Rh(ii)-catalyzed cycloadditions of 1-tosyl 1,2,3-triazoles with 2H-azirines: Switchable reactivity of Rh-azavinylcarbene as [2C]- or aza-[3C]-synthon

Article abstract of DOI:10.1039/c5cc00268k

The Rh(ii)-catalyzed formal [3+2] and [3+3] cycloadditions of 1-tosyl 1,2,3-triazoles with 2H-azirines have been developed, which enable the efficient synthesis of polysubstituted 3-aminopyrroles and 1,2-dihydropyrazines, respectively. The reported [3+2] cycloaddition represents the first application of 1-sulfonyl 1,2,3-triazole as a [2C]-component in relevant cycloaddition reactions. This journal is

Full text of DOI:10.1039/c5cc00268k

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Rh(II)-catalyzed cycloadditions of 1-tosyl 1,2,3-
triazoles with 2H-azirines: switchable reactivity of
Rh-azavinylcarbene as [2C]- or aza-[3C]-synthon†
Cite this: Chem. Commun., 2015,
51, 4507
Received 12th January 2015,
Accepted 9th February 2015
Yuanhao Wang,a Xiaoqiang Leia and Yefeng Tang*abc
DOI: 10.1039/c5cc00268k
www.rsc.org/chemcomm
The Rh(II)-catalyzed formal [3+2] and [3+3] cycloadditions of 1-tosyl Inspired by this seminal work, we envisioned that it was feasible
1,2,3-triazoles with 2H-azirines have been developed, which enable to unite the two 1,3-dipolarophiles Rh-AVC and 2H-azirine in a
the efficient synthesis of polysubstituted 3-aminopyrroles and 1,2- single transformation to realize a formal aza-[3+3] cycloaddition,
dihydropyrazines, respectively. The reported [3+2] cycloaddition which would afford an efficient method for the synthesis of
represents the first application of 1-sulfonyl 1,2,3-triazole as a 1,2-dihydropyrazines (eqn (5), Fig. 1b) as well as related hetero-
[2C]-component in relevant cycloaddition reactions.
cycles (e.g. pyrazine). As a part of our continuing interest in the
development of novel Rh-AVC promoted transformations,9a,13
Readily generated from 1-sulfonyl 1,2,3-triazole through denitro- we report herein the successful implementation of this
genation upon treatment with an Rh(II)-catalyst, Rh-azavinylcarbene design, which leads to the development of unprecedented
(Rh-AVC) has evolved into a versatile reactive intermediate in Rh(II)-catalyzed formal [3+2] and [3+3] cycloadditions of
organic synthesis over the past several years.1 On one hand, it 1,2,3-triazoles with 2H-azirines (Fig. 1b). Of note, the putative
displays typical reactivity of metallocarbene derived from diazo Rh-AVC intermediate in the [3+2] cycloaddition serves as
compound,2 and has been employed as [1C]-synthon in various [2C]- instead of [1C]- or aza-[3C]-synthon.14
reactions including cyclopropanation,3 X–H (X = C, O or N)
The readily accessible triazole 1a and 3-phenyl-2H-azirine 2a
insertion,4 ylide formation and rearrangement5 and others6 were employed as substrates in the initial study.15 Thus, 1a and
(eqn (1), Fig. 1a). On the other hand, owing to its dipolar nature, 2a were treated with 1.5 mol% Rh2(OAc)4 in 1,2-DCE at 140 1C
it could also function as aza-[3C]-synthon in a wide range of for 4 h, which resulted in the formation of a product in 48%
cycloadditions, such as [3+2],7 [3+3],8 [4+3]9 and other multi- yield. Careful analysis of its spectroscopic data suggested that it
component cycloadditions (eqn (2), Fig. 1a).10 Despite such was not the expected [3+3] adduct, but 3-amino-pyrrole deriva-
progress, the utilization of Rh-AVC as [2C]-synthon in cycloaddi- tive 3a (entry 1, Table 1). The structural assignment of 3a was
tion reactions has never been explored so far (eqn (3), Fig. 1a).
