Chiral silver amides as effective catalysts for enantioselective [3+2] cycloaddition reactions

Article abstract of DOI:10.1002/asia.201100246

Asymmetric [3+2] cycloaddition of α-aminoester Schiff bases with substituted olefins is one of the most efficient methods for the preparation of chiral pyrrolidine derivatives in optically pure form. In spite of its potential utility, applicable substrate

Full text of DOI:10.1002/asia.201100246

FULL PAPERS
DOI: 10.1002/asia.201100246
Chiral Silver Amides as Effective Catalysts for Enantioselective [3+2]
Cycloaddition Reactions
Yasuhiro Yamashita, Takaki Imaizumi, Xun-Xiang Guo, and Shu Kobayashi*[a]
¯
Abstract: Asymmetric [3+2] cycloaddi-
tion of a-aminoester Schiff bases with
substituted olefins is one of the most
efficient methods for the preparation
of chiral pyrrolidine derivatives in opti-
cally pure form. In spite of its potential
utility, applicable substrates for this
method have been limited to Schiff
bases that bear relatively acidic a-hy-
drogen atoms. Here we report a chiral
silver amide complex for asymmetric
[3+2] cycloaddition reactions. A silver
complex prepared from silver bis(tri-
methylsilyl)amide (AgHMDS) and
(R)-DTBM-SEGPHOS worked well in
asymmetric [3+2] cycloaddition reac-
tions of a-aminoester Schiff bases with
several olefins to afford the corre-
sponding pyrrolidine derivatives in
high yields with remarkable exo- and
enantioselectivities. Furthermore, a-
aminophosphonate Schiff bases, which
have less acidic a-hydrogen atoms, also
reacted with olefins with high exo- and
enantioselectivities. The stereoselectivi-
ties of the [3+2] cycloadditions with
maleate and fumarate suggested that
the reaction proceeded by means of a
concerted mechanism. An NMR spec-
troscopic study indicated that complex-
ation of AgHMDS with the bisphos-
phine ligand was not complete, and
that free AgHMDS, which did not
show any significant catalytic activity,
existed in the catalyst solution. This
means that significant ligand accelera-
tion occurred in the current reaction
system.
Keywords: amides
·
asymmetric
synthesis · cycloaddition · Lewis
acids · silver
Introduction
However, strong Lewis acids are sometimes not suitable
for catalytic reactions. In Lewis acid catalysis, electrophile/
Lewis acid complexes are formed in transition states, and if
the complexes are too stable, Lewis acid catalysts might be
trapped by electrophiles to suppress the catalyst turnover.
Furthermore, atom-economical reactions have recently
become desirable from environmental viewpoints in organic
transformations, and addition reactions (including cycloaddi-
tion) accompanied by proton transfer are preferable.[3] In
carbon–carbon bond-forming reactions, proton transfer usu-
ally starts from carbanion generation using a catalytic
amount of base. In those cases, external bases have often
been added in the presence of Lewis acids.[2] We envisioned
that if metal or metalloid catalysts with both acidic and
basic characters were developed, more efficient catalytic sys-
tems would be created.[4] Because a simple catalyst structure
is desirable, metal or metalloid catalysts that bear basic li-
gands (counteranions) such as metal amides or alkoxides
are candidates (acid/base catalyst in Scheme 1). However,
typical metal amides or alkoxides, such as alkaline metal
amides or alkoxides, are too basic. Obviously, the choice of
metals or metalloids is a key to achieving this concept.
Metal, including metalloid, catalysts (MX) have played key
roles in synthetic organic chemistry. While many catalysts
based on many metals and metalloids have been developed
in this field, acid/base catalysis has been one of the major
targets in the past two decades.[1] Among them, Lewis acid
catalysis has been of great interest because unique reactivity
and selectivities, especially enantioselectivities, have been
attained under mild reaction conditions.[2] To pursue higher
reactivity and selectivities, a target is stronger Lewis acids,
which are prepared by combining more Lewis acidic metals
or metalloids with less nucleophilic centers. According to
this approach, ligands (counteranions) have evolved from
halides to perchlorate, triflate, triflimide, and so on, thus
leading to stronger Lewis acids.
[a] Dr. Y. Yamashita, T. Imaizumi, Dr. X.-X. Guo, Prof. Dr. S. Kobayashi
Department of Chemistry, School of Science
The University of Tokyo
Hongo, Bunkyo-ku, Tokyo, 113-0033 (Japan)
Fax : (+81)3-5684-0634
E-mail: shu_kobayashi@chem.s.u-tokyo.ac.jp
For such catalysts, we focused on silver bis(trimethylsily-
l)amide (AgHMDS). Silver is in group 11 between copper
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/asia.201100246.
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Scheme 2. Preparation of AgHMDSs.
Scheme 1. Lewis acid catalyst and acid/base catalyst.
A Chiral Silver Amide-Catalyzed [3+2] Cycloaddition of a-
Amino Esters to Olefins
Synthesis of highly substituted pyrrolidine derivatives is very
important in bioorganic and medicinal chemistry because
they are useful building blocks of biologically active mole-
cules and also sometimes show interesting biological activi-
ty.[11] Asymmetric [3+2] cycloaddition of a-aminoester
Schiff bases with substituted olefins is one of the most effi-
cient methods for their preparation in optically pure
form,[12] thus making it possible to introduce various sub-
stituents on the pyrrolidine skeleton stereoselectively. From
pioneering work of Grigg et al., chiral catalyst systems
based on a combination of chiral metal Lewis acids and ter-
tiary amine bases have been reported, and excellent diaster-
eo- and enantioselectivities have been attained in some
cases;[13] however, applicable substrates for this method are
still limited. For example, Schiff bases that bear less acidic
a-hydrogen atoms cannot be used in this reaction. A new
catalyst that allows efficient deprotonation of less acidic a-
hydrogen atoms of Schiff bases is desired, and we decided
to employ AgHMDS in this reaction.
First, we investigated a [3+2] cycloaddition reaction of
the benzaldehyde Schiff base of glycine methyl ester (1a)
with methyl acrylate (2a) in the presence of a chiral com-
plex (10 mol%) prepared from AgHMDS and (R)-BINAP
(L1) in toluene at 308C. The desired reaction proceeded in
82% yield with moderate enantioselectivities (Table 1,
entry 1). In this catalyst system, the endo adduct was ob-
tained as the major diastereomer (endo/exo=72:18). On the
other hand, during our investigation on the ligand structures,
interestingly, we found that use of SEGPHOS-type ligands
afforded the exo adduct preferentially (Table 1, entries 3
and 4); (R)-DTBM-SEGPHOS (L4) in particular showed
high exo selectivity (endo/exo=4:96) and good enantioselec-
tivity (84% ee, Table 1, entry 4). Whereas typical chiral
silver catalysts showed endo selectivity, it is remarkable that
the exo product was obtained selectively.[14] With these
promising results in hand, we optimized the reaction condi-
tions for further improvement of the selectivities. Although
the effect of the ester parts of the substrates was investigat-
ed, bulky substrates such as tert-butyl acrylate (2b) and the
Schiff base of glycine tert-butyl ester (1b) did not give any
improved result (Table 1, entries 5 and 6). Even when the
reaction was conducted in the presence of 5 mol% of the
silver catalyst, the reaction proceeded smoothly in good
yield with slight loss of the selectivities (Table 1, entry 7).
