Structures and ambident reactivities of azolium enolates

Article abstract of DOI:10.1002/anie.201303524

Oxygen versus carbon: Azolium enolates were generated by the reactions of N-heterocyclic carbenes (NHCs) with methyl phenyl ketene and characterized by X-ray crystallography. Kinetic studies show that the enolate oxygen is 20 times more nucleophilic than

Full text of DOI:10.1002/anie.201303524

Angewandte
Chemie
DOI: 10.1002/anie.201303524
Organocatalysis
Structures and Ambident Reactivities of Azolium Enolates**
Biplab Maji* and Herbert Mayr*
Dedicated to Professor Reinhard W. Hoffmann on the occasion of his 80th birthday
[
1]
Since their first isolation as stable species in 1991, N-
heterocyclic carbenes (NHCs, 1) have been used extensively
[
2,3]
as catalysts for CꢀC bond-forming reactions.
In organo-
catalytic applications they mostly serve as “umpolung”
[
3]
[
4,3f]
reagents.
As shown in Scheme 1, their reactions with
Scheme 2. Synthesis of the azolium enolates 2a–c.
tions, including an azolium enolate of type 2b, was brought to
[
12d]
our attention.
Dropwise addition of a diethyl ether solution of methyl
phenyl ketene into a solution of 1,3-dimesitylimidazol-2-
ylidene 1a in toluene at 208C led to the formation of a yellow
Scheme 1. Generation and reactions of azolium enolates 2.
[
6]
[5,7]
[8]
1
ketenes, aldehydes, and esters give rise to the formation
precipitate, which was identified by H NMR analysis as a 4:1
[
3h,5–8]
[6]
of azolium enolates 2,
equivalents of ester enolates,
mixture of two stereoisomers of 2a. When the reaction was
which have recently gained great attention. Enolates 2 are
conducted at ꢀ788C the major stereoisomer of 2a was
1
usually generated in situ and serve as reactive and syntheti-
obtained (purity > 97%, H NMR analysis) in 68% yield
[
6a–e]
[6f]
1
cally useful nucleophiles in [2+2],
[2+3],
and
and
(Scheme 2); compound 2a has a characteristic H NMR
[6g,h,7,8b]
[5–8]
[7e–h]
[
2+4]
cycloadditions,
Michael additions,
Mannich reactions as well as in enantioselective protona-
resonance at d = 1.47 for CMe showing a gHMBC correlation
[
8a]
13
to the C NMR resonances at d = 94.9 and 150.1 for the two
[6i,j,7a]
[6k]
ꢀ
tions
and halogenations (Scheme 1).
enolate carbons MeC=C(O ). The Z configuration of the
Despite numerous theoretical and experimental studies
enolate, which is formed by attack of 1a on the less hindered
[
9]
on the intermediates of NHC-catalyzed reactions, the
side of the ketene, was confirmed by a NOESYexperiment. A
[
10]
[13]
ambident reactivities
of azolium enolates, which may
single-crystal X-ray analysis of (Z)-2a (Figure 1) shows that
react at either oxygen or carbon, have not been investigated.
As part of our ongoing research on structures and reactivities
the phenyl ring is in the plane of the enolate (C4-C5-C6-C11
dihedral angle = 2.928), while the imidazolium moiety is
[
11]
of intermediates of NHC-catalyzed reactions,
report on the synthesis and reactivities of the azolium
we now
[
12]
enolates 2a–c (Scheme 2). After acceptance of this Com-
munication a profound, simultaneously submitted investiga-
tion characterizing intermediates of NHC-catalyzed reac-
[*] Dr. B. Maji, Prof. Dr. H. Mayr
Department Chemie, Ludwig-Maximilians-Universitꢀt Mꢁnchen
Butenandtstrasse 5–13 (Haus F), 81377 Mꢁnchen (Germany)
E-mail: maji.biplab@cup.uni-muenchen.de
herbert.mayr@cup.uni-muenchen.de
Homepage: http://www.cup.uni-muenchen.de/oc/mayr
[
**] We thank the Deutsche Forschungsgemeinschaft (SFB 749, project
B1) for financial support, Dr. P. Mayer for the determination of the
X-ray structures, and Dr. K. Troshin, Dr. D. S. Stephenson, Dr. J.
