Synthesis of novel chiral bidentate hydroxyalkyl-N-heterocyclic carbene ligands and their application in palladium-catalyzed Mizoroki-Heck couplings and asymmetric addition of diethylzinc to benzaldehyde

Article abstract of DOI:10.1016/j.tetlet.2013.11.027

A small library of new chiral bidentate hydroxyalkyl-imidazolium salts 1 is conveniently synthesized on multi-gram scale from inexpensive and commercially available chiral pool amino acids. The corresponding carbenes, generated by deprotonation of imidazolium salts 1, in combination with palladium(II) chloride were tested in the Mizoroki-Heck coupling reaction. The most significant results in terms of yields and reactivities were achieved with low catalyst loading. The catalytic activities of these imidazolium salts were also investigated in the asymmetric addition of diethylzinc to benzaldehyde. The use of MgO nanoparticles as an additive in conjunction with these ligands played a crucial role in increasing the efficiency of these reactions.

Full text of DOI:10.1016/j.tetlet.2013.11.027

Tetrahedron Letters 55 (2014) 346–350
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Synthesis of novel chiral bidentate hydroxyalkyl-N-heterocyclic
carbene ligands and their application in palladium-catalyzed
Mizoroki–Heck couplings and asymmetric addition of diethylzinc
to benzaldehyde
⇑
Laleh Faraji, Khosrow Jadidi , Behrouz Notash
Department of Chemistry, Shahid Beheshti University, G.C. Tehran 1983963113, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 12 July 2013
Revised 26 September 2013
Accepted 7 November 2013
Available online 15 November 2013
A small library of new chiral bidentate hydroxyalkyl-imidazolium salts 1 is conveniently synthesized on
multi-gram scale from inexpensive and commercially available chiral pool amino acids. The correspond-
ing carbenes, generated by deprotonation of imidazolium salts 1, in combination with palladium(II)
chloride were tested in the Mizoroki–Heck coupling reaction. The most significant results in terms of
yields and reactivities were achieved with low catalyst loading. The catalytic activities of these
imidazolium salts were also investigated in the asymmetric addition of diethylzinc to benzaldehyde.
The use of MgO nanoparticles as an additive in conjunction with these ligands played a crucial role in
increasing the efficiency of these reactions.
Keywords:
Chiral N-heterocyclic carbene
Hydroxyalkyl-imidazolium salt
Mizoroki–Heck reaction
MgO nanoparticles
Ó 2013 Elsevier Ltd. All rights reserved.
Asymmetric addition
Since the discovery of the first stable, isolable, and storable
N-heterocyclic carbene (NHC) by Arduengo et al. in 1991,1 NHCs
have become a developing class of ligands due to their various
applications in organometallic reactions.2,3 N-heterocyclic carbenes
have several interesting properties such as low toxicity, high
In addition, in order to assess the ability of this new class of chiral
NHC ligands to induce asymmetry in catalytic reactions, they were
utilized in diethylzinc addition to benzaldehyde. The latter process,
similar to the Mizoroki–Heck reaction, has been the subject of in-
tense scrutiny as a valuable process for CAC bond formation.8,9
For this purpose, a series of novel chiral hydroxyalkyl-imidazo-
lium salts 1 was prepared conveniently by a four-step procedure,
with minimal purification of intermediates, and in high overall
yields and excellent enantiomeric excesses from readily available
(S)-amino acids (Table 1). Firstly, the amino acids were protected
with either the carbobenzoxy (Cbz) or benzoyl (Bz) groups.10 Next,
the resulting hydroxydiamides 4 were obtained in 80–96% yields
from the coupling reaction of the protected amino acids 2 with chi-
ral amino alcohols 3,11 which were themselves easily prepared by
reduction of the corresponding amino acids. The hydroxydiamides
4 were reduced easily with lithium aluminum hydride and cleanly
produced chiral tridentate diamine precursors 5 in 80–90% yields.
