Synthesis of phosphine oxide-carboxylic acid esters bearing 9,10-dihydro-9,10-ethanoanthracene moiety

Article abstract of DOI:10.1080/10426500307810

A bulky type of phosphine oxide-carboxylic acid bearing 9,10-dihydro-9,10-ethanoanthracene moiety was synthesized by the Diels-Alder reaction of 2-anthryldiphenylphosphine oxide and methyl acrylate, for which the structure was confirmed on the basis of

Full text of DOI:10.1080/10426500307810

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Synthesis of Phosphine Oxide-Carboxylic Acid Esters
Bearing 9,10-Dihydro-9,10-ethanoanthracene Moiety
Yoshiharu Okada a , Kazuhiro Okeya a , Yoshiyasu Murata a , Nakahisa Aoki a , Takahiro Aoki a
, Motoko Sugitani a , Satomi Yasui a , Yusuke Sawada a & Fumio Ogura a
a Kinki University , Higashi-hiroshima, Japan
Published online: 27 Oct 2010.
To cite this article: Yoshiharu Okada , Kazuhiro Okeya , Yoshiyasu Murata , Nakahisa Aoki , Takahiro Aoki , Motoko Sugitani ,
Satomi Yasui , Yusuke Sawada & Fumio Ogura (2003) Synthesis of Phosphine Oxide-Carboxylic Acid Esters Bearing 9,10-
Dihydro-9,10-ethanoanthracene Moiety, Phosphorus, Sulfur, and Silicon and the Related Elements, 178:4, 821-829, DOI:
10.1080/10426500307810
To link to this article: http://dx.doi.org/10.1080/10426500307810
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Phosphorus, Sulfur and Silicon, 2003, Vol. 178:821–829
C
Copyright 2003 Taylor & Francis
1042-6507/03 $12.00 + .00
DOI: 10.1080/10426500390197986
SYNTHESIS OF PHOSPHINE OXIDE-CARBOXYLIC
ACID ESTERS BEARING
9,10-DIHYDRO-9,10-ETHANOANTHRACENE MOIETY
Yoshiharu Okada, Kazuhiro Okeya, Yoshiyasu Murata,
Nakahisa Aoki, Takahiro Aoki, Motoko Sugitani, Satomi Yasui,
Yusuke Sawada, and Fumio Ogura
Kinki University, Higashi-hiroshima, Japan
(Received February 22, 2002; accepted September 5, 2002)
A bulky type of phosphine oxide-carboxylic acid bearing 9,10-dihydro-
9,10-ethanoanthracene moiety was synthesized by the Diels-Alder re-
action of 2-anthryldiphenylphosphine oxide and methyl acrylate, for
which the structure was confirmed on the basis of 1H NMR spec-
tral data to be dimethyl 2-diphenylphosphinoyl-9,10-dihydro-9,10-
ethanoanthracene-11,11- and 12,12-dicarboxylates.
Keywords: 9,10-Dihydro-9,10-ethanoanthracene; Diels-Alder reaction;
methyl acrylate; phosphine-carboxylic acid
In the transition metal complex catalyzed asymmetric synthesis, one of
the most important needs is the development of effective chiral phos-
phine ligands. Previously, we have succeeded in the development of chi-
ral phosphine ligands with the carboxyl group, and achieved the high
optical yield in the asymmetric allylic alkylation. In addition, it has
been clarified that the carboxyl group of the ligands plays an important
role for the asymmetric induction.1 We also found that these phosphine-
carboxylic acid ligands had substrate specificity in this alkylation.1d
Therefore, we planned the synthesis of more effective chiral phosphine-
carboxylic acid ligands, which could induce higher enantioselectivity in
asymmetric allylic alkylation of a variety of allylic substrates. Here
We are grateful for financial support of this work by a Grant-in-Aid for Scientific
Research (C) (10650856) from Japan Society for the Promotion of Science and for
Encouragement of Young Scientists (07750959) from the Japan Ministry of Education,
Science, and Culture. We also thank the Center for Instrumental Analysis of KIT (Kyushu
Institute of Technology) for the use of its facilities.
Address correspondence to Yoshiharu Okada, Department of Chemistry and Envi-
ronmental Technology, Faculty of Engineering, Kinki University, Umenobe-1, Takaya,
Higashi-hiroshima 739-2116, Japan.
821

