Organocatalytic Vinyl Azide-Carbonyl [3+2] Cycloaddition: High-Yielding Synthesis of Fully Decorated N-Vinyl-1,2,3-Triazoles

Article abstract of DOI:10.1002/cctc.201601317

For the first time, an enolate-mediated organocatalytic vinyl azide-carbonyl [3+2] cycloaddition (OrgVACC) of various ketones/aldehydes with vinyl azides is reported. It is an efficient intermolecular reaction with excellent outcomes with reference to rat

Full text of DOI:10.1002/cctc.201601317

Accepted Article
Title: An Organocatalytic Vinyl Azide-Carbonyl [3 + 2]-Cycloaddition:
High-yielding Synthesis of Fully Decorated N-Vinyl-1,2,3-
Triazoles
Authors: Dhevalapally Ramachary, Surendra Reddy G., Swamy
Peraka, and Jagjeet Gujral
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: ChemCatChem 10.1002/cctc.201601317
Link to VoR: http://dx.doi.org/10.1002/cctc.201601317
A Journal of
www.chemcatchem.org

10.1002/cctc.201601317
ChemCatChem
COMMUNICATION
An Organocatalytic Vinyl Azide-Carbonyl [3 + 2]-Cycloaddition:
High-yielding Synthesis of Fully Decorated N-Vinyl-1,2,3-Triazoles
Dhevalapally B. Ramachary,* G. Surendra Reddy, Swamy Peraka, and Jagjeet Gujral
Abstract: For the first time, an enolate-mediated organocatalytic vinyl
azide–carbonyl [3+2]-cycloaddition (OrgVACC) of various
disubstituted N-vinyl-1,2,3-triazoles. Functionalized N-vinyl-1,2,3-
triazoles are not only inspiring due to their novel functionality, but
also can become suitable starting materials for N-alkyl-1,2,3-
triazoles synthesis (eq. a-c, Scheme 1). Very little is known about
the regioselective catalytic synthesis of functionalized N-vinyl-
1,2,3-triazoles. In the previous synthetic methods, copper-
ketones/aldehydes with vinyl azides is reported. It is an efficient
intermolecular reaction with excellent outcomes with reference to rate,
yield, selectivity, operation simplicity, substrates scope, simple
catalyst and vast applications.
catalyzed
alkyne-vinylazide
or
alkyne--haloalkyl
azide
cycloaddition gave moderate to poor yields,[8] gold-catalyzed
1,2,3-triazole addition to alkynes gave good yields at higher
temperature,[9] and pre-formed enamine/enolate cycloaddition
with vinyl azide gave moderate to poor yields for longer reaction
times.[10] These drawbacks stimulated us to develop a general
catalytic protocol for high-yielding regioselective synthesis of
Recently, functionalized 1,2,3-triazoles have become important
molecules with many unique chemical/physical properties and are
widely used as pharmaceuticals due to their bio-similarity with
amide bonds.[1] Fully decorated 1,2,3-triazoles have found vast
applications in organic, bio-organic, polymer, medicinal,
pharmaceutical and material chemistry.[2] Pharmacological
outcome of 1,2,3-triazoles is completely based on their 1,4-, 1,5-
or 1,4,5-substitutions and due to this reason, the design and
development of more general green catalytic methods for their
selective fully decorated synthesis are of significant interest
(Scheme 1).[3-6]
1,4,5-/1,4-substituted
revealed an operationally simple, rapid, and general protocol
“organocatalytic vinyl azide–carbonyl [3+2]-cycloaddition
N-vinyl-1,2,3-triazoles.[5]
Herein,
we
(OrgVACC)” for the selective synthesis of fully decorated N-vinyl-
1,2,3-triazoles from the vinyl azides and simple deoxybenzoins,
arylacetones or arylacetaldehydes utilizing organocatalyst (eq. d,
Scheme 1).[5a]
Scheme 1: Reaction design for the vinyl azide-carbonyl [3+2]-cycloaddition.
