Asymmetric Hetero Diels-Alder Reaction Catalyzed by Chiral Cationic Palladium(II) and Platinum(II) Complexes

Article abstract of DOI:10.1021/jo9906680

The hetero Diels-Alder reaction of nonactivated conjugated dienes 1 with arylglyoxals 2 and glyoxylate esters 7 proceeded enantioselectively in the presence of a catalytic amount of cationic chiral BINAP-palladium or -platinum complexes and 3 A molecular sieves (MS3A). The addition of MS3A effectively improved the enantioselectivity of the reaction. Excellent ee's were obtained from the reactions of 2,3-dimethyl-1,3-butadiene (1a) and 1,3-cyclohexadiene (1d) with dienophiles 2 and 7. The square-planar structure of [Pd(S-BINAP)(PhCN)₂](PF₆)₂ was determined by X-ray diffraction, and a chiral induction model involving the square-planar palladium complex coordinated with BINAP and a dienophile is proposed.

Full text of DOI:10.1021/jo9906680

8660
J . Org. Chem. 1999, 64, 8660-8667
Asym m etr ic Heter o Diels-Ald er Rea ction Ca ta lyzed by Ch ir a l
Ca tion ic P a lla d iu m (II) a n d P la tin u m (II) Com p lexes
Shuichi Oi,* Eiji Terada, Kazuei Ohuchi, Tomoko Kato, Yukari Tachibana, and Yoshio Inoue
Department of Materials Chemistry, Graduate School of Engineering, Tohoku University,
Sendai 980-8579, J apan
Received April 21, 1999
The hetero Diels-Alder reaction of nonactivated conjugated dienes 1 with arylglyoxals 2 and
glyoxylate esters 7 proceeded enantioselectively in the presence of a catalytic amount of cationic
chiral BINAP-palladium or -platinum complexes and 3 Å molecular sieves (MS3A). The addition
of MS3A effectively improved the enantioselectivity of the reaction. Excellent ee’s were obtained
from the reactions of 2,3-dimethyl-1,3-butadiene (1a ) and 1,3-cyclohexadiene (1d ) with dienophiles
2 and 7. The square-planar structure of [Pd(S-BINAP)(PhCN)2](PF6)2 was determined by X-ray
diffraction, and a chiral induction model involving the square-planar palladium complex coordinated
with BINAP and a dienophile is proposed.
In tr od u ction
improved hetero DA selectivity and high enantioselec-
tivity.
The hetero Diels-Alder (DA) reaction of conjugated
dienes with carbonyl compounds as dienophiles has been
a fundamental reaction in organic chemistry.1 The reac-
tion between 1-methoxy-3-[(trimethylsilyl)oxy]-1,3-buta-
diene (Danishefsky’s diene) and aldehydes provides
useful access to dihydropyranones, and several groups
have reported an enantioselective catalytic version of this
reaction.2 In contrast, the reaction between nonactivated
dienes and aldehydes gives dihydropyranes. In compari-
son with the reaction between Danishefsky’s diene and
aldehydes, there have been fewer reports on the asym-
metric version of this reaction. Nakai and Mikami et al.
first reported the asymmetric hetero DA reaction of
isoprene, a nonactivated diene, with methyl glyoxylate
catalyzed by a chiral BINOL-titanium complex.3 Al-
though the yield of the hetero DA product was rather low
as a result of the predominant formation of the hetero
ene product, enantioselectivity of the hetero DA product
was very high. J ørgensen and co-workers reported the
asymmetric hetero DA reaction of dienes with glyoxylate
esters catalyzed by bisoxazoline-copper4 and -zinc5 com-
plexes and BINOL-aluminum complexes,6 which showed
Recently, it has been recognized that certain transition
metal complexes display considerable Lewis acidic char-
acter and can be used as catalysts instead of the typical
Lewis acids. These complexes have a number of merits,
i.e., stability to air and moisture, high turnover number,
and a well-defined structure. Copper complexes with
chiral oxazoline-based ligands,4,7 η5-cyclopentadienyl-,2d
η6-arene-,8 and salen-ruthenium9 complexes, η5-pentam-
ethylcyclopentadienyl rhodium complexes,10 and DBFOX-
nickel complexes11 have been developed for use as
transition-metal-based Lewis acid catalysts. Previously,
we demonstrated that the hetero DA reaction of nonac-
tivated simple dienes with aldehydes was catalyzed by
cationic palladium(II) complexes, [PdL2(RCN)2](BF4)2,
affording the corresponding 5,6-dihydro-2H-pyrans12 and
that a highly enantioselective DA reaction of dienes with
N-acryloyloxazolidinone was achieved using a chiral
BINAP complex, [Pd(BINAP)(PhCN)2](BF4)2.13 Cationic
BINAP-palladium complexes have also been reported to
(4) (a) J ohannsen, M.; J ørgensen, K. A. J . Org. Chem. 1995, 60, 5757.
(b) J ohannsen, M.; J ørgensen, K. A. Tetrahedron 1996, 52, 7321. (c)
J ohannsen, M.; J ørgensen, K. A. J . Chem. Soc., Perkin Trans. 2 1997,
1183. (d) Yao, S.; J ohannsen, M.; Hazell, R. G.; J ørgensen, K. A. J .
Org. Chem. 1998, 63, 118.
(5) Yao, S.; J ohannsen, M.; J ørgensen, K. A. J . Chem. Soc., Perkin
Trans. 1 1997, 2345.
(1) For reviews, see: (a) Bednarski, M. D.; Lyssikatos, J . P. In
Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.;
Pergamon Press: Oxford, 1991; Vol. 2, p 661-706. (b) Boger, D. L.;
Weinreb, S. M. In Hetero Diels-Alder Methodology in Organic Syn-
thesis; Blomquist, A. T., Wasserman, H., Eds.; Academic Press: San
Diego, 1987; Vol. 47.
(6) Graven, A.; J ohannsen, M.; J ørgensen, K. A. Chem. Commun.
1996, 2373.
(7) (a) Evans, D. A.; Miller, S. J .; Lectka, T. J . Am. Chem. Soc. 1993,
115, 6460. (b) Evans, D. A.; Lectka, T.; Miller, S. J . Tetrahedron Lett.
1993, 34, 7027. (c) Evans, D. A.; Murry, J . A.; von Matt, P.; Norcross,
R. D.; Miller, S. J . Angew. Chem., Int. Ed. Engl. 1995, 34, 798. (d)
Sagasser, I.; Helmchen, G. Tetrahedron Lett. 1998, 39, 261.
(8) (a) Davies, D. L.; Fawcett, J .; Garratt, S. A.; Russell, D. R. Chem.
Commun. 1997, 1351. (b) Carmona, D.; Cativiela, C.; Elipe, S.; Lahoz,
F. J .; Lamata, M. P.; Lo´pez-Ram de V´ıu, M. P.; Oro, L. A.; Vega, C.;
Viguri, F. Chem. Commun. 1997, 2351.
(9) Odenkilk, W.; Rheingold, A. L.; Bosnich, B. J . Am. Chem. Soc.
1992, 114, 6392.
(10) Davenport, A. J .; Davies, D. L.; Fawcett, J .; Garratt, S. A.; Lad,
L.; Russell, D. R. Chem. Commun. 1997, 2347.
(2) (a) Bednarsky, M.; Maring, C.; Danishefsky, S. Tetrahedron Lett.
1983, 24, 3451. (b) Bednarsky, M.; Danishefsky, S. J . Am. Chem. Soc.
1986, 108, 7060. (c) Maruoka, K.; Itoh, T.; Shirasaka, T.; Yamamoto,
H. J . Am. Chem. Soc. 1988, 110, 310. (d) Faller, J . W.; Smart, C. J .
Tetrahedron Lett. 1989, 30, 1189. (e) Togni, A. Organometallics 1990,
9, 3106. (f) Corey, E. J .; Cywin, C. L.; Roper, T. D. Tetrahedron Lett.
1992, 33, 6907. (g) Gao, Q.; Maruyama, T.; Mouri, M.; Yamamoto, H.
