Diastereoselective access to chiral non-racemic [1,3]oxazolo-[2,3-a] isoindol-5-one ring systems via o-cationic cyclization

Article abstract of DOI:10.1002/jhet.5570390223

The title compounds 4 have been prepared from suitable β-amino-alcohol 2 and phthalic anhydride (5) in a three-step sequence in moderate to good yields (58-94%). The key step of this methodology is based on an intramolecular O-cationic cyclization involving N-acyliminium species. The high levels of the observed chemoselectivity during the intermolecular or intramolecular cyclization were also discussed.

Full text of DOI:10.1002/jhet.5570390223

Mar-Apr 2002
Diastereoselective Access to Chiral Non-Racemic [1,3]Oxazolo-
383
[2,3-a]isoindol-5-one Ring Systems via O-Cationic Cyclization.
a
b
a
c
ˇ
Jana Sikoraiová, Abderrahim Chihab-Eddine, Stefan Marchalín and Adam Daïch*
a
Department of Organic Chemistry, Slovak University of Technology, Radlinského 9,
SK-812 37 Bratislava, Slovakia
Laboratoire de Bio-Organique, Département de Chimie, Université Ibnou Zohr,
b
Faculté des Sciences, B.P. 28/S, Agadir, Morocco
c
Laboratoire de Chimie, URCOM, EA 3221, Faculté des Sciences & Techniques de l'Université du Havre,
B.P: 540, 25 Rue Philippe Lebon, F-76058 Le Havre Cedex, France
Received October 23, 2001
Dedicated to Professor Jean Morel for his retirement
The title compounds 4 have been prepared from suitable β−amino- alcohol 2 and phthalic anhydride (5) in
a three-step sequence in moderate to good yields (58-94%). The key step of this methodology is based on an
intramolecular O-cationic cyclization involving N-acyliminium species. The high levels of the observed
chemoselectivity during the intermolecular or intramolecular cyclization were also discussed.
J. Heterocyclic Chem., 39, 383 (2002).
Scheme 1
As reviewed recently by Meyers et al. [1], the bicyclic
N,O-acetal product, commonly known as the bicyclic lac-
tam, has proven to be an exceptional chiral building block
for the asymmetric construction of a wide variety of nat-
ural and unnatural carbocyclic and heterocyclic com-
pounds containing one or more stereogenic center(s) [1].
However, structurally related aromatic tricyclic lactams
are little explored in the literature, a fact that is reflected
in the few reports of synthetic applications of nitrogen
heterocycles [2-6].
As a consequence of the greater potential of these
bicyclic lactams, notable advances concerning the synthe-
sis and reactivity of these species continue to be made. So,
three general methods have been developed to accede to
these polycyclic systems: 1°)- The most frequently used
method to achieve this reaction, was the cyclodehydration
process between an optically pure amino-alcohol 2 and a
ketoacid 1 (Scheme 1) under azeotropic removal of water
with a catalytic amount of p-toluenesulfonic acid [5] or not
[1-4,6]; 2°)-The aromatic tricyclic lactam unit was also
reported recently according to this second route: a palla-
dium-catalyzed stereoselective synthesis via carbonylative
cyclization process between amino alcohol 2 and 2-bromo-
benzaldehyde (3) under controlled pressure [6]; 3°)-The
third way developed to obtain these lactams 4 was related
to the extensive work involving N-acyliminium species
[7,8]. In all these reported methods, the corresponding
isoindolinones 4 were isolated in moderate to good yields.
Another method based on an intramolecular nucleophilic
substitution was also described for preparation of similar
lactams with oxygen atom as nucleophile. The yields
reported were low and in all cases the starting materials
were recovered [9a]. But with a nitrogen atom as an inter-
nal nucleophile, the azacyclic products were isolated in
good yields [9b].
Because of the flexibility and versatility of the latter
strategy allied with our general interest in development of
synthetic utility on N-acyliminium ion chemistry, we pre-
sent in this paper a facile approach to chiral monosubsti-
tuted oxazoloisoindolinones 4.
Recently, Kumar et al. [10] have reported the dimeriza-
tion of α-hydroxylactam 7a into 9a in acidic medium (i.e.
catalytic trifluoroacetic acid, dichloromethane, room tem-
perature, 16h: Method A) via an unexpected intermolecu-
lar cyclization (Scheme 2). During these investigations the
formation of the N,O-acetal monomer product 4a was not
detected. Based on these observations, our first target was
to re-examine the cationic cyclization to identify the best
formulation to achieve the intramolecular cyclization lead-
ing to the oxa-tricyclic lactam 4a.

ˇ
384
J. Sikoraiová, A. Chihab-Eddine, S. Marchalín and A. Daïch
Vol. 39
Scheme 2
So, the requisite N-acyliminium ion precursor 7a was
The subjection of α-hydroxylactam 7a to weak acetic
acid (Method B) or catalytic p-toluenesulfonic acid
(Method C) in dichloromethane at room temperature for
36 hours or 24 hours (Table 1, entry 2 or 3) afforded only
the dimeric product 9a which showed a (1aS,8R,10aS,17R)
configuration in 42 or 82% yield, respectively. This prod-
uct, which resulted from an intermolecular cyclization of
the N-acyliminium ion intermediate 8a, is identical to that
reported earlier by using conditions i [10]. Thus, we exam-
ined the effect of an R group substituent and its absolute
configuration in the intermolecular cyclization process.
obtained in 2 steps from phthalimide (5), by thermal
amino-anhydride condensation at 200° (95%) (Method I)
or by condensation under azeotropic conditions (89%)
(Method II) [11], followed by sodium borohydride reduc-
tion under mild conditions with regular addition of ethano-
lic hydrogen chloride solution (3 drops of concentrated
hydrochloric acid in 5 ml of ethanol) (i.e., 3 equivalents of
sodium borohydride, methanol, 0-5°, 30 minutes,
hydrochloric acid in ethanol, about 75% in all cases)
[10,12].
Table 1
Screening of the Reaction Conditions of O-Cationic Cyclization of the Ions N-Acyliminium Ion Precursors 7 Leading to
Monomer 4 and Dimer 9 Produced via Scheme 2
Entry
β-amino-alcohol [a]
2a R = Et (R )
conditions
Product [b]
mp°/oil
Yield %
Method
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
i
ii
9a [10]
9a
9a
4a
4a
4a
9b
4b
4b
9c
non indicated
242-243
40
42
82
58
71
61
75
84
88
70
89
84
94
79
82
69
74
A
B
C
D
E
F
B
D
E
B
E
B
E
D
E
D
E
iii
iv
v
vi
ii
iv
v
ii
v
ii
v
iv
v
"
"
"
colourless oil
"
"
"
"
"
"
2b R = Et (S )
228-231
colourless oil
"
"
"
2c R = Me (R )
2d R = Me (S )
2e R = Bn (R )
2e R = Bn (S )
199-203
colourless oil
211-214
colourless oil
130-132
4c
9d
4d
4e
4e
4f
"
"
78-81
"
"
iv
v
4f
"
"
[a] Absolute configuration of amino-alcohol; [b] Solids were purified by recrystallization as indicated in experimental part while
liquids were purified by chromatography on silica gel column using iso-hexane/ethyl acetate 10/3 as eluent.

