Intramolecular asymmetric olefination of binaphthyl phosphonate derivatives of 1,3-diketones

Article abstract of DOI:10.1016/S0957-4166(02)00176-3

Intramolecular asymmetric Wittig-type reactions of some chiral binaphthyl phosphonates of 2,2-disubstituted 1,3-dicarbonyl derivatives were investigated. The base-mediated cyclization occurred with differentiation of two diastereotopic carbonyl groups to

Full text of DOI:10.1016/S0957-4166(02)00176-3

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 13 (2002) 721–727
Intramolecular asymmetric olefination of binaphthyl phosphonate
derivatives of 1,3-diketones
Ashutosh V. Bedekar,a Toshiyuki Watanabe,a Kiyoshi Tanakaa,* and Kaoru Fujib
aSchool of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan
bInstitute for Chemical Research, Kyoto University, Uji 611-0011, Japan
Received 11 March 2002; accepted 1 April 2002
Abstract—Intramolecular asymmetric Wittig-type reactions of some chiral binaphthyl phosphonates of 2,2-disubstituted 1,3-dicar-
bonyl derivatives were investigated. The base-mediated cyclization occurred with differentiation of two diastereotopic carbonyl
groups to give non-racemic dihydronaphthalene derivatives with moderate to good enantiomeric excess. The degree of asymmetric
induction depended upon the substrates and the best result was obtained with the indanedione derivatives having alkyl
substituents in 58–73% yield with 82–88% e.e. The absolute structure of one of the products was unambiguously determined by
X-ray analysis and some mechanistic consideration is also given. © 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
as enzymes or yeast have been employed in one of the
most convenient approaches to optically active com-
pounds.7 Because of a paucity of information about the
structure of the substrate–enzyme complex, it is difficult
to predict the absolute configuration of the major enan-
tiomer produced in such biocatalytic processes. There-
fore, promising non-enzymatic methods are still
required in this field.
Since the first report by Wittig,1 considerable refine-
ments of the original Wittig reaction have been made.
Consequently, the stereo-, regio- and chemoselectivities
can be controlled to a great extent, and as such the
Wittig and related reactions have become one of the
most valuable organic transformations for the creation
of a carbonꢀcarbon bond, introducing a new sp2-car-
bon to the carbonyl group.2,3 It is generally recognized
that reactions to carbonyl compounds occupy a central
position in organic synthesis and hence in asymmetric
synthesis. The Wittig-type reaction4 between nucleo-
philic phosphorous-stabilized carbanions and carbonyl
components is one of the most widely used synthetic
tools for the construction of the carbonꢀcarbon double
bond. The transformation generally occurs at low tem-
perature and covers a large number of carbonyl com-
pounds. However, despite this excellent progress,5 only
a limited number of examples in which Wittig-type
reactions are involved in asymmetric synthesis had been
known before the last decade.
Substantial progress has been made recently in the
development of direct syntheses of optically active
olefinic compounds from achiral carbonyl compounds
using Wittig-type reactions. Apart from the kinetic
resolutions of racemic ketones,8 methods for asymmet-
ric olefination are grouped into two approaches. One is
the enantiotopic face discrimination of the carbonyl
compounds to dissymmetric olefins,9,10 and the differen-
tiation of enantiotopic carbonyl groups of meso-poly-
ketones is alternative. In connection with the latter
approach, we recently observed a marked degree of
discrimination between the enantiotopic carbonyl or
p-face, when optically active phosphonates 1 or 2 pos-
sessing an axially dissymmetric binaphthol were used as
a chiral HWE agent,11 or a Michael donor.12 Since the
Wittig-type reaction proceeds with concomitant elimi-
nation of the phosphonate, a chiral phosphonate
reagent having chirality at the phosphonate moiety has
an advantage of direct production of an optically active
olefin, and no procedure for removal of the auxiliary
group from the diastereomeric products is necessary.
Additionally, unlike the chiral phosphonates bearing a
Discrimination between enantiotopic groups of sym-
metrical substrates such as meso-compounds allows the
simple and direct way to synthetically useful non-
racemic materials.6 For this purpose, biocatalysts such
* Corresponding author. Tel.: +81 54 264 5746; fax: +81 54 264 5745;
e-mail: tanakaki@u-shizuoka-ken.ac.jp
0957-4166/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(02)00176-3

722
A. V. Bedekar et al. / Tetrahedron: Asymmetry 13 (2002) 721–727
stereogenic phosphorous atom,13 reagents of the type 1
or 2 have the advantages of easy preparation and ready
availability of both enantiomers.
annulation15 with the aid of a-amino acids. Recently,
the hydrindenone derivative, a useful building block for
1a,25-dihydroxyvitamin D3, was constructed via
diastereotopic differentiation by intramolecular HWE
reaction.16b Herein, we present our results from the
intramolecular Wittig-type asymmetrization of 1,3-
dicarbonyl compounds bearing axially chiral 1,1%-
binaphthalene-2,2%-diol17 as an auxiliary at the
phosphorous portion.