J . Org. Chem. 1992, 57, 1951. (h) Gao, Q.; Ishihara, K.; Maruyama,
T.; Mouri, M.; Yamamoto, H. Tetrahedron 1994, 50, 979. (i) Motoyama,
Y.; Mikami, K. J . Chem. Soc., Chem. Commun. 1994, 1563. (j) Keck,
G. E.; Li, X.-Y.; Krishnamurthy, D. J . Org. Chem. 1995, 60, 5998. (k)
Ghosh, A. K.; Mathivanan, P.; Cappiello, J .; Krishnan, K. Tetrahe-
dron: Asymmetry 1996, 7, 2165. (l) Ghosh, A. K.; Mathivanan, P.;
Cappiello, J .Tetrahedron Lett. 1997, 38, 2427. (m) Matsukawa, S.;
Mikami, K. Tetrahedron: Asymmetry 1997, 8, 815. (n) Schaus, S. E.;
Brånalt, J .; J acobsen, E. N. J . Org. Chem. 1998, 63, 403.
(11) Kanemasa, S.; Oderaotoshi, Y.; Sakaguchi, S.; Yamamoto, H.;
Tanaka, J .; Wada, E.; Curran, D. P. J . Am. Chem. Soc. 1998, 120, 3074.
(12) Oi, S.; Kashiwagi, K.; Terada, E.; Ohuchi, K.; Inoue, Y.
Tetrahedron Lett. 1996, 37, 6351.
(3) Terada, M.; Mikami, K.; Nakai, T. Tetrahedron Lett. 1991, 32,
935.
(13) Oi, S.; Kashiwagi, K.; Inoue, Y. Tetrahedron Lett. 1998, 39,
6253.
10.1021/jo9906680 CCC: $18.00 © 1999 American Chemical Society
Published on Web 11/12/1999

Asymmetric Hetero Diels-Alder Reaction
J . Org. Chem., Vol. 64, No. 23, 1999 8661
Ta ble 1. Heter o DA Rea ction of 1a w ith 2a Ca ta lyzed by
P a lla d iu m Com p lexes w ith Va r iou s Ch ir a l P h osp h in e
Liga n d sa
Ta ble 2. Heter o DA Rea ction of 1a w ith 2a Ca ta lyzed by
Ca tion ic BINAP -P a lla d iu m a n d -P la tin u m Com p lexes
u n d er Va r iou s Con d ition sa
reaction yield ee
yield
(%)b
ee
(%)b (%)c
entry
ligand (L*)
(S)-BINAP
(S)-TolBINAP
(R,R)-CHIRAPHOS
(-)-DIOP
(S)-(R)-BPPFOAc
(S)-(R)-BPPFA
(S)-(R)-BPPFOH
(%)c
entry
1
catalyst
Pd(PhCN)2Cl2
additive (°C/h)
none
rt/20
69
58
1
2
3
4
5
6
7
69
51
36
35
33
26
42
58
40
4
12
1
(S)-BINAP, AgBF4
2
3
4
5
6
[Pd(S-BINAP)(PhCN)2](BF4)2 none
[Pd(S-BINAP)(PhCN)2](BF4)2 MS3A
[Pd(S-BINAP)(PhCN)2](BF4)2 MS3A
[Pt(S-BINAP)(PhCN)2](BF4)2 none
[Pt(S-BINAP)(PhCN)2](BF4)2 MS3A
rt/20
rt/20
0/24
rt/20
0/24
54
67
70
54
60
79
96
99
93
97
1
17
a
Reaction conditions: 1a (1.5 mmol), 2a (1.0 mmol), catalyst
(0.02 mmol), MS3A (50 mg if used), 2 mL of CHCl3, N2 atmosphere.
b Determined by GLC. c Determined by HPLC using Chiralpak AD,
5% i-PrOH in hexane. (R)-Enantiomer was formed predominantly
by use of (S)-BINAP.
a
Reaction conditions: 1a (3.0 mmol), 2a (2.0 mmol),Pd(PhCN)2Cl2
(0.04 mmol), ligand (0.04 mmol), AgBF4 (0.1 mmol), 4 mL of CHCl3,
rt, 20 h, N2 atmosphere. Determined by GLC. c Determined by
b
HPLC using Chiralpak AD, 5% i-PrOH in hexane.
catalyze the enantioselective addition of enol silyl ethers
to aldehydes14 and aldimines15 with high enantioselec-
tivity.
Herein, we report the highly enantioselective hetero
DA reaction of nonactivated dienes with arylglyoxals and
glyoxylate esters using cationic BINAP-palladium and
-platinum complexes as a chiral catalyst. This is the first
report of enantioselective cyclization of dienes with
arylglyoxals yielding optically active 2-aroyl-3,6-dihydro-
2H-pyranes.
gave 3a a in lower yield and with a lower ee than (S)-
BINAP (entry 2). Other chiral diphosphines such as
(R,R)-CHIRAPHOS, (-)-DIOP, and the series of ferro-
cenyl phosphines gave modest yields but with very low
ee’s (entries 3-7).
The hetero DA reaction of 1a with 2a was carried out
under various reaction conditions using the cationic
palladium complex coordinated with (S)-BINAP and two
benzonitriles, [Pd(S-BINAP)(PhCN)2](BF4)2, which was
prepared separately. Results are summarized in Table
2. The R-enantiomer of 3a a was formed predominantly
by use of the (S)-BINAP complex (vide infra). The use of
the isolated complex increased the ee of 3a a to 79% from
the 58% obtained by the reaction using the catalyst
prepared in situ (entries 1 and 2). To further improve
the enantioselectivity, the reaction was carried out in the
presence of 3 Å molecular sieves (MS3A), which is known
to frequently be effective in improving enantioselectivity
in Lewis acid catalyzed DA and ene reactions.3,16 MS3A
is assumed to remove a trace amount of water and acidic
impurities. The acidic impurities in the present reaction
would be generated from the palladium complex and
water and would catalyze the undesired nonenantiose-
lective reaction path. We found that the ee of 3a a reached
96% when the reaction was carried out in the presence
of 50 mg of MS3A (entry 3). Similar enantioselectivity
was shown in the control examination, in which 2a and
the palladium complex were mixed with MS3A, which
was then filtered off before the addition of 1a . Therefore,
the presence of MS3A is not necessary to obtain the high
enantioselectivity. The reaction at 0 °C in the presence
of MS3A gave 3a a in a good yield of 70% with the highest
ee of 99% (entry 4). The cationic BINAP-platinum
complex was found to also catalyze the enantioselective
reaction of 1a with 2a . The reaction catalyzed by [Pt(S-
BINAP)(PhCN)2](BF4)2 in the absence of MS3A gave a
higher ee, 93% (entry 5), than that obtained by catalysis
with the palladium complex under same reaction condi-
tions (entry 2). The addition of MS3A and the adoption
of lower reaction temperature also improved the yield
and ee, affording 3a a in 60% yield with an ee of 97%
(entry 6).
Resu lts a n d Discu ssion
At first, a variety of chiral diphosphine ligands were
tested for the cationic palladium-catalyzed hetero DA
reaction of 2,3-dimethyl-1,3-butadiene (1a ) with phenyl-
glyoxal (2a ) (eq 1, Table 1). The cationic complexes were
prepared in situ by mixing 2 mol % of Pd(PhCN)2Cl2, 1.0
equiv (for Pd) of the ligands, and 2.5 equiv (for Pd) of
AgBF4 prior to the reaction. The use of (S)-BINAP as the
ligand of palladium gave product 3a a in the highest yield,
69%, with the highest ee, 58% (entry 1). (S)-TolBINAP,
which has p-tolyl groups attached to the phosphorus
atoms instead of the phenyl groups found in (S)-BINAP,
The reactions of various dienes (1a -e) with arylgly-
oxals (2a -d ) were carried out in the presence of 2 mol %
of (S)-BINAP-palladium or -platinum complex and MS3A.
Results are summarized in Table 3. Hetero ene products
(14) (a) Sodeoka, M.; Ohrai, K.; Shibasaki, M. J . Org. Chem. 1995,
60, 2648. (b) Sodeoka, M.; Tokunoh, R.; Miyazaki, F.; Hagiwara, E.;
Shibasaki, M. Synlett 1997, 463.
(15) (a) Hagiwara, E.; Fujii, A.; Sodeoka, M. J . Am. Chem. Soc. 1998,
120, 2474. (b) Ferraris, D.; Young, B.; Dudding, T.; Lectka, T. J . Am.
Chem. Soc. 1998, 120, 4548.
(16) (a) Mikami, K.; Terada, M.; Nakai, T. J . Am. Chem. Soc. 1990,
112, 3949. (b) Mikami, K.; Motoyama, Y.; Terada, M. J . Am. Chem.
Soc. 1994, 116, 2812.

