Asymmetric induction in the electrochemical cross-coupling of aryl halides with α-chloropropionic acid derivatives catalyzed by nickel complexes

Full text of DOI:10.1021/jo971279d

7914
J . Org. Chem. 1997, 62, 7914-7915
Ta ble 1. Nick el-Ca ta lyzed Electr or ed u ctive Cou p lin g
Asym m etr ic In d u ction in th e
betw een r-Ch lor op r op ion ic Acid Der iva tives Bea r in g
Ch ir a l Au xilia r ies a n d Iod oben zen e or
m -Br om o-r,r,r-tr iflu or otolu en ea
Electr och em ica l Cr oss-Cou p lin g of Ar yl
Ha lid es w ith r-Ch lor op r op ion ic Acid
Der iva tives Ca ta lyzed by Nick el Com p lexes
isolated
yieldsb
Muriel Durandetti,* J acques Pe´richon, and
J ean-Yves Ne´de´lec
chiral auxiliary
(Y*) in
entry ClCH(CH3)COY* ArX product
(%) of
coupling
ee (%)
major
(de (%))c confign
Laboratoire d’Electrochimie, Catalyse et Synthe`se
Organique, UMR 28 CNRS, 2, rue Henri-Dunant, 94320
Thiais, France
1
2
3
4
5
6
7
8
9
10
11
12
13
14
1
1
2
3
3
4
5
5
6
7
7
8
9
11
12
12
11
12
11
11
12
11
11
12
12
11
11
60
50
70
50
70
41
45
50
60
57
51
51
64
50
19 (30)
24
45 (50)
5 (10)
3 (6)
1 (6)
5
13
6 (6)
90 (96)
87 (92)
80 (92)
17 (20)
52 (63)
S
S
S
S
Received J uly 15, 1997
S
Several 2-arylpropanoic acids are known as important
nonsteroidal pharmaceuticals exhibiting antiinflamma-
tory activity,1 and many methods of preparation of these
acids have been developed.1,2 These methods lead gener-
ally to racemic compounds, but it has been shown3 that
a higher activity is associated with the S configuration
at the chiral center of, for example, 2-(3-phenoxyphenyl)-
propanoic acid (fenoprofen) or 2-(6-methoxy-2-naphthyl)-
propanoic acid (naproxen).3 Different approaches de-
scribed2 so far to obtain the most active enantiomer
include chemical resolution,4 microbial transformation,5
and various asymmetric syntheses.6
We have previously described the electroreductive
cross-coupling of R-halogeno esters with aryl halides7
catalyzed by nickel complexes in combination with the
sacrificial anode process and leading to R-arylpropionic
esters in one operation in good to high yields (eq 1). The
scope and the mechanism8 of these reactions have already
been reported. In this paper, we now report on a remote
asymmetric induction in this reaction using chiral aux-
iliaries.
R
R
R
R
R
R
S
R
R
10
a
b
For experimental conditions, see text. Based on initial ArX,
after conversion of the product into the corresponding 2-arylpro-
panoic acid methyl ester. All products gave satisfactory NMR and
mass spectra. c Ee was obtained by polarimetry on the methyl ester
derivative; de was determined by GC of the crude product.
as the electrohydrodimerization of cinnamate esters,9 the
Kolbe electrolysis of malonic acids derivatives,10 or the
reduction of glyoxylic acid derivatives.11,12
The auxiliaries used in this study are given in Chart
1. Compounds 1-6 are commercially available. Com-
pound 7 was prepared in one step by fusing (-)-ephe-
drinium chloride with urea13 (yield 50%; [R]D ) -45 (c )
3.5, methanol) (lit. [R]25 ) -44.513)). The same proce-
D
dure was applied to prepare 8, 9, and 10, from (+)-
ephedrine, (2S,3R)-norephedrine, and (R)-2-phenylglyci-
nol, respectively. The 2-chloropropanoic acid derivatives
were obtained in 70-100% yield by reacting (rac)-2-
chloropropanoyl chloride with either the alcohols 1 to 6
or with the lithium salts of 7 to 10. We used either
iodobenzene (11) or m-bromo-R,R,R-trifluorotoluene (12),
which are reactive enough for the coupling reaction to
be conducted at room temperature.
