On the dual role of N-heterocyclic carbenes as bases and nucleophiles in reactions with organic halides

Article abstract of DOI:10.1055/s-0031-1289593

The synthetic consequences of different basicities, nucleophilicities, and sterics of N-heterocyclic carbenes have been studied in reactions of imidazolin-2-ylidenes with organic halides. Highly nucleophilic and less basic carbenes cleanly gave alkyli-deneimidazolines, the deoxy analogues of Breslow-type intermediates. More basic NHCs engaged in unwanted deprotonation or dehydrohalogenation reactions. Georg Thieme Verlag Stuttgart. New York.

Full text of DOI:10.1055/s-0031-1289593

3784
FEATURE ARTICLE
On the Dual Role of N-Heterocyclic Carbenes as Bases and Nucleophiles
in Reactions with Organic Halides
B
enzylidene
s
fromh
Carbenes ristiane E. I. Knappke,a Anthony J. Arduengo, III,b Haijun Jiao,c Jörg-Martin Neudörfl,a
Axel Jacobi von Wangelin*a
a
Department of Chemistry, University of Cologne, Greinstr. 4, 50939 Koeln, Germany
Fax +49(221)4705057; E-mail: axel.jacobi@uni-koeln.de
Department of Chemistry, University of Alabama, Tuscaloosa, AL 35487, USA
Leibniz Institute for Catalysis, Albert-Einstein-Str. 29a, 18059 Rostock, Germany
b
c
Received 11 August 2011; revised 18 September 2011
diamines bear a close conceptual relationship to Breslow-
Abstract: The synthetic consequences of different basicities, nu-
cleophilicities, and sterics of N-heterocyclic carbenes have been
studied in reactions of imidazolin-2-ylidenes with organic halides.
Highly nucleophilic and less basic carbenes cleanly gave alkyli-
deneimidazolines, the deoxy analogues of Breslow-type intermedi-
ates. More basic NHCs engaged in unwanted deprotonation or
dehydrohalogenation reactions.
type intermediates and can be viewed as their formal
deoxy analogues (Scheme 1).7
R1
R2
O
N
Breslow intermediates
NHC catalysis
NHC
NHC
R2
elusive structure
N
OH
Key words: N-heterocyclic carbenes, enamines, umpolung, imida-
zoles, nucleophilicity
R1
R1
R2
H
N
deoxy analogues
some precedents
isolated & characterized
R2
Br
Since their first isolation in 1991 by Arduengo et al.,1 N-
heterocyclic carbenes (NHCs) have been developed into a
highly useful class of carbon nucleophiles with major ap-
plications as ligands in metal complexes and organic cat-
alysts for acylation reactions.2 A large number of
structure–property relationships of metal–NHC complex-
es were established based upon experimental data includ-
ing IR bond stretching frequencies (e.g., trans-CO
ligands), Tolman’s electronic parameters, or buried vol-
umes.3 The paucity of such data for NHC-based organic
catalysts underscores the need for further studies. Howev-
er, some general trends can be deduced from the type of
reactions for which NHCs are competent catalysts: Triaz-
olin-5-ylidenes and thiazolin-2-ylidenes are privileged
catalysts for benzoin and Stetter-type reactions.2g Homo-
enolate chemistry is most effective with thiazolin-2-
ylidenes and imidazolin-2-ylidenes.2f–i The basicities of
several N-heterocyclic carbenes (or acidities of azolium
salts as their conjugate acids) have been determined ex-
perimentally and theoretically,4 but there is still little
known about the gradation of reactivity within a class of
NHCs. A recent report by Mayr et al. established the high
Lewis basicities and the moderate nucleophilicities of
three N-heterocyclic carbenes in comparison with classi-
cal nucleophilic organocatalysts.5 We have studied the nu-
cleophilicity and basicity of various N-heterocyclic
carbenes in irreversible substitution reactions with organ-
ic halides. Such reactions constitute an under-utilized al-
ternative to NHC-mediated umpolung reactions of
carbonyl compounds.6 The resultant nucleophilic ene-1,1-
N
R1
Scheme 1 Formal enediamines derived from N-heterocyclic car-
benes
Base-mediated reactions of imidazolin-2-ylidenes with
primary alkyl halides give 2-substituted imidazolin-2-
ylidenes via sequential substitution and dehydrohalogena-
tion.6 The intermediate imidazolium species cannot be
isolated in most cases, but rather undergo rapid deproto-
nation under the basic reaction conditions. Reactions with
aliphatic alkyl halides are somewhat unselective due to
competitive elimination of hydrogen halide, protonation,
or further alkylation of the reactive enediamine species.8
On the other hand, b,g-unsaturated alkyl halides (i.e., al-
lyl, benzyl halides) can be selectively converted into the
corresponding 2-substituted imidazolinylidenes in good
yields.6 This is a direct consequence of the mesomeric sta-
bilization of the electron-rich ene-1,1-diamine moiety by
the p-substituent.
We have reported an operationally simple protocol for the
synthesis of conjugated 2-alkylideneimidazolines from
imidazolium halides and unsaturated alkyl halides at room
temperature in the presence of two equivalents of potassi-
um tert-butoxide.6a The overall base-mediated umpolung
is documented by the presence of a polarized exocyclic
double bond with nucleophilic a- and g-positions. NMR
spectra and calculations indicate a significant zwitterionic
character of the extended conjugated system that allows
rotation about the exocyclic formal double bond
(Scheme 2).6 The synthesis and characterization of such
formal deoxy analogues of aldehyde-derived Breslow in-
termediates has received little attention,9 but promises
SYNTHESIS 2011, No. 23, pp 3784–3795
x
x.
x
x
.
2
0
1
1
Advanced online publication: 07.11.2011
DOI: 10.1055/s-0031-1289593; Art ID: T79311SS
© Georg Thieme Verlag Stuttgart · New York

FEATURE ARTICLE
Biographical Sketches
Benzylidenes from Carbenes
3785
Christiane E. I. Knappke reagents and materials. Part recognized by the Depart-
studied chemistry at the of this work was performed ment of Chemistry Award
University of Cologne and in
graduated in 2010. Her Anthony J. Arduengo, III at Award (2011) of the Uni-
Ph.D. thesis centered the University of Alabama. versity of Cologne. Chris-
collaboration
with (2008) and the Kurt-Alder-
around new azolylidenes Christiane’s Ph.D. research tiane is currently working
derived from N-heterocy- was supported by a fellow- with Harry L. Anderson at
clic carbenes and their ap- ship of the Fonds der Che- Oxford as a DAAD postdoc-
plication as umpolung mischen Industrie and was toral fellow.
A. J. Arduengo, III present- in the Central Research and in Braunschweig, Germany.
ly holds the Saxon Profes- Development at DuPont in His current research pro-
sorship of Chemistry at the Wilmington, Delaware. He grams include chemical hy-
University of Alabama in is a Fellow of the American drogen storage, materials
Tuscaloosa. He received Association for the Ad- for nonlinear optical appli-
B.S. (1974) and Ph.D. vancement of Science and cations, organic photovolta-
(1976) degrees in chemistry holds an Alexander von ics, and studies of unusual
from the Georgia Institute of Humboldt Senior Research valency.
Technology. He initiated his Prize. He is guest professor
independent research career at the Technical University
Haijun Jiao studied Chem- von Rague-Schleyer. Haijun tational Chemistry group
istry at the Shanxi Normal was a postdoctoral fellow at there. His research interests
University in China and the the Universities of Erlangen are the structure of organo-
University of Erlangen- (v. Rague-Schleyer, Gladysz) metallic complexes and het-
Nürnberg in Germany. He and Rennes (Halet) before erogeneous clusters, and
graduated in 1995 with a joining the Leibniz Institute their catalytic reactivity in
Ph.D. thesis on aromaticity of Catalysis in Rostock as organic transformations.
and anti-aromaticity con- research group leader. Since
cepts in the group of Paul 2002, he heads the Compu-
Jörg-Martin
Neudörfl with work on crystal struc- phy team at the Department
studied Chemistry at the ture analyses and inclusion of Chemistry and since 2007
University of Cologne, properties of organic arene- leads the Crystallographic
where he graduated in the hexacarboxylates. In 2002 Laboratory at the Institute of
group of Prof. O. Ermer he joined the crystallogra- Organic Chemistry.
Axel Jacobi von Wangelin visits to the University of Noether and Heisenberg fel-
hails from Berlin and stud- Cardiff and Degussa AG, lowships of the DFG, the
ied chemistry at the Univer- Axel joined Barry Trost’s Thieme Journal Award, and
sities of Erlangen and Utah. labs at Stanford University the Wissenschaftspreis of
He obtained his Ph.D. with as a DAAD fellow. From the Industrie-Club. Since
Matthias Beller at the Leib- 2005 until 2011, he was a October 2011, Axel is Pro-
niz-Institute of Catalysis on research group leader at the fessor of Organic Chemistry
carbonylation and cycload- University of Cologne. Axel at the University of
dition reactions. After short has
received
Emmy- Regensburg.
Synthesis 2011, No. 23, 3784–3795 © Thieme Stuttgart · New York