For example, 1,4- or 1,5-disubstituted 1,2,3-triazoles and
1,4,5-trisubstituted 1,2,3-triazoles have significant role in
pharmaceutical chemistry [Eq. (1)] and as mentioned previously,
their drug properties mainly depend on their aliphatic or aromatic
substitutions.[2]
Already
four
1,2,3-triazole-based
drugs
[tazobactam, solithromycin, cefatrizine and rufinamide] are
currently in use,[7] which is inspiring us to develop novel
functionalized 1,2,3-triazoles for more properties through
organocatalysis. Herein, we showed interest to develop a single-
step general catalytic protocol for high-yielding regioselective
synthesis of 1,4,5-trisubstituted N-vinyl-1,2,3-triazoles and 1,4-
[]
Prof. Dr. D. B. Ramachary, Mr. G. S. Reddy, Dr. Swamy Peraka and
Mr. Jagjeet Gujral
We commenced the prior optimization of OrgVACC by
screening the organocatalysts for the cycloaddition reaction of
deoxybenzoin 1a with 1.2 equiv. of -azidostyrene 2a (Table 1).
[3+2]-Cycloaddition reaction of 1a with 2a in DMSO under 10-
mol% of proline 3a-catalysis at 25 C for 17 h furnished the
expected N-vinyl-1,2,3-triazole 4aa as a single regioisomer in
only 3% yield (Table 1, entry 1). The same reaction at 25 C for
17 h under 10-mol% of diethyl amine 3b, or pyrrolidine 3c-
catalysis furnished the N-vinyl-1,2,3-triazole 4aa in 8%, and 45%
yields, respectively (Table 1, entries 2-3). After obtaining poor
Catalysis Laboratory, School of Chemistry
University of Hyderabad
Hyderabad-500 046 (India)
Fax: +91-40-23012460
E-mail: ramsc@uohyd.ac.in and ramchary.db@gmail.com
Homepage: http://chemistry.uohyd.ac.in/~dbr/index.htm
Supporting information (experimental procedures and analytical data
for all new compounds) for this article is given via a link at the end of
the document.
1
This article is protected by copyright. All rights reserved.

10.1002/cctc.201601317
ChemCatChem
COMMUNICATION
Table 2: Ketone and vinyl azide scope.[a]
results with secondary amine catalysts 3a-c through enamine-
formation, based on our previous experience,[5] we thought of
exploring the same reaction through in situ enolate formation,
using some tert-amines 3d-f and non-amine bases 3g-h as the
catalysts for the OrgVACC reaction (Table 1). Under DABCO 3d-
catalysis, cycloaddition reaction of 1a with 2a in DMSO at 25 C
for 17 h furnished the expected product 4aa in only 10% yield
(Table 1, entry 4). Intriguingly, the [3+2]-cycloaddition reaction of
1a with 2a in DMSO under 10-mol% of DBU 3e-catalysis at 25 °C
in just 0.5 h furnished the N-vinyl-1,2,3-triazole 4aa in 93% yield
(Table 1, entry 5). The same OrgVACC reaction under the
catalysis of DBU 3e in other solvents like DMF, CHCl3 and
CH3CN at 25 C for 17 h furnished 4aa in 90%, 5% and 22%
yields, respectively (Table 1, entries 6, 7 and 8). Same OrgVACC
reaction under the catalysis of triazabicyclodecene 3f in DMSO at
25 C for 8 h furnished 4aa in 89% yield (Table 1, entry 9).
Interestingly, the reaction under 10-mol% of non-amine bases of
K2CO3 3g and tBuOK 3h-catalysis in DMSO furnished the N-vinyl-
1,2,3-triazole 4aa in good yields at 25 C for 13 and 0.5 h,
respectively (Table 1, entries 10-11). No cycloaddition reaction
was observed under self- or autocatalytic conditions in DMSO
even after 24 h at 25 °C (Table 1, entry 12). Finally, we
envisioned the optimized condition to be 25 C in DMSO under
10-mol% of DBU 3e-catalysis, which furnished the single isomer
of fully decorated N-vinyl-1,2,3-traizole 4aa in 93% yield from 1a
[a] Reactions were carried out in DMSO (0.3 M) with 1.2 equiv. of 2 relative to
and 2a (Table 1, entry 5).
Table 1: Reaction optimization.[a]
[a] Reactions were carried out in solvent (0.3 M) with 1.2 equiv. of 2a relative to
the 1 (0.3 mmol) in the presence of 10-mol% of 3e and yield refers to the
column-purified product.
