Synthesis of highly stable 1,3-diaryl-1 H -1,2,3-triazol-5-ylidenes and their applications in ruthenium-catalyzed olefin metathesis

Article abstract of DOI:10.1021/om200272m

The formal cycloaddition between 1,3-diaza-2-azoniaallene salts and alkynes or alkyne equivalents provides an efficient synthesis of 1,3-diaryl-1H-1,2,3- triazolium salts, the direct precursors of 1,2,3-triazol-5-ylidenes. These N,N-diarylated mesoionic carbenes (MICs) exhibit enhanced stability in comparison to their alkylated counterparts. Experimental and computational results confirm that these MICs act as strongly electron-donating ligands. Their increased stability allows for the preparation of ruthenium olefin metathesis catalysts that are efficient in both ring-opening and ring-closing reactions.

Full text of DOI:10.1021/om200272m

ARTICLE
pubs.acs.org/Organometallics
Synthesis of Highly Stable 1,3-Diaryl-1H-1,2,3-triazol-5-ylidenes and
Their Applications in Ruthenium-Catalyzed Olefin Metathesis
Jean Bouffard,† Benjamin K. Keitz,‡ Ralf Tonner,§ Gregorio Guisado-Barrios,† Gernot Frenking,§
Robert H. Grubbs,*,‡ and Guy Bertrand*,†
†UCRꢀCNRS Joint Research Chemistry Laboratory (UMI 2957), Department of Chemistry, University of California, Riverside,
California 92521, United States
‡Arnold and Mabel Beckman Laboratories of Chemical Synthesis, Division of Chemistry and Chemical Engineering, California Institute
of Technology, Pasadena, California 91125, United States
§Fachbereich Chemie, Philipps-Universit€at Marburg, Hans-Meerwein-Strasse, 35032 Marburg, Germany
S Supporting Information
b
ABSTRACT: The formal cycloaddition between 1,3-diaza-2-
azoniaallene salts and alkynes or alkyne equivalents provides an
efficient synthesis of 1,3-diaryl-1H-1,2,3-triazolium salts, the
direct precursors of 1,2,3-triazol-5-ylidenes. These N,N-diary-
lated mesoionic carbenes (MICs) exhibit enhanced stability in
comparison to their alkylated counterparts. Experimental and
computational results confirm that these MICs act as strongly
electron-donating ligands. Their increased stability allows for
the preparation of ruthenium olefin metathesis catalysts that are
efficient in both ring-opening and ring-closing reactions.
’ INTRODUCTION
Evidently, the stability of the free carbenes is also of the utmost
importance for applications in organocatalysis.13
Since their isolation a little more than two decades ago,1 cyclic
diamino carbenes of type A (Scheme 1), also referred to as
N-heterocyclic carbenes (NHCs), have gained a privileged status
among ancillary ligands for transition metals.2 Particularly success-
ful catalysts, incorporating these ligands, have been developed
for olefin metathesis (e.g., E),3 cross-couplings,4 conjugate
additions,5 telomerization reactions,6 and more recently the gold-
mediated electrophilic activation of alkenes, allenes, and alkynes.7
Integral to the success of these catalysts are the strong donating
properties of carbenes, the strength of the resulting carbonꢀmetal
bonds, and their particular steric properties.8 Besides the given
properties of any ligand, an implied prerequisite is that the desired
catalytically active complexes are synthetically accessible and, thus,
available in useful quantities for the necessary screening and
optimization of the investigated methodologies. Therein lies a
pivotal element to the success of NHC-based catalysts: NHC
complexes are simply and easily prepared by ligand substitution of
a suitable transition metal precursor with the stable free NHCs.
Other synthetic avenues are available when direct ligand substitu-
tion fails, including CꢀX or CꢀH insertions9 and the use of
carbene transfer reagents (e.g., CO2 or Ag(I) adducts).8c,10
However, the former route remains the most versatile and broadly
applicable method to access the target metal carbene complexes.
This readily explains the slower progress in the development
of catalysts based on abnormal NHCs B (aNHCs), remote
NHCs (rNHCs),8c,11 or other nontraditional carbenes,12 which
only recently have become available as stable metal-free species.
In 2010, we reported the preparation of stable free mesoionic
carbenes (MICs), 1H-1,2,3-triazol-5-ylidenes C (Scheme 1).14
While thermally robust, these MICs, alkylated at N3, were found
to be susceptible to intermolecular rearrangement and/or de-
composition pathways involving the alkyl group that limit their
synthetic and catalytic applications. Herein, we present a prac-
tical synthesis of MICs arylated at N3, based on the formal
cycloaddition of 1,3-diaza-2-azoniaallenes salts with alkynes or
alkyne equivalents. The increased stability of these new MICs
enables the synthesis of complexes that were not previously
accessible. This is illustrated by the preparation of ruthenium
olefin metathesis catalysts of type F that display reactivities
comparable to that of their NHC-based counterparts E in ring-
opening and ring-closing reactions.
’ RESULTS AND DISCUSSION
The “abnormal” bonding mode of carbenes B was first
identified in 2001 by Crabtree et al. with the preparation of
iridium complexes in which an imidazolium moiety was coordi-
nated not at C2 but “in the wrong way” at C5.15 Carbenes of this
type were dubbed abnormal since no canonical resonance form
of the free aNHC showing a carbene center can be drawn without
introducing charges (see B0). This atypical coordination mode
Received: March 26, 2011
Published: April 13, 2011
r
2011 American Chemical Society
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Scheme 1. Classes of Compounds Discussed in This Article
Scheme 2. Examples of Complexes of Mesoionic
Carbenes16ꢀ19
Scheme 3. Attempted Deprotonation of 1,3-Dialkyl-1,2,3-
triazolium Salt Ca(Hþ)
solvent did not lead to the desired MIC Ca but to the debenzy-
lated triazole 1 (Scheme 3).25
We first chose to replace the comparatively fragile alkyl
substituent at N1 by more robust aryl groups, but this could
not readily be achieved with the synthetic procedure used for
Ca(Hþ). First, the preparation and purification of aryl azides can
be cumbersome and present safety risks when performed on
scale, especially in the case of sterically hindered substrates. As a
remedy, we opted for the one-pot conversion of anilines to the
desired aryl azides, followed by in situ CuAAC as reported by
Moses et al.26 Second, the alkylation of 1-aryltriazoles requires
stronger alkylating agents than the corresponding 1-alkyltria-
zoles, and consequently alkyl triflates were used in place of alkyl
bromides or iodides.27 As previously reported, these triazolium
salts are cleanly deprotonated with either potassium bis-
(trimethylsilyl)amide or potassium tert-butoxide in ethereal
solutions. The corresponding crystalline MICs Cb,c are stable
enough in the solid state and in dilute solution under an inert
atmosphere to allow for their full characterization (Scheme 4).14
However, more concentrated solutions of the MICs Cb,c, alky-
lated at N3, decompose to give among other products triazoles
2b and 3. These results were rationalized in the case of Cb by an
intermolecular nucleophilic attack leading to the intermediacy of
the ion pair [4bþ5], a rearrangement reminiscent of that
observed for aNHC of type B bearing an electrophilic group in
the 2-position.28,29 Indeed, our gas-phase calculations (MP2/
TZVPP//BP86/SVP) predict that the rearranged product 2b is
features distinct electronic properties, namely, greater σ-dona-
tion and a predicted decreased π-accepting ability than the
corresponding NHCs A. Consequently, since 2001, many other
complexes bearing aNHC ligands have been reported.11,12a The
bonding situation found in aNHC complexes is also present in
adducts or complexes of 1,2,3,4-tetrazol-5-ylidenes,16 pyrazolin-
4-ylidenes,17 1,2,3-triazol-5-ylidenes,18 and 1,2-isoxazol-4-yli-
denes (Scheme 2).19 Since these ligands are in fact mesoionic
compounds,20 we favor the designation of this broad family as
mesoionic carbenes (MICs).14,21
Stimulated by their promising electronic properties, the fact
that Wanzlick-type dimers of MICs have yet to be observed
(which points to relaxed steric requirements),22 and by our
success in the isolation of an aNHC (B1, Table 1) in the free
state,23 we embarked on the preparation of free 1,2,3-triazol-5-
ylidenes C.14 Triazolium salts were quickly identified as ideal
precursors of the desired 1,2,3-triazol-5-ylidenes by analogy with
the classical deprotonation route used in the preparation of
NHCs and related species. Triazoles are conveniently prepared
by the Cu-catalyzed alkyneꢀazide cycloaddition (CuAAC, “click
chemistry”)24 and are readily alkylated at N3 to yield the target
triazolium salts. However, attempted deprotonation of the more
readily prepared 1,3-dialkyl-1,2,3-triazoliums salts did not lead to
the isolation of stable free MICs. For example, treatment of
triazolium Ca(Hþ) with potassium tert-butoxide in an ethereal
energetically more favorable than Cb by 46.5 kcal molꢀ1 and
ꢀ31
that the ion pair [4bþ5] is located 40.9 kcal mol above the
3
starting materials (e.g., 2 ꢁ Cb). Although the intermediate ion
pair is rather high in energy, this could be a viable pathway given
sufficient charge stabilization in solution. The formation of
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Scheme 4. Preparation and Decomposition of 3-Alkyl-1,2,3-triazol-5-ylidenes14 a
a Dipp = 2,6-diisopropylphenyl.
