Chiral bicyclic imidazolium salts as a new class of N-heterocyclic carbene precursors

Article abstract of DOI:10.1016/j.tetlet.2008.02.175

A N(1)-C(5) bridged chiral bicyclic imidazole with a morpholine framework was synthesized from an enantiopure 2-amino alcohol. The resultant imidazole reacted with various electrophiles, including primary and secondary alkyl halides, benzyne, and an electron-deficient aryl halide, to give the corresponding imidazolium salts. Some of the imidazolium salts were found to have potential as the precursor of a chiral N-heterocyclic carbene catalyst; by the direct annulation of an enal and a ketone through the intermediacy of a homoenolate and an activated carboxylate, the target lactone was obtained in an enantiomerically enriched form (up to 66% ee).

Full text of DOI:10.1016/j.tetlet.2008.02.175

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 2985–2989
Chiral bicyclic imidazolium salts as a new class
of N-heterocyclic carbene precursors
Yuki Matsuoka, Yasuhiro Ishida *, Kazuhiko Saigo *
Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-8656, Japan
Received 28 January 2008; revised 21 February 2008; accepted 28 February 2008
Available online 10 March 2008
Abstract
A N(1)–C(5) bridged chiral bicyclic imidazole with a morpholine framework was synthesized from an enantiopure 2-amino alcohol.
The resultant imidazole reacted with various electrophiles, including primary and secondary alkyl halides, benzyne, and an electron-
deficient aryl halide, to give the corresponding imidazolium salts. Some of the imidazolium salts were found to have potential as the
precursor of a chiral N-heterocyclic carbene catalyst; by the direct annulation of an enal and a ketone through the intermediacy of a
homoenolate and an activated carboxylate, the target lactone was obtained in an enantiomerically enriched form (up to 66% ee).
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Asymmetric catalyst; Imidazolium; Homoenolate; N-Heterocyclic carbene; Umpolung
Owing to the unique properties and potential utilities,
N-heterocyclic carbenes (NHCs) have attracted increasing
attention for the last two decades.1 NHCs have been found
to serve as universal ligands for transition metal-based
catalysts,2 of which the enhanced catalytic activities are
originated from the strong r-donating property of the
NHC ligands.3 In addition, NHCs are known to act as
metal-free organocatalysts to promote several kinds of
unique and uncommon organic transformations, which
can hardly occur in other systems.4 As an extension of
these studies, the development of chiral NHCs and their
application to enantioselective organic transformations
are of special importance. In fact, a large number of chiral
azolium salts (imidazolium, imidazolinium, triazolium, and
thiazolium salts) have been developed as precursors of
chiral NHCs, and some of them exhibited an excellent
chiral induction ability.4
the most promising classes to realize high enantioselecti-
vity; N(3)–C(4) bridged thiazolium salts (Fig. 1, A)5 and
C(3)–N(4) bridged triazolium salts (B)6 have been proven
to provide excellent NHC catalysts for various asymmetric
reactions involving the umpolung of aldehydes, such as the
benzoin condensation and the Stetter reaction. Considering
Ar
Ar
Ar
Ar
X
* R
X
n
*
* R
*
N+
N
N
N
A–
A–
A–
A–
N
N+
Ar
N+
S
N+
*
D
*
C
A
B
Ar
R
R
R1
A–
*
*
O
*
*
R2
O
O
O
For the design of chiral NHC organocatalysts, those
with a rigid bicyclic framework are known to be one of
N
N
N
N
N
A–
R1
A–
A–
N+
N+
N+
R2
Ar
*
F
R
*
Corresponding authors. Tel.: +81 3 5841 7266; fax: +81 3 5802 3348
E
G
H
(K.S.).
Fig. 1. Design of chiral azolium salts.
