2,6-dimethoxyphenyl-substituted n-heterocyclic carbenes (NHCs): A family of highly electron-rich organocatalysts

Article abstract of DOI:10.1002/ejoc.201200408

Based on our recent finding that 2,6-dimethoxyphenyl-substituted NHCs show superior reactivity in the hydroacylation reactions of electron-neutral olefins compared with known NHCs, we now report the syntheses and crystal structures of four highly electron

Full text of DOI:10.1002/ejoc.201200408

Job/Unit: O20408
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Date: 18-06-12 15:52:36
Pages: 9
FULL PAPER
DOI: 10.1002/ejoc.201200408
2,6-Dimethoxyphenyl-Substituted N-Heterocyclic Carbenes (NHCs): A Family
of Highly Electron-Rich Organocatalysts
Michael Schedler,[a] Roland Fröhlich,[a,b] Constantin-G. Daniliuc,[a,b] and Frank Glorius*[a]
Keywords: Carbenes / Organocatalysis / Umpolung / Hydroacylation
Based on our recent finding that 2,6-dimethoxyphenyl-sub-
stituted NHCs show superior reactivity in the hydroacylation
reactions of electron-neutral olefins compared with known
NHCs, we now report the syntheses and crystal structures
of four highly electron-rich 2,6-dimethoxyphenyl-substituted
NHCs and show the increase in efficiency caused by the
electron-rich aryl substituent in hydroacylation reactions.
nized that none of the chiral NHCs commonly used in or-
ganocatalysis was reactive and selective enough to achieve
this transformation in a satisfactory manner.[8]
Introduction
The observation that N-heterocyclic carbenes[1] (NHCs,
cf. Scheme 1) are able to catalyze the condensation of two
aldehydes to benzoin[2] has led to widespread interest in the
use of NHCs as organocatalysts.[3] The unique catalytic be-
havior of NHCs can be explained by the formation of the
Breslow intermediate, which leads to the umpolung of an
aldehyde. The ease of handling of azolium salts, which are
convenient NHC precursors, has facilitated the develop-
ment of various NHC-catalyzed reactions.[4] In addition to
the benzoin condensation reaction, the addition of the Bres-
low intermediate to α,β-unsaturated carbonyls (the Stetter
reaction) has been studied extensively.[5]
Thus, we focused on the design of new NHC precursors
following the observation that NHCs with electron-rich
aromatic substituents at one of the nitrogens showed higher
reactivity.[7b] In addition, we hoped that a more electron-
rich substituent would improve the enantioselectivity, as
predicted by the calculations of Hawkes and Yates.[9] Our
synthetic efforts led to the new highly electron-rich NHC
precursor 5 carrying a 2,6-dimethoxyphenyl moiety, which
led to an optimized enantioselectivity and also a quantita-
tive conversion in the catalyzed hydroacylation reaction (cf.
Scheme 2).
Scheme 1. NHCs commonly used in organocatalysis.
These classical NHC-catalyzed reactions have been en-
riched by the reaction between the Breslow intermediate
and rather electron-neutral multiple bonds,[6–8] initially in
intramolecular hydroacylations,[6] but more recently in
intermolecular hydroacylations.[7,8] When investigating the
asymmetric hydroacylation of cyclopropene 2, we recog-
Scheme 2. Effect of the 2,6-dimethoxyphenyl group on the hydro-
acylation reaction of 2.[8]
[a] Westfälische Wilhelms-Universität Münster, Organisch-
Chemisches Institut,
Corrensstrasse 40, 48149 Münster, Germany
Fax: +49-251-8333202
E-mail: glorius@uni-muenster.de
Results and Discussion
[b] Laboratory of Single-Crystal X-ray Structure Determination,
Westfälische Wilhelms-Universität Münster, Organisch-Chem-
isches Institut,
It would be highly desirable to have more of these elec-
tron-rich NHCs at hand, but no other 2,6-dimeth-
oxyphenyl-substituted triazolium salt has been reported be-
fore. Furthermore, no thiazolium or imidazolium salt with
the 2,6-dimethoxyphenyl moiety is known. Only a few ex-
Corrensstrasse 40, 48149 Münster, Germany
Fax: +49-251-83-33293
E-mail: frohlic@uni-muenster.de
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201200408.
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M. Schedler, R. Fröhlich, C.-G. Daniliuc, F. Glorius
FULL PAPER
amples of imidazolinium-derived NHCs with 2,6-dimeth- tron-rich and it should also be irreversible. Secondly, the
oxyphenyl groups are known, and these have only been steric effects of the ortho substituents destabilize the initial
used as ligands in transition-metal catalysis.[11] Lüning and tetrahedral adduct and accelerate the formal 1,2-H-shift to
co-workers used a bimacrocyclic concave imidazolinium-de- the planar Breslow intermediate. In addition, Bode states
rived NHC with 2,6-alkoxy substituents as an organocata- that the electron-rich aryl substituents stabilize the homo-
lyst.[12]
enolate I over the acyl anion II (cf. Scheme 4). Thus, the
Thus, herein we report the synthesis of 2,6-dimeth- positive charge in the azolium core is stabilized by the elec-
oxyphenyl-substituted versions of four commonly used tron-rich 2,6-dimethoxyphenyl substituent III, making the
NHC organocatalysts (cf. Scheme 3), which are representa- aldehyde carbon more nucleophilic and more reactive espe-
tive examples of the four NHC scaffolds (cf. Scheme 1). We cially in the reaction with poor electrophiles like olefins.
wanted to investigate whether our aforementioned findings
were simply a stroke of luck or whether the effect of the
Synthesis of the 2,6-Dimethoxyphenyl-
Substituted NHCs
2,6-dimethoxyphenyl substituent is a general phenomenon
that leads to a new class of NHCs beyond the known mes-
ityl-, phenyl-, and C6F5-substituted NHCs.[13] By using the
newly synthesized NHCs as catalysts we hoped to prove
that the highly electron-rich aryl substituent increases the
nucleophilicity of the carbene and hence amplifies the reac-
tivity of the Breslow intermediate. As shown by Bode et
al.,[13] the electron-rich ortho substituents have two crucial
functions in the formation of the Breslow intermediate.
