Synthesis of new soluble annelated polypyridines

Article abstract of DOI:10.1002/(sici)1099-0690(200003)2000:6<987::aid-ejoc987>3.0.co;2-e

A new octahydroacridine with a tert-butoxypropyl group in the 9-position was prepared and was used in the synthesis of new soluble annelated polypyridines. Quinquepyridine with 11 adjacent rings was prepared in 17-25% yield by condensation of an α-methyle

Full text of DOI:10.1002/(sici)1099-0690(200003)2000:6<987::aid-ejoc987>3.0.co;2-e

FULL PAPER
Synthesis of New Soluble Annelated Polypyridines
[c]
[a]
[b]
[a]
¨
Hassan Aıt-Haddou,* Christophe Fontenas, Elena Bejan, Jean-Claude Daran, and
Gilbert G. A. Balavoine*[a]
Keywords: Michael addition / Octahydroacridine / Polypyridines
A new octahydroacridine with a tert-butoxypropyl group in
densation of an α-methylene ketone and an enolisable ke-
the 9-position was prepared and was used in the synthesis of
tone in the presence of ammonium acetate under basic con-
new soluble annelated polypyridines. Quinquepyridine with ditions.
11 adjacent rings was prepared in 17–25% yield by con-
Introduction
tend the utility of such molecules,[4] we have synthesised
soluble polypyridines by employing the Michael addition of
an enolisable ketone to an α,β-unsaturated ketone followed
by cyclisation of the 1,5-diketone intermediate in the pres-
ence of ammonium acetate.[5] In this paper we present the
synthesis of a new substituted octahydroacridine and its ap-
plication in the preparation of soluble annelated polypyrid-
ines. The present procedure is based on the condensation of
α-methylene ketones with enolisable ketones under basic
conditions.
Our strategy is based on the retrosynthetic analysis
shown in Figure 2. The choice of tert-butyl as a protecting
group for the 9-substituted octahydroacridine was made by
considering its stability under harsh reaction conditions
and its solubility in organic solvents. The protecting group
was easy to remove under mild conditions[6] and the hy-
droxy group can then serve for immobilisation or conjuga-
tion of these molecules to solid supports or biomolecules.
Since the work of Bell[1] and Thummel[2] on the synthesis
of annelated polypyridines and other annelated polyaza
structures, a wide variety of annelated pyridines capable of
selectively binding charged or neutral organic molecules has
been synthesised.[3] A useful approach to the synthesis of
such molecules involves 1,5-diketone intermediates that,
with a nitrogen-containing reagent, undergo ring closure to
the corresponding pyridine. However, few methods have
been developed for the preparation of soluble annelated
polypyridines. The most important method for the con-
struction of soluble annelated polypyridines was that em-
ploying a 9-substituted octahydroacridine, which was used
in the synthesis of the ‘‘Torand’’[1b] and the helicoidal
polypyridine[1g,1f] (Figure 1).
As shown in Scheme 1, the synthesis began with the pre-
paration of 4-tert-butoxybutanal (3). Starting from the
readily available 3-chloropropan-1-ol (1), the aldehyde 3
was obtained in good yield in two steps. The transformation
of 1 to 3-tert-butoxy-1-chloropropane (2) was carried out
using a known procedure.[7] Conversion into the butanal 3
was achieved in 84% yield on a large scale by formylation
of its corresponding Grignard reagent using N-formylpiper-
idine as a formylating agent.[8] 8-(3-tert-Butoxypropyl)-2-
hydroxytricyclo[7.3.1.02,7]tridecan-13-one (4) was prepared
in 87% yield by the aldol condensation of cyclohexanone
with 3.[9] The structure of 4 was confirmed by X-ray ana-
lysis and is shown in Figure 3.
The framework of the three fused rings of the hydroxy-
tricyclotridecanone moiety is closely related to that re-
ported for the 2-hydroxytricyclo[7.3.1.02,7]tridecan-13-one
compounds C14H22O2.[10] As observed in the methyl deriv-
ative, two hydrogen bonds [O(5)–H(5) O(13Ј) and
O(13) H(5Ј)-O(5Ј)] link two enantiomers through an inver-
sion centre. Conversion of 4 to 8-(3-tert-butoxypropyl)-
1,2,3,4,5,6,7,8-octahydroacridine (5) was achieved by reac-
tion with ammonium acetate and copper(II) acetate accord-
ing to the literature procedure.[11]
Figure 1. Synthesis of soluble annelated polypyridines from 9-bu-
tyloctahydroacridine
As part of a programme aimed at the use of annelated
polypyridines in molecular recognition, and in order to ex-
[a]
Laboratoire de Chimie de Coordination-CNRS UPR 8241,
205 Route de Narbonne, F-31077 Toulouse Cedex, France,
Fax: (internat.) ϩ 33-5/61553003,
E-mail: balavoin@lcc-toulouse.fr
[b]
University of Ottawa, Dept. of Chemistry,
10 Marie Curie Street, Ottawa ON K1N 6N5, Canada
[c]
University of Texas at Austin, Dept. of Chemistry and
Biochemistry
Austin, TX 787121167, USA
E-mail: ahhassan@mail.utexas.edu
Eur. J. Org. Chem. 2000, 987Ϫ994
WILEY-VCH Verlag GmbH, D-69451 Weinheim, 2000
1434Ϫ193X/00/0306Ϫ0987 $ 17.50ϩ.50/0
987

H. A¨ıt-Haddou, C. Fontenas, E. Bejan, J.-C. Daran, G. G. A. Balavoine
FULL PAPER
Figure 2. Synthetic strategy for the new annelated polypyridines
Scheme 1. (a) Isobutene, H2SO4 (cat.), CH2Cl2, –78 °C; (b) Mg, (CH2)2Br2, THF, reflux; (c) N-formylpiperidine, THF, –20 °C, 3  HCl;
(d) cyclohexanone, EtONa/EtOH, reflux; (e) AcOH, Cu(OAc)2, NH4OAc; (f) m-chloroperbenzoic acid, CH2Cl2, 0 °C; (g) trifluoroacetic
anhydride, CH2Cl2, room temp.; saponification with 2  K2CO3 solution; (h) DMSO, oxalyl chloride, CH2Cl2, Et3N, –78 °C
Figure 3. View of two enantiomers of 4 linked by hydrogen bonds with atom labelling scheme; ellipsoids are drawn at 30% probability
The transformation of octahydroacridine 5 into 8-(3-tert-
The formation of the heptacyclic terpyridine 13 requires
butoxypropyl)-1H-2,3,5,6,7,8-hexahydroacridin-4-one (8) the coupling of two ketones to create the central pyridine
involves α-CH2 oxidation, which may be effected by the ring. Different methods have been reported for the prepara-
‘‘Boekelheide’’ rearrangement of an acetylated N-oxide.[12] tion of such annelated polypyridines.[15] We concentrated
Unfortunately, treatment of the N-oxide 6 with hot acetic on the Michael addition of an enolisable ketone to an enone
anhydride and hydrolysis of the resulting acetate led to the because it offers access to unsymmetrical terpyridyls from
alcohol 7 in only moderate yield (62%). An alternate pro- two different ketones. Consequently, the benzylidene ketone
cedure, using trifluoroacetic anhydride as a key acylating 10 and the enone 12 were prepared. Ketone 10 was ob-
agent, proved more convenient. The treatment of N-oxide 6 tained in a two step procedure starting from N-oxide 6.[16]
with trifluoroacetic anhydride in dry dichloromethane, fol- A mixture of 6 in acetic anhydride and benzaldehyde was
lowed by saponification of the resulting trifluoroacetate, heated under reflux and subsequent in situ alkaline saponi-
gave 7 in 89% yield.[13] Oxidation of this alcohol using fication of the resulting acetate gave the benzylidene alcohol
modified Swern conditions[14] gave ketone 8 in 91% yield.