2H-Azirines represent a class of highly strained three-
membered cyclic imines that have been employed as versatile
precursors for the synthesis of various heterocycles.11 For
example, Park and co-workers recently reported an interesting
formal [3+3] cycloaddition of vinyl carbenoids with 2H-azirines,
which resulted in the formation of polysubstituted pyridines.12
a The Comprehensive AIDS Research Center and The Department of Pharmacology &
Pharmaceutical Sciences, School of Medicine, Tsinghua University, Beijing 100084,
P. R. China. E-mail: yefengtang@tsinghua.edu.cn; Tel: +86 10 62798236
b Collaborative Innovation Center for Biotherapy, Tsinghua University, Beijing
100084, China
c Collaborative Innovation Center for Biotherapy, West China Hospital,
Sichuan University, Chengdu 610041, P. R. China
† Electronic supplementary information (ESI) available: Detailed experimental
procedures and spectroscopic data of all new compounds. CCDC 1032468 and
Fig. 1 (a) The graphic illustration of versatile reactivities of Rh-AVC; (b) the
cycloaddition developed in current work.
1032469. For ESI and crystallographic data in CIF or other electronic format see
DOI: 10.1039/c5cc00268k
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Table 1 Condition screening of cycloaddition of 1a with 2aa
Table 2 Scope of Rh(II)-catalyzed cycloadditions of 1-tosyl 1,2,3-triazoles
with monosubstituted 2H-azirinesa,b
Entry Cat.
Solvent Other conditions
Yield of 3ab (%)
1
2
3
4
5
6
7
8
9
Rh2(OAc)4
1,2-DCE 140 1C, 4 h
1,2-DCE 120 1C, 10 h
1,2-DCE 160 1C, 1 h
1,2-DCE 160 1C, 1 h
48
38
57
45
Trace
Trace
81
Rh2(OAc)4
Rh2(OAc)4
Rh2(oct)4
Rh2(S-ptad)4 1,2-DCE 160 1C, 1 h
Rh2(S-dosp)4 1,2-DCE 160 1C, 1 h
Rh2(esp)2
Rh2(esp)2
Rh2(esp)2
1,2-DCE 160 1C, 1 h
1,2-DCE 160 1C, 1 h, 4 Å MS 62
1,2-DCE 160 1C, MW, 15 min 50
a
Reaction conditions: 1a (0.30 mmol), 2a (0.6 mmol) and Rh(II)-cat.
b
(0.0045 mmol) in 1,2-DCE (0.8 mL). Isolated yield. DCE = dichloroethane,
oct = octanoate, (S)-ptad = N-phthaloyl-(S)-adamantylglycine, (S)-dosp =
4-(dodecyl-phenyl)sulfonyl-(2S)-prolinate, esp = a,a,a0,a0-tetramethyl-1,3-
benzenedipropanoate, MS = molecular sieves, MW = microwave.
further confirmed by the X-ray crystallographic study of its
derivative 3a0 (structure not shown, for details, see the ESI†).16
The initial discovery deserves further investigation, since
it represents a formal [3+2] cycloaddition, wherein the triazole
partner served as [2C]- instead of the proposed aza-[3C]-component.
Moreover, the resulting 3-amino-pyrrole derivative represents
a
Reaction conditions: 1a (0.30 mmol), 2 (0.60 mmol) and the Rh(II)-catalyst
b
(0.0045 mmol) in 1,2-DCE (0.8 mL). Isolated yield.
a valuable structural motif distributed in natural products 1,2-dihydropyrazine 6a was obtained in 36% and 48% yields,
and bioactive molecules.17 To improve the efficiency of the respectively (entry 1, Table 3). The structure of 6a was con-
transformation, we conducted a systematic condition screening firmed by the X-ray crystallographic study.16 These results
(Table 1). It was shown that lower temperature was detrimental showed that the introduction of the aromatic substituent on
to the reaction (entry 2), while higher temperature afforded 3a the C-2 position of 2H-azirine largely inverted its reactivity.
