Triazabicyclodecene as an Organocatalyst for the Regiospecific Synthesis of 1,4,5-Trisubstituted N-Vinyl-1,2,3-triazoles

Article abstract of DOI:10.1002/ejoc.201601497

Herein we report on the 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) catalyzed enolate-mediated regiospecific synthesis of 1,4,5-trisubstituted N-vinyl-1,2,3-triazoles from simple activated carbonyl compounds and N-vinyl azides through [3+2] cycloaddition; u

Full text of DOI:10.1002/ejoc.201601497

A Journal of
Accepted Article
Title: Triazabicyclodecene as an Organocatalyst for Regiospecific
Synthesis of 1,4,5-Trisubstituted N-Vinyl-1,2,3-Triazoles
Authors: Dhevalapally Ramachary, Jagjeet Gujral, Swamy Peraka, and
Surendra Reddy G.
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201601497
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10.1002/ejoc.201601497
European Journal of Organic Chemistry
COMMUNICATION
Triazabicyclodecene as an Organocatalyst for Regiospecific
Synthesis of 1,4,5-Trisubstituted N-Vinyl-1,2,3-Triazoles
Dhevalapally B. Ramachary,* Jagjeet Gujral, Swamy Peraka, and G. Surendra Reddy
Abstract: Herein, we have reported the TBD-catalyzed enolate-
mediated regiospecific synthesis of 1,4,5-trisubstituted N-vinyl-1,2,3-
triazoles from simple activated carbonyls and N-vinyl azides via [3+2]-
cycloaddition, which on further hydrogenation furnished the 1,4,5-
Present work is an attempt to extend the scope of the azide
partner beyond the aryl azides traditionally used in such reactions
(Scheme 1). In our search for expanding suitable azide partner,
thermal stability versus reactivity of azides was taken as a guiding
light (Scheme 1).
trisubstituted
N-alkyl-1,2,3-triazoles.
Both
organo-click
and
hydrogenation reactions proceeded in excellent yields with high rate
and selectivity within few hours at 25 C.
1,2,3-Triazoles have emerged as a core of considerable interest
for chemists/biologists in the past few decades. This interest
stems from their wide applicability in the fields of medicinal,
organic, polymer and material chemistry.[1] 1,2,3-Triazoles are
also capable of playing an important role as “amide isosteres”
due to their bio-similarity with amide bonds in properties like
relative planarity, dipole moment and amphihydrogen-bonding
capability.[2] Considering these applications, high-yielding
selective synthesis of variety of functionalized 1,2,3-triazoles
becomes a challenge for synthetic chemists.
With the advent of the concept of “click chemistry” there has
been an explosion in the number of reactions leading to the
synthesis of functionalized 1,2,3-triazoles beginning from the
copper-catalysed click reaction reported by Sharpless.[3] Amino
acid- or amine-catalysed [3+2]-cycloaddition entering into this
field has given rise to an “organocatalytic click strategy” for the
synthesis of substituted 1,2,3-triazoles,[4-6] which has proved itself
at par and in many cases ahead of similar metal mediated
transformations in terms of atom-economy and selectivity (eq. a,
Scheme 1).[4-6]
The realm of organocatalytic 1,2,3-triazole synthesis initiated
by our group in 2008 was further enriched by the groups of Pons-
Bressy, Wang, Dehaen, Paixão, Alves, Li and many other groups.
In early years, this field witnessed a surge in enamine-mediated
1,2,3-triazole formation from different carbonyl compounds like
enones, β-ketoesters, ketones and enals with tosyl/aryl azides.[4]
In the year 2014, an approach complimentary to the enamine
based strategy, an enolate-mediated functionally rich 1,2,3-
triazole formation was reported by our group (eq. b, Scheme
1).[5a,b,g,h,l]
Scheme 1: Previous work and present reaction design.