3786
C. E. I. Knappke et al.
FEATURE ARTICLE
new insight into the properties and reactivities of such NCN moiety shows a signal at d = 145.8, the exocyclic a-
enediamines and the relationship to their well-studied CH is more than 75 ppm up-field at d = 70.2. The olefinic
oxygenated counterparts.
a-CH of 4a also exhibits an up-field shifted 1H resonance
at d = 3.76 (in THF-d8). EXSY NMR spectra displayed a
chemical interconversion between the two peripheral di-
isopropylphenyl groups as a result of conjugative stabili-
zation of the zwitterionic resonance structure and free
rotation about the exocyclic double bond.6a Facile substi-
tution reactions with various electrophiles (H+, methyl,
alkyl, prenyl, benzyl) toward new imidazolium salts with
branched side chains also indicated the high nucleophilic-
ity of benzylidene 4a (Scheme 3).6a
Ar
Ar
Ar
X
N
N
N
KOt-Bu (2 equiv)
THF, r.t.
N
N
N
Ar X
Ar
Ar
nucleophilic
α- and γ-carbons
In this study, we have extended the scope of this general
benzylideneimidazoline synthesis to include five N-het-
erocyclic carbenes of the imidazolin-2-ylidene type 1a–e
and three substituted benzyl bromides 2a–c. We estab-
lished a structure–reactivity profile for the underlying
nucleophilic substitution toward enediamines 4a–l
(Table 1). N-Heterocyclic carbenes 1a–e were generated
by potassium tert-butoxide mediated deprotonation of the
corresponding imidazolium chlorides in tetrahydrofuran
solution at room temperature. Nucleophilic substitution
reactions were performed on preparative (0.5–3 mmol) or
analytical (0.02–0.04 mmol) scales, the latter in sealed
NMR tubes under in situ 1H NMR monitoring. Generally,
the electron-withdrawing effect of the imidazolium moi-
ety alone is not sufficient to trigger deprotonation at the
exocyclic a-position in the benzylimidazolium intermedi-
ates 3 by excess carbene, which is in contrast to analogous
reactions with the more basic benzimidazolin-2-ylidenes
and imidazolidin-2-ylidenes.8a,c,f Thus, one equivalent of
base was added to secure full conversion of carbene 1 and
benzyl bromide 2. We observed that the a-benzyl substit-
uent enhances the acidity of the a-proton and facilitates
deprotonation of the intermediate 2-substituted imidazoli-
um salt.6a The choice of base was governed by the reactiv-
ity of the electrophile: potassium tert-butoxide led to
major formation of 4,4¢-dinitrostilbene in reactions with
strongly electrophilic 2c.10 These reactions were run with-
out additional potassium tert-butoxide (1 equiv used for
carbene formation) but with a second equivalent of NHC
acting as base (entries 3, 9).
Scheme 2 Synthesis of ene-1,1-diamines from alk-2-enyl halides
and NHCs with umpolung at exocyclic a- and g-carbons
R3
Br
R1
N
R1
N
R1
N
R3
KOt-Bu
2
THF, r.t.
THF, r.t.
N
N
R2 Cl
R2
N
R2
Br
3
1
R3
R3
R1
R1
N
R4X
KOt-Bu
N
N
R2
N
R2
R4
R
H
4 = H, Me, alkyl,
prenyl, benzyl
X
4
Scheme 3 Base-mediated synthesis of 2-benzylideneimidazoles 4
To extend our knowledge of structure–property relation-
ships, we focused on reactions of N-heterocyclic carbenes
1 with benzyl halides 2 that proved especially selective
giving quantitative yields of the 2-benzylideneimidazo-
lines 4 in most cases (Scheme 3). The resultant structural
motif is formally a deoxygenated relative of the Breslow-
type intermediates derived from the addition of NHCs to
benzaldehydes. 4-Tolyl-derivative 4a was prepared from
1,3-bis(2,6-diisopropylphenyl)imidazolium chloride (1a)
and 4-methylbenzyl bromide (2a) in >99% yield
(Figure 1).6b The electron-donating character of the 6p-
electron heterocycle renders the exocyclic alkene moiety
highly polarized and strongly nucleophilic. To a first ap-
proximation, the electronic nature of the double bond cor-
relates with the 13C NMR resonances.8c,9o The quaternary
The bulky and electron-rich bis(diisopropylphenyl)-sub-
stituted carbene 1a cleanly reacted with all three benzyl
bromides 2a–c to give the desired enediamines 4a–c in
good to excellent yields (entries 1–3). Carbenes 1c and
1d, bearing at least one small N-methyl substituent,
showed a similar behavior with good yields of the result-
ing enediamines 4g–i (entries 7–9). While 4g was formed
as pure E-isomer with the bulky benzylidene and diisopro-
pylaniline substituents adopting a trans-configuration, 4i
showed rapid interconversion on the NMR timescale and
therefore was obtained as an E/Z mixture. The reactivity
of carbenes 1b and 1e was significantly affected by the
tert-butyl groups. Carbene 1b could only be reacted with
the more activated benzyl bromides 2b and 2c affording
enediamines 4e and 4f in moderate yields but exclusively
as Z-stereoisomers (entries 5 and 6).
- quantitative yield
- polarized exocyclic
double bond
N
- partial zwitterionic
character of ground state
145.8 ppm
70.2 ppm
3.76 ppm
N
H
- rotation about
formal double bond
- engages in facile
nucleophilic substitution
4a
Figure 1 Properties of 4-methylbenzylidene derivative 4a
Synthesis 2011, No. 23, 3784–3795 © Thieme Stuttgart · New York

FEATURE ARTICLE
Benzylidenes from Carbenes
3787
Table 1 Reactions of Imidazolin-2-ylidenes 1 with Benzyl Halides 2
R3
R3
R1
R1
R1
N
Br
N
base (1 equiv)
THF, r.t.
N
+
+
R3
N
R2
N
R2
Br
N
R2
1a–e
2a–c
3a–l
4a–l
Entry
Carbene
Electrophile
Enediamine 4a
Yieldb (%) of 4
9
Br
10
11
8
7
1
4a
4b
4c
>99
13
16
24
2a
23
20
R3
12
14
15
17
6
22
N
N
Br
N
2
5
4
21
19
2
3
79
18
Br
2b
N
14'
12'
17'
15'
6'
Br
13'
16'
11'
10'
7'
8'
>99c
O2N
1a
9'
2c
9
d
8
7
4
5
6
2a
2b
2c
4d
–
R3
19
12
N
N
10
11
6
(Z)-4e
(Z)-4f
65e
18
N
2
4
5
16
17
15
N
20e,f
13
14
1b
9
8
7
12
10
11
6
7
2a
(E)-4g
60e
N
N
N
2
5
4
14
15
16
N
17
18
19
13
1c
R3
7
13
g,h
8
9
2a
2c
4h
4i
–
N
N
6
12
N
2
10 11
5
4
89c,i
9
N
1d
8
R3
12
10
11
12
2a
2b
2c
4j
4k
4l
–
7
N
N
11
6
82j
N
2
9
10
5
4
8
N
c
–
1e
a R3 = Me, Br, NO2; atom numbering refers to NMR assignment in the experimental section.
b Extensive purification of compounds proved difficult due to their sensitivity to air and moisture. Thus, products might still contain minor
amounts of inorganic impurities.
c A second equivalent of N-heterocyclic carbene served as base; no KOt-Bu was added.
d 3d was detected by 1H NMR monitoring, yield not determined.
e Yield determined by 1H NMR from conversion of carbene vs. internal standard TMS.
f Use of KOt-Bu led to major formation of 4,4¢-dinitrostilbene.
g Not determined.
h Compound 4h was observed indirectly by trapping with 4-methylbenzyl bromide.6a
i Configurationally unstable; mixture of E- and Z-isomers.
j Yield of 3k.
Synthesis 2011, No. 23, 3784–3795 © Thieme Stuttgart · New York

