Discovery of a robust and efficient homogeneous silver(I) catalyst for the cycloaddition of azides onto terminal alkynes

Article abstract of DOI:10.1002/ejoc.201200930

A highly efficient, chemically stable, and well-defined homogeneous silver(I) catalyst is reported for the cycloaddition of azides onto terminal alkynes (Ag-AAC reaction). The Ag-AAC reaction occurs at room temperature or with heating to deliver exclusive

Full text of DOI:10.1002/ejoc.201200930

Job/Unit: O20930
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Date: 17-08-12 09:53:26
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FULL PAPER
DOI: 10.1002/ejoc.201200930
Discovery of a Robust and Efficient Homogeneous Silver(I) Catalyst for the
Cycloaddition of Azides onto Terminal Alkynes
James McNulty*[a] and Kunal Keskar[a]
Keywords: Cycloaddition / Azides / Alkynes / Click chemistry / Silver
A highly efficient, chemically stable, and well-defined homo- deliver exclusively the corresponding 1,4-triazole. A pro-
geneous silver(I) catalyst is reported for the cycloaddition of
azides onto terminal alkynes (Ag-AAC reaction). The Ag-
AAC reaction occurs at room temperature or with heating to
nounced ligand effect was discovered through systematic
modification to the ligand structure resulting in the discovery
of a chemically stable active catalyst for this reaction.
the cycloaddition to generate metalated triazole C,[4,5] and
this intermediate, upon protonation,[5e] yields 1,4-triazole 3.
Despite the positive attributes of the 1,4-regioselective
Introduction
Since the concept of “click” chemical reactions was de-
scribed by Sharpless,[1a] the copper(I)-catalyzed azide– Cu-AAC process, several problems persist. From a funda-
alkyne cycloaddition (Cu-AAC: i.e., the copper-catalyzed mental viewpoint, isoelectronic gold(I)[6a] and silver(I)[5d,6b]
Huisgen cycloaddition) reaction has emerged as the most acetylides are known to participate in the AAC reaction;
extensively investigated and applied. This reaction permits however, the addition of copper(I) salts is required to effect
the chemoselective, regiocontrolled conjugation of a func- the cycloaddition. No competent silver(I) or gold(I) species
tionalized alkyne 1 to a functionalized azide 2[1] yielding has been reported to promote the AAC reaction
1,4- or 1,4,5-substituted 1,2,3-triazole 3 and occasionally alone,[5d,5f,6b–6d] The rationale for the failure of a competent
1,5-regioisomer 4 (Figure 1). Applications in many areas silver(I) catalyst is not clear.
ranging from functional materials, drug discovery, bio-
In addition, reports of problematic Cu-AAC reac-
logical, and hybrid bioconjugate areas have increased expo- tions[5g,7a–7f] and the toxicity (including genetoxicity) of red-
nentially over the last decade.[2,3] The reaction (Figure 1) ox-active copper(I) species have arisen in relation to bio-
mechanism is complex, proceeding through a stepwise pro- logical applications.[9] Many copper-catalyzed processes are
cess initiated by copper(I) acetylide A, which complexes to heterogeneous and suffer from aggregation problems.
azide 2. Complexation of the copper(I) catalyst to the Cu– Homogeneous copper catalysis has been achieved by using
acetylide/azide leads to intermediate B, which undergoes amine and phosphane ligands, allowing low catalyst load-
Figure 1. The general Cu-AAC reaction.
ings (Ͻ1%).[7g–7j] Despite the unpromising precedents re-
[a] Department of Chemistry and Chemical Biology,
McMaster University
ported for a possible Ag-AAC process, we became inter-
ested in exploring homogeneous complexes of type
[Ag+(L2)(X–)] for several applications and recently discov-
ered the first homogeneous silver(I) catalyst for the AAC
reaction.[8] In accord with issues of copper toxicity, concern
1280 Main Street West, Hamilton, ON, L8S 4M1, Canada
Fax: +1-905-522-2509
E-mail: jmcnult@mcmaster.ca
Homepage: http://www.chemistry.mcmaster.ca/mcnulty/
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201200930.
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has been raised over the potential toxicity of silver nanopar- ligands 5a–i (Table 1) were synthesized by using standard
ticles.[10a] Silver complexes have been shown to be signifi- methods by employing nucleophilic and electrophilic phos-
cantly less cytotoxic than silver salts.[10b] Silver complexes phane coupling (see the Experimental Section). Crystalline
are not expected to participate in analogous (CuI–CuII) complexes 6a–i of ligands 5a–i were formed with silver acet-
one-electron transfer processes, and we were confident that ate (1:1) in all cases. The Ag-AAC process was investigated
a stable, catalytically efficient, suitably ligated silver(I) spe- under a standard set of conditions (10 mol-% catalyst, 48 h,
cies could be developed that would not precipitate metallic r.t. in toluene) with all nine silver complexes (Table 1). The
silver or silver halide under the conditions required. In view first generation of ligands 5a–f consisted of modifications
of these concerns and initial success,[8] we have systemati- to the weak donor ability of the ortho substituent on the
cally evaluated structural effects of the ligand in the Ag- ligand. A slight excess amount of the alkyne (azide/alkyne
mediated AAC process. In this communication, we report = 1.0:1.2) was used in contrast to our earlier requirement
the development of an optimized, chemically stable, highly of an excess amount of the azide (4.8 equiv.). The overall
efficient silver(I) homogeneous catalyst for the Ag-AAC results of screening catalysts 6a–f demonstrated the clear
process.
superiority of the N,N-diisopropylamide substituent, which,
fortuitously, was the first ligand investigated in the series.[8]
Results and Discussion
Table 2. Optimization with catalyst 6g in the Ag-AAC reaction.[a]
We recently reported a homogeneous, well-defined sil-
ver(I) complex derived from silver acetate and N,N-di-
isopropyl(2-diphenylphosphanyl)benzamide (5e) competent
in affecting the Ag-AAC process. Whereas these reactions
proceeded at room temperature in toluene, the catalyst was
inefficient. Full conversion of the alkyne/azide to triazole
required the use of 20 mol-% catalyst and a 4.8-fold excess
amount of azide relative to alkyne. Our vision in developing
hemilabile ligand 5e was to enable push–pull effects on the
metal center, which would allow progression through the
cycle by electrophilic 14-electron to 18-electron intermedi-
ates effecting cyclization through nucleophilic ligand-medi-
ated polarization of the complexed alkyne onto the azide
(vide infra). To probe ligand effects in the Ag-AAC process,
Table 1. Pronounced ligand effect on the Ag-AAC reaction.[a]
[a] Reaction conditions for entries 1–8, 10: Phenyl acetylene
(0.18 mmol, 1.2 equiv.), benzyl azide (0.15 mmol, 1.0 equiv.), ca-
prylic acid (20 mol-%), PhMe (1.0 mL). Reaction conditions for
entries 9, 11–16: Phenyl acetylene (0.09 mmol, 1.0 equiv.), benzyl
azide (0.14 mmol, 1.5 equiv.), caprylic acid (20 mol-%), PhMe
(1.0 mL).
