Chiral rare earth organophosphates as homogeneous Lewis acid catalysts for the highly enantioselective hetero-Diels-Alder reactions

Article abstract of DOI:10.1016/j.tet.2003.06.011

Various trivalent rare earth-chiral phosphate complexes [(R)-1-RE, (R)-3-RE, and (R)-4-Ce] were prepared and evaluated as a Lewis acid catalyst for the asymmetric hetero-Diels-Alder reaction of aldehydes with the Danishefsky's diene. Some of them effectiv

Full text of DOI:10.1016/j.tet.2003.06.011

Tetrahedron 59 (2003) 10509–10523
Chiral rare earth organophosphates as homogeneous Lewis
acid catalysts for the highly enantioselective
hetero-Diels–Alder reactions
†
a
,
a
b
a
Hiroshi Furuno,a Tetsuji Hayano, Takeshi Kambara, Yuichi Sugimoto, Takeshi Hanamoto,
,
*
Yumiko Tanaka,a Yong Zhi Jin,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 8 May 2003; accepted 20 June 2003
Abstract—Various trivalent rare earth-chiral phosphate complexes [(R)-1-RE, (R)-3-RE, and (R)-4-Ce] were prepared and evaluated as a
Lewis acid catalyst for the asymmetric hetero-Diels–Alder reaction of aldehydes with the Danishefsky’s diene. Some of them effectively
promoted the reaction at room temperature in the presence or absence of achiral additives under homogeneous conditions to afford the
corresponding cycloadducts with high ee’s (up to 99% ee). During these reactions, remarkably high asymmetric amplifications (positive
nonlinear effects) were observed as the first example in the metal ion–chiral ligand 1:3 catalytic system. A scandium catalyst bearing the
H8-BNP ligand, (R)-3-Sc, could be recovered after the reaction and successfully reused for the next round of reactions. In addition, the
hetero-Diels–Alder reaction of a-keto esters was effectively catalyzed by the ytterbium complex, (R)-1-Yb, without any additives thus
producing the asymmetric quaternary carbon in excellent enantioselectivities (up to .99% ee).
q 2003 Elsevier Ltd. All rights reserved.
1. Introduction
without any loss of activity. Another important aspect of
rare earths is their high coordination numbers. Their large
ionic radii often allow the accommodation of seven, eight,
or nine ligands in the coordination sphere. These properties
are highly advantageous for assembling various chiral and
achiral ligands around the metal ions, thus creating an
integrated chiral space in which the stereochemistry of the
reaction may effectively be controlled. Actually, recent
intensive studies on the chiral rare earth complexes are
rapidly reporting various successful examples of the highly
efficient asymmetric reactions catalyzed by them.2,10–12 In
most cases, however, the rare earth catalysts used were
prepared in situ by mixing achiral rare earth metal salts such
as RE(OTf)3 and appropriate chiral ligands. In the present
study, we tried to develop isolable and reusable chiral rare
earth Lewis acid catalysts. For this purpose, chiral
organophosphates were employed as a ligand for the rare
earth complex catalysts since the reported pKa value of 2.3
for 1,10-binaphthyl-2,20-diyl hydrogen phosphate (BNP–
H)13 seemed to be acidic enough to let the corresponding
rare earths salts function as effective Lewis acid catalysts for
certain reactions. In this paper are described the full details
of the preparation of the RE[(R)-BNP]3-type complexes and
their application to hetero-Diels–Alder reactions.3,14,15
The trivalent state is the most stable oxidation state for the
rare earths (RE), and according to Pearson’s HSAB
classification, RE3þ ions are considered to be hard acids,
being located between Mg2þ and Ti4þ.1 The effective Lewis
acid catalysis with RE3þ ions may therefore be generally
expected. Especially noteworthy is that the RE(III) salts of
strong acids like the triflates,2 perfluoroalkylsulfonates,3–5
perchlorates,3,6 bis(perfluoroalkylsulfonyl)amides,7 and
tris(perfluoroalkylsulfonyl)methides7a–d,8 are sometimes
able to work as effective Lewis acid catalysts in the
presence of water, alcohols, or even amines, although most
traditional Lewis acids lose their activities under such
circumstances.9 Reflecting such a stability, RE Lewis acids
can often be recovered after the reactions and reused
Keywords: chiral rare earth metal complex; chiral Lewis acid catalyst;
homogeneous catalysis; enantioselective hetero-Diels–Alder reaction;
asymmetric amplification.
*
Corresponding authors. Tel.: þ81-92-642-2733; fax: þ81-92-642-2715;
e-mail: inanaga@ms.ifoc.kyushu-u.ac.jp;
furuno@ms.ifoc.kyushu-u.ac.jp
Present address. Department of Chemistry and Applied Chemistry, Saga
†
University, Honjyo-machi 1, Saga 840-8502, Japan
0040–4020/$ - see front matter q 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2003.06.011

10510
H. Furuno et al. / Tetrahedron 59 (2003) 10509–10523
2. Results and discussion
Ce, was prepared from ammonium cerium(IV) nitrate
(CAN) as shown in Scheme 1. The trivalent structure of
(R)-4-Ce was confirmed by the magnetic susceptibility
measurement. Elementary analysis of this complex
suggested that it contained 0.5 equiv. of sodium nitrate.
2.1. Preparation of the rare earth metal catalysts
A variety of chiral rare earth complexes composed of
different metal ions and chiral phosphate ligands were
prepared. As shown in Figure 1, the three complexes [(R)-1-
RE, (R)-2-RE, and (R)-3-RE] were prepared from trivalent
rare earth metal chlorides or isopropoxides and the
corresponding chiral phosphates according to methods A–
D. For 0instance, a series of rare earth metal complexes of
(R)-1,1 -binaphyly-2,20-diyl phosphate, abbreviated RE[(R)-
BNP]3:(R)-1-RE, and the corresponding (R)-2-RE were
synthesized as follows (method A). To a gently refluxing
solution of (R)-BNP–H and an aqueous sodium hydroxide
in methanol was added a solution of the appropriate rare
earth(III) chloride in methanol or the methanol–water
mixed-solvent, and the resulting mixture was stirred under
the same conditions. The resulting precipitate was collected
by filtration, washed with aqueous methanol, and dried in
vacuo at 1208C to give the desired complex (R)-1-RE as a
colorless or a pale colored powder. Alternatively, the crude
precipitate was subjected to dialysis to remove the
contaminated sodium chloride. Both procedures afforded
the desired complex with a similar activity. In method B,
chiral phosphate salts [e.g. (R)-BNP–Na] were first isolated
and then reacted with RECl3. In methods C and D, (R)-1-RE
was prepared from RE(O-i-Pr)3 and the free acid [(R)-
BNP–H]. Interestingly, a trivalent cerium complex, (R)-4-
Scheme 1. Preparation of (R)-4-Ce.
2.2. The RE[(R)-BNP]3-catalyzed asymmetric hetero-
Diels–Alder reaction
The complexes (R)-1-RE prepared by method A were used
as a chiral Lewis acid catalyst for the hetero-Diels–Alder
reaction of benzaldehyde 5a with the Danishefsky’s diene
6.16,17 The reactions were carried out using 10 mol% of the
catalysts in dichloromethane at room temperature. As
shown in Figure 2, the degrees of the asymmetric induction
are highly dependent on the central metal ions of the
catalysts, and (R)-1-Yb and (R)-1-Sc turned out to be
relatively favorable catalysts affording the desired cyclo-
adduct (R)-7a with 70 and 58% ee, respectively.3
Figure 2. The (R)-1-RE-catalyzed asymmetric hetero-Diels–Alder reac-
tion of 5a with 6.
In all cases, the reactions proceeded under heterogeneous
conditions because of the low solubility of the catalysts in
dichloromethane, which seemed to be one of the reasons for
their unsatisfactory enantioselectivities. Therefore, using
the ytterbium and the scandium catalysts, we examined the
effect of various achiral additives on the solubility and
efficiency of the catalysts. The hetero-Diels–Alder
Figure 1. Novel rare earth metal complexes and their preparations [(R)-1-
RE, (R)-2-RE, and (R)-3-RE].

H. Furuno et al. / Tetrahedron 59 (2003) 10509–10523
10511
reactions were carried out using 10 mol% of each catalyst
and various achiral ligands at room temperature for 16 h.
After many trials, some of the pyridine derivatives were
found to be effectively promoted the desired reaction under
homogeneous conditions. In Table 1 are shown some
selected results.14
As 2,6-lutidine was found to be one of the most effective
additives, the time course of the chemical yield and the
enantioselectivity were investigated in the (R)-1-Yb-cata-
lyzed reaction in the presence of this additive. Figure 3
shows that the reaction was almost completed in 16 h and
essentially the same enantioselectivity was obtained regard-
less of the reaction time, suggesting that no structural
change in the catalyst of the transition state occurs during
the reaction. These results indicate that disaggregation of
the complex catalyst by an appropriate ligand is important
not only to solubilize the catalyst but also to make it
thermodynamically stable so that it can work as the sole
catalytically active species.
Table 1. Effect of the additives on the yield and enantioselectivity in the
(R)-1-RE-catalyzed reaction
Entry
RE
Additive
Yield (%)a
Ee (%)b
1c
2
3
4
Yb
Yb
Yb
Yb
Yb
Yb
Yb
Yb
Yb
Yb
Yb
Yb
Yb
Sc
Sc
Sc
Sc
Sc
Sc
Sc
Sc
Sc
None
Pyridine
2-Picoline
2-Ethylpyridine
2,4-Lutidine
2,6-Lutidine
2,6-Lutidine
3,5-Lutidine
2,4,6-Collidine
2,6-Di-tert-butylpyridine
2,6-Bis(phenylethynyl)pyridine
Quinaldine
7,8-Benzoquinoline
None
Pyridine
2-Picoline
2,4-Lutidine
2,6-Lutidine
2,6-Lutidine
3,5-Lutidine
2,4,6-Collidine
2,6-Di-tert-butylpyridine
2,6-Bis(phenylethynyl)pyridine
77
46
63
56
93
94
76
49
55
59
23
96
69
93
78
81
88
94
86
54
82
85
72
70
37
77
87
79
89
90
78
89
57
26
88
90
56
56
77
78
81
80
56
75
54
53
5
6
7d
8
9
10c
11c
12
13
14c
15
16
17
18
19e
20
21
22c
23c
Sc
Figure 3. Time course of the chemical yield and enantioselectivity in the
(R)-1-Yb-catalyzed reaction in the presence of 2,6-lutidine.
The reaction was carried out using (R)-1-RE (10 mol%) and the additive
(10 mol%) under homogeneous conditions unless otherwise noted.
a
Isolated yield.
Determined by HPLC using a chiral column.
b
The effect of 2,6-lutidine was also examined for the
reactions catalyzed by other (R)-1-RE complexes
(RE¼La, Nd, Gd, and Ho). The observed enantioselectiv-
ities are summarized in Figure 4 by comparison with the
c
The reaction proceeded under heterogeneous conditions.
40 mol% of 2,6-lutidine was used.
30 mol% of 2,6-lutidine was used.
d
e
In the (R)-1-Yb-catalyzed reactions, a notable increase in
the enantioselectivity was observed when methyl- or ethyl-
substituted pyridine derivatives were employed as the
additive (entries 3–9). The effect of 2,6-lutidine was
found to be particularly high thus giving 7a with 89% ee
in 94% yield (entry 6). An increase in the amount of the
additive up to a 4-fold excess to the catalyst produced no
decrease in the enantioselectivity (entry 7). The slightly
reduced reaction rate may be explained by the competitive
ligation of 5a vs. 2,6-lutidine. The use of quinaldine also
afforded a comparable result (entry 12). Interestingly, the
use of pyridine rather decreased both the chemical and
optical yields though the reaction proceeded under homo-
geneous conditions (entry 2). The use of bulkier ligands
such as 2,6-di-tert-butylpyridine and 2,6-bis(phenyl-
ethynyl)pyridine was not effective (entries 10 and 11).
Other additivies having high coordinating abilities suc0h as
4-dimethylaminopyridine, 1,10-phenanthroline, 2,2 -bi-
pyridyl, and HMPA seriously retarded the reaction. In the
(R)-1-Sc-catalyzed reaction, a similarly tendency was
observed, and (R)-7a was obtained in 94% yield and 81%
ee when 2,6-lutidine was used as the additive (entry 18).
Figure 4. Influence of the central metal ions of (R)-1-RE and that of 2,6-
lutidine on the enantioselectivity in the hetero-Diels–Alder reaction.

