Synthesis of substituted imidazolines by an Ugi/Staudinger/aza-Wittig sequence

Article abstract of DOI:10.1016/j.tetlet.2015.01.043

A series of 2-(acetamide-2-yl)-imidazolines (II) with 5 points of diversity were prepared by an Ugi-4CR-Staudinger-aza-Wittig-sequence starting from simple azidoalkylamines. The intramolecular aza-Wittig cyclization between the iminophosphane and the tertiary amide of the Ugi product (I) was effected by short microwave irradiation. Competitive cyclization to the secondary amide was not relevant, however, in some cases subsequent formation of the bicyclic ortho-amidines (III) was observed.

Full text of DOI:10.1016/j.tetlet.2015.01.043

Tetrahedron Letters 56 (2015) 1025–1029
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Tetrahedron Letters
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Synthesis of substituted imidazolines by an Ugi/Staudinger/
aza-Wittig sequence
b
b
b
b
Sebastian J. Welsch a, , Michael Umkehrer , Cedric Kalinski , Günther Ross , Christoph Burdack ,
⇑
Jürgen Kolb b, Martina Wild b, Anja Ehrlich a, Ludger A. Wessjohann a
a Leibniz-Institut für Pflanzenbiochemie, Weinberg 3, 06120 Halle a. d. Saale, Germany
b Priaxon AG, Rupert-Mayer-Str. 46, 81379 Muenchen, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
A series of 2-(acetamide-2-yl)-imidazolines (II) with 5 points of diversity were prepared by an Ugi-4CR–
Staudinger–aza-Wittig-sequence starting from simple azidoalkylamines. The intramolecular aza-Wittig
cyclization between the iminophosphane and the tertiary amide of the Ugi product (I) was effected by
short microwave irradiation. Competitive cyclization to the secondary amide was not relevant, however,
in some cases subsequent formation of the bicyclic ortho-amidines (III) was observed.
Ó 2015 Elsevier Ltd. All rights reserved.
Received 5 November 2014
Revised 29 December 2014
Accepted 6 January 2015
Available online 12 January 2015
Keywords:
Multicomponent reaction
Ugi reaction
Staudinger reaction
Aza-Wittig reaction
ortho-Amidine
Microwave
Introduction
which constrain the Ugi product, thereby enhancing its drug prop-
erties) they offer quick and easy access to a huge and diverse
In the last fifteen years the intramolecular aza-Wittig reaction
has been established as a versatile and reliable organic transforma-
tion for the construction of small and medium sized nitrogen con-
taining heterocycles.1–9 It is usually conducted under mild
conditions (neutral solvent, no acid, base or catalyst), high yielding
and possesses good chemoselectivity, which altogether often
marks it as the reaction of choice for natural product synthe-
ses.10–15 A wide variety of carbonyls can be used as substrates:
aldehydes, ketones, carboxylic anhydrides,6 acyl halides,14 hetero-
cumulenes (ketenes, (thio)isocyanates, CO2, CS2),14,16–18 (thio)e-
ster,6,19–21 urethanes,22 and sulfoxides.6 Amides have long been
considered inert under these conditions23–25 but were found to
be reactive if properly activated by electron withdrawing substitu-
ents, that is, as imides,13,24–28 acylureas,29 or N-tosylated amides.19
Reaction examples for unactivated amides are scarce and usually
suffer from inferior yields.23,30–32
chemical space of pharmacologically relevant scaffolds.35–39
Several examples of MCR-Staudinger–aza-Wittig sequences
have been published with both Ugi30,40–46 and Passerini47–50 reac-
tions. For combinations of an Ugi reaction followed by (Stauding-
er)–aza-Wittig cyclization there is only one report for each, the
use of an alkyl azide (as opposed to aryl azides yielding benzene
annulated products)42 and the involvement of one of the amide
functions generated during the Ugi reaction in the aza-Wittig
cyclization.30
Based on these findings we envisioned the synthesis of 2-
(acetamid-2-yl)-imidazolines with up to five points of diversity
by means of an Ugi/Staudinger/aza-Wittig sequence (Scheme 1).
