Guanidine organocatalyst for the asymmetric mannich-type reaction between α-isothiocyanato imide and sulfonyl imines

Article abstract of DOI:10.1002/chem.201002571

A highly efficient bisguanidine organocatalyst has been developed for the asymmetric Mannich-type reaction of α-isothiocyanato imide with N-Ts-protected imines (Ts=tosyl, see scheme). A series of aromatic, α,β-unsaturated, heteroaromatic, and aliphatic im

Full text of DOI:10.1002/chem.201002571

COMMUNICATION
DOI: 10.1002/chem.201002571
Guanidine Organocatalyst for the Asymmetric Mannich-Type Reaction
between a-Isothiocyanato Imide and Sulfonyl Imines
Xiaohong Chen, Shunxi Dong, Zhen Qiao, Yin Zhu, Mingsheng Xie, Lili Lin,
Xiaohua Liu,* and Xiaoming Feng*[a]
Table 1. Optimization of reaction conditions.
a,b-Diamino acids are key structural components in many
molecules,[1] such as biologically active natural products and
synthetic materials.[2] Various methods for the preparation
of optically active a,b-diamino derivatives have been estab-
lished.[3] Most of these approaches have focused on Mannich
reactions of glycine imines or nitro esters with various
imines, which provide a direct and favorable method for the
construction of these compounds.[4–6] In recent years, a-iso-
thiocyanato imides have been employed as glycine imine
equivalents in Mannich reactions. Willis and co-workers re-
ported the first example of a Mannich reaction of the a-iso-
thiocyanato imide with imines using chiral magnesium com-
plex derivatives from DBFox.[7a] Seidelꢀs group and Zhongꢀs
group both found that quinidine-derived organocatalysts
could catalyze the reaction with good diastereoselectivity
and enantioselectivity.[7b,c] Despite these excellent results,
the design of new catalyst systems remains a considerable
challenge. The guanidine group plays important roles in mo-
lecular recognition and as a catalyst in biological systems
owing to its characteristics, such as high pKa value and dual
hydrogen-bonding.[8] Over the past few years, chiral guani-
dines have become an attractive target in asymmetric orga-
nocatalysis and have been shown to be powerful reagents
for enantioselective reactions.[9–10] Herein, we present a
readily prepared chiral bisguanidine organocatalyst for the
asymmetric Mannich-type reaction of a-isothiocyanato
imide with N-Ts-protected imines, which provides excellent
results under mild conditions.
Entry[a]
Cat
Pg
Yield
[%][b]
trans:cis[c]
ee
[%][d]
1
2
3
4
1a
1b
1c
1d
1d
1d
1d
1d
1d
tosyl
tosyl
tosyl
tosyl
tosyl
phenyl
2-hydroxyphenyl
diphenylmethyl
4-methoxyphenyl
84
96
93
96
94
87
>95:5
90:10
88:12
>95:5
>95:5
82:18
–
68
46
61
82
89
0
–
–
25
5[e]
6[e,f]
7[e]
8[e]
9[e,h]
N.R[g]
N.R[g]
74
–
56:44
[a] Unless otherwise noted, all reactions were carried out with
2
(0.1 mmol), 3 (0.2 mmol), 10 mol% catalyst in THF (1.0 mL) at À208C
for 6 h. [b] Isolated yield of combined diastereomers. [c] Determined by
1H NMR analysis. [d] ee of the trans isomer, measured by chiral HPLC
using Chiracel ADH column. [e] THF/CHCl3 (v/v)=1/1. [f] ee and trans:-
cis of the product, measured by chiral HPLC using Chiracel ADH
column. [g] N.R.=no reaction. [h] ee and trans:cis of the product, mea-
sured by chiral HPLC using Chiracel IA column.
Initially, monoguanidine 1a was synthesized to catalyze
the asymmetric Mannich-type reaction because it could
serve as a bifunctional catalyst.[9f] Moderate results were ob-
tained from a-isothiocyanato imide 2 and N-Ts-imine 3 de-
rived from benzaldehyde (Table 1, entry 1). A series of bis-
guanidines with a chiral or achiral linkage were synthesized
to improve the outcomes (Scheme 1). Chiral bisguanidine
Scheme 1. Catalysts evaluated in this study.