9 in 85% yield. This alcohol was then oxidised to the
988
Eur. J. Org. Chem. 2000, 987Ϫ994

Synthesis of New Soluble Annelated Polypyridines
FULL PAPER
benzylidene ketone 10 in 99% yield. For the preparation tion with tert-butoxybis(dimethylamino)methane.[18] Treat-
of the α-methylene ketone 12, two different methods were ment of 11 with diisobutylaluminium hydride gave the en-
examined: a method employing the Mannich base of 8 and one 12 in 85% yield.[19] The preparation of 13a by the reac-
a method based on the reduction of enaminone 11. For the tion of 8 with 12 (Scheme 2) in hot (90 °C) anhydrous
preparation of 12 via the Mannich base, ketone 8 was DMSO[20] led to 13a in 49% yield, while a 45% yield of 13a
treated with N,N-dimethyl(methylene)immonium chloride was obtained in TMU[21] at 90 °C. It is important to point
in anhydrous acetonitrile at room temperature.[17] This out that in both DMSO and TMU the addition of oxidising
method led, in all cases, to the Mannich base in low yield agent did not improve the yield of 13a. However, the reac-
and was therefore not used for the preparation of 12. As tion of 8 and 12 in anhydrous pyridine at 90 °C gave the
an alternative for the preparation of 12, ketone 8 was first heptacyclic terpyridine 13a in 62% yield. The unsymmet-
converted into enaminone 11 in quantitative yield by reac- rical, homologous compound 13b was obtained in 56%
Scheme 2. (a) Ac2O/PhCHO 2:1, 170 °C; saponification with 2  K2CO3 solution; (b) DMSO, oxalyl chloride, CH2Cl2, Et3N, –78 °C;
(c) tert-butoxybis(dimethylaminomethane), 45 °C, 3 h; (d) diisobutylaluminium hydride, THF, –78 °C, 2 h, NH4Cl; (e) pyridine, NH4OAc,
90 °C
Scheme 3. Synthesis of the annelated quinquepyridine 15 with 11 adjacent rings
Eur. J. Org. Chem. 2000, 987Ϫ994
989

H. A¨ıt-Haddou, C. Fontenas, E. Bejan, J.-C. Daran, G. G. A. Balavoine
FULL PAPER
ASTM), deactivated with 8% of water. Preparative flash chromato-
graphy was performed on Merck Kieselgel.
yield by condensation of 12 with the benzylidene ketone 10
under the same conditions.
This strategy was also used for the preparation of larger
annelated polypyridines such as 15, which is a quinquepyri-
dine with 11 adjacent rings. As shown in Scheme 3, two
routes based on coupling of an enone with an enolisable
3-tert-Butoxy-1-chloropropane (2): A solution of 95 g (1 mol) of 3-
chloropropan-1-ol in 400 mL of anhydrous dichloromethane and
5 mL of concentrated sulfuric acid was added to 90 g (1.60 mol) of
isobutene at –78 °C. The mixture was stirred at room temperature
ketone were used. The first approach was the condensation overnight and neutralised by the required amount of saturated so-
dium bicarbonate. The aqueous layer was extracted twice with
dichloromethane. The combined organic phases were washed with
water and with saturated sodium chloride, dried with MgSO4 and
concentrated under reduced pressure to afford an oil, which was
distilled to yield 150 g (99%) of colourless, odorous liquid 3-tert-
butoxy-1-chloropropane (2); b.p. 52 °C, 15 Torr. – 1H NMR
(CDCl3, 250 MHz): δ ϭ 3.65 (t, 2 H, J ϭ 6.4 Hz), 3.50 (t, 2 H,
J ϭ 5.8 Hz), 1.98 (m, 2 H), 1.20 (s, 9 H). – 13C NMR (CDCl3):
δ ϭ 72.7, 57.8, 42.2, 33.4, 27.5. – C7H15ClO (150.65): calcd. C
55.97, H 10.07, O 10.65; found C 55.76, H 10.20, O 10.70. – MS
of the heptacyclic ketone of 13b with the enone 12. Con-
sequently, ozonolysis of 13b gave 14 in 92% yield. The reac-
tion of ketone 14 with 12 and excess ammonium acetate in
anhydrous pyridine gave 15 in 25% yield. 1H-NMR and
13C-NMR spectra of the product are consistent with the
C2-symmetric structure. A second approach to the prepara-
tion of 15 involved coupling of 12 with diketone 17. This
diketone was prepared in good yield by reaction of 5 with
benzaldehyde to provide its dibenzylidene derivative 16,
which was then ozonolysed to diketone 17.[2d] The con- (CI, NH3); m/z (%): 151 (100) [MHϩ].
densation of 17 with 2 equivalents of 12, under the same
4-tert-Butoxybutanal (3): To a cooled (–20 °C) solution of 9.93 g
conditions as for 14, provided 15 in Ͻ5% yield. The slow
addition of 12 to a mixture of 17 and NH4OAc in hot pyr-
idine led to 15 in 10% yield. The best yield (17%) was ob-
tained when the diketone 17 was preheated with NH4OAc
in pyridine before the addition of 12. In this case, dienamine
(100 mmol) of N-formylpiperidine in 100 mL of anhydrous tetrahy-
drofuran was added, over 30 min, 250 mL (125 mmol, 1.25 equiv.)
of a 0.5  solution of 3-(tert-butoxypropyl)magnesium chloride.