Till now these organocatalytic [3+2]-cycloadditions have been
limited to thermally stable aryl azides [decomposition temperature
140-170 C]. Moving towards the thermally less stable azides, the
observance of the interplay between reactivity and stability is a
worthy goal to pursue. Step towards our vision was initiated by
choosing substituted vinyl azides as the click partners (eq. d,
Scheme 1).[7a] Rationale for this choice has been the fact that
vinyl azides are of medium thermal stability [decomposition
temperature 60-70 C] and are more reactive towards such
transformations than tosyl, aryl or alkyl azides as shown in
Scheme 1. Respective vinyl substituted 1,2,3-triazoles could also
occupy major role in medicinal to material chemistry. According to
the earlier reports,[7b-c,4f] the physicochemical or electronic factors
which need to be considered for reactivity were the existence of
more number of dipolar mesomeric or resonance structures from
the azido moiety with attached group and it has been shown that
more the number of dipolar mesomeric or resonance structures
more is the reactivity of the azide partner. Due to this double-
bond character between N1-N2 in R-N1-N2N3 is decreased by
introducing an acyl, ester or sulfonyl group in conjugation with the
triazo group. Therefore acyl or sulfonyl azides are less stable
than alkyl/aryl azides. This factor renders aliphatic azides though
In all the previous organocatalytic reports, though a wide
range of activated carbonyls substrates have been employed for
the 1,2,3-triazole synthesis, the variability of the reacting partner
azide has been limited to simple aryl azides and tosyl azide.
[]
Prof. Dr. D. B. Ramachary, Mr. Jagjeet Gujral, Dr. Swamy Peraka
and Mr. G. S. Reddy
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
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10.1002/ejoc.201601497
European Journal of Organic Chemistry
COMMUNICATION
thermally highly stable, less reactive in these [3+2]-cycloaddition
reactions. A fine balance of electronic and thermal factors is
achieved in choosing vinyl azides as click partners. If such a
transformation could be achieved this would be a very simple way
of introducing an olefinic functionality directly into the 1,2,3-
triazole moiety of which previous reports have been scarce.[8]
Deviating from this condition, by switching the solvent to DMF,
CHCl3 or CH3CN by using 10-mol% of DBU 3e as the catalyst
was not so successful in promoting the high-yielding click reaction
(Table 1, entries 6, 7, and 8).[5l] These solvent studies clearly
support our hypothesis of involvement of reactive enolate
formation and their stability. With these moderate results, we
thought of using a strong organic base, the commercially
available guanidine 1,5,7-triazabicyclo-[4.4.0]dec-5-ene (TBD) 3f
as the catalyst for [3+2]-cycloaddition. Because, the pKa value of
the conjugate acid of TBD 3f in acetonitrile is close to 26 and also
TBD 3f has been applied as a suitable catalyst for a variety of
Table 1: Reaction optimization.[a]
[a] Reactions were carried out in solvent (0.5 M) with 1.5 equiv. of 2a relative to
reactions,
including Michael, Wittig,
Henry,
Strecker,
transesterification and acyl transfer reactions.[9] Fascinatingly, the
click reaction of 1a with 1.5 equiv. of 2a in DMSO under 10-mol%
of TBD 3f-catalysis at 25 °C for 3.0 h furnished the 1-vinyl-1H-
1,2,3-triazole 4aa in 98% yield (Table 1, entry 9). Relatively less
basic tert-amines like DABCO [pKa 8.8] 3d, and DBU [pKa 12.0]
3e catalysts furnished the 1-vinyl-1H-1,2,3-triazole 4aa with poor
to good yields compared to TBD [pKa 26.0] 3f (Table 1, entries 4
to 9), also no reaction was observed without the catalyst in
DMSO for 24 h at 25 °C (Table 1, entry 12). The same click
reaction under 10-mol% of non-amine bases K2CO3 [pKa 10.33]
3g and tBuOK [pKa 29.4] 3h-catalysis also furnished the 1-vinyl-
1H-1,2,3-triazole 4aa in good yields within 1.5 h at 25 C; but
which is inferior to TBD 3f-catalysis (Table 1, entries 10-11). We
finally envisioned the optimized condition to be 25 C in DMSO
under 10-mol% of TBD 3f-catalysis which furnished the 1-vinyl-
1H-1,2,3-triazole 4aa in 98% yield from 1a and 2a (Table 1,entry
9).