First, electron-rich NHCs are poorer leaving groups than
electron-deficient NHCs, hence the initial addition of the
NHC to the aldehyde is reversible for C6F5-substituted
NHCs but irreversible for mesityl-substituted NHCs. There-
fore the addition of our 2,6-dimethoxy-substituted NHCs
to aldehydes should be faster as the NHC is even more elec-
To synthesize the four new NHCs we had to design three
synthetic routes (the IMes and SIMes derivatives 8b and 9b
could be synthesized from the same precursor). We began
with the synthesis of the new thiazolium-derived NHC 6b
based on the scaffold of the mesityl-substituted Isa-
NHC·HClO4 (6a), which has shown superb reactivity in in-
tramolecular hydroacylation reactions.[6a,6b,6d] Following
the synthesis[14] described for 6a, we synthesized the sought
after thiazolium salt 6b in a two-step process starting from
2,6-dimethoxyaniline (10) . The structure of 6b was unam-
biguously proved by single-crystal X-ray diffraction (cf.
Scheme 5).
Scheme 3. Scaffolds of commonly used NHCs in organocatalysis.
Scheme 5. Synthesis and X-ray crystal structure of the thiazolium
salt 6b. Reagents and conditions: a) aq. NaOH, CS2, DMSO, then
α-bromocycloheptanone, 45%; b) H2O2, aq. HOAc, then NaClO4,
MeOH, H2O, 56%. The counterion has been omitted from the
crystal structure for clarity.[16]
As the triazolium salt 7a is not only one of the most
often used NHC precursors but also very efficient in the
racemic hydroacylation of cyclopropenes,[7b] the synthesis
of the 2,6-dimethoxyphenyl-substituted triazolium salt 7b
was targeted following the procedure described by Struble
and Bode,[15] that was previously adapted by our group to
synthesize 5.[8] Following this protocol yielded only traces
of 7b, which could be attributed to the low stability of the
Scheme 4. Influence of the electron-rich aryl substituents on the
reactivity of NHCs.
2
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Dimethoxyphenyl-Substituted N-Heterocyclic Carbenes
amidrazone 16 at 120 °C, the temperature that is normally variant of the well known IMes-carbene 9a, which is gen-
needed for the cyclization step. Lowering the reaction tem- erally synthesized by a one-pot reaction starting from the
perature to 40 °C was beneficial but did not yield the triazo- corresponding aniline, glyoxal, and triethyl orthofor-
lium salt 7b, instead the water adduct of the NHC was mate.[19] However, this one-pot reaction did not yield any
formed, which was attributed to traces of water present dur- product when the electron-rich 2,6-dimethoxyaniline was
ing the reaction and the fact that 7b is more sensitive to used. Another way of synthesizing imidazolium salts is the
traces of water than known triazolium salts. The addition condensation of glyoxal with an aniline to obtain a diimine
of molecular sieves and an increase in the temperature to and cyclization of this diimine in a second step.[20] Again,
80 °C were finally found to be the best conditions for the this protocol did not work sufficiently well for 2,6-dimeth-
synthesis of 7b.[16] The structure of 7b was verified by X- oxyaniline. Hence, the synthetic route starting from for-
ray structural analysis (cf. Scheme 6).
mamidine 19 that was previously used by our group to syn-
thesize a library of substituted imidazolium salts[21] seems
to be the most efficient protocol for obtaining the imid-
azolium salt 9b (cf. Scheme 8).[22]
Scheme 6. Synthesis and X-ray crystal structure of the triazolium
salt 7b. Reagents and conditions: a) Me3OBF4, CH2Cl2; b) HCl in
dioxane, MeOH; c) HCl in dioxane, MeOH; d) HC(OEt)3, PhCl,
4 Å MS, 80 °C, 16 h, 10% over three steps. The counterion has
been omitted from the crystal structure for clarity.[16]
The imidazolinium salt 8bЈ could be obtained from the
diamine 18, which can be accessed easily by the reaction
of 2,6-dimethoxyaniline (10) with 1,2-dibromoethane. The
cyclization of 18 with triethyl orthoformate and ammonium
tetrafluoroborate yielded the imidazolinium tetrafluorobor-
ate salt 8bЈ.[17] This two-step reaction sequence proceeded
to give a low yield of 16% (cf. Scheme 7), hence alternative
pathways were investigated.
Scheme 8. Divergent synthesis and X-ray crystal structures of the
imidazolinium salt 8b and the imidazolium salt 9b. Reagents and
conditions: a) HC(OEt)3, HOAc, 140Ǟ160 °C, 90%; b) ClCH2-
CH2Cl, Hünig’s base, 47%; c) NaH, bromoacetaldehyde dimethyl
acetal, DMF, 86%; d) BF3·Et2O, MeCN, 77%. The counterions
have been omitted from the crystal structures for clarity.[16]
Performance of the 2,6-Dimethoxy-Substituted
NHCs in Hydroacylation Reactions
Scheme 7. Synthesis of imidazolium salt 8bЈ via the diamine 18.
Reagents: a) 1,2-dibromoethane; b) HC(OEt)3, NH4BF4, 16% over
two steps.
The four new NHCs were tested along with the estab-
An alternative synthetic route uses the formamidine 19, lished NHC precursors 6a and 7a as references in hydro-
which can be easily obtained from the aniline 10 in one acylation reactions that have been previously reported by
step. The reaction of 19 with 1,2-dichloroethane under basic our group.[6a,7b] The performance of the NHCs in the
conditions gave the imidazolinium chloride 8b in an im- hydroacylation of 3-methyl-3-phenylcyclopropene (2) with
proved yield of 47% (cf. Scheme 8).[18] The formamidine 19 p-chlorobenzaldehyde (1) is summarized in Table 1. The re-
can also be used to synthesize 9b, the 2,6-dimethoxyphenyl action proceeded quantitatively with 5 mol-% of 7a (En-
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M. Schedler, R. Fröhlich, C.-G. Daniliuc, F. Glorius
FULL PAPER
try 1), as reported previously;[7b] lowering the catalyst load- Table 2. Hydroacylation with a less reactive aldehyde.[a]
ing of 7a to 2.5 mol-% led to a lower yield (Entry 3). The
electron-rich triazolium salt 7b is evidently a more active
catalyst than 7a as it gave complete conversion with a cata-
lyst loading of 2.5 mol-% (Entry 5). The thiazolium-based
NHCs 6a and 6b yielded only small amounts of product
(Entries 2 and 4) and the 2,6-dimethoxy-substituted NHCs
8bЈ and 9b showed no catalytic activity for this transforma-
tion (Entries 6 and 7). Further lowering of the catalyst load-
Entry
Catalyst
Cat. loading [mol-%]
Yield [%][b]
ing to 1 mol-% of 7b was not tolerated and resulted in a
yield of only 10% (Entry 8).