Ammer, Dr. A. R. Ofial, and the members of COST action CM0905
“
Organocatalysis” for helpful discussions. We are grateful to Prof. L.
Delaude (Univ. Liꢂge) for kindly providing a preprint of Ref. [12c].
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201303524.
Figure 1. Crystal structure of 2a (50% probability ellipsoids). One of
the two asymmetric units shown.
[
13]
Angew. Chem. Int. Ed. 2013, 52, 1 – 6
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1
These are not the final page numbers!

.
Angewandte
Communications
almost perpendicular (N1-C3-C4-C5 dihedral angle = 81.68).
A perpendicular orientation of the azolium ring to the enolate
plane was also found by quantum chemical calculations of
Table 2: Reactions of the azolium enolates 2a,c with the benzhydrylium
ions 3 f–h in CD CN at 208C.
3
[
5,9]
triazolium enolates.
Enolates 2b and 2c were synthesized
analogously from 1,3-dimesitylimidazolidin-2-ylidene 1b and
Endersꢀ carbene 1c, respectively (Scheme 2).
In order to elucidate the relationship between structures
and reactivities of 2a–c we studied the kinetics of their
reactions with the benzhydrylium ions 3 (Table 1), which had
[a]
Entry
2
3
t
Product ratio
1
2
3
4
5
6
7
8
9
2a
2a
3 f
3h
5 min
5 min
2 h
[4af]/[5af]<4:96
[4ah]/[5ah]=76:24
[4ah]/[5ah]=22:78
[4ah]/[5ah]<4:96
[4cf]/[5cf]<4:96
[4cg]/[5cg]=63:37
[4cg]/[5cg]=12:88
[4cg]/[5cg]<4:96
[4ch]/[5ch]=74:26
[4ch]/[5ch]=29:71
[4ch]/[5ch]<4:96
[
b]
[
b]
[
b]
+
24 h
Table 1: Benzhydrylium ions Ar CH employed as reference electrophiles
2
2c
2c
3 f
3g
5 min
5 min
1.5 h
3 h
5 min
24 h
in this work.
+
[a]
Ar CH
2
E
n=1
n=2
3a
3b
ꢀ10.04
ꢀ9.45
2c
3h
1
1
0
1
48 h
n=1
n=2
3c
3d
ꢀ8.76
ꢀ8.22
1
[a] From the H NMR spectrum. [b] The reaction was performed in
D ]DMSO.
[
6
R=N(CH2)4
R=NMe2
3e
3 f
ꢀ7.69
ꢀ7.02
3
3
g
h
ꢀ1.36
0
[a] Electrophilicity parameters E for 3a–h from Ref. [14a].
been used as reference electrophiles for the construction of
comprehensive nucleophilicity scales on the basis of Equa-
tion (1). In Equation (1) nucleophiles are characterized by
two solvent-dependent parameters (nucleophilicity N and
sensitivity s ) and electrophiles by one solvent-independent
N
[
14]
parameter (electrophilicity E).
ꢁ
lg kð20 CÞ ¼ s ðN þ EÞ
ð1Þ
N
1
Addition of 2a to the blue solution of 3 f-BF in CD CN
led to a fading of the blue color due to the exclusive formation
4
3
Figure 2. Time-dependent H NMR spectra for the reaction of 2c with
3h-Cl in CD CN at 208C (Ar=4-MeOC H ).
3
6
4
of the acyl azolium tetrafluoroborate 5af as revealed by the
1
H NMR chemical shift of the benzhydryl proton at d = 4.64
and the NMR signals of two diastereotopic phenyl rings of the
benzhydryl group as well as the C NMR chemical shift for
the carbonyl carbon at d = 193.4 (Table 2, entry 1). Analo-
gave a 63:37 mixture of O- and C-addition products which
rearranged somewhat faster into the thermodynamically
more stable 5cg (Table 2, entries 6–8, Figure S1 in the
Supporting Information). Similar observations were made
for the reaction of 2a with 3h (Table 2, entries 2–4, Fig-
ure S2).