in improved yield (entry 3). The Rh(II)-catalyst also had a Although the efficiency of the reaction was excellent, the poor
notable influence on the reaction. While Rh2(oct)4 displayed selectivity discounted its synthetic utility. Thus, we sought to
reactivity similar to Rh2(OAc)4, the sterically hindered Rh2(S-ptad)4 improve the reaction with the further condition optimization.
and Rh2(S-dosp)4 failed to yield the desired product (entries 4–6). Fortunately, we found that by simply changing the solvent
Gratifyingly, Rh2(esp)2, a dirhodium complex with tethered from 1,2-DCE to toluene notably increased the selectivity of
carboxylate ligands,18 exhibited superior reactivity by giving 3a in [3+3] vs [3+2] from 1.3 : 1 to 6.3 : 1, with 6a obtained in 82%
81% yield (entry 7). We also attempted to perform the reaction in yield (condition B, entry 2).19 Furthermore, the use of sub-
the presence of 4 Å MS or upon microwave irradiation, however, stoichiometric amounts of ClCH2COOH in the reaction could
both of them resulted in inferior yields (entries 8 and 9).
invert the selectivity of the reaction.20 As a result, 5a was
The generality of the cycloaddition was then evaluated with isolated in 86% yield, along with only a small amount of 6a
various monosubstituted 2H-azirines (Table 2). First of all, an (11%) (condition C, entry 3).
array of 3-aryl-2H-azirines were examined with 1a as the reac-
tion partner. Gratifyingly, all of the substrates bearing either
electron withdrawing (4-Br, 2-Cl, 4-F or 4-NO2) or donating
Table 3 Condition screening of cycloaddition of 1a with 4aa
(4-Me or 4-MeO) substituents gave the corresponding products
(3a–g) in good yields. The 2-naphthyl- or 3-indol-derived 2H-azirines
were also tolerated well. Moreover, the reaction could extend to
3-alkyl-2H-azirines, as shown in the cases leading to 3j and 3k.
Besides 1a, a wide range of 1-tosyl-4-aryl-1,2,3-triazoles were also
examined with 2a as a reaction partner. All of the reactions gave
the desired products (3l–p) in satisfying yields, showing little
electronic effect regarding the substituents on aromatic rings.
Furthermore, we explored 2,3-disubstituted substrates in the
reactions. Interestingly, we found that when 2,3-diphenyl-2H-
azirine 4a was subjected to the optimized conditions, a mixture
Entry Conditions
Yield of productsb
1
2
3
a
A: Rh2(esp)2 (1.5 mol%), 1,2-DCE, 160 1C, 5a: 36%; 6a: 48%
1 h
B: Rh2(esp)2 (1.5 mol%), toluene, 160 1C, 5a: 13%; 6a: 82%
1 h
C: Rh2(esp)2 (1.5 mol%), ClCH2CO2H
(50 mol%), 1,2-DCE, 160 1C, 0.5 h
5a: 86%; 6a: 11%
Reaction conditions: 1a (0.30 mmol), 4a (0.60 mmol) and the Rh(II)-
b
of tetrasubstituted 3-amino-pyrrole 5a and 2,3,5-trisubstituted catalyst (0.0045 mmol) in the solvent (0.8 mL). Isolated yield.
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The above discovery was encouraging, since it enabled the
Communication
Table 5 Scope of Rh(II)-catalyzed cycloadditions of 1a with 2-aryl-3-
alkyl-2H-azirines and 2-carboxylate-3-aryl/alkyl-2H-azirinesa,b
divergent synthesis of two different heterocycles from common
precursors simply by tuning reaction conditions. To test its
generality, several other symmetric 2,3-diaryl-2H-azirines
(4b–d) were evaluated under the dual condition systems (Table 4).
To our delight, all of them afforded the expected [3+3] adducts
(6b–d) under condition B and [3+2] adducts (5b–d) under
condition C (entries 2–4) with excellent yields and good selec-
tivity. Besides, a variety of 2-alkyl-3-Ph-2H-azirines (4e–h) were
also tested. Gratifyingly, all of them exhibited propensity
similar to the 2,3-diaryl-2H-azirines, affording satisfying results
(entries 5–8).
