Copper(I)–Phosphinite Complexes in Click Cycloadditions: Three-Component Reactions and Preparation of 5-Iodotriazoles

Article abstract of DOI:10.1002/cctc.201600234

The remarkable activity displayed by copper(I)–phosphinite complexes of general formula [CuBr(L)] in two challenging cycloadditions is reported: a) the one-pot azidonation/cycloaddition of boronic acids, NaN₃, and terminal alkynes; b) the cyclo

Full text of DOI:10.1002/cctc.201600234

DOI: 10.1002/cctc.201600234
Full Papers
Copper(I)–Phosphinite Complexes in Click Cycloadditions:
Three-Component Reactions and Preparation of 5-
Iodotriazoles
[a, b]
[a]
[a]
[a]
Juana M. Pꢀrez,
Peter Crosbie, Steven Lal, and Silvia Dꢁez-Gonzꢂlez*
The remarkable activity displayed by copper(I)–phosphinite
complexes of general formula [CuBr(L)] in two challenging
cycloadditions is reported: a) the one-pot azidonation/cycload-
cloaddition of azides and iodoalkynes. These air-stable catalysts
led to very good results in both cases and the expected tria-
zoles could be isolated in pure form under ‘Click-suitable’
conditions.
dition of boronic acids, NaN , and terminal alkynes; b) the cy-
3
Introduction
Huisgen 1,3-dipolar cycloadditions represent a powerful meth-
odology for the preparation of a wide range of five-mem-
actions: the three-component preparation of 1,4-disubstituted
triazoles from boronic acids, NaN , and terminal alkynes, as
3
[
1,2]
bered-ring heterocycles. These reactions have recently made
a strong comeback owing to the huge interest attracted by
the copper(I)-catalyzed [3+2] cycloaddition of organic azides
and alkynes, unarguably the best Click reaction to date. This
transformation leads to the extremely efficient formation of
well as the cycloaddition of azides and iodoalkynes
(Scheme 1).
[3]
1
,4-disubstituted-[1,2,3]-triazoles as a sole regioisomer. Barely
ten years after the original groundbreaking reports by Sharp-
[
4]
less and Meldal, a myriad of ligandless as well as ligated
copper systems have been reported in the literature and have
[
5]
found applications in diverse fields.
Unsurprisingly, phosphorous ligands, and PPh in particular,
3
Scheme 1. Reactions studied with the phosphi(o)nite–copper(I) complexes.
were among the first ligands applied to the cycloaddition of
[
6,7]
azides and alkynes. We recently reported the excellent activ-
ity in copper-catalyzed azide–alkyne cycloaddition (CuAAC) re-
actions of novel copper(I) complexes bearing phosphinite or
Organic azides are generally stable towards water and
[9]
oxygen, and safe to use, except those of low molecular
[
8]
[10]
phosphonite ligands. These complexes of general formula
CuBr(L)] are stable and can be handled with no particular pre-
weight, which historically caused a tangible azidophobia in
[4b]
[
the chemical community.
As a result, several approaches
cautions to exclude moisture or air. Furthermore, we showed
that they outperformed related complexes with one phosphine
or phosphite ligand in the synthesis of triazoles. This prompted
us to further explore the potential of this family of complexes
in related copper-mediated cycloaddition reactions. Herein, we
report the application of such complexes to two important re-
have been explored to avoid the handling and isolation of or-
ganic azides in [3+2] cycloadditions. These reactions are
straightforward for aliphatic azides as these can be easily ac-
cessed from the corresponding halides or amines through
[11]
[12]
a simple nucleophilic substitution with NaN3, or TfN3, re-
spectively. However, reactions involving aryl azides are signifi-
cantly more limited. Anilines can be reacted with tert-butyl ni-
trite and TMSN3 to generate in situ the corresponding aryl
[a] Dr. J. M. Pꢀrez, P. Crosbie, Dr. S. Lal, Dr. S. Dꢁez-Gonzꢂlez
[13]
Department of Chemistry
Imperial College London
Exhibition Road, South Kensington, London SW7 2AZ (UK)
E-mail: s.diez-gonzalez@imperial.ac.uk
azides, however, the scope of this reaction is limited. Alter-
natively, a proline/copper(I) system has been reported to medi-
ate the one-pot azidonation/cycloaddition reactions from aryl
[14,15]
halides (iodide or bromide).
