Enantioselective intermolecular carbon-carbon bond formation of glyoxylate imines with allylstannanes catalyzed by tropos BIPHEP-gold(I) complexes with Au-Au interactions

Article abstract of DOI:10.1002/chem.201103023

Interactions act: The enantioselective allylation reaction of glyoxylate imines catalyzed by tropos DM-BIPHEP-gold(I) complexes with an Au-Au interaction was developed to give a higher enantioselectivity than the atropos DM-BINAP-gold complexes without an

Full text of DOI:10.1002/chem.201103023

DOI: 10.1002/chem.201103023
Enantioselective Intermolecular Carbon–Carbon Bond Formation of
Glyoxylate Imines with Allylstannanes Catalyzed by tropos BIPHEP–
Gold(I) Complexes with Au–Au Interactions**
Masafumi Kojima and Koichi Mikami*[a]
Over the last decade, a number of gold-catalyzed intra-
and intermolecular reactions have been developed on the
basis of the unique character of gold complexes as carbo-
philic Lewis acids.[1] Despite the current progress in this
area of research, the development of effective chiral gold
catalysts for enantioselective intermolecular carbon–carbon
bond formation (CCF) reactions has been limited, owing to
the unfavorable geometry of gold complexes, namely linear
dicoordination. Bisphosphine ligands with bulky aryl moiet-
ies on the phosphines are generally employed as chiral li-
gands for enantioselective intramolecular reactions. A mon-
odentate phosphoramidite ligand[2] and a chiral counter
anion[3] have also been used for the intramolecular reactions.
As limited examples of enantioselective intermolecular CCF
reactions, Toste[4] and Fꢀrstner[2c] have reported intriguing
examples of cyclopropanation.
We have reported that axial chirality of gold complexes
bearing chirally flexible (tropos) bis(phosphanyl)biphenyl
(BIPHEP) ligands,[5] which are modular, versatile, readily
Figure 1. Comparison of (R)-1a-(AuCl)2 and (R)-DM-BINAP–(AuCl)2.
synthesized without enantiomeric resolution, can be con-
a) (R)-1a-(AuCl)2 shows Au–Au bonding (Ref. [3d], Supporting Informa-
trolled by chiral phosphates and the corresponding N-triflyl
tion). b) Structure of (R)-DM-BINAP–(AuCl)2;[6] Solvent and hydrogen
phosphoramides as chiral anions.[3b] Even after dissociation
atoms are omitted for clarity; Selected bond lengths [ꢁ] and angles [8]:
of the chiral anions, no racemization of BIPHEP–(AuCl)2
complexes takes place, owing to the Au–Au interaction. The
catalytic activity and enantioselectivity of BIPHEP–(AuCl)2
complexes would highly differentiate from the structurally
similar BINAP–(AuCl)2 complexes since the Au–Au interac-
tion was not observed in the corresponding atropos BINAP–
(AuCl)2 complexes (Figure 1).[6] Herein, we report the
highly enantioselective allylation reaction of glyoxylate
imines, a typical and synthetically useful intermolecular
CCF reaction, catalyzed by BIPHEP-gold complexes
through bimetallic activation,[7] as compared to the structur-
ally similar BINAP–(AuCl)2 complexes without Au–Au in-
teraction.[8]
À
À
À
À
Au1 P1 2.230(2), Au2 P2 2.239(2), Au1 Cl1 2.284(2), Au2 Cl2 2.303(3),
P1-Au1-Cl1 175.47(8), P2-Au2-Cl2 176.25(8).
