Chiral bis(2-oxazolinyl)xanthene (xabox)/transition-metal complexes catalyzed 1,3-dipolar cycloaddition reactions and Diels-Alder reactions

Article abstract of DOI:10.1016/j.tet.2007.11.109

A series of chiral 4,5-bis(2-oxazolinyl)-(2,7-di-tert-butyl-9,9-dimethyl)-9H-xanthenes (xabox) and their transition-metal complexes were synthesized. The X-ray analysis of xabox-RhCl₃ complex shows a unique facial type structure. Xabox-Bn-Mn(II

Full text of DOI:10.1016/j.tet.2007.11.109

Available online at www.sciencedirect.com
Tetrahedron 64 (2008) 1813e1822
www.elsevier.com/locate/tet
Chiral bis(2-oxazolinyl)xanthene (xabox)/transition-metal complexes
catalyzed 1,3-dipolar cycloaddition reactions and DielseAlder reactions
Kesiny Phomkeona a, Toshihide Takemoto a, Yosuke Ishima a, Kazutaka Shibatomi a,
b
Seiji Iwasa a, , Hisao Nishiyama
*
a Department of Materials Science, Toyohashi University of Technology, 1-1 Hibarigaoka, Tempaku-cho, Toyohashi, Aichi 464-8603, Japan
b Graduate Schools of Engineering, Department of Applied Chemistry, Nagoya University, Chikusa, Nagoya 464-8600, Japan
Received 6 February 2007; received in revised form 28 November 2007; accepted 29 November 2007
Available online 8 December 2007
Abstract
A series of chiral 4,5-bis(2-oxazolinyl)-(2,7-di-tert-butyl-9,9-dimethyl)-9H-xanthenes (xabox) and their transition-metal complexes were
synthesized. The X-ray analysis of xaboxeRhCl3 complex shows a unique facial type structure. XaboxeBneMn(II) and xaboxeBneMg(II)
complexes were found to be efficient catalysts in nitrone 1,3-dipolar cycloaddition (1,3-D.C.) reaction resulting in good to excellent enantiose-
lectivities ranging from 96:4 to >99:1of endo/exo ratio and 91e96% ee for the endo adduct. The correlation between enantiomeric excess of the
ligand and the product in the nitrone 1,3-D.C. reaction shows a clear linear relationship, which suggests xaboxemetal catalyst worked as a single
molecular catalyst. In addition, xaboxei-PreMn(II) complex was also found to be an active catalyst for DielseAlder (DeA) reaction of acryl-
oyloxazolidinone and cyclopentadiene affording the corresponding cycloadduct in quantitative yield along with 82% ee and 98:2 endo/exo ratio.
Ó 2007 Elsevier Ltd. All rights reserved.
Keywords: 1,3-Dipolar cycloaddition; Chiral ligand; DielseAlder reaction; Oxazoline; Xanthene
1. Introduction
with alkenes is one of the most useful reactions in organic syn-
thesis since the hetero-atoms such as nitrogen and oxygen are
pharmacologically important.4 It offers a straightforward and
efficient synthesis of isoxazolidine derivatives with highly re-
gio- and stereoselective construction of three new continuous
chiral centers in the adduct. And the isoxazolidine formed
can be transformed into many attractive biologically active
compounds such as alkaloids, amino alcohols, amino sugars,
and b-lactams.5
On the other hand, the DielseAlder (DeA) reaction is one of
the most powerful well known method for carbonecarbon bond
formation, which afford cycloadducts having a double bond and
two newly formed CeC single bonds.6 It is also popular and
useful synthetic tool in organic chemistry as well as 1,3-D.C.
reaction, and has a long history compared to 1,3-D.C. reactions.
The progress in number of chiral Lewis acid catalysts em-
ploying chiral ligands based on bis- and tridentate oxazoline-
derived C2-symmetric chiral ligands has been reflected to
the developing of these asymmetric 1,3-D.C.7 and DeA8 reac-
tions. Chiral oxazoline ligands have played an important role
Since chiral catalyst is one of the most efficient and prom-
ising protocols for providing optically pure organic molecules,
asymmetric catalysts are represented as one of the most active
areas in modern organic chemistry.1 The development of chiral
ligand for catalytic asymmetric transformation can create new
strategies to access the target molecules. A number of asym-
metric synthetic methods with a variety of chiral catalysts hav-
ing new chiral ligands have been developed so far, and are
being applied to both the total synthesis of natural products
and biologically active artificial organic compounds with
a high efficiency.2 Among them, asymmetric cycloadditions
are recognized as powerful methods for the synthesis of
optically active complex molecules since multiple asymmetric
centers can be constructed in one-step transformation.3 Espe-
cially, 1,3-dipolar cycloaddition (1,3-D.C.) reaction of nitrones
* Corresponding author. Tel.: þ81 532 44 6817; fax: þ81 532 48 5833.
E-mail address: iwasa@tutms.tut.ac.jp (S. Iwasa).
0040-4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.11.109

1814
K. Phomkeona et al. / Tetrahedron 64 (2008) 1813e1822
in the field of asymmetric induction since these are easily
accessible from amino alcohols and carboxylic acids.9,10
In this report, we present a new series of tridentate chiral
ligands, which was derived from bis(2-oxazolinyl)xanthene
(xabox). The transition-metal complexes prepared from this
enantiopure ligand and various transition-metal(II) perchlo-
rates were found to be an efficient catalyst for 1,3-D.C. reac-
tions of nitrones with 3-alkenoyl-2-oxazolidinones and DeA
reactions of cyclopentadiene with 3-acryloyl-2-oxazolidinone.
With complexes of (S,S)-xaboxeBn and Mn(II), Mg(II), or
Ni(II) perchlorate, respectively, the correlation between
ligands’ ee and product ee was also examined in 1,3-D.C.
reactions to pursue the behavior of catalyst such as homo-
and hetero-chiral complex formation.11
reported from our research group.13 Initially, we have selected
Ni(ClO4)2$6H2O as a central metal and briefly examined the
chiral shielding substituent effect on the oxazoline rings
using a model reaction of nitrone 7a with 3-crotonoyl-2-
oxazolidinone 8a in order to determine the efficiency of the
new ligand system. The catalysts were prepared by heating
a mixture of xabox ligands (5aec) with Ni(ClO4)2$6H2O in
ꢀ
˚
the presence of activated 4 A MS at 40 C for 4 h in
dichloromethane (Scheme 2). After complexation, the MS
were filtered off to obtain a pale blue-green solution, which
was again filtered via membrane filter. The resulting catalyst
˚
solution was then added to pre-activated 4 A MS at room tem-
perature. At this stage, 3-crotonoyl-2-oxazolidinone and ni-
trone were added to the catalyst. The resulting suspension
was stirred at room temperature. The results of xaboxe
Ni(II) catalyzed 1,3-D.C. reactions are summarized in Table
1. xaboxei-PreNi(II) and xaboxeBneNi(II) complexes cata-
lyzed 1,3-D.C. reactions proceeded smoothly, affording the
product 9a in a high yield within 24 h with good endo/exo
ratio and moderate to good enantioselectivities of endo prod-
uct (61% ee and 85% ee), respectively (entries 1 and 3),
whereas xaboxePh shows only poor enantioselectivity (entry
2). As for these results, xaboxeBn 5c was the best ligand
for the nitrone 1,3-D.C. reaction.
