New chiral ferrocenyl p,s-ligands for highly diastereo-/enantioselective catalytic [3 + 2] cycloaddition of azomethine ylides with cyclic and acyclic enones

Article abstract of DOI:10.1021/ol1024647

A new family of chiral ferrocenyl P,S-ligands has been developed and successfully applied in a highly endo-selective catalytic asymmetric cycloaddition of azomethine ylides with various enones, including cyclic and acyclic α-enones. For cyclic α-enones, a

Full text of DOI:10.1021/ol1024647

ORGANIC
LETTERS
2010
Vol. 12, No. 23
5542-5545
New Chiral Ferrocenyl P,S-Ligands for
Highly Diastereo-/Enantioselective
Catalytic [3 + 2] Cycloaddition of
Azomethine Ylides with Cyclic and
Acyclic Enones
Cheng Zhang,†,‡ Sai-Bo Yu,†,‡ Xiang-Ping Hu,*,† Dao-Yong Wang,†,‡ and
Zhuo Zheng*,†
Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan
Road, Dalian 116023, China, and Graduate School of Chinese Academy of Sciences,
Beijing 100039, China
xiangping@dicp.ac.cn; zhengz@dicp.ac.cn
Received October 14, 2010
ABSTRACT
A new family of chiral ferrocenyl P,S-ligands has been developed and successfully applied in a highly endo-selective catalytic asymmetric
cycloaddition of azomethine ylides with various enones, including cyclic and acyclic r-enones. For cyclic r-enones, a [Cu(CH3CN)4]ClO4/
(Rc,SFc)-2f complex catalyzed the cycloaddition to give the sole endo-cycloadducts in perfect enantioselectivities (normally 99% ee), while an
AgOAc/(Rc,SFc)-2f catalytic system exhibited good endo/exo selectivities (endo/exo ) 91/9 to 96/4) and high enantiocontrol (up to 98% ee) for
acyclic r-enones.
The asymmetric [3 + 2] cycloaddition reaction of azomethine
ylides with electron-deficient olefins is one of the most
efficient methods of preparing optically active pyrrolidine
derivatives, which are widely present in many natural
products, pharmaceuticals, and biologically active mol-
ecules.1 Since the first catalytic asymmetric version reported
in 2002,2 great progress has been made in this field with the
development of many outstanding chiral metal catalysts and
organocatalysts.3-8 While high enantio-/diastereoselectivities
(1) (a) Pyne, S. G.; Davis, A. S.; Gates, N. J.; Hartley, J. P.; Lindsay,
K. B.; Machan, T.; Tang, M. Synlett 2004, 2670–2680. (b) Harwood, L. M.;
Vickers, R. J. In Synthetic applications of 1,3-Dipolar cycloaddition
chemistry toward heterocycles and natural products; Padwa, A., Pearson,
W., Eds.; Wiley & Sons: New York, 2002.
(2) (a) Longmire, J. M.; Wang, B.; Zhang, X. J. Am. Chem. Soc. 2002,
124, 13400–13401. (b) Gothelf, A. S.; Gothelf, K. V.; Hazell, R. G.;
Jørgensen, K. A. Angew. Chem., Int. Ed. 2002, 41, 4236–4238.
† Dalian Institute of Chemical Physics.
‡ Graduate School of Chinese Academy of Sciences.