Figure 1. Solid-state structures of Cac(Hþ) (left) and Cag (right) with thermal ellipsoids drawn at 50% probability. For clarity, counterions and
hydrogen atoms, except for the ring hydrogen of Cac(Hþ), were omitted. Calculated values for Cag (BPI, see text for details) are given in italics. Selected
bond lengths (Å) and angles (deg) for Cac(Hþ): N1ꢀN2: 1.3201(16), N2ꢀN3: 1.3278(16), N3ꢀC4: 1.3819(16), C4ꢀC5: 1.3713(19), C5ꢀN1:
1.3523(17), —N1ꢀC5ꢀC4: 106.36(12). Cag: N1ꢀN2: 1.3420(7)/1.352, N2ꢀN3: 1.3302(7)/1.334, N3ꢀC4: 1.3763(8)/1.396, C4ꢀC5: 1.4041(8)/
1.414, C5ꢀN1: 1.3655(8)/1.373, —N1ꢀC5ꢀC4: 100.21(5)/100.8.
triazole 3 from Cb might be ascribed to the incipient protonation
of intermediate 5, while in the case of Cc a base-induced
elimination resulting in the loss of propene is quite likely. In
agreement with these hypotheses, MIC Cc bearing the more
sterically hindered and less electrophilic isopropyl group in the
3-position was found to be much more resistant with respect to
these decomposition pathways. Nevertheless, the stability of Cc
remained inferior to that of classical NHCs A, which hindered its
storage in the free state over extended periods (i.e., > weeks).
Furthermore, we reached the conclusion that the finite stability of
these alkylated MICs was responsible for disappointing results in
our primary attempts at preparing MIC transition metal com-
plexes by direct ligand substitution; in particular the synthesis of
ruthenium complexes was unsuccessful (vide infra).
Synthesis of Arylated MICs. Seeking to improve the stability
of MICs C, we directed our efforts toward the preparation of 1,3-
diarylated-1H-1,2,3-triazolium salts of type CAr(Hþ) (Scheme 5).
Evidently, these target precursors, unlike 3-alkyltriazolium salts
Ca-d(Hþ), are not accessible from the direct arylation of triazoles
at N3. However, Wirschun and Jochims reported the preparation in
moderate to good yields of a number of 1,3-diarylated-1H-1,2,3-
triazolium salts CAr(Hþ) by the formal 1,3-dipolar cycloaddition
between 1,3-diaza-2-azoniaallene salts H and alkynes or synthetic
alkyne equivalents (Scheme 5).30,31
We have found that, under optimized conditions, this reaction
is suitable for the preparation of a broad range of 1,3-diaryl-1H-
1,2,3-triazolium salts CAr(Hþ). Triazenes 6aꢀd were first
prepared by an adaptation of different literature procedures,
including the treatment of anilines with isoamyl nitrite (6a,d),32
the nucleophilic attack of anilines on arenediazonium salts in pH-
buffered aqueous solutions (6c),33 and the nucleophilic attack of
aryl Grignards on aryl azides (6b).34 The cycloaddition is then
best carried out in a single one-pot operation by the addition of
tert-butyl hypochlorite (as the N-chlorinating agent) to a stirred
suspension of the triazene 6aꢀd, alkyne 7aꢀr, and potassium
hexafluorophosphate in dichloromethane at ꢀ78 ꢀC. Warming
to room temperature, filtration of the insoluble inorganic by-
products, and trituration in diethyl ether affords the desired
triazolium salts Cxy(Hþ)35 (Scheme 6). It is noteworthy that this
formal cycloaddition, unlike CuAAC, proceeds rapidly below
room temperature and does not necessitate copper catalysts. The
scope of the reaction is quite broad with respect to the alkyne
partner and tolerates both electron-rich (7j,l) and electron-poor
(7f) alkynes, as well as enynes (7k). Highly sterically demanding
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Table 1. Calculated Properties of MICs and Related Carbenesa
1st PAd
C5
2nd PAd
C5/N2
HOMO (eV)b
HOMO/LUMO gapb
S/T gapc
Erel NꢀC isomerd
C5/C5
q(C)e
Cb
ꢀ4.484
ꢀ4.441
ꢀ4.527
ꢀ5.000c
ꢀ4.403c
55.0
63.2
62.3
55.9
ꢀ21.6
ꢀ22.7
ꢀ25.9
272.5
275.2
1.6
1.6
109.8
119.3
55.7
ꢀ0.12
ꢀ0.14
f
Cag
CH
59.4
252.8
g
1.5
h
ꢀ0.16
23
i
A1
23
j
B1
287.0
144.6
a All energies in kcal molꢀ1 unless otherwise mentioned. b BPI. c BPII. d MPII. e NBO results with BPII. f Structural optimization of the triplet structure
3
always resulted in H-transfer to C5. g Normal imidazolium NHCs 1st PA at C2 range from 228.9 to 274.9 kcal molꢀ1; for IMes, 270.4 kcal molꢀ1 41
.
3
3
h Normal imidazolium NHCs 2nd PA at C2 range from 38.9 to 106.5 kcal molꢀ1; for IMes, 105.3 kcal molꢀ1 41 i Partial charges at carbene center q(C)
.