8662 J . Org. Chem., Vol. 64, No. 23, 1999
Oi et al.
Ta ble 3. Heter o DA Rea ction of Dien es w ith
Ar ylglyoxa ls Ca ta lyzed by Ca tion ic BINAP -P a lla d iu m
a n d -P la tin u m Com p lexesa
Sch em e 1
yield
(%)b
ee
entry
1
2
M
3
(%)c
1
2
3
4
5
6
7
8
9
1a
2a
Pd
Pt
Pd
Pt
Pd
Pt
Pd
Pt
3a a
67
60
50
50
64
65
57
44
21
55
99 (R)
97 (R)
94
93
98
98
97
96
33
91
38
80
1
1a
1a
1a
1b
1c
2b
2c
2d
2a
2a
3a b
3a c
3a d
3ba
3ca
Pd
Pt
Pd
10
11
46 (cis)
20 (trans)
53 (cis)
10 (trans)
69
12
Pt
50
13
14
15
1d
1e
2a
2a
Pd
Pt
Pd
3d a
3ea
>99
>99
98d
74
80
F igu r e 1. ORTEP view of (aS,R,R)-5b. Hydrogen atoms are
only shown for asymmetric carbons. The ellipsoids are drawn
at the 40% probability level.
a
Reaction conditions: 1 (3.0 mmol), 2 (2.0 mmol), catalyst (0.04
mmol), MS3A (100 mg), 4 mL of CHCl3, 0 °C, 24 h, N2 atmosphere.
Isolated yield. c Determined by HPLC using Chiralpak AD, 5%
b
d
i-PrOH in hexane. Determined by HPLC using Chiralcel OD-H,
10% i-PrOH in hexane.
was actually a cis-trans mixture. Therefore, it can be
assumed that another reaction pathway exists, such as
stepwise addition via the zwitter ionic intermediate, as
has been proposed in the cyclization of dienes with
benzaldehyde.12,17 Low enantioselectivity in the reaction
of 1b and 1c may be interpreted in terms of differences
in reaction pathways. Cyclic diexo-1,2-dimethylene sub-
strate 1e could also be applied to the highly enantiose-
lective hetero DA reaction with 1a to give 3a e in 80%
yield with 98% ee (entry 15).
To determine the absolute configuration of the major
enantiomer 3a a of 99% ee obtained from the asymmetric
hetero DA reaction of 1a with 2a catalyzed by (S)-BINAP-
palladium complex, it was reduced with NaBH4 to a
diastereomeric mixture of alcohols (4a , 4b) and then
converted to ester 5 with Miyano’s chiral derivatizing
agent, (aS)-2′-methoxy-1,1′-binaphthyl-2-carboxylic acid
(6) (Scheme 1).18 The ester 5b derived from minor alcohol
4b and (aS)-6 gave a suitable crystal, which was sub-
jected to X-ray crystal structure analysis. The absolute
configuration of 5b was designated as (aS,2R,9R), from
which the absolute configuration of 3a a formed in the
asymmetric hetero DA reaction was determined to be R
(Figure 1).
were not observed in the reaction with arylglyoxals. The
reactions of 1a with p-methyl-, p-methoxy-, and p-chloro-
substituted phenylglyoxals (2b-d ) catalyzed by both the
palladium complex and the platinum complex also pro-
ceeded enantioselectively, affording 3a b, 3a c, and 3a d
in 44-65% isolated yields with 93-98% ee (entries 3-8).
The considerable difference in the enantioselectivity
observed in the reaction of isoprene (1b) and trans-2-
methyl-1,3-pentadiene (1c) may arise from the structural
differences between the palladium and the platinum
complexes. The reaction of 1b with 2a catalyzed by the
palladium complex gave 3ba in low yield of 21% with low
ee of 31% (entry 9), whereas 3ba was isolated in 55%
yield with a high ee of 91% when the platinum complex
was used as catalyst (entry 10). The reaction of 1c with
2a catalyzed by the palladium or the platinum complex
gave 3ca as a cis-trans mixture of a similar ratio;
however, the ee of the major trans form was 38% for the
palladium complex and only 1% for the platinum complex
(entries 11 and 12). 1,3-Cyclohexadiene (1d ), a cyclic
internal diene, reacted with 2a , affording a good isolated
yield of 3d a in almost optically pure form (>99% ee) by
use of both the palladium and the platinum complexes
(entries 13 and 14). In the case of 1d , only the endo
adduct was formed. This result indicates that the reaction
proceeds via the concerted pericyclic mechanism accord-
ing to the endo rule. If the reaction of trans-1c with 2a
also proceeds concertedly, only trans-3ca should be
obtained. However, as mentioned above, the 3ca obtained
(17) Larson, E. R.; Danishefsky, S. J . Am. Chem. Soc. 1982, 104,
6458.
(18) (a) Miyano, S.; Okada, S.; Hotta, H.; Takeda, M.; Kabuto, C.;
Hashimoto, H. Bull. Chem. Soc. J pn. 1989, 62, 1528. (b) Miyano, S.;
Okada, S.; Hotta, H.; Takeda, M.; Suzuki, T.; Kabuto, C.; Yasuhara,
F. Bull. Chem. Soc. J pn. 1989, 62, 3886. (c) Hattori, T.; Hotta, H.;
Suzuki, T.; Miyano, S. Bull. Chem. Soc. J pn. 1993, 66, 613.

Asymmetric Hetero Diels-Alder Reaction
J . Org. Chem., Vol. 64, No. 23, 1999 8663
Ta ble 4. Heter o DA Rea ction of Dien es w ith Glyoxyla te
Ester s Ca ta lyzed by Ca tion ic BINAP -P a lla d iu m
Com p lexesa
DA
ene
yield
(%)b
ee
yield ee
(%)b (%)c
entry
1
7
8
(%)c
9
1
2
3
4
5
6
1a 7a 8a a 34
1a 7b 8a b 36
1a 7c 8a c 43
1a 7d 8a d 42
1b 7b 8bb 33
95 (R)
9a a
9a b 35
9a c 32
9a d
9bb 31
9cb 13
34
57
62
76
64
3
95 (R)
97 (R)
96 (R)
11d
35
1c 7b 8cb 42 (cis)
7d
21
16 (trans) 23
1d 7b 8d b 77 98 (1S,3R,4R)
7
a
Reaction conditions: 1 (4.5 mmol), 6 (3.0 mmol), catalyst (0.06
mmol), MS3A (150 mg), 6 mL of CHCl3, rt, 20 h, N2 atmosphere.
b
Isolated yield. c Determined by GLC using Chrompak Chirasil-
d
DEX CB, N2. Determined by GLC using Astec Chiraldex G-TA,
N2.
The cationic BINAP-palladium complex catalyzed het-
ero DA reaction of dienes (1) with glyoxylate esters (7)
also proceeded enantioselectively. Results are summa-
rized in Table 4. The reactions of the dienes suited for
ene reaction (1a -c) with glyoxylate esters 7 gave almost
the same amount of both hetero DA products 8 and ene
products 9. The ee’s of the all-hetero DA products from
1a with glyoxylate esters 7a -d were excellent, whereas
the ee’s of the ene products were moderate to good
(entries 1-4). A bulkier alkyl moiety in 7 improved the
ee’s of both the hetero DA product and the ene product
and also the hetero DA selectivity. Thus the isopropyl
ester 7c gave 8a c with 97% ee and 9a c with 76% ee, and
the hetero DA/ene ratio came to 1.34/1. Although the
reaction of 1b with 7b gave products 8bb and 9bb in
almost the same yield as the reaction of 1a with 7b, the
ee’s of both 8bb and 9bb were low (entry 5). The reaction
of 1c with 7b gave a cis-trans mixture of 8cb in 58% total
yield with good hetero DA selectivity, but the ee of the
major trans form was only 7% (entry 6). The reaction of
cyclic diene 1d with 7b afforded selectively endo adduct
8d b in a good isolated yield of 77% with an excellent ee
of 98%.
F igu r e 2. ORTEP view of [Pd(S-BINAP)(PhCN)2](PF6)2.
Hydrogen atoms and PF6 anions are omitted for clarity. The
ellipsoids are drawn at the 40% probability level.
in other palladium-, rhodium-, and ruthenium-BINAP
complexes,19 two of the phenyl groups of (S)-BINAP are
oriented axially and the other two phenyl groups equa-
torially with respect to the square-plane of the complex.
