Highly efficient catalytic enantioselective mannich reaction of malonates with N-tert-butoxycarbonyl imines by using Yb(OTf)3/pybox catalysts at room temperature

Article abstract of DOI:10.1002/chem.201300241

Go Mannich! A highly efficient and enantioselective method for the direct asymmetric reaction of dibenzyl malonate with N-tert-butoxycarbonyl aldimines in the presence of Yb(OTf)₃ and iPr-pybox complexes is described (see scheme; pybox=pyridine

Full text of DOI:10.1002/chem.201300241

COMMUNICATION
Asymmetric Synthesis
B. Karimi,* E. Jafari,
D. Enders ...................... &&&& — &&&&
Highly Efficient Catalytic Enantiose-
lective Mannich Reaction of Malo-
nates with N-tert-Butoxycarbonyl
Go Mannich! A highly efficient and
enantioselective method for the direct
asymmetric reaction of dibenzyl malo-
nate with N-tert-butoxycarbonyl ald-
ACHTUGTNRENNiGU mines in the presence of YbAHCUTNGTREN(NGUN OTf)3
and iPr-pybox complexes is described
(see scheme; pybox=pyridine bisoxa-
zoline).
Imines by Using Yb
ACHTUNGRTENUN(NG OTf)3/Pybox
Catalysts at Room Temperature
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DOI: 10.1002/chem.201300241
Highly Efficient Catalytic Enantioselective Mannich Reaction of Malonates
with N-tert-Butoxycarbonyl Imines by Using YbACTHNUTRGENUG(N OTf)3/Pybox Catalysts at
Room Temperature
Babak Karimi,*[a] Ehsan Jafari,[a] and Dieter Enders[b]
The enantioselective catalytic Mannich reaction is a pow-
esters with both aromatic and aliphatic imines by employing
a Yb(OTf)3/pybox catalyst system at room temperature.
erful synthetic method for the preparation of b-amino car-
bonyl compounds, an important class of chiral building
blocks of pharmaceutically and agrochemically relevant
target molecules.[1,2] In particular, the use of malonate deriv-
atives as nucleophiles in the Mannich reaction of imines is
certainly preferable, as it avoids the preformation of eno-
lates or the naked enolate step to access b-amino carbonyl
adducts.[3] Although much attention has been devoted to the
development of a diverse array of chiral organocatalysts for
the asymmetric addition of malonates to imines, the number
of approaches involving chiral metal complexes are quite
limited.[4] Moreover, the enantioselective Mannich reaction
of imines by using chiral YbIII catalysts has been unexplored,
in contrast to the fact that YbIII chiral complexes have given
remarkable results in several asymmetric synthetic transfor-
mations.[5] It is also worth mentioning that most of the
metal-catalyzed asymmetric Mannich reactions require a
very low temperature to produce satisfactory enantioselec-
tivities.[6] While excellent advances have been achieved,
many of the reported protocols have limitations, such as
high catalyst loading, limited substrate scope, or difficult
preparation of catalyst. Therefore, there is still substantial
room for the development of new versions of catalytic asym-
metric Mannich reactions.
ACHTUNGTRENNUNG
At the beginning of our research, we started with the
model reaction of N-tert-butoxycarbonyl (N-Boc) aldimine
1a with dibenzylmalonate 2a in CH2Cl2 at room tempera-
ture in the presence of various Yb
ACHTUNGTRENNUNG
generated in situ from commercially available YbAHCTUNGTRENNUNG
pybox ligands 3a–e (Scheme 1; Table 1, entries 1–5).
Very recently, we have successfully employed a novel
chiral YbACHTUNGTRENNUNG(OTf)3/pybox (pybox=pyridine bisoxazoline) com-
Scheme 1. Enantioselective addition of dibenzyl malonate (2a) to N-Boc
imine (1a) in the presence of various chiral pybox ligands.
plex in the catalytic asymmetric Strecker hydrocyanation of
various types of N-benzhydryl imines to afford the corre-
sponding a-aminonitriles in good to excellent conversions
with enantiomeric excess (ee) values of up to 98%.[5a] In
continuation to these studies, herein we describe a highly
enantioselective direct Mannich-type reaction of malonate
Interestingly, while in all cases the reaction proceeded
smoothly by employing 5 mol% of YbACTHNUTRGENUN(G OTf)3 and 10 mol%
of pybox ligands at room temperature (258C) to give the
b-amino carbonyl compounds 4a in high yields, the catalyst
system comprising of the pybox ligand 3b (with an iPr
group) furnished the product with the highest ee value of
68% (Table 1, entry 2).
