Chiral phosphinooxazolidine ligands for palladium- and platinum-catalyzed asymmetric Diels-Alder reactions

Article abstract of DOI:10.1021/jo049375j

Cationic palladium (Pd)- and platinum (Pt)-phosphinooxazolidine catalysts 13a-c, 15a-d, 17a-c, and 19a-c were prepared from phosphinooxazolidine ligands 1-3, MCl₂ (M = Pd and Pt), and counterions, and the activities of the catalysts in the asymmetric Diels-Alder (DA) reactions of cyclic or acyclic dienes with imide dienophiles were investigated. These catalysts demonstrated high levels of catalytic activity. The cationic Pd-POZ complex 13c provided particularly excellent enantioselectivity (98% ee) in the DA reactions of cyclopentadiene with acryloyl-, crotonyl-, and fumaroyl-1,3-oxazolidin-2-ones (20a-c).

Full text of DOI:10.1021/jo049375j

Ch ir a l P h osp h in ooxa zolid in e Liga n d s for P a lla d iu m - a n d
P la tin u m -Ca ta lyzed Asym m etr ic Diels-Ald er Rea ction s
Hiroto Nakano,*,† Kouichi Takahashi,† Yuko Okuyama,† Chieko Senoo,† Natsumi Tsugawa,†
Yuichiro Suzuki,† Reiko Fujita,† Kazuo Sasaki,‡ and Chizuko Kabuto*,‡
Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, J apan, and
Instrumental Analysis Center for Chemistry, Graduate School of Science, Tohoku University,
Aoba, Aramaki, Aoba-ku, Sendai 980-8578, J apan
hnakano@tohoku-pharm.ac.jp; kabuto@kiki.chem.tohoku.ac.jp
Received April 15, 2004
Cationic palladium (Pd)- and platinum (Pt)-phosphinooxazolidine catalysts 13a -c, 15a -d , 17a -
c, and 19a -c were prepared from phosphinooxazolidine ligands 1-3, MCl2 (M ) Pd and Pt), and
counterions, and the activities of the catalysts in the asymmetric Diels-Alder (DA) reactions of
cyclic or acyclic dienes with imide dienophiles were investigated. These catalysts demonstrated
high levels of catalytic activity. The cationic Pd-POZ complex 13c provided particularly excellent
enantioselectivity (98% ee) in the DA reactions of cyclopentadiene with acryloyl-, crotonyl-, and
fumaroyl-1,3-oxazolidin-2-ones (20a -c).
In tr od u ction
The design of economical and efficient chiral ligands
for highly enantioselective transformations has been a
great challenge in the field of catalytic asymmetric
synthesis.1 Recently, we developed N-P type, chiral
phosphinooxazoline (POZ) ligands 1 and 3 (Figure 1) and
found that the Pd complex of ligand 1 works as an
effective catalyst of Pd-catalyzed asymmetric allylic
alkylation.2 A major advantage of ligand 1 is that either
enantiomeric form can be readily obtained from the
reaction of commercially available (R)- or (S)-1,1-diphen-
yl(2-pyrrolidinyl)methanol with 2-(diphenylphosphino)-
benzaldehyde. The enantioselective Diels-Alder reaction
(DA) is an important and versatile reaction in synthetic
organic chemistry. Many research groups have reported
an enantioselective version that relies on a chiral cata-
lyst.3 However, most DA catalysts have the disadvantage
of working effectively only on a specific subset of sub-
strates. The chiral catalysts that are reported to provide
high enantioselectivity in the DA reaction include cop-
per-C2-symmetrical bis-oxazolines,4 copper-phosphi-
nooxazolines,5 copper-siam,6 borane-BLA,7 titanium-
TADDOL8 catalysts, and others.9 The use of late transition
metals such as palladium(Pd) and platinum(Pt) as chiral
F IGURE 1. Phosphinooxazolidine Ligands.
DA catalysts has not been extensively explored. Only a
few studies on Pd- or Pt-based catalysts have been
reported.10 In this paper we report a detailed investiga-
tion of the design of cationic Pd- and Pt-POZ catalysts
containing POZ ligands 1-3, the application of these
catalysts in the enantioselective DA reaction, and the
transition-state assembly of these catalysts.11
(4) (a) Evans, D. A.; Miller, S. J .; Leckta, T. J . Am. Chem. Soc. 1993,
115, 6460-6461. (b) Ghosh, A. K.; Mathivanan, P.; Cappiello, J .
Tetrahedron Lett. 1996, 37, 3815-3818. (c) Evans, D. A.; Miller, S. J .;
Lectka, T.; Matt, P. V. J . Am. Chem. Soc. 1999, 121, 7559-7573. (d)
Evans, D. A.; Barnes, D. M.; J ohnson, J . S.; Lectka, T.; Matt, P. V.;
Miller, S. J .; Murry, J . A.; Norcross, R. D.; Shaughnessy, E. A.; Campos,
K. R. J . Am. Chem. Soc. 1999, 121, 7582-7594.
(5) Sagasser, I.; Helmchen, G. Tetrahedron Lett. 1998, 39, 261-264.
(6) Owens, T. D.; Souers, A. J .; Ellman, J . A. J . Org. Chem. 2003,
68, 3-10.
(7) (a) Ishihara, K.; Yamamoto, H. J . Am. Chem. Soc. 1994, 116,
1561-1562. (b) Ishihara, K.; Kurihara, H.; Yamamoto, H. J . Am. Chem.
Soc. 1996, 118, 3049-3050.
† Tohoku Pharmaceutical University.
‡ Tohoku University.
(1) For a recent overview, see: (a) Oppolzer, W. Comprehensive
Organic Syntheses: Selectivity, Strategy and Efficiency in Modern
Organic Chemistry; Trost, B. M., Ed.; Pergamon Press: Oxford, 1991;
Vol. 5, p 315 and references therein. (b) Comprehensive Asymmetric
Catalysis; J acobsen, E. J ., Pfaltz, A., Yamamoto, H., Eds., Springer:
New York; 1999.
(2) Okuyama, Y.; Nakano, H.; Hongo, H. Tetrahedron: Asymmetry
2000, 11, 1193-1198.
(3) For a review, see: (a) Pindur, U.; Lutz, G.; Otto, C. Chem. Rev.
1993, 93, 741-761. (b) Dias, L. C. J . Braz. Chem. Soc. 1997, 8, 289-
332. (c) Ghosh, A. K.; Mathivanan, P.; Cappiello, J . Tetrahedron:
Asymmetry 1998, 9, 1-45.
(8) (a) Narasaka, K.; Iwasawa, N.; Inoue, M.; Yamada, T.; Na-
kashima, M.; Sugimori, J . J . Am. Chem. Soc. 1989, 111, 5340-5345.
(b) Narasaka, K.; Tanaka, H.; Kanai, F. Bull. Chem. Soc. J pn. 1991,
64, 387-391. (c) Seebach, D.; Marti. R. E.; Hintermann, T. Helv. Chim.
Acta 1996, 79, 1710-1740.
(9) For a recent overview, see: Lewis Acids in Organic Synthesis;
Yamamoto, H., Ed.; Wiley-VCH: Weinheim, 2001; Vols. 1 and 2.
10.1021/jo049375j CCC: $27.50 © 2004 American Chemical Society
Published on Web 09/16/2004
7092
J . Org. Chem. 2004, 69, 7092-7100

Pd- and Pt-Catalyzed Asymmetric Diels-Alder Reactions
SCHEME 1. P r ep a r a tion of Ch ir a l Liga n d sa
a
Reagents and conditions: (a) PhMgBr, THF, rt, 5 h; (b) KOH, MeOH/H2O, 100 °C, 24 h, 7 72%, 11 90%; (c) 2-(diphenylphosphi-
no)benzaldehyde 8, p-TsOH, benzene, reflux, 24 h, 2a 64%, 2b + 2c (1:1) 59%; (d) 8, CSA, benzene. reflux, 24 h, 2a 77%, 2b:58%; (e)
DIAD, Ph3P, PhCO2H, THF, 0 °C, 5 h, 90%.