Mar-Apr 2002 Diastereoselective Access to Chiral Non-Racemic [1,3]Oxazolo[2,3-a]isoindol-5-one
385
all starting material was consumed (monitored by TLC) and
the expected monomer 4a was obtained in an excellent yield
(95%). These results were comparable to these reported in
the literature [3,4] in which, just now, only Lewis acids such
as titanium tetrachloride, tin tetrachloride, boron trifluoride
diethyl etherate, trimethylsilyl triflate and alkyl aluminum
dichloride were used intensively as CH-O activator for the
generation of N-acyliminium cation from bicyclic lactams.
Thus, α-hydroxylactams 7b-d upon treatment according
method B outlined above (Table 1, entries 7, 10 and 12),
produced after recrystallization (ethanol/water) in the
same manner the dimers 9b-d as a lone reaction products
in comparable yields of 75%, 70%, and 84%, respectively.
Invariably, the cyclization products resulted from an inter-
molecular O-cationic cyclization of the N-acyliminium ion
intermediates 8b-d.
Scheme 3
Scheme 4
In order to rationalize the stereochemical outcome of
On the basis of our precedent work in this area [11] and to
avoid the dimerization process, other reaction conditions
were tested. So, as shown in Table 1 the intramolecular
cyclization leading to tricyclic lactam 4a as a single diastere-
osomer (3R,9bS) occurred when excess trifluoroacetic acid
(Method D) (Table 1, entry 4, 58%), catalytic concentrated
hydrochloric acid (Method E) (Table 1, entry 5, 71%), or cat-
alytic concentrated sulfuric acid (Method F) (Table 1, entry
6, 61%) was used as a proton source. Furthermore, since the
bicyclic lactams could generate N-acyliminium species
under acid catalysis [1], we envisaged the treatment of the
dimeric product 9a with hydrochloric acid (Method E)
(Table 1, conditions v). Under these conditions, interestingly,
these cyclization reactions, we have invoked the kinetic
versus thermodynamic control [13] using the formal
N-acyliminium species as intermediates (Scheme 4).
In fact, under mild conditions such as in the presence of
catalytic trifluoroacetic acid, catalytic p-toluenesulfonic
acid or neat acetic acid (Methods A, B and C), the N-acyli-
minium ion 8a lead to the dimeric product 9a as a single iso-
mer [11] under kinetic process (fast reaction). Similarly,
under harsher conditions such as excess of trifluoroacetic
acid, or a catalytic amount of strong mineral acid (Methods
D, E and F), 8a led in an alternate way to the monomeric
product 4a under thermodynamic control. This latter,

ˇ
386
J. Sikoraiová, A. Chihab-Eddine, S. Marchalín and A. Daïch
Vol. 39
Since it was possible that imides 6a-f could generate
chiral cyclic lactams 4 via an intramolecular α-oxoami-
doalkylation cyclization, we explored the elaboration of
different aromatic imide models, substituted by ethyl,
methyl and benzyl groups with R and S absolute configura-
tion at the carbon adjacent to nitrogen atom, to establish
the generality and versatility of the synthetic sequence
highlighted in Schemes 1 and 2.
For this end and in the same way, α-hydroxylactams
7b-f readily obtained by procedure as outlined for their
analogous ω-carbinol lactam 7a, were treated under condi-
tions iv (Method D) and/or v (Method E) (see Table 1 for
details) and led to the cyclization products 4b, 4c, 4d, 4e
and 4f in appreciable yields. Structures 4b-d, were also
obtained in good yields (70-84%) from the dimer 4b-d by
a consecutive ring opening-ring closure process (RO-RC)
involving N-acyliminium ion intermediates. No epimeriza-
(3R,9bS)-3-ethyl-2,3-dihydro-9bH-oxazolo[2,3-a]isoindol-
5-one (4a), which is the result of a "disfavored" 5-endo-trig-
onal cyclization process [14], was also obtained from corre-
sponding dimer under strong acidic conditions (Method E).
In this scenario, the CH-O linkage of the kinetic product 9 is
cleaved under protic acid activation into N-acyliminium ion
congener 8, which lead thermodynamically to the monomer
4 without epimerization. This fact, suggests that the kinetic
product 9 is formed reversibly depending on the acid condi-
tions, and under strong acid influence there is enough
energy for the kinetic product to get back to the starting
N-acyliminium ion 8. In this case, there will be enough
energy for some thermodynamic product 4 to be formed.
Furthermore, in both intermolecular and intramolecular
O-cyclization process, the reaction proceed under mild
conditions, cleanly and afforded the desired cyclic lactams
4a and 9a with moderate to good yields, and with high
stereocontrol (during this process only one diastereosomer
was obtained).
tion of the angular stereogenic center C was observed
9b
during these transformations.
Structure assignments of all compounds are based on
The diastereoselectivity observed during the O-cationic
cyclization of α-hydroxylactam 7a in acidic medium
seems to proceed probably through Cram's rule (Scheme
3). This, can be explained by assuming that the transition
state TS-(I) is the more one, in which the oxygen atom
attacks the iminium ion 8a (Scheme 3) when the OH group
1
13
their IR, NMR ( H and C-NMR experiments include
NOE Difference and DEPT experiments, respectively),
and GC-MS spectra. In the case of solids, their elemental
analyses were also performed. Finally, for the known prod-
ucts, their characteristics were compared to those reported
in the literature.
is anti the R (-CH -R with R = Me) one [15] to produce
2
1
1
In summary, we have shown that chiral imides 6a-f, as
N-acyliminium ion precursors in an interrupted intermole-
in all cases the expected isoindolinone 4a as a single
diastereosomer (EIMS m/z 203 (M ) [11b].
+•
Scheme 5
cular O-cationic cyclization depending on the acidic con-
ditions, could produce efficiently under thermodynamic
control the expected chiral tricyclic lactams 4a-f in good
yields and an excellent stereocontrol. These latter, were
also obtained from the dimeric products 9 obtained
reversibly as kinetic isomers. Finally, because of the
greater synthetic potential of these bicyclic lactams, the
extension to elaboration of more fused isoindolinones is
possible. Investigation in this way is underway.