The equatorial phenyl groups are extruded toward the
coordination sites of the benzonitriles, and the two
benzonitriles are situated below and above the P-Pd-P
plane, respectively. This structural information shows
that considerable steric hindrance exists between the
equatorial phenyl groups and the coordinating benzoni-
triles.
A proposed chiral induction model is illustrated with
phenylglyoxal (2a ) and the palladium-(S)-BINAP complex
in Figure 3. It is presumed that dicarbonyl compound 2a
would replace the benzonitriles and L2 coordinates to the
palladium-(S)-BINAP complex via the two carbonyl oxy-
gen atoms, affording the square-planar complex as the
intermediate. Because the attack on the si face of the
To gain structural information about the cationic
palladium species coordinated with BINAP, the crystal
structure of [Pd(S-BINAP)(PhCN)2](PF6)2 was deter-
mined by X-ray diffraction. As shown in Figure 2, the
complex has a slightly distorted square-planar geometry,
being coordinated with two phosphorus atoms of (S)-
BINAP and two benzonitriles. The dihedral angle of the
two naphthyl groups of the (S)-BINAP is 69.5(6)°, and
the bite angle (P-Pd-P) is 90.76(5)°. As has been found
(19) Ozawa, F.; Kubo, A.; Matsumoto, Y.; Hayashi, T. Organome-
tallics 1993, 12, 4188.

8664 J . Org. Chem., Vol. 64, No. 23, 1999
Oi et al.
[P d (S-BINAP )(P h CN)2](BF 4)2: IR (KBr) 1065 cm-1. Anal.
Calcd for C58H42B2F8N2P2Pd: C, 62.82; H, 3.82; N, 2.53.
Found: C, 62.26; H, 3.94; N, 2.52.
[P d (S-BINAP )(P h CN)2](P F 6)2: IR (KBr) 838 cm-1. Anal.
Calcd for C58H42F12N2P4Pd: C, 56.85; H, 3.46; N, 2.29. Found:
C, 56.54; H, 3.45; N, 2.26.
[P t(S-BINAP )(P h CN)2](BF 4)2: IR (KBr) 1061 cm-1. Anal.
Calcd for C58H42B2F8N2P2Pt: C, 58.17; H, 3.53; N, 2.34.
Found: C, 57.62; H, 3.63; N, 2.38.
Ca t a lyt ic Het er o DA R ea ct ion of Dien es w it h Ar yl-
glyoxa ls. A typical procedure (Table 3, entry 1) is as follows.
To a mixture of [Pd(S-BINAP)(PhCN)2](BF4)2 (44.3 mg, 0.04
mmol), powder of 3 Å molecular sieves (100 mg), and CHCl3
(4 mL) were added phenylglyoxal (268 mg, 2.0 mmol) and 2,3-
dimethyl-1,3-butadiene (246 mg, 3.0 mmol), and the mixture
was stirred at 0 °C for 24 h under N2 atmosphere. Diethyl ether
(25 mL) was added to the mixture, and the solution was
filtered through a short silica gel column and eluted with
diethyl ether. After the solvent was removed, the residue was
purified by silica gel column chromatography using hexane/
EtOAc (10:1) as the eluent to give the hetero DA product (290
mg, 67%) as a colorless oil.
F igu r e 3. A proposed chiral induction model for the reaction
of 1a with 2a .
formyl group in 2a may be obstructed by the equatorial
phenyl group of the (S)-BINAP, the attack of 1a on the
re face is favored to afford the observed (R)-cycloadduct
3a a .
(R)-(+)-2-Ben zoyl-4,5-d im et h yl-3,6-d ih yd r o-2H-p yr a n
1
(3a a ): H NMR (400 MHz) δ 8.00 (approximate d, 2H, J app
)
Exp er im en ta l Section
7.8 Hz), 7.58-7.44 (m, 3H), 4.91 (dd, 1H, J ) 10.2, 4.0 Hz),
4.19-4.09 (m, 2H), 2.42-2.38 (m, 1H), 2.12 (br d, 1H, J ) 16.2
Hz), 1.68 (s, 3H), 1.57 (s, 3H); 13C NMR (100 MHz) δ 198.1,
135.2, 133.3, 128.8, 128.5, 124.3, 122.9, 76.4, 69.5, 32.9, 18.4,
13.9; IR (neat) 1694, 1114, 694 cm-1; GC-MS (EI, 70 eV,
relative intensity, %) m/z 105 (100), 216 (M+, 1.5). Anal. Calcd
Gen er a l Met h od s. All reactions were carried out in
Schlenk tubes using anhydrous solvents under N2. CHCl3 was
dried over CaH2, distilled, and stored over 4 Å molecular
sieves. NMR spectra were recorded using CDCl3 as the solvent.
Elemental analyses were carried out in the Microanalytical
Laboratory of the Institute for Chemical Reaction Science,
Tohoku University. Spherical silica gel (100-210 µm, Kanto
Chemical) was used for column chromatography. Enantiomer
excess (ee) was determined by GLC or HPLC as described in
the footnotes of the tables.
Ma ter ia ls. 2,3-Dimethyl-1,3-butadiene (1a ), 2-methyl-1,3-
butadiene (1b), and cyclohexa-1,3-diene (1d ) were purchased
from Tokyo Chemical Industry and used as received. trans-2-
Methyl-1,3-pentadiene (1c) was purchased from Aldrich and
used as received. 4,4-Diethoxycarbonyl-1,2-dimethylenecyclo-
pentane (1e) was prepared as described in the literature20 from
4,4-diethoxycarbonylhept-6-ene-1-yne. Phenylglyoxal (2a ) was
purchased from Tokyo Chemical Industry and distilled before
use. Substituted phenylglyoxals (2b-d )21 and glyoxylate esters
(7a -d )22 were prepared as described in the literature and
distilled before use.
P r ep a r a t ion of Ca t ion ic P a lla d iu m a n d P la t in u m
Com p lexes. A mixture of PdCl2 (887 mg, 5.0 mmol) and
acetonitrile (50 mL) was refluxed for about 1.5 h under N2 until
the suspension became clear, and the solution was filtered
while hot to remove insoluble impurities. To the solution was
added (S)-BINAP (3.11 g, 5.0 mmol), and the mixture was
refluxed for 2 h under N2. After the mixture was cooled to room
temperature, the yellow solid was filtered, washed with
acetonitrile, and dried in vacuo to give PdCl2(S-BINAP) in
quantitative yield. To a suspension of PdCl2(S-BINAP) (800
mg, 1.0 mmol) in CH2Cl2 (35 mL) were added benzonitrile (5
mL) and AgBF4 (487 mg, 2.5 mmol) dissolved in nitromethane
(10 mL) with stirring under N2. A white precipitate of AgCl
appeared immediately. After stirring for 3 h the solution was
filtered through a membrane filter (0.45 µm) and reduced to
ca. 5 mL in vacuo. A yellow solid was precipitated by dropwise
addition of diethyl ether (50-100 mL) with stirring, and the
precipitate was filtered, washed with diethyl ether (10 mL),
and dried in vacuo to give up to 90% yield of [Pd(S-BINAP)-
(PhCN)2](BF4)2. [Pd(S-BINAP)(PhCN)2](PF6)2 and [Pt(S-BINAP)-
(PhCN)2](BF4)2 were prepared similarly using AgPF6 and
PtCl2, respectively.
for C14H16O2: C, 77.75; H, 7.46. Found: C, 77.23; H, 7.43. [R]26
D
+155° (c 1.1, CHCl3) 99% ee.
(+)-2-Ben zoyl-4-m eth yl-3,6-dih ydr o-2H-pyr an (3ba): 1H
NMR (500 MHz) δ 8.01 (approximate d, 2H, J app ) 7.8 Hz),
7.59-7.45 (m, 3H), 5.49 (s, 1H), 4.90 (dd, 1H, J ) 9.9, 4.0 Hz),
4.31 (br s, 2H), 2.47-2.41 (m, 1H), 2.14 (br d, 1H, J ) 16.9
Hz), 1.75 (s, 3H); 13C NMR (125 MHz) δ 198.0, 135.2, 133.3,
131.1, 128.9, 128.6, 119.4, 75.8, 65.9, 32.0, 23.0; IR (neat) 1693,
1123, 693 cm-1; GC-MS (EI, 70 eV, relative intensity, %) m/z
105 (100), 202 (M+, 2.9). Anal. Calcd for C13H14O2: C, 77.20;
H, 6.98. Found: C, 77.17; H, 6.96. [R]24 +108° (c 1.0, CHCl3)
D
91%ee.
cis-(+)-2-Ben zoyl-4,6-d im et h yl-3,6-d ih yd r o-2H -p yr a n
(cis-3ca ): This isomer was assigned to the cis form on the basis
of the NOE enhancement of 7.2% to the hydrogen attached to
the 6-position from the hydrogen attached to the 2-position.