The general procedure is as follows, on the basis of our
previous investigations: freshly distilled DMF (40 mL),
Bu4NBF4 (0.6 mmol), NiBr2bipy (1 mmol), the arylhalide
ArX (10 mmol), and a portion of the R-chloropropionic
acid derivative RX (ca. 0.3 mmol) were introduced in a
one-compartment cell fitted with an aluminum rod as the
anode and a nickel sponge as the cathode (cathode area:
ca. 20 cm2). The electricity was supplied at constant
current intensity of 0.25 A, and RX was added constantly
to the solution via a syringe pump at a rate of 4 mmol/h.
We first tried to obtain chiral products by using the
commercially available chiral methyl (R)- or (S)-2-chlo-
ropropanoates in the coupling with iodobenzene but we
only obtained the racemic R-arylpropionic ester. We then
attempted to induce the chirality remotely using chiral
auxiliaries attached to the carboxylic group. There are
some reports in the literature on the successful use of
chiral auxiliaries in anodic or cathodic syntheses such
(1) Rieu, J . P.; Boucherle, A.; Cousse, H.; Mouzin, G. Tetrahedron
1986, 42, 4095.
(2) (a) Giordano, C.; Castaldi, G.; Uggeri, F. Angew. Chem., Int. Ed.
Engl. 1984, 23, 413. (b) Sonawane, H. R.; Bellur, N. S.; Ahuja, J . R.;
Kulkarni, D. G. Tetrahedron: Asymmetry, 1992, 3, 163.
(3) Shen, T. Y. Angew. Chem., Int. Ed. Engl. 1972, 11, 460.
(4) (a) Ahmar, M.; Girard, C.; Bloch, R. Tetrahedron Lett. 1989, 30,
7053. (b) Garcia, M.; del Campo, C.; Clama, E. F.; Sanchez-Montero,
J . M.; Sinistera, J . V. Tetrahedron 1993, 49, 8433.
(9) (a) Utley, J . H. P.; Gu¨llu¨, M.; Motevalli, M. J . Chem. Soc., Perkin
Trans. 1 1995, 1961. (b) Fussing, I.; Gu¨llu¨, M.; Hammerich, O.;
Hussain, A.; Nielsen, M. F.; Utley, J . H. P. J . Chem. Soc., Perkin Trans.
2 1996, 649.
(5) (a) Miyamoto, K.; Tsuchiya, S.; Ohta, H. J . Fluorine Chem. 1992,
59, 225. (b) Ogawa, Y.; Yamazaki, Y.; Okuno, H. Bioorganic Med. Chem.
Lett. 1994, 4, 757.
(6) (a) Parinello, G.; Stille, J . K. J . Am. Chem. Soc. 1987, 109, 7122.
(b) Castaldi, G.; Cavicchioli, S.; Giordano C., Uggeri, F. J . Org. Chem.
1987, 52, 3018. (c) Honda, Y.; Ori, A.; Tsuchihashi, G. Bull. Chem.
Soc. J pn. 1987, 60, 1027. (d) Lubell, W. D.; Rapoport, H. J . Am. Chem.
Soc. 1988, 110, 7447. (e) Galarini, R.; Musco, A.; Pontellini, R.; Santi,
R. J . Molecular Catalysis 1992, 72, L11.
(7) (a) Durandetti, M.; Sibille, S.; Ne´de´lec, J .-Y.; Pe´richon, J . Synth.
Commun. 1994, 2, 145. (b) Durandetti, M.; Ne´de´lec, J .-Y.; Pe´richon,
J . J . Org. Chem. 1996, 61, 1748.
(8) Durandetti, M.; Devaud, M.; Pe´richon, J . New J . Chem. 1996,
20, 659.
(10) Scha¨fer, H. J .; Klotz-Berendes, B.; Letzel, M.; Zielinski, C.;
Schoo, N.; Lo¨hl, T.; Ho¨weler, U. Novel Trends in Electro-organic
synthesis; Torii, S., Ed.; Kodansha: Tokyo, p 149.
(11) (a) Zielinski, C.; Scha¨fer H. J . Tetrahedron Lett. 1994, 35, 5621.
(b) Scha¨fer, H. J . Electrochem. Soc. Abstracts, Los Angeles Meeting,
1996, p 1221.
(12) Other approaches have been reported for asymmetric elec-
trosyntheses such as use of chiral electrodes or chiral solvents or chiral
supporting electrolytes. For rewiews, see: Tallec, A. Bull. Soc. Chim.
Fr. 1985, 15, 743. Nonaka, T. In Organic Electrochemistry, 3rd ed.;
Baizer, M. M., Ed.; Marcel Dekker: New York, 1991; p 1131.