To further explore the substituent effect of 2H-azirines on
the reaction outcomes, an array of 2-aryl-3-alkyl-2H-azirines
(7a–g) were evaluated (Table 5). Unlike the above-mentioned
2,3-disubstituted 2H-azirines, this type of substrate only yielded
the [3+3] adducts (8a–g) in good yields under condition A.
Comparable results were obtained with condition B employed,
however, the usage of condition C failed to invert the selectivity
of the reactions. In sharp contrast, when several 2-carboxylate-
3-aryl/alkyl-2H-azirines 9a–d were employed, they displayed
propensity close to monosubstituted substrates, affording [3+2]
adducts 10a–d in excellent yields (Table 5).
a
Condition A: 1a (0.30 mmol), 8 or 10 (0.60 mmol) and the Rh(II)-catalyst
b
(0.0045 mmol) in 1,2-DCE (0.8 mL) at 160 1C for 1 h. Isolated yield.
generate the zwitterionic intermediate D. After proton transfer followed
by isomerization, D could advance to the pyrrole product (path a). On
the other hand, B could divert into carbocation F via cleavage of the
C2–N2 bond. F then undergoes cyclization to give 1,2-dihydropyrazine
(path b-1).21 Alternatively, B could also transform into 1,4-azatriene G
which further evolves into the 1,2-dihydropyrazine product via 6p
electrocyclization (path b-2). Notably, the above mechanistic
considerations are in good agreement with the experimental
results. For example, for 2H-azirines 2 and 9 (R2 = H or CO2Et),
the formation of carbocation F is disfavored, and thus path b-1 is
excluded. While path b-2 could be envisioned in this scenario,22
path a more readily takes place to afford the thermodynamically
more stable pyrrole product. In contrast, for 2-aryl-3-alkyl-2H-
azirines 7, intermediate B prefers to advance into the more
stable benzylic carbocation F, thus leading to [3+3] adducts via
path b-1. For 2H-azirines 4, both pathways may take place
All the above-mentioned outcomes suggested that the struc-
tural feature of the 2H-azirine partner plays an important role
in determining the reaction pathways. Given that, the plausible
mechanism of the titled reactions is depicted in Scheme 1. The
nucleophilic attack of 2H-azirine on Rh-AVC A leads to azirinium
ylide B. At this point, there are several possibilities for B to evolve
into the final products. On one hand, it could convert into C via
resonant equilibrium, which then undergoes ring expansion to
Table 4 Scope of Rh(II)-catalyzed cycloadditions of 1a with 2,3-diaryl-
2H-azirines and 2-alkyl-3-Ph-2H-azirinesa
Product (yield)b
Entry 2H-Azirine
Condition B
Condition C
1
2
3
4
4a: Ar = Ph
6a: 82% (5a: 13%) 5a: 86% (6a: 11%)
6b: 80% (5b: 14%) 5b: 74% (6b: 14%)
6c: 85% (5c: 11%) 5c: 69% (6c: 21%)
4b: Ar = 4-F-Ph
4c: Ar = 4-Cl-Ph
4d: Ar = 4-Me-Ph
6d: 84% (5d: 9%)
5d: 70% (6d: 10%)
5
6
7
8
4e: alkyl = Me
4f: alkyl = CH2CH2Ph 6f: 79% (5f: 10%)
6e: 83% (5e: 13%) 5e: 60% (6e: 8%)
5f: 50% (6f: 20%)
6g: 80% (5g: 12%) 5g: 65% (6g: 20%)
4g: alkyl = (CH2)4Me
4h: alkyl = (CH)MePhc 6h: 84% (5h: 10%)c 5h: 58% (6h: 20%)
a
Condition B: 1a (0.30 mmol), 4 (0.6 mmol) and Rh-catalyst (0.0045 mmol)
in toluene (0.8 mL); condition C: 1a (0.30 mmol), 4 (0.6 mmol), ClCH2CO2H
Scheme 1 Proposed mechanism of Rh(II)-catalyzed cycloadditions of
1,2,3-triazoles with 2H-azirines.