The catalytic enantioselective allylation reaction of
glyoxylACHTNUTRGNEaNUG te imines is synthetically important as an efficient
route to optically active allylic a-amino acids, because the
resultant g,d-unsaturated double bond can be easily convert-
ed into a variety of functional groups.[9–11] However, only a
few examples on other metal catalyses have been de-
scribed.[12–14] We envisioned that the BIPHEP–gold com-
plexes with intramolecular Au–Au interactions could effec-
tively catalyze the enantioselective allylation reaction of
glyoxylate imines; the glyoxylate imines could be activated
by the two gold atoms in close vicinity through bimetallic
coordination with the nitrogen of the imine and the oxygen
of the ester. The bimetallic chelate structure could lead to
the construction of a compact and rigid asymmetric reaction
field,[8] observed by theoretical calculations of the model
glyoxylate imine and (R)-DM-BIPHEP (1a)–gold complex
(DM=3,5-dimethyl) and fully optimized by the B3LYP/3-
21G* (LanL2DZ for Au, 3-21G* for others) by using Gaus-
sian03 D.01 program. The optimized complex of (R)-DM-
[a] M. Kojima, Prof. Dr. K. Mikami
Department of Applied Chemistry
Tokyo Institute of Technology
O-okayama, Meguro-ku, 152-8552 (Japan)
Fax : (+81)3-5734-2776
E-mail: mikami.k.ab@m.titech.ac.jp
[**] BIPHEP=bis(phosphanyl)biphenyl
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201103023.
13950
ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 13950 – 13953

COMMUNICATION
Table 1. Optimization of the reaction conditions for the enantioselective
allylation reaction of glyoxylate imine 2a.
Entry Au complex
X
Solvent
T
Yield ee
[8C] [%][b] [%][c]
1
2
3
4
5
6
7
8
(R)-1a-(AuCl)2
(R)-1a-(AuCl)2
(R)-1a-(AuCl)2
(R)-1a-(AuCl)2
(R)-1a-(AuCl)2
(R)-1a-(AuCl)2
(R)-1a-(AuCl)2
(R)-1a-(AuCl)2
(R)-1a-(AuCl)2
(R)-1a-(AuCl)2
(R)-1b-(AuCl)2
(R)-1c-(AuCl)2
(R)-1d-(AuCl)2
NTf2
ClO4
SbF6
OTf
BF4
N
0
0
0
0
0
0
0
0
0
0
0
0
0
0
79
73
74
79
70
78
77
85
71
83
80
85
83
77
72
77
75
78
77
77
57
37
51
78
67
64
52
58
79
87
67
OTs
OTf THF
OTf Et2O
OTf toluene
OTf
OTf
OTf
OTf
9
10[a]
11[a]
12[a]
13[a]
14[a]
15[a]
16[a]
17[a]
(R)-DM-BINAP-(AuCl)2 OTf
(R)-1a-(AuCl)2
(R)-1a-(AuCl)2
(R)-1a-(AuCl)2
OTf CH2Cl2
OTf CH2Cl2
OTf CH2Cl2
À20 83
À40 87
À60 78
Figure 2. a) Calculated bimetallic chelate structure of (R)-1a-gold com-
plex and model glyoxylate imine. b) Side view.
[a] Reaction time was 3 h. [b] Isolated yield. [c] Enantiomeric excess was
determined by chiral HPLC analysis. PMP=p-methoxyphenyl.
BIPHEP (1a)–digold and glyoxylate imine indicated that
the bimetallic chelate structure could be formed to give the
(2S)-products through allylation from the convex face
(Figure 2).[15] A similar DM-BINAP–digold complex with
glyoxylate imine could not be optimized in the bimetallic
chelate form.
steric effect on the BIPHEP moiety, both the less demand-
ing (R)-1b-(AuCl)2 complex and the more demanding (R)-
1c-(AuCl)2 or (R)-1d-(AuCl)2 complexes decreased the
enantioselectivity (entries 10–13). As expected, (R)-DM-
BINAP–(AuCl)2, which does not have an Au–Au interac-
tion, led to lower enantioselectivity than the BIPHEP–gold
complexes with Au–Au interactions (entry 14). These results
indicated that the Au–Au interaction plays an essential role
to give higher enantioselectivity. A further improvement in
yield and enantioselectivity was achieved by conducting the
reaction at lower temperature, thereby furnishing the de-
sired product in 87% yield with 87% ee within 3 h (en-
tries 15–17).
Under these optimized conditions, various allylmetal re-
agents were examined (Table 2). Allylstannanes 3b and 3c
reacted with glyoxylate imine 2a smoothly to afford the de-
sired product in good yields, but with lower enantioselectivi-
ty than 3a (entry 1 vs. 2 and 3). When allylboron reagents
3d and 3e were used, the reaction proceeded slowly to give
lower yields with high enantioselectivities (entries 4 and 5).