With the best conditions in hand, the wider scope and the
generality of the novel TBD-catalysed click reactions were
investigated. A variety of functionalized activated carbonyls such
as alkyl acetoacetates 1b-e, ethyl 3-oxo-3-alkyl/aryl-propanoates
1f-k, alkyl/aryl substituted 1,3-diketones 1l-o, 3-oxo-3-alkyl/aryl-
propanenitriles 1p-r, chiral N-alkyl-3-oxo-3-phenylpropanamide
1s and chiral alkyl 3-oxo-3-phenylpropanoate 1t were reacted
with
substituted
-azidostyrenes
2a-g,
or
((2-
the 1a (0.5 mmol) in the presence of 10-mol% of catalyst 3. [b] Yield refers to
the column-purified product. [c] Ethyl acetoacetate 1a was consumed totally.
azidoallyl)oxy)benzenes 2h-i catalysed by 10-mol% of TBD 3f at
25 C in DMSO for 0.5-48 h as shown in Table 2. Interestingly,
the click reaction of alkyl acetoacetates 1b-e containing different
alkyl groups like methyl, allyl, propargyl, and benzyl with -
azidostyrene 2a under 3f-catalysis furnished the expected 1-vinyl-
1H-1,2,3-triazoles 4ba-ea in excellent to good yields within 1.0-
3.0 h (Table 2). In a similar manner, the TBD 3f-catalyzed click
reaction of 2a with ethyl 3-oxo-3-alkyl/aryl-propanoates 1f-k
containing ethyl, n-propyl, trifluoromethyl, phenyl, 4-nitrophenyl
and 4-methoxyphenyl furnished the expected functionalized 1-
vinyl-1H-1,2,3-triazoles 4fa-ka in excellent to moderate yields
from 2.5-48.0 h (Table 2). Yields of the 1-vinyl-1H-1,2,3-triazole
products 4fa-ga were sustained with 93-94%, but the yields
slightly decreased by increasing the reaction time with electron
withdrawing groups such as trifluoromethyl, phenyl, 4-nitrophenyl
and 4-methoxyphenyl compared to methyl group (Table 2). For
example, instead of 10 mol% of TBD 3f, 1.2 equiv. of DBU-
catalysed click reaction of the ethyl 4,4,4-trifluoro-3-oxobutanoate
1h with 2a in DMSO at 25 C for 48 h furnished the 1,2,3-triazole
4ha in only 50% yield (Table 2). Click reaction of symmetric 1,3-
diketones like pentane-2,4-dione 1l and 1,3-diphenylpropane-1,3-
dione 1m with 2a under 10-mol% of 3f-catalysis furnished the
selective products 4la in 77% yield in 2.0 h and 4ma in 70% yield
in 7.0 h, respectively (Table 2).
We optimized the designed organo-click reaction by
screening simple organocatalysts for the [3+2]-cycloaddition of
ethyl acetoacetate 1a with 1.5 equiv. of -azidostyrene 2a under
ambient conditions (Table 1). The reaction of 1a with 1.5 equiv. of
-azidostyrene 2a in DMSO under 10-mol% of proline 3a-
catalysis did not furnished the expected product 4aa even after
24 h at 25 C (Table 1, entry 1). The same reaction under 10-
mol% of diethyl amine 3b-catalysis furnished the 1-vinyl-1H-1,2,3-
triazole 4aa in only 35% yield with complete consumption of
starting materials (Table 1, entry 2). The click reaction of 1a with
1.5 equiv. of 2a in DMSO under 10-mol% of pyrrolidine 3c-
catalysis did not furnished the expected product 4aa; but ethyl
acetoacetate 1a is consumed totally (Table 1, entry 3). After
obtaining discouraging results with the catalysts 3a-c through
enamine-mediated reaction,[4] we thought of investigating the click
reaction through the in situ enolate formation,[5] for which we
tested some tert-amines 3d-f and base 3g-h as the catalysts for
the organo-click reaction. Organo-click reaction of 1a with 2a
under 1,4-diazabicyclo[2.2.2]octane (DABCO) 3d-catalysis didn’t
furnish the expected product 4aa (Table 1, entry 4). Intriguingly,
the reaction of 1a with 1.5 equiv. of 2a in DMSO under 10-mol%
of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) 3e-catalysis at
25 °C for 3.0 h furnished 4aa in 88% yield (Table 1, entry 5).
