Enantioselective Diels-Alder Reaction Using Chiral Mg Complexes Derived from Chiral 2-2-Alkyl- Or 2-[2-[(Arylsulfonyl)amino]phenyl]-4-phenyl-1,3-oxazoline

Article abstract of DOI:10.1021/jo9621276

Magnesium complexes derived from (R)-2-[2-[(alkyl- or (R)-2-[2-[(arylsulfonyl)amino]phenyl]-4- phenyl-1,3-oxazolines and methylmagnesium iodide were found to be efficient Lewis acid catalysts for the Diels-Alder reaction of 3-alkenoyl-1,3-oxazolidin-2-one with cyclopentadiene. Chiral ligands were easily prepared from readily available D-phenylglycinol in good yields. The reaction of 3-acryloyl-1,3-oxazolidin-2-one with cyclopentadiene catalyzed by a stoichiometric amount of the Lewis acid gave exclusively the endo-cycloaddition product in up to 92% ee. The sulfonamide group on the chiral ligand strongly influenced the enantiofacial selectivity: the use of a toluene-, benzene-, 1- or 2-naphthalene-, or methanesulfonamide group in the chiral ligand gave the endo-(2R)- cycloaddition product, while a trifluoromethanesulfonamide group predominantly gave its enantiomer, the endo-(2S)-cycloaddition product, in 65% ee. The scope and limitations of the catalytic effect of chiral Mg(II) complexes on the enantioselectivity of the Diels-Alder reaction were investigated. The reaction mechanism of the Mg(II)-catalyzed reaction is also discussed on the basis of the experimental results.

Full text of DOI:10.1021/jo9621276

J . Org. Chem. 1997, 62, 7937-7941
7937
En a n tioselective Diels-Ald er Rea ction Usin g Ch ir a l Mg
Com p lexes Der ived fr om Ch ir a l 2-[2-[(Alk yl- or
2
-[2-[(Ar ylsu lfon yl)a m in o]p h en yl]-4-p h en yl-1,3-oxa zolin e
Tsuyoshi Ichiyanagi, Makoto Shimizu, and Tamotsu Fujisawa*
Department of Chemistry for Materials, Mie University, Tsu, Mie 514, J apan
Received November 13, 1996X
Magnesium complexes derived from (R)-2-[2-[(alkyl- or (R)-2-[2-[(arylsulfonyl)amino]phenyl]-4-
phenyl-1,3-oxazolines and methylmagnesium iodide were found to be efficient Lewis acid catalysts
for the Diels-Alder reaction of 3-alkenoyl-1,3-oxazolidin-2-one with cyclopentadiene. Chiral ligands
were easily prepared from readily available D-phenylglycinol in good yields. The reaction of
3
-acryloyl-1,3-oxazolidin-2-one with cyclopentadiene catalyzed by a stoichiometric amount of the
Lewis acid gave exclusively the endo-cycloaddition product in up to 92% ee. The sulfonamide group
on the chiral ligand strongly influenced the enantiofacial selectivity: the use of a toluene-, benzene-,
1
- or 2-naphthalene-, or methanesulfonamide group in the chiral ligand gave the endo-(2R)-
cycloaddition product, while a trifluoromethanesulfonamide group predominantly gave its enan-
tiomer, the endo-(2S)-cycloaddition product, in 65% ee. The scope and limitations of the catalytic
effect of chiral Mg(II) complexes on the enantioselectivity of the Diels-Alder reaction were
investigated. The reaction mechanism of the Mg(II)-catalyzed reaction is also discussed on the
basis of the experimental results.
In tr od u ction
enantiomers of [4 + 2] cycloadducts.9 Since one enanti-
omer is prepared from one chiral source and the other
enantiomer is synthesized using another chiral source,
both enantiomers are not always available, e.g., amino
acids, sugars, from most chiral sources. On the other
hand, although Grignard reagents are readily available
and the asymmetric addition to ketones and aldehydes
has been reported by a few groups,10 only one group has
demonstrated that a magnesium complex prepared from
a Grignard reagent is an effective Lewis acid for asym-
The investigation of effective chiral Lewis acid cata-
1
lysts has recently attracted considerable interest. Among
2
3
4
5
6
them, B, Al, Ti, Sn, and lanthanide complexes have
been shown to be effective Lewis acid catalysts for
asymmetric carbon-carbon bond formation. The Diels-
Alder reaction has long been recognized as one of the
most important methods for preparing cyclohexene de-
rivatives, which are versatile chiral building blocks for
the synthesis of numerous natural products because both
the absolute and relative stereochemistry at all four
newly created asymmetric centers can potentially be
controlled.7 The control of enantioselectivity for chiral
Lewis acid-catalyzed Diels-Alder reactions has been
demonstrated by several groups.8 However, only a few
reports are available regarding the preparation of both
1
1
metric carbon-carbon bond-forming reactions.