To further optimize the reaction conditions, several metal
[a] B. Karimi, E. Jafari
triflates, such as Sc
A
ACHUTGTNERN(NGU OTf)2, InHCATUNGTRENN(GUN OTf)3, and Zn-
Department of Chemistry
A
Institute for Advanced Studies in Basic Sciences (IASBS)
Zanjan 45137-6731 (Iran)
later was found to be superior with regard to reaction enan-
tioselectivity under the same conditions (Table 1, entries 2
vs. 6–9). In our recent work, we found that in the course of
catalytic enantioselective Strecker reactions of imines using
Fax : (+98)241-415-3225
E-mail: karimi@iasbs.ac.ir
[b] D. Enders
Institꢁt fꢁr Organische Chemie, RWTH Aachen University
Landoltweg 1, 52074, Aachen (Germany)
a YbACTHUNTRGNENG(U OTf)3/pybox catalyst, both enantioselectivities and
product yields were remarkably improved upon the addition
of stoichiometric amounts of a protic additive to the reac-
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201300241
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Mannich Reaction of Malonates with N-tert-Butoxycarbonyl Imines
COMMUNICATION
Table 1. Effect of various reaction parameters in the enantioselective
Mannich reaction of benzyl malonate 2a with benzaldehyde N-Boc imine
1a at room temperature.[a]
influence of other protecting groups at the imine nitrogen
atom under the reaction conditions in Table 1, entry 11. The
results revealed that no reaction proceeded when using
benzACTHUNRTGNEUNGaldimine bearing a protecting group, such as N-4-meth-
ylphenyl, N-phenyl, or N-2-hydroxyphenyl instead of 1a,
which implied that the presence of the N-Boc moiety is cru-
cial for attaining high enantioselectivities (Table 2, en-
tries 1–4). On the other hand, we found that among a varie-
ty of alternative malonate esters investigated, the benzyl
ester variant delivered the Mannich adducts with the highest
selectivity of 95% (entry 1), whereas those of methyl and
ethyl esters, 2-substituted malonates, and also b-keto esters
led to much lower enantioselectivities (entries 5–8). With
the optimal conditions in hand (Table 2, entry 1), we next
Run Ligand/metal Solvent
Additive
Yield (ee) [%][b,c]
1
2
3
4
5
6
7
8
3a/Yb
3b/Yb
3c/Yb(OTf)3
3d/Yb(OTf)3
3e/Yb(OTf)3
3b/Sc(OTf)3
3b/Cu(OTf)2
3b/In(OTf)3
3b/Zn(OTf)2
(OTf)3
(OTf)3
(OTf)3
(OTf)3
(OTf)3
(OTf)3
(OTf)3
(OTf)3
(OTf)3
(OTf)3
(OTf)3
U
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
THF
–
–
–
–
–
–
–
–
–
81 (46)
83 (68)
88 (50)
79 (10)
82 (61)
87 (37)
88 (7)
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
G
77 (13)
65 (25)
9
ACHTUNGTRENNUNG
10
11
12
13
14
15
16
17
18[d]
19[e]
20[f]
T
MeOH (0.5 equiv) 85 (70)
MeOH (1 equiv) 91 (95)
MeOH (1.5 equiv) 93 (61)
HFIP (1 equiv)
iPrOH (1 equiv)
MeOH (1 equiv)
MeOH (1 equiv)
Table 2. Effect of N-substituent and malonate alkyl group on the enan-
ACHTUNGTRENNUNG
tioselective Mannich reaction of benzaldimine catalyzed by Yb
ACHTUNGTRENNUNG(OTf)3/
pybox complexes.[a]
ACHTUNGTRENNUNG
N
95 (79)
80 (71)
73 (5)
86 (40)
69 (10)
74 (35)
89 (60)
82 (77)
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
N
toluene
CH3CN MeOH (1 equiv)
CH2Cl2
CH2Cl2
CH2Cl2
R
U
MeOH (1 equiv)
MeOH (1 equiv)
MeOH (1 equiv)
Run
PG
R1, R3
Yield [%][b]
ee [%][c,d]
ACHTUNGTRENNUNG
1[e]
2[e]
3[e]
4[e]
5[e]
6[e]
7[e]
8[f]
Boc
4-tolyl
Ph
2-(OH)Ph
Boc
Boc
OBn, Bn
OBn, Bn
OBn, Bn
OBn, Bn
OMe, Me
OEt, Et
Ph, Et
91
95
n.d.