1H NMR (500 MHz) δ 8.02 (approximate d, 2H, J app ) 8.3 Hz),
7.58-7.45 (m, 3H), 5.41-5.40 (m, 1H), 4.89 (dd, 1H, J ) 11.1,
3.6 Hz), 4.42-4.40 (m, 1H), 2.46-2.39 (m, 1H), 2.06 (dt, 1H, J
) 16.9, 2.9 Hz), 1.76 (s, 3H), 1.30 (d, 3H, J ) 6.7 Hz); 13C NMR
(125 MHz) δ 197.7, 135.3, 133.2, 131.3, 129.1, 128.5, 128.1,
125.1, 71.9, 32.1, 22.8, 21.5; IR (neat) 1693, 1118, 697 cm-1
;
GC-MS (EI, 70 eV, relative intensity, %) m/z 105 (100), 216
(M+, 2.0). [R]24 +24° (c 1.0, CHCl3) 38% ee.
D
tr a n s-(+)-2-Ben zoyl-4,6-d im eth yl-3,6-d ih yd r o-2H-p yr -
a n (tr a n s-3ca ): This isomer was assigned to the trans form
on the basis of the NOE enhancement of 1.8% to the methyl
group attached to the 6-position from the hydrogen attached
to the 2-position and 1.0% to the hydrogen attached to the
2-position from the methyl group attached to the 6-position.
1H NMR (400 MHz) δ 8.07 (approximate d, 2H, J app ) 7.8 Hz),
7.59-7.44 (m, 3H), 5.38-5.36 (m, 1H), 5.10 (dd, 1H, J ) 8.4,
6.1 Hz), 4.36-4.30 (m, 1H), 2.41 (dd, 1H, J ) 21.5, 7.6 Hz),
2.18 (dd, 1H, J ) 21.5, 5.4 Hz), 1.75 (s, 3H), 1.27 (d, 3H, J )
(20) Trost, B. M.; Romero, D. L.; Rise, F. J . Am. Chem. Soc. 1994,
116, 4268.
(21) Riley, H. A.; Gray, A. R. In Organic Syntheses; Blatt, A. H.,
Ed.; J ohn Wiley & Sons: New York, 1943; Collect. Vol. 2, p 509.
(22) Kelly, T. R.; Schmidt, T. E.; Haggerty, J . G. Synthesis 1972,
544.
6.7 Hz). [R]24 +17° (c 1.1, CHCl3) 80% ee.
D

Asymmetric Hetero Diels-Alder Reaction
J . Org. Chem., Vol. 64, No. 23, 1999 8665
Ca ta lytic Heter o DA Rea ction of Dien es w ith Glyoxy-
la te Ester s. The reaction was carried out in a method similar
to that used for dienes with arylglyoxals. Typically, 2,3-
dimethyl-1,3-butadiene (370 mg, 4.5 mmol) and ethyl glyoxy-
late (306 mg, 3.0 mmol) were reacted in the presence of [Pd(S-
BINAP)(PhCN)2](BF4)2 (66 mg, 0.06 mmol) and powder of 3 Å
molecular sieves (150 mg) in CHCl3 (6 mL) at room temper-
ature for 20 h under N2 atmosphere. The purification by silica
gel column chromatography using hexane/EtOAc (5:1) gave the
hetero DA product (198 mg, 36%) and the ene product (194
mg 35%), respectively, as colorless oils.
(+)-3-Ben zoyl-2-oxa bicyclo[2.2.2]oct-5-en e (3d a ): This
product was assigned to the endo form on the basis of the NOE
enhancement of 5.9% to the hydrogen attached to the 8-posi-
tion from the hydrogen attached to the 3-position and 10.8%
to the hydrogen attached to the 3-position from the hydrogen
attached to the 8-position. Mp 83-83.5 °C; 1H NMR (500 MHz)
δ 7.91 (approximate d, 2H, J app ) 7.8 Hz), 7.53-7.39 (m, 3H),
6.48-6.45 (m, 1H), 6.27-6.24 (m, 1H), 5.04 (d, 1H, J ) 1.6
Hz), 4.59-4.57 (m, 1H), 3.15-3.13 (m, 1H), 2.20-2.12 (m, 1H),
1.87-1.81 (m, 1H), 1.46-1.36 (m, 2H); 13C NMR (100 MHz) δ
198.7, 135.7, 134.2, 132.9, 131.5, 128.7, 128.4, 78.4, 66.7, 32.9,
25.9, 21.3; IR (KBr) 1688, 1165, 696 cm-1; GC-MS (EI, 70 eV,
relative intensity, %) m/z 77 (100), 105 (74). Anal. Calcd for
(R)-(+)-Meth yl 4,5-d im eth yl-3,6-d ih yd r o-2H-p yr a n -2-
1
ca r boxyla te (8a a ): H NMR (500 MHz) δ 4.22 (dd, 1H, J )
9.9, 4.2 Hz), 4.14-4.05 (m, 2H), 3.78 (s, 3H), 2.35-2.29 (m,
1H), 2.19 (br d, 1H, J ) 15.4 Hz), 1.67 (s, 3H), 1.54 (s, 3H);
13C NMR (125 MHz) δ 172.0, 124.3, 122.5, 72.9, 69.3, 52.1,
33.0, 18.2, 13.8; IR (neat) 1762, 1741, 1196, 1119 cm-1; GC-
MS (EI, 70 eV, relative intensity, %) m/z 55 (100), 170 (M+,
5.6). [R]19 +181° (c 1.1, CHCl3) 95% ee. The absolute config-
D
uration was determined to be R by the reported method.4a
(-)-Met h yl 2-h yd r oxy-5-m et h yl-4-m et h ylen e-5-h ex-
a n oa te (9a a ): 1H NMR (500 MHz) δ 5.25 (s, 1H), 5.12 (s, 1H),
5.10 (s, 1H), 5.04 (s, 1H), 4.38-4.34 (m, 1H), 3.77 (s, 3H), 2.86
(dd, 1H, J ) 14.3, 4.1 Hz), 2.72-2.70 (m, 1H), 2.56 (dd, 1H, J
) 14.3, 8.3 Hz), 1.93 (s, 3H); 13C NMR (125 MHz) δ 175.0,
142.7, 142.1, 115.8, 113.4, 69.6, 52.4, 39.1, 21.1; IR (neat) 3480,
1741, 1216, 1097 cm-1; GC-MS (EI, 70 eV, relative intensity,
C
14H14O2: C, 78.48; H, 6.59. Found: C, 78.19; H, 6.64. [R]23
D
+1.3° (c 1.1, CHCl3) 99.6% ee.
%) m/z 41 (100), 170 (M+, 0.2). [R]20 -5.3° (c 1.3, CHCl3) 57%
D
ee.
(R)-(+)-E t h yl 4,5-d im et h yl-3,6-d ih yd r o-2H -p yr a n -2-
ca r boxyla te (8a b):4a 1H NMR (400 MHz) δ 4.24 (q, 2H, J )
7.1 Hz), 4.19 (dd, 1H, J ) 9.8, 4.2 Hz), 4.14-4.04 (m, 2H),
2.35-2.28 (m, 1H), 2.18 (br d, 1H, J ) 16.1 Hz), 1.67 (s, 3H),
1.54 (s, 3H), 1.30 (t, 3H, J ) 7.1 Hz); IR (neat) 1757, 1738,
1187, 1119 cm-1; GC-MS (EI, 70 eV, relative intensity, %)
m/z 55 (100), 184 (M+, 3.4). [R]26D +159° (c 0.9, CHCl3) 95% ee
(+)-4-Ben zoyl-8,8-d ieth oxyca r bon yl-3-oxa bicyclo[4.3.0]-
n on -1(6)-en e (3ea ): 1H NMR (500 MHz) δ 7.99 (approximate
d, 2H, J app ) 7.8 Hz), 7.59-7.45 (m, 3H), 4.85 (dd, 1H, J )
9.8, 4.0 Hz), 4.31 (br s, 2H), 4.22 (q, 2H, J ) 7.1 Hz), 4.21 (q,
2H, J ) 7.1 Hz), 3.09-2.99 (m, 4H), 2.48-2.43 (m, 1H), 2.25
(br d, 1H, J ) 16.8 Hz), 1.27 (t, 3H, J ) 7.1 Hz), 1.26 (t, 3H,
J ) 7.1 Hz); 13C NMR (100 MHz) δ 197.6, 172.1, 171.7, 135.2,
133.4, 130.4, 129.5, 129.0, 128.6, 75.7, 66.1, 61.7, 58.1, 43.4,
40.5, 28.0, 14.1; IR(neat) 1731, 1691, 1257 cm-1; GC-MS (EI,
(lit.4a [R]20 -138° (c 1.7, CHCl3) 83% ee (S)).