3788
C. E. I. Knappke et al.
FEATURE ARTICLE
Ar
However, reaction of 1b with 4-methylbenzyl bromide
(2a) gave the corresponding 2-benzylimidazolium deriva-
tive 3d according to 1H NMR monitoring, while no depro-
tonation to 4d occurred. Di-tert-butyl-substituted NHC 1e
exhibited no conversion into enediamines with 2a–c (en-
tries 10–12). It is important to note, that carbene 1e has the
highest basicity in the series.4b Consistently, its reaction
with 2c led to major formation of 4,4¢-dinitrostilbene.10
Treatment of 1e with 2a resulted in the formation of a red-
N
1a
Cl
r.t.
N
5 (89%)
but . . .
Ar
Ar
N
1a
H
Br
+
r.t.
N
Br
1
Ar
colored solution which H NMR spectra suggest to be
caused by the deprotonation of the 4-methylbenzyl
bromide by the strongly basic carbene 1e. With more elec-
trophilic 2b, 2-(4-bromobenzyl)-1,3-di-tert-butylimida-
zolium bromide (3k) was formed in 82% yield. Further
addition of base (KOt-Bu, NaH, or KHMDS) effected no
deprotonation to 4k. In the presence of butyllithium, 3k
was subject to lithium–bromine exchange (Scheme 4).11
These observations are in accordance with a high steric
encumbrance about the exocyclic a-carbon (and a low
acidity of the a-CH2 moiety) which impedes deprotona-
tion and planarization to a conjugated benzylidene
system. Generally, the degrees of basicity and nucleophi-
licity of the N-heterocyclic carbene are decisive for the se-
lective formation of the primary substitution products 3 or
the secondary elimination products 4. With highly basic
carbene 1e, deprotonation of the electrophiles 2a and 2c is
the dominant, but nonproductive, pathway (Scheme 4).
An identical observation was made when using allyl bro-
mide as electrophile, while the less reactive allyl chloride
showed no consumption even at elevated temperature (80
°C). In contrast, carbene 1a cleanly reacted with allyl
chloride at room temperature to give 1,3-bis(2,6-diisopro-
pylphenyl)-2-(prop-2-enylidene)imidazoline (5) in 89%
yield. Although carbene 1a is the weakest base in the in-
vestigated NHC series,4 it proved sufficiently basic to
deprotonate 9-bromofluorene (affording 9,9¢-bifluore-
nylidene) and 9-(2-chloroethylidene)fluorene.12 Carbene
1a also induced HBr elimination in reactions with 1-bro-
mo-3,4-epoxybutane and 1,2-dibromobutane (Scheme 5).
R
Cl
N
Cl
1a or 1e
r.t.
H
N
R
(Ar = 2,6-diisopropylphenyl, R = aryl or tert-butyl)
Scheme 5 Behavior of NHCs in reactions with allyl halides
The para-substituents of the benzylidene moieties exert a
significant influence on the stability of the prepared ene-
diamines 4a–c,e–i by actively participating in the conju-
gative stabilization of the extended p-system. Generally,
enediamines of this type are sensitive to air and moisture.
Yellow solid 4a is prone to rapid oxidative degradation
and protonation when exposed to air. Oxidation results in
the formation of 1,3-bis(2,6-diisopropylphenyl)imidazoli-
um and 4-methylbenzoate. Similar oxidative degradations
were reported for Breslow-type intermediates.7c,13 In con-
trast, nitro derivative 4c was subject to much slower oxi-
dative or protolytic degradation which allowed us to grow
crystals suitable for X-ray crystallography under ambient
conditions. Nevertheless, prolonged exposure to air led to
similar degradation products. The extended conjugated
system of 4c exhibits a deep-purple color with metallic
shine. Crystal structure analysis and NMR data are indic-
ative of significant contribution of the zwitterionic struc-
1
ture to the electronic ground state (Figure 2). H NMR
spectra display only one signal set for the syn- and anti-
configuration of diisopropylphenyl substituents and the
imidazoline backbone (C4, C5). This is a direct conse-
quence of a low-bond order of the exocyclic double bond
(partial single bond character) resulting in rapid intercon-
version on the NMR timescale. The exchange in 4a is
slower and gives separate signal sets for the N-aryl rings,
but shows exchange in EXSY-NMR experiments.
Br
t-Bu
or
N
2a
Br
H
KOt-Bu
N
t-Bu
base
t-Bu
4k
Y
Y = Br (3k, 82%)
N
H
H
2b
n-BuLi
1e
KOt-Bu
O
O
N
Y = Li
NO2
N
O
N O
Br
t-Bu
Ar
Ar
N
N
2c
2c
KOt-Bu
r.t.
N
N
O2N
Ar
Ar
4c
Scheme 4 Alternative products from reactions of 1e with 2a–c
Figure 2 Resonance structures of 4c (Ar = 2,6-diisopropylphenyl)
Synthesis 2011, No. 23, 3784–3795 © Thieme Stuttgart · New York

FEATURE ARTICLE
Benzylidenes from Carbenes
3789
uents. Nitrobenzylidene 4c was remarkably stable to-
wards air; attempts to methylate 4c with methyl iodide
were also not successful. This testifies to the delocaliza-
tion of electron density resulting in lower nucleophilicity
at the exocyclic a-carbon. Tolyl derivative 4a and other
benzylidenes without strong electron-withdrawing sub-
stituents exhibited higher nucleophilicities and underwent
facile alkylation.6a
Table 3 Absorption Maxima of 4c in Various Solventsa
Figure 3 Crystal structure of 4c. Only one position of the disor-
dered isopropyl groups is shown
Entry
1
Solvent
DMSO
MeOH
EtOH
eb
lmax (nm)
Table 2 Selected Bond Lengths and Angles of Nitro Derivative 4c
46.7
32.7
24.5
36.7
597
596
593
585
582
580
578
578
570
559
550
548
545
543
535
530
521
513
Bond lengths (pm)
Angles (°)
2
C4–C5
C5–C6
C6–N2
C6–N3
142.5
C4–C5–C6
135.0
105.2
–107.8
81.5
3
139.8
137.1
137.7
N2–C6–N3
4
DMF
C19–N2–C7–C8
C20–N3–C21–C22
5
CHCl3
4.81
8.93
37.5
6
CH2Cl2
MeCN
7
The crystal structure analysis of 4c (Figure 3, Table 2)
supports the zwitterionic character, as the bond length of
the exocyclic double bond is 140 pm (typical styryl sys-
tems: 134 pm).14 The length of the benzylic HC–C6H4NO2
bond is 143 pm (vs. 147 pm).14 Both bond lengths indicate
an average bond order between 1 and 2.15 The nitrophenyl
moiety displays slightly alternating C–C bond lengths,
which correlate with the quinoid structure of the zwitteri-
onic resonance form. Consistently, the terminal CAr–NO2
bond is rather short (143 pm, typically 147 pm).14 The
benzylic ring spans an angle of 23° with the imidazoline.
The molecules form zigzag chains in the crystal. The
shortest distance of 316 pm between two molecules with-
in these chains is located between O1 of one molecule and
C19 of the next. Together with the deep color and its me-
tallic shine (similar to I2 crystals) of the solid, this points
to an intermolecular charge-transfer-stabilized p,p-inter-
action.16 Compound 4c exhibits strong positive solvato-
chromism in solution due to a less polar ground state and
a more polar excited state which roughly correlates with
the solvent polarity (Table 3). The energy and intensity of
the absorption are indicative of a charge-transfer excita-
tion.17 Enediamine 4i has a similar dark color and solvato-
chromic effect, but proved to be much less stable, possibly
due to lesser steric shielding by the small N-alkyl substit-
8
H2O (pH 14)
acetone
THF
80.1
20.7
9
10
11
12
13
14
15
16
17
18
7.58
EtOAc
1,4-dioxane
benzene
toluene
Et2O
6.02
2.25
2.27
2.38
4.33
2.24
2.02
1.84
CCl4
cyclohexane
pentane
a Depicted energy diagram for illustrative purposes only.
b Literature value for the dielectric constant.18
Previously, we described the in situ generation of acry-
lonitrile derivative 6, another enediamine with a distinct
push-pull p-system (Scheme 6). Having ascertained the
relatively great stability of nitrobenzylidene 4c, we per-
Synthesis 2011, No. 23, 3784–3795 © Thieme Stuttgart · New York

3790
C. E. I. Knappke et al.
FEATURE ARTICLE
formed a large-scale synthesis from 1a and bromoacetoni- idazole and the benzyl group influence the acidity of the
trile and isolated 6 as stable, colorless solid in 98% yield. alkylimidazolium species. To support our preparative
The crystal structure analysis revealed significant contri- findings, we have calculated the Gibbs energies DG of the
bution of a zwitterionic structure to the ground state isodesmic reaction between NHCs 1a–c and benzylimida-
(Figure 4, Table 4). The effect is somewhat less pro- zolium species (3, see Table 5).19
nounced than for 4c. Consistently, slow interconversion
Table 5 Calculated DG of the Deprotonation of 2-Benzylimidazoli-
between syn- and anti-N-aryl rings on the NMR timescale
um Cations 3a–i and 3k by Carbenes 1a–ea
was observed.6a
R3
R3
R1
R1
R1
R1
N
N
N
N
Ar
Ar
Ar
ΔG
N
N
+
+
H
1. KOt-Bu
(2 equiv)
C
C
N
N
N
N
N
N
N
R2
N
R2
N
R2
N
R2
H
2.
Br
CN
1
3
4
(1 equiv)
Ar
Entry NHC Benzylimidazolium ion 3b
DG (kcal/mol)
6
Cl
(98%)
R1
R2
R3
(2 equiv)
1
2
1a
1a
1a
1b
1b
1b
1c
1d
1d
1e
Ar
Ar
Me
Br
3a
3b
3c
3d
3e
3f
–2.95
–6.83
–13.63
+0.44
–2.79
–10.88
–1.29
+0.71
–10.85
–0.29
Scheme 6 Synthesis of acrylonitrile derivative 6
Ar
Ar
3
Ar
Ar
NO2
Me
Br
4
Ar
t-Bu
t-Bu
t-Bu
Ar
5
Ar
6
Ar
NO2
Me
Me
NO2
Br
7
Me
Me
Me
t-Bu
3g
3h
3i
8
Et
9
Et
10
t-Bu
3k
a Calculations at the B3LYP/6-31G* level with Gaussian 03.
b Ar = 2,6-diisopropylphenyl.
Figure 4 Crystal structure of 6
Table 5 suggests that N-heterocyclic carbenes 1 are most-
ly stronger bases than the corresponding benzylidene im-
idazolines 4 (negative DG values). The calculated Gibbs
energies clearly mirror the high influence of the para-sub-
stituent R3 on the acidity of the a-position. With 4-methyl
substitution, the basicity of the benzylidene is similar to
the carbene (entries 4, 7, and 8). Strongly negative values
were only obtained for the generation of the nitro deriva-
tives (entries 3, 6, 9). Because all N-substituents in the in-
vestigated series exhibit an inductive effect, their
influence is rather subtle. (Note: Unlike unsubstituted
phenyl rings, the diisopropylphenyl groups are almost
perpendicular to the imidazole plane.20) Carbenes with N-
aryl substituents show a slightly higher preference than N-
alkyl substituents for the formation of enediamines 4. This
is remarkable since alkyl-substituted carbenes are gener-
ally the stronger bases. The steric bulk about the exocyclic
a-CH moiety seems to play a critical role by influencing
the stability of the formed enediamines. The diisopropyl-
phenyl rings can adopt a conformation where repulsion
with the benzylidene substituent is minimized, whereas
the rather ball-like alkyl groups cannot. A simple space-
Table 4 Selected Bond Lengths and Angles of Acrylonitrile 6
Bond lengths (pm)
Angles (°)
C1–C16
C1–N1
137.7
C1–C16–C17
C16–C17–N3
N1–C1–C2
125.3
175.9
105.4
95.6
136.7
136.9
139.9
115.7
C1–N2
C16–C17
C17–N3
C1–N1–C18–C19
C1–N2–C2–C3
–100.5
We assume that reactions of NHCs with organic halides
involve the intermediacy of a 2-alkylimidazolium species.
As already discussed, imidazolium cations induce high
acidity at the a-position of the 2-substituent due to their
electron-deficient aromaticity. Deprotonation can be ef-
fected either by the carbene itself or by additional base
added to the reaction. The nature of substituents at the im-
Synthesis 2011, No. 23, 3784–3795 © Thieme Stuttgart · New York

