Stereoselective synthesis of (R)- and (S)-4-methoxydalbergione via asymmetric catalytic hydrogenation

Article abstract of DOI:10.1021/ol990961m

(Matrix presented) (R)-(+)-and (S)-(-)-4-methoxydalbergione were synthesized in seven steps with an enantiomeric excess of up to 95% using an asymmetric catalytic hydrogenation step with [Rh((S,S)-bdpp)(NBD)]CIO₄ or [Rh((R,R)-bdpp)(NBD)]CIO

Full text of DOI:10.1021/ol990961m

ORGANIC
LETTERS
1999
Vol. 1, No. 8
1283-1285
Stereoselective Synthesis of (R)- and
(S)-4-Methoxydalbergione via
Asymmetric Catalytic Hydrogenation
Philippe Bissel,† Abdesslame Nazih,† Rafae1l Sablong,‡ and
,†
Jean-Pierre Lepoittevin*
Laboratoire de Dermatochimie, UniVersite´ Louis Pasteur, Clinique Dermatologique,
CHU, F-67091 Strasbourg, France, and Laboratoire de Chimie des Me´taux de
Transition et Catalyse, UniVersite´ Louis Pasteur, 4, rue Blaise Pascal,
F-67070 Strasbourg, France
jplepoit@chimie.u-strasbg.fr
Received August 19, 1999
ABSTRACT
(R)-(+)- and (S)-(−)-4-methoxydalbergione were synthesized in seven steps with an enantiomeric excess of up to 95% using an asymmetric
catalytic hydrogenation step with [Rh((S,S)-bdpp)(NBD)]ClO or [Rh((R,R)-bdpp)(NBD)]ClO , respectively, at a hydrogen pressure of 80 bar.
4
4
This method should give an easy access to the other members of the dalbergione family.
During the course of our studies on the stereospecificity of
the reactions involved in allergic contact dermatitis (ACD),1
we became interested in dalbergiones, as it seemed from the
literature that patients sensitized to one enantiomer usually
do not react to the other.2 In the case of R-methylene-γ-
butyrolactones, the stereospecificity of the allergic reaction
has been explained by the stereoselective addition of nu-
cleophilic protein residues on the lactone3 and it has been
shown that the stereoselectivity of addition parallels enan-
tioselectivity in the allergic reaction.4
Dalbergiones belong to a small family of quinones found
in tropical woods5a-b mainly in Dalbergia and Machaerium
species.6 These optically active quinones have been shown
to exist uniquely in either the S or R configuration, except
for 4-methoxyalbergione, which can be found in either form,
depending on its origin. The R product, 1a, is found in
Dalbergia latifolia Roxb.,7 Dalbergia nigra Allem.,8 and
Dalbergia retusa Hemsl.,8 while the S isomer, 1b, is present
in Dalbergia melanoxylon Guill & Perr.9 and Dalbergia
boroni Baker (Figure 1).10
However, quinones are thought to react with proteins via
a 1,4-Michael addition, without creating a new asymmetric
center, and the above explanation cannot therefore be applied
to these molecules.
† Laboratoire de Dermatochimie.
‡ Laboratoire de Chimie des Me´taux de Transition et Catalyse.
(1) (a) Benezra, C.; Stampf, J. L.; Barbier, P.; Ducombs, G. Contact
Dermatitis 1995, 13, 110. (b) Mattes, H.; Hamada, K.; Benezra, C. J. Med.
Chem. 1987, 30, 1948.
(2) Morgan, J. W. W.; Orster, R. J.; Wilkinson, D. S. Br. J. Ind. Med.
1968, 25, 119.
Figure 1. Structures of 4-methoxydalbergiones.
(3) Talaga, P.; Benezra, C.; Stampf, J.-L. Bioorg. Chem. 1990, 18, 199.
(4) Talaga, P.; Schaeffer, M.; Mattes, H.; Benezra, C.; Stampf, J.-L.
Tetrahedron 1989, 45, 5029.
