Azomethine-isocyanide [3+2] cycloaddition to imidazoles promoted by silver and DBU

Article abstract of DOI:10.1039/c7cc00772h

A new silver-promoted [3+2] cycloaddition of azomethine ylides with isocyanides has been described. The methodology provides an efficient and modular approach to 1,2,4-trisubstituted imidazoles of vital bioactive molecules and atypical antipsychotics analogues.

Full text of DOI:10.1039/c7cc00772h

View Article Online
View Journal
ChemComm
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: X. Bi, X. Huang, X.
Cong and P. Mi, Chem. Commun., 2017, DOI: 10.1039/C7CC00772H.
Volume 52 Number
1
4
January 2016 Pages 1–216
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
ChemComm
Chemical Communications
www.rsc.org/chemcomm
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. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
author guidelines.
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, outlined
in our author and reviewer resource centre, 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.
ISSN 1359-7345
COMMUNICATION
Marilyn M. Olmstead, Alan L. Balch, Josep M. Poblet, Luis Echegoyenet al.
Reactivity differences of Sc
first methanofullerene derivatives of Sc
3
N@C2n (2n
=
68 and 80). Synthesis of the
3
N@D5h-C80
rsc.li/chemcomm

Please do not adjust margins
ChemComm
Page 1 of 4
View Article Online
DOI: 10.1039/C7CC00772H
Journal Name
COMMUNICATION
Azomethine-Isocyanide [3+2] Cycloaddition to Imidazoles
Promoted by Silver and DBU
Received 00th January 20xx,
Accepted 00th January 20xx
a
a
a
ab
Xiaoshan Huang, Xuefeng Cong, Pengbing Mi and Xihe Bi*
DOI: 10.1039/x0xx00000x
www.rsc.org/
1
1
A new silver-promoted [3+2] cycloaddition of azomethine ylides metalloenzymes in biological systems , and pharmaceutical
12
with isocyanides has been described. The methodology provides compounds . In addition, they also appeared as critical
1
3
an efficient and modular approach to 1,2,4-trisubstituted skeletons in functional materials . Due to their characteristic
imidazoles of vital bioactive molecules and atypical antipsychotics properties, many impressive investigations have been
analogue.
developed for constructing imidazole scaffolds from basic
1
4
chemical materials . Despite these great achievements having
been made, development of new methodologies for
regioselective synthesis of functionalized imidazoles remains a
The 1,3-dipolar cycloaddition reaction is one of the most
efficient methods of preparing five-membered heterocyclic
1
compounds . Remarkably, owing to its simplicity and atom
1
4,15
challenging task
. Herein, we report the [3+2] cycloaddition
efficiency, 1,3-dipolar [3+2] cycloaddition of azomethine ylides
has been well established as a reliable and powerful tool for
the construction of nitrogen-containing heterocyclic structural
of azomethine ylides with isocyanides promoted by silver and
DBU for the efficient synthesis of 1,2,4-trisubstituted
imidazoles (Fig 1c). In this transformation, silver plays a triple
role: (1) serving as catalyst to activate isocyanides; (2)
employing as oxidant to accomplish the aromatization; and (3)
promoting the formation of metalated azomethine ylides.
2
,3,4,6
motifs with various π-systems
. For example, numerous
2
,3
4
alkenes and imines as dipolarophiles have been subse-
quently explored to achieve optically active pyrrolidines and
imidazolidines by using either chiral metal-based catalysts or
organocatalysts since the pioneering contribution of Allway
(
a) [3+2] cycloaddition of azomethines with alkenens or imines
5
and R. Grigg (Fig 1a). Recently, the cycloaddition of
azomethine ylides with ynones for construction of 2,5-
dihydropyrroles and pyrroles also have been developed by
R1
R2
R2
[
M]/Ligand
X
X
R
N
EWG
+
R1
X = CH, N
[M] = Cu, Ag, Au, etc.
EWG
R
N
H
6
Gong and Deng ect., respectively (Fig 1b) . Isocyanides are
versatile building blocks and have been widely applied in
7
organic synthesis . In particular, aryl isocyanides as
(b) Intermolecular [3+2] cycloaddition of azomethines with alkynes
O
R2
R1
dipolarophiles have proven to be a versatile functionality to
8
undergo [3+2] cycloaddition for heterocycle synthesis .