Resu lts a n d Discu ssion
but a similar reaction in the presence of CSA afforded
only the 5,7-cis ligand 2b with 58% yield, although the
reason for this is not clear. The stereochemical outcomes
of 2a , 2b, and 2c were evaluated by using 1H NMR NOE
difference spectra (NOEDS). H-2 and H-5 were enhanced
in 2a and 2b, while the same positions were not enhanced
in 2c.
Syn th esis of Ch ir a l P OZ Liga n d s. The simplest
chiral POZ ligand, 1, and the bulkiest, 3, were prepared
by using our previously reported procedure.2,11 The
bulkier 7-hydroxy-POZ ligands 2a -c were synthesized
from commercially available 2,4-trans-4-hydroxy-L-pro-
line 4 (Scheme 1).12 Compound 4 was converted to ester
5, and the prolinol 7 was isolated in good yield after a
Grignard reaction and the treatment of 6 with potassium
hydroxide. The condensation of 7 with 2-(diphenylphos-
phino)benzaldehyde 8 in the presence of p-TsOH or
camphorsulfonic acid (CSA) afforded the 5,7-trans POZ
ligand 2a with yields of 55% and 77%, respectively. A
Mitsunobu reaction of 5 gave benzoate 9, inverting the
oxygen configuration at the 7-position, with a 90% yield.
Compound 9 was converted to the prolinol 11 by a
Grignard reaction followed by the treatment of 10 with
potassium hydroxide. The condensation of 11 with 8 in
the presence of p-TsOH afforded a 1:1 mixture of 5,7-cis
POZ 2b and 5,7-trans POZ 2c ligands with 59% yield,
Syn th esis of Ch ir a l P d - a n d P t-P OZ Com p lexes.
We prepared the Pd- and Pt-POZ complexes from POZ
ligands 1-3. The chiral PdCl2- and PtCl2-POZ com-
plexes 12 and 14a ,b were prepared in a convenient and
efficient manner by the reaction of 1 (1 equiv) with PdCl2
(1 equiv) or PtCl2 (1 equiv), respectively (Scheme 2).
Depending on the temperature, the reaction of 1 with
PdCl2 afforded either the N,O-acetal epimer 12 or its
counterpart 14a ; at room temperature the complex 12
was formed in 95% yield with the same stereochemistry
as ligand 1, while under reflux, the epimeric complex 14a
was formed in 90% yield. Complex 12 was easily trans-
formed to the thermodynamically stable complex 14a in
refluxing 1,2-dichloroethane (85%: 14a /12 ) 17/3). Only
the PtCl2-POZ complex 14b, which had the same ster-
eochemistry as ligand 1, was formed in refluxing dichlo-
roethane, with an 80% yield. The chiral PdCl2-POZ
complexes 16a -c were also prepared by reacting 2a -c
with PdCl2, respectively, at both room temperature and
elevated temperature, and complex 16c was easily sepa-
rated from the mixture of 16b and 16c. Similarly, the
reaction of the ligand 3 with PdCl2 gave PdCl2-POZ
(10) (a) Oi, S.; Kashiwagi, K.; Inoue, Y. Tetrahedron Lett. 1998, 39,
6253-6256. (b) Ghosh, A. K.; Matsuda, H. Org. Lett. 1999, 1, 2157-
2159. (c) Hiroi, K.; Watanabe, K. Tetrahedron: Asymmetry 2001, 12,
3067-3071. (d) Nakano, H.; Suzuki, Y.; Kabuto, C.; Fujita, R.; Hongo,
H. J . Org. Chem. 2002, 67, 5011-5014.
(11) The preliminary results were partly reported: Nakano, H.;
Okuyama, Y.; Suzuki, Y.; Fujita, R.; Kabuto, C. Chem. Commun. 2002,
1146-1147.
(12) Bhasker, J . V.; Periasamy, M. Tetrahedron 1993, 49, 5127-
5132.
J . Org. Chem, Vol. 69, No. 21, 2004 7093

Nakano et al.
SCHEME 2. P r ep a r a tion s of Ca tion ic P d -P OZ Ca ta lysts
complex 18 as a single product in 92% yield both at room
temperature and in refluxing 1,2-dichloroethane. The
stereochemical outcomes of these complexes were con-
firmed in X-ray diffraction studies of 12,11 14a ,11 14b,
16b, 16c, and 18 (Figure 2), and in a H NMR NOEDS
experiment of 16a . H-2 and H-5 were enhanced in 5,7-
cis 16a or 16b, while they were not enhanced in 5,7-trans
16c. These results also suggested the stereochemistry of
2a -c determined in the H NMR NOE experiment.
Diels-Ald er Rea ction s. In the catalytic asymmetric
DA reaction of cyclopentadiene with acryloyl-1,3-oxazo-
lidin-2-one 20a catalyzed by cationic catalysts 13a -c, the
antimonate catalyst 13c showed superior catalytic activ-
ity to give the DA adduct 21 in high chemical yield and
1
1
7094 J . Org. Chem., Vol. 69, No. 21, 2004

Pd- and Pt-Catalyzed Asymmetric Diels-Alder Reactions
TABLE 1. Diels-Ald er Rea ction w ith Ca tion ic Ca ta lysts
TABLE 2. Su bstr a te Gen er a lity in th e Diels-Ald er
Rea ction w ith Ca tion ic Ca ta lyst 13c
catalyst
(mol %)
temp (°C)/
time (h)
yielda
(%)
entry
endo/exob
% eec
1
2
3
4
5
6
7
8
9
10
11
12
13
14
13c (10)
13c (5)
13c (2.5)
13c (1)
15a (10)
15b (10)
15c (10)
15d (10)
17a (10)
17b (10)
17c (10)
19a (5)
-45/24
-50/22
-35/24
-45/48
-45/32
-45/90
-45/24
-35/36
-45/24
-45/24
-45/24
-50/24
-50/24
-50/24
96
87
82
76
55
37
5
97/3
97/3
95/5
97/3
94/6
95/5
96/4
95/5
91/9
90/10
97/3
96/4
90/10
94/6
98
97
96
94
55
0
0
0
4
78
75
92
10
70
87
25
93
97
16
85
79
temp (°C)/ yield
% eec
entry
n
substrate adduct temp (h) (%)a endo/exob (config)
19b (5)
19c (5)
1
2
3
4
5
6
1
1
2
-
-
-
20b
20c
20a
20a
20a
20c
22
23
24
25
26
27
-35/36
-35/24
-25/48
0/48
0/48
-45/72
73
95
75
88
70
56
96/4
94/6
95/5
-
98 (2R)
98 (2S)d
93 (2R)e
51 (1R)
50 (1R)f
82 (1R)
a
b
Isolated yields. Endo/exo ratios were determined by HPLC
or 1H NMR. c Ee of endo isomers were determined by chiral HPLC,
using a Daicel OD-H column (21: 0.5 mL/min, hexane:2-propanol
) 90:10).
-
-
a
b
Isolated yields. Endo/exo ratios were determined by HPLC
or 1H NMR. c Ee of endo isomers were determined by chiral HPLC,
enantioselectivity in the range of 10 to 1 mol % (entries
1-4).11 However, the isomeric antimonite complex 15a
was not as effective as 13c (entry 5).11 To test the nature
of the metal, we prepared and examined the use of three
cationic Pt-POZ complexes 15b-d ; when these catalysts
were used, the chemical yields were poor and no enan-
tioselectivity was observed (entries 6-8). Next, the
catalytic abilities of the cationic 7-hydroxy-POZ com-
plexes 17a , 17b, and 17c with antimonate counterions
were tested under the same reaction conditions as for 13c
(10 mol % and -45 °C; entry 1). The use of the 5,7-trans
catalyst 17a resulted in the formation of the DA adduct
21 in 78% yield, but with 25% ee (entry 9). Conversely,
5,7-cis 17b and 5,7-trans 17c showed satisfactory cata-
lytic activity; particularly, 17c gave DA adduct 21 in 92%
and 97% ee (entries 10 and 11). The utility of the more
conformationally constrained cationic POZ catalysts 19a-
c, in which the 2-azanorbornane ring system was fused,
was also tested under the same reaction conditions as
for 13c (entries 12-14). The results indicated that both
the perchlorate and antimonate catalysts, 19b and 19c,
were effective; 19b produced a particularly good ee.
