Pyridine-Catalysed Desulfonylative Addition of β-Diketones to Arylazosulfones via Diaziridine Rearrangement

Article abstract of DOI:10.1002/adsc.202001171

A pyridine-catalysed desulfonylative addition of β-diketones to arylazosulfones was developed to obtain diazenyl β-dicarbonyl compounds. The aryldiazenyl group was observed in the desired product from arylazosulfones, and this diazenylation reaction was achieved via a possible rearrangement process based on diaziridine ring cleavage. The scope of the protocol was investigated and a plausible mechanism was given. (Figure presented.).

Full text of DOI:10.1002/adsc.202001171

Title: Pyridine-Catalysed Desulfonylative Addition of β-Diketones to
Arylazosulfones via Diaziridine Rearrangement
Authors: Xin Ji, Ling-Guo Meng, Hailong Xu, and Lei Wang
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10.1002/adsc.202001171
Advanced Synthesis & Catalysis
UPDATE
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Pyridine-Catalysed Desulfonylative Addition of β-Diketones to
Arylazosulfones via Diaziridine Rearrangement
Xin Ji,a Ling-Guo Meng,a,* Hailong Xu,a and Lei Wanga,b*
a
Key Laboratory of Green and Precise Synthetic Chemistry and Applications, Ministry of Education; School of
Chemistry and Materials Science, Huaibei Normal University, Huaibei, Anhui 235000, P. R. China
b
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Shanghai 200032, P. R.
China
corresponding author: phone: +86-561-380-2069, fax number: +86-561-309-0518, e-mail address: milig@126.com,
leiwang@chnu.edu.cn
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
Abstract: A pyridine-catalysed desulfonylative addition
of β-diketones to arylazosulfones was developed to
obtain diazenyl β-dicarbonyl compounds. The
aryldiazenyl group was observed in the desired product
from arylazosulfones, and this diazenylation reaction
was achieved via a possible rearrangement process based
on diaziridine ring cleavage. The scope of the protocol
was investigated and a plausible mechanism was given.
Keywords: Diketones; arylazosulfones; desulfonylative
addition; pyridine
Finding a direct and simple approach to construct
nitrogen-containing organic compounds has attracted
increasing attention and research interest in synthetic
organic chemistry because nitrogen-containing
organic compounds have wide applications in organic
synthesis, chemical industry, and biological systems.
[1,2]
Among the developed C–N synthetic methods,
the diazenylation reaction is an efficient protocol for
the synthesis of azo compounds and their analogues.
Reflecting on the development of the diazenylation
transformation, general methods that incorporate an
organic compound with a R-N2 moiety are processes
that couple diazonium salts with a suitable carbon-
nucleophile to give carbodiazenylation compounds.[3]
Nevertheless, aryldiazonium salts are unstable to
store due to their potentially dangerous and explosive
chemical property. Although hydrazine salts[4] and
Scheme 1. Arylazosulfones used as versatile partners in
different reactions.
triazenes[5] could be used as diazenyl group
precursors for the synthesis of different nitrogen-
or sulfone sources[9a] via chemical bond (C–N, N–N,
and N–S) cleavage under different conditions
(Scheme 1a–1c). On the other hand, arylazosulfones
also have been demonstrated as versatile radical
partners in photochemical coupling reactions due to
their good photochemical behaviors for constructing
various organic molecules.[9] Recently, we employed
electron-deficient diazene as the electrophile in
phosphine- promoted cyclization to produce nitrogen-
containing compounds, these incorporated diazenyl
transformations should be assisted by a transition-
metal
catalyst
or
complicated
conditions.
Accordingly, finding a stable, alternative and easily
available substrate for use as a diazenyl source under
simple conditions still has significant challenges.
