An efficient synthesis of carbazoles from PtCl2-catalyzed cyclization of 1-(indol-2-yl)-2,3-allenols

Article abstract of DOI:10.1039/b909649c

The PtCl₂-catalyzed reaction of 1-(indol-2-yl)-2,3-allenols occurred smoothly to form carbazoles by connecting the 3-carbon atom of indole with the 4-carbon atom of the allenol moiety, referring to the carbon atom connected to the hydroxyl grou

Full text of DOI:10.1039/b909649c

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An efficient synthesis of carbazoles from PtCl2-catalyzed cyclization
of 1-(indol-2-yl)-2,3-allenolsw
Wangqing Kong, Chunling Fu and Shengming Ma*
Received (in Cambridge, UK) 15th May 2009, Accepted 1st June 2009
First published as an Advance Article on the web 22nd June 2009
DOI: 10.1039/b909649c
The PtCl2-catalyzed reaction of 1-(indol-2-yl)-2,3-allenols
occurred smoothly to form carbazoles by connecting the
3-carbon atom of indole with the 4-carbon atom of the allenol
moiety, referring to the carbon atom connected to the
hydroxyl group.
affording 3a in 80% NMR yield (entry 6, Table 1); other
solvents, such as CH3CN, xylenes, DCE (1,2-dichloroethane)
and THF provided 3a in 20%, 67%, 82% and 38% yields,
respectively (entries 7–10, Table 1). When 2 mol% PtCl2 was
used, the yield of 3a was lower (compare entry 11 with entry 5,
Table 1). Thus, we defined the standard conditions as follows:
the reaction of 1 was conducted with 5 mol% PtCl2 in toluene
at room temperature (entry 5, Table 1).
The tricyclic carbazole ring system is the core structure for
a wide range of alkaloids displaying a variety of biological
activities,1 and are important building blocks for the construction
of polymers with special thermal,2 electrical3 and photoelectrical
properties,4 and polymer-blend additives for the fabrication of
photorefractive materials.5 Thus, the development of simple,
mild, efficient and general methods6 to synthesize the carbazole
ring system from easily available starting materials are of current
interest. On the other hand, we recently observed a PtCl4-
catalyzed intermolecular cyclization reaction of b-allenols in
the presence of indoles affording indole derivatives with a
saturated 6-membered cyclic ether group at the 3-position
(Scheme 1).7 Based on these results, we envisioned that
the reaction of 1-(indol-2-yl)-2,3-allenols 1 would afford poly-
cyclic products 2. However, carbazoles 3 were formed conveniently
at room temperature in toluene (Scheme 1). In this communication,
we wish to report these unique observations.
This new transformation is quite general. Some typical
results are listed in Table 2. The 1-position of indoles may
be substituted with an alkyl (entries 1–12 and entries 14–19,
Table 2) or phenyl group (entry 13, Table 2). R3 could be H
(entries 1–6 and 19, Table 2), an alkyl (entries 8 and 10,
Table 2) or an aryl group (entries 7, 9, 12 and 13, Table 2).
The reaction of 1k (entry 11, Table 2) is especially noteworthy,
since this reaction shows an interesting exclusive cyclization of
the allene instead of the alkene functionality; in addition, this
reaction tolerates many functional groups such as COOMe,
CONMe2 and CH2OH (entries 14–18, Table 2). In entries
16–18, it should also be noted that the secondary hydroxyl
group was exclusively eliminated. R4 could be H (entries 7–19,
Table 2), an alkyl (entries 1–5, Table 2) or a benzyl group
(entry 6, Table 2). Moreover, differently substituted indoles
can also successfully give the corresponding carbazole deriva-
tives (entries 4, 5, 12, 17 and 18, Table 2). The structures of 3
were further confirmed by the X-ray crystal diffraction study
of 3g (Fig. 1).13
The starting materials, 1a–r, are easily available from
the related 1H-indole-2-carbaldehydes based on known
methods (see the ESI for detailsw).8–10 Our initial investigation
was focused on the reaction of 1-(1-ethyl-1H-indol-2-yl)nona-
2,3-dien-1-ol (1a) in toluene under the catalysis of PtCl4
(5 mol%).7 Instead of forming the 2-type of product,
9-ethyl-4-pentyl-9H-carbazole (3a) was unexpectedly formed
in 65% NMR yield (entry 1, Table 1). When PtCl4 was
replaced with AgBF4 (20 mol%), the reaction was complicated