The reaction mixture was then left to reach room temperature over-
night. The mixture was hydrolysed using 30 mL of 3  hydrochloric
or a mixture of mono- and dienamine of 17 is apparently acid. After decantation, the aqueous layer was extracted with di-
ethyl ether (3 ϫ 150 mL). The organic layers were combined and
neutralised with saturated aqueous sodium hydrogencarbonate so-
lution, washed with water and saturated aqueous sodium chloride
solution. After drying (MgSO4), the solution was concentrated un-
der reduced pressure to afford a yellow oil, which gave after distilla-
tion 10.2 g (84%) of a colourless odorous liquid 3; b.p. 54 °C, 5
formed and reacts efficiently with the enone 12 as previ-
ously suggested by Bell.[1h]
In this work we have described the synthesis of a new
octahydroacridine and its application in the preparation of
soluble annelated polypyridines employing a two-step pro-
cedure based on the Michael addition of an α-methylene
ketone and an enolisable ketone. Annelated polypyridines
such as pentadentate 18 (Figure 4) are useful hosts for com-
plexation of alkali metals (Naϩ, Kϩ).[1h] Our octahydroacri-
1
Torr. – IR (nujol): ν˜ ϭ 2723, 1728 (CO) cm–1. – H NMR (CDCl3,
250 MHz): δ ϭ 9.75 (m, 1 H), 3.40 (t, 2 H, J ϭ 6.1 Hz), 2.50 (m,
2 H), 1.85 (m, 2 H), 1.20 (s, 9 H). – 13C NMR (CDCl3): δ ϭ 202.7,
72.8, 60.3, 41.1, 27.4, 23.4. – C8H16O2 (144.21): calcd. C 66.63, H
dine, which contains a protected hydroxy group on the side 11.18, O 22.19; found C 66.33, H 11.13, O 22.54. – MS (CI, NH3);
m/z (%): 145 (100) [MHϩ].
chain, can lead to hosts suitable for polymer immobilisation
or incorporation into a dendrimer.
8-(3-tert-Butoxypropyl)-2-hydroxytricyclo[7.3.1.02,7]tridecan-13-one
(4): A solution of 0.5 g of potassium hydroxide in 50 mL of abso-
lute ethanol was added in one portion to 120 mL of heated cyclo-
hexanone at 75 °C. A solution of 20.59 g (143 mmol) of 3 in
100 mL of absolute ethanol was then added very slowly (6 h). The
mixture was refluxed for 24 h. Removal of the solvent and cyclo-
hexanone under reduced pressure gave an oil, which precipitated in
Figure 4. Annelated polypyridine for the selective complexation of
hexane to give 39.77 g (87%) of 4 as a white microcrystalline pow-
sodium and potassium
der; m.p. 129–130 °C. – IR (KBr): ν˜ ϭ 3382 (OH), 1714 (CO)
cm–1. – 1H NMR (CDCl3, 250 MHz): δ ϭ 3.30 (t, 2 H, J ϭ 6.2 Hz),
2.40 (m, 2 H), 2.00–1.22 (m, 21 H), 1.20 (s, 9 H). – 13C NMR
Experimental Section
(CDCl3): δ ϭ 220.6, 72.4, 61.4, 59.6, 48.3, 45.0, 42.1, 36.5, 29.3,
28.7, 27.7, 27.5, 26.2, 25.4, 25.3, 21.1, 20.3. – C20H34O3 (322.25):
All reactions were carried out under argon. Nuclear magnetic res-
calcd. C 74.49, H 10.63, O 14.88; found C 74.80, H 10.85, O
onance spectra were recorded with Bruker AM-250 (250 MHz) and
AC-200 (200 MHz) spectrometers for 1H, and chemical shifts are
reported in ppm downfield from Me4Si. These instruments were
also used for 13C spectra. IR spectra were obtained with a Perkin–
Elmer 883 or FT-1725X spectrophotometer. CI mass spectra and
FAB mass spectra (m-nitrobenzyl alcohol matrix) were recorded
with a quadripolar Nermag R10-10H instrument. GC mass spectra
15.17. – MS (CI, NH3); m/z (%): 323 (100) [MHϩ].
9-(3-tert-Butoxypropyl)-1,2,3,4,5,6,7,8-octahydroacridine (5):
A
mixture of 4.5 g (146 mmol, 1.25 equiv.) of ammonium acetate,
15.8 g (200 mmol, 1.7 equiv.) of copper(II) acetate and 150 mL of
glacial acetic acid was heated at 100 °C for 15 min. After cooling,
15 g (117 mmol) of 4 was added in small portions and the resulting
were recorded with a Hewlett-Packard HP MSD 7590. C, H, N suspension was heated at 100 °C for 4 h. The solution was cooled
and O elemental analyses were performed by the LCC (Laboratoire
de Chimie de Coordination) Microanalytical Service. Column chro-
matography was performed with Merck alumina (70–230 mesh
to room temperature, filtered, concentrated and diluted with water
(50 mL) and made basic with concentrated sodium hydroxide at 0
°C. The mixture was extracted with dichloromethane (3 ϫ 100 mL).
990
Eur. J. Org. Chem. 2000, 987Ϫ994

Synthesis of New Soluble Annelated Polypyridines
FULL PAPER
The combined organic layers were washed successively with ammo-
nia, water and brine, dried with (MgSO4) and concentrated to yield
a brown oil, which was chromatographed on alumina (ethyl acetate/
(m, 2 H), 1.80 (m, 4 H), 1.60 (m, 2 H), 1.20 (s, 9 H). – 13C NMR
(CDCl3): δ ϭ 198.2, 156.8, 148.7, 136.7, 135.1, 72.8, 61.0, 39.4,
33.5, 29.3, 27.6, 26.5, 25.6, 25.1, 22.8, 22.6. – C20H29NO2 (315.46):
pentane, 15:85) to afford 13.18 g (93%) of a beige crystalline solid calcd. C 76.15, H 9.27, N 4.40, O 10.14; found C 75.86, H 9.35, N
5; m.p. 88–89 °C. – 1H NMR (CDCl3, 250 MHz): δ ϭ 3.40 (t, 2 4.20, O 10.39. – GC/MS; m/z (%): 315 (3%) [Mϩ], 215 (100%).