Table 2: Substrate scope.[a]
2
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10.1002/ejoc.201601497
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COMMUNICATION
[a] Reactions were carried out in DMSO (0.5 M) with 1.5 equiv. of 2 relative to
the 1 (0.5 mmol) in the presence of 10-mol% of 3f and yield refers to the
82% yield (Table 2). The 3f-catalyzed organo-click reaction of 2a
with other two -ketonitriles of 3-oxo-3-(p-tolyl)propanenitrile 1q
and 4,4-dimethyl-3-oxopentanenitrile 1r furnished the expected
products 4qa in 87% yield and 4ra in 70% yield, respectively
(Table 2).
After clear understanding of the electronic factors of activated
carbonyls 1 in the [3+2]-cycloaddition reaction, we investigated
the reaction scope with different -azidostyrenes and -azido
olefins 2b-i with 1e or 1a in the presence of catalytic amount of
TBD 3f at 25 C (Table 2). In this reaction, -azidostyrenes 2b-f
containing different functional groups of 4-F, 4-Cl, 4-CH3, 2-CH3
and 4-OCH3 were used as substrates along with 1e for the
organocatalytic click synthesis of the single isomer of 1,2,3-
triazoles 4eb-ef in excellent to good yields within 1.0-5.0 h (Table
2). Surprisingly, click reaction of -azidostyrenes 2d-f containing
4-CH3, 2-CH3 and 4-OCH3 with 1e under the standard conditions
[10-mol% 3f in DMSO at 25 C] furnished the products 4ed-ef in
moderate to poor yields, but the same reaction under 30-mol% of
3f in neat furnished the expected products 4ed-ef in good yields
(Table 2). Organo-click reaction of 1e with 2-(1-
azidovinyl)naphthalene 2g under 3f-catalysis at 25 C for 4.0 h
furnished the expected product 4eg in 80% yield. With
applications in mind, we performed the organo-click reaction of 1a
or 1e with simple aliphatic -azido olefins 2h-i to furnish the
expected click products in very good yields within 0.85 h as
shown in Table 2. To test the generality of this methodology, we
performed few more click reactions by using -azidostyrenes 2b-
c containing 4-F and 4-Cl with activated carbonyls of pentane-
2,4-dione 1l and 3-oxo-3-phenylpropanenitrile 1p to furnish the
click products 4lb, 4lc, 4pb and 4pc in very good yields as shown
in Table 2. With preparation of chiral functionalized 1-vinyl-1H-
1,2,3-triazoles in mind, we performed the click reaction of (S)-
methyl 2-(3-oxo-3-phenylpropanamido)-3-phenylpropanoate 1s
and
(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl
3-oxo-3-
phenylpropanoate 1t with 2a under 3f-catalysis to furnish the
chiral click products (+)-4sa in 87% and (-)-4ta in 80% yield,
respectively (Table 2). The results furnished in the Table 2
demonstrate the broad scope of this novel methodology covering
a structurally diverse group of activated carbonyls 1a-t and -
azidostyrenes/-azido-olefins
2a-i.
The
structure
and
regiochemistry of the click products 4 were established through
NMR analysis and also finally confirmed by the X-ray structure
analysis on 4ia (Figure S1, see the Supporting Information).[10]
To further understand the electronic nature of azidostyrenes
in the organo-click reaction, we have chosen simple (E)--
azidostyrene 5a, which is having linear conjugation (Table 3).
