(Iminophosphorane)copper(I) complexes as highly efficient catalysts for 1,3-dipolar cycloaddition of azides with terminal and 1-iodoalkynes in water: One-pot multi-component reaction from alkynes and in situ generated azides

Article abstract of DOI:10.1002/ejic.201200789

Treatment of water-soluble phosphanes PTA (1) and DAPTA (2) with an equimolecular amount of azides (RO)₂P(=S)N₃ (R = Et, Ph) leads to high-yield formation of the N-thiophosphorylated iminophosphorane derivatives 3b and 4a,b, respectively. The reaction of these new iminophosphorane ligands with [Cu(NCCH₃)₄][PF₆] (in a 2:1 molar ratio) has been investigated. The resulting (iminophosphorane)copper(I) complexes 5b and 6a,b are efficient catalysts for the three-component cycloaddition reaction (organic halide, NaN₃ and terminal alkynes) in aqueous media to afford regioselectively, under mild and aerobic conditions according to click laws , 1,4-disubstituted triazoles with a broad substrate scope and functional compatibility. The unprecedented application of the analogous (iminophosphorane)copper(I) catalyst 5a to a one-pot three-component reaction with 1-iodoalkynes as an internal alkyne in aqueous medium is also reported. ESI-MS analysis of 5a in water and DFT theoretical calculations [B3LYP/6-31G(d)] have been carried out providing valuable insight into the actual active species responsible for catalytic activity in water. A new family of Cu^I complexes exhibit versatile and efficient catalytic activity in Huisgen cycloadditions of azides and 1-iodoalkynes in aqueous media under mild conditions; these are the first well-defined Cu^I catalysts found to be active in a three-component reaction with 1-iodoalkynes in aerobic aqueous conditions. Copyright

Full text of DOI:10.1002/ejic.201200789

FULL PAPER
DOI: 10.1002/ejic.201200789
(Iminophosphorane)copper(I) Complexes as Highly Efficient Catalysts for 1,3-
Dipolar Cycloaddition of Azides with Terminal and 1-Iodoalkynes in Water:
One-Pot Multi-Component Reaction from Alkynes and in situ Generated
Azides
Joaquín García-Álvarez,*[a] Josefina Díez,[a] Jose Gimeno,[a] Francisco J. Suárez,[a] and
Cristian Vincent[b]
Keywords: Click chemistry / Copper(I) catalysts / Aqueous media / 5-Iodotriazoles / 1-Iodoalkynes / Cycloaddition /
Multicomponent reactions
Treatment of water-soluble phosphanes PTA (1) and DAPTA
(2) with an equimolecular amount of azides (RO)2P(=S)N3 (R
under mild and aerobic conditions according to “click laws”,
1,4-disubstituted triazoles with a broad substrate scope and
= Et, Ph) leads to high-yield formation of the N-thiophosphor- functional compatibility. The unprecedented application of
ylated iminophosphorane derivatives 3b and 4a,b, respec-
tively. The reaction of these new iminophosphorane ligands
with [Cu(NCCH3)4][PF6] (in a 2:1 molar ratio) has been inves-
tigated. The resulting (iminophosphorane)copper(I) com-
plexes 5b and 6a,b are efficient catalysts for the three-com-
ponent cycloaddition reaction (organic halide, NaN3 and ter-
minal alkynes) in aqueous media to afford regioselectively,
the analogous (iminophosphorane)copper(I) catalyst 5a to a
one-pot three-component reaction with 1-iodoalkynes as an
internal alkyne in aqueous medium is also reported. ESI-MS
analysis of 5a in water and DFT theoretical calculations
[B3LYP/6-31G(d)] have been carried out providing valuable
insight into the actual active species responsible for catalytic
activity in water.
starting from a set of building blocks.[4,5] The most genuine
example of this concept is the copper(I)-catalyzed cycload-
dition of azides and terminal alkynes to yield 1,2,3-triazoles
(CuAAC) reported independently in 2002 by Meldal[6] and
Sharpless[7] (see Scheme 1). This achievement represents not
only an outstanding synthetic tool for the regioselective
synthesis of 1,4-disubstituted triazoles,[8] but also a signifi-
cant target reaction, in the context of developing cleaner
and more sustainable processes using an aqueous medium
as an alternative benign solvent.[9]
Introduction
During the last decade a huge amount of effort has been
dedicated to the development of catalytic processes in aque-
ous media.[1] Regardless of the fact that water is a safe, non-
toxic, eco-friendly and cheap solvent, it may give rise to a
completely new reactivity, enabling a variety of highly ef-
ficient and selective synthetic approaches with both aca-
demic and industrial applications.[2] In fact, the search for
new metal-mediated catalytic transformations in aqueous
media has become one of the main goals in organometallic
chemistry, as competitive synthetic approaches compared to
traditional routes using organic solvents.
Simultaneously, the concept of click chemistry, coined by
Sharpless and co-workers in 2001,[3] has emerged as a main
proposal to design thermodynamically driven transforma-
tions, directed to the preparation of more complex products
Scheme 1. Copper-catalyzed 1,3-cycloaddition reaction (CuAAC).
Surprisingly, only a few CuAAC reactions have been per-
formed in pure water as the reaction medium despite the
strong acceleration effect and regioselectivity of many or-
ganic reactions in aqueous media.[10] Typical examples in-
clude a series of well-defined copper(I) complexes contain-
ing N-heterocyclic carbenes,[11] the complex [CuBr-
(PPh3)3][12] and one further example containing a tripodal
tris(triazolyl)methanol derivative as ligand.[10c,13] In this
sense, we have recently reported the synthesis of the hydro-
soluble iminophosphorane ligand 3a and the corresponding
[a] Laboratorio de Química Organometálica y Catálisis (Unidad
Asociada al CSIC), Departamento de Química Orgánica e
Inorgánica, Instituto Universitario de Química Organometálica
“Enrique mol” Facultad de Química, Universidad de Oviedo,
33071 Oviedo, Spain
Fax: +34-985103446
E-mail: garciajoaquin@uniovi.es
Homepage: http://www.unioviedo.es/comorca/Joaquin%20
ingles.htm
[b] Serveis Centrals d’Instrumentació Científica, Universitat Jaume I,
Avenida Sos Baynat s/n, 12071 Castelló, Spain
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejic.201200789.
5854
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Eur. J. Inorg. Chem. 2012, 5854–5863

Efficient Aqueous Click Chemistry with Terminal and 1-Iodoalkynes
copper(I) complex 5a (Figure 1), which is a highly efficient phanes are available, but surprisingly their corresponding
catalyst for Huisgen 1,3-dipolar cycloadditions in pure iminophosphorane derivatives R3P=NRЈ [readily accessible
water.[14] Noteworthy is that 5a also shows chemo- and re- by Staudinger-type reactions between the phosphane and
gioselective activity with 1-iodoalkynes (Scheme 2), a fact the desired azide (RЈN3)],[17] have barely been noticed in
which, to the best of our knowledge, has previously been organometallic chemistry.[18] With this precedent in mind,
reported only for one other catalytic system in an aqueous and applying the procedure previously described for the
medium.[15]
synthesis of the iminophosphorane ligand 3a,[14] we set up
the synthesis of novel iminophosphoranes based on PTA
(3b) or its acetyl derivative DAPTA (4a,b) (Figure 1) to be
used as ligands for the design of new copper(I) catalysts
active in CuAAC reactions in aqueous medium (5b,6a,b,
Figure 1). Thus, using the well-known experimental pro-
cedure, through the classical Staudinger reaction,[17] the
novel N-thiophosphorylated iminophosphorane ligands 3b
and 4a,b, were readily synthesized by treatment of the
water-soluble phosphane PTA (1) or DAPTA (2) with the
corresponding N-thiophosphorylated azide (RO)2P(=S)N3
at room temperature (3b) or refluxing THF (4a,b) (see
Scheme 3).[19] All compounds were isolated as air- and
moisture-stable white solids in 79–86% yield, after a simple
workup (Experimental Section).