FEATURE ARTICLE
Benzylidenes from Carbenes
3791
(THF-d8 at dH = 3.58, dC = 67.4; benzene-d6 at dH = 7.27, dC = 128.0,
CD3CN at dH = 1.93, dC = 1.3, CD2Cl2 at dH = 5.32, dC = 53.5). Ab-
breviations for 13C-APT/DEPTQ-NMR21 data: u = up (CH3 or CH),
d = down (CH2 or Cq). Peaks were assigned based on H,H-COSY,
H,C-HMQC, H,C-HMBC, and H,H-NOESY/EXSY (mixing time
d8 = 500 ms) correlation spectra. For full atom assignments, see
also Supporting Information. Conversions of in situ NMR experi-
ments were determined relative to the carbene via peak integration
against TMS, which was added as internal reference. IR-ATR spec-
troscopy was performed on a Perkin-Elmer 100 Paragon FT-IR.
ESI-MS were measured with a Finnigan MAT 900S and an Agilent
LC/MSD VL G1956A, respectively. Exact masses (HRMS) were
determined by peak matching method. UV/Vis absorptions were re-
corded on an OceanOptics USB2000 Fiber Optic and a Perkin-
Elmer Lambda35. Crystal structure data were collected on a Nonius
KappaCCD diffractometer with phi and omega scans using mono-
chromated Mo-Ka radiation, and the structures were solved by di-
rect methods using SHELXS97 and refined with SHELXL97.22
Melting points were determined with a Büchi B-510 apparatus.
99.998% argon from Linde or N2 was used for manipulations under
inert atmosphere. All described reactions were carried out under in-
ert atmosphere either in a dry box or applying standard Schlenk
techniques. Celite was dried in high vacuum under heating over
night prior to use. The isolated enediamine compounds might still
contain traces of inorganic impurities since extended purification
procedures were hampered by the high sensitivity to air and mois-
ture.
filling model of the elusive 4k supports this hypothesis, as
no planar arrangement of imidazole and 4-bromophenyl
group is feasible, whereas benzylimidazolium species 3k
can relax to a twisted conformation. Despite the experi-
mental results, the calculated DG for the deprotonation of
3k is slightly negative.
In conclusion, a combined synthetic and theoretical study
of the consequences of basicity, nucleophilicity, and ster-
ics of N-heterocyclic carbenes in substitution reactions
with benzyl bromides has been performed. Subtle changes
in the substitution pattern of the NHC can have a dramatic
influence on reaction selectivity and stability of the result-
ant enediamines. The basicity of the investigated NHCs
increases in the order 1a < 1c < 1d < 1b < 1e with the sub-
stitution of N-aryl-substituents by alkyl substituents, es-
pecially bulky ones.4 On the other hand, the steric
shielding of the carbenoid atom increases in the order: 1d
< 1c < 1a < 1b < 1e. Carbenes 1a, 1c, and 1d, bearing not
too sterically demanding N-substituents, showed similar
reactivity with alkyl halides. The N-aryl-substituted ene-
diamines 4a–c derived from 1a showed higher stability
(toward oxidation and protonation) than those derived
from the N-alkyl-substituted carbenes 1c and 1d. This can
be attributed to the effective shielding of the exocyclic
double bond by the ortho-substituted N-aryl groups. The 1,3-Bis(2,6-diisopropylphenyl)-2-(4-methylbenzylidene)-2,3-di-
hydro-1H-imidazole (4a)
introduction of more steric bulk in the carbenes, i.e. the
presence of N-tert-butyl substituents, prompted a lower
propensity to engage in substitution reactions with alkyl
halides. The higher basicity of the carbene facilitates com-
petitive alkyl halide deprotonation. On the other hand we
observed, that the acidity of the intermediate 2-substituted
imidazolium salts 3 derived from 1b and 1e seemed to be
lower. In the case of 1b, an additional electron-withdraw-
ing group at the benzyl group was required for deprotona-
tive enediamine formation. In case of 1e, additional steric
strain inhibits the planarization associated with the forma-
tion of enediamines. These observations result in the fol-
lowing order of reactivity in the investigated series of
benzylidene imidazoline syntheses involving sequential
substitution and deprotonation: 1a ≈ 1c ≈ 1d > 1b >> 1e.
The use of NHCs as nucleophilic organocatalysts is still
an emerging field in the arena of metal-free reaction meth-
odologies, and until now, the choice of catalyst for a par-
ticular reaction is based on wide parameter screenings.
Further investigations into similar structure–property re-
lationships may help to rationalize the (rarely predictable)
influence of peripheral and core modifications of the mod-
ular NHC structure on activity and selectivity in organic
reactions and even suggest new modes of reactivity.
In a dry box, 1,3-bis(2,6-diisopropylphenyl)imidazolin-2-ylidene23
(1.55 g, 4.00 mmol) was dissolved in THF (40 mL). 4-Methylben-
zyl bromide (0.74 g, 4.0 mmol) was added with stirring. KOt-Bu
(0.45 g, 4.0 mmol) was added to the yellow turbid soln. After stir-
ring for 24 h at r.t., the reaction was filtered through Celite. The sol-
vent was removed from the filtrate yielding 4a (4.09 mmol, quant.)
as a yellow solid.
1H NMR (360 MHz, benzene-d6): d = 7.37 (dd, JHH = 6.7 Hz,
3
3JHH = 8.6 Hz, 1 H, H9¢), 7.29–7.25 (m, 3 H, H8¢, H10¢, H9), 7.12
(d, 3JHH = 7.7 Hz, 2 H, H8, H10), 6.71 (d, 3JHH = 8.1 Hz, 2 H, H21,
3
H23), 6.48 (d, JHH = 8.1 Hz,
2 H, H20, H24), 6.03 (d,
3JHH = 2.5 Hz, 1 H, H4), 6.01 (d, 3JHH = 2.5 Hz, 1 H, H5), 4.33 (s, 1
3
H, H18), 3.62 (sept, JHH = 6.8 Hz, 2 H, H12, H15), 3.43 (sept,
3JHH = 6.9 Hz, 2 H, H12¢, H15¢), 2.13 (s, 3 H, H25), 1.47 (d,
3JHH = 6.9 Hz, 6 H, H13¢, H16¢), 1.33 (d, 3JHH = 6.9 Hz, 6 H, H14¢,
3
H17¢), 1.32 (d, JHH = 6.8 Hz,
6 H, H13, H16), 1.29 (d,
3JHH = 6.8 Hz, 6 H, H14, H17).
1H NMR (600 MHz, THF-d8): d = 7.38 (t, 3JHH = 7.8 Hz, 1 H, H9¢),
7.30 (d, 3JHH = 7.8 Hz, 2 H, H8¢, H10¢), 7.25 (t, 3JHH = 7.8 Hz, 1 H,
H9), 7.08 (d, 3JHH = 7.8 Hz, 2 H, H8, H10), 6.38 (d, 3JHH = 2.4 Hz,
1 H, H4), 6.31 (d, 3JHH = 2.4 Hz, 1 H, H5), 6.28 (d, 3JHH = 8.2 Hz, 2
H, H21, H23), 5.97 (d, 3JHH = 8.2 Hz, 2 H, H20, H24), 3.76 (s, 1 H,
3
H18), 3.35 (sept, JHH = 6.7 Hz, 2 H, H12, H15), 3.17 (sept,
3JHH = 6.7 Hz, 2 H, H12¢, H15¢), 1.95 (s, 3 H, H25), 1.28 (d,
3JHH = 6.8 Hz, 6 H, H13¢, H16¢), 1.23 (d, 3JHH = 6.8 Hz, 6 H, H14¢,
3
H17¢), 1.19 (d, JHH = 6.8 Hz, 6 H, H13, H16), 1.08 (d,
3JHH = 6.8 Hz, 6 H, H14, H17).
13C-APT-NMR (151 MHz, THF-d8): d = 149.5 (d, 2 C, C7¢, C11¢),
147.8 (d, 2 C, C7, C11), 145.8 (d, 1 C, C2), 137.7 (d, 1 C, C6), 136.3
(d, 1 C, C19), 135.3 (d, 1 C, C6¢), 130.0 (u, 1 C, C9¢), 129.4 (u, 1 C,
C9), 128.4 (d, 1 C, C22), 127.8 (u, 2 C, C21, C23), 126.2 (u, 2 C,
C20, C24), 125.2 (u, 2 C, C8¢, C10¢), 124.3 (u, 2 C, C8, C10), 118.0
(u, 1 C, C5), 116.2 (u, 1 C, C4), 70.2 (u, 1 C, C18), 29.4 (u, 2 C,
C12¢, C15¢), 29.2 (u, 2 C, C12, C15), 25.0 (u, 2 C, C13, C16), 24.4
(u, 2 C, C13¢, C16¢), 23.9 (u, 2 C, C14¢, C17¢), 22.7 (u, 2 C, C14,
C17), 20.8 (u, 1 C, C25).
All chemicals were purchased from commercial suppliers and used
without further purification unless otherwise noted. THF was dis-
tilled over Na/benzophenone under an argon or N2 atmosphere.
1
THF-d8 was dried over molecular sieves (4 Å). H and 13C NMR
spectra were recorded on Bruker Avance II 600 (600.20 and 150.94
MHz), Bruker DRX 500 (500.13 and 125.77 MHz), and Bruker
Avance 300 (300.13 and 75.48 MHz) spectrometers at 298 K unless
otherwise stated. TopSpin (Version 1.3, 2.0 and 2.1) was used.
Chemical shifts are referenced to TMS or solvent residual peaks
Synthesis 2011, No. 23, 3784–3795 © Thieme Stuttgart · New York