Several racemic syntheses of 4-methoxyalbergione, based
on Claisen transposition,11 Pechmann condensation,12 reduc-
10.1021/ol990961m CCC: $18.00 © 1999 American Chemical Society
Published on Web 09/24/1999

tion of 7-methoxycoumarin,13 or regioselective allylation,14
have been reported in the literature. However, these methods
cannot be used to produce optically active molecules and
we have not found any reports of attempts to prepare these
quinones in an enantiomeric form, probably because of the
difficult access to such an asymmetric center. We therefore
turned our attention to a new synthetic access to these
molecules permitting the introduction of an induction step.
In the past few years, methods for the asymmetric
hydrogenation of double bonds, using optically active
complexes of transition metals, have been extensively
developed.15 This approach has been successfully applied
to the preparation of optically active amino acids, via the
reduction of acrylic acid derivatives,15 and to the asymmetric
reduction of allylic alcohols,16 catalyzed by chiral rhodium
or ruthenium complexes.
Despite the presence of two rather similar aromatic
functions on the allylic alcohol 2, the large enantiomeric
excess obtained opens the way to the synthesis of dalber-
gione-type molecules. We now report the stereoselective
synthesis of (R)- and (S)-4-methoxyalbergione, thus provid-
ing a new access to this family of optically active quinones.
7-Methoxy-4-phenylcoumarin (5)18 was prepared from 2-hy-
droxy-4-methoxybenzophenone (4) and ((ethoxycarbonyl)-
methylene)triphenylphosphorane by a Wittig-type reaction
in refluxing toluene with a 78% yield (Scheme 2). The
Scheme 2a
We have previously investigated whether such an approach
could give access to optically active quinones of the
dalbergione type and found that intermediates 3a and 3b
could be prepared from the allylic alcohol 2 with an
enantiomeric excess of up to 95%, via an asymmetric
hydrogenation step (Scheme 1).17 The enantiomeric excess
a Reagents, conditions, and yields: (a) Ph3PdCHCO2Et, toluene,
reflux, 10 days, 78%; (b) LiAlH4, THF/Et2O, 0 °C, 97%; (c) MeI,
K2CO3, acetone, 100%.
Scheme 1a
coumarin 5 was then reduced at 0 °C using LiAlH4 in a 1/1
mixture of ether and THF to give, in 97% yield, the allylic
alcohol 6.19 Note that the same reaction carried out in THF
alone gave an unseparable mixture of allylic and saturated
alcohols. Subsequent treatment of 6 with MeI and K2CO3 in
refluxing acetone gave the key intermediate 2.
The induction step was carried out on a 2 mmol scale,
using either [Rh((R,R)-bdpp)(NBD)]ClO4 or [Rh((S,S)-bdpp)-
(NBD)]ClO4 as catalyst (substrate/catalyst 10/1) at an
hydrogen pressure of 80 bar with a reaction time of 7 days.
Thus, hydrogenation of 2 provided selective access to both
enantiomers 3a and 3b with enantiomeric excess up to 95%.20
a Reagents: (a) H2, MeOH, [Rh((S,S)-bdpp)(NBD)]ClO4; (b) H2,
MeOH, [Rh((R,R)-bdpp)(NBD)]ClO4.
1
was determined by H NMR using tris[3-(trifluoromethyl-
hydroxymethylene)-(+)-camphorato]europium(III), but at
that time the absolute configuration could not be determined.
(14) Mukerjee, S. K.; Saraja, T.; Seshadri, T. R. Indian J. Chem. 1970,
8, 21.
(15) For review articles see: (a) Valentine, D.; Scott, J. W. Synthesis
1978, 329. (b) Caplar, V.; Comisso, G.; Sunjic, V. Synthesis 1981, 85. (c)
Noyori, R. Chem. Soc. ReV. 1989, 18, 187. (d) Brown, J. M. Chem. Soc.
ReV. 1993, 22, 25.
(5) (a) Hausen, B. Woods Injurious to Human Health; de Gruyter: Berlin.
1981. (b) Woods, B.; Calnan, C. D. Br. J. Dermatol. 1976, 94, 1 (Suppl.