Finally, the desired chiral hydroxyalkyl-imidazolium salts 1 were
obtained by treatment of compounds 5 with anhydrous HCl in
methanol and then refluxing in the presence of triethyl orthofor-
mate in toluene. The diversity of available chiral amino acids made
it possible to create a library of chiral hydroxyalkyl-imidazolium
salts 1 (Table 1). The structures of products 1 were assigned from
their elemental and spectroscopic analyses including IR, 1H NMR,
13C NMR, and mass spectral data. As expected, the 1H NMR and
stability, strong
r-donating and weak p
-accepting abilities,4 and
exceptional electronic and steric effects5 in generating strong bonds
to a metal. Because of these characteristics of metal NHC complexes,
various chiral-NHC ligands have been introduced and their metal
complexes utilized as catalysts for numerous reactions.2,3,6
Among the various types of chiral-NHC ligands, chiral hydroxy-
alkyl-NHC ligands that contain two stereogenic centers on the
N-substituent and on the backbone of the imidazolium ring are
rare.7 To develop this group of catalysts, herein we report a new
protocol for the synthesis of a small library of novel chiral hydrox-
ylalkyl-imidazolium salts 1, containing both a chiral N-substituent
and a stereogenic center on the backbone of the imidazolium ring,
on multi-gram scale from inexpensive and commercially available
chiral pool amino acids (Scheme 1).
The chiral hydroxyalkyl-imidazolium salts were evaluated as
bidentate NHC ligand precursors and were found to be efficient
palladium-NHC catalysts in the Mizoroki–Heck coupling reaction.
⇑
Corresponding author. Tel./fax: +98 021 22431661.
E-mail address: k-jadidi@sbu.ac.ir (K. Jadidi).
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.11.027

L. Faraji et al. / Tetrahedron Letters 55 (2014) 346–350
347
R1
N
Cl -
R2
R1
OH
O
N+ R2
+
R3
P
NH
H2N
OH
HO
1
R2
OH
R1
OH
H2N
O
H2N
O
Scheme 1.
Table 1
Synthesis of chiral pool imidazolium salts 1
R1
iBuOCOCl
O
R1
OH
O
NMM, THF, -15°C
R2
R2
P
HN HN
HO
P
NH
4
2
H2N
OH
3
LiAlH4, THF
reflux, 12 h
R1
Cl -
N+ R2
R1
HCl/MeOH
Et2O
N
R3
R2
NH HN
R3
HO
then HC(OEt)3
toluene, 80 °C
HO
5
1
Figure 1. ORTEP diagram of 1a-PF6. Thermal ellipsoids are at 30% probability level.
CCDC No. 923443.
N-protected amino acid
R1
R2
R3
1 (yield %)
(S)-Cbz-phenyl-Gly
(S)-Cbz-phenyl-Gly
(S)-Cbz-phenyl-Gly
(S)-Cbz-phenyl-Gly
(S)-Cbz-Phe
(S)-Cbz-Val
(S)-Cbz-Leu
(S)-Cbz-Leu
(S)-Bz-Leu
Ph
Ph
Ph
Ph
Ph
Me
Me
Me
Me
Me
Me
Me
Me
Bn
1a (78)
1b (69)
1c (67)
1d (73)
1e (90)
1f (86)
1g (85)
1h (92)
1i (75)
1j (70)
1k (89)
1l (86)
i-Pr
i-Bu
Bn
Ph
Ph
Cl-
N+ Ph
Ph
S8
NaH, THF
N
Bn
Bn
N
N
Ph
N
Ph
..N
i-Pr
i-Bu
i-Bu
i-Bu
i-Bu
i-Bu
i-Bu
i-Pr
i-Bu
Bn
Bn
Ph
S
HO
1a
HO
HO
6
(S)-Bz-Leu
(S)-Bz-Leu
(S)-Bz-Leu
Bn
Bn
Bn
Scheme 2. Trapping of NHC 1a with sulfur to give thiourea 6.
i-Bu
i-Pr
(NaH, THF) in the presence of elemental sulfur led to the formation
of the thiourea 6 in 64% yield (Scheme 2). The NCHN proton signal
of imidazolium chloride 1a (9.86 ppm) was absent in the 1H NMR
spectrum of 6, confirming carbene generation. The molecular
structure of 6 was also confirmed by means of X-ray diffraction
analysis (Fig. 2).
13C NMR spectra of ligands 1 clearly showed the presence of only
one diastereomer. Since the yields of the products were very high
and no other diastereomers were observed the reactions occurred
without racemization. To confirm the lack of racemization, we
grew single crystals of the products for X-ray diffraction studies.