E-mail address: saigo@chiral.t.u-tokyo.ac.jp (K. Saigo).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.02.175

2986
Y. Matsuoka et al. / Tetrahedron Letters 49 (2008) 2985–2989
the strong relationship between the properties of NHCs
(nucleophilicity, basicity, catalytic activity, etc.) and the
structure/species of their parent azolium salts, chiral imid-
azolylidenes, derived from the corresponding imidazolium
salts with a fused-ring structure, should play a role comple-
mentary to traditional NHCs obtained from analogous
thiazolium and triazolium salts (A and B). At the present
time, however, the synthesis of chiral imidazolium salts
with such a constrained structure has been limited com-
pared with other azolium salts; relatively simple imidazo-
lium salts having two 1-arylethyl substituents at the N(1)
and N(3) positions (C and D) were most widely used as
the precursors of chiral imidazolylidenes.7 Rare and note-
worthy exceptions are bicyclic/tricyclic imidazolium salts
(F and G), of which the application to asymmetric induc-
tion in organic transformations is still at a developing
stage.8,9 These aspects prompted us to synthesize bicyclic
imidazolium salts with a N(3)–C(4) bridged structure (H).10
In order to ensure the structural variation for NHCs, it
would be advantageous to incorporate an easily accessible
chiral building block into the skeleton of NHC precursors.
On the basis of such consideration, we envisioned a syn-
thetic route starting from an enantiopure 2-amino alcohol,
as shown in Scheme 1. Imidazole 3 with two hydroxy
groups was synthesized by applying well-established reac-
tions for the preparation of N(3)-substituted and C(4)-
hydroxymethylated imidazoles.11 The cyclocondensation
of (R)-2-amino-2-phenylethanol (1), 1,3-dihydroxypro-
pan-2-one, and potassium thiocyanate in the presence of
aqueous HCl and AcOH gave the corresponding mercapto-
imidazole 2, which was then desulfurized under oxidative
conditions to give imidazole 3.11b The high polarity of 2
and 3 made their purification difficult and lowered the
yields to some extent. This problem might be solved by
proper protection of the hydroxy group in 1.
of the two hydroxy groups into a leaving group (chloro, p-
toluenesulfonato, etc.), followed by the intramolecular con-
densation of this moiety with the other hydroxy group. For
the first step, the treatment of 3 with thionyl chloride or
with p-toluenesulfonyl chloride/pyridine gave a complex
mixture. Therefore, we surveyed several reagents for the
transformation of the hydroxy group into a chloro group
and finally found that the Vilsmeier reagent, generated from
oxalyl chloride/N,N-dimethylformamide, was effective.11c
As a result, diol 3 was easily converted into a mixture of
the monochlorinated products 4a and 4b in almost quanti-
tative yield. Although only a slight chemoselection between
the two hydroxy groups took place (4a:4b = 50:50–60:40),
the dichlorinated byproduct was not generated at a detect-
able level; in this case, the second chlorinations would be a
further slower process than the first chlorinations, proba-
bly because the electronic and/or steric effect of the intro-
duced chlorine atom in the first place retards the second
chlorination.
Concerned with the intramolecular ether formation, the
two monochlorinated imidazoles 4a and 4b were expected
to give the same product 5. Contrary to our expectation,
however, the treatment of the mixture with sodium hydride
(2.0 equiv) gave not only the target compound 5, but also
the N-alkenylimidazole 7 in a considerable extent, which
was undoubtedly generated by the base-promoted elimina-
tion of HCl from 4b. Because the ratio of the two products
in the resultant mixture (5:7 = 50:50–60:40) was almost
identical to that of the monochlorinated imidazoles 4a
and 4b in the starting material, 4a and 4b were likely to
be exclusively converted into 5 and 7, respectively (Scheme
2). Thus, the chiral imidazole with a fused-ring structure 5
was obtained in an overall yield of 43% from the
bis(hydroxy)imidazole 3. The structure of 5 was unequivo-
cally identified by an X-ray crystallographic analysis.12
In the next stage, various electrophiles were applied to
the quaternization of 5, which provided the N(3) substitu-
ent of the target imidazolium salts 6 (Fig. 2). In the synthe-
sis of analogous triazolium/imidazolium salts established
by several research groups (Fig. 1, B and G), only aromatic
groups could be introduced at the N(3) position in conver-
gent synthetic routes.6,8 Compared with this, the synthesis
of the present imidazolium salts has two notable character-
istics: (i) imidazolium salts with various N-substituents can
Then, we attempted the condensation of the two
hydroxy groups in 3 to obtain the target imidazole 5 with
a bicyclic framework. For this transformation, we envis-
aged the following reaction course: the conversion of either
HO
HO
Ph
SH
Ph
HO
N
N
HO
N
N
(i)
(ii) HO
H2N
Ph
28%
(2 steps)
1
2
3
HO
O
Ph
Ph
Y
O
O
Ph
Ph
A–
Ph
NaH
N
N
N
Cl
DMF, 0 °C to rt
N
(iii)
(iv)
N
(v)
N
X
N
5
43%
(2 steps)
N
N
N
4a
R
4
5
6
a: X = Cl, Y = OH
b: X = OH, Y = Cl
Cl
Ph
Ph
NaH
DMF, 0 °C to rt
N
N
HO
HO
Scheme 1. Synthesis of the chiral bicyclic imidazolium salt 6. Reagents
and conditions: (i) 1,3-dihydroxypropan-2-one (dimer), KSCN, HClaq,
AcOH/1-BuOH, 80 °C; (ii) H2O2, AcOH/water, rt; (iii) (COCl)2/DMF,
CH3CN, 0 °C to rt; (iv) NaH, DMF, 0 °C to rt; (v) electrophile (see
Fig. 2).