The absolute configuration of the newly created stereo
center at the 9b-position for the monomer 4a was deter-
mined by NOE difference experiments. In fact, when H
9b
(singlet at δ = 5.86 ppm) was irradiated, no significant
NOE effect was detected for H (quadruplet at δ = 4.07
3
ppm), but a strong NOE effect was observed between H
9b
and the angular ethyl group -CH -CH (quadruplet at δ =
2
3
1.73 ppm). These results demonstrate the trans-orientation
of H and H as shown in Scheme 3.
9b
3

Mar-Apr 2002 Diastereoselective Access to Chiral Non-Racemic [1,3]Oxazolo[2,3-a]isoindol-5-one
387
EXPERIMENTAL
(1'S)-N-(2'-Ethyl-1'-hydroxyethyl)-1H-isoindole-1,3(2H)-dione
(6b).
General.
This product was obtained as a colourless oil in 91 (Method II)
and 92% (Method I) yields; bp 218°/9 torr; ir (neat): ν 3502
All melting points were measured on a Boetius micro hot-stage
and are uncorrected. The infrared spectra of solids (potassium
bromide) were recorded on a Perkin Elmer FT-IR paragon 1000
-1
1
(OH), 1700 ( C=O) cm ; H nmr (deuteriochloroform): δ 0.92 (t,
J = 7.5Hz, 3H, CH ), 1.88 (m, J = 7.5Hz and J = 7.8Hz, 2H, CH ),
3
2
3.02 (s, broad, 1H, OH), 3.86 (dd, J = 11.7Hz and J = 3.6Hz,
1',1'
1',2'
1
13
spectrometer. The H and C NMR spectra were recorded on a
Bruker AC-200 (200 MHz) instrument in deuteriochloroform and
chemical shifts (δ) are expressed in ppm relative to TMS as inter-
nal standard. Ascending thin layer chromatography was per-
formed on pre-coated plates of silica gel 60 F 254 (Merck) and
the spots visualized using an ultraviolet lamp or iodine vapor.
Optical rotations were measured with a Perkin Elmer 241
polarimeter in a 10 cm cell in chloroform at 25°. Mass spectral
measurements were recorded on an AEI MS 902 S spectropho-
tometer. The elemental analyses were carried out by the micro-
analysis laboratory of INSA, F-76130 Mt. St. Aignan, France.
1H, H ), 4.08 (dd, J = 11.7Hz and J = 7.8Hz, 1H, H ), 4.28
1'
1',1'
1',2'
1'
(dd, J
= 3.6Hz and J
= 7.5Hz, 1H, H ), 7.71-7.83 (m, 4H,
2',1'
2',1' 2'
13
H
); C nmr (deuteriochloroform): δ 10.8 (CH ), 21.7 (CH ),
arom
3 2
55.6 (C ), 62.8 (C ), 123.2 (C and C ), 131.7 (C and C ), 134.0
2'
1'
5
6
3a
+•
7a
(C and C ), 169.2 (C and C ); EIMS m/z 219 (M ).
4
7
1
3
Anal. Calcd. for C
H NO (219.24): C, 65.74; H, 5.97; N,
12 13 3
6.39. Found: C, 65.58; H, 5.82; N, 6.11.
(1'R)-N-(1'-hydroxyethyl-2'-methyl)-1H-isoindole-1,3(2H)-
dione (6c).
This product was obtained as a white yellow solid in 88 (Method
II) and 90% (Method I) yields; mp 99-101° (toluene, water or
General Procedure for Synthesis of Imides (6a-f).
-1
ethanol); ir (potassium bromide): ν 3462 (OH), 1739 ( C=O) cm ;
Method I.
1
H nmr (deuteriochloroform): δ 1.43 (d, J = 7.2Hz, 3H, CH ), 3.19
3
(s broad, 1H, OH), 3.85 (dd, J
= 11.7Hz, J
= 3.9Hz, 1H,
1',1'
1',2'
A mixture of powdered phthalic anhydride (5) (1.48 g, 10
mmoles) and (R or S)-β-amino-alcohol 2 (10 mmoles) was heated
without solvent under vigorous stirring at 200° for 3 hours. The
reaction mixture was cooled, poured on crushed ice (50 ml) and
extracted twice with dichloromethane (2x50 ml). After separa-
tion, the organic layer was washed with water, brine, dried over
magnesium sulfate and concentrated in vacuo. The resulting liq-
uid was purified by distillation under reduced pressure to give
imides 6a (95%) and 6b (92%) as colourless oil. The resulting
solid was recrystallized from toluene (water or ethanol) to give
suitable imides 6c-f in 90-94% yield.
H-1'), 4.05 (dd, J
= 11.7Hz, J
= 8.0Hz, 1H, H ), 4.48 (m,
1',1'
1',2' 1'
J
= 3.9Hz, J
= 7.8Hz, 1H, H ), 7.68-7.73 (m, 2H, H
),
2',1'
2',1'
2'
arom
1
7.79-7.82 (m, 2H, H
); H nmr (deuteriochloroform): δ 14.7
arom
(CH ), 49.4 (C ), 64.0 (C ), 123.2 (C and C ), 131.9 (C and
3
2'
1'
5
6
3
+•
C ), 134.0 (C and C ), 168.9 (C and C ); EIMS m/z 205 (M ).
7a
4
7
1
3
Anal. Calcd. for C H NO (205.21): C, 64.38; H, 5.40; N,
11 11
3
6.82. Found: C, 64.24; H, 5.19; N, 6.71.
(1'S)-N-(1'-hydroxyethyl-2'-methyl)-1H-isoindole-1,3(2H)-dione
(6d).
This product was obtained as a white yellow solid in 91 (Method
II) and 93% (Method I) yields; mp 97-100° (toluene, water or
Method II.
-1
ethanol); ir (potassium bromide): ν 3451 (OH), 1723 ( C=O) cm ;
A mixture of (R or S)-β-amino-alcohol 2 (10 mmoles), phthalic
anhydride (5) (1.48 g, 10 mmoles) and triethylamine (0.5 ml, 3.6
mmoles) in toluene (50 ml) was refluxed with a Dean-stark appa-
ratus for 12 hours. The reaction mixture was cooled, then was
concentrated under reduced pressure. The residue was dissolved
into dichloromethane, washed with 10% hydrochloric acid solu-
tion then with a sodium hydrogen carbonate solution. The
organic layer was dried over magnesium sulfate, concentrated
under reduced pressure, and distillation or recrystallization of the
residue from toluene (water or ethanol) gave imides 6c-f same as
above in 85-93% yield.