O
O
O
O
O
O
P
P
CH2CO2Me
CH2CH=CH2
(S)-1
(S)-2
The most serious problem with the Wittig-type reac-
tions comes from the susceptibility of steric hindrance
together with enolization of the ketonic substrates
under the basic conditions. Indeed, no intermolecular
reaction of the hindered carbonyl compounds, such as
2,2-disubstituted cyclohexa- or cyclopenta-1,3-dione,
with the anion of the reagent 1 or 2 occurred. On the
other hand, it is well documented that the intramolecu-
lar process is more entropically favored than the inter-
molecular reaction and the creation of ring systems
through intramolecular cyclization via 5- or 6-exo-trig
processes is energetically preferred. Therefore, the
intramolecular olefination might overcome some con-
comitant problems of the Wittig-type reaction to give a
new five- or six-membered ring system having a sub-
strated olefinic linkage.14
2. Results and discussion
In order to investigate the intramolecular Wittig-type
reactions, five substrates 3–7 were designed and pre-
pared (Scheme 1). Thus, the C-alkylation of appropri-
ate 2-alkyl-1,3-diketones 8–12 was first carried out with
o-xylenedibromide 13, which was employed as a linker
arm to create a dihydronaphthalene ring. In this way,
the C-alkylated benzylbromides 15–19 were unevent-
fully prepared by Triton-B catalyzed selective C-
alkylation18 of 2-alkyl-1,3-dicarbonyl compounds or,
more conveniently, using a combination of lithium
iodide and DBU.19 Subsequent Arbusov reaction of the
methylphosphite derivative 14 of (S)-(−)-1,1%-bi-2-naph-
thol with compounds 15–19 effected connective phos-
phorylation to give the desired substrates 3–7 in
moderate to good yields (Scheme 2).
Based on the idea mentioned above, we investigated the
intramolecular diastereoselective asymmetrization of
symmetric 1,3-dicarbonyl systems to afford a non-
racemic cyclic compound bearing a quaternary stereo-
genic carbon and trisubstituted olefinic bond.
Comparing the enantiotopic functional group differen-
tiation method with enzymes or Baker’s yeasts,7 only a
few reports on the chemical asymmetrization with car-
bonꢀcarbon bond formation have been known,15,16
including Trost’s pioneering work16a of intramolecular
diastereotopic group discrimination as well as Hajos’s
The reaction conditions for the cyclization of these
substrates 3–7 by the intramolecular Wittig-type reac-
tions was next examined using various bases and sol-
vents. The cyclizations of 3–7 occurred and furnished
the corresponding cyclized dihydronaphthalene deriva-
tives 20–24 in moderate to good chemical yields
(Scheme 3). When chelate-controlled conditions with
the weakly basic DBU–LiBr system were employed, the
reaction of 4 afforded the intermediate hydroxyphos-
O
O
O
O
O
O
O
O
O
O
R
P
P
P
O
O
O
Me
O
Me
O
Me
3
4
5; R = Me, 6; R = Et, 7; R = i-Pr
Me
Scheme 1.
O
Br
Me
O
O
O
O
O
R
Br
P OMe
O
Me
O
8
9
10; R = Me, 11; R = Et, 12; R = i-Pr
13
14
O
Br
O
O
Me
O
R'
R'
O
R' =
R
Me
R'
O
15
16
17; R = Me, 18; R = Et, 19; R = i-Pr
Scheme 2.