A suitable single crystal of 1a was obtained by exchanging the
counter anion from chloride to hexafluorophosphate (1a-PF6).
The structure of the latter salt was determined by single-crystal
X-ray analysis (Fig. 1).
Compound 1a-PF6 was found to crystallize in chiral space group
P212121, in which the crystal consists of a single enantiomer of 1a-
PF6. The absolute configuration of the stereogenic centers (S,S) in
product 1a-PF6 was determined by correlation with the known
absolute configuration of the stereogenic center in the starting
amino acid (S) as an internal chiral reference and the Flack
parameter.
The 1H NMR spectra of imidazolium chlorides 1 showed the
presence of characteristic NCHN resonances around 9.16–
9.86 ppm. The counter anions of 1 influenced the chemical shift
of C2-H, for instance, when the counter anion of 1a was changed
to PF6; C2-H shifted to a higher field (1.1 ppm). To prepare the cor-
responding free chiral carbenes from chiral imidazolium chloride
1, 1a was deprotonated with KOt-Bu in CDCl3. Although 1H and
13C NMR spectroscopy indicated that the free carbene was too
unstable to be fully characterized, fortunately, the generated
carbene could be trapped by S8. The deprotonation reaction of 1a
Figure 2. ORTEP diagram of 6. Thermal ellipsoids are at 30% probability level. CCDC
No. 923444.

348
L. Faraji et al. / Tetrahedron Letters 55 (2014) 346–350
Table 2
To prove the ability of the generated free carbene to complex
The effect of the ligand in the Mizoroki–Heck reaction of iodobenzene with ethyl
acrylate
with a palladium salt, an equimolar CDCl3 solution of imidazolium
hexafluorophosphate (1a-PF6) was reacted with palladium chlo-
ride in the presence of KOt-Bu and then monitored by 1H NMR.
The complete disappearance of the diagnostic proton located on
the iminium carbon at 8.78 ppm was an evidence of complete for-
mation of a palladium–carbene complex. Additionally, 31P and 19F
NMR spectra along with elemental analysis showed that the PF6À
ion was not present in the product, and that the palladium-carbene
complex 7 is produced (Scheme 3). Unfortunately, attempts to
grow a single crystal of this complex suitable for X-ray diffraction
were not successful.
In view of previous reports on the use of Pd–NHC complexes as
alternatives to Pd-phosphines as catalysts in various reactions,12
the coordinating ability of the prepared ligands 1a–l toward a pal-
ladium salt and also the catalytic ability of the Pd complexes of the
ligands were investigated in the Mizoroki–Heck reaction. The reac-
tions were carried out by using iodobenzene and ethyl acrylate as
substrates in the presence of ligands 1a–l (0.4 mol %), PdCl2
(0.4 mol %) as the catalyst and KOt-Bu as the base in DMF at
60 °C (Table 2). The reactions were monitored by TLC for the con-
sumption of the aryl iodide. The best results in terms of yields and
reactivities were achieved by employing the chiral NHC ligands 1i
and 1j (entries 10 and 11). Apparently, there is a subtle balance be-
tween steric and electronic factors in these ligands.13 The hexa-
fluorophosphate analogue of 1a reduced the yield from 95% to
80% after 45 min in comparison to its chloride analogue (entry
1). A blank experiment without PdCl2 gave no conversion of the
starting substrates. Similarly, the reaction performed with PdCl2
gave low yields of products without using ligand 1a. The use of
Pd(OAc)2 instead of PdCl2 reduced markedly the yield and reactiv-
ity (entry 3).
Considering 1i and 1j as the best NHC ligands, we next focused
our attention on the effect of the solvent, palladium salts, catalyst
loading, and types of bases and additives to achieve optimized con-
ditions for this reaction. The solvent is normally a very important
parameter determining Heck coupling efficiency, so a range of typ-
ical solvents was screened in this reaction catalyzed by 1i. Among
the solvents tested DMF was the most appropriate during which a
quantitative yield of the corresponding coupling product was
obtained, and the reaction was complete in only 7 min. Relatively
moderate to good yields were observed in other solvents or in
mixed solvents [CH3CN (60%), THF (53%), CH2Cl2 (42%) in 25 min,
H2O (50%) and 50/50 DMF/H2O (70%) in 35 min]. The effects of
catalyst loading were also investigated and the best results were
obtained when a 0.4 mol % catalyst loading was used in the
reaction. The ligand-to-metal ratio of 2:1 using 0.8 mol % of
the NHC ligand was investigated under similar conditions and
the isolated yields remained the same at 93%. The reaction
exhibited high efficiency even when performed using 0.1 mol %
of the catalyst, with a 1000:1 substrate-to-catalyst ratio, giving
the product in a yield of 95% after 15 min.