H, J ϭ 6.05 Hz), 2.90 (m, 4 H), 2.70 (m, 4 H), 2.60 (m, 2 H), 1.80
9-(3-tert-Butoxypropyl)-1,2,3,4,6,7,8-octahydro-5-(phenyl-
(m, 8 H), 1.60 (m, 2 H), 1.2 (s, 9 H). – 13C NMR (CDCl3): δ ϭ
methylene)acridin-4-ol (9): A mixture of 7.11 g (22.4 mmol) of the
N-oxide 6, 20 mL of benzaldehyde (9.3 equiv.) and 40 mL of acetic
anhydride was heated at 160 °C for 7 h. After concentration under
vacuum, the resulting oil was dissolved in 250 mL of absolute eth-
153.7, 148.1, 127.6, 72.7, 61.5, 33.2, 29.3, 27.7, 25.5, 24.8, 23.3,
23.1. – C20H31NO (301.47): calcd. C 79.68, H 10.36, N 4.65, O
5.31; found C 79.30, H 10.49, N 4.66, O 5.54. – MS (CI, NH3);
m/z (%): 302 (100) [MHϩ].
anol. Solid sodium disulfide was added until saturation was
9-(3-tert-Butoxypropyl)-1,2,3,4,5,6,7,8-octahydroacridine N-Oxide
(6): To a solution of 29.6 g (98 mmol) of 5 in 100 mL of dichloro-
methane was added dropwise a solution of 50.38 g (196 mmol, 2
equiv.) of 67% mCPBA. After 2 h of stirring at room temperature,
the mixture was made basic with 15% aqueous sodium hydroxide.
The organic layer was washed with water and dried (MgSO4). After
achieved and the suspension was stirred for 1 h. The white precipit-
ate was filtered off and the mother liquor was concentrated. The
residue was then dissolved in diethyl ether, washed with saturated
sodium hydrogen carbonate, water and brine, dried (MgSO4) and
concentrated to yield an oil, which was filtered (alumina, pentane/
ethyl acetate, 95:5). The resulting residue was dissolved in 300 mL
concentration under reduced pressure, 30.75 g (99%) of 6 was ob- of methanol and was saponified overnight with 100 mL of 2  pot-
tained as a pale yellow solid that slowly crystallised; m.p. 84–85
assium carbonate solution. After removal of methanol, 100 mL of
°C. – 1H NMR (CDCl3, 250 MHz): δ ϭ 3.40 (t, 2 H, J ϭ 6.15 Hz), water was added and the solution was extracted with dichlorome-
2.90 (m, 4 H), 2.80 (m, 4 H), 2.60 (m, 2 H), 1.80 (m, 8 H), 1.60 thane (3 ϫ 200 mL). The organic layers were washed with 100 mL
(m, 2 H), 1.20 (s, 9 H). – 13C NMR (CDCl3): δ ϭ 145.4, 137.5,
of brine and dried with magnesium sulfate to yield, after concentra-
130.3, 72.8, 61.1, 29.6, 27.6, 26.5, 25.7, 25.6, 24.5, 22.3, 21.9. –
tion under reduced pressure, 7.71 g (85%) of 9 as a white solid;
C20H31NO2 (317.47): calcd. C 75.67, H 9.84, N 4.41, O 10.08; m.p. 114–115 °C. – 1H NMR (CDCl3, 250 MHz): δ ϭ 7.94 (s, 1
found C 75.72%, H 9.63, N 4.18, O 9.86. – MS (CI, NH3); m/z (%):
H), 7.38 (m, 4 H), 7.23 (m, 1 H), 4.70 (m, 1 H), 4.60 (s, 1 OH),
3.41 (t, 2 H, J ϭ 6.15 Hz), 2.82 (m, 6 H), 2.65 (m, 2 H), 2.35 (m,
1 H), 2.05 (m, 1 H), 1.84 (m, 2 H), 1.72 (m, 2 H), 1.65 (m, 2 H),
1.22 (s, 9 H). – 13C NMR (CDCl3): δ ϭ 155.0, 149.1, 148.5, 138.0,
135.8, 129.7, 129.6, 128.0, 127.9, 126.6, 126.1, 72.7, 69.5, 61.1, 30.4,
29.2, 27.6, 26.0, 25.6, 25.2, 23.0, 19.7. – C27H35NO2 (405.58): calcd.
C 79.96, H 8.70, N 3.46, O 7.89; found C 79.76, H 8.46, N 3.26,
O 7.52. – MS (CI, NH3); m/z (%): 406 (100) [MHϩ].
318 (100) [MHϩ], 335 (12) [MNH4ϩ].
9-(3-tert-Butoxypropyl)-1,2,3,4,5,6,7,8-octahydroacridin-4-ol (7): To
a solution of 22.42 g (70.4 mmol) of 6 in 400 mL of dry dichloro-
methane was added slowly 25 mL (177 mmol, 2.5 equiv.) of trifluo-
roacetic anhydride. After stirring for 2 h, the mixture was concen-
trated to dryness under reduced pressure. The residue was dissolved
in 100 mL of dichloromethane and saponified with 300 mL of 2 
aqueous potassium carbonate. The biphasic mixture was vigorously
stirred for 3 h, decanted and the aqueous layer was extracted twice
with dichloromethane. The combined organic layers were then
dried (MgSO4) and concentrated under reduced pressure to give
21.38 g of pale yellow crystals, which upon washing with hexane
9-(3-tert-Butoxypropyl)-1H-2,3,6,7,8-hexahydro-5-(phenyl-
methylene)acridine-4-one (10): The same procedure as described for
compound 8 was used with 3.0 g (7.4 mmol) of 9, 1.0 mL of oxalyl
chloride, 1.1 mL of dimethyl sulfoxide and 4.8 mL of triethylamine.
2.96 g (99%) of 10 was obtained as a pale yellow solid that could
be recrystallised from ether; m.p. 119–120 °C. – IR (KBr): ν˜ ϭ 1696
afforded 19.85 g (89%) of analytically pure 7 as beige crystals; m.p.
1
98–99 °C. – H NMR (CDCl3, 250 MHz): δ ϭ 4.60 (m, 1 H), 4.37 (CO), 1614 cm–1. – 1H NMR (CDCl3, 250 MHz): δ ϭ 8.10 (s, 1
(s, 1 H, OH), 3.41 (t, 2 H, J ϭ 6.2 Hz), 2.88 (m, 2 H), 2.71 (m, 2 H), 7.41 (m, 4 H), 7.28 (m, 1 H), 3.44 (t, 2 H, J ϭ 6.21 Hz), 3.04
H), 2.60 (m, 4 H), 2.27 (m, 1 H), 2.04 (m, 1 H), 1.85–1.66 (m, 8 (m, 2 H), 2.92 (m, 2 H), 2.88 (m, 2 H), 2.78 (m, 2 H), 2.74 (m, 2
H), 1.22 (s, 9 H). – 13C NMR (CDCl3): δ ϭ 154.4, 148.9, 129.3,
H), 2.20 (m, 2 H), 1.84 (m, 2 H), 1.68 (m, 2 H), 1.20 (s, 9 H). –
126.9, 69.0, 61.4, 32.8, 30.5, 29.2, 27.7, 25.6, 25.5, 25.1, 23.2, 22.8, 13C NMR (CDCl3): δ ϭ 197.2, 152.0, 148.5, 145.6, 137.8, 137.0,
19.7. – C20H31NO2 (317.47): calcd. C 75.67, H 9.84, N 4.41, O
10.08; found C 75.72, H 9.63, N 4.18, O 9.80. – MS (CI, NH3); m/
z (%): 318 (100) [MHϩ].
135.3, 134.8, 129.6, 128.2, 127.8, 126.5, 72.6, 60.8, 39.4, 29.3, 27.5,
26.6, 25.7, 25.1, 22.5, 22.3. – C27H33NO2 (403.56): calcd. C 80.35,
H 8.24, N 3.47, O 7.93; found C 80.09, H 8.52, N 3.53, O 7.86. –
MS (CI, NH3); m/z (%): 404 (100) [MHϩ].
9-(3-tert-Butoxypropyl)-1H-2,3,5,6,7,8-hexahydroacridin-4-one (8):
A solution of 1.6 mL (19.5 mmol, 1.5 equiv.) of oxalyl chloride in 9-(3-tert-Butoxypropyl)-3-(dimethylaminomethylene)-1H-2,5,6,7,8-
50 mL of dry dichloromethane was cooled to –78 °C. To the above
solution was added dropwise 1.8 mL (26 mmol, 2 equiv.) of di-
methyl sulfoxide. After reaching thermal equilibrium, a solution of
hexahydroacridin-4-one (11): To 3.55 g (11.3 mmol) of 8 was added
4.65 mL (22.6 mmol, 2 equiv.) of tert-butoxybis(dimethylamino)-
methane. The mixture was heated at 45 °C for 3 h under nitrogen.
4.13 g (13.0 mmol) of 7 in 50 mL of dry dichloromethane was ad- The reaction was monitored by IR and, after confirming the ab-
ded and the mixture was stirred at –78 °C for 35 min. 7 mL
(52.0 mmol, 4 equiv.) of anhydrous triethylamine was then added.
After a rapid return to room temperature the mixture was diluted
with 500 mL of ether, washed with water (50 mL), 30 mL of brine
and dried (MgSO4). After filtration and concentration under re-
duced pressure 4.23 g of a light brown oil was obtained. This crude
material was chromatographed on alumina (ethyl acetate/pentane,
15:85) to give 3.7 g (91%) of 8 as a white powder; m.p. 85–86 °C. –
sence of 8, the solution was concentrated under reduced pressure
to yield 4.70 g (Ͼ99%) of a brown amorphous, hygroscopic solid
1
11. – IR (KBr): ν˜ ϭ 1573, 1652 (CO) cm–1. – H NMR (CDCl3,
250 MHz): δ ϭ 7.70 (s, 1 H), 3.4 (t, 2 H), 3.10 (s, 6 H), 2.40 (s, 2
H), 2.90–2.60 (m, 6 H), 1.80 (m, 4 H), 1.60 (m, 4 H), 1.20 (s, 9
H). – 13C NMR (CDCl3): δ ϭ 184.8, 155.2, 149.5, 147.9, 146.1,
132.9, 132.0, 103.6, 72.0, 60.4, 42.9, 32.9, 29.2, 27.0, 25.6, 24.2,
24.1, 23.1, 22.4, 22.2. – C23H34N2O2 (370.53): calcd. C 74.56, H
IR (KBr): ν˜ ϭ 1694 (CO) cm–1. – 1H NMR (CDCl3, 250 MHz): 9.25, N 7.56, O 8.64; found C 74.29, H 8.92, N 7.53, O 8.86. – MS
δ ϭ 3.40 (t, 2 H, J ϭ 6.07 Hz), 3.00 (m, 4 H), 2.80 (m, 6 H), 2.20 (CI, NH3); m/z (%): 371 (100) [MHϩ], 388 (25) [MNH4ϩ].
Eur. J. Org. Chem. 2000, 987Ϫ994
991

H. A¨ıt-Haddou, C. Fontenas, E. Bejan, J.-C. Daran, G. G. A. Balavoine
FULL PAPER
9-(3-tert-Butoxypropyl)-1H-2,3,5,6,7,8-hexahydro-3-
methyleneacridin-4-one (12): A solution of 4.84 g (13.1 mmol) of 11
in 100 mL of dry THF was cooled to –78 °C and 1  diisobutylalu-
acetate/methanol (9:1, v/v), yielding 2.60 g (92%) of 14 as a yellow
powder; m.p. 140–143 °C. – IR (KBr): ν
˜ ϭ 1699 (CO) cm
NMR (CDCl3, 250 MHz): δ ϭ 7.41 (s, 1 H), 5.35 (s, 2 H, br, H2O),
1
–1. – H
minium hydride (15.7 mL, 1.2 equiv.) was added. The mixture was 3.42 (m, 4 H), 3.20 (m, 2 H), 3.00 (m, 8 H), 2.78 (m, 8 H), 2.18
allowed to warm up to room temperature (2 h) and was saturated
with solid NH4Cl and stirred for a further 16 h. The solution was
diluted with water (100 mL) and decanted. The aqueous phase was
extracted with Et2O (3 ϫ 50 mL). The organic phases were com-
bined, washed with brine, dried (MgSO4), filtered and concentrated
under reduced pressure to give 4.85 g of a brown oil. This crude
product was purified by flash column chromatography on silica gel
(EtOAc) to give 3.92 g (92%) of a yellow oil. – IR (nujol): ν˜ ϭ
1684, 1616 cm–1. – 1H NMR (CDCl3, 250 MHz): δ ϭ 6.38 (s, 1 H),
5.47 (m, 1 H), 3.41 (t, 2 H, J ϭ 6.08 Hz), 3.06–3.02 (m, 4 H), 2.83–
2.82 (m, 4 H), 2.71 (m, 2 H), 1.85 (m, 4 H), 1.66 (m, 2 H), 1.20 (s,
9 H). – 13C NMR (CDCl3): δ ϭ 187.1, 157.3, 148.3, 146.0, 144.3,
136.3, 135.0, 121.8, 72.8, 60.9, 33.6, 31.1, 29.5, 28.6, 26.5, 25.0,
22.8, 22.6. – C21H29NO2 (327.47): calcd. C 77.02, H 8.93, N 4.28,
O 9.77; found C 77.32, H 9.23, N 3.95, O 9.54. – MS (CI, NH3);
m/z (%): 328 (100) [MHϩ].
(m, 4 H), 1.82 (s, 4 H), 1.70 (m, 4 H), 1.23 (s, 9 H), 1.20 (s, 9 H). –
13C NMR (CDCl3): δ ϭ 195.8, 156.0, 151.2, 150.4, 148.3, 147.3,
147.0, 146.3, 138.3, 135.8, 134.1, 133.5, 132.9, 130.3, 129.4, 128.2,
72.6, 72.5, 39.0, 32.6, 29.7, 27.6, 27.4, 27.0, 26.0, 25.9, 25.1, 24.8,
24.3, 23.2, 23.0, 22.6, 22.1. – C41H53N3O3 H2O (653.89): calcd. C
75.31, H 8.48, N 6.43, O 9.79; found C 75.15, H 8.28, N 6.41, O
9.86. – MS (CI, NH3); m/z (%): 636 (100) [MHϩ].
Annelated Quinquepyridine 15. – Method A: A mixture of 0.43 g
(1.3 mmol) of 12, 0.83 g (1.3 mmol) of 14 and 0.50 g (6.5 mmol) of
ammonium acetate was refluxed for 8 h. The solution was allowed
to cool to room temperature and then concentrated under reduced
pressure. The residue was dissolved in dichloromethane (50 mL)
and washed with water (2 ϫ 30 mL). The aqueous layers were com-
bined and then extracted with dichloromethane (2 ϫ 25 mL). The
organic layers were combined, washed with saturated aqueous so-
dium hydrogencarbonate, filtered on phase separator paper and
concentrated. The crude product was chromatographed on deactiv-
Heptacyclic Annelated Terpyridine 13a: A mixture of 0.512 g
(1.56 mmol) of 12, 0.50 g (1.6 mmol) of 8, 0.96 g (16.0 mmol) of ated alumina (AcOEt/MeOH, 90:10) and gave a high Rf fraction,
ammonium acetate and 16 mL of anhydrous pyridine was heated
at 90 °C for 6 h. After cooling to room temperature the solution
was diluted with dichloromethane (20 mL) and washed with water
(3 ϫ 20 mL). The aqueous phases were combined and extracted
with dichloromethane (2 ϫ 20 mL). The organic layers were com-
bined, dried (MgSO4), filtered and concentrated under reduced
pressure. The residue was chromatographed on alumina (ethyl acet-
ate) to give 0.600 g (62%) of 13a as beige crystals; m.p. 140–141
°C. – 1H NMR (CDCl3, 250 MHz): δ ϭ 7.35 (s, 1 H), 5.12 (s, 2 H,
H2O), 3.41 (m, 4 H), 3.20 (m, 4 H), 2.93 (m, 8 H), 2.72 (m, 8 H),
1.84 (m, 8 H), 1.68 (m, 4 H), 1.22 (s, 18 H). – 13C NMR (CDCl3):
δ ϭ 155.7, 150.8, 148.5, 147.2, 134.5, 133.0, 130.7, 129.4, 72.7, 61.0,
32.4, 29.8, 27.6, 26.1, 25.0, 23.4, 23.1, 22.7. – C41H55N3O2.H2O
(639.92): calcd. C 76.95, H 8.98, N 6.57, O 7.50; found C 76.77, H
8.84, N 6.53, O 7.22. – MS (CI, NH3) m/z (%): 622 (100) [MHϩ],
639 (25) [MNH4ϩ].
which was identified as a mixture of by-products, and a low Rf
fraction containing the desired product 15. The second fraction was
chromatographed on deactivated alumina (AcOEt/iPrOH/Et3N,
30:5:0.5) to give 0.265 g (25% yield) of the desired product as a
yellow oil, which was triturated with ethyl acetate/dichloromethane
to afford a yellow solid. Recrystallisation of this material by slow
evaporation of a 1:1 dichloromethane/diethyl ether solution af-
forded fine yellow needles; m.p. 114–133 °C.
Method B:
A mixture of 1.5 g (4.55 mmol) of 17, 1.4 g
(18.20 mmol) of ammonium acetate and 50 mL of anhydrous pyr-
idine was heated at 40 °C for 1 h. A solution of 3.24 g (10.01 mmol)
of α-methylene ketone 12 in 10 mL of pyridine was added to the
preheated reaction mixture, and heating was continued at reflux
for an additional 4 h. The solution was allowed to cool to room
temperature and was concentrated under reduced pressure. The res-
idue was dissolved in dichloromethane (100 mL) and washed with
water (2 ϫ 70 mL). The aqueous layers were combined and then
extracted with dichloromethane (2 ϫ 50 mL). The organic layers
were combined, washed with saturated aqueous sodium hydrogen-
carbonate, filtered on phase separator paper and concentrated. The
crude product was chromatographed on deactivated alumina (Ac-
OEt/MeOH, 90:10) to give a high Rf fraction, which was identified
Annelated Terpyridine 13b: This unsymmetrical heptacyclic annel-
ated terpyridine was prepared by using the procedure described for
13a. Reaction of 1.65 g (5.10 mmol) of 12 with 2.03 g (5.9 mmol)
of 10 under these experimental conditions gave, after workup and
purification by chromatography on alumina (ethyl acetate), 1.96 g
(56%) of 13b as a yellow powder; m.p. 135–137 °C. – 1H NMR
(CDCl3, 250 MHz): δ ϭ 8.36 (s, 1 H), 7.57 (m, 2 H), 7.36 (m, 3 as a mixture of by-products, and a low Rf fraction containing the
H), 7.20 (m, 2 H), 3.43 (m, 2 H), 3.41 (m, 2 H), 3.15 (m, 2 H), 2.95 desired product 15. The second fraction was chromatographed as
(m, 10 H), 2.74 (m, 6 H), 1.87 (m, 6 H), 1.71 (m, 4 H), 1.23 (s, 9 described above to give 0.730 g (17% yield) of the desired product
H), 1.22 (s, 9 H). – 13C NMR (CDCl3): δ ϭ 151.5, 149.2, 148.9,
146.2, 138.9, 135.3, 134.2, 132.7, 130.6, 130.1, 129.9, 129.1, 127.8,
as a yellow oil, which was triturated with ethyl acetate/dichlorome-
thane to afford a yellow solid. Recrystallisation of this material by
127.6, 125.9, 72.6, 61.0, 60.9, 33.2, 30.0, 29.9, 27.7, 27.5, 26.5, 26.0, slow evaporation of a 1:1 dichloromethane/diethyl ether solution
25.1, 24.8, 23.9, 23.5, 23.2, 23.0, 22.9. – C48H58N3O2 (709.01):
afforded fine yellow needles; m.p. 113–133 °C. – 1H NMR (CDCl3,
calcd. C 81.31, H 8.25, N 5.93, O 4.51; found C 81.38, H 8.52, N 250 MHz): δ ϭ 7.65 (s, 2 H), 3.45 (m, 4 H), 3.10–2.40 (m, 30 H),
6.03, O 4.21. – FAB (NBA); m/z (%): 710 (79) [MHϩ], 732 (100) 1.90–1.40 (m, 14 H), 1.22 (s, 27 H). – 13C NMR (CDCl3): δ ϭ
[MNaϩ].
154.9, 151.6, 149.7, 149.5, 148.7, 148.4, 147.0, 136.1, 134.4, 134.3,
133.8, 131.3, 129.6, 73.0, 72.9, 60.9, 60.6, 31.7, 30.1, 29.7, 27.6,
26.6, 26.3, 25.6, 25.2, 24.2, 22.5, 22.4, 22.1. – C62H79N5O3 (942.35):
calcd. C 79.02, H 8.45, N 7.43, O 5.09; found C 79.35, H 8.68,
N 7.27, O 5.41. – FAB (NBA); m/z (%): 964 (100) [MNaϩ], 980
(7) [MKϩ].
Heptacyclic Ketone 14: A solution of 3.10 g (4.4 mmol) of 13b in
50 mL of CH2Cl2/methanol (1:1, v/v) was cooled to –78 °C. An
ozone/oxygen mixture was bubbled through the solution for 3 h
and then the solution was purged of ozone by bubbling with oxygen
and argon for 1 h. Dimethyl sulfide (1 mL) was added and the re-
sulting mixture was stored at room temperature overnight. The
mixture was concentrated under reduced pressure (0.1 Torr). The
crude product was chromatographed on alumina, eluting with ethyl
9-(3-tert-Butoxypropyl)-1,2,3,4,4,6,7,8-octahydro-4,5-bis-
(phenylmethylene)acridine (16): A mixture of 18.04 g (60 mmol) of
5, 54.4 mL (538 mmol) of freshly distilled benzaldehyde and 24 mL
992
Eur. J. Org. Chem. 2000, 987Ϫ994

Synthesis of New Soluble Annelated Polypyridines
Table 1. Crystal data and structure refinement
FULL PAPER
by the least-squares refinement of 5000 reflections. Only statistical
fluctuations were observed in the intensity monitors over the course
of the data collections.
Compound
4
The structure was solved by direct methods (SIR92[22]) and refined
by least-squares procedures on F2. All H atoms attached to carbon
were introduced in calculations in idealised positions [d(CH) ϭ 0.96
Empirical formula
Formula mass
Temperature
C20H34O3
322.47
293(2) K
˚
˚
Wavelength
0.71073 A
A] and treated as riding models with isotropic thermal parameters
Crystal system
Space group
Unit cell dimensions
Monoclinic
20% higher than those of the carbon to which they are attached.
Least-squares refinements were carried out by minimising the func-
tion Σw(F2o – Fc2)2, where Fo and Fc are the observed and calculated
structure factors. The weighting scheme used in the last refinement
cycles was w ϭ 1/[σ2(F2o) ϩ (aP)2 ϩ bP] where P ϭ (F2o ϩ 2F2c)/3.
Models reached convergence with R ϭ Σ(||Fo| – |Fc||)/Σ(|Fo|) and
wR2 ϭ {Σw(F2o – F2c)2/Σw(F2o)2}1/2, having values listed in Table 1.
P21/c
˚
a ϭ 13.033(2) A
˚
˚
b ϭ 12.9530(14) A
c ϭ 11.3633(18) A
β ϭ 95.075(19)°
3
˚
Volume
Z
1910.8(5) A
4
Density (calculated)
Absorption coefficient
F(000)
1.121 Mg/m3
0.073 mm–1
712
The calculations were carried out with the SHELXL-97 program[23]
running on a PC. The molecular view was obtained with the help
of CAMERON.[24] Crystallographic data (excluding structure fac-
tors) for the structure(s) reported in this paper have been deposited
with the Cambridge Crystallographic Data Centre as supplement-
ary publication no. CCDC-125052. Copies of the data can be ob-
tained free of charge on application to CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK [Fax: int. code ϩ 44-1223/336-033;
E-mail: deposit@ccdc.cam.ac.uk].
Crystal size
0.40 ϫ 0.30 ϫ 0.12 mm
2.22–24.32
Theta range for data
collection
Index ranges
–15 Յ h Յ 15, –14 Յ k Յ 14, –13 Յ l Յ 13
Reflections collected
Independent reflections
Absorption correction
Refinement method
15013
3053 [R(int) ϭ 0.1261]
None
Full-matrix least squares on F2
Data/restraints/parameters 3053/0/212
Goodness-of-fit on F2
1.119
Final R indices [I Ͼ 2σ(I)] R1 ϭ 0.0860, wR2 ϭ 0.1854
R indices (all data)
R1 ϭ 0.1711, wR2 ϭ 0.2181
–3
˚
Largest diff. peak and hole 0.217 and –0.158 e A
Acknowledgments
We thank Prof. R. P. Thummel for helpful discussions. Financial
support from the CNRS and for Doctoral fellowships (C. F., E. B.)
(254 mmol) of distilled Ac2O was refluxed for 16 h. The solution
was cooled and concentrated under reduced pressure (0.1–1 Torr).
The residue was dissolved in Et2O and cooled to –20 °C. The pre-
cipitate was collected and washed with cooled Et2O to give 27.48 g
`
from the ‘‘Ministere de lЈEducation Nationale, de la Recherche et
`
`
de la Technologie’’ and the ‘‘Ministere des Affaires Etrangeres’’ are
gratefully acknowledged.
1
(96%) of 16 as white powder; m.p. 90–91 °C. – H NMR (CDCl3,
[1] [1a]
[1b]
250 MHz): δ ϭ 8.13 (s, 2 H), 7.40 (m, 8 H), 7.28 (m, 2 H), 3.41 (t,
2 H, J ϭ 6.1 Hz), 2.85 (m, 8 H), 2.68 (t, 2 H, J ϭ 5.9 Hz), 1.95
(m, 4 H), 1.78 (m, 2 H), 1.23 (s, 9 H). – 13C NMR (CDCl3): δ ϭ
149.4, 147.8, 138.4, 136.7, 129.6, 128.0, 126.4, 126.0, 72.7, 61.1,
29.4, 27.7, 27.6, 26.2, 25.0, 23.0. – C34H39NO (477.68): calcd. C
85.49, H 8.23, N 2.93, O 3.35; found C 85.53, H 8.16, N 3.02, O
3.40. – MS (CI, NH3); m/z (%): 479 (100%) [MHϩ].
T. W. Bell, A. Firestone, J. Org. Chem. 1986, 51, 764. –
T. W. Bell, A. Firestone, J. Am. Chem. Soc. 1986, 108, 8109. –
[1c]
[1d]
T. W. Bell, J. Liu, J. Am. Chem. Soc. 1988, 110, 3673. –
T. W. Bell, Y.-M. Cho, A. Firestone, K. Healy, J. Liu, R. Lud-
[1e]
wig, S. D. Rothenberger, Org. Synth. 1990, 69, 226. –
T. W.
Bell, Y.-M. Cho, A. Firestone, K. Healy, J. Liu, R. Ludwig, S.
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[1f]
T. W. Bell, H. Jousselin, J. Am. Chem. Soc. 1991, 113,
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6283. –
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[1h]
T. W. Bell, P. J. T. Cragg, A. Firestone, D.-I. Kwok, J. Liu,
9-(3-tert-Butoxypropyl)-1,2,3,6,7,8-hexahydroacridine-4,5-dione
(17): A solution of 9.57 g (20 mmol) of 16 in 400 mL of CH2Cl2/
methanol (1:1, v/v) was cooled to –78 °C. An ozone/oxygen mixture
was bubbled through the solution for 4 h and then the solution was
purged of ozone by bubbling with oxygen and argon for 2 h. Di-
methyl sulfide (4 mL) was added and the resulting mixture was
stored at 0 °C overnight. The mixture was concentrated under re-
duced pressure (0.1 Torr) by heating on a steam bath (60–70 °C).
The residue was dissolved in CH2Cl2 (200 mL), washed with water
(2 ϫ 50 mL) and dried (MgSO4). Removal of the solvent and dry-
ing under vacuum gave a coloured solid, which was chromato-
graphed on alumina eluting with Ac2O/pentane (15:85, v/v), to give
5.96 g (91%) of 17 as a yellow powder; m.p. 114–115 °C. – IR
R. Ludwig, A. Sodoma, J. Org. Chem. 1998, 63, 2232.
[2] [2a]
[2b]
R. P. Thummel, Tetrahedron 1991, 34, 6851. –
R. P.
Thummel, Synlett 1992, 1. – [2c] V. Hegde, C.-Y. Hung, P. Mad-
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[2g]
[3] [3a]
T. W. Bell, A. Firestone, J. Liu, R. Ludwig, S. D. Rothen-
berger, Inclusion Phenomena and Molecular Recognition (Ed.: J.
L. Atwood), Plenum, New York, 1990, p. 49. – [3b] R. P. Thum-
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[3c]
1988, 110, 7894. –
T. W. Bell, J. Liu, J. Am. Chem. Soc.
[3d]
1
(KBr): ν˜ ϭ 1705 (CO) cm–1. – H NMR (CDCl3, 250 MHz): δ ϭ
1988, 110, 3673. –
C.-Y. Huang, L. A. Cabell, V. L. Lynch,
[3e]
E. V. Anslyn, J. Am. Chem. Soc. 1992, 114, 1900. –
L. S.
3.42 (t, 2 H, J ϭ 6.15 Hz), 3.08 (t, 2 H, J ϭ 6.35 Hz), 2.80 (m, 4
H), 2.79 (m, 4 H), 2.18 (m, 4 H), 1.69 (m, 2 H), 1.20 (s, 9 H). –
13C NMR (CDCl3): δ ϭ 195.7, 150.3, 147.2, 141.5, 72.8, 60.5, 39.1,
29.2, 27.5, 26.1, 25.4, 21.9. – C20H27NO3 (329.44): calcd. C 72.92,
H 8.26, N 4.25, O 14.57; found C 73.04, H 8.28, N 4.22, O 14.46. –
MS (CI, NH3); m/z (%): 330 (100) [MHϩ].
Flatt, L. A. Lynch, E. V. Anslyn, Tetrahedron Lett. 1992, 33,
[3f]
2785. –
114, 8300. –
T. W. Bell, V. J. Santora, J. Am. Chem. Soc. 1992,
[3g]
C.-Y. Huang, L. A. Cabell, E. V. Anslyn, J.
[3h]
Am. Chem. Soc. 1994, 116, 2778. –
V. Hegde, C.-Y. Hung,
P. Madhukar, R. Cunningham, T. Höpfner, R. P. Thummel, J.
Am. Chem. Soc. 1993, 115, 872. – [3i] C.-Y. Huang, T. Höpfner,
[3j]
R. P. Thummel, J. Am. Chem. Soc. 1993, 115, 12601. –
T.
W. Bell, Z. Hou, S. C. Zimmerman, P. A. Thiessen, Angew.
[3k]
X-ray Crystallographic Study: Data for 4 were collected with a Stoe
IPDS diffractometer. The final unit cell parameters were obtained
Chem. Int. Ed. Engl. 1995, 34, 2163. –
T. W. Bell, Z. Hou,
Angew. Chem. Int. Ed. Engl. 1997, 36, 1536.
Eur. J. Org. Chem. 2000, 987Ϫ994
993

H. A¨ıt-Haddou, C. Fontenas, E. Bejan, J.-C. Daran, G. G. A. Balavoine
FULL PAPER
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[14] [14a]
E. Amouyal, F. Penaud-Berruyer, D. Azhari, H. A¨ıt-Had-
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[16]
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.
[5]
[6]
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G. A. Klimov, M. N. Tilichenko, Khim. Geterotsikl. Soedin.
(Engl. Trans.) 1969, 5, 133; see also ref.[1a]
The tert-butyl group was removed by reaction of 5 with
BF3 Et2O at room temperature for 15 min: H. A¨ıt-Haddou, E.
Bejan, J.-C. Daran, G. G. A. Balavoine, unpublished results.
[7a] H. C. Beyerman, J. S. Bontekoe, J. Proc. Chem. 1961, 249. –
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G. A. Olah, M. Arvanaghi, Angew. Chem. Int. Ed. Engl. 1981,
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