O
[Ag]/Ligand
+
R2
R
N
EWG
R1
R
EWG
N
H
However, the 1,3-dipolar [3+2] cycloaddition reaction of
azomethine ylides with isocyanides to valuable heterocycles
(
c) This work: the first [3+2] cycloaddition of azomethines with aryl cyanides
7
d,9
are rare.
N
R
EWG
Imidazoles, especially those with multiple functional
groups, are considered to be special structural motifs, which
are not only prevalent in various highly bioactive natural
2
Ag CO3
R
N
EWG
+
Ar
N
C
N
DBU
Ar
Readily construction of tri-substituted imidazoles
Broad scope, good functional group compatibility
1
0
EWG = CO2R'
products , but also present in many enzymes and
Fig. 1 [3+2] Cycloaddition Reactions of Azomethine ylides
We initiated our investigation with the optimization studies
a.
b.
Jilin Province Key Laboratory of Organic Functional Molecular Design & Synthesis,
Department of Chemistry, Northeast Normal University, 5268 Renmin Street,
of the [3+2] cycloaddition of (E)-methyl 2-((4-
130024 Changchun, China. Email: bixh507@nenu.edu.cn
chlorobenzylidene)amino)acetate
(
1a)
and 1-bromo-4-
State Key Laboratory of Elemento-Organic Chemistry, Nankai University, 300071
Tianjin, China
isocyanobenzene (2a). We were pleased to find that tri-
substituted imidazole 3a was obtained in 30% isolated yield in
Electronic Supplementary Information (ESI) available: [details of any supplementary
information available should be included here]. See DOI: 10.1039/x0xx00000x
2 3
the presence of 30 molꢀ% of Ag CO in 1,4-dioxane at 80ꢀ°C
This journal is © The Royal Society of Chemistry 20xx J. Name., 2013, 00, 1-3 | 1
Please do not adjust margins

Please do not adjust margins
ChemComm
Page 2 of 4
View Article Online
DOI: 10.1039/C7CC00772H
COMMUNICATION Journal Name
(Table 1, entry 1). The employment of 0.2 equiv of DBU as base imidazole 3b in 68% yield. Notably, 3,5-diboromo substituted
only increased the yield to 38% (entry 2), but along with a azomethine could be readily introduced in the reaction,
significant amount of the hydrolytic aldehyde of 1a. Thus, 4Å providing the corresponding product 3k in a prepared useful
molecular sieves were employed to inhibit the hydrolysis of yield. In addition, azomethine containing fused aromatic
azomethine 1a. As expected, yield of imidazole 3a was groups as well as heteroaromatic groups all reacted smoothly
improved to 72ꢀ% yield (entry 3). Compared to Ag
2 3
CO , other to give the desired products (3l-3o). The cinnamyl substituent
silver salts such as AgNO , AgOTf, AgOTFA, and Ag O were less 1p was also allowed to react with isocyanide 2a, providing
3
2
effective or ineffective in this transformation. A base screening alkenyled imidazole in an acceptable yield. Further, other
revealed that DBU remained the best choice in our case (ESI, azomethines with alkyl-substituted ester group were
1
6
Table S1) . Other solvent such as DCE and toluene also gave appreciated the products 3q to 3s under the optimal
the desired product but in low yield, while no reactions conditions (43-85%).
occurred in DMF (ESI, Table S1). In view of this reaction
involving oxidative process, external oxidants were screened.
However, PhI(OAc)
conversation (ESI, Table S1). To our delight, the amount of
Ag CO was increased to 0.5 equiv and 1.0 equiv in the
2 2 2 8 2
, K S O and O could not improve the
2
3
reaction, and, yields of 3a were improved to 78% and 87%,
respectively. The isolated yield can be up to 82% (Table 1,
entries 8-9).
a
Table 1 Optimization of the Reaction Conditions
b
entry
[Ag]
base
-
solvent
yield of 3a
c
1
Ag
2
Ag
2
Ag
2
CO
CO
CO
3
3
3
1,4-Dioxane
35% (30%)
c
2
DBU
DBU
1,4-Dioxane
1,4-Dioxane
38%
72%
3
4
5
6
7
AgNO
AgOTf
DBU
DBU
DBU
DBU
DBU
DBU
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
trace
-
3
Scheme 1 [3+2] Cycloaddition of 2a with different Azomethines.