Following previously described methods, we measured
the rates of the reactions of the carbocations 3 (Table 1) with
the enolates 2a–c photometrically by monitoring the disap-
pearance of the absorbances of the diarylcarbenium ions 3,
using stopped-flow UV/Vis spectrometers. All kinetic experi-
ments were performed at 208C in THF or DMSO with a large
excess of the nucleophiles 2 in order to achieve conditions
corresponding to first-order kinetics.
1
3
gously the reaction of 2c with 3 f-BF exclusively yields the
4
acyl azolium tetrafluoroborate 5cf (Table 2, entry 5).
Different observations were made for the reactions of 2a
and 2c with the more strongly Lewis acidic benzhydrylium
ions 3h and 3g (Table 2, entries 2–4 and 6–11), as illustrated
[14]
for the reaction of 2c and 3h (Figure 2). When 2c was mixed
1
with 3h-Cl in CD CN at 208C, the H NMR spectra showed
3
the formation of the O-addition product 4ch and the C-
addition product 5ch in a 74:26 ratio. When the same mixture
was analyzed after 24 h, the ratio 4ch/5ch changed to 29:71
and after 48 h only the thermodynamically more stable acyl
triazolium chloride 5ch was observed.
For the reactions of 2a,b with carbocations 3a–d, mono-
exponential decays were observed (for an example see,
Figure S3), which correspond to the attack of the electro-
Under the same conditions, the combination of 2c with
the slightly less Lewis acidic benzhydrylium ion 3g initially
2
www.angewandte.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2013, 52, 1 – 6
These are not the final page numbers!

Angewandte
Chemie
philes 3a–d at the b-carbons of the enolates 2a,b to form the
acyl azoliums 5. The first-order rate constants, kobs, were
obtained by least-squares fitting of the function A =
t
ꢀ
kobst
A e
+ C to the time-dependent absorbances of the
0
electrophiles. Plots of kobs versus the concentrations of the
nucleophiles [2a,b] were linear, as exemplified in the inset in
Figure S3. The slopes of these plots gave the second-order
ꢀ
1
ꢀ1
rate constants k (in m s ), which are summarized in Table 3.
Table 3: Second-order rate constants k (C attack) and k’ (O attack) for
the reactions of azolium enolates 2 with the reference electrophiles 3 at
2
08C in THF.
ꢀ1
ꢀ1
ꢀ1 ꢀ1
3
k [m
s
]
k’ [m
s
]
[
a]
2
a
2a
2b
2c
2c
4
4
5
5
4
3
3
3
3
3
3
a
b
c
d
e
f
1.57ꢃ10
4.69ꢃ10
1.37ꢃ10
4.66ꢃ10
1.70ꢃ10
3
4
4
4
5
5
3
4
4
3.88ꢃ10
1.10ꢃ10
2.08ꢃ10
5.42ꢃ10
1.27ꢃ10
3.58ꢃ10
5.58ꢃ10
1.23ꢃ10
2.86ꢃ10
5
5.4ꢃ10
6
1.43ꢃ10
[a] In DMSO.
In contrast, the kinetic behavior of enolate 2c depended
on the nature of the benzhydrylium ions. The less electrophilic
benzhydrylium ions 3c,d react with 2c in a similar way as with
2
a,b (monoexponential decay, Figure S4) to give the second-
order rate constants k for C attack, which are listed in Table 3.
However, the reaction of 2c with the more reactive carben-
ium ion 3e showed bisexponential decay of the absorbance of
3
e. At low concentration, as shown in Figure 3a for a 0.11 mm
solution of 2c, about 20% of the absorbance of 3e disap-
peared within 50 ms, whereas reaching a constant concen-
tration of 3e required 1000 ms. At higher concentrations of 2c
Figure 3. Decrease in the absorbances during the reactions of 3e,f
with 2c in THF at 208C (solid lines) and determination of kobs from the
(
0.40 mm, Figure 3b) about 50% of the absorbance of 3e
disappeared within 10 ms and it was almost completely
extinguished after 500 ms. With the more reactive benzhy-
drylium ion 3 f, the first part of the bisexponential decay
dominated, and about 75% of 3 f was consumed within 15 ms
in the reaction with a 0.23 mm solution of 2c (Figure 3c). In
all cases, kobs was obtained by least-squares fitting of the
monoexponential fit of the absorbance (dashed lines). Insets: Plots of
k
obs versus [2c] yield the second-order rate constants k and k’ in
Table 3.
