Chiral thiophosphoramide and thioamide ligands in catalytic asymmetric carbon-carbon bond-formation reactions

Article abstract of DOI:10.1055/s-2006-956486

Metal complexes with organosulfur ligands exist widely in nature. The high polarizability of the electrons on the sulfur atoms is responsible for a variety of structures and the reactivity of metal complexes with sulfur-containing ligands. Organosulfur-containing chiral ligands have various applications in catalytic asymmetric reactions. Our group has been interested in the applications of a series of thiophosphoramide and thioamide ligands in asymmetric carbon-carbon bond-formation reactions. In this account, we describe the synthesis of chiral thiophosphoramide and thioamide ligands and their applications in catalytic asymmetric carbon-carbon bond formation. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-956486

ACCOUNT
19
Chiral Thiophosphoramide and Thioamide Ligands in Catalytic Asymmetric
Carbon–Carbon Bond-Formation Reactions
Catalytic
Asymmetric
C
e
arbon–Carb
n
on Bond-Formatio
Z
n
R
eactions hang, Min Shi*
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
354 Fenglin Rd, Shanghai 200032, P. R. of China
Fax +86(21)64166128; E-mail: mshi@mail.sioc.ac.cn
Received 2 June 2006
tures and the reactivity of the metal complexes with sul-
Abstract: Metal complexes with organosulfur ligands exist widely
fur-containing ligands. These p-accepting ligands will
in nature. The high polarizability of the electrons on the sulfur at-
oms is responsible for a variety of structures and the reactivity of
decrease the electron density on the metal and thus allow
for an increased electron density in the metal–sulfur bond.
metal complexes with sulfur-containing ligands. Organosulfur-con-
taining chiral ligands have various applications in catalytic asym-
metric reactions. Our group has been interested in the applications
of a series of thiophosphoramide and thioamide ligands in asym-
metric carbon–carbon bond-formation reactions. In this account, we
describe the synthesis of chiral thiophosphoramide and thioamide
ligands and their applications in catalytic asymmetric carbon–car-
bon bond formation.
The coordinating ability of sulfur-containing ligands (i.e.
the stability constants of the complexes) increases with di-
pole moment in the order H2S<RSH<R2S and the stability
of the complexes decreases in the order S2–>RS–>R2S.8
The polarizability and the number of lone electron pairs in
the sulfur-containing ligands are the dominant factors in
coordinating ability and the stability of the metal com-
plexes. In contrast to the large number of complexes using
water as a ligand, very few examples have been reported
containing hydrogen sulfide as a ligand. This could be due
to the fact that the primary product can easily react to yield
sulfhydryl or multinuclear complexes with bridging sulfur
ligands.9 The first stable hydrogen sulfide complexes
were reported in 1976.10 Other sulfur-containing ligands,
such as thioethers,11 oxides of sulfur,12 thioureas,13 dithio-
biurets,14 dithiolenes,15 phosphine sulfides,16 amino-
substituted phosphine sulfides,17 sulfur-containing
oxazolines18 and polysulfides19 are widely utilized in or-
ganic reactions. Among the various sulfur-containing
ligands of interest today, using chiral thiophosphoramides
as ligands in catalytic asymmetric carbon–carbon bond-
formation reactions should be considered. Thiophos-
phoramidates were first utilized as chiral ligands by Soai20
on the basis of his report on the enantioselective synthesis
of chiral dialkyl phosphoramides by the alkylation of
phosphinoyl-imines.21 Since then, more chiral thiophos-
phoramidate ligands have been synthesized and utilized as
1
Introduction
2
3
Synthesis of Chiral Organosulfur-Containing Ligands
Applications in Carbon–Carbon Bond-Formation Reactions
Conjugate Addition of Organozinc Reagents to Enones
Addition of Diethylzinc to Imines
Additon of Diethylzinc to Aldehydes
Addition of Allylic Stannane to Aldehydes
Other Applications
3.1
3.2
3.3
3.4
3.5
4
Conclusion
Key words: organosulfur-containing ligands, thiophosphoramide,
thioamide, asymmetric carbon–carbon bond formation
1
Introduction
Some of the most ubiquitous and diverse metal-containing
structures in biology are iron–sulfur clusters.1 Since the
early 1960s iron–sulfur complexes have been known for
their role in electron transfer, most notably in ferredoxins,
mitochondrial electron transport chains, and photosynthe-
sis.2–4The high affinity of metals for sulfur is clearly dem-
onstrated by the enormous variety of metal–sulfide
minerals that exist in nature.5 Qualitatively this might be
understood using Pearson’s concept of hard and soft acids
and bases.6 However, it is better described by the cova-
lence of the metal–sulfur bond, particularly with the ‘soft’
metals. In contrast to oxygen and nitrogen as donor atoms,
sulfur has low lying, unoccupied 3d-orbitals available.
This influence might be overestimated by molecular orbit-
al calculations reported in the literature.7 However, it has
to be assumed that the high polarizability of the electrons
on the sulfur atoms is responsible for the variety of struc-
R2
R1
Chiral catalyst
Ti(OiPr)4
*
R22Zn
+
R1CHO
OH
up to >98% yield, >98% ee
Chiral catalyst
Me Me
Me
Ph
R3
R3
HO
HN
P
S
OH
R4
NH
S P OEt
(1S, 2R)-1a–c
OEt
a: R3 = OMe
b: R3 = OEt
c: R3 = Me
2a–b
a: R4 = H
b: R4 = Cl
SYNLETT 2007, No. 1, pp 0019–0030
0
4.
0
1.
2
0
0
7
Advanced online publication: 20.12.2006
DOI: 10.1055/s-2006-956486; Art ID: A42806ST
© Georg Thieme Verlag Stuttgart · New York
Scheme 1

20
W. Zhang, M. Shi
ACCOUNT
catalysts for the addition of dialkylzincs to aldehydes in
the presence of titanium(IV) isopropoxide (Scheme 1).22
Additionally, our group has synthesized a series of thio-
phosphoramides in order to examine their use in asym-
metric reactions. Herein, we summarize our efforts in the
synthesis and applications of this series of thiophosphor-
amide and thioamide ligands in asymmetric carbon–
carbon bond-formation reactions.
1) BuLi, THF,
–40 °C, 30 min
S
NH2
N
H
R1
N
P
R1
2) R12P(S)Cl,
–40 °C, r.t.