1
H nmr (deuteriochloroform): δ 1.42 (d, J = 7.1Hz, 3H, CH ), 3.21
3
(s broad, 1H, OH), 3.87 (dd, J
= 11.5Hz, J
= 4.1Hz, 1H,
1',1'
1',2'
H-1'), 4.02 (dd, J
= 11.5Hz, J
= 7.6Hz, 1H, H ), 4.52 (m,
1',1'
1',2' 1'
J
= 4.1Hz, J
= 7.6Hz, 1H, H ), 7.69-7.75 (m, 2H, H
),
2',1'
2',1'
2'
arom
1
7.77-7.84 (m, 2H, H
); H nmr (deuteriochloroform): δ 14.6
arom
(CH ), 49.5 (C ), 64.1 (C ), 123.1 (C and C ), 131.5 (C and
3
2'
1'
5
6
3
+•
C ), 134.1 (C and C ), 168.8 (C and C ); EIMS m/z 205 (M ).
7a
4
7
1
3
Anal. Calcd. for C H NO (205.21): C, 64.38; H, 5.40; N,
11 11
3
6.82. Found: C, 64.29; H, 5.21; N, 6.66.
(1'R)-N-(2'-Benzyl-1'-hydroxyethyl)-1H-isoindole-1,3(2H)-
dione (6e).
(1'R)-N-(2'-Ethyl-1'-hydroxyethyl)-1H-isoindole-1,3(2H)-dione
(6a).
This product was obtained as a white yellow solid in 89
(Method II) and 91% (Method I) yields; mp 89° (toluene, water
or ethanol); ir (potassium bromide): ν 3456 (OH), 1768 ( C=O)
This product was obtained as a colourless oil in 89% (Method
-1
1
II) and 95% (Method I) yields; bp 205°/10 torr; ir (neat): ν 3495
cm ; H nmr (deuteriochloroform): δ 3.20 (d, J = 7.5Hz, 2H,
CH -Ph), 3.85 (s, broad, 1H, OH), 3.90 (dd, J = 17.5Hz and
-1
1
(OH), 1706 ( C=O) cm ; H nmr (deuteriochloroform): δ 0.90 (t,
2
1',1'
J = 7.5Hz, 3H, CH ), 1.86 (m, J = 7.6Hz and J = 7.7Hz, 2H,
J
= 5.0Hz, 1H, H ), 4.08 (dd, J = 17.5Hz and J = 9.0Hz,
3
1',2'
1' 1',1' 1',2'
CH ), 3.83 (dd, J
= 11.7Hz, J
= 3.5Hz, 1H, H ), 4.05 (dd,
1H, H ), 4.62 (m, J = 4.9Hz, and J = 8.9Hz, 1H, H ), 7.12-
2
1',1'
1',2' 1'
1'
2',1'
2',1'
2'
13
J
J
= 11.7Hz, J = 7.7Hz, 1H, H ), 4.22 (m, J = 3.5Hz and
7.21 (m, 5H, H
), 7.69-7.80 (m, 4H, H
); C nmr (deuteri-
1',1'
1',2' 1' 2',1'
arom
arom
= 7.5Hz, 1H, H ), 4.26 (s, broad, 1H, OH), 7.82-7.69 (m,
ochloroform): δ 34.8 (CH ), 55.1 (C ), 62.6 (C ), 123.2 (C and
2',1'
2'
2
2'
1'
5
13
4H, H
); C nmr (deuteriochloroform): δ 10.7 (CH ), 21.7
C ), 126.8 (C ), 128.4 (C and C ), 128.9 (C and C ), 132.0
arom
3
6
4''
2''
6''
3''
5''
(CH ), 55.5 (C ), 62.7 (C ), 123.2 (C and C ), 131.7 (C and
(C and C ), 134.0 (C and C ), 137.3 (C ), 169.0 (C and C );
2
2'
1'
5
6
3a
3a
7a
4
7
1''
1
3
+•
+•
C ), 134.0 (C and C ), 169.1 (C and C ); EIMS m/z 219 (M ).
EIMS m/z 281 (M ).
Anal. Calcd. for C
7a
4
7
1
3
Anal. Calcd. for C
H NO (219.24): C, 65.74; H, 5.97; N,
H
NO (281.31): C, 72.58; H, 5.37; N,
3
12 13 3
17 15
6.39. Found: C, 65.63; H, 5.88; N, 6.17.
4.98. Found: C, 72.49; H, 5.38; N, 4.85.

ˇ
388
J. Sikoraiová, A. Chihab-Eddine, S. Marchalín and A. Daïch
Vol. 39
1
(1'S)-N-(2'-Benzyl-1'-hydroxyethyl)-1H-isoindole-1,3(2H)-dione
(6f).
Minor product: H nmr (deuteriochloroform): δ 1.17 (t, J =
7.1Hz, 3H, CH ), 1.74 (m, J = 7.5Hz, 2H, CH ), 3.50 (s, broad, 1H,
3
2
OH ), 3.75 (dd, J = 14.1Hz and J = 7.2Hz, 2H, H ), 4.54 (m,
1'
1',1'
1',2'
1'
This product was obtained as a white-yellow solid in 85
(Method II) and 94% (Method I) yields; mp 107-108° (toluene or
1H, H ), 4.88 (s, broad, 1H, OH ), 5.79 (s, 1H, H ), 7.32-7.62 (m,
2'
3
3
13
4H, H
); C nmr (deuteriochloroform): δ 10.0 (CH ), 27.4
-1
arom
3
water); ir (potassium bromide): ν 3446 (OH), 1752 ( C=O) cm ;
(CH ), 53.7 (C ), 64.6 (C ), 83.3 (C ), 123.1 (C ), 123.5 (C ),
1
2
2'
1'
3
6
5
H nmr (deuteriochloroform): δ 3.19 (d, J = 7.7Hz, 2H, CH -Ph),
2
129.7 (C ), 130.6 (C ), 132.2 (C ), 143.9 (C ), 170.5 (C ).
7
4
7a
3a
1
3.51 (s, broad, 1H, OH), 3.91 (dd, J
= 11.9Hz and J
=
1',1'
1',2'
3.7Hz, 1H, H ), 4.08 (dd, J
= 12.0Hz and J
= 7.5Hz, 1H,
(1'R,3R and 1'R,3S)-2,3-Dihydro-2-(1'-hydroxyethyl-2'-methyl)-
3-hydroxy-1H-isoindol-1-one (7c).