Re-
cently, we reported that the Mg complex 5a prepared
from chiral 2-[2-[(tolylsulfonyl)amino]phenyl]-4-phenyl-
1
,3-oxazoline (4a ) and methylmagnesium iodide was an
effective Lewis acid catalyst for the enantioselective
Diels-Alder reaction of 3-alkenoyl-1,3-oxazolidin-2-one
with cyclopentadiene.12 In the present work, the scope
and limitations of this reaction and the catalytic effect
of Mg complexes 5a -g on the enantioselectivity of the
Diels-Alder reaction were investigated, and enantiofacial
discrimination was found to be greatly influenced by the
substituent on the sulfonamide group. The details of the
*
To whom correspondence should be addressed. Phone: +81-59-
2
31-9413. Fax: +81-59-231-9471. E-mail: fujisawa@chem.mie-u.ac.jp.
X
Abstract published in Advance ACS Abstracts, October 15, 1997.
(
1) (a) Kagan, H. B.; Riant, O. Chem. Rev. (Washington, D.C.) 1992,
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9
M.; Narisawa, S.; Nakai, T. Synlett 1992, 255. (d) Ishihara, K.;
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4) (a) Nitta, H.; Yu, D.; Kudo, M.; Mori, A.; Inoue, S. J . Am. Chem.
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A.; Lectka, T.; Miller, S. J . Tetrahedron Lett. 1993, 34, 7027. (d) Corey,
E. J .; Imai, N.; Zang, H.-Y. J . Am. Chem. Soc. 1991, 113, 728. (e) Corey,
E. J .; Ishihara, K. Tetrahedron Lett. 1992 33, 6807. (f) Khiar, N.;
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K.; Motoyama, Y.; Terada, M. J . Am. Chem. Soc. 1994, 116, 2812. (h)
Ishihara, K.; Yamamoto, H. J . Am. Chem. Soc. 1994, 116, 1561. (i)
Kobayashi, S.; Araki, M.; Hachiya, I. J . Org. Chem. 1994, 59, 3758. (j)
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Soc. 1989, 111, 5493. (k) Narasaka, K.; Inoue, M.; Okada, N. Chem.
Lett. 1986, 1109. (l) Ghosh, A. K.; Mathivanan, P.; Cappiello, J .
Tetrahedron Lett. 1996, 37, 3815. (m) Ordo n˜ ez, M.; Guerrero-de la
Rosa, V.; Labastida, V.; Llera, J . M. Tetrahedron: Asymmetry 1996,
7, 2675.
1
(
(
1
3
(
Soc. 1992, 114, 7969. (b) Hayashi, M.; Miyamoto, Y.; Inoue, T.; Oguni,
N. J . Org. Chem. 1993, 58, 1515.
(
5) Kobayashi, S.; Mukaiyama, T. Chem. Lett. 1989, 297, and
(9) (a) Kobayashi, S.; Ishitani, H. J . Am. Chem. Soc. 1994, 116, 4083.
(b) Desimoni G.; Faita, G.; Righetti, P. P. Tetrahedron Lett. 1996, 37,
3027. (c) Desimoni G.; Faita, G.; Invernizzi, A. G.; Righetti, P. P.
Tetrahedron 1997, 53, 7671.
references therein.
(
6) Kobayashi, S. Synlett 1994, 689, and references therein.
(7) (a) Vanderwalle, M.; Van der Eycken, J .; Oppolzer, W.; Vullioud,
C. Tetrahedron 1986, 42, 4035. (b) Arai, Y.; Hayashi, Y.; Yamamoto,
M.; Takayama, H.; Koizumi, T. Chem. Lett., 1987 185. (c) Oppolzer,
W.; Dupuis, D.; Poli, G.; Raynham, T. M.; Bernardinelli, G. Tetrahedron
Lett. 1988, 29, 5885. (d) Takayama, H.; Hayashi, K.; Koizumi, T.
Tetrahedron Lett. 1986, 27, 5509.
(10) (a) Nakajima, M.; Tomioka, K.; Koga, K. Tetrahedron 1993, 49,
9751. (b) Weber, B.; Seebach, D. Tetrahedron 1994, 50, 6117.
(11) Corey, E. J .; Wang, Z. Tetrahedron Lett. 1993, 34, 4001.
(12) Fujisawa, T.; Ichiyanagi, T.; Shimizu, M. Tetrahedron Lett.
1995, 36, 5031.
S0022-3263(96)02127-5 CCC: $14.00 © 1997 American Chemical Society

7
938 J . Org. Chem., Vol. 62, No. 23, 1997
Ichiyanagi et al.
1
3
Sch em e 1
Ta ble 1.
C Ch em ica l Sh ifts of Ch ir a l Liga n d 4a a n d
Ma gn esiu m Com p lex 5a a
δ, ppm
4
a
5a
C-CH3
C-5
C-4
21.51
69.59
73.50
21.12
68.43
73.69
21.46
68.70
74.71
a
At 67.5 MHz in CDCl3 at room temperature.
