Asymmetric hetero Diels-Alder reaction of Danishefsky's dienes and glyoxylates with chiral bis(oxazolinyl)phenylrhodium(III) aqua complexes, and its mechanistic studies

Article abstract of DOI:10.1016/S0040-4020(00)01049-8

Asymmetric hetero Diels-Alder reaction of Danishefsky's dienes with glyoxylates is catalyzed in high enantioselectivity and cis (endo)-diastereoselectivity by chiral (Phebox)RhCl₂(H₂O) complexes [Phebox=2,6-bis(oxazolinyl)phenyl], via the concerted [4+2] mechanism with perpendicular conformation of two carbonyl moieties of glyoxylates. Dibromide and difluoride complexes were newly synthesized and found to exhibit a slightly higher enantioselectivity of the hetero Diels-Alder products than the parent dichloride complex (Cl: 80% ee, Br: 82% ee, F: 84% ee).

Full text of DOI:10.1016/S0040-4020(00)01049-8

TETRAHEDRON
Pergamon
Tetrahedron 57 (2001) 853±860
Asymmetric hetero Diels±Alder reaction of Danishefsky's dienes
and glyoxylates with chiral bis(oxazolinyl)phenylrhodium(III)
aqua complexes, and its mechanistic studies
p
Yukihiro Motoyama, Yoshiyuki Koga and Hisao Nishiyama
School of Materials Science, Toyohashi University of Technology, Tempaku-cho, Toyohashi, Aichi 441-8580, Japan
Received 28 April 2000; accepted 4 September 2000
Dedicated to Professor Kenji Itoh on the occasion of his 60th birthday.
AbstractÐAsymmetric hetero Diels±Alder reaction of Danishefsky's dienes with glyoxylates is catalyzed in high enantioselectivity and cis
O) complexes [Pheboxˆ2,6-bis(oxazolinyl)phenyl], via the concerted [412]
(
endo)-diastereoselectivity by chiral (Phebox)RhCl
2
(H
2
mechanism with perpendicular conformation of two carbonyl moieties of glyoxylates. Dibromide and di¯uoride complexes were newly
synthesized and found to exhibit a slightly higher enantioselectivity of the hetero Diels±Alder products than the parent dichloride complex
(
Cl: 80% ee, Br: 82% ee, F: 84% ee). q 2001 Elsevier Science Ltd. All rights reserved.
1
. Introduction
Phebox±Rh(III) complexes 1±3, and its mechanistic studies
on the reaction pathway and the transition state assembly
(Chart 1).
Recently, many transition±metal complexes have been
applied as attractive chiral Lewis acid catalysts for asym-
metric reactions, particularly in terms of carbon±carbon
1
2
. Results and discussion
bond forming reactions. Comparing with traditional
Lewis acids, transition-metal complexes are generally
2
single well-de®ned species, insensitive to water. Therefore,
2
.1. Asymmetric hetero Diels±Alder reaction
identi®cation of their active intermediates being Lewis
acid±base complexes and consideration of their transition
states are easier than those of traditional Lewis acid
complexes.
3
We ®rst examined the reaction of trimethylsilyl (TMS)-
derived diene 4a and n-butyl glyoxylate 5a catalyzed by
i-Pr±Phebox-derived dichloride complex 1a. However,
decomposition of the diene 4a into 4-methoxy-3-buten-2-
one was very fast, and a trace amount of the desired hetero
Diels±Alder adduct was obtained (Table 1, entry 1). While
the reaction of tert-butyldimethylsilyl (TBS)-derived diene
We have already designed a meridional tridentate ligand,
2,6-bis(oxazolinyl)phenyl derivative (abbreviated to
Phebox) as a chiral N±C±N type ligand with one central
4
,5
4
(
b and 5a proceeded smoothly by a catalytic amount
2 mol%) of the complex (S,S)-1a in toluene at 2788C to
covalent bond to a metal, and have demonstrated that
Phebox±Rh(III) complexes 1 acted as chiral Lewis acid
catalysts for the enantioselective addition of allyltributyltin
give dihydropyrone 6a in 86% isolated yield after acid treat-
ment (TFA: tri¯uoroacetic acid) with 26% ee (entry 2). The
enantioselectivity was highly dependent on the substituents
of both the chiral catalysts and the ester moieties of glyoxyl-
ates, and the reaction solvents. The enantioselectivity using
Ph±Phebox-derived complex 1b was decreased to 19% ee,
furthermore, Me- and t-Bu±Phebox-derived complexes 1c
and 1d gave almost racemic products (entries 3±5).