1'
1',1'
1',2'
H ), 4.62 (m, J = 3.7Hz and J = 7.7Hz, 1H, H ), 7.13-7.21
1'
2',1'
2',1'
2'
13
(m, 5H, H
), 7.64-7.76 (m, 4H, H
); C nmr (deuteri-
arom
arom
This product was obtained as an inseparable mixture of two
ochloroform): δ 34.7 (CH ), 55.2 (C ), 62.6 (C ), 123.2 (C and
2
2'
1'
5
1
diastereosomers (1.5/1) as a colourless oil in 88% yield; H nmr
C ), 126.6 (C ), 128.4 (C and C ), 128.9 (C and C ), 131.9
6
4''
2''
6''
3''
5''
(DMSO-d ): δ 1.35 (1.41) (d, J = 7.2Hz, 3H, CH ), 3.44 (4.40) (q,
6
3
(C and C ), 133.9 (C and C ), 137.3 (C ), 168.9 (C and C );
3a
7a
4
7
1''
1
3
J = 7.2Hz, 1H, H ), 3.65 (4.11) (q, J = 6.4Hz, 1H, H ), 4.19-4.25
+•
1'
1'
EIMS m/z 281 (M ).
Anal. Calcd. for C
(4.98-5.12) (m, 1H, H ), 5.94 (6.14) (d, J = 8.8Hz, 1H, H ), 6.59
2'
3
H
NO (281.31): C, 72.58; H, 5.37; N,
3
17 15
(6.63) (d, J = 8.8Hz, 1H, OH ), 6.88 (s, broad, 1H, OH), 7.66-7.72
3
4.98. Found: C, 72.44; H, 5.28; N, 4.91.
13
(m, 4H, H
); C nmr (DMSO-d ): δ 14.5 (16.2) (CH ), 51.2
arom
6
3
General Procedure for the Synthesis of ω-Carbinol Lactams (7a-f).
(51.0) (C ), 62.5 (64.0) (C ), 81.3 (81.7) (C ), 122.7 (122.8)
2'
1'
3
(C ), 123.2 (123.6) (C ), 129.7 (129.5) (C ), 131.6 (131.2) (C ),
5
4
7
7a
To a stirred solution of chiral N-alkylated phthalimide 6a-f (10
mmoles) in dry methanol (40 ml) at 0–5° was added by portions
3 equivalents of sodium borohydride (1.135 g, 30 mmoles). After
addition of sodium borohydride, 3 drops of ethanolic hydrochlo-
ric acid solution was added during 10 minutes (prepared from 9
drops of concentrated hydrochloric acid in 15 ml of ethanol) until
the reaction was complete (30 minutes to 2 hours, monitored by
TLC). The excess of sodium borohydride was decomposed by
careful addition of 10% hydrochloric acid solution to pH = 2.
After removal of the solvent, the residue was diluted with water
(40 ml) and the whole was extracted with 30 ml of
dichloromethane. The organic layers were washed with water,
brine, dried over sodium sulfate and evaporated under reduced
pressure. The resulting oil was purified by chromatography on
silica gel column using dichloromethane/acetone (5/1) as eluent
to give pure ω-carbinol lactams 7a-f.
132.9 (132.0) (C ), 145.9 (146.2) (C ), 166.1 (167.8) (C ).
6
3a
1
(1'S,3R and 1'S,3S)-2,3-Dihydro-2-(1'-hydroxyethyl-2'-methyl)-
3-hydroxy-1H-isoindol-1-one (7d).
This product was obtained as an inseparable mixture of two
1
diastereosomers (1.2/1) as a colourless oil in 82% yield; H nmr
(DMSO-d ): δ 1.31 (1.39) (d, J = 6.9Hz, 3H, CH ), 3.45 (4.33) (q,
6
3
J = 6.9Hz, 1H, H ), 3.61 (4.21) (q, J = 6.6Hz, 1H, H ), 4.20-4.24
1'
1'
(4.96-5.02) (m, 1H, H ), 5.92 (6.04) (d, J = 9.0Hz, 1H, H ), 6.56
2'
3
(6.63) (d, J = 9.0Hz, 1H, OH ), 6.71 (s, broad, 1H, OH), 7.59-7.65
3
13
(m, 4H, H
); C nmr (DMSO-d ): δ 15.0 (16.7) (CH ), 50.0
arom
6
3
(50.2) (C ), 62.9 (64.2) (C ), 81.2 (81.4) (C ), 122.6 (122.9)
2'
1'
3
(C ), 123.1 (123.7) (C ), 129.5 (129.6) (C ), 131.0 (131.9) (C ),
5
4
7
7a
132.4 (132.2) (C ), 145.4 (145.6) (C ), 166.6 (167.4) (C ).
6
3a
1
(1'R,3R and 1'R,3S)-2-(2'-Benzyl-1'-hydroxyethyl)-2,3-dihydro-
3-hydroxy-1H-isoindol-1-one (7e).
(1'R,3R and 1'R,3S)-2,3-Dihydro-2-(2'-ethyl-1'-hydroxyethyl)-3-
hydroxy-1H-isoindol-1-one (7a).
This product was obtained as a inseparable mixture of two
1
diastereosomers (1/1) as a colourless oil in 94% yield; H nmr
This product was obtained as a inseparable mixture of two
1
(deuteriochloroform): δ 3.06 (3.24) (m, 2H, CH -Ph), 3.67 (3.79)
diastereosomers (1/1) as a colourless oil in 75% yield; H nmr
2
(m, 1H, H ), 3.99 (4.50) (m, 2H, H ), 4.75 (4,88) (s, broad, 1H,
(deuteriochloroform): δ 0.82 (1.01) (t, J = 7.3Hz, 3H, CH ), 1.71
2'
1'
3
OH ), 5.10 (5.65) (s, 1H, H ), 5.62 (6.28) (s, broad, 1H, OH ),
(1.92) (m, J = 7.0Hz, 2H, CH ), 2.74 (2.97) (s, broad, 1H, OH ),
1'
3
3
2
1'
13
7.06-7.50 (m, 9H, H
); C nmr (deuteriochloroform): δ 34.7
3.60 (3.83) (dd, J = 9.0Hz, 1H, H ), 3.80 (3.99) (dd, J = 12.0Hz,
arom
1'
(35.1) (CH ), 55.3 (58.1) (C ), 62.8 (63.0) (C ), 81.6 (82.8) (C ),
1H, H ), 4.14 (4.49) (m, J
= 7.2Hz and J
= 8.7Hz,
2
2'
1'
3
1'
2',CH2-CH3
2',1'
122.7 (123.0) (C ), 126.6 (126.8) (C ), 128.5 (128.7) (C and
1H, H ), 4.93 (5.93) (s, broad, 1H, OH ), 5.81 (5.86) (s, 1H, H ),
5
4
2''
2'
3
3
13
C ), 128.8 (128.9) (C ), 129.0 (129.1) (C and C ), 129.4
7.32-7.54 (7.51-7.82) (m, 4H, H
); C nmr (deuteriochloro-
6''
4''
3''
5''
arom
(129.6) (C ), 130.5 (131.2) (C ), 132.3 (132.4) (C ), 137.3
form): δ 10.7 (10.9) (CH ), 21.7 (27.4) (CH ), 55.2 (56.3) (C ),
7
7a
6
3
2
2'
(138.4) (C ), 143.9 (144.4) (C ), 168.8 (169.1) (C ).