10.1021/ol1024647  2010 American Chemical Society
Published on Web 11/11/2010

were observed with many dipolarophiles (i.e., R,ꢀ-unsatur-
ated esters, maleimides, R,ꢀ-unsaturated nitriles, enals,
nitroalkenes, vinyl sulfones, and fullerene), the cycloaddition
of azomethine ylides with enones, in particular cyclic
R-enones, is still rarely explored and remains a great
challenge.9 It was not until very recently that Carretero and
co-workers10 reported the first catalytic asymmetric cycload-
dition of azomethine ylides with R,ꢀ-unsaturated ketones
catalyzed by 5 mol % of CuI/Fesulphos complex. In their
research, endo-cycloadducts for 2-cyclopentenone were
obtained as a major isomer in moderate to good endo/exo
selectivities (endo/exo ) 75/25 to 98/2) and 85-95% ee,
while exo-selectivity (endo/exo ) 40/60 to 98/2) with
81-96% ee for acyclic R-enones was observed. A limitation
of this catalytic system lies in very low activity for a six-
membered cyclic enone such as 2-cyclohexenone. Najera
et al.5d reported that a chiral Ag(I)/phosphoramidite complex
could catalyze the cycloaddition of azomethine ylides with
cyclopentenone and acyclic enones, providing endo-adducts
in moderate to good endo/exo selectivities and enantiose-
lectivities. More recently, Fukuzawa et al.11 found that the
Ag/ThioClickFerrophos complex could catalyze the highly
endo-selective 1,3-dipolar cycloaddition reaction of azome-
thine ylides with acyclic R-enones, having an endo/exo ratio
of 90/10 to 99/1 and ee values of 87-98%. However, this
catalyst was less efficient for the reaction of azomethine
ylides with cyclic enone such as 2-cyclopentenone since a
long reaction time (24 h) and a high catalyst loading (10
mol %) were required, although the endo-cycloadduct was
obtained as the sole isomer in 98% ee and 73% yield. The
development of new, well-designed chiral ligands with high
diastereo-/enantioselectivities and a broad substrate scope for
the enantioselective cycloaddition of azomethine ylides with
R,ꢀ-unsaturated ketones, under low catalyst loadings and
mild reaction conditions, is therefore of great interest.
Recently, Chan et al. have reported a new ferrocenyl P/S
ligand 1, which showed good enantioselectivities in the Pd-
catalyzed asymmetric allylic alkylation (Figure 1).12 We
(3) Reviews on catalytic asymmetric 1,3-dipolar cycloadditon: (a) Engels,
B.; Christl, M. Angew. Chem., Int. Ed. 2009, 48, 7968–7970. (b) Stanley,
´
L. M.; Sibi, M. P. Chem. ReV. 2008, 108, 2887–2902. (c) Alvarez-Corral,
M.; Mun˜oz-Dorado, M.; Rodr´ıguez-Garc´ıa, I. Chem. ReV. 2008, 108, 3174–
3198. (d) Naodovic, M.; Yamamoto, H. Chem. ReV. 2008, 108, 3132–3148.
(e) Pellissier, H. Tetrahedron 2007, 63, 3235–3285. (f) Nair, V.; Suja, T. D.
Tetrahedron 2007, 63, 12247–12275. (g) Pandey, G.; Banerjee, P.; Gadre,
S. R. Chem. ReV. 2006, 106, 4484–4517. (h) Na´jera, C.; Sansano, J. M.
Angew. Chem., Int. Ed. 2005, 44, 6272–6276. (i) Husinec, S.; Savic, V.
Tetrahedron: Asymmetry 2005, 16, 2047–2061.
(4) For recent examples on Cu catalysts: (a) Robles-Machin, R.;
Gonza´lez-Esguevillas, M.; Adrio, J.; Carretero, J. C. J. Org. Chem. 2010,
75, 233–236. (b) Lo´pez-Pe´rez, A.; Adrio, J.; Carretero, J. C. Angew. Chem.,
Int. Ed. 2009, 48, 340–343. (c) Lo´pez-Pe´rez, A.; Adrio, J.; Carretero, J. C.
J. Am. Chem. Soc. 2008, 130, 10084–10085. (d) Wang, C.-J.; Liang, G.;
Xue, Z.-Y.; Gao, F. J. Am. Chem. Soc. 2008, 130, 17250–12751. (e) Llamas,
T.; Ramo´n Go´mez, A.; Carretero, J. C. Synthesis 2007, 950–956. (f) Cabrera,
S.; Go´mez Arraya´s, R.; Mart´ın-Matute, B.; Coss´ıo, F. P.; Carretero, J. C.