N
4b
N
7
Scheme 2. Transformation of 4a,b by the treatment with a base.

Y. Matsuoka et al. / Tetrahedron Letters 49 (2008) 2985–2989
2987
O
O
Ph
Ph
A–
N
N
N
electrophile
N
R
5
6a–e
O
O
Ph
I–
Ph
N
N
N
N
6a: 66%
–OTf 6d: 23%
Fig. 3. X-ray crystal structure of a 6a0; (a) top view and (b) side view. The
counter anion (PF6ꢀ) is omitted for clarity.
Me
Ph
OTf
CH3I, THF, reflux
SiMe3
/ CsF
O
Ph
In order to demonstrate the utility of imidazolylidene
NHCs derived from these new imidazolium salts 6, we
attempted the NHC-catalyzed annulation of an enal and
a ketone.15 This reaction and relatives are expected to pro-
vide us a powerful tool for C–C bond formations in a novel
mode, which involves the catalytic generation of a homo-
enolate from the enal unit, followed by the electrophilic
trapping of the homoenolate (Scheme 3). Among NHCs
derived from azolium salts, however, only imidazolylidenes
are known to be able to catalyze this reaction efficiently,
most likely because of the difference in their physical pro-
perties depending on the parent species.10,15b,d Moreover,
in spite of no less than four years having past since the first
report, there has been only one example of enantioselective
version, where chiral induction with an unsatisfactory level
was reported (up to 25% ee).15b Thus, the catalytic and
asymmetric reaction of a homoenolate with an electrophile
still remains as an unexplored realm in this field, which
motivated us to apply the imidazolium precatalysts 6 for
this reaction.16
CH3CN, reflux
N
–
PF6 6b: 64%
N
O
Ph
Me
Me
N
N
Cl– 6e: 89%
(i) (CH3)2CHI, THF, reflux
(ii) KPF6, acetone/water, rt
O2N
O
Ph
N
N
–
NO2
NO2
PF6 6c: 56%
Ph
Ph
O2N
Cl
(i) (Ph)2CHBr, toluene, reflux
(ii) KPF6, CH3CN, rt
toluene, reflux
Fig. 2. Synthesis of imidazolium salts 6a–e by the treatment of 5 with
various electrophiles.
be derived from a common precursor imidazole in a diver-
gent manner, just upon changing an electrophile for the
quaternization, and (ii) both of aliphatic and aromatic
substituents are potentially introduced at the N(3) of the
parent imidazole by applying conventional methods for
alkylation/arylation.13 In fact, the reaction of primary
and secondary alkyl halides with 5 proceeded very
smoothly to afford the corresponding N(3)-alkylated imid-
azolium salts (6a–c) in acceptable yields. In addition to
this, an aromatic ring could also be introduced at the same
position, although there was room for the improvement in
yield, variation of applicable aryl group, and convenience
in isolation; the reaction of in situ generated benzyne13a
and an electron-deficient aryl halide13b afforded the corres-
ponding imidazolium salts (6d and 6e) in 23% and 89%
yields, respectively.
An analogue of 6a with higher crystallinity (6a0) was
prepared by the anion exchange from Iꢀ to PF6ꢀ, and an
X-ray crystallographic study was conducted for a single
crystal of 6a0 (Fig. 3).12 Noteworthy is the fact that the
phenyl group is placed at the equatorial position of the
six-membered ring taking a pseudo-chair conformation.