[b] Dr. J. M. Pꢀrez
Visiting Ph.D. student from Universidad de Alicante (Spain)
We turned our attention to the in situ preparation of aryl
azides from the corresponding boronic acids because of their
low toxicity and wide availability, supported by the popularity
of Suzuki–Miyaura cross-coupling reactions. To the best of our
knowledge, no homogeneous, ligated copper(I) system has
been reported in this context. To date, reports on this three-
component copper-mediated transformation have focused on
Supporting information and the ORCID identification number(s) for the
author(s) of this article can be found under http://dx.doi.org/10.1002/
cctc.201600234.
ꢃ 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.
This is an open access article under the terms of the Creative Commons At-
tribution License, which permits use, distribution and reproduction in any
medium, provided the original work is properly cited.
ChemCatChem 2016, 8, 1 – 6
1
ꢃ 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
These are not the final page numbers! ÞÞ

Full Papers
heterogeneous systems requiring high metal loadings
starting boronic acid and its corresponding boroxine derivative
were the major products in the crude mixture. Satisfyingly,
very clean reactions were obtained in a mixture of water/
MeOH (1:1). When water or MeOH were used separately the
overall conversion drastically dropped owing to the presence
of intermediate azide and boroxine. It is important to note
that if all materials, phenylacetylene included, were added si-
multaneously, only 15% conversion to the expected triazole
was observed under otherwise identical reaction conditions.
The trimerization of aryl boronic acids to their anhydride
trimers (boroxines) is well established in the literature
[
16,17]
(10 mol% [Cu]) and, often, a large excess of NaN3.
On the other hand, the preparation of 5-iodotriazoles from
the corresponding organic azides and iodoalkynes remains
a challenging transformation as only a handful of efficient cata-
[
18,19]
lysts has been described in the literature so far.
Halogenat-
ed heterocycles are particularly interesting from a synthetic
point of view, and iodotriazoles have indeed been used in sev-
[
20]
eral palladium-mediated cross-coupling reactions.
Despite
the clear similarities, important differences in the reactions of
terminal and iodoalkynes have been reported. Whereas the li-
[22]
gandless combination CuSO /Na ascorbate is very popular for
(Scheme 2), and it is broadly acknowledged that commercial
4
the cycloaddition of terminal alkynes, the presence of coordi-
nating ligands is crucial for any iodotriazole to be formed. In
addition to ancillary ligands, most reported systems also re-
quire an N-additive such as triethylamine or lutidine. These
facts are aligned with the increasing evidence for different
mechanistic pathways in both reactions. Fokin first suggested
that cleavage of the carbon–iodine bond is not required for
Scheme 2. Boronic acid/boroxine equilibrium.
[
21]
the cycloaddition to take place. Our DFT studies supported
this and showed that either formation of a copper(III) metalla-
cycle or direct activation of the iodoalkyne by p-coordination
of the copper catalyst accounted for the copper-acceleration
boronic acids may contain different percentages of the corre-
sponding boroxines. The control of this equilibrium has proven
essential in several cases, either because only the boronic acids
[18e]
effect and regioselectivity of this cycloaddition reaction.
[23]
underwent the desired reaction,
or because the boroxine
[24]
trimer was more reactive than its monomer. Either way, we
did not expect the dehydration of the boronic acid to be prob-
lematic as we ran all reactions in air and in technical solvent,
or even in water.
Results and Discussion
The three-component reaction
A mild and efficient alternative to the thermal dehydration
of boronic acids is the use of Lewis bases for the ligand-facili-
In a first step, we explored the three-component reaction be-
tween boronic acids, NaN , and terminal alkynes for the one-
3
[25]
tated trimerization of aryl boronic acids. Decoordination of
pot preparation of 1,4-disubstituted triazoles. Both steps of
this transformation (azidonation and cycloaddition reactions)
are copper(I)-mediated, and therefore we chose {CuBr[PPh2-
the phosphinite ligand would generate a Lewis base in the re-
action, however, we found no evidence for such behavior by
1
31
H or P NMR spectroscopy. As only the boronic acid, and not
(
OPh-2-OMe)]} A for the initial screening, as it had previously
its trimer reacted efficiently under our reaction conditions, we
recrystallized and dried the starting boronic acids employed in
this study whenever boroxines were observed in the starting
[
8]
shown the highest activity in CuAAC reactions. With para-
methoxyphenylboronic acid and phenylacetylene as model
starting materials, different solvents were screened (Table 1).