[a] Reaction conditions: Phenyl acetylene (0.18 mmol, 1.2 equiv.),
benzyl azide (0.15 mmol, 1.0 equiv.), catalyst (10 mol-%), caprylic
acid (20 mol-%), PhMe (1.0 mL), 48 h, r.t. [b] Yield of triazole 3.
2
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AgI-Catalyzed Cycloaddition of Azides onto Terminal Alkynes
The effect of the ortho substituent is sharp, both on cata- at all. The optimization results for catalyst 6g are summa-
lytic activity and overall stability of the complex. Complex rized in Table 2. The initial reaction provided seven catalyst
6e (most stable) showed only minor silver metal deposition turnovers at room temperature over 48 h (Table 2, entry 1).
after one reaction cycle, whereas catalyst 6c (least stable) Increasing the temperature allowed higher conversion; how-
decomposed rapidly and gave poor conversion. Also, ever, the formation of trace amounts of minor 1,5-re-
stronger and weaker donor appendages at the ortho position gioisomeric triazole 4 was observed at temperatures above
appear detrimental with the amide substituent alone exhib- 100 °C, whereas formation of this product was totally sup-
iting a superior effect on catalyst stability and turnover. The pressed at 90 °C (Table 2, entries 2–7). All other reactions
second generation of ligands 5g–i was therefore prepared were therefore conducted at 90 °C and the catalyst loading
retaining the N,N-diisopropylamide substituent and modu- was now reduced (Table 2, entries 8–16). Modification of
lating the phosphane substituent from diphenyl- (i.e., 5e) to the alkyne/azide stoichiometry showed that a slight excess
di-tert-butyl- (i.e., 5g) and dicyclohexyl- (i.e., 5h), in ad- amount of the azide (alkyne/azide = 1.0:1.5) was superior
dition to phosphadamantane derivative 5i.[11] Screening to a slight excess amount of the alkyne (Table 2, entry 10
new complexes 6g–i derived from the second-generation li- vs. 11). Overall, catalyst 6g proved to be highly active with
gands in the Ag-AAC reaction (Table 1) demonstrated the loadings as low as 0.5 mol-%, providing quantitative con-
superiority of the di-tert-butyl- and dicyclohexyl-containing version (200 turnovers) within 48 h.
ligands.
Using 2–2.5 mol-% of catalyst 6g under otherwise condi-
On the basis of these ligand effects, catalyst 6g was cho- tions of Table 2 (entry 11), Ͼ99% conversion to the 1,4-
sen with the goals of increased catalyst efficiency and ex- triazole was observed after 24 h at 90 °C. To check the effi-
panding scope in the reaction. Silver complex 6g is a solv- ciency of the catalyst, the above reaction was repeated three
ate-free, air-stable white crystalline solid (m.p. 190–200 °C, times on the initial catalyst charge by using identical quan-
decomp.) that is very soluble in toluene and most other or- tities of azide and alkyne to provide Ͼ99, 96, and 95% con-
ganic solvents. It produces clear, colorless solutions in or- version on subsequent runs. The solution remained com-
ganic solvents that remain unaffected for weeks under nor- pletely clear, colorless, and homogeneous, showing no sign
mal laboratory conditions and through various heating/ of silver metal precipitation after the fourth cycle. Control
cooling cycles. No precipitation of silver metal is observed experiments also demonstrated that no Staudinger-type az-
Figure 2. Scope of aryl alkyne participation in Ag-AAC reaction.[a]
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1
ide reduction occurred between catalyst 6g and benzyl azide dition, H NMR spectroscopy showed only clean conver-
under the Ag-AAC reaction conditions, demonstrating fur- sion of the azide/alkyne into the triazole. The role of the
ther the exceptional stability of this complex.
ligand in complex 6g is clearly significant, and we postulate
The silver-mediated AAC reaction proved broad in scope the stepwise catalytic cycle shown in Scheme 2. The pro-
with complex 6g, as summarized in Figure 2. These reac- posed catalytic cycle for the Ag-AAC process provides a
tions were conducted by using 2–2.5 mol-% of catalyst 6g rationale for the effectiveness of the hemilabile ligand on
to achieve high conversions in a 24 h reaction period (i.e., complex 6g. Loss of acetate from 18-electron species 6g
similar to Table 1, entry 11).
yields the active catalyst I (14e–), which forms ligated sil-
The Ag-AAC reaction catalyzed by 6g is successful with ver(I) acetylide II, the electrophilicity of which is modulated
a wide range of substrates including aryl, benzyl, and alkyl by the hemilabile amide substituent.
azides coupling with both phenyl and aliphatic acetylenes.
No restrictions on the generality have been identified on the
process so far.
Earlier, we reported the X-ray crystal structure of com-
plex 6e.[8] To gain potential insight into the reactivity of
complex 6g, crystals suitable for X-ray analysis were grown,
and the crystal structure is shown in Scheme 1. The silver
atom of complex 6e proved to be ligated to the amide donor
through one of the non-bonding lone pairs of the oxygen
atom (2.680 Å). In contrast, highly active complex 6g
showed weak ligation to the amide HOMO with contacts
between Ag–O (3.163 Å) and Ag–N (3.632 Å), whereas
other contacts (Ag–P and Ag–acetate) were very similar.
Scheme 2. Proposed catalytic cycle for the homogeneous AgI-cata-
lyzed AAC reaction.
Nucleophilic attack on II by the azide generates interme-
diate IIIA, shown as the 16e– species. The role of the hemil-
abile nature of the ligand comes into play again from IIIA
by complexation of the amide forming an 18e– intermediate,
which transmits polarization of negative charge through the
filled d orbitals into the acetylide π* orbitals effecting cycli-
zation onto the tethered azide. This process can proceed
through the transient silver metallacycle shown as IIIB,
from which the nitrogen migrates to carbon carrying both
electrons to yield metalated triazole IV, leading to product 3
on protonation and regenerating active catalyst I. A similar
catalytic cycle, without ancillary ligand effects, was pos-
tulated for the Cu-AAC process in accord with DFT calcu-
lations.[6c]
Scheme 1. Synthesis of AgOAc complexes of ligands 5e and 5g
(top) and ball-and-stick plots of 6e and 6g (bottom).