3
3
for normal imidazolium NHCs range from ꢀ0.01 to 0.08; for IMes, 0.08.41 j Abnormal imidazolium NHCs q(C) range from ꢀ0.16 to ꢀ0.19; for 1,3-
dimesitylimidazol-5-ylidene (aIMes), ꢀ0.17.41
Scheme 5. Triazolium Salts from the Formal Cycloaddition
of 1,3-Diaza-2-azoniaallene Salts H and Alkynes According to
Wirschun and Jochims30
Figure 2. Frontier orbitals of Cag and orbital energies in eV at the BPI
level of theory.
triazolium salts can be prepared (Cac(Hþ), Cad(Hþ)), although
yields are depressed in the most difficult cases, as for tert-
Treatment of most 1,3-diaryl-1H-1,2,3-triazoliums salts Cxy(Hþ)
butylacetylene (7g). In addition to terminal alkynes, cycloaddition
with potassium bases such as potassium bis(trimethylsilyl)-
with internal alkynes also proceeds smoothly (Can-aoþ). Tri-
amide or preferably potassium tert-butoxide results in their clean
methylsilyl alkynes participate in this reaction as terminal alkyne
deprotonation and formation of the target stable free MICs Cxy in
surrogates, since protodesilylation occurs readily and the protic
moderate to excellent yields (Scheme 8). However, attempted depro-
triazolium salts are instead obtained (Caa(Hþ), Cae(Hþ), Cai-
tonation of ester- [Caf(Hþ)], fluoro- [Cda(Hþ) and Cdq(Hþ)],
(Hþ)). As indicated by Wirschun and Jochims,30 success in the
and alkenyl-substituted [Cak(Hþ)] triazoliums did not yield the
formation of the heterocycle probably depends on the stability of
corresponding free MICs. Formation of the free MICs is evi-
G andH. Forsomecombinationsoftriazene and alkyne substrates,
denced by the disappearance of the triazolium CH signal in the 1H
we found that the reaction proceeds best at high concentrations in
the presence of an excess of alkyne. Occasionally, as is the case for
dimesityltriazene 6b, performing the cycloaddition in the absence
of potassium hexafluorophosphate, which presumably shifts the
NMR spectra (δ = 8.4ꢀ9.4 ppm) and the appearance of a low-
of carbenes.36 These signals are comparable to those observed for
field signal in the 13C NMR spectra (δ = 200ꢀ206 ppm), typical
MICs alkylated at N3 such as Cb-d (δ = 198ꢀ202 ppm). The
ethoxy-substituted MIC Caj is an exception and features a 13C
NMR signal at a considerably higher field (δ = 179.6 ppm).
Experimental and Calculated Properties of MICs. The
structure of MIC Cag was unambigously established by X-ray
crystallography (Figure 1). Its structural parameters in the solid
state are comparable to those previously reported for the MIC
Cb, alkylated at N3.14 Both mesoionic carbenes display a planar
ring with bond lengths medial between that of single and double
bonds, features indicative of its aromatic character. As previously
observed for Cb(Hþ)/Cb and most carbenes and their conjugate
acids, deprotonation is accompanied by a contraction of the
endocyclic angle at the carbene center (Cac(Hþ): 106ꢀ; Cag:
100ꢀ), which reflects the increased s-character of the carbene σ
lone pair orbital.8c,12a
GꢀH equilibrium toward the more stable chlorotriazene, and
performing the anion exchange in a subsequent step results in
higher yields. Finally, this reaction is readily scaled-up, as exem-
plified by the preparation of Cbb(Hþ) at the 20 mmol scale in
excellent yields (10.1 g, 88%).
Since some alkynes are either expensive or less practically
accessible, it may be advantageous to use vinyl halides (8aꢀq) as
synthetic alkyne equivalents in a cognate preparation of MIC
precursors (Scheme 7A). The cycloaddition proceeds under the
aforementioned conditions, during which spontaneous elimina-
tion of hydrogen halide occurs. Allyl halides (e.g., 9) can also be
used; in this case dehydrohalogenationꢀaromatization of the
intermediate adduct (10) is not complete, but is readily achieved
by treatment with an amine base in a second step (Scheme 7B).
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Scheme 6. Preparation of 1,3-Diaryl-1,2,3-triazolium Salts from Triazenes and Alkynes
a Performed with either PhCCH (7a) or PhCCSiMe3 (7r); b With Me3SiCCH (7e); c With CH3CCSiMe3.
Scheme 7. Preparation of 1,3-Diaryl-1,2,3-triazolium Salts from Triazenes and Synthetic Alkyne Equivalents
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Scheme 8. Preparation of MICs Cxy by Deprotonation of
Triazolium Precursors Cxy(Hþ)
BP86/def2-SVP level of theory (hereafter designated BPI), and
single-point energies and bonding analyses were carried out using an
extended basis set at BP86/def2-TZVPP//BP86/def2-SVP (BPII)
and MP2/def2-TZVPP//BP86/def2-SVP (MPII) levels of theory.
Further computational details can be found in the Supporting
Information. As can be seen from the caption of Figure 1, the
calculated geometry for Cag is in excellent agreement with the
experimental values. The theoretical data are summarized in Table 1,
along with the results for representative carbenes of type A and B.23
The stability of MICs of type C is corroborated by their large
singletꢀtriplet gap (55.4ꢀ59.4 kcal molꢀ1) and the correspond-
3
ingly large HOMOꢀLUMO gap (note that for Cag the triplet state
is not an energy minimum; the geometry optimization led to
rearrangement of substituents). The stability of C derives in part
from its sizable aromatic character, as evidenced by NICS calcula-
tions for CH (NICS(0) = ꢀ14.93; NICS(1)zz = ꢀ36.06). These
indices are comparable to those of other aromatic five-membered
heterocycles including pyrrole, thiophene, and 1,2-pyrazol-4-yli-
denes devoid of exocyclic π-donating substituents.39 The calcula-
tions reveal that 1,2,3-triazol-5-ylidenes C are higher in energy by
21.6 to 25.9 kcal molꢀ1 than the corresponding 1,2,4-triazol-
3
5-ylidene isomers (Enders’ NHCs).40 In comparison, the aNHC
B1 is only 14.1 kcal molꢀ1 higher in energy than its normal NHC
3
isomer A1.23 Analysis of the frontier orbitals of Cag (Figure 2) shows
that the HOMO can be characterized as a σ lone pair at carbon
(ꢀ4.441 eV), as found in classical NHCs (e.g., A1; ꢀ5.000 eV) and
their abnormal isomers (e.g., B1; ꢀ4.403 eV). The relative lone pair
energy levels are in agreement with the assessment of electronic
properties derived from the CO stretching frequencies of
[(carbene)Ir(CO)2Cl] complexes. The highest occupied π-orbital
is the C4ꢀC5 bonding HOMOꢀ1 (ꢀ5.770 eV), which is signifi-
cantly lower than the HOMO, and exhibits antibonding conjugation
with the substituent at C4 as observed for B1.23 The LUMO has a
rather small orbital coefficient at C5. The greater partial negative
charge [q(C)] for carbenes of types B and C is consistent with their
preferred representation as mesoionic compounds. The calculated
second proton affinity is very small;41 in fact, the second proton
The free carbenes proved to be very robust and could be stored
in the solid state at room temperature under an inert atmosphere
for several weeks. In contrast to Cb-c (Scheme 4), MIC Cba (mp =
154ꢀ156 ꢀC dec) shows no sign of decomposition upon heating
in benzene solution for 12 h at 50 ꢀC. This illustrates the efficacy
of introducing aryl substituents at N3 to shut down undesired
decomposition pathways. Consistent with previous results,14 no
dimerization of these carbenes was observed in solution.