Sch em e 2
asymmetric Diels-Alder reaction promoted by a chiral
magnesium catalyst are discussed.
Resu lts a n d Discu ssion
Chiral 2-[2-[(aryl- or [2-[(alkylsulfonyl)amino]phenyl]-
4
-phenyl-1,3-oxazolines were easily prepared from com-
mercially available D-phenylglycinol (1) in a two-step
procedure (Scheme 1). In the presence of zinc chloride,
the reaction of D-phenylglycinol (1) and 2-aminobenzoni-
trile (2) in chlorobenzene gave oxazoline 3 in 63% yield.13
The amino group was then sulfonylated by treatment
with aryl- or alkylsulfonyl chloride or trifluoromethane-
sulfonic anhydride in the presence of triethylamine and
DMAP in dichloromethane to give the corresponding
sulfonamides 4a -g in moderate to good yields. Com-
pounds 4a ,c-f could be purified by recrystallization from
ethyl acetate and hexane.
Mg(II)-containing complexes were readily prepared by
the reaction of methylmagnesium iodide with chiral
ligands in dry dichloromethane at 0 °C for 5 min under
an argon atmosphere. NMR investigations of the com-
plexes were performed under the following conditions.
To a solution of the chiral ligand 4a in dichloromethane
was added a solution of MeMgI in ether at 0 °C (Scheme
F igu r e 1.
The 13C chemical shifts of chiral ligand 4a and magne-
sium complex 5a are shown in Table 1. The ratio of the
peak intensities of the two diastereotopic carbons at CH
of the tolyl group was 7:3. This ratio did not agree well
with that based on the calculated difference of 0.904 kcal/
mol, which implies a roughly 8:2 mixture of the two
complexes. These findings strongly suggest the presence
of six-membered ring chelation between the chiral ligand
and magnesium, which reflects the observed ratio of the
conformers. There seem to be two stable conformations
3
3
at room temperature in CDCl due to hindered rotation
1
5
of the sulfonyl group. Using MM2 calculations, two
stable conformations A and B of magnesium complex
were found, as shown in Figure 1. Conformation A was
more stable (0.904 kcal/mol) than conformation B. There-
2
). After stirring for 15 min, the solvent was removed
under reduced pressure (0.8 mmHg) at rt for 30 min,
CDCl
was then added to the resulting white powder, and
the whole mixture was transferred to an NMR tube.
2
fore, this catalyst probably behaves like a C -symmetric
ligand and is responsible for the highly asymmetric
induction observed in the Diels-Alder reactions (vide
infra).
3
1
13
3-(2′-Propenoyl)-1,3-oxazolidin-2-one (6),16 which is
highly reactive as a dienophile, was chosen for the
cycloaddition reaction with cyclopentadiene 7 (Scheme
3). In all cases, the reaction was carried out at -78 °C
in the presence of stoichiometric amounts of complex
without removal of diethyl ether derived from Grignard
Peaks of diethyl ether were detected by H and C NMR
despite repeated evaporation under highly reduced pres-
sure, which suggests that coordination or interaction of
ether with the magnesium complex is likely.14 The signal
of the acidic proton (δ 12.31 ppm) of the sulfonamide
1
group disappeared in the H NMR spectrum, while two
different sets of diastereotopic carbons were seen in the
1
3
(14) In the 13C NMR spectrum, an upfield shift of the diethyl ether
C NMR spectrum for complex 5a prepared from 4a and
methylmagnesium iodide in CDCl at room temperature.
Mg complex 5a (δ 65.8, CH
the original peaks (δ 67.4, CH
15) These conformations were supported by MM-2 calculations
2
CH
3
; 14.9, CH
2
CH
3
) was observed from
3
2
CH
3
; 17.1, CH
2
CH
3
).
(
(
13) (a) Dawson, G. J .; Frost, C. G.; Williams, J . M. J . Tetrahedron
perfomed on the CAChe system.
Lett. 1993, 34, 3149. (b) McKennon, M. J .; Meyers, A. I.; Drauz, K.;
Schwarm, M. J . Org. Chem. 1993, 58, 3568. (c) Allen, J . V.; Dawson,
G. J .; Frost, C. G.; Williams, J . M. J .; Coote, S. J . Tetrahedron 1994,
(16) (a) Evans, D. A.; Chapman, K. T.; Bisaha, J . J . Am. Chem. Soc.
1984, 106, 4261. (b) Evans, D. A.; Chapman, K. T.; Bisaha, J . J . Am.
Chem. Soc. 1988, 110, 1238. (c) Evans, D. A.; Bartroli, J .; Shih, T. L.
J . Am. Chem. Soc. 1981, 103, 2127.
5
0, 799.