When the reaction was conducted at 08C for 24 hours using
5 mol% of the silver catalyst, the desired product was ob-
tained in only 37% yield but with excellent exo selectivity
and very high enantioselectivity (Table 1, entry 8). Several
solvents were then examined, and it was found that a less
(Cu) and gold (Au). Except for cases that require an ex-
change of counteranions (AgCl forms in most cases), silver
salts have mainly been used as Lewis acid catalysts to acti-
vate carbonyls, imines, and carbon–carbon multiple bonds.[5]
When silver salts are combined with chiral ligands, excellent
asymmetric environments can be created; AgOTf with
chiral bidentate ligands such as 2,2’-bis(diphenylphosphino)-
1,1’-binaphthyl (BINAP) has been successfully used in asym-
metric catalysis.[6] On the other hand, silver species as chiral
Brønsted bases are very limited. Until now, chiral silver
Brønsted bases have mostly been prepared by silver acetate
or the combination of an appropriate silver salt with an ex-
ternal tertiary amine base, which could show high stereose-
lectivities in some asymmetric reactions; however, activity
as a base has been insufficient.[7] Based on this background,
we focused on the use of a chiral silver amide, in particular
AgHMDS with chiral ligands, as a strong silver base catalyst
in asymmetric reactions. If the silver cation worked as an ef-
fective Lewis acid and at the same time the amide anion
worked as a strong Brønsted base, the silver amide might
work as an efficient catalyst even to achieve asymmetric cat-
alysis with appropriate ligands.
Here we describe a detailed study of a chiral silver bis(tri-
methylsilyl)amide-catalyzed asymmetric [3+2] cycloaddition
reaction of Schiff bases of a-amino esters or a-amino-
phosphonates with olefins. The desired reactions proceeded
smoothly to afford the desired cycloadducts in high yields
with high diastereo- and enantioselectivities.[8]
Results and Discussion
Preparation of Silver Bis(trimethylsilyl)amide (AgHMDS)
In 1996, Hitchcock, Lappert, and Pierssens reported the syn-
thesis of AgHMDS from silver isocyanate (AgCNO) and di-
methyltin diACHTUNGTRENNUNG[bis(trimethylsilyl)amide] (Me2SnACHTUNGTERN(NUGN HMDS)2),
and showed that it formed a tetrameric complex in crys-
tals.[9] Since then, however, no report on AgHMDS has ap-
peared that involves catalysis. We anticipated unique cata-
lytic activity of silver amides as mentioned above and tried
to prepare AgHMDS. First, we conducted the preparation
according to the literature method; however, the starting
materials were found to be uncommon. Therefore, we decid-
ed to develop a new preparation method for AgHMDS and
found that AgHMDS can be readily prepared from AgOTf
and LiHMDS (Scheme 2). AgHMDS thus prepared is a col-
orless powder, is fully characterized, and can be stored at
room temperature.[10]
Chem. Asian J. 2011, 6, 2550 – 2559
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www.chemasianj.org
2551

S. Kobayashi et al.
FULL PAPERS
Table 1. Asymmetric [3+2] cycloaddition reaction of glycine Schiff base
1a with methyl acrylate 2a.[a]
Entry (R)- Solvent
T
t
Yield
endo/
exo
ee [%] (endo/
exo)
L
[8C] [h] [%]
1[b]
2[b]
3[b]
4[b]
5[b,c]
6[b,d]
7
8
9
10
11
L1
L2
L3
L4
L4
L4
L4
L4
L4
L4
L4
L4
L4
L4
L4
L4
toluene 30
toluene 30
toluene 30
toluene 30
toluene 30
toluene 30
toluene 30
2
2
2
2
2
2
2
82
90
91
90
92
89
87
72:18 45:52
40:60 17:30
18:82 –:77
4:96 –:84
2:98 –:77
18:82 –:78
9:91 –:79
Table 2. Asymmetric [3+2] cycloaddition of 1 with olefin 2a.[a]
toluene
CH2Cl2
THF
0
0
0
24 37
24 34
24 38
24 40
24 41
72 78
24 78
24 71
24 91
48 76
1:99 –:94
4:96 –:79
10:90 –:88
<1:>99 –:98
20:80 –:91
<1:>99 –:98
8:92 –:95
<1:>99 –:97
1:99 –:98
<1:>99 –:97
Et2O
0
Entry R1
R2
1
3
Yield exo/
ee [%]
(exo)
12
13
tBuOMe
Et2O
0
0
[%]
endo
1
2
3
4
5
6
7
8
4-MeC6H4
H
H
H
H
H
H
H
H
H
H
H
H
H
H
1c 3ca
1d 3da
1e 3ea
1 f 3 fa
1g 3ga
1h 3ha
1i 3ia
1j 3ja
1k 3ka
1l 3la
1m 3ma
1n 3na
1o 3oa
1p 3pa
90
91
93
82
86
88
90
98
92
90
88
97
96
90
78
87
81
71
43
64
70
60
62
36
>99:<1
>99:<1
>99:<1
>99:<1
>99:<1
97:3
>99:<1
>99:<1
>99:<1
>99:<1
>99:<1
94:6
99
99
98
95
90
92
91
96
90
94
82
99
92
98
97
94
90
97
80
88
92
79
82
84
14
Et2O
Et2O
10
0
15[e]
16[f]
2-MeC6H4
4-MeOC6H4
4-FC6H4
4-ClC6H4
4-BrC6H4
4-CF3C6H4
4-NCC6H4
3-pyridyl
2-furyl
2-thiophenyl
1-naphthyl
2-naphthyl
cinnamyl
Ph
Et2O
0
17[f,g] L4
Et2O
0
18[f]
–
Et2O
0
72
6
>99:<1
–
[a] Asymmetric [3+2] cycloaddition of 1a with 2a in the presence of
5 mol% of the catalyst prepared from AgHMDS or AgOTf and
KHMDS, and the chiral phosphine ligand at 0.2m unless otherwise noted.
[b] 10 mol% AgHMDS and the ligand were used. [c] tButyl acrylate (2b)
was used instead of 2a. [d] The Schiff base of glycine tert-butyl ester (1b)
was used instead of 1a. [e] 0.4m. [f] 0.6m. [g] 1 mol% of the catalyst was
used.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
>99:<1
>99:<1
>99:<1
97:3
Me[b] 1q 3qa
iBu[b] 1r 3ra
Bn[b] 1s 3sa
polar solvent, dichloromethane, did not give a promising
result (Table 1, entry 9). On the other hand, ether solvents
gave better selectivities (Table 1, entries 10–12), and use of
diethyl ether (Et2O) was finally found to be the best. Excel-
lent diastereo- and enantioselectivities (endo/exo=<1/>99,
98% ee (exo)) were obtained (Table 1, entry 11). We further
optimized the reaction time and temperature to improve the
yield; however, no conclusive improvement of the reactivity
was observed (Table 1, entries 13 and 14). Finally, we found
that the reactions at higher concentrations were effective in
improving the yield without significant loss of selectivities
(Table 1, entries 15 and 16), and high yield and high stereo-
selectivities were attained in the reaction at 0.6m (Table 1,
entry 16). Under these conditions, 1 mol% of the catalyst
also worked well to afford the desired product (Table 1,
entry 17). Interestingly, AgHMDS itself showed very low
catalytic activity in the absence of the phosphine ligand
(Table 1, entry 18).
With the optimal reaction conditions in hand, we then ex-
amined the scope of the substrates (Table 2). First, several
Schiff bases of the glycine ester were tested in the reaction
of methyl acrylate 2a in the presence of the silver complex.