0.4 mol% 1, 0.4 mol% PdCl2
Ph
Ph-I
CO2Et
+
CO2Et
DMF, KOt-Bu, 60°C
Entry
Ligand
Time (min)
Yield (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
1a
1b
1b
1c
1d
1e
1f
1g
1h
1i
45
17
45
20
35
45
13
35
45
7
95 (80)a
96
73b
97
96
95
95
97 (85)a
95
93
93
88
85
1j
1k
1l
7
7
7
a
The hexafluorophosphate salt of the imidazolium ligand was used.
Pd(OAc)2 was used for catalyst formation.
b
To improve the efficiency of other ligands and to obtain an ob-
servable difference in the Mizoroki–Heck reaction, we next inves-
tigated the effect of numerous additives such as molecular sieves,
MgO14 and CuO15 nanoparticles, and mesoporous MCM-4116 and
SBA-1517 silica in the presence of NHC ligand 1a. It was found that
utilizing the metal oxides and molecular sieves as additives re-
sulted in higher reaction rates in comparison with MCM-41 and
SBA-15 mesoporous silica. Since a quantitative yield was obtained
only in 15 min in the presence of MgO nanoparticles, we concluded
it to be the best additive. It is well known that MgO has Lewis acid
and Lewis base sites in addition to lattice and isolated hydroxyl
groups.18 Therefore, the efficiency of this additive most likely can
be explained by several phenomena simultaneously, including
activation of the proton located on the iminium carbon (C2-H) by
the Lewis base (O2À/O), the carbonyl of acrylates by the Lewis acid
(Mg2+/Mg+), and the metal center of the palladium-carbene com-
plex by the hydroxy group.
Using the optimized reaction conditions (0.4% mol of the imi-
dazolium salt 1i and PdCl2 as catalyst, KOt-Bu as base, MgO nano-
particles as additive, and DMF as solvent), we next examined the
scope and limitations of this reaction with various haloaromatic
derivatives and several reactive alkenes (Table 3). As expected, aryl
iodides reacted with the various alkenes more rapidly and gave the
corresponding coupling products in excellent yields; the aryl bro-
mides and chlorides resulted in lower yields of the products and
increased reaction times in comparison with the iodide analogues.
Higher yields were obtained for the aryl bromides or aryl chlorides
with a strong electron-withdrawing group or by utilizing 20 mol %
of Bu4NBr as a cocatalyst. The trans products, as confirmed by 1H
NMR analysis, were obtained exclusively in all the cases presented
in this article. As shown in Table 3, the MgO nanoparticles in con-
junction with these ligands played a crucial role in increasing the
efficiency of the reaction.
The effect of various bases was also investigated and KOt-Bu
proved to be the best (93% in 7 min), while bases such as Et3N,
K2CO3, NaOAc, and NaOH led to lower yields (75–85%).
Since the prepared ligands bear two stereogenic centers, they
were also tested in the asymmetric addition of diethylzinc to
benzaldehyde. As Table 4 shows, the best results were obtained
in toluene with 10 mol % of 1i, which afforded the desired prod-
uct in 78% yield and 26% ee in 15 h (entry 5). At higher temper-
ature, the yield and reactivity of the reaction were improved to
88% in 12 h, but the enantioselectivity dropped to 10% (compare
entries 2 and 3). Decreasing the reaction temperature resulted in
a decrease in reactivity and yield without any considerable
increase in enantioselectivity. Furthermore, base-free conditions
were tested and no reaction occurred, which clearly indicates
Ph
Ph
-
PF6
N+
PdCl2, ,KOt-Bu
N
Ph
N
N
Ph
CDCl3
Cl
Pd
HO
1a-PF6
O
H
7
Cl
Scheme 3. NHC palladium complex 7.