Figure 1. Structure of ligands 3,4a,b and their copper(I) complexes
5,6a,b.
Scheme 2. (Iminophosphorane)copper(I)-catalyzed formation of 5-
iodo-1,2,3-triazoles in water.
In the context of our explorations into this type of trans-
formation in an aqueous medium, we report herein the syn-
thesis and catalytic activity in water of a series of novel
copper(I) complexes 5b,6a,b (Figure 1) containing imino-
phosphorane ligands 3b,4a,b [based on 1,3,5-triaza-7-phos-
phaadamantane (PTA) and 3,7-diacetyl-1,3,7-triaza-5-bicy-
clo[3.3.1]nonane (DAPTA)]. The following features are
noteworthy: (i) all are water- and air-stable efficient cata-
lysts and active in the three-component reaction (organic
bromide, NaN3 and terminal alkynes); (ii) complex 5a is
also active in the regio- and chemoselective synthesis of 5-
iodo-1,2,3-triazoles through the one-pot 1,3-cycloaddition
reaction of in situ generated azides with 1-iodoalkynes. As
far as we know, this is the first example reported of an
isolated copper(I) catalyst active with internal alkynes.
Scheme 3. Synthesis of the iminophosphorane ligands 3b and 4a,b.
Characterization of compounds 3b and 4a,b was ac-
complished in a straightforward fashion by analysis of their
analytical and spectroscopic data (Experimental Section).
In particular, imination of the phosphorus atom of both
PTA (1) and DAPTA (2) phosphanes was clearly reflected
in the 31P{1H} NMR spectra, showing the presence of two
well-separated doublets (2JPP = 6.7–24.8 Hz) at δP = –34.27
to –12.40 ppm for the iminophosphorane group (R3P=N)
and 52.72–62.38 ppm for the thiophosphoryl group
1
[(RO)2P=S]. In the H and the 13C{1H} NMR spectra, the
expected signals for the corresponding phosphane back-
bone (PTA and DAPTA, respectively) are found. It is im-
portant to note that only iminophosphorane 4a was found
to be soluble in water (312 mg/mL vs. 201 mg/mL for 3a),
with solubility values lower than for DAPTA (1696 mg/
mL). The insoluble nature of derivatives 3,4b in water is
Results and Discussion
Synthesis and Characterization of N-Thiophosphorylated
Iminophosphorane Ligands (PTA)=NP(=S)(OPh)2 (3b) and
(DAPTA)=NP(=S)(OR)2 [R = Et (4a), Ph (4b)]
A large variety of water-soluble organometallic com- probably due to the enriched carbon character acquired by
plexes have been synthesized and applied as efficient cata- changing ethyl for phenyl groups in the units –P(=S)(OR)2
lysts.[2,16] The most common strategy to obtain such deriva- (R = Et, Ph).[20]
tives consists of using hydrophilic P-donor ligands.[16] To
Moreover, the molecular structures of compounds 3b
date a large number of water-soluble monodentate phos- and 4b have been determined by X-ray diffraction methods.
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FULL PAPER
Figure 2. ORTEP-type view of the structure of compounds 3b (left) and 4b (right) showing the crystallographic labelling scheme. Hydrogen
atoms have been omitted for clarity. Thermal ellipsoids are drawn at 10% probability level. Selected bond lengths [Å] and angles [°] for
3b: P(1)–N(4) 1.569(3), N(4)–P(2) 1.584(3), P(2)–S(1) 1.935(1); P(1)–N(4)–P(2) 130.9(2), N(4)–P(2)–S(1) 121.5(1). Selected bond lengths
[Å] and angles [°] for 4b: P(1)–N(4) 1.572(2), N(4)–P(2) 1.592(3), P(2)–S(1) 1.935(1), C(6)–O(1) 1.218(3), C(8)–O(2) 1.225(3); P(1)–N(4)–
P(2) 130.5(1), N(4)–P(2)–S(1) 118.9(1), N(1)–C(8)–O(2) 121.0(3), N(3)–C(6)–O(1) 121.0(2).
ORTEP plots of the structures are shown in Figure 2; se- framework.[23] The two C(=O)CH3 groups in 4b are in an
lected bonding parameters are listed in the caption. The anti disposition as they have also been found previously in
most noticeable features of these structures are the follow- the solid-state X-ray crystal structure of DAPTA.[19]
ing: (i) the P=S bond lengths of the N-thiophosphorylated
groups [P(2)–S(1) 1.935(1) Å for both 3b and 4b], which fall
within the expected range for a phosphorus–sulfur double
Synthesis of (Iminophosphorane)copper(I) Complexes
bond,[21] are in a good agreement with those previously re-
[Cu{μ2-N,S-(PTA)=NP(=S)(OPh)2}2][PF6] (5b) and [Cu{μ2-
ported for other N-thiophosphorylated iminophosphoranes
N,S-(DAPTA)=NP(=S)(OR)2}2][PF6] [R = Et (6a), Ph
(6b)]
[R3P=N–P(=S)(ORЈ)2],[22] and (ii) the similarity between
the lengths of the formal single [N(4)–P(2) 1.584(3) (3b) and
1.592(3) Å (4b)] and double [P(1)–N(4) 1.569(3) (3b) and
The new (iminophosphorane)copper(I) complexes 5b and
1.572(2) Å (4b)] phosphorus–nitrogen bonds in the N-thio- 6a,b have been prepared by treatment of [Cu(NCCH3)4]-
phosphorylated units P=NP(=S)(OPh)2. This fact is proba- [PF6] with 2 equiv. of the corresponding iminophosphorane
bly determined by the strong π-acceptor nature of the thio- ligand 3b,4a,b in dichloromethane at room temperature (see
phosphoryl group, which enhances the delocalization of Scheme 4). All complexes were isolated as air-stable white
the electron pair of the nitrogen atom along the P=N–P=S solids in 73–79% yield. In accordance with the hydrosolu-
Scheme 4. Synthesis of the copper(I) complexes 5,6a,b.
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Efficient Aqueous Click Chemistry with Terminal and 1-Iodoalkynes
bility of the iminophosphorane ligand 4a, the correspond- torted tetrahedral geometry. The X-ray analysis unambigu-
ing copper(I) complex 6a was also found to be soluble in ously confirmed the formation of a 14-membered ring
water (384 mg/mL vs. 219 mg/mL for 5a) and to behave as CuSPNPCNCuSPNPCN, constructed by two CuI atoms
1:1 electrolyte in aqueous solution (ΩM
= 109 vs. bridged by two ligands in a head-to-tail conformation (see
117 Ω–1 cm2 mol–1 for 5a). In contrast, complexes 5b and 6b Scheme 4). The tetracoordinate copper(I) atoms allowed for
were scarcely soluble in water. Complexes 5b,6a,b have been connection of two 14-membered rings giving rise to a poly-
characterized by means of standard spectroscopic tech- meric chain.
