Sulfide synthesis through copper-catalyzed C-S bond formation under biomolecule-compatible conditions

Article abstract of DOI:10.1039/c4cc08367a

We report here an efficient and mild method for constructing C-S bonds. The reactions were carried out with Na₂S₂O₃ as a sulfurating reagent, CuSO₄ as a catalyst, and water as solvent without any surfactant. The products were achieved in moderate to excellent yields at room temperature under air. Notably, this reaction is compatible with various biomolecules including amino acids, oligosaccharides, nucleosides, proteins, and cell lysates. This journal is

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Sulfide Synthesis through Copper-Catalyzed C-S
Bonds Formation under Biomolecule-Compatible
Conditions
Cite this: DOI: 10.1039/x0xx00000x
Yonghong Zhang†a,c,d, Yiming Li†a, Xiaomei Zhangc and Xuefeng Jianga,b*
Received 00th January 2012,
Accepted 00th January 2012
DOI: 10.1039/x0xx00000x
www.rsc.org/
After elaborate screening, we developed an efficient method for
constructing C–S bonds by cross coupling among 1ꢀ
aryltriazenes, Na2S2O3 and alkyl halides, which employ CuSO4
as catalyst, BF3·Et2O as promoter and use water as solvent without
surfactant at room temperature under air (eq b, Scheme 1).
We report here an efficient and mild method for constructing
C–S bonds. The reactions were carried out with Na2S2O3 as
sulfurating reagent, CuSO4 as catalyst, and water as solvent
without surfactant. The products were achieved in moderate
to excellent yields at room temperature under air. Notably,
this reaction is compatible with various biomolecules
including amino acids, oligosaccharides, nucleosides,
proteins, and cell lysates.
Previous work
Na2S2O3.5H2O
S
I
Pd DMSO 120 o
C
N2
Alkyl
+
+
(a)
(b)
Ar
Ar
Ar
Alkyl-Cl
This work: multielements greenization
R
Recently, biomoleculeꢀcompatible chemical reaction1 have
been applied to many different life science areas including
chemical modification of proteins,2 DNA or RNAꢀtemplated
reactions,3 live cell imaging and biological labeling.4 Although
recent breakthroughs in the area of thiolꢀyne and thiolꢀene
“Click” chemistry have been made as a tool for sulfurꢀ
containing biomolecules synthesis,5 the current methods are far
from adequate. Meanwhile, C–S bonds formation has attracted
extensive attentions due to the importance of thioether.6 It
widely exists in numerous biologically and pharmaceutically
active compounds,7 especially for treatment of HIV, breast
cancer, inflammatory disease, diabetes and Alzheimer’s
disease.8 To date, sulfurꢀcontaining molecules are typically
prepared by the following methods: (a) substitution reactions in
polar solvents at elevated temperatures,9 (b) arylꢀsulfur
coupling reactions catalyzed by transitionꢀmetals based on
palladium,10 nickel,11 copper,12 cobalt13 and iron,14 (c) thiolꢀyne
and thiolꢀene click reactions.5 Traditional sulfide construction
involving thiols, which is unavoidable of metalꢀpoisoning,
Na2S2O3.5H2O
S
N
N
Cu
H2O
rt
Alkyl
air
R'
N
+
+
Ar
Alkyl-X
Catalyst Solvent Energy Atmosphere
1-Aryltriazenes
Scheme 1 Dual CꢀS bonds formations with Na2S2O3.
We commenced our study by using pꢀanisyltriazene (1d) as
model substrate to test our hypothesis (Table 1). Initially, we
examined the influence of the catalysts (entries 1ꢀ4).
CuSO4·5H2O was found to be superior to the others (entry 4),
which produced the desired product 2d in 65% isolated yield.
In the absence of catalyst and ligand, only 20% of 2d was
obtained (entry 5). The reaction could not proceed without
BF3·OEt2 (entry 6). A ligand free system afforded the crossꢀ
coupling reaction sluggishly in 46% isolated yield (entry 7).
