Tert -Butoxide mediated cascade desulfonylation/arylation/hydrolysis of cyclic sulfonyimines using diaryliodonium salts: Synthesis of diaryl ether derivatives bearing a 2-aldehyde group

Article abstract of DOI:10.1039/c6ra19313g

Cascades of cyclic sulfonyimines mediated by ^tBuOK with diaryliodonium salts has been developed, giving the diaryl ethers in good yields. Furthermore, bulky ortho-substituted diaryl ethers with an aldehyde group can be obtained easily in comparision with metal-catalyzed protocols.

Full text of DOI:10.1039/c6ra19313g

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DOI: 10.1039/C6RA19313G
Journal Name
COMMUNICATION
tert-Butoxide Mediated Cascade Desulfonylation/Arylation/
Hydrolysis of Cyclic Sulfonyimines Using Diaryliodonium Salts:
Synthesis of Diaryl Ether Derivatives Bearing a 2-Aldehyde Group
Received 00th January 20xx,
Accepted 00th January 20xx
Xiaofei Qian,a Jianwei Hana,b* and Limin Wanga*
DOI: 10.1039/x0xx00000x
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Cascades of cyclic sulfonyimines mediated by tBuOK with developed a practical approach for the synthesis of ortho-CHO diaryl
diaryliodonium salts has been developed, giving the diaryl ethers ethers by a three component sequential coupling of arynes, N,N-
in good yields. Furthermore, bulky ortho-substituted diaryl ethers dimethylformamide and diaryliodonium salts.10 In this context, we
with aldehyde group can be obtained easily in comparision of reported N-arylations of carbazoles and hydroxylamines, O-arylation
metal-catalyzed protocols.
of oximes and C-arylations of tetrahydrocarbazoles, pyrazolin-5-
ones, cyanoacetates and 1-acetylindolin-3-ones by using
diaryliodonium salts.11 With our continuous interest in arylations
under metal-free conditions, we were intrigued by the possibility of
arylation with cyclic imines to synthesize ortho-CHO diaryl ethers.
Herein, we reported the detail results that potassium tert-butoxide
mediated arylation of cyclic imines, giving an efficient access to
ortho-CHO diaryl ethers.
Aryl ethers as common structural motifs can be found in various
biological compounds, drug candidates and functional material
molecules.1 For example, D-phenothrin and Oxyfluorfen including
diarylether skeleton are well-known insecticide and herbicide,
respectively. α-mangostin is a natural xanthonoid which was studied
for the potential usage in pharmaceutical research (Figure 1).2
Therefore, construction of diaryl ethers attracted considerable
interest.3 The typical procedure in synthesis of diaryl ethers was
proceeded by Ullmann-type reactions.4 However, the Ullmann
reactions usually required stoichiometric amounts of copper
catalysts and harsh reaction conditions.4, 5 Hence, the development
of new methods to access aryl ethers is still in demand. Despite
various powerful synthetic approaches of cross-coupling reactions
mediated by copper or palladium complexes were recorded in
recent decades,6 the use of heavy metals limits the practical
application due to the purification and economic cost. Therefore,
Figure 1. Selected samples of diaryl ether structures.
We began our study by chosen benzo[e][1,2,3]oxathiazine-2,2-
the Ullmann ether synthesis with metal-free method by using highly dioxide (1a) and diphenyliodonium triflate (2a) as model substrates
activated aryl fluorides was also reported, 7 while most cases were to optimize the reaction conditions. To our delight, the reaction
limited to the electron-rich or neutral phenols.
gave the desired product in 40% yield in presence of K2CO3 as the
Recently, Olofsson and coworkers pioneered the arylation of base and MeCN as solvent at 60 oC (table 1, entry 1). After screening
phenols under the mild and metal-free conditions by using several bases, it was found that strong inorganic bases worked well,
diaryliodonium salts.8 The methodology was further extended to for example, the base of BuOK gave 3a in 55% yield (table 1, entry
t
the O-arylation of N-hydroxyphthalimides and carboxylic acids.9 2-4). When the organic bases of lutidine and DMAP were employed,
However, the synthesis of ortho-substituted diaryl ethers with steric the reaction cannot occur at all (table 1, entry 5-6). Screening of
hindrance still remained a challenge. In 2014, Jiang and coworkers solvents showed that potassium tert-butoxide in dichloroethane
(DCE) delivered the desired product 3a in the most efficient manner
(table 1, entry 5-12). We also tried to increase the reaction
temperature, however, the yield of 3a was slightly decreased (table
a.Key Laboratory for Advanced Materials and Institute of Fine Chemicals, East China
University of Science and Technology, 130 Meilong Road, Shanghai 200237, P. R.
