Metal-free DBU promoted regioselective synthesis of isoxazoles and isoxazolines

Article abstract of DOI:10.1039/c4ra14694h

A new simple and efficient metal-free 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) promoted regioselective synthesis of 3,5-disubstituted isoxazoles and isoxazolines from aldoximes has been described. This method allows the reaction to proceed efficiently on aldoximes containing unprotected phenolic hydroxyl groups. Furthermore, with the use of higher equivalents of N-chlorosuccinimide, chloro-substituted isoxazoles and isoxazolines were obtained as the only products via tandem one-pot 1,3-dipolar cycloaddition followed by regioselective chlorination. This journal is

Full text of DOI:10.1039/c4ra14694h

View Article Online
View Journal
RSC Advances
This article can be cited before page numbers have been issued, to do this please use: S. Mohammed,
R. A. Vishwakarma and S. B. Bharate, RSC Adv., 2014, DOI: 10.1039/C4RA14694H.
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
Accepted Manuscripts are published online shortly after
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. This Accepted Manuscript will be replaced by the edited,
formatted and paginated article as soon as this is available.
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the Ethical guidelines still
apply. In no event shall the Royal Society of Chemistry be held
responsible for any errors or omissions in this Accepted Manuscript
or any consequences arising from the use of any information it
contains.
www.rsc.org/advances

RSC Advances
Page 1 of 4RSC Advances
Dynamic Article Links ►
View Article Online
DOI: 10.1039/C4RA14694H
Cite this: DOI: 10.1039/c0xx00000x
www.rsc.org/xxxxxx
Communication
Metal-free DBU promoted regioselective synthesis of isoxazoles and
isoxazolines†‡
Shabber Mohammed,ab Ram A. Vishwakarma,ab Sandip B. Bharateab*
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
5
DOI: 10.1039/b000000x
4
hypervalent iodine.2g, Many hypervalent iodine reagents are
A
new
simple
and
efficient
metal-free
1,8-
explosive and have chemical reactivity issues.5 Apart from the
use of hypervalent iodine, only two other metalꢀfree conditions
35 (Et3N,6 NaOCl/Et3N7) have been reported. However, the former
reaction was not suitable for phenolic hydroxyl comtaining
aldoximes; and later condition has been reported for only one
example. The detailed substrate scope has never been established.
In this context, we thought of exploiting this reaction to establish
40 an efficient and elegant metalꢀfree protocol for synthesis of
isoxaxoles and isoxazolines with broad substrate scope. Our
efforts identified 1,8ꢀdiazabicyclo[5.4.0]undecꢀ7ꢀene (DBU) as
an excellent reagent which promotes 1,3ꢀdipolar addition of
nitrile oxides with alkynes/ alkenes without need of any metal
45 catalyst. DBU has been reported to promote synthesis of variety
of heterocyclic scaffolds such as isoquinolinones8 and and
benzothiazoles.9 Herein, we report DBUꢀpromoted synthesis of
3,5ꢀdisubstituted isoxazoles. Furthermore, we also report an
interesting DBUꢀpromoted tandem oneꢀpot 1,3ꢀdipolar
50 cycloaddition reaction followed by regioselective chlorination
(Figure 2).
diazabicyclo[5.4.0]undec-7-ene
regioselective synthesis of 3,5-disubstituted isoxazoles and
isoxazolines from aldoximes has been described. This method
10 allows reaction to proceed efficiently on aldoximes containing
unprotected phenolic hydroxyl group. Furthermore, with the
use of higher equivalents of N-chlorosuccinimide, chloro-
substituted isoxazoles and isoxazolines were obtained as the
only products via tandem one-pot 1,3-dipolar cycloaddition
15 followed by regioselective chlorination.