With the best catalytic conditions in hand, the scope and
generality of the enolate-mediated OrgVACC reaction were
investigated. Firstly, substituted deoxybenzoins 1b-d were
reacted with -azidostyrene 2a catalyzed by 10-mol% of DBU 3e
at 25 C in DMSO for 0.5-0.75 h (Table 2, entries 1-3). Intriguingly,
the deoxybenzoins containing different functional groups (H, alkyl,
halogen and NO2) 1b-d furnished the expected fully substituted
N-vinyl-1,2,3-traizoles 4ba-da in excellent yields within 0.5-0.75 h
(Table 2, entries 1-3). Further, DBU 3e-catalyzed OrgVACC
reaction of substituted arylacetones 1e-i with -azidostyrene 2a
at 25 C in DMSO for 0.5-0.6 h furnished the fully substituted N-
vinyl-1,2,3-traizoles 4ea-ia in very good yields (Table 2, entries 4-
8). In this reaction, we did not observe any substitution effect on
the phenyl ring and OrgVACC reaction worked well for different
substitutions (H, CH3, OCH3, Cl and NO2) of phenylacetones 1e-i
(Table 2, entries 4-8). In
arylketones, 1-(naphthalen-2-yl)propan-2-one
a
similar manner, functionalized
1j and 1-
phenylpentan-2-one 1k with 2a furnished the functionally rich N-
vinyl-1,2,3-traizoles 4ja and 4ka in very good yields within 0.5 h
(Table 2, entries 9-10). After comprehending the OrgVACC
reaction by probing the electronic factors of deoxybenzoins or
arylacetones 1a-k with 2a, we further showed interest to
investigate the electronic factors of -azidostyrenes 2b-i with
deoxybenzoin 1a (Table 2, entries 11-18). Functionalized -
azidostyrenes 2b-g were reacted with deoxybenzoin 1a catalyzed
by 10-mol% of DBU 3e at 25 C in DMSO for 0.25-1.0 h (Table 2,
entries 11-16). Uneventfully, the -azidostyrenes containing
different functional groups on the aryl ring (4-F, 4-Cl, 4-Me, 2-Me,
the 1a (0.3 mmol) in the presence of 10-mol% of catalyst 3. [b] Yield refers to
the column-purified product. [c] Ketone 1a and azide 2a was not consumed
totally.
2
This article is protected by copyright. All rights reserved.

10.1002/cctc.201601317
ChemCatChem
COMMUNICATION
4-OMe, and 2-naphthyl) 2b-g furnished the expected fully
substituted N-vinyl-1,2,3-triazoles 4ab-ag in excellent to good
yields (Table 2, entries 11-16). Though the N-vinyl-1,2,3-triazoles
4ab-ag were obtained in good yields for all the different
substituted -azidostyrenes 2, reaction rate and yield were
noticeably decreased with EDG substitution. Interestingly, the
DBU 3e-catalyzed OrgVACC reaction of 1a with aliphatic vinyl
naphthyl) 2b-g to furnish the 1,4-disubstituted-N-vinyl-1,2,3-
triazoles 6ab-ag in excellent to good yields (Table 3, entries 9-14).
The Table 3 results demonstrate the broad scope of this protocol
covering a structurally diverse group of aryl acetaldehydes 5 and
-azidostyrenes 2 to furnish the 1,4-disubstituted-N-vinyl-1,2,3-
triazoles 6. In most of the cases, the product 6 yields obtained
were excellent compared to the previously available multi-step
methods.[8-10] The structure and regiochemistry of the products 6
were established by NMR analysis and also finally confirmed by
the X-ray structure analysis on 6ag (Figure S2, see the
azides
4-((2-azidoallyl)oxy)-1,1'-biphenyl
2h
and
1-((2-
azidoallyl)oxy)-4-nitrobenzene 2i furnished the expected N-vinyl-
1,2,3-triazoles 4ah in 75% and 4ai in 80%, respectively under the
optimized reaction conditions (Table 2, entries 17-18). This
serves one of the important applications from OrgVACC, where
we can generate a library of aliphatic substituted N-alkyl-1,2,3-
triazoles from the corresponding N-vinyl-1,2,3-triazoles 4. The
structure and regiochemistry of the OrgVACC products 4 were
established by NMR analysis and also finally confirmed by the X-
ray structure analysis on 4ia as shown in Figure S1 (see the
Supporting Information).[11]
Table 4: -Azidostyrene scope.[a]
[a] Reactions were carried out in DMSO (0.3 M) with 1.2 equiv. of 7a relative to
Supporting Information).[11]
Table 3: Aldehyde and vinyl azide scope.[a]
[a] Reactions were carried out in DMSO (0.3 M) with 1.2 equiv. of 2 relative to
the 5 (0.3 mmol) in the presence of 10-mol% of 3e and yield refers to the
column-purified product.
the 1/5 (0.3 mmol) in the presence of 10-mol% of 3e and yield refers to the
column-purified product.