AgOTFA
Ag
17%
2
O
26%
In view of these interesting results, we further extended
the substrate scope of this strategy to isocyanides (Scheme 2).
We found that varied aryl isocyanides bearing electron-
donating and -withdrawing groups, could smoothly react with
d
8
Ag
CO
78% (76%)
87% (82%)
2
2
3
3
e
9
Ag
CO
a
Reaction conditions: 1a (0.75 mmol), 2a (0.5 mmol), [Ag] (30 mol %), DBU (20
Ag2CO3 (1.0 equiv)
DBU (20 mol%)
PMP
N
mol %), 4Å MS (200.0 mg) in Dioxane (5 mL) at 80 °C for 24 h under Ar.
b
1
1f
+
Ar NC
CO Me
2
Determined by H-NMR spectroscopy using 1,3,5-trimethoxybenzene as an
N
4Å MS, Ar
Ar
c
2
1,4-Dioxane, 80 oC
4
internal standard; isolated yield are given in parentheses. without 4Å MS; under
(1.5 equiv) (1.0 equiv)
PMP = 4-CH3OC6H4
d
e
air. Ag
2 3 2 3
CO (0.5 equiv) was used. Ag CO (1.0 equiv) was used. DBU = 1,8-
diazabicyclo[5.4.0]undec-7-ene.
PMP
N
PMP
N
4
b (R = Ph), 86%
CO2Me
N
2
CO Me
4c (R = OCH3), 33%
N
I
4
4
d (R = NO2), 65%
e (R = I), 78%
With the optimal conditions in hand, the substrate scope
toward this cycloaddition was further investigated, and the
results were listed in scheme 2. A wide array of azomethines
were examined in the reaction with 2a, affording the
corresponding 1,2,4-trisubstituted imidazoles in moderate to
excellent yields (Scheme 1). Firstly, wide variation of the
substituents on the benzene ring at para position including
electron-donating (e.g., MeO and Me) and -withdrawing
R
4f, 74%
PMP
N
PMP
N
PMP
N
CO2Me
CO2Me
2
CO Me
N
N
N
MeO2C
4g, 48%
4h, 65%
4i, 68%
groups (e.g., Ph, F, Br, and CN) allowed the formation of Scheme 2 [3+2] Cycloaddition of 1f with different substituted aryl isocyanides.
diverse highly functionalized 1,2,4-trisubstituted imidazols
azomethine 1f to afford the corresponding 1,2,4-trisubstituted
imidazoles in moderate to excellent yields (4b, 4c, 4d). It was
(
3d−3j) in 46-90% yields. This transformation is not sensitive to
the ortho steric hindrance, affording the corresponding
2
| J. Name., 2012, 00, 1-3This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 3 of 4
ChemComm
Please do not adjust margins
View Article Online
DOI: 10.1039/C7CC00772H
Journal Name
COMMUNICATION
(
(
a) Radical scavenger experiment
noticed that functional groups involving iodo (4e, 4f),
methoxycarbonyl (4g), and nitro could be well tolerated in our
case, affording the functionalized imidazole in 48-78% yields.
PMP
N
TEMPO (2 equiv)
PMP
N
CO
2
Me
+
2a
2
CO Me
N
standard conditions
1
f
2,6-dimethyl phenyl (4h) and 1-naphenyl (4i) isocyanides were
Br
3f, 86%
PMP = 4-CH
3 6 4
OC H
also readily employed under the optimal condition, thus
suggesting our system was not influenced by steric factors. It is
worth noting that trace amount of desired product was
obtained with tert-butyl and benzyl isocyanides.
