A synthesis of a 1,1′-desymmetrised ferrocene backbone and its facile one-pot double- click functionalisation

Article abstract of DOI:10.1039/c3ra43054e

A one-pot, four-component, copper-catalysed double- click functionalisation of a novel 1,1′-desymmetrised ferrocene backbone is reported. Using an array of alkynes and azides, a library of ferrocene compounds was developed, demonstrating the scope of this methodology for its potential application in the assembly of novel materials, ligands or biological sensors.

Full text of DOI:10.1039/c3ra43054e

RSC Advances
View Article Online
View Journal | View Issue
PAPER
A synthesis of a 1,19-desymmetrised ferrocene
backbone and its facile one-pot double-‘‘click’’
Cite this: RSC Advances, 2013, 3,
17081
functionalisation3
Gennadiy Ilyashenko,*a Rawan Al-Safadi,a Robert Donnan,b Rostyslav Dubrovka,b
Jessica Pancholi,a Michael Watkinsona and Andrew Whitingc
Received 15th April 2013,
Accepted 3rd July 2013
A one-pot, four-component, copper-catalysed double-‘‘click’’ functionalisation of a novel 1,19-desym-
metrised ferrocene backbone is reported. Using an array of alkynes and azides, a library of ferrocene
compounds was developed, demonstrating the scope of this methodology for its potential application in
the assembly of novel materials, ligands or biological sensors.
DOI: 10.1039/c3ra43054e
www.rsc.org/advances
Introduction
Results and discussion
Ferrocene, and its derivatives, occupy a central role in
chemistry1 as demonstrated by their widespread use as ligand
scaffolds,2a–d pharmaceutical candidates,2e,f anti-knock for-
mulations in fuel additives,2g precursors to materials2h
(including nano-formulations),2i and redox reagents.2j As a
result synthetic methods directed towards the selective
functionalisation of the ferrocene backbone have been widely
reported.2a–d,3 However, despite the fact that an array of
synthetic transformations have been extensively explored and
exploited,2a–d,3 practically useful methods towards the
1,19-desymmetrisation of ferrocene are scarce.4 Yet such
methodology would represent a potent tool, particularly for
the development of new ferrocene ligand scaffolds and
pharmaceutical agents. In order for such methodology to be
of use the introduction of the 1- and 19-substituents must be
facile and the substituents must then readily undergo further
modification selectively in order to develop structural diver-
sity. With this in mind, we were particularly attracted by the
Cu(I) catalysed 1,3-dipolar cycloaddition ‘‘click’’ of azides and
alkynes,5 which if performed iteratively on the same backbone,
could deliver novel, unsymmetrically-substituted systems.
Herein, we report a facile one-pot, four-component functiona-
lisation of a novel 1,19-desymmetrised ferrocene backbone
using ‘‘click’’ chemistry.
We viewed 1-azido-19-(trimethylsilyl)-acetyleneferrocene 1 as
an ideal starting point from which wide structural variation
could be derived. However, due to the inherent instability of
azides and the dangers associated with their manipulation,6
we felt that the in situ generation of 1 from a more stable
precursor, such as boronic acid 2, was more appealing. Hence,
the synthesis of the key intermediate 2 from 1,19-dibromo-
ferrocene 3 was achieved in three clean and efficient steps
(Scheme 1).
The initial lithium-halogen exchange on dibromoferrocene
3,4a followed by quenching with I2, produced desymmetrised
1-bromo-19-iodoferrocene
4 in high yield (78%). It was
essential to carefully control the initial concentration of
1,19-dibromoferrocene at 0.06 M as higher concentrations
resulted in the di-lithiated species 6, which precipitated from
aThe Joseph Priestley Building, School of Biological and Chemical Sciences, Queen
Mary University of London, Mile End Road, London, E1 4NS, UK.
E-mail: g.ilyashenko@qmul.ac.uk
bSchool of Electronic Engineering and Computer Sciences, Queen Mary University of
London, Mile End Road, London, E1 4NS, UK
cChemistry Department, Science Laboratories, Durham University, South Road,
Durham, DH1 3LE, UK
Scheme 1 Synthesis of ‘‘clickable’’ ferrocene backbone 2. i) n-BuLi (1.0 equiv.),
THF, 278 uC, 6 h; ii) I2, 278 to 25 uC, (78%); iii) TMS-CCH, CuI (1.0 mol%),
Pd(PPh3)2Cl2 (0.5 mol%), Et3N : THF (4 : 1), 60 uC, 16 h (85%); iv) n-BuLi (1.0
equiv.), THF, 278 uC, 1 h; v) B(O–i–Pr)3, 278 to 25 uC over 3 h; vi) H2O (77%).
Electronic supplementary information (ESI) available: Full experimental
3
procedures, spectroscopical and analytical data with 1H and 13C NMR spectra of
all novel compounds is provided. See DOI: 10.1039/c3ra43054e
This journal is ß The Royal Society of Chemistry 2013
RSC Adv., 2013, 3, 17081–17087 | 17081

View Article Online
Paper
RSC Advances
Table 1 Conditions used to optimise the formation of 8 from 2
Entry Catalyst (10 mol%) t (h) Solventc Conv. (%) Yield of 8 (%)d
1a
CuSO4?5H2O
CuSO4
CuI
Cu(PPh3)3Br
Cu(OAc)2?H2O
CuPF6
CuI
CuI
CuSO4
CuSO4
2
2
2
2
2
MeOH 100
MeOH 100
MeOH 100
10
30
45
—
45
—
—
21
—
30
—
25
45
43
47
2a
3b
4b
MeOH
0
5a
MeOH 100
6b
2
MeOH
0
0
Scheme 2 Stepwise conversion of boronic acid 2 into azide 1 and in situ ‘‘click’’
cycloaddition, followed by deprotection and further functionalisation via a
second ‘‘click’’ cycloaddition. i) CuSO4, NaN3, MeOH; ii) NaAsc, Ph-CCH (30%); iii)
TBAF, THF (90%); iv) CuSO4?5H2O, NaAsc, BnN3, THF, H2O (69%).