(DBU)
promoted
Isoxazoles1 and isoxazolines are fiveꢀmembered nitrogen
containing heterocycles commonly found in variety of natural
products and drugs and are known to exhibit wide range of
pharmacological activities. The structures of biologically active
20 isoxazoles/ isoxazolines A-E are shown in Figure 1.1
O
N
O
N
O
S
O
O
O
O
N
O
NH2
N
N
Cl
Ph
EtO
Ph
O
N
R2 "metal-free"
1,3-dipolar
O
Valdecoxib (C)
B
N
A
OH
Cl
O
NSAID, COX-2 inhibitor
COX-1 inhibitor
N
DBU
HCl
anti-TB
+
R2
N
cycloaddition
Ar
O
O
N
O
Ar
N
O
Ph
HO
Cl
Isoxazoles
Isoxazolines
O
N
Ar
OMe
1.2 equiv.
NCS
HN
F
Nitrile oxide
N
E
O
F
D
OH
O
Tandem
1,3-dipolar
cycloaddition
&
Regioselective
chlorination
O
N
Nicotinic receptor modulators
Antiviral
MIF inhibitor
N
DBU
R2
extra equiv. of NCS
Cl
Ar
Aldoximes
Ar
"metal-free"
Figure 1. Examples of bioactive isoxazoles and isoxazolines
Chloro-isoxazoles
Chloro-isoxazolines
Although numerous methods have been reported for synthesis of
isoxazoles,2 the cycloaddition of alkynes with nitrile oxides is
25 probably the most direct route to access these heterocycles.
Uncatalyzed thermal cycloaddition reaction of nitrile oxide with
Figure 2. DBU promoted synthesis of isoxazoles and isoxazolines
Our investigations were started with the reaction of chloroꢀ
55 aldoxime 2a with phenylacetylene 3a in presence of 1 equiv DBU
in chloroform, which produced desired 3,5ꢀdisubstituted
isoxazole 4a in 10 min in 95% yield (Figure 3). Next, we
elaborated this method for direct synthesis of isoxazole 4a from
aldoxime 1a. Under similar reaction conditions, when the
60 reaction of 4ꢀhydroxyphenyl aldoxime 2a with phenylacetylene
3a in presence of 1.2 equiv NCS was performed, multiple
products were formed. Further, optimization studies indicated
that DMF10 is the best solvent for this reaction and sequential
addition is required to get desired product in good yield (Figure
65 3). The sequential addition (1a+ NCS+DMF, rt, 1 h followed by
addition of DBU and 3a, rt, 10 min) was followed, to get product
4a in good yield, without formation of sideꢀproducts. However,
when we performed this reaction (from 1a) in presence of Et3N
(in place of DBU) under similar reaction conditions, multiple
alkyne is neither chemoꢀ nor regioselective and, as
a
consequence, leads to formation of multiple products. Mostly the
regioselectivity in this reaction has been achieved using Cu
30 catalysts.3 There also exists few metalꢀfree protocols for synthesis
of isoxazoles; however most of these reports involve use of
aMedicinal Chemistry Division, CSIRꢀIndian Institute of Integrative
Medicine, Canal Road, Jammuꢀ180001, India.
bAcademy of Scientific & Innovative Research (AcSIR), CSIRꢀIndian
Institute of Integrative Medicine, Canal Road, Jammuꢀ180001, India.
*Eꢀmail: sbharate@iiim.ac.in
†IIIM Publication number IIIM/1723/2014
Fax: +91ꢀ191ꢀ2569333; Tel: +91ꢀ191ꢀ2569111
‡Electronic supplementary information (ESI) available: NMR spectra of
all compounds. See DOI: 10.1039/xxxx
This journal is © The Royal Society of Chemistry [year]
[journal], [year], [vol], 00–00 | 1

RSC Advances
Page 2 of 4
View Article Online
DOI: 10.1039/C4RA14694H
products were formed; which clearly indicated the superiority of
our protocol over earlier Et3N6 method. The addition of DBU is
slightly exothermic and quickly converts aldoximes to nitrile
oxides which subsequently reacts with respective alkynes/alkenes
to produce desired heterocycles. It is noteworthy to mention that
the direct synthesis of hydroxyꢀsubstituted phenyl isoxazole 4a
from corresponding nitrile oxide has never been reported. The
limitation of earlier methods for hydroxyꢀsubstituted phenyl nitrle
oxides has also been mentioned.3a However, the present DBUꢀ
Further, we examined the scope of this reaction for synthesis of
various substituted isoxazolines using similar reaction conditions
45 (Figure 5). Phenyl, pꢀtolyl and mꢀtolyl aldoximes gave good
yields, irrespective of the location of alkyl substituent (examples
6f, 6g, 6i, 6k, 6l, 6n and 6p). Similarly, the electronꢀrich styrenes
(examples 6h, 6i and 6p) and haloꢀsubstituted styrenes gave good
yields. Among heteroaryl aldoximes, the pyridine aldoxime
50 produced corresponding isoxazoline 6m in good yield, whereas
indole aldoxime produced corresponding isoxazoline 6q,
comparatively in a lesser yield.