1
2
3
4
5
6
7
7a
6a
7a
6b
7b
8bЈ
9b
20
10
10
10
10
10
10
67/5
5/0
34/2
Table 1. Hydroacylation of cyclopropene 2 with the new NHCs.[a]
20/0
62/3 (64[c])
7/0
0/0
[a] General reaction conditions: 21 (0.1 mmol, 1 equiv.),
2
(0.15 mmol, 1.5 equiv.), NHC·HX (x mol-%), K2CO3 (1 equiv.),
THF (0.25 m), 40 °C, 24 h. [b] The yields were determined by 1H
NMR spectroscopy with CH2Br2 as internal standard. For some
catalysts the second diastereomer could also be detected (second
yield). [c] The reaction was performed on a 0.5 mmol scale. Yield
after purification.
Entry
Catalyst
Cat. loading [mol-%]
Yield [%][b]
1
2
3
4
5
6
7
8
7a
6a
5
96/4
4/0
85/4
2.5
2.5
2.5
2.5
2.5
2.5
1
and 7b gave yields of 44 and 62% (Entries 3 and 5, respec-
tively). The two other dimethoxy-substituted NHCs 8bЈ and
9b gave lower yields (Entries 6 and 7).
7a
6b
7b
2/0
97/3 (96[c])
0/0
8bЈ
9b
Table 3. Intramolecular hydroacylation of 23.[a]
0/0
10/0
7b[d]
[a] General reaction conditions:
1
(0.2 mmol, 1 equiv.), 2
(0.3 mmol, 1.5 equiv.), NHC·HX (x mol-%), K2CO3 (1 equiv.),
THF (0.25 m), 40 °C, 24 h. [b] The yields were determined by 1H
NMR spectroscopy with CH2Br2 as internal standard. For some
catalysts the second diastereomer could also be detected (second
yield). [c] The reaction was performed on a 0.5 mmol scale. Yield
after purification. [d] Reaction performed on a 0.5 mmol scale.
Entry
Catalyst
Cat. loading [mol-%]
Yield [%][b]
The superiority of 7b was validated by using the less reac-
tive o-chlorobenzaldehyde (21) in the hydroacylation of 3-
methyl-3-phenylcyclopropene (2; cf. Table 2). This reaction
yielded, as previously reported,[7b] 67% of the acylcyclo-
propane 22 with 20 mol-% of 7a (Entry 1). The reaction
proceeded with only 10 mol-% of 7b to give a similar yield
of 62% (Entry 5), whereas the known catalyst 7a gave a
yield of only 34% with the lower catalyst loading (En-
try 3).[7b] Again, 8bЈ and 9b showed only low catalytic ac-
tivity (Entries 6 and 7), but the thiazolium salt 6b yielded
20% of the product 22 (Entry 4), whereas the mesityl-sub-
stituted NHC 6a only yielded 5% of the product (Entry 2).
The efficiency of the new catalysts was also investigated
in the intramolecular hydroacylation of 23 (Table 3). With
20 mol-% of 6a (Entry 1), a yield similar to the 57% re-
1
2
3
4
5
6
7
8
9
10
6a
6a
7a
6b
7b
8bЈ
9b
6a
6b
6b
20
10
10
10
10
10
10
1
51
98
44
quant.
62
23
9
15
quant. (91[c])
20
1
0.5
[a] General reaction conditions: 23 (0.1 mmol, 1 equiv.), NHC·HX
(x mol-%), DBU (2x mol-%), 1,4-dioxane (0.5 m), 120 °C, 2 h. [b]
The yields were determined by 1H NMR spectroscopy with CH2Br2
as internal standard. [c] The reaction was performed on a 0.5 mmol
scale. Yield after purification.
When lowering the catalyst loading to 1 mol-%, the di-
ported previously was obtained.[6a] Performing this reaction methoxy-substituted NHC 6b still gave a quantitative yield
with only 10 mol-% NHC revealed the superiority of 6b as (Entry 9), whereas the mesityl-substituted NHC 6a only
the hydroacylation proceeded with full conversion (En- gave a yield of 15% (Entry 8).[16] Further lowering the cata-
try 4). Surprisingly, 6a gave a higher yield of 98% with a lyst loading led to a reduced yield (20% of 24 with 0.5 mol-
lower catalyst loading (cf. Entries 2 and 4). This unexpected % 6b, Entry 10). The efficiency of 6b in this reaction is quite
relationship between yield and catalyst loading is the sub- remarkable and we wished to investigate whether the high
ject of ongoing research.[16] The triazolium-based NHCs 7a reactivity even at the unusually low catalyst loading of
4
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Dimethoxyphenyl-Substituted N-Heterocyclic Carbenes
1
with a Bruker AV 300 or AV 400 spectrometer. H chemical shifts
are reported in parts per million (δ scale) and are referenced to
residual protium in the NMR solvent [CDCl3: δ = 7.26 ppm
(CHCl3)]. Data are reported as follows: chemical shift [multiplicity
(s = singlet, d = doublet, t = triplet, sp = septet, m = multiplet, br.
= broad signal), coupling constant(s) (Hz), integration]. 13C NMR
spectra were recorded with a Bruker AV 300 or AV 400 spectrome-
ter. 13C chemical shifts are reported in parts per million (δ scale)
and are referenced to the carbon resonances of the solvent [δ =
77.16 ppm (CDCl3)]. IR spectra were obtained with a Varian Asso-
1 mol-% is only a result of the increased nucleophilicity of
the dimethoxy-substituted NHC or whether the electron-
rich aryl substituent also increased the stability of the
NHC. We hence carried out the hydroacylation of 23 with-
out the inert gas. Under these conditions no conversion was
observed with 10 mol-% of 6a and Ͻ5% of 24 was obtained
with the new NHC 6b (with 10 mol-% catalyst loading).
Thus, it seems that the 2,6-dimethoxy substituent has no or
little influence on the air/water-stability of the NHC and
inert gas techniques are mandatory for NHC-catalyzed hy- ciated FT-IR 3100 Excalibur spectrometer with an ATR unit and
are reported in frequency of absorption (cm–1). GC–MS spectra
were recorded with an Agilent Technologies 7890A GC system with
an Agilent 5975C VL MSD or 5975 inert Mass Selective Detector
droacylation reactions.
(EI) on a HP-5MS column (0.25 mm ϫ30 m; film: 0.25 μm).
Method A began with an injection at temperature T0 (50 °C),
Conclusions
which is held for 3 min. The column was then heated to tempera-
ture T1 (290 °C, ramp: 40 °C), which is held for 3 min. HRMS were
recorded with a Bruker Daltonics MicroTof spectrometer using an
electrospray (ESI) ionization source.
Four new NHCs with an electron-rich 2,6-dimeth-
oxyphenyl substituent have been synthesized and represent
the four classes of commonly used NHC organocatalysts.
Their structures were determined by X-ray diffraction
analysis. The first applications of these new NHCs in catal-
ysis showed the potential superiority of this new family of
NHCs over known catalysts and the higher efficiency of the
dimethoxy-substituted NHCs was proven by the full con-
versions observed for hydroacylation reactions with catalyst
loadings as low as 1 mol-%. This higher reactivity can be
explained by the higher nucleophilicity of both the NHC
and the Breslow intermediate. Further research to improve
the efficiency of known NHC-catalyzed reactions by using
the new catalysts is ongoing. In addition, these catalysts
should enable transformations that were out of reach with
the previously known NHCs.
3-(2,6-Dimethoxyphenyl)-5,6,7,8-tetrahydro-4H-cyclohepta[d]thi-
azol-3-ium Perchlorate (6b):[14] 2,6-Dimethoxyaniline (10; 453 mg,
2.96 mmol, 1 equiv.) was dissolved in DMSO (1.5 mL, 2 m) and
20 m aq. NaOH (150 μL, 3 mmol, 1 equiv.) was added. CS2
(179 μL, 2.96 mmol, 1 equiv.) was added and the resulting black
solution was stirred for 1 h at room temperature. 2-Bromocyclohep-
tanone (566 mg, 2.96 mmol, 1 equiv.) was added to the reaction
and the mixture was stirred overnight. H2O (3 mL) was added lead-
ing to a precipitate. The water was decanted and the precipitate
washed twice with water. The precipitate was suspended in EtOH
(3.5 mL) and concentrated HCl (0.15 mL) was added. The mixture
was heated at reflux for 1 h and after cooling to room temperature
was stored in the fridge overnight to complete the precipitation.
The precipitate was filtered off and washed with pentane, resulting
in 11 as a beige solid (429 mg, 1.34 mmol, 45%), which was used
in the next step without further purification. Rf (pentane/EtOAc,
Experimental Section
7:3) = 0.22 (UV, KMnO ). FTIR (ATR): ν = 3005, 2925, 2842,
˜
4
General: All reactions were performed in oven- or flame-dried reac-
tion vessels, modified Schlenk flasks, or round-bottomed flasks.
The flasks were fitted with Teflon screw caps and reactions were
conducted under argon. Gas-tight syringes with stainless-steel
needles or cannulae were used to transfer air- and moisture-sensi-
tive liquids. All moisture- and/or air-sensitive solid compounds
were manipulated inside an argon-filled glovebox. Flash column
chromatography was performed on silica gel (40–63 μm, 230–
400 mesh, Merck). Analytical TLC was performed on silica gel 60
F254 aluminum plates (Merck) containing a 254 nm fluorescent in-
dicator. TLC plates were visualized by exposure to short-wave ul-
traviolet light (254 nm) and to a solution of KMnO4 (1 g of
KMnO4, 6 g of K2CO3, and 0.1 g of KOH in 100 mL of H2O) or
vanillin (2 g of vanillin and 4 mL of concentrated H2SO4 in 100 mL
of EtOH) followed by heating.
1593, 1481, 1460, 1434, 1330, 1297, 1260, 1233, 1209, 1106, 1053,
1027, 983, 925, 841, 822, 780, 747, 696, 659, 609 cm–1. 1H NMR
(300 MHz, CDCl3): δ = 7.40 (t, J = 8.5 Hz, 1 H), 6.68 (d, J =
8.5 Hz, 2 H), 3.80 (s, 6 H), 2.62–2.59 (m, 2 H), 2.26–2.24 (m, 2 H),
1.79–1.74 (m, 4 H), 1.60–1.52 (m, 2 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 186.9, 156.4, 142.1, 131.2, 123.0, 115.8, 104.9, 56.4,
31.1, 29.0, 27.5, 27.3, 26.0 ppm. GC–MS (Method A): RT
=
11.83 min (321, 290, 288, 273, 260, 166, 154. 133, 197, 97. 91, 77,
65, 39). HRMS (ESI): calcd. for C16H19NO2S2H+ 322.0930; found
322.0932; calcd. for C16H19NO2S2Na+ 344.0749; found 344.0751.
Compound 11 (408 mg, 1.34 mmol, 1 equiv.) was suspended in
acetic acid (5.5 mL, 0.25 m) and H2O2 (35% in H2O, 378 μL,
4.42 mmol, 3.3 equiv.) was added slowly while keeping the reaction
mixture at room temperature. The resulting red solution was stirred
for 45 min at room temperature. All volatiles were removed in
vacuo and the resulting red oil was dissolved in methanol (1 mL).