1
niques [IR and 31P(1H), H, and 13C(1H) NMR] and ele-
mental analysis, which support the proposed formulations
(Experimental Section).
Spectroscopic data are particularly relevant for the deter-
mination of the ligands’ coordination modes, which are
Chemical Speciation in Water: ESI Mass Spectrometry and
DFT Analysis
consistent with the S-coordination of the thiophosphoryl
In order to gain more information about the integrity
fragment [(RO)2P=S] and with the N-coordination of one and nature of the species present in aqueous solution, mass
nitrogen atom from the adamantane ring. These features spectrometric measurements (ESI-MS) of a solution of 5a
are clearly reflected in their 31P{1H} NMR spectra by: (i) in water were performed.[25] Positive ESI mass spectra re-
slight variations in the P=N (Δδ = 2–6 ppm) and (RO)2P=S corded upon gentle ionization conditions (cone voltage Uc
(Δδ = 2–5 ppm) resonances, and (ii) conversion of the doub- = 10 V) revealed a monomeric species [Cu{(PTA)=NP-
let signals of the P=N and (RO)2P=S groups in the free (=S)(OEt)2}2]+ with m/z = 711 as the base peak. Assign-
ligand into two broad singlets in complexes 5a,b. As ex- ment was based on the m/z value as well as its characteristic
1
pected, H and the 13C{1H} NMR spectra display the cor- isotopic pattern (see Figure SI-1 in Supporting Infor-
responding phosphane backbone signals of PTA and mation). Additional ESI mass spectra were collected upon
DAPTA. The observed preference for the S- vs. N-coordi- varying the ionization conditions [typically the cone voltage
nation of the iminophosphoranyl units P=N–P(=S)(OR)2 (Uc) in the Uc = 5–35 V range]. It is interesting to note that
in complexes 5b,6a,b is in complete accord with the known polynuclear or loosely solvated aquo complexes were not
coordination chemistry of N-thiophosphorylated imino- observed in these ESI mass spectra, thus suggesting that,
phosphoranes R3P=N–P=S(ORЈ)2, which is almost entirely unlike in the solid state, complex 5a is dismantled in the
dominated by the coordination of the sulfur atom.[24] As we aqueous solution to give predominantly the monomeric
have previously reported,[14] the real nature of these com- complex [Cu{(PTA)=NP(=S)(OEt)2}2]+. Since three coor-
plexes could only be determined by single-crystal X-ray dif- dination isomers can be proposed for these monomeric spe-
fraction methods. These data confirmed that the coordina- cies, namely [Cu{κ1-S-(PTA)=NP(=S)(OEt)2}2]+ (I),
tion sphere around the copper atom consists of: (i) two S- [Cu{κ1-S-(PTA)=NP(=S)(OEt)2}{κ1-N-(PTA)=NP(=S)-
coordinated (EtO)2P=S units, and (ii) two N-coordinated (OEt)2}]+ (II) and [Cu{κ1-N-(PTA)=NP(=S)(OEt)2}2]+ (III)
amino groups from the adamantane ring, displaying a dis- (see Figure 3), theoretical calculations on the relative stabi-
Figure 3. Structure of the three coordination isomers proposed [Cu{κ1-S-(PTA)=NP(=S)(OEt)2}2]+ (I), [Cu{κ1-S-(PTA)=NP(=S)-
(OEt)2}{κ1-N-(PTA)=NP(=S)(OEt)2}]+ (II) and [Cu{κ1-N-(PTA)=NP(=S)(OEt)2}2]+ (III).
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FULL PAPER
lization energies have been analyzed by B3LYP/6-31G(d) cial, as the efficiency of the reaction was markedly lower
DFT studies (details are given in the Supporting Infor- when complexes 5,6a,b were replaced by other CuI sources
mation). The theoretical data have been obtained using such as CuI.[30b]
bond lengths and angles from the X-ray data of complex
Table 1. One-pot multicomponent reaction of PhCH2Br, NaN3 and
5a. Frequency calculations for the optimized geometries
have been performed and are consistent with minima on the
potential energy surface. In this theoretical study, we found
that the isomer [Cu{κ1-S-(PTA)=NP(=S)(OEt)2}2]+ (I) with
a selective κ1-S coordination of the ligand 3a is: (i)
8.3 kcalmol–1 more stable than the mixed κ1-S,κ1-N-mono-
PhCϵCH catalyzed by complexes 5,6a,b in water.[a]
mer
[Cu{κ1-S-(PTA)=NP(=S)(OEt)2}{κ1-N-(PTA)=NP-
(=S)(OEt)2}]+ (II), and (ii) 11.8 kcalmol–1 more stable than
the κ1-N-monomer [Cu{κ1-N-(PTA)=NP(=S)(OEt)2}2]+
(III). This fact is in agreement with the relatively longer
Cu–N bonds observed in complex 5a, which apparently are
easily cleaved in water.[14,26] It is apparent that these species
are readily formed and therefore can be proposed as the
active catalytic species in aqueous medium (see below).
Entry
Catalyst
mol-% [Cu]
Time [h]
Yield [%][b]
1
2
3
4
5a
5b
6a
6b
0.5
0.5
0.5
0.5
6
97
99
96
99
15
12
17
[a] General conditions: 2,6-lutidine (10 mol-%), PhCϵCH
(1 mmol), NaN3 (1.1 mmol), PhCH2Br (1 mmol-%), water (2 mL),
air, room temp. [b] Isolated yields.
The scope of applications for catalyst 5a in the three-
component reaction was investigated under the optimized
reaction conditions (see Table 2). Thus, satisfactory cata-
lytic activities have been found for a wide variety of alkynes
containing a plethora of functional groups such as, alkyl
(7b), hydroxy (7c), halide (7d), and ester (7e) substituents,
which react with in situ generated benzyl azide leading with
almost quantitative yields to the corresponding triazoles in
5–7 h. This catalytic methodology is also feasible for the
synthesis of triazoles with different in situ generated azides.
Satisfyingly, an array of activated organic bromides
(Table 2, Entries 6–9) were tested leading nicely to the for-
mation of corresponding triazoles in near quantitative
yields bearing either electron-withdrawing (Table 2, En-
try 7) or electron-donating groups (Table 2, Entries 8 and
9).