Considering the stability of catalyst species, we examined the
influence of different pyridine ligands (entries 8ꢀ10). 2,2'ꢀ
Bipyridine L1 was superior to 1,10ꢀphenanthroline L2, pyridine
L3 or 6,6'ꢀdimethylꢀ2,2'ꢀbipyridine L4. Due to biocompatible
consideration, we decided to investigate the effect of water
(entries 11, 12). Inspiring, it still results moderate yield with
pure water as solvent (entry 13). But phase transfer catalyst
TBAB could not make contribution to the transformation (entry
14). Based on the above results, extensive screening was
conducted. Finally, the reaction yield dramatically improved to
88% by increasing the reaction concentration (entry 15). Only
trace amount of product was formed under neat condition,
which might own to insolubility of sulfurating reagent (entry
16). Considering readily hydrolytic property of BF3, HBF4 was
used as promoter with a lower yield (82%, entry 17).
unpleasant odor and apt oxidation impeding their applications.
15
To overcome these disadvantages, Na2S2O3
has been
successfully used for introducing sulfur atom by transition
metal catalyzed reaction. In previous work (eq a, Scheme 1), we
reported novel oneꢀpot palladiumꢀcatalyzed dual CꢀS bonds
formation reaction at 120 oC using Na2S2O3 as sulfurating
reagent. Aiming to further imply our method in biocompatible
reactions, much milder conditions need to be developed.
Aqueous solvent, 16 life benign catalysts and room temperature
should be applicable in vitro and in vivo. In addition, a readilyꢀ
prepared, easilyꢀhandling and bench stable starting material is
preferred in which aromatic triazenes are good candidates.17
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DOI: 10.1039/C4CC08367A
Table 1 Optimization of Reaction Conditionsa
Table 2 Substrate Scope for Nꢀsubstitution 1ꢀAryltriazenea
aReaction conditions: CuSO4·5H2O (10 mol%), bipy (10 mol%), BnCl (1
o
mmol), Na2S2O3·5H2O (1 mmol), H2O (1 mL), 80 C, 2 h, then 1d' (0.2
mmol), BF3·Et2O (0.2 mmol) was added, and stirred at room temperature for
certain hours. bIsolated yields.
Table 3 Substrate Scope for Aryl Substitution of 1ꢀAryltriazenea
aReaction conditions: catalyst (10 mol%), ligand (10 mol%), BnCl (1 mmol),
o
Na2S2O3·5H2O (1 mmol), MeOH/H2O = 1/1 (2 mL), 80 C, 2 h, then 1d (0.2
mmol), BF3·Et2O (0.2 mmol) was added, and stirred at room temperature.
bIsolated yields. cMeOH/H2O = 1/2 (2 mL). dMeOH/H2O = 2/1 (2 mL).
eTBAB (0.2 mmol) was added.
Under the optimized conditions, we firstly investigated the
Nꢀsubstituted groups of 1ꢀaryltriazenes (Table 2). For cyclic
substitution, the ring size exhibited almost no influence on yield
(entries 1, 2). The ring containing additional heteroatom, such
as morpholine, could also produce moderate yield (entry 3).
What’s more, the substrate with two separate cyclohexyl ring
on nitrogen atom was tolerated as well (entry 4). In addition to
the cyclic substitutions, the nonꢀcyclic ones are also scrutinized.
The compounds with various linear and branched chains, such
as methyl, ethyl, propyl, butyl and isopropyl could produce the
desired compound in above 70% yields (entries 5ꢀ9). Even the
one with heteroalkyl substitution on nitrogen atom was efficient
too (entry 10). Considering the free alcohol groups might have
additional covalent binding effect and be helpful for increasing
solubility in water, the ethyl alcohol substituted 1ꢀaryltriazenes
was checked (entry 11). The diversified reactive substitutions,
such allyl and benzyl, seemed not largely influence the
transformation (entries 12, 13). Beside the sp3 substituent
groups, the sp2 ones could also complete the translation (entry
14).
Once different Nꢀsubstituted groups of 1ꢀaryltriazenes were
examined, the aryl substitutions were also comprehensively checked,
the results were summarized in Table 3. A broad range of 1ꢀ
aryltriazenes were conducted with Na2S2O3 and BnCl to afford the
corresponding products in moderate to excellent yields. The
unsubstitued and electronꢀneutral substituted compounds produced
good to excellent yields (2a-2c). The electronꢀdonating and electronꢀ
withdrawing groups in orthoꢀ, metaꢀ and paraꢀ positions were well
compatible, for example, alkyl, alkyloxyl, alkylmercapto, nitrile,
nitro and ester (2d-2k). It is worth mentioning that the substrate
containing active hydrogen group, such as carboxyl acid (2i), could
aReaction conditions: CuSO4·5H2O (10 mol%), bipy (10 mol%), BnCl (1
mmol), Na2S2O3·5H2O (1 mmol), H2O (1 mL), 80 oC, 2 h, then 1 (0.2 mmol),
BF3·Et2O (0.2 mmol) was added, and stirred at room temperature for 12 h,
unless otherwise noted. bStep 2, 50 oC, 12 h. cStep 2, 80 oC, 6 h.