When allylsilane 3 f was used, only a trace amount of the de-
sired product was obtained, even at 08C (entry 6). Under
these conditions, the ene reaction of glyoxylate imines did
not take place with a-methylstyrene or isobutene.
Next, the effect of the N-substituent on the glyoxylate
imine was examined (Table 3). When the reaction was per-
formed at 08C, the reaction with N-3,4,5-trimethoxyphenyl
glyoxylate imine 2b as a substrate proceeded to afford the
allylated product in good yield, but with low enantioselectiv-
ity (entry 3). The reaction of N-benzyl glyoxylate imine 2c
gave the desired product with moderate yield and low enan-
As an initial experiment, the reaction of glyoxylate imine
2a and allyltributylstannane (3a) was catalyzed by (R)-1a-
(AuCl)2 after treatment with silver salts to afford the allylat-
ed product 4a in good yield and with moderate to high
enantioselectivity (Table 1). Under the reaction conditions,
the formation of an allyl–gold species was not observed by
1H NMR analyses. In the reaction of cationic gold complex
(R)-1a-(AuNTf2)2 with 3a (1–10 equiv), no significant shift
was observed for the allylic methylene protons, while a large
shift was observed for the olefinic protons, presumably be-
cause of the complexation with the cationic gold. After a
screening of silver salts, AgOTf was found to give the high-
est yield and enantioselectivity (entries 1–6).
The use of THF, diethyl ether, and toluene instead of di-
chloroethane did not improve the enantioselectivity. Haloal-
kane solvents, such as dichloroethane and dichloromethane,
were thus the best solvents (entries 7–9). Regarding the
Chem. Eur. J. 2011, 17, 13950 – 13953
ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
13951

M. Kojima and K. Mikami
Table 2. Reaction of 2a with various allylmetal reagents.
groups gave lower enantioselectivity, although the high
yields maintained. These results imply that large ester
groups prevent the construction of the closed asymmetric re-
action field or the approach of the allylstannanes from the
convex face of the digold chelate complex with the glyoxyl-
Entry
M
Yield [%][b]
ee [%][c]
AHCTUNGTRENNUNG
1
2
3
4
nBu3Sn (3a)
Ph3Sn (3b)
A
87
73
84
42
44
trace
87
78
72
80
83
–
termolecular carbon–carbon bond formation of glyoxylate
imines with allylstannanes catalyzed by tropos BIPHEP–
gold(I) complexes with Au–Au interactions. The present
study clearly reveals the advantage of BIPHEP–gold com-
plexes with intramolecular Au–Au interactions in enantiose-
lective CCF reactions compared to the structurally similar
BINAP–gold complexes without the Au–Au interaction.
Further mechanistic studies and applications of the
BIPHEP–gold catalyst to other enantioselective reactions
are now in progress.
5
A
6[a]
[a] The reaction was performed at 08C for 20 h. [b] Isolated yield.
[c] Enantiomeric excess was determined by chiral HPLC analysis. Pin=
pinacol, TMS=trimetylsilyl.
Table 3. Effect of the N-substituent on the glyoxylate imine.
Experimental Section
Dichloromethane (0.6 mL) was added to a mixture of (R)-1a-(AuCl)2
(5.5 mg, 0.005 mmol) and AgOTf (2.6 mg, 0.010 mmol) at 08C under an
argon atmosphere. After the mixture was stirred at 08C for 30 min, a so-
lution of glyoxylate imine 2a (20.7 mg, 0.10 mmol) in dichloromethane
(0.4 mL) and then allyltributylstannane (3a, 34 mL, 0.11 mmol) were
added at À408C. After being stirred at À408C for 3 h, the reaction mix-
ture was directly loaded on a silica gel column and eluted with hexane/
ethyl acetate to give 4a (21.8 mg, 87% yield). The enantiomeric excess
was determined by chiral HPLC analysis (87% ee).
Entry
1[a]
2
3
4
R1[b]
Product
Yield [%][c]
ee [%][d]
PMP (2a)
PMP (2a)
TMP (2b)
Bn (2c)
4a
4a
4b
4c
4d
87
83
76
46
56
87
78
19
37
11
5
Ts (2d)
[a] The reaction was performed in dichloromethane at À408C. [b] PMP=
p-methoxyphenyl, TMP=3,4,5-trimethoxyphenyl, Bn=benzyl, Ts=p-tol-
uenesulfonyl. [c] Isolated yield. [d] Enantiomeric excess was determined
by chiral HPLC analysis.