L. Faraji et al. / Tetrahedron Letters 55 (2014) 346–350
349
Table 3
(entries 8 and 9). The effects of higher catalyst loadings and various
bases (KHMDS and NaHMDS) were also investigated but did not
lead to any observable changes in the results. Efforts to optimize
the conditions to improve the catalytic activation of 1 in this reac-
tion and to extend the utility of these groups of ligands in different
reactions are underway in our laboratory.
The scope and generality of the NHC-Pd catalyzed Mizoroki–Heck reaction
0.4 mol% 1i, 0.4 mol% PdCl2
Ar
Ar-X
+
X′
X′
MgO, KOt-Bu, DMF, 60°C
8
Ar-X
X
Product
Timea
Yielda (%)
In conclusion, we have presented the preparation of a new class
of chiral hydroxyalkyl-NHC ligands that contain two stereogenic
centers on the N-substituent and on the imidazolium ring back-
bone, on a multi-gram scale, from inexpensive and commercially
available chiral pool amino acids. The employed modular synthe-
ses allowed the isolation of small libraries of chiral hydroxyalkyl-
imidazolium salts and the corresponding free chiral carbenes were
prepared by deprotonation of these salts and in one example, the
carbene, 1a, was detected by trapping with S8. The coordination
of these chiral hydroxyalkyl-NHC ligands with Pd salts provided
a novel catalytic and efficient system for the Mizoroki–Heck
coupling reaction. Also, these chiral hydroxyalkyl-NHC ligands
were studied in enantioselective additions of diethylzinc to benzal-
dehyde. The use of MgO nanoparticles as an additive with these
ligands played a crucial role in increasing the efficiency of the
reactions.
Ph-I
Ph-I
Ph-I
Ph-I
2-Me-C6H4 -I
4-Me-C6H4-I
4-NO2-C6H4-I
Ph-Br
Ph-Br
Ph-Br
CO2Et
CO2Me
CN
8a
8b
8c
8d
8e
8f
8g
8a
8a
8b
8c
8d
8e
8f
3 (7) min
5 (15) min
25 (55) min
40 (60) min
10 (45) min
10 (40) min
5 (15) min
2 (5) h
8 (20) h
8 (20) h
9 (24) h
9 (24) h
8 (20) h
2 (5) h
8 (20) h
2 (6) h
7 (20) h
12 (40) h
12 (40) h
>95 (93)
95 (87)
80 (72)
84 (70)
96 (90)
95 (88)
98 (90)
74 (50)b
92 (65)c
90 (62)c
77 (55)c
74 (62)c
80 (60)c
55 (30)b
87 (60)c
85 (72)b
55 (30)b
72 (47)c
75 (50)b
Ph
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Me
CN
Ph-Br
Ph-Br
Ph
2-Me-C6H4-Br
4-Me-C6H4-Br
4-Me-C6H4-Br
4-NO2-C6H4-Br
Ph-Cl
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
8f
8g
8a
8a
8g
Ph-Cl
4-NO2-C6H4-Cl
a
Time and yields in parentheses refer to reactions in the absence of MgO
nanoparticles.
Acknowledgment
b
Experiments were carried out at 120 °C.
c
We gratefully acknowledge financial support from the Research
Council of Shahid Beheshti University.
20 mol % of Bu4NBr was used as a cocatalyst at 120 °C.
Table 4
Supplementary data
Enantioselective addition of diethylzinc to benzaldehyde catalyzed by ligand 1
Supplementary data (general procedures and IR, mass, 1H and
13C NMR data and crystallographic tables of the reaction products)
associated with this article can be found, in the online version, at
http://dx.doi.org/10.1016/j.tetlet.2013.11.027. These data include
MOL files and InChiKeys of the most important compounds
described in this article.
