Experimental evidence for the involvement of dinuclear alkynylcopper(I) complexes in alkyne-azide chemistry

Article abstract of DOI:10.1002/chem.201000447

Dinuclear alkynylcopper(I) ladderane complexes are prepared by a robust and simple protocol involving the reduction of Cu₂(OH)₃OAc or Cu-(OAc)₂ by easily oxidised alcohols in the presence of terminal alkynes; they function

Full text of DOI:10.1002/chem.201000447

DOI: 10.1002/chem.201000447
Experimental Evidence for the Involvement of Dinuclear Alkynylcopper(I)
Complexes in Alkyne–Azide Chemistry
Benjamin R. Buckley, Sandra E. Dann, and Harry Heaney*[a]
Abstract: Dinuclear alkynylcopper(I)
ladderane complexes are prepared by a
robust and simple protocol involving
the reduction of Cu2(OH)3OAc or Cu-
catalysts are formed during reactions
by using the Sharpless–Fokin protocol.
The experimental results also provide
evidence that sodium ascorbate func-
tions as a base to deprotonate terminal
alkynes and additionally give a con-
vincing alternative explanation for the
fact that the CuI-catalysed reactions of
certain 1,3-diazides with phenylacety-
lene give bis(triazoles) as the major
products. The same dinuclear alkynyl-
copper(I) complexes also function as
catalysts in cycloaddition reactions of
azides with 1-iodoalkynes.
ACHTUNGTRENNUNG(OAc)2 by easily oxidised alcohols in
the presence of terminal alkynes; they
function as efficient catalysts in copper-
catalysed alkyne–azide cycloaddition
reactions as predicted by the Ahlquist–
Fokin calculations. The same copper(I)
Keywords: alkynes · azides · cataly-
sis · click chemistry · copper
Introduction
The rapid development of the use of organocopper reagents
in organic synthesis over the past fifty years has been com-
prehensively documented in a number of reviews.[1] In par-
ticular, 1,3-dipolar cycloaddition reactions, pioneered by
Huisgen,[2] have re-emerged recently as a major area of re-
search as a result of the search for atom efficiency,[3] espe-
cially the so-called click reactions that involve terminal al-
kynes and high energy organic azides that were found by
Sharpless and Fokin[4a] and Meldal[4b] and their co-workers
to be accelerated by the use of copper(I) catalysts. The ma-
jority of the examples of copper-catalysed alkyne–azide cy-
cloaddition (CuAAC) reactions reported have involved the
reduction of copper(II) to copper(I), for example, by using
sodium ascorbate as shown in Scheme 1.[4a] Thermal 1,3-di-
polar cycloaddition reactions normally give 1:1 mixtures of
regioisomers, whereas the copper-catalysed reactions are
highly regioselective and give 1,4-disubstituted triazoles.
Scheme 1. The CuAAC reaction.
Additional reactions have also been reported that involve
the direct introduction of copper(I) salts,[5] the oxidation of
metallic copper to copper(I),[6] or the use of Cu0/CuII as a
method of generating copper(I).[7] These reactions continue
to find wide use in organic synthesis, biology and materials
science,[8] and the reviews on the subject indicate that the
copper(I) oxidation state is required.[9] However, although
there is an explicit statement that copper(II) salts do not
catalyse the reactions,[4b] there are a limited number of re-
ports of the direct use of copper(II) salts.[10] A careful kinet-
ic investigation of the copper(I)-catalysed reaction of phen-
AHCTUNGTRENNUNG
ylacetylene and benzyl azide[11] revealed a second-order de-
pendence on copper that required a modification of an earli-
er mechanism.[12] More recent calculations, based on the re-
quirement of two copper atoms in the transition-state
complex, gave a significantly reduced value for the activa-
tion energy for the reaction of methyl azide and propyne co-
ordinated to two copper(I) atoms, each of which had identi-
cal spectator ligands.[13] We noted that hydrogen peroxide
was used to quench the aliquots taken to obtain the kinetic
data;[11] these measurements exclude the possibility that cop-
per(II) can catalyse CuAAC reactions and encouraged us to
[a] Dr. B. R. Buckley, Dr. S. E. Dann, Prof. Dr. H. Heaney
Department of Chemistry
Loughborough University
Loughborough, Leicestershire
LE11 3TU (UK)
Fax : (+44)1509-223925
E-mail: h.heaney@lboro.ac.uk
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201000447.