Surprisingly, the click reaction of ethyl acetoacetate 1a with (E)--
azidostyrene 5a under TBD 3f-catalysis at 25 °C within 0.1 h
furnished the expected 1-styryl-1H-1,2,3-triazole 6aa in 80% yield
(Table 3, entry 1). Likewise, the click reaction of propargyl
acetoacetate 1d and benzyl acetoacetate 1e with (E)--
azidostyrene 5a under TBD 3f-catalysis furnished the 1-styryl-1H-
1,2,3-triazoles 6da and 6ea in 85% yield within 0.75 h,
respectively (Table 3, entries 2 and 3). We have also tested six
more examples of functionalized activated carbonyls 1h-r for the
organo-click reaction with (E)--azidostyrene 5a, which furnished
the expected substituted 1-styryl-1H-1,2,3-triazoles 6ha-6ra in
good to excellent yields (Table 3, entries 4-9). Key point to
mention here in all the above nine click reactions is that the
reaction rates are very high with shorter times compared to -
azidostyrene 2a. The observed high reactivity of 5a compared to
2a in the [3+2]-cycloaddition is mainly due to their differences in
conjugation like linear versus cross; because polarizability in 5a is
column-purified product. [b] 1.2 equiv. of DBU 3e was used as catalyst. [c]
Reaction performed in neat with 30 mol% of 3f. [d] Ethyl acetoacetate 1a was
used.
Surprisingly, click reaction of non-symmetrical 1,3-diketones
like 1-phenylbutane-1,3-dione 1n with 2a under 10-mol% of 3f-
catalysis furnished a mixture of two products 4na in 32% yield
and 4’na in 21% yield in 7.0 h (Table 2). Similarly, reaction of 1-
phenyl-3-(3,4,5-trimethoxyphenyl)propane-1,3-dione 1o with 2a
under 10-mol% of 3f-catalysis furnished a mixture of two products
4oa in 21% yield and 4’oa in 21% yield in 5.5 h (Table 2).
Interestingly, the click reaction of 3-oxo-3-phenylpropanenitrile 1p
with 2a under 10-mol% of 3f-catalysis for 7.0 h furnished 4pa in
3
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10.1002/ejoc.201601497
European Journal of Organic Chemistry
COMMUNICATION
more compared to 2a, which is inducing the quick reaction with in
situ generated enolates.
Table 3: Vinyl azide scope.[a]
[a] Reactions were carried out in DMSO (0.5 M) with 1.5 equiv. of 5a relative to
In order to further extend the understanding of catalytic power
of TBD 3f and also electronic nature of vinyl-azides 2/5, we have
done a few controlled experiments as shown in Scheme 3.
Surprisingly, there is no triazole 12 formation from the reaction of
ethyl acetoacetate 1a with benzyl azide 11 under TBD 3f-
catalysis at 25 to 60 C even after 12 h (Scheme 3). At the same
time, the click reaction of ethyl acetoacetate 1a with phenyl azide
13 under TBD 3f-catalysis in DMSO at 25 °C within 1.0 h
furnished the single isomer of 1,2,3-triazole 14 in 99% yield
(Scheme 3). The same product 14 was synthesised by Wang et
al in 91% yield under enamine-catalysis by using 20 mol% of
diethyl amine 3b in DMSO at 70 C in 24 h,[4c] which is rationally
inferior to the present enolate-catalysis. Many of the products 4/6
yields/selectivity obtained were excellent through enolate-
intermediate compared to the previous methods and vinyl-azides
reactivity towards enolates was similar to the aryl azides than
aliphatic azides.
the 1 (0.5 mmol) in the presence of 10-mol% of 3f and yield refers to the
column-purified product. [b] 1.2 equiv. of DBU 3e was used as catalyst.
The versatility of the organo-click reaction was further
exemplified by synthesizing a few useful compounds 7la, 8aa,
9aa, 10ea and 10la (Scheme 2). We explored the utilization of 4
bearing 1,2,3-triazole-Ac in the synthesis of aldol product 7 via
enolate-mediated aldol reaction (Scheme 2). Direct DBU-
catalysed aldol reaction of 1-(5-methyl-1-(1-phenylvinyl)-1H-1,2,3-
triazol-4-yl)ethanone 4la with 0.7 equiv. of 4-nitrobenzaldehyde in
DMSO at 80 C for 12 h furnished the aldol product 7la in 50%
yield (Scheme 2). Aldol products containing the 1,2,3-triazole ring
will be promising probes to study the medicinal and material
properties.[2] As shown in Scheme 2, ethyl 1-(1,2-dibromo-1-
phenylethyl)-5-methyl-1H-1,2,3-triazole-4-carboxylate 8aa was
synthesized in good yield from the treatment of 1.2 equiv. of
bromine with 1-vinyl-1H-1,2,3-triazole 4aa in DCM at 0-25 C for
2 h; which on further treatment with 1.0 equiv. of triethylamine in
CHCl3 at 0-25 C for 21 h furnished the synthetically useful
triazole-based vinylbromide 9aa in 40% yield along with fully
debrominated product 4aa in 40% yield through elimination of
bromine (Scheme 2). Further, we synthesized the N-alkyl
substituted 1,2,3-triazoles 10ea and 10la through hydrogenation
reaction of fully substituted 1-vinyl-1H-1,2,3-triazole 4ea and 1-
styryl-1H-1,2,3-triazole 6la using hydrogen balloon under 10-
mol% of Pd/C in methanol at 25 °C for 1 h. In a single step,
Scheme 3: Controlled experiments.
compound
of
5-methyl-1-(1-phenylethyl)-1H-1,2,3-triazole-4-
The mechanism for the selective synthesis of 4/6 through the
reaction of 1, 2/5 and 3f is illustrated in Scheme 4.[5l] Reaction of
the catalyst TBD 3f (pKa = 26.03 in CH3CN) with activated
carbonyls 1 generates the enolate 15, which on in situ treatment
with reactive vinyl-N3 2/5 furnishes selectively the functionalized
1,2,3-triazolines 16 via concerted [3+2]-cycloaddition or stepwise
amination-cyclization reaction, which further transforms into the
carboxylic acid 10ea was isolated in 90% yield and 1-(5-methyl-1-
phenethyl-1H-1,2,3-triazol-4-yl)ethanone 10la was isolated in
85% yield (Scheme 2). These results highlights advantages of the
organo-click reactions, which enables a quick synthesis of N-alkyl
substituted 1,2,3-triazoles.
Scheme 2: Reaction application.
4
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10.1002/ejoc.201601497
European Journal of Organic Chemistry
COMMUNICATION
stable 1,2,3-triazole 4/6 through rapid elimination of water
induced by the basic nature of 3f.
[2]
For the 1,2,3-triazoles as amide isosteres, 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.
[3]
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.
V. Fokin, K. B. Sharpless, Angew. Chem. Int. Ed. 2002, 41, 2596-2599;
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) S. T. Laughlin,
J. M. Baskin, S. L. Amacher, C. R. Bertozzi, Science 2008, 320, 664-
667; h) B. Gold, G. B. Dudley, I. V. Alabugin, J. Am. Chem. Soc. 2013,
135, 1558-1569.
Scheme 4: Reaction mechanism.
In summary, for the first time we have developed the TBD-
catalyzed regiospecific synthesis of 1,4,5-trisubstituted N-vinyl-
1,2,3-triazoles 4/6 from simple activated carbonyls 1 and N-vinyl
azides 2/5 via [3+2]-cycloaddition reaction. The click reaction
proceeds in excellent yields with high rate and selectivity using
TBD 3f as the organocatalyst within a few hours at 25 C. Further
work is in progress to develop the application of these products in
medicinal to material chemistry.
[4]
For the enamine-mediated organocatalytic click 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;
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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.
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We thank
SERB,
DST
(New Delhi)
[Grant
No.:
EMR/2015/000860] for financial support. JG and GSR thank
CSIR (New Delhi) and UGC (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))
Keywords: click reaction • carbonyls • organocatalysis • 1,2,3-
triazoles • vinyl azides
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European Journal of Organic Chemistry
COMMUNICATION
Entry for the Table of Contents
N-Vinyl-1,2,3-Triazoles (OR)
Organocatalytic Click Reactions
D. B. Ramachary,* Jagjeet Gujral,
Swamy Peraka and G. S. Reddy__Page
– Page
Triazabicyclodecene as an
Organocatalyst for Regiospecific
Synthesis of 1,4,5-Trisubstituted N-
Vinyl-1,2,3-Triazoles
Simple organocatalyst, TBD-catalysed an enolate-mediated vinyl azide–
carbonyl [3+2]-cycloaddition of various activated carbonyls with vinyl azides to
furnish the functionally rich N-vinyl-1,2,3-triazoles.
7
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