Tetrahedron 2007, 63, 6587–6602. (g) Shi, M.; Shi, J.-W. Tetrahedron:
Asymmetry 2007, 18, 645–650. (h) Yan, X.-X.; Peng, Q.; Zhang, Y.; Zhang,
K.; Hong, W.; Hou, X.-L.; Wu, Y.-D. Angew. Chem., Int. Ed. 2006, 45,
1979–1983. (i) Cabrera, S.; Arraya´s, R. G.; Carretero, J. C. J. Am. Chem.
Soc. 2005, 127, 16394–16395. (j) Gao, W.; Zhang, X.; Raghunath, M. Org.
Lett. 2005, 7, 4241–4244.
Figure 1. Structure of Chan’s ligand 1 and (Rc,SFc)-ImiFerroS 2.
(5) For recent examples on Ag Catalysts: (a) Yamashita, Y.; Guo, X.-
X.; Takashita, R.; Kobayashi, S. J. Am. Chem. Soc. 2010, 132, 3262–3263.
(b) Xie, Z.-Y.; Liu, T.-L.; Lu, Z.; Huang, H.; Tao, H.-Y.; Wang, C.-J. Chem.
Commun. 2010, 46, 1727–1729. (c) Robles-Mach´ın, R.; Alonso, I.; Adrio,
J.; Carretero, J. C. Chem.sEur. J. 2010, 16, 5286–5291. (d) Na´jera, C.;
Retamosa, M. G.; Mart´ın-Rodr´ıguez, M.; Sansano, J. M.; Co´zar, A.; Coss´ıo,
F. P. Eur. J. Org. Chem. 2009, 5622–5634. (e) Yu, S.-B.; Hu, X.-P.; Deng,
J.; Wang, D.-Y.; Duan, Z.-C.; Zheng, Z. Tetrahedron: Asymmetry 2009,
20, 621–625. (f) Wang, C.-J.; Xue, Z.-Y.; Liang, G.; Lu, Z. Chem. Comumm.
2009, 2905–2907. (g) Liang, G.; Tong, M,-C.; Wang, C.-J. AdV. Synth.
Catal. 2009, 351, 3101–3106. (h) Zeng, W.; Chen, G.-Y.; Zhou, Y.-G.; Li,
Y.-X. J. Am. Chem. Soc. 2007, 129, 750–751. (i) Zeng, W.; Zhou, Y.-G.
Tetrahedron Lett. 2007, 48, 4619–4622. (j) Na´jera, C.; Retamosa, M. D. G.;
Sansano, J. M. Org. Lett. 2007, 9, 4025–4028. (k) Garner, P.; Kaniskan,
envision that these new ligands may also be efficient for the
catalytic asymmetric cycloaddition of azomethine ylides with
cycloenones because of the good performance of chiral
ferrocenyl P,S-ligands in the catalytic asymmetric [3 + 2]
cycloaddition. However, the results proved to be highly
disappointing, and only very low enantioselectivity (26% ee
for endo-adducts) was achieved in the Cu-catalyzed [3 + 2]
cycloaddition of N-(4-chlorobenzylidene)glycine methyl ester
(5a) with 2-cyclopentenone (6a) (entry 1, Table 1). By
reversing the position of P- and S-donor atoms, herein we
report a new family of chiral ferrocenyl P,S-ligands [(Rc,SFc)-
ImiFerroS 2] for the highly endo-selective catalytic asym-
metric cycloaddition of azomethine ylides with various
enones, including cyclic and acyclic R-enones, in which
excellent diastereo-/enantioselectivities (only endo-cycload-
ducts with normally >99% ee for cyclic R-enones) were
achieved for a broad scope of azomethine ylides.