63.7 (64.1) (C ), 80.1 (90.7) (C ), 123.2 (123.9) (C ), 123.2
1''
3a
1
1'
3
6
(124.4) (C ), 129.5 (130.5) (C ), 132.3 (132.8) (C ), 130.9
5
7
4
(1'S,3R and 1'R,3S)-2-(2'-Benzyl-1'-hydroxyethyl)-2,3-dihydro-
3-hydroxy-1H-isoindol-1-one (7f).
(133.4) (C ), 143.2 (143.9) (C ), 168.8 (169.2) (C ).
7a
3a
1
(1'S,3R and 1'S,3S)-2,3-Dihydro-2-(2'-ethyl-1'-hydroxyethyl)-3-
hydroxy-1H-isoindol-1-one (7b).
This product was obtained as an inseparable mixture of two
diastereosomers (1/1) as a colourless oil in 78% yield; H nmr
1
(deuteriochloroform): δ 2.94 (3.12) (m, 2H, CH -Ph), 3.65 (3.76)
This product was obtained as an inseparable mixture of two
diastereosomers (2/1) as a colourless oil in 84% yield.
Major product: H nmr (deuteriochloroform): δ 0.88 (t, J =
2
(m, 1H, H ), 3.95 (4.54) (m, 2H, H ), 4.75 (4.95) (s, broad, 1H,
2'
1'
1
OH ), 5.10 (5.80) (s, 1H, H ), 5.56 (6.18) (s, broad, 1H, OH ),
1'
3
3
13
7.12-7.57 (m, 9H, H
); C nmr (deuteriochloroform): δ 34.7
7.3Hz, 3H, CH ), 1.74 (m, J = 7.5Hz, 2H, CH ), 3.50 (s, broad, 1H,
arom
3
2
(34.9) (CH ), 54.3 (58.0) (C ), 62.7 (63.1) (C ), 80.7 (83.4) (C ),
OH ), 3.64 (dd, J = 14.1Hz and J = 7.2Hz, 2H, H ), 4.22 (m,
2
2'
1'
3
1'
1',1'
1',2'
1'
122.8 (123.1) (C ), 126.5 (126.6) (C ), 128.5 (128.6) (C and
1H, H ), 4.78 (s, broad, 1H, OH ), 5.83 (s, 1H, H ), 7.32-7.62 (m,
5
4
2''
2'
3
3
13
C ), 128.6 (128.8) (C ), 129.0 (129.1) (C and C ), 129.2
4H, H
); C nmr (deuteriochloroform): δ 10.9 (CH ), 21.6
6''
4''
3''
5''
arom
3
(129.5) (C ), 130.7 (131.3) (C ), 132.3 (132.4) (C ), 137.4
(CH ), 56.3 (C ), 64.2 (C ), 80.0 (C ), 123.2 (C ), 123.3 (C ),
7
7a
6
2
2'
1'
3
6
5
(138.3) (C ), 143.8 (144.1) (C ), 168.5 (168.7) (C ).
129.6 (C ), 130.9 (C ), 132.3 (C ), 143.1 (C ), 168.8 (C ).
1''
3a
1
7
4
7a
3a
1

Mar-Apr 2002 Diastereoselective Access to Chiral Non-Racemic [1,3]Oxazolo[2,3-a]isoindol-5-one
389
25
General Procedure for O-Cationic Cyclization (9a) and (4a-f).
[α]
= +63.90 (c 1M, CHCl ); UV (λ nm, (logε)): 245
max
D
3
1
(2.71); H nmr (deuteriochloroform): δ 1.10 (t, J = 7.2Hz, 3H,
CH ), 1.73 (q, J = 7.3Hz, 2H, CH ), 3.90 (dd, J = 8.7Hz and
= 6.6Hz, 1H, H ), 4.07 (q, J = 6.6Hz and J = 7.2Hz, 1H,
H ), 4.50 (dd, J = 8.7Hz and J = 7.2Hz, 1H, H ), 5.86 (s, 1H,
), 7.53-7.61 (m, 3H, H
(deuteriochloroform): δ 10.7 (CH ), 27.4 (CH ), 56.3 (C ), 76.2
(C ), 90.7 (C ), 123.9 (C ), 124.3 (C ), 130.6 (C ), 132.8 (C ),
133.4 (C ), 142.2 (C ), 173.6 (C ); EIMS m/z 203 (M ).
To a stirred solution of hydroxylactam 7a-f (10 mmoles) as a
mixture of two diastereosomers was added neat acid (10 ml of
acetic acid (Method B) or trifluoroacetic acid Method D) in 10
ml of dichloromethane) or catalytic amount of acid (p-toluene-
sulfonic acid (Method C), concentrated hydrochloric acid
(Method E) or sulfuric acid (Method F)) in 10 ml of
dichloromethane or chloroform and allowed to react over times
as indicated in Scheme 2. In the case of concentrated hydrochlo-
ric acid and sulfuric acid, only two to three drops were neces-
sary. After complete reaction at room temperature under stirring,
the reaction mixture was diluted with water (30 ml) and neutral-
ized with 10% sodium hydroxide aqueous solution. The solution
was extracted twice with dichloromethane or chloroform (20
ml). The organic layer was washed with water, brine, separated,
dried over magnesium sulfate and evaporated under reduced
pressure. The resulting crude residue was purified by chro-
matography on silica gel column for oils or recrystallization for
solids to give the tricyclic product 4a-f and the dimer product 9a
in moderate to good yields.
3
2
2,2
J
2,3
2 3,2 3,2
3
2,2
2,3
2
13
H
), 7.79 (d, J = 6.9Hz, H ); C nmr
9b
arom 9
3
2
3
2
9b
7
9
6
8
+•
5a
9a
5
Anal. Calcd. for C
6.89. Found: C, 70.66; H, 6.41; N, 6.79.
H NO (203.24): C, 70.91; H, 6.45; N,
12 13 2
(3R,9bS)-2,3-Dihydro-3-methyl-9bH-oxazolo[2,3-a]isoindol-5-
one (4c).