Arylazosulfones, which are important building
blocks,[6] were widely applied as aryl,[7] arylamine,[8]
1
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10.1002/adsc.202001171
Advanced Synthesis & Catalysis
Table 1. Optimization of the reaction conditions.a)
Entry
1
2
3
4
5
6
7
Catalyst
Pyridine
Pyridine
Pyridine
Pyridine
Pyridine
Pyridine
Pyridine
Solvent
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CHCl3
DCE
Yield (%)b
31c
72
42d
41e
27f
39
62
Pyridine
Et2O
8
51
Pyridine
Pyridine
Pyridine
Pyridine
Benzene
DMF
9
40
20
63
55
37
32
43
30
10
11
12
13
14
15
16
17
18
19
DMSO
Methanol
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
(2-Me)Pyridine
(4-MeO)Pyridine
DBU
DMAP
DABCO
Et3N
32
< 5
NDg
Ph3P
a)
Reaction conditions: 1a (0.20 mmol), 2a (0.20 mmol),
catalyst (0.04 mmol, 20 mol %), solvent (2.0 mL), rt, for
Scheme 2. The Scope of arylazosulfones. [a) Reaction
conditions: 1a (0.20 mmol), 2 (0.20 mmol), pyridine (0.02
mmol, 20 mol %), CH2Cl2 (2.0 mL), rt, for 12 h. b) Isolated
yield. c) 20 mol % DBU was used.]
b)
12 h. Isolated yield. c) 10 mol% pyridine was used. d) 50
e)
f)
g)
mol% pyridine was used. At 0 °C. At 40 °C. No
desired product was detected.
containing heterocycles.[10] Due to our ongoing
research interest in the reaction of arylazosulfones,
we explored the possibility of other cyclization
reactions via multicomponent reaction processes.
carbodiazenylation product 3aa with a 31% yield;
this compound was characterized by NMR
spectroscopy and HRMS analysis (Table 1, entry 1).
The amount of pyridine had an obvious effect on the
product yield; an 72% yield of 3aa was obtained by
increasing the amount of pyridine to 20 mol%, but a
better yield was not achieved with a further
improvement in the catalyst loading amount (Table 1,
entries 2 and 3). The efficiency of the reaction is
sensitive to temperature; 41% and 27% yields were
obtained when the reaction was carried out at 0 °C
and 40 °C, respectively (Table 1, entries 4 and 5).
Furthermore, we attempted to examine the reaction
efficiency by screening various solvents, and CH2Cl2
was confirmed to be the best solvent while using
pyridine as the catalyst; low yields of condensation
product 3aa were obtained when another chlorinated
(DCE and CHCl3), or nonpolar/weak polar solvent
was used as the medium (Table 1, entries 6-9). With
the utilization of a polar solvent, such as DMF or
DMSO, 20% and 63% yields of 3aa were obtained,
respectively (Table 1, entries 10 and 11). Furthermore,
a 55% yield of 3aa was obtained when the reaction
was performed in the protonic solvent (Table 1, entry
12). When we switched the substituents in pyridine,
better yields were not afforded (Table 1, entries 13
and 14). Upon further investigation of the effect of
other tertiary amides on the reaction, pyridine was
Unexpectedly,
an
unusual
desulfonylative
transformation was observed when arylazosulfones
were mixed with β-diketones in the presence of a
pyridine catalyst, producing an unimaginable
carbodiazenylation product, but the conventional
Michael addition product was not observed (Scheme
1d and 1e).[11] Combined with the above-mentioned
results, we speculated that this rearrangement process
should be carried out during coupling transformation
for the generation of carbodiazenylation products,
and as far as we know, in reported pioneering studies,
rearrangement reactions have never occurred in the
reaction of arylazosulfones. Herein, we report a
pyridine-catalysed desulfonylative condensation
reaction of β-diketones with arylazosulfones for the
preparation of carbodiazenylation products via
diaziridine rearrangement.
Initially, we selected 1,3-diphenylpropane-1,3-dione
(1a) and phenyl-2-tosyldiazene (2a) as the model
substrates to begin our investigation of the optimized
reaction conditions, and the results are listed in Table
1. The addition of 10 mol % pyridine to a solution of
1a and 2a at room temperature gave the desired
2
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10.1002/adsc.202001171
Advanced Synthesis & Catalysis
employed, the reaction also occurred and generated
the desired products 3ap and 3aq in modest yields.
However, only a trace amount of desired product (3ar)
was observed when the substituent was deformed to a
stronger electron-poor group (NO2).