The [3+2] reactions using the Schiff base with electron-do-
nating groups such as methyl and methoxy groups on the ar-
omatic ring gave almost identical results to the Schiff base
from benzaldehyde, and the desired products were obtained
Ph
Ph
cC6H11
AHCTUNGTRENNUNG
94:6
H
H
H
H
H
H
H
1t 3ta
1u 3ua
1v 3va
1w 3wa
1x 3xa
1y 3ya
1z 3za
>99:<1
>99:<1
>99:<1
>99:<1
>99:<1
>99:<1
>99:<1
AHCTUNGTRENNUNG
CH
CH
CH
G
[a] The reaction of 1 with 2a was conducted in the presence of the Ag
catalyst (5 mol%) at 08C for 24 h at 0.6m unless otherwise noted. [b] l-
Amino acid ester was used.
in high yields with high stereoselectivities (Table 2, en-
tries 1–3). Not only the Schiff bases with electron-donating
groups but also the Schiff bases with electron-withdrawing
groups reacted with 2a to afford the desired products in
good yields with excellent exo selectivities and over 90%
enantiomeric excesses (Table 2, entries 4–8). The Schiff
bases that contained hetero atoms in their aromatic rings
also worked well without significant loss of selectivities
(Table 2, entries 9–11). Bulky aromatics, 1-naphthyl and 2-
naphthyl, did not affect the asymmetric environment, and
good to high exo selectivities and high enantiomeric excess-
es were observed (Table 2, entries 12 and 13). The Schiff
base with an alkenyl substituent also reacted in high yield
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Chiral Silver Amides
Table 3. Asymmetric [3+2] cycloaddition of 1a with olefins 2.[a]
with high diastereo- and enantioselectivities (Table 2,
entry 14). It is noteworthy that the Schiff bases prepared
from other amino acid esters worked well and that the cy-
cloadducts with quaternary carbon centers were obtained
with high stereoselectivities (Table 2, entries 15–17). Next,
we tried to expand our methodology to reactions of Schiff
bases prepared from aliphatic aldehydes. Usually, [3+2] cy-
cloaddition reactions that use aliphatic Schiff bases are rec-
ognized to be difficult because the a-hydrogen is not acidic
enough for deprotonation by amine bases. Furthermore, ali-
phatic imines, especially primary alkyl imines, are easily con-
verted into enamines in the presence of bases, which lead to
undesired side reactions such as self-condensation, and so
on. In fact, successful examples of asymmetric [3+2] cyclo-
additions of aliphatic Schiff bases of glycine esters are quite
limited, and high enantioselectivities were obtained only in
the cases of secondary alkyl Schiff bases.[15] On the other
hand, we envisioned that the current silver amide system
could be applied to aliphatic Schiff bases, because the
system has a unique acid/base character. We tested the reac-
tion of cyclohexylcarboxyaldehyde Schiff base 1t and were
delighted to find that the reaction proceeded well in the
presence of the AgHMDS catalyst to afford the desired cy-
cloadduct in good yield with high enantioselectivity under
the same reaction conditions as for the Schiff base prepared
from benzaldehyde (Table 2, entry 18). The isopropylalde-
hyde Schiff base 1u also reacted with 2a in moderate yield
with high diastereo- and good enantioselectivities (Table 2,
entry 19). We then tried to use the most challenging primary
alkylaldehyde Schiff bases (Table 2, entries 20–24) and
found that the desired reactions also proceeded well to give
the adducts in moderate to good yields with good to high
enantioselectivities. In contrast, the [3+2] cycloaddition of
1y with 2a using typical silver catalyst systems (AgOT-
Entry R3
2
3
Yield [%] exo/endo ee [%]
(exo)
ACHTUNGTRENNUNG
1
2
3
4
5
6
CO[N
CONMe2
COMe
(CH2)2O
E
92
97
82
83
80
96
>99:<1
>99:<1
>99:<1
>99:<1
>99:<1
>99:<1
96
95
97
97
98
99
SO2Ph
P(O)
CN
ACHTUNGERTN(NUNG OEt)2
[a] The reaction of 1a with 2 was conducted in the presence of the Ag
catalyst (5 mol%) at 08C for 24 h in 0.6m.
Asymmetric [3+2] Cycloaddition of Imines of a-
Aminophosphonate with Olefins
Next, we focused on the asymmetric [3+2] cycloaddition of
a Schiff base that bore less acidic a-hydrogen atoms. The
phosphonic analogues of a-aminoesters, a-aminophospho-
nates, are interesting compounds as chiral building blocks
for constructing structures that mimic peptides. However,
application of the [3+2] cycloaddition methodology to a-
aminophosphonate Schiff bases is difficult because the acidi-
ty of their a-hydrogen is not high enough to be deprotonat-
ed.[16] To the best of our knowledge, all previous methods
use more than stoichiometric amounts of bases to conduct
stereoselective [3+2] cycloaddition of Schiff bases of a-ami-
nophosphonates.[17]
First, we applied the AgHMDS–(R)-DTBM-SEGPHOS
catalyst system to the reaction of Schiff bases of a-amino-
phosphonates 4 with acrylates. It was found that the reaction
of 4a with tert-butyl acrylate 2b gave excellent diastereo-
and enantioselectivities in the presence of 3 mol% of the
silver catalyst (Table 4, entry 1). In this reaction, only
1 mol% silver catalyst worked well to afford the desired
product in high yield with high diastereo- and enantioselec-
tivities (Table 4, entry 2). It is noted that the reaction of an
a-aminophosphonate Schiff base proceeded well in the pres-
ence of a catalytic amount of the silver complex. Schiff
bases 4 with electron-donating or electron-withdrawing
groups on their aromatic rings reacted with 2b smoothly to
afford the desired cycloadducts in high yields with high exo
selectivities and enantioselectivities (Table 4, entries 3–7).
Bulkiness of the aromatic group was found to affect the re-
action slightly, and the reaction of 1-naphthyl Schiff base 4g
required further optimal reaction conditions, whereas 2-
naphthyl Schiff base 4e showed similar reactivity to other
aromatic Schiff bases (Table 4, entries 8 and 9). The hetero-
aromatic moiety, 3-pyridyl, also did not affect the results
through some extra coordination to the silver atom (Table 4,
entry 10). The sterically less-hindered alkenyl group also
gave high reactivity and selectivity (Table 4, entry 11). When
the Schiff bases with alkyl substituents, isopropyl, cyclohex-
yl, and isobutyl groups were employed, the reactions also
f+Et3N or 1,8-diazabicycloACTHNUTRGNEUGN[5.4.0]undec-7-ene (DBU),
AgOAc) with (R)-DTBM-SEGPHOS did not proceed at all
under the same reaction conditions. It is worth noting that,
to the best of our knowledge, this is the first successful ex-
ample of asymmetric [3+2] cycloaddition of primary alkyl
Schiff bases.
The current catalyst system was also successfully applied
to asymmetric [3+2] cycloadditions with other olefins 2
(Table 3). Methyl acrylate 2a as well as acryl amides (2c
and 2d) reacted with 1a in high yields with high diastereo-
and enantioselectivities (Table 3, entries 1 and 2). The reac-
tion of methyl vinyl ketone (2e) also gave the desired prod-
uct with high selectivities (Table 3, entry 3). These results in-
dicated that the coordination ability of the carbonyl oxygen
of the olefins did not affect asymmetric environments in the
transition states. Other olefins with electron-withdrawing
groups were also examined, and the olefins that bear sulfo-
nyl, phosphonyl, and cyano groups reacted with 1a to afford
the corresponding pyrrolidine derivatives in high yields with
high selectivities. Thus, the wide scope of both substrates,
Schiff bases, and olefins in this chiral silver amide system is
remarkable. In addition, it is noteworthy that the reactions
proceeded smoothly without addition of any external bases.