13).
(6) (a) Benezra, C.; Ducombs, G.; Sell, Y.; Foussereau, J. Plant Contact
Dermatitis; Decker: Toronto, Philadelphia, 1985. (b) Lepoittevin, J.-P.;
Benezra, C. Pharm. Weekbl., Sci. Ed. 1991, 13, 119.
(7) Eyton, W. B.; Ollis, W. D.; Sutherland, I. O.; Jackman, L. M.;
Gottlieb, O. R.; Magalhaes, M. T. Proc. Chem. Soc. 1962, 301.
(8) (a) Eyton, W. B.; Ollis, W. D.; Sutherland, I. O.; Gottlieb, O. R.;
Magalhaes, M. T.; Jackman, L. M. Tetrahedron 1965, 21, 2683. (b) Eyton,
W. B.; Ollis, W. D.; Fineberg, M.; Gottlieb, O. R.; Salignac de Souza
Guimaraes, I.; Magalhaes, M. T. Tetrahedron 1965, 21, 2697.
(9) (a) Donnely, B. J.; Donnely, D. M. X.; O’Sullivan, A. M.; Prender-
gast, J. P. Tetrahedron 1969, 25, 4409. (b) Donnely, D. M. X.; O’Reilly,
J. Phytochemistry 1975, 14, 2287.
(10) Donnelly, B. J.; Donnely, D. M. X.; Sharkey, C. B. Phytochemistry
1965, 4, 337.
(11) Barnes, M. F.; Ollis, W. D.; Sutherland, I. O.; Gottlieb, O. R.;
Magalhaes, M. T. Tetrahedron 1965, 21, 2707.
(12) Mageswaran, S.; Ollis, W. D.; Roberts, R. J.; Sutherland, I. O.
Tetrahedron Lett. 1969, 34, 2897.
(13) Narata, Y.; Uno, H.; Maryjama, K. Nippon Kagaku Kaishi 1981,
831.
(16) Takaya, H.; et al. J. Am. Chem. Soc. 1987, 109, 1596.
(17) Bissel, P.; Sablong, R.; Lepoittevin, J.-P. Tetrahedron Asym. 1995,
6, 835.
(18) 7-Methoxy-4-phenylcoumarin (5): white crystals, mp 105-106 °C;
1H NMR (CDCl3, 200 MHz) δ 3.86 (s, 3H), 6.15 (s, 1H), 6.40 (dd, 1H, J
) 9.0 Hz, J ) 2.4 Hz), 6.50 (d, 1H, J ) 2.4 Hz), 7.45-7.86 (m, 6H). 13
C
NMR (CDCl3, 50 MHz) δ 55.7, 101.1, 111.7, 112.2, 112.4, 128.3, 128.7,
129.5, 135.5, 155.7, 155.9, 161.0, 161.1, 182.7. Anal. Calcd for C16H12O3:
C, 76.18; H, 4.80. Found: C, 75.94; H, 4.71.
(19) 3-(2′-Hydroxy-4′-methoxyphenyl)-3-phenyl-2-propenol (6): white
crystals, mp 136-137 °C; 1H NMR ((CD3)2CO, 200 MHz) δ 2.85 (bt, 1H,
J ) 6.5 Hz), 3.78 (s, 3H), 4.07 (dd, tlike, J ) 6.6 Hz), 6.33 (t, J ) 6.6 Hz),
6.46-6.53 (m, 2H), 6.88 (d, 1H, J ) 8.2 Hz), 7.20-7.29 (m, 5H), 7.92 (s,
1H); 13C NMR ((CD3)2CO, 50 MHz) δ 55.5, 61.0, 102.5, 106.2, 119.4,
127.5, 127.8, 128.9, 130.9, 132.6, 139.0, 142.8, 156.5, 161.4. Anal. Calcd
for C16H16O3: C, 74.98; H, 6.29. Found: C, 74.59; H, 6.39.