Acknowledgements
tioselectivity (entry 4). The more reactive N-tosyl glyoxylate
imine 2d gave the corresponding product in only moderate
yield, owing to the decomposition of the glyoxylate imine
substrate (entry 5). Thus, N-p-methoxyphenyl in glyoxylate
imine 2a was the best substituent (entries 1 and 2).
The scope of N-p-methoxyphenyl glyoxylate imine sub-
strates was examined under the optimized reaction condi-
tions (Table 4). Methyl, ethyl, isopropyl, n-butyl, and benzyl
ester substrates were also shown to give high yields and
enantioselectivities. For the glyoxylate imines larger ester
This work was supported by Grant-in-Aid for JSPS fellowship. We thank
Assoc. Prof. Dr. S. Ito of Tokyo Institute of Technology for theoretical
calculations and Dr. K. Hasegawa of Rigaku Co. for X-ray analyses.
Keywords: allylation · asymmetric catalysis · BIPHEP ·
glyoxylate imines · gold
[1] For reviews on enantioselective gold catalysis, see: a) N. Bongers, N.
Krause, Angew. Chem. 2008, 120, 2208; Angew. Chem. Int. Ed. 2008,
47, 2178; b) R. A. Widenhoefer, Chem. Eur. J. 2008, 14, 5382; c) S.
Sengupta, X. Shi, ChemCatChem 2010, 2, 609; d) A. Pradal, P. Y.
Toullec, V. Michelet, Synthesis 2011, 10, 1501.
Table 4. The scope of N-p-methoxyphenyl glyoxylate imine substrates.
[2] a) I. Alonso, B. Trillo, F. Lꢃpez, S. Montserrat, G. Ujaque, L. Caste-
do, A. Lledꢃs, J. L. MascareÇas, J. Am. Chem. Soc. 2009, 131, 13020;
b) A. Z. Gonzꢄlez, F. D. Toste, Org. Lett. 2010, 12, 200; c) H. Teller,
S. Flꢀgge, R. Goddard, A. Fꢀrstner, Angew. Chem. 2010, 122, 1993;
Angew. Chem. Int. Ed. 2010, 49, 1949; d) A. Z. Gonzꢄlez, D. Beni-
tez, E. Tkatchouk, W. A. Goddard III, F. D. Toste, J. Am. Chem.
Soc. 2011, 133, 5500; e) H. Teller, A. Fꢀrstner, Chem. Eur. J. 2011,
17, 7764.
[3] a) G. L. Hamilton, E. J. Kang, M. Mba, F. D. Toste, Science 2007,
317, 496; b) K. Aikawa, M. Kojima, K. Mikami, Angew. Chem. 2009,
121, 6189; Angew. Chem. Int. Ed. 2009, 48, 6073; c) R. L. LaLonde,
Z. J. Wang, M. Mba, A. D. Lackner, F. D. Toste, Angew. Chem. 2010,
122, 608; Angew. Chem. Int. Ed. 2010, 49, 598; d) K. Aikawa, M.
Kojima, K. Mikami, Adv. Synth. Catal. 2010, 352, 3131.
Entry
R2
Product
Yield [%][a]
ee [%][b]
1
2
3
4
5
Me (2e)
Et (2a)
iPr (2 f)
nBu (2g)
Bn (2h)
4e
4a
4 f
4g
4h
83
87
81
79
83
87
87
85
82
80
[a] Isolated yield. [b] Enantiomeric excess was determined by chiral
HPLC analysis.
13952
www.chemeurj.org
ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 13950 – 13953

Enantioselective Allylation of Glyoxylate Imines
COMMUNICATION
[4] M. J. Johansson, D. J. Gorin, S. T. Staben, F. D. Toste, J. Am. Chem.
Soc. 2005, 127, 18002.
[5] For a review, see: K. Mikami, K. Aikawa, Y. Yusa, J. J. Jodry, M. Ya-
manaka, Synlett 2002, 1561.