Reactions in acetone or acetonitrile only led to mixtures of var-
ious unknown byproducts. Reactions were cleaner in toluene
but only 28% of the expected triazole was observed as the
1
[26]
boronic acids by H NMR spectroscopy.
We next screened different phosphinite and phosphonite
complexes in the model reaction (Scheme 3). With most of the
catalysts tested, significant amounts of boronic acid and/or
boroxine were recovered in the crude products, whereas the
intermediate azide, 2a, was only found with catalyst C. In gen-
eral, phosphonite complexes performed better than the corre-
sponding phosphinite ones, with the exception of complexe-
s A and B. Even if high conversions were obtained with phos-
phonite complexes B and G, A still outperformed all other
complexes in the series.
Table 1. Solvent screening in the three-component reaction.
[
a]
[a]
[a]
[a]
[a]
Entry
Solvent
ArÀB(OH)
%]
2
Boroxine
[%]
Azide
[%]
Triazole
[%]
When the loading of A was halved, 40% of the starting bor-
onic acid was recovered, but still no azide was observed. This
clearly shows that it is the azidonation, and not the cycloaddi-
tion step, that requires a higher metal loading. With an opti-
mized catalytic system in hand, we next explored the scope of
the reaction (Scheme 4). After hydrolysis and extraction with
ethyl acetate, the crude solid products were washed with
water, ether, and pentane to isolate the expected triazoles in
[
1
2
3
4
toluene
MeOH/water
MeOH
37
–
–
35
–
18
22
–
–
27
25
28
>95
54
water
–
53
1
[
a] H NMR conversions are the average of at least two independent
experiments.
&
ChemCatChem 2016, 8, 1 – 6
www.chemcatchem.org
2
ꢃ 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!

Full Papers
1
Scheme 5. Catalyst screening in the preparation of 5-iodotriazoles. H NMR
conversions are the average of at least two independent experiments.
even poorer results. No reaction was observed in different sol-
vents including MeCN, EtOH, toluene, and water, and only
1
Scheme 3. Catalyst screening in the three-component reaction. H NMR
conversions are the average of at least two independent experiments.
12% conversion was found in THF.
Several reports in the literature feature the importance of ni-
trogen additives in this reaction, including our own work with
[18e]
the related [CuI(PPh ) ] complex.
3
3
No improvement, however, was observed with 5 mol% of
N,N-diisopropylethylamine, 2,6-lutidine, or triethylamine. In the
presence of 1,10-phenanthroline, the reaction conversion drop-
ped to 25%. Nevertheless, during the catalyst screening we
noticed that complexes B and C remained active over several
[27]
days
and by simply raising the reaction temperature to
408C, full conversion into triazole 6a was obtained overnight
with C. By contrast, only 20% conversion into 6a was observed
with B, which indicates that this complex is significantly more
heat sensitive.
The optimized reaction conditions were next applied to dif-
ferent pairs of azides and iodoalkynes (Scheme 6). In all cases,
either high or complete conversions into 5-iodotriazoles were
obtained. Interestingly, whereas dehalogenated triazoles were
[18e]
sometimes observed in the reactions with [CuI(PPh ) ],
this
3
3
Scheme 4. Scope of the three-component reaction. Isolated yields are the
was never the case with phosphinite catalyst C. This allowed
us to use iodoalkynes with R’=cyclopropyl, N,N-dimethylami-
nomethyl, and butyl, which with our previous phosphine
system produced ꢀ5–10% of 5-H-triazoles (Table 2, entries 1–
2). The formation of such byproducts is problematic not only
because it is undesired, but also because 5-H- and 5-I-triazoles
are inseparable even by using chromatographic techniques. In
this work, all formed iodotriazoles 6 could be easily isolated
after a simple extraction and washing with pentane.
average of at least two independent experiments. [a] Conversion determined
1
by H NMR spectroscopy.
an analytically pure form with no need for further purification.