Whereas, the remarkably high enantiomeric excess (80%
ee) of 6a was determined by HPLC analysis (Daicel
CHIRALPAK AD) using Bn±Phebox-derived complex 1e
5
to aldehydes. In this catalytic allylation, the (Phebox)RhCl2
fragments A, generated by releasing H O from
2
(Phebox)RhCl (H O) complexes 1, are active Lewis acid
2 2
catalysts. Furthermore, these air-stable and water-tolerant
aqua complexes 1 could be recovered quantitatively from
the reaction media. Now we wish to report herein the
6
synthesis of (Phebox)RhX (H O) complexes (2: XˆBr,
2
2
3
Danishefsky's dienes and glyoxylates catalyzed by the
: XˆF), the asymmetric hetero Diels±Alder reaction of
7
,8
(
entry 6). Although the reaction proceeded smoothly in
Keywords: bis(oxazolinyl)phenyl; rhodium; aqua complex; hetero Diels±
Alder reaction; Danishefsky's diene; glyoxylate.
dichloromethane, the enantiomeric excess of the dihydro-
pyrone 6a decreased to 36% (entry 7). The enantioselec-
tivity of the reaction with methyl glyoxylate 5b, which is
*
Corresponding author. Tel.: 181-532-44-6818; fax: 181-532-48-5833;
e-mail: hnishi@tutms.tut.ac.jp
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)01049-8

8
54
Y. Motoyama et al. / Tetrahedron 57 (2001) 853±860
Chart 1.
1
0
the small ester substituent, fell to 68% ee (entry 8). While
the reaction of bulky iso-propyl glyoxylate 5c made the
enantiomeric excess of dihydropyrone 6c slightly increased
to 82%, the chemical yield was remarkably decreased to
tronic, structural and bonding properties. So we next
synthesized the dibromide and di¯uoride complexes (2
and 3), and examined the counter ion effect on catalytic
activity and enantioselectivity of the present reaction.
76% isolated yield (entry 9). The absolute con®gurations
of the dihydropyrones 6a±c were proved to be 2R (re-face
Both dibromide and di¯uoride complexes 2 and 3 were
prepared from the dichloride complex 1e. The reaction of
1e with carbon tetrabromide in methanol gave the dibro-
mide complex 2 in 91% isolated yield. While 1e was ®rst
reacted with silver acetate, then the corresponding diacetate
complex was led to the di¯uoride complex 3 by treatment
with tetrabutylammonium ¯uoride and hydro¯uoroboric
acid in dichloromethane (Scheme 1).
attack of the diene) by comparisons of the optical rotation
with the literature values. This re-face attack of the diene
9
4b to the aldehyde's CvO planes is the opposite enantio-
face-selection in the allylation of aldehydes with allyltri-
butyltin catalyzed by (S,S)-1.
5
Recently, much attention has been focused on the effect of
counter ions on catalytic activity and enantioselectivity.
Especially, a ¯uoride counterion shows distinctive elec-
The reaction of diene 4b and glyoxylate 5a catalyzed by
Table 1. Asymmetric hetero Diels±Alder reaction of Danishefsky's dienes 4 and glyoxylates 5 catalyzed by Phebox±Rh(III) complexes 1 (all reactions were
carried out using 0.6 mmol of diene 4, 0.5 mmol of glyoxylate 5, and 0.01 mmol of complexes 1 in 2 mL of solvent in the presence of MS 4A (250 mg) at
2788C for 1 h)
a
b
Entry
Complex
Diene
Glyoxylate
Product
% Yield
% Ee
Abs. con®g.
1
2
3
4
5
6
7
8
9
1a
1a
1b
1c
1d
1e
1e
1e
1e
4a
4b
4b
4b
4b
4b
4b
4b
4b
5a
5a
5a
5a
5a
5a
5a
5b
5c
6a
6a
6a
6a
6a
6a
6a
6b
6c
Trace
86
87
56
87
90
95
93
76
±
±
R
R
R
S
R
R
R
R
26
19
5
3
80
36
68
82
c
a
Determined by HPLC analysis using Daicel CHIRALPAK AD.
Determined by comparison of the [a]
In CH Cl
b
c
D
value with reported data: see Experimental.
2
2
.
Scheme 1.

Y. Motoyama et al. / Tetrahedron 57 (2001) 853±860
855
Table 2. Asymmetric hetero Diels±Alder reaction of Danishefsky's diene 4b and glyoxylate 5a catalyzed by (Bn±Phebox)RhX (H
2
2
O) complexes 1±3 (all
reactions were carried out using 0.6 mmol of diene 4b, 0.5 mmol of glyoxylate 5a, and 0.01 mmol of complexes 1±3 in 2 mL of solvent in the presence of MS
A (250 mg) at 2788C for 1 h)
4
a
b
Entry
Complex
% Yield
% Ee
Abs. con®g.
1
2
3
1e (XˆCl)
2 (XˆBr)
3 (XˆF)
90
99
90
80
82
84
R
R
R
a
Determined by HPLC analysis using Daicel CHIRALPAK AD.
