One-pot oxidative heteroannulations of N-sulfonylanilines with styrenes for the construction of 5-aminocoumaran derivatives

Article abstract of DOI:10.1002/adsc.200800280

An efficient one-pot oxidative heteroannulation of N-sulfonylaniline derivatives with styrene derivatives for the rapid construction of 5-aminocoumaran derivatives is reported. Copper trifluoromethanesulfonate was found to be an excellent catalyst for the

Full text of DOI:10.1002/adsc.200800280

FULL PAPERS
DOI: 10.1002/adsc.200800280
One-Pot Oxidative Heteroannulations of N-Sulfonylanilines with
Styrenes for the Construction of 5-Aminocoumaran Derivatives
Renhua Fan,a,* Weixun Li,a Yang Ye,a and Linfei Wanga
a
Department of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433, Peopleꢀs Republic of China
Fax : (+86)-216-510-2412; e-mail: rhfan@fudan.edu.cn
Received: May 7, 2008; Published online: June 23, 2008
Supporting information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
Abstract: An efficient one-pot oxidative heteroannu- for the oxidative heteroannulation reactions with low
lation of N-sulfonylaniline derivatives with styrene reactive styrenes.
derivatives for the rapid construction of 5-aminocou-
maran derivatives is reported. Copper trifluorome- Keywords: aromatic substitution; cycloaddition; het-
thanesulfonate was found to be an excellent catalyst erocycles; hypervalent compounds; oxidation
Introduction
The widespread availability and inherent functionality
of aniline derivatives makes them attractive substrates
in organic synthesis. Oxidative functionalization reac-
Scheme 1. One-pot oxidative heteroannulation of aniline de-
rivatives with alkenes to construct 5-aminocoumaran deriva-
tives.
tions of phenols are well-known and useful synthetic
processes,[1] and the elegance of these strategies
prompted us to contemplate the possibilities for the
oxidative functionalizations of aniline derivatives.[2]
As a part of our work on the synthetic application of
sulfonamides in the presence of hypervalent iodine,[3]
in this communication, we present an efficient one- ronmental problems of these heavy metal analogues.[7]
pot oxidative heteroannulation of N-sulfonylaniline Moreover, trifluoroacetic acid, the metabolite of PhI-
derivatives with styrene derivatives for the rapid con-
struction of 5-aminocoumaran derivatives.
ACHTREUNG
Compounds which have the 5-aminocoumaran (5- ophilicity.
amino-2,3-dihydrobenzofuran) structure are reported
to be efficient antioxidants and to have protective ef-
fects against central nervous system trauma and ische- Results and Discussion
mia.[4] The general synthetic pathways for the prepa-
ration of 5-aminocoumaran derivatives have involved In testing this strategy, a one-pot reaction was tested
multi-step procedures or relatively harsh reaction but failed [Scheme 2, Eq. (1)]. N-Tosylaniline 1a was
conditions. Our one-pot oxidative heteroannulation recovered in 96% yield from the reaction, and some
strategy, which involves an oxidative carbon-oxygen oxidation products of 4-methoxystyrene were isolated
bond-forming reaction[5] and an oxidative carbon- as the by-products. Since N-tosylaniline showed a
carbon bond-forming reaction[6] of aniline derivatives, lower reactivity toward the PhI
ACHTRE(UNG OCOCF3)2, to avoid
is shown in Scheme 1. The oxidation of aniline deriva- the consumption of oxidant by 4-methoxystyrene, the
tives normally depends on the nature of the oxidant.[2] one-pot oxidative heteroannulation reaction was then
Iodobenzene bis(trifluoroacetate) [PhIACHTERNU(G OCOCF3)2] carried out in a stepwise way. PhIAHCTRE(UGN OCOCF3)2 was
was initially elected as the oxidant for the one-pot ox- added into the solution of N-tosylaniline 1a and H2O
idative heteroannulation due to its similar oxidative in acetonitrile. After N-tosylaniline had disappeared,
properties to those of Tl
ACHTREUNG
rivatives, but without the toxic and concomitant envi- methoxyAHCTREUNG
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Renhua Fan et al.