5
10 promoted synthesis provided this product in excellent yield.
2
1
O
DBU (1 equiv.)
NCS (1.2 equiv.)
OH
+
N
N
3
R2
5
R2
Ar
DMF, rt, 1-8 h
O
N
4
Ar
1
5
6
Figure 3. DBUꢀpromoted synthesis of 4ꢀhydroxy substituted isozaxole
4a. Reagents and conditions: (a) 1 equiv DBU, CHCl3, rt, 10 min, 95%;
(b) 1 equiv DBU, 1.2 equiv NCS, DMF, 1 h, 80%.
O
OEt
N
O
N
Ph
F
F
6b
(70%)
O
6c
(71%)
6a (85%)
HO
15
N
O
O
N
O
N
N
Ph
Ph
Ph
Ph
Next, the substrate scope of the reaction was investigated for
variety of aldoximes and phenylacetylenes (Figure 4). The
optimized reaction condition involving the use of 1 equiv of DBU
and 1.2 equiv of NCS was employed. Phenyl aldoxime along with
20 those substituted with alkyl electronꢀdonating groups produced
isoxazoles in excellent yields (examples 4b, 4d, 4e, and 4i). In
case of aldoximes substituted with other electronꢀdonating groups
such as OH, OMe (examples 4a, 4c, 4f, 4g and 4j), desired
products were formed in 65ꢀ80% yield. Interestingly, in latter
25 reactions, additionally a ringꢀchlorinated isoxazole products were
obtained as side products in 10ꢀ20% yield. Heterocyclic
aldoximes also participated well in this reaction, producing
desired products 4k and 4l in good yields. It is noteworthy to
mention that the pyridine linked isoxazole 4l prepared herein, has
30 a close structural similarity to that of nicotine receptor modulator
(structure D, Figure 1). Aliphatic oximes (example 4m) and
phenyl aldoxime with electronꢀwithdrawing group (example 4n)
does not participated in this reaction. Among alkynes, all
substituted phenylacetylenes participated well in this reaction,
35 whereas aliphatic alkynes such as propargyl alcohol (example 4j)
and Nꢀpropargylated isatin (example 4h) produced lower yields.
MeO
OMe
OMe
HO
6g
(80%)
6f
6d
(82%)
OMe
(72%)
6e
(70%)
O
N
O
O
N
N
F
OMe
MeO
6h
6j
(70%)
(78%)
6i (80%)
O
N
O
N
O
N
F
F
N
N
F
O
Ph
6n (82%)
6l (85%)
6m
(80%)
OMe
OMe
6k (82%)
Ph
Ph
O
OMe
OMe
N
O
N
O
N
N
6q
(63%)
MeO
6o (72%)
6p
(78%)
H
Figure 5. Scope of the reaction for synthesis of isoxazolines. Reagents
55 and conditions: aldoxime (1 equiv.), styrene (1.2 equiv.), DBU (1 equiv.),
NCS (1.2 equiv.), DMF, 1ꢀ8 h, 63ꢀ85%. Reaction time:1 h for 6b and 6d;
and 8 h for other examples.
Next, we sought to explore the observed finding of oneꢀpot 1,3ꢀ
60 dipolar cycloaddition reaction followed by ring chlorination to
produce chlorinated isoxazoles and isozaxolines (Figure 6). For
this, we thought to use higher equivalents of NCS than the
required amount, to get increased yields of chlorinated products.