Diels-Alder Reaction Using Chiral Mg Complexes
J . Org. Chem., Vol. 62, No. 23, 1997 7939
Sch em e 3
Ta ble 3. Diels-Ald er Rea ction betw een
-((E)-2′-Bu ten oyl)-1,3-oxa zolin -2-on e (9) a n d
3
Cyclop en ta d ien e Ca ta lyzed by 5a To P r ovid e
Cycloa d d u ct 10a
yield
%
c
b
23
entry additive
1
amine (equiv)
solvent (%) ee [R]
D
(c, CCl
4
)
CH
CH
CH
CH
CH
CH
CH
CH
2
2
2
2
2
2
2
2
2
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
2
2
2
2
2
2
2
2
2
10 11 +20.0 (0.10)
2
3
4
5
6
7
8
9
AgSbF
NaBPh
6
68 57 +118.5 (0.60)
61 84 +175.0 (0.54)
62 72 +152.7 (0.55)
79 89 +183.9 (0.69)
82 88 +181.9 (0.72)
70 70 +145.2 (0.62)
61 72 +147.3 (0.54)
56 70 +146.6 (0.50)
4
I
2
I
2
2
2
2
2
3
Et N (0.1)
DMAP (0.1)
pyridine (0.1)
2
iPr NEt (0.1)
I
I
I
I
N-ethylpiperidine CH
(0.1)
1
1
1
13
1
15
16
17
0
1
2
I
2
DMAP (0.05)
DMAP (0.2)
DMAP (0.3)
DMAP (0.4)
DMAP (0.1)
DMAP (0.1)
DMAP (0.1)
DMAP (0.1)
CH
CH
CH
CH
Et O
2
THF
2
2
2
2
Cl
Cl
Cl
Cl
2
2
2
2
77 82 +169.6 (0.68)
63 91 +188.5 (0.56)
73 89 +184.0 (0.62)
62 88 +181.9 (0.51)
50 25 +52.0 (0.44)
23 10 +21.0 (0.20)
50 43 +88.3 (0.44)
Ta ble 2. Effect of a Su bstitu en t on th e Ch ir a l Liga n d in
I
I
I
I
I2
I
I
2
2
2
2
th e Diels-Ald er Rea ction betw een 6 a n d 7a
yield (%)b
entry
additive
ligand
% ee
config
4
1
2
3
4
5
6
7
8
9
none
NaBPh4
AgSbF6
4a
4a
4a
4a
4a
4a
4b
4c
4d
4e
4f
60
70
80
69
81
7
17
60
92
91
0
89
29
14
86
62
65
R
R
R
R
2
CHCl
3
2
toluene 68 72 +149.3 (0.60)
I2
I2
I2
I2
I2
I2
I2
I2
I2
a
c
All reactions were carried out with 0.2 mmol of 9, 3.0 equiv of
R
d
7, 1.0 equiv of additive, 1.0 equiv of 4a , and 1.0 equiv of MeMgI
64
at 0 °C for 16-20 h. b Isolated yield. c Determined by comparison
82
71
55
81
70
44
R
S
R
R
R
S
1
8
of the optical rotation with that reported in the literature.
Sch em e 4
1
1
1
0
1
2
4g
a
The reaction was carried out with 0.2 mmol of 6, 3.0 equiv of
7
, 1.0 equiv of additive, 1.0 equiv of 4a -g, and 1.0 equiv of MeMgI
b
c
at -78 °C for 2-3 h. Isolated yield. With the use of 50 mol %
of the complex. Carried out at -93 °C.
d
reagent under an argon atmosphere. The results are
1
7
The enantioselectivity of the Diels-Alder adduct was
influenced by the substituent on the sulfonamide group
of the chiral ligand. Except for the cases using sulfona-
mide 4c and 4g (entries 8 and 12), the reaction gave the
summarized in Table 2. The endo-adduct was obtained
exclusively under these conditions. The enantioselectiv-
ity was determined by HPLC analysis using a chiral
column (Chiralcel OJ ), and the absolute configuration of
2
R-product exclusively. The benzenesulfonamide 4b and
the endo-adduct was determined by comparison of the
optical rotation with that reported in the literature.18 To
the 2-naphthalenesulfonamide 4e also provided high
enantioselectivity (89% ee and 86% ee, entries 7 and 10),
and the methanesulfonamide 4f gave a cycloadduct with
good yield and selectivity (70% yield and 62% ee, entry
obtain high enantioselectivity and high yield, strong
conformational rigidity of the dienophile and an increase
in the Lewis acidity of the magnesium complex were
necessary. Therefore, additives were used to try to
1
1), whereas the results with the 1-naphthyl derivative
4
d were disappointing (14% ee, entry 9). Surprisingly,
increase the Lewis acidity of the magnesium cationic
complex.19 Although the use of 1 equiv of catalyst 5a
reversal of the enantioselectivity was observed when
catalysts 4c and 4g were used, and the 2S-product was
predominantly obtained (29% ee and 65% ee, entries 8
and 12).
gave cycloaddition product 8 in 60% yield with 7% ee
(
entry 1), the use of sodium tetraphenyl borate as an
additive slightly increased the enantioselectivity (entry
), and silver hexafluoroantimonate improved the selec-
As shown in Table 3, the reaction of 3-((E)-2′-butenoyl)-
2
1
,3-oxazolidin-2-one (9)16 with cyclopentadiene 7 was
tivity up to 60% ee (entry 3). The highest enantioselec-
tivity of 92% ee was obtained using iodine (entry 4).