(20) The enantiomeric excess was determined using 1H NMR by adding
0.4 equiv of tris[3-(trifluoromethylhydroxymethylene)-(+)-camphorato]-
europium(III) to 5 mg of 3a or 3b in CDCl3 (0.5 mL). 3a: ee ) 95%, [R]D
) +49° (c ) 0.82, CHCl3). 3b: ee ) 94%, [R]D ) -49° (c ) 0.82, CHCl3).
1284
Org. Lett., Vol. 1, No. 8, 1999

Alcohols 3a and 3b were then transformed into seleno-
ethers21 7a and 7b, respectively, by reaction with PhSeCN
and n-Bu3P in THF22 with 81% yields (Scheme 3); subse-
4-Methoxyalbergiones 1a and 1b were obtained by selec-
tive deprotection of a methoxy group with 1 equiv of BBr3
in CH2Cl2 at 0 °C and oxidation of the crude phenols with
salcomine25 in DMF under oxygen. The sign and absolute
value of the optical rotation of the products26 showed them
to be the (+)-(R)-4-methoxyalbergione 1a and the (-)-(S)-
4-methoxyalbergione 1b (synthesized in seven steps) and
confirmed the enantiomeric excess of about 95%.
Thus, hydrogenation of the intermediate 2 using either
[Rh((S,S)-bdpp)(NBD)]ClO4 or [Rh((R,R)-bdpp)(NBD)]ClO4
gives access, respectively, to the R or S chiral center, yielding
products of similar optical purity, and this method should
give an easy access to the other members of the dalbergione
family.
Scheme 3a
OL990961M
(24) 3-(2′,4′-Dimethoxyphenyl)-3-phenyl-1-propene (8): colorless oil.
1H NMR (CDCl3, 200 MHz): δ 3.74 (s, 3H), 3.80 (s, 3H), 4.89 (ddd, dt
like, 1H, J ) 1.6 Hz, J ) 1.6 Hz, J ) 17.0 Hz), 5.07 (ddd, dt like, 1H, J
) 6.6 Hz, J ) 1.6 Hz, J ) 1.6 Hz), 5.17 (ddd, dt like, 1H, J ) 1.6 Hz, J
) 1.6 Hz, J ) 10 Hz), 6.37 (ddd, 1H, J ) 6.6 Hz, J ) 10.0 Hz, J ) 17
Hz), 6.43-6.48 (m, 2H), 7.01 (d, 1H, J ) 9.0 Hz), 7.16-7.25 (m, 5H).13C
NMR (CDCl3, 50 MHz): δ 47.3, 55.4, 55.6, 99.0, 104.2, 115.8, 124.4,
126.0, 128.2, 128.7, 129.8, 140.8, 143.6, 158.0, 159.6. Anal. Calcd for
C17H18O2: C, 80.28; H, 7.13. Found: C, 80.20; H, 7.26. 8a: [R]D ) +1°
(c ) 1.0, CHCl3). 8b: [R]D ) -1° (c ) 1.0, CHCl3).
a Reagents, conditions, and yields: (a) PhSeCN, n-Bu3P, THF,
81%; (b) NaIO4, NaHCO3, H2O/MeOH, 100%; (c) BBr3, CH2Cl2,
0 °C; (d) salcomine, O2, DMF.
(25) Van Dort, H. M.; Geursen, H. J. Recl. TraV. Chim. Pays-Bas 1967,
86, 520. De Jonge, C. R.; Hageman, H. J.; Hoentjen, G.; Mijs, W. J. Org.
Synth. 1983, 57, 78.