ꢀ
kobst
function A = A e
+ C to the time-dependent absorbances
t
0
of the electrophiles in the particular range, and the second-
order rate constants were obtained from the slopes of the kobs
versus [2c] plots (insets in Figure 3).
This behavior can be rationalized by the mechanism
depicted in Scheme 3. The fast and incompletely proceeding
reactions correspond to the attack of the electrophiles at the
oxygen center of the enolate 2c, while the slower reactions
correspond to the attack at the b-carbon atom of 2c. With the
less Lewis acidic carbenium ions 3c,d the equilibrium for the
fast reaction, which yields the benzhydryl enol ethers 4, is
completely on the side of the reactants and attack at the
oxygen of 2c does not affect the slow process (C attack),
which is then observed exclusively. The more Lewis acidic
carbenium ion 3 f, on the other hand, is converted into the
benzhydryl enol ether 4 to a large extent, before its
quantitative conversion into 5, the thermodynamically more
stable product of C attack (Figure 3c).
Scheme 3. Ambident reactivity of the azolium enolate 2c.
As shown by entry 5 in Table 2, the conversion of 4cf to
5cf is complete within 5 min. With 3e, a borderline situation is
encountered: At low concentrations of 2c the equilibrium for
O attack is on the side of reactants and one can observe the
slow C attack (Figure 3a), whereas at higher concentrations
of 3e the faster O attack becomes observable (Figure 3b).
Figure 4 shows that the logarithms of the rate constants
(lgk) for the reactions of 2a,b with the carbenium ions 3a–d
(in THF) correlate linearly with the empirical electrophilicity
parameters E (* and ^ in Figure 4), indicating that Equa-
tion (1) is applicable and can be used to determine N and sN
Angew. Chem. Int. Ed. 2013, 52, 1 – 6
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
3
These are not the final page numbers!

.
Angewandte
Communications
Scheme 5. Relative reactivities of the free carbenes 1 (Ref. [11a]) and
comparison with the corresponding azolium enolates 2 and deoxy
[
a]
Breslow intermediates 6 (Ref. [11b]) (THF, 208C). krel towards 5’-(4-
(dimethylamino)benzylidene)-[1,1’:3’,1’’-terphenyl]-2’(5’H)-one.
Figure 4. Plot of lgk (solid symbols, C attack) and lgk’ (open triangles,
O attack) for the reaction of azolium enolates 2a–c with the benzhy-
drylium ions 3 in THF at 208C.
In conclusion, we have synthesized and elucidated the
structures of the azolium enolates 2a–c and investigated the
kinetics of their reactions with benzhydrylium ions. By using
the rule of thumb that electrophile–nucleophile combinations
parameters for the C-reactivity of the enolates 2a,b which are
listed in Scheme 4. Two correlation lines are found for 2c,
which correspond to the two sites of attack. Table 3 and
Figure 4 show that the enolate oxygen in 2c is approximately
[
14]
may take place at room temperature when E + N > ꢀ5 and
when the N values for the enolate carbon of the azolium
enolates 2a–c are between 14.4 and 15.9, we can explain their
[15a]
2
0-times more reactive than carbon.
reactions with N-activated imines (ꢀ11.5 > E > ꢀ15.1),
azodicarboxylates (ꢀ8.9 > E > ꢀ12.2), enones (E ꢂ
18.8), and 2,3,4,5,6,6-hexachlorocyclohexa-2,4-dienone
E = ꢀ6.8)
From the kinetic data, one can derive that benzhydrylium
[
15b]
[15a]
ꢀ
[
15c]
(
as electrophilic partners.
ions attack the enolate oxygen of 2c 20 times faster than the
enolate carbon to give the benzhydryl ethers 4 as the initial
products, which subsequently rearrange to the thermodynam-
ically stable products of C attack (5). The higher nucleophi-
licity of the enolate oxygen, which is a consequence of the
Scheme 4. N and sN parameters as defined by Equation (1) for the
azolium enolates 2a–c in THF (for 2a in DMSO: N=14.40, s =0.64).