¨
H. U.; Hu, J.; Youngs, W. J.; Panzner, M. Org. Lett. 2006, 8, 3647–3650.
(l) Nyerges, M.; Bendell, D.; Arany, A.; Hibbs, D. E.; Coles, S. J.;
Hursthouse, M. B.; Groundwater, P. W.; Meth-Cohn, O. Tetrahedron 2005,
61, 3745–3753. (m) Zeng, W.; Zhou, Y.-G. Org. Lett. 2005, 7, 5055–5058.
(n) Alemparte, C.; Blay, G.; Jørgensen, K. A. Org. Lett. 2005, 7, 4569–
4572.
¨
(6) For recent examples on zinc catalysts: (a) Dogan, O.; Koyuncu, H.;
Garner, P.; Bulut, A.; Youngs, W. J.; Panzner, M. Org. Lett. 2006, 8, 4687–
¨
¨
¨
4690. (b) Dogan, O.; Oner, I.; Ulku¨, D.; Arici, C. Tetrahedron: Asymmetry
2002, 13, 2099–2104.
(7) For recent example on nickel catalysts: Shi, J.-W.; Zhao, M.-X.;
Lei, Z.-Y.; Shi, M. J. Org. Chem. 2008, 73, 305–308.
(8) For recent examples on organocatalysts: (a) Liu, Y. K.; Liu, H.; Du,
W.; Yue, L.; Chen, Y.-C. Chem.sEur. J. 2008, 14, 9873–9877. (b) Xue,
M.-X.; Zhang, X.-M.; Gong, L.-Z. Synlett 2008, 691–694. (c) Chen, X.-
H.; Zhang, W.-Q.; Gong, L.-Z. J. Am. Chem. Soc. 2008, 130, 5652–5654.
(d) Ibrahem, I.; R´ıos, R.; Vesely, J.; Co´rdova, A. Tetrahedron Lett. 2007,
48, 6252–6257. (e) Vicario, J. L.; Reboredo, S.; Bad´ıa, D.; Carrillo, L.
Angew. Chem., Int. Ed. 2007, 46, 5168–5170.
The modular synthesis of these new chiral ferrocenyl P,S-
ligands is outlined in Scheme 1. In the first step, N,N-dimethyl
(11) Oura, I.; Shimizu, K.; Ogata, K.; Fukuzawa, S. Org. Lett. 2010,
12, 1752–1755.
(12) (a) Cheung, H. Y.; Yu, W.-Y.; Lam, F. L.; Au-Yeung, T. T.-L.;
Zhou, Z.; Chan, T. H.; Chan, A. S. C. Org. Lett. 2007, 9, 4295–4298. (b)
Cheung, H. Y.; Yu, W.-Y.; Au-Yeung, T. T.-L.; Zhou, Z.; Chan, A. S. C.
AdV. Synth. Catal. 2009, 351, 1412–1422.
(9) Grigg, R. Tetrahedron: Asymmetry 1995, 6, 2475–2486.
(10) Herna´ndez-Toribio, J.; Go´mez Arraya´s, R.; Mart´ın-Matute, B.;
Carretero, J. C. Org. Lett. 2009, 11, 393–396.
Org. Lett., Vol. 12, No. 23, 2010
5543

robenzylidene)glycine methyl ester (5a) with 2-cyclopen-
tenone (6a) was examined using 5 mol % of [Cu(CH3CN)4]-
ClO4 and 5.5 mol % of ligand in the presence of 18 mol %
of Et3N as base in dichloromethane (DCM) at room tem-
perature, and the representative results are shown in Table
1. To our delight, endo-7a was obtained as the only
cycloadduct with these newly developed P,S-ligands 2. The
results indicated that the thio group in these (Rc,SFc)-
ImiFerroS ligands has a significant influence on the enan-
tioselectivity, and a catalyst combining [Cu(CH3CN)4]ClO4
and (Rc,SFc)-2f bearing an i-propylthio group provided the
highest enantioselectivity of >99% ee (entry 7). With (Rc,SFc)-
2f, we next optimized the reaction conditions. Solvent
screening showed that dichloromethane was the best sol-
vent.14 Lowering catalyst loadings to 3 mol % has less effect
on the catalytic activity and enantioselectivity (>99% ee)
(entry 8). This result demonstrated the high efficiency of the
[Cu(CH3CN)4]ClO4/(Rc,SFc)-2f catalytic system for the cata-
lytic asymmetric 1,3-dipolar cycloaddition of azomethine
ylides with cyclic R-enones. However, a further reduction
in catalyst loadings to 1 mol % resulted in a significantly
decreased reactivity and enantioselectivity (entry 9). The
reaction with AgOAc as Lewis acid proceeded more slowly,
giving lower chemical yield and enantioselectivity (entry 10).