Different aryl boronic acids could be efficiently used in this
preparation of triazoles 3, including heteroaromatic ones. Simi-
larly, both functionalized alkynes as well as simple aliphatic
ones were successfully used under these reaction conditions.
Catalyst C was also efficient with aryl azides, even sterically
hindered ones such as mesityl azide (Table 2, entry 3). Another
important advantage of this catalytic system is that it shows
a wider functional group tolerance. Unsaturated C=C bonds, or
pyridines did not prevent the reaction from taking place and
the respective iodotriazoles could be easily isolated, whereas
no reaction whatsoever had previously been observed with
a phosphine catalyst (Table 2, entries 4–6). In several instances,
C also outperformed the N-heterocyclic carbene (NHC)-based
Cycloaddition of azides and iodoalkynes
We started screening different phosphinite and phosphonite
complexes with benzyl azide and iodoethynylbenzene as the
model substrates. Reactions were carried out neat at room
temperature (Scheme 5).
No reactivity trends could be drawn from the obtained re-
sults. Average conversions were observed with complexes B
and C, whereas complexes with no functionalized ligands gave
[18e]
catalyst [CuCl(IPr)].
Such an unequivocal change in reactivity
ChemCatChem 2016, 8, 1 – 6
www.chemcatchem.org
3
ꢃ 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
These are not the final page numbers! ÞÞ

Full Papers
Conclusions
The utility of phosphinite–copper(I) complexes in cycloaddition
reactions has been explored. In particular, we have developed
two competent catalytic systems for the 1,3-dipolar cycloaddi-
tion of terminal alkynes with aryl azides generated in situ from
the corresponding boronic acids as well as azides and iodoal-
kynes. These rely on robust air-stable copper complexes that
can be handled in air with no particular precautions. Impor-
tantly, both the reaction conditions as well as the isolation of
the desired product are ‘Click-friendly’.
Phosphinite–copper complex A represents the first homoge-
nous copper(I) complex for the one-pot azidonation/cycloaddi-
tion of boronic acids and allows the clean formation of the de-
sired 5-H-triazoles with a lower metal loadings than reported
for heterogeneous alternatives. On the other hand, our results
in the synthesis of 5-iodotriazoles clearly show that phosphin-
ite–copper complex C is not a mere analog of [CuI(PPh ) ],
3
3
with somewhat improved reactivity. Even if slightly higher
metal loadings (5 instead of 1 mol%) and mild heating are re-
quired, the use of a phosphinite ligand has a profound impact
on the scope of the catalytic system, both in terms of steric
hindrance and functional group tolerance.
Scheme 6. Scope of the azido–iodoalkyne cycloaddition. Isolated yields are
the average of at least two independent experiments. H NMR conversions
are shown in brackets for reactions that did not reach completion.
1
[a] Reaction time=48 h.
Compared with ubiquitous phosphine ligands, phosphinites
(
or phosphonite) ligands have only been used in a handful of
[28]
Table 2. Comparison of phosphine and phosphinite systems in the
preparation of 5-iodotriazoles.
copper-catalyzed transformations. Moreover, to the best of
our knowledge, no other pre-formed copper complexes with
these ligands have found applications in catalysis to date.
However, the remarkable improvement in reactivity and ap-
plicability make these system attractive candidates for other
copper-mediated processes. Efforts in this direction are cur-
rently ongoing in our laboratory and will be reported in due
course.
Entry
6
[Cu]
t
Conv.
[%]
Yield
[%]
[
a]
[a]
[h]
[
b]
[
C
CuI(PPh
3
3
3
)
)
)
3
]
3
]
3
]
18
18
74
70
n.d.
62
1
2
Experimental Section
[
b]
[CuI(PPh
18
18
79
88
n.d.
80
C
Catalytic reactions were carried out in air and by using technical
solvents without any particular precautions to exclude moisture or
oxygen. The reported isolated yields for the catalytic studies are an
average of two independent reactions.
[CuI(PPh
48
48
24
>95
n.d.
88
C
3
CAUTION: Although we did not experience any problems, the
cycloaddition of azides and (iodo)alkynes is highly exothermic and,
as a consequence, adequate cooling should always be available
when performing these reactions in the absence of solvent.