1d derived from benzene-1,3-diamine was superior to 1b
and 1c derived from (1S,2S)-1,2-diphenylethylenediamine
and (1S,2S)-cyclohexane-1,2-diamine, respectively, giving the
desired product in 96% yield, >95:5 d.r. and 82% ee
(Table 1, entry 4 vs. entries 2 and 3); the linkage was able to
adjust the spatial arrangement of the two guanidine moieties
to meet the proper asymmetric induction. A solvent survey
revealed that adducts could be obtained with the best re-
sults, 94% yield, >95:5 d.r. and 89% ee using CHCl3 as co-
solvent (Table 1, entry 5, for details, see Supporting Infor-
[a] X. Chen, S. Dong, Z. Qiao, Y. Zhu, M. Xie, Dr. L. Lin, Dr. X. Liu,
Prof. Dr. X. Feng
Key Laboratory of Green Chemistry & Technology
Ministry of Education, College of Chemistry
Sichuan University, Chengdu 610064 (P. R. China)
Fax : (+86)28-8541-8249
E-mail: liuxh@scu.edu.cn
xmfeng@scu.edu.cn
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201002571.
Chem. Eur. J. 2011, 17, 2583 – 2586
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2583

mation). The influence of other protecting groups of imines
were also investigated (Table 1, entries 6–9). On replace-
ment of the tosyl group with the phenyl group, no ee value
was obtained, although the yield was satisfactory, which im-
plied that the interaction between the tosyl group and the
catalyst was crucial for stereo-induction (Table 1, entry 6).
On employing the 2-hydroxyphenyl and diphenylmethyl
protecting groups, no reaction occurred (Table 1, entries 7
and 8). The Mannich-type reaction of 4-methoxyphenyl-pro-
tected imine also proceeded with low stereoselectivity
(Table 1, entry 9).
surrounding to optimum. Moreover, when catalyst loading
was decreased from 10 mol% to 5 mol%, the enantioselec-
tivity of the reaction decreased slightly (Table 2, entry 6 vs.
2). Fortunately, when the dosage of additive 5b was in-
creased to 7.5 mol%, the results were generally maintained,
while further increasing the amount of acid 5b to 10 mol%
resulted in loss of yield (Table 2, entry 8 vs. 6, 7). The influ-
ence of the sulfonyl group of the imine was tested. Use of
the benzenesulfonyl group protected imine gave 92% ee,
whereas the sterically smaller mesyl group protected imine
afforded the product with greatly reduced enantioselectivity
(65% ee) and comparative yield (entry 9 vs. entries 8 and
10), which might result from the more flexible conformation
of the imine with a methanesulfonyl group. The poor results
of other imines without sulfonyl substituents (Table 1, en-
tries 6–9) clearly illustrated the important role of the sulfo-
nyl group on the stereoselectivity. Screening of other reac-
tion conditions identified that the optimal conditions were
5 mol% bisguanidine 1d, 7.5 mol% additive 5b, 0.1 mmol
a-isothiocyanato imide 2, and 0.2 mmol N-Ts-protected
imine 3a in 1.0 mL THF/CHCl3 (v/v, 1/1) at À208C (Table 2,
entry 8). In addition, the configuration of the product 4a
was assigned to be (4S, 5R) by comparison of the optical ro-
tation to the reported value of the corresponding enantio-
mer.[7c]
To further improve the enantioselectivity of the reaction,
some achiral additives were employed.[11] The Brønsted ba-
sicity of guanidine was crucial for the activation of the iso-
thiocyanato imide, since no product was detected if guani-
À
dine salt 1e with two BF4 counteranions was used. Interest-
ingly, weak acids were found to have positive effect on the
reaction. When p-CNC6H4CO2H (5b) was used as additive,
the enantioselectivity was improved, but the yield was re-
tained (94% yield, 97% ee, Table 2, entry 2). Compared
Table 2. Acidic additives screened in this reaction.
A series of representative N-Ts-protected imines were in-
vestigated under the optimized conditions (Table 3). A vari-
ety of aldimine substrates provided the corresponding prod-
ucts in good to excellent yields, with high diastereoselectiv-
ity (up to >95:5 d.r.) and excellent ee values (up to 99%).