7b
24
24
24
24
24
24
1
1
1
2
2
e
8b
EtOH
100
0
9a
e
10a
11a
12a
13f
14b
15f
16b
17f
18f
19i
EtOH
100
0
e
Cu(OAc)2?H2O
Cu(OAc)2?H2O
CuSO4
EtOH
100
MeOH 100
MeOH 100
MeOH 100
MeOH 100
MeOH 100
MeOH 100
MeOH 100
CuI
The low yield for the conversion of boronic acid 2 to
‘‘clickate’’ 8 prompted us to investigate the reaction conditions
for this transformation further. We began the optimisation by
screening a range of available copper catalysts (Table 1, entries
1–6) using the conditions we had adapted from Guo.9
Anhydrous CuSO4, CuI and Cu(OAc)2?H2O all showed
promising catalytic activity in anhydrous methanol, producing
a mixture of 8 together with a proto-deboronated species and
Cu(OAc)2?H2O
CuIg
10–30h
10–35h
10–40h
49
g
CuSO4
Cu(OAc)2?H2Og
Cu(OAc)2?H2O
2
16
a
NaAsc in H2O and Ph-CCH added to the reaction mixture after 45
b
c
min. Ph-CCH added at the start of the reaction. Anhydrous
solvents produced better results. Isolated yields. NMP, DMF, THF
(THF/H2O), MeCN and IPA were also tested. NaAsc and Ph-CCH
added after 15 min. Additives such as DMEDA, TMEDA, pyridine,
bipyridine, NaOAc, Et3N and NaOH were screened. Yields
dependent on additive used. 1 mol% of Cu(OAc)2?H2O was used
and NaAsc and Ph-CCH were added after 1 h; the side-product
results from proto-deboronation (44% yield, see ESI ).
d
e
f
g
small amounts of other contaminants (see ESI ). Such Cu-
3
h
catalysed proto-deboronations are known to occur in the
presence of protic solvents11 and are further exacerbated by
the presence of water.12 Hence, we hoped that using polar
anhydrous aprotic solvents, such as DMF and NMP, (Table 1,
entries 7, 9 and 11) would hinder this process. Unfortunately,
even after 24 h no reaction was observed, and we recovered the
starting boronic acid 2. Ethanol also proved to be a suitable
solvent for the transformation, though still less effective then
methanol (Table 1, entries 8, 10 and 12).
Analysis of the reaction mixtures indicated that the
formation of the species which we assigned to be ferrocene-
azide 1, was effectively complete within 15–20 min. Therefore,
we decided to try to reduce its subsequent decomposition by
initiating the ‘‘click’’ reaction at this point, through the
addition of NaAsc and Ph-CCH. This indeed proved to increase
the yield of the ‘‘clickate’’ 8 and reduce the formation of other
side products (Table 1, entries 13–15). We then investigated
whether the addition of ligands or additives commonly
reported13 to improve these click reactions could further
improve the yields of the desired product (Table 1, entries 16–
18). However, none of the additives or ligands screened
resulted in any further improvement. Finally, by lowering the
catalytic loading of Cu(OAc)2?H2O to 1 mol% and adjusting the
reaction time we were able to isolate 8 in 49% yield (Table 1,
i
3
solution, whereas lower concentrations and prolonged reac-
tion times resulted in the additional formation of 7.7 These
side reactions resulted in significant product contamination
and the formation of intractable mixtures from which the
product could not be separated by means of chromatography
or distillation.
We then found that although the Sonogashira coupling of 4
to give 5 proceeded under a variety of reaction conditions,8 the
yields were generally low (7–45%) (see ESI Table 1). After
screening conditions and catalysts, we established that the use
of Et3N : THF (4 : 1) gave the best results (85% yield), together
with using low Pd(PPh3)2Cl2 catalyst loading (0.5 mol%).
Ferrocene boronic acid 2 was then readily prepared from 5
using simple lithium-halogen exchange followed by quenching
with triisopropyl borate.3j After a simple work up, the desired
product 2 precipitated upon addition of Et2O–hexane (1 : 1)
and after isolation by filtration, it could be stored on the bench
for prolonged periods of time without decomposition.
Boronic acid 2 was then treated with NaN3 in anhydrous
methanol in the presence of CuSO4 following the method
reported by Guo9 in order to generate 1 in situ, followed by the
addition of sodium ascorbate (NaAsc) and phenylacetylene
(PhCCH) (Scheme 2). Although, the boronic acid 2 was
completely consumed, 8 could only be isolated in low yield
(30%). After isolation, 8 was deprotected with TBAF10 and
subjected to a second ‘‘click’’ reaction to form the 1,19-desym-
metrised bifunctionalised ferrocene 10.
3
entry 19) from
a significantly cleaner crude mixture.
Subsequently we attempted to carry out a one-pot reaction
starting from 2 to obtain double ‘‘clickate’’ 10 (Table 2).
As expected, the one-pot reaction proceeded to give the
desired product in 50% greater yield than the corresponding
stepwise process. Furthermore, the one-pot procedure removes
the necessity for purification of the intermediates, therefore
reducing the overall process time, materials required and the
amount of waste produced.
17082 | RSC Adv., 2013, 3, 17081–17087
This journal is ß The Royal Society of Chemistry 2013

View Article Online
RSC Advances
Paper
distilled prior to use. MeOH was stirred over silica (10% w/v)
for at least 24 h under a N2 atmosphere, filtered and stored
over 4 Å-molecular sieves. Et3N was stored over KOH under a
N2 atmosphere. All other anhydrous solvents were obtained
from an MBRAUN MB SPS-800 solvent purifying system. PE
refers to the fraction of petroleum ether boiling in the range
40–60 uC; EA refers to ethyl acetate. All water was obtained
from an Elga Purelab Option distillation system. 1H-NMR
spectra were recorded on Bruker Avance 600 MHz NMR
spectrometer (with an auto-tuning broad-band/inverse obser-
vation probe with a Z-gradient) or a Bruker AV400 (s = singlet,
d = doublet, t = triplet, q = quartet, m = multiplet). 13C-NMR
spectra were recorded on a 150.8 MHz Bruker Avance or a
100.2 MHz Bruker AV400. The spectra were referenced with
respect to residual solvent (CHCl3). IR spectra were recorded
on an Agilent Technologies Cary 630 FTIR spectrometer
equipped with ATR accessory. UV-Vis spectra were obtained
on a U-3020 spectrophotometer, with absorption maxima
(lmax) expressed in nm, and molar extinction coefficients (e)
are expressed in Lmol21cm21. Mass spectra were obtained
using a Waters (UK) TQD mass spectrometer (low resolution
Table 2 Novel one-pot double functionalisation of the ferrocene backbone via
iterative ‘‘click’’ cycloaddition reactions. i) Cu(OAc)2?H2O (1 mol%), NaN3,
MeOH, 1 h; ii) R9CCH, NaAsc (10 mol%), H2O, 16 h; iii) TBAF, THF (7 h); iv) R99N3,
CuSO4?5H2O (9 mol%), NaAsc (20 mol%).