Catalytic 1,3-Dipolar Cycloaddition of in Situ Generated
Azides (Organic Halide and NaN3) with Terminal Alkynes
in Water
Due to the danger, difficulty in handling and isolation
problems of low-molecular weight organic azides,[27]
a
number of methodologies have been developed for the syn-
thesis of 1,4-disubstituted triazoles using [3+2] cycload-
ditions, avoiding the use of pre-isolated azides. In this re-
gard, the use of a three-component reaction (organic halide,
NaN3 and terminal alkyne) catalyzed by different copper(I)
species has been reported.[11a,12,13,28] Thus, inspired by these
precedents, we tested the catalytic activity of complexes
5,6a,b in three-component reactions of in situ generated az-
ides and terminal alkynes under very mild reaction condi-
tions (pure water as solvent, at room temperature and under
aerobic conditions).[29] In a typical experiment, the multi-
component model reaction of benzyl bromide, NaN3 and
phenylacetylene was performed, using 0.5 mol-% of the
complexes as catalyst loadings in the presence of 2,6-lut-
idine (2,6-dimethylpyridine).[30a] The course of the reaction
was monitored by gas chromatography, and the results ob-
tained are summarized in Table 1. To our satisfaction, all
the complexes (Table 1, Entries 1–4) were found to be active
and selective catalysts at room temperature, affording 4-
phenyl-1-(phenylmethyl)-1H-1,2,3-triazole (7a) as the
unique reaction product. The addition of an amine ligand
to act as a base was crucial since no reaction was observed
in its absence. Interestingly, the catalytic activity of complex
5a (containing the ligand PTA-iminophosphorane) is higher
than that of complex 6a (containing the ligand DAPTA-
iminophosphorane) (Table 1, Entries 1 and 3; 6 vs. 12 h,
respectively). A similar catalytic trend has also been found
in their water-insoluble counterpart catalysts 5b and 6b
(Table 1, Entries 2 and 4; 15 vs. 17 h, respectively), demon-
strating the influence of the iminophosphorane ligand on
Table 2. One-pot multicomponent synthesis of 1,2,3-triazoles cata-
lyzed by complex 5a in water.[a]
Entry
R
RЈ
Time
[h]
Yield
[%][b]
1
2
3
4
5
6
7
8
9
Ph
nBu
C(OH)Ph2
p-FC6H4
CO2Et
Ph
CH2Ph
CH2Ph
CH2Ph
CH2Ph
CH2Ph
7a
7b
7c
7d
7e
7f
7g
7h
7i
6
7
7
6
5
4
8
5
4
97
95
97
96
95
96
94
92
97
allyl
Ph
Ph
Ph
3-Cl-C6H4CH2
3-Me-C6H4CH2
3-MeO-C6H4CH2
[a] General conditions: 2,6-lutidine (10 mol-%), alkyne (1 mmol),
NaN3 (1.1 mmol), RЈ–Br (1 mmol), H2O (2 mL), air, room temp.
the reaction rate. The nature of the copper catalyst was cru- [b] Isolated yields.
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Efficient Aqueous Click Chemistry with Terminal and 1-Iodoalkynes
Catalytic 1,3-Dipolar Cycloaddition of in Situ Generated
Azides (Organic Halide and NaN3) with Internal 1-Iodo-
alkynes in Water
fluoride (8d) and ester (8e) groups. Moreover, this catalytic
system can also promote the cycloaddition reaction using
different organic bromides (Table 3, Entries 6–9). Again, re-
actions proceeded to completion in water with both elec-
tron-withdrawing (Table 3, Entry 7) and electron-donating
groups (Table 3, Entries 8 and 9), although longer reaction
times were required, relative to their terminal counterparts.
At this point, it is important to note that, as far as we are
aware, no precedent for a multicomponent reaction using
1-iodoalkynes has been previously reported.
As expected, the 5-iodo-1,2,3-triazole 8a was sub-
sequently functionalized easily using a Suzuki cross-cou-
pling reaction with the organoboronic acid PhB(OH)2; the
corresponding 1-benzyl-4,5-diphenyl-1H-1,2,3-triazole was
generated in almost quantitative yield (95%) (Scheme 5).
This result clearly shows that 5-iodo-1,2,3-triazoles can be
readily functionalized by cross-coupling reactions and con-
firms their utility for construction of new organic deriva-
tives.[37]
The formation of intermediates based on copper(I) acet-
ylide species is postulated as the first step in CuAAC reac-
tions.[31] In accordance with this proposed mechanism, in-
ternal alkynes are not able to undergo the required cycload-
dition, a limitation generally observed with conventional
copper catalysts.[32] As a matter of fact, only one example
of an efficient catalytic system for chemo- and regioselective
cycloaddition of azides with 1-iodoalkynes in an aqueous
medium, namely the equimolar mixture of CuI and TTTA
{TTTA
=
tris[(1-tert-butyl-1H-1,2,3-triazolyl)methyl]-
amine},[15,33] has been described to date.[34] 5-Iodo-1,2,3-
triazoles synthesized by application of this click reaction[35]
are versatile synthetic intermediates amenable to further
functionalization providing an appealing synthetic ap-
proach to different substituted 1,2,3-triazoles.[36] Taking
into account the efficiency of 5a in the three-component
reaction of in situ generated azides and terminal alkynes,
and our previously gained experience in the CuAAC of az-
ides and 1-iodoalkynes in an aqueous medium,[14] we de-
cided to focus our attention on the three-component reac-
tion with iodoalkynes; as far as we are aware, such systems
have not been previously reported. The reaction of benzyl
Scheme 5. Suzuki cross coupling of 5-iodotriazole 8a with
bromide (PhCH2Br), sodium azide (NaN3) and PhCϵCI, PhB(OH)2.
in pure water, in air and at room temperature, was used
as a model reaction. To our delight, this new process was
catalyzed by 5a (2 mol-%) affording chemoselectively (no
Conclusions
by-products or products derived from reductive dehaloge-
nation were detected by GC, i.e. 5-H-1,2,3-triazoles) the
corresponding 5-iodo-1,2,3-triazole in excellent yield
(Table 3, Entry 1). As in the aforementioned three-compo-
nent reaction with terminal alkynes catalyzed by 5a, the
reaction tolerates a diverse array of functional groups in the
1-iodoalkyne (Table 3), including alkyl (8b), hydroxy (8c),
In the present work we have described a high-yielding
synthesis of new N-thiophosphorylated iminophosphorane
ligands 3b,4a,b and their corresponding copper(I) com-
plexes 5b,6a,b in which these heterodifunctional ligands
adopt a bridging μ2-(N,S) coordination mode giving rise to
a polymeric structure in the solid state. These complexes,
along with partner complex 5a, are efficient catalysts in
multicomponent one-pot CuAAC reactions in water of in
situ generated azides with alkynes to selectively afford 1,2,3-
triazoles. The following features are noteworthy. (i) The
high stability of these copper(I) complexes precludes their
oxidation or disproportionation, which allows the catalytic
reactions to be performed in the presence of air and in
aqueous media. This property represents an important con-
tribution to click chemistry, since these processes are gen-
erally associated with most polyamine copper(I) catalysts in
CuAAC reactions. (ii) Complex 5a is a highly efficient cata-
lyst for one-pot three-component reactions in aqueous me-
dia (organic halide, NaN3 and alkynes) under mild and aer-
obic conditions displaying broad substrate scope and func-
tional compatibility. (iii) Complex 5a is the first example of
an isolated and crystallographically characterized copper(I)
pre-catalyst active in the multicomponent CuAAC reactions
of 1-iodoalkynes in water in a one-pot manner to give ex-
clusively 5-iodo-1,2,3-triazoles according to “click” laws.