To our surmise, when aldoxime 1a was treated with
65 phenylacetylene 3a in presence of 2.2 equivalents of NCS and 1
equiv of DBU, exclusively the chloroꢀsubstituted product 7a was
obtained (88% yield). Similarly, we prepared other chlorinated
isoxazoles 7b, 7c, 7f and 7g using higher equivalents of NCS.
The tandem oneꢀpot 1,3ꢀdipolar cycloaddition followed by
70 regioselective chlorination also worked well for synthesis of
chlorinated isoxazolines (Figure 6; examples 7d, 7e and 7h). In
case of furanꢀ2ꢀaldoxime, the isoxazole product 7g was formed in
good yield (90%), however lower yield (60%) was obtained for
isoxazoline product 7h. In case of indoleꢀ3ꢀaldoxime and
75 pyridineꢀ2ꢀaldoxime, ring chlorination product was not formed
even after using higher equivalents of NCS. It is noteworthy to
mention that the furyl compound 7g has a structural similarity
with reported COXꢀ1 inhibitor (structure B, Figure 1).
Figure 4. Scope of the reaction for synthesis of isoxazoles. Reagents and
conditions: aldoxime (1 equiv.), alkyne (1.2 equiv.), DBU (1 equiv.),
40 NCS (1.2 equiv.), DMF, 1ꢀ8 h, 50ꢀ88%. Reaction time:1 h for 4a, 4f, 4g
and 4j; and 8 h for other examples.
2
| Journal Name, [year], [vol], 00–00
This journal is © The Royal Society of Chemistry [year]

Page 3 of 4
RSC Advances
View Article Online
DOI: 10.1039/C4RA14694H
aldoximes. Additionally, an interesting oneꢀpot protocol for
tandem 1,3ꢀdipolar cycloaddition followed by regioselective ring
35 chlorination has been reported. This methodology was applied to
oneꢀpot synthesis of 4ꢀchloroꢀfurylꢀisoxazole and pyridineꢀ
isoxazole scaffold which are reported to possess potent biological
activities.
Experimental Section
40 General procedure for preparation of isoxazoles 4a-4l,
isoxazolines 6a-6q and chlorinated isoxazole/ isoxazoline
products 7a-7h. To the stirred solution of aldoximes (100 mg, 1
equiv.) in DMF (3 ml) was added Nꢀchlorosuccinimide (1.2 or
2.2 equiv.) at room temperature and reaction was stirred for 0.5ꢀ1
45 h. Then, DBU (1 equiv.) and styrenes or alkynes (1.2 equiv.)
were added and reaction was further stirred for 1ꢀ8 h. After
completion of the reaction (confirmed by TLC), chilled water (20
ml) was added and product was extracted with EtOAc (3 × 10
ml). The organic layer was collected, dried on anhydrous sodium
50 sulphate and solvent was evaporated on rotary evaporator to get
the crude product. The crude product was purified by silica gel
(#100ꢀ200) column chromatography using 2 to 20% EtOAc:
hexane to get pure isoxazoles 4a-4l, isoxazolines 6a-6q or
chlorinated isoxazole/ isoxazoline products 7a-7h in 50ꢀ90%
55 yield. The spectral data of representative compounds 4a, 6a and
7a is shown here. Spectral data of other compounds 4b-4l, 6b-6q
and 7b-7h is provided in ESI.
Figure 6. Oneꢀpot synthesis of chloroꢀsubstituted isoxazoles and
isoxazolines. Reagents and conditions: aldoxime (1 equiv.), styrene or
alkyne (1.2 equiv.), DBU (1 equiv.), NCS (2.2 equiv.), DMF, 8 h, 60ꢀ
90%.