Yield (%)a
Entry Product R9
R99
Stepwise One-pot
1
2
3
4
5
6
7
8
10
11
12
13
14
15
16
17
18
19
20
21
Ph
Ph
Ph
C6H13
C6H13
C6H13
HOCH2
HOCH2
HOCH2
Bn
TEG 17
Ad
Bn
TEG 19
Ad
Bn
TEG 28
30
45
37
43
33
37
45
38
42
41
44
30
43
31
18
19
31
9
Ad
17
15
10
11
12
3,5-di-tert-butylphenyl Bn
3,5-di-tert-butylphenyl TEG 11
3,5-di-tert-butylphenyl Ad 15
ESI , electrospray in positive ion mode) and a Waters (UK) LCT
3
premier XE (high resolution ESI , electrospray in positive ion
3
a
Isolated yields.
mode, ESI ); or Electrospray ionisation mass spectrometry was
3
obtained from the EPSRC National Mass Spectrometry Service,
University of Wales, Swansea on a Thermofisher LTQ Orbitrap
XL. Melting points were measured on a Stuart SMP3 melting
point apparatus and are uncorrected. Flash column chroma-
tography, unless otherwise stated, was performed using Fluka
silica gel 60 (220–240 mesh), and TLC was carried out using
pre-coated aluminium backed plates with Merck Kiesegel 60
F254. The plates were visualized under a UV lamp (254 nm), or
by staining with basified aqueous KMnO4 solution followed by
gentle heating.
The robustness of the one-pot reaction was tested on the
synthesis of twelve other, 1,19-di-substituted, ferrocenes 10–21
(Table 2). For comparison, these were also prepared using a
step-wise protocol. The conversion of the boronic acid 2 to its
corresponding azide 1 and the subsequent formation of the
first ‘‘clickate’’ was carried out using four different acetylenes,
including propargyl alcohol and the very bulky 3,5-di-tert-
butylphenylacetylene. The resulting reaction mixtures were
then treated with TBAF, split as stock solutions three ways, to
which each partnering azide and NaAsc was added. After 24 h,
the crude products were isolated by simple filtration and
purified by flash chromatography. In all cases, the desired
compounds were isolated after the one-pot procedure in
significantly better yields than the corresponding stepwise
route (Table 2). More importantly, the methodology was shown
to be tolerant to a variety of substituents, including alcohols,
water-soluble (triethyleneglycol (TEG)) and insoluble (hexyl)
chains, as well as sterically-demanding groups (adamantyl and
3,5-di-tert-butylphenylacetylene) showing the utility of this
approach.
1-bromo,19-iodoferrocene (4)
A solution of n-BuLi (2.5 M in hexane, 1.2 mL, 2.9 mmol, 1.0
equiv.) was slowly added to a solution of 1,19-dibromoferro-
cene (1.0 g, 2.9 mmol, 1.0 equiv.) in anhydrous THF (50 mL) at
278 uC under N2. During the addition and for 3 h afterwards,
the reaction was carefully maintained between 280 and 275
uC. The reaction was monitored by collecting aliquots,
quenching them with water and analysing by TLC in hexane
against 3. After the lithiation was complete, a solution of I2 (2.0
g, 7.9 mmol, 2.7 equiv.) in THF (15 mL) was added dropwise,
maintaining the reaction temperature below 275 uC. After the
addition was complete, the reaction was stirred at 278 uC for a
further hour and allowed to warm up to r.t. Once at r.t.,
aqueous sodium thiosulphate (20% w/v, 50 mL) was added to
the reaction vessel followed by Et2O (50 mL), and the mixture
was shaken very vigorously. After separation, the organic layer
was washed with aqueous sodium thiosulphate (3 6 100 mL),
dried over MgSO4, filtered and the solvent removed in vacuo.
The product 4 was isolated after flash column chromatography
(PE, 100%) as a dark brown oil (0.92 g, 81%): 1H NMR: 600
MHz, CDCl3: dH 4.45–4.41 (m, 2H), 4.40–4.36 (m, 2H), 4.24–
4.21 (m, 2H), 4.15–4.11 (m, 2H); 13C NMR: dC 78.3, 77.2, 73.2,
Experimental section
All reagents were purchased from Aldrich, Acros, Merck or
Fluka and were used without further purification unless
otherwise stated. I2 was sublimed prior to use.
Triisopropylborate was distilled prior to use. Hexane was
dried by refluxing over CaH2 for a minimum of 6 h and
This journal is ß The Royal Society of Chemistry 2013
RSC Adv., 2013, 3, 17081–17087 | 17083

View Article Online
Paper
RSC Advances
71.8, 71.1, 70.6; IR: nmax/cm21 3103, 1407, 1379, 1350, 1178,
1152, 1106, 1052, 1020, 1010, 872, 864, 820; HRMS m/z
mmol, 10 mol%) were dissolved in anhydrous MeOH (1.0 mL)
and stirred at r.t. for 1 h, until all of 2 was consumed (judged
by TLC analysis). Water (10 mL) was added in one portion and
the products were extracted with Et2O (3 6 5 mL). The extracts
were combined, washed with brine (20 mL) and dried over
MgSO4. The solvents were removed in vacuo and the residue
was purified by flash column chromatography (1% EA in PE).
During chromatography the product degrades, hence fractions
containing product 1 were combined and dried in vacuo.
Finally, product 1 was isolated after recrystallization from hot
PE as red crystals (13 mg, 39%): m.p. decomposition above 117
uC; 1H NMR: 400 MHz, CDCl3: dH 4.32 (s, 2H), 4.23 (s, 2H), 4.19
(s, 2H), 4.02 (s, 2H), 0.23 (s, 9H); 13C NMR: dC 104.0, 90.3, 84.1,
72.8, 69.8, 69.7, 68.5, 65.0, 0.00; IR: nmax/cm21 3085, 2955,
2897, 2146, 2110, 1451, 1418, 1247, 1109, 1035, 998, 923, 822,
756, 723; HRMS m/z calculated for: C15H1954FeN3Si [M]+
321.0582, found 321.0581; LRMS: m/z 324.0 [M + H]+; UV/vis:
lmax(DCM)/nm (e/mol21cm21dm3) 252 (10.7 6 103), 269 (8.94
6 103), 302 (5.10 6 103), 340 (1.19 6 103), 445 (497).
calculated for: C10H854Fe79Br127
I [M]+ 387.8250, found
387.8253; LRMS: m/z 413.2 [M + Na]+; UV/vis: lmax(DCM)/nm
(e/mol21cm21dm3) 254 (8.38 6 103), 244 (9.69 6 103), 280
(3.07 6 103), 325 (685), 438 (144).