(13) (a) Close, W. J . J . Org. Chem. 1950, 15, 1131. (b) Roder, H.;
Helmchen, G.; Peters, E. M.; Peters, K.; von Schnering, H.-G. Angew.
Chem., Int. Ed. Engl. 1984, 23, 898.
S0022-3263(97)01279-6 CCC: $14.00 © 1997 American Chemical Society

Communications
J . Org. Chem., Vol. 62, No. 23, 1997 7915
Ta ble 2. Nick el-Ca ta lyzed Electr or ed u ctive Cou p lin g betw een th e Ch ir a l Im id e P r ep a r ed fr om 8 a n d Ar om a tic
Br om id esa
a
b
For experimental conditions, see text. Based on initial ArX, after conversion of the product into the corresponding 2-arylpropanoic
acid methyl ester. All products gave satisfactory NMR and mass spectra. c Ee was obtained by polarimetry on the methyl ester derivative;
de was determined by GC of the crude product.
Ch a r t 1
Ch a r t 2
6 are poor inductors in this coupling reaction, since the
product was obtained with low (<15%) diastereomeric
excess (entries 4-9, Table 1). With a menthol skeleton
a higher de can be obtained providing that a phenyl group
is on C8 (entries 2 and 3, Table 1), in keeping with other
studies.15,16 Medium de was obtained with the oxazoli-
dinone as chiral auxiliary, and with a phenyl group close
enough to the R-position to the propionic acid derivative
(10 in Chart 1). The best results were, however, obtained
from imidazolidinone derivatives. In addition to the high
asymmetric induction obtained, the easy access to both
enantiomers 7 and 8 of the imidazolidinone from (-)- or
(+)-ephedrine, respectively, makes this process efficient
to obtain the R or S isomer of the desired R-arylpropionic
acid.
We have previously shown7b that when aryl bromides
are used in this type of coupling the reaction may be best
conducted at 60 °C. So we carried out the coupling
between m-bromo-R,R,R-trifluorotoluene and the chiral
imidazolidinone from 8 at 60 °C in order to check the
possible effect of the temperature on de. We obtained
68% of R-[m-(trifluoromethyl)phenyl]propionic acid de-
rivative, with a de of 88% (S major isomer), compared to
a de of 92% at room temperature (entry 12, Table 1).
Therefore, an increase of the reaction temperature does
not significantly affect the diastereoselectivity of the
cross-coupling reaction.
We finally applied the reaction to the preparation of
two commonly used drugs (S)-naproxen (13) and (S)-
flurbiprofen (14). Results are reported in Table 2. These
compounds were obtained in good yield and high dia-
stereomeric excess at room temperature using only 1
equiv of R-chloroimide prepared from 8. Since the
diastereomers can be easily separated by silica gel
column chromatography, the acid can thus be obtained
enantiomerically pure.
The electrolyses were run at room temperature under
argon until the aromatic halide was totally consumed.
Results are given in Table 1.
The diastereomer ratio (de) was determined by gas
chromatography and by NMR. The enantiomeric excess
was determined by polarimetry after conversion of the
product, either an ester (entries 1-9, Table 1) or an imide
(entries 10-14, Table 1), into the corresponding 2-aryl-
propanoic acid methyl ester by reaction in methanol in
the presence of K2CO3. No racemization occurred during
this reaction. The measured rotation for the methyl ester
derivative of the 2-arylpropanoic acid obtained was
compared to the value found in the literature, i.e.,
+103.5° for (S)-methyl R-phenyl propionate14 and +53°
for (S)-methyl R-[m-(trifluoromethyl)phenyl]propionate.5a
The product was also obtained in the carboxylic acid form,
without racemization, by reaction of the crude product
with LiOH in THF and then hydrolysis.
Ack n ow led gm en t . We gratefully acknowledge
Rhoˆne-Poulenc Rorer and Electricite de France for
financial support.
J O971279D
Chemical yields are moderate to good and were not
optimized for these model reactions. The auxiliaries 3-
(15) (a) d’Angelo, J .; Maddaluno, J . J . Am. Chem. Soc. 1986, 108,
8112. (b) Whitesell, J . K. Chem. Rev. 1992, 92, 953.
(14) Angres, I.; Zieger, H. E. J . Org. Chem. 1975, 40, 1457.
(16) Corey, E. J .; Ensley, H. E. J . Am. Chem. Soc. 1975, 97, 6908.