(iv) 5-Iodo-1,2,3-triazole 8a was successfully used in a palla-
dium-catalyzed cross-coupling reaction with an organo-
Table 3. One-pot multicomponent synthesis of 5-iodo-1,2,3-tri-
azoles catalyzed by complex 5a in water.[a]
Entry
R
RЈ
Time
[h]
Yield
[%][b]
1
2
3
4
5
6
7
8
9
Ph
nBu
C(OH)Ph2
p-FC6H4
CO2Et
Ph
CH2Ph
CH2Ph
CH2Ph
CH2Ph
CH2Ph
8a
8b
8c
8d
8e
8f
8g
8h
8i
10
9
9
8
7
7
12
9
94
96
98
93
95
98
96
93
94
allyl
Ph
Ph
Ph
3-ClC6H4CH2
3-MeC6H4CH2
3-MeOC6H4CH2
9
[a] General conditions: 2,6-lutidine (10 mol-%), 1-iodoalkyne
(1 mmol), NaN3 (1.1 mmol), RЈ–Br (1 mmol), H2O (2 mL), air,
room temp. [b] Isolated yields.
Eur. J. Inorg. Chem. 2012, 5854–5863
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjic.org
5859

J. García-Álvarez, J. Díez, J. Gimeno, F. J. Suárez, C. Vincent
FULL PAPER
2
CHarom), 151.76 (d, JCP = 9.5 Hz, Cipso of OPh) ppm. 4a: Yield
boronic acid, demonstrating that this methodology is ame-
nable to further functionalizations of synthetic interest.
86% (0.681 g). C13H26N4O4P2S (396.38): calcd. C 39.39, H 6.61, N
14.13; found C 39.30, H 6.57, N 14.15. IR (KBr): ν = 464, 483,
˜
518, 560, 592, 624, 668, 702, 780, 838, 894, 951, 990, 1042, 1094,
1123, 1161, 1223, 1258, 1300, 1332, 1355, 1422, 1651, 2140, 2360,
2898, 2931, 2978 cm–1. 31P{1H} NMR (121.5 MHz, D2O): δ =
Experimental Section
2
2
–12.40 (d, JPP
(EtO)2P=S] ppm. H NMR (300 MHz, D2O): δ = 1.36 (t, JHH
=
6.7 Hz, P=N), 60.58 [d, JPP
= 6.7 Hz,
General Methods: Synthetic procedures were performed under dry
nitrogen using vacuum-line and standard Schlenk techniques. Sol-
vents were dried by standard methods and distilled under nitrogen
before use. All reagents were obtained from commercial suppliers
and used without further purification with the exception of com-
pounds DAPTA[19] and N3P(=S)(OR)2 (R = Et, Ph),[38] which were
prepared by applying the method reported in the literature. Infra-
red spectra were recorded with a Perkin–Elmer 1720-XFT spec-
trometer. The conductivities were measured at room temp., in ca.
10–3 moldm–3 acetone or water solutions, with a Jenway PCM3
conductimeter. The C, H and N analyses were carried out with a
Perkin–Elmer 2400 microanalyzer. NMR spectra were recorded
using a Bruker DPX300 instrument at 300 MHz (1H), 121.5 MHz
(31P) or 75.4 MHz (13C) using SiMe4 or 85% H3PO4 as standards.
DEPT experiments have been carried out for all the compounds
reported in this paper. For electrospray ionization mass spectrome-
try (ESI-MS) studies, a QTOF Premier instrument with an orthog-
onal Z-spray-electrospray interface (Waters, Manchester, UK) was
1
3
=
7.0 Hz, 6 H, OCH2CH3), 2.18 and 2.19 (s, 3 H each, COCH3), 3.84
(m, 1 H, NCH2N), 4.22 (m, 8 H, 4 H for OCH2CH3 and 4 H for
PCH2NCO), 4.67, 5.16, 5.64 (d, JHH = 14.3 Hz, 1 H, each,
NCH2N), 4.91 and 5.57 (m, 1 H, each, PCH2N) ppm. 13C{1H}
3
NMR (75.4 MHz, D2O): δ = 14.91 (d, JCP = 8.2 Hz, OCH2CH3),
20.47 and 20.27 (s, COCH3), 39.49 (dd, 1JCP = 70.0, 3JCP = 4.3 Hz,
1
3
PCH2N), 44.63 (dd, JCP = 68.4, JCP = 4.5 Hz, PCH2N), 49.14
1
3
3
(dd, JCP = 60.7, JCP = 3.5 Hz, PCH2N), 61.20 (d, JCP = 7.1 Hz,
2
3
NCH2N), 63.41 (d, JCP = 6.4 Hz, OCH2CH3), 66.22 (d, JCP
=
3
6.7 Hz, NCH2N), 171.81 and 172.46 (d, JCP = 2.5 Hz, COCH3)
ppm. 4b: Yield 83% (0.817 g). C21H26N4O4P2S (492.47): calcd. C
51.22, H 5.32, N 11.38; found C 51.26, H 5.37, N 11.34. IR (KBr):
ν = 464, 488, 517, 555, 575, 599, 618, 690, 705, 743, 782, 839, 878,
˜
891, 907, 931, 945, 988, 1022, 1041, 1070, 1095, 1123, 1162, 1200,
1243, 1267, 1306, 1320, 1349, 1378, 1397, 1421, 1460, 1484, 1585,
1633, 1652, 1898, 1965, 2893, 2989, 3008, 3066 cm–1. 31P{1H}
2
NMR (121.5 MHz, CD2Cl2): δ = –18.66 (d, JPP = 24.8 Hz, P=N),
used operating in the W-mode at
a
resolution of ca.
2
52.72 [d, JPP = 24.8 Hz, (PhO)2P=S] ppm. 1H NMR (300 MHz,
15000 (FWHM). The drying and cone gas was nitrogen set to flow
rates of 300 and 30 L/h, respectively. A capillary voltage of 3.5 kV
was used in the positive scan mode, and the cone voltage varied in
the Uc = 5–35 V range. CCDC-891690 (for 3b), and -891691 (for
4b) contain the supplementary crystallographic data for this paper.
These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_
request/cif.
CD2Cl2): δ = 2.01 and 2.06 (s, 3 H each, COCH3), 3.38, 4.83 and
5.63 (d, JHH = 14.0 Hz, 1 H, each, NCH2N), 4.34 (m, 2 H, 1 H,
for NCH2N and 1 H, for PCH2N), 3.88 (m, 4 H, PCH2NCO), 5.47
(m, 1 H, PCH2N), 6.86–7.40 (m, 10 H, CHarom) ppm. 13C{1H}
NMR (75.4 MHz, CD2Cl2): δ = 21.00 and 21.36 (s, COCH3), 40.02
1
3
1
(dd, JCP = 73.5, JCP = 5.6 Hz, PCH2N), 45.02 (dd, JCP = 68.6,
3JCP = 5.2 Hz, PCH2N), 51.01 (d, JCP = 58.3 Hz, PCH2N), 61.60
1
3
3
(d, JCP = 7.2 Hz, NCH2N), 66.66 (d, JCP = 6.4 Hz, NCH2N),
115.32–129.53 (m, CHarom), 151.50 (d, 2JCP = 8.8 Hz, Cipso of OPh),
General Procedure for the Synthesis of the N-Thiophosphorylated
Iminophosphorane Ligands (PTA)=NP(=S)(OPh)2 (3b) and (DAP-
TA)=NP(=S)(OR)2 [R = Et (4a), Ph (4b)]: For 3b, a solution of
the water-soluble phosphane ligand PTA (0.314 g, 2 mmol) in THF
(40 mL) was treated with the thiophosphorylated azide
N3P=S(OPh)2 (2.1 mmol) at room temp. for 4 h. Then, the solvent
was evaporated to dryness to give a colourless oil, which was dis-
solved in CH2Cl2 (ca. 5 mL). The addition of diethyl ether (ca.