As a result, the phenyl group efficiently shields a half space
around the imidazolium C(2), which seems advantageous
for efficient chiral induction.14
At the beginning of this study, the condensations of cin-
namaldehyde (8) with 2,2,2-trifluoroacetophenone (9) were
conducted, by using imidazolylidene NHCs generated from
O
O
O
O
NHC
O
O
+
+
H
Ph
CF3
Ph
CF3
CF3
Ph
Ph
Ph
Ph
8
trans-10
cis-10
9
NHC
NHC
O
O
Ph
Ph
OH
OH
N
N
N
9
N
Ph
Ph
R
R
(i) 6 (0.20 eq), KN(SiMe3)2 (0.20 eq), THF, –78 °C, 1 h;
(ii) 8 (1.0 eq), 9 (4.0 eq), THF, –78 °C to rt, 16 h.
NHC from 6a
NHC from 6c
33% (14% ee)
11% (15% ee)
23% (66% ee)
5% (59% ee)
trans-10:
cis-10:
trans-10:
cis-10:
Scheme 3. NHC-catalyzed annulation of an enal with a ketone.

2988
Y. Matsuoka et al. / Tetrahedron Letters 49 (2008) 2985–2989
Chem. Rev. 2000, 100, 39; (d) Nair, V.; Bindu, S.; Sreekumar, V.
Angew. Chem., Int. Ed. 2004, 43, 5130.
2. For reviews of NHCs as ligands, see: (a) Herrmann, W. A.; Ko¨cher,
C. Angew. Chem., Int. Ed. 1997, 36, 2162; (b) Herrmann, W. A.
6a and 6c with potassium hexamethyldisilazane (Scheme
3).15b In both these cases, the desired condensate 10 was
obtained in acceptable yields (as mixtures of trans and cis
isomers; 44% and 28% yields, respectively).17 As for the
stereochemical outcome of the condensations, however,
there was a significant difference between the two catalytic
systems; the NHC from 6c achieved diastereo- and enanti-
oselectivities much higher than did that from 6a, which
suggests that the NHC catalyst with a bulky N-substituent
is advantageous for the control of the relative orientation
of the homoenolate intermediate and the electrophile 9
(Scheme 3). Worth noting is the fact that diastereo- and
enantio-controls achieved by the NHC from 6c were the
most excellent for the present condensation, as far as we
know (dr = 84:16, eemajor = 66%, eeminor = 59%). In addi-
tion, the dramatic change in stereochemical outcome
between the two precatalysts 6a and 6c implies that we
can further optimize the N-substituent, taking advantage
of the divergent synthetic route from 5 to 6.
In conclusion, we developed precursors (6a–e) for novel
chiral imidazolylidenes, which have a bicyclic structure
with a morpholine framework. The NHC derived from 6c
catalyzed the annulation of enal 8 and ketone 9 to give
the lactone 10 with good diastereo- and enantioselectivities.
Considering the peculiar reactivity of imidazolylidenes
compared with those of thiazolylidenes and triazolylidenes,
as well as the conformationally fixed structure advanta-
geous for efficient chiral induction, we believe that the
imidazolium salts 6a–e would be widely useful as the
precursors of chiral organocatalysts for various organic
transformations.
´
Angew. Chem., Int. Ed. 2002, 41, 1290; (c) Cesar, V.; Bellemin-
´
Laponnaz, S.; Gade, L. H. Chem. Soc. Rev. 2004, 33, 619; (d) Dıez-
´
Gonzalez, S.; Nolan, S. P. Coord. Chem. Rev. 2007, 251, 874.
3. (a) Huang, J.; Stevens, E. D.; Nolan, S. P.; Petersen, J. L. J. Am.
Chem. Soc. 1999, 121, 2674; (b) Huang, J.; Schanz, H.-J.; Stevenes, E.
D.; Nolan, S. P.; Capps, K. B.; Bauer, A.; Hoff, C. D. Inorg. Chem.
2000, 39, 1042; (c) Huang, J.; Jafarpour, L.; Hillier, A. C.; Stevens, E.
D.; Nolan, S. P. Organometallics 2001, 20, 2878.
4. For reviews of NHCs as organocatalysts, see: (a) Enders, D.;
Balensiefer, T. Acc. Chem. Res. 2004, 37, 534; (b) Jonson, J. S.