3792
C. E. I. Knappke et al.
FEATURE ARTICLE
MS (ESI): m/z (%) = 493 (100) [M + H]+.
UV/Vis (THF): lmax = 350 nm.
131.4 (2 C, C9), 125.6 (4 C, C8, C10), 124.6 (2 C, C21, C23), 121.5
(2 C, C20, C24), 120.4 (2 C, C4, C5), 76.0 (1 C, C18), 29.6 (4 C,
C12, C15), 24.5 (4 C, C13, C16), 23.1 (4 C, C14, C17).
2-(4-Bromobenzylidene)-1,3-bis(2,6-diisopropylphenyl)-2,3-di-
hydro-1H-imidazole (4b)
MS (ESI): m/z (%) = 524 (100) [M + H]+, 389 (15).
HRMS (ESI): m/z [M + H]+ calcd for C34H42N3O2: 524.3277; found:
In a dry box, 4-bromobenzyl bromide (0.17 g, 0.68 mmol) was dis-
solved in THF (10 mL). 1,3-Bis(2,6-diisopropylphenyl)imidazolin-
2-ylidene23 (0.26 g, 0.68 mmol) was added. KOt-Bu (0.08 g,
0.6 mmol) was added to the yellow turbid soln and the mixture was
stirred for 4 d at r.t. After filtration through Celite, the solvent was
removed from the filtrate affording 4b (0.54 mmol, 79%) as a
yellow-orange oil.
524.327 (error: 5 ppm).
UV/Vis: lmax(solvent) = 597 (DMSO), 593 (EtOH), 585 (DMF),
585 (CH2Cl2), 582 (CHCl3), 578 (MeCN), 578 (H2O, pH > 10), 570
(acetone), 559 (THF), 550 (EtOAc), 548 (1,4-dioxane), 545 (ben-
zene), 543 (toluene), 535 (Et2O), 530 (CCl4), 521 (cyclohexane),
513 nm (pentane).
1H NMR (500 MHz, benzene-d6): d = 7.37 (‘t’, 3JHH = 7.8 Hz, 1 H,
XRD: empirical formula: C34H41N3O2, monoclinic, P21/c, Z = 4,
a = 18.7758(7) Å, b = 9.1454(4) Å, c = 18.7758(7) Å, a = 90°,
b = 102.084(2)°, g = 90°.24
3
H9¢), 7.27 (d, JHH = 7.5 Hz,
2 H, H8¢, H10¢), 7.21 (‘t’,
3JHH = 7.9 Hz, 1 H, H9), 7.07 (d, 3JHH = 7.8 Hz, 2 H, H8, H10), 6.95
(d, 3JHH = 8.7 Hz, 2 H, H21, H23), 6.13 (d, 3JHH = 8.7 Hz, 2 H, H20,
H24), 5.99 (d, 3JHH = 2.5 Hz, 1 H, H5), 5.98 (d, 3JHH = 2.5 Hz, 1 H,
H4), 4.14 (s, 1 H, H18), 3.45 (sept, 3JHH = 6.9 Hz, 2 H, H12, H15),
3.28 (sept, 3JHH = 6.9 Hz, 2 H, H12¢, H15¢), 1.41 (d, 3JHH = 6.9 Hz,
6 H, H13¢, H16¢), 1.30 (d, 3JHH = 6.9 Hz, 6 H, H14¢, H17¢), 1.23 (d,
(Z)-2-(4-Bromobenzylidene)-1-tert-butyl-3-(2,6-diisopropyl-
phenyl)-2,3-dihydro-1H-imidazole (4e)
Under anaerobic conditions, an NMR tube was charged with 1-tert-
butyl-3-(2,6-diisopropylphenyl)imidazolium
tetrafluoroborate25
3
3JHH = 6.9 Hz, 6 H, H13, H16), 1.21 (d, JHH = 6.9 Hz, 6 H, H14,
(16.1 mg, 43.2 mmol) and sealed with a rubber septum. KOt-Bu
(10 mg, 89 mmol) dissolved in THF-d8 (0.6 mL) was added. Ultra-
sonification gave a beige soln after 5 min to which 4-bromobenzyl
bromide (10.8 mg, 43.2 mmol) dissolved in THF-d8 (0.2 mL) was
added giving a yellow mixture. Conversion: 65%.
1H NMR (600 MHz, THF-d8): d = 7.15 (t, 3JHH = 7.8 Hz, 1 H, H9),
7.03 (d, 3JHH = 7.8 Hz, 2 H, H8), 6.68 (d, 3JHH = 2.4 Hz, 1 H, H5),
6.62 (d, 3JHH = 8.5 Hz, 2 H, H18), 6.26 (d, 3JHH = 8.5 Hz, 2 H, H17),
6.14 (‘s’, 1 H, H4), 4.51 (s, 1 H, H15), 3.10 (sept, 3JHH = 6.9 Hz, 2
H, H10), 1.62 (s, 9 H, H14), 1.17 (d, 3JHH = 6.9 Hz, 6 H, H11), 1.07
(d, 3JHH = 6.9 Hz, 6 H, H12).
13C-APT-NMR (151 MHz, THF-d8): d = 146.8 (d, 2 C, C7), 146.4
(d, 1 C, C2), 139.5 (d, 1 C, C16), 137.4 (d, 1 C, C6), 129.8 (u, 2 C,
C18), 129.3 (u, 1 C, C9), 127.0 (u, 2 C, C17), 124.8 (u, 2 C, C8),
116.6 (u, 1 C, C4), 113.4 (u, 1 C, C5), 110.8 (d, 1 C, C19), 72.1 (u,
1 C, C15), 56.2 (d, 1 C, C13), 29.1 (u, 2 C, C10), 28.6 (u, 3 C, C14),
25.7 (u, 2 C, C 12), 22.5 (u, 2 C, C11).
H17).
13C{1H}-NMR (126 MHz, benzene-d6): d = 148.7 (2 C, C7¢, C11¢),
147.1 (2 C, C7, C11), 145.8 (1 C, C2), 137.7 (1 C, C19), 136.4 (1
C, C6), 134.1 (1 C, C6¢), 130.0 (2 C, C21, C23), 129.9 (1 C, C9¢),
129.5 (1 C, C9), 127.1 (2 C, C20, C24), 124.9 (2 C, C8¢, C10¢),
124.1 (2 C, C8, C10), 117.3 (1 C, C5), 115.6 (1 C, C4), 112.0 (1 C,
C22), 69.7 (1 C, C18), 28.8 (2 C, C12¢, C15¢), 28.7 (2 C, C12, C15),
24.7 (2 C, C13, C16), 24.2 (2 C, C14¢, C17¢), 23.7 (2 C, C13¢, C16¢),
22.5 (2 C, C14, C17).
MS (ESI): m/z (%) = 559 (100) [M + H]+, 557 (100) [M + H]+, 389
(90).
HRMS (ESI): m/z [M + H]+ calcd for C34H42BrN2: 557.2531; found:
557.253 (error: 0.0015).
1,3-Bis(2,6-diisopropylphenyl)-2-(4-nitrobenzylidene)-2,3-di-
hydro-1H-imidazole (4c)
MS (ESI): m/z (%) = 455 (22) [M + H]+, 453 (22) [M + H]+, 285
(100).
HRMS (ESI): m/z [M + H]+ calcd for C26H34N2Br: 453.1905; found:
453.190 (error <5 ppm).
1,3-Bis(2,6-diisopropylphenyl)imidazolium chloride23 (2.55 g,
6.00 mmol) was placed in a Schlenk flask under an inert atmo-
sphere. KOt-Bu (0.673 g, 6.00 mmol) dissolved in THF (15 mL)
was added. The resulting orange soln was stirred at r.t. for 8 h. 4-
Bromobenzyl bromide (0.648 g, 3.00 mmol) dissolved in THF
(8 mL) was added to the carbene soln whereupon it turned dark pur-
ple. After stirring at r.t. for 38 h, the mixture was filtered through
Celite. The solvent was evaporated to give 4c (3.1 mmol, quant.) as
a dark purple solid with metallic shine; mp 61 °C (mp determination
was delicate due to the dark color of the compound).
(Z)-1-tert-Butyl-3-(2,6-diisopropylphenyl)-2-(4-nitroben-
zylidene)-2,3-dihydro-1H-imidazole (4f)
Under anaerobic conditions, an NMR tube was charged with 1-tert-
butyl-3-(2,6-diisopropylphenyl)imidazolium
tetrafluoroborate25
(16.5 mg, 44.3 mmol) and sealed with a rubber septum. KOt-Bu
(10 mg, 89 mmol) dissolved in THF-d8 (0.6 mL) was added. Ultra-
sonification gave a beige soln to which 4-nitrobenzyl bromide
(10.0 mg, 46.3 mmol) dissolved in THF-d8 (0.2 mL) was added giv-
ing a dark purple mixture. Conversion: 20%.
IR (ATR): 3071, 2962, 2914, 2866, 1731, 1683, 1619, 1585, 1536,
1466, 1364, 1333, 1247, 1225, 1184, 1167, 1105, 1079, 803, 752,
725 cm–1.
1H NMR (500 MHz, CD3CN): d = 7.51 (t, 3JHH = 7.8 Hz, 2 H, H9),
7.36 (d, 3JHH = 7.8 Hz, 4 H, H8, H10), 7.22 (d, 3JHH = 9.4 Hz, 2 H,
H21, H23), 6.87 (s, 2 H, H4, H5), 5.75 (d, 3JHH = 9.4 Hz, 2 H, H20,
H24), 4.13 (s, 1 H, H18), 2.91 (sept, 3JHH = 6.9 Hz, 4 H, H12, H15),
1.21 (d, 3JHH = 6.9 Hz, 12 H, H13, H16), 1.17 (d, 3JHH = 6.9 Hz, 12
H, H14, H17).
1H NMR (300 MHz, THF-d8) : d = 7.48 (t, 3JHH = 7.8 Hz, 2 H, H9),
7.34 (d, 3JHH = 7.8 Hz, 4 H, H8, H10), 7.25 (d, 3JHH = 9.0 Hz, 2 H,
H21, H23), 6.84 (s, 2 H, H4, H5), 5.77 (d, 3JHH = 9.0 Hz, 2 H, H20,
H24), 4.12 (s, 1 H, H18), 3.04 (sept, 3JHH = 6.8 Hz, 4 H, H12, H15),
1.24 (d, 3JHH = 6.8 Hz, 12 H, H13, H16), 1.20 (d, 3JHH = 6.8 Hz, 12
H, H14, H17).
3
1H NMR (600 MHz, THF-d8): d = 7.32 (d, JHH = 9.1 Hz, 2 H,
H18), 7.27 (t, 3JHH = 7.7 Hz, 1 H, H9), 7.22 (d, 3JHH = 2.4 Hz, 1 H,
H5), 7.18 (d, 3JHH = 7.7 Hz, 2 H, H8), 6.72 (d, 3JHH = 2.4 Hz, 1 H,
3
H4), 6.09 (d, JHH = 9.1 Hz, 2 H, H17), 4.81 (s, 1 H, H15), 2.85
3
(sept, JHH = 6.9 Hz, 2 H, H10), 1.71 (s, 9 H, H14), 1.23 (d,
3JHH = 6.9 Hz, 6 H, H11), 1.09 (d, 3JHH = 6.8 Hz, 6 H, H12).
13C-APT-NMR (151 MHz, THF-d8): d = 149.0 (d, 1 C, C2), 147.4
(d, 1 C, C16), 146.0 (d, 2 C, C7), 135.9 (d, 1 C, C19), 135.8 (d, 1 C,
C6), 130.5 (u, 1 C, C9), 125.5 (u, 2 C, C8), 124.3 (u, 2 C, C18),
120.1 (u, 2 C, C17), 119.3 (u, 1 C, C4), 116.5 (u, 1 C, C5), 76.5 (u,
1 C, C15), 58.7 (d, 1 C, C13), 29.6 (u, 2 C, C10), 29.0 (u, 3 C, C14),
25.8 (u, 2 C, C12), 22.6 (u, 2 C, C11).
13C{1H}-NMR (126 MHz, CD3CN): d = 149.1 (1 C, C2), 147.9 (4
C, C7, C11), 147.2 (1 C, C19), 136.2 (1 C, C22), 134.4 (2 C, C6),
MS (ESI): m/z (%) = 420 (9) [M + H]+, 364 (5), 285 (100), 229 (36).
Synthesis 2011, No. 23, 3784–3795 © Thieme Stuttgart · New York