b) Plausible mechanism for imidazole synthesis
Ag OR
Ar
Ag
2
CO
3
N
O
Ar NC
Ar
N
C
Ag
+
N
Ag
n
2
B
R
C
To further demonstrate the practical usefulness of the
Ag
2 3
CO
−
DBU-H+
method,
a
gram-scale reaction was performed with
OR
DBU
R
N
+
R
N
COOMe
azomethine ylide 1a and 2a. Under the optimized reaction
conditions, the reaction could proceed smoothly, affording the
desired product 3a in 74% yield (Scheme 3a). It is worth
O
Protonation
Ag
1
DBU-H+
A
DBU
Ar
H
OR
Ag
R
N
R
mentioning that 1,2,4-trisubstituted imidazoles
derivatives are more specific GABA receptor ligands in
compared with classical anesthetics such as etomidate,
3
and their
Oxidation
N
isomerisation
Cyclization
N
O
+
N
Ag
O
2
CO Me
N
N
A
Ar
Ar
OR
R
3
E
D
1
7
propofol, and alphaxalone . These imidazoles have previously
7a
1
been synthesized in a three-step process . By contrast, this
cycloaddition strategy allowed the corresponding imidazoles
3
Fig. 2 Plausible mechanism
to be synthesized directly from readily available substrates in a
single step in good isolated yield. The resulting ethyl ester 3a
can undergo the saponification with hydro alcoholic NaOH,
giving the corresponding carboxylic acids 3aa in 83% isolated
yield. Notably, the product 3aa is a known intermediate for
accessing a series of atypical antipsychotics analogue in
In conclusion, we have developed the first azomethine-
isocyanide [3+2] cycloaddition reaction promoted by silver and
DBU to achive 1,2,4-trisubstituted imidazoles. This method
allows modular access to 1,2,4-trisubstituted imidazoles
starting from the readily available aryl isocyanides and
azomethine ylides with broad substrate scope and good
1
7b
previous report (Scheme 3b).
2 3
functional group compatibility. Ag CO plays key role as the
catalyst and oxidant in this transformation. Furthermore, the
target scaffolds containing ester group at C4 position are more
A
specific GABA receptor ligands, and easily access to a series of
atypical antipsychotics analogue. Considering the extreme
importance of 1,2,4-trisubstituted imidazoles in medicinal
chemistry, the methodology presented herein undoubtedly
will find wide applications in future synthetic endeavors and
pharmaceutical synthesis.
This work was supported by the NSFC (21522202, 21372038),
the Ministry of Education of the People’s Republic of China
(NCET-13-0714), the Jilin Provincial Research Foundation for
Basic Research (20140519008JH), and the Fundamental
Research Funds for the Central Universities (2412015BJ005).
Scheme 3 Gram scale and Synthetic Applications
As shown in Figure 2a, the [3+2] cycloaddition still carries
out smoothly when the addition of TEMPO (2,2,6,6-
tetramethylpiperidine-1-oxyl) into the system, implying that
the radical pathway may be excluded in the this
transformation. Therefore, a plausible reaction mechanism is
proposed on the basis of the above experiments and related
Notes and references
1
2
3
1,3-Dipolar Cycloaddition Chemistry, (a) K. V. Gothelf and K.
A. Jørgensen, Chem. Rev. 1998, 98, 863. (b) M. Pichon and B.
Figadere, Tetrahedron: Asymmetry, 1996, 7, 927. (c) G.
Broggini and G. Zecchi, Synthesis, 1999, 905. (d) S. Husinec
and V. Savic, Tetrahedron: Asymmetry, 2005, 16, 2047. (e) S.
Kanemasa, Synlett, 2002, 1371.
8
2e,18
reports (Figure 2b) . Initially, the intermediate
and attacks to the complex Ag CO (RNC) , giving the imidoyl
After the protonation of
, the intermediate is formed and followed by
isomerisation and cyclization to give intermediate
Intermediate then experiences an oxidation to yield the
desired product . Compared to classical [3+2] cycloaddition,
this process occurs in a stepwise manner and the complex
Ag CO (RNC) is formed initially to promote the nucleophilic
attack of intermediate
A
is formed
2
3
n
B
(a) F. J. Sardina and H. Rapoport, Chem. Rev. 1996, 96, 1825.
b) I. Coldham and R. Hufton, Chem. Rev. 2005, 105, 2765.