These additives may act by dissociating the iodine anion
examined to increase the utility of the chiral Lewis acid
(Scheme 4). The endo-adduct was obtained exclusively,
and no exo-isomer could be detected. The enantioselec-
tivity and absolute configuration of the endo-adduct were
determined by comparison of the optical rotation with
that reported in the literature.20 The presence of a
tertiary amine was crucial for good chiral induction in
this reaction, in which DMAP and triethylamine were
effective additives to give the cycloadduct with high
enantiofacial selectivity (88% ee and 89% ee, entries 5
and 6). The enantiomeric purity of the products was
affected by the amount of the amine. The use of 20 mol
% of the amine gave the cycloadduct in up to 91% ee,
while no improvement in enantioselectivity was observed
with the use of greater amounts of DMAP to 30 and 40
mol % (entries 12 and 13). In the present system, the
as an iodinate, as reported by Corey.8
d,e
The use of 50
mol % of the catalyst was also effective to give the product
in high yield and enantioselectivity (entry 5), while
reducing the amount of the complex to 20 or 10 mol %
decreased the enantioselectivity of the product (82% yield,
8
0% ee, and 95% yield, 51% ee). The reaction tempera-
ture was important in this magnesium-catalyzed Diels-
Alder reaction, and the best result for the reaction of 6
with 7 was obtained at -78 °C. Interestingly, at -93
°
C, a racemic cycloaddition product was obtained when
magnesium complex 5a was used (entry 6).
(
(
(
2 2 2
17) The solvent proportion was CH Cl -Et O ) 30:1.
18) Pikul, S.; Corey, E. J . Org. Synth. 1992, 71, 30.
19) Recently Corey et al. reported that a cationic oxazaborinane
catalyst was an effective catalyst for enantioselective Diels-Alder
reactions: Hayashi, Y.; Rohde, J . J .; Corey, E. J . J . Am. Chem. Soc.
(20) Narasaka, K.; Iwasawa, N.; Inoue, M.; Yamada, T.; Nakashima,
1
996, 118, 5502.
M.; Sugimori, J . J . Am. Chem. Soc. 1989, 111, 5340.

7
940 J . Org. Chem., Vol. 62, No. 23, 1997
Ichiyanagi et al.
coordination of the oxygen atom of the sulfonyl group at
the chiral ligand.22 In the case of the Mg complex derived
from ligand 4g, coordination of the fluorine or oxygen
presumably occupies one of the equatorial positions, and
the dienophile coordinates with the oxygen at the equato-
rial and axial positions, as depicted in B (Figure 2). On
the basis of this molecular arrangement, the endo-Re-
attack of the dienes appears to be favored, providing the
2
S-configuration. The use of catalyst 5c gave the cy-
cloadduct with low S-enantioselectivity due to shielding
of the coordination site of the magnesium cation by the
methyl group of the arylsulfonyl group, and the dieno-
phile could not bind to the metal by its two carbonyl
groups. Several conformations of the dienophile would
be involved under these circumstances. 3-((E)-2′-Cin-
namoyl)-1,3-oxazolidin-2-one, which was used as a di-
enophile in the present reaction, also gave a cycloaddition
product in moderate yield and with high enantioselec-
tivity (51% yield, 88% ee) at room temperature.
A new chiral ligand was developed for the Diels-Alder
reaction of cyclopentadiene 7 with 3-alkenoyl-1,3-oxazo-
lidin-2-ones 6 and 9. The chiral ligand was prepared
from optically active amino acid by a straightforward
procedure. The magnesium Lewis acid was easily pre-
pared from readily available Grignard reagent with the
new chiral ligand, and promoted the cycloaddition reac-
tion between cyclopentadiene 7 and dienophile 6 or 9 to
give the endo-isomer as a sole product. The addition of
iodine, sodium tetraphenylborate, or silver hexafluoro-
antimonate was crucial to dissociate the iodinate anion
from the magnesium cation to provide high enantiose-
lectivity during the Diels-Alder process. The reaction
of acryloyl derivative 6 and cyclopentadiene 7 also gave
cycloaddition products with good enantioselectivity.
Changing the sulfonamide moiety of the chiral ligand
resulted in a reversal of the observed enantioselectivity.
The addition of a catalytic amount of tertiary amine,
DMAP, or triethylamine was necessary for the reaction
of crotonoyl derivative 9 and cyclopentadiene 7 to proceed
at an appreciable rate due in part to its ability to solvate
iodine.
F igu r e 2.
solubility of iodine was very low, and upon addition of
these amines, the reaction mixture became homogeneous.