The metal effect was screened for further optimization with
xaboxeBn 5c in the 1,3-D.C. reaction. Among the metal
screened, the best results in both diastereo- and enantioselec-
tivities were obtained in the case of Mn(II) and Mg(II) with
92:8 of endo/exo ratio with 93% ee for endo and 99:1 endo/
exo ratio with 85% ee for endo (entries 7 and 10), respectively.
The use of xaboxeBneCu(OTf)2 complex gave 9a in 86:14
endo/exo ratio with 77% ee for endo (entry4). However
xaboxeBneSc complexes gave 9a as a racemate, although
higher than the use of Cu(OTf)2 (entries 5 and 6).
Next, the temperature effects on the catalyst activity were
investigated for both Mn(II) and Mg(II) (entries 7e12). The
nitrone 1,3-D.C. reactions proceeded smoothly at 0 ꢀC to
room temperature in the presence of 10 mol % of 5c and
metals to afford the cycloadducts in high yields as well as
high stereoselectivities though the reaction time was length-
ened at low temperature. According to the marked results
from both diastereo- and enantioselectivity, we examined the
optimized catalytic conditions for catalytic asymmetric 1,3-
2. Results and discussion
2.1. Synthesis of bis(2-oxazolinyl)xanthene ligands
Chiral bis(2-oxazolinyl)xanthene (xabox) ligands having
a xanthene backbone were synthesized from the corresponding
commercially available xanthene carboxylic acid 1 and amino
alcohols derived from the reduction of natural amino acids in
three steps. Then excess thionyl chloride was removed under
reduced pressure followed by the reaction with amino alcohols
under basic conditions resulting in the corresponding amide
alcohols in 80e90% yield. There are two different methods
for oxazoline ring formation. One is mesylation of the amide
alcohols with mesylchloride followed by oxazoline ring for-
mation in one-pot procedure (method A) and the other is chlo-
rination of the hydroxyl group with thionyl chloride to prepare
the chloethyl moiety followed by oxazoline ring formation
with sodium hydride (6 equiv) in tetrahydrofuran (method
B). Both methods A and B gave (S,S)-xaboxeR ligands as
a new entry in tridentate oxazoline chiral ligands in 98%
yields (Scheme 1).12
2.2. Xabox/transition-metal complex catalyzed 1,3-D.C.
reactions of nitrones with oxazolidinone
Recently, highly enantioselective 1,3-D.C. reactions of
nitrones with alkenoyl oxazolidinone employing chiral bis-
(oxazolinyl)pyridine (pybox)eNi(II) complexes have been
H2N
R
OH
3a : R=i-Pr
3b : R=Ph
3c : R=Bn
t-Bu
t-Bu
t-Bu
t-Bu
SOCl2, reflux, 3h
quant.
CHCl3, 0 °C-r.t, 5 h.
>98%
O
O
HOOC
COOH
ClOC
COCl
1
2
A. MsCl, Et3N
CHCl3, 5 h.
B. 1) SOCl2, reflux, 4 h.
t-Bu
OH
t-Bu
t-Bu
t-Bu
Total yield from 1
HO
O
O
5a : R=i-Pr (82%)
5b : R=Ph ( 76%)
5c : R=Bn (78%)
2) NaH, THF, 1.5 h.
R
N
H
O
O
N
H
R
O
N
N
O
4
R
R
Scheme 1.

K. Phomkeona et al. / Tetrahedron 64 (2008) 1813e1822
1815
2+
t-Bu
t-Bu
t-Bu
t-Bu
MS4A
CH2Cl2, 40 °C. 4 h.
2-
(ClO4)2
+
M(ClO4)2.6H2O
M = Mn, Mg, Ni
O
O
M
L
O
N
N
O
O
N
N
O
R
R
R
R
L = 3H2O
6 xabox-R-M
5a-c
Scheme 2.
D.C. reaction of various nitrones 7bed with 3-crotonoyl-2-
oxazolidinones 8a (entries 13e15). Cycloadducts 9bed were
obtained in a high yield with excellent stereoselectivities.
Acryloyl dienophile 8b also reacted with nitrone 7a to afford
cycloadduct 9e in 97% yield with a high enantioselectivity
(up to 96% ee) (entries 16 and 17). However, endo cycload-
duct was observed in a 77:23 endo/exo ratio, when Mn(II)
was used as a metal (entry 16).
N-Acryloyl-2-pyrrolidinones 10a,b with nitrones 7a and 12
can be similarly reacted in the presence of (S,S)-xaboxeBne
Mn(II) or Mg(II) complex to give the corresponding cycload-
ducts 11 and 13, respectively, the former reaction provided
a high chemical yield with an excellent diastereo- and enantio-
selectivity (Scheme 3). The benzyl group on the nitrogen atom
of nitrone is exchanged to another functional group using Pd/
CeH2 reaction condition.