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Scheme 2.
reaction was completed in 30 min and afforded 5-ami- Table 1. Optimization of the one-pot oxidative heteroannu-
lation.
nocoumaran 2a in 34% yield [Scheme 2, Eq (2)].
This promising result encouraged us to optimize the
reaction conditions. Additional water was not neces-
sary since the trace of water in solvent could play the
role (Table 1, entry 1). No product 2a was detected
when acetone, MeOH, t-BuOH, DMSO, DMF and
EtOAc were used as the solvent while the reaction
could proceed with varied efficiency in THF,
ClCH2CH2Cl2 and toluene (Table 1, entries 2–10).
Lower temperatures were better for the first-step oxi-
dation, but not for the second-step heteroannulation
(Table 1, entries 11–13). Since some oligomers of N-
tosylaniline were isolated as by-products, the influ-
ence of the concentration on the reaction was investi-
gated (Table 1, entries 14–16). A lower concentration
inhibited the deleterious side reactions, but slowed
down the intermolecular heteroannulation.
In order to understand the reaction pathway, sever-
al control experiments were done. When 4 Š molecu-
lar sieves were introduced into the reaction, a compli-
cated reaction was observed. The reaction gave 2a in
a lower yield but oligomers of N-tosylaniline in
higher yields (Table 1, entry 17). Only a trace amount
of product 2a was formed when 4 equivalents of t-
BuOK were added to the reaction mixture before 4-
methoxystyrene (Table 1, entry 18). When PhI-
Entry Solvent
Temp. [oC] Time
Yield [%][a]
1
2
3
4
5
6
7
8
CH3CN
Acetone
MeOH
t-BuOH
DMSO
DMF
25
25
25
25
25
25
25
25
30 min 36
30 min
30 min
30 min
30 min
30 min
30 min
30 min 10
30 min 24
30 min 18
0
0
0
0
0
0
EtOAc
THF
9
10
ClCH2CH2Cl 25
Toluene
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
25
11[b]
12[b]
13[b]
14[c]
15[d]
16[e]
17[d,f]
18[d,g]
19[d,h]
0–25
1 h
3 h
10 h
3 h
4 h
5 h
4 h
6 h
4 h
46
58
51
65
75
72
32
trace
25
À10–25
À20–25
À10–25
À10–25
À10–25
À10–25
À10–25
À10–25
[a]
A
G
Isolated yield base on the N-tosylaniline.
[b]
[c]
[d]
[e]
[f]
The concentration of N-tosylaniline was 0.25M.
The concentration of N-tosylaniline was 0.125M.
The concentration of N-tosylaniline was 0.063M.
The concentration of N-tosylaniline was 0.031M.
4 Š molecular sieve was added.
the oxidant, the reaction was complicated. Acetate-
substituted N-tosylaniline derivatives were isolated as
by-products (Table 1, entry 19).
A proposed reaction pathway for the one-pot oxi-
dative heteroannulation of N-tosylaniline with 4-me-
thoxystyrene is outlined in Scheme 3. In situ oxidation
of N-tosylaniline in the presence of H2O gives an in-
termediate A, which undergoes aromatization to form
[g]
[h]
4 equivalents of t-BuOK were added.
PhIACHTERNGU(OCOCH3)2 was used instead of PhIAHCTRE(UGN OCOCF3)2.
N-tosyl-p-aminophenol. This is followed by further dition of intermediate C with 4-methoxystyrene and a
oxidation to afford an electrophilic intermediate p- subsequent intramolecular cyclization.[9]
quinone monosulfonimide C.[8] With the catalysis of
Trace amounts of N-tosyl-p-aminophenol were de-
the CF3COOH generated in the oxidation reactions, tected during the oxidation reaction. Analysis of the
5-aminocoumaran is constructed from the Michael ad- reaction mixture of the first-step oxidation by
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One-Pot Oxidative Heteroannulations of N-Sulfonylanilines with Styrenes
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Scheme 3. A proposed pathway for the oxidative heteroannulation of N-tosylaniline with 4-methoxystyrene.