To further evaluate the scope of this diazenylation
reaction, the scope of the reaction was expanded to
include other β-diketones (1), and the reactions
proceeded smoothly to give the desired products with
satisfactory yields in most of the cases, as illustrated
in Scheme 3. In general, the efficiency of the reaction
was insensitive to the substituents on the aromatic
rings in diverse aromatic β-diketones. For example,
aromatic β-diketones with an electron-rich group,
such as MeO or Me, on the phenyl ring reacted with
2a to afford the corresponding products 3ba and 3ca
with 72% and 77% yields, respectively. As expected,
β-diketones with different halogen groups, could
react smoothly with 2a to generate the desired
products (3da−3fa) in 52−80% yields. For the CF3-
substituted aromatic β-diketones involved in the
reaction, the desired product 3ga was afforded in a 48%
yield. Furthermore, by using a substrate with a
halogen group on the meta-position (1h−1j) of the
phenyl ring, the efficiency of the reaction was still
maintained (3ha vs 3da, 3ia vs 3ea and 3ja vs 3fa).
For β-diketone 1 having a heteroaromatic group, the
anticipated product (3ka) was isolated in 80% yield.
A 30% yield of the desired product 3la was obtained
when aliphatic β-diketone (acetylacetone) was used
in the reaction. On the other hand, when
benzoylacetone (1m) was employed to react with
phenyl-2- and 4-methoxyphenyl-2-tosyldiazene,
corresponding products existing with two
stereoisomers were obtained in 50% and 37% yields
with ratios of 1:6 and 1:9, respectively.
Scheme 3. The scope of β-diketones. [a) Reaction
conditions: 1 (0.20 mmol), 2 (0.20 mmol), pyridine (0.02
mmol, 20 mol %), CH2Cl2 (2.0 mL), rt, for 12 h. b) Isolated
yield. cThe ratio was determined by 1H NMR.]
found to be the best one (Table 1, entries 15–18). On
the other hand, Ph3P is ineffective in the reaction
(Table 1, entry 19).
By using the optimized conditions, a variety of
arylazosulfones were employed to react with 1,3-
diphenylpropane-1,3-dione (1a) to explore the
substrate
desulfonylative reaction, and the results are listed in
Scheme 2. Arylazosulfone with different
scope
of
the
pyridine-catalysed
According to the above-mentioned observations and
corresponding reported work, a plausible reaction
mechanism was proposed in Scheme 4. β-Diketone
1a was transferred to its anionic form, intermediate A,
in the presence of the pyridine catalyst and
concomitantly formed pyridine salt. Subsequent
addition of the anionic intermediate A to phenyl-2-
tosyldiazene 2a generated intermediate B, which
transformed to the unstable diaziridine derivative C
2
substituents on the phenyl rings could couple well
with 1a and provide the corresponding diazenylative
products in moderate to good yields. Arylazosulfone
2 with an electron-rich group, such as MeO and Me,
on the para-position of the phenyl rings reacted with
1a to afford the desired products 3ab and 3ac in
moderate to good yields. Meanwhile, substrate 2 with
a halogen group (F, Cl or Br) on the para-position of
the benzene rings afforded the corresponding
products (3ad−3af) in 61−72% yields. When the
substituent (MeO, F, Cl or Br) was located at the
meta-position of the benzene rings in substrate 2, the
corresponding product (3ag−3aj) was obtained in
55−70% yields. When the substituent (MeO, Me, or
Cl) was further moved to the ortho-position of the
benzene ring, however, lower yields (30−59%) were
afforded owing to the steric hindrance (3ak vs. 3ab
and 3ag; 3al vs. 3ac; 3am vs. 3ae and 3ai).
Furthermore, the reactions of substrate 2 with two
halogen groups afforded the desired products 3an and
3ao in 43% and 37% yield, respectively. On the other
Scheme 4 Proposed mechanism.
hand,
when
1-(naphthalen-1-yl)-
and
were
(benzo[d][1,3]dioxol-5-yl)-2-tosyldiazene
3
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10.1002/adsc.202001171
Advanced Synthesis & Catalysis
via intramolecular tandem H+ transfer and a
nucleophilic substituted desulfonylation procedure.