FEATURE ARTICLE
Benzylidenes from Carbenes
3793
HRMS (ESI): m/z [M + H]+ calcd for C26H34N3O2: 420.2651; found:
420.265 (error: 0.003).
1,3-Bis(2,6-diisopropylphenyl)-2-(prop-2-enylidene)-2,3-dihy-
dro-1H-imidazole (5)
In a dry box, 1,3-bis(2,6-diisopropylphenyl)imidazolin-2-ylidene23
(2.00 g, 5.15 mmol) was dissolved in THF (60 mL). Freshly dis-
tilled allyl chloride (0.21 mL, 2.6 mmol) was added to the yellow
soln. The mixture was stirred at r.t. for 20 h. After filtration over
Celite, the solvent was removed yielding an orange solid that con-
tained the product, but was contaminated with starting material
(carbene). The ratio of product and carbene was determined by 1H
NMR; corrected yield of 5: 2.29 mmol (89%).
(E)-1-(2,6-Diisopropylphenyl)-3-methyl-2-(4-methylben-
zylidene)-2,3-dihydro-1H-imidazole (4g)
In a dry box, 1-(2,6-diisopropylphenyl)-3-methylimidazolium
iodide26 (9.15 mg, 24.7 mmol) and KOt-Bu (5.84 mg, 51.9 mmol)
were placed in a septum-capped vial. Under an inert atmosphere
THF-d8 (0.6 mL) was added. After ultrasonification the slightly yel-
low soln was transferred into a rubber septum-capped inert NMR
tube. 4-Methylbenzyl bromide (4.57 mg, 24.7 mmol) dissolved in
THF-d8 (0.2 mL) was added. Conversion: 60%.
1H NMR (500 MHz, benzene-d6): d = 7.34 (‘t’, 3JHH = 7.6 Hz, 2 H,
3
H9, H9¢), 7.24 (‘t’, JHH = 7.3 Hz, 4 H, H8, H10, H8¢, H10¢), 5.95
1H NMR (600 MHz, THF-d8): d = 7.32 (t, 3JHH = 7.8 Hz, 1 H, H9),
7.23 (d, 3JHH = 7.8 Hz, 2 H, H8), 6.76 (d, 3JHH = 7.8 Hz, 2 H, H17),
6.65 (d, 3JHH = 7.8 Hz, 2 H, H16), 6.32 (d, 3JHH = 1.9 Hz, 1 H, H4),
6.27 (d, 3JHH = 1.9 Hz, 1 H, H5), 3.75 (s, 1 H, H14), 3.02 (s, 3 H,
H13), 2.91 (sept, 3JHH = 6.9 Hz, 2 H, H10), 2.14 (s, 3 H, H19), 1.17
(d, 3JHH = 2.5 Hz, 1 H, H4 or H5), 5.91 (d, 3JHH = 2.5 Hz, 1 H, H4
3
or H5), 5.89–5.82 (m, 1 H, H19), 4.42 (dd, JHH = 16.1 Hz,
2JHH = 2.6 Hz, 1 H, H20cis), 4.25 (d, 3JHH = 11.8 Hz, 1 H, H18), 4.08
3
2
(dd, JHH = 10.1 Hz, JHH = 2.6 Hz, 1 H, H20trans), 3.45 (sept,
3JHH = 6.9 Hz, 2 H, H12, H15), 3.32 (sept, 3JHH = 6.9 Hz, 2 H, H12¢,
3
3
(d, JHH = 6.9 Hz, 6 H, H12), 1.14–1.12 (d, 6 H, H11; signal ob-
H15¢), 1.49 (d, JHH = 6.9 Hz,
6
H, H14, H17), 1.44 (d,
scured by t-BuOH resonance; coupling constant not determined).
3JHH = 6.9 Hz, 6 H, H14¢, H17¢), 1.32 (d, 3JHH = 6.9 Hz, 6 H, H13,
H16 or H13¢, H16¢), 1.30 (d, 3JHH = 6.9 Hz, 6 H, H13, H16 or H13¢,
H16¢).
13C-APT-NMR (151 MHz, THF-d8): d = 150.3 (d, 1 C, C2), 149.2
(d, 2 C, C7), 138.9 (d, 1 C, C15), 135.3 (d, 1 C, C6), 129.8 (u, 1 C,
C9), 128.7 (u, 2 C, C17), 128.3 (d, 1 C, C18), 125.8 (u, 2 C, C16),
125.0 (u, 2 C, C8), 117.9 (u, 1 C, C4), 117.1 (u, 1 C, C5), 66.9 (u, 1
C, C14), 37.5 (u, 1 C, C13), 29.1 (u, 2 C, C10), 24.6 (u, 2 C, C11),
23.9 (u, 2 C, C12), 21.0 (u, 1 C, C19).
1H NMR (600 MHz, THF-d8): d = 7.39–7.35 (m, 2 H, H9, H9¢),
7.27–7.24 (m, 4 H, H8, H10, H8¢, H10¢), 6.35 (s, 1 H, H4), 6.30 (s,
1 H, H5), 5.29 (m, 1 H, H19), 3.78 (d, 3JHH = 16.0 Hz, 1 H, H20cis),
3
3
3.67 (d, JHH = 11.8 Hz, 1 H, H18), 3.38 (d, JHH = 9.9 Hz, 1 H,
3
H20trans), 3.21 (sept, JHH = 6.9 Hz, 2 H, H12, H15), 3.09 (sept,
1-Ethyl-3-methyl-2-(4-nitrobenzylidene)-2,3-dihydro-1H-imi-
dazole (4i)
3JHH = 6.9 Hz, 2 H, H12¢, H15¢), 1.29–1.16 [m, 24 H, CH(CH3)2].
13C{1H}-NMR (126 MHz, benzene-d6): d = 148.7 (2 C, C7¢, C11¢),
148.1 (2 C, C7, C11), 145.8 (1 C, C2), 136.2 (1 C, C6), 134.0 (1 C,
C6¢), 131.9 (1 C, C19), 129.7 (2 C, C9, C9¢), 124.7 (2 C, C8¢, C10¢),
124.5 (2 C, C8, C10), 116.7 (1 C, C4 or C5), 115.3 (1 C, C4 or C5),
96.9 (1 C, C20), 72.3 (1 C, C18), 29.0 (2 C, C12, C15), 28.8 (2 C,
C12¢, C15¢), 24.2 (4 C, C13, C16, C13¢, C16¢), 23.8 (2 C, C14¢,
C17¢), 23.3 (2 C, C14, C17).
13C NMR (151 MHz, THF-d8): d = 149.2 (d, 2 C, C7¢, C11¢), 148.7
(d, 2 C, C7, C11), 146.5 (d, 1 C, C2), 136.9 (d, 1 C, C6), 134.7 (d,
1 C, C6¢), 132.7 (u, 1 C, C19), 130.0 (u, 2 C, C9, C9¢), 125.0 (u, 2
C, C8 and C10 or C8¢ and C10¢), 124.8 (u, 2 C, C8 and C10 or C8¢
and C10¢), 117.6 (u, 1 C, C5), 116.2 (u, 1 C, C4), 95.1 (d, 1 C, C20),
72.2 (u, 1 C, C18), 29.5 (u, 2 C, C12, C15), 29.4 (u, 2 C, C12¢,
C15¢), 24.3 [u, 2 C, CH(CH3)2], 23.9 [u, 2 C, CH(CH3)2], 23.7 [u, 2
C, CH(CH3)2], 23.4 [u, 2 C, CH(CH3)2].
Under inert conditions, KOt-Bu (62 mg, 0.55 mmol) dissolved in
THF (3 mL) was added to 1-ethyl-3-methylimidazolium bromide
(104.7 mg, 0.548 mmol). After ultrasonification, 4-nitrobenzyl bro-
mide (59.8 mg, 0.277 mmol) dissolved in THF (3 mL) was added to
the colorless turbid carbene soln. Thereupon this turned deep pur-
ple. After stirring over night at r.t. the mixture was filtered through
Celite under argon followed by washing with THF (4 mL). The sol-
vent was removed from the filtrate to give 4i (0.245 mmol, 89%) as
a dark purple glittery solid. The product was highly sensitive to air.
Exposure resulted in immediate color change to black.
3
1H NMR (600 MHz, THF-d8): d = 7.68 (d, JHH = 9.2 Hz, 2 H,
H12), 6.95 (d, 3JHH = 2.3 Hz, 1 H, H5), 6.92 (d, 3JHH = 2.2 Hz, 1 H,
H4), 6.31 (d, 3JHH = 9.2 Hz, 2 H, H11), 4.52 (s, 1 H, H9), 3.79 (q,
3JHH = 7.2 Hz, 2 H, H6), 3.36 (s, 3 H, H8), 1.29 (t, 3JHH = 7.2 Hz, 3
H, H7).
MS (ESI): m/z (%) = 429 (100) [M + H]+, 403 (46), 389 (100).
13C-APT-NMR (151 MHz, THF-d8): d = 150.3 (d, 1 C, C2), 149.8
(d, 1 C, C10), 134.9 (d, 1 C, C13), 125.7 (u, 2 C, C12), 120.0 (u, 1
C, C4), 118.7 (u, 2 C, C11), 117.7 (u, 1 C, C5), 69.0 (u, 1 C, C9),
43.4 (d, 1 C, C6), 35.9 (u, 1 C, C8), 14.5 (u, 1 C, C7).
[1,3-Bis(2,6-diisopropylphenyl)-2,3-dihydro-1H-imidazol-2-
ylidene]acetonitrile (6)
Under inert conditions, 1,3-bis(2,6-diisopropylphenyl)imidazolium
chloride23 (2.00 g, 4.71 mmol) was reacted with KOt-Bu (530 mg,
4.72 mmol) dissolved in THF (15 mL). The orange, turbid mixture
was ultrasonificated followed by stirring at r.t. for 1.5 h. Chloro-
acetonitrile (149 mL, 2.36 mmol) was added. After stirring at r.t. for
3 d the mixture was filtered through Celite under argon. The solvent
was removed from the filtrate. The resulting orange solid was dis-
solved in benzene (15 mL) and filtered again. The red filtrate was
concentrated and colorless crystals of 6 formed (2.31 mmol, 98%);
mp 208 °C.
2-(4-Bromobenzyl)-1,3-di-tert-butylimidazolium Bromide (3k)
In a dry box, 1,3-di-tert-butylimidazolin-2-ylidene27 (0.50 g,
2.8 mmol) was dissolved in THF (10 mL). 4-Bromobenzyl bromide
(0.70 g, 2.8 mmol) was added resulting in a slightly yellow, turbid
soln. KOt-Bu (0.31 g, 2.8 mmol) was added. After stirring at r.t.
overnight the mixture was filtered through Celite. The solvent was
removed from the slightly yellow filtrate to give 3k (2.32 mmol,
82%) as an off-white solid.
3
1H NMR (360 MHz, benzene-d6): d = 7.42 (d, JHH = 8.5 Hz, 2 H,
IR (ATR): 3085, 2959, 2921, 2860, 2167, 1741, 1596, 1559, 1473,
1381, 1362, 1330, 1211, 1123, 1058, 936, 805, 766, 752, 688 cm–1.
H11), 7.09 (d, 3JHH = 8.5 Hz, 2 H, H10), 6.86 (s, 2 H, H4, H5), 4.18
(s, 2 H, H8), 1.19 (s, 18 H, H7).
1H NMR (600 MHz, THF-d8): d = 7.43 (t, 3JHH = 7.8 Hz, 1 H, H9¢),
13C{1H}-NMR (126 MHz, benzene-d6): d = 160.9 or 155.7 (1 C,
C2), 139.7 (1 C, C9), 131.5 (2 C, C11), 129.1 (2 C, C10), 120.9 (1
C, C12), 115.1 (2 C, C4, C5), 73.1 (2 C, C6), 63.3 (1 C, C8), 27.6
(6 C, C7).
3
3
7.37 (t, JHH = 7.8 Hz, 1 H, H9), 7.32 (d, JHH = 7.8 Hz, 2 H, H8¢,
H10¢), 7.21 (d, 3JHH = 7.8 Hz, 2 H, H8, H10), 6.70 (d, 3JHH = 2.2 Hz,
1 H, H4), 6.68 (d, 3JHH = 2.2 Hz, 1 H, H5), 2.98 (sept, 3JHH = 6.8 Hz,
2 H, H12, H15), 2.88 (sept, 3JHH = 6.9 Hz, 2 H, H12¢, H15¢), 2.38 (s,
1 H, H18), 1.34 (d, 3JHH = 6.8 Hz, 6 H, H13, H16), 1.27–1.20 [m, 18
H, CH(CH3)2].
Synthesis 2011, No. 23, 3784–3795 © Thieme Stuttgart · New York