[
C
CuI(PPh
3
)
3
]
18
18
<5
76
–
65
4
5
[CuI(PPh
3
3
)
)
3
]
]
18
18
<5
>95
–
88
C
A. Three-component reaction (boronic acid, NaN , alkyne)
3
[CuI(PPh
3
18
18
<5
76
–
69
In a vial fitted with a screw cap, {CuBr[PPh (OPh-2-OMe)]} A
C
2
6
(
(
11 mg, 5 mol%),
0.5 mmol), water (1.5 mL), and MeOH (1.5 mL) were added and
a boronic acid (0.5 mmol), sodium azide
1
[
a] H NMR conversions and isolated yields are the average of at least two
independent experiments. [b] 5–10% of 5-H-triazole formed.
stirred for 18 h. Then, a terminal alkyne (0.5 mmol) was added and
the solution was stirred for 18 h. The precipitate was extracted
with ethyl acetate, stirred vigorously in aqueous saturated ammo-
nium chloride solution (10 mL) for 3 h. After separation, the organ-
ic layer was concentrated under reduced pressure and the result-
ing solid residue was washed with water, diethyl ether and
pentane, then dried under reduced pressure. In all examples, the
is striking and evidence for the key role of the phosphinite
ligand in the outcome of the reactions.
&
ChemCatChem 2016, 8, 1 – 6
www.chemcatchem.org
4
ꢃ 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!

Full Papers
1
crude products were estimated to be >95% pure by H NMR
ꢅzÅubukÅu, E. Ozkal, C. Jimeno, M. A. Pericꢆs, Org. Lett. 2009, 11, 4680–
4683.
spectroscopy.
[
[
12] a) C. J. Cavender, V. J. Shiner, Jr., J. Org. Chem. 1972, 37, 3567–3569;
b) P. B. Alper, S.-C. Hung, C.-H. Wong, Tetrahedron Lett. 1996, 37, 6029–
6032.
B. [3+2] Cycloaddition of azides and iodoalkynes
13] a) K. Barral, A. D. Moorhouse, J. E. Moses, Org. Lett. 2007, 9, 1809–1811;
b) S. Guo, M. H. Lim, H. V. Huynh, Organometallics 2013, 32, 7225–7233.
{
CuBr[PPh (OPh-4-OMe)]} C (11 mg, 5 mol%), azide (0.5 mmol), and
2
iodoalkyne (0.5 mmol) were loaded into a vial fitted with a screw
cap. The reaction was allowed to proceed at 408C for 18 h. Then,
saturated aqueous ammonium chloride solution (10 mL) was
added and the resulting mixture was stirred vigorously for 3 h. The
resulting precipitate was filtered and washed with water and
pentane, then dried under reduced pressure. In all examples, the
[14] a) W. Zhu, D. Ma, Chem. Commun. 2004, 888–889; b) A. K. Feldman, B.
Colasson, V. V. Fokin, Org. Lett. 2004, 6, 3897–3899. See also: c) J. An-
dersen, S. Bolving, X. Liang, Synlett 2005, 2941–2947.
[
15] For the use of diaryliodonium salts, see: D. Kumar, V. B. Reddy, Synthesis
010, 1687–1691.
16] a) C.-Z. Tao, X. Cui, J. Li, A.-X. Liu, L. Liu, Q. X. Guo, Tetrahedron Lett.
007, 48, 3525–3529; b) B. Kaboudin, Y. Abedi, T. Yokomatsu, Org.
2
[
2
1
crude products were estimated to be >95% pure by H NMR
spectroscopy.
Biomol. Chem. 2012, 10, 4543–4548; c) S. Mohammed, A. K. Padala,
B. A. Dar, B. Singh, B. Sreedhar, R. A. Vishwakarma, S. B. Bharate, Tetrahe-
dron 2012, 68, 8156–8162; d) N. Mukherjee, S. Ahammed, S. Bhadra,
B. C. Ranu, Green Chem. 2013, 15, 389–397; e) A. S. Kumar, M. A. Reddy,
M. Knorn, O. Reiser, B. Sheedhar, Eur. J. Org. Chem. 2013, 4674–4680;
f) B. S. P. Anil Kumar, K. H. V. Reddy, K. Karnakar, G. Satish, Y. V. D. Nages-
war, Tetrahedron Lett. 2015, 56, 1968–1972.