5
Next, we sought to investigate the mechanistic sequence of 1,3ꢀ
dipolar cycloaddition and ring chlorination (Figure 7) reactions
using LCMS analysis. For this, we first performed reaction of
10 aldoxime 1a with phenylacetylene 3a under optimized reaction
conditions (1.2 equiv NCS). The LCMS chromatogram after 30
min reaction time (figure 7a) indicated formation of desired
product 4a (tR = 9.4 min). However, with the use of 2.2 equiv
NCS, the LCMS chromatogram after 40 min indicated formation
15 of chlorinated isoxazole 7a (tR = 10.5 min) along with product 4a
(tR = 9.4 min). Further, when this reaction was monitored after 8
h, the LCMS chromatogram showed solely the formation of
chlorinated product 7a. This study indicated that the chlorination
reaction must be occuring after formation of isoxazole skeleton.
20 In order to further understand the other possibility of first
chlorination and then 1,3ꢀdipolar cycloaddition, we treated
aldoxime 1a with 2.2 equiv of NCS and stirred for 8 h, which
indicated formation of ringꢀchlorinated aldoxime only in 15%,
which further indicates that in oneꢀpot tandem protocol,
25 chlorination occurs after 1,3ꢀdipolar cycloaddition reaction.
4ꢀ(5ꢀPhenylisoxazolꢀ3ꢀyl) phenol (4a).6 White solid; yield 80%;
m. p. 187 – 189 °C ; 1H NMR (400 MHz, CDCl3, ppm): δ 7.83
60 (dd, J = 4, 8Hz, 2H), 7.76 (d, J = 8 Hz), 2H), 7.47 ( m, 3H), 6.95
(d, J = 8 Hz, 2H), 6.78 (s, 1H); 13C NMR (CDCl3 +CD3OD, 125
MHz): δ 170.0, 162.9, 158.8, 130.2, 128.9, 128.2, 127.2, 125.7,
120.0, 115.7, 97.3; IR (CHCl3): νmax 3433, 2925, 1631, 1450,
1353, 1095, 1017 cmꢀ1; ESIꢀMS: m/z 238.08 [M+H]+; HRMS:
65 m/z 238.0864 calcd for C15H11NO2+H+ (238.0864).
3,5ꢀDiphenylꢀ4,5ꢀdihydroisoxazole (6a).4a White solid; yield
85%; m. p. 72ꢀ74 °C; 1H NMR (400 MHz, CDCl3, ppm): δ 7.70
(dd, J = 4.0, 8.0 Hz, 2H), 7.30ꢀ 7.42 (m, 8H), 5.75 (dd, J = 11.0,
8.3 Hz, 1H), 3.79(dd, J = 16.6, 11.0 Hz, 1H), 3.35 (dd, J = 16.6,
70 8.3 Hz, 1H); 13C NMR (CDCl3, 100 MHz): δ 156.1, 140.9, 130.2,
129.4, 128.8, 128.2, 126.7, 125.9, 82.6, 43.2; IR (CHCl3): νmax
3433, 2920, 1730, 1446, 1352, 1120, 893, 751, 686 cmꢀ1; ESIꢀ
MS: m/z 224.10 [M+H]+; HRMS: m/z 224.1084 calcd for
C15H13NO+H+ (224.1070).
75 2ꢀChloroꢀ4ꢀ(5ꢀphenylisoxazoleꢀ3ꢀyl)phenol (7a). White solid;
yield 88%; m. p. 193ꢀ196 °C ; 1H NMR (400 MHz, CDCl3,
ppm): δ 7.89 (d, J = 4.1, Hz, 1H), 7.82ꢀ7.84 (m, 2H), 7.68ꢀ7.71
(m, 1H), 7.47ꢀ7.50 (m, 3H), 7.13 (d, J = 8 Hz, 1H), 6.77(s, 1H),
5.78 (s, 1H); 13C NMR (CDCl3+CD3OD, 125 MHz): δ 170.3,
80 161.9, 154.4, 130.3, 128.9, 128.3, 127.1, 126.3, 125.7, 121.0,
116.7, 97.2; IR (CHCl3): νmax 3346, 2922, 2851, 1594, 1422,
1019 cmꢀ1; ESIꢀMS: m/z 272.04 [M+H]+; HRMS: m/z 272.0481
calcd for C15H10ClNO2+H+ (272.0473).
