), 7.89 (s, 1 H, H-5), 7.97 (d, 1 H, J = 7.5
Hz, H-3′), 8.13 [dd, 2 H, J
m
= 2.0
Hz, J
o
= 7.5
Hz, H-6′ (overlapped with NH)]. ¹³C
NMR (125 MHz, CDCl3): δ = 21.29
(CH3), 110.66, 117.57, 117.98, 119.24, 120.29, 122.04,
123.52, 126.27, 127.38, 127.66, 129.18, 131.28, 131.68, 131.96,
133.25, 134.54, 135.59, 137.88, 163.93 (C=O). LC-MS: m/z = 380 [M + H+].
Anal. Calcd (%) for C20H14BrNO2:
C, 63.32; H, 3.69; N, 3.69. Found: C, 63.36; H, 3.70; N, 3.72.
General Procedure
for the Preparation of 8
To a mixture of 4 or 5 (1 mmol),
Bu4NBr (1.5 equiv), and Cs2CO3 (1.5
equiv) in anhyd DMF (8 mL) was added Pd(OAc)2 (10 mol%)
and the flask placed in a pre-heated
oil bath at 110 ˚C
for 2 h. After completion of the reaction, the mixture was cooled
and diluted with H2O. This was extracted with EtOAc.
The combined organic extracts were washed with 1 M HCl, H2O,
brine and dried (Na2SO4). The solvent was
removed by distillation, and the crude product was purified by column
chromatography over silica gel using PE as the eluent to give the
final compound 8.
13-Methylbenzo[
f
][1,4]oxazepino[4,3,2-
l
,
m
]carbazol-9-one
(8a)
White solid; mp 141 ˚C; yield
0.269 g, 90%. IR (KBr): ν = 1666 (C=O)
cm-¹. ¹H NMR (500
MHz, CDCl3): δ = 2.44
(s, 3 H, CH3), 7.12 (d, 1 H, J = 8.0
Hz, H-3), 7.18 (t, 1 H, J = 8.0 Hz,
H-2), 7.19 (t, 1 H, J = 7.5
Hz, H-7), 7.23 (d, 1 H, J = 8.0 Hz,
H-5), 7.28 (d, 1 H, J = 8.0
Hz, H-12), 7.48 (t, 1 H, J = 7.5 Hz,
H-6), 7.60 (d, 1 H, J = 7.0
Hz, H-1), 7.67 (s, 1 H, H-14), 8.05 (dd, 1 H, J
m
= 1.5
Hz, J
o
= 8.0
Hz, H-8), 8.55 (d, 1 H, J = 8.5
Hz, H-11). ¹³C NMR (125 MHz, CDCl3): δ = 21.42 (CH3),
115.84, 116.94, 117.69, 120.07, 121.34, 124.73, 125.06, 125.52,
126.59, 128.89, 129.27, 129.79, 133.36, 134.51, 134.89, 137.66,
145.62, 156.51, 164.73 (C=O). LC-MS: m/z = 300 [M + H+].
Anal. Calcd (%) for C20H13NO2:
C, 80.27; H, 4.35; N, 4.68. Found: C, 80.21; H, 4.37; N, 4.73.
Complete cif files for compounds 4a and 9a were deposited with the Cambridge Crystallographic Data Centre, CCDC Deposit numbers 796527 and 796520. Copies of the data can be obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK [fax: +44 (1223)336033 or e-mail: deposit@ccdc.cam.ac.uk].
22
General Procedure
for the Preparation of 9
To a mixture of 6 or 7 (1 mmol),
Ph3P (20 mol%), and Cs2CO3 (2
equiv) in anhyd DMF (8 mL) was added Pd(OAc)2 (10 mol%),
and the mixture was placed in a pre-heated oil bath at 110 ˚C
for 4 h. After completion of the reaction, the mixture was cooled
and diluted with H2O. This was extracted with EtOAc.
The combined organic extracts were washed with 1 M HCl, H2O,
brine and dried (Na2SO4). The solvent was
removed by distillation, and the crude was purified by column chromatography
over silica gel using PE as eluent to give compound 9 as
white solid.
10-Methylisochromeno[3,4-
a
]carbazol-2(13
H
)-one
(9a)
Mp >300 ˚C; yield
0.254 g, 85%. IR (KBr): ν = 3305 (NH), 1719
(OC=O) cm-¹. ¹H
NMR (500 MHz, CDCl3): δ = 2.49 (s,
3 H, CH3), 7.25 (d, 1 H, J = 8.0
Hz, H-11), 7.37 (d, 1 H, J = 8.0
Hz, H-12), 7.50 (t, 1 H, J = 8.0
Hz, H-4), 7.54 (d, 1 H, J = 8.0
Hz, H-7), 7.78 (d t, 1 H, J
m
= 2.0
Hz, J
o
= 8.0
Hz, H-5), 7.89 (s, 1 H, H-9), 7.93 (d, 1 H, J = 8.5
Hz, H-3), 8.16 (d, 1 H, J = 8.0
Hz, H-8), 8.38 (dd, 1 H, J
m
= 1.5
Hz, J
o
= 8.0 Hz,
H-6), 8.56 (br s, 1 H, NH). ¹³C NMR
(125 MHz, CDCl3): δ = 21.34
(CH3), 102.32, 111.02, 116.10, 118.38, 118.66, 119.20,
120.46, 121.09, 124.52, 125.52, 126.92, 127.15, 128.00, 128.41,
132.07, 132.45, 133.05, 136.76, 158.12 (C=O). LC-MS: m/z = 300 [M + H+].
Anal. Calcd (%) for C20H13NO2:
C, 80.27; H, 4.35; N, 4.68. Found: C, 80.17; H, 4.33; N, 4.61.