However, 19b did not result in a higher catalytic activity
than 13c, in which the pyrrolidine ring system was fused.
The above results indicate that the simplest antimonate
POZ catalyst 13c was the most effective in the DA
reaction of cyclopentadiene with dienophile 20a .
d
using a Daicel OD-H column. After conversion to the correspond-
ing iodolactone (I2, KI, NaHCO3, yield 63%), the ee and absolute
configuration were determined by comparison with known optical
rotation: [R]20 +39.1 (c 3.3; CHCl3) {lit.3 [R]23 -39.2 (c 4.65;
D
D
CHCl3)}. e After conversion to the corresponding amide [(R)-(+)-
R-methylbenzylamine, Me3Al, yield 60%). f After conversion to the
corresponding benzyl ester, the absolute configuration and ee were
determined by comparison with known optical rotation.4d
system allowed the formation of DA adduct 24 with 70%
yield and 93% ee from the relatively unreactive cyclo-
hexadiene (Table 2, entry 3). Catalyst 13c was also used
in DA reactions of acyclic dienes, 2,3-dimethyl-1,3-
butadiene, and isoprene with dienophiles 20a and 20c
(entries 4-6). However, the reaction with dienophile 20a
was sluggish and gave only DA adducts 25 and 26 in
moderate chemical yield and poor enantioselectivity
(68%, 51% ee, entry 4; 60%, 50% ee, entry 5). Conversely,
the reaction of 2,3-dimethyl-1,3-butadiene with 20c
proceeded smoothly, even at -45 °C, giving the desired
DA adduct 27 in moderate yield, but with good enantio-
selectivity (56% yield, 82% ee, entry 6).
Next, the DA reaction of furan with dienophile 20a was
investigated (Table 3). 7-Oxabicyclo[2.2.1]hept-2-enes
formed from the DA reaction with furan are attractive
intermediates in organic synthesis.13 When furan was
reacted with dienophile 20a at room temperature, the
DA adducts endo-2813,14 and exo-28 were obtained as a
4.5:1 mixture of endo/exo isomers, both of which were
almost racemic (entry 1). By reducing the temperature
to -30 °C, the enantioselectivity was improved remark-
ably to 90% ee for endo-28 and 88% ee for exo-28 (entry
2). Furthermore, satisfactory enantioselectivity was ob-
tained for both the endo-28 and exo-28 forms at -50 °C,
Su bstr a te Scop e. The superior cationic antimonate
catalyst 13c was then tested with a series of substituted
dienophiles, such as crotonoyl-1,3-oxazolidin-2-one 20b
and fumaroyl-1,3- oxazolidin-2-one 20c (Table 2). The
reactions with 5 mol % of catalyst 13c gave the desired
DA adducts 22 and 23 in good isolated yields and with
excellent enantioselectivities (20b: 73% yield, 98% ee,
entry 1; 20c: 95% yield, 98% ee, entry 2). Notwithstand-
ing the work of Evans et al.,4c note that such enantiose-
lectivities for 20b and 20c are notoriously difficult to
obtain. Furthermore, the high catalytic activity of our
(13) (a) Evans, D. A.; Barnes, D. M. Tetrahedron Lett. 1997, 38, 57.
(b) Yamamoto, I.; Narasaka, K. Chem. Lett. 1995, 1129.
(14) Ogawa, S.; Yoshikawa, M.; Taki, T. Chem. Commun. 1992,
406-408.
J . Org. Chem, Vol. 69, No. 21, 2004 7095

Nakano et al.
TABLE 3. Diels-Ald er Rea ction of F u r a n e w ith
starting models and, somewhat surprisingly, the opti-
mized geometries corresponded very well to the X-ray
structures. The optimizations predict that 14a is pre-
ferred to 12 by 6.21 kcal/mol, which is in agreement with
the experimental results that 14a is thermodynamically
more stable than 12 (Scheme 2). Thus, we considered that
semiempirical MO calculation using the PM5 method
might be applicable for this system including transition
Pd metal. As summarized in Figure 3, the results suggest
that, in all cases, the [2S]-forms (14a , 16a , and 16b) are
energetically preferred to the corresponding [2R]-forms
(12, 16d , and 16c, respectively), and in the 7-hydroxy
position, 16a and 16d (R1 ) OH) are preferred to 16b
and 16c (R2 ) OH), respectively. It is very interesting
that the complexes with the higher energy (12 and 16c)
produced the high enantioselectivity (97% ee, entries 2
and 11 in Table 1) and, conversely, the complexes with
the lower energy (14a and 16a ) resulted in low enenti-
oselectivity (entries 5 and 9).
Ca tion ic Ca ta lyst 13c
temp
(°C)
time
(h)
yield
(%)a
endo
exo
entry
endo/exob
% eec,d
% eec,e
1
2
3
rt
-30
-50
6
24
48
84
76
20
18/82
28/72
43/57
7
90
96
6
88
95
a
b
Isolated yields. Endo/exo ratios were determined by HPLC.
c Ee were determined by chiral HPLC, using a Daicel OD-H
d
column. After conversion to the corresponding iodolactone (I2, KI,
NaHCO3), the absolute configuration was determined by compari-
son with known optical rotation.14 e The absolute configuration
was not determined.
Con clu sion
Our results demonstrate that the cationic POZ catalyst
is effective in DA reactions on various substrates. Both
the reactivity and enantioselectivity were influenced by
the structure of the POZ and counterion. Notably, the
cationic antimonate complex 13c, derived from phosphi-
nooxazolidine ligand 1, PdCl2, and silver hexafluoroan-
timonate, gave superior results. A major feature of this
catalyst is that the chiral ligand 1 is readily obtained
from the reaction of commercial (R)- or (S)-1,1-diphenyl-
(2-pyrrolidinyl)methanol with 2-(diphenylphosphino)ben-
zaldehyde. Additionally, the low molar ratios of catalyst
13c are sufficient for efficient reactions, and enantiose-
lectivities of up to 98% ee were achieved for the DA
reactions of cyclopentadiene with the dienophiles 20a -
c. This is a superlative result for a DA reaction with Pd-
and Pt-complex catalysts. The Pd and Pt complexes with
POZ ligands that we explored have a characteristic
structure; therefore, they should prove useful not only
for other DA reactions but also for other asymmetric
processes.
SCHEME 3. Diels-Ald er Rea ction w ith
Meth yla cr yla te a s a Dien op h ile
although the chemical yield and diastereoselectivity were
poor (entry 3). Finally, the utility of a monodentate
dienophile in this reaction was tested (Scheme 3). How-
ever, the reaction with methylacrylate 29 as a monoden-
tate dienophile was sluggish and the result indicated the
importance of the bidentate activation as the dienophile.