Chem. Asian J. 2011, 6, 2550 – 2559
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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2553

S. Kobayashi et al.
FULL PAPERS
Table 4. Asymmetric [3+2] cycloaddition of Schiff bases of a-amino-
phosphonate 4 with 2b.[a]
Table 5. Asymmetric [3+2] cycloaddition of 4a with olefins 2.[a]
Entry R3
2
5
Yield exo/endo ee [%]
Entry R1
R2
4
5
Yield [%] exo/endo ee [%]
(exo)
[%]
ACHTUNGTRENNUNG(exo)
AHCTUNGTRENNUNG
1
2
3
4
5
6
7
CO2Et
CO(N(CH2)2O
CONMe2
COMe
2i
5ai
95
93
97
81
98
85
91
>99:<1
>99:<1
>99:<1
>99:<1
>99:<1
>99:<1
>99:<1
97
99
98
99
99
98
97
G
(CH2)2-) 2c 5ac
1
Ph
Ph
H
H
H
H
H
H
H
H
H
H
H
H
H
H
4a
4a
4b 5bb
4c 5cb
4d 5 db
4e
4 f
4g
4h 5hb
4i
4j
4k 5kb
4l 5lb
4m 5mb
5ab
5ab
94
94
99
91
94
93
91
80
85
74
77
56
73
43
81
80
72
>99:<1
>99:<1
>99:<1
>99:<1
>99:<1
>99:<1
>99:<1
96
96
94
96
97
95
95
2[b]
3
2d 5ad
2e 5ae
2 f 5af
2g 5ag
2h 5ah
4-MeC6H4
4-MeOC6H4
4-FC6H4
4-BrC6H4
4-CF3C6H4
1-naphthyl
2-naphthyl
3-pyridyl
cinnamyl
4[c,e]
5
6
SO2Ph
P(O)
CN
ACHTUNGERTN(NUNG OEt)2
5eb
5 fb
5gb
7
[a] The reaction of 4 with 2b was conducted in the presence of the Ag
catalyst (3 mol%) in toluene at 258C for 2 h in 0.2m unless otherwise
noted.
8[c,f]
9
94:6 >99
>99:<1
97
90
97
82
86
90
98
91
90
10
5ib
5jb
>99:<1
>99:<1
>99:<1
>99:<1
97:3
>99:<1
>99:<1
>99:<1
11[c,f]
12[d,g] iPr
13[d,g] cC6H11
14[d,g] iBu
15[c,h]
16[c,h]
17[c,h]
Ph
Ph
Ph
Me 4n 5nb
iBu 4o 5ob
Bn 4p 5pb
[a] The reaction of 4 with 2b was conducted in the presence of the Ag
catalyst (3 mol%) in toluene at 258C for 2 h at 0.2m unless otherwise
noted. [b] The Ag complex (1 mol%) was used. [c] The Ag complex
(5 mol%) was used. [d] The Ag complex (10 mol%) was used. [e] 20 h.
[f] 4 h. [g] 08C for four days. [h] 15 h.
proceeded to afford the desired pyrrolidine derivatives with
high diastereo- and good to high enantioselectivities
(Table 4, entries 12–14). Moreover, it is worth noting that
Schiff bases prepared from a-alkyl-a-aminophosphonates
also worked well and that the desired cycloadducts with
quaternary carbon centers were obtained in high diastereo-
and enantioselectivities (Table 4, entries 15–17). To the best
of our knowledge, this is the first example of catalytic asym-
metric [3+2] cycloaddition of a-aminophosphonate Schiff
bases with olefins.
Scheme 3. Possible mechanisms for the [3+2] cycloaddition reaction.
Furthermore, we tested the [3+2] cycloaddition with
other olefins 2 (Table 5). Similar to the case of Schiff bases
of glycine ester 1, the reactions of olefins substituted with
carbonyl, sulfonyl, phosphonyl, and cyano groups proceeded
smoothly to afford the desired products in high yields with
high enantioselectivities. These results indicated that the
chiral silver amide catalyst was also effective for the [3+2]
cycloadditions of various Schiff bases of the a-aminophosph-
onate, and the wide substrate scope was confirmed.
followed by an intramolecular Mannich reaction of the
formed enolate with the imine part of the Schiff base. This
mechanism has been supported by experimental or theoreti-
cal calculation in some cases.[18] The other possibility is a
concerted mechanism, in which the 1,3-dipole formed in situ
reacts with the olefin at two positions simultaneously. To
obtain information on the mechanism, we carried out the
[3+2] cycloaddition reactions of the Schiff base of glycine
ester 1 or a-aminophosphonate 4 in the presence of the
chiral silver catalyst (Scheme 4). Interestingly, the reaction
using dimethyl fumarate gave a 1:1 mixture of exo and endo
adducts with high enantioselectivities, and no other diaste-
reomers were observed in the reaction systems, which
means that no epimerization of the stereocenters occurred
[Eqs. (1) and (2)]. In contrast, the reactions with dimethyl
maleate gave single exo isomers with high enantioselectivi-
ties [Eqs. (3) and (4)]. These results clearly indicated that
the current [3+2] cycloaddition reactions proceeded by
Reaction Mechanism
We then investigated the reaction pathways of the present
chiral silver-catalyzed [3+2] cycloadditions. There are two
typical mechanisms for the [3+2] cycloaddition of azome-
thine ylides with olefins (Scheme 3). One is a stepwise
mechanism, which consists of an initial 1,4-addition of the
anion species of the Schiff base to an olefin double bond,
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Chem. Asian J. 2011, 6, 2550 – 2559

Chiral Silver Amides
Scheme 5. Proposed transition states.
Scheme 4. The [3+2] cycloaddition reactions with dimethyl fumarate (2j)
and dimethyl maleate (2k).
means of the concerted mechanism under control of the
silver catalyst. On the basis of the concerted mechanism, we
assumed the transition states of the [3+2] cycloaddition re-
actions (Scheme 5). The azomethine ylide prepared from
the chiral silver amide and the Schiff base interacts with the
olefin at two positions simultaneously in the transition state,
and carbon–carbon bond formation occurred at the same
time. Large steric bulkiness on the phosphine atom might
control the orientation of the olefin substituent, and the azo-
methine ylide would react with the olefin without any signif-
icant chelation control, thereby avoiding large steric repul-
sion between the ligand substituents and the olefin substitu-
ent.
A proposed catalytic cycle for the reaction of Schiff base
1a with 2a is shown in Scheme 6. First, the chiral silver
amide species (A) deprotonates the active a-hydrogen of
the Schiff base to form the azomethine ylide with chiral
silver complex B and free H-HMDS. The silver complex A
further reacts with olefin 2a to form silver amide species C,
which is then protonated by H-HMDS to release the prod-
Scheme 6. Proposed catalytic cycle.
uct 3aa along with regeneration of the silver amide complex
A.
Catalyst Structure
The structure of the chiral silver amide complex was investi-
gated by 31P NMR spectroscopic experiments (Figures 1 and
2). When AgHMDS and DTBM-SEGPHOS were mixed in
[D8]toluene in 1:1 molar ratio, two double doublet peaks
were newly observed (d=0.3 and 2.7 ppm) and accompa-
nied a peak of free DTBM-SEGPHOS (d=À12.3 ppm)
Chem. Asian J. 2011, 6, 2550 – 2559
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2555

S. Kobayashi et al.
FULL PAPERS
It is interesting that in all cases, large amounts of the free
ligand still existed in the reaction solution even after addi-
tion of 1a. This fact indicated that free AgHMDS existed in
the catalyst solution but did not show any significant effects
on the asymmetric reactions (see Table 1, entry 18), and that
significant reaction rate acceleration occurred by the ligand.
Moreover, it was also suggested that the amount of the
actual active chiral silver catalyst in the reaction solutions
was much less than we expected.
At this stage, we assumed that the species A1 is the
AgHMDS–DTBM-SEGPHOS 1:1 complex and that A2 is a
higher aggregation state of A1 (e.g., tetramer).[9] When we
prepared the catalyst species from the AgOTf–DTBM-SEG-
PHOS complex (Figure 2a) and KHMDS, only a peak of
species A1 was observed at d=0.3 ppm (Figure 2b), and
species A2 appeared after one week (Figure 2c). These re-
sults indicated that the species A2 was much more thermo-
dynamically stable than species A1, and the species A1 was
formed under kinetic conditions. To obtain further informa-
tion on the actual AgHMDS species, we conducted many
trials using mass spectrometry analysis and 109Ag NMR spec-
troscopic analysis of the complex, and so on; however, no
useful result was obtained. One reason for these disappoint-
ing results may be the low population of the active catalyst
complex.
Figure 1. 31P NMR spectroscopic study of an AgHMDS–(R)-DTBM-
SEGPHOS complex in [D8]toluene (1). Methods: a) AgHMDS+DTBM-
SEGPHOS (1:1) were mixed in [D8]toluene; b) the sample prepared in
a) was heated at 808C for 3 h; c) AgHMDS+DTBM-SEGPHOS (1:1)
were mixed in [D8]toluene, then 1a was added. L=DTBM-SEGPHOS.