1-bromo-19-trimethylsilylethynylferrocene (5)
1-Bromo-19-iodoferrocene 4 (0.92 g, 2.3 mmol, 1.0 equiv.), CuI
(4.5 mg, 0.023 mmol, 0.010 equiv.), Pd(PPh3)Cl2 (8.3 mg, 0.012
mmol, 0.005 equiv.) and PPh3 (12.3 mg, 0.047 mmol, 0.02
equiv.) were dissolved in thoroughly degassed Et3N/THF (4/1,
mL) and placed under N2. Trimethylsilylacetylene (0.49 mL,
0.35 g, 3.5 mmol, 1.5 equiv.) was added in one portion and the
reaction vessel was sealed and heated at 60 uC for 16 h. The
reaction was cooled to r.t., diluted with Et2O (30 mL) and
filtered. The filtrate was then washed with aqueous HCl (5%, 3
6 50 mL), dried over MgSO4, filtered and concentrated in
vacuo. The product 5 was obtained following purification by
flash column chromatography (1% EA in PE) as a brown-red
solid (0.56 g, 85%): 1H NMR: 600 MHz, CDCl3: dH 4.45 (m, 2H),
4.39 (m, 2H), 4.23 (m, 2H), 4.13 (m, 2H), 0.23 (s, 9H); 13C NMR:
dC 102.9, 91.7, 78.2, 74.1, 72.1, 71.6, 70.3, 69.6, 67.3, 0.3; IR:
nmax/cm21 3925, 3100, 2958, 2148, 1454, 1410, 1352, 1248,
1153, 1024, 926, 836, 757, 724, 697; HRMS m/z calculated for:
C15H18BrFeBrSi [M + H]+ 360.9707, found 360.9697; LRMS: m/z
360.97 [M + H]+; UV/vis: lmax(DCM)/nm (e/mol21cm21dm3) 238
(12.01 6 103), 246 (10.01 6 103), 274 (7.74 6 103), 338 (347),
442 (271).
General one-pot procedure for a double
‘‘click’’-functionalisation as represented by the synthesis of 1-
(1-benzyl-1H-,1,2,3-triazol-4-yl)-19-(4-phenyl-1H-1,2,3-triazol-1-
yl)-ferrocene (10)
Boronic acid 2 (15 mg, 0.046 mmol, 1.0 equiv.), NaN3 (3.0 mg,
0.047 mmol, 1.02 equiv.) and Cu(OAc)2?H2O (0.092 mg, 4.6 6
1024 mmol, 1.0 mol%) were dissolved in anhydrous MeOH (1
mL) and stirred at r.t. for 1 h, until all of 2 was consumed as
judged by TLC. Phenylacetylene (5.1 mg, 0.051 mmol, 1.1
equiv.) was added to the reaction mixture, followed by the
addition of a solution of sodium ascorbate (1.8 mg, 9.2 6 1023
mmol, 20 mol%) in water (500 mL). The reaction mixture was
stirred at r.t. for 16 h. A solution of TBAF (1.0 M in THF, 46 mL,
1.0 equiv.) was then added to the mixture and stirred for a
further 7 h. Finally, benzyl azide (1.0 equiv.) was added to the
mixture followed by a solution of CuSO4?5H2O (10 mol%) and
sodium ascorbate (1.8 mg, 9.2 6 1023 mmol, 20 mol%) in
water (100 mL). The mixture was stirred at r.t. for 24 h and then
filtered through a grade 4 sinter funnel. The brown solid was
washed with a 1.0 M solution of EDTA in saturated NaHCO3
until the washings became clear. The solid was dissolved in
DCM (20 mL), dried over MgSO4 and concentrated in vacuo.
The product 10 was isolated after flash column chromato-
graphy (40% EA in PE) as a yellow solid (18 mg, 45%): m.p.
>220 uC; 1H NMR: 600 MHz, CDCl3: dH 7.89 (dd, J = 8.1, 1.0 Hz,
2H), 7.65 (s, 1H), 7.49 (m, 2H), 7.37 (m, 1H), 7.29 (m, 3H), 6.95
(s, 1H), 4.96 (s, 2H), 4.90 (m, 2H), 4.82 (m, 2H), 4.36 (m, 2H),
4.27 (m, 2H); 13C NMR: dC: 147.0, 143.9, 134.6, 130.2, 129.0,
128.5, 128.3, 128.0, 125.7, 119.3, 118.1, 70.0, 68.1, 67.4, 62.1,
53.6; IR: nmax/cm21 3122, 3097, 3033, 2952, 1607, 1588, 1519,
1496, 1480, 1452, 1440, 1393, 1329, 1223, 1192, 1096, 1039,
970, 920, 882, 872, 816, 767, 710; HRMS m/z calculated for:
19-(1-trimethylsilylethynyl)ferroceneboronic acid (2)
n-BuLi (2.5 M in hexane, 0.66 mL, 1.7 mmol, 1.1 equiv.) was
added dropwise to a solution of 6 (0.54 g, 1.5 mmol, 1.0 equiv.)
in anhydrous THF (20 mL) at 278 uC under N2. The reaction
was allowed to stir for 1 h at 278 uC and B(OiPr)3 (1.0 mL, 4.5
mmol, 3.0 equiv.) was added slowly, while maintaining the
temperature. After the addition was complete the reaction was
left to stir at 278 uC for an additional hour followed by slow
warming to r.t., and a further 2 h of stirring. The reaction
mixture was hydrolysed with water (20 mL) and the product
was extracted with Et2O (3 6 30 mL). The extracts were
combined, dried over MgSO4 and solvent was removed in vacuo
to afford a dark brown solid. Finally, dissolution of the crude
solid in a small amount of warm Et2O and precipitation with
n-hexane, followed by filtration afforded 2 as an orange solid
1
(0.37 g, 77%): m.p. decomposes >190 uC; H NMR: 600 MHz,
CDCl3: dH 4.71–4.66 (m, 2H), 4.60–4.55 (m, 2H), 4.45–4.40 (m,
2H), 4.22–4.17 (m, 2H), 0.23 (s, 9H); 13C NMR: dC 103.13, 91.21,
75.95, 75.64, 72.06, 69.20, 65.77, 0.0; IR: nmax/cm21 3101, 2955,
2898, 2149, 1436, 1378, 1340, 1309, 1244, 1194, 1117, 1053,
1022, 926, 832, 757, 722, 697; HRMS m/z calculated for:
C15H20BFeO2Si [M + H]+ 327.0670, found 327.0664; LRMS: m/z
327.07 [M + H]+; UV/vis: lmax(DCM)/nm (e/mol21cm21dm3) 236
(14.88 6 103), 241 (11.85 6 103), 273 (9.40 6 103), 343 (414),
448 (348).