(0.15 mmol) and the Rh-catalyst (0.0045 mmol) in 1,2-DCE (1.0 mL).
b
c
Isolated yield. Obtained as a mixture of diastereoisomers (1 : 1).
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( j) M. Zibinsky and V. V. Fokin, Angew. Chem., Int. Ed., 2013,
52, 1507; (k) T. Miura, Y. Funakoshi and M. Murakami, J. Am. Chem.
Soc., 2014, 136, 2272; (l) C. Kim, S. Park, D. Eom, B. Seo and P. H. Lee,
Org. Lett., 2014, 16, 1900; (m) S. Rajasekar and P. Anbarasan, J. Org.
Chem., 2014, 79, 8428; (n) R.-Q. Ran, J. He, S.-D. Xiu, K.-B. Wang and
C.-Y. Li, Org. Lett., 2014, 16, 3704.
concurrently due to the comparable stability of intermediates
F and C.
In summary, the Rh(II)-catalyzed formal [3+2] and [3+3]
cycloadditions of 1-tosyl 1,2,3-triazoles with 2H-azirines have
been developed, which enable the efficient synthesis of poly-
substituted 3-amino-pyrroles and 1,2-dihydropyrazines. The
selectivity of the cycloadditions is mainly determined by the
structural feature of 2H-azirine partners, and in some cases,
could be controlled by tuning the reaction conditions. The
reported [3+2] cycloaddition represents a proof-of-concept case
that utilizes 1-sulfonyl 1,2,3-triazole as a [2C]-component in
cycloaddition reactions, which may inspire the development of
some other new transformations. Such efforts are undertaken
in our lab and will be reported in due course.
8 X. J. Ma, S. F. Pan, H. X. Wang and W. Z. Chen, Org. Lett., 2014,
16, 4554.
9 (a) H. Shang, Y. Wang, Y. Tian, J. Feng and Y. Tang, Angew. Chem.,
Int. Ed., 2014, 53, 5662; (b) E. E. Schultz, V. N. Lindsay and
R. Sarpong, Angew. Chem., Int. Ed., 2014, 53, 9904; (c) S. Kim,
J. Mo, J. Kim, T. Ryu and P. H. Lee, Asian J. Org. Chem., 2014, 3, 926.
10 (a) D. J. Lee, H. S. Han, J. H. Shin and E. J. Yoo, J. Am. Chem. Soc.,
2014, 136, 11606; (b) Y. Jiang, X. Y. Tang and M. Shi, Chem.
Commun., 2015, 51, 2122.
11 For selected reviews, see: (a) F. Palacios, A. M. O. de Retana, E. M. de
Marigorta and J. M. de los Santos, Eur. J. Org. Chem., 2001, 2401;
(b) G. S. Singh, M. D’Hooghe and N. De Kimpe, Chem. Rev., 2007,
107, 2080. For selected examples, see: (c) A. F. Khlebnikov,
M. V. Golovkina, M. S. Novikov and D. S. Yufit, Org. Lett., 2012,
14, 3768; (d) D. A. Candito and M. Lautens, Org. Lett., 2010, 12, 3312;
(e) F. A. F. Khlebnikov, M. S. Novikov and A. A. Amer, Tetrahedron
Lett., 2004, 45, 6003; ( f ) A. Padwa and T. Stengel, Tetrahedron Lett.,
2004, 45, 5991.
We gratefully acknowledge the financial support from the
NSFC (21102081, 21272133), the Beijing Natural Science Foun-
dation (2132037) and the New Teachers’ Fund for Doctor
Stations, Ministry of Education (20110002120011).
12 N. S. Y. Loy, A. Singh, X. X. Xu and C. M. Park, Angew. Chem., Int. Ed.,
2013, 52, 2212.
Notes and references
1 For leading reviews, see: (a) B. Chattopadhyay and V. Gevorgyan, Angew.
Chem., Int. Ed., 2012, 51, 862; (b) A. V. Gulevich and V. Gevorgyan,
Angew. Chem., Int. Ed., 2013, 52, 1371; (c) H. M. L. Davies and J. S. Alford,
Chem. Soc. Rev., 2014, 43, 5151.