X-r a y Cr ysta l Str u ctu r e Deter m in a tion . Previously
we reported detailed X-ray structures of the two PdCl2-
POZ complexes 12 and 14a and proposed that the
marked difference in their enantioselectivity might be
explained by the difference in the distortion of the planar
Pd coordination and by the difference in the steric
congestion of the structures.11 We also compared X-ray
analyses of the PtCl2-POZ complex 14b, which produced
no enantioselectivity (entries 9-11 in Table 1), and the
corresponding Pd complex 12, which produced the highest
enantioselectivity (catalyst 13c, entries 3). As shown in
Figure 2a, the structures were very similar and displayed
no significant difference in the bond lengths and angles
of the coordination geometries. However, the degree of
distortion in the coordination geometry was notably
different, as demonstrated by the dihedral angle between
the two planes of N-metal-Cl1 and P-metal-Cl2 (2.3°
for 14b and 10.2° for 12). Furthermore, the structures
of 16b and 16c with 7-hydroxy-POZ were determined
by X-ray analysis (Figure 2, parts b and c), showing that
the dihedral angles are 2.4° and 3.1°, respectively.
Sem iem pir ica l P M5 Ca lcu la tion s.15 We used semiem-
pirical PM5 calculations to predict the stabilities of Pd-
Cl2-POZ complexes. X-ray structures were used as the
Finally, semiempirical PM5 calculations for PdCl2
complexes indicate that the stabilities of the complexes
are closely related to the enantioselectivities of the
catalysts.
Exp er im en ta l Section
X-r a y Cr ysta llogr a p h y. X-ray data were collected on a
Rigaku/MSC Mercury CCD diffractometer with graphite-
monochromated Mo KR radiation (λ ) 0.71069 Å). Low-
temperature equipment was used to maintain the stability of
crystals (173 K). The data were corrected for Lorenz and
polarization effects. The structures were solved by direct
method and refined by the full-matrix least-squares method.
Crystal data of compound 14b : MF ) C36H32NOPPtCl2-
(15) Semiempirical PM5 (transition metal) calculations were per-
formed with the WinMOPAC version 3.9 program [MOPAC2002,
version 1.5, J . J . Stewart, Fujitsu, Tokyo, J apan, 2003]. First, we
examined PM3 calculations of 12 and 14a ; however, the results
disagreed with the experimental results.
7096 J . Org. Chem., Vol. 69, No. 21, 2004

Pd- and Pt-Catalyzed Asymmetric Diels-Alder Reactions
F IGURE 2. (a) X-ray structure of 14b. Hydrogen atoms except for one hydrogen atom of the POZ ligand were omitted for clarity.
Selected bond lengths (Å) and bond angles (deg): Pt-Cl1 ) 2.302(1), Pt-Cl2 ) 2.382(1), Pt-P ) 2.203(1), Pt-N ) 2.107(4),
Cl1-Pt-Cl2 ) 88.34(4), Cl1-Pt-N ) 175.7(1), Cl2-Pt-N ) 87.6(1), Cl1-Pt-P ) 88.51(4), Cl2-Pt-P ) 176.33(4), P-Pt-N )
95.6(1). Maximum deviation from the least-squares plane of five atoms in Pd coordination is 0.044 and the dihedral angle between
the two planes N-Pt-Cl2 and P-Pt-Cl1 is 2.37°. (b) X-ray structure of 16b. Hydrogen atoms except for three hydrogen atoms
of the POZ ligand were omitted for clarity. Selected bond lengths (Å) and bond angles (deg) averaging over two independent
molecules: Pd-Cl1 ) 2.289(0), Pd-Cl2 ) 2.356(0), Pd-P ) 2.246(0), Pd-N ) 2.109(2), Cl1-Pd-Cl2 ) 89.23(3), Cl1-Pd-N )
177.39(7), Cl2-Pd-N ) 92.96(7), Cl1-Pd-P ) 85.46(3), Cl2-Pd-P ) 174.33(3), P-Pd-N ) 92.38(7). Maximum deviation from
the least-squares plane of five atoms in Pd coordination is 0.052 and the dihedral angle between the two planes N-Pd-Cl2 and
P-Pd-Cl1 is 2.35°. (c) X-ray structure of 16c. Hydrogen atoms except for three hydrogen atoms of the POZ ligand were omitted
for clarity. Selected bond lengths (Å) and bond angles (deg): Pd-Cl1 ) 2.298(0), Pd-Cl2 ) 2.372(0), Pd-P ) 2.232(0), Pd-N )
2.112(2), Cl1-Pd-Cl2 ) 89.32(3), Cl1-Pd-N ) 178.24(6), Cl2-Pd-N ) 89.05(5), Cl1-Pd-P ) 86.99(2), Cl2-Pd-P ) 175.18(3),
P-Pd-N ) 94.68(6). Maximum deviation from the least-squares plane of five atoms in Pd coordination is 0.049 and the dihedral
angle between the two planes N-Pt-Cl2 and P-Pt-Cl1 is 3.12°. (d) X-ray structure of 18. Hydrogen atoms except for one hydrogen
atom of the POZ ligand were omitted for clarity. Selected bond lengths (Å) and bond angles (deg): Pd-Cl1 ) 2.295(2), Pd-Cl2
) 2.374(2), Pd-P ) 2.249(2), Pd-N ) 2.128(6), Cl1-Pd-Cl2 ) 89.28(7), Cl1-Pd-N ) 176.9(2), Cl2-Pd-N ) 93.4(2), Cl1-
Pd-P ) 84.42(7), Cl2-Pd-P ) 173.29(8), P-Pd-N ) 92.8(2). Maximum deviation from the least-squares plane of five atoms in
Pd coordination is 0.047 and the dihedral angle between the two planes N-Pt-Cl2 and P-Pt-Cl1 is 2.75°.
F IGURE 3. PM5 geometry optimation for Cl2 complexes.
CHCl3, colorless prism, sizes ) 0.20 × 0.20 × 0.20 mm,
orthorhombic, a ) 11.253(2) Å, b ) 14.021(2) Å, c ) 22.776(3)
Å, V ) 3593.8(9) Å3, space group ) P212121 (no. 19), Z ) 4,
Dcalcd ) 1.684 g/cm3, µ(Mo KR) ) 43.36 cm-1. Of the 28435
reflections measured, 7936 were unique (Rint ) 0.051). The
final R factor was 0.020 (Rw ) 0.024) for 6481 reflections with
I > 5σ(I). Crystal data of compound 16b: MF ) C36H32NO2-
PPdCl2‚C4H8O2, colorless prism, sizes ) 0.20 × 0.20 × 0.10
mm, orthorhombic, a ) 30.160(1) Å, b ) 14.1000(4) Å, c )
17.3200(5) Å, V ) 7365.4(4) Å3, space group ) P212121 (no. 19),
J . Org. Chem, Vol. 69, No. 21, 2004 7097

Nakano et al.
Z ) 8, Dcalcd ) 1.455 g/cm3, µ(Mo KR) ) 7.34 cm-1. Two
independent Pd complexes and two CH3COOEt solvents are
present in asymmetric unit of the crystal structure. Of the
MS m/z 541 (M+); HRMS calcd for C36H32NO2P (M+) 541.2171,
found 541.2186.
(2S,4S)-4-Ben zoyloxy-2-m et h oxyca r b on yl-N-et h oxy-
ca r bon ylp yr r olid in e (9). To a solution of 512 (1.0 g, 2.91
mmol), PPh3 (1.3 g, 5.06 mmol), and benzoic acid (618 mg, 5.06
mmol) in THF (15 mL) was added azodicarboxylic acid diethy-
lester (40% in toluene, 2.2 mL, 5.06 mmol) at 0 °C and the
reaction mixture was stirred for 5 h. The solution was diluted
with ether and washed with saturated aqueous NH4Cl and
brine. The organic layer was dried over anhydrous MgSO4 and
filtered. The filtrate was concentrated under reduced pressure
to give a residue, which was chromatographed on silica gel
(1:1 hexane/EtOAc as eluent) to give the pure product 9 as a
colorless oil: [R]23D +33.33 (c 0.54, CHCl3); IR (NaCl) 716, 1712,
56264 reflections were measured, 16743 were unique (Rint
)
0.032). The final R1 factor was 0.034 for reflections with I >
2σ(I) and wR2 was 0.094 for all reflections. Crystal data of
compound 16:, MF ) C36H32NO2PPdCl2, colorless prism, sizes
) 0.20 × 0.25 × 0.15 mm, monoclinic, a ) 12.259(3) Å, b )
10.597(2) Å, c ) 12.465(3) Å, â ) 93.697(1), V ) 1615.9(6) Å3,
space group ) P21 (no. 4), Z ) 2, Dcalcd ) 1.477 g/cm3, µ(Mo
KR) ) 8.22 cm-1. Of the 24969 reflections measured, 7248 were
unique (Rint ) 0.037). The final R1 factor was 0.022 for
reflections with I > 2σ(I) and wR2 was 0.047 for all reflections.