n.d.
n.d.
45
69
68
66
ACHTUNGTRENNUNG
trace
trace
trace
89
88
89
[a] Conditions: YbACHTUNGTRENNUNG(OTf)3 (5 mol%), pybox (10 mol%), 1a (1 equiv), 2
(1.1 equiv). The reaction was performed at room temperature for 12 h.
[b] Isolated yield. [c] Enantiomeric excesses were determined by HPLC
analysis on
pybox (5 mol%). [e] Yb
ACHTUNGTRENNUNG(OTf)3 (5 mol%), pybox (7.5 mol%).
a
CHIRALPAK AS column. [d] Yb
ACHTUNGRTEN(NGNU OTf)3 (2.5 mol%),
AHCTUNGTRENNUNG
Boc
Boc
OBn, Bn
87
[a] Conditions: YbACTHNUTRGNEUNG(OTf)3 (5 mol%)/pybox 3b (10 mol%), 1 (1 equiv), 2a
tion mixture.[4a] In the present study, it was also revealed
that the protic additives exhibited more or less the same sig-
nificant effect on the observed enantioselectivities (en-
tries 10–14), although the yields were comparable to the re-
action in the absence of protic additives (entry 2).
(1.1 equiv), MeOH (1 equiv), The reaction was performed at room tem-
perature for 12 h in dichloromethane. [b] Isolated yields. [c] Enantiomeric
excesses were determined by HPLC analysis on a CHIRALPAK AS
column. [d] Absolute configuration was determined to be R according to
the literature data.[7] [e] R2 =H. [f] R2 =Me.
Among the protic additives investigated, MeOH (1 equiv)
was the best, giving 4a in 91% yield with an excellent ee
value of 95% (Table 1, entry 11). Higher or lower MeOH
loading also afforded 4a in comparable yields, albeit with
much inferior enantioselectivities (entries 10–13). We are
currently working towards the mechanistic insight into the
effect of protic additive and the results will be appearing in
due course.
managed to examine further the scope and limitations of
this novel asymmetric Mannich reaction. A survey of elec-
tronically and sterically varied aryl and heteroaryl N-Boc
imines revealed a high degree of sterochemical consistency
in their reaction with benzyl malonate 2a, giving excellent
enantioselectivities of >95% ee in most cases at room tem-
perature (Table 3).
In the next stage, the effect of solvent and additive to-
gether, YbACHTUNGTRENNUNG(OTf)3/3b ratio, and amount of the catalyst were
evaluated in the reaction. As can be clearly seen, this reac-
tion was sensitive to solvent, and CH2Cl2 was the optimum
choice (Table 1, entries 11 vs. 15–17). We also found that the
reaction still reached completion by changing either the cat-
alyst loading or the YbACTHNUTRGNEUNG(OTf)3/3b ratio, although significant
loss of enantioselectivity was observed in all cases (en-
tries 11 vs. 18–20). These results also highlight the notion
that a 2:1 ratio of 3b ligand to YbACHTNUTRGNEUNG(OTf)3 is very important
for obtaining high enantioselectivities. Facing the challenge
of achieving higher enantioselevities, we next examined the
Apparently, the position and electronic nature of the sub-
stituent on the aromatic ring has a very limited influence on
the enantioselectivities. In particular, the reaction was suc-
cessfully applicable to the electron-rich aldimines, which are
known to be less prone to the nucleophilic addition reaction,
furnishing the corresponding Mannich adducts in high yields
(83–92%) with good to excellent enantioselectivities of up
to 99% (Table 3, entries 7–11). Noticeably, up to a 93% ee
was still obtained even for the challenging ortho-substitued
substrates and 1-naphthyl N-Boc aldimines without any sig-
nificant drop in both selectivities and the product yields irre-
spective to the electronic properties of the substituents at
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B. Karimi et al.
