Highly enantioselective homogeneous catalysis of chiral rare earth phosphates in the hetero-Diels-Alder reaction

Article abstract of DOI:10.1016/S0040-4039(03)01460-6

Two types of novel rare earth (RE) complexes were synthesized and used as a chiral Lewis acid catalyst for the hetero-Diels-Alder reaction of carbonyl compounds with the Danishefsky's diene under homogeneous conditions. The Y[(R)-H₈-BNP]_3<

Full text of DOI:10.1016/S0040-4039(03)01460-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 6129–6132
Highly enantioselective homogeneous catalysis of chiral rare
earth phosphates in the hetero-Diels–Alder reaction
Hiroshi Furuno,a Takeshi Kambara,b Yumiko Tanaka,a Takeshi Hanamoto,a Takumi Kagawab and
Junji Inanagaa,*
aInstitute for Materials Chemistry and Engineering (IMCE), Kyushu University, Hakozaki, Higashi-ku, Fukuoka 812-8581,
Japan
bNanyo Research Laboratory, Tosoh Co. Ltd, Kaisei-cho, Shin-nanyo, Yamaguchi 746-8501, Japan
Received 7 May 2003; revised 4 June 2003; accepted 6 June 2003
Abstract—Two types of novel rare earth (RE) complexes were synthesized and used as a chiral Lewis acid catalyst for the
hetero-Diels–Alder reaction of carbonyl compounds with the Danishefsky’s diene under homogeneous conditions. The Y[(R)-H8-
BNP]3 (3-Y)-catalyzed reaction of aromatic aldehydes and the Yb[(R)-BNP]3 (1-Yb)-catalyzed reaction of phenylglyoxylates
afforded the corresponding cycloadducts with excellent optical purities (up to 99% ee) in high yields at room temperature. The
successful recycling uses of the scandium catalyst (3-Sc) are also described.
© 2003 Elsevier Ltd. All rights reserved.
The recent development of chiral rare earth metal com-
plexes as Lewis acid catalysts is of significant interest in
asymmetric synthesis.1 While some of them are isolable
and storable in air, no successful example of a reusable
chiral rare earth complex as a homogeneous Lewis acid
catalyst has been reported although a homogeneous
catalyst is generally thought to be superior to the
corresponding heterogeneous one in terms of efficiency
and reproducibility of the reaction. We recently synthe-
sized a series of rare earth metal (RE) complexes having
(R)-1,1%-binaphthyl-2,2%-diyl phosphate (BNP) as a chi-
ral ligand, RE[(R)-BNP]3 (1-RE, Fig. 1),2 and found
that the Yb[(R)-BNP]3 (1-Yb)-catalyzed hetero-Diels–
Alder reaction of aldehydes 7 with the Danishefsky’s
diene 8 proceeded, in the presence of 2,6-lutidine, under
homogeneous conditions in dichloromethane at room
temperature to afford the corresponding cycloadducts 9
with high ee’s (up to 94% ee) and high yields.3–6 How-
ever, the presence of basic additives such as 2,6-lutidine
made the reuse of the Lewis acid catalyst difficult.
Actually, both the enantioselectivity and the chemical
yield were significantly decreased in the reaction using
the recovered catalyst. Therefore, we prepared two
novel chiral rare earth phosphates, 2-RE and 3-RE,
expecting that the 2,6-xylyl substituents on the binaph-
thyl ring of the former or the octahydrobinaphthyl
ring7 of the latter would play an important role not
only in increasing the solubility of the catalysts in
dichloromethane without 2,6-lutidine, but also in
providing a more effective chiral space for the reaction
than the catalyst 1-RE. Also, these catalysts were
expected to be easily recoverable after the reaction and
could be successfully reused without decreasing the
original activity.
In this paper, we report the 3-Y catalyzed highly enan-
tioselective hetero-Diels–Alder reaction of aromatic
aldehydes with the Danishefsky’s diene and also the
reaction of phenylglyoxylates catalyzed by 1-Yb, both
of which proceeded under homogeneous conditions at
room temperature without any additives.
Figure 1. The chiral rare earth phosphates synthesized.
Keywords: asymmetric hetero-Diels–Alder reaction; chiral rare earth
metal phosphate; Lewis acid catalyst; reusable catalyst.
* Corresponding author. Tel.: +81-92-642-2733; fax: +81-92-642-2715;
e-mail: inanaga@ms.ifoc.kyushu-u.ac.jp
The chiral ligand precursor of 2, (R)-6,6%-di(2,6-xylyl)-
1,1%-binaphthyl-2,2%-diyl hydrogen phosphate 6, was
0040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)01460-6

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H. Furuno et al. / Tetrahedron Letters 44 (2003) 6129–6132
tion compared with the 1-Yb catalyzed reaction thus
affording 9 with an S configuration, although the two
xylyl groups at the 6,6%-positions of the ligand of 2-Yb
appeared to be rather far from the catalytic center
(entries 5 versus 3 or 4). On the other hand, the
3-RE-catalyzed reactions afforded the cycloadduct 9
with an R configuration in excellent ee’s (entries 6–16).
The catalyst prepared in situ (Method C) showed
almost the same activity and enantioselectivity as the
once-isolated one (Method B) (entries 13 versus 12).
The effect of the metal ions of the complex 3-RE on the
enantioselectivity was not high, but the heavy lan-
thanides tended to afford higher ee’s than the lighter
ones (entries 10–11 versus 15–16). The yttrium complex
3-Y afforded the highest ee of 99% (entry 12).
Based on the fact that the complex 1-Yb becomes
soluble in dichloromethane with the addition of 1
equiv. of a Lewis base like 2,6-lutidine, we anticipated
that the reaction of glyoxylates would be effectively
catalyzed by 1-Yb under homogeneous conditions
because of the favorable coordination of the substrate
to the catalyst as a bidentate ligand. As expected and
shown in Table 2, 1-Yb worked as a highly efficient
homogeneous catalyst for the asymmetric reaction of
phenylglyoxylates 10 with the diene 8 to give almost
enantiopure cycloadducts 11 in excellent yields (entries
1 and 5). Thus, quaternary asymmetric carbon centers
Scheme 1. Synthesis of the novel chiral phosphoric acid 6.
Reagent and conditions: (a) BnBr, NaH, THF–DMF, rt, 94%;
(b) ArB(OH)2, Pd(PPh3)4, Ba(OH)2, DME–H2O, 80°C, 99%;
(c) H2, Pd/C, i-Pr2NEt, AcOEt, rt, 95%; (d) Cl3PO, NEt3,
CH2Cl2, rt; (e) Na2CO3, H2O, 80°C; (f) HCl(aq.), 95°C, 33%
from 5 after recrystallization (ethanol).
Table 1. Asymmetric hetero-Diels–Alder reaction of 7
with 8 catalyzed by 1–3
Entry
Catalyst
Method
Yield (%)a
Ee (%)b
1c
2d
3c
4d
5
1-Sc
1-Sc
1-Yb
1-Yb
2-Yb
3-Sc
3-Sc
3-Sc
3-Yb
3-Yb
3-Er
3-Y
A
A
A
A
A
A
A
B
A
B
B
B
C
B
B
B
93
94
77
94
76
99
99
64
92
73
76
81
80
58
79
68
56
81
70
89
ent-57
93
6
7e
8
94f
84
Scheme 2. The preparation methods of the catalysts.
9
91
98
98
99
98
91
93
92
10
11
12
13
14
15
16
synthesized from the commercially available (R)-6,6%-
dibromo-1,1%-bi-2-naphthol 4 in six steps (Scheme 1),
and that of 3, (R)-H8-BNP–H, was similarly prepared
via the phosphorylation of (R)-octahydro-1,1%-bi-2-
naphthol.8 The corresponding rare earth complexes 1–3
were prepared using three types of methods according
to Scheme 2.9,10
3-Y
3-Dy
3-Sm
3-La
The reaction proceeded under homogeneous conditions unless other-
wise noted.
a Isolated yield.
As we expected, the asymmetric hetero-Diels–Alder
reaction of benzaldehyde 7 with the Danishefsky’s
diene 8 catalyzed by complex 2 or 3 proceeded under
homogeneous conditions in dichloromethane without
any additives (Table 1). It is interesting to note that the
catalyst 2-Yb caused the opposite sense of enantioselec-
b Determined by HPLC using Daicel CHIRALCEL OD except entry
7.
c The reaction proceeded under heterogeneous conditions.
d 2,6-Lutidine was used as an additive.
e 4-Methoxybenzaldehyde was used instead of 7.
f Determined by HPLC using Daicel CHIRALPAK AD.

H. Furuno et al. / Tetrahedron Letters 44 (2003) 6129–6132
6131
Table 2. Asymmetric hetero-Diels–Alder reaction of 10
with 8 catalyzed by 1-Yb
retained even in the third round of reactions thus
affording 9 with an 87% ee in 95% yield.
In conclusion, we succeeded in the development of
novel chiral rare earth metal complexes that function as
excellent homogeneous Lewis acid catalysts for the
asymmetric hetero-Diels–Alder reactions. Further
investigation into the development of reusable chiral
homogeneous Lewis acid catalysts is now in progress.
Entry
Keto Ester
Catalyst
(mol%)
Yield (%)a
Ee (%)b
Acknowledgements
1
10a
10a
10a
10a
10b
10b
10
10
5
2
10
5
90
80
88
89
99
99
>99
91
>99
96
98
97
2c
3
This work was supported by a Grant-in-Aid for Scien-
tific Research on Priority Areas from the Ministry of
Education, Culture, Sports, Science and Technology,
Japan, the Japan Society for the Promotion of Science,
and also by the Kyushu University P&P Programs
‘Green Chemistry’ (to J.I.).
4
5
6
a Isolated yield.
b Determined by HPLC using chiral column (Daicel CHIRALPAK
AD).
c The reaction was carried out in the presence of 2,6-lutidine.
References
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Finally, the recycling use of the catalyst 3-Sc was
examined as shown in Figure 2. After the hetero-Diels–
Alder reaction of 7 with 8 in dichloromethane, the
solvent was evaporated. To the residue was added ether
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Figure 2. The recovery and the reuse of the catalyst 3-Sc.

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