2.3. X-ray analysis of xaboxeRhCl3
In order to pursue molecular structure of xaboxeRetransi-
tion-metal complex, single X-ray analysis was carried out
since NMR spectroscopic information as for xaboxeMn(II),
Mg(II), and Ni(II) is not available because of their strong para-
magnetic properties. Fortunately, xaboxei-PreRhCl3 complex
was isolated as a single crystal after equimolar amount of rho-
dium trichloride and xaboxei-Pr 5a in ethanol at 60 ꢀC for
1.5 h in 83% yield. The structure of rhodium complex 14 de-
termined by X-ray analysis shows a unique facial coordination
Table 1
(S,S)-xaboxeBn and Mn(II) and Mg(II) catalyzed 1,3-D.C. reaction of nitrones 7aed and oxazolidinone 8a,b
O 5R
4S
R2
O
O
N
3R
cat. 10 mol%
MS4A
CH2Cl2
R2
N
-
O
+
O
+
exo
N
O
+
N
O
O
H
R1
R1
7a: R1= Ph
9a-e
8a: R2= CH3
8b: R2= H
7b: R1= CH3
7c: R1= OCH3
7d: R1= Br
Entry
Ligand
Metal
7
8
Product
Temp (ꢀC)
Time (h)
Yield (%)a
endo/exob
endo eec
1
5a
5b
5c
5c
5c
5c
5c
5c
5c
5c
5c
5c
5c
5c
5c
5c
5c
Ni(ClO4)2$6H2O
Ni(ClO4)2$6H2O
Ni(ClO4)2$6H2O
Cu(OTf)2
7a
7a
7a
7a
7a
7a
7a
7a
7a
7a
7a
7a
7b
7c
7d
7a
7a
8a
9a
9a
9a
9a
9a
9a
9a
9a
9a
9a
9a
9a
9b
9c
9d
9e
9e
rt
rt
rt
rt
rt
rt
rt
10
0
24
24
24
24
6
72
80
94
55
99
81
85
85
78
96
88
85
90
95
81
98
97
78:22
88:12
93:7
86:14
86:14
83:17
92:8
96:4
96:4
99:1
99:1
99:1
96:4
97:3
98:2
77:23
96:4
61
3
2
8a
8a
8a
8a
8a
8a
8a
8a
8a
8a
8a
8a
8a
8a
8b
8b
3
85
77
d
2
4
5
Sc(OTf)3
6
Sc(ClO4)3$nH2O
Mn(ClO4)2$6H2O
Mn(ClO4)2$6H2O
Mn(ClO4)2$6H2O
Mg(ClO4)2$6H2O
Mg(ClO4)2$6H2O
Mg(ClO4)2$6H2O
Mn(ClO4)2$6H2O
Mn(ClO4)2$6H2O
Mn(ClO4)2$6H2O
Mn(ClO4)2$6H2O
Mg(ClO4)2$6H2O
24
21
48
72
12
24
48
12
12
24
8
7
93
95
93
85
92
92
94
95
91
94
96
8
9
10
11
12
13
14
15
16
17
a
rt
10
0
rt
rt
rt
rt
rt
6
Isolated yield.
The ratios were determined by 1H NMR (300 MHz).
The ees were determined by chiral HPLC analysis.
b
c

1816
K. Phomkeona et al. / Tetrahedron 64 (2008) 1813e1822
O
5R
R
O
O
cat. 10 mol%
MS4A
CH2Cl2, 10 °C
-
N
3R
+
O
4S
N
+
R
N
N
H
O
O
10a: R= H
10b: R= CH3
7a
11a-b
Cat., 6a.3H2O 48 h
Cat., 6b.3H2O 4 h
Cat., 6b.3H2O 24 h
11a; 92% (endo:exo = 96:4), endo 91% ee
11a; 90% (endo:exo = 96:4), endo 94% ee
11b; 88% (endo:exo = >99:1), endo 90% ee
O
5R
4S
O
O
-
cat. 10 mol%
MS4A
CH2Cl2, r.t. 48 h
N
3R
+
O
N
+
N
N
O
H
O
12
10b
13
Cat., 6a.3H2O
Cat., 6b.3H2O
99% (endo:exo = 96:4), endo 82% ee
94% (endo:exo = >99:1), endo 86% ee
Scheme 3.
of the xabox ligand to rhodium, which was different from
known tridentate-transition-metal complexes such as pyboxe
Rh(III)14 and DBFOXeNi(II)8f (Scheme 4 and Fig. 1). The
selected bond lengths and angle are summarized in Table 2.
Furthermore, on the basis of 1H NMR analysis, the proton sig-
nal of dimethyl groups on the xanthene skeleton appears as
two singlets at 1.67 (3H) and 1.90 (3H) ppm, respectively. In
addition, the proton signals of the oxazoline rings appear as
four sets of multiplet signals resulting from asymmetrical
chemical environments for each protons. As for these results,
xaboxetransition metal behaves as facial structure in solution
phase. And recently, we have clarified on the facial system
of the xabox ligand in the oxidative addition reactions on
(xabox)/rhodium(I) complex by using excess of chloroacetate
in THF, which proved to be s-symmetric on the basic of NMR
study.15 We now believe that the interaction between xaboxe
metal complex and the substrates might include a facial coor-
dination intermediate in the 1,3-D.C. reactions of nitrone with
dienophile, although different metals are used.
linear relationship was observed for 5c with all of the metal(II)
perchlorate used (Fig. 2). There was no possibility that the
mixture of doubly coordinated homo-chiral and hetero-chiral
[metal(xabox-Bn)2] or other complicated complexes could
be formed. A mixture of xabox ligand and metal(II) can
O
Cl
Cl
Rh
O
N
N
O
Cl
2.4. The correlation between enantiomeric excess of chiral
ligand and product
We also investigated the relationship of xaboxeBn 5c to
the enantioselectivity of product 9a endo and observed
a non-linear effect from this point of view, but a completely
Figure 1. Crystal structure of xabox-i-Pr-RhCl3 complex.
t-Bu
t-Bu
t-Bu
t-Bu
EtOH
60 °C, 1.5 h.
+
RhCl3(H2O)3
O
O
Rh
Cl
N
Cl
N
O
O
N
N
O
O
Cl
i-Pr
i-Pr i-Pr
i-Pr
5a
14 (83% yield)
Scheme 4. Complexation of xaboxei-Pr 5a and RhCl3(H2O)3 and it crystal structure 14.

K. Phomkeona et al. / Tetrahedron 64 (2008) 1813e1822
1817
Table 2
Selected bond length (A) and angles ( ) for [(S,S)-xaboxei-Pr]RhCl3 14
dichloromethane. After complexation, the MS were filtered
off to give a pale yellow solution, which was again filtered
via membrane filter. The catalyst solution was then added to
ꢀ
˚
O1eRh1
N2eRh1
Cl2eRh1
N1eRh1eO1
N2eRh1eCl3
N1eRh1eCl1
N2eRh1eCl2
O1eRh1eCl1
O1eRh1eCl2
2.129(7)
2.07(1)
2.331(4)
86.9(4)
92.1(3)
89.1(3)
86.8(3)
90.8(2)
91.5(2)
N1eRh1
Cl1eRh1
Cl3eRh1
O1eRh1eN2
N1eRh1eCl3
Cl1eRh1eCl2
N1eRh1eN2
Cl1eRh1eCl3
Cl2eRh1eCl3
2.05(1)
2.330(4)
2.270(4)
83.7(4)
91.6(3)
90.2(1)
93.8(4)
93.4(2)
90.1(1)
˚
pre-activated 4 A MS at room temperature. To this was added
a solution of 3-crotonoyl-2-oxazolidinone in dichloromethane
followed by addition of cyclopentadiene (10 equiv) at ꢁ78 ꢀC.
xaboxetransition-metal complexes catalyzed DielseAlder re-
actions gave [4þ2] cycloadduct in quantitative yields with
preferentially endo selectivities along with good enantioselec-
tivities. Among xabox-R ligands, the combination of xabox-i-Pr
5a with Mn(II) complex was found to be the most effective
catalyst that gave highest enantioselectivity (82% ee) for the
endo of cycloadduct 15 (entry 1). In the case of 5c with
Mn(II) gave 70% ee of 15 (entry 3). The enantioselectivity
was decreased when xaboxePh 5b was used (32% ee). Using
20 mol % catalysts does not improve the enantioselectivity
(entries 4 and 8). According to the results obtained above,
we have used xabox ligands 5a and 5c for further optimiza-
tion (entries 4e14). The enantioselectivity was significantly
affected by changing the solvent from dichloromethane to
1,2-dichloroethane and the enantioselectivity was decreased
to 36% ee (entry 7). The reaction temperature also effected
the enantioselectivity of the product, when the temperature
was increased from 0 ꢀC to room temperature. The reaction
proceeded slowly and the enantioselectivity of the cycload-
duct 15 was dramatically decreased. When the metal was
changed, the enantioselectivity of the product was also
produce only a singly coordinated complex in the preparation
of the catalyst.