This product was obtained as a colourless oil in 89% yield
(Method B); ir (neat): ν 1705 (CO) cm ; [α]
-1
25
= -24.30 (c 1M,
D
1
CHCl ); H nmr (deuteriochloroform): δ 1.41 (d, J = 6.3Hz, 3H,
3
CH ), 3.86 (dd, J = 8.7Hz and J = 6.3Hz, 1H, H ), 4.21-4.29
3
2,2
2,3
2
(m, J = 6.3Hz and J = 7.1Hz, 1H, H ), 4.52 (dd, J = 8.7Hz
3,2
3,2
3
2,2
and J = 7.1 Hz, 1H, H ), 5.93 (s, 1H, H ), 7.57-7.66 (m, 3H,
2,3
2
9b
13
H
), 7.81 (d, J = 7.2 Hz, 1H, H ); C nmr (deuteriochloro-
arom
9
(3R,9bS)-Bis-3-ethyl-2,3-dihydro-9bH-oxazolo[2,3-a]isoindol-
5-one (9a).
form): δ 19.9 (CH ), 50.1 (C ), 77.5 (C ), 90.4 (C ), 124.4 (C ),
3
3
2
9b
8
124.5 (C ), 130.1 (C ), 132.2 (C ), 133.0 (C ), 142.2 (C ),
9
6
7
5a
9a
+•
173.3 (C ); EIMS m/z 189 (M ).
5
This product was obtained as white solids in 42% (Method
B) or 82% (Method C) yield; mp 242-243° (ethanol/N,N-
dimethylformamide); ir (potassium bromide): ν 1700 (CO)
Anal. Calcd. for C H NO (189.21): C, 69.82; H, 5.86; N,
11 11
2
7.40. Found: C, 69.77; H, 5.59; N, 7.29.
-1
35
25
cm ; [α]
= -300.00 (c 1M, CHCl ) ([α]
= -14.00 (c
nm, (logε)): 250
max
D
3
D
(3S,9bR)-2,3-Dihydro-3-methyl-9bH-oxazolo[2,3-a]isoindol-5-
one (4d).
0.5M, CHCl ), reference [10]); UV (λ
(2.96); H nmr (deuteriochloroform): δ 0.91 (t, J = 7.3Hz, 3H,
3
1
This product was obtained as a colourless oil in 94% yield
CH ), 1.83 (m, 2H, CH ), 3.42 (d, J = 5.1Hz, 2H, H ), 4.37 (m,
3
2
2
-1
25
(Method E); ir (neat): ν 1702 (CO) cm ; [α]
= +22.30 (c 1M,
D
1H, H ), 6.00 (s, 1H, H ), 7.51-7.60 (m, 3H, H ), 7.82 (d, J
3
9b
arom
1
CHCl ); H nmr (deuteriochloroform): δ 1.43 (d, J = 6.6Hz, 3H,
13
3
= 7.5Hz, 1H, H ); C nmr (deuteriochloroform): δ 10.8 (CH ),
9
3
CH ), 3.82 (dd, J = 8.4Hz and J = 6.6Hz, 1H, H ), 4.23-4.30
3
2,2
2,3
2
22.1 (CH ), 52.0 (C ), 64.1 (C ), 84.6 (C ), 123.1 (C ), 123.8
2
3
2
9b
7
(m, J = 6.6Hz and J = 6.9Hz, 1H, H ), 4.50 (dd, J = 8.4Hz
3,2
3,2
3
2,2
(C ), 129.8 (C ), 131.8 (C ), 132.2 (C ), 141.1 (C ), 168.1
9
6
5a
8
9a
and J = 6.9Hz, 1H, H ), 5.91 (s, 1H, H ), 7.55-7.61 (m, 3H,
+•
+•
2,3
2
9b
(C ); EIMS m/z 1/2M +2 = 205 (11%), 1/2M +1 = 204
5
13
H
), 7.79 (d, J = 6.9Hz, 1H, H ); C nmr (deuteriochloro-
+•
+•
arom
9
(100%), 1/2M -CH = 190 (5%), 1/2M -OH = 188 (2%), 172
3
form): δ 19.7 (CH ), 50.5 (C ), 77.7 (C ), 90.6 (C ), 124.0 (C ),
3
3
2
9b
8
(35%), 132 (29%), 117 (3%), 104 (5%).
124.4 (C ), 130.6 (C ), 132.8 (C ), 133.4 (C ), 142.2 (C ),
9
6
7
5a
9a
Anal. Calcd. for C
H N O (406.46): C 70.92%, H 6.45%,
24 26 2 4
+•
173.5 (C ); EIMS m/z 189 (M ).
5
N 6.89%. Found: C 71.1%, H 6.58%, N 6.99%.
Anal. Calcd. for C H NO (189.21): C, 69.82; H, 5.86; N,
11 11
2
(3R,9bS)-3-Ethyl-2,3-dihydro-9bH-oxazolo[2,3-a]isoindol-5-
one (4a).
7.40. Found: C, 69.77; H, 5.59; N, 7.29.
(3R,9bS)-3-Benzyl-2,3-dihydro-9bH-oxazolo[2,3-a]isoindol-5-
one (4e).
This product was obtained as a colourless oil in 58% (Method
D), 61% (Method E) or 71% (Method B) yield; ir (neat): ν 1712
-1
25
This product was obtained as a white solids in 79% (Method
D), or 82% (Method E) yield; mp 130-132° (diethyl
ether/hexane) (non indicated in reference [4a]); ir (potassium
(CO) cm ; [α]
= -58.70 (c 1M, CHCl ); UV (λ
nm,
D
3
max
1
(logε)): 245 (2.71); H nmr (deuteriochloroform): δ 1.10 (t, J =
7.2Hz, 3H, CH ), 1.73 (q, J = 7.3Hz, 2H, CH ), 3.90 (dd, J
=
=
3
2
2,2
3,2
-1
25
bromide): ν 1706 (CO) cm ; [α]
= -38.50 (c = 1, CHCl )
8.7Hz and J = 6.6Hz, 1H, H ), 4.07 (q, J = 6.6Hz and J
D
3
2,3
2
3,2
25
1
([α]
= -44.20 (c 3.48 M, dichloromethane), reference [4a]); H
7.2Hz, 1H, H ), 4.50 (dd, J = 8.7Hz and J = 7.2Hz, 1H, H ),
D
3
2,2
2,3
2
nmr (deuteriochloroform): δ 2.98 (dd, J = 13.9Hz and J = 7.9Hz,
1H, CH ), 3.16 (dd, J = 13.9Hz and J = 5.6Hz, 1H, CH ), 3.98
5.86 (s, 1H, H ), 7.53-7.61 (m, 3H, H
), 7.79 (d, J = 6.9Hz,
9b
arom
13
H ); C nmr (deuteriochloroform): δ 10.7 (CH ), 27.4 (CH ),
2
2
9
3
2
(dd, J = 8.7Hz and J = 6.4Hz, 1H, H ), 4.31 (dd, J = 8.7Hz
56.3 (C ), 76.2 (C ), 90.7 (C ), 123.9 (C ), 124.3 (C ), 130.6
2,2
2,3
2
2,2
3
2
9b
7
9
and J = 6.9Hz, 1H, H ), 4.44-7.49 (m, J = 6.9Hz and J =
(C ), 132.8 (C ), 133.4 (C ), 142.2 (C ), 173.6 (C ); EIMS m/z
2,3
2
3,2
6
8
5a
9a
5
+•
13.4Hz, 1H, H ), 5.74 (s, 1H, H ), 7.30-7.32 (m, 5H, H
),
203 (M )