NaClO4·H2O (753 mg, 5.36 mmol, 4 equiv.) dissolved in a mixture
of methanol (3.1 mL) and water (1.6 mL) was added to the reaction
at 0 °C. After stirring for 30 min the mixture was warmed to room
temperature and water (2.5 mL) was added. The mixture was ex-
tracted with CH2Cl2 (3ϫ 5 mL). The combined organic phases
were dried with MgSO4, filtered, and the volatiles removed in
vacuo. The resulting red oil was purified by flash column
chromatography (CH2Cl2/MeOH, 95:5) on silica gel resulting in 6b
as a beige solid (292 mg, 0.75 mmol, 56%). Rf (CH2Cl2/MeOH,
Organic solutions were concentrated at 40 °C on Heidolph 4000
rotary evaporators at about 10 mbar followed by drying by means
of a vacuum pump (p Ͻ 1 mbar). Commercial reagents and sol-
vents were used as received with the following exceptions: THF was
purified by heating at reflux over Na/benzophenone under a posi-
tive argon pressure followed by distillation; CH2Cl2 was purified
by heating at reflux over CaH2 under a positive argon pressure
followed by distillation; K2CO3 was dried by heating at 110 °C for
12 h, cooling under argon, and storing inside an argon-filled
glovebox; triethyl orthoformate was purified by distillation under
argon and stored under argon. 1H NMR spectra were recorded
95:5) = 0.31 (UV). FTIR (ATR): ν = 3074, 2930, 2851, 1604, 1592,
˜
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1485, 1303, 1264, 1075, 958, 780, 732, 621, 566 cm–1. 1H NMR
(ATR): ν = 2999, 2934, 2831, 1664, 1581, 1461, 1430, 1311, 1256,
˜
(400 MHz, CDCl3): δ = 9.41 (s, 1 H), 7.49 (t, J = 8.6 Hz, 1 H), 1204, 1108, 1033, 984, 801, 768, 715, 616 cm–1. 1H NMR
6.71 (d, J = 8.6 Hz, 2 H), 3.77 (s, 6 H), 3.02–3.00 (m, 2 H), 2.53–
2.50 (m, 2 H), 1.92–1.77 (m, 4 H), 1.61–1.56 (m, 2 H) ppm. 13C
NMR (101 MHz, CDCl3): δ = 156.6, 154.6, 149.1, 138.2, 133.6,
113.5, 104.6, 56.5, 30.8, 27.9, 27.1, 26.5, 25.0 ppm. HRMS (ESI):
calcd. for C16H20NO2S+ 290.1209; found 290.1217.
(300 MHz, C6D6): δ = 9.04 (s, 1 H), 6.79 (t, J = 8.3 Hz, 2 H), 6.36
(d, J = 8.3 Hz, 4 H), 3.26 (s, 12 H) ppm. 13C NMR (101 MHz,
C6D6): δ = 154.7, 152.3, 125.5, 122.2, 100.5, 55.6 ppm. HRMS
(ESI): calcd. for C17H20N2O4H+ 317.1496; found 317.1500.
1,3-Bis(2,6-dimethoxyphenyl)-4,5-dihydro-1H-imidazol-3-ium Chlor-
ide (8b):[18] Formamidine 19 (268 mg, 0.85 mmol, 1 equiv.) was dis-
solved in dry 1,2-dichloroethane (670 μL, 8.46 mmol, 10 equiv.) in
a flame-dried Schlenk tube. Hünig’s base (158 μL, 0.93 mmol,
1.1 equiv.) was added to the mixture and the Schlenk tube was
evacuated until the solvent started bubbling. The tube was sealed
under static vacuum and the mixture stirred at 120 °C for 24 h. All
the volatiles were removed in vacuo and the resulting yellow solid
was purified by flash column chromatography (CH2Cl2/MeOH,
95:5 to 90:10) on silica gel and 8b was obtained as an off-white
solid (152 mg, 0.40 mmol, 47%). Rf (CH2Cl2/MeOH, 90:10) = 0.18
2-(2,6-Dimethoxyphenyl)-2,5,6,7-tetrahydropyrrolo[2,1-c][1,2,4]tri-
azol-4-ium Chloride (7b):[8,16] 2-Pyrrolidone (12; 779 μL,
10.1 mmol, 1 equiv.) was dissolved in CH2Cl2 (50 mL, 0.2 m) and
Me3OBF4 (1793 mg, 12.1 mmol, 1.2 equiv.) was added. The mix-
ture was stirred at room temperature overnight. Saturated
NaHCO3 solution (50 mL) was added slowly (15 min) to the reac-
tion mixture. The organic phase was separated and the aqueous
phase was extracted with CH2Cl2 (3ϫ 50 mL). The combined or-
ganic phases were dried with Na2SO4 and filtered. Most of the
CH2Cl2 was removed on a rotary evaporator at 40 °C and a pres-
sure of Ն200 mbar (the imidate is volatile!) to give 13 as a colorless
oil, which was used directly without further purification.
(UV, KMnO ). FTIR (ATR): ν = 3006, 2941, 2838, 1614, 1597,
˜
4
1479, 1449, 1251, 1169, 1106, 981, 854, 774, 728, 558, 533 cm–1. 1H
NMR (300 MHz, CDCl3): δ = 8.26 (s, 1 H), 7.33 (t, J = 8.5 Hz, 2
Di-tert-butyl 1-phenylhydrazine-1,2-dicarboxylate (14; 3.72 g,
10.1 mmol, 1 equiv.) was dissolved in methanol (25 mL) and HCl
(4 m in 1,4-dioxane, 25 mL, 101 mmol, 10 equiv.) was added slowly
to the solution. The mixture was stirred for 4 h at room tempera-
ture. Thereafter, all the volatiles were removed in vacuo to give the
hydrazine hydrochloride 15 as an orange solid.[23]
H), 6.65 (d, J = 8.6 Hz, 4 H), 4.62 (s, 4 H), 3.93 (s, 12 H) ppm. 13
C
NMR (75 MHz, CDCl3): δ = 160.4, 155.2, 131.2, 112.8, 104.7, 56.7,
+
51.6 ppm. HRMS (ESI): calcd. for C19H23N2O4 343.1652; found
343.1666.
1,3-Bis(2,6-dimethoxyphenyl)-4,5-dihydro-1H-imidazol-3-ium Tetra-
fluoroborate (8bЈ):[17] 2,6-Dimethoxyaniline (10; 872 mg,
5.69 mmol, 2 equiv.) was dissolved in 1,2-dibromoethane (245 μL,
2.85 mmol, 1 equiv.) in a flame-dried Schlenk tube and the flask
was sealed under argon. The mixture was stirred at 100 °C for
14.5 h resulting in a solid reaction mixture, which was dissolved in
CH2Cl2 (20 mL) and 1 m aq. NaOH (20 mL). The aqueous phase
was extracted with CH2Cl2 (3ϫ 20 mL) and the mixed organic
phases were washed with brine, dried with Na2SO4, and filtered.
Removal of all the volatiles in vacuo resulted in diamine 18 as a
red-colored oil, which was used directly in the next step without
further purification.
The imidate 13 was dissolved in methanol (40 mL, 0.4 m) and
added to the hydrazine hydrochloride 15. HCl (4 m in 1,4-dioxane,
250 μL, 1.01 mmol, 0.1 equiv.) was added to the reaction and the
mixture was stirred at room temperature overnight. All the volatiles
were removed in vacuo and the resulting amidrazone 16 was used
without purification in the next step. Rf (CH2Cl2/MeOH, 90:10) =
0.19 (UV, KMnO4).
The amidrazone 16 was dissolved in chlorobenzene (10 mL, 1 m)
and activated molecular sieves (4 Å) were added to the solution.
Triethyl orthoformate (13.3 mL, 80 mmol, 8 equiv.) and HCl (4 m
in 1,4-dioxane, 2.50 mL, 10 mmol, 1 equiv.) were added to the reac-
tion mixture. The mixture was heated to 80 °C overnight resulting
in a homogeneous solution. The molecular sieves were filtered off,
washed with CH2Cl2, and the filtrate was concentrated in vacuo.
The resulting oil was purified by flash column chromatography
(CH2Cl2/MeOH, 95:5 to 90:10) on silica gel resulting in 7b as a
colorless solid (273 mg, 0.97 mmol, 10% over three steps). Rf
The diamine 18 was dissolved in triethyl orthoformate (5 mL,
30 mmol, 10 equiv.) in a flame-dried Schlenk tube and ammonium
tetrafluoroborate (312 mg, 2.97 mmol, 1.05 equiv.) was added. The
sealed tube was stirred at 120 °C for 16.5 h. All the volatiles were
removed in vacuo and the resulting brown oil was purified by flash
column chromatography (toluene/MeOH, 90:10) on silica gel re-
sulting in 8bЈ as an off-white solid (195 mg, 0.45 mmol, 16% over
two steps). Rf (toluene/MeOH, 90:10) = 0.05 (UV, KMnO4). FTIR
(CH Cl /MeOH, 90:10) = 0.08 (UV, KMnO ). FTIR (ATR): ν =
˜
2
2
4
3437, 3014, 2947, 2843, 1674, 1588, 1526, 1585, 1549, 1434, 1384,
1303, 1265, 1176, 1106, 1017, 969, 907, 781, 727, 640, 597 cm–1. 1H
NMR (300 MHz, CDCl3): δ = 11.23 (s, 1 H), 7.48 (t, J = 8.6 Hz,
1 H), 6.66 (d, J = 8.6 Hz, 2 H), 4.92–4.90 (m, 2 H), 3.81 (s, 6 H),
3.22 (t, J = 7.7 Hz, 2 H), 2.92–2.82 (m, 2 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 161.5, 155.7, 144.4, 133.6, 113.3, 104.3, 56.5,
(ATR): ν = 3098, 3017, 2951, 2847, 1614, 1599, 1484, 1435, 1316,
˜
1300, 1258, 188, 1113, 1051, 1024, 775, 723 cm–1. 1H NMR
(300 MHz, CDCl3): δ = 8.02 (s, 1 H), 7.36 (t, J = 8.5 Hz, 2 H),
6.67 (d, J = 8.5 Hz, 4 H), 4.55 (s, 4 H), 3.94 (s, 12 H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 160.4, 155.2, 131.3, 112.7, 104.7, 56.7,
+
+
51.3 ppm. HRMS (ESI): calcd. for C19H23N2O4 343.1652; found
48.7, 27.0, 22.2 ppm. HRMS (ESI): calcd. for C13H16N3O2
343.1669.
246.1237; found 246.1246.
N,NЈ-Bis(2,6-dimethoxyphenyl)formamidine (19):[21] Triethyl ortho-
formate (689 μL, 4.14 mmol, 1 equiv.) and acetic acid (12 μL,
0.21 mmol, 0.05 equiv.) were added to a round-bottomed flask con-
taining 2,6-dimethoxyaniline (10; 1.26 g, 8.27 mmol, 2 equiv.). The
flask was equipped with a distillation apparatus and flushed with
argon. The mixture was heated at 140 °C for 3 h and afterwards
at 160 °C for 0.5 h. Upon cooling the reaction mixture to room
temperature it solidified. Pentane (20 mL) was added, the mixture
was stirred, and the resulting precipitate was filtered off and
1,3-Bis(2,6-dimethoxyphenyl)-1H-imidazol-3-ium Iodide (9b):[22]
Formamidine 19 (511 mg, 1.62 mmol, 1 equiv.) was dissolved in
DMF (16 mL, 0.1 m) and the solution was cooled to 0 °C. After
adding NaH (60% dispersion in mineral oil, 116 mg, 2.91 mmol,
1.8 equiv.), the mixture was stirred for 5 min at 0 °C, warmed to
room temperature, and stirred for 100 min. Bromoacetaldehyde di-
methyl acetal (380 μL, 3.23 mmol, 2 equiv.) was added and the mix-
ture was heated at 76 °C for 90 min. All the volatiles were removed
in vacuo and acetonitrile (20 mL) was added to the resulting yellow
washed with pentane resulting in 1.18 g (3.72 mmol, 90%) of 19 as solid. The mixture was filtered and the colorless precipitate was
a colorless solid. Rf (CH2Cl2/MeOH, 95:5) = 0.24 (UV). FTIR washed with acetonitrile. The solvent of the filtrate was removed
6
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Dimethoxyphenyl-Substituted N-Heterocyclic Carbenes
Chem. 2008, 120, 3166–3216; Angew. Chem. Int. Ed. 2008, 47,
in vacuo and the resulting yellow oil was purified by flash column
chromatography (CH2Cl2 to CH2Cl2/MeOH, 95:5) on silica gel to
yield 20 (563 mg, 1.39 mmol, 86%). Rf (CH2Cl2/MeOH, 90:10) =
0.41 (UV).
3122–3172; d) T. Dröge, F. Glorius, Angew. Chem. 2010, 122,
7094–7107; Angew. Chem. Int. Ed. 2010, 49, 6940–6952; for the
use of NHCs as ligands in transition-metal catalysis and orga-
nometallic chemistry, see: e) S. P. Nolan, in: N-Heterocyclic
Carbenes in Synthesis (Ed.: S. P. Nolan), Wiley-VCH,
Weinheim, Germany, 2006; f) F. Glorius, in: N-Heterocyclic
Carbenes in Transition Metal Catalysis (Ed.: F. Glorius),
Springer, Berlin, 2007; g) E. A. B. Kantchev, C. J. O’Brien,
M. G. Organ, Angew. Chem. 2007, 119, 2824–2970; Angew.
Chem. Int. Ed. 2007, 46, 2768–2813; h) S. Würtz, F. Glorius,
Acc. Chem. Res. 2008, 41, 1523–1533; i) S. Díez-González, N.
Marion, S. P. Nolan, Chem. Rev. 2009, 109, 3612–3676.