China.
1, entries 13). Furthermore, different counteranions of
b.Shanghai-Hong Kong Joint Laboratory in Chemical Synthesis, Shanghai Institute of
diphenyliodonium salts were also evaluated on the reactivity, only a
Organic Chemistry, The Chinese Academy of Sciences, 345 Ling Ling Road,
negligible influence on the yields was observed (Table 1, entries 14–
Shanghai 200237, P. R. China.
† Footnotes relating to the title and/or authors should appear here.
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
16).
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Table 1. Screening of reaction conditions for arylation of Table 2.
benzo[e][1,2,3]oxathiazine 2,2-dioxide.a
Scope of diverse iodonium salts inVieawryAlratitciloe nOnlionef
benzo[e][1,2,3]oxathiazine 2,2-dioxidea
DOI: 10.1039/C6RA19313G
Entry
1
2
3
4
5
6
7
8
Ar1(Ar2)
(4-tBuC6H4)2
(4-MeC6H4)2
(3-MeC6H4)2
(Mesityl)2
(4-CF3C6H4)2
(4-FC6H4)2
(4-ClC6H4)2
X
Product
3b
3c
3d
3e
3f
3g
3h
3i
3j
%Yieldb
49
50
48
44
50
69
80
74
80
62
N.D.
40
32
Entry
1
2
3
4
5
6
7
8
X
Base
Solvent
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
Toluene
CH2Cl2
DCE
THF
DMF
MeCN
DCE
DCE
%Yieldb
40
44
50
55
-
OTf
OTf
OTf
OTf
BF4
OTf
OTf
BF4
OTf
PF6
PF6
OTf
OTf
OTf
OTf
OTf
OTf
OTf
OTf
OTf
OTf
OTf
OTf
OTf
OTf
PF6
OTs
BF4
K2CO3
Cs2CO3
NaOH
tBuOK
lutidine
DMAP
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
tBuOK
-
24
35
62
40
25
36
55
61
55
59
(3,4-Cl2C6H3)2
(4-BrC6H4)2
(3-CO2EtC6H4)2
(3-NO2C6H4)2
4-CO2EtC6H4(Mesityl)
Mesityl(4-MeC6H4)
9
9
10
11
12
13
3k
3l
3m
10
11
12
13 c
14
15
16
OTf 3e : 3c > 20 : 1
aUnless otherwise specified, reaction conditions: 1a (0.3 mmol),
tBuOK (0.33mmol) iodonium salt (0.33 mmol, 1.1 equiv.), and DCE
(2 mL); 60 oC, 30min. bIsolated yield.
DCE
DCE
a Unless otherwise specified, reaction conditions: 1a (0.3 mmol),
iodonium salt (0.33 mmol, 1.1 equiv.), base (0.33 mmol) and solvent
(2 mL); 60 oC, 30min. bIsolated yield. cFor 80 oC
For further exploring the scope of this reaction, a wide range of
benzoxathiazine derivatives were employed under standard
reaction conditions. The electron-donating substituents such as
alkyl, benzene, methoxy or N, N-diethyl amino groups, gave the
desired products 4a-4e in 59 - 68% yields (table 3, entry 1-5). When
the substituents (R) were halogen atoms, the desired products were
furnished in moderate yields of 41-52% (table 3, entry 6-10).
Furthermore, the reaction it is noted that benzoxathiazines carrying
the electron-withdrawing substituents, can also reacted well. For
example, the product 4j was achieved in 45% yield when 1j was
used with the standard procedure. Additionally, naphthalene
derivative 4k was obtained in 50% yield under the standard reaction
conditions.
With the optimal conditions in hand, we then investigated
various diaryliodonium salts as arylation partners. Generally, the
reaction condition proved to be efficient to
a variety of
functionalities of diaryliodonium salts, and the reactions were
completed in the short time of 30 minutes as determined by thin
layer chromatography. For symmetrical diaryliodonium salts, it was
found that the diaryliodonium salts bearing the alkyl including the
trifluoromethyl on the phenyl ring furnished 3b-f in moderate yields
of 44 - 50% (table 2, entry 1-5). Notably, when the substitute groups
changed to halogen, the desired products were obtained in good
yields of 69 – 80% (table 2, entry 6 - 9). The electron-withdrawing
groups such as ester gave a moderate yield of 62% (table 1, entry
10). When 2l was used as reactant, no product was observed; and it
was found that the reaction lead to decompose the substrate 2l to
give a complicated mixtures as shown in thin layer chromatography
(table 1, entry 11). Next, unsymmetrical diaryliodonium salts were
employed in the reaction, it is interesting found that electron-
withdrawing groups were transferred to the desired products, for
example, only 3m bearing a ester substituent was obtained when
[4-CO2EtC4H4I(mesityl)]OTf was employed in the reaction, the
product of mesityl ether was not observed. In order to prove the
steric effect of mesityl group on the selectivity, [4-
MeC6H4I(mesityl)]OTf was used in the reaction, both products of 3e
and 3c was yielded. Surprisingly the major product is 3e and the
ratio of 3e/3a is more than 20/1.