OH
O
Et2Zn/10 mol% 1
(S)
Et
H
10 mol% KOt-Bu/ solvent
15 h, -10°C
9
Entry
Ligand
Solvent
Yield (%)
ee (%)
a
1
2
3
4
5
6
7
8
9
1a
1a
1a
1c
1i
1k
1i
1i
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
THF
—
—
References and notes
88
75
50
78
70
95
35
—
10b
15
Trace
26
1. Arduengo, A. J., III; Harlow, R. L.; Kline, M. J. Am. Chem. Soc. 1991, 113, 361.
2. (a) Herrmann, W. A. Angew. Chem. 2002, 114, 1342. Angew. Chem. Int. Ed. 2002,
41, 1290; (b) Nolan, S. P. N-Heterocyclic Carbenes in Synthesis; Wiley-VCH:
Weinheim, 2006; (c) Glorius, F. N-Heterocyclic Carbenes in Transition Metal
Catalysis; Springer: Berlin, 2007; (d) Diez-Gonzalez, S.; Marion, N.; Nolan, S. P.
Chem. Rev. 2009, 109, 3612; (e) Bourissou, D.; Guerret, O.; Gabbai, F. P.;
Bertrand, G. Chem. Rev. 2000, 100, 39; (f) César, V.; Bellemin-Laponaz, S.; Gade,
L. H. Chem. Soc. Rev. 2004, 33, 619.
3. (a) Gao, F.; McGrath, K. P.; Lee, Y.; Hoveyda, A. H. J. Am. Chem. Soc. 2010, 132,
14315; (b) Akiyama, K.; Gao, F.; Hoveyda, A. H. Angew. Chem., Int. Ed. 2010, 49,
419; (c) Tominaga, S.; Oi, Y.; Kato, T.; Keun An, D.; Okamoto, S. Tetrahedron Lett.
2004, 45, 5585; (d) Park, J. K.; Lackey, H. H.; Rexford, M. D.; Kovnir, K.; Shatruk,
M.; McQuade, D. T. Org. Lett. 2010, 12, 5008; (e) Germain, N.; Magrez, M.;
Kehrli, S.; Mauduit, M.; Alexakis, A. Eur. J. Org. Chem. 2012, 5301.
4. (a) Hillier, A. C.; Nolan, S. P. Platinum Met. Rev. 2002, 46, 50; (b) Hillier, A. C.;
Grasa, G. A.; Viciu, M. S.; Lee, H. M.; Yang, C.; Nolan, S. P. J. Organomet. Chem.
2002, 653, 69; (c) Weskamp, T.; Bohm, V. P. W.; Herrmann, W. A. J. Organomet.
Chem. 2000, 600, 12.
5. (a) Scott, N. M.; Nolan, S. P. Eur. J. Inorg. Chem. 2005, 1815; (b) Dorta, R.;
Stevens, E. D.; Scott, N. M.; Costabile, C.; Cavallo, L.; Hoff, C. D.; Nolan, S. P. J. Am.
Chem. Soc. 2005, 127, 2485; (c) Diez-Gonzalez, S.; Nolan, S. P. Coord. Chem. Rev.
2007, 251, 874.
6. (a) Hoveyda, A. H.; Gillingham, D. G.; Van Veldhuizen, J. J.; Kataoka, O.; Garber,
S. B.; Kingsbury, J. S.; Harrity, J. P. A. Org. Biomol. Chem. 2004, 2, 8; (b)
Gillingham, D. G.; Kataoka, O.; Garber, S. B.; Hoveyda, A. H. J. Am. Chem. Soc.
2004, 126, 12288; (c) Rix, D.; Labat, S.; Toupet, L.; Crévisy, C.; Mauduit, M. Eur. J.
Inorg. Chem. 2009, 1989; (d) Larsen, A. O.; Leu, W.; Oberhuber, C. N.; Campbell,
J. E.; Hoveyda, A. H. J. Am. Chem. Soc. 2004, 126, 11130.
15
33c
—
1i
1,4-Dioxane
—
(4 mg) Nanoparticles were used as the additive and the reaction was carried out
over 8 h.
a
In the absence of base.
Reaction was carried out at rt.
MgO.
b
c
that generation of the carbene is essential for the reaction to
proceed (entry 1).
As shown above in the Mizoroki–Heck reaction, a higher effi-
ciency was achieved in the presence of MgO nanoparticles. Accord-
ing to an XRD powder diffraction study, the nature of the
nanoparticles is periclase phase.14 This encouraged us to employ
MgO nanoparticles in conjunction with ligand 1i in diethylzinc
addition to benzaldehyde in order to further improve the results.
Interestingly, when the reaction was performed in the presence
of MgO as an additive (4 mg/mmol), the enantioselectivity of the
reaction was improved up to 33% and the reaction was complete
in only 8 h providing the product in quantitative yield (entry 7).