13 (a) J. Feng, Y. H. Wang, Q. G. Li, R. W. Jiang and Y. F. Tang,
Tetrahedron Lett., 2014, 55, 6455; (b) Y. Tian, Y. H. Wang, H. Shang,
X. D. Xu and Y. F. Tang, Org. Biomol. Chem., 2015, 13, 612.
14 While this manuscript was under review, several related work were
disclosed elsewhere. For references, see: (a) Y. Z. Zhao, H. B. Yang,
X. Y. Tang and M. Shi, Chem. – Eur. J., 2015, DOI: 10.1002/chem.201406460;
(b) T. Ryu, Y. Baek and P. H. Lee, J. Org. Chem., DOI: 10.1021/
acs.joc.5b00036; (c) N. S. Y. Loy, S. Kim and C. M. Park, Org. Lett.,
2015, 17, 395.
2 For selected reviews, see: (a) H. M. L. Davies and R. E. J. Beckwith,
Chem. Rev., 2003, 103, 2861; (b) H. Lebel, J. Marcoux, M. Carmela
and A. B. Charette, Chem. Rev., 2003, 103, 977; (c) M. P. Doyle,
R. Duffy, M. Ratnikov and L. Zhou, Chem. Rev., 2010, 110, 704.
3 (a) S. Chuprakov, S. W. Kwok, L. Zhang, L. Lercher and V. V. Fokin,
J. Am. Chem. Soc., 2009, 131, 18034; (b) N. Grimster, L. Zhang and
V. V. Fokin, J. Am. Chem. Soc., 2010, 132, 2510; (c) M. Zibinsky and
V. V. Fokin, Org. Lett., 2011, 13, 4870; (d) J. S. Alford and H. M. L.
Davies, Org. Lett., 2012, 14, 6020.
4 (a) S. Chuprakov, J. A. Malik, M. Zibinsky and V. V. Fokin, J. Am.
Chem. Soc., 2011, 133, 10352; (b) T. Miura, T. Biyajima, T. Fujii and
M. J. Murakami, J. Am. Chem. Soc., 2012, 134, 194; (c) T. Miura,
T. Tanaka, T. Biyajima, A. Yada and M. Murakami, Angew. Chem.,
Int. Ed., 2013, 52, 3883; (d) S. Chuprakov, B. T. Worrell, N. Selander,
R. K. Sit and V. V. Fokin, J. Am. Chem. Soc., 2014, 136, 195.
5 (a) J. K. Fu, H. J. Shen, Y. Y. Chang, C. C. Li, J. X. Gong and Z. Yang,
Chem. – Eur. J., 2014, 20, 12881; (b) A. Boyer, Org. Lett., 2014, 16, 1660.
6 (a) Y. Funakoshi, M. Morimoto, T. Biyajima and M. Murakami,
J. Am. Chem. Soc., 2012, 134, 17440; (b) N. Selander, B. T. Worrell,
S. Chuprakov, S. Velaparthi and V. V. Fokin, J. Am. Chem. Soc., 2012,
134, 14670; (c) N. Selander, B. T. Worrell and V. V. Fokin, Angew.
Chem., Int. Ed., 2012, 51, 13054; (d) T. Miura, T. Tanaka, T. Biyajima,
A. Yada and M. Murakami, Angew. Chem., Int. Ed., 2013, 52, 3883;
(e) R. H. Liu, M. Zhang, G. Winston-McPherson and W. P. Tang, Chem.
Commun., 2013, 49, 4376; ( f ) J. Yang, C. Zhu, X. Tang and M. Shi,
Angew. Chem., Int. Ed., 2014, 53, 5142; (g) F. Medina, C. Besnard and
15 For details of the preparation of the 2H-azirines involved in this
work, see the ESI†.