Not only would this transformation reduce the peptide charac-
ter of the primary Ugi product but also enable the rapid
synthesis of (dihydro-)imidazolines. This interesting scaffold has
found numerous uses, that is, in natural product chemistry,10
pharmaceutical chemistry,51 organic synthesis,19 coordination
chemistry, and heterogeneous catalysis.52 It should be noted
that another MCR-based synthesis for this compound class has
been published by Hulme et al. using their UDC-strategy
(Ugi-DeBOC-Cyclization).53 In comparison our approach produces
Multicomponent reactions in general and especially the highly
versatile and robust Ugi reaction33,34 are well-established tools
for the generation of screening libraries. In combination with suit-
able post-condensation modifications (i.e., usually cyclizations
a
different substitution pattern and has the advantage of
⇑
Corresponding author.
E-mail addresses: Sebastian.Welsch@student.uni-halle.de (S.J. Welsch), Ludger.
neutral cyclization conditions which enable the use of acid
labile substrates.
Wessjohann@ipb-halle.de (L.A. Wessjohann).
http://dx.doi.org/10.1016/j.tetlet.2015.01.043
0040-4039/Ó 2015 Elsevier Ltd. All rights reserved.

1026
S. J. Welsch et al. / Tetrahedron Letters 56 (2015) 1025–1029
Table 1
Results and discussion
Evaluation of reaction conditions
Therefore we started with an Ugi reaction between suitably
substituted amines, isobutyraldehyde, benzoic acid, and benzyl
isocyanide in methanol (1 M) at room temperature (Scheme 2).
While 2-bromoethylamine (used as its hydrobromide salt and lib-
erated in situ with 1 equiv of NEt3) gave no product formation at
all, 2-aminoethanol reacted smoothly to the desired product and
was isolated after column chromatography in 72% yield. Transfor-
mation into the azide was effected with known methods:54 After
activation with MsCl in dry THF and subsequent treatment with
an excess of sodium azide at room temperature, 1a was obtained
in 81% yield. Reacting 1a with 1 equiv of triphenylphosphine in
dry toluene led to visible gas evolution and the intermediate imi-
nophosphane, this was then heated in a microwave reactor to
150 °C for 20 min. HPLC/MS analysis indicated (1) that iminophos-
phane formation was complete after 1 h, and (2) that the aza-Wit-
tig cyclization yielded only a single product without any side
products. Analysis by NMR spectroscopy (gHMBC, NOESY) con-
firmed the imidazoline structure. Crosspeaks were found in the
gHMBC spectrum between all of the –CH2CH2– protons and only
one C(@X)N carbon, and in the NOESY spectrum between one
methyl group, the isopropyl-H, and two protons of the ethylene
bridge (cf. supporting information). Especially the latter rules out
the aminopiperazine structure as the respective groups are placed
at opposite sides of the core cycle. Furthermore these findings are
consistent with the observation of Zhong et al. who found that only
the tertiary amide of an Ugi product reacts in an intramolecular
aza-Wittig cyclization.30
Entry Conditions
Resulta
1
2
3
4
5
6
7
50 °C
80 °C
110 °C
130 °C
No reaction
No reaction
Conversion <10%
Conversion >95%
Clean, complete conversion
Clean, complete conversion
Slight side product formation
150 °C
Reflux, 1 h
Ambient
atmosphere
8
9
Non-dry toluene Slight side product formation
Resin bound
Longer reaction time for iminophosphane
formation, clean, complete conversion
PPh3 (1 equiv)
Reaction conditions unless noted otherwise: 1 equiv PPh3, dry toluene, nitrogen
atmosphere, microwave, 150 °C, 10 min unless stated otherwise.
a
Estimated by HPLC/MS.
observe any side product formation or other adverse effects at this
temperature.
The reaction can be run with conventional heating, too (Table 1,
entry 6). Exclusion of air and moisture is not strictly necessary but
advantageous as far as side product formation is concerned
(entries 7 and 8).