Furthermore, two different solvents, 1,4-dioxane and THF, were
also tested. In 1,4-dioxane, the reaction did not give any product,
and in THF only a 35% yield of a racemic product was obtained
7. Gilani, M.; Wilhelm, R. Tetrahedron: Asymmetry 2008, 19, 2346.
8. (a) Whitcombe, N. J.; Hii, K. K.; Gibson, S. E. Tetrahedron 2001, 57, 7449; (b)
Beletskaya, I. P.; Cheprakov, A. V. Chem. Rev. 2000, 100, 3009.
9. (a) Noyori, R.; Kitamura, M. Angew. Chem. 1991, 103, 34–55. Angew. Chem. Int.
Ed. Engl. 1991, 30, 49; (b) Soai, K.; Niwa, S. Chem. Rev. 1992, 92, 833; (c) Bräse,
S.; Dahmen, S.; Hofener, S.; Lauterwasser, F.; Kreis, M.; Ziegert, R. E. Synlett
2004, 2647.

350
L. Faraji et al. / Tetrahedron Letters 55 (2014) 346–350
10. (a) Smith, C. S.; Brown, A. E. J. Am. Chem. Soc. 1941, 63, 2605; (b) Duguet, N.;
Donaldson, A.; Leckie, S. M.; Kallström, E. A.; Campbell, C. D.; Shapland, P.; Brown,
T. B.; Slawin, A. M. Z.; Smith, A. D. Tetrahedron: Asymmetry 2010, 21, 601.
11. McKennon, M. J.; Meyers, A. I. J. Org. Chem. 1993, 58, 3568.
12. (a) Herrmann, W. A.; Elison, M.; Fischer, J.; Köcher, C.; Artus, G. R. J. Angew.
Chem., Int. Ed. Engl. 1995, 34, 2371; (b) Sakaguchi, S.; Yoo, K. S.; O’Neill, J.; Lee, J.
H.; Stewart, T.; Jung, K. W. Angew. Chem., Int. Ed. 2008, 47, 9326; (c) Viciu, M. S.;
Kelly, R. A., III; Stevens, M. S.; Naud, F.; Studer, M.; Nolan, S. P. Org. Lett. 2003, 5,
1479; (d) OBrien, C. J.; Kantchev, E. A. B.; Valente, C.; Hadei, N.; Chass, G. A.;
Lough, A.; Hopkinson, A. C.; Organ, M. G. Chem. Eur. J. 2006, 12, 4743; (e) Wang,
W.; Zhang, T.; Shi, M. Organometallics 2009, 28, 2640; (f) Organ, M. G.; Avola, S.;
Dubovyk, I.; Hadei, N.; Kantchev, E. A. B.; O’Brien, C. J.; Valente, C. Chem. Eur. J.
2006, 12, 4749; (g) Metallinos, C.; Barrett, F. B.; Chaytor, J. L.; Heska, M. E. A.
Org. Lett. 2004, 6, 3641; (h) Andrus, M. B.; Song, C. Org. Lett. 2001, 3, 3761; (i)
Sato, Y.; Yoshino, T.; Mori, M. Org. Lett. 2003, 5, 31.
13. Hadei, N.; Kantchev, E. A. B.; O’Brien, C. J.; Organ, M. G. Org. Lett. 2005, 7, 1991.
14. Heidari, H.; Abedini, M.; Nemati, A.; Amini, M. M. Catal. Lett. 2009, 130, 266.
15. Hong, Z. S.; Cao, Y.; Deng, J. F. Mater. Lett. 2002, 52, 34.
16. Kumar, D.; Schumacher, K.; Grun, M.; Unger, K. K. Colloids Surf. 2001, 187, 109.
17. (a) Nguyen, T. P. B.; Lee, J.; Shim, W. G.; Moon, H. Micropor. Mesopor. Mater.
2008, 110, 560; (b) Samadi, S.; Jadidi, K.; Notash, B. Tetrahedron: Asymmetry
2013, 24, 269.
18. Choudary, B. M.; Ranganath, K. V. C.; Pal, U.; Kantam, M. L.; Sreedhar, B. J. Am.
Chem. Soc. 2005, 127, 13167.