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FULL PAPER
investigate the use of copper(II) hydroxyacetate as a pre-
catalyst in microwave-assisted CuAAC reactions carried out
at high temperatures in acetonitrile. That investigation re-
vealed the involvement of polymeric alkynylcopper(I) lad-
derane complexes.[14] As part of our ongoing interest in cop-
per(I)-catalysed reactions, we were interested to obtain ex-
perimental evidence to support the calculated involvement
of dinuclear copper(I) complexes in CuAAC reactions car-
ried out using the mild ambient temperature, tert-butanol/
water reaction conditions.[4a] It is informative to note that
the Meldal method uses Hꢁnigꢂs base and sodium hydrox-
ide, whereas the Sharpless–Fokin CuAAC protocol uses a
large excess of sodium ascorbate: we reasoned that the com-
ment made by Knçpfel and Carreira,[15] that ascorbate may
have an important role in addition to that involved in reduc-
ing CuII, is justified. We now report results relating to both
of the above issues. We were also intrigued by the impres-
sive recent discovery of copper(I)-catalysed reactions of or-
ganic azides with 1-iodoalkynes that result in the formation
1,4-disubstituted-5-iodotriazoles,[16] and report additional
data on the use of alkynylcopper(I) ladderane complexes as
catalysts in reactions of organic azides with 1-iodoalkynes.
ACHTUNGTRENNUNG
AHCTUNGTREGNyNNU lacetylene in tBuOH/H2O in the absence of air and at am-
bient temperature is essentially unchanged after one year.
However, a suspension of copper(II) hydroxyacetate in
tBuOH at 328C was partially converted, after 120 d, into
ladderane polymer 1 in the presence of phenylacetylene;
1,4-diphenylbuta-1,3-diyne was isolated from that reaction
in 50% yield. The methods that involve the use of alcohols
as reductants are general and we were able to prepare
yellow copper(I) derivatives from a range of terminal al-
kynes (Scheme 2), as shown in the Supporting Information.
Results and Discussion
In connection with CuAAC reactions carried out under mild
reaction conditions and predicted by Ahlquist and Fokin to
involve an intermediate with two CuI atoms,[13] we noted
that a number of yellow or orange organocopper(I) species
are known and have short CuI–CuI distances; some are sta-
bilised by ligands.[17] Polymeric alkynylcopper(I) complexes
have been known for many years,[18] and were originally pre-
pared by the interaction of copper(I) iodide with alkali
metal derivatives of terminal alkynes.[19] Although a number
of other methods have been used to prepare alkynylcop-
per(I) derivatives, the majority involve reactions of cop-
per(I) salts with terminal alkynes or derivatives.[20] We have
prepared alkynylcopper(I) derivatives as co-products in
Glaser reactions of terminal alkynes by using copper(II) hy-
droxyacetate in acetonitrile.[14] The detailed structure of the
yellow phenylethynylcopper(I) [{PhCCCu}2]n (1), deter-
mined by using X-ray powder diffraction (XRD), was re-
ported recently by Che and co-workers[21] and is shown to
have a ladderane structure in which the phenylethynyl resi-
dues are linked to two copper(I) atoms that are separated
by distances of between 2.49 and 2.83 ꢃ, ideally positioned
to take part in click CuAAC reactions.
Scheme 2. Formation of CuI ladder polymers.