N
[
10]
lower intrinsic barrier for O attack, may also be the origin
of the oxyanion steering effect (interaction of the enolate
oxygen with the carbonyl carbon of acrolein), derived by
Bode, Kozlowski et al. from quantum chemical calculations
for the Diels–Alder reaction of a triazolium enolate with
Table 3 shows that the reactions of 2a with the electro-
philes 3 are about one order of magnitude slower in DMSO
than in THF. Table 3, Figure 4, and Scheme 4 furthermore
show that the azolium enolates 2a and 2b derived from
imidazol-2-ylidene 1a and imidazolidin-2-ylidene 1b, respec-
tively, have similar reactivities and are 50 times more
nucleophilic than the triazole-derived enolate 2c (C-nucleo-
philicity).
[9g]
acrolein.
Received: April 25, 2013
Revised: May 15, 2013
Published online: && &&, &&&&
The different ranking of the nucleophilic reactivities of
[
11a]
Keywords: acylazolium ions · kinetics ·
N-heterocyclic carbenes · nucleophilicity · zwitterions
the carbenes (1a ꢂ 1b @ 1c, Scheme 5, middle)
and the
.
corresponding deoxy Breslow intermediates (6a @ 6c > 6b,
[
11b]
Scheme 5, right)
has been explained by inductive effects
(
reduced reactivities of 1c and 6c) and the fact that electro-
[
1] A. J. Arduengo III, R. L. Harlow, M. Kline, J. Am. Chem. Soc.
philic attack at 6a and 6c is associated with the gain of
aromaticity. Since the corresponding carbenes 1a and 1c are
already aromatic, electrophilic attack at these carbenes is not
associated with a gain of aromaticity.
1991, 113, 361 – 363.
[
2] For selected examples: a) W. A. Herrmann, Angew. Chem. 2002,
114, 1342 – 1363; Angew. Chem. Int. Ed. 2002, 41, 1290 – 1309;
b) V. Cꢁsar, S. Bellemin-Laponnaz, L. H. Gade, Chem. Soc. Rev.
2004, 33, 619 – 636; c) N-Heterocyclic Carbenes in Synthesis (Ed.:
As the azolium ring is perpendicular to the plane of the
enolate double bond (Figure 1) the reactivity order 2a ꢂ 2b >
S. P. Nolan), Wiley-VCH, Weinheim, 2006; d) E. A. B. Kantchev,
C. J. OꢀBrien, M. G. Organ, Angew. Chem. 2007, 119, 2824 –
2
c (Scheme 5, left) is not related to the different aromaticities
2870; Angew. Chem. Int. Ed. 2007, 46, 2768 – 2813; e) Topics in
of the azolium rings and can be explained by the stronger
Heterocyclic Chemistry, Vol. 21 (Ed.: F. Glorius), Springer,
Berlin, 2007, pp. 1 – 231; f) F. E. Hahn, M. C. Jahnke, Angew.
Chem. 2008, 120, 3166 – 3216; Angew. Chem. Int. Ed. 2008, 47,
[11b]
inductive electron-withdrawing effect of the triazole ring.
4
www.angewandte.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2013, 52, 1 – 6
These are not the final page numbers!

Angewandte
Chemie
3122 – 3172; g) S. Dꢂez-Gonzꢃlez, N. Marion, S. P. Nolan, Chem.
12333; l) J. Mo, R. Yang, X. Chen, B. Tiwari, Y. R. Chi, Org. Lett.
Rev. 2009, 109, 3612 – 3676; h) “N-Heterocyclic Carbenes in
Transition Metal Catalysis and Organocatalysis”: Catalysis by
Metal Complexes, Vol. 32 (Ed.: C. S. J. Cazin), Springer, Dor-
drecht, 2011.