Acknowledgments
This research was financially supported by Imperial College. The
Royal Society (RG140579) and EPSRC (EP/K030760/1) are ac-
knowledged for further funding. J. M. P. thanks the MICINN
[
17] For the isolation of aryl azides from the corresponding boronic acids,
see: a) Y. Li, L.-X. Gao, F.-S. Han, Chem. Eur. J. 2010, 16, 7969–7972; b) H.
Yang, Y. Li, M. Jiang, J. Wang, H. Fu, Chem. Eur. J. 2011, 17, 5652–5660.
18] a) J. E. Hein, J. C. Tripp, L. B. Krasnova, K. B. Sharpless, V. V. Fokin, Angew.
Chem. Int. Ed. 2009, 48, 8018–8021; Angew. Chem. 2009, 121, 8162–
[
(Spain, FPI program, EEBB-I-14–08372) for an internship
fellowship.
8165; b) J. Garcꢁa-ꢇlvarez, J. Dꢁez, J. Gimeno, Green Chem. 2010, 12,
2127–2130; c) B. R. Buckley, S. E. Dann, H. Heaney, Chem. Eur. J. 2010,
16, 6278–6284; d) D. Wang, S. Chen, B. Chen, Tetrahedron Lett. 2014,
55, 7026–7028; e) S. Lal, H. S. Rzepa, S. Dꢁez-Gonzꢂlez, ACS Catal. 2014,
4, 2274–2287.
Keywords: azides · chemistry · copper · cycloaddition · P
ligands
[
19] For an early example of bromoalkyne cycloaddition, see: B. H. M. Kuijp-
ers, G. C. T. Dijkmans, S. Groothuys, P. J. L. M. Quaedflieg, R. H. Blaauw,
F. L. van Delft, F. P. J. T. Rutjes, Synlett 2005, 3059–3062.
[
[
[
[
1] A. Padwa in Comprehensive Organic Synthesis, Vol. 4 (Ed.: B. M. Trost),
Pergamon, Oxford, 1991, pp. 1069–1109.
2] R. Huisgen in 1,3-Dipolar Cycloaddition Chemistry (Ed.: A. Padwa), Wiley,
New York, 1984, pp. 1–176.
3] For the first report of a copper(I)-catalyzed [3+2] cycloaddition reaction,
see: G. L’abbꢀ, Bull. Soc. Chem. Belg. 1984, 93, 579–592.
4] a) C. W. Tornøe, C. Christensen, M. Meldal, J. Org. Chem. 2002, 67, 3057–
[20] a) E. Schwartz, K. Breitenkamp, V. V. Fokin, Macromolecules 2011, 44,
4735–4741; b) J. M. Schulman, A. A. Friedman, J. Panteleev, M. Lautens,
Chem. Commun. 2012, 48, 55–57; c) Y. Carcenac, F. David-Quillot, M.
Abarbri, A. DuchÞne, J. Thibonnet, Synthesis 2013, 45, 633–638.
[21] B. T. Worrell, J. A. Malik, V. V. Fokin, Science 2013, 340, 457–460.
[22] a) H. R. Snyder, M. S. Konecky, W. J. Lennarz, J. Am. Chem. Soc. 1958, 80,
3611–3616; b) A. L. Korich, P. M. Iovine, Dalton Trans. 2010, 39, 1423–
1431.
[23] For a representative example, see: A. Antoft-Finch, T. Blackburn, V.
Snieckus, J. Am. Chem. Soc. 2009, 131, 17750–17752.
[24] For a representative example, see: N. Selander, B. T. Worrell, S. Chupra-
kov, S. Velaparthi, V. V. Fokin, J. Am. Chem. Soc. 2012, 134, 14670–
14673.
[25] a) Y. Qin, C. Cui, F. Jꢄkle, Macromolecules 2007, 40, 1413–1420; b) J. Kua,
M. N. Fletcher, P. M. Iovine, J. Phys. Chem. A 2006, 110, 8158–8166.
[26] M. Storgaard, J. A. Ellman, Org. Synth. 2009, 86, 360–373.
[27] With catalyst C: 52% after 16 h, 65% after 40 h, 76% after 60 h. Identi-
cal conversions were observed with catalyst B.