3794
C. E. I. Knappke et al.
FEATURE ARTICLE
3
1H NMR (300 MHz, benzene-d6): d = 7.44 (t, JHH = 7.4 Hz, 1 H,
H9¢), 7.27 (m, 3 H, H9, H8¢, H10¢), 7.12 (d, 3JHH = 7.8 Hz, 2 H, H8,
H10), 5.94 (d, 3JHH = 2.3 Hz, 1 H, H4), 5.87 (d, 3JHH = 2.3 Hz, 1 H,
Biju, A. T.; Sinu, C. R.; Paul, R. R.; Jose, A.; Sreekumar, V.
Chem. Soc. Rev. 2011, 40, DOI: 10.1039/c1cs15139h.
(j) Chiang, P.-C.; Bode, J. W. In N-Heterocyclic Carbenes:
From Laboratory Curiosities to Efficient Synthetic Tools,
RSC Catalysis Series No. 6; Díez-González, S., Ed.; Royal
Society of Chemistry: Cambridge, 2010, 399–435. (k) Biju
A. T., Kuhl N., Glorius F.; Acc. Chem. Res.; DOI: 10.1021/
ar2000716. (l) Hirano, K.; Piel, I.; Glorius, F. Chem. Lett.
2011, 40, 786. (m) Hahn, F. E.; Jahnke, M. C. Angew. Chem.
Int. Ed. 2008, 47, 3122; Angew. Chem. 2008, 120, 3166.
(n) Díez-González, S.; Marion, N.; Nolan, S. P. Chem. Rev.
2009, 109, 3612. (o) Moore, J. L.; Rovis, T. Top. Curr.
Chem. 2010, 291, 77.
3
H5), 3.15 (sept, JHH = 6.9 Hz, 2 H, H12, H15), 2.95 (sept,
3JHH = 6.9 Hz, 2 H, H12¢, H15¢), 2.80 (s, 1 H, H18), 1.64 (d,
3JHH = 6.9 Hz, 6 H, H13, H16), 1.31 [d, JHH = 6.7 Hz, 6 H,
3
3
CH(CH3)2], 1.29 [d, JHH = 6.7 Hz, 6 H, CH(CH3)2], 1.18 [d,
3JHH = 6.9 Hz, 6 H, CH(CH3)2].
1H NMR (300 MHz, CD2Cl2): d = 7.49–7.39 (m, 2 H, H9, H9¢), 7.30
(d, 3JHH = 7.8 Hz, 2 H, H8¢, H10¢), 7.26 (d, 3JHH = 7.8 Hz, 2 H, H8,
3
H10), 6.49 (s, 2 H, H4, H5), 2.92 (sept, JHH = 6.9 Hz, 2 H, H12,
3
H15), 2.81 (sept, JHH = 6.9 Hz, 2 H, H12¢, H15¢), 2.47 (s, 1 H,
H18), 1.35–1.20 [m, 24 H, CH(CH3)2].
(3) (a) Gusev, D. G. Organometallics 2009, 28, 6458.
(b) Dröge, T.; Glorius, F. Angew. Chem. Int. Ed. 2010, 49,
6940; Angew. Chem. 2010, 122, 7094. Analogy to
13C{1H}-NMR (151 MHz, THF-d8): d = 153.5 (d, 1 C, C2), 148.4
(d, 2 C, C7, C11), 148.4 (d, 2 C, C7¢, C11¢), 133.4 (d, 1 C, C6),
133.0 (d, 1 C, C6¢), 130.9 (u, 1 C, C9 or C9¢), 130.0 (u, 1 C, C9 or
C9¢), 125.4 (u, 2 C, C8¢, C10¢), 124.4 (u, 2 C, C8, C10), 120.0 (d, 1
C, C19), 118.7 (u, 1 C, C5), 117.5 (u, 1 C, C4), 33.2 (u, 1 C, C18),
29.7 (u, 2 C, C12, C15), 29.5 (u, 2 C, C12¢, C15¢), 24.5 (u, 2 C, C13,
C16), 24.3 (u, 2 C, C13¢, C16¢), 23.8 (u, 2 C, C14¢, C17¢), 23.5 (u, 2
C, C14, C17).
phosphines: (c) Kühl, O. Coord. Chem. Rev. 2005, 249,
693. (d) Tolman, C. A. Chem. Rev. 1977, 77, 373.
(4) (a) Magill, A. M.; Cavell, K. J.; Yates, B. F. J. Am. Chem.
Soc. 2004, 126, 8717. (b) Chu, Y.; Deng, H.; Cheng, J.-P.
J. Org. Chem. 2007, 72, 7790. (c) Amyes, T. L.; Diver,
S. T.; Richard, J. P.; Rivas, F. M.; Toth, K. J. Am. Chem. Soc.
2004, 126, 4366. (d) Alder, R. W.; Allen, P. R.; Williams, S.
J. J. Chem. Soc., Chem. Commun. 1995, 1267. (e) Kim,
Y.-J.; Streitwieser, A. J. Am. Chem. Soc. 2002, 124, 5757.
(f) Higgins, E. M.; Sherwood, J. A.; Lindsay, A. G.;
Armstrong, J.; Massey, R. S.; Alder, R. W.; O’Donoghue, A.
C. Chem. Commun. 2011, 47, 1559.
MS (ESI): m/z (%) = 428 (8) [M + H]+, 389 (100).
HRMS (ESI): m/z [M + H]+ calcd for C29H38N3: 428.3066; found:
428.306 (error: 5 ppm).
Anal. Calcd for C29H37N3: C, 81.45; H, 8.72; N, 9.83. Found: C,
81.38; H, 8.92; N, 9.73.
(5) The studied triazolin-5-ylidene showed a similar
nucleophilicity as DMAP and DBU, whereas the imidazolin-
2-ylidene and imidazolidin-2-ylidene were 1000 times more
nucleophilic: Maji, B.; Breugst, M.; Mayr, H. Angew. Chem.
Int. Ed. 2011, 50, 6915; Angew. Chem. 2011, 123, 7074.
(6) (a) Knappke, C. E. I.; Neudörfl, J. M.; Jacobi von Wangelin,
A. Org. Biomol. Chem. 2010, 8, 1695. (b) Knappke, C. E. I.
Untersuchungen zur Umpolung von Alkylhalogeniden durch
N-heterocyclische Carbene. Dissertation, University of
Cologne, Germany; Verlag Dr. Hut: München, 2011.
(c) Knappke, C. E. I.; Jacobi von Wangelin, A. unpublished
results. For precedences of deoxy-Breslow intermediates
derived from a,b-unsaturated esters see: (d) Fischer, C.;
Smith, S. W.; Powell, D. A.; Fu, G. C. J. Am. Chem. Soc.
2006, 128, 1472. (e) Matsuoka, S.-i.; Ota, Y.; Washio, A.;
Katada, A.; Ichioka, K.; Takagi, K.; Suzuki, M. Org. Lett.
2011, 13, 3722. (f) Biju, A. T.; Padmanaban, M.; Wurz, N.
E.; Glorius, F. Angew. Chem. Int. Ed. 2011, 50, 8412;
Angew. Chem. 2011, 123, 8562.
XRD: (note: compound co-crystallized with one equivalent of ben-
zene) empirical formula: C35H43N3, monoclinic, P21/n, Z = 4,
a = 11.7791(4) Å, b = 17.7014(9) Å, c = 15.0895(8) Å, a = 90°,
b = 99.687(3)°, g = 90°.24
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.
Acknowledgment
This work was supported by the Emmy-Noether program of the
Deutsche Forschungsgemeinschaft (DFG). We thank the Fonds der
Chemischen Industrie (FCI) for a scholarship (to C.E.I.K.), Dr. N.
Schlörer and Prof. H.-G. Schmalz (both University of Cologne) for
excellent technical support. A.J.A. gratefully acknowledges the
support of the Saxon Endowment of The University of Alabama and
a grant from the National Science Foundation (CHE0413521).
(7) (a) Breslow, R. J. Am. Chem. Soc. 1958, 80, 3719.
(b) Breslow, R.; Kim, R. Tetrahedron Lett. 1994, 35, 699.
(c) Chen, Y.-T.; Barletta, G. L.; Haghjoo, K.; Cheng, J. T.;
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Melder, J.-P.; Ebel, K.; Schneider, R.; Gehrer, E.; Harder,
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(g) Berkessel, A.; Elfert, S.; Etzenbach-Effers, K.; Teles, J.
H. Angew. Chem. Int. Ed. 2010, 49, 7120; Angew. Chem.
2010, 122, 7275.
(8) Reaction of NHCs with alkyl halides: (a) Begtrup, M. Bull.
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A. J. III; Davidson, F.; Dias, H. V. R.; Goerlich, J. R.;
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Synthesis 2011, No. 23, 3784–3795 © Thieme Stuttgart · New York