10512
H. Furuno et al. / Tetrahedron 59 (2003) 10509–10523
data obtained in the reactions without using 2,6-lutidine (cf.
Fig. 2). Different from the scandium and the ytterbium
catalysts, the lanthanum, neodymium and gadolinium
complexes did not completely dissolve in dichloromethane
in the presence of 1 equiv. of 2,6-lutidine, therefore, the
reactions catalyzed by these complexes proceeded under
heterogeneous conditions. In the case of the holmium
complex-catalyzed reaction, an initially clear solution of the
catalyst containing 2,6-lutidine became clouded when
benzaldehyde was added. Whatever the appearance of the
reaction mixture was, the addition of 2,6-lutidine uniformly
increased the R-selectivity in all cases.
lutidine was added, although the chemical yield was
significantly improved in the latter case (entry 13).
2.3. Modifications of the chiral phosphate ligand
One of our concerns in this study is to develop new chiral
rare earth complexes which may work as a reusable Lewis
acid catalyst. Although (R)-1-Yb could be quantitatively
recovered after the reaction and successfully reused for the
second round of reactions without losing its activity, the
enantioselectivity itself was not as satisfactorily high as
previously mentioned. On the other hand, the addition of
2,6-lutidine to (R)-1-Yb significantly enhanced the enantio-
selectivity, but the recovery of the postulated (R)-1-Yb·2,6-
lutidine adduct turned out to be difficult while maintaining
its high catalytic activity. Therefore, two novel chiral rare
earth phosphates, (R)-2-RE and and (R)-3-RE (Fig. 1), were
prepared expecting that the 2,6-xylyl substituents on the
binapthyl ring of the former or the octahydrobinaphthyl ring
of the latter would play an important role not only in
increasing the solubility of the catalysts in dichloromethane
without 2,6-ltidine but also in providing a more effective
chiral space for the reaction than the catalyst (R)-1-RE.
Also, these catalysts were expected to be easily recovered
after the reaction by changing the solvent and successfully
reused if they do not require any additives to attain a high
enantioselectivity. Based on these expectations, a new
phosphate 12 was synthesized from 6,60-dibromo-BINOL 8
in six steps using the stand0ard conditions as shown i0n
Scheme 2. Similarly, (R)-5,5 ,6,60,7,70,8,80-octahydro-1,1 -
binaphthyl-2,20-diyl hydrogen phosphate [(R)-H8-BNP–H],
the ligand of the (R)-3-RE complex, was also prepared from
the corresponding octahydro-BINOL.18
As the (R)-1-Yb/2,6-lutidine (1:1) system was found to be
quite effective for the reaction of benzaldehyde (5a), the
temperature effect on the enantioselectivity and also the
effectiveness of the catalyst system to other aldehydes was
examined (Table 2).
Table 2. The (R)-1–Yb-catalyzed hetero-Diels–Alder reaction of various
aldehydes 5 with 6
Entry
R
5/7
Yield (%)a
Ee (%)b
1
Ph
Ph
Ph
Ph
5a/7a
5a/7a
5a/7a
5a/7a
5b/7b
5c/7c
5d/7d
5e/7e
5f/7f
94 (77)
79
45
89 (70)
91
91
2c
3d
4e
5
92
91
4-MeO-C6H4
4-Me-C6H4
4-Biphenylyl
4-Cl-C6H4
4-NO2-C6H4
2-Naphthyl
2-Furyl
86 (56)
79 (26)
83 (44)
70 (57)
84 (60)
79 (58)
83 (58)
59 (19)
90 (68)
93 (65)f
89 (57)f
89 (64)f
88 (61)f
65 (33)f
84 (68)f
76 (35)f
72 (35)
11 (11)
6
7
8
9
10
11
12
13
5g/7g
5h/7h
5i/7i
(E)-PhCHvCH
Ph(CH2)2
5j/7j
The reaction was carried out using (R)-1-Yb (10 mol%) and 2,6-lutidine
(10 mol%) at room temperature for 16 h unless otherwise noted.
a
Isolated yield. In parentheses is shown the yield obtained in the reaction
without 2,6-lutidine.
Determined by HPLC using a chiral column. In parentheses is shown the
ee obtained in the reaction without 2,6-intidine.
The reaction was carried out at 08C for 16 h.
The reaction was carried out at 2258C for 80 h.
2 Mol% each of (R)-1-Yb and 2,6-lutidine was used.
The absolute configuration is tentatively assigned.
b
c
d
e
f
As can be seen in entries 1–3, the effect of the reaction
temperature on the enantioselectivity is almost negligible.
In most cases, both the chemical and optical yields were
significantly improved by the addition of 2,6-lutidine, and
up to 93% ee was realized in the reaction of 4-
methoxybenzaldehyde (5b, entry 5). The amount of the
catalyst could be reduced to 2 mol% without affecting the
product yield and enantioselectivity (entry 4). The reaction
of 4-nitrobenzaldehyde (5f) afforded a somewhat low ee
(entry 9). A negative effect of the p-nitro substituent on the
enantioselectivity suggests that the strong coordination of
substrates to the chiral catalyst is crucial to gain a higher
ee’s, though a non-catalyzed process is also involved in this
case. Unfortunately, the reaction of an aliphatic aldehyde
did not afford a satisfactory optical yield even when 2,6-
Scheme 2. Preparation of (R)-12 (Ar¼2,6-xylyl). Reagent: (a) BnBr, NaH;
(b) ArB(OH)2, Pd(PPh3)4, Ba(OH)2; (c) H2, Pd–C, i-Pr2NEt; (d) Cl3PO3
NEt3; (e) Na2CO3 aq.; (f) HCl aq.
The hetero-Diels–Alder reaction of 5a with 6 using the
catalyst (R)-2-RE or (R)-3-RE proceeded under homo-
geneous conditions in dichloromethane without any addi-
tives, as expected. These results are shown in Table 3.
Interestingly, the (R)-2-Yb-catalyzed reaction showed the
opposite sense of enantioselection to afford0(S)-7a with 57%
ee, although the xylyl substituents at the 6,6 -positions of the
ligand on the catalyst appears to be rather far from the

H. Furuno et al. / Tetrahedron 59 (2003) 10509–10523
10513
Table 3. The hetero-Diels–Alder reaction using the new catalysts bearing
modified chiral ligands
After evaporation of the solvent, the residual complex was
dried under vacuum at room temperature for 3 h (52%
recovery). The recovered catalyst was used for the next
round of reactions, in which 10 equiv of 5a and 15 equiv of
6 for the catalyst was utilized. Although the conditions for
the recovery of the catalyst was not optimized, the high
catalytic activity of (R)-3-Sc was retained even in the third
round of reactions thus affording (R)-7a with an 87% ee in
95% yield.
Entry
Catalyst
Method
Yield (%)a
Ee (%)b
1
(R)-2-Yb
(R)-3-Sc
(R)-3-Sc
(R)-3-Sc
(R)-3-Yb
(R)-3-Yb
(R)-3-Er
(R)-3-Y
A
B
B
C
B
C
C
C
D
C
C
C
76
99
99
64
92
73
76
81
80
58
79
68
ent-57c
93
94
2
3d
4
84
91
98
98
99
98
91
93
2.5. The Ce(III)–BNP complex prepared from CAN
5
6
7
8
Although cerium is one of the most economical rare earth
elements, littlehas beendeveloped regarding thechiralcerium
complexes that can work as effective Lewis acid catalysts.19
The cerium complex (R)-1-Ce, prepared from CeCl3 by
method A, also turned out not to be effective for the reaction of
5a with 6 (see Fig. 2), and the enantioselectivity could not be
improved by the addition of 2,6-lutidine. The low catalytic
activity of the Ce(III) complex prompted us to examine the
corresponding Ce(IV) complex, because it can be a stronger
Lewis acid by having a capacity of four chiral ligands and
provide a higher selectivity. Therefore, we tried to prepare a
chiral Ce(IV) complex from ammonium cerium(IV) nitrate
(CAN) and (R)-BNP–Na (see Scheme 1).20 Unfortunately,
the desired Ce(IV) complex could not be produced but the
corresponding Ce(III) complex [(R)-4-Ce] was generated; the
Ce/P ratio was analyzed to be ca. 1:3.2 using as inductively
coupled plasma (ICP) mass spectrometer, and the electron
spectroscopy for chemical analysis (ESCA) study and
magnetic susceptibility measurement also indicated the
trivalent cerium structure.
9
(R)-3-Y
10
11
12
(R)-3-Dy
(R)-3-Sm
(R)-3-La
92
a
Isolated yield.
Determined by HPLC using a chiral column.
The absolute configuration is S.
4-Methoxybenzaldehyde (5b) was used instead of 5a.
b
c
d
catalytic center (entry 1). Fortunately, the (R)-3-RE-
catalyzed reactions afforded (R)-7a with good to excellent
ee’s (up to 99% ee) regardless of the type of central metal
ions (entries 2–12). Although (R)-3-Sc prepared by method
B gave a higher enantioselectivity than that prepared by
method C (entries 2 vs. 4), the method-dependency was
reserved in the corresponding ytterbium catalyst [(R)-3-Yb]
(entries 5 vs. 6).
2.4. Repeated use of the Lewis acid catalyst
Since the complexes (R)-3-RE were found to work as a
highly efficient homogeneous Lewis acid catalyst in the
absence of additives, we briefly examined the reusability of
(R)-3-Sc for the reaction of 5a with 6 (Fig. 5). After the first
round of reaction, the solvent was evaporated. To the
residue was added ether, and the resulting precipitate was
filtered through a Celite column and then eluted with THF.
Using various aldehydes, the (R)-4-Ce-catalyzed asym-
metric hetero-Diels–Alder reaction was carried out at room
temperature in the absence of an additive (Table 4). All the
reactions proceeded under homogeneous conditions and, in
the case of the aromatic aldehydes, generally high
enantioselectivities were obtained (entries 1 and 3–12).
The addition of 2,6-lutidine rather lowered the enantio-
selectivity (entry 2). The high performance of the cerium
catalyst clearly indicated that the structure of (R)-4-Ce is
different from the of (R)-1-Ce. It should be noted that (R)-4-
Ce is so stable that its original activity could be maintained
even after two years from its preparation (entry 10). Thus,
(R)-4-Ce was proved to be the first successful example of
the isolable and storable chiral cerium catalyst that can
afford a high level of enantioselectivity. The relatively low
ee’s observed in the reactions of aliphatic aldehydes suggest
the importance of some p–p interactions between the
aromatic ring of the aldehydes and that of the catalyst in the
transition state. Although we do not have a clear explanation
for the higher activity of (R)-4-Ce than (R)-1-Ce, the
existence of a small amount of nitrate ion derived from
CAN seems to play an important role in increasing the
solubility of the catalyst and the selectivity during the
reaction. Actually, when (R)-1-Ce was used for the reaction
of 5a with 6 in the presence of nitrate ions, the reaction
mixture became clear and the enantioselectivity increased to
73% ee (with NH4NO3) and 68% ee (with NaNO3). The use
of the cerium complex prepared from CAN and (R)-BNP–
Na (1:3) (cf. Scheme 1) did not show a meaningful result,
e.g. 7n with 51% ee was obtained in 57% yield.
Figure 5. The recovery and reuse of the catalyst (R)-3-Sc.