2013, 15, 50 – 53.
[8] a) Y. Kawanaka, E. M. Phillips, K. A. Scheidt, J. Am. Chem. Soc.
2009, 131, 18028 – 18029; b) L. Hao, Y. Du, H. Lv, X. Chen, H.
Jiang, Y. Shao, Y. R. Chi, Org. Lett. 2012, 14, 2154 – 2157.
[9] For selected examples see: a) K. J. Hawkes, B. F. Yates, Eur. J.
Org. Chem. 2008, 5563 – 5570; b) M. Schumacher, B. Goldfuss,
Tetrahedron 2008, 64, 1648 – 1653; c) L. R. Domingo, M. J.
Aurell, M. Arnꢄ, Tetrahedron 2009, 65, 3432 – 3440; d) K. Tang,
J. Wang, Q. Hou, X. Cheng, Y. Liu, Tetrahedron: Asymmetry
2011, 22, 942 – 947; e) P. Verma, P. A. Patni, R. B. Sunoj, J. Org.
Chem. 2011, 76, 5606 – 5613; f) A. Berkessel, S. Elfert, V. R.
Yatham, J.-M. Neudçrfl, N. E. Schlçrer, J. H. Teles, Angew.
Chem. 2012, 124, 12537 – 12541; Angew. Chem. Int. Ed. 2012, 51,
12370 – 12374; g) S. E. Allen, J. Mahatthananchai, J. W. Bode,
M. C. Kozlowski, J. Am. Chem. Soc. 2012, 134, 12098 – 12103;
h) O. Hollꢄczki, Z. Kelemen, L. Nyulꢃszi, J. Org. Chem. 2012, 77,
6014 – 6022; i) Y. Reddi, R. B. Sunoj, Org. Lett. 2012, 14, 2810 –
2813; j) Y.-M. Zhao, M. S. Cheung, Z. Lin, J. Sun, Angew. Chem.
2012, 124, 10505 – 10509; Angew. Chem. Int. Ed. 2012, 51, 10359 –
10363; k) W. Zhang, Y. Zhu, D. Wei, Y. Li, M. Tang, J. Org.
Chem. 2012, 77, 10729 – 10737; l) C. J. Collett, R. S. Massey,
O. R. Maguire, A. S. Batsanov, A. C. OꢀDonoghue, A. D. Smith,
Chem. Sci. 2013, 4, 1514 – 1522.
[10] a) M. Breugst, H. Zipse, J. P. Guthrie, H. Mayr, Angew. Chem.
2010, 122, 5291 – 5295; Angew. Chem. Int. Ed. 2010, 49, 5165 –
5169; b) H. Mayr, M. Breugst, A. R. Ofial, Angew. Chem. 2011,
123, 6598 – 6634; Angew. Chem. Int. Ed. 2011, 50, 6470 – 6505.
[11] a) B. Maji, M. Breugst, H. Mayr, Angew. Chem. 2011, 123, 7047 –
7052; Angew. Chem. Int. Ed. 2011, 50, 6915 – 6919; b) B. Maji, M.
Horn, H. Mayr, Angew. Chem. 2012, 124, 6335 – 6339; Angew.
Chem. Int. Ed. 2012, 51, 6231 – 6235; c) B. Maji, H. Mayr, Angew.
Chem. 2012, 124, 10554 – 10558; Angew. Chem. Int. Ed. 2012, 51,
10408 – 10412; d) R. C. Samanta, B. Maji, S. De Sarkar, K.
Bergander, R. Frçhlich, C. Mꢅck-Lichtenfeld, H. Mayr, A.
Studer, Angew. Chem. 2012, 124, 5325 – 5329; Angew. Chem. Int.
Ed. 2012, 51, 5234 – 5238; e) H. Mayr, S. Lakhdar, B. Maji, A. R.
Ofial, Beilstein J. Org. Chem. 2012, 8, 1458 – 1478.
[
3] Applications as organocatalysts: a) D. Enders, O. Niemeier, A.