D
(-)-Eth yl 2-h ydr oxy-5-m eth yl-4-m eth ylen e-5-h exan oate
(9a b):4a 1H NMR (400 MHz) δ 5.24 (s, 1H), 5.13 (s, 1H), 5.10
(s, 1H), 5.04 (s, 1H), 4.35-4.30 (m, 1H), 4.26-4.20 (m, 2H),
2.85 (dd, 1H, J ) 14.3, 4.2 Hz), 2.69 (d, 1H, J ) 6.5 Hz), 2.55
(dd, 1H, J ) 14.3, 8.2 Hz), 1.94 (s, 3H), 1.30 (t, 3H, J ) 7.1
Hz); IR (neat) 3478, 1732, 1209, 1095 cm-1; GC-MS (EI, 70
70 eV, relative intensity, %) m/z 105 (100), 372 (M+, 6.0). [R]21
D
+68° (c 1.2, CHCl3) 98% ee.
(+)-4,5-Dim eth yl-2-(4′-m eth ylben zoyl)-3,6-d ih yd r o-2H-
eV, relative intensity, %) m/z 41 (100), 184 (M+, 0.2). [R]24
D
1
p yr a n (3a b): H NMR (400 MHz) δ 7.90 (d, 2H, J ) 8.2 Hz),
-0.9° (c 1.1, CHCl3) 62% ee (lit.4a [R]20D +1° (c 1.7, CHCl3) 88%
7.25 (d, 2H J ) 8.2 Hz), 4.89 (dd, 1H, J ) 10.1, 3.9 Hz), 4.19-
4.09 (m, 2H), 2.44-2.38 (m, 4H), 2.11 (br d, 1H, J ) 16.3 Hz),
1.69 (s, 3H), 1.57 (s, 3H); 13C NMR (100 MHz) δ 197.7, 144.1,
132.7, 129.3, 129.0, 124.3, 123.0, 76.4, 69.6, 33.0, 21.7, 18.4,
13.9; IR (neat) 1694, 1229, 1007 cm-1; GC-MS (EI, 70 eV,
relative intensity, %) m/z 119 (100), 230 (M+, 1.0). Anal. Calcd
ee).
(R)-(+)-Isop r op yl 4,5-d im eth yl-3,6-d ih yd r o-2H-p yr a n -
2-ca r boxyla te (8a c): 1H NMR (400 MHz) δ 5.11 (sept, 1H, J
) 6.2 Hz), 4.15 (dd, 1H, J ) 9.7, 4.3 Hz), 4.12-4.03 (m, 2H),
2.32-2.26 (m, 1H), 2.16 (br d, 1H, J ) 16.6 Hz), 1.67 (s, 3H),
1.54 (s, 3H), 1.27 (d, 6H, J ) 6.2); 13C NMR (100 MHz) δ 171.2,
124.3, 122.5, 73.0, 69.2, 68.4, 33.1, 27.8, 18.3, 13.8; IR (neat)
1755, 1731, 1188, 1107 cm-1; GC-MS (EI, 70 eV, relative
for C15H18O2: C, 78.23; H, 7.88. Found: C, 77.98; H, 7.72. [R]25
D
+134° (c 1.0, CHCl3) 93% ee.
(+)-4,5-Dim et h yl-2-(4′-m et h oxyb en zoyl)-3,6-d ih yd r o-
1
intensity, %) m/z 55 (100), 198 (M+, 1.9). [R]28 +157° (c 1.1,
D
2H-p yr a n (3a c): mp 109.5-111.0 °C; H NMR (400 MHz) δ
CHCl3) 97% ee. The absolute configuration was determined
8.01 (d, 2H, J ) 8.9 Hz), 6.94 (d, 2H J ) 8.9 Hz), 4.86 (dd, 1H,
J ) 10.2, 3.9 Hz), 4.19-4.09 (m, 2H), 3.87 (s, 3H), 2.46-2.39
(m, 1H), 2.11 (br d, 1H, J ) 16.3 Hz), 1.69 (s, 3H), 1.58 (s,
3H); 13C NMR (100 MHz) δ 196.5, 163.6, 131.3, 128.2, 124.2,
123.0, 113.7, 76.4, 69.5, 55.5, 33.0, 18.4, 13.9; IR (KBr) 1675,
1605, 1262 cm-1; GC-MS (EI, 70 eV, relative intensity, %)
m/z 135 (100), 218 (15). Anal. Calcd for C15H18O3: C, 73.15;
to be R by the reported method.4a
Isopr opyl 2-h ydr oxy-5-m eth yl-4-m eth ylen e-5-h exan oate
(9a c): 1H NMR (400 MHz) δ 5.24 (s, 1H), 5.14 (s, 1H), 5.10 (s,
1H), 5.11-5.05 (m, 1H), 5.04 (s, 1H), 4.31-4.26 (m, 1H), 2.84
(dd, 1H, J ) 14.3, 4.2 Hz), 2.68 (d, 1H, J ) 6.4), 2.52 (dd, 1H,
J ) 14.3, 8.2 Hz), 1.94 (s, 3H), 1.28 (d, 3H, J ) 6.2), 1.27 (d,
3H, J ) 6.2); 13C NMR (100 MHz) δ 174.2, 142.9, 142.2, 115.6,
113.4, 69.6, 69.5, 39.2, 21.8, 21.2; IR (neat) 3483, 1732, 1215,
1107 cm-1; GC-MS (EI, 70 eV, relative intensity, %) m/z 43
(100), 198 (M+, 0.1). Optical rotation was too small to measure
correctly.
H, 7.37. Found: C, 73.08; H, 7.47. [R]26 +129° (c 1.1, CHCl3)
D
98% ee.
(+)-2-(4′-Ch lor oben zoyl)-4,5-d im eth yl-3,6-d ih yd r o-2H-
p yr a n (3a d ): mp 56.5-57.5 °C; 1H NMR (250 MHz) δ 7.96 (d,
2H, J ) 8.6 Hz), 7.43 (d, 2H J ) 8.6 Hz), 4.83 (dd, 1H, J )
9.9, 4.0 Hz), 4.20-4.05 (m, 2H), 2.48-2.37 (m, 1H), 2.12 (br d,
1H, J ) 15.5 Hz), 1.69 (s, 3H), 1.57 (s, 3H); 13C NMR (62.5
MHz) δ 197.0, 139.6, 133.4, 130.4, 128.8, 124.2, 122.8, 76.6,
69.4, 32.5, 18.3, 13.8; GC-MS (EI, 70 eV, relative intensity,
(R)-(+)-Bu t yl 4,5-d im et h yl-3,6-d ih yd r o-2H -p yr a n -2-
ca r boxyla te (8a d ): 1H NMR (400 MHz) δ 4.21-4.18 (m, 3H),
4.15-4.03 (m, 2H), 2.34-2.28 (m, 1H), 2.18 (br d, 1H, J ) 16.4
Hz), 1.69-1.62 (m, 5H), 1.54 (s, 3H), 1.39 (sext, 2H, J ) 7.4
Hz), 0.94 (t, 3H, J ) 7.4 Hz); 13C NMR (100 MHz) δ 171.7,
124.3, 122.5, 72.9, 69.2, 64.9, 33.0, 30.7, 19.1, 18.3, 13.8, 13.7;
IR (neat) 1759, 1736, 1185, 1119 cm-1; GC-MS (EI, 70 eV,
%) m/z 55 (100), 250 (M+, 1.9); IR (KBr) 1693, 1588, 1087 cm-1
.
Anal. Calcd for C14H15ClO2: C, 67.07; H, 6.03; Cl, 14.14.