C
27H23FeN6 [M + H]+ 487.1334, found 487.1341; LRMS: m/z
487.1 [M + H]+; UV/vis: lmax(DCM)/nm (e/mol21cm21dm3) 245
(16.85 6 103), 293 (5.68 6 103), 330 (1.25 6 103), 442 (220).
19azido-(1-trimethylsilylethynyl)ferrocene (1)
Boronic acid 2 (33 mg, 0.10 mmol, 1.0 equiv.), NaN3 (10 mg,
0.15 mmol, 1.5 equiv.) and Cu(OAc)2?H2O (1.8 mg, 0.010
17084 | RSC Adv., 2013, 3, 17081–17087
This journal is ß The Royal Society of Chemistry 2013

View Article Online
RSC Advances
Paper
(m, 2H), 2.90 (t, J = 5.9 Hz, 1H), 2.65 (t, J = 7.9 Hz, 2H), 1.63 (m,
2H), 1.39–1.24 (m, 6H), 0.88 (t, J = 6.8 Hz, 3H); 13C NMR: dC
148.1, 143.9, 127.5, 121.0, 119.9, 94.7, 78.2, 72.7, 70.7, 70.5,
70.1, 69.5, 68.3, 67.5, 62.4, 61.8, 50.1, 31.7, 29.4, 29.1, 25.8,
22.7, 14.2; IR: nmax/cm21 3415 (broad), 3122, 3094, 2925, 2857,
1517, 1446, 1377, 1351, 1221, 1116, 1104, 1067, 1041, 929, 882,
872, 816, 755, 719; HRMS m/z calculated for: C26H37FeN6O3 [M
+ H]+ 537.2271, found 537.2258; LRMS: m/z 559.21 [M + Na]+;
UV/vis: lmax(DCM)/nm (e/mol21cm21dm3) 236 (17.30 6 103),
242 (15.97 6 103), 275 (9.18 6 103), 330 (1.18 6 103), 439
(333).
1-(1-(2-(2-Ethoxyethoxyl)ethanol)-1H-,1,2,3-triazol-4-yl)-19-(4-
phenyl-1H-1,2,3-triazol-1-yl)-ferrocene (11)
Product was isolated after flash column chromatography (10%
MeOH in EA) as a yellow oil (37%): m.p. 139–141 uC; 1H NMR:
600 MHz, CDCl3: dH 7.82 (dd, J = 8.3, 1.1 Hz, 2H), 7.64 (s, 1H),
7.46–7.43 (m, 2H), 7.36–7.33 (m, 2H), 4.91 (m, 2H), 4.88 (m,
2H), 4.37 (m, 2H), 4.27 (m, 2H), 4.02 (t, J = 5.4 Hz, 2H), 3.76 (t, J
= 4.8 Hz, 2H), 3.62–3.57 (m, 6H), 3.53–3.51 (m, 2H); 13C NMR:
dC 146.9, 143.4, 130.2, 129.0, 128.4, 127.5, 127.4, 125.8, 120.8,
118.4, 94.2, 78.3, 72.7, 70.5, 70.4, 70.1, 69.2, 68.2, 67.5, 62.2,
61.8, 49.8; IR: nmax/cm21 3398 (broad), 3119, 2866, 1522, 1479,
1452, 1349, 1391, 1226, 1100, 1066, 1038, 1028, 971, 880, 871,
810, 762, 688; HRMS m/z calculated for: C26H28FeN6NaO3 [M +
Na]+ 551.1470, found 551.1470; LRMS: m/z 551.1 [M + Na]+; UV/
vis: lmax(DCM)/nm (e/mol21cm21dm3) 237 (24.26 6 103), 246
(23.95 6 103), 290 (8.33 6 103), 327 (1.99 6 103), 441 (331).
1-(1-Adamantyl-1H-,1,2,3-triazol-4-yl)-19-(4-hexyl-1H-1,2,3-
triazol-1-yl)-ferrocene (15)
Product was isolated after flash column chromatography (10%
1
EA in PE) as a yellow solid (45%): m.p. 156–158 uC; H NMR:
600 MHz, CDCl3: dH 7.49 (s, 1H), 7.42 (s, 1H), 4.69 (m, 2H),
4.67 (m, 2H), 4.33 (m, 2H), 4.20 (m, 2H), 2.69 (t, J = 7.8 Hz, 2H),
2.27 (bs, 3H), 2.23 (m, 6H), 1.83–1.77 (m, 6H), 1.70–1.64 (m,
2H), 1.42–1.26 (m, 6H), 0.88 (t, J = 7.0 Hz, 3H); 13C NMR: dC
148.3, 143.5, 127.5, 120.5, 116.4, 94.9, 78.6, 71.3, 70.1, 68.6,
67.6, 63.1, 59.6, 43.0, 36.1, 31.7, 29.6, 29.5, 29.2, 25.9, 22.7,
14.2; IR: nmax/cm21 3122, 3088, 2909, 2853, 1725, 1519, 1452,
1425, 1377, 1360, 1310, 1222, 1188, 1164, 1098, 1041, 1014,
984, 882, 816, 729, 691; HRMS m/z calculated for: C30H3954FeN6
[M + H]+ 537.2632, found 537.2621; LRMS: m/z 537.3 [M + H]+;
UV/vis: lmax(DCM)/nm (e/mol21cm21dm3) 236 (25.20 6 103),
244 (21.04 6 103), 274 (13.67 6 103), 325 (1.78 6 103), 440
(471).
1-(1-Adamantyl-1H-,1,2,3-triazol-4-yl)-19-(4-phenyl-1H-1,2,3-
triazol-1-yl)-ferrocene (12)
Product was isolated after flash column chromatography (40%
EA in PE) as a yellow solid (43%): m.p. decomposes >190 uC; 1H
NMR: 600 MHz, CDCl3: dH 7.86–7.82 (m, 3H), 7.45–7.40 (m,
2H), 7.34–7.30 (m, 1H), 7.26 (s, 1H), 4.83 (m, 2H), 4.80 (m, 2H),
4.38 (m, 2H), 4.27 (m, 2H), 2.07 (bs, 3H), 1.96 (m, 6H), 1.67 (d, J
= 12.5 Hz, 3H), 1.59 (d, J = 11.7 Hz, 3H); 13C NMR: dC 147.2,
142.9, 130.5, 128.9, 128.2, 127.5, 125.9, 118.9, 116.2, 94.6, 78.9,
70.0, 68.4, 67.5, 62.8, 59.6, 42.6, 35.9, 29.5; IR: nmax/cm21 3122,
3082, 2907, 2849, 1609, 1523, 1478, 1450, 1420, 1389, 1358,
1308, 1226, 1186, 1160, 1096, 1027, 1014, 968, 906, 873, 819,
762, 728, 691; HRMS m/z calculated for: C30H30FeN6Na [M +
Na]+ 553.1779, found 553.1719; LRMS: m/z 553.2 [M + Na]+, UV/
vis: lmax(DCM)/nm (e/mol21cm21dm3) 246 (30.65 6 103), 275
(15.83 6 103), 290 (11.33 6 103), 327 (2.67 6 103), 438 (701).
