Ferric chloride-catalyzed C-N bond cleavage for the cyclization of arylallenes leading to polysubstituted indenes

Article abstract of DOI:10.1039/c2cc36048a

A range of arylallenes undergo carbocation-initiated cyclization reaction with N-benzylic and N-allylic sulfonamides in the presence of 10 mol% ferric chloride to give structurally diverse polysubstituted indenes in good yields with extremely high regioselectivity.

Full text of DOI:10.1039/c2cc36048a

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COMMUNICATION
Ferric chloride-catalyzed C–N bond cleavage for the cyclization of
arylallenes leading to polysubstituted indenesw
Cong-Rong Liu,ab Ting-Ting Wang,a Qing-Biao Qia and Shi-Kai Tian*ac
Received 21st August 2012, Accepted 12th September 2012
DOI: 10.1039/c2cc36048a
A range of arylallenes undergo carbocation-initiated cyclization
reaction with N-benzylic and N-allylic sulfonamides in the
presence of 10 mol% ferric chloride to give structurally diverse
polysubstituted indenes in good yields with extremely high
regioselectivity.
in the presence of carbon electrophiles (benzylic alcohols6a or
ethenetricarboxylates6k),8 the reaction requires a stoichiometric
6a
amount of Lewis acid (ZnCl2 or SnCl46k) and the substrates
are limited to terminal arylallenes. In sharp contrast, in our
reaction, a catalytic amount of FeCl3 is employed and 1,3-di-
and 1,1,3-trisubstituted arylallenes serve as suitable substrates.
A number of Brønsted and Lewis acids (10 mol%) were
examined in the model reaction of arylallene 1a with N-benzhydryl-
p-toluenesulfonamide (2a) in nitromethane at 90 1C, and to
our delight, FeCl3 was identified as the catalyst of choice,
which promoted the formation of indene 3a in 84% yield
(Table 1, entry 7). The reaction was also performed in a
common organic solvent other than nitromethane, but a much
lower yield was obtained (Table 1, entries 9–12). Moreover,
the reaction gave a lower yield or even resulted in no desired
product at all when replacing the p-toluenesulfonyl group
in substrate 2a with a methanesulfonyl group, a diphenyl-
phosphinyl group, an acyl group, or an alkoxycarbonyl group
(Table 1, entries 13–16).
N-Benzylic and N-allylic sulfonamides are able to undergo sp3
C–N bond cleavage to generate the corresponding carbo-
cations under a number of acidic conditions, and they have
recently emerged as useful carbon electrophiles to couple with
carbon and sulfur nucleophiles in an SN1 manner.1 Such
reactions yield primary sulfonamides as neutral byproducts,
and hence N-benzylic and N-allylic sulfonamides can serve as
unique carbocation sources with regard to reducing undesired
side reactions, such as overalkylation and elimination, that can
be caused by strongly acidic byproducts such as hydrogen
halides when benzylic and allylic halides are employed as
carbocation sources.2 Moreover, the choice of acidic catalysts
largely depends on the nature of both N-benzylic (or N-allylic)
sulfonamides and nucleophiles.
Table 1 Optimization of reaction conditionsa
Indenes are present in many biologically relevant molecules,3
catalysts,4 and materials.5 Although much attention has been
paid to their synthesis,6 there remains room for the develop-
ment of new methods that can expand the scope, employ
inexpensive catalysts, and/or simplify synthetic manipulations.
In this context, we recently investigated the sp3 C–N bond
cleavage of N-benzylic and N-allylic sulfonamides in the
presence of arylallenes and found that polysubstituted indenes
were formed with extremely high regioselectivity in the
presence of an iron Lewis acid catalyst that is inexpensive and
environmentally benign.7 Although arylallenes have recently
been reported to undergo cyclization to form indene derivatives
Entry
2a–ae, X
Catalyst
Solvent
Yieldb (%)
1
2
3
4
5
6
7
8
2a, Ts
2a, Ts
2a, Ts
2a, Ts
2a, Ts
2a, Ts
2a, Ts
2a, Ts
2a, Ts
2a, Ts
2a, Ts
2a, Ts
2ab, SO2Me
2ac, POPh2
2ad, COPh
2ae, CO2Bn
PhCO2H
TsOH
TfOH
ZnCl2
AlCl3
MeNO2
MeNO2
MeNO2
MeNO2
MeNO2
MeNO2
MeNO2
MeNO2
(ClCH2)2
MeCN
Dioxane
DMF
MeNO2
MeNO2
MeNO2
MeNO2
0
70
61
75
39
23
84
33
59
Trace
12
48
80
43
31
0
BiCl3
FeCl3
Fe(OTf)3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
a Joint Laboratory of Green Synthetic Chemistry, Department of
Chemistry, University of Science and Technology of China, Hefei,
Anhui 230026, China. E-mail: tiansk@ustc.edu.cn;
9
10
11
12
13
14
15
16
Fax: +86 551-360-1592; Tel: +86 551-360-0871
b Department of Environmental Engineering, Nanjing Institute of
Technology, Nanjing, Jiangsu 211167, China
c Key Laboratory of Synthetic Chemistry of Natural Substances,
Shanghai Institute of Organic Chemistry, Chinese Academy of
Sciences, Shanghai 200032, China
a
w Electronic supplementary information (ESI) available: Experimental
procedures, characterization data, and copies of 1H and 13C NMR for
products. CCDC 889428. For ESI and crystallographic data in CIF or
other electronic format see DOI: 10.1039/c2cc36048a
Reaction conditions: arylallene 1a (0.30 mmol), amine derivative
2a–ae (0.20 mmol), catalyst (10 mol%), solvent (2.0 mL), 90 1C, 12 h.
Isolated yield.
b
c
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Chem. Commun., 2012, 48, 10913–10915 10913