The amounts of Glaser products formed in the reactions are
low if reactions are carried out in closed vessels in the ab-
sence of air. The production of an unidentified copper(I)
catalyst from a copper(II) salt in easily oxidised alcohols
was also reported recently.[26] A qualitative indication of the
rates of reduction of copper(II) hydroxyacetate in alcohols
is given by the fact that the reactions are fastest in methanol
and slowest in isopropanol. The copper(I) derivative from 3-
hydroxy-3-methylbut-1-yne was not formed by using cop-
per(II) hydroxy acetate in methanol: a red precipitate,
which was not investigated, was formed, presumably be-
cause the alkyne, a protected form of ethyne, was deprotect-
ed by hydroxyl ions. However, 3-hydroxy-3-methylbut-1-
ynylcopper(I) must have been formed in the reaction shown
below (compound 7 in Table 1, entry 11). Alkynylcopper(I)
derivatives, for example, compound 1 can be prepared from
copper(II) acetate in methanol, in reactions that proceed
The use of easily oxidised alcohols as reducing agents in
the presence of metal salts has been known for many years.
For example, isopropanol is used together with aluminium
isopropoxide in the Meerwein–Pondorf–Verley reduction of
ketones,[22] and more recently in the reduction of a phenan-
throline–copper(II) complex to the related copper(I) com-
plex.[23] Less well known is the reduction of aromatic nitro-
compounds by ethanol in the presence of iron/iron(II) chlo-
ride.[24] We found that a suspension of copper(II) hydroxy-
more slowly than the reactions that use copper(II) hy
AHCTUNGTREGaNNNU cetate. We assume that the acetic acid produced in reac-
ACHTUNGTRENNUNGdroxy-
tions that use copper(II) acetate retards the reduction pro-
cess. Compound 1 was not formed when a mixture of cop-
per(II) sulfate pentahydrate and phenylacetylene was al-
lowed to stand in methanol at ambient temperature over a
period of 30 d.
Phenylethynylcopper(I) is a stable material and forcing
reaction conditions are required in Stevens–Castro reac-
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H. Heaney et al.
phenylacetylene with [CuI
ence of sodium ascorbate gave a small amount of a yellow
precipitate. When we used [CuI
(MeCN)4] as the source of
ACHTUNGTNER(NUGN MeCN)4] (5 mol%) in the pres-
Table 1. CuAAC reactions with dinuclear copper(I) ladderane com-
ACHTUNGTRENNUNG
plexes.[a]
AHCTUNGTRENNUNG
copper(I) in a reaction of phenylacetylene and benzyl azide
in tBuOH/H2O, together with an excess of sodium ascorbate,
we obtained the CuAAC product (2), but in only 31% yield
after 24 h. We presume that the low yield shown in
Scheme 3 resulted from the strong ligation of acetonitrile to
Entry
Product
Yield[b] [%]
1
2
79
76[c]
3
77
ACTHNUTRGNEUNG
Scheme 3. CuAAC reaction with CuI(MeCN)4 as the source of CuI.
4
5
6
7
8
9
78
81[c]
75[d]
70[e]
91
copper(I) and that only a very low concentration of 1 was
formed. Importantly, the result shown in Scheme 3 estab-
lished that sodium ascorbate initiates the formation of an
alkyne–copper(I) ladderane complex by facilitating the de-
protonation of the required amount of alkyne. In connection
with this, it is interesting to note that CuAAC reactions can
be carried out by using tetrakis(acetonitrile)copper(I) in the
presence of a series of triazolylmethylamine derivatives; we
conclude that the amine acts as a base to deprotonate the
required amount of alkyne.[31]
98[d]
10
11
89
86[e]
We have prepared 1 by using the Owsley–Stevens proto-
col,[20d] and by reducing copper(II) sulfate in tBuOH/H2O
with sodium ascorbate in the presence of phenylacetylene.
A reaction of PhCCH with Cu2O in MeCN to which we
added five drops of aqueous NH3 also gave a quantitative
yield of 1. The materials prepared by each of these methods
have been used successfully as catalysts in the CuAAC reac-
tions reported below.