The electronic properties of the new arylated triazolylidenes
were evaluated by preparing the iridium carbonyl complexes
11ac and 11aj (Scheme 9). The CO vibration frequencies (11ac:
νav = 2018 cmꢀ1; 11aj: νav = 2020 cmꢀ1) are comparable to
would bind at N2 (2nd PA: 55.7ꢀ119.3 kcal molꢀ1) and not at C5
3
(1.5ꢀ1.6 kcal molꢀ1). Finally, the calculated PAs of Cb (272.5
3
those found for complex [(Cb)Ir(CO)2Cl] (νav = 2019 cmꢀ1
)
kcal molꢀ1) and Cag (275.2 kcal molꢀ1) are closer to that of
3
3
imidazol-2-ylidenes [270.4 kcal molꢀ1 for 1,3-dimesitylimidazol-
and for the analogous iridium complex of a 1,3-dialkylated-1,2,3-
3
2-ylidene (IMes)] than to that of B1 (287.0 kcal molꢀ1). Accord-
triazol-5-ylidene previously reported by Albrecht et al. (νav
=
3
2021 cmꢀ1).18d From these results, it can be concluded that
(i) the electronic properties of CAr are not strongly influenced by
the nature of substituents at N1, N3, and C5 and (ii) the donor
properties of CAr are greater than those of NHCs A (νav = 2022ꢀ
2031 cmꢀ1),37 but lesser than those of aNHC B (νav = 2003ꢀ
ingly, the conjugate acids of the first three are experimentally found
to be deprotonated with mild alkoxide bases, while the latter requires
stronger amide bases.
MICꢀRuthenium Complexes and Olefin Metathesis.
Having established the synthesis and electronic structure of
several MICs C, we turned our attention to their application as
ligands. Olefin metathesis with ruthenium-based catalysts, a
well-known and synthetically useful reaction, was chosen in
order to demonstrate the effectiveness of MICs in a catalytic
setting.3dꢀh Previous work has demonstrated that the structure
of the ligand can have a profound effect on the reactivity and
stability of the catalyst (e.g., D1 versus E1).3h,42 Furthermore, the
use of carbenes with unusual bonding modes or structure such as
cyclic amino alkyl carbenes (CAACs) has been shown to affect
the selectivity of ruthenium metathesis catalysts.43
2006 cm )
ꢀ1 38 and pyrazolin-4-ylidenes (aka cyclic bent-allenes;
νav = 2002 cmꢀ1).17e The solid-state structure of complex 11ac
(Scheme 9, right) is illustrative of the large steric demands
imposed by ligand Cac, bearing three 2,6-diisopropylphenyl sub-
stituents. As a result, the iridium center deviates from coplanarity
by 19ꢀ and is located 0.55 Å above the plane of the heterocycle.
The consequence of these steric requirements also manifests itself
in the solution NMR spectra with a broadening of peaks indicative
of restricted rotation at the NMR time scale for 11ac, but not for
the less hindered 11aj.
To gain greater insight into the structure and properties of free
MICs of type C, gradient-corrected density functional theory
calculations were performed on models of MIC Cb alkylated at
N3, MIC Cag arylated at N3, and the parent MIC CH bearing only
hydrogen substituents. Molecular geometries were optimized at the
Free MICs of type C bearing flanking aryl groups of varying
steric demand were selected for the synthesis by simple ligand
substitution of the target complexes of type F, which represent
MIC-based analogues of the standard NHC-based metathesis
catalyst E2. Early attempts using the MIC Cd alkylated at N3 (SI)
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Scheme 9. Preparation of Iridium Carbonyl Complexesa
a Center and right: Molecular views of 11ac in the solid state under different angles, with thermal ellipsoids drawn at 50% probability. For clarity,
hydrogen atoms were omitted.
resulted in complete decomposition, but gratifyingly, the use of
more robust MICs arylated at N3, Caa, Cab, Cad, and Cba,
provided the targets Faa, Fab, Fad, and Fba (Scheme 10). Com-
Scheme 10. Synthesis of Ruthenium Complexes by Ligand
Substitution
44
bining a free MIC with complex D2 in benzene resulted in
100% conversion after several hours. The resulting complexes
were isolated by recrystallization from CH2Cl2ꢀpentane (Faa,
Fab, Fba) or pentane (Fad) at ꢀ30 ꢀC without the need for
column chromatography. The complexes were found to decom-
pose relatively quickly in solution upon exposure to oxygen, but
were indefinitely stable in the solid state under an inert atmo-
sphere. NMR spectroscopy studies on the ligand displacement
reaction with D2 indicated that a MICꢀphosphine complex,
where the MIC initially displaces the chelating ether moiety, was
formed before subsequently yielding the desired complex.45 This
intermediate usually persisted for several hours before forming
the desired complex.
Complexes Faa and Fad were characterized by single-crystal
X-ray diffraction (Figure 3). Bond lengths in Faa and Fad are very
similar to those found in E2. The MIC carbonꢀRu bond length
(1.99 Å versus 1.98 Å in E2), the benzylidene CꢀRu bond length
(1.82 Å versus 1.82 Å), and the OꢀRu bond length (2.27 Å
versus 2.26 Å) are largely conserved across the three species.46
Notably, the smaller aryl substituent (on C4 in Faa and N1 in Fad)
is positioned above the ClꢀRuꢀCl plane in order to minimize
steric interactions with the chlorines, while the larger substituent
is positioned above the benzylidene.47
To evaluate the catalytic activity of these complexes, they were
subjected to several standard metathesis screens.48 Catalysts Faa,
Fab, and Fba showed good ring-opening metathesis polymeriza-
tion (ROMP) activity (Figure 4), while catalyst Fad reached only
low conversions, even after a period of several days. Comparing
the ROMP conversion profiles of MIC-based catalysts to stan-
dard catalyst E2 reveals a few similarities and differences. For
instance, Fab shows an almost identical conversion profile to E2,
while Fba is slightly slower, but still relatively fast, and Faa is much
slower, although it does reach 100% conversion after ca. 1 h.
The most surprising result is the difference in reactivity
between catalysts Faa and Fab, since the only difference between
the two is the substitution of a mesityl group for a phenyl at C4.
We hypothesized that the observed behavior might be largely due
to a difference in initiation rates, and in order to probe this, we
constructed several Eyring plots for the reaction of each catalyst
with butyl vinyl ether.42a,49 The results for the initiation para-
meters are given in Table 2.
Catalysts Faa, Fab, Fba, and Fad all exhibited a negative ΔS‡,
which is consistent with an associative or associative interchange
initiation mechanism previously reported for catalysts incorpor-
ating a Hoveyda-type chelate.50 Interestingly, while catalysts Faa
and Fad were found to have very similar activation entropies,
catalysts Fab and Fba differed by ca. 10 eu from these. Further-
more, the activation enthalpy for Faa was found to be lower than
that for Fab. Nevertheless, a 1.4 kcal molꢀ1 difference in ΔG‡
3
between Faa and Fab was observed when combining the ΔH‡ and
ΔS‡ parameters at RT. This difference accounts nicely for the
observed variations in initiation while also explaining the almost
complete inactivity of catalyst Fad at RT. Unfortunately, while it is
clear that sterics play a significant role in catalyst initiation, so far a
qualitative model that accounts for the observed differences in
initiation, particularly between Faa and Fab, has eluded us.51
Following the initiation studies, the performance of each
catalyst in RCM was assessed (Figure 5). Again, catalyst Fad
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Figure 3. Solid-state structures of Faa (left) and Fad (right) with thermal ellipsoids drawn at 50% probability. Selected bond lengths (Å) for Faa:
C23ꢀRu: 1.9913(1), C22ꢀRu: 1.8235(1), OꢀRu: 2.2696(1). For Fad: C21ꢀRu: 1.9852(1), C40ꢀRu: 1.8157(1), OꢀRu: 2.3176(1).