A. V. Bedekar et al. / Tetrahedron: Asymmetry 13 (2002) 721–727
723
Me
Me
22 ; R = Me
23 ; R = Et
*
*
Me
O
Me
21
25
20
24 ; R = i-Pr
O
O
R
O
P
O
O
R*
NaH, THF
LiBr / DBU
THF, 0 °C
OH
4
21
R* =
Me
O
Scheme 3.
phonate 25, which without isolation was then converted
to 21 by treatment with NaH. Generally, the best
results were obtained in THF with 1.2 equiv. of potas-
sium bases such as KDA or KH in the presence of a
catalytic amount of 18-crown-6. These results including
the e.e.s of products are summarized in Table 1.
occurs from the favored face opposite the substituent R
(anti-attack). Regarding the p-face of the anion,
approach to the si-face is sterically favored due to the
chiral environment created by the optically active
binaphthyl moiety. Taking two possible conformations,
s-cis and s-trans, of the carbanion, as well as the
approach to each carbonyl into account, four plausible
transition state models (a)–(d) are considered. Among
them (a) is the most energetically favored process lead-
For the reactions of 3 and 4, no satisfactory results with
respect to both chemical and enantiomeric excesses
could be obtained. On the other hand, higher e.e.s were
observed with the indanedione derivatives independent
of the identity of the alkyl substituents R (Scheme 4).
The absolute structures of the cyclized major enan-
tiomers were deduced and determined by chemical
transformation from the product 24 followed by X-ray
crystallographic analysis of the product 26. Thus, com-
pound 24 was converted to its Cr-complex 26 through
ligand exchange reaction with h6-(naphthalene)-
chromium tricarbonyl 27, and crystals of the com-
plex 26 from benzene were subjected to X-ray analysis
(Fig. 1). In this way, using anomalous dispersion of the
chromium atom, the absolute stereostructure of the
product 24 was clearly elucidated to have an S-configu-
ration at the stereogenic carbon. The stereochemistry of
the other related products 22 and 23 was estimated to
have the same configuration based on the above X-ray
analysis as well as the mechanistic considerations men-
tioned below.
Scheme 4.
The observed stereostructure of the cyclized products
22–24 can be explained as follows. The intramolecular
nucleophilic attack of the carbanion to the carbonyl
Figure 1. Crystal structure of 26.
Table 1. Asymmetric intramolecular Wittig-type reactions of 3–7 to give 20–24
Entry
Substrate
Conditionsa
Product
Chemical yieldb
(%) e.e.c
1
2
3
4
5
6
7
3
4
4
4
5
6
7
A
A
B
C
A
A
A
20
21
21
21d
22
23
24
44
38
20
16d
58
72
73
17
50
51
81d
88
82
86
a All reactions were carried out in THF. A: KDA (1.2 equiv.), 18-crown-6 (0.2 equiv.) at −78°C for 2–24 h. B: KH (1.2 equiv.) at −78°C for 2
h. C: DBU–LiBr (excess) at 0°C for 18 h.
b Isolated yield.
c Determined by HPLC with 1.0% hexane–2-PrOH on Chiralpak AD or Chiralcel OD (Daicel Chemical Inc. LTD) at the flow rate of 0.5 mL/min.
d After treatment with NaH.

724
A. V. Bedekar et al. / Tetrahedron: Asymmetry 13 (2002) 721–727
4.2. 2-Alkyl-2-(2%-bromomethyl)benzylindane-1,3-diones,
17, 18 and 19
ing to the preferential formation of 22–24, since the
other models impose a severe steric repulsion between
some parts of the dicarbonyl substrate (Fig. 2).
To a stirred solution of 12 (1.5 g, 8.00 mmol) and
o-xylenedibromide 13 (2.3 g, 8.80 mmol) in acetone (15
mL) was added dropwise a solution of benzyltrimethyl-
ammonium hydroxide (Triton B) in water (40% in
water, 4.4 mL, 9.60 mmol, 1.2 equiv.) and the mixture
was stirred for 12 h at room temperature. The mixture
was concentrated under reduced pressure and extracted
with EtOAc. The organic extracts were washed succes-
sively with water and brine, and then evaporated.
Column chromatography of the residue on silica gel
with hexane/EtOAc (4/1) gave 19 as crystals (2.60 g,
87%). Mp 118–119°C; colorless prisms (from CHCl3/
3. Conclusion
In summary, we have examined the asymmetric
intramolecular cyclization of a number of 1,3-dicar-
bonyl compounds having a chiral binaphthyl phospho-
nate group by Wittig-type reaction. The carbanion
effectively discriminated the diastereotopic carbonyls to
afford the dihydronaphthalene derivatives with satisfac-
tory levels of e.e. This approach is applicable to the
asymmetric construction of new five- or six-membered
fused ring systems possessing a quaternary stereogenic
carbon centre and an olefinic linkage to which the
synthetic approach is difficult by other methods.