12
78
[a] General conditions: see table scheme. [b] Isolated yield. [c] Condi-
tions: copper(II) sulfate (1 mol%), sodium ascorbate (10 mol%), tert-bu-
tanol/water (1:1), RT, 15 h. [d] Reaction carried out in the absence of
sodium ascorbate. [e] Crossover experiment with 3-(4-methoxyphenoxy)-
prop-1-ynylcopper(I) (10; 1 mol%) as the catalyst.
We next carried out a series of reactions at ambient tem-
perature in which we stirred a suspension of a catalytic
quantity of an alkynylcopper(I) derivative, the appropriate
alkyne and benzyl azide (BnN3) in tBuOH/H2O (1:1) to
which we added an excess of sodium ascorbate. We were
pleased to obtain the anticipated CuAAC derivatives (2–8)
in excellent yields after about 15 h, as shown in Table 1.
We also carried out reactions of phenylpropargyl ether
and phenylacetylene, each with BnN3, under the conditions
used in the original report by Sharpless, Fokin and co-work-
ers (Table 1, entries 2 and 5).[4a] We noted that a transient
yellow colour persisted for about 30 s when using 1 mol%
of copper(II) sulfate, which was soon obscured by a white
suspension. When we carried out reactions with larger
amounts of copper(II) sulfate, the reaction mixtures re-
mained lemon yellow at the end of the reaction times and
the yields of 2 were, within experimental error, constant. In
the latter reactions, we were able to isolate alkynylcopper(I)
ladderane complexes. The yield of the CuAAC products in
our hands were comparable to those obtained by using
either 3-phenoxyprop-1-ynylcopper(I) (9) or 1 as the cata-
lyst.
tions; for example, 2-phenylindole was obtained in 89%
yield when 2-iodoaniline and phenylethynylcopper(I) were
heated together in dimethylformamide at 1758C.[27] We also
found phenylethynylcopper(I) to be very stable and 1,4-di-
phenylbuta-1,3-diyne was formed in 62% yield only when
we heated a suspension in dimethylformamide at reflux for
24 h. A yellow material, which was assumed to be a CuI p-
complex of 1,4-diphenylbuta-1,3-diyne, was reported to give
1,4-diphenylbuta-1,3-diyne after being heated under reflux
in dimethylformamide;[28] it is likely that that material was
also phenylethynylcopper(I).
In connection with the use of sodium ascorbate, we noted
that tetrakis(acetonitrile)copper(I) (10 mol%) in toluene
does not function as a catalyst in CuAAC reactions.[29] Ace-
tonitrile is known to be a strong ligand for copper(I),[30] and
we anticipated that acetonitrile might, as a result, also act as
a competing ligand in the CuAAC process. We also rea-
soned that an added base would be required. A reaction of
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Alkynylcopper(I) Complexes in Alkyne–Azide Chemistry
FULL PAPER
When we carried out a reaction of 4-methoxyphenylpro-
pargyl ether with BnN3 in the presence of 3-(4-methoxy-
ACHTUNGTRENNUNGphenACHTUNGTRENNUNGoxy)prop-1-ynylcopper(I) (10) without adding sodium
ascorbate, we obtained the anticipated triazole in an excel-
lent yield. This reaction shows that once the dinuclear lad-
derane complex is formed, external deprotonation of the
alkyne is no longer required for the catalytic cycle, as con-
firmed by our earlier deuteriation experiment.[14]
Crossover experiments in which an alkyne, such as phen-
ACHTUNGTRENNUNGylpropargyl ether, and benzyl azide were used together with
1 mol% of a catalyst (e.g., 10) established that the alkyne is
incorporated into the catalyst to produce the isolated prod-
uct (Scheme 4). The contaminant derived from the initial
Scheme 5. Mechanism of the CuAAC reaction with dinuclear CuI ladder-
ane complexes.