Angew. Chem., Int. Ed. 2004, 43, 1326; (c) Christmann, M. Angew.
Chem., Int. Ed. 2005, 44, 2632; (d) Zeitler, K. Angew. Chem., Int. Ed.
´
´
2005, 44, 7506; (e) Marion, N.; Dıez-Gonzalez, S.; Nolan, S. P.
Angew. Chem., Int. Ed. 2007, 46, 2988.
5. For examples, of thiazolium-based chiral NHCs with a bicyclic
structure, see: (a) Knight, R. L.; Leeper, F. J. Tetrahedron Lett. 1997,
38, 3611; (b) Gerhard, A. U.; Leeper, F. J. Tetrahedron Lett. 1997, 38,
3615; (c) Dvorak, C. A.; Rawal, V. H. Tetrahedron Lett. 1998, 39,
2925; (d) Pesch, J.; Harms, K.; Bach, T. Eur. J. Org. Chem. 2004,
2025.
6. For examples, of triazolium-based chiral NHCs with a bicyclic
structure, see: (a) Enders, D.; Breuer, K.; Runsink, J.; Teles, J. H.
Helv. Chim. Acta 1996, 79, 1899; (b) Knight, R. L.; Leeper, F. J. J.
Chem. Soc., Perkin Trans. 1 1998, 1891; (c) Enders, D.; Kallfass, U.
Angew. Chem., Int. Ed. 2002, 41, 1743; (d) Kerr, M. S.; Read de
Alaniz, J.; Rovis, T. J. Am. Chem. Soc. 2002, 124, 10298; (e) Kerr, M.
S.; Rovis, T. Synlett 2003, 1934; (f) Kerr, M. S.; Read de Alaniz, J.;
Rovis, T. J. Org. Chem. 2005, 70, 5725; (g) Read de Alaniz, J.; Rovis,
T. J. Am. Chem. Soc. 2005, 127, 6284; (h) Enders, D.; Niemeier, O.;
Balensiefer, T. Angew. Chem., Int. Ed. 2006, 45, 1463; (i) Takikawa,
H.; Hachisu, Y.; Bode, J. W.; Suzuki, K. Angew. Chem., Int. Ed. 2006,
45, 3492.
7. (a) Suzuki, Y.; Yamauchi, K.; Muramatsu, K.; Sato, M. Chem.
Commun. 2004, 2770; (b) Kano, T.; Sasaki, K.; Maruoka, K. Org.
Lett. 2005, 7, 1347; (c) Chan, A.; Scheidt, K. A. Org. Lett. 2005, 7,
905; (d) Suzuki, Y.; Abu Bakar, M. D.; Muramatsu, K.; Sato, M.
Tetrahedron 2006, 62, 4227.
Further optimization of the N-substituent in 6 and
detailed studies on the physical properties, such as nucleo-
philicity, basicity, r-donating property, and dimerization
propensity, are under investigation.
8. Glorius, F.; Altenhoff, G.; Goddard, R.; Lehmann, C. Chem.
Commun. 2002, 2704.
9. For recent studies on the development of new chiral imidazole/
imidazolium salts with potential applications as NHC precursors, see:
Acknowledgments
´
(a) Furstner, A.; Alcarazo, M.; Cesar, V.; Lehmann, C. W. Chem.
¨
Commun. 2006, 2176; (b) Matsuoka, Y.; Ishida, Y.; Sasaki, D.; Saigo,
K. Tetrahedron 2006, 62, 8199; (c) Schmidt, M. A.; Movassaghi, M.
We acknowledge Dr. M. Yamazaki (Rigaku Corpora-
tion) for the X-ray crystallography of 6a0. We would also
like to thank Professor Y. Nishibayashi and Dr. Y. Miyake
(The University of Tokyo) for MS spectroscopy.
Tetrahedron Lett. 2007, 48, 101; (d) Furstner, A.; Alcarazo, M.;
¨
Krause, H.; Lehmann, C. W. J. Am. Chem. Soc. 2007, 129, 12676.
10. During the reviewing process of this Letter, the development of a
chiral bicyclic imidazolium salt with a framework quite similar to that
of our imidazolium salts has been reported (type H in Figure 1,
R2 = mesityl). See: Struble, J. R.; Kaeobamrung, J.; Bode, J. W. Org.