1
hexane); H NMR (200 MHz, CDCl3) l 7.82–7.68 (m,
4H), 7.16 (d, 1H, J=7.0 Hz), 7.00–6.87 (m, 3H), 4.70
(s, 2H), 3.43 (s, 2H), 2.41 (quintet, 1H, J=7.0 Hz), 1.05
(d, 6H, J=6.9 Hz); IR (CHCl3) 2970, 1740, 1704, 1595,
1250 cm−1. Anal. calcd for C20H19BrO2: C, 64.70; H,
5.16. Found: C, 64.97; H, 5.15%.
4. Experimental
4.1. General
Compounds 17 and 18 were prepared in the same way
from the corresponding indanedione as described above
for the preparation of 19, in 73 and 85% yield, respec-
tively. While, 15 and 16 were prepared by C-alkylation
of 3-methyl-penta-2,4-dione 8 and 2-methyl-cyclo-1,3-
hexadione 9 in 40 and 32% yield.
Melting points are uncorrected. Proton nuclear mag-
netic resonance (1H NMR) spectra were taken at 200 or
270 MHz in CDCl3 with chemical shifts being reported
as l ppm from tetramethylsilane as an internal stan-
dard and couplings are expressed in hertz. Infrared (IR)
spectra were measured in CHCl3 solution. THF was
distilled from sodium benzophenone ketyl and
dichloromethane was from calcium hydride. Unless
otherwise noted, all reactions were run under an argon
atmosphere. All extractive organic solutions were dried
over anhydrous MgSO4. Flash column chromatography
was carried out with silica gel 60 (spherical, 150–325
mesh), and silica gel 60 F254 plates (Merck) were used
for preparative TLC (pTLC).
Compound 15: Colorless oil; 1H NMR (200 MHz,
CDCl3) l 7.35–7.45 (m, 1H), 7.20–7.30 (m, 2H), 7.05
(m, 2H), 4.54 (s, 2H), 3.40 (s, 2H), 2.16 (s, 6H), 1.36 (s,
3H); IR (CHCl3) 2960, 2945, 1726, 1697, 1460, 1360,
1250 cm−1; anal. MS (m/z) 298, 296, 255, 253, 234, 209,
191, 173, 159, 138, 131 (100%), 117, 104, 91, 78, 59.
Compound 16: Mp 99–100°C; colorless prisms (from
1
AcOEt/hexane); H NMR (200 MHz, CDCl3) l 7.14–
Figure 2. Possible mechanism of the intramolecular cyclization of anions of 5–7.

A. V. Bedekar et al. / Tetrahedron: Asymmetry 13 (2002) 721–727
725
7.37 (m, 3H), 6.94–7.03 (m, 1H), 4.60 (s, 2H), 3.33 (s,
2H), 2.53–2.73 (m, 2H), 2.30–2.46 (m, 2H), 1.61–1.95
(m, 2H), 1.37 (s, 3H); 13C NMR (75 MHz, CDCl3) l
16.5, 23.3, 32.1, 37.7, 39.0, 49.4, 64.9, 127.6, 128.9,
130.1, 130.3, 131.1, 131.3, 211.9. IR (CHCl3) 3030,
3015, 2960, 1725, 1693, 1605, 1230, 1215, 780 cm−1; MS
(m/z) 310, 308, 293, 267, 265, 246.
Compound 3: Mp 185–186°C (from AcOEt/hexane);
white crystals; [h]1D8 −6.14 (c 0.53, CHCl3, >99% e.e.);
1H NMR (200 MHz, CDCl3) l 7.90–8.10 (m, 4H),
7.04–7.60 (m, 10H), 6.94–7.04 (m, 2H), 3.52 (d, 2H,
J=21.5 Hz), 3.19 (dd, 2H, J=33.0, 15.0 Hz), 1.90 (s,
3H), 1.88 (s, 3H), 1.15 (s, 3H); IR (CHCl3) 3020, 1741,
1708, 1592, 1280, 1220 cm−1; MS (m/z) 549 (M++1),
530, 507, 463, 435, 391, 307, 154. Anal. calcd for
C34H29O5P: C, 74.44; H, 5.33. Found: C, 74.06; H,
5.13%.
Compound 17: Mp 99–100°C; colorless prisms (from
1
AcOEt/hexane); H NMR (200 MHz, CDCl3) l 7.89–
7.74 (m, 4H), 7.21 (m, 1H), 7.02–6.97 (m, 3H), 4.68 (s,
2H), 3.38 (s, 2H), 1.48 (s, 3H); IR (CHCl3) 3020, 1740,
1710, 1598, 1378, 1258 cm−1. Anal. calcd for
C18H15BrO2: C, 62.99; H, 4.40. Found: C, 63.36; H,
4.30%.