Scheme 4. Crossover experiment.
ladder catalyst (triACTHUNRGTNEUNGazole 5)
would be produced in no more
than 1% yield (see the Sup-
porting Information).
Our experimental results es-
tablish that isolable dinuclear
copper(I) ladderane complexes
act as efficient catalysts under
Scheme 6. CuI-catalysed reaction of a 1,3-diazide and phenylacetylene.
the mild reaction conditions
originally formulated by Sharp-
less, Fokin and co-workers,[4a] and that they fulfil the experi-
mentally determined[11] and calculated[13] requirements for a
dinuclear copper(I) complex. We propose a minor change to
the previously published mechanism of CuAAC reactions
that requires sodium ascorbate to deprotonate an initial cop-
per(I) p-complexed alkyne that then collapses to the true
catalyst depicted in Scheme 5.
tute[16] with particular emphasis on the use of a wide variety
of amines, suggested that the nucleophilicity of the amine
used could be of key importance and we concluded that
tris(triazolylmethyl)amine derivatives are not only strong
bases,[31] but also powerful nucleophiles. We allowed a mix-
ture of iodophenylethyne (11) and benzyl azide to react in
THF, with 1 and triethylamine as the catalyst system; the re-
action gave a disappointing 20% yield of 1-benzyl-5-iodo-4-
phenyltriazole. However, a similar reaction with 3-trifluoro-
methylbenzyl azide (12) in place of benzyl azide gave 1-(3-
trifluoromethyl)benzyl-5-iodo-4-phenyltriazole (13) in 88%
Our results also provide a convincing alternative explana-
tion, shown in Scheme 6, for the fact that the CuI-catalysed
reactions of certain 1,3-diazides with phenylacetylene give
the bis(triazoles) as major products; in one case even when
a reaction was carried out with a tenfold excess of a di-
yield, as shown in Scheme 7. The yield of 1-(3-trifluoroACHTUNGTRENNUNGmeth-
ACHTUNGTRENNUNG
that, as a result of the efficiency with which alkynylcop-
per(I) catalysts such as 1 take part in CuAAC reactions; re-
actions of 1-iodoalkynes with azides should be investigated
by using our polymeric alkynylcopper(I) ladderane catalysts.
Two possible mechanisms have been suggested for the iodo-
ACHTUNGTRENNUNG
alkyne–azide cycloaddition reactions.[16] Although it is not
possible to prove a particular mechanism, experimental re-
sults can exclude potential mechanisms. Analysis of the re-
sults of the investigation carried out at the Scrippꢂs insti-
Scheme 7. Formation of 1-(3-trifluoromethyl)benzyl-5-iodo-4-phenyltri-
AHCTUNGTRENNUNG
azole with a dinuclear CuI ladderane complex.
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H. Heaney et al.
ACHTUNGTRENNUNGyl)benzyl-5-iodo-4-phenyltriazole (13) obtained in our reac-
Experimental Section
tion is the same as that reported earlier with copper(I)
iodide, within experimental error.[16]
General experimental detail: All infrared spectra were obtained by using
a Perkin–Elmer Paragon 1000 FT-IR spectrophotometer; thin-film spec-
tra were acquired by using sodium chloride plates. All 1H and 13C NMR
spectra were measured at 400.13 and 100.62 MHz by using a Bruker DPX
400 MHz spectrometer or a Bruker Avance 400 MHz spectrometer. The
solvent used for NMR spectroscopy was CDCl3 unless stated otherwise,
with TMS (tetramethylsilane) as the internal reference. Chemical shifts
are given in parts per million (ppm) and J values are given in Hertz
(Hz). GCMS analysis was performed by using a Fisons GC 8000 series
(AS 800), with a 15 mꢄ0.25 mm DB-5 column and an electron-impact
low-resolution mass spectrometer. Melting points were recorded by using
a Stuart Scientific melting point apparatus (SMP3) and are uncorrected.