1H NMR spectroscopy indicated the formation of p-
quinone monosulfonimide.[10] The oxidative heteroan-
nulation
smoothly even using 1.2 equivalents of PhI-
ACHTREUNG(OCOCF3)2, and gave product 2a in a nearly quantita-
of
N-tosyl-p-aminophenol
proceeded
tive yield.
When the C-4 position of N-tosylaniline was
blocked with a methyl group, the reaction was very
complicated, and did not give any isolable amounts of
product (Table 2, entry 1). However, it was notewor-
thy that the reaction of N-tosyl-4-anisidine proceeded
very well and gave product 2a in 95% yield (Table 2,
entry 2). No indoline product was isolated from the
reaction.[11]
Scheme 4. A proposed pathway for the oxidative heteroan-
nulation of C-4 substituted N-tosylaniline derivatives with 4-
The influence of C-4 substitution of the N-tosylani-
line on the reaction was investigated. The reactivity methoxystyrene.
Table 2. One-pot oxidative heteroannulation of various aniline derivatives with 4-methoxystyrene.
Entry
R1
R2
R3
Product
Yield [%][a]
1
2
3
4
5
6
7
8
p-CH3C6H4SO2
p-CH3C6H4SO2
p-CH3C6H4SO2
p-CH3C6H4SO2
p-CH3C6H4SO2
p-CH3C6H4SO2
p-CH3C6H4SO2
p-CH3C6H4SO2
p-CH3C6H4SO2
p-CH3C6H4SO2
p-CH3C6H4SO2
p-NO2C6H4SO2
CH3SO2
H
H
H
H
H
H
H
H
p-CH3
p-MeO
p-BuO
p-PhCH2O
-
0
2a
2a
2a
2a
2a
2a
-
2b
2c
-
95
85
88
44
70
73
0
35
18
0
p-CH3COO
p-Cl
p-Br
P-F
H
H
H
H
H
H
H
9
o-MeO
m-MeO
2,6-di-CH3
H
H
H
H
10
11
12
13
14
15
2d
2e
-
70
78
0
PhCO
CF3CO
-
0
[a]
Isolated yield base on the N-tosylaniline derivative.
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of 4-butoxy- or 4-benzyloxy-substituted derivative was
When N-tosyl-2-anisidine and N-tosyl-3-anisidine
similar to that of N-tosyl-4-anisidine (Table 2, en- were used as the substrates, the reactions were com-
tries 3 and 4). Acetate substitution resulted in a plicated. The corresponding N-tosyl-2,3-dihydro-5-
slower reaction and a lower yield of 2a (Table 2, benzofuranamine derivatives were isolated in low
entry 5). More notably, 4-chloro- and 4-bromo-substi- yields (Table 2, entries 9 and 10). Sterically hindered
tuted N-tosylaniline derivatives were found to be ef- N-(2,6-dimethylphenyl)-4-methylbenzenesulfonamide
fective substrates. Their reactions also afforded N- showed no reactivity toward the oxidant (Table 2,
tosyl-2,3-dihydro-5-benzofuranamine 2a in good entry 11). Sulfonyl protection of the aniline was im-
yields (Table 2, entries 6 and 7). No reaction occurred portant for the oxidative heteroannulation since nei-
in the case of N-(4-fluorophenyl)-4-methylbenzenesul- ther N-phenylbenzamide nor 2,2,2-trifluoro-N-phenyl-
fonamide (Table 2, entry 8).
Table 3. One-pot oxidative heteroannulation of N-(4-methoxyphenyl)-4-methylbenzenesulfonamide with various alkenes.
Entry
1
Cu
0
(OTf)2 (equivalents)
Alkene
Product
Yield [%][a]
92
2a
2f
2
0
91
3
0
2g
2h
2h
2h
2i
81
4
0
trace
28
5[b]
6
0
0.1
0.1
0.1
80
7
72
8
2j
75
9
0.1
2k
84
10
11
0.1
0.1
2l
72
65
2m
12
13
0.1
0.1
no reaction
no reaction
[a]
Isolated yield.
[b]
The reaction mixture was warmed up to reflux after the addition of styrene.