Crystal data of compound 18: MF ) C38H34NOPPdCl2‚CHCl3,
colorless prism, sizes ) 0.20 × 0.20 × 0.20 mm, orthorhombic,
a ) 12.785(3) Å, b ) 14.625(4) Å, c ) 19.215(5)Å, V ) 3593(1)
Å3, space group ) P212121 (no. 19), Z ) 4, Dcalcd ) 1.568 g/cm3,
µ(Mo KR) ) 9.66 cm-1. Of the 33784 reflections measured, 8125
1
1758 cm-1; H NMR (CDCl3) δ 1.21-1.31 (m, 3H), 2.49-2.58
(m, 2H), 3.67 (d, J ) 6.8 Hz, 3H), 3.73-3.91 (m, 2H), 4.07-
4.25 (m, 2H), 4.60 (ddd, J ) 3.1, 7.9, 23.3 Hz, 1H), 5.55 (s,
1H), 7.40-7.45 (m, 2H), 7.52-7.59 (m, 1H), 7.96 (d, J ) 8.2
Hz, 2H); 13C NMR (CDCl3) δ 14.7, 35.8, 52.4, 57.7, 61.5, 72.3,
73.3, 128.3, 129.5, 133.2, 154.7, 165.6, 171.7; MS m/z 321 (M+);
HRMS calcd for C16H19NO6 (M+) 321.1212, found 321.1185.
were unique (Rint ) 0.037). The final R factor was 0.046 (Rw
0.054) for 5256 reflections with I > 5σ(I).
)
All calculations were made with TeXsan software (TEXRAY
Structure Analysis Package, Molecular Structure Corp., 1985)
and Crystal Structure software [Crystal Structure Analysis
Package, Rigaku and RigakuMSC (2000-2004). 9009 New
Tails Dr., The Woodlands, TX 77381].
(2S,4S)-4-H yd r oxy-r,r-d ip h en yl-2-p yr r olid in em et h a -
n ol (11). To a solution of 9 (206 mg, 0.64 mmol) in dry THF
(10 mL) was added PhMgBr (1 M in THF, 13 mL, 12.82 mmol)
under Ar. After being stirred for 5 h, the reaction solution was
diluted with ether and washed with saturated aqueous NH4-
Cl. The organic layer was dried over anhydrous MgSO4 and
filtered. The filtrate was concentrated under reduced pressure
to give a residue, which was chromatographed on silica gel
(1:1 hexane/EtOAc as eluent) to give the crude product 10,
which was used for the next step without further purification.
A suspension of the crude product 10 (157 mg) and KOH (72
mg, 1.28 mmol) in H2O (5 mL)-methanol (10 mL) was heated
at 100 °C for 24 h. After the solution was cooled, water was
added and the precipitate was removed by filtration and dried
under high vacuum to give the amino alcohol (37) (112 mg,
(2S,4R)-4-Hyd r oxy-r,r-d ip h en yl-2-p yr r olid in em et h a -
n ol (7). To a solution of 512 (500 mg, 2.30 mmol) in dry THF
(10 mL) was added PhMgBr (1 M in THF, 23 mL, 23.02 mmol)
at 0 °C under Ar. After being stirred for 5 h, the reaction
solution was diluted with ether and washed with saturated
aqueous NH4Cl. The organic layer was dried over anhydrous
MgSO4 and filtered. The filtrate was concentrated under
reduced pressure to give a residue, which was chromato-
graphed on silica gel (1:1 hexane/EtOAc as eluent) to give the
crude product 6, which was used for the next step without
further purification. A suspension of the crude product 6 (440
mg) and KOH (258 mg, 4.60 mmol) in H2O (5 mL)-methanol
(10 mL) was heated at 100 °C for 24 h. After the solution was
cooled, water was added and the precipitate was removed by
filtration and dried under high vacuum to give the amino
alcohol (7) (343 mg, 55%) as a colorless powder: mp 176 °C;
65%) as a colorless powder: mp 174 °C; [R]23 -18.00 (c 2.00,
D
DMSO); IR (KBr) 696, 750, 1448, 3332 cm-1; 1H NMR (CDCl3)
δ 1.60-1.68 (m, 1H), 1.92-2.10 (m, 2H), 2.99-3.10 (m, 1H),
4.25-4.29 (m, 1H), 4.38 (dd, J ) 5.1, 9.4 Hz, 1H), 7.14-7.48
(m, 6H), 7.55 (d, J ) 0.7 Hz, 2H), 7.58 (d, J ) 1.3 Hz, 2H); 13
C
NMR (CDCl3) δ 36.4, 55.6, 63.4, 71.2, 125.3, 125.7, 126.4, 126.5,
126.8, 127.3, 127.7, 128.0, 128.1,144.9, 146.8; MS m/z 269 (M+);
HRMS calcd for C17H19NO2 (M+) 269.1416, found 269.1398.
[R]20 -32.03 (c 1.28, DMSO); IR (KBr) 707, 1420, 1454, 1612
D
1
cm-1; H NMR (CDCl3) δ 1.26 (s, 1H), 1.47 (dd, J ) 6.4, 13.6
Hz, 1H), 1.63 (br s, 2H), 1.80-1.90 (m, 1H), 2.99 (d, J ) 11.5,
1H), 3.19 (dd, J ) 4.2, 11.5 Hz, 1H), 4.39 (m, 1H), 4.65 (dd, J
) 6.2, 9.7 Hz, 1H), 7.13-7.33 (m, 6H), 7.47 (d, J ) 7.3 Hz,
2H), 7.58 (d, J ) 7.4 Hz, 2H); 13C NMR (CDCl3) δ 36.4, 55.6,
63.4, 69.7, 71.2, 125.3, 125.7, 126.4, 126.5, 126.8, 126.9, 127.3,
127.9, 128.1, 135.6, 144.9, 146.8; MS m/z 269 (M+); HRMS
calcd for C17H19NO2 (M+) 269.1416, found 269.1400.