Found: C, 66.76; H, 6.04; Cl, 14.23. [R]24D +121° (c 1.0, CHCl3)
97% ee.
relative intensity, %) m/z 41 (100), 212 (M+, 2.2). [R]26 +139°
D

8666 J . Org. Chem., Vol. 64, No. 23, 1999
Oi et al.
Ta ble 5. Su m m a r y of Cr ysta l Da ta a n d Da ta ils of
In ten sity Collection a n d Lea st-Squ a r es Refin em en t
P a r a m eter s for (a S,2R,9R)-5b a n d
(c 1.0, CHCl3) 96% ee. The absolute configuration was deter-
mined to be R by the reported method.4a
Bu t yl 2-h yd r oxy-5-m et h yl-4-m et h ylen e-5-h exa n oa t e
(9a d ): 1H NMR (400 MHz) δ 5.24 (s, 1H), 5.13 (s, 1H), 5.10 (s,
1H), 5.04 (s, 1H), 4.35-4.31 (m, 1H), 4.20-4.14 (m, 2H), 2.86
(dd, 1H, J ) 14.3, 4.2 Hz), 2.72 (d, 1H, J ) 6.3 Hz), 2.54 (dd,
1H, J ) 14.3, 8.2 Hz), 1.93 (s, 3H), 1.65 (quint, 2H, J ) 7.4
Hz), 1.39 (sext, 2H, J ) 7.4 Hz), 0.95 (t, 3H, J ) 7.4 Hz); 13C
NMR (100 MHz) δ 174.8, 142.8, 142.2, 115.6, 113.3, 69.7, 65.4,
39.2, 30.6, 21.1, 19.1, 13.7; IR (neat) 3483, 1736, 1207, 1095
cm-1; GC-MS (EI, 70 eV, relative intensity, %) m/z 41 (100),
194 (0.8). Optical rotation was too small to measure correctly.
(+)-Eth yl 4-m eth yl-3,6-d ih yd r o-2H-p yr a n -2-ca r boxy-
la te (8bb):4a 1H NMR (400 MHz) δ 5.44-5.42 (m, 1H), 4.35-
4.15 (m, 5H), 2.35-2.28 (m, 1H), 2.23-2.18 (m, 1H), 1.73 (s,
3H), 1.31 (t, 3H, J ) 7.1 Hz); IR (neat) 1758, 1736, 1186, 1135
cm-1; GC-MS (EI, 70 eV, relative intensity, %) m/z 41 (100),
170 (M+, 1.7). [R]24 +25° (c 1.1, CHCl3) 11% ee (lit.4a [R]20
[P d (S-BINAP )(P h CN)2](P F 6)2
[Pd(S-BINAP)-
(aS,2R,9R)-5b
(PhCN)2](PF6)2
empirical formula
formula weight
crystal dimensions
(mm)
C38H32O4
528.65
C58H42F12N2P4Pd
1225.26
0.40 × 0.15 × 0.40 0.40 × 0.40 × 0.40
crystal system
space group
a (Å)
orthorhombic
P212121 (No. 19)
14.337(2)
18.281(2)
10.827(2)
2837.9(6)
4
orthorhombic
P212121 (No. 19)
16.420(4)
20.972(4)
15.491(3)
5334(1)
b (Å)
c (Å)
V (Å3)
Z
D
4
calc (g/cm3)
1.237
1.526
D
D
µ(Mo KR) (cm-1
F(000)
)
0.79
5.51
-90° (c 1.8, CHCl3) 80% ee).
1120.00
2472.00
Eth yl 2-h yd r oxy-4-m eth ylen e-5-h exa n oa te (9bb):4a 1H
NMR (400 MHz) δ 6.40 (dd, 1H, J ) 17.7, 10.8 Hz), 5.29 (d,
1H, J ) 17.7 Hz), 5.27-5.10 (m, 3H), 4.35 (ddd, 1H, J ) 8.0,
6.2, 4.1 Hz), 4.29-4.18 (m, 2H), 2.81-2.76 (m, 2H), 2.51 (ddd,
1H, J ) 14.5, 8.0, 0.7 Hz), 1.31 (t, 3H, J ) 7.1 Hz); IR (neat)
3479, 1737, 1207, 1097 cm-1; GC-MS (EI, 70 eV, relative
intensity, %) m/z 41 (100), 170 (M+, 2.2). Optical rotation was
radiation
Mo KR
Mo KR
(λ ) 0.71069 Å)
graphite
monochromated
23
(λ ) 0.71069 Å)
graphite
monochromated
23
temp (°C)
scan type
ω- 2θ
ω- 2θ
scan width (deg)
2θmax (deg)
no. of unique
reflections
no. of observations
(I > 3.00σ(I))
no. of variables
R
1.78 + 0.30 tan θ
1.26 + 0.30 tan θ
too small to measure correctly (lit.4a [R]20 +2° (c 0.9, CHCl3)
55.0
3672
55.0
6755
D
91% ee).
cis-(+)-Eth yl 4,6-d im eth yl-3,6-d ih yd r o-2H-p yr a n -2-ca r -
boxyla te (cis-8cb): 1H NMR (400 MHz) δ 5.33 (br s, 1H),
4.27-4.17 (m, 4H), 2.31-2.24 (m, 1H), 2.12 (br d, 1H, J ) 16.7
Hz), 1.72 (s, 3H), 1.30 (t, 3H, J ) 7.1 Hz), 1.28 (d, 3H, J ) 6.6
Hz); 13C NMR (100 MHz) δ 171.4, 130.9, 125.1, 73.2, 71.6, 61.0,
1740
5198
369
694
0.046
0.042
1.44
0.03
0.033
0.033
1.05
0.01
Rw
GOF
max shift/
32.5, 22.7, 21.4, 14.2; IR (neat) 1759, 1736, 1184, 1126 cm-1
;
GC-MS (EI, 70 eV, relative intensity, %) m/z 43 (100), 184
(M+, 0.9). [R]28 +13° (c 1.2, CHCl3) 12% ee.
D
error in final cycle
tr a n s-(+)-Eth yl 4,6-d im eth yl-3,6-d ih yd r o-2H-p yr a n -2-
min and max peak in -0.20, 0.35
-0.26, 0.33
1
final diff. map (e-/Å3)
ca r boxyla te (tr a n s-8cb): H NMR (400 MHz) δ 5.36 (br s,
1H), 4.51-5.54 (m, 1H), 4.41 (t, 1H, J ) 4.7 Hz), 4.23 (q, 2H,
J ) 7.1 Hz), 2.27-2.25 (m, 2H), 1.72 (s, 3H), 1.29 (t, 3H, J )
7.1 Hz), 1.23 (d, 3H, J ) 6.7 Hz); GC-MS (EI, 70 eV, relative
(2R,9S)-(+)-4,5-Dim eth yl-2-(1-h yd r oxyben zyl)-3,6-d ih y-
d r o-2H-p yr a n (4a ): 1H NMR (500 MHz) δ 7.38-7.31 (m, 4H),
7.28-7.24 (m, 1H), 4.92 (t, 1H, J ) 3.3 Hz), 4.09 (br d, 1H, J
) 15.3 Hz), 4.00 (br d, 1H, J ) 15.3 Hz), 3.73 (dt, 1H, J )
10.9, 3.6 Hz), 2.76 (d, 1H, J ) 2.8 Hz), 2.26-2.20 (m, 1H), 1.56
(s, 3H), 1.50 (s, 3H), 1.40 (br d, 1H, J ) 17.0 Hz); 13C NMR
(125 MHz) δ 140.1, 128.2, 127.4, 126.3, 123.65, 123.59, 77.4,
intensity, %) m/z 43 (100), 184 (M+, 1.4). [R]29 +34° (c 0.9,
D
CHCl3) 33% ee.
tr a n s-(-)-Eth yl 2-h yd r oxy-4-m eth ylen e-5-h ep ten oa te
1
(9cb): H NMR (400 MHz) δ 6.10 (d, 1H, J ) 15.8 Hz), 5.79
(dq, 1H, J ) 15.8, 6.6 Hz), 5.04 (s, 1H), 4.97 (s, 1H), 4.34-
4.32 (m, 1H), 4.26-4.20 (m, 2H), 2.76 (dd, 1H, J ) 14.3, 4.2
Hz), 2.68 (d, 1H, J ) 6.3 Hz), 2.48 (dd, 1H, J ) 14.3, 8.1 Hz),
1.78 (d, 3H, J ) 6.6 Hz), 1.30 (t, 3H, J ) 7.1 Hz); 13C NMR
(100 MHz) δ 174.5, 141.0, 132.7, 125.7, 116.2, 69.4, 61.6, 37.6,
18.2, 14.2; IR (neat) 3500, 1737, 1204, 1105 cm-1; GC-MS (EI,
75.0, 70.1, 29.0, 18.4, 13.8; IR (neat) 3443, 1103, 701 cm-1
;
GC-MS (EI, 70 eV, relative intensity, %) m/z 111 (100), 218
(M+, 3.2). Anal. Calcd for C14H18O2: C, 77.03; H, 8.31. Found:
C, 77.05; H, 8.48. [R]25 +134° (c 1.1, CHCl3).