822
Y. Okada et al.
we describe the synthesis of a bulky type of 2-diphenylphosphino-
9,10-dihydro-9,10-ethanoanthracene-12-carboxylic acid.
In order to know the spectral feature of the desired phosphine-
carboxylic acid, the reaction of 2-anthryldiphenylphosphine oxide (1)
with dimethyl methylenemalonate was first carried out. In the pres-
ence of copper(II) acetate, reaction of 1 with dimethyl malonate and
paraformaldehyde afforded a mixture of two regioisomers, dimethyl
2-diphenylphos-phinoyl-9,10-dihydro-9,10-ethanoanthracene-12,12-
dicarboxylate (2a), and 11,11-dicarboxylate (2b) in 89% yield (Eq. 1).2
Recrystallization of the mixture from ethyl acetate-hexane resulted in
separation of 2a and 2b. The stereochemical assignment of 2a and 2b
was made on the basis of 1H NMR and x-ray analysis.
(1)
In the 1H NMR spectrum of 2a, characteristic resonances of methyl
and H11 protons were observed at 3.45 (s, 3H, OCH3) and 3.57 (s, 3H,
OCH3), and 2.46 (dd, J = 2.9 and 13.1 Hz, 1H, CH2) and 2.54 (dd,
J = 2.9 and 13.1 Hz, 1H, CH2) ppm respectively. In contrast, in that
of 2b, characteristic resonances of methyl and H12 protons were ob-
served at 3.58 (s, 3H, OCH3) and 3.59 (s, 3H, OCH3), and 2.35 (dd,
J = 2.6 and 13.1 Hz, 1H, CH2) and 2.62 (dd, J = 2.9 and 13.1 Hz,
1H, CH2) ppm respectively. On the other hand, the corresponding
methyl signals in dimethyl 9,10-dihydro-9,10-ethanoanthracene-11,11-
dicarboxylate and the mixture of dimethyl 2-methyl-9,10-dihydro-9,10-
ethanoanthracene-11,11- and 12,12-dicarboxylates were observed at
3.58 (s, 6H, OCH3) [2], and 3.53 (s, 3H, OCH3), and 3.55 (s, 3H, OCH3)
ppm respectively. Owing to the ring current of the phenyl group of
A mixture of two regioisomers, dimethyl 2-methyl-9,10-dihydro-9,10-ethanoanth-
racene-11,11- and 12,12-dicarboxylates prepared by the reaction of 2-methylanthracene,
dimethyl malonate, and paraformaldehyde in the presence of copper(II) acetate in 92%
yield, 1H NMR (CDCl3) 2.25 and 2.26 (s, 3H CH3), 2.47 and 2.48 (br s, 2H, CH2), 3.53
and 3.55 (s, 6H, OCH3), 4.26 and 4.27 (br t, 1H, CH), 4.92 and 4.94 (s, 1H, CH), 6.85–7.31
(m, 7H, ArH).

Synthesis of Phosphine Oxide-Carboxylic Acid Esters
823
FIGURE 1 ORTEP diagram of 2a.
the phosphorus functional group, one methyl signal in 2a and one pro-
ton signal of H12 in 2b, which were close to the phosphorus functional
group, were shifted to the higher field. The signals of the two methyl
groups in 2b and methylene protons in 2a were observed comparatively
close to each other. The stereochemistry of 2a was also confirmed by
x-ray crystallographic analysis (Figure 1).
1
In order to obtain the H NMR spectral data to elucidate the struc-
ture of the target monophosphine oxide-monocarboxylic acid with 9,10-
dihydro-9,10-ethanoanthracene skeleton, 1 was reacted with dimethyl
fumarate at reflux for 2 days in xylene to afford a mixture of dimethyl
2-diphenyl-phosphinoyl-9,10-dihydro-9,10-ethanoanthracene-11(anti),
12(syn)- and 11(syn),12(anti)-dicarboxylates (3a and 3b) in a quanti-
tative yield (Eq 2).
(2)