Table 3. Scope of diverse benzoxathiazine derivatives in arylationa.
Entry
1
1
Product
%Yieldb
68
4a
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67
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DOI: 10.1039/C6RA19313G
Scheme 1. Synthesis of xanthone
4b
3
4
60
63
Conclusions
4c
In summary, we developed a new O-arylation method through a
cascade reaction of benzo[e][1,2,3]oxathiazine 2,2-dioxides by using
diaryliodonium salts under metal-free condition. Various diaryl
ethers bearing a variety of functional groups could be obtained with
this procedure. Moreover, the products of 2-phenoxybenzaldehyde
were important intermediates for valuable chemicals. It was
demonstrated by a further conversion of diaryl ether into an
xanthone.
4d
5
59
4e
6
7
8
9
52
44
43
41
Experimental Section
4f
General Methods
4g
4h
All reagents were obtained from commercial sources without
further purification. The diaryliodonium salts and substrates were
prepared according to the literature report.13, 14 All reactions were
performed in glassware under air. 1H NMR and 13C NMR spectra
were respectively recorded at 400 and 100 MHz, using
tetramethylsilane as an internal reference. Chemical shifts (δ) and
coupling constants (J) were expressed in parts per million and hertz,
respectively. High-resolution mass spectrometry (HRMS) was
performed on an EI-TOF spectrometer. Mass spectra were recorded
by the mass spectrometry service of Shanghai Institute of Organic
Chemistry. Column chromatography was performed on silica gel
(Huang-hai, 300-400 mesh).
4i
10
11
45
50
4j
4k
aUnless otherwise specified, reaction conditions: 1 (0.3 mmol),
tBuOK (0.33mmol) 2a (0.33 mmol, 1.1 equiv.), and DCE (2 mL); 60 oC,
30min. bIsolated yield.
Typical procedure for arylation of benzo[e][1,2,3]oxathiazine 2,2-
dioxide and the derivatives
A Schlenk tube was charged with benzo[e][1,2,3]oxathiazine 2,2-
dioxide (54.9 mg, 0.3 mmol, 1 equiv.), potassium tert-butoxide (37.0
mg, 0.33 mmol, 1.1 equiv), diaryliodonium salts (0.33 mmol, 1.1
equiv), then 2 ml DCE was added under air. Then the tube was
sealed with a rubber under air, and the reaction was heated to 60
oC for 30 min. After cooling to room temperature, the solvent was
removed in vacuo and the residue was purified by silica gel using a
proper eluent to afford the desired products.
Finally, the utility of the arylation products for conversion into
useful skeleton was attempted. Xanthones are the core structures
of many naturally occurred compounds exhibiting biological and
pharmaceutical activities.1c,2b Therefore, 2-phenoxybenzaldehyde
was tried in a preparative scale of 50 mmol, which was obtained in
62% yield. Then, the xanthone was prepared under oxidative
conditions via a dehydrogenative coupling reaction,12 the final
product of 5 was achieved in 60% yield.
Typical procedure for synthesis of xanthone
A Schlenk tube was charged with 2-phenoxybenzaldehyde (198.2
mg, 1.0 mmol), tetrabutylammonium bromide (161.2 mg, 0.5
mmol), H2O (5 mL), TBHP (70% solution in water, 2 mL). Then the
tube was sealed with a teflon plug, the reaction was heated to 120
oC over night. After cooling to room temperature, the solvent was
removed in vacuo and the residue was purified by silica gel using a
proper eluent to afford xanthone.
Acknowledgements
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This work was supported by grants from the National Nature
Science Foundation of China (NSFC Nos. 21272069, 21472213,
21202186) and the Fundamental Research Funds for the Central
Universities, Key Laboratory of Organofluorine Chemistry, Shanghai
Institute of Organic Chemistry, Chinese Academy of Sciences.
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DOI: 10.1039/C6RA19313G
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