Microanalyses were performed by using an Exeter Analytical CE-440 El-
emental Analyser. All chromatographic manipulations used silica gel as
the adsorbent. Reactions were monitored by using thin layer chromatog-
raphy (TLC) on aluminium-backed plates with Merck Kiesel 60 F254
silica gel. TLC plates were visualised by using UV radiation at l=
254 nm, or stained by exposure to an ethanolic solution of phosphomo-
lybdic acid (acidified with conc. sulfuric acid), followed by charring
where appropriate. Purification by column chromatography used Merck
Kiesel 60H silica adsorbent. Reactions requiring anhydrous conditions
were carried out by using flame-dried glassware under a nitrogen atmos-
phere unless otherwise stated. Reaction solvents were obtained commer-
cially dry, except for light petroleum (b.p. 40–608C), which was distilled
from calcium chloride prior to use. Ethyl acetate was distilled over calci-
um sulfate or chloride. Dichloromethane was distilled over calcium hy-
dride. THF was distilled under a nitrogen atmosphere from the sodium/
benzophenone ketyl radical. 1-Iodoalkynes were prepared by using the
method described by Hein, Fokin and co-workers[16] XRD data were re-
corded by using a Bruker Avance powder defractometer operating with
monochromated CuKa1 radiation over the 2q range 5–608 with a 0.0147 2q
step. Mass spectra were recorded by using a Thermo Fisher Exactive
with an ion max source and ESI probe fitted with a Advion triversa
nanomate; the mass range was 20–2000 with a resolution of better than
100000.
Although we cannot comment on the mechanistic sugges-
tions reported for reactions of iodoalkynes with azides car-
ried out with, for example, tris(triazolylmethyl)amines,[16]
a
minor modification of the mechanism shown in Scheme 5 is
in accord with the results of our investigation of copper(I)-
catalysed reactions by using 1-iodoalkynes and azides with
ladderane catalyst 1, and is shown in Scheme 8. Our results
Scheme 8. Possible mechanism of the iodoalkyne–azide reaction with di-
nuclear CuI ladderane complexes.
Cu2(OH)3OAc·H2O: CuACTHNURGTNEUNG(OAc)2·H2O (4.00 g, 20.1 mmol) was dissolved in
H2O (200 mL) and stirred at RT, then NaOH (200 mL, 0.1m) was added
slowly with vigorous stirring. The reaction mixture was left to stir for 7 d,
then centrifuged at 2000 rpm for 15 min. The aqueous phase was de-
also have a bearing on recently reported reactions of al-
kynes and azides in the presence of stoichiometric amounts
of copper(I) iodide.[33]
A crossover reaction in which we allowed benzyl azide to
compete for 1-iodophenylethyne (0.5 equiv) and 4-methoxy-
phenylpropargyl ether (0.5 equiv) in the presence of 1 re-
sulted in the formation of four anticipated products, namely,
AHCTUNGERTGcNNUN anted and replaced with deionised water and the mixture was centri-
fuged for a further 15 min. The process was repeated with ethanol and fi-
nally dichloromethane to give the product as a pale green solid. The
structure was then confirmed by XRD (below) and found to be monohy-
drated by combustion analysis (calcd (%) for Cu2(OH)3OAc·H2O C 9.41,
H 3.16; found: C 9.31, H 2.86).
Representative synthesis of the ladder polymers
1-benzyl-4-phenyltriazole (2), 1-benzyl-4-(p-methoxy
oxy)methyltriazole (5), 1-benzyl-5-iodo-4-phenyltriazole,
and 1-benzyl-5-iodo-4-(p-methoxyphenoxymethyl)triazole
ACHTUNGTNERpNUNG hen-
AHCTUNGERTNNG[UN (CuCCPh)2]n (1): Cu2(OH)3OAc·H2O (0.30 g, 1.17 mmol) was suspended
ACHTUNGTRENNUNG
in methanol (50 mL), then phenylacetylene (0.40 g, 3.92 mmol) was
added and the reaction mixture was stirred at 328C for 48 h before being
filtered and washed with dichloromethane. The yellow filter cake was
dried and analysed by XRD and found to be 1 (0.193 g, 99%). The fil-
trate was evaporated under reduced pressure to afford the Glaser prod-
uct (1,4-diphenylbuta-1,3-diyne) as a colourless crystalline solid (0.009 g,
8%).