824
Y. Okada et al.
FIGURE 2 ORTEP diagram of 3a.
Recrystallization of the mixture from ethyl acetate-hexane succeeded
to separate 3b as the first crystal and 3a as the second crystal. The
1
structures of 3a and 3b were assigned on the basis of their H NMR
1
spectrum. That is, the H NMR spectrum of 3a shows a signal for one
methyl (s, 3H) at 3.52, and the other methyl signal (s, 3H) at 3.63,
while that of 3b exhibits the corresponding peaks at 3.62 (s, 3H) and
3.63 (s, 3H). One methyl group of 3a is shifted to higher field, suggesting
that the methyl group is closed to the phosphorus functional group.
The stereochemistry of 3a was also confirmed by x-ray crystallographic
analysis (Figure 2).
Next we attempted the synthesis of a phosphine oxide monocar-
boxylic acid bearing the 9,10-dihydro-9,10-ethanoanthracene moiety.
Reaction of 1 with methyl acrylate in the presence of anhydrous
AlCl3 as a Lewis acid catalyst3 gave an isomer mixture of methyl
2-diphenylphosphinoyl-9,10-dihydro-9,10-ethanoanthracene-12- and
-11-carboxylates (4a, 4b, 4c, and 4d) in 95% yield (Eq. 3). Recrystal-
lization of the mixture from ethyl acetate-hexane succeeded to give
1
pure 4b as the first crystal. On the basis of the mentioned H NMR
spectrum of 2a,b and 3a,b, the structure of 4b was assigned as methyl
2-diphenylphosphinoyl-9,10-dihydro-9,10-ethanoanthracene-12(anti)-
carboxylate. That is, characteristic resonances of methyl, methylene
H11, and methine H12 protons in 4b were observed at 3.58 (s, 3H,

Synthesis of Phosphine Oxide-Carboxylic Acid Esters
825
OCH3), 2.16–2.22 (m, 1H, CH2) and 2.84–2.88 (m, 1H, CH2), and
1.95–2.00 (m, 1H, CH) ppm, respectively. Since the methyl signal is
not shifted to higher field, the methyl group is not situated close to the
phosphorus functional group.
(3)
And the methine proton, H12, is on the syn side to the phosphorus
functional group, so its signal shifts to the higher field.
Unfortunately, isolation of stereoisomers 4a, 4c, and 4d has not
succeeded yet.
Reduction of the isolated 4b with trichlorosilane afforded methyl
2-diphenylphosphino-9,10-dihydro-9,10-ethanoanthracene-12(anti)-
carboxylate (5b) in 79% yield. Subsequent hydrolysis of 5b with NaOH
gave racemic ( )-2-diphenylphosphino-9,10-dihydro-9,10-ethanoanth-
racene-12(anti)-carboxylic acid (6b) in 55% yield.
SCHEME 1
Thus, methyl 2-diphenylphosphinoyl-9,10-dihydro-9,10-ethanoanth-
racene-12(anti)-carboxylate (4b) was easily isolated by recrystallization
of the mixture of Diels-Alder adducts 4a–d from ethyl acetate-hexane
to derive the phosphine-carboxylic acid 6b. The structure of 4b was
confirmed on the basis of 1H NMR spectral data of 2a,b and 3a,b.
EXPERIMENTAL
General Procedures
1H NMR and 31P NMR spectra were obtained on a JEOL JNM-EX400
spectrometer in CDCl3 operating at 400 Mz and 160 Mz respectively,

826
Y. Okada et al.
with Me4Si and H3PO4 as internal standard. IR spectra were recorded
with a Shimadzu FTIR-8100A instrument. X-Ray analysis was made on
a Rigaku AFC7R and AFC6S diffractometers with graphite monochro-
mated Mo-K radiation (0.71069). Melting points were measured in
open capillary tubes and are uncorrected. All reactions were carried
out using degassed solvents under an argon atmosphere.
Materials
Tetrahydrofuran (THF) was purified by distillation from benzophenone
ketyl under an argon atmosphere before use. Dichloromethane was dis-
tilled from P2O5. 2-Bromoanthracene was synthesized by the successive
reduction of 2-bromoanthraquinone with stannous(II) chloride dihy-
drate in hydrochloric acid-acetic acid and with zinc powder in sodium
hydroxide aqueous solution containing catalytic amount of copper(II)
sulfonate, which was prepared by the reaction of 4-bromophthalic anhy-
dride with benzene in the presence of anhydrous AlCl3 and subsequent
ring closure with concentrated sulfuric acid.
Synthesis of 2-Anthryldiphenylphosphine oxide (1)
To a suspension of magnesium (0.29 g, 12 mmol) and a piece of io-
dine in dry THF (2 ml) was added dropwise a solution of 2-bromo-
anthracene (3.54 g, 10 mmol) in dry THF (15 ml) under an argon at-
mosphere. After the mixture was stirred at room temperature for 14 h,
chlorodiphenylphosphine (1.98 ml, 11 mmol) was added dropwise to
the mixture. After being stirred for 2 h at reflux, the reaction mixture
was quenched by the addition of 2M HCl. The mixture was extracted
with CHCl3, washed with water, dried over anhydrous Na2SO4, and
evaporated in vacuo. The residue was chromatographed on silica gel
using CHCl3 to give crude phosphine product. To an acetone solution
of the crude phosphine was added dropwise 30% hydrogen peroxide so-
lution (2 ml). After the mixture had been stirred at room temperature
for 12 h, the reaction mixture was extracted with CHCl3, washed with
water, dried over anhydrous Na2SO4, and evaporated in vacuo. The
residue was chromatographed on silica gel using CHCl3/AcOEt (1/1, v/v)
to give 1 (2.83 g, 8 mmol) in 89% yield, m.p. 205 C (AcOEt-hexane)
1
1
(lit. 206–207 C [5]); IR (KBr) cm 1117, 1179; H NMR 7.26–8.47
(m, 19H, ArH); 31P NMR 29.83 (s).
Synthesis of Dimethyl 2-Diphenylphosphinoyl-9,10-
dihydro-9,10-ethanoanthracene-11,11- (2a)
and 12,12-dicarboxylate (2b)
A mixture of 1 (1.51 g, 4.0 mmol), dimethyl malonate (0.91 ml,
8.0 mmol), paraformaldehyde (0.48 g, 16.0 mmol), and copper(II)