Figure 5. RCM performance of catalysts Faa (red), Fab (blue), Fba
Figure 4. ROMP of COD with catalysts Faa (red), Fab (blue), Fba
(black), and E2 (white). Conditions: 1 mol % catalyst, 0.1 M substrate,
30 ꢀC, in C6D6.
(black), and E2 (white). Conditions: 0.1 mol % catalyst, 30 ꢀC, 0.1 M
(substrate) in C6D6.
was found to be almost completely inactive at 30 ꢀC. Other catalysts
Table 2. Comparison of Activation Parameters for Catalysts
Faa, Fab, Fad, and Fba
displayed conversion profiles consistent with their initiation activation
a
energies. For instance, Fab shows a fast increase in conversion followed
catalyst
ΔG‡298 (kcal molꢀ1
)
ΔH‡0 (kcal molꢀ1
)
ΔS‡ (eu)
by a plateau that most likely results from catalyst decomposition. On
the other hand, Faa exhibits an induction period characteristic of a slow
initiation followed by a gradual increase toward 100% conversion.
Notably, even though Faa initiates at a slower rate than Fab, it is able to
reach 100% conversion under the examined conditions while Fab is
not. For this assay, Fba appears to be the best catalyst, as it displays fast
initiation and good stability throughout the reaction. In fact, Fba closely
matches the performance of E2.
3
3
Faa
Fab
Fad
Fba
21.6 ( 0.8
20.2 ( 0.2
23.5 ( 0.1
20.8 ( 0.3
12.1 ( 0.5
13.5 ( 0.8
13.6 ( 0.6
14.6 ( 0.5
ꢀ31.9 ( 1.5
ꢀ22.5 ( 2.7
ꢀ33.0 ( 1.9
ꢀ21.0 ( 1.6
a Conditions: catalyst (0.003 mmol), butyl vinyl ether (0.09 mmol, 0.15 M)
in d8-toluene at varying temperatures.
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cylic alkenes. The catalytic properties of the MICꢀRu complexes
F, in particular with respect to their rates of initiation and
resistance to deactivation, are strongly influenced by the nature
of the MIC substituents and in several cases may rival the
performance of well-established NHC ruthenium olefin meta-
thesis catalysts E. The combination of their practical, versatile,
and modular preparation, enhanced stability, and advantageous
electronic properties and the demonstration of their effectiveness
in a catalytic setting foreshadow the development of numerous
MIC transition metal complexes for catalytic applications.
’ ASSOCIATED CONTENT
S
Supporting Information. Full experimental details in-
b
cluding synthesis, characterization, and X-ray data. This material
is available free of charge via the Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: guy.bertrand@ucr.edu; rhg@caltech.edu.
Figure 6. Trisubstituted RCM performance for catalysts Faa (red), Fab
(blue), Fba (black), and E2 (white). Conditions: 1 mol % catalyst, 0.1 M
in substrate, 30 ꢀC, in C6D6.
’ ACKNOWLEDGMENT
We thank Dr. Vincent Lavallo for technical assistance. Lawrence
M. Henling, Dr. Michael Day, and Dr. Bruno Donnadieu are
acknowledged for X-ray crystallographic analysis. We are grateful to
NIH (R01 GM 68825), FQRNT (fellowship to J. B.), and NDSEG
(fellowship to B.K.K.) for the financial support of this work. G.F. and
R.T. acknowledge financial support of this work by the Deutsche
Forschungsgemeinschaft (FR 641/26). Instrumentation facilities on
which this work was carried out were supported by the NSF (CHE-
0541848, CHE-0742001, CHE-0639094, and CHE-9724392), NIH
(RR027690), and the AFOSR (F49620-98-1-0475).
To further examine the differences in reactivity between the
catalysts, trisubstituted RCM was attempted (Figure 6). As
expected, Faa and Fab exhibited the same behavior as stated above,
with Faa displaying a lengthy induction period, while Fab begins
conversion to product almost immediately. Catalyst Fab reached a
maximum conversion of ca. 50%, while Faa was able to reach 100%
conversion after a period of ca. 16 h. These results confirm that not
only does the change from a Ph (Faa) to Mes (Fab) have a
profound effect on the initiation rate but it also impacts the relative
stability of the catalysts. Catalyst Fba was relatively sluggish over
the time period examined but was able to reach 100% conversion
after ca. 24 h at 30 ꢀC. Overall, in the trisubstituted RCM assay, the
MIC-based catalysts were clearly inferior to E2, in contrast to the
previous assays, where they displayed comparable activity.
’ REFERENCES
(1) Arduengo, A. J., III; Harlow, R. L.; Kline, M. J. Am. Chem. Soc.
1991, 113, 361–363.
(2) (a) N-Heterocyclic Carbenes in Transition Metal Catalysis; Glorius,
F., Ed.; Topics in Organometallic Chemistry; Springer-Verlag: Berlin,
2007; Vol. 21, pp 1ꢀ218. (b) Díez-Gonzꢀalez, S.; Marion, N.; Nolan,
S. P. Chem. Rev. 2009, 109, 3162–3676.
(3) (a) Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett. 1999,
1, 953–956. (b) Huang, J.; Stevens, E. D.; Nolan, S. P.; Petersen, J. L. J. Am.
Chem. Soc. 1999, 121, 2674–2678. (c) Garber, S. B.; Kingsbury, J. S.; Gray,
B. L.; Hoveyda, A. H. J. Am. Chem. Soc. 2000, 122, 8168–8179.
(d) F€urstner, A. Angew. Chem., Int. Ed. 2000, 39, 3012–3043. (e) Trnka,
T. M.; Grubbs, R. H. Acc. Chem. Res. 2001, 34, 18–29. (f) Samojtowicz, C.;
Bieniek, M.; Grela, K. Chem. Rev. 2009, 109, 3708–3742. (g) Monfette,
S.; Fogg, D. E. Chem. Rev. 2009, 109, 3783–3816. (h) Vougioukalakis,
G. C.; Grubbs, R. H. Chem. Rev. 2010, 110, 1746–1787.
’ CONCLUSIONS
The presence of N-alkyl substituents was found to be a
predominant factor limiting the stability of 1H-1,2,3-triazol-5-
ylidenes C. Introduction of N-aryl substituents in place of these
alkyl groups vitiates these decomposition pathways and results in
MICs exhibiting stabilities approaching that of NHCs A. A wide
variety of 1,3-diaryl-substituted MICs are conveniently prepared
through the scalable WirschunꢀJochims formal cycloaddition
between 1,3-diaza-2-azoniaallene salts and alkynes or synthetic
alkyne equivalents, followed by deprotonation with mild alkoxide
bases. By this method, MICs bearing highly sterically demanding
(Tipp, tBu), as well as polar and functionalized substituents in
R-position to the carbene center can be obtained. The enhanced
stability of N-arylated MICs allows for the preparation of
ruthenium olefin metathesis catalysts by simple ligand substitu-
tion. MICs-bearing ruthenium benzylidene complexes F are
proficient room-temperature catalysts for the ring-opening me-
tathesis polymerization of cyclic olefins and for ring-closing
olefin metathesis reactions leading to both di- and trisubstituted
(4) (a) Hillier, A. C.; Grasa, G. A.; Viciu, M. S.; Lee, H. M.; Yang, C.;
Nolan, S. P. J. Organomet. Chem. 2002, 653, 69–82. (b) Herrmann,
€
W. A.; Ofele, K.; v. Preysing, D.; Schneider, S. K. J. Organomet. Chem.
2003, 687, 229–248. (c) Kantchev, E. A. B.; O’Brien, C. J.; Organ, M. G.
Angew. Chem., Int. Ed. 2007, 46, 2768–2813. (d) Marion, N.; Nolan, S. P.