1-(1-Benzyl-1H-,1,2,3-triazol-yl)-19-(4-(methyl-1-ol)-1H-1,2,3-
triazol-1-yl)-ferrocene (16)
Product was isolated after flash column chromatography (10%
MeOH in EA) as a yellow solid (38%): m.p. 110–113 uC; 1H
NMR: 600 MHz, CDCl3: dH 7.55 (s, 1H), 7.40–7.32 (m, 3H),
7.29–7.24 (m, 2H), 7.12 (s, 1H), 5.51 (s, 2H), 4.81 (m, 2H), 4.79–
4.73 (m, 4H), 4.34 (m, 2H), 4.24 (m, 2H), 3.34 (bs, 1H); 13C
NMR: dC 147.3, 143.9, 134.6, 129.2, 128.8, 128.3, 121.0, 120.3,
94.4, 77.9, 70.1, 67.9, 67.4, 61.8, 56.6, 54.2; IR: nmax/cm21 3293
(broad), 3122, 3095, 2931, 2868, 2234, 1718, 1662, 1591, 1555,
1523, 1497, 1456, 1442, 1391, 1329, 1260, 1223, 1189, 1075,
1051, 1036, 1029, 1022, 999, 955, 927, 882, 871, 848, 810, 769,
726; HRMS m/z calculated for: C22H21FeN6O [M + H]+ 441.1121,
1-(1-Benzyl-1H-,1,2,3-triazol-4yl)-19-(4-hexyl-1H-1,2,3-triazol-1-
yl)-ferrocene (13)
Product was isolated after flash column chromatography (33%
1
EA in PE) as a yellow solid (45%): m.p. 140–142 uC; H NMR:
600 MHz, CDCl3: dH 7.39–7.33 (m, 3H), 7.31 (s, 1H), 7.27–7.24
(m, 2H), 7.14 (s, 1H), 5.48 (s, 2H), 4.73 (m, 4H), 4.32 (m, 2H),
4.20 (m, 2H), 2.69 (t, J = 7.8 Hz, 2H), 1.70–1.63 (m, 2H), 1.42–
1.26 (m, 6H), 0.92–0.86 (m, 3H); 13C NMR: dC 148.3, 144.6,
134.9, 129.2, 128.8, 128.2, 127.5, 119.9, 119.7, 94.7, 77.9, 70.2,
found 441.1107; LRMS: m/z 441.11 [M
+
H]+; UV/vis:
lmax(DCM)/nm (e/mol21cm21dm3) 238 (14.41 6 103), 246
(11.98 6 103), 277 (6.46 6 103), 323 (1.26 6 103), 440 (271).
68.3, 67.5, 62.4, 54.1, 31.7, 29.5, 29.2, 25.6, 22.7, 14.2; IR: nmax
/
cm21 3125, 3092, 2926, 2857, 1517, 1496, 1465, 1442, 1393,
1328, 1223, 1189, 1143, 1092, 1074, 1052, 1040, 880, 848, 813,
718, 665; HRMS m/z calculated for: C27H31FeN6 [M + H]+
495.1954, found 495.1940; LRMS: m/z 495.2 [M + H]+; UV/vis:
lmax(DCM)/nm (e/mol21cm21dm3) 237 (28.09 6 103), 272
(14.70 6 103), 318 (2.38 6 103), 441 (490).
1-(1-(2-(2-Ethoxyethoxyl)ethanol)-1H-,1,2,3-triazol-4-yl)-19-(4-
(methyl-1-ol)-1H-1,2,3-triazol-1-yl)-ferrocene (17)
Product was isolated after flash column chromatography (30%
MeOH in EA) as a yellow solid (42%): m.p. 50–52 uC; 1H NMR:
600 MHz, CDCl3: dH 7.54 (s, 1H), 7.44 (s, 1H), 4.82–4.79 (m,
4H), 4.70 (d, J = 5.8 Hz, 2H), 4.52 (t, J = 5 Hz, 2H), 4.36 (m, 2H),
4.25 (m, 2H), 3.89 (m, 2H), 3.79–3.75 (m, 2H), 3.70–3.59 (m,
6H), 3.28 (t, J = 5.9 Hz, 1H), 2.10 (bs, 1H); 13C NMR: dC 147.3,
143.5, 127.5, 121.5, 121.1, 94.4, 78.2, 72.7, 70.6, 70.4, 70.0,
69.3, 68.1, 67.4, 62.1, 61.7, 56.5, 50.2; IR: nmax/cm21 3312
(broad), 3122, 3098, 2916, 2868, 1654, 1519, 1444, 1380, 1349,
1218, 1177, 1101, 1026, 925, 881, 814, 760, 728, 687; HRMS m/z
1-(1-(2-(2-Ethoxyethoxyl)ethanol)-1H-,1,2,3-triazol-4-yl)-19-(4-
hexyl-1H-1,2,3-triazol-1-yl)-ferrocene (14)
Product was isolated after flash column chromatography (10%
EA in PE) as a yellow solid (37%): m.p. 52–55 uC; 1H NMR: 600
MHz, CDCl3: dH 7.50 (s, 1H), 7.30 (s, 1H), 4.79 (m, 2H), 4.75 (m,
2H), 4.49 (t, J = 5.1 Hz, 2H), 4.33 (m, 2H), 4.21 (m, 2H), 3.87 (t, J
= 5.1 Hz, 2H), 3.77 (dd, J = 9.3, 5.3 Hz, 2H), 3.65 (s, 4H), 3.61
This journal is ß The Royal Society of Chemistry 2013
RSC Adv., 2013, 3, 17081–17087 | 17085

View Article Online
Paper
RSC Advances
calculated for: C21H26FeN6O4 [M + H]+ 483.1438, found
483.1431; LRMS: m/z 505.12 [M + Na]+; UV/vis: lmax(DCM)/
nm (e/mol21cm21dm3) 240 (16.70 6 103), 245 (14.85 6 103),
276 (8.10 6 103), 326 (1.46 6 103), 440 (370).