Under the optimal reaction conditions, the scope of the
1,3-dipolar cycloaddition with the present catalytic system
was investigated. As shown in Table 2, a wide array of imino
esters 5 from aromatic aldehydes reacted with 2-cyclopen-
Table 1. Asymmetric [3 + 2] Cycloaddition of 5a with 6aa
time yield
ee
entry ligand
M (mol %)
(h)
(%)b
(%)c
1
2
3
4
5
6
7
8
9
1
[Cu(CH3CN)4]ClO4 (5)
[Cu(CH3CN)4]ClO4 (5)
[Cu(CH3CN)4]ClO4 (5)
[Cu(CH3CN)4]ClO4 (5)
[Cu(CH3CN)4]ClO4 (5)
[Cu(CH3CN)4]ClO4 (5)
[Cu(CH3CN)4]ClO4 (5)
[Cu(CH3CN)4]ClO4 (3)
[Cu(CH3CN)4]ClO4 (1)
AgOAc (3)
3
67
83
78
82
87
86
84
91
21
48
26
83
84
89
97
2a
2b
2c
2d
2e
2f
2f
2f
2f
1.5
1.5
1.5
1.5
1.5
1.5
2
92
>99
>99
92
8
12
10
95
a The reaction was performed in DCM at room temperature using 5a
(0.3 mmol) and 6a (0.36 mmol) in the presence of a Cu catalyst, prepared
in situ from [Cu(CH3CN)4]ClO4 and ligand, and Et3N (18 mol %), unless
otherwise noted. b Isolated yield of endo-7a after column chromatography.
c Determined by HPLC on a chiral column.
(R)-1-[(S)-2-(diphenylphosphino)ferrocenyl]ethylamine [(Rc,SFc)-
PPFA 3] was converted into the corresponding (Rc,SFc)-4 in
high yield by the treatment of (Rc,SFc)-3 with benzimidazole in
HOAc.13 Subsequent lithiation of (Rc,SFc)-4 with n-BuLi,
followed by the treatment with various disulfides, gave the
desired ferrocenyl P,S-ligands 2 [(Rc,SFc)-ImiFerroS]. These
ligands are stable toward air and moisture and can be held at
ambient temperature in open air for over 1 month. The structure
of (Rc,SFc)-ImiFerroS 2a was confirmed by X-ray analysis.14
Table 2. Catalytic Asymmetric [3 + 2] Cycloaddition Reactions
of Imino Esters 5 with Cyclic R-Enones 6a
entry
5 (R1, R2)
6 (n)
7
yield (%)b ee (%)c
Scheme 1
.