50 mL) precipitated a white microcrystalline solid, which was
washed with diethyl ether (3ϫ10 mL) and dried in vacuo. For 4a,b,
a solution of the phosphane ligand DAPTA (0.458 g, 2 mmol) in
THF (40 mL) was refluxed in the presence of the corresponding
thiophosphorylated azide N3P=S(OR)2 (R = Et, Ph) (2.1 mmol)
for 6 h. Again, the solvent was removed under vacuum to yield a
colourless oil, which was dissolved in CH2Cl2 (ca. 5 mL). The ad-
dition of diethyl ether (ca. 50 mL) precipitated a white microcrys-
talline solid, which was washed with diethyl ether (3ϫ10 mL), and
dried in vacuo. 3b: Yield 79% (0.664 g). C18H22N4O2P2S (420.40):
calcd. C 51.42, H 5.27, N 13.33; found C 51.51, H 5.20, N 13.39.
2
151.56 (d, JCP = 5.9 Hz, Cipso of OPh), 169.32 and 169.82 (s,
COCH3) ppm.
Synthesis of [Cu{μ2-N,S-(PTA)=NP(=S)(OPh)2}][SbF6] (5b) and
[Cu{μ2-N,S-(DAPTA)=NP(=S)(OR)2}][SbF6] [R = Et (6a), Ph (6b)]:
A solution of the corresponding iminophosphorane ligand 3b or
4a,b (2 mmol) in CH2Cl2 (30 mL) was treated with [Cu(NCCH3)4]-
[PF6] (0.343 g, 1 mmol) and stirred for 1 h to yield a pale-yellow
clear solution. The mixture was then concentrated (ca. 1 mL) in
vacuo and the addition of diethyl ether (ca. 50 mL) precipitated a
white solid, which washed with diethyl ether (3ϫ10 mL) and dried
in vacuo. 5b: Yield 75% (0.786 g). CuC36H44F6N8O4P5S2 (1049.32):
calcd. C 41.21, H 4.23, N 10.68; found C 41.31, H 4.27, N 10.61.
Conductivity (acetone, 20 °C): 109 Ω–1 cm2 mol–1. IR (KBr): ν =
˜
454, 484, 495, 559, 578, 607, 628, 631, 669, 691, 736, 769, 838, 899,
921, 1009, 1024, 1071, 1097, 1167, 1196, 1229, 1250, 1271, 1288,
1359, 1409, 1453, 1488, 1590, 1629, 2872, 2934, 2959, 3059 cm–1.
31P{1H} NMR [121.5 MHz, (CD3)2C=O]: δ = –143.88 (sept, JPF
=
IR (KBr): ν = 461, 494, 539, 565, 581, 607, 631, 668, 692, 736, 759, 707.2 Hz, PF6), –32.80 (br. s, P=N), 50.88 [br. s, (PhO)2P=S] ppm.
˜
768, 782, 816, 840, 898, 921, 971, 1009, 1032, 1071, 1090, 1167,
1194, 1233, 1248, 1271, 1286, 1359, 1409, 1440, 1452, 1488, 1590,
1H NMR [300 MHz, (CD3)2C=O]: δ = 4.10 (br. s, 6 H, PCH2N),
4.16 and 4.37 (AB spin system, JHA,HB = 10.7 Hz, 3 H each,
NCH2N), 7.20–7.43 (m, 10 H, CHarom) ppm. 13C{1H} NMR
1653, 1749, 1816, 1869, 1941, 2874, 2912, 2931, 2951, 3057 cm–1.
31P{1H} NMR (121.5 MHz, CD2Cl2): δ = –34.27 (d, JPP
=
[75.4 MHz, (CD3)2C=O]: δ = 53.29 (br. s, PCH2N), 71.70 (br. s,
2
14.7 Hz, P=N), 55.64 [d, JPP = 14.7 Hz, (PhO)2P=S] ppm. 1H NCH2N), 122.00–129.96 (m, CHarom), 152.14 (d, JCP = 9.5 Hz,
2
2
2
NMR (300 MHz, CD2Cl2): δ = 3.97 (d, JHP = 9.2 Hz, 6 H, Cipso of OPh) ppm. 6a: Yield 79% (0.791 g). CuC26H52F6N8O8P5S2
PCH2N), 4.12 and 4.30 (AB spin system, JHA,HB = 13.4 Hz, 3 H
(1001.27): calcd. C 31.19, H 5.23, N 11.19; found C 31.24, H 5.30,
each, NCH2N), 7.16–7.38 (m, 10 H, CHarom) ppm. 13C{1H} NMR N 11.24. Conductivity (water, 20 °C): 115 Ω–1 cm2 mol–1. IR (KBr):
1
3
(75.4 MHz, CD2Cl2): δ = 53.92 (dd, JCP = 51.9, JCP = 3.7 Hz,
ν = 474, 483, 500, 529, 557, 603, 625, 706, 743, 786, 804, 841, 877,
˜
3
PCH2N), 72.25 (d, JCP = 9.5 Hz, NCH2N), 120.25–129.81 (m,
904, 960, 991, 1022, 1096, 1124, 1161, 1192, 1234, 1263, 1301, 1343,
5860
www.eurjic.org
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Inorg. Chem. 2012, 5854–5863

Efficient Aqueous Click Chemistry with Terminal and 1-Iodoalkynes
1364, 1431, 1651, 1718, 2905, 2933, 2985 cm–1. 31P{1H} NMR
Acknowledgments
[121.5 MHz, (CD3)2C=O]: δ = –144.30 (sept, JPF = 707.5 Hz, PF6),
2
2
–16.65 (d, JPP
= 9.9 Hz, P=N), 54.80 [d, JPP = 9.9 Hz,
We are indebted to the Ministerio de Ciencia e Innovación (MIC-
INN) of Spain (Projects CTQ2008-00506 and RYC-2011-08451)
and Consolider Ingenio 2010 (CSD2007-00006) for financial sup-
port. J. G.-A. thanks the MICINN and the European Social Fund
for the award of a “Juan de la Cierva” and a “Ramón y Cajal”
contract. We thank for the support of the Scientific and Technical
Services (UniOvi) X Ray Single Crystal Diffraction. The authors
are also grateful to the Serveis Centrals d’Instrumentació Científica
(SCIC) of the Universitat Jaume I for providing the mass spectrom-
etry facilities.