We also examined the relationship between ee value of
the ligand and ee value of the product, which could provide
information on the complex aggregation in the catalyst solu-
tion (NLE study).[19] As a result, we observed an almost per-
fect linear relationship between the ee values (Table 6 and
Table 6. NLE study.[a]
Entry ee value of the ligand [%] Yield [%] exo/endo ee [%] (exo)
1
2
3
4
29
50
77
90
90
92
91
>99:<1
>99:<1
>99:<1
>99:<1
29
50
77
98
>99
[a] The reactions were conducted using 1a and 2a in the presence of the
Ag catalyst (5 mol%) at 08C for 24 h.
Figure 3). This result may indicate that the silver complex
does not form any stable heterooligomeric complexes. The
result of the NLE study may support the hypothesis that the
observed silver species are the AgHMDS–ligand (1:1) com-
plex (A1) and its aggregated form (A2). The species A2
could be deaggregated into A1 and form the active species
in the presence of the glycine Schiff base 1a.
Figure 2. 31P NMR spectroscopic study of an AgHMDS–(R)-DTBM-
SEGPHOS complex in [D8]toluene (2). Methods: a) AgOTf+DTBM-
SEGPHOS (1:1) were mixed in [D8]toluene; b) AgOTf+DTBM-SEG-
PHOS (1:1) were mixed in [D8]toluene, then KHMDS (1 equiv) was
added after 30 min stirring; c) the sample prepared in b) was stored
under Ar for one week at room temperature. L=DTBM-SEGPHOS.
(Figure 1a). We assumed that these two peaks might be de-
rived from two Ag–DTBM-SEGPHOS complexes (species
A1 (d=0.3 ppm) and species A2 (d=2.7 ppm)), on the basis
of observation of 31P, 107Ag or 31P, 109Ag coupling. Interesting-
ly, the peak ratio changed at 808C (Figure 1b). We added
the glycine Schiff base 1a to the complex solution and
found the peaks moved to another position (Figure 1c). The
newly appeared peak might be derived from a reactive Ag–
DTBM-SEGPHOS–1a complex (complex B in Scheme 3).
Conclusion
We have demonstrated successful asymmetric [3+2] cycload-
dition reactions of Schiff bases using a chiral silver amide
catalyst. AgHMDS was easily prepared from AgOTf and
LiHMDS or KHMDS, and a silver complex prepared from
AgHMDS and a chiral phosphine ligand worked as an effi-
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Chiral Silver Amides
H2O (20:1) mixture (1 mL), and the quenched mixture was passed
through a silica-celite-Na2SO4 pad using a solvent mixture of CHCl3 and
methanol (1:1). After concentration under reduced pressure, the residue
was purified by preparative thin-layer chromatography (PTLC) with
hexane/ethyl acetate (3:1) as an eluent to give the desired product 3.
A Typical Procedure for Silver-Catalyzed [3+2] Cycloaddition of Schiff
Bases of a-Aminomethylphosphnates to Vinyl Compounds
Under an Ar atmosphere, a solution of AgHMDS (0.0090 mmol) and
(R)-DTBM-SEGPHOS (0.0090 mmol) in toluene (1.0 mL) or a solution
of AgOTf (0.0090 mmol), (R)-DTBM-SEGPHOS (0.0090 mmol), and
KHMDS (0.0090 mmol) in toluene (1.0 mL) in a flame-dried glass tube
with aluminum foil was stirred for 15 min at room temperature. Schiff
base of a-aminomethylphosphonate
4 (0.30 mmol) and acrylate 2
(0.36 mmol) were added successively, and the reaction mixture was then
stirred at 258C for 2 h. The reaction mixture was quenched with saturat-
ed aqueous NH4Cl (10 mL) and extracted with CH2Cl2 (15 mLꢁ3). The
organic phases were combined and dried over MgSO4. After filtration
and concentration under reduced pressure, the residue was purified by
preparative thin-layer chromatography (PTLC) with EtOAc/hexane (2:1)
as an eluent to give the desired product 5.
Figure 3. Relationship between the ee value of the ligand and the ee
value of the product.
Acknowledgements
cient base catalyst without any additional tertiary amine.
Examination of the ligand structure has revealed that a
large and bulky bidentate phosphine ligand, (R)-DTBM-
SEGPHOS, was effective in forming excellent asymmetric
environments, and a-aminoester Schiff bases including those
derived from aliphatic imines successfully reacted with sev-
eral olefins to afford the corresponding pyrrolidine deriva-
tives in high yields with high exo selectivities and high enan-
tioselectivities. Furthermore, a-aminophosphonate Schiff
bases, which have less acidic hydrogen atoms at the a posi-
tions, also reacted smoothly in the presence of a catalytic
amount of the silver amide complex to give the desired cy-
cloadducts in high stereoselectivities. A mechanistic study
indicated that the [3+2] cycloaddition proceeded by means
of a concerted mechanism, and an NMR spectroscopic study
indicated that complexation of AgHMDS and the bisphos-
phine ligand was not complete and that free AgHMDS,
which did not show any significant activity, existed in the
catalyst solution. Therefore, significant ligand acceleration
occurred in the current reaction system. This is the first ex-
ample of chiral silver amides as catalysts for asymmetric re-
actions.
This work was partially supported by a Grant-in-Aid for Science Re-
search from the Japan Society for the Promotion of Science (JSPS) and
Global COE Program (Chemistry Innovation through Cooperation of
Science and Engineering), the University of Tokyo, MEXT, Japan. We
thank Takasago Int. Co. for supply of (R)-DTBM-SEGPHOS. We also
appreciate the support of Prof. Dr. Kyoko Nozaki and Dr. Makoto Yama-
shita with the 109Ag NMR spectroscopic experiments. We also thank Mr.
Ryuta Takashita for his contribution in the initial stage of this work.
[1] Comprehensive Organic Synthesis (Ed.: B. M. Trost), Pergamon
Press, Oxford, 1991.
[2] Recent reviews, see: a) Lewis Acid Reagents: A Practical Approach
(Ed.: H. Yamamoto), Oxford, New York, 1999; b) Lewis Acids in
Organic Synthesis (Ed.: H. Yamamoto), Wiley-VCH, Weinheim,
2000; c) Acid Catalysis in Modern Organic Synthesis (Eds: H. Yama-
moto, K. Ishihara), Wiley-VCH, Weinheim, 2008.
[3] B. M. Trost, Science 1991, 254, 1471.
[4] For recent reviews of highly functionalized metal acid/base com-
bined catalysts, see: a) G. J. Rowlands, Tetrahedron 2001, 57, 1865;
b) M. Shibasaki, N. Yoshikawa, Chem. Rev. 2002, 102, 2187; c) J.-A.
Ma, D. Cahard, Angew. Chem. 2004, 116, 4666; Angew. Chem. Int.
Ed. 2004, 43, 4566; representative works: d) Y. Ito, M. Sawamura, T.
Hayashi, J. Am. Chem. Soc. 1986, 108, 6405; e) H. Sasai, T. Suzuki,
S. Arai, T. Arai, M. Shibasaki, J. Am. Chem. Soc. 1992, 114, 4418;
f) Y. M. A. Yamada, N. Yoshikawa, H. Sasai, M. Shibasaki, Angew.
Chem. 1997, 109, 1942; Angew. Chem. Int. Ed. Engl. 1997, 36, 1871;
g) B. M. Trost, H. Ito, J. Am. Chem. Soc. 2000, 122, 12003; h) N. Ku-
magai, S. Matsunaga, T. Yoshikawa, T. Ohshima, M. Shibasaki, Org.
Lett. 2001, 3, 1539.
[5] For recent reviews of chiral silver catalysts, see: a) M. Sawamura, Y.