1
Compound 4: Mp 215–216°C (from Et2O/hexane); H
NMR (200 MHz, CDCl3) l 6.90–8.15 (m, 16H), 3.51–
3.61 (d, 2H, J=20.8 Hz), 3.16 (dd, 2H, J=24.6, 14.3
Hz), 2.42–2.60 (m, 2H), 2.16–2.36 (m, 2H), 1.45–1.83
(m, 2H), 0.97 (s, 3H); IR (CHCl3) 3060, 3015, 1721,
1692, 1621, 1590, 1511, 1465, 1280, 1221 cm−1; MS
(m/z) 561 (M++1), 560 (M+), 544, 532, 517, 286, 268
(100%), 239, 55. Anal. calcd for C35H29O5P (560): C,
74.99; H, 5.18. Found; C, 74.79; H, 5.10%.
Compound 18: Mp 93–94°C; colorless prisms (from
1
AcOEt/hexane); H NMR (200 MHz, CDCl3) l 7.87–
7.72 (m, 4H), 7.20 (brd, 1H, J=6.5 Hz), 7.04–6.93 (m,
3H), 4.67 (s, 2H), 3.35 (s, 2H), 2.08 (q, 2H, J=7.4 Hz),
0.78 (t, 3H, J=7.6 Hz); IR (CHCl3) 3010, 1740, 1705,
1595, 1462, 1360, 1255 cm−1. Anal. calcd for
C19H17BrO2: C, 63.88; H, 4.80. Found: C, 64.08; H,
4.77%.
Compound 5: Amorphous; [h]1D8 +317 (c 2.2, CHCl3,
>99% e.e.); H NMR (200 MHz, CDCl3) l 8.14–6.89
(m, 20H), 3.60 (d, 2H, J=20.6 Hz), 3.09 (dd, 3H,
J=48.8, 14.4 Hz), 1.05 (s, 3H); IR (CHCl3) 3020, 1741,
1708, 1592, 1280, 1220 cm−1; MS (m/z) 594 (M+);
HRMS (m/z) calcd for C38H27O5P (M+) 594.1596.
Found: 594.1573.
1
4.3. Synthesis of phosphonates 3–7
A solution of (S)-(−)-1,1%-bi-2-naphthol (750 mg, 2.60
mmol) and diisopropylethylamine (740 mg, 5.70 mmol,
2.2 equiv.) in CH2Cl2 (30 mL) was stirred at 0°C for 15
min and dichloromethylphosphite (380 mg, 2.90 mmol,
1.2 equiv.) was added. The mixture was stirred for 1.5
h at room temperature, and concentrated at ambient
temperature to afford crude 14, which was used in the
next reaction without purification.
Compound 6: Amorphous; [h]1D8 +223 (c 1.4, CHCl3,
1
>99% e.e.); H NMR (200 MHz, CDCl3) l 8.16–6.84
(m, 20H), 3.60 (dd, 2H, J=19.9, 5.94 Hz), 3.02 (dd, 3H,
J=49.1, 14.3 Hz), 1.50 (m, 2H), 0.45 (t, 3H, J=7.5
Hz); IR (CHCl3) 3015, 1740, 1706, 1621, 1592, 1230
cm−1; MS (m/z) 608 (M+); HRMS (m/z) calcd for
C39H29O5P (M+) 608.1752. Found: 608.1744.
A mixture of crude 14, 19 (1.20 g, 3.30 mmol, 1.3
equiv.), hydroquinone (10.0 mg) and dichlorobenzene
(2.0 mL) was heated at 160°C under an argon atmo-
sphere with stirring for 24 h. The reaction mixture was
diluted with CH2Cl2 (70 mL) and the resulting solution
was washed with water and brine and then dried.
Evaporation under reduced pressure gave the oily
residue, which was subjected to column chromatogra-
phy on silica gel with hexane/EtOAc (1/1). Compound
7 was obtained as an amorphous solid (660 mg, 41%).
The absence of racemization was confirmed by the
HPLC analysis of the sample obtained in this way.
4.4. Asymmetric cyclization to afford 20–24
The preparation of compounds 20–24 was carried out
by the cyclization described in Table 1. A representative
example is as follows: a solution of 7 (768 mg, 1.23
mmol) and 18-crown-6 (70.1 mg, 0.27 mmol, 0.2 equiv.)
in THF (18 mL) was treated with KDA (6.2 mL, 0.24
M in THF, 1.48 mmol, 1.2 equiv.) at −78°C under
argon and the resulting mixture was stirred for 24 h at
the same temperature. The mixture was quenched by
addition of a sat. NH4Cl solution and extracted with
EtOAc. The organic extract was washed with water and
brine, and then evaporated. The residue was purified by
preparative TLC (hexane/EtOAc, 5/1) to give 24 (18.3
mg, 64%). The sample was analyzed by HPLC on a
chiral stationary phase.