(EtO)2P=S] ppm. 1H NMR [300 MHz, (CD3)2C=O]: δ = 1.30 (t,
3JHH = 6.8 Hz, 6 H, OCH2CH3), 2.06 and 2.09 (s, 3 H each,
COCH3), 3.85 (m, 1 H, NCH2N), 4.07 (m, 4 H, OCH2CH3), 4.33
(m, 4 H, PCH2NCO), 4.67 and 5.06 (d, JHH = 13.7 Hz, 1 H, each,
NCH2N), 4.84 (m, 1 H, PCH2N), 5.63 (m, 2 H, 1 H, for NCH2N
and
1
H, for PCH2N) ppm. 13C{1H} NMR [75.4 MHz,
3
(CD3)2C=O]: δ = 17.48 (d, JCP = 8.5 Hz, OCH2CH3), 22.64 and
23.07 (s, COCH3), 42.10 (dd, 1JCP = 70.5, JCP = 2.7 Hz, PCH2N),
3
1
3
1
47.37 (dd, JCP = 70.5, JCP = 4.3 Hz, PCH2N), 52.43 (dd, JCP
59.3, JCP = 1.6 Hz, PCH2N), 63.00 (d, JCP = 7 Hz, NCH2N),
65.09 (d, JCP = 6.9 Hz, OCH2CH3), 68.26 (d, JCP = 6.9 Hz,
NCH2N), 170.88 (s, COCH3), 171.28 (d, JCP = 2.1 Hz, COCH3)
=
3
3
2
3
[1] Catalytic processes in water are genuine examples of green
chemistry. For fundamental principles see, for example: a) P. T.
Anastas, J. C. Warner in Green Chemistry: Theory and Practice,
Oxford University Press, Oxford, 1998; b) A. S. Matlack in In-
troduction to Green Chemistry, Marcel Dekker, New York,
2001; c) M. Lancaster in Green Chemistry: An Introductory
Text, RSC Editions, London, 2002.
[2] a) F. Joó in Aqueous Organometallic Catalyst, Kluwer, Dord-
recht, 2001; b) Aqueous-Phase Organometallic Catalysis (Eds.:
B. Cornils, W. A. Hermann), Wiley-VCH, Weinheim, 2004; c)
M. Wang, C.-J. Li, Top. Organomet. Chem. 2004, 11, 312; d)
Multiphase Homogeneous Catalysis (Eds.: B. Cornils, W. A.
Hermann, I. T. Horváth, W. Leitner, S. Mecjing, H. Olivier-
Bourbigou, D. Vogt), Wiley-VCH, Weinheim, 2005; e) C.-J. Li,
Chem. Rev. 2005, 105, 3095–3165; f) C.-J. Li, L. Chen, Chem.
Soc. Rev. 2006, 35, 68–82; g) L. Chen, C.-J. Li, Adv. Synth.
Catal. 2006, 348, 1459–1484; h) Comprehensive Organic Reac-
tions in Aqueous Media, 2nd ed. (Eds.: C.-J. Li, T.-H. Chan),
Wiley, Hoboken, New Jersey, USA, 2007; i) Organic Reactions
in Water (Ed.: U. M. Lindström), Blackwell Publishing, Ox-
ford, 2007; j) Organic Reactions in Water – Principles, Strate-
gies and Applications (Ed.: V. M. Lindström), Wiley-Blackwell,
Chichester, West Sussex, UK, 2007.
[3] H. C. Kolb, M. G. Finn, K. B. Sharpless, Angew. Chem. 2001,
113, 2056; Angew. Chem. Int. Ed. 2001, 40, 2004–2021.
[4] Click chemistry has found wide chemical applications in many
fields like synthetic and medicinal chemistry, bioconjugations,
materials science and polymer chemistry. For reviews in this
field, see for example: a) Macromol. Rapid Commun. 2008, 29,
943, special thematic issue; b) QSAR Comb. Sci. 2007, 26,
1110, special thematic issue; c) Y. L. Angell, K. Burgess, Chem.
Soc. Rev. 2007, 36, 1674–1689; d) J. E. Moses, A. D. Moor-
house, Chem. Soc. Rev. 2007, 36, 1249–1262; e) J.-F. Lutz, An-
gew. Chem. 2007, 119, 1036; Angew. Chem. Int. Ed. 2007, 46,
1018–1025; f) P. Wu, V. V. Fokin, Aldrichim. Acta 2007, 40, 7–
17; g) J. Broggi, S. Díez-González, J. L. Petersen, S. Berteina-
Raboin, S. P. Nolan, L. Agrofoglio, Synthesis 2008, 141–148;
h) C. O. Kappe, E. Van der Eicken, Chem. Soc. Rev. 2010, 39,
1325–1337; i) C. Spiteri, J. E. Moses, Angew. Chem. 2010, 122,
33; Angew. Chem. Int. Ed. 2010, 49, 31–33; j) J. E. Hein, V. V.
Fokin, Chem. Soc. Rev. 2010, 39, 1302–1315; k) Chem. Asian
J. 2011, 6, special thematic issue.
3
ppm. 6b: Yield 73% (0.871 g). CuC42H52F6N8O8P5S2 (1193.44):
calcd. C 42.27, H 4.39, N 9.39; found C 42.35, H 4.42, N 9.43.
Conductivity (acetone, 20 °C): 109 Ω–1 cm2 mol–1. IR (KBr): ν =
˜
462, 499, 558, 617, 691, 739, 778, 843, 896, 921, 993, 1024, 1043,
1070, 1091, 1124, 1160, 1193, 1228, 1261, 1303, 1335, 1349, 1407,
1429, 1488, 1652, 2925, 2960 cm–1. 31P{1H} NMR [121.5 MHz,
(CD3)2C=O]: δ = –144.16 (sept, JPF = 707.1 Hz, PF6), –14.89 (d,
2
1
2JPP = 9.8 Hz, P=N), 54.42 [d, JPP = 9.8 Hz, (RO)2P=S] ppm. H
NMR [300 MHz, (CD3)2C=O]: δ = 1.99 and 2.02 (s, 3 H each,
COCH3), 3.52 (m, 1 H, NCH2N), 4.07 (m, 4 H, PCH2NCO), 4.58
(m, 2 H, 1 H, for NCH2N and 1 H, for PCH2N), 4.99 and 5.59 (d,
JHH = 14.1 Hz, 1 H, NCH2N), 5.47 (m, 1 H, PCH2N), 7.18–7.40
(m, 10 H, CHarom) ppm. 13C{1H} NMR [75.4 MHz, (CD3)2C=O]:
1
3
δ = 21.04 and 21.42 (s, COCH3), 40.04 (dd, JCP = 70.5, JCP
=
1
3
3.2 Hz, PCH2N), 45.23 (dd, JCP = 69.1, JCP = 4.0 Hz, PCH2N),
1
3
50.81 (dd, JCP = 60.4, JCP = 2.7 Hz, PCH2N), 61.54 and 66.77
(d, 3JCP = 7.4 Hz, NCH2N), 122.04–129.80 (m, CHarom), 152.32 (d,
2JCP = 7.9 Hz, Cipso of OPh), 152.37 (d, JCP = 8.5 Hz, Cipso of
2
OPh), 169.29 (d, 3JCP = 2.1 Hz, COCH3), 169.71 (d, 3JCP = 1.6 Hz,
COCH3) ppm.