When triphenylphosphine is replaced with its polymer bound
equivalent (1.2–1.5 mmol/g, crosslinked with 1% divinylbenzene,
200–400 mesh) the reaction time of the Staudinger reaction is sig-
nificantly increased but in return the pure product can be obtained
by simple filtration and washing with dichloromethane in near
quantitative yield.
With these promising results we turned to examine the reaction
conditions (Table 1). First several runs at different temperatures for
10 min were performed: unsurprisingly, no reaction took place at
lower temperatures. At 110 °C the conversion started, at 130 °C
the reaction was nearly complete, and at 150 °C no more starting
material could be detected. Given the fact that 10 min. at 130 °C
led to near complete conversion we assumed that the reaction is
probably finished within a minute at 150 °C. Nonetheless we did
not reduce the reaction time further for two reasons: first to keep
a safety margin for substituents that do not perform as well as
those in this single example, and second because we did not
With this optimized protocol at hand we started synthesizing a
small library to evaluate the influence of the different substituents.
In order to further simplify the synthesis we switched from 2-ami-
noethanol to 2-azidoethylamine which can be easily prepared in
multigram quantities in one step from cheap 2-bromoethyl-
amine.55 Substituted azidoethylamines were synthesized from
the corresponding amino alcohols according to Wannaporn et al.54
The Ugi reactions with these azidoalkylamines were noticeably
exothermic and surprisingly fast—in most cases the reaction was
finished in less than 5 min, yet clean and high yielding. The yield
primarily depends on the isocyanide (benzyl isocyanide gave the
R1
R2 R2'
R2 R2'
R1
H
N
H
N
1. Staudinger
2. aza-Wittig
1. Ugi-4CR
(2. SN)
NH2
R4
R1
R2
R2'
R3
N
R3
O
N
X
CN
N
R3
+
OH
+
+
N3
O
O
R4
O
O
R4'
X = N3, Br, OH
R4
R4'
R4'
Scheme 1. Imidazoline synthesis by an Ugi–Staudinger–aza-Wittig sequence.
H
N
N
O
H
N
N
NH2
O
1b 54%
(i)
(iii)
N
+
+
+
CN
O
O
X
O
O
OH
H
N
X
N
1a'' X = Br
1a' X = OH
1a X = N3
0%
72%
81%
N
(ii)
Scheme 2. Reagents and conditions: (i) (MeOH), rt, 22 h, 72%; (ii) (a) MsCl, NEt3, (dry THF), rt, overnight, (b) NaN3, (dry DMF), rt, 6 h, 81%; (iii) (a) PPh3, (dry toluene), rt, 2 h,
(b) microwave, 150 °C, 20 min, 54%.

S. J. Welsch et al. / Tetrahedron Letters 56 (2015) 1025–1029
1027
best results of our set). The relatively low yield for entry 16 can be
attributed to the fact that this amine had to be used as its hydro-
chloride salt and was liberated in situ with 1 equiv of triethyl-
amine. Since Ugi reactions perform best in acidic and not well in
basic medium,35 this is not ideal, but generation of the free base
prior to the Ugi reaction leads to no product formation at all. In
two instances the two diastereomers could be separated (entries
15 and 16).
giving mixtures with a de of 1/3. One remarkable difference in
the cyclization of the two diastereomers of 15a is that d1 reacted
quantitatively without any side products or o-amidine formation
whereas d2 produced not only less 15b but also a significant
amount of 15c. In general the amount of o-amidine formed seems
to be dependent on the size of R1 (steric shielding of the amidine),
0
0
R2/R2 (Thorpe–Ingold effect), and the steric repulsion of R4/4 and
R2 (Scheme 3 and Table 2).
The cyclization proved to be very reliable, producing the desired
imidazolines in often quantitative amount. In some cases an addi-
tional purification by column chromatography was required which
is reflected in reduced yields (entries 7, 12, 13). Both electron rich
and poor aromatic substituents are tolerated for R1 (entries 2–5).