Compound 7: amorphous; [h]1D8 +235.0 (c 1.30, CHCl3,
1
>99% e.e.); H NMR (200 MHz, CDCl3) l 8.17–6.80
(m, 20H), 3.69 (dd, 1H, J=45.7, 15.4 Hz), 3.59 (dd, 1H,
J=48.4, 15.3 Hz), 3.05 (dd, 2H, J=42.8, 14.3 Hz), 1.73
(m, 1H), 0.54 (t, 6H, J=6.5 Hz); IR (CHCl3) 3015,
1738, 1730, 1592, 1509, 1228 cm−1; MS (m/z) 622 (M+);
HRMS (m/z) calcd for C40H31O5P (M+) 622.1909.
Found: 622.1901.
Compound 24: Mp 64°C; colorless needle (from Et2O);
1
[h]1D6 +184 (c 0.44, CHCl3, >99% e.e.); H NMR (200
MHz, CDCl3) l 7.81 (m, 2H), 7.68 (brt, 1H, J=7.6
Hz), 7.44 (brt, 1H, J=7.1 Hz), 7.24 (m, 4H), 7.00 (s,
1H), 3.34 (d, 1H, J=15.8 Hz), 2.80 (d, 1H, J=15.8
Hz), 1.95 (m, 1H), 1.01 (d, 3H, J=7.0 Hz), 0.54 (d, 3H,
J=7.0 Hz); IR (CHCl3) 3015, 2965, 1703, 1600, 1470,
1215 cm−1. Anal. calcd for C20H18O: C, 87.59; H, 6.57.
Found: C, 87.57; H, 6.79%.
Compounds 3, 4, 5 and 6 were afforded from 15, 16, 17
and 18, respectively, without racemization via treat-
ment with 14 in a similar manner to that described
above for the preparation of 7.

726
A. V. Bedekar et al. / Tetrahedron: Asymmetry 13 (2002) 721–727
Compound 20: Colorless oil; 1H NMR (200 MHz,
CDCl3) l 6.95–7.20 (m, 4H), 6.37 (m, 1H), 2.97 (dd,
2H, J=89.4, 15.7 Hz), 2.11 (s, 3H), 1.87 (d, 3H, J=1.5
Hz), 1.23 (s, 3H). MS (m/z) 201, 200 (M+), 175, 169,
142, 115, 91, 77. HRMS (m/z) calcd for C14H16O (M+)
200.1201. Found: 200.1197.
factor of ent-26 (R=0.109), and furthermore, by the
Flack parameter20 of 26 (X=−0.0079). Crystallographic
data for the structure 26 have been deposited with
Cambridge Crystallographic Data Centre (deposition
number CCDC 183967).
Compound 21: Colorless oil; [h]1D8 +45.8 (c 0.6, CHCl3,
Acknowledgements
1
51% e.e.); H NMR (200 MHz, CDCl3) l 7.10–7.25 (m,
3H), 6.98–7.06 (m, 1H), 6.27 (m, 1H), 2.98 (dd, 2H,
J=29.0, 16.0 Hz), 2.45–2.70 (m, 4H), 1.60–1.85 (m,
2H), 1.16 (s, 3H) IR (CHCl3) 2950, 2880, 1708, 1642,
1488, 1455, 910 cm−1.
We thank the Ministry of Education, Science, Sports
and Culture, Japan for financial support. One of the
authors (A.V.B.) is grateful to JSPS for financial sup-
port. The authors are also grateful to Drs. Y. Hata, Y.
Kawai and T. Fujii (Kyoto University) for their helpful
advice on X-ray analysis.
Compound 22: 58% yield, mp 114–116°C; colorless
needle (from Et2O); [h]1D8 +100.9 (c 0.59, CHCl3, 88%
1
e.e.); H NMR (200 MHz, CDCl3) l 7.91 (m, 2H), 7.73
(brt, 1H, J=5.9 Hz), 7.50 (brt, 1H, J=6.4 Hz), 7.31 (m,
4H), 7.03 (s, 1H), 3.07 (d, 1H, J=15.5 Hz), 2.89 (d, 1H,
J=15.3 Hz), 1.14 (s, 3H); IR (CHCl3) 3018, 2970, 1712,
1603, 1216 cm−1; MS (m/z) 246 (M+); HRMS (m/z)
calcd for C18H14O (M+) 246.1044. Found: 246.1050.