Synthesis of Phosphine Oxide-Carboxylic Acid Esters
827
acetate monohydrate (0.08 g, 0.4 mmol) in acetic acid (1.8 ml) and xy-
lene (1.8 ml) was heated at reflux for 12 h. The mixture was extracted
with CHCl3, washed with water, dried over anhydrous Na2SO4, and
evaporated in vacuo. The residue was passed through a short silica gel
column with CHCl3/AcOEt (1/1, v/v) to give the mixture 2a,b (1.86 g, 3.6
mmol) in 89% yield. The mixture was recrystallized from AcOEt-hexane
to give pure 2a and 2b.
Dimethyl 2-diphenylphosphinoyl-9,10-dihydro-9,10-ethanoanthra-
1
cene-12,12-dicarboxylate (2a) had m.p. 181 C; IR (KBr) cm 1734;
1H NMR 2.46 (dd, J = 2.9 and 13.1 Hz, 1H, CH2), 2.54 (dd, J = 2.9 and
13.1 Hz, 1H, CH2), 3.45 (s, 3H, OCH3), 3.57 (s, 3H, OCH3), 4.41 (t, 1H,
CH), 4.97 (s, 1H, CH), 7.12–7.66 (m, 17H, ArH); 31P NMR 29.68 (s);
Anal. calcd. for C32H27O5P: C, 73.55; H, 5.21. Found: C, 73.47; H, 5.19.
Crystal Data: monoclinic, C-centered, a = 13.300(5), b = 27.884(6), c =
3
˚
˚
˚
8.486(6) A, = 122.88(3) , V = 2642(2) A , Mo-K (0.71069 A), Resid-
uals: R = 0.050, Rw = 0.065.
Dimethyl 2-diphenylphosphinyl-9,10-dihydro-9,10-ethanoanthra-
1
cene-11,11-dicarboxylate (2b) had m.p. 215 C; IR (KBr) cm 1744;
1H NMR 2.35 (dd, J = 2.6 and 13.1 Hz, 1H, CH2), 2.62 (dd, J = 2.9
and 13.1 Hz, 1H, CH2), 3.58 (s, 3H, OCH3), 3.59 (s, 3H, OCH3), 4.36
(t, 1H, CH), 5.04 (s, 1H, CH), 7.11–7.66 (m, 17H, ArH); 31P NMR
29.95 (s); Anal. calcd. for C32H27O5P: C, 73.55; H, 5.21. Found: C,
73.35; H, 5.21.
Reaction of 1 with Dimethyl Fumarate
A solution of 1 (0.76 g, 2.0 mmol) and dimethyl fumarate (4.0 mmol) in
xylene (6 ml) was refluxed for 2 days. The mixture was chromatographed
on silica gel using CHCl3/AcOEt (1/1, v/v) to give a mixture of
dimethyl 2-diphenylphosphinyl-9,10-dihydro-9,10-ethanoanthracene-
11(anti),12(syn)- and -11(syn),12(anti)-dicarboxylate (3a and 3b) in a
quantitative yield. Recrystallization of the mixture from AcOEt-hexane
gave pure 3a and 3b.
3a: 0.61 g (21%); m.p. 166–167 C; 1H NMR 3.40–3.60 (m, 2H, CH),
3.52 (s, 3H OCH3), 3.63 (s, 3H, OCH3), 4.72 (br d, 1H, CH), 4.80 (br d,
1H, CH), 7.14-7.63 (m, 17H, ArH); 31P NMR 29.83 (s); Anal. calcd. for
C32H27O5P: C, 73.55; H, 5.21. Found: C, 73.53; H, 5.17. Crystal Data:
˚
orthorhombic, Primitive, a = 19.232(4), b = 8.887(2), c = 15.323(3) A,
3
˚
˚
V = 2619.0(9) A , Mo-K (0.71069 A), Residuals: R = 0.077, Rw = 0.055.
3b: 0.84 g (29%); m.p. 209–210 C; 1H NMR 3.37–3.38 (m, 1H, CH),
3.43–3.44 (m, 1H, CH), 3.62 (s, 3H, OCH3), 3.63 (s, 3H, OCH3), 4.72 (d,
J = 2.4 Hz, 1H, CH), 4.80 (d, J = 2.4 Hz, 1H, CH), 7.12–7.68 (m, 17H,
ArH); 31P NMR 29.83 (s); Anal. calcd. for C32H27O5P: C, 73.55; H, 5.21.
Found: C, 73.40; H, 5.20.