Henseler, Chem. Rev. 2007, 107, 5606 – 5655; b) N. Marion, S.
Dꢂez-Gonzꢃlez, S. P. Nolan, Angew. Chem. 2007, 119, 3046 –
3058; Angew. Chem. Int. Ed. 2007, 46, 2988 – 3000; c) J. L.
Moore, T. Rovis in Topics in Current Chemistry, Vol. 291 (Ed.: B.
List), Springer, Berlin, 2009, pp. 77 – 144; d) P.-C. Chiang, J. W.
Bode in N-Heterocyclic Carbenes: From Laboratory Curiosities
to Efficient Synthetic Tools (Ed.: S. S. Dꢂez-Gonzꢃlez), Royal
Society of Chemistry, Cambridge 2010, pp. 399 – 435; e) V. Nair,
R. S. Menon, A. T. Biju, C. R. Sinu, R. R. Paul, A. Jose, V.
Sreekumar, Chem. Soc. Rev. 2011, 40, 5336 – 5346; f) X. Bugaut,
F. Glorius, Chem. Soc. Rev. 2012, 41, 3511 – 3522; g) A.
Grossmann, D. Enders, Angew. Chem. 2012, 124, 320 – 332;
Angew. Chem. Int. Ed. 2012, 51, 314 – 325; h) J. Douglas, G.
Churchill, A. D. Smith, Synthesis 2012, 2295 – 2309; i) C. E. I.
Knappke, A. Imami, A. Jacobi von Wangelin, ChemCatChem
2012, 4, 937 – 941; j) S. De Sarkar, A. Biswas, R. C. Samanta, A.
Studer, Chem. Eur. J. 2013, 19, 4664 – 4678.
[
[
[
4] D. Seebach, Angew. Chem. 1979, 91, 259 – 278; Angew. Chem.
Int. Ed. Engl. 1979, 18, 239 – 258.
5] J. Kaeobamrung, M. C. Kozlowski, J. W. Bode, Proc. Natl. Acad.
Sci. USA 2010, 107, 20661 – 20665.
6] a) Y.-R. Zhang, L. He, X. Wu, P.-L. Shao, S. Ye, Org. Lett. 2008,
10, 277 – 280; b) N. Duguet, C. D. Campbell, A. M. Z. Slawin,
A. D. Smith, Org. Biomol. Chem. 2008, 6, 1108 – 1113; c) L. He,
H. Lv, Y.-R. Zhang, S. Ye, J. Org. Chem. 2008, 73, 8101 – 8103;
d) X.-N. Wang, P.-L. Shao, H. Lv, S. Ye, Org. Lett. 2009, 11, 4029 –
4031; e) X.-L. Huang, X.-Y. Chen, S. Ye, J. Org. Chem. 2009, 74,
7585 – 7587; f) P.-L. Shao, X.-Y. Chen, S. Ye, Angew. Chem. 2010,
122, 8590 – 8594; Angew. Chem. Int. Ed. 2010, 49, 8412 – 8416;
g) X.-L. Huang, L. He, P.-L. Shao, S. Ye, Angew. Chem. 2009,
21, 198 – 201; Angew. Chem. Int. Ed. 2009, 48, 192 – 195; h) T.-Y.
1
Jian, P.-L. Shao, S. Ye, Chem. Commun. 2011, 47, 2381 – 2383;
i) X.-N. Wang, H. Lv, X.-L. Huang, S. Ye, Org. Biomol. Chem.
[12] a) M. Regitz, J. Hocker, B. Weber, Angew. Chem. 1970, 82, 394 –
395; Angew. Chem. Int. Ed. Engl. 1970, 9, 375; b) Y.-G. Lee, J. P.
Moerdyk, C. W. Bielawski, J. Phys. Org. Chem. 2012, 25, 1027 –
1032; c) M. Hans, J. Wouters, A. Demonceau, L. Delaude, Chem.
Eur. J. 2013, 19, 9668 – 9676; d) A. Berkessel, V. R. Yatham, S.
Elfert, J.-M. Neudçrfl, Angew. Chem. 2013, DOI: 10.1002/
ange.201303107; Angew. Chem. Int. Ed. 2013, DOI: 10.1002/
anie.201303107.