Anal. calcd for C18H14O: C, 87.78; H, 5.73. Found: C,
87.50; H, 5.66%.
References
1. (a) Wittig, G.; Geissler, G. Liebigs Ann. Chem. 1953, 580,
44; (b) Wittig, G. Science 1980, 210, 600; (c) Maercker,
A. Org. React. 1965, 14, 270.
2. Maryanoff, B. E.; Reitz, A. B. Chem. Rev. 1989, 89, 863
and references cited therein.
3. Kelly, S. E. In Comprehensive Organic Synthesis; Trost,
B. M.; Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 1,
pp. 755–782.
Compound 23: 72% yield, mp 64–65°C; colorless needle
1
(from Et2O); [h]2D0 +82.7 (c 1.3, CHCl3, 82% e.e.); H
NMR (200 MHz, CDCl3) l 7.83 (d, 2H, J=8.4 Hz),
7.69 (brt, 1H, J=8.3 Hz), 7.45 (brt, 1H, J=8.1 Hz),
7.25 (m, 4H), 7.00 (s, 1H), 3.14 (d, 1H, J=15.5 Hz),
2.85 (d, 1H, J=15.8 Hz), 1.58 (s, 2H), 0.67 (t, 3H,
J=7.5 Hz); IR (CHCl3) 3015, 2986, 1708, 1600, 1470,
1217 cm−1. Anal. calcd for C19H16O: C, 87.66; H, 6.19.
Found: C, 87.27; H, 6.42%.
4. Wadsworth, W. S. Org. React. 1977, 25, 73.
5. For reviews on asymmetric synthesis, see: (a) Asymmetric
Synthesis; Morrison, J. D., Ed.; Academic: New York,
1983–85; Vols. 1–5; (b) Seebach, D. Angew. Chem., Int.
Ed. Engl. 1990, 29, 1320; (c) Corey, E. J. Pure Appl.
Chem. 1990, 62, 1209; (d) Hassner, A. Advances in Asym-
metric Synthesis; JAI Press: Greenwich, 1995; Vol. 1.
6. Ward, R. S. Chem. Soc. Rev. 1990, 19, 1.
Cr-complex 26. The cyclized compound 24 mentioned
above was first purified to give an enantiomerically
pure sample by preparative HPLC with a Chiralcel OD
preparative column. A mixture of purified 24 (75 mg,
0.27 mmol, 100% e.e.), complex 27 (106 mg, 0.40 mmol,
1.5 equiv.) and Et2O/THF mixture (1/10, 5.5 mL) was
heated at 90°C under an argon atmosphere in a sealed
tube for 40 h. After cooling the mixture was filtered and
the filtrate was concentrated to give a residue, which
was subjected to p-TLC on silica gel with the solvent
system of Et2O/hexane (1/5) to afford 26 as crystals
(23.7 mg, 21%).
7. (a) Ohno, M. In Organic Synthesis and Interdisciplinary
Challenge; Strieth, J.; Prinzbach, H.; Schill, G., Eds.;
Blackwell Scientific: Oxford, 1985; p. 189; (b) Csuk, R.;
Glanzer, B. I. Chem. Rev. 1991, 91, 49; (c) Johnson, C.
R.; Harikrishnan, L. S.; Golebiowski, A. Tetrahedron
Lett. 1994, 35, 7735 and references cited therein; (d)
Bestmann, H. J.; Bauriegel, L. Tetrahedron Lett. 1995, 36,
853; (e) Heiss, L.; Gais, H.-J. Tetrahedron Lett. 1995, 36,
3833.
8. (a) Narasaka, K.; Hidai, E.; Hayashi, Y.; Gras, J.-L. J.
Chem. Soc., Chem. Commun. 1993, 102; (b) Rein, N.;
Kann, N.; Kreuder, R.; Gangloff, B.; Reiser, O. Angew.
Chem., Int. Ed. Engl. 1994, 33, 556; (c) Rein, T.; Kreuder,
R.; von Zezschwitz, P.; Wulff, C.; Reiser, O. Angew.
Chem., Int. Ed. Engl. 1995, 34, 1023; (d) Yamaguchi, M.;
Hirama, M. CHEMTRACTS-Org. Chem. 1994, 7, 401;
(e) Tanaka, K.; Watanabe, T.; Shimamoto, K.; Sahakit-
pichan, P.; Fuji, K. Tetrahedron Lett. 1999, 40, 6599; (f)
Pedersen, T. M.; Hansen, E. L.; Kane, J.; Rein, T.;
Helquist, P.; Norrby, P.-O.; Tanner, D. J. Am. Chem.