The aromatic imines underwent the Mannich-type reactions
to yield the optically active adducts in excellent yields and
90–>99% ee. It is noteworthy that not only the electronic
properties of the substitutions at the aromatic ring, but also
the steric hindrance, had no obvious effect on the diastereo-
selectivity and enantioselectivity (Table 3, entries 1–17).
While the condensed-ring imines reacted smoothly with a-
isothiocyanato imide, giving the products with 96% ee and
93% ee (Table 3, entries 18 and 19), the a,b-unsaturated
imines showed a slightly reduced reactivity and diastereose-
lectivity (Table 3, entry 20). Heteroaromatic substituted var-
iants delivered the Mannich-type adduct with a high selec-
tivity of 95–98% ee (Table 3, entries 21 and 22). Both acyclic
and cyclic aliphatic imines could also be converted to the
corresponding adducts with excellent results (Table 3, en-
tries 23 and 24). Other substrates such as N-Ts-protected ke-
toimine also were explored, but the adducts were not detect-
ed.[13]
[b]
Entry[a] Acid
pKa
Yield
[%][c]
trans: cis[d] ee
[%][e]
1
C6H5CO2H (5a)
4.20
3.55
3.42
4.38
95 (4a)
94 (4a)
88 (4a)
96 (4a)
90 (4a)
92 (4a)
86 (4a)
92 (4a)
>95:5
>95:5
>95:5
>95:5
>95:5
>95:5
>95:5
>95:5
91
2
3
4
p-CNC6H4CO2H (5b)
p-NO2C6H4CO2H (5c)
p-MeC6H4CO2H (5d)
97
93
90
92
93
95
96
65
92
5
p-MeOC6H4CO2H (5e) 4.47
6[f]
7[g]
8[h]
9[h,i]
10[h,j]
p-CNC6H4CO2H (5b)
p-CNC6H4CO2H (5b)
p-CNC6H4CO2H (5b)
p-CNC6H4CO2H (5b)
p-CNC6H4CO2H (5b)
3.55
3.55
3.55
3.55
3.55
85 (4a’) >95:5
80 (4a’’) >95:5
[a] Unless otherwise noted, all reactions were carried out with
2
(0.1 mmol), 3a (0.2 mmol), 10 mol% additive, 10 mol% 1d in THF/
CHCl3 (v/v, 1/1, 1.0 mL) at À208C for 10 h. [b] Relative pKa in water.[12]
1
[c] Isolated yield of combined diastereomers. [d] Determined by H NMR
analysis. [e] ee of the trans isomer, measured by chiral HPLC using Chira-
cel ADH column. [f] 5 mol% catalyst loading, 5 mol% additive.
[g] 5 mol% catalyst loading, 10 mol% additive. [h] 5 mol% catalyst load-
ing, 7.5 mol% additive. [i] Mesyl group protected imine 3a’ was used.
[j] Benzenesulfonyl-protected imine 3a’’ was used.
with acid 5b, the slightly less acidic C6H5CO2H (5a), p-
MeC6H4CO2H (5d), and p-MeOC6H4CO2H (5e) led to less
improvement of the ee values (Table 2, entries 1, 4, 5, vs. 2),
whereas the more acidic p-NO2C6H4CO2H (5c) exhibited
lower reactivity and enantioselectivity (Table 2, entry 3 vs.
2). The influence of the protonic acid might by partly associ-
ated with the formation of a guanidinium salt, which could
activate the imines through hydrogen bonding.[10] The car-
boxylate anion adhering nearby might fine tune the stereo-
The low catalyst loading, mild reaction conditions, and
the inexpensive starting materials and available catalyst for
this Mannich-type reaction offered a practical way to scale-
up production. In the presence of 5 mol% of bisguanidine
1d, 7.5 mol% of p-CNC6H4CO2H (5b), 10 mmol of a-iso-
thiocyanato imide 2 reacted with 2.0 equivalents of N-Ts-
protected imine 3a to provide the desired product 4a in
82% yield without any loss in the enantioselectivity and dia-
stereoselectivity (Scheme 2).
2584
www.chemeurj.org
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 2583 – 2586

Asymmetric Mannich-Type Reaction
COMMUNICATION
Table 3. Substrate scope for the catalytic asymmetric Mannich-type reac-
tion.