Therefore, amines do not seem to coordinate or interact
with the catalyst, but rather merely improve its solubil-
ity. The use of nonpolar solvents was suitable for this
reaction, and among them dichloromethane was effective,
whereas solvents with an oxygen atom which could
potentially interact with magnesium led to the formation
of cycloaddition product with poor yields and lower
enantioselectivities due to the low solubility of the chiral
magnesium complex.
The high degree of enantioselection of the Diels-Alder
reaction may be explained as follows: a bis(oxazoline)-
magnesium complex with the S-configuration gives Di-
els-Alder product 8 with predominantly an R-configu-
ration, as previously reported by Corey et al.8e On the
other hand, in the presence of magnesium perchlorate
and 2 equiv of water, a bis(oxazoline) with an R-
configuration predominantly produces the cycloadduct 8
with R-stereochemistry. This stereochemical outcome
was explained by Desimoni et al. in terms of a catalysis
via an octahedral coordination, which is in contrast to
the opposite stereochemical results obtained by Corey
Exp er im en ta l Section
Infrared spectra were determined on a J ASCO IR-810
1
13
spectrometer. H and C NMR spectra were recorded with
J EOL R-500 and J NM EX-270 spectrometers using tetra-
methylsilane or trichlorofluoromethane as an internal stan-
dard. High performance liquid chromatography (HPLC) was
carried out using a Hitachi L-4000 detector, Hitachi L-6000
pump, and a Daicel Chiralcel OJ column. Optical rotations
were measured with a Union PM-101 polarimeter. Exact mass
spectra were taken on a J EOL J MS-DX303-HF spectrometer.
All melting points are uncorrected. Tetrahydrofuran (THF)
and diethyl ether were distilled from sodium benzophenone
ketyl immediately before use. Dichloromethane was pre-
and Desimoni in the absence of water, which involved a
tetrahedral coordination.9
b,c
In the present case, mag-
nesium complexes 5a -g probably form an octahedral
complex with chiral ligands 4a -g, bidentate dienophiles
and 9, and diethyl ether.17 In fact, H and C NMR
1
13
6
spectra showed the coordination of Et
metal of chiral magnesium complexes. Thus, the present
2
O to the center
treated with diphosphorus pentoxide, distilled from CaH
stored over 4A molecular sieves. Pyridine was pretreated with
potassium hydroxide, distilled from CaH , and stored over 4A
2
, and
magnesium complexes 5a -g probably assume an octa-
2
hedral arrangement.9
b,c,14
molecular sieves. Purification of products was performed by
column chromatography on silica gel Wakogel C-300 or Merck
Silica Gel-60, and/or preparative TLC on silica gel Merck Kisel
Gel PF254 or Wakogel B-5F. The starting materials 3-((E)-
On the other hand, the dieno-
phile assumes an s-cis conformation (A, Figure 2), and
the endo-Si-attack of cyclopentadiene from the sterically
less-hindered side appears to be favored, leading to the
observed 2R-configuration. The reversal of enantiose-
lectivity using the magnesium complex derived from
trifluoromethyl ligand 4g may be explained as follows:
16
2
′-butenoyl)-1,3-oxazolidin-2-one and 3-(2′-propenoyl)-1,3-
1
6,17
oxazolidin-2-one
were synthesized according to the litera-
ture procedures. Methylmagnesium iodide in diethyl ether
2
3
was prepared according to a typical procedure.
Iodine,
the trifluoromethyl group could coordinate or interact
weakly with the magnesium cation.21 Furthermore, the
(21) Ooi, T.; Kagoshima, N.; Maruoka, K. J . Am. Chem. Soc. 1997,
19, 5754.
1
use of a (trifluoromethyl)sulfonyl group increased the
Lewis acidity of the center metal, which may have led to
(22) Corey, E. J .; Sarshar, S.; Bordner, J . J . Am. Chem. Soc. 1992,
114, 7938.

Diels-Alder Reaction Using Chiral Mg Complexes
-(N,N-dimethylamino)pyridine and triphenylphosphine were
used as received from Wako Pure Chemical Industrial Ltd.
All reactions were carried out under an argon atmosphere.
Reaction flasks were sealed with a red rubber septum, unless
otherwise mentioned. Anhydrous solvents and reaction mix-
tures were transferred by an oven-dried syringe or cannula.