10514
H. Furuno et al. / Tetrahedron 59 (2003) 10509–10523
Table 4. The (R)-4-Ce-catalyzed hetero-Diels–Alder reaction of various
aldehydes with 6
Entry
R
5/7
Yield (%)a
Ee (%)b
1
Ph
Ph
5a/7a
5a/7a
5b/7b
5c/7c
5k/7k
5l/7l
5m/7m
5d/7d
5n/7n
5e/7e
5o/7o
5g/7g
5i/7i
91
91
39
96
95
61
75
46
91
93
80
42
50
36
58
80
74
2c
3
4-MeO-C6H4
4-Me-C6H4
4-Et-C6H4
4-i-Bu-C6H4
4-i-Bu-C6H4
4-Biphenylyl
4-F-C6H4
4-Cl-C6H4
4-Br-C6H4
2-Naphthyl
(E)-PhCH¼CH
n-Pr
87d
88d
93d
93d
94d
93d
85d
88d
92d
89d
44
4
5
6
7
8
9
10e
11
12
13f
14
15f
5p/7p
5q/7q
61d
45d
c-Hex
The reaction was carried out for 15 h unless otherwise noted.
a
Isolated yield.
Determined by HPLC using a chiral column.
10 mol% of 2,6-lutidine was used as an additive.
The absolute configuration is tentatively assigned.
The catalyst (R)-4-Ce stored in air for two years was used.
The reaction time was 105 h.
b
c
d
e
f
2.6. Asymmetric amplifications (positive nonlinear
effect)
Since the first example reported by Kagan and co-workers,21
the positive nonlinear effect has frequently been observed in
various asymmetric reactions using chiral metal cata-
lysts.10a,11,22,23 However, most of them are limited to the
central metal ion-chiral ligand 1:1 system, and a high degree
of asymmetric amplification concerning the 1:3 system has
never been reported although mathematical treatment
allows one to expect a considerable nonlinear effect in this
system. We investigated the linear-nonlinear effect for the
hetero-Diels–Alder reactions catalyzed by (R)-rich 1-Yb
and 4-Ce. In all cases, the amount of the catalyst was
adjusted for the excess enantiomer to be 10 mol% for the
substrate, e.g., 20 mol% of the catalyst was used for the
reaction when it was 50% ee.
Figure 6. The asymmetric amplification observed in the hetero-Diels–
Alder reaction catalyzed by 13 and 14.
To gain an insight into the mechanism of the present highly
positive nonlinear effect, we carried out the reactions shown
in Figure 7. The ytterbium complex 15-Yb prepared from
50% ee of the BNP–Na (R/S 3:1) was isolated, and then
treated with 2,6-lutidine in dichloromethane. Separation of
the CH2Cl2-soluble part (16) from the insoluble part (17) by
centrifugation (16/17 41:59) followed by LiAlH4 reduction
of each part afforded the corresponding BINOLs with 98
and 7% ee, respectively. In addition, while 16-catalyzed the
hetero-Diels–Alder reaction to give the product (R)-7a with
First, the 1-Yb-catalyzed reaction was checked.15 As shown
in Figure 6, the optically impure catalysts 13 and 14 were
prepared by methods I and II, respectively. When solutions
of enantiopure (R)-1-Yb and (S)-1-Yb containing 2,6-
lutidine were mixed in different ratios (method I), the
system became heterogeneous due to the resulting precipi-
tates. The direct use of the suspension as a catalyst 13 for the
reaction of 5a with 6 showed a notable asymmetric
amplification (Fig. 6). Very interestingly, the catalysts 14
prepared from the chiral ligands with various ee’s according
to method II further promoted the amplification under
heterogeneous conditions, e.g., using only 20% ee of the
BNP–Na (R/S 3:2), the adduct (R)-7a with 90% ee was
obtained. These results strongly suggest that the active
catalyst generated from an enantiomerically impure ligand
has the same structure as that of the catalyst prepared from
the enantiopure ligand.
Figure 7. Correlation between solubility and optical purity of the catalysts.

H. Furuno et al. / Tetrahedron 59 (2003) 10509–10523
10515
90% ee in 98% yield, 17 hardly promoted the reaction under
the same reaction conditions (Scheme 3). These results
clearly indicate that the active catalyst 16 is composed
entirely of the enantiopure ligands, whereas the inactive 17
is made up of almost a 1:1 mixture of enantiomers.
Figure 8. A possible chirality discrimination process for the formation of
[Yb(LR)3]n.
Scheme 3. Correlation between catalytic activity and solubility of the
catalysts.
based on an excess amount of the enantiomer, Yb(LR)3,
would remain in solution as the catalyst.
The experiment shown in Scheme 4 indicates how easily the
ligands of the complex (R)-1-Yb can be exchanged by the
sodium salt (BNP–Na) of the opposite enantiomer, giving
the heterochiral complex, i.e., when enantiopure (R)-1-Yb
was refluxed with racemic BNP-Na under similar conditions
for the preparation of (R)-1-Yb (see Fig. 1), the resulting
precipitate (complex 18, 95% recovery) contained the chiral
ligand with only 13% ee, which was clarified by converting
18 to the corresponding BINOL. On the other hand,
complex 19 prepared from racemic BNP–H hardly
promoted such a ligand exchange reaction with enantiopure
(R)-BNP–Na under similar conditions (Scheme 5). These
results demonstrate the remarkable thermodynamic stability
of the heterochiral complex.
This autogenetic chiral discrimination process, which can
afford a solution of the enantiopure complex [Yb(LR)3], was
found to also occur in THF instead of the 2,6-lutidine-
containing dichloromethane, as shown by entry 6 of Table 5.
It is interesting to note that this phenomenon is quite general
within the lanthanide metal ions with similar ionic radii to
that of the ytterbium ion like neodymium, gadolinium, and
holmium ions (entries 3–5). On the other hand, the
lanthanum and the cerium complexes, the metal ions of
which have larger ionic radii, were sparingly soluble in THF
indicating that they might exist as oligomeric mixtures with
high molecular weights (entries 1 and 2). In the case of the
scandium complex, which contains the smallest rare earth
metal ion, almost half of the complex was soluble in THF,
but the LiAlH4 reduction of it revealed that the autogenetic
process to form the enantiopure complex did not effectively
operate in this system (entry 7).
Table 5. Correlation between the THF-soluble complex 21 and optical
purity of the ligand
Scheme 4. The ligand exchange reaction of (R)-1-Yb with (^)-BNP–Na.
Entry
RE
21:22
Ee of (R)-BINOL (%)a
1
2
3
4
5
6
7
La
Ce
Nd
Gd
Ho
Yb
Sc
3:97
3:97
–
–
99
98
97
36:64
37:63
41:59
46:54
54:46
98 (5)b
64
Scheme 5. The ligand exchange reaction of the complex 19 with (R)-BNP–
Na.
The complexes 15–RE was prepared from 50% ee of (R)-BNP–H.
Ee of the BINOL derived from 21–RE unless otherwise noted.
a
Determined by HPLC using a chiral column.
Ee of the BINOL derived from 22–Yb.
b
Taking all these facts into consideration, we propose the
origin of the present asymmetric amplification as shown in
Figure 8. For the formation of YbL3, there are four
possibilities in choosing three chiral ligands: (LR)3,
(LR)2LS, LR (LS)2, and (LS)3, where LR¼(R)-BNP, and
LS¼(S)-BNP. From these four complexes, heterochiral pairs
such as Yb(LR)3 and Yb(LS)3 and/or Yb(LR)2LS and
YbLR(LS)2 seem to irreversibly assemble, forming the
thermodynamically very stable complexes which have
almost no catalytic activity for the hetero-Diels–Alder
reaction. As a result, the enantiopure ytterbium complex
Since the cerium complex [(R)-4-Ce] prepared from CAN is
soluble in dichloromethane, the linear-nonlinear effect was
also investigated for the 4-Ce-catalyzed reaction of 4-
ethylbenzaldehyde (5k) with the Danishefsky’s diene (6).20
The procedure and the results are shown in Figure 9.
Different from the previous case using the 1-Ce catalyst
(entry 2 in Table 5), significant positive nonlinear effects
were observed. For example, when the optically impure
complex 23 prepared by mixing the optically pure (R)-and

10516
H. Furuno et al. / Tetrahedron 59 (2003) 10509–10523
Table 6. The (R)-1-Yb-catalyzed hetero-Diels–Alder reaction of a-keto
esters 28 with 6
Entry a-Keto ester Catalyst (mol%) Time (h) Yield (%)a Ee (%)b
1
28a
28a
28a
28a
28b
28b
10
10
5
2
10
5
11
26
12
60
11
21
90
80
88
89
99
99
.99
91
.99
96
98
97
2c
3
4
5
6
a
Isolated yield.
Determined by HPLC using a chiral column.
The reaction was carried out in the presence of 2,6-lutidine (10 mol%).
b
c
no example of its highly enantioselective version until the
recent report by Jfrgensen and co-workers.24d The (R)-1-
Yb-catalyzed reactions of phenylglyoxylates (28a and 28b)
proceeded at room temperature under homogeneous con-
ditions in the absence of 2,6-lutidine, and almost enantio-
pure products (29a and 29b) were obtained. Different from
the reactions of aldehydes (see Table 2), the addition of 2,6-
lutidine rather decreased the enantioselectivity as well as the
reaction rate (entry 2). These results suggest that the
substrate may coordinate to the catalyst as a bidentate ligand
and the resulting rigid transition structure may be respon-
sible for such high enantioselectivities. The quantity of the
catalyst could be reduced to 2 mol% and still maintain its
high enantioselectivity (entries 3, 4, and 6).
Figure 9. The relation between optical purities of the Ce-catalyst and ee’s
of (R)-7k obtained by using it.
(S)-4-Ce complexes in 9:1 (80% ee) and 4:1 (60% ee) ratios
were used (see method I in Fig. 6), the product 7k was
produced in 90 and 81% ee, respectively. These reactions
proceeded under heterogeneous conditions because the
mixing of (R)- and (S)-4-Ce produced precipitates. There-
fore, the precipitate was separated by centrifugation, and the
soluble complex 24 and the insoluble one 25 were
independently used as a catalyst for the hetero-Diels–
Alder reaction. As anticipated form the results of the 13-Yb-
catalyzed reactions (see Fig. 6), the soluble complex 24
showed a high asymmetric amplification, and also the
LiAlH4 reduction of 24 afforded the almost enantiopure
(R)-BINOL (26). Unexpectedly, however, the insoluble
complex 25 also exhibited considerable catalytic activity
and the enantioselectivity linearly increased. More
interestingly, the (R)-rich-BINOLs (27) derived from 25
showed uniformly lower ee’s than the corresponding
products [(R)-7k] obtained using 25 as a catalyst. These
behaviors are much different from those observed in the
1-Yb-catalyzed reactions (cf. Fig. 7 and Scheme 3). There
must be a rapid ligand exchange process effectively
promoted by the nitrate ion.
3. Conclusion
We succeeded in developing four kinds of chiral rare earth
metal complexes that can work as isolable and storable
Lewis acid catalysts. These catalysts effectively promoted,
in some cases with the aid of 2,6-lutidine, the hetero-Diels–
Alder reactions of aromatic aldehydes and a-keto esters
with the Danishefsky’s diene at room temperature to give
the corresponding cycloadducts with excellent enantio-
selectivities (up to .99% ee). In the two cases examined,
remarkably high asymmetric amplifications were observed
as the first notable example of the metal-chiral ligand 1:3
system. These results strongly suggest that aggregation and
disaggregation processes play an extremely important role
in creating a certain chiral space that would be favorable for
a high enantioselectivity. We also demonstrated the high
potential of the (R)-3-Sc complex as a reusable Lewis acid
catalyst. These findings would lead to a new phase of
asymmetric catalysis using chiral metal (especially rare
earth) complexes.
2.7. Asymmetric hetero-Diels–Alder reaction of a-keto
esters
4. Experimental
Finally, we briefly checked the effectiveness of (R)-1-Yb for
the hetero-Diels–Alder reaction of a-keto esters 28 with the
Danishefsky’s diene 6 (Table 6).24 Although such a reaction
can produce a quaternary stereogeneic center, there has been
4.1. General methods
Melting points were measured with a Yanako MP-500D
micro melting point apparatus and are uncorrected. IR