Entry[a]
R
Product
Yield
[%][b]
trans:cis[c]
ee
[%][d]
1
2
3-BrC6H4
4-BrC6H4
4-FC6H4
3-ClC6H4
4-ClC6H4
2-MeOC6H4
4-MeOC6H4
2-MeC6H4
3-MeC6H4
4-MeC6H4
3-PhOC6H4
3-NO2C6H4
4-NO2C6H4
4-CF3C6H4
4-CNC6H4
4-PhC6H4
4b
4c
4d
4e
4 f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
4q
90
94
96
88
90
85
89
80
83
90
93
91
90
89
94
99
92:8
92:8
>95:5
90:10
>95:5
95:5
>95:5
>95:5
94:6
>95:5
>95:5
>95:5
>95:5
90:10
95:5
94
93
90
>99
90
93
>99
93
92
90
97
3[e]
4
5[e]
6
Figure 1. The proposed transition state mode of Mannich-type reaction of
a-isothiocyanato imide with N-Ts-protected imine 3a.
7
8[e]
9[e]
10[e]
11
12[e]
13
14[e]
15
16
via hydrogen bonding to the nitrogen of the imine associat-
ed with the hydrogen bonding between the amide and tosyl
group. On the other hand, the other guanidine moiety de-
protonates the active hydrogen atom from a-isothiocyanato
imide, which then stabilizes the a-isothiocyanato imide by
91
91
90
98
À
an intermolecular hydrogen bond. Meanwhile, the N H
>95:5
96
moiety of the amide on the same side of the guanidine
might act as a Brønsted acid to locate the imide. In this tran-
sition state, the activated a-isothiocyanato imide was much
more accessible to attack the Si-face of the activated N-Ts-
protected imine to form the major (4S,5R) product, in ac-
cordance with the experimental results.
In summary, we have developed a highly efficient bisgua-
nidine organocatalyst for the Mannich-type reaction of a-
isothiocyanato imide with N-Ts-protected imines. Significant
progress has been made with an extremely broad substrate
scope, giving optically active a,b-diamino acid derivatives in
excellent yields with high diastereoselectivities (up to >95:5
d.r.) and excellent enantioselectivities (up to 99% ee) under
mild conditions. The possible transition state of the reaction
was proposed. Further studies on the reaction mechanism
and the application of this catalyst to other reactions are un-
derway.
17
4r
92
92:8
96
18
19
2-naphthyl
1-naphthyl
4s
4t
90
94
93:7
>95:5
96
93
20[e]
4u
86
80:20
93
21
22
23
24
2-thienyl
3-furyl
n-pentyl
cyclohexyl
4v
4w
4x
4y
90
86
82
90
>95:5
>95:5
85:15
85:15
95
98
98
95
[a] Unless otherwise noted, all reactions were carried out with
2
(0.1 mmol), 3 (0.2 mmol), 5 mol% catalyst 1d, 7.5 mol% additive 5b in
THF/CHCl3 (v/v, 1/1, 1.0 mL) at À208C for 8–24 h. [b] Isolated yield of
combined diastereomers. [c] Determined by 1H NMR analysis. [d] ee of
the trans isomer, measured by chiral HPLC using Chiracel ADH column.
[e] 10 mol% catalyst loading, 10 mol% additive.
Experimental Section
Typical experimental procedure: A mixture of 1d (3.7 mg, 0.005 mmol),
a-isothiocyanato imide (18.6 mg, 0.1 mmol), and p-CNC6H4CO2H (5b;
1.1 mg, 0.0075 mmol) in THF/CHCl3 (v/v, 1/1, 1.0 mL) was stirred in an
open vessel at ambient temperature for 10 min. The temperature was
then lowered to À208C and after 15 min, N-benzylidene-4-methylbenze-
nesulfonamide (51.8 mg, 0.2 mmol) was added, and the mixture was
stirred for a further 6 h at À208C. The mixture of trans and cis products
was isolated by column chromatography on silica gel (CH2Cl2/EtOAc:
9:1) to provide 4a as colorless crystal.
Scheme 2. Scaled-up version of the Mannich-type reaction of a-isothio-
cyanato imide with N-Ts-protected imine 3a.