D
(2R,9R)-(+)-4,5-Dim et h yl-2-(1-h yd r oxyb en zyl)-3,6-d i-
70 eV, relative intensity, %) m/z 55 (100), 184 (M+, 4.9). [R]28
-1.6° (c 1.1, CHCl3) 30% ee.
1
D
h yd r o-2H-p yr a n (4b): H NMR (500 MHz) δ 7.38-7.30 (m,
5H), 4.49 (dd, 1H, J ) 8.1, 1.6 Hz), 4.11-4.03 (m, 2H), 3.57
(ddd, 1H, J ) 11.1, 8.1, 3.4 Hz), 3.25 (d, 1H, J ) 1.6 Hz), 2.00-
1.94 (m, 1H), 1.54 (s, 3H), 1.53 (s, 3H), 1.37 (br d, 1H, J )
16.8 Hz); 13C NMR (125 MHz) δ 139.9, 128.4, 128.1, 127.3,
124.3, 123.1, 78.7, 77.5, 69.8, 32.5, 18.3, 13.8; IR (neat) 3451,
1107, 701 cm-1; GC-MS (EI, 70 eV, relative intensity, %) m/z
111 (100), 218 (M+, 3.2). Anal. Calcd for C14H18O2: C, 77.03;
(1S,3R,4R)-(+)-Eth yl 2-oxa bicyclo[2.2.2]oct-5-en e-3-ca l-
boxyla te (8d b):4a 1H NMR (400 MHz) δ 6.55-6.51 (m, 1H),
6.29-6.26 (m, 1H), 4.59-4.56 (m, 1H), 4.30 (br s, 1H), 4.15 (q,
2H, J ) 7.1 Hz), 3.11-3.09 (m, 1H), 2.10-2.01 (m, 1H), 1.78-
1.72 (m, 1H), 1.43-1.26 (m, 2H), 1.25 (t, 3H, J ) 7.1 Hz); IR
(neat) 1757, 1723, 1191, 1053 cm-1; GC-MS (EI, 70 eV,
relative intensity, %) m/z 79 (100), 182 (M+, 1.6). [R]23 +5.2°
H, 8.31. Found: C, 77.01; H, 8.49. [R]26 +46° (c 1.1, CHCl3).
D
D
(c 1.1, CHCl3) 98% ee (lit.4a [R]20 -3.4° (c 3.0, CHCl3) 60% ee
D
P r ep a r a tion of Ester (a S,2R,9R)-5b. A mixture of 4b
(49.5 mg, 0.227 mmol), the acid chloride of (aS)-6 prepared
from (aS)-6 with SOCl2 (87 mg, 0.251 mmol),18a and 4-(dim-
ethylamino)pyridine (42 mg, 0.344 mmol) in benzene (1 mL)
was stirred at room temperature for 15 h. The reaction mixture
was diluted with EtOAc (30 mL) and THF (20 mL), washed
with 2 M HCl (30 mL × 2), 1 M Na2CO3 (30 mL × 2), and
saturated NaCl (30 mL × 2), and then dried over MgSO4. After
the solvent was removed in vacuo, the residue was recrystal-
lized from MeOH/CH2Cl2 to give 5b (96.3 mg, 80%) as white
(1R,3S,4S)).
Red u ction of (R)-(+)-3a a . A mixture of 3a a (99% ee, 516
mg, 2.39 mmol) and NaBH4 (91 mg, 2.4 mmol) in methanol
(25 mL) was stirred at room temperature for 2 h. After the
reaction was quenched by adding a small amount of water,
the solvent was removed in vacuo. The residue was dissolved
in ether (20 mL), washed with saturated NaCl (20 mL × 3),
and then dried over MgSO4. After the solvent was removed in
vacuo, the residue was purified by medium-pressure prepara-
tive liquid chromatography (Yamazen Corp., Ultra Pack
column, silica gel, 40 µm, 60 Å, 26 mm × 300 mm) eluting
with hexane/EtOAc (2:1) to give 4a (309 mg, 59%) and 4b (136
mg, 26%), respectively, as colorless oils.
1
crystals: mp 205.5-207.0 °C; H NMR (500 MHz) δ 8.23 (d,
1H, J ) 8.7 Hz), 8.02 (d, 1H, J ) 9.0 Hz), 7.96 (d, 1H, J ) 8.7
Hz), 7.93-7.90 (m, 2H), 7.52-7.48 (m, 1H), 7.44 (d, 1H, J )
9.0 Hz), 7.37-7.34 (m, 1H), 7.25-7.23 (m, 2H), 7.17-7.14 (m,

Asymmetric Hetero Diels-Alder Reaction
J . Org. Chem., Vol. 64, No. 23, 1999 8667
1H), 7.12-7.08 (m, 1H), 7.01 (t, 2H, J ) 7.6 Hz), 6.92 (d, 1H,
J ) 8.5 Hz), 6.48 (d, 2H, J ) 7.9 Hz), 5.61 (d, 1H, J ) 7.6 Hz),
3.89-3.82 (m, 2H), 3.70 (s, 3H), 3.07 (ddd, 1H, J ) 11.2, 7.6,
3.6 Hz), 1.61-1.53 (m, 1H), 1.49 (s, 3H), 1.44 (s, 3H), 1.00 (br
d, 1H, J ) 16.6 Hz); 13C NMR (125 MHz) δ 166.97, 154.28,
137.02, 136.97, 135.29, 134.21, 132.98, 129.12, 128.90, 128.80,
127.97, 127.96, 127.87, 127.81, 127.76, 127.62, 127.60, 127.46,
127.16, 126.57, 126.53, 125.45, 124.16, 123.48, 122.682, 122.679,
113.93, 78.35, 75.11, 69.21, 56.54, 32.16, 18.19, 13.92; IR (KBr)
1696, 1272, 1125 cm-1. Anal. Calcd for C36H32O4: C, 81.79; H,
6.10. Found: C, 81.71; H, 6.26.
X-r a y Cr ysta l Str u ctu r e Deter m in a tion . (aS,2R,9R)-5b
was crystallized from MeOH/EtOAc, and [Pd(S-BINAP)(PhCN)2]-
(PF6)2 was crystallized from CH2Cl2 layered with hexane. A
summary of selected crystallographic data is given in Table
5. Data were collected on a Rigaku AFC7R diffractometer with
graphite monochromated Mo KR radiation and a rotating
anode generator. Unit cell dimensions were obtained from a
least-squares refinement using the setting angles of 25 reflec-
tions in the range 22° < 2θ < 25° for 5b and 28° < 2θ < 30°
for [Pd(S-BINAP)(PhCN)2](PF6)2. The intensities of three
representative reflections, measured after every 150 reflec-
tions, showed no decay. The data were corrected for absorption
and for Lorentz and polarization effects.
tion. The structures were solved by direct methods (SIR92)
and expanded using Fourier techniques (DIRDIF94). The
structures were refined by full-matrix least squares with
anisotropic thermal parameters for all non-hydrogen atoms.
Hydrogen atoms attached to asymmetric carbons on 5b (H1
and H12) were refined isotropically, and all the other hydrogen
atoms were included in calculated positions and were not
refined.
Ack n ow led gm en t. This work was supported in part
by a Grant-in-Aid for Scientific Research (08455421 and
08651015) from the Ministry of Education, Science,
Sports, and Culture, J apan, and by the Sankyo Award
in Synthetic Organic Chemistry, J apan. We thank
Takasago Perfumery Co., Ltd. for the gift of BINAP and
Prof. S. Miyano for the gift of (aS)-6.
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra for new compounds lacking analyses and X-ray crys-
tallographic data for 5b and [Pd(S-BINAP)(PhCN)2](PF6)2.
This material is available free of charge via the Internet at
http://pubs.acs.org.
Calculations were performed using the teXsan crystal-
lographic software package from Molecular Structure Corpora-
J O9906680