R2
N
R3
R2
R3
R2
R3
R3
H
Yield
95%
R2
H
R1
(R)-BINAM
H
H
Me
L1
L2
H
Et
(R)-3
(R)-4
Me
Ph
H
Et
H
90%
92%
93%
51%
88%
Me
Me
2
Synthesis of Chiral Organosulfur-Contain-
ing Ligands
H
L3
L4
L5
L6
H
Ph
Et
Me
H
Ph
Me
H
The chiral binaphthylthiophosphoramide ligands L1–L7
were synthesized from (R)-1,1¢-binaphthyl-2,2¢-diamine
OEt
(BIMAM),23
(R)-N2-ethyl-1,1¢-binaphthalenyl-2,2¢-di-
OEt
H
Et
97%
L7
amine (3) and (R)-N2¢,N2¢-dimethyl-1,1¢-binaphthalenyl-
2,2¢-diamine (4) in very high yields via the lithiation of
relevant diamines with butyllithium and then phosphory-
lation with dialkyl-, dialkoxyl- or diarylthiophosphoryl
chloride (Scheme 2). Synthesis of the C2-symmetric chiral
phosphoramide from BINAM was unsuccessful. Howev-
er, similar phosphoramide ligands L8–L11 synthesized
from (1R,2R)-(–)-1,2-diaminocyclohexane (5) and
(1S,2S)-(–)-1,2-diphenylethylenediamine24 (6) were ob-
tained in good yields in the presence of diisopropyl-
ethylamine or triethylamine in dichloromethane or
butyllithium in tetrahydrofuran, respectively (Scheme 3).
Chiral C1-symmetric diaminothiophosphoramide ligands
L12–L15 were obtained from (1R,2R)-(–)-1,2-diami-
nocyclohexane (5) and (1R,2R)-(+)-1,2-diphenylethyl-
enediamine (6) through similar methods as those
described above (Scheme 4). N-Substituted dimethyl-
Scheme 2
thiophosphoramide ligand L16 was prepared from
(1R,2R)-(–)-N-(2-aminocyclohexyl)acetamide (9), after
reduction of (1R,2R)-(–)-N-(2-aminocyclohexyl)-acet-
amide (8) using lithium aluminium hydride (LAH) in
tetrahydrofuran (Scheme 5).25
The unsubstituted amino group in L12 was easily modi-
fied to give a series of chiral thiophosphoramide ligands
through one-step reactions. Chiral imino-thiophosphor-
amide ligands L17–L29 were readily synthesized in mod-
erate to good yields by reaction of L12 with various
arylaldehydes in ethanol either at room temperature or un-
der reflux (for sterically bulky arylaldehydes) for four to
five hours (Scheme 6).
Biographical Sketches
Wen Zhang was born in Key Laboratory of Organo- concerned with the synthe-
1978 in Hubei, China and metallic Chemistry, Shang- sis of chiral sulfur and phos-
graduated from Wuhan Uni- hai Institute of Organic phine ligands and their
versity in 2001. She is cur- Chemistry (SIOC) under the applications in the asym-
rently in the final stage of supervision of Professor metric addition of diethyl-
her PhD degree in the State Min Shi. Her research is zinc to enones and imines.
Dr. Min Shi was born in search experience was with 1996–1998. He is currently
1963 in Shanghai, China. Prof. Kenneth M. Nicholas a group leader in the State
He received his BS in 1984 at the University of Oklaho- Key Laboratory of Organo-
from the Institute of Chemi- ma (1995–1996). He then metallic Chemistry, Shang-
cal Engineering of East Chi- worked as an ERATO Re- hai Institute of Organic
na and his PhD in 1991 from searcher in the Japan Sci- Chemistry (SIOC).
Osaka University, Japan. ence
and
Technology
His first postdoctoral re- Corporation (JST) from
Synlett 2007, No. 1, 19–30 © Thieme Stuttgart · New York

ACCOUNT
Catalytic Asymmetric Carbon–Carbon Bond-Formation Reactions
21
NH·HCI
S
H
N
N
PPh2
S
Me
OEt
EtOH, H2O
BuLi, THF, –40 °C, 30 min
(1R,2R)-(–)-5
Me
(R)-BINAM
H
N
∆
PPh2
N
H
Ph2P(S)Cl, –40 °C, r.t.
7
NH2
S
NH2
LiAlH4, THF
reflux, 4 h
NH2
NH PPh2
S
Ph2P(S)Cl
NHEt
NHAc
iPr2NEt, CH2Cl2, 0 °C, 6 h
8
9: 96% yield
NH2
NH
PPh
2
L8: 92% yield
S
(1R,2R)-(–)-5
NH PMe2
1) BuLi, THF, 0 °C, 30 min
2) Me2P(S)Cl, 0 °C to r.t.
S
NH P(OEt)2
NHEt
(EtO)2P(S)Cl
S
(1R,2R)-(–)-5
iPr2NEt, CH2Cl2, 0 °C, 6 h
L16: 45% yield
P(OEt)2
NH
Scheme 5
L9: 96% yield
S
S
Ph
Ph
NH P(OiPr)2
NH P
(iPrO)2P(S)Cl
ArCHO, EtOH, reflux
or 2-HOArCHO, EtOH, r.t.
L12
(1R,2R)-(–)-5
S
BuLi, THF, –40 °C, 6 h
NH P(OiPr)2
N
Ar
L10: 86% yield
L23: Ar = 2-HOC6H4 (75%)
L24: Ar = 5-tBu-2-HOC6H3 (62%)
L25: Ar = 3,5-tBu2-2-HOC6H2 (51%)
L26: Ar = 3,5-Cl2-2-HOC6H2 (80%)
L27: Ar = 5-Br-2-HOC6H3 (54%)
L28: Ar = 2-HO-1-naphthyl (57%)
L29: Ar = 6-Me-2-HO-1-naphthyl (52%)
L17: Ar = Ph (62%)
Ph
Ph
Ph
Ph
Ph2P(S)Cl
L18: Ar = 2,3-Cl2C6H3 (60%)
L19: Ar = 2,6-Cl2C6H3 (60%)
L20: Ar = 2-furyl (66%)
L21: Ar = 1-naphthyl (55%)
L22: Ar = 2-pyridyl (58%)
S
S
Et3N, CH2Cl2, 0 °C, 6 h
NH PPh2
Ph2P HN
NH2
H2N
L11: 95% yield
(1S,2S)-(–)-6
Scheme 3
Scheme 6
S
H
N
S
NH PPh2
O
PPh2
1) BuLi, THF, 0 °C, 30 min
2) Ph2P(S)Cl, 0 °C, r.t.
(1R,2R)-(–)-5
Et3N, DMAP
RSO2Cl, CH2Cl2, 0 °C, 12 h
NH2
L12
NH S
O
R
L12: 61% yield
L30: R = 4-tolyl (72%)
L31: R = 4-NO2C6H4 (70%)
L32: R = 2-NO2C6H4 (65%)
L33: R = Me (80%)
S
H
N
PPh2
K2CO3, MeCN, r.t.
EtBr, 24 h
L12
NHEt
L13: 55% yield
S
H
L34: R =
(76%)
N
PPh2
NaBH4, HCHO, r.t.
THF, H2SO4, 3 h
O
NMe2
S
L14: 35% yield
Ph
Ph
NH PPh2
1) BuLi, THF, –40 °C
(1R,2R)-(+)-6
2) Ph2P(S)Cl, –40 °C to r.t.
NH2
S
H
Ph
Ph
N
1) BuLi, THF, 0 °C, 30 min
PPh2
S
(1R,2R)-(+)-6
NHPPh2
Ph
Ph
2) Ph2P(S)Cl, 0 °C to r.t.
3) EtBr, K2CO3, MeCN, r.t.
Et3N, DMAP
NHEt
O
NH S R
O
RSO2Cl, CH2Cl2
0 °C, 12 h
L35: R = 4-tolyl (85%)
L36: R = Me (83%)
L15: 30% yield
Scheme 4
Scheme 7
Moreover, chiral sulfonamide-thiophosphoramide ligands
L30–L36 were readily synthesized from the reaction of
L12 and (1R,2R)-(+)-6 with various sulfonyl chlorides in
the presence of triethylamine and a catalytic amount of 4-
(N,N-dimethylamino)pyridine. Moderate to good yields
were obtained in 12 hours in dichloromethane at 0 °C
(Scheme 7).26
Synlett 2007, No. 1, 19–30 © Thieme Stuttgart · New York

22
W. Zhang, M. Shi
ACCOUNT
The axially chiral thioamide ligands L37–L41 were readi- an efficient and highly enantioselective functionalization
ly synthesized in moderate yields from the reaction of (S)- protocol of not only six- and seven-membered cyclic
BINAM with arylaldehydes or acyl chlorides and phos- enones, but also cyclopentenone, acyclic aromatic enones
phorus pentasulfide (P2S5). This presumably coordinates and aliphatic enones.30 Chiral binaphthylthiophosphor-
to the metal center by interaction with either the sulfur and amide ligand L2 proved to be the best ligand in the asym-
nitrogen atom or with two sulfur atoms in the catalytic metric addition reaction of a diethylzinc reagent to
asymmetric carbon–carbon bond formation (Scheme 8).27
enones. This gave 75–93% yields with 97–98% ee for
five-, six- and seven-membered cyclic enones using
Cu(MeCN)4BF4 as a precursor in toluene (Table 1).30a
3
Applications in Carbon–Carbon Bond-
Formation Reactions
Table 1 Asymmetric 1,4-Addition Reaction of Enones with
Diethylzinc Catalyzed by Cu(MeCN)4BF4 and Chiral Ligand L2
under Optimal Conditions
3.1
Conjugate Addition of Organozinc Reagents
to Enones
O
O
Cu(MeCN)4BF4 (3 mol%), L2 (6 mol%)
3.1.1 Utilization of Thiophosphoramide and Thio-
amide Ligands in the Addition of Organozinc
Reagents to Enones
Et2Zn (1.5 equiv), toluene
*
n
n
11: n = 1
13: n = 2
15: n = 0
12: n = 1
14: n = 2
16: n = 0
The conjugate addition of various organometallic re-
agents to a,b-unsaturated carbonyl compounds is an im-
portant process in catalytic enantioselective carbon– Entry
n
Temp
(°C)
Time
(h)
Yield
(%)a
ee
Configc
(%)b
carbon bond-forming reactions.28 A critical aspect of
these investigations is the utilization of such asymmetric
1
1
2
0
0
20
0
0.5
0.5
0.5
95
93
75
97
R
R
R
methods in the total synthesis of biologically active mole-
cules.29 We have explored the catalytic enantioselective
2
97
conjugate addition of dialkylzinc or diphenylzinc to
enones with our organosulfur-containing ligands. We
found that these organosulfur-containing ligands provide
3
98
a Isolated yield.
b Determined by GC.
c Determined by the sign of the specific rotation.
1) PhCOCl or
MeCOCl, Et3N, THF
NHEt
S
NHEt
NH2
Chiral ligands L2 and L4 were also used in the addition
reaction of diethylzinc to acyclic aromatic and aliphatic
enones (Table 2). The enantioselectivities and yields were
very high for acyclic aromatic enones and these reactions
were complete within ten minutes. In the case of acyclic
aliphatic enones, the yields were 82–92% with 80–93% ee
within three hours.
2) P2S5, pyridine, 120 °C
NH C R
(S)-3
L37: R = Ph, 59% yield
L38: R = Me, 44% yield
1) PhCHO, NaBH4,
H2SO4, THF, r.t.
NHBn
S
NHAc
NH2
Organozinc compounds represent ideal reagents for cop-
per-catalyzed enantioselective Michael addition reactions
because of their low reactivity towards the substrate in the
absence of a copper catalyst. Diethylzinc is nearly always
the alkylating agent used in asymmetric conjugate addi-
tion reactions of dialkylzinc reagents to enones catalyzed
by copper salts. Dimethylzinc and diphenylzinc have sel-
dom been used, as they are much less reactive and gener-
ally need longer reaction times for the asymmetric
Michael addition reaction.31 In order to clarify the scope
and limitations of organozinc reagents in our copper(I)–
thiophosphoramide ligand system. We examined the
asymmetric conjugate addition reaction of dimethylzinc
and diphenylzinc to 2-cyclohexen-1-one (11) in the pres-
ence of L2 or L4 under our optimized conditions. The re-
sults are shown in Table 3. The relatively less reactive
dimethylzinc and diphenylzinc can be employed in the
asymmetric conjugate addition of 11 efficiently with ap-
preciable asymmetric induction in our catalytic system.
Using L2 or L4 as the chiral ligand, transformation with
2) P2S5, pyridine, 120 °C
NH C Me
(S)-10
L39: 69% yield
NHBn
1) PhCHO, NaBH4, H2SO4, THF, r.t.
S
NH C Ph
2) NaOH, EtOH, reflux
3) PhCOCl, Et3N, THF
4) P2S5, pyridine, 120 °C
L40: 62% yield
S
NH C Ph
1) PhCOCl, Et3N, THF
S
(S)-BINAM
2) P2S5, pyridine, 120 °C
NH
C
Ph
L41: 68% yield
Scheme 8
Synlett 2007, No. 1, 19–30 © Thieme Stuttgart · New York

ACCOUNT
Catalytic Asymmetric Carbon–Carbon Bond-Formation Reactions
23
Table 2 Asymmetric 1,4-Addition Reaction of Acyclic Enones with
Diethylzinc Catalyzed by Cu(MeCN)4BF4 and Chiral Ligands L2 and
L4 under Optimal Conditions
better than results previously reported in the literature32
(Table 3, entries 5 and 6).
Chiral sulfonamide-thiophosphoramide ligands L30–L36
were also utilized as chiral ligands in the
Cu(MeCN)4ClO4-promoted catalytic asymmetric addition
of diethylzinc to cyclic enones. Using ligand L30 and lith-
ium chloride as an additive, up to 90% ee was realized at
room temperature (25 °C) within half an hour for a six-
membered cyclic enone (Scheme 9).30b In the absence of
lithium chloride, 62% ee was achieved under identical
conditions.30b The improvement on chiral induction with
the addition of lithium chloride may be due to the fact that
lithium can coordinate to the oxygen atom in the sulfona-
mide ligand L30, leading to a rigid transition state that im-
proves enantioselectivity. However, this additive is not
always beneficial when used with other phosphoramide
ligands. When cyclopentenone and cycloheptenone were
used, only moderate enantioselectivities were achieved,
presumably due to the fact that sterically rigid or flexible
cyclic enones can not join perfectly into the chiral pockets
derived from these sulfonamide-thiophosphoramide
ligands.
Cu(MeCN)4BF4 (3 mol%),
L (6 mol%)
O
O
R1
R2
R1
R2
*
Et2Zn (1.5 equiv), toluene,
20 °C, 10 min or 3 h
17
18
Entry R1
R2
Product Ligand Yield ee
(%)a (%)b
1
2
Ph
Ph
18a
18b
18c
L4
L4
L4
L4
L4
L4
L2
L2
L2
L2
98
98
99
98
97
97
89
82
92
92
96
96
96
96
95
97
93
90
85
80
1-naphthyl
Ph
Ph
3
p-BrC6H4
4
Ph
p-MeOC6H4 18d
5
p-BrC6H4
Ph
18e
18f
18g
18h
18i
6
p-MeOC6H4 Ph
7c
8c
9c
10c
Me
n-Bu
Me
i-Pr
i-Bu
i-Bu
n-Bu
n-Bu
O
O
18j
Cu(MeCN)4ClO4 (3 mol%),
L30 (6 mol%), LiCl (10 mol%)
(S)
a Isolated yield.
b Determined by chiral GC.
Et2Zn (2.0 equiv), Et2O, 25 °C, 0.5 h
n
n
c Diethylzinc was first added into the reaction mixture before the ad-
dition of the corresponding enones.
11: n = 1
13: n = 2
15: n = 0
12: 95% yield, 90% ee
14: 95% yield, 73% ee
16: 64% yield, 47% ee
Table 3 Asymmetric 1,4-Addition Reaction of 2-Cyclohexen-2-one
with R2Zn Catalyzed by Cu(MeCN)4BF4 and Chiral Ligands
Scheme 9
O
O
In the presence of a catalytic amount of chiral imino-thio-
phosphoramide ligands L17–L29 (6 mol%) and copper(I)
salt (3 mol%), the asymmetric addition of diethylzinc to
a,b-unsaturated carbonyl compounds could be achieved
in good yields and moderate ee (up to 75% ee using L17
as ligand) at –20 °C in toluene (Scheme 10).30c
Cu(MeCN)4BF4 (3 mol%), L (6 mol%)
R2Zn (1.5 equiv), toluene
*
R
11
19: R = Me
20: R = Ph
Entry Ligand R
Temp Time Yield ee
Configc
(°C)
(h)
(%)a
(%)b
O
O
1
2
3
4
5
6
L2
L2
L4
L4
L2
L4
Me
Me
Me
Me
Ph
0
6
77
85
87
79
85
89
77
R
R
R
R
R
R
Cu(MeCN)4ClO4 (3 mol%), L17 (6 mol%)
(S)
Et2Zn (2.0 equiv), toluene, –20 °C, 6 h
20
0
4
71
n
n
11: n = 1
13: n = 2
15: n = 0
12: 97% yield, 75% ee
14: 96% yield, 52% ee
16: 71% yield, 22% ee
6
73
20
0
4
70
Scheme 10
8
97
Ph
0
8
98
The axially chiral thioamide ligands L37–L41 have also
been widely used in the asymmetric addition of diethyl-
zinc to 2-cyclohexen-1-one (11) and various chalcone de-
rivatives 17 to achieve moderate to good yields and ee
values (Schemes 11 and 12).30d
a Isolated yield.
b Determined by chiral HPLC or GC.
c Determined by the sign of the specific rotation.
dimethylzinc gave the desired product in 70–77% yields
with 79–87% ee within four to six hours (Table 3, entries
1–4). Using diphenylzinc in the presence of L2 or L4, the
reaction was more sluggish, but still gave the desired
product in almost quantitative yields with up to 89% ee,
It should be noted that all the chiral thiophosphoramide
and thioamide ligands utilized in the addition of orga-
nozinc reagents to enones are easily available, quite stable
and recoverable. They can be recovered by column
Synlett 2007, No. 1, 19–30 © Thieme Stuttgart · New York

24
W. Zhang, M. Shi
ACCOUNT
O
ligand L42 showed no enantioselectivity in this conjugate
addition reaction under the same conditions
(Scheme 14).36 This may be due to the fact that the oxygen
atom is a harder ligand than the sulfur atom and can not
smoothly coordinate to a softer metal center, such as the
copper(I) center, according to the soft–hard acid and base
theory.37 On the other hand, according to this theory, sul-
fur and selenium atoms are thought to have great affinities
for copper(I) compounds. We therefore believe that chiral
ligand L43 should have similar catalytic abilities to ligand
L4. As can be seen from Scheme 14, when using L43 as a
chiral ligand under these optimal reaction conditions, 95%
yield and 90% ee were also obtained within 20 minutes at
room temperature (20 °C), very similar results to those
seen in the conjugate addition of diethylzinc to enones us-
ing L4 as the chiral ligand.
O
Cu(MeCN)4ClO4 (3 mol%), L37–L41
(6 mol%)
(S)
Et2Zn (1.5 equiv), toluene, 10 °C, 9 h
11
12
L37: 96% yield, 28% ee
L38: 85% yield, 5% ee
L41: 15% yield, 4% ee
Scheme 11
O
Et
O
Cu(I) (3 mol%), L37–L41 (6 mol%)
Ar'
Ar
Ar
Ar'
*
Et2Zn (1.5 equiv), toluene, 10 °C, 48 h
17
18: 25–47% yield,
51–73% ee
Scheme 12
X
chromatography and reused in similar addition reactions
without loss of yield and enantioselectivity.
H
Ph
N
P
Ph
NHEt
L42: X = O
L43: X = Se
3.1.2 Mechanistic Studies
O
O
According to previous literature,33 the proposed pathway
for the catalytic asymmetric conjugate addition is as
shown in Scheme 13. The mechanism of the reaction calls
for the transfer of an alkyl group from zinc to a chiral cop-
per complex, which is subsequently capable of delivering
the alkyl group to the enone with enantioselectivity.
Cu(MeCN)4BF4 (3 mol%), L (6 mol%)
Et2Zn (1.5 equiv), toluene , 20 °C, 20 min
*
12
11
L42: 64% yield, 0% ee
L43: 95% yield, 90% ee
Scheme 14
ZnR2
In order to better understand the coordination of the thio-
phosphoramide ligands to copper(I), the 31P NMR spectra
measurements of ligands L2, L4 and L7 were carried out
in the absence and presence of the copper(I) salt. The ap-
parent changes in chemical shift were observed by com-
paring the corresponding 31P NMR spectra of chiral
ligands L2, L4 and L7 with those run in the presence of
Cu(MeCN)4BF4 (1:1 mixture) in deutero-chloroform at
room temperature. In the absence of Cu(MeCN)4BF4, the
phosphorus signal of L2, L4 and L7 appeared at 56.68
ppm, 53.28 ppm and 66.57 ppm, respectively. In the pres-
ence of Cu(MeCN)4BF4, there was a downfield shift of the
phosphorus signal to 62.37 ppm and 55.52 ppm for L2 and
L4, respectively and an upfield shift to 64.99 ppm for L7.
However, for L42, where the phosphorus atom is connect-
ed to oxygen, no chemical shift was observed under simi-
lar conditions. These results suggest that the sulfur atom
on the thiophosphoramide is probably coordinated to the
copper(I) metal center.
OZnR
L
L
L
L
Cu
Cu
RZnX
+
*
*
X
R
R
H+
O
O
L
O
Cu
*
L
R
XZn
R
R
Scheme 13
It is well known that sulfur atoms can strongly coordinate
to late transition metals.34 For example, copper(I) com-
pounds have a greater affinity for soft ligands (olefins,
sulfur, phosphorus and selenium atoms).35 In order to fur-
ther verify this speculation, we synthesized diphenylphos-
phoramide ligand L42 and diphenylselenophosphoramide
ligand L43 from (R)-BINAM using the same method as
described above and applied them in the asymmetric con-
jugate addition reaction of diethylzinc to 2-cyclohexen-1-
one (11) (Scheme 14). It was found that the sulfur atom
bonded to the phosphorus atom was crucial in order for
the catalytic asymmetric reaction to be effective because
the corresponding axially chiral diphenylphosphoramide
Besides the sulfur atom, another precoordinative atom in
our chiral thiophosphoramide ligand system is the nitro-
gen atom in ArNR2R3. 13C NMR studies of the L4/
Cu(MeCN)4BF4 complex (1:1 mixture) in deutero-chloro-
form at room temperature were carried out. In the absence
of Cu(MeCN)4BF4, the carbon signals of the two carbons
in the ethyl group of L4 appeared at 38.31 ppm and 15.00
ppm, but the two corresponding carbon signals appeared
Synlett 2007, No. 1, 19–30 © Thieme Stuttgart · New York

ACCOUNT
Catalytic Asymmetric Carbon–Carbon Bond-Formation Reactions
25
R
at 40.92 ppm and 14.88 ppm in the presence of
Cu(MeCN)4BF4. Another new carbon signal was also ob-
served at 1.88 ppm, which was attributed to the carbon of
the methyl group in acetonitrile. These results suggest that
Cu(MeCN)4BF4 could potentially be coordinated by both
S and N atoms in the thiophosphoramide ligands, al-
though at the present stage, we do not have a crystal
structure of this chiral copper(I)–ligand complex.
Zn
O
N
PR2
S
*
Cu
R
Figure 1
Noyori and Kitamura have reported that using a mixture
of copper cyanide and N-benzylbenzenesulfonamide as
additive catalyzed the conjugate addition of dialkylzincs
or diarylzincs to enones to give the desired products in
nearly quantitative yields with high efficiency.38 They
found that N-monosubstituted sulfonamides worked
much better than N-unsubstituted compounds, but a bulky
group on the nitrogen atom considerably lowered the re-
action rate. Moreover, N,N-dibenzylbenzenesulfonamide
was totally ineffective. In their proposed catalytic cycle,
they suggested that a bimetallic catalytic cycle accelerated
the reaction and the acidic proton in N-benzylbenzene-
sulfonamide played a significant role in their catalytic sys-
tem. In order to verify the postulation, we synthesized the
ligand L44 from N2,N2¢-dimethyl[1,1¢]binaphthalenyl-
2,2¢-diamine23 using the same method as described above
and applied it in the same addition reaction of diethylzinc
to 2-cyclohexen-1-one (11) (Scheme 15). Under these
optimal reaction conditions, chiral ligand L44 showed no
asymmetric induction effect for the addition of diethyl-
zinc to cyclohexenone (<2% ee), although the reaction
was complete after 30 minutes at room temperature.
The study of nonlinear effects in asymmetric catalysis has
become an important mechanistic tool.39 The enantiomer-
ic excess observed in the product can be linearly propor-
tional to the enantiomeric excess of the catalyst or have a
non-linear relationship which can be either positive
(asymmetric amplification) or negative (asymmetric de-
pletion) according to Kagan’s models.40 We next exam-
ined the relationship between the enantiomeric excess of
the product and that of the ligand. A clear linear effect was
observed in our reaction system. Such a linear correlation
between product ee and ligand ee indicates that the active
species was a monomeric copper(I) complex bearing a
single chiral ligand [copper(I)–ligand, 1:1]. These results
suggest that our thiophosphoramide ligand system in the
copper(I)-promoted conjugate addition reaction was a sin-
gle S,N-bidentate ligand to copper(I) combined with a bi-
metallic catalytic cycle.
Mechanistic studies on the chiral sulfonamide-thiophos-
phoramide ligands L30–L36 to the copper center using 1H
NMR, 31P NMR and 13C NMR spectroscopic experiments
also indicated this type of ligand to be an S,O-bidentate
ligand. In addition, the linear relationship between ligand
ee and product ee revealed that the active species was a
monomeric copper(I) complex bearing a single ligand,
similar to the binaphthylthiophosphoramide ligands in our
reaction system.
Me S
Me
N
P
Me
NHMe
L44
O
O
3.2
Addition Reaction of Diethylzinc to Imines
Cu(MeCN)4BF4 (3 mol%), L44 (6 mol%)
*
Et2Zn (2.0 equiv), toluene, 20 °C, 30 min
3.2.1 Addition Reaction of Diethylzinc to
Et
12
11
N-Sulfonylimines
96% yield, <2% ee
The efficient and catalytic asymmetric preparation of
amines is one of the most promising methodologies in ho-
mogeneous catalysis.41 Enantioselective addition of orga-
nometallic reagents to the C=N of imines is a convenient
route to obtaining optically active amines.42 This ap-
proach maintains good enantioselectivity and has been
used in chiral amine ligand-catalyzed asymmetric addi-
tion of alkyllithium,43 chiral aminoalcohol ligands,44 cop-
per-amidophosphines,45 zirconium-peptide-based chiral
ligands,46 chiral allylpalladium-catalyzed allylation by
allylstannanes47 and rhodium-monophosphine-catalyzed
arylation by arylstannanes.48
Scheme 15
From this remarkable change in enantioselectivity, caused
by modification of the ligand structure, we concluded that
the acidic proton of thiophosphoramide in our ligand sys-
tem also played a significant role in the catalytic reaction
process, very similar to previously reported work.32,38 In
addition, we also confirmed that in the 1H NMR spectrum
of L2, the acidic proton in the NH-P(S)Me2 moiety at 4.61
ppm disappeared in the presence of diethylzinc and its 31P
NMR spectrum with copper(I) clearly indicated a down-
field chemical shift from 56.68 ppm to 61.56 ppm in the
presence of diethylzinc. These results suggest that the ac-
tive species shown in Figure 1 might exist in the reaction
system.
We examined this asymmetric addition of N-sulfo-
nylimines with diethylzinc in toluene under various
reaction conditions using copper sources and binaphthyl-
thiophosphoramide ligands L1–L749 or C1-symmetric
diaminothiophosphoramides L12–L15.50 These are easily
Synlett 2007, No. 1, 19–30 © Thieme Stuttgart · New York

26
W. Zhang, M. Shi
ACCOUNT
Table 4 Asymmetric Addition Reactions of Diethylzinc to Various
N-Sulfonylimines 21 in the Presence of Copper(I) (3 mol%) and
Chiral Ligand L2 (6 mol%)
available, stable, recoverable and reusable chiral ligands
used in asymmetric addition reactions. These ligands and
reaction conditions have been carefully screened and ex-
amined to develop the best reaction conditions. Under
these optimized reaction conditions, good yields and up to
93% ee with ligand L2 (Scheme 16) and 74% ee with
ligand L16 (Scheme 17) were obtained in toluene at 0 °C.
The best results are shown in Table 4, these use L2 as the
chiral ligand in the asymmetric addition reaction of dieth-
ylzinc to various aryl and aliphatic substituted N-sulfo-
nylimines. As can be seen from Table 4, high yields and
good enantioselectivities could be achieved for various ar-
omatic N-sulfonylimines 21 having either electron-donat-
ing or electron-withdrawing groups on the benzene ring
(Table 4, entries 1–12). These results are comparable with
the best literature values hitherto reported for the asym-
metric addition of diethylzinc to N-sulfonylimines. Using
methanesulfonylimine and 2-trimethylsilylethanesulfo-
nylimine (SES), 96% yield (87% ee) and 94% yield (80%
ee) could also be realized (Table 4, entries 13 and 14). In
the case of the aliphatic sulfonylimine, only a moderate ee
(63% ee) for the corresponding addition product 22o was
obtained (Table 4, entry 15).
NR'
Cu(MeCN)4BF4 (3 mol%), L2 (6 mol%)
R
CH NR'
*
R
Et2Zn (2 equiv), toluene, 0 °C, 8 h
21
22
Entry
R
R¢
Product Yield ee
Configc
(%)a
93
95
93
81
96
93
95
91
94
96
95
93
96
94
86
(%)b
86
86
86
90
91
86
93
92
85
90
82
88
87
80
63
1
2
Ph
Ts
Ts
Ts
Ts
Ts
Ts
Ts
Ts
Ts
Ts
Ts
Ts
Ms
SES
Ts
22a
22b
22c
22d
22e
22f
Sc
d
p-MeC6H4
m-MeC6H4
p-MeOC6H4
p-ClC6H4
m-ClC6H4
p-CF3C6H4
p-BrC6H4
m-FC6H4
p-FC6H4
2-furyl
–
d
3
–
d
4
–
d
5
–
d
6
–
d
7
22g
22h
22i
–
d
8
–
d
9
–
d
10
11
12
13
14
15
22j
–
SO2R'
SO2R'
HN
*
Cu(MeCN)4BF4 (3 mol%), L2 (6 mol%)
d
N
22k
22l
–
Et2Zn (2 equiv), toluene, 0 °C, 8 h
R
Et
d
R
1-naphthyl
Ph
+
21
22
d
22m
22n
22o
–
81–96% yield, 63–93% ee
d
p-ClC6H4
Me2CH
–
Scheme 16
d
–
SO2R'
HN
a Isolated yields.
SO2R'
N
Cu(MeCN)4ClO4 (3 mol%), L16 (6 mol%)
Et2Zn (2 equiv), toluene, 0 °C, 13 h
b Determined by chiral HPLC.
R
Et
c The absolute configuration was assigned by comparison of the opti-
cal rotation with reported data.
*
R
22
21
d Sign of the optical rotation.
69–99% yield, 50–74% ee
Scheme 17
P(O)Ph2
P(O)Ph2
Cu(OTf)2 (5 mol%), L7 (5.5 mol%)
HN
Ar
N
3.2.2 Addition Reaction of Diethylzinc to N-Phos-
Et2Zn (3 equiv), toluene, 0 °C, 48 h
* Et
24
61–89% yield, 66–85% ee
Ar
phinoylimines
23
The enantioselective synthesis of a-chiral amines is of pri-
mary importance because these chiral synthons are among
the most commonly found and important subunits in
chiral drugs.42 In addition to the asymmetric reduction of
imines, the enantioselective addition of alkylmetals to
imines is a convenient route to optically active amines.
Recently, the use of N-phosphinoylimines as activated
substrates in combination with diethylzinc as the nucleo-
philic reagent and amino alcohol as the promoter is re-
ceiving increasing attention because the phosphoryl group
can be easily removed under acidic conditions.44,51
Scheme 18
phinoylimines (Scheme 18).52 This method provides an
alternative synthetic approach to the corresponding a-
chiral amines.
3.3
Addition Reaction of Diethylzinc to
Aldehydes
The catalytic enantioselective addition of organozinc re-
agents to aldehydes is a versatile method in the synthesis
of optically active secondary alcohols during carbon–car-
bon bond-forming reactions.53,54 Chiral zinc and titanium
complexes can catalyze this reaction when used in combi-
nation with amino alcohols (N,O ligands),55 diamines
We used our binaphthylthiophosphoramide ligands L1–
L7 in the catalytic asymmetric addition of diethylzinc to
N-phosphinoylimines. Using L7 as the chiral ligand in
toluene at 0 °C, 61–89% yields and up to 85% ee were
obtained with various aromatic substituted N-phos-
Synlett 2007, No. 1, 19–30 © Thieme Stuttgart · New York

ACCOUNT
Catalytic Asymmetric Carbon–Carbon Bond-Formation Reactions
27
(N,N ligands)56 or diols (O,O ligands),57 which act as ex- stannanes,64 allyllation using a BINAP silver(I) complex65
cellent chiral ligands. Binaphthylthiophosphoramide and chiral phosphoramides.66
ligands, which were successfully utilized in the addition
We previously reported a catalytic enantioselective allyla-
of diethylzinc to enones or imines, were applied in the ad-
tion reaction of aldehydes with allyltributyltin promoted
dition of diethylzinc to aldehydes (Scheme 19).58 Using
by silver(I) (AgOTf)-chiral thiophosphoramide L1–L9, in
which a high enantioselectivity (up to 98% ee) was at-
various arylaldehydes as substrates and in the presence of
L3 (20 mol%), 71–80% yields with 52–64% ee were ob-
tained using ligand L4 (Scheme 21).67 This is a novel ex-
tained at –20 °C in toluene in 48 hours.
ample using a chiral organosulfur-containing ligand in the
catalytic asymmetric allylation of aldehydes.
Ti(OiPr)4 (1.4 equiv), L3 (20 mol%)
OH
O
(R)
Ar
*
Et
Ar
H
Et2Zn (1.8 equiv), toluene, –20 °C, 48 h
3.5
The intramolecular hydroamination of alkenes constitutes
powerful method for the synthesis of azacy-
Other Applications
26
25
71–80% yield, 52–64% ee
a
Scheme 19
cles.68Livinghouse reported the structure of the first low-
coordinate yttrium–bis(thiophosphinic amidate) complex
determined by X-ray diffraction.69 The complex had a dis-
torted square-pyramidal geometry with the bis(trimethyl-
silyl)amido ligand at the apex. In addition, the use of this
complex, as well as related chelates of representative
group 3 and lanthanide metals (yttrium, neodymium, and
dysprosium),69 or neutral zirconium(IV) metal70 for the
efficient catalysis of intramolecular alkene hydroamina-
tions was studied in his group (Schemes 22 and 23). The
corresponding cyclized amination products were obtained
in good yields using these thiophosphoramide ligands.
These ligands have pseudotetrahedral bonding geometry
at phosphorus for increased steric shielding of the com-
plexed metal relative to the planar central carbon present
As well as the C1-symmetric thiophosphoramide ligands,
several C2-symmetric thiophosphoramide ligands L8–
L10 were also successfully applied in this addition reac-
tion (Scheme 20).59 Good yields with moderate ee values
were obtained in this Ti(Oi-Pr)4-ligand catalytic system
for a variety of arylaldehydes at –50 °C → –20 °C.
OH
Ti(OiPr)4 (1.4 equiv), L (20 mol%)
O
R
Et
R
H
Et2Zn (1.8 equiv) –50 °C to –20 °C
*
26
25
L8: 80–96% yield, 32–50% ee (S)
L9: 82–90% yield, 10–30% ee (S)
L10: 74–87% yield, 33% ee (R)
Scheme 20
iPr
iPr
N
P
P
3.4
Asymmetric Addition of Allylic Stannane to
Aldehydes
S
Ln N(TMS)2
29: Ln = Y
30: Ln = Nd
31: Ln = Dy
Catalytic asymmetric synthesis is a valuable method in the
preparation of optically active substances, particularly in
the asymmetric allylation of carbonyl compounds to give
optically active secondary homoallylic alcohols.60 The
stereoselective addition of allylic organometallics to one
of the two heterotopic faces of a carbonyl group has been
extensively studied and the enantioselective allylation of
various aldehydes is of particular importance in organic
synthesis. Although significant results have been
achieved using a stoichiomeric amount of chiral Lewis ac-
id,61 there are only a few methods reported that use a cat-
alytic process. These include using chiral (acyloxy)borane
(CAB) complex/allylic silanes,62 allylic stannanes,63 bi-
naphthol-derived chiral titanium complexes with allylic
N
S
iPr
iPr
H
catalyst (5 mol%)
125 °C
NH2
N
33
32
29: t = 14 h, >95% yield
30: t = 15 h, >95% yield
31: t = 14 h, 78% yield
Scheme 22
iPr
S
iPr
N
P
NMe2
Zr
NMe2
34
AgOTf (20 mol%),
L (20 mol%)
N
O
OH
S
P
+
Bu3Sn
iPr
iPr
Ar
H
*
Ar
–20 °C, THF, 48 h
25
27
28
H
N
NH2
34 (5 mol%)
C6D5CD3, 150 °C, 2.5 h
L3: 65–84% yield, 54–63% ee (R)
L4: 56–80% yield, 68–98% ee (S)
L8: 68% yield, 9% ee (R)
36: 98% yield
L9: 40–70% yield, 12–15% ee (R)
35
Scheme 21
Scheme 23
Synlett 2007, No. 1, 19–30 © Thieme Stuttgart · New York

28
W. Zhang, M. Shi
ACCOUNT
(9) Vahrenkamp, H. Angew. Chem., Int. Ed. Engl. 1975, 14,
in the more familiar amidinato71 group and a diminished
predisposition toward aggregate formation with oxophilic
metals by virtue of terminal sulfur (versus oxygen) substi-
tution. These advantages mean that there is higher effi-
cient catalytic activity than when amine ligands are used
in the intramolecular alkene hydroaminations. In addition,
up to 89% ee has been achieved in the asymmetric in-
tramolecular hydroamination of alkenes.72
322.
(10) (a) Kuehn, C. C.; Taube, H. J. Am. Chem. Soc. 1976, 98,
689. (b) Herberhold, M.; Suss, G. Angew. Chem., Int. Ed.
Engl. 1976, 15, 366.
(11) (a) Soai, K.; Niwa, S. Chem. Rev. 1992, 92, 833. (b)Hof,R.
P.; Poelert, M. A.; Peper, N. C. M. W.; Kellogg, R. M.
Tetrahedron: Asymmetry 1994, 5, 31. (c) Allen, J. V.;
Coote, S. J.; Dawson, G. J.; Frost, C. G.; Martin, C. J.;
Williams, J. M. J. J. Chem. Soc., Perkin Trans. 1 1994,
2065. (d) Orejon, A.; Masdeu-Bulto, A. M.; Echarri, R.;
Dieguez, M.; Fornies-Camer, J.; Claver, C.; Cardin, C. J. J.
Organomet. Chem. 1998, 559, 23. (e) Hiroi, K.; Suzuki, Y.
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Vranken, D. L. J. Org. Chem. 2001, 66, 7270.
4
Conclusion
For a long time, asymmetric carbon–carbon bond-forma-
tion reactions have been useful methods in modern organ-
ic synthesis. In the past two decades, various phosphorus,
nitrogen and sulfur ligands have been widely used in
asymmetric addition reactions. However, thiophosphora-
mide and thioamide ligands have had few applications in
asymmetric catalytic reactions. Our group has made much
effort in the synthesis of thiophosphoramide and thioam-
ide ligands, which are easily available, quite stable, recov-
erable and reusable. We have also looked at their use in
the conjugate addition of organozinc reagents to enones,
addition of diethylzinc to imines, addition of diethylzinc
to aldehydes, and addition of allylic stannane to alde-
hydes. As these methods are now available, they can be
expected to be applied in the asymmetric synthesis of nat-
ural products in the near future.
(12) (a) Knorr, M.; Strohmann, C. Organometallics 1999, 18,
248. (b) Gbor, P. K.; Ahmed, I. B.; Jia, C. Q. Ind. Eng.
Chem. Res. 2002, 41, 1861.
(13) (a) Berkessel, A.; Gröger, H. In Metal-Free Organic
Catalysts in Asymmetric Synthesis; Wiley-VCH: Weinheim,
2004. (b) Special issue: Asymmetric Organocatalysis, Acc.
Chem. Res. 2004, 37, 487–631. (c) Special feature:
Asymmetric Catalysis, Proc. Natl. Acad. Sci. U.S.A. 2004,
101, 5347–5487. (d) For selected reviews, see: Dalko, P. I.;
Moisan, L. Angew. Chem. Int. Ed. 2001, 40, 3726.
(e) Benaglia, M.; Puglisi, A.; Cozzi, F. Chem. Rev. 2003,
103, 3401. (f) Dalko, P. I.; Moisan, L. Angew. Chem. Int. Ed.
2004, 43, 5138. (g) Seayad, J.; List, B. Org. Biomol. Chem.
2005, 3, 719. (h) Taylor, M. S.; Jacobsen, E. N. Angew.
Chem. Int. Ed. 2006, 45, 1520.
(14) For example, see: Victoriano, L. I.; Garland, M. T.; Vega, A.
Inorg. Chem. 1997, 36, 688.
Acknowledgment
(15) For example, see: (a) Schrauzer, G. N. Acc. Chem. Res.
1969, 2, 72. (b) Bucheler, J.; Zeug, N.; Kisch, H. Angew.
Chem., Int. Ed. Engl. 1982, 21, 783. (c) Battaglia, R.;
Henning, R.; Dinh-Ngoc, B.; Schlamann, W.; Kisch, H. J.
Mol. Catal. 1983, 21, 239.
(16) Li, G. Y.; Marshall, W. J. Organometallics 2002, 21, 590.
(17) For selected examples, see: (a) Gilbertson, S. R.; Chen, G.;
McLoughlin, M. J. Am. Chem. Soc. 1994, 116, 4481.
(b) Gilbertson, S. R.; Wang, X. J. Org. Chem. 1996, 61, 434.
(c) Gilbertson, S. R.; Pawlick, R. V. Angew. Chem., Int. Ed.
Engl. 1996, 35, 902.
(18) (a) Dawson, G. J.; Frost, C. G.; Martin, C. J.; Williams, J. M.
J.; Coote, S. J. Tetrahedron Lett. 1993, 34, 7793. (b) Allen,
J. V.; Bower, J. F.; Williams, J. M. J. Tetrahedron:
Asymmetry 1994, 5, 1895. (c) Sprinz, J.; Kiefer, M.;
Helmchen, G.; Reggelin, M.; Huttner, G.; Walter, O.;
Zsolnai, L. Tetrahedron Lett. 1994, 35, 1523.
We thank the State Key Project of Basic Research (Project 973)
(No. G2000048007), Shanghai Municipal Committee of Science
and Technology (04JC14083), Chinese Academy of Sciences
(KGCX2-210-01), and the National Natural Science Foundation of
China for financial support (20472096, 203900502 and 20272069).
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