quent treatment of these selenoethers with NaIO4 in a mixture
23
of water and MeOH in the presence of NaHCO3 gave a
(26) 4-Methoxydalbergione 1: To a solution of 8a or 8b (100 mg, 0.39
mmol) in CH2Cl2 (5 mL) at 0 °C was added a solution of BBr3 in CH2Cl2
(0.4 mL, 1 equiv, 0.40 mmol). The reaction mixture was stirred for 1 h,
hydrolyzed using a saturated solution of NaHCO3 (1 mL), and filtered on
Celite; then CH2Cl2 (10 mL) was added. The organic layer was washed
with water (2 × 10 mL), dried over MgSO4, and concentrated under reduced
pressure. To the crude quinol in distilled DMF (3 mL) under an atmosphere
of O2 was added a suspension of salcomine (13 mg, 0.039 mmol) in DMF
(2 mL). The reaction mixture was stirred for 4 h and concentrated under
reduced pressure. The crude quinone was purified by chromatography over
silica using degassed solvents (hexane 80%, AcOEt 20%), then crystallized
in cyclohexane to give 62 mg (0.24 mmol, 61% yield) of dalbergione 1a
or 1b as yellow crystals. 1H NMR (CDCl3, 400 MHz): δ 3.81 (s, 3H),
4.93 (ddd, dt like, 1H, J ) 1.7 Hz, J ) 1.7 Hz, H ) 6.8 Hz), 5.00 (ddd, dt
like, J ) 1.7 Hz, J ) 1.7 Hz, J ) 17.0 Hz), 5.27 (ddd, dt like, 1H, J ) 1.7
Hz, J ) 1.7 Hz, J ) 10.0 Hz), 5.91 (s, 1H), 6.10 (ddd, 1H, J ) 6.8 Hz, J
) 10.0 Hz, J ) 17.0 Hz), 6.48 (s, 1H), 7.18-7.34 (m, 5H). 13C NMR
(CDCl3, 50 MHz) δ 47.1, 55.3, 107.0, 118.2, 127.2, 128.6, 128.8, 131.6,
137.3, 139.4, 151.1, 158.6, 182.4, 186.3. (R)-4-Methoxydalbergione 1a: mp
115-116 °C (lit.8 mp 114-116 °C), [R]D ) +13° (c ) 1.3, CHCl3, lit.8
[R]D ) +13°). (S)-4-methoxydalbergione 1b: mp 116-117 °C (lit.10 mp
118-119 °C), [R]D ) -12° (c ) 1.3, CHCl3, lit.10 [R]D ) -13°).
quantitative yield of compounds 8a and 8b.24
(21) 1-Phenylseleno-3-(2′,4′-dimethoxyphenyl)-3-phenylpropane
(7): To a solution of alcohol 3a or 3b (500 mg, 1.8 mmol) in THF (20
mL) was added PhSeCN (669 mg, 2 equiv, 3.7 mmol) and n-Bu3P (0.92
mL, 2 equiv, 3.7 mmol). The reaction mixture was stirred for 2 h, the solvent
removed under reduced pressure, and the crude product purified by column
chromatography over silica (hexane 90%, AcOEt 10%) to give 600 mg
(1.5 mmol, 81% yield) of the seleno derivative 7a or 7b, respectively, as a
1
colorless oil. H NMR (CDCl3, 200 MHz): δ 2.34-2.43 (m, 2H), 2.80-
2.88 (m, 2H), 3.74 (s, 3H), 3.77 (s, 3H), 4.28 (t, 1H, J ) 7.6 Hz), 6.39-
6.45 (m, 2H), 7.02 (d, 1H, J5′,6′ ) 9.0 Hz), 7.14-7.25 (m, 8H), 7.40-7.45
(m, 2H). 13C NMR (CDCl3, 50 MHz): δ 26.1, 35.6, 43.3, 55.4, 55.5, 98.8,
104.2, 125.2, 126.0, 126.6, 128.2, 128.3, 129.0, 130.6, 132.4, 144.4, 158.1,
159.3. 77Se NMR (CDCl3, 76 MHz): δ 24.0. Anal. Calcd for C23H24O2Se:
C, 67.15; H, 5.88. Found: C, 67.21; H, 5.85. 7a: [R]D ) +7° (c ) 0.94,
CHCl3). 7b: [R]D ) -7° (c ) 0.94, CHCl3).
(22) Paquette, L. A.; Poupart, M. A. J. Org. Chem. 1993, 58, 4245.
(23) Reich, H. J.; Reich, I. L.; Rengo, J. M. J. Am. Chem. Soc. 1973,
95, 5813.
Org. Lett., Vol. 1, No. 8, 1999
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