Table 3. Scope of the enantioselective Mannich reaction of benzyl malo-
nate with N-Boc imines catalyzed by Yb(OTf)3/3b at room
temperature.[a]
AHCTUNGTRENNUNG
Run
R
Yield [%][b]
ee [%][c,d]
1
2
3
4
5
6
7
8
Ph (1a)
2-Br-C6H4 (1b)
91
88
95
94
91
95
88
88
92
83
92
85
91
59
95
93
97
98
93
96
92
95
99
98
93
89
96
69
3-Br-C6H
4-Br-C6H
2-Cl-C6H
4A
4A(1d)
4A(1e)
4A(1 f)
4A(1g)
4A(1h)
4A(1i)
4A(1j)
(1k)
(1l)
(1m)
cyclohexyl(1n)
CHTUNGTRENNUNG
Scheme 2. Asymmetric one-pot Mannich reaction of 5 with 2a.
N
4-Cl-C6H CHTUNGTRENNUG
2-Me-C6H
3-Me-C6H
4-Me-C6H
CHTUNGTRENNUNG
CHTUNGTRENNUNG
periments, the asymmetric Mannich reaction of benzylmalo-
nate to benzaldehyde-N-Boc imine 1a using 1:1 pybox/Yb-
ACHUTNGREN(NUG OTf)3 and 2:1 pybox/YbCAHTUNGTRNE(NUGN OTf)3 was quenched at an early
stage after 2 h and the yields and ee values of the Mannich
9
G
10
11
12
13
14
4-MeO-C6H
4-iso-propyl
1-naphthyl
2-furyl
CHTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
ACHTUNGTRENNUNG
products were compared accordingly. It was found that the
AHCTUNGTRENNUNG
reaction using 1:1 pybox/Yb
much slower than the other reactions using 2:1 pybox/Yb-
AHCTUNGRTEG(NNUN OTf)3 (10:5 mol%) catalyst system (29 vs. 48% yields after
2 h), but it also resulted in much inferior enantioselectivity
of the Mannich products (35 vs. 89% ee values after 2 h).
On the other hand, for the purpose of comparison we have
ACHTUNGRTEN(NUNG OTf)3 (5 mol%) is not only
[a] Conditions: YbACHTUNGTRENNUNG(OTf)3 (5 mol%)/pybox 3b (10 mol%), 1 (1 equiv), 2a
(1.1 equiv), MeOH (1equiv). The reaction was performed at room tem-
perature for 12 h in dichloromethane. [b] Isolated yields. [c] Enantiomeric
excesses were determined by HPLC analysis on a CHIRALPAK AS
column. [d] Absolute configuration was determined to be R according to
the literature data.[7]
also tested the same reaction by using 1:1 pybox/YbACHTUNGTRENNUNG(OTf)3
(5 mol%) by adding 10 mol% triethylamine (Et3N) as an
exogenous base. Interestingly, we found that by adding
10 mol% Et3N to a 1:1 pybox/YbACTHNUGTRENUNG(OTf)3 (5 mol%) catalyst
system a significant improvement was observed in the final
enantioselectivity after 12 h, giving the corresponding Man-
nich adducts in 88% yield with 79% ee. Based on these ob-
servation, we may conclude that in the present protocol, an
additional 5 mol% of ligand is most likely acting as a chiral
Brønsted base catalyst. Therefore, the proposed transition
state of this reaction is outlined in Scheme 3 (front iPr
the aromatic rings (entries 2, 5, 7, and 12). Another interest-
ing feature of this protocol is the remarkable tolerance for
heteroaryl N-Boc aldimines since excellent yield (91%) and
enatioselectivity (96% ee) was still attained in the reaction
of 2-furyl N-Boc imine as a model substrate (entry 13). On
the other hand, both the yield and the enantioselectivity
were sacrificed to some extent when aliphatic aldehyde-de-
rived N-Boc imines were employed. The low yield (59%)
and low enantioselectivity (69% ee) was attributed in the
case of aliphatic N-Boc imines to isomerization of the imine
to the corresponding enamine form under the reaction con-
ditions.[7]
Following the interesting discovery of Ricci and others,[8]
we reasoned that it might be possible to circumvent this
problem by employing a-amido sulfone 5 for the in situ
preparation of the corresponding N-Boc imine under the re-
action conditions, in which it would be gradually condensed
with nucleophilic malonate through our described asymmet-
ric Mannich protocol (Scheme 2). However, while this ap-
proach led to the corresponding Mannich adduct in high
yield (85%), the selectivity was rather disappointing. We
are currently working on this topic to improve the results.