Ito in Catalytic Asymmetric Synthesis, 2nd ed. (Ed.: I. Ojima),
Wiley-VCH, New York, p. 493; b) H. Yamamoto, M. Wadamoto,
Chem. Asian J. 2007, 2, 692; c) A. Yanagisawa, T. Arai, Chem.
Commun. 2008, 1165; d) A. Yanagisawa in Acid Catalysis in Modern
Organic Synthesis, Vol. 2 (Eds.: H. Yamamoto, K. Ishihara), Wiley-
VCH, Weinheim, 2008, p. 987.
Experimental Section
A Typical Procedure for Silver-Catalyzed [3+2] Cycloaddition of Schiff
Bases of a-Aminoglycinate to Vinyl Compounds
Under an Ar atmosphere, a solution of AgHMDS (0.015 mmol) and (R)-
DTBM-SEGPHOS (0.015 mmol) in Et2O (0.3 mL) or
a solution of
AgOTf (0.015 mmol), KHMDS (0.015 mmol), and (R)-DTBM-SEG-
PHOS (10.6 mg, 0.015 mmol) in Et2O (0.3 mL) in a flame-dried glass
tube with aluminum foil was stirred for 30 min at room temperature.
Schiff base of a-aminoglycinate 1 (0.30 mmol) and acrylate 2 (0.36 mmol)
were added successively at 08C, and the mixture was then stirred for 24 h
at the same temperature. The reaction mixture was quenched with THF/
[6] For examples of catalytic asymmetric reactions using chiral Ag
Lewis acids: a) M. Sawamura, H. Hamashima, Y. Ito, J. Org. Chem.
1990, 55, 5935; b) T. Hayashi, Y. Uozumi, A. Yamazaki, M. Sawa-
mura, H. Hamashima, Y. Ito, Tetrahedron Lett. 1991, 32, 2799; c) A.
Yanagisawa, H. Nakashima, A. Ishiba, H. Yamamoto, J. Am. Chem.
Chem. Asian J. 2011, 6, 2550 – 2559
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemasianj.org
2557

S. Kobayashi et al.
FULL PAPERS
Soc. 1996, 118, 4723; d) C. Bianchini, L. Glendenning, Chemtracts:
Inorg. Chem. 1997, 10, 339; e) P. G. Cozzi, E. Tagliavini, A. Umani-
Ronchi, Gazz. Chim. Ital. 1997, 127, 247; f) A. Yanagisawa, A.
Ishiba, H. Nakashima, H. Yamamoto, Synlett 1997, 88; g) A. Yanagi-
sawa, Y. Nakatsuka, H. Nakashima, H. Yamamoto, Synlett 1997,
933; h) A. Yanagisawa, Y. Matsumoto, H. Nakashima, K. Asakawa,
H. Yamamoto, J. Am. Chem. Soc. 1997, 119, 9319; i) D. Ferraris, Y.
Young, T. Dudding, T. Lectka, J. Am. Chem. Soc. 1998, 120, 4548;
j) W. J. Drury, III, D. Ferraris, D. C. Cox, B. Young, T. Lectka, J.
Am. Chem. Soc. 1998, 120, 11006; k) S. Yao, X. Fang, K. A. Jørgen-
sen, Chem. Commun. 1998, 2547; l) S. Yao, M. Johannsen, R. G.
Hazell, K. A. Jørgensen, Angew. Chem. 1998, 110, 3318; Angew.
Chem. Int. Ed. 1998, 37, 3121; m) A. Yanagisawa, H. Kageyama, Y.
Nakatsuka, K. Asakawa, Y. Matsumoto, H. Yamamoto, Angew.
Chem. 1999, 111, 3916; Angew. Chem. Int. Ed. 1999, 38, 3701; n) A.
Yanagisawa, Y. Matsumoto, K. Asakawa, H. Yamamoto, J. Am.
Chem. Soc. 1999, 121, 892; o) Y. Yamashita, H. Ishitani, S. Kobaya-
shi, Can. J. Chem. 2000, 78, 666; p) T.-P. Loh, J.-R. Zhou, Tetrahe-
dron Lett. 2000, 41, 5261; q) M. Shi, W.-S. Sui, Tetrahedron: Asym-
metry 2000, 11, 773; r) M. Ohkouchi, M. Yamaguchi, T. Yamagishi,
Enantiomer 2000, 5, 71; s) M. Ohkouchi, D. Masui, M. Yamaguchi,
T. Yamagishi, J. Mol. Catal. A 2001, 170, 1; t) A. Yanagisawa, H. Na-
kashima, Y. Nakatsuka, A. Ishiba, H. Yamamoto, Bull. Chem. Soc.
Jpn. 2001, 74, 1129; u) A. Yanagisawa, Y. Nakatsuka, K. Asakawa,
H. Kageyama, H. Yamamoto, Synlett 2001, 69; v) A. Yanagisawa, Y.
Nakatsuka, K. Asakawa, M. Wadamoto, H. Kageyama, H. Yamamo-
to, Bull. Chem. Soc. Jpn. 2001, 74, 1477; w) N. Momiyama, H. Yama-
moto, Angew. Chem. 2002, 114, 3112; Angew. Chem. Int. Ed. 2002,
41, 2986; x) N. J. Patmore, C. Hague, J. H. Cotgreave, M. F. Mahon,
C. G. Frost, A. S. Weller, Chem. Eur. J. 2002, 8, 2088; y) N. Momiya-
ma, H. Yamamoto, Org. Lett. 2002, 4, 3579; z) A. Yanagisawa, Y.
Matsumoto, K. Asakawa, H. Yamamoto, Tetrahedron 2002, 58, 8331;
aa) N. Ozawa, M. Wadamoto, K. Ishiara, H. Yamamoto, Synlett
2003, 2219; ab) N. S. Josephsohn, M. L. Snapper, A. H. Hoveyda, J.
Am. Chem. Soc. 2003, 125, 4018; ac) M. Wadamoto, N. Ozawa, A.
Yanagisawa, H. Yamamoto, J. Org. Chem. 2003, 68, 5593; ad) N.
Momiyama, H. Yamamoto, J. Am. Chem. Soc. 2003, 125, 6038;
ae) N. S. Josephsohn, M. L. Snapper, A. H. Hoveyda, J. Am. Chem.
Soc. 2004, 126, 3734; af) N. Momiyama, H. Yamamoto, J. Am.
Chem. Soc. 2004, 126, 5360; ag) Y. Yamamoto, N. Momiyama, H.
Yamamoto, J. Am. Chem. Soc. 2004, 126, 5962; ah) P. Merino, T.
Tejero, Angew. Chem. 2004, 116, 3055; Angew. Chem. Int. Ed. 2004,
43, 2995; ai) N. Momiyama, H. Torii, S. Saito, H. Yamamoto, Proc.
Natl. Acad. Sci. USA 2004, 101, 5374; aj) H. Yamamoto, N. Momiya-
ma, Chem. Commun. 2005, 3514; ak) A. Yanagisawa, T. Touge, T.
Arai, Angew. Chem. 2005, 117, 1570; Angew. Chem. Int. Ed. 2005,
44, 1546; al) N. S. Josephsohn, E. L. Carswell, M. L. Snapper, A. H.
Hoveyda, Org. Lett. 2005, 7, 2711; am) M. Wadamoto, H. Yamamo-
to, J. Am. Chem. Soc. 2005, 127, 14556; an) M. Chen, S. Guo, Y.
Zheng, L. Chen, F. Tang, W. Hua, Heterocycl. Commun. 2005, 11,
285; ao) K. Kundu, M. P. Doyle, Tetrahedron: Asymmetry 2006, 17,
574; ap) L. C. Akullian, M. L. Snapper, A. H. Hoveyda, J. Am.