FEATURE ARTICLE
R.; Marshall, W. J.; Tamm, M.; Schmutzler, R. Helv. Chim.
Benzylidenes from Carbenes
3795
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Furthermore, we have also tested single-point energy
calculations at the B3LYP/6-311+G* level on B3LYP/6-
31G* optimized geometries. Since both B3LYP/6-311+G*
and B3LYP/6-31G* gave approximately the same results for
the exchange reactions, we used only the B3LYP/6-31G*
Gibbs free energy for discussion and comparison. All
calculations have been carried out by using the Gaussian 03
program package: Frisch, M. J.; Trucks, G. W.; Schlegel, H.
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(11) See Supporting Information for further details on the
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(24) Crystal structure data of compounds 4c and 6 are available
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Crystallographic Data Centre via www.ccdc.cam.ac.uk/
conts/retrieving.html.
(15) Similar, but even more pronounced bond orders were
reported for related 1,3-dimethylimidazolin-2-ylidene
acetophenone. See ref. 9g.
(16) A classical example of charge transfer-stabilized p,p-
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(26) Synthesized according to: Flahaut, A.; Roland, S.;
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(27) Arduengo, A. J. III; Bock, H.; Chen, H.; Denk, M.; Dixon,
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Synthesis 2011, No. 23, 3784–3795 © Thieme Stuttgart · New York