with 3a being formed in only 13% yield (entry 2, Table 1), and
AuCl(PPh3) was totally inactive (entry 3, Table 1). With the
addition of 10 mol% AgOTf, 1a decomposed quickly, probably
due to the presence of the free hydroxyl group in 1a, and the
yield of 3a was o7%, if any, based on NMR analysis of the
crude reaction mixture (entry 4, Table 1).11 Further study led
to the observation that PtCl2 is a much better catalyst for this
reaction, affording 3a in 83% isolated yield (entry 5,
Table 1).12 Several solvents were tested for the PtCl2-catalyzed
reaction of 1a at room temperature: CH2Cl2 was also effective
A plausible mechanism involving a metal carbene inter-
mediate 7 is depicted in Scheme 2. The reaction of PtCl2 with
1 would form intermediate 5 from the coordination of the
allene moiety to the platinum atom followed by nucleophilic
attack of indolyl C3 to the metal-activated electrophilic CQC
double bond. Subsequent protonation of the hydroxyl group
followed by elimination of H2O in intermediate 6 affords cyclic
vinylic platinum carbene intermediate 7.14 A 1,2-H shift15 of
intermediate 7 would afford the final product 3, with
regeneration of the catalytically active species PtCl2.
Laboratory of Molecular Recognition and Synthesis, Department of
Chemistry, Zhejiang University, Hangzhou 310027, Zhejiang, Peoples
Republic of China. E-mail: masm@mail.sioc.ac.cn
w Electronic supplementary information (ESI) available: The experi-
mental procedures, characterization data, and copies of 1H and 13C
NMR spectra for all products. CCDC 713481. For ESI and crystallo-
graphic data in CIF or other electronic format, see: 10.1039/b909649c
Scheme 1
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Table 1 Optimization of the reaction conditions for the cyclization
reaction of 1-(1-ethyl-1H-indol-2-yl)nona-2,3-dien-1-ol 1a
Fig. 1 ORTEP representation of product 3g.
Entry
Catalyst (mol%)
Solvent
Time/h
Yield of 3a (%)a
1
2
3
4
5
6
7
8
PtCl4 (5)
Toluene
Toluene
Toluene
Toluene
Toluene
CH2Cl2
CH3CN
Xylenes
DCE
1
3
10
4
2
3
3
3
3
65
13
AgBF4 (20)
AuCl(PPh3) (10)
AuCl(PPh3)(10)c
PtCl2 (5)
PtCl2 (5)
PtCl2 (5)
b
—
o7
90 (83d)
80
20
PtCl2 (5)
PtCl2 (5)
67
82
9
10
11
PtCl2 (5)
PtCl2 (2)
THF
Toluene
3
5
38
79 (74d)
a 1H NMR yield was determined by using CH2Br2 as the internal
b
standard. The recovery of 1a was 92%. AgOTf (10 mol%) was
c
d
added. Isolated yield.
In conclusion, we have developed a simple and mild PtCl2-
catalyzed reaction of 1-(indol-2-yl)-2,3-allenols, providing an
efficient route to differently substituted carbazoles in good
isolated yields under very mild conditions. Due to the easy
availability of the starting materials (see the ESI for detailsw)8,9
Scheme 2 Proposed mechanism.
and the potential of the products,1–5 this method may be useful
in organic synthesis and medicinal chemistry. Further studies
Table 2 PtCl2-catalyzed cyclization reaction of 1-(indol-2-yl)-2,3-allenols
1
R1
R2
R3
R4
R5
Entry
Time/h
Yield of 3 (%)
1
2
3
4
5
6
7
8
Et
Et
Et
Et
Et
Et
Et
Et
Me
Me
Et
Et
Ph
Et
Et
Et
Et
Et
Et
H
H
Me
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Ph
n-C4H9
Ph
n-C4H9
allyl
Ph
n-C5H11
Me
n-C6H13
n-C6H13
n-C6H13
Bn
H
H
H
H
H
H
H
H
H
H
H
H
H
H (1a)
H (1b)
H (1c)
5-Me (1d)
5-OMe (1e)
H (1f)
H (1g)
H (1h)
H (1i)
H (1j)
H (1k)
5-Me (1l)
H (1m)
H (1n)
H (1o)
H (1p)
4-Me (1q)
7-Me (1r)
H (1s)
2
2
2
2
3
5
4
3
4
83 (3a)
86 (3b)
81 (3c)
75 (3d)
75 (3e)
50 (3f)
70 (3g)
74 (3h)
81 (3i)
71 (3j)
74 (3k)
70 (3l)
78 (3m)
67 (3n)
83 (3o)
64 (3p)
81 (3q)
68 (3r)
70 (3s)
9
10
11
12
13
14
15
16
17
18
19
4
3
17
19
36
24
23
20
21
4
Ph
COOMe
CONMe2
CH2OH
CH2OH
CH2OH
H
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on the mechanism and synthetic applications of this reaction
are being carried out in our laboratory.
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Financial support from the Major State Basic Research and
Development Program (2009CB825300) and the National
Natural Science Foundation of China (20732005) is greatly
appreciated. Shengming Ma is a Qiu Shi Adjunct Professor at
Zhejiang University. We thank Mr Guobi Chai in this group
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4574 | Chem. Commun., 2009, 4572–4574