J . Org. Chem., Vol. 62, No. 23, 1997 7941
4
MeMgI in ether (0.98 M, 0.2 mL)23 at 0 °C. After stirring for
30 min, iodine (0.2 mmol) and additives were added to the
resulting solution in one portion at the same temperature
(without removal of diethyl ether!). The reaction mixture was
cooled to -78 °C. After 5 min a dichloromethane solution (2
mL) of 3-(2′-propenoyl)-1,3-oxazolidin-2-one (0.2 mmol) was
added and the mixture was stirred for 30 min. A solution of
cyclopentadiene (0.6 mmol) in dichloromethane (2 mL) was
added to the mixture over 40 min and stirred for 2-3 h. A
solution of triphenylphosphine (0.4 mmol) in dichloromethane
(2 mL) was added to remove iodine and to quench the reaction
at the same temperature. The color of reaction mixture
changed from brown to yellow, and aqueous sodium thiosulfate
was added. The organic materials were extracted with ethyl
acetate, and the combined extracts were dried over anhydrous
sodium sulfate. After evaporation of the solvent, the crude
product was purified on thin layer silica gel chromatography
(
4R)-2-(2-Am in op h en yl)-4-p h en yloxa zolin e (3). To a
mixture of D-(-)-phenylglycinol (8.1 g, 59 mmol) and 2-ami-
nobenzonitrile (7.0 g, 59 mmol) in dichloromethane (140 mL)
was added zinc chloride (8.0 g, 59 mmol) at room temperature,
and the reaction mixture was heated at 140 °C for 2 days. The
reaction mixture was cooled to room temperature and was
quenched with 50 mL of saturated aqueous ammonium
chloride. The resultant mixture was extracted 3 times with
5
0 mL of ethyl acetate. The combined organic layers were
dried over anhydrous sodium sulfate, filtered, and concen-
trated. The crude product was purified by flash column
chromatography on silica gel using 20% ethyl acetate-hexane
as eluent to afford 8.9 g (63%) of the title compound as a
(hexane-ethyl acetate ) 2:1, R
3-[((1′R,2′R,4′S)-bicyclo[2.2.1]hept-5′-en-2′-yl)carbonyl]-1,3-ox-
azolin-2-one (8). H NMR (270 MHz, CDCl ) δ 1.39-1.50 (m,
f
) 0.3) to give the pure
2
3
1
colorless solid. [R]
D
) -189.5 (c 1.01, CHCl
3
); mp 71 °C; R
f
3
1
3H), 1.95 (ddd, J ) 12.6, 9.3, 3.7 Hz, 1H), 2.92-2.93 (m, 1H),
3.29-3.30 (m, 1H), 3.90-4.00 (m, 3H), 4.35-4.41 (m, 2H), 5.87
(dd, J ) 5.5, 2.8 Hz, 1H), 6.24 (dd, J ) 5.5, 3.1 Hz, 1H); IR
)
0.5 (20% ethyl acetate-hexane); H NMR (270 MHz, CDCl
δ 4.13 (t, J ) 8.25 Hz, 1H), 4.69 (dd, J ) 8.25, 1.65 Hz, 1H),
.45 (dd, J ) 8.25, 1.65 Hz, 1H), 6.15 (br s, 2H), 6.66-6.73
m, 2H), 7.21-7.22 (m, 6H), 7.74-7.78 (m, 1H); C NMR (125
MHz, CDCl ) δ 70.17, 73.04, 108.64, 115.67, 115.97, 126.58,
27.51, 128.67, 129.75, 132.25, 142.73, 148.76, 165.00; IR
neat) 3295, 1628, 1490 cm ; MS (EI) m/z (relative intensity)
38 (100), 207 (36), 118 (47), calcd for C15 O 238.1106;
found 238.1111. Anal. Calcd for C15 O: C, 75.61; H, 5.92;
3
)
5
(
1
3
(CHCl ) 1775, 1696 cm-1. The enantioselectivity was deter-
3
mined by HPLC analysis using a chiral column (Chiralcel OJ ,
hexane-i-PrOH ) 10:1), and the absolute configuration of the
endo-adduct was determined by comparison of the optical
3
1
(
2
-
1
H
14
N
2
rotation value with that reported in the literature ([R]
D
-152.0
H
14
N
2
(c 1.5, CHCl
3
)) [89% ee (1′S,2′S,4′R)].18
N, 11.76. Found: C, 75.80; H, 5.83; N, 11.75.
Gen er a l P r ot ocol for t h e Su lfon yla t ion of (4R)-2-(2-
Am in op h en yl)-4-p h en yloxa zolin e. To a solution of (4R)-
Gen er a l P r oced u r e for th e Asym m etr ic Diels-Ald er
R ea ct ion b et w een 9 a n d 7 Usin g a St oich iom et r ic
Am ou n t of th e Mg(II) Com p lex. To a solution of 1.0 equiv
of a chiral ligand in dichloromethane was added a solution of
MeMgI in ether (0.98 M, 0.2 mL) at 0 °C. After stirring for
2
(
0
-(2-aminophenyl)-4-phenyloxazoline in dry dichloromethane
∼0.15 M) at 0 °C were added 5 equiv of triethylamine and
.01 equiv of 4-(N,N-dimethylamino)pyridine, and after 5 min
3
0 min, iodine (0.2 mmol) and additives were added to the
resulting solution in one portion at the same temperature. A
dichloromethane solution (2 mL) of 3-((E)-2′-butenoyl)-1,3-
oxazolidin-2-one (0.2 mmol) was added to the reaction mixture
followed by cyclopentadiene (0.6 mmol), and the mixture was
stirred overnight at 0 °C. A solution of triphenylphosphine
the appropriate sulfonyl chloride (1.2 equiv) was added. The
mixture was stirred for 24-48 h at room temperature. The
reaction was quenched with excess saturated aqueous am-
monium chloride and extracted with ethyl acetate. The
organic layer was dried over anhydrous sodium sulfate,
filtered, and concentrated in vacuo. The product was purified
by flash chromatography on silica gel and recrystallized from
ethyl acetate-hexane to afford the desired compounds.