Chem. Soc. 2006, 128, 6532; aq) E. L. Carswell, M. L. Snapper,
A. H. Hoveyda, Angew. Chem. 2006, 118, 7388; Angew. Chem. Int.
Ed. 2006, 45, 7230; ar) M. Kawasaki, H. Yamamoto, J. Am. Chem.
Soc. 2006, 128, 16482; as) S. Shirakawa, S. Kobayashi, Synlett 2006,
1410; at) A. Yanagisawa, T. Touge, T. Arai, Pure Appl. Chem. 2006,
78, 519; au) L. Jimꢂnez-Gonzꢃlez, S. Garcꢄa-Munoz, M. ꢅlvarez-
Corral, M. Munoz-Dorado, I. Rodrꢄguez-Garcꢄa, Chem. Eur. J. 2006,
12, 8762; av) F. Colombo, R. Annunziata, M. Benaglia, Tetrahedron
Lett. 2007, 48, 2687; aw) R. Umeda, A. Studer, Org. Lett. 2008, 10,
993; ax) M. Kawasaki, P. Li, H. Yamamoto, Angew. Chem. 2008,
120, 3855; Angew. Chem. Int. Ed. 2008, 47, 3795; ay) H. Mandai, K.
Mandai, M. L. Snapper, A. H. Hoveyda, J. Am. Chem. Soc. 2008,
130, 17961; az) T. Ashizawa, T. Yamada, Chem. Lett. 2009, 38, 246;
ba) Z.-L. Yuan, J.-J. Jiang, M. Shi, Tetrahedron 2009, 65, 6001;
bb) A. Yanagisawa, Y. Terajima, K. Sugita, K. Yoshida, Adv. Synth.
Catal. 2009, 351, 1757; bc) M. Naodovic, M. Wadamoto, H. Yama-
moto, Eur. J. Org. Chem. 2009, 5129; bd) M. Wadamoto, M. Nao-
dovic, H. Yamamoto, Eur. J. Org. Chem. 2009, 5132; be) H.-P. Deng,
Y. Wei, M. Shi, Adv. Synth. Catal. 2009, 351, 2897; bf) B.-H. Zheng,
C.-H. Ding, X.-L. Hou, L.-X. Dai, Org. Lett. 2010, 12, 1688.
[7] For asymmetric [3+2] cycloaddition reactions using a combination
of AgX+additional base, see: a) R. Grigg, Tetrahedron: Asymmetry
1995, 6, 2475; b) J. M. Longmire, B. Wang, X. Zhang, J. Am. Chem.
Soc. 2002, 124, 13400; c) C. Chen, X. Li, S. L. Schreiber, J. Am.
Chem. Soc. 2003, 125, 10174; d) T. F. Knçpfel, P. Aschwanden, T.
Ichikawa, T. Watanabe, E. M. Carreira, Angew. Chem. 2004, 116,
6097; Angew. Chem. Int. Ed. 2004, 43, 5971; e) C. Alemparte, G.
Blay, K. A. Jørgensen, Org. Lett. 2005, 7, 4569; f) C. Nꢃjera, M. de
Gracia Retamosa, J. M. Sansano, Org. Lett. 2007, 9, 4025; g) C.
Nꢃjera, M. de Gracia Retamosa, J. M. Sansano, A. de Cꢆzar, F. P.
Cossꢄo, Tetrahedron: Asymmetry 2008, 19, 2913; h) C. Nꢃjera, M. de
Gracia Retamosa, J. Sansano, Angew. Chem. 2008, 120, 6144;
Angew. Chem. Int. Ed. 2008, 47, 6055; i) S.-B. Yu, X.-P. Hu, J. Deng,
D.-Y. Wang, Z.-C. Duan, Z. Zheng, Tetrahedron: Asymmetry 2009,
20, 621; j) C. Nꢃjera, M. de Gracia Retamosa, M. Martꢄn-Rodrꢄguez,
J. M. Sansano, A. de Cꢆzar, F. P. Cossꢄo, Eur. J. Org. Chem. 2009,
5622; k) G. Liang, M.-C. Tong, C.-J. Wang, Adv. Synth. Catal. 2009,
351, 3101; l) Z.-Y. Xue, T.-L. Liu, Z. Lu, H. Huang, H.-Y. Tao, C.-J.
Wang, Chem. Commun. 2010, 46, 1727; m) I. Oura, K. Shimizu, K.
Ogata, S. Fukuzawa, Org. Lett. 2010, 12, 1752; asymmetric reactions
using AgOAc, see: n) R. Stohler, F. Wahl, A. Pfaltz, Synthesis 2005,
1431; o) W. Zeng, Y.-G. Zhou, Org. Lett. 2005, 7, 5055; p) W. Zeng,
G.-Y. Chen, Y.-G. Zhou, Y.-X. Li, J. Am. Chem. Soc. 2007, 129, 750;
q) W. Zeng, Y.-G. Zhou, Tetrahedron Lett. 2007, 48, 4619: r) C.-J.
Wang, Z.-Y. Xue, G. Liang, Z. Lu, Chem. Commun. 2009, 2905;
s) Q.-A. Chen, W. Zeng, D.-W. Wang, Y.-G. Zhou, Synlett 2009,
2236; t) H. Y. Kim, H.-J. Shih, W.-E. Knabe, K. Oh, Angew. Chem.
2009, 121, 7556; Angew. Chem. Int. Ed. 2009, 48, 7420; u) S. Fili-
ppone, E. E. Maroto, A. Martin-Domenech, M. Suarez, N. Martin,
Nat. Chem. 2009, 1, 578; v) Q.-A. Chen, W. Zeng, Y.-G. Zhou, Tetra-
hedron Lett. 2009, 50, 6866.
[8] Preliminary communications: a) Y. Yamashita, X.-X. Guo, R. Taka-
shita, S. Kobayashi, J. Am. Chem. Soc. 2010, 132, 3262; b) Y. Yama-
shita, T. Imaizumi, S. Kobayashi, Angew. Chem. 2011, 123, 4995;
Angew. Chem. Int. Ed. 2011, 50, 4893.
[9] P. B. Hitchcock, M. F. Lappert, L. J.-M. Pierssens, Chem. Commun.
1996, 1189.
[10] Silver catalysts prepared from Ag salts and KOtBu or LiHMDS
have been reported in alkyne cyclization reactions: a) Y. Tamaru,
M. Kimura, S. Tanaka, S. Kure, Z.-i. Yoshida, Bull. Chem. Soc. Jpn.
1994, 67, 2838; b) Y. Koseki, S. Kusano, T. Nagasaka, Tetrahedron
Lett. 1998, 39, 3517.
[11] a) U. Obst, P. Betschmann, C. Lerner, P. Seiler, F. Diederich, Helv.
Chim. Acta 2000, 83, 855; b) C. Alvarez-Ibarra, A. G. Csꢃkꢇ, I.
Lꢈpez, M. L. Quiroga, J. Org. Chem. 1997, 62, 479; c) P. P. Waid,
G. A. Flynn, E. W. Huber, J. S. Sabol, Tetrahedron Lett. 1996, 37,
4091; d) A. Bianco, M. Maggini, G. Scorrano, C. Toniolo, G. Marco-
ni, C. Villani, M. Prato, J. Am. Chem. Soc. 1996, 118, 4072; e) S. A.
Kolodziej, G. V. Nikiforovich, R. Skeean, M. F. Lignon, J. Martinez,
G. R. Marshall, J. Med. Chem. 1995, 38, 137; f) W. H. Pearson, in
Studies in Natural Product Chemistry, Vol. 1 (Ed.: A. Urrahman),
Elsevier, New York, 1998, p. 323; g) P. R. Sebahar, R. M. Williams,
J. Am. Chem. Soc. 2000, 122, 5666; h) D. J. Denhart, D. A. Griffith,
C. H. Heathcock, J. Org. Chem. 1998, 63, 9616; i) L. E. Overman,
J. E. Tellew, J. Org. Chem. 1996, 61, 8338; j) J. Sisko, J. R. Henry,
S. M. Weinreb, J. Org. Chem. 1993, 58, 4945.
[12] For recent reviews on catalytic asymmetric [3+2] cycloaddition reac-
tions, see: a) A. Padwa, W. H. Pearson, Synthetic Applications of
1,3-Dipolar Cycloaddition Chemistry Toward Heterocycles and Natu-
ral Products, Wiley, New York, 2002; b) K. V. Gothelf, K. A. Jørgen-
sen, Chem. Rev. 1998, 98, 863; c) I. Coldham, R. Hofton, Chem. Rev.