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Table 2 Synthesis of polysubstituted indenes from arylallenes and
N-alkyl sulfonamidesa
Scheme 1 Proposed reaction pathway.
not applicable to less reactive N-alkyl sulfonamides such as
N-benzyl-p-toluenesulfonamide, N-allyl-p-toluenesulfonamide,
N-cyclohexyl-p-toluenesulfonamide, and N-(1-adamantyl)-
p-toluenesulfonamide. It could be attributable to the relatively
low stability of the corresponding carbocations generated via
C–N bond cleavage.
Entry
1
2
Product
Time (h) Yieldb (%)
1
1a 2a
1b 2a
1c 2a
1d 2a
12
24
12
20
84
65
72
88
2
On the basis of our results and previous studies, we propose
the reaction pathway depicted in Scheme 1 for the synthesis of
polysubstituted indenes from arylallenes and N-alkyl sulfon-
amides. N-Alkyl sulfonamide 2 is subjected to FeCl3-catalyzed
sp3 C–N bond cleavage to form carbocation 4,6h which is
attacked by arylallene 1 to give allylic carbocation 5.6a
Friedel–Crafts cyclization of carbocation 5 followed by
aromatization affords indene 3.
3c
4
5
1e 2a
24
62
6
7
8
9
1f 2a
1g 2a
1h 2a
1i 2a
24
24
24
24
60
72
71
75
In summary, we have developed a pathway for an unprece-
dented synthesis of polysubstituted indenes from arylallenes
and N-alkyl sulfonamides through iron-catalyzed cleavage of
sp3 C–N bonds. A range of arylallenes undergo carbocation-
initiated cyclization reaction with N-benzylic and N-allylic
sulfonamides in the presence of 10 mol% ferric chloride to
give structurally diverse polysubstituted indenes in good yields
with extremely high regioselectivity. Current efforts are direc-
ted toward further methodological refinement and synthetic
applications.
10
11
12
13
1a 2b
1a 2c
1a 2d
1a 2e
1a 2f
1a 2g
1a 2h
1a 2i
1a 2j
1a 2k
1a 2l
6
24
12
12
12
30
15
24
36
12
24
71
73
75
59
89
87
73
85
81
66
70
14
15d
16e
17f
18g
19h
20i
We are grateful for the financial support from the National
Natural Science Foundation of China (21172206 and 20972147),
the National Basic Research Program of China (973 Program
2010CB833300), and the Program for Changjiang Scholars and
Innovative Research Team in University (IRT1189).
a
Reaction conditions: arylallene 1 (0.30 mmol), N-alkyl sulfonamide 2
b
(0.20 mmol), FeCl3 (10 mol%), nitromethane (2.0 mL), 90 1C. Isolated
yield. The structure of compound 3c was confirmed by single crystal
c
Notes and references
d
X-ray analysis (CCDC 889428). 54 : 46 dr. 55 : 45 dr. 93 : 7 dr.
e
f
g
h
65 : 35 dr. 50 : 50 dr. 55 : 45 dr.
i
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In the presence of 10 mol% FeCl3, a range of 1,3-di- and
1,1,3-trisubstituted arylallenes were reacted with N-benzylic
sulfonamide 2a to give structurally diverse polysubstituted indenes
in good yields with extremely high regioselectivity (Table 2,
entries 1–9). Moreover, N-bisbenzylic, N-monobenzylic, and
N-allylic sulfonamides were demonstrated to serve as suitable
substrates (Table 2, entries 10–20). It is noteworthy that both
electron-withdrawing and electron-donating groups were
successfully introduced into the indene products by employing
the sulfonamides bearing such groups on the aromatic rings,
and importantly, no isomerization was observed for the
carbon–carbon double bonds. Nevertheless, the reaction was
c
10914 Chem. Commun., 2012, 48, 10913–10915
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Chem. Commun., 2012, 48, 10913–10915 10915