Synthesis of New Chiral Ferrocenyl P,S-Ligands,
(Rc,SFc)-ImiFerroS 2
1
2
3
4
5
6
7
8
9
5a: Me, 4-ClC6H4
5b: Et, 4-ClC6H4
5c: i-Pr, 4-ClC6H4
5d: Me, 2-ClC6H4
5e: Me, 3-ClC6H4
5f: Me, Ph
5g: Me, 4-BrC6H4
5h: Me, 4-FC6H4
5i: Me, 4-CF3C6H4 6a (n ) 1) 7i
5j: Me, 4-NO2C6H4 6a (n ) 1) 7j
6a (n ) 1) 7a
6a (n ) 1) 7b
6a (n ) 1) 7c
6a (n ) 1) 7d
6a (n ) 1) 7e
6a (n ) 1) 7f
6a (n ) 1) 7g
6a (n ) 1) 7h
91
88
88
93
85
88
86
82
85
82
89
86
82
89
-
>99
>99
>99
>99
99
>99
>99
>99
>99
>99
>99
99
10
11d 5k: Me, 4-MeC6H4 6a (n ) 1) 7k
12d 5l: Me, 4-MeOC6H4 6a (n ) 1) 7l
13d 5m: Me, 2-thienyl
6a (n ) 1) 7m
5n: Me, 2-naphthyl 6a (n ) 1) 7n
5o: Me, Cy
>99
>99
-
14
15
6a (n ) 1) 7o
6b (n ) 2) 7p
16d 5a: Me, 4-ClC6H4
87
>99
With these newly developed P,S-ligands in hand, a
catalytic asymmetric 1,3-dipolar cycloaddition of N-(4-chlo-
a The reaction was performed in DCM at room temperature using 5
(0.3 mmol) and 6 (0.36 mmol) in the presence of a Cu catalyst, prepared
in situ from [Cu(CH3CN)4]ClO4 (3 mol %) and 2f (3.3 mol %), and Et3N
(18 mol %), unless otherwise noted. b Isolated yield. c Determined by HPLC
on a chiral column. d Catalyst loading: 5 mol %.
(13) Wang, D.-Y.; Hu, X.-P.; Hou, C.-J.; Deng, J.; Yu, S.-B.; Duan,
Z.-C.; Huang, J.-D.; Zheng, Z. Org. Lett. 2009, 11, 3226–3229.
(14) See Supporting Information.
5544
Org. Lett., Vol. 12, No. 23, 2010

tenone 6a to give the corresponding endo-adducts 7a-n in
high yields and perfect enantioselectivities (normally >99%
ee) (entries 1-14). The ester group on imino esters showed
no influence on the yield and enantioselectivity. In all cases,
excellent enantioselectivities (>99% ee) were achieved
(entries 1-3). It also appears that the position and the
electronic property of the substituent on the phenyl ring have
a smaller effect on the enantioselectivities (entries 3-12).
However, the substrates bearing an electron-withdrawing
substituent tended to show higher reactivity than those with
an electron-donating group. Thus, the reactions for most of
the substrates finished in 2 h, but for the substrate 5l with a
methoxy group extending the reaction time to 36 h was
required to complete the reaction (entry 12). Heteroaryl imino
ester 5m also proved to be a suitable substrate, exclusively
undergoing the endo cycloaddition with excellent enanti-
oselectivity (>99% ee), although the catalyst loading should
be increased to 5 mol % (entry 13). An azomethine ylide
from 2-naphthylaldehyde also worked well in this transfor-
mation, producing endo-cycloadduct in >99% ee (entry 14).
Unfortunately, no cycloaddition was observed in the case
of azomethine ylides derived from the aliphatic cyclohex-
anecarbaldehyde(entry15).Remarkably,theCu(CH3CN)4ClO4/
(Rc,SFc)-2f complex can also effectively catalyze the cy-
cloaddition of azomethine ylides with 2-cyclohexenone (6b),
providing endo-cycloadduct 7p as the sole isomer in >99%
ee (entry 16). These results represent the best outcome in
the catalytic asymmetric 1,3-dipolar cycloaddition of azome-
thine ylides with cyclic R-enones reported so far.