3
a,18a
silver intermediate
intermediate
C
.
(
C
D
(c) G. Pandey, P. Banerjee and S. R. Gadre, Chem. Rev. 2006,
106, 4484. (d) J. Adrio and J. C. Carretero, Chem. Commun.
2011, 47, 6784. (e) J. Adrio and J. C. Carretero, Chem.
Commun. 2014, 50, 12434.
(a) P. E. Ana, A. D. Cózar, F. P. Cossío, j. Adrio and J. C.
Carretero, Angew. Chem. Int. Ed. 2016, 55, 15334. (b) B. Xu,
Z.-M. Zhang, S. Xu, B. Liu, Y.-J. Xiao and J.-L. Zhang, ACS
E
.
E
3
2
3
n
A
.
Catal. 2017, 7, 210. (c) L. P. Ana, S. Marwin, J. Adrioand and
J. C. Carretero, J. Org. Chem. 2011, 76, 1945. (d) J.-X. Zhang,
This journal is © The Royal Society of Chemistry 20xx J. Name., 2013, 00, 1-3 | 3
Please do not adjust margins

Please do not adjust margins
ChemComm
Page 4 of 4
View Article Online
DOI: 10.1039/C7CC00772H
COMMUNICATION Journal Name
H.-Y. Wang, W.-Q. Jin, J.-C. Wu, Z.-G. Zhao and Y.-J. Shang,
Org. Lett. 2016, 18, 4774. (e) Z.-M. Zhang, B. Xu, S. Xu, H.-H.
A. Pau, S. Sanna, R. Cerri, M. P. Mascia, E. Sanna and G.
Biggio, J. Med. Chem. 2005, 48, 2638.
Wu and J. Zhang, Angew. Chem. Int. Ed. 2016, 55, 6324; 18 (a) H. Liu, Y. Wu, Y. Zhao, Z. Li, L. Zhang, W. Yang, H. Jiang, C.
Angew. Chem. Int. Ed. 2016, 128, 6432.
Jing, H. Yu, B. Wang, Y. Xiao and H. Guo, J. Am. Chem. Soc.
2014, 136, 2625. (b) W. Zeng and Y.-G. Zhou, Org. Lett. 2005,
4
(a) H.-B. Xie, J.-T. Zhu, Z.-X. Chen, S. Li and Y.-M. Wu, J. Org.
Chem. 2010, 75, 7468. (b) Q.-H. Li, L. Wei, X. Chen and C.-J.
Wang, Chem. Commun. 2013, 49, 6277. (c) W.-J. Liu, X.-H.
Chen and L.-Z. Gong, Org. Lett. 2008, 10, 5357.
7
X.-L. Hou and Y.-D. Wu, Angew. Chem. Int. Ed. 2006, 45
, 5055. (c) X.-X. Yan, Q. Peng, Y. Zhang, K. Zhang, W. Hong,
,
1979.
5
6
P. Allway and R. Grigg, Tetrahedron Lett. 1991, 32, 5817.
(a) Z. Wang, Y. Shi, X.-Y. Luo, D.-M. Han and W.-P. Deng, New
J. Chem. 2013, 37, 1742. (b) F.-F. Tang, W.-L. Yang, X.-X. Yu
and W.-P. Deng, Catal. Sci. Technol. 2015,
G.-J. Xing, W. Tan, R.-Y. Zhu and S.-J. Tu, Org. Biomol. Chem,
013, 11, 1482. (d) F. Shi, S.-W. Luo, Z.-L. Tao, L. He, J. Yu, S.-
J. Tu and L.-Z. Gong, Org. Lett. 2011, 13, 4680. (e) F. Shi, Z.-L.
Tao, J. Yu and S.-J. Tu, Tetrahedron: Asymmetry, 2011, 22
056.
5, 3568. (c) F. Shi,
2
,
2
7
8
(a) Isocyanide Chemistry Applications in Synthesis and
Materials Science (Ed.: V. Nenajdenko), Wiley-VCH,
Weinheim, 2012. (b) A. V. Lygin and A. D. Meijere, Angew.
Chem. Int. Ed. 2010, 49, 9094. (c) A. Dömling, Chem. Rev.
2
006, 106, 17. (d) V. P. Boyarskiy, N. A. Bokach, K. V.
Luzyanin and V. Y. Kukushkin, Chem. Rev. 2015, 115, 2698.
e) B. Zhang and S. Armido, Chem. Soc. Rev. 2015, 44, 3505.
(
(a) R. Grigg, M. I. Lansdell and M. Thornton-Pett,
Tetrahedron, 1999, 55, 2025 (b) C. Kanazawa, S. Kamijo and
Y. Yamamoto, J. Am. Chem. Soc. 2006, 128, 10662. (c) B.
Pooi, J. Lee, K. Choi, H. Hirao and S.-H. Hong, J. Org. Chem.
2
014, 79, 9231. (d) H.-W. Wang, R.K. Kumar, Y. Yu, L. Zhang,
Z.-H. Liu, P.-Q. Liao and X.-H. Bi, Chem. Asian J. 2016, 11
841.
,
2
9
1
(a) A. V. Gulevich, A. G. Zhdanko, R. V. A. Orru and V. G.
Nenajdenko, Chem. Rev., 2010, 110, 5235. (b) R. Manzano, F.
Rominger and A. S. K. Hashmi, Organometallics, 2013, 32
199. (c) D. Moderhack, Synthesis, 1985, 12, 1083. (d) V. S.
Korotkov, O. V. Larionov and A. D. Meijere, Synthesis, 2006,
542.
,
2
3
0
(a) S. Sarshar, C. Z. Zhang, E. J. Moran, S. Krane, J. C.
Rodarte, K. D. Benbatoul, R. Dixon and A. M. M. Mjalli,
Bioorg. Med. Chem. Lett. 2000, 10, 2599. (b) S. A. Laufer, W.
Zimmermann and K. J. Ruff, J. Med. Chem. 2004, 47, 6311.
(a) E. C. Long, Acc. Chem. Res. 1999, 32, 827. (b) R. H. Holm,
P. Kennepohl and E. I. Solomon, Chem. Rev. 1996, 96, 2239.
(a) L. Zhang, X.-M. Peng, G. L. V. Damu, R. X. Geng and C.-H.
Zhou, Med. Res. Rev. 2014, 34, 340; (b) G.-C. Wang, Z.-Y.
Peng, J. Wang, J. Li and X. Li, Bioorg. Med. Chem. Lett. 2016,
1
1
2
1
2
6
, 5719.
(a) J. Dupont,; R. F. de Souza and P. A. Z. Suarez, Chem. Rev.
13
2002, 102, 3667. (b) A. S. Amarasekara, Chem. Rev. 2016,
116, 6133. (c) K. Goossens, K. Lava, C. W. Bielawski and K.
Binnemans, Chem. Rev. 2016, 116, 4643.
S. Kamijo and Y. Yamamoto, Chem. Asian J. 2007, 2, 568.
1
1
4
5
(a) F. Bellina and R. Rossi, Adv. Synth. Catal. 2010, 352, 1223.
b) F. Bellina, S. Cauteruccio and R. Rossi, Tetrahedron, 2007,
, 4571. (c) L. Xiang, Y. Niu, X. Pang, X. Yang and R. Yan,
(
63
Chem. Commun. 2015, 51, 6598. (d) A. R. Siamaki and B. A.
Arndtsen, J. Am. Chem. Soc. 2006, 128, 6050.
1
6 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) gives the best
performance in comparison with other bases in the reaction.
The reason might be that the DBU has better solubility in
organic solvents compared with other inorganic bases, and
shows stronger alkalinity than Et
system.
3
N and DABCO in this
17
(a) B. Asproni, A. Pau, M. Bitti, M. Melosu, R. Cerri, L. Dazzi,
E. Seu, E. Maciocoo, E. Sanna, F. Busonero, G. Talani, L.
Pusceddu, C. Altomare, G. Trapani and G. Biggio, J. Med.
Chem. 2002, 45, 4655. (b) B. Asproni, G. Talani, F. Busonero,
4
| J. Name., 2012, 00, 1-3This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins