N-methyl-3,4-dihydro-[3,1]oxazinoacridine, a useful intermediate in the synthesis of polysubstituted acridines

Article abstract of DOI:10.1081/SCC-100104417

3,4-Dihydro-4-methyl-1H-[3,1]oxazinoacridine was prepared in four steps from 3-aminoacridine. DDQ induced opening of the dihydrooxazine ring yielded the 3-methylamino-4-formyl derivative. The same strategy was applied to 11-aminobenzo-[b][1,7]phenanthroli

Full text of DOI:10.1081/SCC-100104417

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N-METHYL-3,4-DIHYDRO-[3,1]OXAZINOACRIDINE,
A USEFUL INTERMEDIATE IN THE SYNTHESIS OF
POLYSUBSTITUTED ACRIDINES
Franck Charmantray a , Martine Demeunynck b , Abderrahim Wardani c & Jean Lhomme a
a Université Joseph Fourier , Laboratoire de Chimie Bioorganique, LEDSS, Grenoble,
cedex 9, 38041, France
b Université Joseph Fourier , Laboratoire de Chimie Bioorganique, LEDSS, Grenoble,
cedex 9, 38041, France
c Département de Chimie , Université Chouaib Doukkali, Faculté des Sciences , El
Jadida, Maroc
Published online: 09 Nov 2006.
To cite this article: Franck Charmantray , Martine Demeunynck , Abderrahim Wardani & Jean Lhomme (2001) N-
METHYL-3,4-DIHYDRO-[3,1]OXAZINOACRIDINE, A USEFUL INTERMEDIATE IN THE SYNTHESIS OF POLYSUBSTITUTED
ACRIDINES, Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
31:13, 2001-2009, DOI: 10.1081/SCC-100104417
To link to this article: http://dx.doi.org/10.1081/SCC-100104417
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SYNTHETIC COMMUNICATIONS, 31(13), 2001–2009 (2001)
N-METHYL-3,4-DIHYDRO-[3,1]OXAZINO-
ACRIDINE, A USEFUL INTERMEDIATE IN
THE SYNTHESIS OF POLYSUBSTITUTED
ACRIDINES
1
FranckCharmantray, Martine Demeunynck,1,
*
Abderrahim Wardani,2 and Jean Lhomme1
1Laboratoire de Chimie Bioorganique, LEDSS, Universite
Joseph Fourier, 38041 Grenoble, cedex 9, France
2Universite Chouaib Doukkali, Faculte des Sciences,
Departement de Chimie, El Jadida, Maroc
ABSTRACT
3,4-Dihydro-4-methyl-lH-[3,1]oxazinoacridine was prepared
in four steps from 3-aminoacridine. DDQ induced opening
of the dihydrooxazine ring yielded the 3-methylamino-4-
formyl derivative. The same strategy was applied to 11-ami-
nobenzo-[b][1,7]phenanthroline.
Polysubstituted acridines constitute a large family of compounds of
biological interest (antitumor, antimalarial agents . . .). In most cases, the
substituents are introduced in an early stage of the synthesis, prior to the
formation of the acridine ring. In the course of a program dedicated to the
search for new antitumor agents, we applied electrophilic aromatic substitu-
tion to introduce various substituents onto the acridine ring.1–4 The reac-
tions were regioselective. 3-Aminoacridine (1) or 3,6-diaminoacridine
*Corresponding author.
2001
Copyright & 2001 by Marcel Dekker, Inc.
www.dekker.com