To extend this asymmetric protocol, the cycloaddition of
N-(4-chlorobenzylidene)glycine methyl ester (5a) with acy-
clic enones was also conducted, and the results are shown
in Table 3. Initially, we performed the reaction of 5a with
chalcone 8a, under the same reaction conditions as those
used with 2-cyclopentenone 6a. The reaction proceeded very
quickly and completed in 10 min even at low temperature
(-30 °C) and low catalyst loadings (1 mol %), to give the
endo-cycloadduct preferentially in the perfect enantioselec-
tivity (99% ee) (entry 1). However, a relatively low endo-
selectivity (endo/exo ) 2/1) was not so satisfactory. The
diastereoselectivity with the present Cu-catalytic system is
different from that reported by Carretero, in which exo-
adducts were formed preferentially with a Cu/Fesulphos
complex.10 By replacing [Cu(CH3CN)4]ClO4/(Rc,SFc)-2f with
AgOAc/(Rc,SFc)-2f as the catalyst, the endo-selectivity can
be significantly increased to endo:exo ) 93:7 (entry 2).
Reactions with a series of substituted chalcones 8 were then
carried out by use of this Ag catalyst. The results indicated
that this Ag catalyst was efficient for these chalcone-type
substrates, giving endo-cycloadducts in high endo-selectivity
(endo/exo ) 91/9 to 96/4) and high enantioselectivity (up
to 98% ee) (entries 2-6).
Table 3. Catalytic Asymmetric [3 + 2] Cycloaddition Reactions
of 5a with Chalcones 8a
endo-9
entry
8 (Ar1, Ar2)
8a (Ph, Ph)
endo/exob yield (%)c ee (%)d
1e
2
3
4
5
6
2/1
65
81
78
81
86
83
99
97
91
93
98
98
8a (Ph, Ph)
93/7
91/9
96/4
95/5
96/4
8b (Ph, 4-ClC6H4)
8c (4-ClC6H4, Ph)
8d (4-MeOC6H4, Ph)
8e (4-MeC6H4, Ph)
a The reaction was performed in ClCH2CH2Cl at -10 °C for 2 h using
0.3 mmol of 5a and 0.36 mmol of 8 in the presence of an Ag catalyst,
prepared in situ from AgOAc (3 mol %) and (Rc,SFc)-2f (3.3 mol %), and
Et3N (10 mol %), unless otherwise noted. b Determined by 1H NMR.
c Isolated yield of endo-9 after column chromatography. d Determined by
HPLC on a chiral column. e The reaction was performed in CH2Cl2 at -30
°C for 10 min using 0.3 mmol of 5a and 0.36 mmol of 8a in the presence
of a Cu catalyst, prepared in situ from [Cu(CH3CN)4]ClO4 (1 mol %) and
2f (1.1 mol %), and Et3N (10 mol %).
In conclusion, we have developed a new family of chiral
ferrocenyl P,S-ligands for a highly endo-selective catalytic
asymmetric cycloaddition of azomethine ylides with various
enones, including cyclic and acyclic R-enones. For cyclic
R-enones, a [Cu(CH3CN)4]ClO4/(Rc,SFc)-2f complex cata-
lyzed the cycloaddition to give the sole endo-cycloadducts
in perfect enantioselectivities (normally 99% ee). For acyclic
R-enones, the [Cu(CH3CN)4]ClO4/(Rc,SFc)-2f complex dis-
played excellent enantioselectivity (99% ee) but relatively
low endo-selectivity (endo/exo ) 2/1), while an AgOAc/
(Rc,SFc)-2f catalytic system exhibited good endo/exo selec-
tivities (endo/exo ) 91/9 to 96/4) and high enantiocontrol
(up to 98% ee). Further reaction scope and mechanistic origin
of high diastereo- and enantioselectivity are underway.
Acknowledgment. We are grateful for the generous
financial support from the National Natural Science
Foundation of China (20972156, 20873145, and 20802076)
and the Planned Science and Technology Project of Dalian
(2009E11SF132).
Supporting Information Available: Full Experimental
details, spectroscopic data, and X-ray analysis of (Rc,SFc)-
2a. This material is available free of charge via the Internet
at http://pubs.acs.org.
OL1024647
Org. Lett., Vol. 12, No. 23, 2010
5545