Determined by comparison of the [a] value with reported data: see Experimental.
D
b
(
Bn±Phebox)RhX (H O) complexes was carried out in a
2
lyzed (or promoted) reaction of Danishefsky's dienes 4
and aldehydes. One is a concerted [412] cycloaddition
(pericyclic) mechanism like the classical all-carbon
2
1
1
similar manner as above (Table 2). Both dibromo and
di¯uoro complexes 2 and 3 show the high catalytic activity
similar to the parent dichloride catalyst 1e. The optical
purity of the dihydropyrone 6a was slightly increased
using the di¯uoro complex 3 (Cl: 80% ee, Br: 82% ee, F:
1
2
Diels±Alder process. In this case, cycloadduct B is
directly produced. The other is a stepwise mechanism; a
Mukaiyama-aldol reaction leads to intermediates C (LˆSi
1
3
8
4% ee, respectively).
or H), followed by cyclization (Scheme 2). Danishefsky et
al. concluded that the reactions with stronger Lewis acids
such as BF occur via a stepwise mechanism, whereas ZnCl
Although these Phebox±Rh(III) complexes 1±3 are
effective chiral Lewis acid catalysts for the reaction of
Danishefsky's diene 4b with highly reactive glyoxylates 5,
other simple or activated aldehydes or ketones such as
benzaldehyde, (benzyloxy)acetaldehyde or ethyl pyruvate
can not react with an activated diene 4b under in¯uence
of the complexes 1±3.
3
2
1
1b
or lanthanides-catalyzed reactions are concerted. So, we
next checked the intermediate of the present Phebox±
Rh(III) catalyzed reaction.
1
The H NMR spectrum of the crude product, obtained by the
reaction of diene 4b and glyoxylate 5a using 2 mol% of
complex 1e in toluene at 2788C for 1 h, revealed no acyclic
(Mukaiyama-aldol) intermediates 8. The signals of the
2
.2. Reaction mechanism
1
2b
cycloadduct 7 appeared exclusively with .9:1 diastereo
mixtures at an anomeric C-2 position (Scheme 3). The major
There are two reaction pathways for the Lewis acid-cata-
Scheme 2.
Scheme 3.

8
56
Y. Motoyama et al. / Tetrahedron 57 (2001) 853±860
Chart 2.
product of 7 could be isolated by silica gel chromatography
in 77% yield, and the isolated adduct was readily converted
to the dihydropyrone 6a by treatment with tri¯uoroacetic
acid. These results showed that the present catalytic reaction
of Danishefsky's diene 4b with glyoxylate 5a proceeds via
the concerted [412] cycloaddition pathway, in contrast
to the stepwise (Mukaiyama-aldol) mechanism catalyzed
glyoxylates 5. If both the carbonyl groups of 5 are the
parallel conformation (Fig. 1, D), the dienes 4 approach
the carbonyl si-face like allylation of aldehydes with allyltin
5
b
reagents (Fig. 1, F). The molecular orbital calculation of
the protonated methyl glyoxylate 5b using the PM3 method
in WinMOPAC Ver. 214 resulted in only the perpendicular
conformation obtained (Fig. 1, E). In such a case, the steric
repulsion between the ester moiety of glyoxylates 5 and one
substituent on the oxazoline rings exists (Fig. 1, G). When
the CvO plane of glyoxylates bound to the rhodium atom is
shifted to the Cl±Rh±Cl plane for avoiding the steric
8
o
by bis(oxazoline)-Cu(OTf)
Yb(OTf)3 system (Chart 2).
or bis(oxazolinyl)pyridine-
2
8
n
2.3. Transition state assembly
0
repulsion (Fig. 1, G ), one of the substituents on the oxazo-
line rings plays the crucial role of shielding re-face of the
CvO plane from attack of the dienes 4. This perpendicular
structure is consistent with the substituent effect of the ester
moieties on the enantioselectivity of the products 6. The
bulky ester moiety increases the steric repulsion toward
the benzyl group on the Phebox ligand, so the conformation
In order to clarify the direction of diene-approach to glyoxyl-
ates 5 bound to the (Phebox)RhX fragments, including the
2
endo or exo orientation and the CvO enantioface, we ®rst
examined the diastereoselectivity of this catalytic system
using 2,4-dimethyl diene 4c and n-butyl glyoxylate 5a.
Reactivity of the 2,4-disubstituted diene 4c was relatively
lower than that of 4b, although the reaction temperature
rising 2308C resulted in 67% yield of 6d with cis/trans
ratio of 93:7 (Scheme 4). This cis-selectivity and Diels±
Alder mechanism imply that the reaction with Phebox±
Rh(III) complexes proceeds via endo-transition state;
endo-orientation of the ester group of glyoxylate relative
to the diene. The cis (endo)-6d indicated 83% ee by chiral
HPLC analysis (Daicel CHIRALPAK AD), but the enan-
tioselectivity of trans (exo)-isomer was only 20%.
