Rhodium/Silver-Cocatalyzed Transannulation of N-Sulfonyl-1,2,3-triazoles with Vinyl Azides: Divergent Synthesis of Pyrroles and 2 H-Pyrazines

Article abstract of DOI:10.1002/asia.201601164

The first cyclization reaction between vinyl azides and N-sulfonyl-1,2,3-triazoles is reported. A Rh/Ag binary metal catalyst system proved to be necessary for the successful cyclization. By varying the structure of vinyl azides, such reaction allows the divergent synthesis of pyrroles and 2H-pyrazines. The cyclization reactions feature a broad substrate scope, good functional group tolerance, high reaction efficiency, and good to high product yields.

Full text of DOI:10.1002/asia.201601164

CHEMISTRY
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Accepted Article
Title: Rhodium/Silver-Cocatalyzed Transannulation of N-Sulfonyl-1,2,3-triazoles with
Vinyl Azides: Divergent Synthesis of Pyrroles and 2H-Pyrazines
Authors: Xihe Bi; Lin Zhang; Ge Sun
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To be cited as: Chem. Asian J. 10.1002/asia.201601164
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COMMUNICATION
Rhodium/Silver-Cocatalyzed Transannulation of N-Sulfonyl-1,2,3-
triazoles with Vinyl Azides: Divergent Synthesis of Pyrroles and
2H-Pyrazines
Lin Zhang,a Ge Sunc and Xihe Bi*a,b
Abstract: The first cyclization reaction between vinyl azides and N-
sulfonyl-1,2,3-triazoles is reported. A Rh/Ag binary metal catalyst
system was proved to be necessary for the successful cyclization.
By varying the structure of vinyl azides, this reaction allows the
divergent synthesis of pyrroles and 2H-pyrazines. Both of these
cyclization reactions feature in broad substrate scope, good
functional group tolerance, and high reaction efficiency and good-to-
high product yields.
2H-pyrazines, in which a Rh/Ag binary metal catalyst system
was employed.
Vinyl azide is a class of versatile synthetic intermediates with
unique molecule structure.[14] They could convert to 2H-azirines
easily under a heating condition.[15] In a quite long period, the
preparation method for vinyl azides is mainly dependent on the
Hassner’s reaction.[16] Disadvantages of this method lies in
tedious two two-step operation and depends on the use of
explosive IN3 or BrN3 reagent. Recently, our group addressed
this issue by developing the silver-catalyzed hydroazidation of
terminal alkynes, which constitutes a powerful method for the
synthesis of α-substituted vinyl azides.[17] Based on this
discovery and our continued interest in the silver-catalyzed
The chemistry of α-imino rhodium carbenoids based on N-
sulfonyl-1,2,3-triazoles has attracted much attention in the past
years, which resulted in a great number of novel organic
reactions.[1] Many categories of organic chemicals, such as
alkenes,[2] alkynes,[3] allenes,[4] aldehydes,[5] nitriles,[6] boronic
acid,[7] amines,[8] 2H-azirines,[9] etc, have been exploited in the
reaction with in situ generated α-imino rhodium carbenoids.
These allow for the synthesis of diverse molecule frameworks,
especially for the construction of azacompounds.[1a] Pyrroles
and 2H-pyrazines are two classes of important azoheterocycles,
with wide applications in organic synthesis, medical chemistry,
and material science.[10] Some pioneering efforts to synthesize
these heterocycles from N-sulfonyl-1,2,3-triazoles have been
reported (Figure 1). For instance, Lee, Anbarasan, and Tang
reported the synthesis of pyrroles by the cyclization of N-
sulfonyl-1,2,3-triazoles with vinyl ethers under the rhodium
catalysis.[11] In addition, the groups of Shi and Tang
simultaneously reported the [3+2] cycloaddition reaction of N-
sulfonyl-1,2,3-triazoles and 2H-azirines, which led to the
synthesis of 3-aminopyrroles.[9a-9b] 2H-Azirines were also
capable of proceeding by [3+3] transannulation with N-sulfonyl-
12]
1,2,3-triazoles to afford pyrazines and dihydropyrazines.[9c,
Another notable report is the synthesis of pyrroles by Gevorgyan
and coworkers, who realized the transannulation of N-sulfonyl-
1,2,3-triazoles with electron-rich aryl alkynes using Rh/Ag co-
catalyst system.[3b] This is an impressive advance because it
implies the addition of a co-catalyst may be the right way to
expand the chemistry of α-imino rhodium carbenoids.[13] Herein,
we report the first reaction between N-sulfonyl-1,2,3-triazoles
and vinyl azides leading to divergent synthesis of pyrroles and
Figure 1. Synthesis of Pyrroles and 2H-Pyrazines from N-Sulfonyl-1,2,3-
triazoles
organic reactions,[18] we investigated the cyclization of α-
substituted vinyl azides with N-sulfonyl-1,2,3-triazoles. As
summarized in Table 1, we first studied this reaction of triazole
1a with vinyl azide 2a and varied metal catalysts in 1,2-
o
dichloroethane (DCE) at 80 C under nitrogen atmosphere. We
[a]
Dr. L. Zhang, Prof. X. Bi
found Rh2(oct)4 alone resulted in 27% yield of pyrrole 3a (entry
1). While the combination of Rh2(oct)4 and AgCO2CF3
significantly improved the yield to 78% (entry 2). These results
demonstrated the silver catalyst played a crucial role in the
cyclization process. Other silver salts such as Ag2CO3, AgOTf,
and AgNO3 were then tested, which either gave lower yields or
trace amount of product 3a (entries 3-5). Compared to Rh2(oct)4,
Rh2(OAc)4 proved to be ineffective (entry 6). The solvent was
also screened and showed that toluene resulted in 63% yield of
3a, whereas n-hexane was not useful (entries 7, 8).