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(proflavine) were shown to react at positions 4 or 4 and 5, ortho to the
amino groups. No reaction products corresponding to substitution in the
2 (and 7) position could be detected. We took advantage of this reactivity
and regioselectivity to prepare a new heterocycle, 10-aminobenzo[b][1,7]-
phenanthroline (2), from proflavine.5
Reaction of the amino-heterocycles 1 and 2 with formaldehyde was
also studied. Depending on the stoichiometry in formaldehyde and on the
nature of the acid used as the solvent, various types of molecules were
obtained: Troger’s bases, tetrahydroquinazoline and dihydro-[3,1]oxazine
derivatives.6,7 We report here the synthesis of the N-methyl analogues of
dihydro-[3,1]oxazine (9 and 10), prepared from 3-methylaminoacridine 7
and 10-methylaminobenzo[b][1,7]phenanthroline 8 and show that DDQ
induced ring cleavage yields the corresponding aldehydes in good yields.
RESULTS AND DISCUSSION
The N-methylamino heterocycles were obtained in three steps from the
amino derivatives. The reaction with para-toluenesulfonyl chloride in pyr-
idine afforded the para-toluenesulfonamides 3 and 4, which were alkylated
with methyl iodide in the presence of potassium carbonate to give 5 and 6 in
excellent yields. Hydrolysis of the para-toluenesulfonamide in sulfuric acid
afforded 7 and 8 in quantitative yield. The reaction with formaldehyde was
performed in methanesulfonic acid for 8 or 12 N hydrochloric acid for 7. In
both solvents, the reactions proceeded smoothly to give the N-methyl-
dihydro-[3,1]oxazines 9 and 10 in good yields (78% and 97% respectively).
These compounds were characterized by nmr spectroscopy and mass
1
spectrometry. In the H nmr spectra of 9 and 10, the two methylenes of
the dihydrooxazine rings appeared as two singlets at 5.47 and 5.43 ppm
respectively for ArCH2O, and 4.72 and 4.73 ppm for NCH2O.
The N-methyl-dihydro-[3,1]oxazine ring in 9 or 10 was shown to be
stable in basic conditions (1 N aqueous sodium hydroxide) and to decompose
in strong acidic medium (6 N hydrochloric acid). No reaction occurred with

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2003
Figure 1.
lithium aluminium hydride, in conditions where the N-unsubsti-
tuted analogues were readily cleaved to the corresponding amino-alcohols.8
Cleavage could be achieved by oxidation with 2,3-dichloro-5,6-dicyano-
benzoquinone (DDQ), which is known to oxidize benzyl positions.9–11
To our knowledge, this reagent has never been used to open heterocyclic
rings such as dihydrooxazines. Different reaction conditions were tested.
As depicted in Figure 2, compound 9 was reacted at room temperature
with DDQ in dioxane. The reaction was followed by hplc. When all the
starting dihydrooxazine 9 had reacted, the black solid that was formed in
solution was separated and vigorously stirred in hot water to achieve hydro-
lysis of the hemiacetal intermediate. The aldehyde 11 was thus obtained in
good yield (70%). The reaction of 10 with DDQ was performed in metha-
nol. The reaction proceeds smoothly at room temperature. In these con-
ditions, it was possible to isolate the acetal intermediate 12 in 95% yield.
Formation of the aldehyde 13 was obtained by acidic hydrolysis of 12
(quantitative yield) or in a one-pot reaction from 10 in 85% yield.
CONCLUSION
We designed an efficient strategy to prepare polycyclic N-methyl-
dihydro-[3,1]oxazine derivatives. The two compounds described in this

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CHARMANTRAY ET AL.
Figure 2.
paper have been tested as anticancer agents. They display significant cyto-
toxicity on L1210 (IC50 2 mM and 1.3 mM for 9 and 10 repectively).
The dihydrooxazine ring was shown to react with DDQ in a regioselective
way to afford the corresponding aldehyde. It is to our knowledge the
first example of oxidative ring opening achieved by DDQ producing an ortho-
amino substituted heteroaromatic aldehyde. These type of compounds should be
very useful to prepare a large variety of polysubstituted derivatives.
EXPERIMENTAL
Melting points (uncorrected) were determined using the capillary tube.
1
Unless mentioned otherwise H NMR spectra were taken at 200 MHz on
Bruker AC 200 spectrometer. DMSO-d6 or CDCl3 were used as solvent and
TMS as an internal standard. The chemical shifts are reported in ppm, in d
units. The mass spectra were recorded on a Varian Mat 311 and AET MS 30
instruments. Thin layer chromatography (tlc) was carried out on ‘‘Merck
Kieselgel 60F254’’ plates and scanned under ultraviolet light at 254 nm and
365 nm. Column chromatography was carried out with silica gel ‘‘Merk
Kieselgel 60’’.
Synthesis of N-Methylamino Heterocycles 7 and 8
3-( para-Toluenesulfonylamino)acridine 3
Para-toluenesulfonyl chloride (6 g, 31 mmol) dissolved in pyridine
(30 mL) was added dropwise to a solution of 3-aminoacridine 1 (3 g,

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2005
15 mmol) in pyridine (100 mL) cooled at 0ꢀC. After 4 h stirring at room
temperature, compound 3 was precipitated by pouring the solution into a
large volume of ether-hexane (1–1 mixture). After filtration, 3 was dissolved
in the minimum of methanol and crystallized by adding diethylether.
Compound 3 was obtained in 85% yield (9.15 g, 26 mmol).
Mp 185–190ꢀC; H nmr (DMSO-d6) d 11.8(1H, s, NH), 9.80 (1H,
1
s, H-9), 9.20–8.90 (3H, m, H-1, H-5 and H-8), 8.65 (1H, m, H-6),
8.63 (2H, m, Ts-H), 8.58 (1H, d, H-4), 8.38 (1H, m, H-7), 8.25 (1H, m,
H-2), 8.20 (2H, m, Ts-H), 2.40 (3H, s, CH3); ms (EI) m/z 348(M þ);
Anal. Calcd. for C20H16N2O2S: C-68.70, H-4.67, N-7.74, Found: C-68.95,
H-4.63, N-8.04.
( para-Toluenesulfonylamino) Benzo[b][1,7]phenanthroline 4
The same procedure was used starting from 2 (1 g, 4 mmol). Com-
pound 4 (1.5 g, 3.76 mmol) was obtained in 92% yield.
1H nmr (DMSO-d6, 60 MHz) d 11.4 (1H, s, NH), 9.5 (1H, dd, J ¼ 8.2
and J ¼ 1.7 Hz, H-1), 9.0 (1H, dd, J ¼ 4.4 and J ¼ 1.7 Hz, H-3), 8.9 (1H,
s, H-7), 8.1 (1H, d, J ¼ 9.2 Hz, H-6), 7.9–7.2 (9H, m, H-8, H-5, H-2, H-9,
H-11 and TsH), 2.2 (3H, s, TsCH3); ms (EI) m/z 399 (Mþ); Anal. Calcd. for
C23H17N3O2S: C-69.15, H-4.29, N-10.52, S-8.03 Found: C-69.35, H-4.41,
N-10.71, S-7.86.
3-(N-Methyl-N-para-toluenesulfonylamino) Acridine 5
Compound 3 (0.5 g, 1.4 mmol) was dissolved in DMF (20 mL) in the
presence of potassium carbonate (6 mmol). Methyl iodide (4.5 mmol) was
added and the solution was stirred at room temperature for 1 h. Salts were
removed by filtration and the solvent was evaporated under reduced pressure
to dryness. The residue was purified by column chromatography on silica gel.
Compound 5 was eluted with ethyl acetate, and was obtained in 85% yield
(0.44 g, 1.2 mmol).
Mp 160ꢀC; 1H nmr (DMSO-d6) d 8.70 (1H, s, H-9), 8.07 (1H, m, H-5),
7.94 (1H, m, H-8), 7.91 (1H, d, J ¼ 9 Hz, H-1), 7.77 (1H, dd, J ¼ 9 and
2.2 Hz, H-2), 7.71 (1H, m, H-6), 7.52 (1H, d, J ¼ 2.2 Hz, H-4), 7.47 (1H,
m, H-7), 7.38(2H, d, J ¼ 8Hz, Ts-H), 7.12 (2H, d, J ¼ 8Hz, Ts-H), 3.26 (3H,
s, NCH3), 2.31 (3H, s, TsCH3); ms (Cl, NH3, isobutane) m/z 363 (M þ 1)þ;
Anal. Calcd. for C21H18N2O2S, 0.25 H2O: C-68.74, H-5.08, N-7.63, Found:
C-68.60, H-5.07, N-7.47.

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10-(N-Methyl-N-para-toluenesulfonylamino) benzo[b][1,7]-
phenanthroline 6
The same method was used to prepare 6 from 4 (0.8g, 2 mmol) in 90%
yield after purification.
Mp 218–219ꢀC; H nmr (DMSO-d6, 60 MHz) d 9.5 (1H, m, H-1),
1
9.0 (1H, m, H-3), 8.9 (1H, s, H-7), 8.1 (1H, d, J ¼ 9.2 Hz, H-6), 7.9–7.2
(9H, m, H-2, H-5, H-8, H-9, H-11 and Ts-H), 3.4 (3H, s, NCH3), 2.3
(3H, s, TsCH3); Anal. Calcd. for C24H19N3O2S: C-69.71, H-4.63, N-10.16,
S-7.75, Found: C-69.41, H-4.68, N-10.26, S-7.64.
3-Methylaminoacridine 7
Compound 5 (0.2 g, 0.5 mmol) dissolved in sulfuric acid (1 mL) was
stirred at room temperature for 90 min. The solution was added dropwise
to cold diluted aqueous ammonium hydroxide and compound 7 was
extracted with methylene chloride. The solvent was concentrated and com-
pound 7 precipitated by adding diethyl ether, it was obtained in quantitative
yield (0.113 g, 0.5 mmol).
Mp 225–227ꢀC; 1H nmr (DMSO-d6) d 8.71 (1H, s, H-9), 7.98
(1H, m, H-5), 7.88 (1H, m, H-8), 7.80 (1H, d, J ¼ 9 Hz, H-1), 7.70 (1H, m,
H-6), 7.38(1H, m, H-7), 7.07 (1H, d, J ¼ 9 Hz, H-2), 6.85 (1H, s, NH), 6.68
(1H, s, H-4), 2.84 (3H, s, NCH3); ms (FABþ, NBA) m/z 209 (M þ 1)þ;
Anal. Calcd. for C14H12N2: C-79.71, H-5.88, N-13.28, Found: C-79.93,
H-5.72, N-13.40.
10-(Methylamino)benzo[b][1,7]phenanthroline 8
The same method was used to prepare 8 in quantitative yield starting
from 6 (0.2 g, 0.48mmol).
Mp 286ꢀC: 1H nmr (DMSO-d6) d 9.50 (1H, ddd, J ¼ 8.2, 1.8 and
0.6 Hz, H-1), 8.93 (1H, dd, J ¼ 4.5 and 1.8Hz, H-3), 8.64 (1H, s, H-7),
8.00 (1H, d, J ¼ 9.2 Hz, H-6), 7.81 (1H, d, J ¼ 9 Hz, H-8), 7.68 (1H, d,
J ¼ 9.2 Hz, H-5), 7.64 (1H, dd, J ¼ 8.2 and 4.5 Hz, H-2), 7.13 (1H, dd,
J ¼ 9 and 2.1Hz, H-9), 6.90 (1H, d, J ¼ 2.1 Hz, H-11), 6.58(1H, m, NH),
2.90 (3H, d, J ¼ 4.9 Hz, CH3); ms (EI) m/z 259 (100, Mþ); Anal.
Calcd. for C17H13N3: C-78.74, H-5.05, N-16.21, Found: C-78.53, H-4.92,
N-15.94.

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Obtention of the N-Methyl-dihydro[3,1]oxazine ring
3,4-Dihydro-4-methyl-1H-[3,1]oxazinoacridine 9
Compound 7 (0.64 g, 3.2 mmol) was dissolved in 12 N hydrochloric
acid (6 mL) in the presence of paraformaldehyde (0.6 g, 20 mmol). The mix-
ture was stirred at room temperature for 45 min and then basified with
diluted aqueous ammonium hydroxide. Compound 9 was extracted with
dichloromethane. Concentration of the solvent afforded 9 as a yellow
powder in 78% yield (0.62 g, 2.5 mmol).
Mp 154ꢀC; 1H nmr (CDCl3) d 8.50 (1H, s, H-9), 8.05 (1H, d,
J ¼ 8.7 Hz, H-5), 7.84 (1H, d, J ¼ 8.3Hz, H-8), 7.72 (1H, d, J ¼ 9.2 Hz,
H-1), 7.63 (1H, m, H-6), 7.38(1H, m, H-7), 7.18(1H, d, J ¼ 9.2 Hz, H-2),
5.47 (2H, s, ArCH2O), 4.72 (2H, s, NCH2O), 3.00 (3H, s, NCH3); ms
(FABþ, NBA) m/z 251 (M þ 1)þ; Anal. Calcd. for C16H14N2O: C-76.23,
H-5.68, N-11.11, Found: C-76.27, H-5.64, N-10.70.
3,4-Dihydro-4-methyl-1H-[3,1]benzooxazino[5,6-b][1,7]-
phenanthroline 10
Compound 8 (1 g, 3.9 mmol) was dissolved in 5 mL of methanesulfonic
acid (98%) in the presence of paraformaldehyde (0.3 g, 10 mmol). The mix-
ture was stirred at room temperature for 10 min and then basified with
diluted aqueous ammonium hydroxide. Compound 10 was extracted twice
with dichloromethane. Concentration of the solvent afforded 10 as a yellow
powder in 97% yield (1.12 g, 3.7 mmol).
Mp 183ꢀC; H nmr (DMSO-d6, 300 MHz) d 9.42 (1H, d, J ¼ 8.2 Hz,
1
H-13), 8.96 (1H, dd, J ¼ 4.4 and 1.6 Hz, H-11), 8.73 (1H, s, H-7), 8.0 (1H, d,
J ¼ 9.2 Hz, H-8), 7.89 (1H, d, J ¼ 9.1 Hz, H-6), 7.71 (1H, d, J ¼ 9.2 Hz, H-9),
7.65 (1H, dd, J ¼ 8.2 Hz and 4.4 Hz, H-12), 7.36 (1H, d, J ¼ 9.1Hz, H-5), 5.43
(2H, s, ArCH2O), 4.73 (2H, s, NCH2O), 3.03 (3H, s, NCH3); ms (EI) m/z
301 (98, Mþ); Anal. Calcd. for C19H15N3O: C-75.73, H-5.02, N-13.94,
Found: C-75.87, H-5.12, N-13.72.
Oxidative Ring Cleavage
4-Formyl-3-methylaminoacridine 11
A mixture of 9 (1.5 g, 6 mmol) and DDQ (12 mmol) in dioxane was
stirred at room temperature for 3 h. The black solid that deposited was

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CHARMANTRAY ET AL.
filtered, and suspended in water (2 L). The mixture was stirred at 85ꢀC for
7 h. After cooling to room temperature, dichloromethane was added (1 L)
and the solution was stirred overnight. The organic layer was then sepa-
rated, washed with water, dried over sodium sulfate and concentrated under
reduced pressure. Compound 11 was precipitated by adding diethyl ether
and was obtained in 70% yield (0.991 g, 4.2 mmol).
Mp 233ꢀC; 1H nmr (CDCl3) d 11.40 (1H, s, CHO), 10.55 (1H, s, NH) ,
8.37 (1H, s, H-9), 8.05 (1H, d, J ¼ 8.4 Hz, H-5), 7.85 (1H, d, J ¼ 9.0 Hz, H-1),
7.80 (1H, d, J ¼ 8.0 Hz, H-8), 7.70 (1H, m, H-6), 7.40 (1H, m, H-7) 7.08 (1H,
d, J ¼ 9.0 Hz, H-2), 3.10 (3H, s, NCH3); ms (FABþ, glycerol) m/z 237
(Mþ1)þ; Anal. Calcd. for C15H12N2O: C-76.25, H-5.12, N-11.86, Found:
C-76.21, H-5.16, N-11.68.
Ring Cleavage of 3,4-Dihydro-4-methyl-1H-[3,1]benzoxazino[5,6-b]
[1,7] Phenanthroline 10 in Methanol: Formation of 3,4-Dihydro-1-
methoxy-4-methyl-1H-[3,1]benzooxazino[5,6-b][1,7]phenanthroline 12
and 4-Formyl-3-methylamino-benzo[b][1,7]phenanthroline 13
DDQ (0.2 g, 0.8mmol) was added to a solution of 10 (0.1 g,
0.33 mmol) dissolved in 50 mL of dried methanol. The reaction was kept
at room temperature for 1 h. The insoluble fraction was filtered off and
washed with water and methylene chloride. The organic layer was separated,
dried over sodium sulfate, and concentrated. The residue was purified by
column chromatography on silica gel using ethyl acetate as eluent.
Acetal derivative 12 was thus isolated in 95% yield (0.106 g,
0.32 mmol). One-pot benzylic oxidation and hydrolysis of the acetal was
achieved by acidic treatment of the methanolic solution with 2 N HCl
(1 mL), for 1 h, under stirring. The insoluble fraction was filtered off and
the filtrate basified with aqueous sodium hydrogenocarbonate. The aqueous
solution was extracted with methylene chloride, the organic phase was con-
centrated and subjected to column chromatography using the same con-
ditions as described above. Compound 13 was isolated as pure product
(0.081 g, 0.28 mmol) in 85% global yield.
12. Mp 190–192ꢀC; H nmr (DMSO-d6, 300 MHz) d 9.59 (1H, dd,
1
J ¼ 8.2 Hz and 1.8 Hz, H-13), 8.93 (1H, dd, J ¼ 4.5 Hz and J ¼ 1.8Hz,
H-11), 8.41 (1H, s, H-7), 7.87–7.76 (3H, m, H-6, H-8, H-9), 7.57 (1H, dd,
J ¼ 8.2 Hz and J ¼ 4.5 Hz, H-12), 7.17 (1H, d, J ¼ 9.2 Hz, H-9), 6.41 (1H, s,
H-1), 4.87 (2H, dd, J ¼ 8.8 Hz, H-3), 3.83 (3H, s, OCH3), 3.11 (3H, s,
NCH3); ms (EI) m/z 331 (56, Mþ); Anal. Calcd. for C20H17N3O2:
C-72.49, H-5.17, N-12.68, Found: C-72.22, H-5.01, N-12.59.

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13. Mp 260ꢀC; 1H nmr (DMSO-d6, 300 MHz) d 11.47 (1H, s,
CHO), 10.23 (1H, q, J ¼ 5.1Hz, NH), 9.52 (1H, dd, J ¼ 8.2 Hz
and J ¼ 1.7 Hz, H-1), 8.97 (1H, dd, J ¼ 4.4 Hz and J ¼ 1.7 Hz, H-3), 8.77
(1H, s, H-7), 8.17 (1H, d, J ¼ 9.3 Hz, H-6), 8.05 (1H, d, J ¼ 9.3 Hz, H-8),
7.77 (1H, d, J ¼ 9.3 Hz, H-5), 7.68(1H, dd, J ¼ 8.2 Hz and J ¼ 1.7 Hz, H-2),
7.36 (1H, d, J ¼ 9.3Hz, H-9), 3.10 (3H, d, J ¼ 5.1Hz, NCH3); ms (EI) m/z
287 (40, Mþ); Anal. Calcd. for C18H13N3O: C-75.25, H-4.56, N-14.62,
Found: C-75.03, H-4.67, N-14.49.
REFERENCES
1. Wardani, A.; Lhomme, J.; Bigg, D.C.H. and Salez, H. Patent PCT Int
APP. WO 91 07, 403.
2. Duflos, A.; Bigg, D.C.H.; Lhomme, J.; Fixler, N.; Etievant, C. and
Demeunynck, M. Patent FR 2712 290A, 1993.
3. Lhomme, J.; Bigg, D.C.H.; Duflos, A.; Bonnaud, B.; Demeunynck, M.;
Etievant, C. and Kiss, R. Patent PCT Int APP. WO 94 25439.
4. Duflos, A.; Bigg, D.C.H.; Lhomme, J.; Bonnaud, B. and Etievant, C.
Patent Fr 2716454.
5. Wardani, A. and Lhomme, J. Tetrahedron Lett. 1993, 34, 6411.
6. Salez, H.; Wardani, A.; Demeunynck, M.; Tatibouet, A. and
Lhomme, J. Tetrahedron Lett. 1995, 36, 1271.
7. Tatibouet, A.; Fixler, N.; Demeunynck, M. and Lhomme, J.
Tetrahedron 1997, 53, 28 91.
8. Fixler, N. PhD Thesis, Grenoble, 1994.
9. Oikawa, Y. and Yonemitsu, O. J. Org. Chem. 1977, 42, 1213.
10. Oikawa, Y.; Yoshioka, T. and Yonemitsu, O. Tetrahedron Lett. 1982,
23, 885.
11. Xu, Y.-C.; Lebeau, E.; Gillard, J.W. and Attardo, G. Tetrahedron
Lett. 1993, 34, 3841.
Received in the UK July 17, 2000

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