Acc. Chem. Res. 2008, 41, 1440–1449. (e) W€urtz, S.; Glorius, F. Acc.
Chem. Res. 2008, 41, 1523–1533.
(5) (a) Wencel, J.; Mauduit, M.; Hꢀenon, H.; Kehrli, S.; Alexakis, A.
Aldrichim. Acta 2009, 42, 43–50. (b) Alexakis, A.; B€ackvall, J. E.; Krause,
N.; Pꢁamies, O.; Diꢀeguez, M. Chem. Rev. 2008, 108, 2796–2823.
(c) Harutyunyan, S. R.; den Hartog, T.; Geurts, K.; Minnaard, A. J.;
Feringa, B. L. Chem. Rev. 2008, 108, 2824–2852.
2625
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Organometallics
ARTICLE
(6) (a) Jackstell, R.; Gꢀomez Andreu, M.; Frisch, A.; Selvakumar, K.;
Zapf, A.; Klein, H.; Spannenberg, A.; R€ottger, D.; Briel, O.; Karch, R.;
Beller, M. Angew. Chem., Int. Ed. 2002, 41, 986–989.(b) Clement, N. D.;
Rotaboul, L.; Grotevendt, A.; Jackstell, R.; Beller, M. Chem.—Eur. J.
2008, 14, 7408ꢀ7420, and references therein.
G. Angew. Chem., Int. Ed. 2008, 47, 5411–5414. (d) Han, Y.; Lee, L. J.;
Huynh, H. V. Organometallics 2009, 28, 2778–2786. (e) Melaimi, M.;
Parameswaran, P.; Donnadieu, B.; Frenking, G.; Bertrand, G. Angew.
Chem., Int. Ed. 2009, 48, 4792–4795. (f) Han, Y.; Huynh, H. V. Dalton
Trans. 2011, 40, 2141–2147. (g) Han, Y.; Yuan, D.; Teng, Q.; Huynh,
H. V. Organometallics 2011, 30, 1224–1230.
(7) (a) Marion, N.; Nolan, S. P. Chem. Soc. Rev. 2008, 37, 1776–1782.
(b) Gorin, D. J.; Sherry, B. D.; Toste, F. D. Chem. Rev. 2008,
108, 3351–3378. (c) Nolan, S. P. Acc. Chem. Res. 2011, 44, 91–100.
(d) Raubenheimer, H. G.; Cronje, S. Chem. Soc. Rev. 2008, 37, 1998–2011.
(8) (a) Hillier, A. C.; Sommer, W. J.; Yong, B. S.; Petersen, J. L;
Cavallo, L.; Nolan, S. P. Organometallics 2003, 22, 4322–4326. (b) Viciu,
M. S.; Navarro, O.; Germaneau, R. F.; Kelly, R. A.; Sommer, W. J.;
Marion, N.; Stevens, E. D.; Cavallo, L.; Nolan, S. P. Organometallics
2004, 23, 1629–1635. (c) Hahn, E.; Jahnke, M. C. Angew. Chem., Int. Ed.
2008, 47, 3122–3172. (d) Dr€oge, T.; Glorius, F. Angew. Chem., Int. Ed.
2010, 49, 6940–6952. (e) Díez-Gonzꢀalez, S.; Nolan, S. P. Coord. Chem.
Rev. 2007, 251, 874–883. (f) de Frꢀemont, P.; Marion, N.; Nolan, S. P.
Coord. Chem. Rev. 2009, 253, 862–892.
(18) (a) Begtrup, M.; Kristensen, P. A. Acta Chem. Scand. 1969,
23, 2733–2740. (b) Begtrup, M. Acta Chem. Scand. B 1975,
29, 141–144. (c) Begtrup, M. J. Chem. Soc., Chem. Commun.
1975, 334–335. (d) Mathew, P.; Neels, A.; Albrecht, M. J. Am. Chem.
Soc. 2008, 130, 13534–13535. (e) Karthikeyan, T.; Sankararaman, S.
Tetrahedron Lett. 2009, 50, 5834–5837. (f) Nakamura, T.; Ogata, K.;
Fukuzawa, S.-i. Chem. Lett. 2010, 39, 920–922. (g) Lalrempuia, R.;
McDaniel., N. D.; M€uller-Bunz, H.; Bernhard, S.; Albrecht, M. Angew.
Chem., Int. Ed. 2010, 49, 9765–9768. (h) Kilpin, K. J.; Paul, U. S. D.; Lee,
A.-L.; Crowley, J. D. Chem. Commun. 2011, 47, 328–330. (i) Nakamura, T.;
Terashima, T.; Ogata, K.; Fukuzawa, S.-i. Org. Lett. 2011, 13, 620–623. (j)
Poulain, A.; Canseco-Gonzalez, D.; Hynes-Roche, R.; M€uller-Bunz, H.;
Schuster, O.; Stoeckli-Evans, H.; Neels, A.; Albrecht, M. Organometallics
2011, 30, 1021–1029. (k) Prades, A.; Peris, E.; Albrecht, M. Organome-
tallics 2011, 30, 1162–1167. (l) Saravanakumar, R.; Ramkumar, V.;
Sankararaman, S. Organometallics 2011, 30, 1689–1694.
(19) Iglesias, M.; Albrecht, M. Dalton Trans. 2010, 39, 5213–5215.
(20) According to IUPAC, mesoionic compounds are “dipolar five-
(possibly six-) membered heterocyclic compounds in which both the
negative and the positive charge are delocalized, for which a totally
covalent structure cannot be written and which cannot be represented
satisfactorily by any one polar structure. The formal positive charge is
associated with the ring atoms, and the formal negative charge is
associated with ring atoms or an exocyclic nitrogen or chalcogen atom.”
Compendium of Chemical Terminology, 2nd ed.; McNaught, A. D.;
Wilkinson, A, Eds.; Blackwell Scientific: Oxford, 1997; XML on-line
corrected version: http://goldbook.iupac.org (2006) created by M. Nic,
J. Jirat, B. Kosata; updates compiled by A. Jenkins [http://goldbook.
iupac.org/M03842.html].
(9) (a) Gr€undemann, S.; Albrecht, M.; Kovacevic, A.; Faller, J.
W.; Crabtree, R. H. J. Chem. Soc., Dalton Trans. 2002, 2163–2167.
(b) McGuinness, D. S.; Cavell, K. J.; Yates, B. F. Chem. Commun. 2001,
355–356. (c) McGuinness, D. S.; Cavell, K. J.; Yates, B. F.; Skelton, B. W.;
White, A. H. J. Am. Chem. Soc. 2001, 123, 8317–8328.
(10) (a) Voutchkova, A. M.; Appelhans, L. N.; Chianese, A. R.;
Crabtree, R. H. J. Am. Chem. Soc. 2005, 127, 17624–17625.
(b) Voutchkova, A. M.; Feliz, M.; Clot, E.; Eisenstein, O.; Crabtree,
R. H. J. Am. Chem. Soc. 2007, 129, 12834–12846. (c) Wang, H. M. J.; Lin,
I. J. B. Organometallics 1998, 17, 972–975. (d) Lin, J. C. Y.; Huang,
R. T. W.; Lee, C. S.; Bhattacharyya, A.; Hwang, W. S.; Lin, I. J. B. Chem.
Rev. 2009, 109, 3561–3598. (e) Garrisson, J. C.; Youngs, W. J. Chem. Rev.
2005, 105, 3978–4008. (f) Duong, H. A.; Tekavec, T. N.; Arif, A. M.;
Louie, J. Chem. Commun. 2004, 112–113.