1-(1-Adamantyl-1H-,1,2,3-triazol-4-yl)-19-(4-(3,5-di-tert-
butylphenyl)-1H-1,2,3-triazol-1-yl)-ferrocene (21)
Product was isolated after flash column chromatography (30%
1
EA in PE) as a yellow solid (43%): m.p. 203–205 uC; H NMR:
600 MHz, CDCl3: dH 7.80 (s, 1H), 7.68 (d, J = 1.86 Hz, 2H), 7.40
(t, J = 1.8 Hz, 1H), 7.22 (s, 1H), 4.84–4.82 (m, 4H), 4.37 (m, 2H),
4.26 (m, 2H), 2.04–2.00 (m, 3H), 1.95–1.92 (m, 6H), 1.65–1.59
(m, 3H), 1.53–1.48 (m, 3H), 1.38 (s, 18H); 13C NMR: dC 151.4,
148.0, 142.9, 129.7, 127.5, 122.6, 120.2, 118.9, 116.2, 94.7, 78.8,
1-(1-Adamantyl-1H-,1,2,3-triazol-4-yl)-19-(4-(methyl-1-ol)-
1H-1,2,3-triazol-1-yl)-ferrocene (18)
Product was isolated after flash column chromatography (60%
to 75% EA in PE) as a yellow solid (41%): m.p. 65–67 uC; H
1
NMR: 600 MHz, CDCl3: dH 7.74 (s, 1H), 7.40 (s, 1H), 4.79 (st,
2H), 4.77–4.75 (m, 2H), 4.74 (m, 2H), 4.34 (m, 2H), 4.24 (m,
2H), 3.50 (bs, 1H), 2.29–2.20 (m, 9H), 1.81–1.76 (m, 6H); 13C
NMR: dC 147.4, 142.7, 127.5, 121.6, 116.9, 94.6, 78.8, 69.9, 68.0,
67.4, 62.3, 59.9, 56.8, 42.9, 35.9, 29.5; IR: nmax/cm21 3326
(broad), 3132, 2910, 2854, 2244, 1718, 1518, 1451, 1422, 1359,
1341, 1309, 1220, 1188, 1099, 1040, 1027, 1016, 907, 879, 813,
724; HRMS m/z calculated for: C25H2954FeN6O [M + H]+
483.1799, found 483.1810; LRMS: m/z 485.1 [M + H]+; UV/vis:
lmax(DCM)/nm (e/mol21cm21dm3) 237 (15.77 6 103), 245
(13.38 6 103), 277 (7.33 6 103), 326 (1.24 6 103), 438 (383).
70.0, 68.4, 67.5, 62.8, 59.5, 42.7, 35.8, 35.1, 31.6, 29.4; IR: nmax
/
cm21 3117, 3068, 2914, 2854, 1594, 1523, 1477, 1454, 1424,
1389, 1361, 1309, 1285, 1229, 1190, 1165, 1099, 1071, 1058,
1042, 1026, 907, 882, 875, 835, 822, 767, 729; HRMS m/z
calculated for: C38H47FeN6 [M + H]+ 643.3212, found 643.3232;
LRMS: 643.3 [M
+
H]+; UV/vis: lmax(DCM)/nm (e/
mol21cm21dm3) 250 (19.93 6 103), 287 (10.61 6 103), 295
(7.22 6 103), 330 (1.58 6 103), 440 (365).
Conclusions
1-(1-Benzyl-1H-,1,2,3-triazol-4yl)-19-(4-(3,5-di-tert-butylphenyl)-
1H-1,2,3-triazol-1-yl)-ferrocene (19)
We have developed a novel one-pot, four-component, Cu(II–I)-
mediated methodology that provides 1,19-functionalised ferro-
cenes from the parent 19-(1-trimethylsilylethynyl)ferrocene-
boronic acid 2, alkynes and azides. The method is
straightforward, robust and versatile, giving products in better
overall yields than the equivalent stepwise protocol, and
provides rapid access to highly functionalised ferrocenes.
Using this semi-combinatorial approach, we have prepared an
array of ferrocenes, exemplifying the utility of the methodology
which could be easily exploited for the synthesis of novel
materials, ligands for catalysis or biological sensors using
structurally diverse, and readily available, building blocks.
Whilst we elected to use the Huisgen–Meldal–Fokin–Sharpless
Product was isolated after flash column chromatography (40%
1
EA in PE) as a yellow solid (44%): m.p. >220 uC; H NMR: 600
MHz, CDCl3: dH 7.75 (d, J = 1.8 Hz, 2H), 7.61 (s, 1H), 7.45 (t, J =
1.8 Hz, 1H), 7.28–7.25 (m, 3H), 7.04–7.01 (m, 2H), 6.91 (s, 1H),
4.92 (m, 2H), 4.85 (s, 2H), 4.82 (m, 2H), 4.35 (m, 2H), 4.26 (m,
2H), 1.42 (s, 18H); 13C NMR: dC 151.6, 147.9, 143.9, 134.8,
129.5, 129.0, 128.6, 128.1, 127.5, 122.5, 120.3, 119.5, 117.9,
94.4, 78.1, 70.1, 68.1, 67.5, 62.1, 53.6, 35.2, 31.7; IR: nmax/cm21
3115, 2953, 2904, 2867, 1595, 1512, 1458, 1419, 1392, 1362,
1332, 1283, 1239, 1216, 1097, 1072, 1055, 1045, 1023, 876, 842,
824, 767, 717, 708, 696; HRMS m/z calculated for: C35H39FeN6
[M + H]+ 599.2580, found 599.2564; LRMS: m/z 599.25 [M + H]+;
UV/vis: lmax(DCM)/nm (e/mol21cm21dm3) 237 (26.18 6 103),
251 (20.38 6 103), 277 (11.08 6 103), 326 (2.89 6 103), 438
(510).
[3
+ 2] azide-alkyne cycloaddition ‘‘click’’ reaction, we
anticipate that the boronic acid 2 could also be subjected to
various Pd-catalysed cross-couplings, with the products being
subsequently ‘‘clicked’’ in the 19-position to give even more
diverse materials.