At this stage, the precise explanation and exact mechanis-
tic feature for this reaction is unclear for us. However, we
have performed three typical experiments in order to gain
more insight into the actual catalyst species and hopefully
find a reasonable explanation for the higher loading of
Scheme 3. Proposed transition state for the enantioselective Mannich re-
action of benzyl malonate with N-Boc imines catalyzed by YbACHTUNGTRENNUNG(OTf)3/3b
at room temperature. The front iso-propyl group has been omitted for
simplicity.
group has been omitted for simplicity). Further studies to
clarify the actual mechanism of this reaction in which the
role of MeOH in improving the enantioselectivity of the de-
scribed reaction is being investigated are currently ongoing
in our laboratories.
ligand in our protocol (2:1 pybox/Yb
which is necessary in obtaining high enatioselectivities of
the products. To obtain a reliable result, in the first two ex-
(OTf)3; 10:5 mol%),
In conclusion, we have developed a highly efficient cata-
lytic enantioselective Mannich reaction of dibenzyl malo-
nate with N-Boc aldimines employing the readily available
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Mannich Reaction of Malonates with N-tert-Butoxycarbonyl Imines
COMMUNICATION
ric Mannich reactions e) H. Ishitani, M. Ueno, S. Kobayashi, J. Am.
Chem. Soc. 1997, 119, 7153; f) E. Hagiwara, A. Fujii, M. Sodeoka, J.
Am. Chem. Soc. 1998, 120, 2474; g) D. Ferraris, B. Young, T. Dud-
ding, T. Lectka, J. Am. Chem. Soc. 1998, 120, 4548; h) S. Xue, S. Yu,
Y. H. Deng, W. D. Wulff, Angew. Chem. 2001, 113, 2331; Angew.
Chem. Int. Ed. 2001, 40, 2271; i) S. Kobayashi, T. Hamada, K.
Manabe, J. Am. Chem. Soc. 2002, 124, 5640; j) N. S. Josephsohn,
M. L. Snapper, A. H. Hoveyda, J. Am. Chem. Soc. 2004, 126, 3734;
selected examples on asymmetric organocatalysis: k) P. I. Dalko, L.
Moisan, Angew. Chem. 2001, 113, 3840; Angew. Chem. Int. Ed. 2001,
40, 3726; l) B. List, Tetrahedron 2002, 58, 5573; m) P. I. Dalko, L.
Moisan, Angew. Chem. 2004, 116, 5248; Angew. Chem. Int. Ed. 2004,
43, 5138; n) J. Seayad, B. List, Org. Biomol. Chem. 2005, 3, 719.
[3] a) F. Fini, L. Bernardi, R. P. Herrera, D. Pettersen, V. Sgarzani, A.
Ricci, Adv. Synth. Catal. 2006, 348, 2043; b) K. Takada, S. Tanaka, K.
Nagasawa, Synlett 2009, 1643; c) Y. Sohtome, S. Tanaka, K. Takada,
T. Yamaguchi, K. Nagasawa, Angew. Chem. 2010, 122, 9440; Angew.
Chem. Int. Ed. 2010, 49, 9254; d) W. Li, B. Song, P. S. Bhaduri, L. Li,
Z. Wang, X. Zhnag, D. Hu, Z. Chen, Y. Zhang, S. Bai, J. Wu, S.
Yang, Chirality 2012, 24, 223; e) N. Probst, A. Valkonen, ꢄ. Ma-
darꢃzs, I. Pꢃpai, K. Rissanen, A. Neuvonen, P. M. Pihko, Angew.