[10] For reviews on the synthesis of optically active amino acids by ene
reactions with glyoxylate imines, see: a) R. M. Borzilleri, S. M.
Weinreb, Synthesis 1995, 347; b) S. M. Weinreb, Top. Curr. Chem.
1997, 190, 131.
[6] Crystal data for (R)-DM-BINAP–(AuCl)2: C52H48Au2Cl2P2·0.18
CH2Cl2, orthorhombic, space group P212121, a=12.6153(4), b=
19.0684(5), c=38.0466(12) ꢁ, V=9152.2(5) ꢁ3, Z=8, 1calcd =1.763
gcmÀ3, and m=66.699 cmÀ1. All measurements were made on a
XtaLAB mini diffractometer with graphite monochromated MoKa
radiation at 93 K. Of the 74851 reflections that were collected,
20900 were unique (Rint =0.0823). R1 =0.0487, wR2 =0.1227, good-
ness of fit=1.155, Flack parameter=À0.039(6), shift/error=0.002.
CCDC 838021 contains the supplementary crystallographic data for
this paper. These data can be obtained free of charge from the Cam-
bridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_-
request/cif. (See also: M. A. Tarselli, A. R. Chianese, S. J. Lee, M. R.
Gagnꢅ, Angew. Chem. 2007, 119, 6790; Angew. Chem. Int. Ed. 2007,
46, 6670.).
[7] For an enantioselective gold-catalyzed reaction through bimetallic
activation, see: M. Bandini, A. Eichholzer, Angew. Chem. 2009, 121,
9697; Angew. Chem. Int. Ed. 2009, 48, 9533.
[8] The dinuclear gold complexes having Au–Au interaction were re-
cently reported to provide higher enantioselectivity than the dinu-
clear gold complexes without Au–Au interaction, see: a) F. Liu, D.
Qian, L. Li, X. Zhao, J. Zhang, Angew. Chem. 2010, 122, 6819;
Angew. Chem. Int. Ed. 2010, 49, 6669; b) M-Z. Wang, C-Y. Zhou, Z.
Guo, E. L-M. Wong, M-K. Wong, C-M. Che, Chem. Asian J. 2011,
6, 812.
[11] For reviews on the synthesis of optically active amino acids, see:
a) A. E. Taggi, A. M. Hafez, T. Lectka, Acc. Chem. Res. 2003, 36,
10; b) J. Michaux, G. Niel, J-M. Campagne, Chem. Soc. Rev. 2009,
38, 2093, and references therein.
[12] For enantioselective allylation reactions using copper catalysts, see:
a) D. Ferraris, T. Dudding, B. Young, W. J. Drury III, T. Lectka, J.
Org. Chem. 1999, 64, 2168; b) X. Fang, M. Johannsen, S. Yao, N.
Gathergood, R. G. Hazell, K. A. Jørgensen, J. Org. Chem. 1999, 64,
4844; c) D. Ferraris, B. Young, C. Cox, T. Dudding, W. J. Drury III,
T. L. Ryzhkov, A. E. Taggi, T. Lectka, J. Am. Chem. Soc. 2002, 124,
67; d) H. Kiyohara, Y. Nakamura, R. Matsubara, S. Kobayashi,
Angew. Chem. 2006, 118, 1645; Angew. Chem. Int. Ed. 2006, 45,
1615.
[13] For enantioselective allylation reactions using zinc catalysts, see:
a) T. Hamada, K. Manabe, S. Kobayashi, Angew. Chem. 2003, 115,
4057; Angew. Chem. Int. Ed. 2003, 42, 3927; b) M. Fujita, T. Nagano,
U. Schneider, T. Hamada, C. Ogawa, S. Kobayashi, J. Am. Chem.
Soc. 2008, 130, 2914.
[14] For enantioselective allylation reaction using a silver catalyst, see: F.
Colombo, R. Annunziata, M. Benaglia, Tetrahedron Lett. 2007, 48,
2687.
[15] Based on our experimental data in ref. 3d.
[9] R. M. Williams, Synthesis of Optically Active a-Amino Acids, Perga-
mon, Oxford, 1989.
Received: September 27, 2011
Published online: November 14, 2011
Chem. Eur. J. 2011, 17, 13950 – 13953
ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
13953