85 Acknowledgements
Figure 7. LC chromatograms of reaction of 1a with 3a with the change in
NCS equivalents. MS spectras are provided in ESI. The products 4a and
Authors thank analytical department, IIIM for NMR and MS
analysis of our compounds. This work was supported by CSIR
12th FYP grant # BSCꢀ0205. SM is thankful to CSIR for the
award of research fellowship. Authors are grateful to Dr. Ajai P.
90 Gupta and Manoj Kushwaha for LCMS analysis.
7a appears at tR 9.4 and 10.5 min, respectively
.
30
In conclusion, we have developed a new metalꢀfree DBUꢀ
promoted synthesis of isoxazole and isoxazolines from
References and notes
This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00 | 3

RSC Advances
Page 4 of 4
View Article Online
DOI: 10.1039/C4RA14694H
70 10.
K. E. Larsen and K. B. G. Torssell, Tetrahedron, 1984, 40, 2985ꢀ
2988.
1.
For biological activities of isoxazoles and isoxazolines, see: (a) Y.
AlꢀAbed, D. Dabideen, B. Aljabari, A. Valster, D. Messmer, M.
Ochani, M. Tanovic, K. Ochani, M. Bacher, F. Nicoletti, C. Metz,
V. A. Pavlov, E. J. Miller and K. J. Tracey, J. Biol. Chem., 2005,
280, 36541ꢀ36544; (b) R. Kakarla, J. Liu, D. Naduthambi, W.
Chang, R. T. Mosley, D. Bao, H. M. Micolochick Steuer, M.
Keilman, S. Bansal, A. M. Lam, W. Seibel, S. Neilson, P. A.
Furman and M. J. Sofia, J. Med. Chem., 2014, 57, 2136–2160; (c)
A. P. Kozikowski, Acc. Chem. Res, 1984, 17, 410ꢀ416; (d) V. Nair
and T. D. Suja, Tetrahedron, 2007, 63, 12247ꢀ12275; (e) K.
Takenaka, T. Nagano, S. Takizawa and H. Sasai, Tetrahedron:
Asymm., 2010, 21, 379ꢀ381; (f) S. Tapadar, R. He, D. N. Luchini,
D. D. Billadeau and A. P. Kozikowski, Bioorg. Med. Chem. Lett.,
2009, 19, 3023ꢀ3026; (g) K. A. El Sayed, P. Bartyzel, X. Shen, T.
L. Perry, J. K. Zjawiony and M. T. Hamann, Tetrahedron, 2000,
56, 949ꢀ953; (h) M. Gopalakrishnan, J. Ji, C.ꢀH. Lee, T. Li and K.
Sippy, B, 2009, WO2009/149135A1 (Abbott Laboratories); (i) P.
Proksch, A. Putz, S. Ortlepp, J. Kjer and M. Bayer, Phytochem
Rev, 2010, 9, 475ꢀ489; (j) V. Jager and P. A. Colinas, in:
Synthetic applications of 1,3ꢀdipolar cycloaddition chemistry
toward heterocycles and natural products, eds. A. Padwa and W.
H. Pearson, Wiley: Hoboken, NJ, 2002, pp. 361ꢀ472.
5
10
15
20
2.
For synthetic reports on isoxazoles, see: (a) M. P. Bourbeau and J.
T. Rider, Org. Lett., 2006, 8, 3679ꢀ3680; (b) L. Cecchi, F. De
Sarlo and F. Machetti, Eur. J. Org. Chem., 2006, 2006, 4852ꢀ4860;
(c) C.ꢀy. Chen, T. Andreani and H. Li, Org. Lett., 2011, 13, 6300ꢀ
6303; (d) J. A. Crossley and D. L. Browne, J. Org. Chem., 2010,
75, 5414ꢀ5416; (e) E. Gayon, O. Quinonero, S. Lemouzy, E.