16 CCDC 1032468 (3a0) and 1032469 (6a).
17 For selected reviews, see: (a) P. G. Baraldi, D. Preti, F. Fruttarolo,
M. A. Tabrizi and R. Romagnoli, Bioorg. Med. Chem., 2007, 15, 17;
(b) T. Bando and H. Sugiyama, Acc. Chem. Res., 2006, 39, 935. For
selected examples, see: (c) M. D. Rosa and D. Arnold, J. Org. Chem.,
2013, 78, 8614; (d) A. A. Kanakis and V. Sarli, Org. Lett., 2010, 12, 4872;
(e) C. Dose, M. E. Farkas, D. M. Chenoweth and P. B. Dervan, J. Am.
Chem. Soc., 2008, 130, 6859; ( f ) K. Schneider, S. Keller, F. E. Wolter,
L. Roeglin, W. Beil, O. Seitz, G. Nicholson, C. Bruntner, J. Riedlinger,
H.-P. Fiedler and R. D. Su¨essmuth, Angew. Chem., Int. Ed., 2008,
47, 3258.
18 (a) C. G. Espino, K. W. Fiori, M. Kim and J. Du Bois, J. Am. Chem.
Soc., 2004, 126, 15378; (b) D. N. Zalatan and J. Du Bois, J. Am. Chem.
Soc., 2009, 131, 7558.
19 The usage of a nonpolar solvent (toluene) might disfavour path a via
zwitterionic intermediates. Instead, path b-2 via the azatriene
intermediate may occur dominantly under this condition. For some
relevant references, see: (a) D. A. Colby, R. G. Bergman and J. A.
Ellman, J. Am. Chem. Soc., 2008, 130, 3645; (b) Y. J. Jiang, C.-M. Park
and T.-P. Loh, Org. Lett., 2014, 16, 3432.
J. Lacour, Org. Lett., 2014, 16, 3232; (h) Y. S. Zhang, X. Y. Tang and 20 While the exact function of ClCH2COOH in the reaction remains
M. Shi, Chem. Commun., 2014, 50, 15971; (i) X. Y. Tang, Y. S. Zhang,
L. He, Y. Wei and M. Shi, Chem. Commun., 2015, 51, 133.
7 (a) T. Horneff, S. Chuprakov, N. Chernyak, V. Gevorgyan and V. V.
Fokin, J. Am. Chem. Soc., 2008, 130, 14972; (b) T. Miura, M. Yamauchi
unclear at this stage, we speculated that it may facilitate path a
(Scheme 1) by (1) accelerating the ring-expansion of C through
activation of the imine moiety and (2) promoting the proton-
transfer and double bond isomerization.
and M. Murakami, Chem. Commun., 2009, 1470; (c) B. Chattopadhyay 21 While the direct nucleophilic attack of the nitrogen atom of the
and V. Gevorgyan, Org. Lett., 2011, 13, 3746; (d) T. Miura, K. Hiraga,
T. Biyajima, T. Nakamuro and M. Murakami, Org. Lett., 2013,
15, 3298; (e) S. Chuprakov, S. W. Kwok and V. V. Fokin, J. Am. Chem.
Soc., 2013, 135, 4652; ( f ) E. E. Schultz and R. Sarpong, J. Am. Chem.
imine moiety at the C-2 position of azirine could also afford the
1,2-dihydropyrazine products, the observed notable electronic effect
at the C-2 position is in agreement with the mechanism via carbo-
cation intermediate F (path b-1).
Soc., 2013, 135, 4696; (g) B. T. Parr, S. A. Green and H. M. J. Davies, 22 Actually, formal [3+3] adducts were obtained with similar substrates
J. Am. Chem. Soc., 2013, 135, 4716; (h) J. E. Spangler and H. M. L.
Davies, J. Am. Chem. Soc., 2013, 135, 6802; (i) J. S. Alford, J. E. Spangler
and H. M. L. Davies, J. Am. Chem. Soc., 2013, 135, 11712;
in references 14a and 14b, indicating that the reaction pathways of
the cycloadditions of 1-sulfonyl 1,2,3-triazoles and 2H-azirines are
very sensitive to the substrates and reaction conditions.
4510 | Chem. Commun., 2015, 51, 4507--4510
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