2009, 7, 346 – 350; j) C. Concellꢄn, N. Duguet, A. D. Smith, Adv.
Synth. Catal. 2009, 351, 3001 – 3009; k) J. Douglas, K. B. Ling, C.
Concellꢄn, G. Churchill, A. M. Z. Slawin, A. D. Smith, Eur. J.
Org. Chem. 2010, 5863 – 5869.
[
7] a) H. U. Vora, T. Rovis, J. Am. Chem. Soc. 2010, 132, 2860 – 2861;
b) M. He, G. J. Uc, J. W. Bode, J. Am. Chem. Soc. 2006, 128,
15088 – 15089; c) S. Kobayashi, T. Kinoshita, H. Uehara, T. Sudo,
I. Ryu, Org. Lett. 2009, 11, 3934 – 3937; d) M. He, J. R. Struble,
J. W. Bode, J. Am. Chem. Soc. 2006, 128, 8418 – 8420; e) M.
Wadamoto, E. M. Phillips, T. E. Reynolds, K. A. Scheidt, J. Am.
Chem. Soc. 2007, 129, 10098 – 10099; f) E. M. Phillips, M.
Wadamoto, A. Chan, K. A. Scheidt, Angew. Chem. 2007, 119,
[13] CCDC 938823 contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge from
The Cambridge Crystallographic Data Centre via www.ccdc.
cam.ac.uk/data_request/cif.
[14] a) H. Mayr, T. Bug, M. F. Gotta, N. Hering, B. Irrgang, B. Janker,
B. Kempf, R. Loos, A. R. Ofial, G. Remennikov, H. Schimmel, J.
Am. Chem. Soc. 2001, 123, 9500 – 9512; b) H. Mayr, B. Kempf,
A. R. Ofial, Acc. Chem. Res. 2003, 36, 66 – 77; c) H. Mayr, A. R.
Ofial, Pure Appl. Chem. 2005, 77, 1807 – 1821; d) H. Mayr, A. R.
Ofial, J. Phys. Org. Chem. 2008, 21, 584 – 595.
3
167 – 3170; Angew. Chem. Int. Ed. 2007, 46, 3107 – 3110; g) Y.
Li, X.-Q. Wang, C. Zheng, S.-L. You, Chem. Commun. 2009,
823 – 5825; h) V. Nair, R. R. Paul, K. C. Seetha Lakshmi, R. S.
Menon, A. Jose, C. R. Sinu, Tetrahedron Lett. 2011, 52, 5992 –
5
5994; i) X. Fang, X. Chen, Y. R. Chi, Org. Lett. 2011, 13, 4708 –
4711; j) H. Lv, J. Mo, X. Fang, Y. R. Chi, Org. Lett. 2011, 13,
5366 – 5369; k) X. Zhao, K. E. Ruhl, T. Rovis, Angew. Chem.
2012, 124, 12496 – 12499; Angew. Chem. Int. Ed. 2012, 51, 12330 –
[15] a) R. Appel, H. Mayr, J. Am. Chem. Soc. 2011, 133, 8240 – 8251;
b) T. Kanzian, H. Mayr, Chem. Eur. J. 2010, 16, 11670 – 11677;
c) X.-H. Duan, H. Mayr, Org. Lett. 2010, 12, 2238 – 2241.
Angew. Chem. Int. Ed. 2013, 52, 1 – 6
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
These are not the final page numbers!

.
Angewandte
Communications
Communications
Organocatalysis
B. Maji,* H. Mayr*
&&&& — &&&&
Structures and Ambident Reactivities of
Azolium Enolates
Oxygen versus carbon: Azolium enolates
were generated by the reactions of N-
heterocyclic carbenes (NHCs) with
methyl phenyl ketene and characterized
by X-ray crystallography. Kinetic studies
show that the enolate oxygen is 20 times
more nucleophilic than the carbon but
under thermodynamic control exclusive
C-addition products were formed.
6
www.angewandte.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2013, 52, 1 – 6
These are not the final page numbers!