be well tranformated, which is a big challenge in many coupling
reactions. In addition, the corresponding product could be further
converted through various decarboxyl coupling. Halogen
substitutions in different position also performed well (2l-2o, 2q-2s),
which showed that this method have great potential in further
transformation. The polysubsititued thioethers could also be
achieved (2p), in which the steric effect not seemed to be a big
problem (2t). Beside those above, some sensitive groups were (2v)
2 | J. Name., 2012, 00, 1-3
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detected. Diazo (2u) which is unstable in radical reactions and Bpin
For the sake of the latent chemical biology study, we tested the
which is an efficient Suzuki coupling precursor resulted reasonable compatibility of this sulfuration reaction with various biomolecules
yields. In addtion, the condensed ring (2w) and heteroaromatic ring (Table 5).3d,18 Gladly, the addition of stoichiometric (mole or mass)
(2x) were also tolerated.
amount of biomolecules including amino acids, oligosaccharides,
nucleosides and protein did not significantly affect the reactions both
in aqueous and buffered conditions except those with nucleosides
and bovine serum albumin in pure water (Table 3, entries 1ꢀ7).
Futhermore, hela cell lysates which contained various endogenous
biomolecules was conducted under aqueous and buffered conditions
(Table 3, entry 8), both experiments resulted 63% yield.
After systematically investigating the substrate scope of 1ꢀ
aryltriazenes, the alkyl halides for sulfuration were tested. As shown
in Table 4, a variety of 1ꢀaryltriazenes could be freely combined
with different halides. In light of the important role of sulfur and
fluorine compounds in medicinal chemistry,7c we would like to
construct a robust and reliable method for introducing both sulfur
and fluorine atom into one molecular. The data showed that various
fluroꢀ and trifluromethylꢀ substitued benzylic halides could be
flexible coupled with 1ꢀaryltriazenes (3aꢀ3k). Other halide (3l),
electronꢀwithdrawing group (3m, 3n) and electronꢀdonating (3o)
were also fit well in this system. Remarkably, unactivated alkyl
halides were also good coupling partners, which can be smoothly
converted to the corresponding thioethers in moderate yields (3p-3r).
Table 5 Sulfuration under Aqueous Conditions and in the Presence of
Biomoleculea
S
N
N
1. CuSO4.5H2O (10 mol%), bipy (10 mol%)
BnCl, Na2S2O3.5H2O, solvent, 80 oC, 2 h
Bn
N
MeO
2. Biomolecules, BF3.Et2O, rt, 12 h
MeO
1d
2d
Yield (%)c
54
Yield (%)b
83
conditions
entry
Table 4 Substrate Scope of Halidesa
1
2
3
4
5
6
7
8
1.0 equiv. L-tyrosine
1.0 equiv. L-cysteine
63
50
65
61
57
67
63
81
71
74
65
39
39
63
1.0 equiv.L-methionine
1.0 equiv. L-histidine
1.0 equiv. guanosine
1.0 equiv. naringin
40 mg/mL bovine serum albumin
8 mg/mL hela cell lysates
aReaction conditions: CuSO4·5H2O (10 mol%), bipy (10 mol%), BnCl (1
mmol), Na2S2O3·5H2O (1 mmol), H2O (1 mL), 80 oC, 2 h, then 1d (0.2
mmol), stoichiometric amount of biomolecules, BF3·Et2O (0.2 mmol) was
added, and stirred at room temperature for 12 h. bIsolated yields with H2O (1
mL) as solvent. cIsolated yields with 1 mL pH 7.4 10X PBS as solvent.
For mechanistic study, two equivlent of TEMPO was conducted
in this system with a diminished yield (16 %). On the basis of our
results15 and relevant report17, a plausible reaction pathway is
depicted as below. Firstly, aryl triazene was activated by acid, which
intermediate A was then transformed to copper complex B through
the release of N2 and amine. On the other side, the alkyl thiolsulfate
was produced from alkyl halide and Na2S2O3. Ligand exchange
between copper complex B and sulfur species C resulted in the
crucial copper sulfide intermediate D. The specificity of this sulfur
atom transfer reaction was exhibited in this step. The electronꢀ
withdrawing group on sulfur atom functioned as a “mask” which
decreased its electron density and subsequently weakened the strong
aReaction Conditions: CuSO4·5H2O (10 mol%), bipy (10 mol%), RX, (1
mmol), Na2S2O3·5H2O (1 mmol), H2O (1 mL), 80 oC, 2 h, then 1 (0.2 mmol),
BF3·Et2O (0.2 mmol) was added, and stirred at room temperature for 12 h,
unless otherwise noted.
In order to further demonstrate the applicability of the current
protocol, gram scale experiments were carried out under modified
reaction conditions. As highlighted in scheme 2, 2a was obtained
smoothly in quantitative yield at room temperature with 0.4 M
concentration, in which 5 mol% of catalyst and ligand were
sufficient (eq a). Moreover, sulfamethoxazole as
a famous
bacteriostatic antibiotic was reactive under standard conditions. The
late stage sulfuration of it was completed smoothly (0.2 mmol scale,
65% yield). Encouragingly, the results obtained in gram scale
reactions are better than those in small scale ones.
Scheme 2 Gram Scale reactions and Late Stage Sulfuration.
Scheme 3. Proposed Mechanism.
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Liu and S. S. Badsara, Chem. Asian J., 2014, 9, 706; (c) F. Dénès, M.
Pichowicz, G. Povie and P. Renaud, Chem. Rev., 2014, 114, 2587; (d) A.
Correa, O. G. Macheño and C. Bolm, Chem. Soc. Rev., 2008, 37, 1108; (e)
T. Kondo and T. A. Mitsudo, Chem. Rev., 2000, 100, 3205.
coordination from sulfur to copper. Finally, the product was
generated through the reductive elimination which accompanied
with the regeneration of copper catalyst.
7 (a) T. Kondo and T. Mitsudo, Chem. Rev., 2000, 100, 3205; (b) I. P.
Beletskaya and V. P. Ananikov, Chem. Rev., 2011, 111, 1596; (c) E. A.
Ilardi, E. Vitaku and J. T. Njardarson, J. Med. Chem., 2014, 57, 2832.
8 (a) S. Pasquini, C. Mugnaini, C. Tintori, M. Botta, A. Trejos, R. K. Arvela,
M. Larhed, M. Witvrouw, M. Michiels, F. Christ, Z. Debyser and F. J.
Corelli, Med. Chem., 2008, 51, 5125; (b) M. L. Alcaraz, S. Atkinson, P.
Cornwall, A. C. Foster, D. M. Gill, L. A. Humphries, P. S. Keegan, R.
Kemp, E. Merifield, R. A. Nixon, A. J. Noble, D. O’Beirne, Z. M. Patel, J.
Perkins, P. Rowan, P. Sadler, J. T. Singleton, J. Tornos, A. J. Watts and I.
A. Woodland, Org. Process Res. Dev., 2005, 9, 555; (c) G. De Martino, G.
La Regina, A. Coluccia, M. C. Edler, M. C. Barbera, A. Brancale, E.
Wilcox, E. Hamel, M. Artico and R. Silvestri, J. Med. Chem., 2004, 47,
6120; (d) G. Liu, J. T. Link, Z. Pei, E. B. Reilly, S. Leitza, B. Nguyen, K.
C. Marsh, G. F. Okasinski, T. W. von Geldern, M. Ormes, K. Fowler and
M. Gallatin, J. Med. Chem., 2000, 43, 4025; (e) P. C. Tang, J. Y. Ramphal,
G. D. Jr. Harris and A. S. Nematalla, Patent WO/1998/27092 A1, June 25,
1998; (f) S. F. Nielsen, E. O. Nielsen, G. M. Olsen, T. Liljefors and D.
Peters, J. Med. Chem., 2000, 43, 2217.
Conclusions
In summary, we have developed an efficient, economical, and
mild procedure for constructing C–S bonds through copperꢀ
catalyzed BF3·Et2Oꢀinduced directly coupling among 1ꢀaryltriazenes,
Na2S2O3 and alkyl halides at room temperature, in which water
functions as a green solvent. The simple preparation of the starting
material, novel sulfur source, cheap catalyst and the fairly mild
reaction conditions without volatile organic solvents make this
process effective and convenient for organic synthesis and industrial
applications. Its compatibility with amino acids, nucleosides,
oligosaccharides, proteins, and cell lysates indicated its promising
ability in bioorthogonal study.
Financial support was provided by NBRPC (973 Program,
2015CB856600), NSFC (21472050, 21272075), NCET (120178),
DFMEC (20130076110023), Fok Ying Tung Education Foundation
(141011), the program for Professor of Special Appointment
9 C. Paradisi, B. M. Trost and I. Fleming, In Comprehensive Organic
Synthesis, Vol. 4; Pergamon Press: Oxford. U.K., 1991.
(Eastern Scholar) at Shanghai Institutions of Higher Learning, and 10 (a) T. S. T. Migita, Y. Asami, J. Shiobara, Y. Kato and M. Kosugi, Bull.
Chem. Soc. Jpn., 1980, 53, 1385; (b) G. Y. Li, Angew. Chem. Int. Ed.,
2001, 40, 1513; (c) M. A. FernándezꢀRodríguez, Q. Shen and J. F. Hartwig,
Chem. Eur. J., 2006, 12, 7782; (d) J.ꢀY. Lee and P. H. Lee, J. Org. Chem.,
2008, 73, 7413; (e) G. Bastug and S. P. Nolan, J. Org. Chem., 2013, 78,
9303.
the program for the Changjiang Scholar and Innovative Research
Team in University.
Notes and references
11 (a) V. Percec, J.ꢀY. Bae and D. H. Hill, J. Org. Chem., 1995, 60, 6895;
(b) Y. Zhang, K. C. Ngeow and J. Y. Ying, Org. Lett., 2007, 9, 3495.
12 (a) F. Y. Kwong and S. L. Buchwald, Org. Lett., 2002, 4, 3517; (b) C. G.
Bates, P. Saejueng, M. Q. Doherty and D. Venkataraman, Org. Lett.,
2004, 6, 5005; (c) Y. Chen and H. Chen, Org. Lett., 2006, 8, 5609; (d) L.
Rout, T. K. Sen and T. Punniyamurthy, Angew. Chem. Int. Ed., 2007, 46,
5583; (e) D. Ma and Q. Cai, Acc. Chem. Res., 2008, 41, 1450; (f) C. Chen,
Y. Chen, C. Lin, H. Lin and C. Lee, Chem. Commun., 2010, 46, 282; (g)
D. Ma, X. Lu, L. Shi, H. Zhang, Y. Jiang and X. Liu, Angew. Chem. Int.
Ed., 2011, 50, 1118.
a Shanghai Key Laboratory of Green Chemistry and Chemical Process,
Department of Chemistry, East China Normal University, Shanghai 200062,
P. R. China, E-mail : xfjiang@chem.ecnu.edu.cn
b Stake Key Laboratory of Organometallic Chemistry, Shanghai Institute of
Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, P. R.
China
c Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences,
Chengdu 610041, P. R. China
d University of Chinese Academy of Sciences, Beijing 100049, P. R. China
13 Y. Wong, T. T. Jayanth and C. Cheng, Org. Lett., 2006, 8, 5613.
14 (a) A. Correa, M. Carril and C. Bolm, Angew. Chem. Int. Ed., 2008, 47,
2880; (b) W. Wu, J. Wang and F. Tsai, Green Chem., 2009, 11, 326; (c) J.
Wu, C. Lin and C. Lee, Chem. Commun., 2009, 4450.
15 (a) Z. Qiao, H. Liu, X. Xiao, Y. Fu, J. Wei, Y. Li and X. Jiang, Org. Lett.,
2013, 15, 2594; (b) Z. Qiao, J. Wei and X. Jiang, Org. Lett., 2014, 16,
1212; (c) J. T. Reeves, K. Camara, Z. S. Han, Y. Xu, H. Lee, C. A.
Busacca and C. H. Senanayake, Org. Lett., 2014, 16, 1196.
† These authors contributed equally to the work.
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/c000000x/
1 (a) E. M. Sletten and C. R. Bertozzi, Angew. Chem. Int. Ed., 2009, 48, 6974;
(b) E. M. Sletten and C. R. Bertozzi, Acc. Chem. Res., 2011, 44, 666.
2 (a) J. Li, J. Yu, J. Zhao, J. Wang, S. Zheng, S. Lin, L. Chen, M. Yang, S.
Jia, X. Zhang and P. Chen, Nat. Chem., 2014, 6, 352; (b) M. Yang, J. Li
and P. Chen, Chem. Soc. Rev., 2014, 43, 6511; (c) S. Sato and H.
Nakamura, Angew. Chem. Int. Ed., 2013, 52, 8681; (d) T. Hayashi and I.
Hamachi, Acc. Chem. Res., 2012, 45, 1460; (e) G. M. Fang, H. K. Cui, J. S.
Zheng and L. Liu, Chem. Bio. Chem., 2010, 11, 1061; (f) J. S. Zheng, H. K.
Cui, G. M. Fang, W. X. Xi and L. Liu, Chem. BioChem., 2010, 11, 511.
3 (a) K. Gorska and N. Winssinger, Angew. Chem. Int. Ed., 2013, 52, 6820;
(b) Y. Chen, A. S. Kamlet, J. B. Steinman and D. R. Liu, Nature Chem.,
2011, 3, 146; (c) R. Naylor and P. T. Gilham, Biochemistry, 1966, 5, 2722;
(d) L. E. Orgel, Acc. Chem. Res., 1995, 28, 109.
4 (a) B. N. G. Giepmans, S. R. Adams, M. H. Ellisman and R. Y. Tsien,
Science, 2006, 312, 217; (b) R. H. Newman, M. D. Fosbrink and J. Zhang,
Chem. Rev., 2011, 111, 3614; (c) K. K. Sadhu, T. Eierhoff, W. Römer and
N. Winssinger, J. Am. Chem. Soc., 2012, 134, 20013; (d) Q. Li, T. Dong,
X. Liu and X. Lei, J. Am. Chem. Soc., 2013 , 135 , 4996.
5 (a) H. C. Kolb, M. G. Finn and K. B. Sharpless, Angew. Chem. Int. Ed.,
2001, 40, 2004; (b) V. V. Rostovtsev, L. G. Green, V. V. Fokin and K. B.
Sharpless, Angew. Chem. Int. Ed., 2002, 41, 2596; (b) V. T. Huynh, G.
Chen, P. Souza and M. H. Stenzel, Biomacromolecules, 2011, 12, 1738; (c)
Y.ꢀX. G. Triola and H. Waldmann, Acc. Chem. Res., 2011, 44, 762; (d) D.
M. Beal and L. H. Jones, Angew. Chem. Int. Ed., 2012, 51, 6320.
16 For reactions under aqueous conditions: (a) S. Kobayashi and I. J.
Hachiya, Org. Chem., 1994, 59, 3590; (b) T.ꢀP. Loh and X.ꢀR. Li, Chem.
Comm., 1996, 16, 1929; (c) T.ꢀP. Loh and X.ꢀR. Li, Angew. Chem. Int.
Ed., 1997, 36, 980; (d) W. G. Lewis, L. G. Green, F. Grynszpan, Z. Radic,
P. R. Carlier, P. Taylor, M. G. Finn and K. B. Sharpless, Angew. Chem.
Int. Ed. 2002, 41, 1053; (e) S. Kobayashi and K. Manabe, Acc. Chem.
Res., 2002, 35, 209; (f) S. Narayan, J. Muldoon, M. G. Finn, V. V. Fokin,
H. C. Kolb and K. B. Sharpless, Angew. Chem. Int. Ed., 2005, 44, 3275;
(g) C. Li, Chem. Rev., 2005, 105, 3095; (h) C. Li, L. Chen, Chem. Soc.
Rev., 2006, 35, 68; (i) A. Chanda and V. V. Fokin, Chem. Rev., 2009, 109,
725; (j) E. M. Sletten and C. R. Bertozzi, Angew. Chem. Int. Ed., 2009,
48, 6974; (k) S. V. Kostjuk and F. Ganachaud, Acc. Chem. Res., 2010, 43,
357; (l) S. Kobayashi, Pure Appl. Chem., 2013, 85, 1089.
17 (a) D. B. Kimball and M. M. Haley, Angew. Chem. Int. Ed., 2002, 41,
3338; (b) T. Saeki, E.ꢀC. Son and K. Tamao, Org. Lett., 2004, 6, 617; (c)
C. Wang, H. Sun, Y. Fan and Y. Huang, Angew. Chem., Int. Ed., 2013, 52,
7242. (d) W. Li, M. Beller and X. Wu, Chem. Commun., 2014, 50, 9513.
18 (a) K. D. Collins and F. Glorius, Nature Chem., 2013, 5, 597; (b) H.
Huang, G. Zhang, L. Gong, S. Zhang and Y. Chen, J. Am. Chem. Soc.
2014, 136, 2280.
6 (a) H, Liu and X. Jiang, Chem. Asian J., 2013,
8, 2546; (b) C. Lee, Y.
4 | J. Name., 2012, 00, 1-3
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