828
Y. Okada et al.
Reaction of 1 with Methyl Acrylate
To a cold solution of 1 (0.50 g, 1.41 mmol) and methyl acrylate
(0.25 ml, 2.82 mmol) in dry CH2Cl2 (15 ml) was added anhydrous alu-
minum chloride (0.39 g, 2.96 mmol). After the mixture was stirred at
room temperature for 3 days, the reaction mixture was poured into
2M HCl. The mixture was extracted with CHCl3, washed with water,
dried over anhydrous Na2SO4, and evaporated in vacuo. The residue
was chromatographed on silica gel using CHCl3/AcOEt (1/1, v/v) to give
a mixture of 4a–d in 95% yield. The mixture was recrystallized from
AcOEt-hexane to give pure 4b in 10% yield.
Methyl
2-diphenylphosphinoyl-9,10-dihydro-9,10-ethanoanthra-
1
cene-12(anti)-carboxylate (4b) had m.p. 203–204 C; H NMR 1.95–
2.00 (m, 1H, CH), 2.16–2.22 (m, 1H, CH2), 2.84–2.88 (m, 1H, CH2),
3.58 (s, 3H, OCH3), 4.40 (t, J = 2.4 Hz, 1H, CH), 4.69 (d, J = 2.4 Hz,
1H, CH), 7.09–7.68 (m, 17H, ArH); 31P NMR 30.06 (s); Anal. calcd.
for C30H25O3P: C, 77.57; H, 5.43. Found: C, 77.36; H, 5.42.
Reduction of 4b
To a solution of 4b (1.3 mmol) in dry benzene (20 ml) in a sealed tube
was added trichlorosilane (0.5 ml, 5.2 mmol) at 0 C under argon atmo-
sphere. After the mixture was heated at 65 C for 5 h, the reaction mix-
ture was poured into ice water. The mixture was extracted with CHCl3
and dried over anhydrous Na2SO4. This CHCl3 solution was passed
through a short silica gel column with CHCl3 to give methyl 2-diphenyl-
phosphino-9,10-dihydro-9,10-ethanoanthracene-12(anti)-carboxylate
(5b).
5b: 0.46 g (79%); 1H NMR 1.96–1.98 (m, 1H, CH2), 2.13–2.16 (m, 1H,
CH2), 2.83–2.85 (m, 1H, CH), 3.55 (s, 3H, OCH3), 4.33 (t, 1H, CH), 4.59
(d, J = 2.0 Hz, 1H, CH), 7.06–7.34 (m, 17H, ArH); 31P NMR
4.53 (s).
Hydrolysis of 5b
A solution of 5b (0.67 g, 1.5 mmol) and NaOH (0.30 g, 7.5 mmol) in
ethanol-H2O (1:1, 20 ml) was heated at reflux for 12 h under an argon
atmosphere. The reaction mixture was quenched by the addition of 2M
HCl, then extracted with CHCl3. The extract was dried over anhy-
drous Na2SO4, and evaporated in vacuo. The residue was passed
through a short silica gel column with CHCl3/AcOEt (1/1, v/v) to give
2-diphenylphosphino-9,10-dihydro-9,10-ethanoanthracene-12(anti)-
1
carboxylic acid (6b) in 55% yield: H NMR 1.90–1.95 (m, 1H, CH2),
2.04–2.08 (m, 1H, CH2), 2.78–2.82 (m, 1H, CH), 4.27 (br t, 1H, CH),
4.56 (d, J = 2.4 Hz, 1H, CH), 7.00–7.27 (m, 17H, ArH), 11.56 (br s, 1H,
COOH); 31P NMR
4.64 (s).

Synthesis of Phosphine Oxide-Carboxylic Acid Esters
829
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