(2S,5S,7S)-1-Aza-4-h ydr oxy-2-(diph en ylph osph in o)ph en -
yl-3-oxa -4,4-d ip h en ylbicyclo[3.3.0]octa n e (2b). Compound
11 (50 mg, 0.19 mmol), 2-(diphenylphosphino)benzaldehyde 8
(54 mg 0.19 mmol), p-TsOH (7 mg, 0.04 mmol) or CSA (9 mg,
0.04 mmol) and benzene (10 mL) were placed in a flask
equipped with a Dean-Stark trap and the mixture was
refluxed for 24 h. The solvent was removed under reduced
pressure and the residue was purified by preparative TLC (1:1
hexane/EtOAc) to give the products [p-TsOH: 2b + 2c (59 mg),
59%; CSA: 2b (58 mg), 58%]. 2b: colorless prisms, mp 93 °C;
(2S,5S,7R)-1-Aza -4-h yd r oxy-2-(d ip h en ylp h osp h in o)-
p h en yl-3-oxa -4,4-d ip h en ylbicyclo[3.3.0]octa n e (2a ). Com-
pound 7 (30 mg, 0.11 mmol), 2-(diphenylphosphino)benzalde-
hyde 8 (36 mg 0.12 mmol), p-TsOH (4 mg, 0.02 mmol) or DL-
camphor-10-sulfonic acid (CSA)(5 mg, 0.02 mmol) and benzene
(10 mL) were placed in a flask equipped with a Dean-Stark
trap and the mixture was refluxed for 24 h. The solvent was
removed under reduced pressure and the residue was purified
by preparative TLC (1:1 hexane/EtOAc) to give the product
2a (p-TsOH: 33 mg, 55%; CSA: 46 mg, 77%) as colorless
prisms; mp 92 °C; [R]20D -43.20 (c 0.81, CHCl3); IR (KBr) 697,
745, 1434 cm-1; 1H NMR (CDCl3) δ 0.99 (d, J ) 18.7 Hz, 1H),
1.42-1.51 (m, 1H), 1.62 (d, J ) 10.1 Hz, 1H), 18.54 (dd, J )
8.4, 13.9 Hz, 1H), 2.51 (dd, J ) 3.4, 10.0 Hz, 1H), 3.71-3.76
(m, 1H), 4.63 (dd, J ) 6.1, 8.2 Hz, 1H), 6.19 (d, J ) 5.4 Hz,
1H), 7.04-7.16 (m, 4H), 7.18-7.26 (m, 5H), 7.28-7.53 (m,
12H), 7.56-7.59 (m, 2H), 8.17 (q, J ) 3.9 Hz, 1H); 13C NMR
(CDCl3) δ 39.7, 66.4, 71.8, 73.3, 90.7, 92.6, 124.0, 124.8, 126.2,
126.5, 126.6, 127.2, 127.2, 127.5, 127.7, 128.3, 128.3, 128.4,
128.6, 128.7, 128.8, 128.8, 129.9, 131.5, 131.5, 131.7, 131.7,
132.0, 132.0, 133.4, 133.5, 133.7, 134.8, 135.0, 136.6, 140.9;
[R]20 -44.30 (c 1.58, CHCl3); IR (KBr) 696, 745, 1434 cm-1
;
D
1H NMR (CDCl3) δ 1.20-1.29 (m, 2H), 2.09-2.16 (m, 2H), 2.39
(t, J ) 8.7 Hz, 1H), 3.89-4.00 (m, 1H), 4.56 (t, J ) 7.5 Hz,
1H), 5.91 (d, J ) 4.0 Hz, 1H), 7.03-7.37 (m, 17H), 7.46-7.97
(m, 6H), 8.17 (dd, J ) 3.6, 7.1 Hz, 1H); 13C NMR (CDCl3) δ
38.8, 63.8, 71.1, 72.0, 87.4, 89.7, 113.1, 118.6, 126.1, 126.6,
126.8, 126.8, 127.0, 128.1, 128.2, 128.4, 128.6, 128.7, 129.0,
132.9, 133.2, 134.0, 134.1, 134.2, 134.5, 135.9, 136.0, 144.1,
145.4, 147.0; MS m/z 541 (M+); HRMS calcd for C36H32NO2P
(M+) 541.2171, found 541.2153.
Dich lor o[(2R,5S)-1-a za -2-(d ip h en ylp h osp h in o)p h en yl-
3-oxa -4,4-d ip h en ylbicyclo[3.3.0]octa n e]p a lla d iu m (12). A
mixture of POZ 1 (52.6 mg, 0.1 mmol) and PdCl2 (17.7 mg, 0.1
mmol) in dichloromethane was stirred for 72 h at room
temperature under Ar. The resulting suspension was filtered,
and the filtrate was condensed under a reduced pressure. The
residue was recrystallized from hexane-CHCl3 to afford yellow
crystals 12 (66.8 mg, 95%): mp 198 °C; [R]20D -395.96 (c 1.24,
7098 J . Org. Chem., Vol. 69, No. 21, 2004

Pd- and Pt-Catalyzed Asymmetric Diels-Alder Reactions
CHCl3); IR (KBr) 590, 747, 1584 cm-1; 1H NMR (CDCl3) δ 1.44
(m, 1H), 1.88 (m, 1H), 2.08 (m, 1H), 2.62 (m, 1H), 2.92 (m,
1H), 4.41 (m, 1H), 4.95 (s, 1H), 6.84-6.90 (m, 2H), 7.00 (t, J )
7.6 Hz, 2H), 7.07-7.19 (m, 6H), 7.22-7.39 (m, 12H), 7.51 (t, J
) 7.6 Hz, 1H), 7.59 (dd, J ) 4.4, 6.6 Hz, 1H), 7.68 (t, J ) 7.4
Hz, 1H); 13C NMR (CDCl3) δ 27.0, 28.9, 54.9, 77.4, 89.2, 94.4,
124.9, 126.2, 126.6, 126.7, 127.1, 127.3, 128.0, 128.2, 128.5,
128.5, 128.6, 130.7, 130.7, 130.8, 130.8, 132.1, 132.2, 132.2,
132.8, 133.3, 133.4, 133.7, 133.9, 134.0, 136.0, 136.0, 137.3,
137.4, 142.2, 143.5. Anal. Calcd for C36H32Cl2NOPPd: C, 61.51;
H, 4.59; N, 1.99. Found: C, 61.21; H, 4.76; N, 1.71.
5.27 (br s, 1H), 5.68 (s, 1H), 6.33 (t, J ) 8.7 Hz, 1H), 6.95 (dd,
J ) 7.8, 10.0 Hz, 1H), 7.15-7.52 (m, 16H), 7.63-7.73 (m, 5H),
8,01 (dd, J ) 4.1, 7.8 Hz, 1H); 13C NMR (CDCl3) δ 39.0, 62.5,
69.3, 73.0, 90.2, 91.7, 123.8, 124.6, 126.3, 126.6, 126.8, 127.1,
127.3, 127.4, 127.7, 128.1, 128.3, 128.3, 128.5, 128.6, 128.7,
128.8, 129.9, 131.3, 131.3, 131.7, 131.7, 132.0, 132.0, 133.4,
133.5, 133.6, 134.7, 134.9, 136.2, 141.0; calcd for C36H32NO2-
PPd requires m/z 647.1205, found m/z 647.1051 ([M - Cl2]+)
(FAB with p-nitrobenzyl alcohol added).
Dich lor o[(2R,5S,7S)-1-a za -4-h yd r oxy-2-(d ip h en ylp h os-
p h in o)p h en yl-3-oxa -4,4-d ip h en ylb icyclo[3.3.0]oct a n e]-
p a lla d iu m (16c). PdCl2 (39 mg, 0.22 mmol) and the mixture
of 2b and 2c (118 mg, 0.22 mmol) were suspended in
anhydrous toluene (5 mL) under Ar. The mixture was stirred
at 100 °C for 24 h and the resulting yellow solution was cooled
and filtered. The filtrate was concentrated under reduced
pressure to give a residue, which was chromatographed on
silica gel (1:1 CHCl3/EtOAc as eluent) to give the products 16b
and 16c (16b: 72 mg, 46%; 16c: 48 mg, 47%), respectively.
16c: yellow prisms; mp 232 °C; [R]23D -291.37 (c 2.32, DMSO);
Dich lor o[(2R,5S)-1-a za -2-(d ip h en ylp h osp h in o)p h en yl-
3-oxa -4,4-d ip h en ylbicyclo[3.3.0]octa n e]p a lla d iu m (14a )
a n d Dich lor o[(2R,5S)-1-a za -2-(d ip h en ylp h osp h in o)p h e-
n yl-3-oxa-4,4-diph en ylbicyclo[3.3.0]octan e]platin u m (14b).
A mixture of POZ 1 (52.6 mg, 0.1 mmol) and PdCl2 (17.7 mg,
0.1 mmol) or PtCl2 (26.5 mg, 0.1 mmol) in 1,2-dichloroethane
was refluxed for 24 h under Ar. The resulting suspension was
filtered, and the filtrate was condensed under reduced pres-
sure. The residue was recrystallized from hexane-CHCl3 to
afford yellow crystals of 14a (63.3 mg, 90%) or 14b (53.7 mg,
68%). 14a : mp 229-231 °C; [R]20D -231.29 (c 1.31, CHCl3); IR
1
IR (KBr) 691, 1435, 1670, 3058, 3472 cm-1; H NMR (CDCl3)
δ 1.56-1.64 (m, 1H), 1.68 (br s, 1H), 2.33 (b t, J ) 8.1, 13.9
Hz, 1H), 2.89 (dd, J ) 4.2, 12.9 Hz, 1H), 4.66 (dd, J ) 7.6,
12.9 Hz, 1H), 5.03-5.10 (m, 1H), 5.51 (d, J ) 1.2 Hz, 1H),
6.81-6.88 (m, 2H), 6.97-7.01 (m, 2H), 7.07-7.10 (m, 3H), 7,-
12-7.20 (m, 2H), 7.23-7.41 (m, 13H), 7.47-7.51 (m, 1H),
7.63-7.68 (m, 1H), 7.70-7.73 (m, 1H); 13C NMR (CDCl3) δ
38.2, 62.0, 73.1, 77.1, 89.4, 94.2, 122.5, 123.1, 124.7, 125.8,
126.3, 126.6, 126.9, 127.1, 127.8, 128.0, 128.1, 128.4, 128.5,
130.5, 130.6, 131.7, 131.8, 132.0, 132.7, 133.1, 133.3, 133.6,
1
(KBr) 692, 755, 1584 cm-1; H NMR (CHCl3) δ 1.24 (m, 1H),
1.62 (m, 1H), 2.02 (m, 1H), 2.44 (m, 1H), 2.87 (m, 1H), 3.56
(m, 1H), 5.71 (s, 1H), 6.35 (t, J ) 7.6 Hz, 1H), 6.96 (t, J ) 8.8
Hz, 1H), 7.17-7.53 (m, 18H), 7.67-7.73 (m, 4H), 7.98 (dd, J
) 3.9, 7.6 Hz, 1H); 13C NMR (CDCl3) δ 25.6, 31.5, 43.5, 58.8,
74.2, 90.5, 92.4, 124.6, 126.5, 126.5, 127.5, 127.7, 128.2, 128.3,
128.4, 128.5, 128.6, 128.8, 128.9, 129.0, 130.0, 130.1, 131.5,
131.5, 131.8, 131.8, 132.0, 132.0, 133.7, 133.8, 135.0, 135.1,
136.9, 137.0, 141.6, 141.7. Anal. Calcd for C36H32Cl2NOPPd:
C, 61.51; H, 4.59; N, 1.99. Found: C, 61.32; H, 4.61; N, 1.71.
133.8, 134.1, 134.2, 135.5, 136.9, 137.1, 141.9; calcd for C36H32
-
NO2PPd requires m/z 647.1205, found m/z 647.1232 ([M-Cl2]+)
(FAB with p-nitrobenzyl alcohol added).
14b: mp 222 °C; [R]20 -243.60 (c 2.11, CHCl3); IR (KBr) 690,
D
747 cm-1; H NMR (CDCl3) δ 1.41-1.52 (m, 2H), 1.58 (br s,
1
Dich lor o[(1R,3S,6S,7S)-2-a za -3-(2-diph en ylph osp h in o)-
p h e n yl-4-oxa -5,5-d ip h e n ylt r icyclo[5.2.1.02,6]d e ca n e ]-
p a lla d iu m (18). A mixture of POZ 3 (118 mg, 0.12 mmol) and
PdCl2 (38 mg, 0.12 mmol) in CH2Cl2 (4 mL) was refluxed for
24 h under Ar. The resulting suspension was filtered, and the
filtrate was condensed under reduced pressure. The residue
was recrystallized from hexane-CHCl3 to afford yellow crys-
1H), 1.90 (m, 1H), 2.13 (m, 1H), 2.63 (m, 1H), 3.04 (m, 1H),
4.55 (m, 1H), 4.93 (s, 1H), 6.89-7.34 (m, 21H), 7.53-7.57 (m,
2H), 7.65 (m, 1H); 13C NMR (CDCl3) δ 27.6, 29.5, 57.4, 78.6,
88.8, 94.7, 124.6, 126.3, 126.7, 126.8, 127.6, 127.7, 128.2, 128.2,
128.4, 130.0, 130.1, 130.5, 130.5, 130.6, 131.4, 131.4, 131.8,
131.9, 132.7, 132.8, 133.3, 133.5, 133.7, 133.9, 135.1, 135.1,
136.4, 136.6, 141.8, 143.2; HRMS calcd for C36H32Cl2NOPPt
requires m/z 790.1246, found m/z 720.1741 [M - Cl2]+ (FAB
with p-nitrobenzyl alcohol added).
tals of 18 (153 mg, 98%): mp 224 °C; [R]20 -172.72 (c 1.43,
D
CHCl3); IR (KBr) 691, 748, 1586 cm-1; 1H NMR (CHCl3) δ 0.84
(d, J ) 10.6 Hz, 1H), 1.34 (m, 1H), 1.64 (m, 1H), 1.83 (d, J )
4.0 Hz, 1H), 2.08 (d, J ) 10.6 Hz, 1H), 2.31 (m, 1H), 3.27 (s,
1H), 3.35 (m, 1H), 6.07 (s, 1H), 6.10 (s, 1H), 7.12 (t, J ) 8.6
Hz, 1H), 7.20 (td, J ) 2.6, 7.9 Hz, 2H), 7.24-7.60 (m, 12H),
7.68 (t, J ) 7.7 Hz, 1H), 7.76 (dd, J ) 7.3, 12.1 Hz, 2H), 7.98
(dd, J ) 4.0, 7.7 Hz, 1H); 13C NMR (CDCl3) δ 25.8, 31.2, 36.4,
38.3, 66.5, 73.5, 91.0, 94.3, 125.1, 125.5, 126.4, 126.4, 127.4,
127.8, 128.0, 128.3, 128.4, 128.6, 128.7, 128.7, 128.7, 128.9,
130.1, 130.1, 131.4, 131.5, 131.6, 131.7, 131.9, 131.9, 133.2,
133.5, 135.6, 135.6, 136.2, 136.2, 141.2, 141.8; HRMS calcd
for C38H34Cl2NOPPd requires m/z 727.0790, found m/z 657.1339
[M - Cl2]+ (FAB with p-nitrobenzyl alcohol added).
Dich lor o[(2S,5S,7R)-1-a za -4-h yd r oxy-2-(d ip h en ylp h os-
p h in o)p h en yl-3-oxa -4,4-d ip h en ylb icyclo[3.3.0]oct a n e]-
palladiu m (16a) an d Dich lor o[(2S,5S,7S)-1-aza-4-h ydr oxy-
2-(d ip h e n ylp h osp h in o)p h e n yl-3-oxa -4,4-d ip h e n ylb i-
cyclo[3.3.0]oct a n e]p a lla d iu m (16b ). PdCl2 (15 mg, 0.085
mmol) and 2a or 2b (46 mg, 0.085 mmol) were suspended in
anhydrous toluene (5 mL) under Ar. The mixture was stirred
at 100 °C for 5 h and the resulting yellow solution was cooled
and filtered. The filtrate was concentrated under reduced
pressure to give a residue, which was chromatographed on
silica gel (1:1 CHCl3/EtOAc as eluent) to give the products 16a
or 16b (16a : 50 mg, 82%; 16b: 48 mg, 79%). 16a : yellow
Gen er a l P r oced u r e for En a n tioselective P d - a n d P t-
Ca ta lyzed Diels-Ald er Rea ction s. PdCl2-POZ complexes
12, 14a , 16a -c, 18 (1 equiv) or PtCl2-POZ complex 14b (1
equiv) and the appropriate silver salt (2 equiv) in CH2Cl2 (1
mL) were stirred at room temperature under Ar for 1 h. The
catalyst complex was then cooled to the temperature as shown
in Table 1 and acryloyl-20a (50 mg, 0.36 mmol), crotonyl-
20b (56 mg, 0.36 mmol), or fumaroyl-1,3-oxazolidin-2-one-
20c (77 mg, 0.36 mmol) in CH2Cl2 (1 mL) followed by
cyclopentadiene (150 mg, 1.80 mmol), cyclohexadiene (144 mg,
1.80 mmol), 2,3-dimethyl-1,3-butadiene (148 mg, 1.80 mmol),
or isoprene (148 mg, 1.80 mmol) were added, respectively. The
reaction mixture was stirred for the specified amount of time
and quenched with saturated NaHCO3 aq. The mixture was
extracted with CHCl3. The organic layer was washed with
brine and dried over MgSO4. Evaporation of the solvent under
a reduced pressure afforded a crude residue that was purified
by column chromatograpy on silica gel (elution with AcOEt:
prisms; mp 247 °C, [R]22 +114.45 (c 0.90, DMSO); IR (KBr)
D
687, 749, 1095, 1224, 1435 cm-1 1H NMR (CDCl3) δ 1.53-
;
1.64 (m, 2H), 2.00 (dd, J ) 8.6, 14.8 Hz, 1H), 2.97 (dd, J )
2.5, 12.2 Hz, 1H), 3.55 (d, J ) 11.9 Hz, 1H), 4.21 (br s, 1H),
5.38 (d, J ) 11.1 Hz, 1H), 5.93 (s, 1H), 6.61 (t, J ) 8.7 Hz,
1H), 7.04 (t, J ) 8.7 Hz, 1H), 7.19-7.56 (m, 17H), 7.66-7.73
(m, 4H), 7.95 (dd, J ) 4.2, 7.5 Hz, 1H); 13C NMR (CDCl3) δ
39.6, 66.4, 71.8, 73.3, 90.7, 92.6, 123.9, 124.8, 126.1, 126.5,
126.6, 127.2, 127.2, 127.5, 127.6, 128.3, 128.3, 128.4, 128.6,
128.7, 128.8, 128.8, 130.0, 131.5, 131.5, 131.7, 131.8, 132.0,
132.0, 133.4, 133.5, 133.7, 134.8, 135.0, 136.5, 140.9; calcd for
C
36H31NO2PPd requires m/z 646.11280, found m/z 646.0972
([M - HCl2]+) (FAB with p-nitrobenzyl alcohol added). 16b:
yellow prisms; mp 229 °C; [R]22 +110.69 (c 0.73, DMSO); IR
D
(KBr) 692, 748, 1097, 1435 cm-1 1H NMR (CDCl3) δ 1.29-
;
1.36 (m, 1H), 1.64 (br s, 1H), 2.15-2.24 (m, 1H), 2.33 (br s,
1H), 2.76 (t, J ) 10.0 Hz, 1H), 3.57 (dd, J ) 5.6, 10.2 Hz, 1H),
J . Org. Chem, Vol. 69, No. 21, 2004 7099

Nakano et al.
hexane ) 1:4) to give the cycloadducts 21-27. The ee values
of 21, 22, 24, 25, and 27 were determined by HPLC (21:
Chiralcel OD-H, 1.0 mL/min, hexane:2-propanol ) 90:10; 22:
Chiralcel OD, 1.0 mL/min, hexane:2-propanol ) 96:4; 24:
Chiralpak AD, 1.0 mL/min, hexane:2-propanol ) 95:5; 25:
Chiralpak AS, 1.0 mL/min, hexane:2-propanol ) 97:3; 27:
Chiralpak AD, 1.0 mL/min, hexane:2-propanol ) 90:10).4d,6 The
ee of 23 was determined by comparison of the known optical
rotation of iodolactonization product derived from 23.3c The
ee of 26 was determined by comparison of the known optical
rotation of product 26.4c
Diels-Ald er Rea ction of F u r a n w ith N-Acr yloylox-
a zolid in on e (20a ) Ca ta lyzed by Ca tion ic P d -P OZ (13c).
A suspension of PdCl2-POZ complex (20 mg, 0.071 mmol) and
AgSbF6 (25 mg, 0.177 mmmol) in CH2Cl2 (1 mL) was stirred
at room temperature for 1 h under Ar. The catalyst complex
was then cooled to the temperature shown in Table 3 and
acryloyl-20a (40 mg, 0.283 mmol) in CH2Cl2 (1 mL) followed
by furan (0.2 mL, 2.83 mmol) in CH2Cl2 (1 mL) were added.
The reaction mixture was stirred for the specified amount of
time and quenched with saturated NH4Cl. The mixture was
extracted with ether. The organic layer was washed with brine
and dried over MgSO4. Evaporation of the solvent under a
reduced pressure afforded a crude residue that was purified
by preparative TLC (AcOEt:hexane ) 2:1) to give the mixture
of DA adducts, endo-284c,14 and exo-28. The endo/exo rate and
enantioselectivity were determined by HPLC (Chiralcel OD-
H, 0.65 mL/min, hexane:AcOEt ) 70:30, tR[2S-endo-28] ) 15.1
min, tR[2R-endo-28] ) 17.6 min, tR[2S or 2R-exo-28] ) 20.0
min, tR[2S or 2R-exo-28] ) 28.9 min. The mixture of DA
adducts (45 mg of endo-28/exo-28 ) 28:72) was allowed to stand
at room temperature for 48 h, and was purified by preparative
TLC (AcOEt:hexane ) 2:1) to give exo-28 (22 mg, 68%). exo-
28: colorless oil; [R]20 -85.23 (c 1.50, CHCl3); IR (film) 759,
D
1216, 1388, 1700, 1779, 3020 cm-1; H NMR (CDCl3) δ 1.59
1
(1H, dd, J ) 8.3, 11.5 Hz), 2.30 (1H, dt, J ) 4.3, 11.5 Hz), 3.41
(1H, dd, J ) 4.0, 8.3 Hz), 4.02-4.13 (2H, m), 4.14-4.51 (2H,
m), 5.09 (1H, d, J ) 4.6 Hz), 5.13 (1H, s), 6.39-6.48 (2H, m);
13C NMR (CDCl3) δ 28.8, 42.9, 43.6, 62.3, 78.3, 81.3, 135.1,
137.3, 153.8, 173.1; MS m/z 209 (M+); HRMS calcd for C10H11
-
NO4 (M+) 209.0688, found 209.0695.
Diels-Ald er Rea ction of Cyclop en ta d ien e w ith Me-
th yla cr yla te (29) Ca ta lyzed by Ca tion ic P d -P OZ (13c).
A suspension of PdCl2-POZ complex (80 mg, 0.11 mmol) and
AgSbF6 (0.78 mg, 0.177 mmmol) in CH2Cl2 (1 mL) was stirred
at room temperature for 1 h under Ar. Methylacrylate (29)
(100 mg, 1.16 mmol) in CH2Cl2 (1 mL) followed by cyclopen-
tadiene (380 mL, 5.8 mmol) in CH2Cl2 (1 mL) were added at 0
°C and the solution was stirred for 72 h. The reaction was
chromatographed on silica gel (8:1 hexane/EtOAc as eluent)
to give 30 (60 mg, 25%). The ee and absolute configration of
30 were determined by comparison of the known optical
rotation of 30.4c
Su p p or tin g In for m a tion Ava ila ble: General methods,
1H and 13C NMR spectra for compounds 2a , 2b, 7, 9, 11, 12,
14a , 14b, 16a , 16b, 16c and 18, and X-ray data for 12, 14a ,
14b, 16b, 16c and 18 in CIF format and ORTEP drawings.
This material is available free of charge via the Internet at
http://pubs.acs.org.
J O049375J
7100 J . Org. Chem., Vol. 69, No. 21, 2004