For the cyclization of 6a and 7a two scouting experiments were
performed with normal triphenylphosphine to ensure that the
reaction time is sufficient. While 6a was completely converted
within the given 10 min, 7a required 30 min. Both reactions show
in their HPL chromatograms some side product formation. In the
course of the subsequent purification by column chromatography
6b hydrolyzed completely. When the experiment was repeated,
we noticed that (1) the product obtained was actually a 1/1 mix-
ture of amidine 6b and ortho-amidine 6c (vide infra), and (2) that
6b was converted for the most part upon standing in CDCl3 at room
temperature to 6c within one day (Fig. 1). Further attempts to iso-
The o-amidines were identified and characterized by NMR-
spectroscopy. In the 1H spectrum of 6c, the signals of the benzylic
protons exhibit only a geminal coupling of 2J = 14.6 Hz and are
more separated than the dd correlating to the NHCH2Ph group of
the aza-Wittig product. This indicates a reaction of the amid-NH
of 6a with concomitant conformational fixation. Additionally, there
is a new singlet at 5.20 ppm which is linked to a carbon-signal at
91.0 ppm; both values are similar to what is expected for a
CHNN0N00 moiety and described in the only publication we have
found for this type of structure.56 Further another new, broad sin-
glet for the CHNHN0N00 shows at 2.1 ppm. This signal shows cou-
pling in a NOESY experiment to the imidazoline –CH2-through
spin diffusion (cross peak with the same phase as the diagonal
peaks). Isolation of the o-amidines was attempted but failed due
to hydrolysis of the product (6c), re-equilibration (10b/c), or insuf-
ficient yield (15c).
late 6c were unfruitful due to rapid hydrolysis of the product.
Attempts to expand this methodology to the synthesis of larger
ring cyclic amidines were unsuccessful (Scheme 4). 3-Azidopropyl-
amine was prepared in analogy to 2-azidoethylamine55 and
reacted as smoothly in the Ugi reaction. Iminophosphorane forma-
tion was unproblematic but the cyclization yielded only a mixture
of (eventually) hydrolyzed or otherwise deteriorated products.
Finally we examined the synthesis of amidines with different
substitution patterns by placing the azido group at other residues
of the Ugi product (scheme 5). Unfortunately all attempts were
met with failure. Chloroacetone (scheme 5, (1)) could be reacted
with 2-methoxyethylamine, benzoic acid, and benzyl isocyanide
in an Ugi reaction but reacted during the reaction to give i.a. 18a
0
The carbonyl residues R2, R2 have no adverse influence either as
long as at least one of them is an H (entries 8 and 9). For geminal
substitutions (entry 10) exerting a strong Thorpe–Ingold effect for
the second cyclization, the formation to the ortho-amidine 10c
occurred in varying amounts (50% and 17% NMR yield in two sep-
arate runs); that is, obviously the rate of equilibration depends on
subtle influences like pH. Substitution at the azide side chain is tol-
erated in both
a- and b-positions. Unlike the a-carbon which
retains its stereochemical configuration during the aza-Wittig
cyclization even with R4 = Ph (entry 15) the b-carbon is configura-
tionally not stable: Both diastereomers of 16a racemized partially
Figure 1. 1H NMR spectra of the cyclization products of 6a. Top: directly after the cyclization: 6b/6c = 3/2. Bottom: same sample after standing 24 h at room temperature: 6b/
6c = 1/5.
R1
R2
R2'
O
R1
R2 R2'
R3
R2 R2'
R1
H
N
N
H
N
R2
1. Staudinger
2. aza-Wittig
O
OH
O
O
N
R3
R1
HN
N
R3
Ugi-4CR
R2'
+
+
N
N
NH2
R4
N3
O
R4
O
R4
N3
CN
R4
R4'
R3
R4'
R4'
R4'
Scheme 3. General reaction scheme.