2005, 105, 2765; d) G. Pandey, P. Banerjee, S. R. Gadre, Chem. Rev.
2006, 106, 4484; e) H. Pellissier, Tetrahedron 2007, 63, 3235; f) L. M.
Stanley, M. P. Sibi, Chem. Rev. 2008, 108, 2887.
[13] For catalytic asymmetric [3+2] cycloaddition reactions, see: Co:
a) P. Allway, R. Grigg, Tetrahedron Lett. 1991, 32, 5817; Cu: b) S.-I.
2558
www.chemasianj.org
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Asian J. 2011, 6, 2550 – 2559

Chiral Silver Amides
Fukuzawa, H. Oki, Org. Lett. 2008, 10, 1747; c) S. Cabrera, R. G.
Arrayꢃs, B. Martꢉn-Matute, F. P. Cossꢄo, J. C. Carretero, Tetrahedron
2007, 63, 6587; d) T. Llamas, R. G. Arrayꢃs, J. C. Carretero, Synthesis
2007, 950; e) T. Llamas, R. G. Arrayꢃs, J. C. Carretero, Org. Lett.
2006, 8, 1795; f) X.-X. Yan, Q. Peng, Y. Zhang, K. Zhang, W. Hong,
X.-L. Hou, Y.-D. Wu, Angew. Chem. 2006, 118, 2013; Angew. Chem.
Int. Ed. 2006, 45, 1979; g) S. Cabrera, R. G. Arrayꢃs, J. C. Carretero,
J. Am. Chem. Soc. 2005, 127, 16394; h) Y. Oderaotoshi, W. Cheng, S.
Fujitomi, Y. Kasano, S. Minakata, M. Komatsu, Org. Lett. 2003, 5,
5043; i) W. Gao, X. Zhang, M. Raghunath, Org. Lett. 2005, 7, 4241;
j) A. Lꢆpez-Pꢂrez, J. Adrio, J. C. Carretero, J. Am. Chem. Soc. 2008,
130, 10084; k) C.-J. Wang, G. Liang, Z.-Y. Xue, F. Gao, J. Am.
Chem. Soc. 2008, 130, 17250; l) J. Hernꢃndez-Toribio, R. Gꢆmez
Arrayꢃs, B. Martꢄn-Matute, J. C. Carretero, Org. Lett. 2009, 11, 393;
m) A. Lꢆpez-Pꢂrez, J. Adrio, J. C. Carretero, Angew. Chem. 2009,
121, 346; Angew. Chem. Int. Ed. 2009, 48, 340; n) R. Robles-Machꢄn,
M. Gonzꢃlez-Esguevillas, J. Adrio, J. C. Carretero, J. Org. Chem.
2010, 75, 233; o) T. Arai, A. Mishiro, N. Yokoyama, K. Suzuki, H.
Sato, J. Am. Chem. Soc. 2010, 132, 5338. Zn: p) A. S. Gothelf, K. V.
Gothelf, R. G. Hazell, K. A. Jørgensen, Angew. Chem. 2002, 114,
4410; Angew. Chem. Int. Ed. 2002, 41, 4236; q) O. Dogan, H. Koyun-
cu, P. Garner, A. Bulut, W. J. Youngs, M. Panzner, Org. Lett. 2006,
8, 4687; Ni: r) J.-W. Shi, M.-X. Zhao, Z.-Y. Lei, M. Shi, J. Org.
Chem. 2008, 73, 305. Ca: s) S. Saito, T. Tsubogo, S. Kobayashi, J.
Am. Chem. Soc. 2007, 129, 5364; t) T. Tsubogo, S. Saito, K. Seki, Y.
Yamashita, S. Kobayashi, J. Am. Chem. Soc. 2008, 130, 13321; orga-
nocatalyst: u) J. L. Vicario, S. Reboredo, D. Badꢄa, L. Carrillo,
Angew. Chem. 2007, 119, 5260; Angew. Chem. Int. Ed. 2007, 46,
5168; v) I. Ibrahem, R. Rios, J. Vesely, A. Cꢆrdova, Tetrahedron
Lett. 2007, 48, 6252; w) X.-H. Chen, W.-Q. Zhang, L.-Z. Gong, J.
Am. Chem. Soc. 2008, 130, 5652; x) C. Guo, M.-X. Xue, M.-K. Zhu,
L.-Z. Gong, Angew. Chem. 2008, 120, 3462; Angew. Chem. Int. Ed.
2008, 47, 3414; y) Y.-K. Liu, H. Liu, W. Du, L. Yue, Y.-C. Chen,
Chem. Eur. J. 2008, 14, 9873.
[14] For exo selective asymmetric [3+2] cycloadditions of glycine Schiff
bases, see: Refs. [13b,h,i,j,m,n].
[15] For examples of asymmetric [3+2] cycloaddition reactions of ali-
phatic Schiff bases, see: Refs. [7b,e,o], [13b,c,d,j].
[16] For reactions using Schiff bases of a-aminophosphonate, see: a) A.
Dehnel, G. Lavielle, Tetrahedron Lett. 1980, 21, 1315; b) A. Dehnel,
J.-M. Kanabus-Kaminska, Can. J. Chem. 1988, 66, 310; c) J. P.
Genet, J. Uziel, A. M. Touzin, S. Juge, Synthesis 1990, 41; d) D. Y.
Kim, K. H. Suh, S. C. Huh, K. Lee, Synth. Commun. 2001, 31, 3315;
e) H. A. Dondas, Y. Durust, R. Grigg, M. J. Slater, M. A. B. Sarker,
Tetrahedron 2005, 61, 10667; asymmetric reactions, see: f) I. C. Bald-
win, J. M. J. Williams, R. P. Beckett, Tetrahedron: Asymmetry 1995,
6, 679; g) Z. M. Jꢃszay, G. Nꢂmeth, T. S. Pham, I. Pentnehꢃzy, A.
Grꢈn, L. Tçke, Tetrahedron: Asymmetry 2005, 16, 3837.
[17] We have reported the Mannich-type reaction of a-aminophosphate
activated by fluorenylidene, see: S. Kobayashi, R. Yazaki, K. Seki,
Y. Yamashita, Angew. Chem. 2008, 120, 5695; Angew. Chem. Int.
Ed. 2008, 47, 5613.
[18] a) A. Tatsukawa, K. Kawatake, S. Kanemasa, J. M. Rudzinski, J.
Chem. Soc. Perkin Trans. 2 1994, 2525; b) F. Neumann, C. Lambert,
P. von R. Schleyer, J. Am. Chem. Soc. 1998, 120, 3357; c) S. Vivanco,
B. Lecea, A. Arrieta, P. Prieto, I. Morao, A. Linden, F. P. Cossꢄo, J.
Am. Chem. Soc. 2000, 122, 6078; d) A. Zubia, L. Mendoza, S. Vivan-
co, E. Aladaba, T. Carrascal, B. Lecea, A. Arrieta, T. Zimmerman,
F. Vidal-Vana-clocha, F. P. Cossꢄo, Angew. Chem. 2005, 117, 2963;
Angew. Chem. Int. Ed. 2005, 44, 2903.
[19] V. Girard, H. B. Kagan, Angew. Chem. 1998, 110, 3088; Angew.
Chem. Int. Ed. 1998, 37, 2922.
Received: March 9, 2011
Published online: July 20, 2011
Chem. Asian J. 2011, 6, 2550 – 2559
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemasianj.org
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