0
of G is more favored than that of G.
3. Conclusion
It has been shown that the (Phebox)RhCl (H O) complexes
2
2
are ef®cient chiral Lewis acid catalysts for the reaction of
Danishefsky's dienes with glyoxylate. We have newly
synthesized the (Phebox)RhX (H O) complexes (XˆBr,
2
2
F), and found that these dibromo and di¯uoro catalysts are
found to exhibit a slightly higher enantioselectivity than the
parent dichloride complex. We have also clari®ed that
the present reaction proceeds via the concerted [412]
A transition state that accounts for the observed re-face
selectivity of the glyoxylate's CvO plane is explained by
the perpendicular conformation of two carbonyl moieties of
Scheme 4.

Y. Motoyama et al. / Tetrahedron 57 (2001) 853±860
857
Figure 1.
mechanism with the perpendicular conformation of the both
0
accomplished by UV light (254 nm), anisaldehyde, and
phosphomolybdic acid. All reactions were carried out
under a nitrogen or argon atmosphere. (Phebox)RhCl (H O)
carbonyl moieties of glyoxylates G .
2
2
5
complexes 1 were prepared by our method. Danishefsky's
dienes 4 were prepared by the literature method.
Glyoxylates 5 were prepared by the literature method.
1
5
4
. Experimental
1
6
4.1. General methods
4
.1.1. (Bn±Phebox)RhBr (H O) (2). To a stirred solution
2 2
Anhydrous toluene and dichloromethane were purchased
Ê
from Kanto Chemical Co. 4A Molecular Sieves (activated
of (Bn±Phebox)RhCl (H O) (1e) (317.0 mg, 0.54 mmol) in
2 2
methanol (50 mL) was added carbon tetrabromide (1.79 g,
5.40 mmol) at room temperature under argon atmosphere.
After stirring for 72 h, the reaction mixture was concen-
trated under reduced pressure. Puri®cation by silica gel
chromatography (hexane/ethyl acetateˆ3:1) gave (Bn±
Phebox)RhBr (H O) (2) in 91% yield (333.1 mg,
2 2
powder) and silver acetate were purchased from Aldrich
Chemical Co. Hydro¯uoroboric acid (HBF ) was purchased
4
from Kishida Chemical Co. Carbon tetrabromide and tetra-
butylammonium ¯uoride (TBAF) were purchased from
1
13
Tokyo Chemical Industry Co. H and C NMR spectra
were measured on Varian Mercury 300 (300 MHz) and
Inova 400 (400 MHz) spectrometers. Chemical shifts for
0.49 mmol); pale yellow solid. Mp. .3008C. IR (KBr) n
3437, 2924, 1618, 1487, 1330, 1149, 970, 737, 704 cm2 .
1
1
1
H NMR were described in parts per million down®eld
from tetramethylsilane as an internal standard (dˆ0) in
H NMR (270 MHz, CDCl
14.2, 9.8 Hz, 2H), 3.65 (dd, Jˆ14.2, 3.9 Hz, 2H), 4.51±4.76
3
) d 2.36 (bs, 2H), 2.81 (dd, Jˆ
13
1
3
CDCl , unless otherwise noted. Chemical shifts for C
NMR were expressed in parts per million in CDCl as an
(m, 6H), 7.23±7.36 (m, 11H), 7.63 (d, Jˆ7.3 Hz, 2H).
C
3
NMR (67.8 MHz, CDCl
128.0, 129.0, 131.4, 136.8, 171.4 (JRh±Cˆ2.9 Hz), 180.8
(JRh±Cˆ25.4 Hz). Anal. Br Rh: Found
46.10, H 3.47, N 4.13%; Calcd C 46.18, H 3.73, N 4.14%.
) d 40.2, 63.5, 75.1, 122.9, 126.6,
3
3
internal standard (dˆ77.1), unless otherwise noted. IR
spectra were measured on a JASCO FT/IR-230 spectro-
meter. High-performance liquid chromatography (HPLC)
analyses were performed on a JASCO PU-980 HPLC
pump, UV-975 and 980 UV/VIS detector, and CO-966
column thermostat (at 258C) using Daicel CHIRALPAK
AD or AS columns. Optical rotations were measured on a
JASCO DIP-140 polarimeter. Column chromatography was
performed with silica gel (Merck, Art 7734). Elemental
analyses were performed on a Yanaco CHN corder MT-6.
Analytical thin-layer chromatography (TLC) was
performed on glass plates and aluminum sheets precoated
with silica gel (Merck, Kieselgel 60 F254, layer thickness
C
H
N
25
O
2
C
26
3
2
4.1.2. (Bn±Phebox)Rh(OAc)
of (Bn±Phebox)RhCl (H O) (1e) (84.2 mg, 0.143 mmol) in
(H O). To a stirred solution
2 2
2
2
dichloromethane (8 mL) was added silver acetate (95.7 mg,
0.573 mmol) at room temperature under argon atmosphere.
After stirring for 1 day, the reaction mixture was ®ltered
through a pad of Celite, then concentrated under reduced
pressure. Puri®cation by silica gel chromatography
(dichloromethane/ethyl acetateˆ3:1) gave (Bn±Phebox)-
Rh(OAc) (H O) in 84% yield (76.5 mg, 0.121 mmol); pale
2 2
0.25 and 0.2 mm, respectively). Visualization was
yellow solid. Mp. 115±1178C (decomp). IR (KBr) n 3343,

8
58
Y. Motoyama et al. / Tetrahedron 57 (2001) 853±860
2
926, 1616, 1486, 1397, 1327, 1148, 969, 740, 703 cm .
1
2
CHIRALPAK AD, UV detector 254 nm, hexane/i-PrOHˆ
1
H NMR (400 MHz, CDCl ) d 1.75 (s, 6H), 2.63 (dd, Jˆ
9:1, ¯ow rate 1 mL/min) t ˆ12.2 min (2R), 16.4 min (2S),
3
R
1
(
3.9, 9.7 Hz, 2H), 3.70 (dd, Jˆ13.9, 3.0 Hz, 2H), 4.52±4.68
or (Daicel CHIRALPAK AS, UV detector 254 nm, hexane/
i-PrOHˆ3:1, ¯ow rate 1 mL/min) t ˆ13.2 min (2S),
m, 6H), 6.45 (bs, 2H), 7.22±7.32 (m, 11H), 7.62 (d,
R
1
3
Jˆ7.7 Hz, 2H). C NMR (100 MHz, CDCl ) d 23.9, 40.0,
15.2 min (2R).
3
6
1
4.1, 75.4, 123.3, 126.9, 127.9, 128.9, 129.4, 131.9, 137.0,
72.4 (JRh±Cˆ4.2 Hz), 182.7, 189.1 (JRh±Cˆ24.3 Hz).
4.2.2. 2,3-Dihydro-2-carbomethoxy-4H-pyran-4-one (6b).
2
4
8i
[
a]D2 ˆ230.88 (c 0.65, CHCl ; 68% ee, 2R); lit.
3
1
[a]D 1122.88 (c 0.60, CHCl ; 94% ee, 2S). IR (neat) n
4
.1.3. (Bn±Phebox)RhF (H O) (3). To a stirred solution of
2
2
3
(
7
Bn±Phebox)Rh(OAc) (H O) (159.7 mg, 0.25 mmol) and
2
0% TBAF in water (1.87 g, 5.0 mmol) in dichloromethane
2962, 1756, 1682, 1601, 1441, 1406, 1280, 1220, 1042,
886, 804 cm . H NMR (400 MHz, CDCl ) d 2.86 (d,
2
2
1
1
3
(
10 mL) was added 42% HBF solution (443 mL, 2.5 mmol)
4
Jˆ8.0 Hz, 2H), 3.80 (s, 3H), 5.04 (t, Jˆ8.0 Hz, 1H), 5.48
1
3
at room temperature under argon atmosphere. After stirring
for 6 h, the organic layer was separated and concentrated
under reduced pressure. Puri®cation by silica gel chromato-
graphy (dichloromethane/ethyl acetateˆ20:1) gave (Bn±
Phebox)RhF (H O) (3) in 73% yield (109.2 mg,
(d, Jˆ6.0 Hz, 1H), 7.39 (d, Jˆ6.0 Hz, 1H). C NMR
(100 MHz, CDCl ) d 38.4, 53.1, 76.1, 108.1, 161.8, 168.5,
3
189.4. Anal. C H O : Found C 53.70, H 5.30%; Calcd C
7
8
4
53.85, H 5.16%.
2
2
0.18 mmol); pale yellow solid. Mp. 177±1808C (decomp).
IR (KBr) n 3430, 2924, 1618, 1592, 1487, 1399, 1149, 969,
The ee was determined by HPLC analysis (Daicel
CHIRALPAK AD, UV detector 254 nm, hexane/i-PrOHˆ
2
36, 704 cm . H NMR (400 MHz, CDCl ) d 2,69 (bs,
1
1
7
2
4
9:1, ¯ow rate 1 mL/min) t ˆ17.2 min (2R), 36.4 min (2S),
3
R
H), 2.81 (dd, Jˆ14.0, 10.0 Hz, 2H), 3.67 (dd, Jˆ14.0,
or (Daicel CHIRALPAK AS, UV detector 254 nm, hexane/
i-PrOHˆ3:1, ¯ow rate 1 mL/min) t ˆ19.5 min (2S),
.0 Hz, 2H), 4.52±4.76 (m, 6H), 7.19±7.37 (m, 11H), 7.61
R
1
3
(
6
1
d, Jˆ7.6 Hz, 2H). C NMR (100 MHz, CDCl ) d 40.6,
25.2 min (2R).
3
3.7, 75.6, 123.3, 127.0, 128.4, 129.0, 129.2, 131.5, 137.0,
71.4 (JRh±Cˆ3.4 Hz), 179.5 (JRh±Cˆ22.3 Hz). Anal.
4.2.3. 2,3-Dihydro-2-carboisopropoxy-4H-pyran-4-one
2
D
4
8i
C H N O F Rh´(CH Cl ) : Found C 46.75, H 3.80, N
2
(6c). [a] ˆ2119.08 (c 0.45, CHCl ; 82% ee, 2R); lit.
[a]D 144.28 (c 1.20, CHCl ; 46% ee, 2S). IR (neat) n
3
6
25
2
3
2
2
2 2
3
2
1
3.88%; Calcd C 46.43, H 4.04, N 3.87%.
2
1 1
2986, 1746, 1682, 1601, 1406, 1280, 1220, 1106 cm . H
NMR (400 MHz, CDCl
4.2. General procedure for the hetero Diels±Alder
3
) d 1.28 (d, Jˆ6.4 Hz, 3H), 1.29 (d,
reaction of Danishefsky's dienes 4 and glyoxylates 5
catalyzed by Phebox±Rh(III) complexes 1±3
Jˆ6.4 Hz, 3H), 2.84 (d, Jˆ7.8 Hz, 2H), 4.98 (t, Jˆ7.8 Hz,
1H), 5.14 (sept, Jˆ6.4 Hz, 1H), 5.47 (d, Jˆ6.0 Hz, 1H),
1
3
7
21.72, 21.74, 38.4, 70.3, 76.3, 108.0, 161.9, 167.6, 189.6.
.39 (d, Jˆ6.0 Hz, 1H). C NMR (100 MHz, CDCl ) d
3
4.2.1. Butyl 3,4-dihydro-4-oxo-2H-pyran-2-carboxylate
(
(
6a). To a suspension of MS 4A (250 mg) in toluene
2 mL) was added (S,S)-(Bn±Phebox)RhCl (H O) complex
Anal. C
6.57%.
H O : Found C 58.71, H 6.55%; Calcd C 58.69, H
9 12 4
2
2
1e (0.01 mmol) and freshly distilled n-butyl glyoxylate 5a
(
65 mg, 0.5 mmol) at room temperature. The solution was
The ee was determined by HPLC analysis (Daicel
CHIRALPAK AD, UV detector 254 nm, hexane/i-PrOHˆ
cooled down to 2788C, then 1-methoxy-3-[(t-butyldi-
methylsilyl)oxy]-1,3-butadiene 4b (129 mg, 0.6 mmol)
was added. After the mixture was stirred for 1 h at
9:1, ¯ow rate 1 mL/min) t
ˆ13.5 min (2R), 26.2 min (2S).
R
2
788C, tri¯uoroacetic acid (45 mL, 0.59 mmol) was
4.2.4. 2,3-Dihydro-2-carbobutoxy-3,5-dimethyl-4H-pyran-
2
4
added. Then the reaction mixture was warmed to room
temperature and quenched by the addition of saturated
aqueous NaHCO (1 mL). The solution was ®ltered through
4-one. cis-6d. [a]
D
ˆ262.78 (c 1.00, CHCl
3
), (83% ee,
2R,3R). IR (neat) n 2966, 1760, 1676, 1624, 1462, 1386,
2
1 1
1309, 1174, 1013, 754 cm . H NMR (300 MHz, CDCl ) d
3
3
a pad of Celite and Florisil, and the ®ltrate was extracted
three times with ether (totally 10 mL). The combined
organic layer was washed with brine (5 mL), dried over
0.93 (t, Jˆ7.4 Hz, 3H), 1.10 (d, Jˆ7.6 Hz, 3H), 1.38 (tq,
Jˆ7.9, 7.4 Hz, 2H), 1.59~1.71 (m, 2H), 1.67 (d, Jˆ1.1 Hz,
3H), 2.23 (qd, Jˆ7.6, 3.7 Hz, 1H), 4.16±4.31 (m, 2H), 4.90
1
3
MgSO and evaporated under reduced pressure. Puri®cation
4
(d, Jˆ3.7 Hz, 1H), 7.24 (q, Jˆ1.1 Hz). C NMR (75 MHz,
by silica gel chromatography (hexane/ethyl acetateˆ2:1)
CDCl
113.4, 157.3, 167.7, 195.3. Anal. C12
63.67, H 7.90%; Calcd C 63.70, H 8.02%.
) d 10.4, 10.9, 13.5, 19.0, 30.5, 41.9, 65.7, 79.6,
3
gave butyl 3,4-dihydro-4-oxo-2H-pyran-2-carboxylate 6a
H O
18 4
: Found C
2
4
in 90% yield. [a] ˆ238.68 (c 1.00, CHCl ; 80% ee,
D
3
8
l
21
R); lit. [a]D 145.38 (c 1.00, CHCl ; 45% ee, 2S). IR
3
2
(
neat) n 2966, 1756, 1684, 1601, 1404, 1278, 1210,
The ee was determined by HPLC analysis (Daicel
CHIRALPAK AD, UV detector 254 nm, hexane/i-PrOHˆ
2
1
1
1
7
6
5
040 cm . H NMR (400 MHz, CDCl ) d 0.94 (t, Jˆ
3
.2 Hz, 3H), 1.39 (tq, Jˆ6.0, 7.2 Hz, 2H), 1.66 (tt, Jˆ6.8,
.0 Hz, 2H), 2.86 (d, Jˆ7.7 Hz, 2H), 4.23 (t, Jˆ6.8 Hz, 2H),
.02 (t, Jˆ7.7 Hz, 1H), 5.48 (d, Jˆ6.2 Hz, 1H), 7.40 (d,
9:1, ¯ow rate 0.5 mL/min) t ˆ16.0 min (2R,3R), 19.6 min
R
(2S,3S).
1
3
Jˆ6.2 Hz, 1H). C NMR (100 MHz, CDCl ) d 13.7, 19.1,
4.2.5. trans-6d. IR (neat) n 2966, 1752, 1676, 1628, 1460,
1 1
3
2
30.5, 38.4, 66.2, 76.2, 108.1, 161.9, 168.1, 189.6. Anal.
C H O : Found C 60.71, H 7.15%; Calcd C 60.59, H
1390, 1311, 1166, 1021, 754 cm . H NMR (300 MHz,
CDCl
) d 0.93 (t, Jˆ7.4 Hz, 3H), 1.22 (d, Jˆ7.2 Hz, 3H),
1
0
14
4
3
7
.12%.
1.36 (tq, Jˆ7.5, 7.4 Hz, 2H), 1.58±1.69 (m, 2H), 1.66 (d,
Jˆ1.2 Hz, 3H), 2.87 (qd, Jˆ8.4,, 7.2 Hz, 1H), 4.20 (ddd,
Jˆ8.4, 6.7, 1.7 Hz, 2H), 4.62 (d, Jˆ8.4 Hz, 1H), 7.21
The ee was determined by HPLC analysis (Daicel

Y. Motoyama et al. / Tetrahedron 57 (2001) 853±860
859
1
3
(
q, Jˆ1.2 Hz). C NMR (75 MHz, CDCl ) d 10.5, 12.7,
(g) Kretzschmar, E. A.; Kipke, J.; Sundermeyer, J. Chem.
Commun. 1999, 2381. (h) Oi, S.; Terada, E.; Ohuchi, K.;
Kato, T.; Tachibana, Y.; Inoue, Y. J. Org. Chem. 1999, 64,
8660.
3
13.5, 19.0, 30.4, 41.5, 65.9, 82.0, 113.5, 157.3, 168.6, 193.6.
Anal. C H O : Found C 63.80, H 7.96%; Calcd C 63.70, H
1
2
18
4
8
.02%.
3
. The analysis of chiral Lewis acid±base complexes, see: NOE
analysis: (a) Corey, E. J.; Sarsher, S. J. Am. Chem. Soc. 1992,
114, 7938. (b) Corey, E. J.; Loh, T.-P.; Roper, T. D.;
Azimioara, M. D.; Noe, M. C. J. Am. Chem. Soc. 1992, 114,
8290. (c) Ishihara, K.; Gao, Q.; Yamamoto, H. J. Am. Chem.
Soc. 1993, 115, 10412. X-ray analysis: (d) Knight, D. A.;
Dewey, M. A.; Stark, G. A.; Bennet, B. K.; Arif, A. M.;
Gladysz, J. A. Organometallics 1993, 12, 4523.
(e) Gothelf, K. V.; Hazell, R. D.; Jùrgensen, K. A. J. Am.
Chem. Soc. 1995, 117, 4435. (f) Evans, D. A.;
Kozlowski, M. C.; Murry, J. A.; Burgey, C. S.;
Campos, K. R.; Connell, B. T.; Staples, R. J. J. Am. Chem.
Soc. 1999, 121, 669 (and Ref. 2d).
The ee was determined by HPLC analysis (Daicel
CHIRALPAK AD, UV Detector 254 nm, hexane/i-PrOHˆ
9
:1, Flow Rate 0.5 mL/min) t ˆ15.1 min (2R,3S), 25.4 min
R
(
2S,3R).
4.2.6. Isolation of the hetero Diels±Alder adduct (7) of
Danishefsky's diene 4b with n-butyl glyoxylate 5a. To a
suspension of MS 4A (250 mg) in toluene (2 mL) was added
Bn±Phebox)RhCl (H O) complex 1e (0.01 mmol) and
2 2
(
freshly distilled n-butyl glyoxylate 5a (65 mg, 0.5 mmol)
at room temperature. The solution was cooled down to
2
788C, then 1-methoxy-3-[(t-butyldimethylsilyl)oxy]-1,3-
butadiene 4b (129 mg, 0.6 mmol) was added. After stirring
for 1 h at 2788C, the reaction was quenched by the addition
of triethylamine (2 mL). The resultant mixture was ®ltered
through a pad of Celite and Florisil, then the ®ltrate was
concentrated under reduced pressure to give crude cyclo-
adduct 7 (.9:1 diastereo mixture). Puri®cation by silica gel
4. (a) Motoyama, Y.; Makihara, N.; Mikami, Y.; Aoki, K.;
Nishiyama, H. Chem. Lett. 1997, 951. (b) Motoyama, Y.;
Mikami, Y.; Kawakami, H.; Aoki, K.; Nishiyama, H.
Organometallics 1999, 18, 3584. Phebox±Pd complexes
were reported, see: (c) Denmark, S. E.; Stavenger, R. A.;
Faucher, A.-M.; Edwards, J. P. J. Org. Chem. 1997, 62, 3375.
(d) Stark, M. A.; Richards, C. J. Tetrahedron Lett. 1997,
38, 5881. (e) Stark, M. A.; Jones, G.; Richards, C. J.
Organometallics 2000, 19, 1282.
chromatography (hexane in 1% Et N/ethyl acetateˆ2:1)
3
gave pure major-7 in 77% yield. IR (neat) n 2958, 2868,
1
7
0
741, 1677, 1468, 1375, 1259, 1211, 1134, 1060, 840
2
82 cm . H NMR (400 MHz, CDCl ) d 0.18 (s, 6H),
1
1
3
5. (a) Motoyama, Y.; Narusawa, H.; Nishiyama, H. Chem.
Commun. 1999, 131. (b) Motoyama, Y.; Okano, M.;
Narusawa, H.; Makihara, N.; Aoki, K.; Nishiyama, H.
Submitted for publication.
.92 (s, 9H), 0.94 (t, Jˆ7.8 Hz, 3H), 1.40 (m, 2H), 1.66
(
m, 2H), 2.30 (dd, Jˆ16.8, 5.1 Hz, 1H), 2.48 (dd, Jˆ16.8,
7
5
1
1
1
.0 Hz, 1H), 3.46 (s, 3H), 4.1±4.2 (m, 2H), 4.36 (dd, Jˆ7.0,
.1 Hz, 1H), 4.80 (d, Jˆ1.8 Hz, 1H), 5.14 (d, Jˆ1.8 Hz,
6. Other examples of the recoverable chiral complexes; Ru
complex for the oxidation of sul®des: (a) Schenk, W. A.;
D uÈ rr, M. Chem. Eur. J. 1997, 3, 713. Ru complex for the
Diels±Alder reaction: (b) K uÈ ndig, E. P.; Saudan, C. M.;
Bernardinelli, G. Angew. Chem., Int. Ed. 1999, 38, 1220. Pd
complex for the aldol and Mannich-type reactions: (c) Fujii,
A.; Sodeoka, M. Tetrahedron Lett. 1999, 40, 8011. Pd
complexes for the allylation of aldimines: (d) Bao, M.; Naka-
mura, H.; Yamamoto, Y. Tetrahedron Lett. 2000, 41, 131.
7. (a) Danishefsky, S. Aldrichimica Acta 1986, 19, 59.
(b) Danishefsky, S.; DeNinno, M. P. Angew. Chem., Int. Ed.
Engl. 1987, 26, 15. Also see: (c) Boger, D. L.; Weinreb, S. N.
Hetero Diels±Alder Methodology in Organic Synthesis;
Academic: San Diego, 1987. (d) Kametani, T.; Hibino, S.
Advances in Heterocyclic Chemistry, Vol. 42; Academic:
New York, 1987, Chapter 4.
1
H). C NMR (100 MHz, CDCl ) d 24.3, 24.2, 13.9,
3
3
8.2, 19.3, 25.8, 30.8, 31.4, 55.4, 65.3, 70.1, 98.9, 102.7,
52.0, 170.9. Anal. C H O Si: Found C 59.18, H 9.35%;
1
7
32
5
Calcd C 59.27, H 9.36%.
Acknowledgements
This work was partly supported by a Grant-in-Aid for
Scienti®c Research from the Ministry of Education,
Science, Sports and Culture, Japan.
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(
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