1028
S. J. Welsch et al. / Tetrahedron Letters 56 (2015) 1025–1029
Table 2
Compounds synthesized by Ugi–Staudinger–aza-Wittig-sequence
0
0
Entry
R1
R2, R2
R3
R4, R4
Ugi product
Yielda
Imidazoline
Yielda
o-Amidine
Yieldb
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
Ph
4-Cl-Ph
4-Meo-Ph
2-Thiophenyl
4-Pyridyl
H
Me
Ph
Ph
Ph
iPr, H
iPr, H
iPr, H
iPr, H
iPr, H
iPr, H
iPr, H
H, H
Ph, H
Me, Me
iPr, H
iPr, H
iPr, H
iPr, H
iPr, H
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Bn
H, H
H, H
H, H
H, H
H, H
H, H
H, H
H, H
H, H
H, H
H, H
H, H
H, H
Bn, H
Ph, H
1a
2a
3a
4a
5a
6a
7a
8a
90%
85%
92%
84%
90%
79%
87%
89%
85%
87%
64%
60%
59%
93%
d1: 54%
d2: 36%
d1: 21%
d2: 22%
1b
2b
3b
4b
99%
97%
99%
69%
92%
0%
60%
99%
1c
2c
3c
4c
0%
< 2%
0%
0%
7%
80%.
4%
0%
0%
15–50%
0%
7%
10%
5%
d1: 0%
d2: 25%
d1: 0%
d2: 0%
5b
5c
6b
6c
7bc
8b
7cc
8c
Bn
Bn
9a
9b
99%
9c
10a
11a
12a
13a
14a
15a
10b
11b
12b
13b
14b
15b
0% (50–85%)b
99%
10c
11c
12c
13c
14c
15c
Ph
Ph
Ph
Ph
Ph
tBu
79%
72%
93%
d1: 99%
d2: 36%d
d1: 74%
d2: 97%
–(CH2)2OMe
Bn
Bn
Ph
16
Ph
iPr, H
Bn
H, Me
16a
16b
16c
a
b
c
Isolated yield.
Determined by 1H NMR analysis of the reaction mixture.
Reaction time: 30 min.
TFA salt.
d
O
O
H
N
Ph
1) PS-PPh3, rt
2) MW, 150 °C
(abs. tol.)
OH
NH2
H
N
O
N
hydrolyis
N
N
(MeOH)
RT
O
+
O
N3
17a 86%
CN
N3
Scheme 4. Attempted tetrahydropyrimidine synthesis.
N3
Cl
HO
NH2
H
N
H
(1)
+
N
+
+
O
N
(MeOH)
CN
O
N
O
RT
O
O
O
O
OH
O
O
18a 13%
Cl
Cl
Cl
O
O
OH
OH
O
O
NH2
(2)
+
H
N
+
+
+
H
N
(MeOH)
RT
CN
HO
O
O
N
HN
O
OH
O
19a
19a'
H
OH
N
NH2
CN
N
(3)
+
+
+
(MeOH)
RT
O
O
O
O
Cl
X
20a' X = Cl 75%
20a N3 99%
Scheme 5. Permutations examined.

S. J. Welsch et al. / Tetrahedron Letters 56 (2015) 1025–1029
1029
13. He, F.; Foxman, B. M.; Snider, B. B. J. Am. Chem. Soc. 1998, 120, 6417.
14. Molina, P.; Díaz, I.; Tárraga, A. Synlett 1995, 1031.
15. Molina, P.; Fresneda, P. M.; García-Zafra, S.; Almendros, P. Tetrahedron Lett.
1994, 35, 8851.
16. Kochubey, V. S.; Blochin, Y. S.; Rodin, O. G.; Perevalov, V. P. Chem. Heterocycl.
Compd. 2006, 42, 897.
17. Molina, P.; Fresneda, P. M.; Sanz, M. A. J. Org. Chem. 1999, 64, 2540.
18. Molina, P.; Fresneda, P. M.; Almendros, P. Synthesis 1993, 54.
19. Loos, P.; Ronco, C.; Riedrich, M.; Arndt, H.-D. Eur. J. Org. Chem. 2013, 3290
20. Okawa, T.; Eguchi, S. Tetrahedron Lett. 1996, 37, 81.
21. Kurita, J.; Iwata, T.; Yasuike, S.; Tsuchiya, T. J. Chem. Soc., Chem. Commun. 1992,
81
22. Majumdar, K. C.; Ganai, S. Beilstein J. Org. Chem. 2013, 9, 503.
23. Alajarín, M.; Molina, P.; Vidal, A.; Tovar, F. Synlett 1998, 1288.
24. Eguchi, S.; Takeuchi, H. J. Chem. Soc., Chem. Commun. 1989, 602
25. Molina, P.; Alajarín, M.; López-Leonardo, C.; Madrid, I.; Foces-Foces, C.; Cano, F.
Tetrahedron 1989, 45, 1823.
in a low yield. Activation with mesyl chloride and subsequent
treatment with sodium azide in dry DMF at 50 °C led to complete
degradation of the starting material within 5 h. We reasoned that
this might be attributed to the quaternary carbon next to the leav-
ing group. Therefore we tried to substitute chloroacetone with gly-
colaldehyde. The Ugi reaction with its dimer yielded a mixture of
the regular Ugi-4CR product 19a and an isomer 19a0, resulting from
an alternative Mumm-type rearrangement with the alcohol as the
internal nucleophile. The mixture proved inseparable by standard
column chromatography and was therefore abandoned.57,58 As last
permutation we tried to place the azide at the acid derived side
chain. Ugi reaction with chloroacetic acid gave 20a which was eas-
ily converted into azide 20a0. Treatment with triphenylphosphine
led to the corresponding iminophosphane which refused to cyclize.
Even at 180 °C for 1 h neither traces of the desired product nor any
degradation products were formed. Seemingly the steric hindrance
26. Chan, J.; Faul, M. Tetrahedron Lett. 2006, 47, 3361.
27. Ortiz Barbosa, Y. A.; Hart, D. J.; Magomedov, N. A. Tetrahedron 2006, 62, 8748.
28. Takeuchi, H.; Hagiwara, S.; Eguchi, S. Tetrahedron 1989, 45, 6375.
_
29. Üngören, Sß. H.; Kani, I.; Günay, A. Tetrahedron Lett. 2012, 53, 4758.
with an isopropyl and a tert-butyl group
respectively, are sterically too demanding.
a
and a0 to the carbonyl,
30. Zhong, Y.; Wang, L.; Ding, M.-W. Tetrahedron 2011, 67, 3714.
31. Kumagai, N.; Matsunaga, S.; Shibasaki, M. Angew. Chem., Int. Ed. 2004, 43, 478.
32. Gololobov, Y.; Gusar’, N.; Chaus, M. Tetrahedron 1985, 41, 793.
33. Ugi, I.; Steinbrückner, C. Chem. Ber. 1961, 94, 2802.
34. Ugi, I.; Steinbrückner, C. Angew. Chem. 1960, 72, 267.
35. Wessjohann, L. A.; Kaluderovic, G. N.; Neves Filho, R. A. W.; Morejon, M. C.;
Lemanski, G.; Ziegler, T. In Science of Synthesis; Müller, T. J. J., Ed.; Thieme
Chemistry: New York, 2013.
Conclusion
In summary we have developed a novel route to substituted 2-
(acetamid-2-yl)-imidazolines with up to five points of diversity by
an Ugi–Staudinger–aza-Wittig sequence. This 3-step procedure
offers a quick and high yielding (up to 91% overall yield) entry to
this important structural class. In some cases intramolecular cycli-
zation to the corresponding ortho-amidines was observed.
36. Dömling, A. Chem. Rev. 2006, 106, 17.
37. Ayaz, M.; de Moliner, F.; Dietrich, J.; Hulme, C. In Applications of Isocyanides in
IMCRs for the Rapid Generation of Molecular Diversity; Nenajdenko, V. G., Ed.;
Wiley-VCH: Weinheim, 2012; pp 335–384.
38. Hulme, C.; Gore, V. Curr. Med. Chem. 2003, 10, 51.
39. Multicomponent reactions; Zhu, J., Bienaymé, H., Eds.; Wiley-VCH: Weinheim,
2005.
40. He, P.; Nie, Y.-B.; Wu, J.; Ding, M.-W. Org. Biomol. Chem. 2011, 9, 1429.
41. He, P.; Wu, J.; Nie, Y.-B.; Ding, M.-W. Eur. J. Org. Chem. 2010, 1088
42. Lecinska, P.; Corres, N.; Moreno, D.; García-Valverde, M.; Marcaccini, S.;
Torroba, T. Tetrahedron 2010, 66, 6783.
43. Sañudo, M.; García-Valverde, M.; Marcaccini, S.; Delgado, J. J.; Rojo, J.; Torroba,
T. J. Org. Chem. 2009, 74, 2189.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2015.01.
043.
44. Corres, N.; Delgado, J. J.; García-Valverde, M.; Marcaccini, S.; Rodríguez, T.;
Rojo, J.; Torroba, T. Tetrahedron 2008, 64, 2225.
45. Ramazani, A.; Rezaei, A. Org. Lett. 2010, 12, 2852.
46. Wang, Y.; Xie, H.; Pan, Y.-R.; Ding, M.-W. Synthesis 2014, 46, 336.
47. He, P.; Wu, J.; Nie, Y.-B.; Ding, M.-W. Tetrahedron 2009, 65, 8563.
48. de Moliner, F.; Crosignani, S.; Banfi, L.; Riva, R.; Basso, A. J. Comb. Chem. 2010,
12, 613.
49. Wang, L.; Ren, Z.-L.; Chen, M.; Ding, M.-W. Synlett 2014, 721.
50. Wu, J.; Liu, J.-C.; Wang, L.; Ding, M.-W. Synlett 2011, 2880.
51. Vassilev, L. T. Science 2004, 303, 844.
52. Liu, H.; Du, D.-M. Adv. Synth. Catal. 2009, 351, 489.
53. Hulme, C.; Ma, L.; Romano, J.; Morrissette, M. Tetrahedron Lett. 1999, 40, 7925.
54. Wannaporn, D.; Ishikawa, T. Mol. Divers. 2005, 9, 321.
55. Sinha, M. K.; Reany, O.; Yefet, M.; Botoshansky, M.; Keinan, E. Chem. Eur. J.
2012, 18, 5589.
References and notes
1. Tron, G. C. Eur. J. Org. Chem. 2013, 1849
2. Qingyun, R.; Xiaosong, T.; Hongwu, H. Curr. Org. Synth. 2011, 8, 752.
3. Organic Azides; Bräse, S., Banert, K., Eds.; John Wiley: Chichester, 2010; pp 1–
507.
4. Palacios, F.; Aparicio, D.; Rubiales, G.; Alonso, C.; de los Santos, J. M. Curr. Org.
Chem. 2009, 13, 810.
5. Hajos, G.; Nagy, I. Curr. Org. Chem. 2008, 12, 39.
6. Palacios, F.; Alonso, C.; Aparicio, D.; Rubiales, G.; de los Santos, J. M. Tetrahedron
2007, 63, 523.
7. Bräse, S.; Gil, C.; Knepper, K.; Zimmermann, V. Angew. Chem., Int. Ed. 2005, 44,
5188.
56. Kosasayama, A.; Konno, T.; Higashi, K.; Ishikawa, F. Chem. Pharm. Bull. 1979, 27,
848.
57. Mossetti, R.; Pirali, T.; Tron, G. C. J. Org. Chem. 2009, 74, 4890.
58. Kim, Y. B.; Choi, E. H.; Keum, G.; Kang, S. B.; Lee, D. H.; Koh, H. Y.; Kim, Y. Org.
Lett. 2001, 3, 4149.
8. Eguchi, S. ARKIVOC 2005, 98.
9. Molina, P.; Vilaplana, M. J. Synthesis 1994, 1197.
10. Guinchard, X.; Vallée, Y.; Denis, J.-N. J. Org. Chem. 2007, 72, 3972.
11. Fresneda, P. M.; Molina, P.; Delgado, S. Tetrahedron 2001, 57, 6197.
12. Fresneda, P. M.; Molina, P.; Delgado, S. Tetrahedron Lett. 1999, 40, 7275.