1-(1-(2-(2-Ethoxyethoxyl)ethanol)-1H-,1,2,3-triazol-4-yl)-19-(4-
(3,5-di-tert-butylphenyl-1-yl)-1H-1,2,3-triazol-1-yl)-ferrocene
(20)
Product was isolated after flash column chromatography (5%
MeOH in EA) as a yellow solid (30%): m.p. 92–95 uC; 1H NMR:
600 MHz, CDCl3: dH 7.67 (m, 2H), 7.62 (s, 1H), 7.41 (m, 1H),
7.34 (s, 1H), 4.92 (m, 2H), 4.88 (m, 2H), 4.36 (m, 2H), 4.27 (m,
2H), 3.97 (t, J = 5.1 Hz, 2H), 3.75 (m, 2H), 3.70–3.50 (m, 8H),
2.79 (t, J = 6.0 Hz, 1H), 1.40 (s, 18H); 13C NMR: dC 151.5, 147.9,
143.5, 129.4, 127.5, 122.4, 120.8, 120.3, 118.2, 94.4, 78.3, 72.6,
70.5, 70.4, 70.1, 69.1, 68.2, 67.5, 62.2, 61.8, 49.7, 35.1, 31.6; IR:
nmax/cm21 3363 (broad), 3117, 2952, 2904, 2866, 1594, 1521,
1460, 1423, 1392, 1362, 1350, 1285, 1227, 1113, 1069, 1055,
1044, 1025, 879, 845, 820, 800, 768, 709; HRMS m/z calculated
for: C35H45FeN6O3 [M + H]+ 641.2897, found 641.2893; LRMS:
m/z 641.29 [M + H]+; UV/vis: lmax(DCM)/nm (e/mol21cm21dm3)
248 (17.27 6 103), 278 (8.46 6 103), 298 (5.61 6 103), 330 (1.47
6 103), 440 (331).
Acknowledgements
We thank the EPSRC National Mass Spectrometry Service
Centre (Swansea University) and Oleg Ilyashenko for financial
support provided to GI.
Notes and references
1 For example see: (a) T. A. Hayashi, Ferrocenes, VSH,
Weinheim, Germany, 1995; (b) R. C. J. Atkinson, V.
C. Gibson and N. J. Long, Chem. Soc. Rev., 2004, 33, 313.
2 For examples see: (a) T. J. Colacot, Chem. Rev., 2003, 103,
3101; (b) P. Barbaro, C. Bianchini, G. Giambastiani and S.
L. Parisel, Coord. Chem. Rev., 2004, 248, 2131; (c) R.
G. Arrayas, J. Adrio and J. C. Carretero, Angew. Chem., Int.
Ed., 2006, 45, 7674; (d) I. R. Butler, Eur. J. Inorg. Chem.,
17086 | RSC Adv., 2013, 3, 17081–17087
This journal is ß The Royal Society of Chemistry 2013

View Article Online
RSC Advances
Paper
2012, 4387; (e) S. Top, B. Dauer, J. Vaissermann and G.
J. Jaouen, J. Organomet. Chem., 1997, 541, 355; (f) C. Roux
and C. Biot, Future Med. Chem., 2012, 4, 783; (g) US Patent
4,104,036; (h) O. N. Kadkin and Y. G. Galyametdinov, Russ.
Chem. Rev., 2012, 81, 675; (i) S. W. Chee and R. Sharma,
Micron, 2012, 43, 1181; (j) P. Zanello, Inorganic
Electrochemistry, RSC, Cambridge, UK, 2003, p. 193.
3 Selected examples include, but not limited to (a)
D. Marquarding, H. Klusacek, G. Gokel, P. Hoffmann and
I. Ugi, J. Am. Chem. Soc., 1970, 92, 5389; (b) O. Riant,
O. Samuel and H. B. Kagan, J. Am. Chem. Soc., 1993, 115,
5835; (c) B. Ferber and H. B. Kagan, Adv. Synth. Catal.,
2007, 349, 493; (d) C. J. Richards, T. Damalidis, D. E. Hibbs
and M. B. Hursthouse, Synlett, 1995, 74; (e) M. Tsukazaki,
M. Tinkl, A. Roglans, B. J. Chapell, N. J. Taylor and
V. Snieckus, J. Am. Chem. Soc., 1996, 118, 685; (f)
M. Widhalm, K. Mereiter and M. Bourghida, Tetrahedron:
Asymmetry, 1998, 9, 2983; (g) A. Farrell, R. Goddard and P.
J. Guiry, J. Org. Chem., 2002, 67, 4209; (h) D. Enders,
R. Peters, R. Lochtman and G. Raabe, Angew. Chem., Int.
Ed., 1999, 38, 2421; (i) C. Bolm, M. Kesselgruber and
K. Muniz, Organometallics, 2000, 19, 1648; (j) A.
S. Batsanov, D. Herault, J. A. K. Howard, L. G. F. Patrick,
M. R. Probert and A. Whiting, Organometallics, 2007, 26,
2414.
C. Caballero, P. Gerner and C. H. Greenwell, J. Organomet.
Chem., 2003, 679, 59; (e) A. Cheiffi, J. V. Commaseto and
V. Snieckus, Synlett, 2000, 269; (f) M. W. Wright,
Organometallics, 1990, 9, 853.
5 H.C. Kolb, M. G. Finn and K. B. Sharpless, Angew. Chem.,
Int. Ed., 2001, 40, 2004.
6 (a) Organic Azides: Synthesis and Applications, S. Brase and
K. Benert, ed., John Wiley & Sons, Chichester, UK, 2010; (b)
Azide 1 was isolated and characterised (see ESI ).
3
7 I. R. Butler, Inorg. Chem. Commun., 2008, 11, 15.
8 J. K. Pudelski and M. R. Callstrom, Organometallics, 1994,
13, 3095.
9 C.-Z. Tao, X. Cui, J. Li, A.-X. Liu, L. Liu and Q.-X. Guo,
Tetrahedron Lett., 2007, 48, 3525.
10 C. Cai and A. Vasella, Helv. Chim. Acta, 1995, vol. 78, p. 732;
the deprotection can also be carried out using K2CO3 (see
ESI ), however we found that it was not suitable for the use
3
in the one-pot double-‘‘click’’ as the addition of K2CO3
completely inhibited the subsequent ‘‘click’’.
11 D. G. Hall, Boronic Acids, Wiley-VCH Veriag GmbH & Co,
Weinheim, Germany, 2005, p. 62.
12 The screening showed that the increase of water concen-
tration in the reaction mixture had a detrimental effect
upon formation of the azide. This was also observed in
previous work (ref. 9).
13 (a) Z. Gonda and Z. Novak, Dalton Trans., 2010, 39, 726; (b)
C. Shao, X. Wang, Q. Zhang, S. Luo, J. Zhao and Y. Hu, J.
Org. Chem., 2011, 76, 6832; (c) S. Lal and S. Diez-Gonzales,
J. Org. Chem., 2011, 76, 2367.
4 (a) T. Y. Dong and L. L. Lai, J. Organomet. Chem., 1996, 509,
131; (b) I. R. Butler and M. G. B. Drew, Inorg. Chem.
Commun., 1999, 2, 234; (c) I. R. Butler, A. L. Boyes, G. Kelly,
S. C. Quale, T. Herzig and J. Szewczyk, Inorg. Chem.
Commun., 1999, 2, 403; (d) I. R. Butler, M. G. B. Drew, A.
This journal is ß The Royal Society of Chemistry 2013
RSC Adv., 2013, 3, 17081–17087 | 17087