H. Furuno et al. / Tetrahedron 59 (2003) 10509–10523
10517
spectra were taken with JASCO FT/IR-420, JEOL JIR-
1
4.2.5. Neodymium(III) (R)-1,10-binaphthyl-2,20-diyl
phosphate, Nd[(R)-BNP]3 [(R)-1-Nd]. Colorless solid.
[a]2D5¼2389.9 (c 1.08, THF). IR (KBr): 3062, 1592,
1058, 1466, 1329, 1238, 1213, 1104, 1071, 992, 966, 946,
868, 817, 750, 568 cm21. Anal. calcd for C60H36O12P3-
Nd·2H2O: C, 58.97; H, 3.30. Found: C, 58.84; H, 3.27.
WINSPEC 50 or Shimadzu FTIR-8600. H and 13C NMR
spectra were measured on JEOL JMN-EX 400 at 400 and
100 MHz, respectively. Chemical shifts are given by d
relative to that of internal tetramethylsilane in CDCl3 or the
solvent signal of CDCl3 or CD3OD. High performance
liquid chromatography (HPLC) was done with a Shimadzu
LC-9A or a LC-10ATVP using f 0.46 cm£25 cm chiral
column (Daicel CHIRALCEL OD, CHIRALPAK AD or
CHIRALPAK AS). The spectra were analyzed on a
Shimadzu C-R6A. Optical rotations were measured on a
Horiba SEPA-300 polarimeter. FAB mass spectra were
obtained with JEOL JMS-HX110A. Thin layer chromato-
graphy (TLC) was performed on a silica gel plates (Merck
Kieselgel 60 F-254, 20 cm£20 cm£0.25 mm). Column
chromatography was carried out with silica gel as an
absorbent (Merck Kieselgel 60, 70–230 mesh or Kanto
Chemical, silica gel 60N 70–230 mesh). Dichloromethane
was dried over calcium hydride.
4.2.6. Gadolinium(III) (R)-1,10-binaphthyl-2,20-diyl
phosphate, Gd[(R)-BNP]3 [(R)-1-Gd]. Colorless solid.
[a]2D5¼2398.0 (c 1.00, THF). IR (KBr): 3068, 1620,
1592, 1508, 1467, 1329, 1238, 1209, 1108, 1071, 992,
966, 946, 868, 817, 750, 568 cm21. Anal. calcd for
C60H36O12P3Gd·3H2O: C, 57.51; H, 3.38. Found: C,
57.88; H, 3.27.
4.2.7. Holmium(III) (R)-1,10-binaphthyl-2,20-diyl phos-
phate, Ho[(R)-BNP]3 [(R)-1-Ho]. Pale orange solid.
[a]2D5¼2359.4 (c 1.03, THF). IR (KBr): 3065, 1621,
1592, 1508, 1466, 1329, 1238, 1212, 1109, 1071, 992,
966, 948, 869, 817, 750, 720, 659, 568 cm21. Anal. calcd
for C60H36O12P3Ho·2H2O: C, 57.99; H, 3.24. Found: C,
58.29; H, 3.14.
4.2. Preparation of catalysts
4.2.1. Typical procedure for the preparation of chiral
rare earth metal phosphate (method A): Ytterbium(III)
(R)-1,10-binaphthyl-2,20-diyl phosphate, Yb[(R)-BNP]3
[(R)-1-Yb]. To a refluxing solution of (R)-BNP–H
(506 mg, 1.45 mmol) and 3N aqueous sodium hydroxide
(0.470 ml, 1.41 mmol) in methanol (12 ml) was slowly
added a solution of ytterbium chloride hexahydrate
(179 mg, 0.461 mmol) in methanol, and the resulting
mixture was stirred for 12 h under the same conditions.
After cooling, the precipitate was filtered, washed with
methanol, and dried at 1208C for 15 h in vacuo to give the
complex (R)-1-Yb (535 mg, 96%) as colorless solids.
Gradually decomposes around 1458C. [a]2D1¼395.0 (c
1.00, THF). IR (KBr): 3616, 3065, 1621, 1592, 1509,
1466, 1329, 1238, 1215, 1112, 1071, 967, 945, 870, 817,
750, 568 cm21. Anal. calcd for C60H36O12P3Yb·H2O: C,
58.45; H, 3.11. Found: C, 58.17; H, 3.11.
4.2.8. Ytterbium(III) (R)-6,60-bis(2,6-xylyl)-1,10-bina-
phthyl-2,20-diyl phosphate, [(R)-2-Yb]. Gradually decom-
poses around 2758C. [a]D25¼217.7 (1.00, CHCl3). IR (KBr):
3853, 3649, 3307, 1240, 1103 cm21. Anal. calcd for
C108H84O12P3Yb·5H2O: C, 67.22; H, 4.91. Found: C,
67.08; H, 4.71.
4.2.9. Typical procedure for the preparation of chiral
rare earth metal phosphate (method B): Scandium(III)
(R)-5,50,6,60,7,70,8,80-octahydro-1,10-binaphthyl-2,20-diyl
phosphate, Sc[(R)-H8-BNP]3 [(R)-3-Sc]. To a solution of
(R)-H8-BNP–Na (351 mg, 0.928 mmol) in methanol (3 ml)
and water (1 ml) was slowly added a solution of scandium
chloride hexadydrate (77.8 mg, 0.300 mmol) in water (1 ml)
and then methanol (3 ml) at 708C, and the resulting
suspension was stirred for 12 h under the same conditions.
After cooling, the precipitate was filtered, washed with a
mixture of methanol and water (4:1), and dried in vacuo at
1208C to give (R)-3-Sc (278 mg, 83.3%) as colorless solids.
Gradually decomposes around 2488C. [a]2D5¼2246.8 (c
1.02, ethanol). IR (KBr): 2931, 2858, 1471, 1448, 1437,
1423, 1252, 1225, 1111, 1057, 962, 889, 877, 833,
812 cm21. Anal. calcd for C60H60O12P3Sc·4H2O: C,
60.91; H, 5.79. Found: C, 61.05; H, 5.45.
4.2.2. Scandium(III) (R)-1,10-binaphthyl-2,20-diyl phos-
phate, Sc[(R)-BNP]3 [(R)-1-Sc]. Colorless solid.
[a]2D5¼2492.2 (c 1.06, THF). IR (KBr): 3060, 1621,
1592, 1509, 1466, 1328, 1237, 1210, 1155, 1109, 1071,
993, 968, 949, 888, 871, 816, 750, 722, 659, 568, 542,
486 cm21. Anal. calcd for C60H36O12P3Sc·3H2O: C, 63.17;
H, 3.71. Found: C, 63.27; H, 3.55.
4.2.3. Lanthanum(III) (R)-1,10-binaphthyl-2,20-diyl phos-
phate, La[(R)-BNP]3 [(R)-1-La]. Colorless solid.
[a]2D5¼356.0 (c 1.00, THF). IR (KBr): 3060, 1620, 1592,
1508, 1466, 1329, 1238, 1215, 1103, 1071, 992, 965, 945,
4.2.10. Typical procedure for the preparation of chiral
rare earth metal phosphate (method C and D).
Yttrium(III) (R)-5,50,6,60,7,70,8,80-octahydro-1,10-
binaphthyl-2,20-diyl phosphate, Y[(R)-H8-BNP]3 [(R)-3-
867, 841, 817, 750, 720, 659, 595, 582, 568, 538, 495, cm21
.
Sc]. To a suspension of (R)-H8-BNP–H (830 mg,
Anal. calcd for C60H36O12P3La·H2O: C, 60.12; H, 3.20.
Found: C, 59.72; H, 3.30.
2.33 mmol) in dichloromethane (10 ml) was added a
solution of yttrium isopropoxide (207 mg, 0.775 mmol) in
dichloromethane (12 ml) at room temperature under argon,
and the resulting solution was refluxed for 1 min. After
cooling, the mixture was directly for 1 min. After Diels–
Alder reaction as a 0.05M solution of the catalyst (method
D). Alternatively, the solvent was removed under reduced
pressure, and the colorless solid was dried in vacuo at 1208C
for 6 h to give (R)-3-Y (953 mg, 100%) (method C).
[a]2D5¼298.2 (c 1.07, THF). Anal. calcd for C60H60O12P3Y·
4.2.4. Cerium(III) (R)-1,10-binaphthyl-2,20-diyl phos-
phate, Ce[(R)-BNP]3 [(R)-1-Ce]. Colorless solid.
[a]2D5¼2325.0 (c 1.00, THF). IR (KBr): 3065, 1621,
1592, 1508, 1466, 1329, 1238, 1215, 1103, 1071, 991,
966, 948, 868, 817, 750, 568 cm21. Anal. calcd for
C60H36O12P3Ce·3H2O: C, 58.30; H, 3.43. Found: C,
58.24; H, 3.28.

10518
H. Furuno et al. / Tetrahedron 59 (2003) 10509–10523
C3H7OH·H2O: C, 61.37; H, 5.72; P, 7.54; Y, 7.2. Found: C,
61.4; H, 5.7; P, 7.3; Y, 7.6.
Found: C, 75.89; H, 5.75. CAS registry no. 88198-68-9 (R),
124578-13-8 (S), 40989-96-6 (rac).
4.2.11. Dysprosium(III) (R)-5,50,6,60,7,70,8,80-octahydro-
1,10-binaphthyl-2,20-diyl phosphate, Dy[(R)-H8-BNP]3
[(R)-3-Dy]. [a]2D5¼2122.2 (c 0.157, THF). Anal. calcd for
C60H60O12P3Dy·C3H7OH·2H2O: C, 57.12; H, 5.48; P, 7.01;
Dy, 12.27. Found: C, 57.5; H, 5.6; P, 7.0; Y, 12.
4.3.2. 2,3-Dihydro-2-(4-methoxyphenyl)-4H-pyran-4-
one (7b). [a]2D0¼2129.0 (c 1.07, CHCl3, 89.1% ee by
HPLC analysis). HPLC (CHIRALPAK AD, 2-propanol–
hexane 1:9, 0.5 ml/min): tR 25.2 min for the major
enantiomer (28.4 min for the minor one), (CHIRALCEL
OD, 2-propanol–hexane 1:9, 0.5 ml/min): tR 45.0 min for
the major enantiomer (40.5 min for the minor one). 1H
NMR (CDCl3, d): 7.46 (d, J¼6.10 Hz, 1H), 7.33 (dt,
J¼8.79, 2.44 Hz, 2H), 6.94 (dt, 2H, J¼8.79, 2.44 Hz), 5.51
(dd, J¼0.98, 6.10 Hz, 1H), 5.38 (dd, J¼3.42, 14.16 Hz, 1H),
3.83 (s, 3H) 2.93 (dd, J¼14.16, 16.85 Hz, 1H), 2.63 (ddd,
J¼0.98, 3.42, 16.85 Hz, 1H). Anal calcd for C12H12O3: C,
70.58; H, 5.92. Found: C, 70.63; H, 6.09. CAS registry no.
256222-20-5 (R), 333719-17-8 (S), 60380-11-2 (rac or
undetermined).
4.2.12. Samarium(III) (R)-5,50,6,60,7,70,8,80-octahydro-
1,10-binaphthyl-2,20-diyl phosphate, Sm[(R)-H8-BNP]3
[(R)-3-Sm]. [a]2D5¼288.2 (c 0.103, THF). Anal. calcd for
C60H60O12P3Sm·C3H7OH·2H2O: C, 57.65; H, 5.53; P, 7.08;
Sm, 11.46. Found: C, 57.9; H, 5.8; P, 6.9; Sm, 11.
4.2.13. Preparation of the Ce(III)-BNP complex from
CAN [(R)-4-Ce]. To a solution of (R)-BNP–H (2.19 g,
6.3 mmol) and 3N aqueous sodium hydroxide (2.0 ml,
6.0 mmol) in methanol (45 ml) was slowly added a solution
of CAN (822 mg, 1.5 mmol) in methanol at room
temperature, and the resulting mixture was stirred for
12 h. The precipitate was filtered, washed with methanol,
and dried in vacuo at 1208C for 15 h to give the complex 4
(1.34 g, 59%) as pale gray solids. [a]1D6¼2490.8 (c 1.00,
CHCl3). Anal. calcd for C60H36CeO12P3·3H2O·0.5NaNO3:
C, 56.37; H, 3.31; N, 0.55. Found: C, 56.24; H, 3.50; N,
0.39. ICP spectrometry analysis: Ce, 10; P, 7.0 (calculated
data for the composition ratio: Ce/P 1:3.2). Effective
magnetic moment (rt): meff, 2.35 mB.
4.3.3. 2,3-Dihydro-2-(4-tolyl)-4H-pyran-4-one (7c).
[a]2D1¼2114.7 (c 2.41, CHCl3, 91.9% ee by HPLC
analysis). HPLC (CHIRALCEL OD, 2-propanol–hexane
1:9, 0.5 ml/min): tR 25.3 min for the major enantiomer
(22.5 min for the minor one). 1H NMR (CDCl3, d): 7.47 (d,
J¼5.86 Hz, 1H), 7.30 (d, J¼8.06 Hz, 2H), 7.23 (d,
J¼8.06 Hz, 2H), 5.52 (dd, J¼0.98, 5.86 Hz, 1H), 5.40
(dd, J¼3.42, 14.65 Hz, 1H), 2.92 (dd. J¼14.65, 17.09 Hz,
1H), 2.64 (ddd, J¼0.98, 3.42, 17.09 Hz, 1H), 2.38 (s, 3H).
Anal. calcd for C12H12O2: C, 76.57; H, 6.43. Found: C,
76.27; H, 6.59. CAS registry no. 478488-10-7 (R), 188116-
41-8 (rac or undetermined).
4.3. Asymmetric hetero-Diels–Alder reaction of
aldehydes
4.3.4. 2-(1,10-Biphenyl-4-yl)-2,3-dihydro-4H-pyran-4-
one (7d). [a]2D2¼2106.5 (c 0.808, CHCl3, 89.9% ee by
HPLC analysis). HPLC (CHIRALPAK AD, 2-propanol–
hexane 1:9, 0.5 ml/min): tR 24.3 min for the major
enantiomer (32.8 min for the minor one). 1H NMR
(CDCl3, d): 7.66–7.59 (m, 4H), 7.51–7.44 (m, 5H), 7.37
(tt, J¼1.95, 7.32 Hz, 1H), 5.55 (dd, J¼0.97, 5.85 Hz), 5.49
(dd, J¼3.42, 14.16 Hz, 1H), 2.96 (dd, J¼14.16, 17.09 Hz,
1H), 2.71 (ddd, J¼0.97, 3.42, 17.09 Hz, 1H). CAS registry
no. 244614-14-0 (S), 188116-42-9 (undetermined).
4.3.1. Typical procedure for the chiral rare earth metal
phosphate-catalyzed asymmetric hetero-Diels–Alder
reaction of aldehydes. Synthesis of (R)-2,3-dihydro-2-
phenyl-4H-pyran-4-one [(R)-7a] using (R)-1-Yb and 2,6-
lutidine. Yb[(R)-BNP]3 [(R)-1-Yb] (12.2 mg, 0.01 mmol)
was dried in vacuo at ca. 1008C, and dichloromethane (1 ml)
and 0.515 M solution of 2,6-lutidine in dichloromethane
(20.0 ml, 0.01 mmol), which was prepared by mixing 2,6-
lutidine (27.6 mg, 0.258 mmol) and dichloromethane
(0.470 ml), was added to the catalyst under argon. To the
resulting solution were added 5a (10.4 mg, 0.098 mmol)
and 6 (26.6 mg, 0.154 mmol), and the mixture was stirred at
room temperature for 16 h. The reaction mixture was
successively treated with two drops of trifluoroacetic acid
and three drops of pyridine, and the resulting mixture was
directly subjected to column chromatography to give the
desired product (R)-7a (16.1 mg, 94%) as a colorless oil. Rf
0.35 (ethyl acetate–hexane 3:7). [a]2D7¼297.9 (c 1.55,
CHCl3, 96.3% ee by HPLC analysis), [a]2D0¼292.4 (c 1.49,
THF, 90.8% ee by HPLC analysis), [a]2D0¼297.7 (c 1.39,
CH3OH, 90.8% ee by HPLC analysis). HPLC (CHIRAL-
CEL OD, 2-propanol–hexane 1:9, 1.0 ml/min): tR 16.6 min
for the (R)-7a [14.4 min for (S)-7a]. IR (neat): 3063, 2901,
1676, 1593, 1404, 1269, 1227, 1038, 991, 935, 795, 758,
4.3.5. 2-(4-Chlorophenyl)-2,3-dihydro-4H-pyran-4-one
(7e). [a]2D0¼2105.8 (c 0.675, CHCl3, 92.0% ee by HPLC
analysis). HPLC (CHIRALCEL OD, 2-propanol–hexane
1:9, 0.5 ml/min): tR 35.6 min for the major enantiomer
(29.7 min for the minor one). 1H NMR (CDCl3, d): 7.47 (d,
J¼5.85 Hz, 1H), 7.41–7.33 (mm, 4H), 5.54 (dd, J¼0.98,
5.85 Hz, 1H), 5.41 (dd, J¼3.41, 14.16 Hz, 1H), 2.86 (dd,
J¼14.16, 16.60 Hz, 1H), 2.65 (ddd, J¼0.98, 3.41, 16.60 Hz,
1H). CAS registry no. 335609-84-2 (R), 244614-13-9 (S),
188116-43-0 (undetermined).
4.3.6. 2,3-Dihydro-2-(4-nitrophenyl)-4H-pyran-4-one
(7f). [a]2D4¼234.5 (c 1.29, CHCl3, 59.1% ee by HPLC
analysis). HPLC (CHIRALPAK AD, 2-propanol–hexane
1:4, 1.0 ml/min): tR 17.2 min for the major enantiomer
(21.7 min for the minor one). 1H NMR (CDCl3, d): 8.30 (d,
J¼8.79 Hz, 2H), 7.60 (d, J¼8.79 Hz, 2H,), 7.51 (d,
J¼6.34 Hz, 1H), 5.59 (dd, J¼0.97, 6.35 Hz, 1H), 5.55
(dd, J¼3.90, 14.16 Hz, 1H), 2.85 (dd, J¼14.16, 16.85 Hz,
1H), 2.73 (ddd, J¼0.98, 3.90, 16.85 Hz, 1H). Anal. calcd for
1
698 cm21. H NMR (CDCl3, d): 7.49 (d, J¼5.86 Hz, 1H),
7.45–7.37 (m, 5H), 5.53 (dd, J¼1.46, 5.86 Hz, 1H), 5.44
(dd, J¼3.42, 14.16 Hz, 1H), 2.92 (dd, J¼14.16, 16.84 Hz,
1H), 2.67 (ddd, J¼1.46, 3.42, 16.84 Hz 1H). 13C NMR
(CDCl3, d): 192.09, 163.15, 137.81, 128.87, 126.07, 107.35,
81.06, 43.36. Anal. calcd for C11H10O2: C, 75.83; H, 5.80.