Jilin Province Key Laboratory of Organic Functional Molecular
Design & Synthesis, Department of Chemistry, Northeast Normal
University, Renmin Str. 5268#, Changchun 130024, China
E-mail: bixh507@nenu.edu.cn
Homepage: http://www.bigroup.com.cn/
[b]
[c]
Prof. X. Bi
State Key Laboratory of Elemento-Organic Chemistry, Nankai
University, Tianjin 300071, China
Prof. G. Sun
College of Pharmacy, Qiqihar Medical University, 333 Bukui Street,
161006, Qiqihar, China.
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Table 1. Optimization of the reaction conditions.[a]
Entry
[Rh]
[Ag]
--
Solvent
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
toluene
3a (%)[b]
27
1
2
3
4
5
6
7
8
Rh2(oct)4
Rh2(oct)4
Rh2(oct)4
Rh2(oct)4
Rh2(oct)4
Rh2(oAc)4
Rh2(oct)4
Rh2(oct)4
AgCO2CF3
Ag2CO3
AgOTf
78
45
52
AgNO3
trace
trace
63
AgCO2CF3
AgCO2CF3
AgCO2CF3
n-hexane
trace
[a] Reaction conditions: 1a (0.5 mmol), 2a (1.0 mmol), rhodium catalyst
(0.01 mmol) and silver salt (0.025 mmol) in solvent (2.0 mL), and the
reactions were stirred at 80 oC for 24 h under N2 atmosphere. [b] Isolated
yields.
With the optimal conditions in hand, we next studied the scope
with respect to triazoles and vinyl azides (Scheme 1). A range of
N-sulfonyl-1,2,3-triazoles could be applied in the reactions with
2-azidooct-1-ene 2a to give the corresponding pyrroles in good-
to-high yields (3b-3k, 52-89%). The R1 groups, being electron-
deficient or electron-rich aryl, fused aryl, or heteroaryl groups,
were all well tolerant (3b-3f). In addition, the cyclohexenyl and
fused aryl N-sulfonyl-1,2,3-triazoles also proved to be suitable in
the cyclization reaction, affording the products 3g and 3h in 84%
and 52% yields. Furthermore, the variation of sulfonyl group had
no significant effect on the reaction outcome (3i-3k, 65-89%).
We then examined the scope of α-substituted vinyl azides. A
variety of aryl, cyclohexenyl, and fused aryl group-substituted
vinyl azides were all applicable in the reaction with N-tosyl-1,2,3-
triazole 1a, leading to the corresponding pyrroles (3l-3p) in 71-
87% yields. The structure of 3p was unambiguously confirmed
by single-crystal X-ray diffraction analysis.
Scheme 1. Reactions of N-Sulfonyl-1,2,3-triazoles with α-Substituted Vinyl
Azides.
In addition to α-substituted vinyl azides, the internal vinyl
azides 4 were also examined under the binary metal catalysis.
Unexpectedly, we obtained 2H-pyrazines 5, instead of the
desired pyrroles. This constitutes a new and efficient route to
access multi-substituted 2H-pyrazines. As shown in Scheme 2,
the reaction scope is broad and suitable for a range of α-acyl
internal vinyl azides. The R5 group could be aryl groups, even
cyclopropyl could also be tolerated and afforded the
corresponding 2H-pyrazines in good yields (5a-5f). The structure
of products was confirmed through the X-ray analysis of product
5b.