(see the Supporting Information).
Conclusion
1,4-Diphenylbuta-1,3-diyne:[34] 1H NMR (400 MHz, CDCl3, 258C, TMS):
d=7.54–7.52 (m, 2H), 7.38–7.26 ppm (m, 3H); 13C NMR (400 MHz,
CDCl3, 258C, TMS): d=132.5, 129.2, 128.4, 121.8, 81.6, 73.9 ppm.
In summary, we have demonstrated that dinuclear alkynyl-
copper(I) ladderane complexes can be prepared by using a
robust and simple protocol and that they are efficient cata-
lysts in CuAAC reactions carried out under mild tBuOH/
H2O reaction conditions, as predicted by the Ahlquist–Fokin
calculations. We established that the same copper(I) deriva-
tives are formed during reactions by using the Sharpless–
Fokin protocol and also that they function as catalysts in the
related iodoalkyne–azide cycloaddition reactions.
Formation of 1 by using the Sharpless–Fokin click reaction protocol:
Phenyl acetylene (0.310 g, 3.0 mmol) was suspended in a 1:1 mixture of
water and tert-butyl alcohol (12 mL) and sodium ascorbate (0.3 mmol,
300 mL of freshly prepared 1m solution in water) was added, followed by
copper(II) sulfate pentahydrate (7.5 mg, 0.03 mmol, in 100 mL of water).
The heterogeneous mixture was stirred vigorously and turned brown and
viscous. After ꢀ15 min, a yellow precipitate was formed. The reaction
mixture was centrifuged at 2000 rpm for 15 min. The aqueous/tert-butanol
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Alkynylcopper(I) Complexes in Alkyne–Azide Chemistry
FULL PAPER
phase was decanted, replaced with deionised water and centrifuged for a
further 15 min. The process was then repeated by using ethanol and final-
ly dichloromethane to afford the product as a yellow solid that was char-
acterised by XRD to be ladder complex 1.
Acknowledgements
This work was supported by Loughborough University. B.R.B. thanks Re-
search Councils UK for a RCUK Fellowship.
Representative procedure for the synthesis of triazoles by using sodium
ascorbate: 3-(4-methoxyphenoxy)prop-1-yne (486.0 mg, 3.0 mmol) and
benzyl azide (399.0 mg, 3.0 mmol) were suspended in a 1:1 mixture of
water and tert-butyl alcohol (12 mL). Sodium ascorbate (0.3 mmol,
300 mL of freshly prepared 1m solution in water) was added, followed by
3-(4-methoxyphenoxy)prop-1-ynylcopper(I) (6.7 mg, 0.03 mmol). The
heterogeneous mixture was stirred vigorously overnight, then diluted
with water (50 mL), cooled in ice and the white precipitate collected by
filtration. After washing the precipitate with cold water, it was dried
under vacuum to afford triazole 4 as an off-white powder (0.77 g, 91%).