[28] a) E. Guimet, M. Diꢀgez, A. Ruiz, C. Claver, Tetrahedron: Asymmetry 2005,
16, 2161–2165; b) A. Alexakis, J. Burton, J. Vastra, C. Benhaim, X. Four-
nioux, A. van den Henvel, J.-M. LevÞque, F. Mazꢀ, S. Rosset, Eur. J. Org.
Chem. 2000, 4011–4027; c) A. Martorell, R. Naasz, B. L. Feringa, P. G.
Pringle, Tetrahedron: Asymmetry 2001, 12, 2497–2499; d) A. Weickge-
nannt, M. Mewald, T. W. T. Muesmann, M. Oestreich, Angew. Chem. Int.
Ed. 2010, 49, 2223–2226; Angew. Chem. 2010, 122, 2269–2272.
3
064; b) V. V. Rostovtsev, L. G. Green, V. V. Fokin, K. B. Sharpless, Angew.
Chem. Int. Ed. 2002, 41, 2596–2599; Angew. Chem. 2002, 114, 2708–
711.
5] a) S. Chassaing, V. Bꢀnꢀteau, P. Pale, Catal. Sci. Technol. 2016, 6, 923–
57; b) S. Dꢁez-Gonzꢂlez, Catal. Sci. Technol. 2011, 1, 166–178; c) M.
2
[
[
9
Meldal, C. W. Tornøe, Chem. Rev. 2008, 108, 2952–3015.
6] a) F. Pꢀrez-Balderas, M. Ortega-MuÇoz, J. Morales-Sanfrutos, F. Hernꢂn-
dez-Mateo, F. G. Calvo-Flores, J. A. Calvo-Asꢁn, J. Isac-Garcꢁa, F. Santoyo-
Gonzꢂlez, Org. Lett. 2003, 5, 1951–1954; b) S. Lal, S. Dꢁez-Gonzꢂlez, J.
Org. Chem. 2011, 76, 2367–2373.
7] For other relevant P-based systems, see: a) L. S. Campbell-Verduyn, L.
Mirfeizi, R. A. Dierckx, P. H. Elsinga, B. L. Feringa, Chem. Commun. 2009,
[
2
139–2141; b) Z. Gonda, Z. Novꢂk, Dalton Trans. 2010, 39, 726–729;
c) D. Wang, N. Li, M. Zhao, W. Shi, C. Ma, B. Chen, Green Chem. 2010, 12,
120–2123.
8] S. Lal, J. McNally, A. J. P. White, S. Dꢁez-Gonzꢂlez, Organometallics 2011,
0, 6225–6232.
9] S. Brꢄse, C. Gil, K. Knepper, V. Zimmermann, Angew. Chem. Int. Ed. 2005,
4, 5188–5240; Angew. Chem. 2005, 117, 5320–5374.
2
[
[
3
4
[
10] a) E. F. V. Scriven, K. Turnbull, Chem. Rev. 1988, 88, 297–368; b) E. Saxon,
C. R. Bertozzi, Science 2000, 287, 2007–2010.
[
11] For selected examples, see: a) P. Appukkuttan, W. Dehaen, V. V. Fokin, E.
Van der Eycken, Org. Lett. 2004, 6, 4223–4225; b) S. Dꢁez-Gonzꢂlez, A.
Correa, L. Cavallo, S. P. Nolan, Chem. Eur. J. 2006, 12, 7558–7564; c) S.
Received: February 28, 2016
Published online on && &&, 0000
ChemCatChem 2016, 8, 1 – 6
www.chemcatchem.org
5
ꢃ 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
These are not the final page numbers! ÞÞ

FULL PAPERS
J. M. Pꢀrez, P. Crosbie, S. Lal,
S. Dꢁez-Gonzꢂlez*
&& – &&
Copper(I)–Phosphinite Complexes in
Click Cycloadditions: Three-
Component Reactions and Preparation
of 5-Iodotriazoles
Copper(I)–phosphinite complexes have
been applied to the one-pot azidona-
tion/cycloaddition of boronic acids,
kynes. These air-stable catalysts dis-
played remarkable activities in these
challenging reactions and the expected
products could be isolated pure form
under ‘Click-suitable’ conditions.
NaN , and terminal alkynes and also to
3
the cycloaddition of azides and iodoal-
&
ChemCatChem 2016, 8, 1 – 6
www.chemcatchem.org
6
ꢃ 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!