(0.4 mmol) in dichloromethane (2 mL) was added to remove
iodine and to quench the reaction. The color of reaction
mixture changed from brown to yellow, and aqueous sodium
thiosulfate was added. The organic materials were extracted
with ethyl acetate, and the combined extracts were dried over
anhydrous sodium sulfate. After evaporation of the solvent,
the crude product was purified on thin layer silica gel chro-
(
4R)-2-[2-[(Tolylsu lfon yl)a m in o]p h en yl]-4-p h en ylox-
2
3
a zolin e (4a ): yield 100%; [R]
D
3
) -49.3 (c 0.75, CHCl ); mp
1
1
(
1
34-135 °C; R
f
) 0.3 (25% ethyl acetate-hexane); H NMR
) δ 2.34 (s, 3H), 4.20 (dd, J ) 1.83, 7.94 Hz,
H), 4.71 (dd, J ) 1.83, 8.55 Hz, 1H), 5.49 (dd, J ) 7.94, 8.55
Hz, 1H), 7.00-7.42 (m, 9H), 7.66-7.82 (m, 4H), 12.31 (s, 1H);
500 MHz, CDCl
3
matography (hexane-ethyl acetate ) 2:1, R
f
) 0.3) to give pure
3
-[((1′R,2′R,3′S,4′S)-3′-methylbicyclo[2.2.1]hept-5′-en-2′-yl)car-
1
1
3
bonyl]-1,3-oxazolin-2-one (10). H NMR (270 MHz, CDCl
3
) δ
.13 (d, J ) 6.92 Hz, 3H), 1.44-1.48 (m, 1H), 1.67-1.73 (m,
H), 2.07-2.17 (m, 1H), 2.53-2.54 (m, 1H), 3.28-3.29 (m, 1H),
C NMR (125 MHz, CDCl
18.02, 122.41, 126.46, 127.17, 127.86, 128.82, 129.46, 129.55,
32.72, 136.86, 139.41, 141.47, 143.47, 164.55; IR (CHCl ):
630, 1600 cm ; MS (EI) m/z (relative intensity) 392 (100),
28 (39), 208 (41), 91 (52), calcd for C22 S 392.1259;
S: C, 67.33; H,
3
) δ 21.51, 69.59, 73.50, 113.30,
1
1
1
1
1
3
3
-
1
3.53-3.55 (m, 1H), 3.88-4.13 (m, 2H), 4.38-4.44 (m, 2H), 5.78
dd, J ) 2.64, 5.61 Hz, 1H), 6.36-6.39 (dd, J ) 3.30, 5.61 Hz,
(
1
20 2 3
H N O
H N O
20 2 3
-
1
H); IR (neat) 1775, 1695 cm . The enantioselectivity and
found 392.1234. Anal. Calcd for C22
the absolute configuration of the endo-adduct were determined
5
.14; N, 7.14. Found: C, 67.60; H, 4.92; N, 7.09.
by comparison of the optical rotation with that reported in the
3
NMR Stu d y of Ma gn esiu m Com p lex 5a in CDCl . To
1
8
literature ([R]
D
4
-191 (c 3.6, CCl ) [(92% ee (1′S,2′S,3′R,4′R)].
a solution of the chiral ligand 4a (78.5 mg, 0.2 mmol) in
dichloromethane (3 mL) was added a solution of MeMgI23 in
ether (0.98 M, 0.2 mL) at 0 °C. After stirring for 15 min, the
solvent was removed in vacuo (0.8 mmHg at rt) and dried over
Ack n ow led gm en t. We would like to thank Mr.
Takatoshi Ito for his careful exact mass spectra analy-
ses.
3
3
0 min. Anhydrous CDCl (1 mL) was added to the residue
and transferred into NMR tube.
Su p p or tin g In for m a tion Ava ila ble: 1H NMR, 13C NMR,
and 19F NMR spectra of chiral ligands 3 and 4a -g (21 pages).
This material is contained in libraries on microfiche, im-
mediately follows this article in the microfilm version of the
journal, and can be ordered from the ACS; see any current
masthead page for ordering information.
Gen er a l P r oced u r e for th e Asym m etr ic Diels-Ald er
R ea ct ion b et w een 6 a n d 7 Usin g a St oich iom et r ic
Am ou n t of th e Mg(II) Com p lex. To a solution of 1.0 equiv
of a chiral ligand in dichloromethane was added a solution of
(23) Callen, J . E.; Dornfeld, C. A.; Coleman, G. H. Org. Synth. 1965,
Collect. Vol. III, 26.
J O9621276