After investigation of the OrgVACC reaction by probing the
electronic factors of alkyl or aryl ketones 1 with -azidostyrenes 2,
we further showed interest to investigate the electronic factors of
aryl or alkyl acetaldehydes 5a-h by reacting with -azidostyrenes
2 in the OrgVACC reaction (Table 3). Fascinatingly, the reaction
of aryl acetaldehydes 5a-g, containing different functional groups
of alkyl, halogen, EWG’s, and EDG’s on aryl ring with simple -
azidostyrene 2a under 10-mol% of 3e-catalysis furnished the
single isomer of 1,4-disubstituted-N-vinyl-1,2,3-triazoles 6aa-ga in
excellent yields similar to the deoxybenzoin 1a/phenylacetone 1e
(Table 3, entries 1-7). Although, the aliphatic aldehyde, 3-
phenylpropanal 5h didn’t furnished the expected product under
3e-catalysis, under the catalysis of tBuOK 3h at 25 C for 6.0 h
furnished the expected N-vinyl-1,2,3-triazole 6ha in 85% yield
(Table 3, entry 8). After these results, we further investigated the
scope of this reaction by treating phenylacetaldehyde 5a with
functionalized -azidostyrenes containing different functional
groups on the aryl ring (4-F, 4-Cl, 4-Me, 2-Me, 4-OMe, and 2-
To further develop the diverse library of fully decorated N-
vinyl-1,2,3-triazoles 8/9 and also to understand the electronic
factors of -azidostyrenes 7 in the OrgVACC reaction, we have
chosen -azidostyrene 7a, which is more reactive towards
carbonyls compared to -azidostyrenes 2 due to the linear
conjugation (Table 4). The OrgVACC reaction of deoxybenzoin
1a with -azidostyrene 7a under the optimized conditions
furnished the expected N-vinyl-1,2,3-triazole 8aa in 85% yield
(Table 4, entry 1). We have also tested two more examples of
halogen-, and methyl-substituted deoxybenzoins 1b-c for the
OrgVACC reaction with 7a, which furnished the N-vinyl-1,2,3-
triazoles 8ba-ca in excellent yields (Table 4, entries 2-3). The
OrgVACC reaction of hydrogen-, methyl-, methoxy-, chloro-, and
nitro-substituted arylketones 1e-i with 7a under the 3e-catalysis
furnished the fully decorated N-vinyl-1,2,3-triazoles 8ea-ia in 70-
92% yields without showing much of electronic factors (Table 4,
entries 4-8). Likewise, functionalized arylketones, 1-(naphthalen-
2-yl)propan-2-one 1j and 1-phenylpentan-2-one 1k with 7a
3
This article is protected by copyright. All rights reserved.

10.1002/cctc.201601317
ChemCatChem
COMMUNICATION
furnished the 1,4,5-trisubstituted-N-vinyl-1,2,3-traizoles 8ja and
8ka in 90% yield, respectively (Table 4, entries 9-10). Reaction of
phenylacetaldehyde 5a with -azidostyrene 7a under 10-mol% of
3e-catalysis furnished the single isomer of 1,4-disubstituted-N-
vinyl-1,2,3-triazole 9aa in 90% yield (Table 4, entry 11).
In summary, we have developed a versatile organocatalytic
enolate-mediated vinyl azide-carbonyl [3+2]-cycloaddition to
furnish the functionally-rich 1,4,5-trisubstituted-N-vinyl-1,2,3-
triazoles
and
1,4-disubstituted-N-vinyl-1,2,3-triazoles
with
medicinally useful functional groups. Present method of
OrgVACC highlights the metal-free conditions, high rate and
selectivity, and easy access to the library of N-vinyl-1,2,3-
triazoles. Moreover, many of the reported syntheses have the
disadvantage of requiring multiple synthetic steps, harsh reaction
conditions, heavy metals and less available unsymmetric internal
alkynes; therefore, this OrgVACC protocol is very convenient to
practice. Further work is in progress to utilize the enolate-
mediated OrgVACC reactions in medicinal and material chemistry.