Note that the pyridine catalyst regenerated by the
reaction of Ts− with the pyridine salt. Finally, the
desired product 3aa was obtained via C–N bond
cleavage rearrangement in diaziridine derivative C
and another intramolecular H+ transfer pathway. In
order to perform in-depth research on the reaction
mechanism, necessary control experiments were
conduced (see the ESI for details), which implied that
we could not determine whether there is another
reaction path (e.g. underwent the diazonium salt
102, 4139; c) A. A. Beharry, G. A. Woolley, Chem. Soc.
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procedure) to generate carbodiazenylation product.[3,6-
[3] For selected examples: a) A. D. Mitchell, D. C.
Nonhebel, Tetrahedron Lett. 1975, 16, 3859; b) S. Devi,
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9]
In conclusion, we have developed a pyridine-
catalysed desulfonylative addition of β-diketones to
arylazosulfones for obtaining diazenyl β-dicarbonyl
compounds, and arylazosulfone was first successfully
employed as an aryldiazenyl source through a
rearrangement process to achieve an unprecedented
interesting addition reaction. Further investigations
on the potential value of arylazosulfones in organic
synthesis are underway in our laboratory.
[4] D. S. Barak, S. U. Dighe, I. Avasthi, S. Batra, J. Org.
Chem. 2018, 83, 7, 3537.
[5] C. Liu, J. Lv, S. Luo, J.-P. Cheng, Org. Lett. 2014, 16,
5458.
Experimental Section
[6] a) M. J. Evers, L. E. Christiaens, M. R. Guillaume, M. J.
Renson, J. Org. Chem. 1985, 50, 1779; b) M. J. Evers,
L. E. Christiaens, M. J. Renson, J. Org. Chem. 1986, 51,
5196.
General Procedure for this diazenylation reaction: To a
stirred solution of β-diketone (0.20 mmol) with
arylazosulfone (0.20 mmol) in 2.0 mL of CH2Cl2 at room
temperature was added pyridine (0.04 mmol). The reaction
mixture was stirred at room temperature for 12 h. Then the
solvent was removed in vacuo and the residue was purified
by column chromatography on silica gel (10:1 petroleum
ether/EtOAc) to give the pure product. It should be noted
that the products 3ad−3af and 3ah−3aj were purified by
column chromatography on silica gel (6:1 petroleum
ether/CH2Cl2).
[7] For selected reports: a) J.-B. Liu, H. Yan, H. X. Chen,
Y. Luo, J. Weng, G. Lu, Chem. Commun. 2013, 49,
5268; b) J.-B. Liu, L. Nie, H. Yan, L.-H. Jiang, J. Weng,
G. Lu, Org. Biomol. Chem. 2013, 11, 8014.
[8] For selected examples: a) C. Dell’Erba, M. Novi, G.
Petrillo, C. Tavani, Tetrahedron 1995, 51, 3905; b) P.
Sinha, C. C. Kofink, P. Knochel, Org. Lett. 2006, 8,
3741.
Acknowledgements
[9] a) Q. Liu, F. Liu, H. Yue, X. Zhao, J. Li, W. Wei, Adv.
Synth. Catal. 2019, 361, 5277; b) H. O. Abdulla, S.
Scaringi, A. A. Amin, M. Mella, S. Protti, M. Fagnoni,
Adv. Synth. Catal. 2020, 362, 2150; c) Y. Xu, X. Yang,
H. Fang, J. Org. Chem. 2018, 83, 12831.
We gratefully acknowledge the Natural Science Foundation of
Educational Committee of Anhui Province (KJ2020A0045) and
the Scientific Research Project of Anhui Provincial Education
Department (KJ2015TD002) for financial support of this work.
[10] a) Q. Zhang, L.-G. Meng, K. Wang, L. Wang, Org.
Lett. 2015, 17, 872; b) Q. Zhang, L.-G. Meng, J. Zhang,
L. Wang, Org. Lett. 2015, 17, 3272; c) Y. Ren, L.-G.
Meng, T. Peng, L. Zhu, L. Wang, Adv. Synth. Catal.
2018, 360, 3176.
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4
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10.1002/adsc.202001171
Advanced Synthesis & Catalysis
UPDATE
Pyridine-Catalysed Desulfonylative Addition of
β-Diketones to Arylazosulfones via Diaziridine
Rearrangement
Adv. Synth. Catal. Year, Volume, Page – Page
Xin Ji, Ling-Guo Meng, Hailong Xu, and Lei
Wang
5
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