Compound 20 (563 mg, 1.39 mmol, 1 equiv.) was dissolved in
acetonitrile (14 mL, 0.1 m) and BF3·Et2O (1.05 mL, 8.35 mmol,
6 equiv.) was added to the solution. After stirring the mixture at
70 °C for 3 h, additional BF3·Et2O (3 equiv.) was added. The mix-
ture was stirred at 70 °C for 16 h. After cooling to room tempera-
ture all the volatiles were removed in vacuo and methanol (14 mL,
0.1 m) and sodium iodide (1.04 g, 6.95 mmol, 5 equiv.) were added
to the residue. The mixture was heated at reflux for 30 min and
subsequently all the volatiles were removed in vacuo. The residue
was purified by flash column chromatography (CH2Cl2/MeOH,
97.5:2.5 to 90:10) on silica gel to obtain 9b (503 mg, 1.07 mmol,
77%) as a slightly yellow solid. Rf (CH2Cl2/MeOH, 95:5) = 0.20
[2]
[3]
a) F. Wöhler, J. Liebig, Ann. Pharm. 1832, 3, 249–282; b) A.
Lapworth, J. Am. Chem. Soc. 1903, 25, 995–1005.
For reviews on NHC organocatalysis, see: a) K. Zeitler, Angew.
Chem. 2005, 117, 7674–7678; Angew. Chem. Int. Ed. 2005, 44,
7506–7510; b) N. Marion, S. Díez-González, S. P. Nolan, An-
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46, 2988–3000; c) D. Enders, O. Niemeier, A. Henseler, Chem.
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Scheidt, Aldrichim. Acta 2009, 42, 55–66; e) J. L. Moore, T.
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Rovis, Aldrichim. Acta 2011, 44, 3–11; g) K. Hirano, I. Piel, F.
Glorius, Chem. Lett. 2011, 40, 786–791; h) V. Nair, R. S.
Menon, A. T. Biju, C. R. Sinu, R. R. Paul, A. Jose, V. Sreeku-
mar, Chem. Soc. Rev. 2011, 40, 5336–5346; i) A. T. Biju, N.
Kuhl, F. Glorius, Acc. Chem. Res. 2011, 44, 1182–1195; j) P.-
C. Chiang, J. W. Bode, TCI Mail 2011, 149, 2–17; k) D. T. Co-
hen, K. A. Scheidt, Chem. Sci. 2012, 3, 53–57; l) X. Bugaut, F.
Glorius, Chem. Soc. Rev. 2012, DOI: 10.1039/C2CS15333E.
For selected most recent advances, see: a) A. T. Biju, M. Pad-
manaban, N. E. Wurz, F. Glorius, Angew. Chem. 2011, 123,
8562–8565; Angew. Chem. Int. Ed. 2011, 50, 8412–8415; b) T. Y.
Jian, L. He, C. Tang, S. Ye, Angew. Chem. 2011, 123, 9270–
9273; Angew. Chem. Int. Ed. 2011, 50, 9104–9107; c) X. Fang,
X. Chen, H. Lv, Y. R. Chi, Angew. Chem. 2011, 123, 11986–
11989; Angew. Chem. Int. Ed. 2011, 50, 11782–11785; d) L.
Candish, D. W. Lupton, Chem. Sci. 2012, 3, 380–383; e) D. A.
DiRocco, E. L. Noey, K. N. Houk, T. Rovis, Angew. Chem.
2012, 124, 2441–2444; Angew. Chem. Int. Ed. 2012, 51, 2391–
2394; f) C. A. Rose, S. Gundala, C.-L. Fagan, J. F. Franz, S. J.
Connon, K. Zeitler, Chem. Sci. 2012, 3, 735–740; g) J. Mahat-
thananchai, J. Kaeobamrung, J. W. Bode, ACS Catal. 2012, 2,
494–503.
For reviews, see: a) H. Stetter, H. Kuhlmann, in: Organic Reac-
tions (Ed.: L. A. Paquette), Wiley, New York, 1991, vol. 40, pp.
407–496; b) J. Read de Alaniz, T. Rovis, Synlett 2009, 1189–
1207.
a) K. Hirano, A. T. Biju, I. Piel, F. Glorius, J. Am. Chem. Soc.
2009, 131, 14190–14191; b) A. T. Biju, N. E. Wurz, F. Glorius,
J. Am. Chem. Soc. 2010, 132, 5970–5971; c) I. Piel, M. Stein-
metz, K. Hirano, R. Fröhlich, S. Grimme, F. Glorius, Angew.
Chem. 2011, 123, 5087–5091; Angew. Chem. Int. Ed. 2011, 50,
4983–4987; d) I. Piel, M. D. Pawelczyk, K. Hirano, R.
Fröhlich, F. Glorius, Eur. J. Org. Chem. 2011, 5475–5484; e)
D. A. DiRocco, T. Rovis, Angew. Chem. 2011, 123, 8130–8132;
Angew. Chem. Int. Ed. 2011, 50, 7982–7983; f) M. Padmana-
ban, A. T. Biju, F. Glorius, Org. Lett. 2011, 13, 5624–5627.
(UV). FTIR (ATR): ν = 3188, 3168, 3016, 2982, 2943, 2841, 1676,
˜
1596, 1551, 1484, 1434, 1330, 1301, 1262, 1110, 1085, 1051, 1023,
1
959, 783, 753, 728, 651, 605 cm–1. H NMR (300 MHz, CDCl3): δ
= 8.92 (t, J = 1.5 Hz, 1 H), 7.63 (d, J = 1.5 Hz, 2 H), 7.45 (t, J =
8.6 Hz, 2 H), 6.74 (d, J = 8.6 Hz, 4 H), 3.90 (s, 12 H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 154.1, 138.9, 132.5, 124.1, 111.8,
+
104.9, 56.9 ppm. HRMS (ESI): calcd. for C19H21N2O4 341.1496;
found 341.1499.
General Procedure for the Catalysis
Hydroacylation of Cyclopropene 2: A flame-dried Schlenk tube was
charged with aldehyde (1 equiv.), K2CO3 (1 equiv.), and the NHC
precursor (x mol-%). Dry THF (0.25 m) and 3-methyl-3-phenylcy-
clopropene (2; 1.5 equiv.) were added through a syringe. The tube
was sealed under argon and stirred at 40 °C for 24 h. The reaction
mixture was filtered through a short pad of silica and all the vola-
tiles of the filtrate were removed in vacuo. The yield was either
measured by 1H NMR spectroscopy using CH2Br2 as internal stan-
dard or by isolation of the acylcyclopropane by flash column
chromatography on silica gel (pentane/ethyl acetate, 98:2).