The reaction could readily be followed by NMR spec-
troscopy in [D8]toluene. Interruption at various times dur-
Conclusions
ing the progress of the standard reaction and analysis by
In summary, we report a chemically robust and effective
31P NMR spectroscopy showed only the presence of com- general homogeneous catalyst for the Ag-AAC reaction. A
plex 6g, with no other aggregate species observable. In ad- pronounced ligand effect is observed and a significant role
4
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AgI-Catalyzed Cycloaddition of Azides onto Terminal Alkynes
8.1 mmol, 1 equiv.) was dissolved in water (2.5 mL) that contained
concentrated HCl (4.1 mL). This solution was cooled to below 5 °C
in an ice bath and diazotized with a solution of NaNO2 (0.850 g,
12.1 mmol, 1.5 equiv.) in distilled water (2.5 mL). The mixture was
stirred in an ice bath for 1 h. A solution of NaN3 (1.05 g,
16.2 mmol, 2 equiv.) in water (6 mL) was added at 0 °C, and the
mixture was stirred for 30 min. The mixture was warmed up to
room temperature and stirred for an additional 3 h. The reaction
mixture was extracted with EtOAc (2ϫ50 mL). The combined or-
ganic layers was dried with anhydrous Na2SO4, filtered, and con-
is attributed to the hemilabile nature of ligand 5g in both
the stability and efficiency of catalyst 6g. The catalyst is
effective at loadings as low as 0.5 mol-% and is stable ther-
mally over repeated catalytic cycles showing no silver metal
precipitation. A mechanism is proposed involving con-
tinuous coordination of the phosphane donor of the ligand
to silver and proceeding through intermediates that allow
coordination and polarization of the acetylide/azide to ef-
fect the stepwise cyclization. Further studies to probe the
mechanism and extension of the reaction scope are under centrated under reduced pressure. The crude 4-methoxyazidobenz-
ene was further purified by flash column chromatography over a
short plug of silica gel (5% EtOAc/hexanes) to afford a yellow li-
quid in 80% yield. An identical procedure was followed for the
synthesis of 2g and 2i.
investigation.
Experimental Section
4-Chlorophenyl Azide (2g):[18] 1H NMR (600 MHz, CDCl3): δ =
7.32 (d, J = 8.2 Hz, 2 H), 6.96 (d, J = 8.2 Hz, 2 H) ppm.
General Information: All reactions were carried out under a nitro-
gen atmosphere in oven-dried glassware. Toluene (dry) was distilled
from sodium/benzophenone. AgOAc (purity Ն99.0%) and AgOTf
(purity = 99.95%) were purchased from Fluka Chemicals, Switzer-
land, and Sigma–Aldrich, Canada, respectively. DMSO (dry) was
obtained from Sigma–Aldrich (Sure-seal), and dichloromethane
was distilled from calcium hydride. Phenyl acetylenes were obtained
commercially from Sigma–Aldrich or Alfa Aesar. Melting points
were recorded in open capillary using a calibrated Büchi melting
point B540 apparatus. Thin-layer chromatography (TLC) was car-
ried out by using aluminum sheets precoated with silica gel 60F254
(Merck) and was visualized under 254 nm UV light. 1H NMR
and13C NMR spectra were recorded with an AV 600 spectrometer
in CDCl3 with TMS as internal standard. Chemical shifts (δ) are
reported in ppm downfield of TMS.
General Procedure for the Preparation of Starting Azides 2a–f:[12]
Sodium azide (1.0 g, 15.3 mmol, 1 equiv.) was dissolved in DMSO
(25 mL) by stirring in a flame-dried, 100-mL round-bottomed flask
under a nitrogen atmosphere for 12 h. A solution of the corre-
sponding benzyl bromide/chloride (13.8 mmol, 0.9 equiv.) was
added, and the reaction mixture was stirred for 10 h. Water (20 mL)
was added slowly to quench the reaction (exothermic process), and
the mixture was stirred until it cooled to room temperature. The
mixture was poured into water (50 mL) and extracted with Et2O
(3ϫ30 mL). The organic layer was separated, washed with brine,
dried with sodium sulfate, filtered, and concentrated in vacuo to
afford azides 2a–h as oils.
4-Methoxyphenyl Azide (2h):[18] 1H NMR (600 MHz, CDCl3): δ =
6.96 (d, J = 8.8 Hz, 2 H), 6.89 (d, J = 8.8 Hz, 2 H), 3.80 (s, 3
H) ppm.
Azidobenzene (2i):[18] 1H NMR (400 MHz, CDCl3): δ = 7.34 (t, J
= 8.0 Hz, 2 H), 7.12 (t, J = 7.2 Hz, 1 H), 7.02 (d, J = 7.6 Hz, 2
H) ppm.
Synthesis of (2-Methoxyphenyl)diphenylphosphane (5b):[19] To a
clear solution of 1-iodo-2-methoxybenzene (0.100 g, 0.42 mmol) in
THF (2.0 mL) was added nBuLi (1.6 m in hexanes, 0.530 mL,
0.854 mmol) at –78 °C under a nitrogen atmosphere. The resulting
solution was stirred at –78 °C for 1 h. A solution of chlorodiphenyl-
phosphane (76.0 μL, 0.427 mmol) in THF (2.0 mL) was added at
–78 °C. Then the mixture was warmed to room temperature and
stirred for an additional 3 h. Water was added to quench the reac-
tion, and the mixture was extracted with Et2O (3ϫ15 mL). The
organic layers were combined, washed with brine, dried with
Na2SO4, and concentrated. The resulting residue was purified by
column chromatography on silica gel to obtain 5b (0.075 g, 60%)
as crystalline white solid. M.p. 120–122 °C (ref.[19] m.p. 124–
126 °C). 1H NMR (200 MHz, CDCl3): δ = 6.40–7.40 (m, 14 H,
ArH), 3.65 (s, 3 H, OMe) ppm. 31P NMR (80 MHz, CDCl3): δ =
–16.74 ppm.
Synthesis of [2-(Diphenylphosphanyl)phenyl]methanol (5c):[20] To a
suspension of 2-(diphenylphosphanyl)benzoic acid (0.100 g,
0.32 mmol) in THF (2.0 mL) was added lithium aluminum hydride
(0.027 g, 0.71 mmol). The resulting reaction mixture was stirred at
room temperature for 2 h. The reaction mixture was then quenched
by adding saturated solution of sodium potassium tartarate. The
mixture was extracted with EtOAc (3ϫ15 mL). The organic layers
were combined, washed with brine, dried with Na2SO4, and con-
centrated. The resulting residue was purified by column chromatog-
raphy on silica gel to give 5c[21] (0.076 g) as a colorless oil in 80%
1-(Azidomethyl)benzene (2a):[12] 1H NMR (200 MHz, CDCl3): δ =
7.43–7.25 (m, 5 H), 4.35 (s, 2 H) ppm.