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One-Pot Oxidative Heteroannulations of N-Sulfonylanilines with Styrenes
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acetamide gave the corresponding cycloaddition prod- and 11). The structure of compound 2m was deter-
uct (Table 2, entries 12–15).
mined with the help of a single-crystal diffraction
A proposed reaction pathway for the oxidative het- analysis[12] which clearly showed the cis junction of
eroannulation of C-4 substituted N-tosylaniline deriv- the dihydrobenzofuran and the tetrahydronaphtha-
atives is outlined in Scheme 4. In situ oxidation of C-4 lene ring (Figure 1). We next applied our optimized
substituted N-tosylaniline derivatives in the presence CuACHTRE(UNG OTf)2-catalyzed oxidative heteroannulation condi-
of H2O gives an intermediate E, which undergoes tions to aliphatic olefins. Unfortunately, neither cyclic
elimination of an XH to form intermediate p-quinone nor acyclic aliphatic olefins gave a corresponding
monosulfonimide C (Scheme 4). Although acetate, product (Table 3, entries 12 and 13).
chloride and bromide are better leaving groups than
ethers, electron-withdrawing substitution decreases
the reactivity of the corresponding N-tosylaniline de- Conclusions
rivatives towards the oxidant.
The scope of the oxidative heteroannulation with In summary, we report here an efficient one-pot oxi-
respect to the alkenes was then investigated. In the dative heteroannulation of N-sulfonylaniline deriva-
presence of 1.2 equivalents of PhI
actions of N-tosyl-4-anisidine with electron-rich sty- tion of 5-aminocoumaran derivatives. Cu
ACHTREUNGrenes proceeded smoothly even at room temperature. found to be an excellent catalyst for the oxidative het-
ACHTREUNG
AHCTREUNG
The corresponding N-tosyl-2,3-dihydro-5-benzofuran- eroannulation reactions with low reactive styrenes.
amine derivatives were obtained in high yields The potential of this reaction system can be evaluated
(Table 3, entries 1–3). Under the same conditions, sty- by its mild conditions and simple process. The scope,
rene showed a lower reactivity (Table 3, entry 4). Al- mechanism, synthetic application, and CuCAHTREU(GN OTf)2-cata-
though the heteroannulation occurred at a higher lyzed asymmetric reactions are the subject of ongoing
temperature, product 2h was formed in a low yield investigations and will be reported in due course.
(Table 3, entry 5).
Based on the tentative reaction pathway, Lewis
acid-promoted heteroannulations were tested. Various Experimental Section
Lewis acids were examined, and CuACHTRE(UNG OTf)2 was finally
found to be the best catalyst for the heteroannulation Typical Experimental Procedure
of styrene. In the presence of 10 mol% Cu(OTf)2, the
AHCTREUNG
PhIACTHREU(GN OCOCF3)2 (1.25 mmol) was added to the solution of N-
reaction was completed in 2 h at room temperature,
and afforded product 2h in 80% yield (Table 3,
entry 6). Further investigation indicated that even
electron-poor or sterically hindered styrene deriva-
tosylaniline 1a (0.5 mmol) in acetonitrile (8 mL) at À108C.
The mixture was allowed to stir at À108C. Upon completion
as shown by TLC, the reaction mixture was treated with 4-
methoxystyrene (1.5 mmol). This was then allowed to stir at
258C for 15 min. The reaction was then quenched with satu-
rated NaHCO3, and extracted by ethyl acetate (100 mL”3).
The organic layer was dried over Na2SO4, and concentrated
under vacuum. The residue was purified by column chroma-
tography on silica gel (30% ethyl acetate in hexanes) to pro-
vide the desired product. The characterization data are
available in the Supporting Information file.
tives were effective substrates in CuACTHRE(UNG OTf)2-catalyzed
oxidative heteroannulation (Table 3, entries 7–9). It
was noticeable that tetracyclic products 2l and 2m
could be formed when bicyclic indene and 1,2-dihy-
dronaphthalene were employed (Table 3, entries 10
Acknowledgements
Financial support from National Natural Science Foundation
of China (20702006), the Shanghai Rising-Star program
(07QA14007), and Fudan University are gratefully acknowl-
edged.
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