Chem. Int. Ed. 2012, 51, 8495.
ytterbium complex prepared from YbACTHNUTRGENUG(N OTf)3 and chiral
pybox ligand as a catalyst. Using the current protocol, vari-
ous aldimines including heteroaryl N-Boc aldimines could
be converted to the corrsponding b-amino carbonyl products
in high yields with good to excellent enantioselectivities at
room temperature. To the best our knowledge this method
can be considered as the first example of a highly enantiose-
lective metal-catalyzed Mannich reaction of malonate esters
at room temperature. Further investigations aimed at devel-
oping new applications of this catalyst system in other im-
portant asymmetric transformations are currently underway
in our laboratory.
Experimental Section
General catalytic procedure of the asymmetric Mannich reaction: A well-
dried glass tube was charged with Yb
corresponding pybox ligand (44 mg, 0.096 mmol) under Argon atmo-
sphere. After dichloromethane (1.0 mL) had been added to the mixture,
ACHTUNGERTN(NUNG OTf)3 (30 mg, 0.048 mmol) and the
[4] a) C. Dubs, Y. Hamashima, N. Sasamoto, T. M. Seidel, S. Suzuki, D.
Hashizume, M. Sodeoka, J. Org. Chem. 2008, 73, 5859; b) M. Hatano,
T. Horibe, K. Ishihara, Org. Lett. 2010, 12, 3502; c) M. Hatano, T.
Horibe, K. Ishihara, J. Am. Chem. Soc. 2010, 132, 56.
ACHTUNGTRENNUNG
it was stirred vigorously at room temperature for 1 h until the reaction
became homogeneous. The corresponding imine (1 mmol) and dibenzyl-
malonate (neat, 0.312 g, 1.1 mmol) was added in dichloromethane to a
solution of complex, under an Argon atmosphere. After that methanol
(1 mmol) was injected in one portion to the reaction mixture. After 12 h,
the reaction mixture was purified by flash chromatography through a
short column of silica gel by using hexane/ethyl acetate as an eluent to
obtain the corresponding products.
[5] a) B. Karimi, A. Maleki, Chem. Commun. 2009, 5180; b) B. Karimi,
A. Maleki, D. Elhamifar, J. H. Clark, A. J. Hunt, Chem. Commun.
2010, 46, 6947; c) G. Grach, A. Dinut, S. Marque, J. Marrot, R. Gil,
D. Prim, Org. Biomol. Chem. 2011, 9, 497; d) Y. Xu, L. Lin, M.
Kanai, S. Matsunaga, M. Shibasaki, J. Am. Chem. Soc. 2011, 133,
5791; e) I. Aillaud, J. Collin, C. Duhayon, R. Guillot, D. Lyubov, E.
Schulz, A. Trifonov, Chem. Eur. J. 2008, 14, 2189; f) W. Chen, Y. Hui,
X. Zhou, J. Jiang, Y. Cai, X. Liu, L. Lin, X. Feng, Tetrahedron Lett.
2010, 51, 4175; for more recent leading references of using pybox as a
chiral ligand in different asymmetric transformations, see : g) J. Yu,
Z. Li, K. Jia, Z. Jiang, M. Liu, W. Su, Tetrahedron Lett. 2013, 54,
2006; h) C. Aubert, C. Dallaire, G. Pepe, E. Levillain, G. Felix, M.
Gingras, Eur. J. Org. Chem. 2012, 6145; i) A. S. Dudnik, G. C. Fu, J.
Am. Chem. Soc. 2012, 134, 10693; j) N. V. Hanhan, Y. C. Tang, N. T.
Tran, A. K. Franz, Org. Lett. 2012, 14, 2218; k) A. J. Oelke, J. Sun,
G. C. Fu, J. Am. Chem. Soc. 2012, 134, 2966; l) S. K. Ray, P. K. Singh,
N. Molleti, V. K. Singh, J. Org. Chem. 2012, 77, 8802.
Acknowledgements
The authors acknowledge the IASBS research council and Iranian Na-
tional Science Foundation (INSF) for support of this work.