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Angew. Chem. Int. Ed. 2003, 42, 5400; f) H. Heaney, S. Christie in
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Representative procedure for the synthesis of triazoles: 3-(4-methoxy-
phenoxy)prop-1-yne (486.0 mg, 3.0 mmol) and benzyl azide (399.0 mg,
3.0 mmol) were suspended in a 1:1 mixture of water and tert-butyl alco-
hol (12 mL). 3-(4-Methoxyphenoxy)prop-1-ynylcopper(I) (6.7 mg,
0.03 mmol) was added and the heterogeneous mixture stirred vigorously
overnight. The reaction mixture was diluted with water (50 mL), cooled
in ice and the white precipitate collected by filtration. After washing the
precipitate with cold water, it was dried under vacuum to afford triazole
4 as an off-white powder (0.84 g, 98%). M.p. 112.0–113.28C; 1H NMR
(400 MHz, CDCl3, 258C, TMS): d=7.52 (s, 1H), 7.35–7.37 (m, 3H), 7.26–
7.27 (m, 2H), 6.89–6.91 (m, 2H), 6.80–6.84 (m, 2H), 5.53 (s, 2H), 5.13 (s,
2H), 3.76 ppm (s, 3H); 13C NMR (400 MHz, CDCl3, 258C, TMS): d=
154.2, 152.3, 144.9, 134.5, 129.2, 128.8, 128.1, 122.5, 115.9, 114.7, 62.9,
55.7, 54.2 ppm; UV (film): n˜ =3054.3, 2986.1, 2305.8, 1506.4, 1265.1,
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1230.7, 1040.0 cmÀ1
; HRMS: m/z calcd for C17H18N3O2: 296.1394
[M+H]+; found: 296.1391; elemental analysis calcd (%) for C17H17N3O2:
AHCTUNGTREGcNNUN ente, Org. Lett. 2008, 10, 3081; c) A. Qin, J. W. Y. Lam, L. Tang,
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Crossover experiment—Triazole (6)[35] prepared from 2-methyl-3-butyn-
2-ol and benzyl azide: 2-Methyl-3-butyn-2-ol (252.0 mg, 3.0 mmol) and
benzyl azide (399.0 mg, 3.0 mmol) were suspended in a 1:1 mixture of
water and tert-butyl alcohol (12 mL). Sodium ascorbate (0.3 mmol,
300 mL of freshly prepared 1m solution in water) was added, followed by
3-(4-methoxyphenoxy)prop-1-ynylcopper(I) (6.7 mg, 0.03 mmol). The
heterogeneous mixture was stirred vigorously overnight. The reaction
mixture was extracted with dichloromethane (2ꢄ20 mL), dried over
MgSO4, filtered and evaporated under reduced pressure to give 6 as col-
ourless crystals (560.0 mg, 86%). 1H NMR (400 MHz, CDCl3, 258C,
TMS): d=7.27–7.41 (m, 6H), 5.49 (s, 2H), 1.63 ppm (s, 6H); 13C NMR
(400 MHz, CDCl3, 258C, TMS): d=156.1, 134.6, 129.1, 128.8, 128.2,
119.1, 68.5, 54.2, 30.5 ppm.
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Representative procedure for the synthesis of 5-iodotriazoles: Iodo
ACHTUNGTRENNUNG
ACHTUNGTNERpNUNG hen-
dissolved in THF (5 mL). The solution was treated sequentially with 1
(8.2 mg, 0.05 mmol) and triethylamine (0.28 mL, 2.00 mmol) and then al-
lowed to stir at RT for 15 h. After this time, the reaction was quenched
by addition of aqueous NH4OH (10%, 1 mL). The volatile components
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afforded 1-benzyl-5-iodo-4-phenyltriazole[16] as a colourless solid (0.04 g,
20%).
1-(3-Trfluoromethy)benzyl-5-iodo-4-phenyltriazole (13):[16] Compound 13
was prepared according to the representative procedure from 3-trifluoro-
methylbenzyl azide (0.20 g, 1.00 mmol), and obtained as a colourless
1
solid (0.38 g, 88%). H NMR (400 MHz, CDCl3, 258C, TMS): d=7.94 (d,
J=8.6 Hz, 2H), 7.60–7.64 (m, 2H), 7.40–7.53 (m, 5H), 5.73 ppm (s, 2H);
13C NMR (400 MHz, CDCl3, 258C, TMS): d=150.4, 135.3, 131.5, 131.2,
130.0, 129.6, 128.8, 128.6, 127.4, 125.5 (q, J=3.7 Hz), 124.8 (q, J=3.8 Hz),
122.4, 76.4, 53.8 ppm.
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Published online: April 15, 2010
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