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unknown, it is believed to play a role as a Lewis acid in the
rearrangements of intermediates C, E, F, or G.
Scheme 2. Reactions of N-Sulfonyl-1,2,3-triazoles with Internal Vinyl Azides.
Regarding the reaction mechanism, the source of nitrogen
atom of pyrroles 3 is a crucial issue. One possibility is that azido
group of vinyl azides acts as a leaving group. To test this
hypothesis, we selected α-bromostyrene 6a and 1-phenylvinyl
tosylate 6b as the substrates applied in the reaction with triazole
1a. Delightfully, the pyrrole 3l was obtained in 78% and 89%
yields, respectively. Clearly, the bromine atom and the OTs
group played a role of leaving group. Therefore, the azido group
might play the same role in the cyclization with N-sulfonyl-1,2,3-
triazoles.
Scheme 3. A plausible reaction mechanism.
In summary, we have developed a new cyclization reaction
between the easily available vinyl azides and N-sulfonyl-1,2,3-
triazoles using a Rh/Ag binary metal catalyst system. This
reaction is capable of divergently affording pyrroles and 2H-
pyrazines, dependent on choosing terminal or internal vinyl
azides. Both of two transformations feature in broad substrates,
good functional group tolerance, high reaction efficiency and
high product yields, thus providing a novel and powerful method
for the synthesis of pyrroles and 2H-pyrazines. Further
exploration on the synthetic potency of vinyl azides using silver-
based binary metal catalyst system is under way and will be
reported in due course.
12]
Based on above results and related precedents,[11a,
Experimental Section
plausible mechanisms were proposed (Scheme 3). The N-
sulfonyl-1,2,3-triazoles 1 was first converted to α-diazo imines A
by a reversible ring-opening process. Subsequently, the α-imino
rhodium(II) carbenoid B is generated in the presence of a
General Procedure for the Synthesis of Compounds 3 and 5 (with 3a
as an example): A mixture of 1a (299 mg, 1.0 mmol), 2a (306 mg, 2.0
mmol), Rh2(oct)4 (16 mg, 0.02 mmol) and AgCO2CF3 (11 mg, 0.05 mmol)
in 1,2-DCE (4.0 mL) stirred at 80 oC under nitrogen atmosphere. The
mixture was stirred until substrate 1a consumed as indicated by TLC.
The resulting mixture was taken up in DCM. The organic layer was
collected and washed with brine, dried over with MgSO4 and
concentrated. The resulted reaction product was purified by column
chromatography to afford 3a in 78% yield.
rhodium catalyst. For the α-substituted vinyl azides,
a
cyclopropanation reaction takes place to give an intermediate
C.[19] Following intramolecular rearrangement, intermediate 2,3-
dihydropyrrole D is formed. Finally, pyrroles 3 are formed by
eliminating one molecule HN3. Regarding the internal vinyl
azides, α-acyl vinyl azides 4 are first converted to 2H-azirines E
by losing one nitrogen molecule. Following the nucleophilic
addition of
2 to the Rh(II) carbene B, the zwitterionic
intermediate F is generated. Subsequently, concerted release of
the Rh(II) cation and the cyclization at the azacarbenium
position on intermediate F affords a bicyclic intermediate G, with
the release of Rh(II) catalyst. Finally, the highly strained E
quickly converts to dihydropyrazine 5 by a rearrangement
reaction. Although the exact role of silver co-catalyst remains
Acknowledgements
This work was supported by the NSFC (21522202, 21502017,
21372038), the Ministry of Education of the People’s Republic of
China (NCET-13-0714), the Jilin Provincial Research
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Keywords: rhodium/silver cocatalysis
•
N-sulfonyl-1,2,3-
triazoles • vinyl azides • pyrroles • 2H-pyrazines
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COMMUNICATION
COMMUNICATION
The first cyclization reaction between
vinyl azides and N-sulfonyl-1,2,3-
triazoles is reported. A Rh/Ag binary
metal catalyst system was proved to
be necessary for the successful
cyclization. By varying the structure of
vinyl azides, this reaction allows the
divergent synthesis of pyrroles and
2H-pyrazines.
Lin Zhang, Ge Sun and Xihe Bi*
Page No. – Page No.
Rhodium/Silver-Cocatalyzed
Transannulation of N-Sulfonyl-1,2,3-
triazoles with Vinyl Azides: Divergent
Synthesis of Pyrroles and 2H-
Pyrazines
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