Keywords: asymmetric catalysis enantioselectivity
·
·
imines · Mannich reactions · pybox · YbACHUTGNTERN(NNUG OTf)3
[6] a) S. Kobayasi, M. Ueno, H. Ishitani, J. Am. Chem. Soc. 2000, 122,
8180; b) T. Yoshida, H. Morimoto, N. Kumagai, S. Matsunaga, M.
Shibasaki, Angew. Chem. 2005, 117, 3536; Angew. Chem. Int. Ed.
2005, 44, 3470; Angew. Chem. 2005, 117, 3536; c) K. Ishihara, M.
Hatano, T. Horibe, J. Am. Chem. Soc. 2010, 132, 56; d) M. C. Willis,
G. A. Cutting, N. E. Stainforth, M. P. John, G. Kociok-Kçhn, J. Am.
Chem. Soc. 2007, 129, 10632; e) M. Shibasaki, H. Morimoto, S. Mat-
sunaga, G. Lu, Angew. Chem. 2008, 120, 6953; Angew. Chem. Int. Ed.
2008, 47, 6847; Angew. Chem. 2008, 120, 6953; f) C. J. Wang, G.
Liang, M. C. Tong, H. Tao, Adv. Synth. Catal. 2010, 352, 1851; g) Y.
Suzuki, R. Yazaki, N. Kumagai, M. Shibasaki, Angew. Chem. 2009,
121, 5126; Angew. Chem. Int. Ed. 2009, 48, 5026; Angew. Chem. 2009,
121, 5126; h) T. Poisson, T. Tsubogo, Y. Yamashita, S. Kobayashi, J.
Org. Chem. 2010, 75, 963.
[1] Selected reviews a) M. Arend, B. Westermann, N. Risch, Angew.
Chem. 1998, 110, 1096; Angew. Chem. Int. Ed. 1998, 37, 1044; b) S.
Kobayashi, H. Ishitani, Chem. Rev. 1999, 99, 1069; c) A. Cꢂrdova,
Acc. Chem. Res. 2004, 37, 102; d) A. Ting, S. Schaus, Eur. J. Org.
Chem. 2007, 5797; for selected recent reports of catalytic asymmetric
Mannich reactions, see; e) T. Hamada, K. Manabe, S. Kobayashi, J.
Am. Chem. Soc. 2004, 126, 7768; f) S. Matsunaga, T. Yoshida, H.
Morimoto, N. Kumagai, M. Shibasaki, J. Am. Chem. Soc. 2004, 126,
8777; g) Y. Hamashima, N. Sasamoto, D. Hotta, H. Somei, N. Ume-
bayashi, M. Sodeoka, Angew. Chem. 2005, 117, 1549; Angew. Chem.
Int. Ed. 2005, 44, 1525; h) J. Song, Y. Wang, L. Deng, J. Am. Chem.
Soc. 2006, 128, 6048; i) Y. Chi, S. H. Gellman, J. Am. Chem. Soc.
2006, 128, 6804; j) M. Hatano, K. Ishihara, Synthesis 2010, 22, 3785.
[2] Selected reviews : a) R. G. Arrayꢃs, J. C. Carretero, Chem. Soc. Rev.
2009, 38, 1940; b) J. M. M. Verkade, L. J. C. van Hemert, P. J. L. M.
Quaedflieg, F. P. J. T. Rutjes, Chem. Soc. Rev. 2008, 37, 29; c) S. Mu-
kherjee, J. W. Yang, S. Hoffmann, B. List, Chem. Rev. 2007, 107, 5471;
d) M. M. B. Marques, Angew. Chem. 2006, 118, 356; Angew. Chem.
Int. Ed. 2006, 45, 348; selected examples of metal-catalyzed asymmet-
[7] T. Mecozzi, M. Petrini, Synlett 2000, 73.
[8] O. Marianacci, G. Micheletti, L. Bernardi, F. Fini, M. Fochi, D. Pet-
tersen, V. Sgarzani, A. Ricci, Chem. Eur. J. 2007, 13, 8338 and the ref-
erences cited therein.
Received: January 22, 2013
Revised: May 7, 2013
Published online: && &&, 0000
Chem. Eur. J. 2013, 00, 0 – 0
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
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