Soc. 2001, 123, 9738.
Compound 26: mp 171–178°C (decomp.); reddish
prisms (from benzene); [h]1D6 −1791 (c 0.35, CHCl3,
1
ꢀ100% e.e.); H NMR (200 MHz, CDCl3) l 7.80 (m,
3H), 7.52 (t, 1H, J=6.6 Hz), 6.64 (s, 1H), 5.57 (d, 1H,
J=6.0 Hz), 5.44 (d, 2H, J=3.4 Hz), 5.25 (dd, 1H,
J=6.5, 3.7 Hz), 3.13 (d, 1H, J=15.9 Hz), 2.91 (d, 1H,
J=15.8 Hz), 1.96 (m, 1H), 1.00 (d, 3H, J=6.9 Hz),
0.59 (d, 3H, J=7.0 Hz); IR (CHCl3) 1967, 1897, 1713,
1600, 1470 cm−1. Anal. calcd for C23H18CrO4: C, 67.32;
H, 4.42. Found: C, 66.97; H, 4.45%. Crystallized as
9. (a) Hanessian, S.; Delorm, D.; Beaudoin, S.; Leblanc, Y.
J. Am. Chem. Soc. 1984, 106, 5754 and references cited
therein; (b) Hanessian, S.; Beaudoin, S. Tetrahedron Lett.
1992, 33, 7655.
10. (a) Denmark, S. E.; Chen, C.-T. J. Am. Chem. Soc. 1992,
114, 10674; (b) Denmark, S. E.; Rivera, I. J. Org. Chem.
1994, 59, 6887 and references cited therein; (c) Yamazaki,
orthorhombic, space group P212121 with a=14.280 (1),
3
,
,
b=18.265 (2), c=7.507 (2) A, V=1957.9 (5) A , Z=4,
D
calcd=1.392 g/cm3. The structure was refined to R=
0.055, Rw=0.075, goodness of fit=1.51. The structure
elucidated was supported by comparison with the R

A. V. Bedekar et al. / Tetrahedron: Asymmetry 13 (2002) 721–727
727
J.; Watanabe, T.; Tanaka, K. Tetrahedron: Asymmetry
2001, 12, 669.
11. (a) Tanaka, K.; Ohta, Y.; Fuji, K.; Taga, T. Tetrahedron
Lett. 1993, 34, 4017; (b) Tanaka, K.; Watanabe, T.; Ohta,
Y.; Fuji, K. Tetrahedron Lett. 1997, 38, 8943; (c) Tanaka,
K.; Ohta, Y.; Yoshiuchi, T.; Fuji, K., manuscript in
preparation.
3489; (c) Elliott, M. R.; Dhimane, A.-L.; Hamon, L.;
Malacria, M. Eur. J. Org. Chem. 2000, 155; (d)
Comins, D. L.; Ollinger, C. G. Tetrahedron Lett. 2001,
42, 4115.
15. Hajos, Z. G.; Parrish, D. R. Org. Synth. 1985, 63, 26.
16. (a) Trost, B. M.; Curran, D. P. J. Am. Chem. Soc. 1980,
102, 5699; (b) Mandai, T.; Kaihara, Y.; Tsuji, J. J. Org.
Chem. 1994, 59, 5847; (c) Kann, N.; Rein, T. J. Org.
Chem. 1993, 58, 3802.
12. Tanaka, K.; Ohta, Y.; Fuji, K. J. Org. Chem. 1995, 60,
8036.
17. Whitesell, K. Chem. Rev. 1989, 89, 1571.
18. Rajamannar, N.; Palani, N.; Balasubramaniam, K. K.
Synth. Commun. 1993, 23, 3095.
19. Bedekar, A. V.; Watanabe, T.; Tanaka, K.; Fuji, K.
Synthesis 1995, 1069.
20. Flack, H. D. Acta Crystallogr. 1983, A37, 734.
13. (a) Parrish, D. R. J. Org. Chem. 1974, 39, 1615; (b) Real,
S. D.; Kronenthal, D. R.; Wu, H. Y. Tetrahedron Lett.
1993, 34, 8063.
14. (a) Piperlier, M.; Ermolenko, M. S.; Zampella, A.;
Olesker, A.; Lukacs, G. Synlett 1996, 24; (b) Gourves,
J.-P.; Couthon, H.; Sturtz, G. Eur. J. Org. Chem. 1999,