[4]
Intramolecular Hydroacylation of 23: A flame-dried Schlenk tube
was charged with the aldehyde 23 (1 equiv.) and the NHC precursor
(x mol-%) in a glovebox. Dry dioxane (0.5 m) and DBU (2x mol-
%) were added through a syringe. The tube was sealed and stirred
at 120 °C for 2 h. The reaction mixture was filtered through a short
pad of silica and all the volatiles were removed in vacuo. The yield
was either measured by 1H NMR spectroscopy using CH2Br2 as
internal standard or by isolation of the chromanone 24 by flash
column chromatography on silica gel (pentane/ethyl acetate, 95:5).
[5]
[6]
Supporting Information (see footnote on the first page of this arti-
cle): Details of the synthesis of the starting materials, description
of the catalysis, NMR spectra, and crystallographic data.
Acknowledgments
We are indebted to the Fonds der Chemischen Industrie for a pre-
doctoral fellowship (M. S.). We thank Nathalie E. Wurz for helpful
discussions, Karin Gottschalk for skillful technical assistance, and
the Deutsche Forschungsgemeinschaft (DFG) (SPP 1179) for gen-
erous financial support. The research of F. G. was supported by
the Alfried Krupp von Bohlen und Halbach Foundation (Alfried
Krupp Prize for Young University Teachers).
[7]
[8]
a) A. T. Biju, F. Glorius, Angew. Chem. 2010, 122, 9955–9958;
Angew. Chem. Int. Ed. 2010, 49, 9761–9764; b) X. Bugaut, F.
Liu, F. Glorius, J. Am. Chem. Soc. 2011, 133, 8130–8133.
F. Liu, X. Bugaut, M. Schedler, R. Fröhlich, F. Glorius, Angew.
Chem. 2011, 123, 12834–12838; Angew. Chem. Int. Ed. 2011,
50, 12626–12630.
[9]
K. J. Hawkes, B. F. Yates, Eur. J. Org. Chem. 2008, 5563–5570.
[10]
[1] a) A. J. Arduengo III, Acc. Chem. Res. 1999, 32, 913–921; b)
D. Bourissou, O. Guerret, F. P. Gabbaï, G. Bertrand, Chem.
Rev. 2000, 100, 39–92; c) F. E. Hahn, M. C. Jahnke, Angew.
By using K3PO4 instead of K2CO3 and changing the solvent
from THF to 1,4-dioxane, the yield was increased to 98% and
the ee to 94%.
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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/KAP1
Date: 18-06-12 15:52:36
Pages: 9
M. Schedler, R. Fröhlich, C.-G. Daniliuc, F. Glorius
FULL PAPER
[11]
[17] K. V. S. Ranganath, J. Kloesges, A. H. Schäfer, F. Glorius, An-
gew. Chem. 2010, 122, 7952–7956; Angew. Chem. Int. Ed. 2010,
49, 7786–7789.
[18] K. M. Kuhn, R. H. Grubbs, Org. Lett. 2008, 10, 2075–2077.
[19] a) A. J. Arduengo III, U.S. Pat. 5077414, 1991; b) M. H. Voges,
C. Rømming, M. Tilset, Organometallics 1999, 18, 529–533.
[20] a) M. E. Günay, M. Aygün, A. Kartal, B. Çetinkaya, E. Kendi,
Cryst. Res. Technol. 2006, 41, 615–621; b) G. Berthon-Gelloz,
M. A. Siegler, A. L. Spek, B. Tinant, J. N. H. Reek, I. E.
Markó, Dalton Trans. 2010, 39, 1444–1446.
a) N. Gürbüz, I. Özdemira, B. Çetinkaya, Tetrahedron Lett.
2005, 46, 2273–2277; b) A. P. Blum, T. Ritter, R. H. Grubbs,
Organometallics 2007, 26, 2122–2124; c) N. Stylianides, A. A.
Danopoulos, D. Pugh, F. Hancock, A. Zanotti-Gerosa, Orga-
nometallics 2007, 26, 5627–5635; d) Y. Matsumoto, K. Yam-
ada, K. Tomioka, J. Org. Chem. 2008, 73, 4578–4581.
a) O. Winkelmann, C. Näther, U. Lüning, Eur. J. Org. Chem.
2007, 981–987; b) O. Winkelmann, U. Lüning, Supramol.
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Lüning, Org. Biomol. Chem. 2009, 7, 553–556.
[12]
[13]
[21] K. Hirano, S. Urban, C. Wang, F. Glorius, Org. Lett. 2009, 11,
1019–1022.
J. Mahatthananchai, J. W. Bode, Chem. Sci. 2012, 3, 192–197.
[14] R. Lebeuf, K. Hirano, F. Glorius, Org. Lett. 2008, 10, 4243–
[22] A. Bertogg, F. Camponovo, A. Togni, Eur. J. Inorg. Chem.
2005, 347–356.
4246.
[15] J. R. Struble, J. W. Bode, Org. Synth. 2010, 87, 362–376.
[16] See the Supporting Information for further information.
CCDC-867802 (for 7b), -867803 (for 8bЈ), -867804 (for 9b),
and -867805 (for 6b) contain the supplementary crystallo-
graphic 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.
[23] As reported previously (see ref.[8]), deprotection also yields
about 15% of 4-chloro-2,6-dimethoxyaniline. As this byprod-
uct was unreactive in the following steps and easily removed
in the subsequent reactions, the crude mixture of 15 and the
chlorinated aniline was used without further purification.
Received: March 29, 2012
Published Online: ᭿
8
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/KAP1
Date: 18-06-12 15:52:36
Pages: 9
Dimethoxyphenyl-Substituted N-Heterocyclic Carbenes
Organocatalysts
The synthesis and crystal structures of four
highly electron-rich 2,6-dimethoxyphenyl-
substituted NHCs are reported. These
NHCs should have interesting applications
as ligands or in NHC organocatalysis.
M. Schedler, R. Fröhlich, C.-G. Daniliuc,
F. Glorius* ........................................ 1–9
2,6-Dimethoxyphenyl-Substituted N-Het-
erocyclic Carbenes (NHCs): A Family of
Highly Electron-Rich Organocatalysts
Keywords: Carbenes / Organocatalysis /
Umpolung / Hydroacylation
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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