2.5. Asymmetric DielseAlder reactions catalyzed xabox/
transition-metal complexes
After we achieved the good results for 1,3-D.C. reaction, we
did further studies on catalytic asymmetric DielseAlder
reactions using xaboxeR with transition metal complexes.
We attempted the typical DielseAlder reaction between cyclo-
pentadiene and 3-acryloyl-2-oxazolidinon 8b with a combina-
tion of xabox ligands 5aec and Mn(ClO4)2$6H2O as
a catalyst, the results are summarized in Table 3.
The catalysts were prepared by reacting 10 mol % of the
corresponding ligands (5aec) with Mn(ClO4)2$6H2O in the
presence of activated 4 A MS at 40 ꢀC for 4 h in
˚
Mn(ClO4)2.6H2O
100
Ni(CO4)2.6H2O
100
80
60
40
20
0
80
60
40
20
0
0
20
40
(S ,S )-xabox-Bn (% ee)
60
80
100
120
0
20
40
60
(S ,S )-xabox-Bn (% ee)
80
100
Mg(ClO4)2.6H2O
100
80
60
40
20
0
0
20
(S ,S )-xabox-Bn (% ee)
40
60
80
100
Figure 2.

1818
K. Phomkeona et al. / Tetrahedron 64 (2008) 1813e1822
Table 3
(S,S)-xaboxeR and Mn(II) catalyzed DielseAlder reaction of cyclopentadiene with acryloy-2-oxazolidinone 8b
O
O
cat. 10 mol %
MS4A
H
+
exo
+
N
O
CH2Cl2
N
O
O
(10 equiv.)
(1 equiv.)
O
8b
15
Entry
Ligand
Metal
Temp (ꢀC)
Time (h)
Yielda (%)
endo/exob
endo eec
1
5a
5b
5c
5a
5a
5a
5a
5c
5c
5c
5a
5a
5a
5a
Mn(ClO4)2$6H2O
Mn(ClO4)2$6H2O
Mn(ClO4)2$6H2O
Mn(ClO4)2$6H2O
Mn(ClO4)2$6H2O
Mn(ClO4)2$6H2O
Mn(ClO4)2$6H2O
Mn(ClO4)2$6H2O
Mn(ClO4)2$6H2O
Mn(ClO4)2$6H2O
Ni(ClO4)2$6H2O
Cu(OTf)2
ꢁ78 to rt
ꢁ78 to rt
ꢁ78 to rt
ꢁ78 to rt
0 to rt
24
24
24
24
32
42
24
24
36
43
24
24
24
24
98
>99
>99
>99
>99
93
98:2
98:2
97:3
95:5
89:11
91:9
95:5
97:3
97:3
88:12
82:18
82:18
93:7
93:7
82
32
74
76
55
19
36
70
56
27
13
48
d
9
2
3
4d
5
6
rt
7e
8d
9
ꢁ20 to rt
ꢁ78 to rt
0 to rt
97
>99
94
10
11
12
13
14
a
rt
94
ꢁ78 to rt
ꢁ78 to rt
ꢁ78 to rt
ꢁ78 to rt
>99
66
Sc(OTf)3
Mg(ClO4)2$6H2O
91
95
Isolated yield.
b
c
d
e
The ratios were determined by 1H NMR (300 MHz).
The ees were determined by chiral HPLC analysis.
Catalyst of 20 mol % was used.
1,2-Dichloroethane was used as a solvent.
decreased. Specifically changing to Cu(OTf)2 gave lower yield
of 66% with 48% ee (entry 12). Ni(II), Mg(II), and Sc(OTf)2
gave very low enantiomeric excess of endo product in 13% ee,
9% ee and 1% ee, respectively (entries 11, 13, and 14).
Unfortunately, this xabox/Mn(II) complexes can work well
only in asymmetric DeA reaction of cyclopentadiene and very
active dienophile such as 3-acryloyl-2-oxazolidionone, but in
the case of 3-crotonoyl-2-oxazolidionone and 3-methacry-
loyl-2-oxazolidinone, the reaction rate was very slow and
gave only small amount of cycloadducts.
and CH2Cl2 (anhydrous) are commercially available from Kanto
Chemical Co. Ltd, and were used without further purification. All
reagents were of reagent grade and purified when necessary. Re-
actionsweremonitoredbyTLCusing250 mmMerck(Art. 5715)
precoated silica gel. Flash column chromatography was per-
formed over Merck (Art. 7734) silica gel. Melting points were
measured on a Yanaco MP-J3melting point apparatus and are un-
1
corrected. H and 13C NMR spectra were recorded on Varian
Mercury-300 (300 MHz) spectrometer. 1H NMR chemical shifts
are reported as d values (ppm) relative to internal tetramethyl-
silane and splitting patterns are designated as: s¼singlet,
d¼doublet, t¼triplet, q¼quartet, m¼multiplet, br¼broad. Cou-
pling constants are given in hertz. IR spectra were recorded
with JASCO FT/IR-230 spectrometer and are reported in recipro-
cal centimeter (cmꢁ1). Elemental analyzes were performed with
Yanagimoto MT-3 CHN corder. Optical rotations were measured
on JASCO DIP-140 polarimeter at the sodium D line (1 mL sam-
ple cell). High performance liquid chromatographic (HPLC)
analysis was performed with a JASCO PU-980 HPLC pump,
UV-975 and 980 UV/VIS detector using DAICEL CHIRALCEL
OD, CHIRALCEL OD-H, CHIRALPAK AD and CHIRALPAK
AS columns. Visualization was accomplished by UV light
(254 nm), anisaldehyde, and phosphomolybdic acid.
3. Conclusion
We found a novel catalytic system for asymmetric 1,3-D.C.
reaction of nitrones with oxazolidinone and DielseAlder reac-
tion of cyclopentadiene with acryloyloxazolidinone by the use
of a xaboxeMn(II) or Mg(II) complex resulted in good to excel-
lent stereoselectivities. X-ray analysis of the complex revealed
a facial coordination of xabox ligand to metal, which may
give information on the mechanism of both 1,3-D.C. reactions
and DielseAlder reactions for the transition state. A series of
tridentate chiral xanthene backbones, xabox, can be used for
other catalytic asymmetric reactions as new chiral inducers.
4. Experimental section
4.2. Synthesis of ligand and xaboxeRhCl3 complex
4.1. General methods
4.2.1. 4,5-Bis[40-(S)-iso-propyl-20-oxazolin-20-yl]-2,7-di-
tert-butyl-9,9-dimethyl-xanthene (S,S)-xaboxei-Pr 5a
A mixture of xanthene dicarboxylic acid 1 (1.0 g,
2.44 mmol) and thionyl chloride (15 mL) was refluxed for
All reactions were carried out under nitrogen atmosphere.
Common solvents were purified before use. THF (anhydrous)

K. Phomkeona et al. / Tetrahedron 64 (2008) 1813e1822
1819
3 h. Thionyl chloride was removed under reduced pressure to
give the acid chloride as a white solid. A CHCl3 (20 mL) so-
lution of the acid chloride was then added to the solution of
2-aminoethanol (L-valinon, 622 mg, 6.025 mmol) in CHCl3
(15 mL). The mixture was stirred for 2.5 h at room tempera-
ture. After concentration of the solvent, the residue was puri-
fied by silica-gel column chromatography and eluted with
hexane/ethyl acetate 10:1 to ethyl acetate only to give xan-
thene diamide alcohol 4a of 1.21 g (2.08 mmol, 85.2%) as
white solid; mp¼117.4 ꢀC; 1H NMR (300 MHz, CDCl3)
d 7.75 (d, J¼2.5 Hz, 2H), 7.56 (d, J¼2.5 Hz, 2H), 7.29e
7.21 (m, 2H), 4.11e3.72 (m, 8H), 2.22e2.04 (m, 2H), 1.67
(s, 18H), 1.08 (d, J¼6.6 Hz, 6H), 1.01 (d, J¼6.6 Hz, 6H) ppm;
13C NMR (75 MHz, CDCl3) d 167.44, 146.08, 145.79, 130.18,
126.11, 125.63, 121.98, 63.51, 57.77, 34.6, 34.55, 32.78, 31.40,
29.08, 19.90, 19.41 ppm; IR (KBr): n¼3280, 2963, 2873, 1718,
(s, 18H) ppm; 13C NMR (75 MHz, CDCl3) d 167.12, 146.11,
146.02, 139.56, 130.22, 128.66, 127.44, 126.91, 126.23, 125.93,
121.65, 65.49, 56.75, 34.59, 34.54, 32.72 ppm; IR (KBr):
n¼3299, 2962, 2871, 1640, 1525, 1441, 1267, 1130, 699 cmꢁ1
.
To a solution of the xanthene diamide alcohol 4b (1.235 g,
2.08 mmol) in dichloromethane (20 mL) was added triethyl-
amine (2.7 mL) and then methanesulfonyl chloride (0.323 mL,
4.18 mmol). The mixture was stirred for 5 h at room tempera-
ture. The mixture was poured into aq K2CO3 solution (2 N) at
0 ꢀC, and was extracted with dichloromethane. After the or-
ganic layer was dried over Na2SO4 and concentrated, the res-
idue was purified by recrystallization with dichloromethane
and ether to give the xanthene bisoxazoline (xabox) 5b
(1144 mg, 2.10 mmol) in 86.06% yield (total yield, 86.77%)
as white solid; [a]D18.5 ꢁ38.2 (c 1.06, CH3OH); mp¼176.9 ꢀC;
1H NMR (300 MHz, CDCl3) d 7.70 (d, J¼2.5 Hz, 2H), 7.55
(d, J¼2.5 Hz, 2H), 7.324e7.36 (m, 10H), 5.27 (dd, J¼10.2,
8.2 Hz, 2H), 4.52 (dd, J¼10.2, 8.2 Hz, 2H), 4.52 (dd, J¼
10.2, 8.2 Hz, 2H), 4.05 (d, J¼8.2 Hz, 2H), 1.68 (s, 6H), 1.34
(s, 18H) ppm; 13C NMR (75 MHz, CDCl3) d 165.07, 147.30,
145.61, 142.77, 130.59, 128.80, 127.59, 126.94, 126.63,
125.60, 116.41, 75.24, 70.02, 34.89, 34.66, 32.17, 31.55 ppm;
IR (KBr): n¼2963, 2884, 1650, 1446, 1362, 1267, 1093, 988,
757, 700 cmꢁ1. Anal. Calcd for C41H44N2O3: C, 80.31; H,
7.24; N, 4.57. Found: C, 80.31; H, 7.32; N, 4.49.
1629, 1534, 1440, 1364, 1268, 1128, 1080, 859 cmꢁ1
.
To a solution of the xanthene diamide alcohol 4a (1.21 g,
2.08 mmol) in dichloromethane (20 mL) were added triethyl-
amine (2.9 mL) and then methanesulfonyl chloride
(0.354 mL, 4.58 mmol). The mixture was stirred for 5 h at
room temperature. The mixture was poured into aq K2CO3
solution (2 N) at 0 ꢀC and was extracted with dichlorome-
thane. After the organic layer was dried over Na2SO4 and con-
centrated, the residue was purified by recrystallization with
dichloromethane and ether to give the xanthene bisoxazoline
(xabox) 5a (1107.0 mg, 2.03 mmol) in 97.8% yield (total
yield, 83%) as white solid; [a]2D3.0 ꢁ3.7 (c 0.995, CH3OH);
mp¼237.5 ꢀC; 1H NMR (300 MHz, CDCl3) d 7.57 (d, J¼
2.5 Hz, 2H), 7.48 (d, J¼2.5 Hz, 2H), 4.47 (dd, J¼9.6, 8.0 Hz,
2H), 4.20 (t, J¼8.0 Hz, 2H), 4.10 (ddd, J¼9.6, 8.0, 6.1 Hz,
2H), 1.94 (dsept, J¼6.6, 6.1 Hz, 2H), 1.62 (s, 18H), 1.08 (d,
J¼6.6 Hz, 6H), 0.97 (d, J¼6.6 Hz, 6H) ppm; 13C NMR
(75 MHz, CDCl3) d 163.73, 147.08, 145.33, 130.46, 126.29,
125.17, 116.70, 75.55, 70.53, 34.77, 34.53, 32.09, 32.00,
31.47, 19.33, 18.17 ppm; IR (KBr): n¼3382, 2962, 1659, 1450,
1364, 1275, 1242, 1133, 1094, 984, 891, 863 cmꢁ1. Anal.
Calcd for C43H48N2O3: C, 77.17; H, 8.88; N, 5.14; C, 75.96;
H, 8.78; N, 5.00 (1/2H2O). Found: C, 75.91; H, 8.92; N, 5.06.
4.2.3. 4,5-Bis[40-(S)-benzyl-20-oxazolin-20-yl]-2,7-di-tert-
butyl-9,9-dimethylxanthene (S,S)-xaboxeBn 5c
A mixture of the xanthene dicarboxylic acid 1 (1.0 g,
2.44 mmol) and thionyl chloride (15 mL) was refluxed for
3 h. Thionyl chloride was removed under reduced pressure
to give the acid chloride as a white solid. A CHCl3 (20 mL)
solution of the acid chloride was then added to solution of
2-aminoethanol (L-phenylalaninol, 834 mg, 5.52 mmol) in
CHCl3 (15 mL). The mixture was stirred for 3.5 h at room
temperature. After concentration of the solvent, the residue
was purified by silica-gel column chromatography and eluted
with hexane/ethyl acetate 10:1 to ethyl acetate only to give the
xanthene diamide alcohol 4c of 1.172 g (1.73 mmol, 71.3%) as
white solid; mp¼107.0 ꢀC; 1H NMR (300 MHz, CDCl3)
d 7.58 (d, J¼2.4 Hz, 2H), 7.53 (d, J¼2.4 Hz, 2H), 7.39e
7.20 (m), 4.62e4.58 (m, 2H), 3.85 (dd, J¼4.0, 11.6 Hz, 2H),
3.70 (dd, J¼5.6, 11.6 Hz, 2H), 3.17 (dd, J¼7.6, 13.6 Hz,
2H), 3.03 (dd, J¼6.8, 13.6 Hz, 2H), 2.57e2.39 (m, 2H), 1.63
(s, 6H), 16.3 (s, 6H), 1.32 (s, 18H) ppm; 13C NMR (75 MHz,
CDCl3) d 167.14, 146.13, 145.8, 138.09, 130.18, 129.49,
128.65, 126.62, 126.06, 125.60, 121.69, 63.98, 53.51, 37.14,
34.64, 34.54, 32.59, 31.41 ppm; IR (KBr): n¼3319, 2961,
2870, 1634, 1527, 1441, 1364, 1268, 1130, 1039, 891, 855,
749, 700 cmꢁ1. Anal. Calcd for C41H44N2O3: C, 76.30; H,
7.74; N, 4.14. Found: C, 76.32; H, 7.75; N, 4.15.
4.2.2. 4,5-Bis[40-(S)-phenyl-20-oxazolin-20-yl]-2,7-di-tert-
butyl-9,9-dimethylxanthene (S,S)-xaboxePh 5b
A mixture of the xanthene dicarboxylic acid 1 (1.0 g,
2.44 mmol) and thionyl chloride (15 mL) was refluxed for
3 h. Thionyl chloride was removed under reduced pressure
to give the acid chloride as a white solid. A CHCl3 (20 mL)
solution of the acid chloride was then added to solution of
2-aminoethanol ((S)-(þ)-2-phenyl, 830 mg, 6.05 mmol) in
CHCl3 (15 mL). The mixture was stirred for 3.5 h at room
temperature. After concentration of the solvent, the residue
was purified by silica-gel column chromatography and eluted
with hexane/ethyl acetate 10:1 to ethyl acetate only to give the
xanthene diamide alcohol 4b of 1.235 g (2.08 mmol, 78.7%)
To a solution of the xanthene diamide alcohol 4c (1.172 g,
1.73 mmol) in dichloromethane (20 mL) were added triethyl-
amine (2.3 mL) and then methanesulfonyl chloride
(0.323 mL, 4.18 mmol). The mixture was stirred for 5 h at
room temperature. The mixture was poured into aq K2CO3
solution (2 N) at 0 ꢀC and was extracted with
1
as white solid; mp¼124.1 ꢀC; H NMR (300 MHz, CDCl3)
d 7.85 (d, J¼7.7 Hz, 2H), 7.78 (d, J¼2.5 Hz, 2H), 7.57 (d,
J¼2.5 Hz, 2H), 7.40e7.22 (m, 10H), 5.31e5.25 (m, 2H),
4.05e3.92 (m, 4H), 3.61e3.57 (m, 2H), 1.67 (s, 6H), 1.34

1820
K. Phomkeona et al. / Tetrahedron 64 (2008) 1813e1822
˚
the presence of activated 4 A MS (250 mg). After cooling
the flask to room temperature, the pale light yellow suspension
was filtered off via a membrane filter. The filtrate was added to
dichloromethane. After the organic layer was dried over
Na2SO4 and concentrated, the residue was purified by recrys-
tallization with dichloromethane and ether to give the xan-
thene bisoxazoline (xabox) 5c (1043 mg, 1.63 mmol) in
98.4% yield (total yield, 66.80%) as white solid; [a]D20.4
˚
activated 4 A MS (250 mg). To this were added oxazolidinone
8b (35.3 mg, 0.25 mmol) and nitrone 7a (49.3 mg, 0.25 mmol)
at room temperature. The resulting mixture was stirred for 6 h
at room temperature. The reaction was monitored by TLC
(eluted with CH2Cl2). At the end of this period, the reaction
mixture was purified by flask column chromatography on sil-
ica gel (eluted with CH2Cl2) to afforded the resulting product
9e (81.7 mg, 0.242 mmol) as a white solid with 96.8% yield
(endo: 3R, 4S), endo/exo¼94:6, 95.8% ee. The endo/exo ratio
1
þ24.8 (c 1.03, CH3OH); mp¼194.2 ꢀC; H NMR (300 MHz,
CDCl3) d 7.58 (d, J¼2.5 Hz, 2H), 7.50 (d, J¼2.5 Hz, 2H),
7.33e7.19 (m, 10H), 4.60 (dddd, J¼9.3, 9.1, 8.0, 4.4 Hz,
2H), 4.37 (dd, J¼9.3, 8.4 Hz, 2H), 4.18 (dd, J¼8.4, 8.0 Hz,
2H), 13.32 (dd, J¼13.7, 4.4 Hz, 2H), 2.79 (dd, J¼13.7,
9.1 Hz, 2H), 1.63 (s, 6H), 1.34 (s, 18H) ppm; 13C NMR
(75 MHz, CDCl3) d 164.02, 147.29, 145.43, 138.14, 130.67,
129.30, 128.69, 126.58, 126.28, 125.18, 116.46, 72.19,
67.92, 41.82, 34.87, 34.59, 31.74, 31.49 ppm; IR(KBr):
n¼3420, 2963, 2906, 1652, 1446, 1364, 1243, 1094, 986,
860, 702 cmꢁ1. Anal. Calcd for C43H48N2O3: C, 80.59; H,
7.55; N, 4.37. Found: C, 80.30; H, 7.49; N, 4.32.
1
was determined by H NMR spectrum and the enantiomeric
purity was determined by HPLC analysis (DAICEL CHIRAL-
PAK AD, 254 nm (UV), eluted with hexane/IPA¼5:1, flow
rate¼1 mL/min).
1
The H and 13C NMR of compounds 9aec,7e 9d,13c 9e,16
11a,b,13c 13,7e and 158f are referred to the literature.
4.3. 4,5-Bis[40-(R)-benzyl-20-oxazolin-20-yl]-2,7-di-tert-butyl-
9,9-dimethylxanthene (R,R)-xaboxeBn 5c0
4.4.1. (3R,4S)-3-Phenyl-4-(2-oxo-1,3-oxazolidine-1-carbo-
nyl)-2-phenylisoxazolidine (9e)16
The synthesis procedure was same as (S,S)-xaboxeBn 5c;
Table 1, entry 17; 97% yield, 96:4 (endo/exo ratio), 96% ee
determined by HPLC analysis (DAICEL CHIRALPAK AD,
UV¼254 nm, eluted with hexane/IPA¼5:1, flow rate¼1 mL/
min); tminor¼55.30 min (3S,4R,5S), tmajor¼46.04 min (3R,4S).
1
[a]2D3.5 ꢁ24.7 (c 1.04, CH3OH); mp¼192.8 ꢀC; H and 13C
NMR are the same as 3c; IR (KBr): n¼3419, 3029, 2964,
1651, 1452, 1365, 1276, 1093, 984, 928, 891, 862, 729,
700 cmꢁ1. Anal. Calcd for C43H48N2O3: C, 80.59; H, 7.55;
N, 4.37. Found: C, 80.41; H, 7.46; N, 4.27.
4.5. Typical procedure for nitrone 1,3-dipolar cycloaddition
reaction with crotonoyl oxazolidinone catalyzed by (S,S)-
xaboxeBn/Mn(II) complex
4.3.1. [(S,S)-xaboxei-Pr]RhCl3 14
A mixture of (S,S)-xaboxei-Pr 5a (54.5 mg, 0.1 mmol) and
RhCl3(H2O)3 (26.3 mg, 0.1 mmol) in ethanol was stirred for
2 h at 60 ꢀC to give light brown precipitate, which was filtered
and washed with hexane and ether. The solid was dried under
reduced pressure to give the complex 14 (62.9 mg,
0.0834 mmol) in 83.4% yield; light brown solid; mp¼
A mixture of Mn(ClO4)2$6H2O (9.0 mg, 0.025 mmol) and
(S,S)-xaboxeBn 5c (16.0 mg, 0.025 mmol) in CH2Cl2
(1.5 mL) was refluxed for 4 h under nitrogen atmosphere in
˚
the presence of activated 4 A MS (250 mg). After cooling
the flask to room temperature, the pale light yellow suspension
was filtered off via a membrane filter. The filtrate was added to
1
247.3 ꢀC; H NMR (300 MHz, CDCl3) d 7.84 (d, J¼2.2 Hz,
˚
activate the 4 A MS (250 mg). To this were added oxazoli-
1H), 7.80 (d, J¼2.2 Hz, 1H), 4.62 (t, J¼2.5 Hz, 2H), 5.26e
5.20 (m, 1H), 4.82e4.77 (m, 2H), 4.66e4.55 (m, 2H), 4.38
(m, 1H), 3.09e2.99 (m, 1H), 2.41e2.31 (m, 1H), 1.90 (s, 3H),
1.67 (s, 3H), 1.35 (s, 9H), 1.33 (s, 9H), 1.03 (d, J¼7.1 Hz, 3H),
0.96 (d, J¼7.1 Hz, 3H), 0.88 (d, J¼6.9 Hz, 3H), 0.81 (d,
J¼6.9 Hz, 3H) ppm; 13C NMR (75 MHz, CDCl3) d 163.64,
161.10, 149.53, 149.43, 149.31, 148.83, 137.58, 137.01,
126.70, 125.60, 126.63, 125.99, 124.87, 115.10, 114.05,
73.69, 68.18, 68.02, 36.23, 35.06, 31.35, 30.72, 29.89,
29.15, 22.79, 18.87, 18.81, 15.12, 14.63 ppm; IR (KBr):
n¼3473, 2964, 1621, 1454, 1376, 1236, 1188, 1097, 999,
956, 857, 729, 652 cmꢁ1. Anal. Calcd for C35H46Cl3N2O3:
C, 55.75; H, 6.42; N, 3.72. Found: C, 55.70; H, 6.42; N, 3.60.
dinone 8a (38.9 mg, 0.25 mmol) and nitrone 7a (49.3 mg,
0.25 mmol) at 10 ꢀC. The resulting mixture was stirred at
48 h at 10 ꢀC. The reaction was monitored by TLC (eluted
with CH2Cl2). At the end of this period, the reaction mixture
was purified by flask column chromatography on silica gel
(eluted with CH2Cl2) to afford the resulting product 9a
(68.7 mg, 0.195 mmol) as a white solid with 85% yield
(endo: 3R,4S,5R), endo/exo¼96:4, 95.0% ee. The endo/exo
1
ratio was determined by H NMR spectrum and the enantio-
meric purity was determined by HPLC analysis (DAICEL
CHIRALPAK AD, 254 nm (UV), eluted with hexane/
IPA¼5:1, flow rate¼1 mL/min).
4.4. Typical procedure for nitrone 1,3-dipolar cycloaddition
reaction with acryloyl oxazolidinone catalyzed by (S,S)-
xaboxeBn/Mg(II) complex
4.5.1. (3R,4S,5R)-5-Methyl-3-phenyl-4-(2-oxo-1,3-oxazo-
lidine-3-carbonyl)-2-phenylisoxazolidine (9a)7e
Table 1, entry 11; 88% yield, 99:1 (endo/exo ratio), 92% ee
determined by HPLC analysis (DAICEL CHIRALPAK OD,
UV¼254 nm, eluted with hexane/IPA¼5:1, flow rate¼1 mL/
A mixture of Mg(ClO4)2$6H2O (8.3 mg, 0.025 mmol) and
(S,S)-xaboxeBn 5c (16.0 mg, 0.025 mmol) in CH2Cl2
(1.5 mL) was refluxed for 4 h under nitrogen atmosphere in
min);
(3R,4S,5R).
tminor¼13.20 min
(3S,4R,5S),
tmajor¼19.24 min

K. Phomkeona et al. / Tetrahedron 64 (2008) 1813e1822
1821
4.5.2. (3R,4S,5R)-5-Methyl-3-p-methylphenyl-4-(2-oxo-
1,3-oxazolidine-3-carbonyl)-2-phenylisoxazolidine (9b)7e
Table 1, entry 13; 90% yield, 96:4 (endo/exo ratio), 94% ee
determined by HPLC analysis (DAICEL CHIRALPAK OD-H,
UV¼254 nm, eluted with hexane/IPA¼9:1, flow rate¼1 mL/
min); tminor¼29.9 min (3S,4R,5S), tmajor¼20.2 min (3R,4S,5R).
At the end of this period, the reaction mixture was purified
by flask column chromatography on silica gel (eluted with
CH2Cl2) to afford the resulting product 15 (73.38 mg,
0.354 mmol) as a white solid with 98.36% yield (endo:
1S,2S,4S), endo/exo¼98:2, 82% ee. The endo/exo ratio was de-
1
termined by H NMR spectrum and the enantiomeric purity
was determined by HPLC analysis (DAICEL CHIRALPAK
OD, 240 nm (UV), eluted with hexane/IPA¼90:1, flow
rate¼1 mL/min).
4.5.3. (3R,4S,5R)-5-Methyl-3-p-methoxylphenyl-4-(2-oxo-
1,3-oxazolidine-3-carbonyl)-2-phenylisoxazolidine (9c)7e
Table 1, entry 16; 95% yield, 97:3 (endo/exo ratio), 95% ee
determined by HPLC analysis (DAICEL CHIRALPAK AD,
UV¼254 nm, eluted with hexane/IPA¼5:1, flow rate¼1 mL/
min); tminor¼36.5 min (3S,4R,5S), tmajor¼27.2 min (3R,4S,5R).
4.6.1. (1S,2S,4S)-3-Bicyclo[2.2.1]hept-5-en-2-
oxazolidinone (15)8f
Table 2, entry 1; 98% yield, 98:2 (endo/exo ratio), 82% ee
determined by HPLC analysis (DAICEL CHIRALPAK OD,
UV¼240 nm, eluted with hexane/IPA¼90:1, flow rate¼
1 mL/min); tminor¼64.99 min (1R,2R,4R), tmajor¼72.96 min
(1S,2S,4S).
4.5.4. (3R,4S,5R)-5-Methyl-3-p-bromophenyl-4-(2-oxo-
1,3-oxazolidine-3-carbonyl)-2-phenylisoxazolidine (9d)13c
Table 1, entry 15; 81% yield; 98:2 (endo/exo ratio); 91% ee
determined by HPLC analysis (DAICEL CHIRALPAK AD,
UV¼254 nm, eluted with hexane/IPA¼3:1, flow rate¼1 mL/
min); tminor¼12.4 min (3S,4R,5S), tmajor¼17.2 min (3R,4S,5R).
4.7. X-ray analysis of [(S,S)-xaboxei-Pr]RhCl3
A single crystal (0.15ꢂ0.2ꢂ0.6 mm) was obtained by re-
4.5.5. (3R,4S)-3-Phenyl-4-(2-oxo-pyrrolidine-1-carbonyl)-
2-phenylisoxazolidine (11a)13c
crystallization from CHCl3/ether/hexane. Selected bond
˚
˚
lengths and angle: 2.129 A, RheO; 2.05 A, RheN1; 2.07 A,
˚
Yield 90%, 96:4 (endo/exo ratio), 94% ee determined by
HPLC analysis (DAICEL CHIRALPAK AD, UV¼254 nm,
˚
˚
˚
RheN2; 2.330 A, RheCl1; 2.331 A, RheCl2; 2.270 A,
RheCl3; 93.8ꢀ, N1eRheN2; 86.9ꢀ, N1eRheO; 83.7ꢀ,
N2eRheO; 89.1ꢀ, N1eRheCl1; 178.2ꢀ, N1eRheCl2; 91.6ꢀ,
N1eRheCl3; 173.7ꢀ, N2eRheCl1; 86.8ꢀ, N2eRheCl2;
92.1ꢀ, N2eRheCl3; 90.8ꢀ, OeRheCl1; 91.5ꢀ, OeRheCl2;
175.5ꢀ, OeRheCl3.
eluted with hexane/IPA¼5:1, flow rate¼1 mL/min); tminor
31.0 min (3S,4R,5S), tmajor¼35.3 min (3R,4S,5R).
¼
4.5.6. (3R,4S,5R)-5-Methyl-3-phenyl-4-(2-oxo-pyrrolidine-
1-carbonyl)-2-phenylisoxazolidine (11b)13c
Yield 88%, >99:1 (endo/exo ratio), 90% ee determined by
HPLC analysis (DAICEL CHIRALPAK AD, UV¼254 nm,
4.7.1. Crystal data
C39H48N2O3Cl6Rh, orthorhombic, space group P212121
eluted with hexane/IPA¼5:1, flow rate¼1 mL/min); tminor
30.1 min (3S,4R,5S), tmajor¼22.7 min (3R,4S,5R).
¼
˚
˚
˚
(No. 19), a¼16:735(2) A, b¼27:482(6) A, c¼9:067(2) A,
V¼4169(1) A , rcalcd¼1:447 g cmꢁ1
,
Z¼4, m¼8:31 cmꢁ1
.
3
˚
The crystal contains a 1:1 mole ratio of 8 and CHCl3: the sol-
vent molecules in the crystal were omitted in Figure 1. The
intensity data (28:99<#<29:88ꢀ) were collected on a Riigaku
AFC-7R diffractometer with graphite-monochromated Mo Ka
4.5.7. (3R,4S,5R)-3-Phenyl-4-(2-oxo-pyrrolidine-1-carbonyl)-
2-benzylisoxazolidine (13)7e
Yield 94%, >99:1 (endo/exo ratio), 86% ee determined by
HPLC analysis (DAICEL CHIRALPAK AD, UV¼254 nm,
˚
radiation (l¼0:71069 A) and the structure was solved by Pat-
eluted with hexane/IPA¼5:1, flow rate¼1 mL/min); tminor
31.7 min (3S,4R,5S), tmajor¼46.6 min (3R,4S,5R).
¼
terson methods (DIRDIF92, PATTY). The final cycle of refine-
ment was based on 2686 observed reflections (I>3:00s(I)) and
433 variable parameters and converged with R¼5.6% and
Rw¼6.1%. Crystallographic data for 4 have been deposited
with the Cambridge Crystallographic Data Center as supple-
mentary publication number CCDC-199961. Copies of the
data can be obtained on application to CCDC, 12 Union
Road, Cambridge CB21EZ, UK [fax: þ44(0) 1223336033 or
e-mail: deposit@ccdc.cam.ac.uk].
4.6. Typical procedure for DielseAlder reaction of
cyclopentadiene with acryloyl oxazolidinone catalyzed
by (S,S)-xaboxei-Pr/Mn(II) complex
A mixture of Mn(ClO4)2$6H2O (52 mg, 0.144 mmol) and
(S,S)-xaboxei-Pr 5c (20 mg, 0.036 mmol) in CH2Cl2
(1.5 mL) was refluxed for 4 h under nitrogen atmosphere in
˚
the presence of activated 4 A MS (250 mg). After cooling
the flask to room temperature, the pale light yellow suspension
was filtered off via a membrane filter. The filtrate was added to
References and notes
˚
activate 4 A MS (250 mg). To this was added oxazolidinone
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