Anal. Calcd. for C
3
9b
arom
13
7.52-7.57 (m, 3H, H
), 7.76 (d, J = 6.9Hz, 1H, H ); C nmr
H
NO (203.24): C, 70.91; H, 6.45; N,
arom
9
12 13
2
(deuteriochloroform): δ 39.7 (CH ), 55.4 (C ), 75.1 (C ), 90.9
6.89. Found: C, 70.79; H, 6.38; N, 6.82.
2
3
2
(C ), 123.9 (C ), 124.4 (C ), 126.8 (C ), 128.6 (C and C ),
9b
8
9
4''
2''
6''
(3S,9bR)-3-Ethyl-2,3-dihydro-9bH-oxazolo[2,3-a]isoindol-5-
one (4b).
129.5 (C- and C ), 130.6 (C ), 132.8 (C ), 133.2 (C ), 136.8
3''
5''
6
7
5a
+•
(C ), 142.3 (C ), 173.42 (C ); EIMS m/z 265 (M ).
1''
9a
5
Anal. Calcd. for C
5.28. Found: C, 76.88; H, 5.61; N, 5.19.
H NO (265.13): C, 76.96; H, 5.70; N,
This product was obtained as a colourless oil in 84% (Method
D) or 88% (Method E) yield; ir (neat): ν 1708 (CO) cm ;
17 15 2
-1

ˇ
390
J. Sikoraiová, A. Chihab-Eddine, S. Marchalín and A. Daïch
Vol. 39
Northfield, M. I. Page and A. M. Z. Slawin, Tetrahedron Lett., 39,
4905 (1998); [c] S. M. Allin, C. J. Northfield, M. I. Page and A. M.
Z. Slawin, Tetrahedron Lett., 40, 141 (1999); [d] S. M. Allin, C. J.
Northfield, M. I. Page and A. M. Z. Slawin, Tetrahedron Lett., 40,
143 (1999); [e] S. M. Allin, C. J. Northfield, M. I. Page and A. M. Z.
Slawin, J. Chem. Soc., Perkin Trans. 1, 1715 (2000); [f] S. M. Allin,
S. L. James, W. P. Martin and T. A. D. Smith, Tetrahedron Lett., 42,
3943 (2001).
[5a] P. Aeberli, and W. J. Houlihan, J. Org. Chem., 34, 165
(1969); [b] A. Mertens, H. Zilch, B. König, W. Schäfer, T. Poll, W.
Kampe, H. Seidel, U. Leser and H. Leinert, J. Med. Chem., 36, 2526
(1993).
(3S,9bR)-3-Benzyl-2,3-dihydro-9bH-oxazolo[2,3-a]isoindol-5-
one (4f).
This product was obtained as a white solids in 69% (Method D)
or 74% (Method E) yield; mp 79-81° (ethanol/tetrahydrofuran)
-1
(86-87°, reference [4a]); ir (potassium bromide): ν 1703 (CO) cm ;
25
[α] = +44.00 (c 1 M, CHCl ) (([α]
= +43.90 (c 2 M, CHCl ),
D
3
D
3
1
see reference [4a]); H nmr (deuteriochloroform): δ 2.98 (dd, J =
13.9Hz and J = 7.9Hz, 1H, CH ), 3.16 (dd, J = 13.9Hz and J =
2
5.6Hz, 1H, CH ), 3.98 (dd, J = 8.7Hz and J = 6.4Hz, 1H, H ),
2
2,2
2,3
2
4.31 (dd, J = 8.7Hz and J = 6.9Hz, 1H, H ), 4.44-4.49 (m, J
2,2
2,3
2
3,2
= 6.9Hz and J = 13.4Hz, 1H, H ), 5.74 (s, 1H, H ), 7.30-7.32 (m,
3
9b
[6] C. S. Cho, D. Y. Chu, D. Y. Lee, S. C. Shim, T. J. Kim, W.
T. Lim and N. H. Heo, Synth. Commun., 27, 4141 (1997).
[7a] D. Romo, J. L. Romine, W. Midura and A. I. Meyers,
Tetrahedron, 46, 4951 (1990); [b] A. I. Meyers, B. A. Lefker, T. J.
Sowin and L. J. Westrum, J. Org. Chem., 54, 4243 (1989).
[8] S. K. Mishra, T. R. Vani and R. B. Rao, Ind. J. Chem. B,
32, 641 (1993).
[9a] C. J. Wharton and R. Wrigglesworth, J. Chem. Soc.,
Perkin Trans. 1, 809 (1985); [b] T. Goto, S. Utsunomiya, H. Aiba, H.
Hayasaka, M. Endo, R. Watanabe, T. Ishizaki, R. Sato and M. Saito,
Bull. Chem. Soc. Jpn., 64, 1901 (1991).
5H, H
), 7.52-7.57 (m, 3H, H
), 7.76 (d, J = 6.9Hz, 1H, H );
arom
arom 9
13
C nmr (deuteriochloroform): δ 39.7 (CH ), 55.4 (C ), 75.1 (C ),
90.9 (C ), 123.9 (C ), 124.4 (C ), 126.8 (C ), 128.6 (C and
2
3
2
9b
8
9
4''
2''
C ), 129.5 (C- and C ), 130.6 (C ), 132.8 (C ), 133.2 (C ),
6''
3''
5''
6
7
5a
+•
136.8 (C ), 142.3 (C ), 173.42 (C ); EIMS m/z 265 (M ).
Anal. Calcd. for C
5.28. Found: C, 76.90; H, 5.56; N, 5.21.
1''
9a
5
H NO (265.13): C, 76.96; H, 5.70; N,
17 15 2
Acknowledgements.
The authors thank the Scientific Council of University of Le
Havre and the Slovak Grant Agency (Grant Number:
1/9249/2002), Slovak republic, for their financial support. We
also thank Professor Bernard Decroix for helpful comments and
discussions made during the course of this work.
[10] G. B. Kumar, A. Shah and T. Pilati, Tetrahedron Lett., 38,
3297 (1997), and references cited therein.
ˇ
[11a] A. Daïch, S. Marchalín, P. Pigeon and B. Decroix,
Tetrahedron Lett., 39, 9187 (1998); [b] A. Chihab-Eddine, A. Daïch,
A. Jilale and B. Decroix, Heterocycles, 51, 2907 (1999); [c] S.
ˇ
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†
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