The important evidence of the influence of additives dem-
onstrated that hydrogen as well as the guanidine moiety
both played crucial roles in the reactivity and asymmetric in-
ductivity. Based on the experimental results and our previ-
ous work,[9f,i] we proposed the possible transition state of the
reaction. As shown in Figure 1, one of the guanidine moiet-
ies is protonated by the weakly acidic additive 5b to form a
guanidinium salt, which activates the N-Ts-protected imine
Acknowledgements
We appreciate the National Natural Science Foundation of China (Nos.
20732003, 21021001, and 21072133), and the National Basic Research
Program of China (973 Program: No. 2010CB833300) for financial sup-
Chem. Eur. J. 2011, 17, 2583 – 2586
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
2585

X. Feng, X. Liu et al.
port. We also thank the Sichuan University Analytical & Testing Center
for NMR analysis and the State Key Laboratory of Biotherapy for
HRMS analysis.
506–517; c) C. Nꢄjera, J. M. Sansano, Chem. Rev. 2007, 107, 4584–
4671; d) T. Shibuguchi, H. Mihara, A. Kuramochi, T. Ohshima, M.
Shibasaki, Chem. Asian J. 2007, 2, 794–801; e) S. Kobayashi, R.
Yazaki, K. Seki, Y. Yamashita, Angew. Chem. 2008, 120, 5695–5697;
Angew. Chem. Int. Ed. 2008, 47, 5613–5615; f) X. X. Yan, Q. Peng,
Q. Li, K. Zhang, J. Yao, X. L. Hou, Y. D. Wu, J. Am. Chem. Soc.
2008, 130, 14362–14363; g) J. Hernꢄndez-Toribio, R. Gꢆmez-
Arrayꢄs, J. C. Carretero, J. Am. Chem. Soc. 2008, 130, 16150–16151;
h) D. J. Shang, Y. L. Liu, X. Zhou, X. H. Liu, X. M. Feng, Chem.
Eur. J. 2009, 15, 3678–3681.
Keywords: amino acids · asymmetric catalysis · guanidine ·
Mannich-type reactions · organocatalysis
[1] For reviews see: a) D. Lucet, T. Le Gall, C. Mioskowski, Angew.
Chem. 1998, 110, 2724–2772; Angew. Chem. Int. Ed. 1998, 37, 2580–
2627; b) Y. Ohfune, T. Shinada, Eur. J. Org. Chem. 2005, 24, 5127–
5143; c) C. Cativiela, M. D. Dꢂaz-de-Villegas, Tetrahedron: Asymme-
try 2007, 18, 569–623; d) H. Vogt, S. Brꢃse, Org. Biomol. Chem.
2007, 5, 406–430; e) A. Viso, R. Fernꢄndez de La Pradilla, A.
Garcꢂa, A. Flores, Chem. Rev. 2005, 105, 3167–3196.
[2] For selected examples, see: a) C. D. Carroll, T. O. Johnson, S. Tao,
G. Lauri, M. Orlowski, I. Y. Gluzman, D. E. Goldberg, R. E. Dolle,
Bioorg. Med. Chem. Lett. 1998, 8, 3203–3206; b) M. Cheng, B. De,
S. Pikul, N. G. Almstead, M. G. Natchus, M. V. Anastasio, S. J.
McPhail, C. E. Snider, Y. O. Taiwo, L. Chen, C. M. Dunaway, F. Gu,
M. E. Dowty, G. E. Mieling, M. J. Janusz, S. Wang-Weigand, J. Med.
Chem. 2000, 43, 369–380; c) K. Shreder, L. Zhang, M. Goodman,
Tetrahedron Lett. 1998, 39, 221–224; d) M. Falorni, G. Giacomelli,
Synlett 1996, 143–144; e) N. C. Harris, J. Davies, Brain Res. 1992,
594, 176–180; f) J. R. Hammond, Naunyn-Schmiedeberg’s Arch.
Pharmacol. 2000, 361, 377–382; g) J. L. Duffy, N. J. Kevin, B. A.
Kirk, K. T. Chapman, W. A. Schleif, D. B. Olsen, M. Stahlhut, C. A.
Rutkowski, L. C. Kuo, L. Jin, J. H. Lin, E. A. Emini, J. R. Tata,
Bioorg. Med. Chem. Lett. 2002, 12, 2423–2426.