Lett. 2008, 10. doi:10.1021/ol800006m.
Supplementary data
11. (a) Marckwald, W. Ber. Dtsch. Chem. Ges. 1892, 25, 2354; (b)
Maligres, P. E.; Waters, M. S.; Weissman, S. A.; McWilliams, J. C.;
Lewis, S.; Cowen, J.; Reamer, R. A.; Volante, R. P.; Reider, P. J.;
Askin, D. J. Heterocycl. Chem. 2003, 40, 229; (c) Xi, N.; Xu, S.;
Cheng, Y.; Tasker, A. S.; Hungate, R. W.; Reider, P. J. Tetrahedron
Lett. 2005, 46, 7315.
Experimental details for the synthesis and characteri-
zation of 2–6 and for the enantioselective annulation of 8
and 9 to form 10 are available. Supplementary data associ-
ated with this article can be found, in the online version, at
doi:10.1016/j.tetlet.2008.02.175.
12. Crystallographic data for 5 and 6a0 have been deposited with the
Cambridge Crystallographic Data Centre as Supplementary Publica-
tion Numbers CCDC 672454 and CCDC 672455, respectively. These
data can be obtained free of charge via www.ccdc.cam.ac.uk/
data_request/cif, by emailing data_request@ccdc.cam.ac.uk, or by
contacting the Cambridge Crystallographic Data Centre, 12 Union
Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
References and notes
1. (a) Arduengo, A. J., III; Harlow, R. L.; Kline, M. J. Am. Chem. Soc.
1991, 113, 361; (b) Arduengo, A. J., III. Acc. Chem. Res. 1999, 32,
913; (c) Bourissou, D.; Guerret, O.; Gabba¨ı, F. P.; Bertrand, G.

Y. Matsuoka et al. / Tetrahedron Letters 49 (2008) 2985–2989
2989
13. (a) Yoshida, H.; Sugiura, S.; Kunai, A. Org. Lett. 2002, 4, 2767; (b)
Claramunt, R. M.; Elguero, J.; Meco, T. J. Heterocycl. Chem. 1983,
20, 1245.
14. The imidazolium ring of 6a takes a slightly distorted shape most likely
because of the constrained bicyclic structure. The bond angle of N(1)–
C(2)–N(3) in an imidazolium ring: 6a0, 107.8°; usual N(1),N(3),C(5)-
trialkylimidazoliums, 109°.
15. (a) Sohn, S. S.; Rosen, E. L.; Bode, J. W. J. Am. Chem. Soc. 2004,
126, 14370; (b) Burstein, C.; Glorius, F. Angew. Chem., Int. Ed. 2004,
43, 6205; (c) He, M.; Bode, J. W. Org. Lett. 2005, 7, 3131; (d) Sohn, S.
S.; Bode, J. W. Org. Lett. 2005, 7, 3873; (e) Nair, V.; Vellalath, S.;
Poonoth, M.; Mohan, R.; Suresh, E. Org. Lett. 2006, 8, 507; (f) Nair,
V.; Vellalath, S.; Poonoth, M.; Suresh, E. J. Am. Chem. Soc. 2006,
128, 8736.
NHC-catalyzed homoenolate formation have been published. See: (a)
Phillips, E. M.; Reynolds, T. E.; Scheidt, K. A. J. Am. Chem. Soc.
2008. doi:10.1021/ja710521m; (b) Seayad, J.; Patra, P. K.; Zhang, Y.;
Ying, J. Y. Org. Lett. 2008, 10. doi:10.1021/ol800003n; (c) Chan, A.;
Scheidt, K. A. J. Am. Chem. Soc. 2008, 130. doi:10.1021/ja711130p.
In some of these examples, enantioselectivity much better than that in
Ref. 15b was achieved (up to 93% ee) by using special electrophiles.
However, it seems still difficult to realize satisfactory selectivity by
using a simple aldehyde or ketone as an electrophile unit (up to 34%
ee).
17. In both the cases, enal 8 was consumed almost completely, but the
formation of another c-lactone via the homo-annulation of 8 took
place to reduce the yield of 10. This problematic side reaction was
commonly observed in the case of other imidazolylidene catalysts (see
Ref. 15a).
16. During the reviewing process of this Letter, four reports (Ref. 10 and
the following three papers) for enantioselective reactions involving