(11) (a) Arnold, P. L.; Pearson, S. Coord. Chem. Rev. 2007,
251, 596–609. (b) Albrecht, M. Chem. Commun. 2008, 3601–3610.
(c) Schuster, O.; Yang, L.; Raubenheimer, H. G.; Albrecht, M. Chem.
Rev. 2009, 109, 3445–3478. (d) Albrecht, M. Chimia 2009, 63, 105–110.
For comparisons of the properties of normal, abnormal, and remote
carbenes, see for examples:(e) Heydenrych, G.; von Hopffgarten, M.;
Stander, E.; Schuster, O.; Raubenheimer, H. G.; Frenking, G. Eur. J.
Inorg. Chem. 2009, 1892–1904. (f) Stander-Grobler, E.; Schuster, O.;
Heydenrych, G.; Cronje, S.; Tosh, E.; Albrecht, M.; Frenking, G.;
Raubenheimer, H. G. Organometallics 2010, 29, 5821–5833.
(21) The term “mesoionic carbene” was originally coined by Araki
et al. (refs 16cꢀ16e), unbeknownst to us at the time or our previous
publication (ref 14).
(22) Alder, R. W.; Blake, M. E.; Chaker, L.; Harvey, J. N.; Paolini, F.;
Sch€utz, J. Angew. Chem., Int. Ed. 2004, 43, 5896–5911.
(23) Aldeco-Perez, E.; Rosenthal, A. J.; Donnadieu, B; Parameswaran,
P.; Frenking, G.; Bertrand, G. Science 2009, 326, 556–559.
(12) (a) Melaimi, M.; Soleilhavoup, M.; Bertrand, G. Angew. Chem.,
Int. Ed. 2010, 49, 8810–8849. (b) Vignolle, J.; Catto€en, X.; Bourissou, D.
Chem. Rev. 2009, 109, 3333–3384.
(13) For reviews, see: (a) Enders, D.; Niemeier, O.; Henseler, A.
Chem. Rev. 2007, 107, 5606–5655. (b) Marion, N.; Diez-Gonzalez, S.;
Nolan, S. P. Angew. Chem., Int. Ed. 2007, 46, 2988–3000. (c) Moore, J. L.;
Rovis, T. Carbene Catalysts. Top. Curr. Chem. 2010, 291, 77ꢀ144.
Applications of free MICs in organocatalysis will be reported elsewhere.
(14) Guisado-Barrios, G.; Bouffard, J.; Donnadieu, B.; Bertrand, G.
Angew. Chem., Int. Ed. 2010, 49, 4759–4762.
(15) (a) Grundemann, S.; Kovacevic, A.; Albrecht, M.; Faller, J. W.;
Crabtree, R. H. Chem. Commun. 2001, 2274–2275. (b) Grundemann, S.;
Kovacevic, A.; Albrecht, M.; Faller, J. W.; Crabtree, R. H. J. Am. Chem.
Soc. 2002, 124, 10473–10481.
(16) (a) Norris, W. P.; Henry, R. A. Tetrahedron Lett. 1965,
6, 1213–1215. (b) Weiss, R.; Lowack, R. H. Angew. Chem., Int. Ed.
1991, 30, 1162–1163. (c) Araki, S.; Wanibe, Y.; Uno, F.; Morikawa, A.;
Yamamoto, K.; Chiba, K.; Butsugan, Y. Chem. Ber. 1993, 126,
1149–1155. (d) Araki, S.; Yamamoto, K.; Yagi, M.; Inoue, T.; Fukagawa,
H.; Hattori, H.; Yamamura, H.; Kawai, M.; Butsugan, Y. Eur. Chem. Org.
J. 1998, 121–127. (e) Araki, S.; Yokoi, K.; Sato, R.; Hirashita, T.;
Setsune, J.-I. J. Heterocycl. Chem. 2009, 46, 164–171. (f) Jothibasu, R.;
Huynh, H. V. Organometallics 2009, 28, 2505–2511.
(24) (a) Tornøe, C. W.; Christensen, C.; Meldal, M. J. Org. Chem.
2002, 67, 3057–3064. (b) Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.;
Sharpless, K. B. Angew. Chem., Int. Ed. 2002, 41, 2596–2599. For a recent
review:(c) Meldal, M.; Tornøe, C. W. Chem. Rev. 2008, 108, 2952–3015.
(25) Note that the formation of 1 does not necessarily imply the
transient formation or intermediacy of the corresponding free MIC.
(26) Barral, K.; Moorhouse, A. D.; Moses, J. E. Org. Lett. 2007, 9,
1809–1811.
(27) For recent examples, see: (a) Mullen, K. M.; Mercurio, J.;
Serpell, C. J.; Beer, P. D. Angew. Chem., Int. Ed. 2009, 48, 4781–4784. (b)
Schulze, B.; Friebe, C.; Hager, M. D.; G€unther, W.; K€ohn, U.; Jahn,
B. O.; G€oris, H.; Schubert, U. S. Org. Lett. 2010, 12, 2710–2713.
(28) (a) Mendoza-Espinosa, D.; Donnadieu, B.; Bertrand, G. J. Am.
Chem. Soc. 2010, 132, 7264–7265. (b) Arduengo, A. J., III; Davidson, F.;
Dias, H. V. R.; Goerlich, J. R.; Khasnis, D.; Marshall, W. J.; Prakasha,
T. K. J. Am. Chem. Soc. 1997, 119, 12742–12749. (c) Cole, M. L.; Jones,
C.; Junk, P. C. New J. Chem. 2002, 26, 1296–1303.
(29) Note that the base-induced reactions of alkylated triazolium
salts such as Ca-b(Hþ) provide indirect routes for the preparation of
substituted triazoles that are not directly accessible by CuAAC chemistry
(ref 24). For a related example of preparation of heterocycles that
proceed through the rearrangement of unstable carbenes: Schmidt, A.;
M€unster, N.; Dreger, A. Angew. Chem., Int. Ed. 2010, 49, 2790–2793.
(30) (a) Wirschun, W.; Winkler, M.; Lutz, K.; Jochims, J. C. J. Chem.
Soc., Perkin Trans. 1 1998, 1755–1761. (b) Wirschun, W. J. Prakt. Chem.
1998, 340, 300–308. (c) Al-Masoudi, N.; Hassan, N. A.; Al-Soud, Y. A.;
(17) (a) Han, Y.; Huynh, H. V. Chem. Commun. 2007, 1089–1091.
(b) Han, Y.; Huynh, H. V.; Tan, G. K. Organometallics 2007,
26, 6581–6585. (c) Lavallo, V.; Dyker, C. A.; Donnadieu, B.; Bertrand,
2626
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Organometallics
ARTICLE
Schmidt, P.; Gaafar, A. E.-D. M.; Weng, M.; Marino, S.; Schoch, A.;
Amer, A.; Jochims, J. C. J. Chem. Soc., Perkin Trans. 1 1998, 947–953. For
related reactions, see also:(d) Wirschun, W.; Jochims, J. C. Synthesis
1997, 233–241. (e) Wirschun, W.; Maier, G.-M.; Jochims, J. C. Tetra-
hedron 1997, 53, 5755–5766. (f) Weng, M.; Geyer, A.; Friemel, A.;
Jochims, J. C.; Lutz, M. J. Prakt. Chem. 2000, 342, 486–493.
(31) Wirschun and Jochims (ref 30) present evidence in support of a
concerted, inverse electron demand [3þ2] cycloaddition mechanism.