Experimental Section
Experimental procedures, and compound characterization data (1H NMR,
13C NMR, and HRMS). This material is available free of charge in the
Supporting Information.
Scheme 2: Reaction application.
The importance of OrgVACC reactions was further
exemplified by synthesizing compounds 10aa and 11aa (Scheme
2).[2] Catalytic hydrogenation of 1,4,5-trisubstituted-N-vinyl-1,2,3-
triazole 4aa with hydrogen balloon under 10-mol% of Pd/C in
methanol at 25 C for 1.0 h furnished the functionalized N-alkyl-
1,2,3-triazole 10aa in 92% yield. Similarly, treatment of 8aa with
hydrogen balloon in the presence of Pd/C in methanol at 25 C
for 1.0 h furnished the functionalized N-alkyl-1,2,3-triazole 11aa in
85% yield. On the contrary, the literature synthesis of this triazole
Acknowledgements
We thank DST, SERB, New Delhi [Grant No. EMR/2015/000860]
for financial support. GSR and JG thank UGC (New Delhi) and
CSIR (New Delhi) for their research fellowships, respectively. SP
thank SERB, DST (New Delhi) for his N-PDF fellowship.
Received: ((will be filled in by the editorial staff))
Published online on ((will be filled in by the editorial staff))
11aa
starting
from
the
diphenylacetylene
and
(2-
azidoethyl)benzene requires costly Ru-catalyst, high temperature
and a long reaction time (Scheme 2).[12] These results clearly
demonstrate the exceptional advantages and more applications
of OrgVACC protocol, which enables the simple high-yielding
synthesis of fully substituted N-alkyl-1,2,3-triazoles, which are not
easily accessible from other methods.
Keywords: [3+2]-cycloaddition • ketones • organocatalysis • 1,2,3-
triazoles • vinyl azides
[1]
For the 1,2,3-triazoles as amide bond mimics, see: a) Y. L. Angell, K.
Burgess, Chem. Soc. Rev. 2007, 36, 1674–1689; b) A. Tam, U. Arnold,
M. B. Soellner, R. T. Raines, J. Am. Chem. Soc. 2007, 129, 12670-
12671; c) J. M. Holub, K. Kirshenbaum, Chem. Soc. Rev. 2010, 39,
1325–1337; d) I. E. Valverde, A. Bauman, C. A. Kluba, S. Vomstein, M.
A. Walter, T. L. Mindt, Angew. Chem. 2013, 125, 9126–9129; Angew.
Chem. Int. Ed. 2013, 52, 8957–8960.
[2]
For the applications of 1,2,3-triazoles, see: a) A. C. Tome, Sci. Synth.
2004, 13, 415-601; b) L. S. Kallander, et al. J. Med. Chem. 2005, 48,
5644-5647; c) S. Ito, A. Satoh, Y. Nagatomi, Y. Hirata, G. Suzuki, T.
Kimura, A. Satow, S. Maehara, H. Hikichi, M. Hata, H. Kawamoto, H.
Ohta, Bioorg. Med. Chem. 2008, 16, 9817–9829; d) S. Ito, Y. Hirata, Y.
Nagatomi, A. Satoh, G. Suzuki, T. Kimura, A. Satow, S. Maehara, H.
Hikichi, M. Hata, H. Ohta, H. Kawamoto, Bioorg. Med. Chem. Lett. 2009,
19, 5310–5313; e) T. Tsuritani, H. Mizuno, N. Nonoyama, S. Kii, A. Akao,
K. Sato, N. Yasuda, T. Mase, Org. Process Res. Dev. 2009, 13, 1407-
1412; f) S. G. Agalave, S. R. Maujan, V. S. Pore, Chem. Asian J. 2011, 6,
2696–2718; g) see also: Chem. Asian J. 2011, 6, Issue 10. Special
edition devoted to click chemistry; h) M. Fujinaga, T. Yamasaki, K.
Kawamura, K. Kumata, A. Hatori, J. Yui, K. Yanamoto, Y. Yoshida, M.
Ogawa, N. Nengaki, J. Maeda, T. Fukumura, M. –R. Zhang, Bioorg. Med.
Chem. 2011, 19, 102–110; i) A. Lauria, R. Delisi, F. Mingoia, A. Terenzi,
A. Martorana, G. Barone, A. M. Almerico, Eur. J. Org. Chem. 2014,
3289–3306; j) S. Li, Y. Huang, Curr. Med. Chem. 2014, 21, 113-123.
For CuAAC reactions, see: a) C. W. Tornoe, C. Christensen, M. Meldal,
J. Org. Chem. 2002, 67, 3057-3064; b) V. V. Rostovtsev, L. G. Green, V.
Scheme 3: Reaction mechanism.
The mechanism for the OrgVACC is illustrated in Scheme 3.
Reaction of the deoxybenzoins/arylacetones/arylacetaldehydes
1/5 with catalyst DBU 3e in DMSO generates the stable enolate
12, which on in situ treatment with vinyl-azides 2/7 furnishes
selectively the functionally-rich adduct 1,2,3-triazolines 13 by
[3+2]-cycloaddition.[13] The adduct 13 further transforms into the
fully decorated N-vinyl-1,2,3-triazoles 4/6/8/9 through rapid
elimination of water under ambient conditions.
[3]
4
This article is protected by copyright. All rights reserved.

10.1002/cctc.201601317
ChemCatChem
COMMUNICATION
V. Fokin, K. B. Sharpless, Angew. Chem. Int. Ed. 2002, 41, 2596-2599;
Angew. Chem. Int. Ed. 2013, 52, 13324-13328; c) Z. –J. Cai, X. –M. Lu,
Y. Zi, C. Yang, L. –J. Shen, J. Li, S. –Y. Wang, S. –J. Ji, Org. Lett. 2014,
16, 5108−5111; d) Z. Chen, Q. Yan, Z. Liu, Y. Zhang, Chem. Eur. J.
2014, 20, 17635–17639; e) J. Thomas, J. John, N. Parekh, W. Dehaen,
Angew. Chem. 2014, 126, 10319–10323; Angew. Chem. Int. Ed. 2014,
53, 10155–10159; f) A. Ali, A. G. Corrêa, D. Alves, J. Zukerman-
Schpector, B. Westermann, M. A. B. Ferreira, M. W. Paixao, Chem.
Commun. 2014, 73, 11926-11929; g) X. –J. Quan, Z. –H. Ren, Y. –Y.
Wang, Z. –H. Guan, Org. Lett. 2014, 16, 5728−5731; h) G. Cheng, X.
Zeng, J. Shen, X. Wang, X. Cui, Angew. Chem. 2013, 125, 13507–
13510; Angew. Chem. Int. Ed. 2013, 52, 13265–13268; i) J. John, J.
Thomas, N. Parekh, W. Dehaen, Eur. J. Org. Chem. 2015, 4922-4930; j)
J. Thomas, V. Goyvaerts, S. Liekens, W. Dehaen, Chem. Eur. J. 2016,
22, 9966-9970.
c) L. V. Lee, M. L. Mitchell, S. J. Huang, V. V. Fokin, K. B. Sharpless, C.
H. Wong, J. Am. Chem. Soc. 2003, 125, 9588-9589; d) A. E. Speers, G.
C. Adam, B. F. Cravatt, J. Am. Chem. Soc. 2003, 125, 4686-4687; e) J. -
F. Lutz, Z. Zarafshani, Adv. Drug Deliv. Rev. 2008, 60, 958-970; For a
strain-promoted AAC reactions, see: f) N. J. Agard, J. A. Preschner, C. R.
Bertozzi, J. Am. Chem. Soc. 2004, 126, 15046-15047; g) N. J. Agard, J.
M. Baskin, J. A. Prescher, A. Lo, C. R. Bertozzi, ACS Chem. Biol. 2006,
1, 644-648; h) J. M. Baskin, C. R. Bertozzi, QSAR Comb. Sci. 2007, 26,
1211-1219; i) S. T. Laughlin, J. M. Baskin, S. L. Amacher, C. R. Bertozzi,
Science 2008, 320, 664-667; j) B. Gold, G. B. Dudley, I. V. Alabugin, J.
Am. Chem. Soc. 2013, 135, 1558-1569.
[4]
For the enamine-mediated organocatalytic [3+2]-cycloaddition reactions,
see: a) D. B. Ramachary, K. Ramakumar, V. V. Narayana, Chem. Eur. J.
2008, 14, 9143–9147; b) M. Belkheira, D. E. Abed, J.-M. Pons, C. Bressy,
Chem. Eur. J. 2011, 17, 12917–12921; c) L. J. T. Danence, Y. Gao, M. Li,
Y. Huang, J. Wang, Chem. Eur. J. 2011, 17, 3584–3587; d) L. Wang, S.
Peng, L. J. T. Danence, Y. Gao, J. Wang, Chem. Eur. J. 2012, 18, 6088–
6093; e) N. Seus, L. C. Goncalves, A. M. Deobald, L. Savegnago, D.
Alves, M. W. Paixao, Tetrahedron 2012, 68, 10456-10463; f) D. B.
Ramachary, A. B. Shashank, Chem. Eur. J. 2013, 19, 13175–13181; g)
W. Li, Q. Jia, Z. Du, J. Wang, Chem. Commun. 2013, 49, 10187-10189;
h) D. K. J. Yeung, T. Gao, J. Huang, S. Sun, H. Guo, J. Wang, Green
Chem. 2013, 15, 2384-2388; i) N. Seus, B. Goldani, E. J. Lenardão, L.
Savegnago, M. W. Paixão, D. Alves, Eur. J. Org. Chem. 2014, 1059–
1065; j) W. Li, Z. Du, J. Huang, Q. Jia, K. Zhang, J. Wang, Green Chem.
2014, 16, 3003-3006; k) W. Li, Z. Du, K. Zhang, J. Wang, Green Chem.
2015, 17, 781-784; l) Q. Jia, G. Yang, L. Chen, Z. Du, J. Wei, Y. Zhong,
J. Wang, Eur. J. Org. Chem. 2015, 3435-3440; m) X. Xu, Z. Shi, W. Li,
New J. Chem. 2016, 40, 6559-6563.
[7]
[8]
B. Gopalan, K. K. Balasubramanian, Click Reactions in Organic
Synthesis, 2016, 25-76 (DOI: 10.1002/9783527694174.ch2).
a) S. Kamijo, Z. Huo, T. Jin, C. Kanazawa, Y. Yamamoto, J. Org. Chem.
2005, 70, 6389-6397; b) M. Kavitha, B. Mahipal, P. S. Mainkar, S.
Chandrasekhar, Tetrahedron Lett. 2011, 52, 1658–1662; c) L. Kupracz, J.
Hartwig, J. Wegner, S. Ceylan, A. Kirschning, Beilstein J. Org. Chem.
2011, 7, 1441–1448; d) M. –H. Wei, D. Wu, R. Sun, S. –R. Sheng, J.
Chem. Res. 2013, 37, 422-424; e) F. Alonso, Y. Moglie, G. Radivoy, M.
Yus, J. Org. Chem. 2013, 78, 5031−5037; f) C. Vidal, J. García-Álvarez,
Green Chem. 2014, 16, 3515–3521; g) A. K. Shil, S. Kumar, S. Sharma,
A. Chaudhary, P. Das, RSC Adv. 2015, 5, 11506-11514.
[9]
a) H. Duan, W. Yan, S. Sengupta, X. Shi, Bioorg. Med. Chem. Lett. 2009,
19, 3899–3902; b) D. Sikora, T. Gajda, Tetrahedron 1998, 54, 2243-
2250.
[10] a) G. Labbe, A. Hassner, J. Heterocycl. Chem. 1970, 7, 361-366; b) T. L.
Gilchrist, G. E. Gymer, C. W. Rees, J. Chem. Soc., Perkin Trans. 1, 1975,
1-8; c) Y. Nomura, Y. Takeuchi, S. Tomoda, M. M. Ito, Bull. Chem. Soc.
Jpn. 1981, 54, 261-266; d) E. P. J. Ng, Y. –F. Wang, B. W. –Q. Hui, G.
Lapointe, S. Chiba, Tetrahedron 2011, 67, 7728-7737.
[5]
For the enolate-mediated organocatalytic [3+2]-cycloaddition reactions,
see: a) D. B. Ramachary, A. B. Shashank, S. Karthik, Angew. Chem.
2014, 126, 10588-10592; Angew. Chem. Int. Ed. 2014, 53, 10420–
10424; b) A. B. Shashank, S. Karthik, R. Madhavachary, D. B.
Ramachary, Chem. Eur. J. 2014, 20, 16877–16881; c) W. Li, J. Wang,
Angew. Chem. 2014, 126, 14410–14414; Angew. Chem. Int. Ed. 2014,
53, 14186–14190; d) S. S. V. Ramasastry, Angew. Chem. 2014, 126,
14536-14538; Angew. Chem. Int. Ed. 2014, 53, 14310-14312; e) C. G. S.
Lima, A. Ali, S. S. van Berkel, B. Westermann, M. W. Paixão, Chem.
Commun. 2015, 51, 10784-10796; f) J. John, J. Thomas, W. Dehaen,
Chem. Commun. 2015, 51, 10797-10806; g) P. M. Krishna, D. B.
Ramachary, P. Sruthi, RSC Adv. 2015, 5, 62062-62066; h) D. B.
Ramachary, P. M. Krishna, J. Gujral, G. S. Reddy, Chem. Eur. J. 2015,
21, 16775–16780; i) D. González-Calderón, A. Fuentes-Benítes, E. Díaz-
Torres, C. A. González-González, C. González-Romero, Eur. J. Org.
Chem. 2016, 668–672; j) X. Zhou, X. Xu, K. Liu, H. Gao, W. Wang, W. Li,
Eur. J. Org. Chem. 2016, 1886–1890; k) X. Zhou, X. Xu, Z. Shi, K. Liu, H.
Gao, W. Li, Org. Biomol. Chem. 2016, 14, 5246-5250; l) for the [3+2]-
cycloaddition of activated -keto esters with vinyl azides, see: D. B.
Ramachary, J. Gujral, S. Peraka, G. S. Reddy, Chem. Eur. J. 2016,
manuscript number: chem.201604497, submitted on 22nd Sep 2016,
presently under review.
[11] CCDC-1503961 (4ia) and CCDC-1503956 (6ag) contains the
supplementary crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif.
[12] For RuAAC and IrAAC reactions, see: a) L. Zhang, X. Chen, P. Xue, H.
H. Y. Sun, I. D. Williams, K. B. Sharpless, V. V. Fokin, G. Jia, J. Am.
Chem. Soc. 2005, 127, 15998-15999; b) L. K. Rasmussen, B. C. Boren,
V. V. Fokin, Org. Lett. 2007, 9, 5337-5339; c) B. C. Boren, S. Narayan, L.
K. Rasmussen, L. Zhang, H. Zhao, Z. Lin, G. Jia, V. V. Fokin, J. Am.
Chem. Soc. 2008, 130, 8923–8930; d) E. Rasolofonjatovo, S.
Theeramunkong, A. Bouriaud, S. Kolodych, M. Chaumontet, F. Taran,
Org. Lett. 2013, 15, 4698–4701; e) S. Ding, G. Jia, J. Sun, Angew. Chem.
Int. Ed. 2014, 53, 1877–1880.
[13] a) J. Tajabadi, M. Bakavoli, M. Gholizadeh, H. Eshghi, Org. Biomol.
Chem. 2016, 14, 7324-7333; b) K. Anebouselvy, D. B. Ramachary, Click
Reactions
in
Organic
Synthesis,
2016,
99-140
(DOI:
10.1002/9783527694174.ch4); c) B. Hu, S. G. DiMagno, Org. Biomol.
Chem. 2015, 13, 3844-3855.
[6]
a) S. S. van Berkel, S. Brauch, L. Gabriel, M. Henze, S. Stark, D. Vasilev,
L. A. Wessjohann, M. Abbas, B. Westermann, Angew. Chem. 2012, 124,
5437-5441; Angew. Chem. Int. Ed. 2012, 51, 5343-5346; b) Z. Chen, Q.
Yan, Z. Liu, Y. Xu, Y. Zhang, Angew. Chem. 2013, 125, 13566-13570;
5
This article is protected by copyright. All rights reserved.

10.1002/cctc.201601317
ChemCatChem
COMMUNICATION
Entry for the Table of Contents
N-Vinyl-1,2,3-Triazoles
D. B. Ramachary,* G. S. Reddy, Swamy
Peraka, and Jagjeet Gujral __Page –
Page
An Organocatalytic Vinyl Azide-
Carbonyl [3+2]-Cycloaddition: High-
yielding Synthesis of Fully Decorated N-
Vinyl-1,2,3-Triazoles
An enolate-mediated organocatalytic vinyl azide–carbonyl [3+2]-cycloaddition
(OrgVACC) of various ketones/aldehydes with vinyl azides is reported. It is an
efficient catalytic intermolecular OrgVACC reaction for the synthesis of N-vinyl-
1,2,3-triazoles.
6
This article is protected by copyright. All rights reserved.