1-(Azidomethyl)-4-methoxybenzene (2b):[13] 1H NMR (600 MHz,
CDCl3): δ = 7.28 (d, J = 8.6 Hz, 2 H), 6.94 (d, J = 8.6 Hz, 2 H),
4.30 (s, 2 H), 3.85 (s, 3 H) ppm.
1-(Azidomethyl)-4-chlorobenzene (2c):[14] 1H NMR (600 MHz,
CDCl3): δ = 7.39 (d, J = 8.3 Hz, 2 H), 7.28 (d, J = 8.3 Hz, 2 H),
4.35 (s, 2 H) ppm.
1
yield. H NMR (200 MHz, CDCl3: δ = 7.46–7.57 (m, 1 H, ArH),
7.14–7.39 (m, 12 H, ArH), 6.83–6.95 (m, 1 H, ArH), 4.82 (s, 1
H), 2.04 (br. s, 1 H, -OH) ppm. 31P NMR (80 MHz, CDCl3): δ =
–16.29 ppm.
1-(Azidomethyl)-3-bromobenzene (2d):[15] 1H NMR (600 MHz,
CDCl3): δ = 7.51 (d, J = 1.9 Hz, 2 H), 7.28 (d, J = 1.4 Hz, 2 H),
4.35 (s, 2 H) ppm.
Synthesis of Methyl 2-(Diphenylphosphanyl)benzoate (5d):[20] In a
50-mL flame-dried pear-shaped Schlenk flask equipped with a
magnetic stir bar, rubber septum, and an argon inlet, cesium car-
bonate (0.190 g, 0.58 mmol, 1.25 equiv.) and CuI (10 mol-% with
respect to diphenylphosphane) were charged, and the vessel was
sealed with a rubber septum. Toluene (5.0 mL), methyl-2-bromo-
benzoate (0.1 g, 0.46 mmol, 1 equiv.), and diphenylphosphane
(0.72 g, 0.38 mmol, 0.8 equiv.) were injected into the tube through
Methyl 2-Azidoacetate (2e):[16] 1H NMR (600 MHz, CDCl3): δ =
3.91 (s, 2 H), 3.83 (s, 3 H) ppm.
1-(2-Azidoethyl)benzene (2f):[17] 1H NMR (600 MHz, CDCl3): δ =
7.37 (t, J = 7.4 Hz, 2 H), 7.33–7.28 (m, 1 H), 7.28–7.24 (m, 2 H),
3.55 (t, J = 7.3 Hz, 2 H), 2.94 (t, J = 7.3 Hz, 2 H) ppm.
General Procedure for the Preparation of Starting Azides 2g–i:[18] In
a
100-mL round-bottomed flask, 4-methoxyaniline (1.0 g,
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the septum. The rubber septum was replaced with a dry argon
flushed reflux condenser. The reaction mixture was then heated at
110 °C for 24 h. The reaction mixture was then cooled to room
temperature and filtered with dichloromethane to remove any in-
soluble residues. The filtrate was concentrated in vacuo; the residue
was purified by flash chromatography on silica gel to obtain pure
5d[22] as a colorless solid in 60% yield. M.p. 97.5–99 °C (ref.[22] m.p.
96 °C). 1H NMR (200 MHz, CDCl3): δ = 8.10–8.12 (m, 1 H), 7.32–
7.37 (m, 12 H), 6.96–6.99 (m, 1 H), 3.78 (s, 3 H) ppm. 31P NMR
(80 MHz, CDCl3): δ = –4.41 ppm.
added dropwise. The reaction mixture was stirred for 30 min at
–78 °C. Chloro-di-tert-butylphosphane (0.585 mL, 2.65 mmol) was
added to the reaction mixture followed by stirring at –78 °C for
2 h. The reaction mixture was further stirred at 1 h at room tem-
perature. The reaction mixture was filtered through a pad of Celite,
and the filtrate was concentrated under reduced pressure to give
the crude product, which was purified by flash chromatography to
afford 5g as a white solid in 78% yield. 1H NMR (600 MHz,
CDCl3): δ = 7.66 (d, J = 7.4 Hz, 1 H), 7.24 (t, J = 7.4 Hz, 1 H),
7.18 (t, J = 7.3 Hz, 1 H), 7.05 (d, J = 5.9 Hz, 1 H), 3.57 (hept., J
= 6.6 Hz, 1 H), 3.38 (hept., J = 6.8 Hz, 1 H), 1.47 (dd, J = 9.6,
6.8 Hz, 6 H), 1.17–1.04 (m, 21 H), 0.95 (d, J = 6.6 Hz, 3 H) ppm.
31P NMR (243 MHz, CDCl3): δ = 23.09 ppm.
Synthesis of (N,N-Diisopropyl-2-diphenylphosphanyl)benzamide
(5e):[20] Into a flame-dried flask, containing a magnetic stirring bar,
was weighed N,N-diisopropylbenzamide (0.100 g, 0.48 mmol,
1 equiv.) under an argon atmosphere and anhydrous THF (2 mL)
was added. The flask was stirred for 15 min at –78 °C whereupon
sBuLi (1.4 m in cyclohexane, 0.417 mL, 0.58 mmol, 1.2 equiv.) was
added dropwise followed by TMEDA (0.088 mL, 0.58 mmol,
1.2 equiv.). The resultant solution was stirred at –78 °C for 30 min.
Chlorodiphenylphosphane (0.090 mL, 0.48 mmol, 1 equiv.) was
added dropwise at –78 °C. The reaction mixture was stirred for an
additional 1 h at –78 °C and then allowed to reach room tempera-
ture with continuous stirring. The reaction mixture was quenched
with saturated solution of NH4Cl and extracted with EtOAc. The
organic phase was washed with water followed by brine, dried with
sodium sulfate, and concentrated in vacuo. Purification through
column chromatography (hexane/EtOAc) gave 5e[23] as a colorless
Synthesis of N,N-Diisopropyl-2-(dicyclohexylphosphanyl)benzamide
(5h):[23] To a flame-dried flask with a stirring bar was added N,N-
diisopropylbenzamide (0.454 mg, 2.2 mmol) and THF (4 mL) un-
der an argon atmosphere. The resultant solution was cooled to
–78 °C and nBuLi (1.6 m in hexanes, 1.66 mL, 2.65 mmol) was
added dropwise. The reaction mixture was stirred for 30 min at
–78 °C. Chlorodicyclohexylphosphane (0.585 mL, 2.65 mmol) was
added to the reaction mixture followed by stirring at –78 °C for
2 h. The reaction mixture was further stirred at 1 h at room tem-
perature. The reaction mixture was filtered through a pad of Celite,
and the filtrate was concentrated under reduced pressure to give
the crude product, which was purified by flash chromatography to
afford 5h as a white solid in 75% yield. 1H NMR (600 MHz,
CDCl3): δ = 7.62–7.41 (m, 1 H), 7.32 (s, 2 H), 7.15 (s, 1 H), 3.56
(d, J = 20.2 Hz, 1 H), 3.52–3.35 (m, 1 H), 2.11–1.03 (m, 34 H) ppm.
1
solid in 91% yield. M.p. 95–97 °C. H NMR (200 MHz, CDCl3):
δ = 1.07 (m, 6 H), 1.59 (d, 6 H), 3.51 (m, 1 H), 3.71 (d, 1 H), 7.13–
7.43 (m, 14 H) ppm. 13C NMR (51 MHz, CDCl3): δ = 20.44, 20.78, 31P NMR (243 MHz, CDCl3): δ = –9.22 ppm.
20.86, 45.96, 51.10, 125.18, 125.24, 125.70, 128.29, 128.46, 128.56,
Synthesis of 1,3,5,7-Tetramethyl-2,4,8-trioxa-6-(2Ј-N,N-diisoprop-
ylbenzamide)-6-phosphaadamantane (5i): mixture containing
1,3,5,7-tetramethyl-2,4,8-trioxa-6-phosphaadamantane (0.152 g,
129.28, 133.44, 133.56, 133.77, 134.10, 134.21, 134.98, 137.13,
137.68, 145.65, 145.89, 169.99 ppm. 31P NMR (80 MHz, CDCl3):
δ = –14.13 ppm. HRMS: calcd. for C25H28NOP [M]+ 389.1894;
found 389.1909.
A
0.70 mol, 2 equiv.), 2-bromo-N,N-diisopropylbenzamide (0.100 g,
0.35 mol, 1 equiv.), triethylamine (0.106 g, 0.70 mol, 2 equiv.),
nickel acetate tetrahydrate (0.272 g, 1.09 mmol, 3.1 equiv.), and tol-
uene (2.0 mL) was heated to reflux under a nitrogen atmosphere
with magnetic stirring. During this time the nickel acetate dis-
solved, generating a reddish brown solution. After 60 h at reflux,
the mixture was filtered through a pad of Celite. The organic sol-
vent was evaporated to yield a crude mass, which was purified by
flash chromatography (10–15% EtOAc/hexanes) to yield a color-
less, crystalline solid in 60% yield. M.p. 180–183 °C. 1H NMR
(600 MHz, CDCl3): δ = 8.26 (d, J = 7.8 Hz, 1 H), 7.38 (t, J =
7.4 Hz, 1 H), 7.33 (td, J = 7.6, 1.5 Hz, 1 H), 7.16 (ddd, J = 7.4,
3.0, 1.3 Hz, 1 H), 3.55–3.43 (m, 2 H), 2.06–1.97 (m, 2 H), 1.92 (dd,
J = 25.1, 13.1 Hz, 1 H), 1.60 (d, J = 6.8 Hz, 3 H), 1.57–1.52 (m, 4
H), 1.45 (s, 3 H), 1.41 (s, 3 H), 1.36 (d, J = 12.7 Hz, 3 H), 1.34 (d,
J = 12.7 Hz, 3 H), 1.19 (d, J = 6.7 Hz, 3 H), 1.03 (d, J = 6.6 Hz, 3
H) ppm. 31P NMR (243 MHz, CDCl3): δ = –35.84 ppm. 13C NMR
(151 MHz, CDCl3): δ = 169.97 (d, J = 4.7 Hz), 148.61 (d, J =
37.75 Hz), 133.92 (d, J = 2.8 Hz), 130.3 (d, J = 33.22 Hz), 129.93
(s), 127.85 (s), 125.66 (d, J = 8.7 Hz), 96.84 (s), 96.19 (s), 73.90 (d,
J = 4.5 Hz), 73.79 (d, J = 16.61 Hz), 51.04 (s), 45.95 (s), 45.84 (s),
36.45 (s), 28.65 (d, J = 21.3 Hz), 28.10 (s), 27.85 (s), 26.62 (d, J =
Synthesis of [(2-N,N-Dimethylaminomethyl)phenyl]diphenylphos-
phane (5f):[24] The ligand was synthesized according to a published
procedure with slight modification. To a solution of nBuLi (1.6 m
in hexanes, 10.2 mL, 16.3 mmol, 1.2 equiv.) at room temperature
was added dimethylbenzylamine (1.84 g, 13.6 mmol, 1 equiv.). The
reaction mixture was diluted with freshly distilled Et2O (15 mL)
and allowed to stand for 24 h. The lithiated benzylamine deposited
on the flask as a mass of yellow crystals leaving an orange solution.
The crystalline mass was resuspended in solution with vigorous
stirring. The solution was cooled in an ice water bath and diphenyl-
chlorophosphane (3.0 mL, 16.3 mmol, 1.2 equiv.) was added slowly.
The reaction mixture was stirred for 1 h in an ice bath and then
warmed to room temperature over 20 min. The mixture was reco-
oled in ice, and the reaction was cautiously quenched by the slow
addition of water. The reaction mixture was partitioned between
2 m HCl and Et2O. The HCl extracts were adjusted to pH 12 with
NaOH. The resultant aqueous solution was extracted with CH2Cl2.
The CH2Cl2 extracts were dried, filtered, and concentrated in vacuo
to give an orange oil. The crude product was crystalized by adding
ethanol (8.0–10.0 mL) and cooling at –20 °C to give 5f in 90%
yield. 1H NMR (200 MHz, CDCl3): δ = 2.08 (s, 6 H), 3.64 (s, 2 H), 10.9 Hz), 20.77 (s), 20.73 (s), 20.55 (s), 20.25 (s) ppm. HRMS:
6.90 (m, 1 H), 7.13–7.31 (m, 12 H), 7.48 (m, 1 H) ppm. 31P calcd. for C23H34NO4P [M]+ 419.2223; found 419.2225.
(80 MHz, CDCl3): δ = –15.43 ppm.
General Procedure for the Preparation of the Ligand/AgOAc Com-
Synthesis of N,N-Diisopropyl-2-(di-tert-butylphosphanyl)benzamide
(5g):[23] To a flame-dried flask with a stirring bar was added N,N-
diisopropylbenzamide (0.454 mg, 2.2 mmol) and THF (4 mL) un-
der an argon atmosphere. The resultant solution was cooled to
plex (1:1):[8] To an oven-dried flask was added the corresponding
ligand (0.100 g, 1.00 equiv.), silver acetate (1.00 equiv.), and freshly
distilled dichloromethane (5.0 mL), and the solution was stirred at
room temperature for 10–12 h in the dark. The resultant homogen-
–78 °C and nBuLi (1.6 m in hexanes, 1.66 mL, 2.65 mmol) was eous reaction mixture was filtered through a pad of Celite to re-
6
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Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O20930
/KAP1
Date: 17-08-12 09:53:26
Pages: 10
AgI-Catalyzed Cycloaddition of Azides onto Terminal Alkynes
move any insoluble impurities. The organic layer was evaporated, 1-Benzyl-4-phenyl-1H-1,2,3-triazole (3a):[5e] 1H NMR (600 MHz,
further treated with dry pentane (2.0 mL), and concentrated. The
complex obtained was dried under high vacuum to yield the silver
acetate complex.
6a: Yield: 99%. 1H NMR (600 MHz, CDCl3): δ = 7.49–7.38 (m,
15 H), 2.09 (s, 3 H) ppm. 31P NMR (243 MHz, CDCl3): δ = 16.28
(br. s) ppm.
6b: Yield: 99%. 1H NMR (600 MHz, CDCl3): δ = 7.57–7.34 (m,
11 H), 7.00–6.86 (m, 2 H), 6.79–6.65 (m, 1 H), 3.78 (s, 3 H), 2.09
(s, 3 H) ppm. 31P NMR (243 MHz, CDCl3): δ = 2.12 (d, J =
670.6 Hz) ppm.
CDCl3): δ = 7.79 (dd, J = 8.2, 1.1 Hz, 2 H), 7.65 (s, 1 H), 7.43–
7.34 (m, 5 H), 7.34–7.27 (m, 3 H), 5.57 (s, 2 H) ppm. 13C NMR
(151 MHz, CDCl3): δ = 148.24, 134.68, 130.51, 129.18, 128.82,
128.20, 128.09, 125.73, 119.48, 54.28 ppm.
1-(4-Methoxybenzyl)-4-phenyl-1H-1,2,3-triazole (3b):[25] 1H NMR
(600 MHz, CDCl3): δ = 7.79–7.71 (m, 2 H), 7.58 (s, 1 H), 7.35 (t,
J = 7.6 Hz, 2 H), 7.27 (d, J = 7.4 Hz, 1 H), 7.23 (d, J = 8.7 Hz, 2
H), 6.87 (d, J = 8.7 Hz, 2 H), 5.47 (s, 2 H), 3.77 (s, 3 H) ppm. 13C
NMR (151 MHz, CDCl3): δ = 159.95, 148.07, 130.50, 129.65,
128.75, 128.11, 126.56, 125.67, 119.22, 114.50, 55.32, 53.80 ppm.
6c: Yield: 82%. 1H NMR (600 MHz, CDCl3): δ = 7.56 (d, J =
6.8 Hz, 1 H), 7.45 (t, J = 7.3 Hz, 3 H), 7.42–7.29 (m, 8 H), 7.22 (t,
J = 7.5 Hz, 1 H), 6.84 (t, J = 8.5 Hz, 1 H), 4.75 (s, 2 H), 1.93 (s, 3
H) ppm. 31P NMR (243 MHz, CDCl3): δ = 4.21 (s) ppm.
1-(4-Chlorobenzyl)-4-phenyl-1H-1,2,3-triazole (3c):[25] 1H NMR
(600 MHz, CDCl3): δ = 7.84–7.76 (m, 2 H), 7.66 (s, 1 H), 7.43–
7.38 (m, 2 H), 7.38–7.34 (m, 2 H), 7.32 (dt, J = 9.1, 4.3 Hz, 1 H),
7.25 (s, 2 H), 5.55 (s, 2 H) ppm. 13C NMR (151 MHz, CDCl3): δ
= 149.09, 135.55, 133.84, 131.02, 130.05, 130.04, 129.51, 128.96,
126.39, 120.05, 54.17 ppm.
1
6d: Yield: 99%. H NMR (600 MHz, CDCl3): δ = 8.17 (ddd, J =
7.7, 4.2, 1.1 Hz, 1 H), 7.56 (t, J = 7.6 Hz, 1 H), 7.50–7.36 (m, 11
H), 6.99–6.87 (m, 1 H), 3.73 (s, 3 H), 2.08 (s, 3 H) ppm. 31P NMR
(243 MHz, CDCl3): δ = 17.77 (d, J = 833.49 Hz) ppm.
6e: Data previously reported.[8]
1-(3-Bromobenzyl)-4-phenyl-1H-1,2,3-triazole (3d):[5e] 1H NMR
(600 MHz, CDCl3): δ = 7.87–7.80 (m, 2 H), 7.72 (s, 1 H), 7.53 (d,
J = 7.7 Hz, 1 H), 7.50 (s, 1 H), 7.44 (t, J = 7.6 Hz, 2 H), 7.39–7.33
(m, 1 H), 7.32–7.23 (m, 2 H), 5.58 (s, 2 H) ppm. 13C NMR
(151 MHz, CDCl3): δ = 148.48, 136.88, 131.99, 131.00, 130.74,
130.34, 128.86, 128.33, 126.56, 125.76, 123.16, 119.49, 53.48 ppm.
1
6f: Yield: 99%. H NMR (600 MHz, CDCl3): δ = 7.49–7.38 (m, 6
H), 7.36 (dd, J = 10.5, 4.0 Hz, 4 H), 7.31 (t, J = 7.5 Hz, 1 H), 7.24–
7.11 (m, 2 H), 6.84–6.73 (m, 1 H), 3.26 (s, 2 H), 2.09 (s, 6 H),
2.04 (s, 3 H) ppm. 31P NMR (243 MHz, CDCl3): δ = 5.29 (d, J =
690.12 Hz) ppm.
6g: Yield: 99%. 1H NMR (600 MHz, CDCl3): δ = 7.81 (d, J =
5.8 Hz, 1 H), 7.44 (d, J = 6.3 Hz, 1 H), 7.37 (t, J = 6.5 Hz, 1 H),
7.20 (d, J = 1.0 Hz, 1 H), 3.60–3.35 (m, 2 H), 1.98 (s, 3 H), 1.76
(d, J = 6.1 Hz, 3 H), 1.44 (d, J = 6.3 Hz, 3 H), 1.39–1.24 (m, 21
H), 1.06 (d, J = 6.0 Hz, 3 H) ppm. 31P NMR (243 MHz, CDCl3):
δ = 46.63 (d, J = 692.55 Hz) ppm. M.p. Ͼ170 °C (complex decom-
poses slightly at this temperature), melts at 190–200 °C.
1-Benzyl-4-(4-fluorophenyl)-1H-1,2,3-triazole (3e):[26] 1H NMR
(600 MHz, CDCl3): δ = 7.77 (dd, J = 8.9, 5.3 Hz, 2 H), 7.61 (s, 1
H), 7.42–7.35 (m, 3 H), 7.33–7.30 (m, 2 H), 7.09 (t, J = 8.7 Hz, 2
H), 5.57 (s, 2 H) ppm. 13C NMR (151 MHz, CDCl3): δ = 162.82
(d, J = 247.3 Hz), 147.53 (s), 134.73 (s), 129.34 (s), 129.00 (s),
128.24 (s), 127.59 (d, J = 8.1 Hz), 126.91 (d, J = 2.7 Hz), 119.34
(s), 115.93 (d, J = 21.7 Hz), 54.44 (s) ppm.
1-Benzyl-4-(4-bromophenyl)-1H-1,2,3-triazole (3f):[27] 1H NMR
(600 MHz, CDCl3): δ = 7.70 (m, 3 H), 7.58–7.53 (m, 2 H), 7.45–
7.38 (m, 3 H), 7.34 (d, J = 6.3 Hz, 2 H), 5.60 (s, 2 H) ppm. 13C
NMR (151 MHz, CDCl3): δ = 147.36 (s), 134.63 (s), 132.11 (s),
129.64 (s), 129.37 (s), 129.06 (s), 128.28 (s), 127.38 (s), 122.22 (s),
119.66 (s), 54.49 (s) ppm.
Development of X-ray Crystals of 6g: Compound 6g was dissolved
in dichloromethane followed by slow addition of pentane (10ϫ)
over it. Crystals were developed after slow evaporation of the sol-
vents.
6h: Yield: 99%. 1H NMR (600 MHz, CDCl3): δ = 7.59 (t, J =
7.1 Hz, 1 H), 7.51–7.41 (m, 2 H), 7.25 (dd, J = 3.5, 1.4 Hz, 1 H),
3.67–3.40 (m, 2 H), 2.39–2.24 (m, 1 H), 2.14–1.96 (m, 6 H), 1.87
(t, J = 13.8 Hz, 1 H), 1.82 (d, J = 6.7 Hz, 3 H), 1.71 (m, 4 H), 1.62
(d, J = 11.8 Hz, 1 H), 1.51 (d, J = 6.7 Hz, 5 H), 1.42–1.17 (m, 12
H), 1.13 (d, J = 6.4 Hz, 4 H) ppm. 31P NMR (243 MHz, CDCl3):
δ = 23.84 (d, J = 711.99 Hz) ppm.
1-Benzyl-4-m-tolyl-1H-1,2,3-triazole (3g):[25] 1H NMR (600 MHz,
CDCl3): δ = 7.66 (s, 1 H), 7.64 (s, 1 H), 7.57 (d, J = 7.7 Hz, 1 H),
7.42–7.34 (m, 3 H), 7.33–7.30 (m, 2 H), 7.28 (t, J = 7.7 Hz, 1 H),
7.13 (d, J = 7.6 Hz, 1 H), 5.58 (s, 2 H), 2.38 (s, 3 H) ppm. 13C
NMR (151 MHz, CDCl3): δ = 148.46 (s), 138.65 (s), 134.82 (s),
130.46 (s), 129.31 (s), 129.13 (s), 128.90 (d, J = 13.9 Hz), 128.22
(s), 126.55 (s), 122.97 (s), 119.60 (s), 54.42 (s), 21.54 (s) ppm.
1
1-Benzyl-4-(2-chlorophenyl)-1H-1,2,3-triazole (3h):[28] 1H NMR
(600 MHz, CDCl3): δ = 8.18 (dd, J = 7.9, 1.6 Hz, 1 H), 8.04 (s, 1
H), 7.37–7.27 (m, 5 H), 7.26–7.22 (m, 2 H), 7.19 (m, 1 H), 5.54 (s, 2
H) ppm. 13C NMR (151 MHz, CDCl3): δ = 144.44, 134.69, 131.18,
130.17, 129.83, 129.23, 129.16, 129.04, 128.77, 127.95, 127.17,
123.19, 54.25 ppm.
6i: Yield: 85% yield. H NMR (600 MHz, CDCl3): δ = 8.44 (t, J
= 6.6 Hz, 1 H), 7.57–7.51 (m, 1 H), 7.47 (t, J = 7.6 Hz, 1 H), 7.31–
7.27 (m, 1 H), 3.64–3.48 (m, 2 H), 2.70 (dd, J = 14.0, 6.4 Hz, 1 H),
2.12–1.97 (m, 5 H), 1.89–1.72 (m, 4 H), 1.57–1.43 (m, 17 H), 1.34
(m, 3 H), 1.15 (m, 3 H) ppm. 31P NMR (243 MHz, CDCl3): δ =
–9.29 (d, J = 721.71 Hz) ppm.
General Procedure for the AgI Complex Catalyzed Synthesis of
Ethyl 2-(4-Phenyl-1H-1,2,3-triazol-1-yl)acetate (3i):[5c] 1H NMR
(600 MHz, CDCl3): δ = 7.94 (s, 1 H), 7.90–7.85 (m, 2 H), 7.46 (t,
J = 7.7 Hz, 2 H), 7.38 (t, J = 7.4 Hz, 1 H), 5.26 (s, 2 H), 3.86 (s, 3
H) ppm. 13C NMR (151 MHz, CDCl3): δ = 166.72, 148.37, 130.32,
128.87, 128.35, 125.85, 120.90, 53.11, 50.84 ppm.
1,2,3-Triazoles: To
a mixture of phenyl acetylene (0.010 g,
0.09 mmol, 1 equiv.) and benzyl/aryl azide (0.14 mmol, 1.5 equiv.)
in toluene (1 mL) was added sequentially catalyst 6g (2–2.5 mol-%)
and caprylic acid (20 mol-%.) The mixture was then stirred with
heating at 90 °C for 24 h. The reaction mixture was diluted and
extracted with EtOAc (2ϫ20 mL), washed with sodium hydrogen 1-(2-Phenylethyl)-4-phenyl-1H-1,2,3-triazole (3j):[29] 1H NMR
carbonate (5 mL) and brine, dried with anhydrous sodium sulfate,
and concentrated under reduced pressure. The resulting residue was
purified through silica gel column chromatography (10–20%
EtOAc/hexanes) to afford the desired product.
(600 MHz, CDCl3): δ = 7.79 (dd, J = 8.3, 1.1 Hz, 2 H), 7.49 (s, 1
H), 7.43 (t, J = 7.7 Hz, 2 H), 7.38–7.31 (m, 3 H), 7.31–7.26 (m, 1
H), 7.17 (d, J = 7.4 Hz, 2 H), 4.67 (t, J = 7.3 Hz, 2 H), 3.29 (t, J
= 7.2 Hz, 2 H) ppm. 13C NMR (151 MHz, CDCl3): δ = 147.49,
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
7

Job/Unit: O20930
/KAP1
Date: 17-08-12 09:53:26
Pages: 10
J. McNulty, K. Keskar
FULL PAPER
137.08, 130.63, 128.88, 128.82, 128.75, 128.10, 127.17, 125.72,
119.90, 51.78, 36.82 ppm.
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1-Benzyl-4-butyl-1H-1,2,3-triazole (3k):[30] 1H NMR (600 MHz,
CDCl3): δ = 7.32–7.25 (m, 3 H), 7.19 (m, 2 H), 7.11 (s, 1 H), 5.42
(s, 2 H), 2.65–2.57 (m, 2 H), 1.62–1.50 (m, 2 H), 1.35–1.22 (m, 2
H), 0.84 (t, J = 7.4 Hz, 3 H) ppm. 13C NMR (151 MHz, CDCl3):
δ = 149.14 (s), 135.21 (s), 129.29 (s), 128.85 (s), 128.20 (s), 120.72
(s), 54.25 (s), 31.73 (s), 25.62 (s), 22.55 (s), 14.03 (s) ppm.
1-(4-Chlorobenzyl)-4-butyl-1H-1,2,3-triazole (3l): 1H NMR
(600 MHz, CDCl3): δ = 7.36–7.31 (m, 2 H), 7.18 (m, 3 H), 5.46 (s,
2 H), 2.74–2.64 (m, 2 H), 1.67–1.57 (m, 2 H), 1.43–1.31 (m, 2 H),
0.91 (t, J = 7.4 Hz, 3 H) ppm. 13C NMR (151 MHz, CDCl3): δ =
149.23 (s), 134.80 (s), 133.62 (s), 129.40 (s), 120.58 (s), 53.39 (s),
31.60 (s), 25.49 (s), 22.44 (s), 13.92 (s) ppm. HRMS: calcd. for
C13H16ClN3 [M]+ 249.1034, found 249.1033. M.p. 52–54 °C.
1-(4-Chlorophenyl)-4-(4-fluorophenyl)-1H-1,2,3-triazole (3m): 1H
NMR (600 MHz, DMSO): δ = 9.33 (s, 1 H), 8.03–7.94 (m, 4 H),
7.77–7.68 (m, 2 H), 7.36 (t, J = 8.9 Hz, 2 H) ppm. 13C NMR
(151 MHz, DMSO): δ = 162.03 (d, J = 245.0 Hz), 146.56 (s), 135.39
(s), 132.99 (s), 129.92 (s), 127.42 (s), 127.36 (s), 126.67 (d, J =
2.5 Hz), 126.66 (s), 121.64 (s), 119.63 (s), 116.06 (s), 115.92 (s) ppm.
HRMS: calcd. for C14H9ClFN3 [M]+ 273.0479; found 273.0469.
M.p. 205–208 °C
[3]
1-(4-Chlorophenyl)-4-phenyl-1H-1,2,3-triazole (3n):[31] 1H NMR
(600 MHz, DMSO): δ = 9.34 (s, 1 H), 8.01 (d, J = 8.9 Hz, 2 H),
7.95 (dd, J = 8.2, 1.1 Hz, 2 H), 7.73 (d, J = 8.9 Hz, 2 H), 7.51 (t,
J = 7.7 Hz, 2 H), 7.42–7.37 (m, 1 H) ppm. 13C NMR (151 MHz,
DMSO): δ = 147.44 (s), 135.44 (s), 132.96 (s), 129.92 (s), 129.02
(s), 128.33 (s), 125.34 (s), 121.66 (s), 119.71 (s) ppm.
1-(4-Methoxyphenyl)-4-phenyl-1H-1,2,3-triazole (3o):[31] 1H NMR
(600 MHz, CDCl3): δ = 8.14 (s, 1 H), 7.93 (d, J = 6.6 Hz, 2 H),
7.71 (dd, J = 7.0, 1.7 Hz, 2 H), 7.48 (t, J = 6.8 Hz, 2 H), 7.39 (s, 1
H), 7.07 (dd, J = 6.9, 1.8 Hz, 2 H), 3.91 (s, 3 H) ppm. 13C NMR
(151 MHz, CDCl3): δ = 160.01 (s), 148.37 (s), 130.70 (s), 130.52
(s), 129.04 (s), 128.48 (s), 125.97 (s), 122.35 (s), 117.98 (s), 114.95
(s), 55.79 (s) ppm.
[4]
[5]
4-(4-Fluorophenyl)-1-phenyl-1H-1,2,3-triazole (3p): 1H NMR
(600 MHz, DMSO): δ = 9.30 (s, 1 H), 8.00 (dd, J = 8.9, 5.5 Hz, 2
H), 7.97–7.93 (m, 2 H), 7.69–7.62 (m, 2 H), 7.54 (dd, J = 10.6,
4.2 Hz, 1 H), 7.36 (t, J = 8.9 Hz, 2 H) ppm. 13C NMR (151 MHz,
DMSO): δ = 161.99 (d, J = 244.9 Hz), 146.44 (s), 136.61 (s), 129.94
(s), 128.76 (s), 127.38 (d, J = 8.2 Hz), 126.84 (s), 120.01 (s), 119.56
(s), 116.04 (s), 115.89 (s) ppm. HRMS: calcd. for C14H10FN3 [M]+
239.0850; found 239.0859. M.p. 198–200 °C.
CCDC-843618 (for 6e) and -882589 (for 6g) contain the supple-
mentary 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.
Supporting Information (see footnote on the first page of this arti-
1
cle): Copies of H, 13C and 31P NMR spectra of complex 6g and
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Acknowledgments
We thank Hilary Jenkins for the X-ray crystallographic analyses
and the Natural Sciences and Engineering Research Council
(NSERC) of Canada, Cytec Canada, Inc., and McMaster Univer-
sity for financial support of this work.
8
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Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O20930
/KAP1
Date: 17-08-12 09:53:26
Pages: 10
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Received: July 13, 2012
Published Online: ᭿
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9

Job/Unit: O20930
/KAP1
Date: 17-08-12 09:53:26
Pages: 10
J. McNulty, K. Keskar
FULL PAPER
Click Chemistry
J. McNulty,* K. Keskar .................. 1–10
Discovery of
a Robust and Efficient
Homogeneous Silver(I) Catalyst for the
Cycloaddition of Azides onto Terminal
Alkynes
A highly efficient, chemically stable, and
well-defined homogeneous silver(I) catalyst
is reported for the cycloaddition of azides
onto terminal alkynes (Ag-AAC reaction).
Keywords: Cycloaddition / Azides / Alk-
ynes / Click chemistry / Silver
10
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