For recent computational studies, see also: (a) Yang, S.-Y.; Lin, X.-F.;
Sun, C.-K.; Fang, D.-C. J. Mol. Struct. (THEOCHEM) 2007,
815, 127–133. Nevertheless, a stepwise mechanism in which CꢀN
bond formation is followed by ring-closure may not be entirely
discounted at this point.
R. H. J. Am. Chem. Soc. 2003, 125, 2546–2558. (c) Stewart, I. C.; Ung, T.;
Pletnev, A. A.; Berlin, J. M.; Grubbs, R. H.; Schrodi, Y. Org. Lett. 2007,
9, 1589–1592. (d) Chung, C. K.; Grubbs, R. H. Org. Lett. 2008,
10, 2693–2696. (e) Kuhn, K. M.; Bourg, J.-B.; Chung, C. K.; Virgil,
S. C.; Grubbs, R. H. J. Am. Chem. Soc. 2009, 131, 5313–5320.
(43) (a) Anderson, D. R.; Lavallo, V.; O’Leary, D. J.; Bertrand,
G.; Grubbs, R. H. Angew. Chem., Int. Ed. 2007, 46, 7262–7265. (b) Anderson,
D. R.; Ung, T.; Mkrtumyan, G.; Bertrand, G.; Grubbs, R. H.; Schrodi, Y.
Organometallics 2008, 27, 563–566. See also:(c) Vougioukalakis, G. C.;
Grubbs, R. H. J. Am. Chem. Soc. 2008, 130, 2234–2245. (d) Despagnet-
Ayoub, E.; Grubbs, R. H. Organometallics 2005,24, 338–340. (e) Rosen, E. L.;
Sung, D. H.; Chen, Z.; Lynch, V. M.; Bielawski, C. W. Organometallics 2010,
29, 250–256.
(44) Kingsbury, J. S.; Harrity, J. P. A.; Bonitatebus, P. J., Jr.; Hoveyda,
A. H. J. Am. Chem. Soc. 1999, 121, 791–799.
(45) Gessler, S.; Randl, S.; Blechert, S. Tetrahedron Lett. 2000, 41,
9973–9976.
(46) Van Veldhuizen, J. J.; Garber, S. B.; Kingsbury, J. S.; Hoveyda,
A. H. J. Am. Chem. Soc. 2002, 124, 4954–4955.
(47) Ragone, F.; Poater, A.; Cavallo, L. J. Am. Chem. Soc. 2010, 132,
4249–4258.
(48) Ritter, T.; Hejl, A.; Wenzel, A. G.; Funk, T. W.; Grubbs, R. H.
For examples related to the latter pathway(s), see:(b) Ung, G.; Mendoza-
Espinosa, D.; Bouffard, J.; Bertrand, G. Angew. Chem., Int. Ed. 2011, DOI:
10.1002/anie.201100420. (c) Krasinski, A.; Fokin, V. V.; Sharpless, K. B.
Org. Lett. 2004, 6, 1237–1240. (d) Kwok, S. W.; Fotsing, J. R.; Fraser, R. J.;
Rodionov, V. O.; Fokin, V. V. Org. Lett. 2010, 12, 4217–4219. (e) de Jong,
R. L. P.; Meijer, J.; Sukhai, R. S.; Brandsma, L. Recl. Trav. Chim. Pays-Bas
1982, 101, 310–313. (f) Drenth, W.; Nieuwdorp, G. H. E. Recl. Trav. Chim.
Pays-Bas 1969, 88, 307–312. (g) Mayer, R.; Gebhardt, B.; Fabian, J.; M€uller,
A. K. Angew. Chem., Int. Ed. Engl. 1964, 3, 134.
Organometallics 2006, 25, 5740–5745.
(49) Hejl, A. S. Thesis, California Institute of Technology, 2007.
(50) Vorfalt, T.; Wannowius, K.-J.; Plenio, H. Angew. Chem., Int. Ed.
2010, 49, 5533–5536.
(51) For a discussion on the effects of sterics on ruthenium-based
metathesis catalysts see ref 42.
(32) (a) Vernin, G.; Siv, C.; Metzger, J. Synthesis 1977, 691–693.
(b) Nimitsiriwat, N.; Gibson, V. C.; Marshall, E. L.; Takolpockdee, P.;
Tomov, A. K.; White, A. J. P.; Williams, D. J.; Elsegood, M. R. J.; Dale,
S. H. Inorg. Chem. 2007, 46, 9988–9997. (c) Barrett, A. G.; Crimmin,
M. R.; Hill, M. S.; Hitchcock, P. B.; Kociok-K€ohn, G.; Procopiou, P. A.
Inorg. Chem. 2008, 47, 7366–7376.
(33) Hartman, W. W.; Dickey, J. B. Org. Synth. 1934, 14, 163.
(34) (a) Hauber, S.-O.;Lissner, F.;Deacon, G. B.;Niemeyer, M.Angew.
Chem., Int. Ed. 2005, 44, 5871–5875. (b) Alexander, S. G.; Cole, M. L.;
Forsyth, C. M.; Furfari, S.; Konstas, K. Dalton Trans. 2009, 2326–2336.
(35) Throughout this article we use the notation Cxy to refer to
triazoliums and their derivatives wherein x refers to the triazene 6aꢀd,
and y the alkyne 7aꢀq (or alkyne equivalent) from which they are
derived (Scheme 5). Thus, for example, MIC Cab is derived from
triazene 6a and alkyne 7b.
(36) Tapu, D.; Dixon, D. A.; Roe, C. Chem. Rev. 2009, 109, 3385–3407.
(37) Kelly, R. A., III; Clavier, H.; Giudice, S.; Scott, N. M.; Stevens,
E. D.; Bordner, J.; Samardjiev, I.; Hoff, C. D.; Cavallo, L.; Nolan, S. P.
Organometallics 2008, 27, 202–210.
(38) (a) Chianese, A. R.; Kovacevic, A.; Zeglis, B. M.; Faller, J. M.;
Crabtree, R. H. Organometallics 2004, 23, 2461–2468. (b) Song, G.;
Zhang, Y.; Li, X. Organometallics 2008, 27, 1936–1943.
(39) (a) von Raguꢀe Schleyer, P.; Maerker, C.; Dransfeld, A.; Jiao, H.;
van Eikema Hommes, N. J. R. J. Am. Chem. Soc. 1996, 118, 6317–6318.
(b) Fernꢀandez, I.; Dyker, C. A.; DeHope, A.; Donnadieu, B.; Frenking,
G.; Bertrand, G. J. Am. Chem. Soc. 2009, 131, 11875–11881. (c) Caution
is warranted in the interpretation of NICS values, as their magnitude
does not quantitatively scale across different aromatic systems: (d) Gomes,
J. A. N. F.; Mallion, R. B. Chem. Rev. 2001, 101, 1349–1383.
(e)Katritzky, A. R.; Jug, K.;Oniciu, D. C.Chem. Rev. 2001, 101, 1421–1449.
(40) Enders, D.; Breuer, K.; Raabe, G.; Runsink, J.; Teles, J. H.; Melder,
J.-P.; Ebel, K.; Brode, S. Angew. Chem., Int. Ed. Engl. 1995, 34, 1021–1023.
(41) Tonner, R.; Heydenrych, G.; Frenking, G. ChemPhysChem
2008, 9, 1474–1481.
(42) (a) Sanford, M. S.; Love, J. A.; Grubbs, R. H. J. Am. Chem. Soc.
2001, 123, 6543–6554. (b) Trnka, T. M.; Morgan, J. P.; Sanford, M. S.;
Wilhelm, T. E.; Scholl, M.; Choi, T.-L.; Ding, S.; Day, M. W.; Grubbs,
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