[3] For selected examples, see: a) A. Viso, R. Fernꢄndez de La Pradilla,
C. Guerrero-Strachan, M. Alonso, M. Martꢂnez-Ripoll, I. Andrꢅ, J.
Org. Chem. 1997, 62, 2316–2317; b) Y. Luo, M. A. Blaskovich, G. A.
Lajoie, J. Org. Chem. 1999, 64, 6106–6111; c) T.-H. Chuang, K. B.
Sharpless, Org. Lett. 1999, 1, 1435–1437; d) D. Ferraris, B. Young, C.
Cox, T. Dudding, W. J. Drury III, L. Ryzhkov, A. E. Taggi, T.
Lectka, J. Am. Chem. Soc. 2002, 124, 67–77; e) A. G. Wenzel, E. N.
Jacobsen, J. Am. Chem. Soc. 2002, 124, 12964–12965; f) N. S. Jo-
sephsohn, M. L. Snapper, A. H. Hoveyda, J. Am. Chem. Soc. 2004,
126, 3734–3735; g) F. A. Davis, Y. Zhang, H. Qiu, Org. Lett. 2007, 9,
833–836; h) T. Akiyama, J. Itoh, K. Yokota, K. Fuchibe, Angew.
Chem. 2004, 116, 1592–1594; Angew. Chem. Int. Ed. 2004, 43, 1566–
1568; i) S. Kobayashi, R. Matsubara, Y. Nakamura, H. Kitagawa, M.
Sugiura, J. Am. Chem. Soc. 2003, 125, 2507–2515; j) N. S. Chowdari,
M. Ahmad, K. Albertshofer, F. Tanaka, C. F. Barbas III, Org. Lett.
2006, 8, 2839–2842; k) A. Okada, T. Shibuguchi, T. Ohshima, H.
Masu, K. Yamaguchi, M. Shibasaki, Angew. Chem. 2005, 117, 4640–
4643; Angew. Chem. Int. Ed. 2005, 44, 4564–4567; l) T. Ooi, M.
Kameda, J.-I. Fujii, K. Maruoka, Org. Lett. 2004, 6, 2397–2399;
n) L. Bernardi, A. S. Gothelf, R. G. Hazell, K. A. Jørgensen, J. Org.
Chem. 2003, 68, 2583–2591.
[4] Selected examples of Mukaiyama-type Mannich reaction, see: a) Y.
Suto, M. Kanai, M. Shibasaki, J. Am. Chem. Soc. 2007, 129, 500–
501; b) K. Saruhashi, S. Kobayashi, J. Am. Chem. Soc. 2006, 128,
11232–11235; c) Y. Ihori, Y. Yamashita, H. Ishitani, S. Kobayashi, J.
Am. Chem. Soc. 2005, 127, 15528–15535; d) M. M. Salter, J. Ko-
bayashi, Y. Shimizu, S. Kobayashi, Org. Lett. 2006, 8, 3533–3536; for
selected examples of Mannich reactions employing enolate surro-
gates, see: e) A. Singh, J. N. Johnston, J. Am. Chem. Soc. 2008, 130,
5866–5867; f) A. Singh, R. A. Yoder, B. Shen, J. N. Johnston, J. Am.
Chem. Soc. 2007, 129, 3466–3467.
[6] For selected other examples, see: a) D. Uraguchi, Y. Ueki, T. Ooi, J.
Am. Chem. Soc. 2008, 130, 14088–14089; b) X.-T. Zhou, Y.-R. Lin,
L.-X. Dai, J. Sun, L.-J. Xia, M.-H. Tang, J. Org. Chem. 1999, 64,
1331–1334; c) J. Aydin, A. Rydꢅn, K. J. Szabꢆ, Tetrahedron: Asym-
metry 2008, 19, 1867–1870; d) M. Rueping, A. P. Antonchick, Org.
Lett. 2008, 10, 1731–1734.
[7] a) G. A. Cutting, N. E. Stainforth, M. P. John, G. Kociok-Kçhn,
M. C. Willis, J. Am. Chem. Soc. 2007, 129, 10632–10633; b) L. Li,
M. Ganesh, D. Seidel, J. Am. Chem. Soc. 2009, 131, 11648–11649;
c) Z.-G. Shi, P.-Y. Yu, P.-J. Chua, G.-F. Zhong, Adv. Synth. Catal.
2009, 351, 2797–2800.