Vrancken and J.ꢀM. Campagne, Org. Lett., 2011, 13, 6418ꢀ6421;
(f) O. Jackowski, T. Lecourt and L. Micouin, Org. Lett., 2011, 13,
5664ꢀ5667; (g) S. Minakata, S. Okumura, T. Nagamachi and Y.
Takeda, Org. Lett., 2011, 13, 2966ꢀ2969; (h) M. S. Mohamed
Ahmed, K. Kobayashi and A. Mori, Org. Lett., 2005, 7, 4487ꢀ
4489; (i) C. Praveen, A. Kalyanasundaram and P. T. Perumal,
Synlett, 2010, 2010, 777ꢀ781; (j) S.ꢀR. Sheng, X.ꢀL. Liu, Q. Xu
and C.ꢀS. Song, Synthesis, 2003, 2763ꢀ2764; (k) B. J. Stokes, C.
V. Vogel, L. K. Urnezis, M. Pan and T. G. Driver, Org. Lett.,
2010, 12, 2884ꢀ2887; (l) S. Tang, J. He, Y. Sun, L. He and X. She,
Org. Lett., 2009, 11, 3982ꢀ3985; (m) M. Ueda, A. Sato, Y. Ikeda,
T. Miyoshi, T. Naito and O. Miyata, Org. Lett., 2010, 12, 2594ꢀ
2597; (n) J. P. Waldo and R. C. Larock, J. Org. Chem., 2007, 72,
9643ꢀ9647; (o) B. Willy, F. Rominger and T. J. J. Müller,
Synthesis, 2008, 293ꢀ303.
25
30
35
40
3.
(a) S. B. Bharate, A. K. Padala, B. A. Dar, R. R. Yadav, B. Singh
and R. A. Vishwakarma, Tetrahedron Lett., 2013, 54, 3558ꢀ3561;
(b) T. V. Hansen, P. Wu and V. V. Fokin, J. Org. Chem., 2005, 70,
7761ꢀ7764; (c) F. Himo, T. Lovell, R. Hilgraf, V. V. Rostovtsev,
L. Noodleman, K. B. Sharpless and V. V. Fokin, J. Am. Chem.
Soc., 2004, 127, 210ꢀ216.
45
50 4.
(a) A. Yoshimura, K. R. Middleton, A. D. Todora, B. J. Kastern,
S. R. Koski, A. V. Maskaev and V. V. Zhdankin, Org. Lett., 2013,
15, 4010ꢀ4013; (b) A. Yoshimura, C. Zhu, K. R. Middleton, A. D.
Todora, B. J. Kastern, A. V. Maskaev and V. V. Zhdankin, Chem.
Commun., 2013, 49, 4800ꢀ4802; (c) B. A. Mendelsohn, S. Lee, S.
Kim, F. Teyssier, V. S. Aulakh and M. A. Ciufolini, Org. Lett.,
2009, 11, 1539ꢀ1542; (d) A. M. Jawalekar, E. Reubsaet, F. P. J. T.
Rutjes and F. L. van Delft, Chem. Commun., 2011, 47, 3198ꢀ3200.
55
5.
R. D. Richardson, J. M. Zayed, S. Altermann, D. Smith and T.
Wirth, Angew. Chem. Int. Ed., 2007, 46, 6529–6653.
60 6.
M. A. WeidnerꢀWells, T. C. Henninger, S. A. FragaꢀSpano, C. M.
Boggs, M. Matheis, D. M. Ritchie, D. C. Argentieri, M. P.
Wachter and D. J. Hlasta, Bioorg. Med. Chem. Lett., 2004, 14,
4307–4311.
7.
D. E. Kizer, R. B. Miller and M. J. Kurth, Tetrahedron Lett., 1999,
40, 3535ꢀ3538.
65
8.
9.
W. Chen, J. Cui, Y. Zhu, X. Hu and W. Mo, J. Org. Chem., 2012,
77, 1585−1591.
F. Wang, S. Cai, Z. Wang and C. Xi, Org. Lett., 2011, 13, 3202–
3205.
4
| Journal Name, [year], [vol], 00–00
This journal is © The Royal Society of Chemistry [year]