Typical Procedure for the Synthesis of 1,2,3-Triazoles Using a
Three-Component Reaction; Synthesis of 1-Benzyl-4-phenyl-1H-
1,2,3-triazole (7a): Catalyst 5a (0.0042 g, 0.5 mol-%) was dissolved
in H2O (2 mL) in air. Phenylacetylene (1 mmol, 0.110 mL), NaN3
(1.1 mmol, 0.0072 g) and benzyl bromide (1 mmol, 0.119 mL) were
added in the presence of 2,6-lutidine (0.012 mL, 10 mol-%). The
course of the reaction was monitored by regular sampling and
analysis by NMR spectroscopy and GC. The mixture was stirred
at room temp. for 6 h, after which time a yellow oil had formed.
The crude of the reaction was washed with CH2Cl2 (3ϫ10 mL),
and the combined organic fractions were concentrated by solvent
evaporation to give 7a as a yellow oil (0.228 g, 97%).
Typical Procedure for the Synthesis of 5-Iodo-1,2,3-triazoles Using
a Three-Component Reaction; Synthesis of 5-Iodo-4-phenyl-1-(phen-
ylmethyl)-1H-1,2,3-triazole (8a): Catalyst 5a (0.0168 g, 2 mol-%)
was dissolved in H2O (2 mL) in air. 1-Iodo-2-phenylacetylene
(1 mmol, 0.228 g), NaN3 (1.1 mmol, 0.0072 g) and benzyl bromide
(1 mmol, 0.119 mL) were added in the presence of 2,6-lutidine
(0.012 mL, 10 mol-%). The mixture was stirred at room temp. for
10 h, after which time a yellow powder had formed. The crude of
the reaction was washed with CH2Cl2 (3ϫ10 mL), and the com-
bined organic fractions were concentrated by solvent evaporation
to give 8a as a white solid (0.339 g, 94%).
[5] For reactions to be considered “click” they must fulfill a
number of basic requirements: (i) they must demonstrate no
sensitivity towards moisture or oxygen, (ii) they must afford
products in high yields and with stereospecificity, and (iii) they
must proceed in the absence of solvent (or use of a benign one)
and lend themselves to simple product isolation.
[6] a) M. Meldal, C. Christensen, C. W. Tornoe, J. Org. Chem.
2002, 67, 3057–3064; b) M. Meldal, C. W. Tornoe, Chem. Rev.
2008, 108, 2952–3015.
[7] K. B. Sharpless, V. V. Fokin, L. G. Green, V. V. Rostovtset, An-
gew. Chem. Int. Ed. 2002, 114, 2708–2711.
[8] In contrast to the classical 1,3-dipolar cycloadditions (Huisgen
reactions), displaying a strong thermodynamic driving force,
which leads to mixtures of regioisomers usually obtained under
Supporting Information (see footnote on the first page of this arti-
cle): ESI mass spectrum of aqueous solutions of 5a; Cartesian coor-
dinates, total electronic energies and figures of coordination iso-
mers I, II and III for [Cu{(PTA)=NP(=S)(OEt)2}2]+; crystallo-
graphic data for 3b and 4b.
Eur. J. Inorg. Chem. 2012, 5854–5863
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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J. García-Álvarez, J. Díez, J. Gimeno, F. J. Suárez, C. Vincent
FULL PAPER
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[19]
[20]
Iminophosphoranes derived from DAPTA are, to the best of
our knowledge, unknown. The synthesis of its corresponding
oxide [O=(DAPTA)] has been previously reported but, organo-
metallic complexes containing this oxide ligand appear to be
unpublished. D. J. Darensbourg, C. G. Ortiz, J. W. Kamplain,
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[9]
In regards to this consideration, the application of the concept
of atom economy (term used to describe the complete transfor-
mations of all atoms of the reactants into the final product)
has become one of the most desirable goals in chemical reac-
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Most of the reactions proceed either in organic solvents or mix-
tures with water (i.e. water/tBuOH) using catalytic active spe-
cies generated in situ (traditionally a mixture of CuSO4 and
sodium ascorbate is used) with concomitant addition of an ex-
cess of N-polydentate ligands, usually necessary to achieve op-
timal catalytic performances. See, for example: a) V. O. Ro-
dionov, S. I. Preloski, S. Gardinier, Y.-H. Lim, M. G. Finn, J.
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Chem. Soc. 2007, 129, 12705–12712. For an isolated complex
of this type, see: c) N. Candelon, D. Lastérouères, A. K. Diallo,
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6
A similar solubility trend has been previously reported in (η -
arene)RuII complexes containing monodentate phosphanes or
phosphites, as the reported ruthenium(II) complexes contain-
ing alkylphosphanes were soluble in water, whereas their aryl
analogues were completely insoluble; a) B. Lastra-Barreira, P.
Crochet, Green Chem. 2010, 12, 1311–1314; b) B. Lastra-Bar-
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[10]
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See, for example: a) F. H. Allen, O. Kennard, D. G. Watson, L.
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A. G. Orpen, R. Taylor in International Tables for X-ray Crys-
tallography (Ed.: E. Prince), Kluwer Academic Publishers,
Dordrecht, The Netherlands, 2004, vol. C, p. 790.
We have described a series of: (i) iminophosphorane–phos-
phane ligands Ph2PCH2P{=NP(=S)(OR)2}Ph2 (R = Et, Ph);
(ii) bis(iminophosphorane)methane ligands CH2[P{=NP(=S)-
(OR)2}Ph2]2 (R = Et, Ph), and (iii) mixed (iminophosphor-
anyl)(thio- or selenaphosphoranyl)methane ligands Ph2P(=X)-
CH2P{=NP(=S)(OR)2}Ph2 (X = S, Se; R = Et, Ph) in: a) V.
Cadierno, P. Crochet, J. Díez, J. García-Álvarez, S.-E. García-
Garrido, S. García-Granda, J. Gimeno, M. A. Rodriguez, Dal-
ton Trans. 2003, 3240–3249; b) V. Cadierno, J. Díez, J. García-
Álvarez, J. Gimeno, Organometallics 2004, 23, 3425–3436; c) V.
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[23]
[24]
Extensive electronic delocalization is a classical feature of N-
thiophosphorylated
iminophosphorane
units
–P=N–
P(=S)(OR)2. See, for example: a) V. Maraval, R. Laurent, B.
Donnadieu, M. Mauzac, A.-M. Caminade, J.-P. Majoral, J.
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dieu, A.-M. Caminade, J.-P. Majoral, Chem. Eur. J. 2003, 9,
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[12]
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a) C. Larré, B. Donnadieu, A.-M. Caminade, J.-P. Majoral,
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ligands described in ref.[22] also showed preferential S-coordi-
nation of the P=N–P=S framework in (arene)RuII fragments.
ESI-MS has become an important technique in solution speci-
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ample: a) P. Chen, Angew. Chem. 2003, 115, 2938; Angew.
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To the best of our knowledge, only one example, namely
RN=PTA (R = Et, Ph), has been reported, and as far as we are
aware, the coordination chemistry of this type of hydrosoluble
[16]
[17]
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© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Inorg. Chem. 2012, 5854–5863

Efficient Aqueous Click Chemistry with Terminal and 1-Iodoalkynes
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Received: July 13, 2012
Published Online: October 10, 2012
[34] Ruthenium-catalyzed cycloaddition reactions of azide and in-
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Eur. J. Inorg. Chem. 2012, 5854–5863
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