[8] For reviews, see: a) C. L. Hannon, E. V. Anslyn, in Bioorganic
Chemistry Frontiers, Springer, Heidelberg, 1993, Vol. 3, pp. 193–255;
b) Y. Yamamoto, S. Kojima in The Chemistry of Amidines and Imi-
dates, Vol. 2 (Eds.: S. Patai, Z. Rappoport), Wiley, New York, 1991,
pp. 485–526; c) T. Ishikawa, T. Isobe, Chem. Eur. J. 2002, 8, 552–
557; d) K. A. Schug, W. Lindner, Chem. Rev. 2005, 105, 67–114;
e) P. Blondeau, M. Segura, R. Pꢅrez-Fernꢄndez, J. de Mendoza,
Chem. Soc. Rev. 2007, 36, 198–210; f) A. G. Doyle, E. N. Jacobsen,
Chem. Rev. 2007, 107, 5713–5743; g) D. Leow, C.-H. Tan, Chem.
Asian J. 2009, 4, 488–507; h) R. G. Arrayꢄs, J. C. Carretero, Chem.
Soc. Rev. 2009, 38, 1940–1948.
[9] For selected examples on chiral-guanidine-catalyzed enantioselec-
tive reactions, see: a) E. J. Corey, M. J. Grogan, Org. Lett. 1999, 1,
157–160; b) T. Ishikawa, Y. Araki, T. Kumamoto, H. Seki, K.
Fukuda, T. Isobe, Chem. Commun. 2001, 245–246; c) T. Kita, A.
Georgieva, Y. Hashimoto, T. Nakata, K. Nagasawa, Angew. Chem.
2002, 114, 2956–2958; Angew. Chem. Int. Ed. 2002, 41, 2832–2834;
d) M. T. Allingham, A. Howard-Jones, P. J. Murphy, D. A. Thomas,
P. W. R. Caulkett, Tetrahedron Lett. 2003, 44, 8677–8680; e) M.
Terada, T. Ikehara, H. Ube, J. Am. Chem. Soc. 2007, 129, 14112–
14113; f) Z. P. Yu, X. H. Liu, L. Zhou, L. L. Lin, X. M. Feng,
Angew. Chem. 2009, 121, 5297–5300; Angew. Chem. Int. Ed. 2009,
48, 5195–5198; g) H. Ube, N. Shimada, M. Terada, Angew. Chem.
2010, 122, 1902–1905; Angew. Chem. Int. Ed. 2010, 49, 1858–1861;
h) T. Misaki, G. Takimoto, T. Sugimura, J. Am. Chem. Soc. 2010,
132, 6286–6287; i) S. X. Dong, X. H. Liu, X. H. Chen, F. Mei, Y. L.
Zhang, B. Gao, L. L. Lin, X. M. Feng, J. Am. Chem. Soc. 2010, 132,
10650–10651.
[10] For selected examples on chiral guanidinium salt-catalyzed reac-
tions, see: a) V. Alcꢄzar, J. R. Morꢄn, J. de. Mendoza, Tetrahedron
Lett. 1995, 36, 3941–3944; b) C. Uyeda, E. N. Jacobsen, J. Am.
Chem. Soc. 2008, 130, 9228–9229; c) X. Fu, W. T. Loh, Y. Zhang, T.
Chen, T. Ma, H. J. Liu, J. M. Wang, C. H. Tan, Angew. Chem. 2009,
121, 7523–7526; Angew. Chem. Int. Ed. 2009, 48, 7387–7390.
[11] E. M. Vogl, H. Grçger, M. Shibasaki, Angew. Chem. 1999, 111,
1672–1680; Angew. Chem. Int. Ed. 1999, 38, 1570–1577.
[12] J. Jover, R. Bosque, J. Sales, QSAR Comb. Sci. 2007, 26, 385–397.
[13] The product was not obtained when the 1-phenylethylidene-4 meth-
ylbenzenesulfonamide was tested as substrate using this catalyst
system.
[5] For selected examples of Mannich reactions employing glycine
imines, see: a) M. J. OꢀDonnell, T. M. Eckrich, Tetrahedron Lett.
1978, 19, 4625–4628; b) M. J. OꢀDonnell, Acc. Chem. Res. 2004, 37,
Received: September 4, 2010
Published online: January 26, 2011
2586
www.chemeurj.org
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 2583 – 2586