H. Furuno et al. / Tetrahedron 59 (2003) 10509–10523
10519
C11H9NO4: C, 60.28; H, 4.14; N, 6.39. Found: C, 60.43; H,
4.39; N, 6.10. CAS registry no. 350688-07-2 (R), 162299-
82-3 (S), 188116-44-1 (rac or undetermined).
1H), 2.71–2.63 (m, 3H), 1.25 (t, J¼7.32 Hz, 3H). 13C NMR
(CDCl3, d): 192.01, 163.02, 144.97, 134.85, 128.11, 126.05,
107.09, 80.92, 43.16, 28.51, 15.43. HRMS-FAB (m/z):
[MþH]þ calcd for C13H15O2, 203.1072. Found: 203.1071.
Anal. calcd for C13H14O2: C, 77.20; H, 6.98. Found: C,
77.03; H, 6.97.
4.3.7. 2,3-Dihydro-2-(2-naphthyl)-4H-pyran-4-one (7g).
[a]2D2¼274.2 (c 0.708, CHCl3, 92.3% ee by HPLC
analysis). HPLC (CHIRALCEL OD, 2-propanol–hexane
1:4, 1.0 ml/min): tR 23.2 min for the major enantiomer
4.3.12. 2,3-Dihydro-2-(4-isobutylphenyl)-4H-pyran-4-
one (7l). A pale yellow oil. Rf 0.57 (ethyl acetate–hexane
1:1). [a]2D1¼270.1 (c 0.63 CHCl3, 87.9% ee by HPLC
analysis). HPLC (CHIRALPAK OD, 2-propanol–hexane
1:19, 0.25 ml/min): tR 50.7 min for the major enantiomer
(45.8 min for the minor one). IR (KBr): 2955, 2869, 1680,
1596, 1517, 1466, 1402, 1271, 1228, 1211, 1038, 989, 934,
1
(15.5 min for the minor one). H NMR (CDCl3, d): 7.93–
7.86 (m, 4H), 7.54–7.50 (m, 4H), 5.61 (dd, J¼3.42,
14.16 Hz, 1H) 5.57 (dd, J¼0.98, 5.86 Hz, 1H), 3.02 (dd,
J¼14.16, 16.60 Hz, 1H), 2.76 (ddd, J¼0.98, 3.42, 16.60 Hz,
1H). Anal. calcd for C15H12O2: C, 80.34; H, 5.39. Found:
C, 80.31; H, 5.43. CAS registry no. 188116-45-2
(undetermined).
1
847, 790, 550, 483cm21. H NMR (CDCl3, d): d 7.47 (d,
J¼6.11 Hz, 1H), 7.30 (d, J¼8.24 Hz, 2H), 7.20 (d,
J¼8.23 Hz, 2H), 5.52 (d, J¼6.11 Hz, 1H), 5.40 (dd,
J¼3.35, 14.35 Hz, 1H), 2.92 (dd, J¼14.65, 16.78 Hz, 1H),
2.65 (dd, J¼2.74, 16.78 Hz, 1H), 2.50 (d, J¼7.02 Hz, 2H)
1.91–1.83 (m, 1H), 0.91 (d, J¼6.41 Hz, 6H). 13C NMR
(CDCl3, d): 192.19, 163.13, 142.61, 134.93, 129.45, 125.93,
107.23, 81.09, 45.11, 43.27, 30.22, 22.38. HRMS-FAB (m/
z): [MþH]þ calcd for C15H19O2, 231.1385. Found:
231.1388. Anal. calcd for C15H18O2: C, 78.23; H, 7.88.
Found: C, 78.07; H, 7.89.
4.3.8. 2,3-Dihydro-2-(2-furyl)-4H-pyran-4-one (7h).
[a]2D1¼2286.9 (c 2.57, CHCl3, 84.4% ee by HPLC
analysis). HPLC (CHIRALPAK AD, 2-propanol–hexane
1:9, 0.5 ml/min): tR 17.6 min for the major enantiomer
(25.8 min for the minor one). 1H NMR (CDCl3, d): 7.48 (dd,
J¼0.98, 1.95 Hz, 1H), 7.37 (d, J¼6.34 Hz, 1H), 6.45 (dd,
J¼0.98, 3.42 Hz, 1H), 6.41 (dd, J¼1.95, 3.42 Hz, 1H), 5.51
(dd, J¼0.98, 6.35 Hz, 1H), 5.48 (dd, J¼3.90, 12.69 Hz, 1H),
3.09 (dd, J¼12.69, 17.09 Hz, 1H), 2.74 (ddd, J¼0.98, 3.91,
17.09 Hz, 1H). Anal. calcd for C9H8O3: C, 65.85; H, 4.91.
Found: C, 65.79; H, 4.80 CAS registry no. 145624-55-1 (R),
85613-03-2 (rac or undetermined).
4.3.13. 2,3-Dihydro-2-(4-tert-butylphenyl)-4H-pyran-4-
one (7m). Colorless solid. Mp 86.0–87.08C. Rf 0.57
(ethy1 acetate–hexane 1:1). [a]2D1¼280.6 (c 0.73, CHCl3,
87.7% ee by HPLC analysis). HPLC (CHIRALPAK OD, 2-
propanol–hexane 1:9, 0.5 ml/min): tR 24.1 min for the
major enantiomer (15.8 min for the minor one). IR (KBr):
3060, 2960, 2902, 2868, 1673, 1594, 1515, 1462, 1410,
1362, 1273, 1230, 1041, 996, 637, 835, 572, 492 cm21. 1H
NMR (CDCl3, d): 7.47 (d, J¼6.10 Hz, 1H), 7.45 (d,
J¼8.24 Hz, 2H), 7.33 (d, J¼8.24 Hz, 2H), 5.52 (d,
J¼5.80 Hz, 1H), 5.41 (dd, J¼3.66, 14.65 Hz, 1H), 2.93
(dd, J¼14.64, 17.09 Hz, 1H), 2.66 (dd, J¼3.36, 16.79 Hz,
1H), 1.33 (s, 9H). 13C NMR (CDCl3, d): 192.20, 163.16,
152.05, 134.63, 125.92, 125.71, 107.24, 81.00, 43.19, 34.72,
31.31. HRMS-FAB (m/z): [MþH]þ calcd for C15H19O2,
231.1385. Found: 231.1386. Anal. calcd for C15H18O2; C,
78.23; H, 7.88. Found: C, 78.11; H, 7.85.
4.3.9. (R)-2,3-Dihydro-2-[(E)-styryl]-4H-pyran-4-one
[(R)-7i]. HPLC (CHIRALPAK AD, 2-propanol–hexane
1:9, 0.5 ml/min): tR 35.1 min for (R)-7n [43.0 min for (S)-
1
7n]. H NMR (CDCl3, d): 7.42 (d, J¼6.35 Hz, 1H), 7.37–
7.28 (m, 5H), 6.73 (d, J¼16.11 Hz), 6.31 (dd, J¼6.84,
16.11 Hz, 1H), 5.48 (d, J¼6.35 Hz, 1H), 5.11–5.05 (m,
1H), 2.74 (dd, J¼12.69, 17.09 Hz, 1H), 2.63 (dd, J¼3.91,
17.09 Hz, 1H). CAS registry no. 139627-54-6 (R), 122046-
62-2 (R), 190835-53-1 (S), 85613-04-3 (rac or undeter-
mined), 82093-23-0 (rac).
4.3.10. (S)-2,3-Dihydro-2-(2-phenylethyl)-4H-pyran-4-
one [(S)-7j]. [a]2D1¼220.9 (c 0.717, CHCl3, 9.3% ee by
HPLC analysis).HPLC (CHIRALPAK AD, 2-propanol–
hexane 1:50, 1.0 ml/min): tR 16.4 min for (S)-7j [21.4 min
1
for (R)-7j]. H NMR (CDCl3, d): 7.38 (d, J¼5.86 Hz, 1H),
4.3.14. 2,3-Dihydro-2-(4-fluorophenyl)-4H-pyran-4-one
(7n). [a]2D1¼241.7 (c 0.52, CHCl3, 75.8% ee by HPLC
analysis). HPLC (CHIRALPAK OD, 2-propanol–hexane
1:9, 0.5 ml/min): tR 29.1 min for the major enantiomer
(25.8 min for the minor one). 1H NMR (CDCl3, d): 7.48 (d,
J¼5.86 Hz, 1H), 7.39 (d, J¼8.79 Hz, 2H), 7.12 (d,
J¼8.79 Hz, 2H), 5.55 (d, J¼5.86 Hz, 1H), 5.42 (dd,
J¼3.42, 14.65 Hz, 1H), 2.90 (dd, J¼14.65, 17.09 Hz, 1H),
2.66 (dd, J¼3.42, 17.09 Hz, 1H). HRMS-FAB (m/z):
[MþH]þ calcd for C11H10FO2, 193.0665. Found:
193.0650. CAS registry no. 226714-93-8 (rac).
7.35–7.18 (m, 5H), 5.41 (dd, J¼0.98, 5.86 Hz, 1H), 4.43–
4.36 (m, 1H), 2.87–2.71 (m, 2H) 2.55 (dd, J¼13.19,
16.60 Hz, 1H), 2.43 (ddd, J¼0.98, 3.91, 16.60 Hz, 1H),
2.20–2.11 (m, 1H), 2.00–1.91 (m, 1H). Anal calcd for
C13H14O2: C, 77.20; H, 6.98. Found: C, 77.09; H, 7.07. CAS
registry no. 145624-57-3 (S), 366463-10-7 (R), 188116-46-
3 (undetermined).
4.3.11. 2,3-Dihydro-2-(4-ethylphenyl)-4H-pyran-4-one
(7k). A colorless oil. Rf 0.43 (ethyl acetate–hexane 3:7).
[a]2D4¼258.8 (c 0.55, CHCl3, 77.7% ee by HPLC analysis).
HPLC (CHIRALPAK OD, 2-propanol–hexane 1:9, 0.5 ml/
min): tR 24.4 min for the major enantiomer (20.4 min for
minor one). IR (KBr): 2966, 2360, 1678, 1595, 1402, 1271,
4.3.15. 2-(4-Bromophenyl)-2,3-dihydro-4H-pyran-4-one
(7o). [a]2D1¼242.0 (c 0.53, CHCl3, 78.8% ee by HPLC
analysis). HPLC (CHIRALPAK OD, 2-propanol–hexane
1:9; 0.5 ml/min: tR 43.9 min for the major enantiomer
(35.1 min for the minor one). 1H NMR (CDCl3, d): 7.56 (d,
J¼7.32 Hz, 2H), 7.47 (d, J¼4.89 Hz, 1H), 7.28 (d, J¼7.81,
2H), 5.53 (d, J¼4.39 Hz, 1H), 5.40 (d, J¼13.18 Hz, 1H),
1
1228, 1211, 1038, 988, 934, 837, 793, 482cm21. H NMR
(CDCl3, d): 7.47 (d, J¼6.34 Hz, 1H), 7.32 (d, J¼8.30 Hz,
2H), 7.25 (d, J¼6.35 Hz, 2H), 5.52 (d, J¼5.58 Hz, 1H), 5.41
(dd, J¼3.42, 14.64 Hz, 1H), 2.93 (dd, J¼14.65, 17.09 Hz,

10520
H. Furuno et al. / Tetrahedron 59 (2003) 10509–10523
2.85 (dd, J¼14.65, 16.11 Hz, 1H), 2.65 (d, J¼16.60 Hz,
1H). HRMS-FAB (m/z): [MþH]þ calcd for C11H10BrO2,
252.9864. Found: C, 252.9863. Anal. calcd for C11H9BrO2:
C, 52.20; H, 3.58. Found: C, 52.25; H, 3.62. CAS registry
no. 387388-81-0 (undetermined).
[a]2D7¼262.9 (c 1.0, CHCl3). IR (KBr): 3521, 1720, 1621,
1598, 1483, 767 cm21 1H NMR (CDCl3, d): 7.97 (d,
.
J¼8.79 Hz, 2H), 7.68 (s, 2H), 7.42 (d, J¼8.79 Hz, 2H). 7.33
(d, J¼8.79 Hz, 2H), 7.21–7.14 (m, 8H), 2.07 (s, 12H). 13C
NMR (CDCl3, d): 152.69, 141.34, 136.82, 136.31, 132.10,
131.35, 129.56, 129.30, 128.23, 127.35, 127.16, 124.29,
117.87, 110.92, 21.06. HRMS-FAB (m/z): [M]þ calcd for
C36H30O2, 494.2246. Found: 494.2240. Anal. calcd for
C36H30O2·H2O: C, 84.35; H, 6.29. Found: C, 84.05; H, 6.19.
4.3.16. 2,3-Dihydro-2-propyl-4H-pyran-4-one (7p).
HPLC (CHIRALPAK AD, 2-propanol–hexane 1:50,
0.5 ml/min): tR 24.2 min for the major enantiomer
1
(33.9 min for the minor one). H NMR (CDCl3, d): 7.35
(d, J¼6.34 Hz, 1H), 5.40 (d, J¼6.34 Hz, 1H), 4.42–4.41
(m, 1H), 2.52 (dd, J¼13.67, 16.60 Hz, 1H), 1.83–1.45 (m,
4H), 0.97 (t, J¼7.32 Hz, 3H). CAS registry no. 129548-17-0
(S), 89171-64-2 (undetermined).
4.4.3. (R)-6,60-Di(2,6-xylyl)-1,10-binaphthyl-2,20-diyl
chlorophosphate. To a cold solution of 11 (614 mg,
1.24 mmol) and phosphoryl chloride (355 mg, 2.32 mmol)
in dichloromethane (2.8 ml) was added dropwise triethyla-
mine (326 mg, 3.22 mmol), and the mixture was stirred at
08C for 40 min under argon. After additional stirring for
4.5 h at room temperature, water was added, and the crude
product was extracted with dichloromethane. The organic
layer was washed with water, dried over anhydrous
magnesium sulfate, and concentrated to give0 the analyti-
cally almost pure (R)-6,60-di(2,6-xylyl)-1,1 -binaphthyl-
2,20-diyl chlorophosphate (719 mg) as colorless solids,
which was used for the next hydrolysis without further
purification. Rf 0.55 (ethyl acetate–hexane 4:1). IR (KBr):
4.3.17. 2-Cyclohexyl-2-3,dihydro-4H-pyran-4-one (7q).
HPLC (CHIRALPAK AD, 2-propanol–hexane 1:50,
0.25 ml/min): tR 25.4 min for the major enantiomer
1
(21.6 min for the minor one). H NMR (CDCl3, d): 7.37
(d, J¼5.86 Hz, 1H), 5.39 (d, J¼5.86 Hz, 1H), 4.17 (d,
J¼14.16 Hz, 1H), 2.56 (dd, J¼14.65, 16.60 Hz, 1H), 2.40
(dd, J¼2.93, 16.60 Hz, 1H), 1.90–1.69 (m, 5H), 1.26–1.06
(m, 6H). Anal. calcd for C11H16O2: C, 73.30; H, 8.91.
Found: C, 73.20; H, 8.89. CAS registry no. 145624-56-2
(R), 60380-10-1 (rac).
3733, 3338, 3020, 2975, 1475, 1461, 1317, 960, 687 cm21
.
1H NMR (CDCl3, d): 8.08 (q, J¼4.40 Hz, 2H), 7.79 (d,
J¼5.86 Hz, 2H), 7.67 (d, J¼8.79 Hz, 1H), 7.58 (d,
J¼8.79 Hz, 2H), 7.55 (d, J¼8.79 Hz, 1H), 7.22–7.12 (m,
8H), 2.13 (s, 6H), 2.01 (s, 3H), 1.98 (s, 3H). 13C NMR
(CDCl3, d): 146.17, 140.62, 139.23, 136.09, 135.96, 135.85,
132.38, 132.19, 131.85, 131.61, 130.93, 128.96, 128.33,
127.44, 127.37, 127.27, 127.15, 126.32, 121.57, 120.42,
119.98, 20.95, 20.89, 20.82. HRMS-FAB (m/z): [M]þ calcd
for C36H28ClO3P, 574.1465. Found: 574.1460.
4.4. Synthesis of the chiral ligand
4.4.1. (R)-2,20-Bis(benzyloxy)-6,60-di(2,6-xylyl)-1,100-
binaphthyl (10). A mixture of 2,20-bis(benzyloxy)-6,6 -
dibromo-1,10-binaphthyl (9)25 (4.80 g, 7.69 mmol), 2,6-
xylylboronic acid (3.00 g, 20.0 mmol), tetrakis(triphenyl-
phosphine)palladium (889 mg, 0.760 mmol) and a solution
of barium hydroxide octahydrate (7.28 g, 23.1 mmol) in 1,2-
dimethoxyethane (DME) (46.2 ml) and water (7.7 ml) was
stirred at 808C for 2.5 h under argon. After cooling, the
resulting mixture was extracted with toluene. The organic
layer was washed with brine, dried over anhydrous
magnesium sulfate, and concentrated. The residue was
subjected to column chromatography to give the desired
product 10 (5.3 g, 99%) as a colorless crystalline. Mp 93–
948C. Rf 0.44 (ethyl acetate–hexane 1:9). [a]2D0¼þ89.0 (c
1.0, CHCl3). IR (KBr): 3712, 3061, 3030, 2947, 2918, 1589,
1483, 1452 cm21. 1H NMR (CDCl3, d): 7.92 (d, J¼8.79 Hz,
2H), 7.66 (s, 2H), 7.45 (dd, J¼8.79, 8.30 Hz, 4H), 7.20–7.07
(m, 14H), 6.96 (d, J¼6.83 Hz, 4H), 5.08 (s, 4H), 2.08 (d,
J¼4.39 Hz,2H).13CNMR(CDCl3,d):153.85,141.78,137.41,
136.35, 132.94, 129.54, 129.27, 128.99, 128.19, 128.06,
127.55, 127.29, 127.24, 126.98, 126.78, 125.77, 120.69,
115.94, 71,02, 21.04, 21.00. HRMS-FAB (m/z): [M]þ calcd
for C50H42O2, 674.3185. Found: 674.3142. Anal. calcd for
C50H42O2·H2O: C, 86.67; H, 6.40. Found: C, 86.60; H, 6.15.
4.4.4. (R)-6,60-di(2,6-xylyl)-1,10-binaphthyl-2,20-diyl
hydrogen phosphate (11). To a suspension of (R)-6,60-
di(2,6-xylyl)1,10-binaphthyl-2,20-diyl
chlorophosphate
(1.57 g, 2.73 mmol) in 2% aqueous sodium carbonate was
stirred at 908C for 1 h, and the reaction mixture was placed in
refrigerator for 12 h. The precipitate was filtered, washed with
2% aqueous sodium carbonate and added to water (22 ml). To
the mixture was added 35% aqueous hydrochloric acid
(1.7 ml), and the resulting suspension was stirred at 958C for
1 h. After cooling, the mixture was extracted with dichlor-
omethane, and the organic layer was washed with water, dried
over anhydrous magnesium sulfate, and concentrated. The
residue was purified by recrystallization from ethanol and
dried in vacuo at 1208C for 16 h to give the desired phosphoric
acid 11 (495 mg, 33%) as colorless solids. Mp 246–2488C.
[a]2D6¼2267.0 (c 1.0, CHCl3). IR (KBr): 3853, 3648, 3307,
1226, 1207, 1027, 950, 892, 767 cm21. 1H NMR (CDCl3, d):
8.03 (d, J¼8.79 Hz, 2H), 7.76 (s, 2H), 7.64 (d, J¼8.79 Hz,
2H), 7.58 (d, J¼8.79 Hz, 2H), 7.22–7.12 (m, 8H) 2.14 (s, 6H),
1.99 (s, 6H). 13C NMR (CDCl3, d): 147.28, 147.19, 140.94,
138.32, 136.07, 135.96, 131.85, 131.10, 131.02, 128.32,
128.10, 127.38, 127.31, 127.24, 121.61, 120.91, 20.91, 20.80.
HRMS-FAB (m/z): [M]þ calcd for C36H29O4P, 557.1882.
Found: 557.1879.
4.4.2. (R)-6,60-Di(2,6-xylyl)-1,10-bi-2-naphthol (11). To a
mixture of 10 (1.49 g, 2.21 mmol) and 10% palladium
carbon (149 mg) were added ethyl acetate (22 ml) and N,N-
diisopropylethylamine (286 mg, 2.21 mmol) under argon,
and then the atmosphere was changed to hydrogen. After
stirring at room temperature for 12 h, the reaction mixture
was passed through Celite. The filtrate was concentrated,
and subjected to column chromatography to give the desired
product 11 (1.07 g, 95%) as a colorless crystalline. Mp
133–1358C. Rf 0.31 (ethyl acetate–hexane 1:4).
4.4.5. (R)-5,50,6,60,7,70,8,80-Octahydro-1,10-binaphthyl-
2,200-diyl chlorophosphate. 0To
a
solution of (R)-
(1.14 g,
5,5 ,6,60,7,70,8,80-octahydro-1,1 -bi-2-naphthol

H. Furuno et al. / Tetrahedron 59 (2003) 10509–10523
10521
3.87 mmol)18 and phosphoryl chloride (1.17 g, 7.62 mmol)
in dichloromethane (8 ml) was added dropwise triethyl-
amine (1.16 g, 11.5 mmol) at room temperature under
argon, and the resulting mixture was vigorously stirred for
12 h under the same conditions. After quenching with water,
the product was extracted with dichloromethane. The
organic layer was washed with water, dried over anhydrous
magnesium sulfate, concentrated, and dried in vacuo to give
the analytically almost pure (R)-chlorophosphate (1.45 g,
99.9%) as colorless voluminous solids, which was used for
in dichloromethane (2 ml) were added 5a (20.9 mg,
0.197 mmol) and 6 (53.1 mg, 0.308 mmol) under argon,
and the reaction mixture was stirred at room temperature for
16 h. After concentration, the residue was diluted with ether
(4 ml) and passed through Celite using additional ether. The
filtrate was successively treated with three drops of
trifluoroacetic acid and four drops of pyridine, and the
resulting mixture was directly subjected to column chro-
matography to give 93% ee of the cycloadduct (R)-7a
(34.0 mg, 99%) as a colorless oil. On the other hand, the
precipitate on the Celite was eluted with THF. After
concentration of the solvent, the complex (11.5 mg, 52%
recovery) was dried in vacuo at room temperature for 3 h,
and that was used for the next round of reactions.
1
the following hydrolysis without further purification. H
NMR (CDCl3, d): 7.19–7.17 (m, 3H), 7.06 (dd, J¼1.95,
8.30 Hz, 1H), 2.90–2.78 (m, 4H), 2.72–2.63 (m, 2H), 2.28
(dt, J¼5.37, 16.11 Hz, 2H), 1.86–1.77 (m, 6H), 1.63–1.51
(m, 2H); (CD3OD, d): 7.32 (dd, J¼3.91, 8.30 Hz, 2H), 7.18
(ddd, J¼1.95, 5.86, 8.30 Hz, 2H), 2.97–2.87 (m, 4H), 2.82–
2.74 (m, 2H), 2.34–2.25 (m, 2H), 1.93–1.82 (m, 6H), 1.66–
1.57 (m, 2H). CAS registry no. 39648-65-2.
4.6. Asymmetric amplifications and the related
experiments
4.6.1. Typical procedure for the hetero-Diels–Alder
reaction using the catalyst 13 (a537, Fig. 6). To a solution
of the catalyst (S)-1-Yb (7.5 mg, 0.0062 mmol) and 2,6-
lutidine (0.715 mg, 0.0067 mmol) in dichloromethane
(0.35 ml) was added a solution of the catalyst (R)-1-Yb
(16.3 mg, 0.0134 mmol) and 2,6-lutidine (1.42 mg,
0.0133 mmol) in dichloromethane (0.40 ml) under argon.
To the resulting suspension (the catalyst 13) were added
5a (8.4 mg, 0.079) and 6 (21.2 mg, 0.123 mmol), and the
mixture was stirred at room temperature for 16 h. The
reaction mixture was successively treated with two drops
of trifluoroacetic acid and three drops of pyridine, and the
resulting mixture was directly subjected to column
chromatography to give the desired product (R)-7a
(9.7 mg, 71%), the enantiomeric purity of which was
determined to be 84% ee by HPLC using Daicel
CHIRALCEL OD.
4.4.6. Sodium (R)-5,50,6,60,7,70,8,80-octahydro-1,10-
binaphthyl-, 2,20 diyl phosphate [(R)-H8-BNP–Na]. To a
mixture of (R)-5,50,6,60,7,70,8,80-octahydro-1,10-binaphthyl-
2,20-diyl cholorophosphate (1.45 g, 3.87 mmol) and 2%
aqueous sodium carbonate (85 ml) was added THF (ca.
10 ml), and if necessary, water and additional THF, enough
to make a clear solution of the reaction mixture at 658C. The
resulting solution was stirred for 3 h under same conditions
and further 10 h at room temperature. Most of the THF was
evaporated under reduced pressure, and the resulting
suspension was warmed at 708C to make a clear solution
of the mixture, and cooled at 08C for 12 h. The precipitate
was filtered, washed with 2% aqueous sodium carbonate,
and dried in vacuo at 708C to give (R)-H8-BNP-Na (1.42 g,
97%) as colorless solids. IR (KBr): 2932, 2857, 2839, 1653,
1633, 1472, 1436, 1254, 1228, 1104, 1058, 955, 854, 710,
592, 485 cm21
.
4.6.2. Typical procedure for the preparation of
Yb(BNP)3 from optically impure ligands (method II,
b534, Fig. 6). To a refluxing solution of 34% ee of (R)-
BNP-H (224 mg, 0.624 mmol) and 3N aqueous sodium
hydroxide (0.208 ml, 0.624 mmol) in methanol (4 ml) was
slowly added a solution of ytterbium chloride hexahydrate
(78.7 mg, 0.203 mmol) in methanol, and the resulting
mixture was stirred for 9 h under the same conditions.
After cooling, the resulting precipitate was centrifuged and
wash with methanol. The colorless solid was dried at 1208C
for 12 h in vacuo to give the desired complex (235 mg,
95%).
4.4.7. (R)-5,50,6,60,7,70,8,80-Octahydro-1,10-binaphthyl-
2,20-diyl hydrogen phosphate [(R)-H8-BNP–H]. To a
solution of the sodium phosphate (1.01 g, 2.67 mmol) in
water (45 ml) was slowly added 35% hydrochloric acid
(6 ml), and the resulting suspension was vigorously stirred
at 708C for 2 h. After cooling, the precipitate was filtered,
washed with water, and dried in vacuo at 1208C for 10 h to
give (R)-H8-BNP-H (892 mg, 94%) as colorless solids.
Gradually decomposes around 2898C. [a]2D0¼2249.9 (c
1.00, ethanol). IR (KBr): 2935, 2858, 1471, 1439, 1423,
1311, 1063, 1252, 1227, 1157, 1056, 1049, 962, 904, 895,
833, 816, 710 cm21 1H NMR (CDCl3, d): 7.12 (d,
.
J¼8.30 Hz, 2H), 7.08 (d, J¼8.30 Hz, 2H), 3.20 (brs),
2.87–2.77 (m, 4H), 2.67 (ddd, J¼4.88, 8.30, 16.60 Hz, 2H),
2.28 (dt, J¼4.88, 16.60 Hz, 2H), 1.82–1.76 (m, 6H), 1.58–
1.52 (m, 2H); (CD3OD, d): 7.22 (d, J¼8.30 Hz, 2H), 7.08
(d, J¼8.30 Hz, 2H), 2.91–2.86 (m, 4H), 2.80–2.72 (m, 2H),
2.30–2.23 (m, 2H), 1.89–1.80 (m, 6H), 1.61–1.55 (m, 2H).
13C NMR (CD3OD, d): 147.98, 147.88, 139.45, 136.86,
131.11, 127.47, 119.34, 30.02, 28.87, 23.60, 23.47. HRMS-
FAB (m/z): [MþH]þ calcd for C20H22O4P, 357.1256.
Found: 357.1255. CAS registry no. 39648-63-0.
4.6.3. Typical procedure for the hetero-Diels–Alder
reaction using the catalyst 14 (b534 Fig. 6). To a
suspension of Yb(BNP)3 (36.6 mg, 0.0301 mmol), prepared
above in 4.6.2, and 2,6-lutidine (3.31 mg, 0.0309 mmol) in
dichloromethane (1 ml) were added 5a (10.4 mg,
0.0984 mmol) and 6 (26.6 mg, 0.154 mmol) under argon,
and the mixture was stirred at room temperature for 16 h.
The reaction mixture was successively treated with two
drops of trifluoroacetic acid and three drops of pyridine, and
the resulting mixture was directly subjected to column
chromatography to give the desired product (R)-7a
(12.4 mg, 73%), the enantiomeric purity of which was
determined to be 90.2% ee by HPLC using Daicel
CHIRALCEL OD.
4.5. Repeated use of the catalyst
To a solution of the catalyst (R)-3-Sc (22.2 mg, 0.02 mmol)

10522
H. Furuno et al. / Tetrahedron 59 (2003) 10509–10523
4.6.4. Complex 15-Yb prepared from 50% ee of (R)-rich
BNP-H. Colorless solid. Anal. calcd for C60H36O12P3-
Yb·H2O: C, 58.45; H, 3.11. Found: C, 58.09; H, 3.14.
4.7.2. Methyl 3,4-dihydro-4-oxo-2-phenyl-2H-pyran-2-
carboxylate (29b). Colorless needle. Mp 77.5–78.58C. Rf
0.37 (ethyl acetate–hexane 3:7). [a]2D3¼234.3 (c 1.00,
CHCl3, 97.1% ee for HPLC analysis). HPLC (CHIRAL-
PAK AD, 2-propanol–hexane 1:50, 0.5 ml/min): tR
48.3 min for the major enantiomer (53.3 min for the minor
one). IR (KBr): 3082, 1749, 1736, 1677, 1599, 1451, 1401,
1273, 1229, 1212, 1125, 1024, 993, 892, 858, 812, 777, 725,
695 cm21. 1H NMR (CDCl3, d): 7.54–7.50 (m, 3H), 7.45–
7.37 (m, 3H), 5.52 (dd, J¼0.98, 6.35 Hz, 1H), 3.74 (s, 3H),
3.45 (dd, J¼0.98, 16.60 Hz, 1H) 3.08 (d, J¼16.60 Hz, 1H).
13C NMR (CDCl3 d): 189.42, 169.89, 161.23, 136.45,
129.07, 128.77, 124.85, 108.25, 85.61, 53.48, 44.27.
4.6.5. Typical procedure for the determination of the
enantiopurity of the chiral ligand of the complex
RE(BNP)3: Complex 16. To a solution of the complex 16
[18.9 mg, 0.0156 mmol as Yb(BNP)3] in THF was added a
1.0 M solution of LiA1H4 in ether (0.160 ml, 0.160 mmol)
at 08C under argon. The regulating mixture was stirred for
46 h at room temperature, and then quenched with dilute
hydrochloric acid. The crude product was extracted with
dichloromethane, and the organic layer was dried over
anhydrous magnesium sulfate. After concentration, the
residue0 was subjected to column chromatography to give
(R)-1,1 -bi-2-naphthol (13.2 mg, 99%), the enantiomeric
purity of which was determined to be 98.0% ee by HPLC
using Daicel CHIRALPAK AD (ethanol–hexane 1:9,
0.5 ml/min): tR 44.5 min for the R isomer (49.4 min for
the S isomer).
Acknowledgements
This work was supported by a Grant-in-Aid for Scientific
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.). We are grateful to Dr M. Ohba and Professor
H. Okawa, Faculty of Sciences, Kyushu University,
Professor H. Kanno of National Defense Academy in
Japan, Mr S. Watanabe of Shimadzu Corporation, Japan,
and Tosoh Analysis and Research Center, Japan for the
measurements of the magnetic susceptibility, Raman
spectrum, the ESCA, and the ICP-MS of 4-Ce, respectively.
4.6.6. Complex 18. This complex was prepared according
to Scheme 4 and isolated in a similar way to the preparation
of (R)-1-Yb. Colorless solid. Anal. calcd for C60H36O12P3-
Yb·2H2O: C, 57.61; H, 3.22. Found: C, 57.30; H, 3.10.
4.6.7. Complex 20. This complex was prepared via the
complex 19 according to Scheme 5 and isolated in a similar
way to the preparation of (R)-1-Yb. Colorless solid. Anal.
calcd for C60H36O12P3Yb·H2O: C, 58.45; H, 3.11. Found: C,
58.67; H, 3.04.
4.6.8. Complexes 21-Yb and 22-Yb. These complexes
were derived from 15-Yb (Section 4.6.4) as described in
Table 5. For 21-Yb. Anal. calcd for C60H36O12P3Yb·H2-
O·C4H8O [vYb(BNP)3·H2O·THF]: C, 58.90; H, 3.55.
Found: C, 58.62; H, 3.63. For 22-Yb. Anal. calcd for
C60H36O12P3Yb·H2O: C, 58.45; H, 3.11. Found: C, 58.67;
H, 3.02.
References
1. Hard and Soft Acids and Bases. Pearson, R. G., Ed.; Dowden,
Hutchinson & Ross: Stroundsburg, 1973.
2. For reviews, see: (a) Kobayashi, S.; Sugiura, M.; Kitagawa,
H.; Lam, W. W.-L. Chem. Rev. 2002, 102, 2227–2302.
(b) Kobayashi, S. Top. Organomet. Chem. 1999, 2, 63–118.
(c) Kobayashi, S. Eur. J. Org. Chem. 1999, 15–27.
(d) Kobayashi, S. Synlett 1994, 689–701.
4.7. Asymmetric Hetero-Diels–Alder reaction of a-keto
esters
3. Inanaga, J.; Sugimoto, Y.; Hanamoto, T. New J. Chem. 1995,
19, 707–712.
4.7.1. Typical procedure for the asymmetric hetero-
Diels–Alder reaction of a-keto esters. Synthesis of ethyl
3,4-dihydro-4-oxo-2-phenyl-2H-pyran-2-carboxylate
(29a). To a suspension of the catalyst (R)-1-Yb (12.2 mg,
0.0100 mmol) in dichloromethane (1 ml) was added 28a
(18.0 mg, 0.101 mmol) and 6 (26.6 mg, 0.154 mmol), and
the reaction mixture was stirred at room temperature for
11 h. The mixture was successively treated with two drops
of trifluoroacetic acid and three drops of pyridine, and the
resulting solution was directly subjected to column
chromatography to give the desired product 29a (22.2 mg,
90%). [a]2D2¼246.8 (c 1.00, CHCl3, 99.6% ee for HPLC
analysis). HPLC (CHIRALPAK AD, 2-propanol–hexane
1:50, 0.5 ml/min): tR 40.8 min for the major enantiomer
4. Hanamoto, T.; Sugimoto, Y.; Jin, Y. Z.; Inanaga, J. Bull.
Chem. Soc. Jpn. 1997, 70, 1421–1426.
5. (a) Kobayashi, S.; Tsuchiya, T.; Komoto, I.; Matsuo, J.-i.
J. Organomet. Chem. 2001, 624, 392–394. (b) Shi, M.; Shen,
Y.-M. J. Fluorine Chem. 2001, 109, 195–200. (c) Matsuo, J.;
Tsuchiya, T.; Odashima, K.; Kobayashi, S. Chem. Lett. 2000,
29, 178–179.
6. (a) Kobayashi, S.; Aoyama, N.; Manabe, K. Synlett 2002,
483–485. (b) Hachiya, I.; Kobayashi, S. Tetrahedron Lett.
1994, 35, 3319–3320.
7. (a) Nishikido, J.; Nanbo, M.; Yoshida, A.; Nakajima, H.;
Matsumoto, Y.; Mikami, K. Synlett 2002, 1613–1616.
(b) Nishikido, J.; Kamishima, M.; Matsuzawa, H.; Mikami,
K. Tetrahedron 2002, 58, 8345–8349. (c) Mikami, K.;
Mikami, Y.; Matsuzawa, H.; Matsumoto, Y.; Nishikido, J.;
Yamamoto, F.; Nakajima, H. Tetrahedron 2002, 58,
4015–4021. (d) Duris, F.; Barbier-Baudry, D.; Dormond, A.;
Desmurs, J. R.; Bernard, J. M. J. Mol. Catal. A 2002, 188,
97–104. (e) Yamanoi, T.; Nagayama, S.; Ishida, H.-K.;
Nishikido, J.; Inazu, T. Synth. Commun. 2001, 31, 899–903.
1
(44.9 min for the minor one). H NMR (CDCl3, d): 7.57–
7.50 (m, 3H), 7.44–7.36 (m, 3H), 5.52 (dd, J¼0.97,
5.86 Hz, 1H), 4.20 (dq, J¼0.97, 7.32 Hz, 2H), 3.45 (dd.
J¼0.97, 16.60 Hz, 1H) 3.07 (d, J¼16.60 Hz, 1H), 1.20 (t,
J¼7.32 Hz, 3H). CAS registry no. 200421-47-2 (R),
238737-21-8 (undetermined).

H. Furuno et al. / Tetrahedron 59 (2003) 10509–10523
10523
(f) Nie, J.; Xu, J.; Zhou, G. J. Chem. Res., Synop. 1999,
446–447. (g) Nie, J.; Zhao, Z.; Xu, J.; Liu, D. J. Chem. Res.,
Synop. 1999, 160–161. (h) Nishikido, J.; Nakajima, H.; Saeki,
T.; Ishii, A.; Mikami, K. Synlett 1998, 1347–1348. (i)
Mikami, K.; Kotera, O.; Motoyama, Y.; Tanaka, M. Inorg.
Chem. Commun. 1998, 1, 10–11. (j) Ishihara, K.; Karumi, Y.;
Kubota, M.; Yamamoto, H. Synlett 1996, 839–841. (k)
Ishihara, K.; Kubota, M.; Yamamoto, H. Synlett 1996,
265–266.
(a) Yamashita, Y.; Saito, S.; Ishitani, H.; Kobayashi, S. J. Am.
Chem. Soc. 2003, 125, 3793–3798. (b) Yuan, Y.; Long, J.;
Sun, J.; Ding, K. Chem. Eur. J. 2002, 8, 5033–5042. (c) Kii,
S.; Hashimoto, T.; Maruoka, K. Synlett 2002, 931–932.
(d) Wang, B.; Feng, X.; Huang, Y.; Liu, H.; Cui, X.; Jiang, Y.
J. Org. Chem. 2002, 67, 2175–2182. (e) Du, H.; Long, J.; Hu,
J.; Li, X.; Ding, K. Org. Lett. 2002, 4, 4349–4352. (f) Doyle,
M. P.; Phillips, I. M.; Ju, W. J. Am. Chem. Soc. 2001, 123,
5366–5367. (g) Aikawa, K.; Irie, R.; Katsuki, T. Tetrahedron
2001, 57, 845–851. (h) Kezuka, S.; Mita, T.; Ohtsuki, N.;
Ikeno, T.; Yamada, T. Bull. Chem. Soc. Jpn 2001, 74,
1333–1342. (i) Bednarski, M.; Maring, C.; Danishefsky, S.
Tetrahedron Lett. 1983, 24, 3451–3454.
8. (a) Barrett, A. G. M.; Bouloc, N.; Braddock, D. C.; Catterick,
D.; Chadwick, D.; White, A. J. P.; Williams, D. J. Tetrahedron
2002, 58, 3835–3840. (b) Barrett, A. G. M.; Braddock, D. C.;
Catterick, D.; Chadwick, D.; Henschke, J. P.; McKinnell, R. M.
Synlett 2000, 847–849. (c) Ishihara, K.; Hiraiwa, Y.;
Yamamoto, H. Synlett 2000, 80–82. (d) Barrett, A. G. M.;
Braddock, D. C.; Ducray, R.; McKinnell, R. M.; Waller, F. J.
Synlett 2000, 57–58. (e) Nishikido, J.; Yamamoto, F.;
Nakajima, H.; Mikami, Y.; Matsumoto, Y.; Mikami, K.
Synlett 1999, 1990–1992.
18. Cram, D. J.; Helgeson, R. C.; Peacock, S. C.; Kaplan, L. J.;
Domeier, L. A.; Moreau, P.; Koga, K.; Mayer, J. M.; Chao, Y.;
Siegel, M. G.; Hoffman, D. H.; Sogah, G. D. Y. J. Org. Chem.
1978, 43, 1930–1946.
19. (a) Kobayashi, S.; Hamada, T.; Nagayama, S.; Manabe, K.
Org. Lett. 2001, 3, 165–167. (b) Desimoni, G.; Faita, G.;
Filippone, S.; Mella, M.; Zampori, M. G.; Zema, M.
Tetrahedron 2001, 57, 10203–10212.
9. Kobayashi, S.; Nagayama, S.; Busujima, T. J. Am. Chem. Soc.
1998, 120, 8287–8288.
10. For recent reviews, see: (a) Inanaga, J.; Furuno, H.; Hayano, T.
Chem. Rev. 2002, 102, 2211–2225. (b) Aspinall, H. C. Chem.
Rev. 2002, 102, 1807–1850.
20. Hayano, H.; Sakaguchi, T.; Furuno, H.; Ohba, M.; Okawa, H.;
Inanaga, J. Chem. Lett. 2003, 32, 608–609.
21. Puchot, C.; Samuel, O.; Dun˜ach, E.; Zhao, S.; Agami, C.;
Kagan, H. B. J. Am. Chem. Soc. 1986, 108, 2353–2357.
22. For recent reviews, see: (a) Kagan, H. B. Synlett 2001,
888–899. (b) Noyori, R.; Suga, S.; Oka, H.; Kistamura, M.
Chem. Rec. 2001, 1, 85–100. (c) Blackmond, D. G. Acc.
Chem. Res. 2000, 33, 402–411. (d) Fenwick, D. R.; Kagan,
H. B. Top Stereochem. 1999, 22, 257–296.
11. For our recent reports in this area, see: (a) Jin, X. L.; Sugihara,
H.; Daikai, K.; Tateishi, H.; Jin, Y. Z.; Furuno, H.; Inanaga, J.
Tetrahedron 2002, 58, 8321–8329, corrigendum: 2003, 59,
877. (b) Sugihara, H.; Daikai, K.; Jin, X. L.; Furuno, H.;
Inanaga, J. Tetrahedron Lett. 2002, 43, 2735–2739.
12. For some recent reports contributed from other laboratorys,
see: (a) Suga, H.; Inoue, K.; Inoue, S.; Kakehi, A. J. Am.
Chem. Soc. 2002, 124, 14836–14837. (b) Evans, D. A.; Wu,
J.; Masse, C. E.; MacMillan, D. W. C. Org. Lett. 2002, 4,
3379–3382. (c) Evans, D. A.; Masse, C. E.; Wu, J. Org. Lett.
2002, 4, 3375–3378. (d) Sibi, M. P.; Manyem, S. Org. Lett.
2002, 4, 2929–2932. (e) Fukuzawa, S.-i.; Fujimoto, K.;
Komuro, Y.; Matsuzawa, H. Org. Lett. 2002, 4, 707–709.
(f) Desimoni, G.; Faita, G.; Guala, M.; Pratelli, C. Tetrahedron
2002, 58, 2929–2935. (g) Desimoni, G.; Faita, G.; Filippone,
S.; Mella, M.; Zampori, M. G.; Zema, M. Tetrahedron 2001,
57, 10203–10212. (h) Evans, D. A.; Sweeney, Z. K.; Rovis,
T.; Tedrow, J. S. J. Am. Chem. Soc. 2001, 123, 12905–12906.
13. Leclercq, M.; Jacques, J. Nouv. J. Chim. 1979, 3, 629–635.
14. Hanamoto, T.; Furuno, H.; Sugimoto, Y.; Inanaga, J. Synlett
1997, 79–80.
23. For some recent reports of asymmetric amplification, see:
(a) Wipf, P.; Jayasuriya, N.; Ribe, S. Chirality 2003, 15,
208–212. (b) Daikai, K.; Hayano, T.; Kino, R.; Furuno, H.;
Kagawa, T.; Inanaga, J. Chirality 2003, 15, 83–88.
(c) Villano, R.; De Rosa, M.; Salemo, C.; Soriente, A.; Scettri,
A. Tetrahedron: Asymmetry 2002, 13, 1949–1952. (d)
Sarvary, I.; Wan, Y.; Frejd, T. J. Chem. Soc., Prekin Trans.
1 2002, 645–651. (e) Saito, B.; Katsuki, T. Tetrahedron Lett.
2001, 42, 8333–8336. (f) Chen, Y. K.; Costa, A. M.; Walsh,
P. J. J. Am. Chem. Soc. 2001, 123, 5378–5379. (g) Nemoto,
T.; Ohshima, T.; Yamaguchi, K.; Shibasaki, M. J. Am. Chem.
Soc. 2001, 123, 2725–2732.
24. (a) Dalko, P. I.; Moisan, L.; Cossy, J. Angew. Chem., Int. Ed.
Engl. 2002, 41, 625–628. (b) Ghosh, A. K.; Shirai, M.
Tetrahedron Lett. 2001, 42, 6231–6233. (c) Yao, S.;
Johannsen, M.; Audrain, H.; Hazell, R. G.; Jørgensen, K. A.
J. Am. Chem. Soc. 1998, 120, 8599–8605. (d) Johannsen, M.;
Yao, S.; Jørgensen, K. A. Chem. Commun. 1997, 2169–2170.
´
25. (a) Cuntze, J.; Owens, L.; Alcazar, V.; Seiler, P.; Diederich, F.
Helv. Chim. Acta 1995, 78, 367–390. (b) Hamada, T.; Fukuda,
T.; Imanishi, H.; Katsuki, T. Tetrahedron 1996, 52, 515–530.
15. Furuno, H.; Hanamoto, T.; Sugimoto, Y.; Inanaga, J. Org. Lett.
2000, 2, 49–52.
16. For a review, see: Jørgensen, K. A. Angew. Chem., Int. Ed.
Engl. 2000, 39, 3358–3388.
17. For some recent reports of the highly enantioselective hetero-
Diels–Alder reaction of aldehydes with the diene 6, see: