A stereoselective synthesis of (Z)-3-aryl and alkylmethylidene-1H- isoindolin-1-ones

Article abstract of DOI:10.1055/s-2006-926413

A series of Z-configured (hetero)aryl and alkylmethylideneisoindolin-1-ones has been efficiently prepared by treatment of N-methoxycarbonylisoindolin-1- ones with a base and reaction with selected aldehydes. The parent N-acylated isoindolin-1-ones have be

Full text of DOI:10.1055/s-2006-926413

PAPER
1333
A Stereoselective Synthesis of (Z)-3-Aryl and Alkylmethylidene-1H-isoindolin-
1-ones
Methylidene-1H
-isoind
a
olin-1-one
r
c Lamblin, Axel Couture,* Eric Deniau, Pierre Grandclaudon
UMR 8009 ‘Chimie Organique et Macromoléculaire’, Laboratoire de Chimie Organique Physique, Université des Sciences et Technologies
de Lille, Bâtiment C3(2), 59655 Villeneuve d'Ascq cedex, France
Fax +33(320)336309; E-mail: axel.couture@univ-lille1.fr
Received 14 October 2005; revised 5 December 2005
the Horner reaction of phosphorylated isoindolinones,5 a
Abstract: A series of Z-configured (hetero)aryl and alkylmeth-
combination of carbonylation and nitrogenation applied
ylideneisoindolin-1-ones has been efficiently prepared by treatment
of N-methoxycarbonylisoindolin-1-ones with a base and reaction
with selected aldehydes. The parent N-acylated isoindolin-1-ones
to o-halophenylalkylketones16 and a Parham-type cycliza-
tion of N-acyl-2-bromo-benzamides17 have been used oc-
have been assembled by a Parham-type cyclization of N-(2-io- casionally. Most of these methods involve simple
doarylmethyl)dicarbamates.
experimental procedures and the corresponding reactions
proceed in good yields. Unfortunately, their applicability
is generally unsatisfactory mainly because of restrictions
in the choice of substituents, namely in their number and
position on the aromatic nucleus, and in the selection of
the aromatic, heteroaromatic and aliphatic units connect-
ed to the pendant methylidene moiety. The issues raised
by elaboration of aryl and alkylmethylideneisoindoli-
nones may not be simply addressed by comparison with
phthalides as precursors. The synthetic methods relying
upon nucleophilic additions to phthalimides lack regiose-
Key words: carbanions, Mitsonobu reaction, cyclizations, olefina-
tion, stereoselectivity
In recent years the 3-(hetero)aryl and alkylmethylidene-
isoindolin-1-one systems have become a desirable syn-
thetic target since they represent the central structural
feature of a very large number of natural and synthetic
products displaying a wide range of biological activities.1–5
For example, compound 1 (AKS 186) has been reported
to inhibit vasoconstriction induced by the thromboxane
A2 analogue (U–46619)1 and the 4-acetoxyphenylmeth-
ylidene derivative 2 has been claimed to exhibit local an-
esthetic activity superior to that of procaine.2 Moreover,
3-(hetero)aryl and alkylmethylideneisoindolin-1-ones
possess potential utility as versatile key building blocks in
the synthesis of various classes of alkaloids such as isoin-
dolobenzazepines, e.g. lennoxamine (3),6 and aristolac-
tames, e.g. cepharanone A (4),7 aristoyagonine (5)8
(Figure 1).
O
O
N
N
N
OH
AcO
1 (AKS 186)
2
The existing methods for the synthesis of aryl and/or alkyl-
methylideneisoindolin-1-ones (general formula I) differ
mainly but not merely in the type of reaction giving rise to
the pendant ylidene unit. Thus, these highly conjugated
lactams can be obtained from the corresponding phthal-
ides by treatment with a primary amine.7,9 The most con-
venient routes, however, rely upon the reaction of an N-
substituted phthalimide either with a Grignard reagent1,10
or with arylacetates involved in a photodecarboxylative
addition process.11 They are also accessible by making use
of a Wittig reagent12 which offers the advantage of avoid-
ing the dehydration step. More recently, several groups
have developed elegant synthetic methods that hinge upon
O
MeO
O
O
O
MeO
NH
N
O
4 (Cepharanone A)
3 (Lennoxamine)
O
O
N
O
Me
MeO
NH
the
intramolecular
cyclization
of
o-(1-alkyn-
O
yl)benzamide13 or benzonitrile derivatives14 and upon the
domino reaction of aromatic ynamides.15 Besides these
main synthetic approaches, other procedures involving
R
MeO
I
MeO
SYNTHESIS 2006, No. 8, pp 1333–1338
Advanced online publication: 28.03.2006
x
x
.
x
x
.2
0
0
6
5 (Aristoyagonine)
DOI: 10.1055/s-2006-926413; Art ID: T14305SS
© Georg Thieme Verlag Stuttgart · New York
Figure 1

1334
M. Lamblin et al.
PAPER
R1
R1
O
R2
R3
R2
R3
I
O
O
OMe
OMe
N
R5-CH=O
+
R6 = H
N
OMe
9
R1
O
R4
R4
R2
R3
O
6–8
10–12
N
R6
R1
R4
O
R5
R2
R3
R6 = H
/
N
R6
I
H
OR7
R4
13
R5
Scheme 1 For the definitions of R groups, see Scheme 2.
lectivity and hence have been confined to the elaboration Table 1).We were then pleased to observe that treatment
of bare or symmetrically substituted models. Further- of 10–12 with n-BuLi at –90 °C spared the carbamate
more, most of these methods require a rather problematic functionalities and that the initially formed aromatic anion
deprotection step18 in order to deliver the N-unsubstituted 18 was trapped intramolecularly to afford the desired
products of general formula I.
N-methoxycarbonylisoindolin-1-ones 6–8 with very satis-
factory yields (Scheme 2, Table 1).
We wish to delineate in this paper an alternative, efficient
and tactically new approach to these highly conjugated Interestingly, the presence of a large amount of the
lactams that is based on the retrosynthetic analysis shown hemiketal-type intermediate 19 was observed upon annu-
in Scheme 1. This new synthetic strategy relies upon the lation of 12, but it was quantitatively converted into the
treatment of N-methoxycarbonyl-isoindolin-1-ones 6–8 desired parent model 8 under acidic conditions. The for-
with a base and subsequent reaction with an appropriate mation of this compound may be tentatively explained by
aldehyde 9. The acylated isoindolin-1-ones 6–8 could be coordination of lithium by the adjacent aromatic methoxy
conceivably assembled by a Parham-type cyclization ap- group after anionic cyclization.
plied to the dimethyl dicarbamates 10–12. The present
We next planned to install the pendant (hetero)aryl and
work originated from the following premises. (i) Isoindo-
alkylmethylidene unit on the isoindolin-1-one framework
lin-1-ones have been successfully metalated at the benzyl-
by treatment of the parent isoindolinone 6–8 with a base
and subsequent reaction with the appropriate aldehyde
9a–h. After considerable experimentation with various
temperatures, solvents (THF, Et2O, EtOH) and bases
ic position of the heterocyclic five-membered ring thus
permitting the connection of a range of electrophiles and,
in particular, aldehydes that allow the installation of an
hydroxyalkyl appendage.19 (ii) The N-acylated carbamate
(KHMDS, LHMDS, EtONa) it was found that the best re-
group is resistant towards basic and nucleophilic reagents
sults were obtained by treatment of the N-acylated isoin-
dolin-1-ones 6–8 with NaH in DMF followed by slow
addition of the appropriate aldehyde 9a–h and ultimate re-
fluxing in DMF for eight hours (Scheme 3). The method
intermolecularly20 but is endowed with a remarkable pro-
pensity to react with nucleophiles in an intramolecular
fashion.21 This operation releases an alkoxide that can fur-
ther act as a base. (iii) It has been shown that the base-in-
tolerates a wide variety of carbonyl compounds and a rep-
duced dehydration of erythro and threo adducts
resentative series of compounds which have been pre-
pared by this method are presented in Table 2. This simple
procedure thus gives indiscriminate access to aryl, het-
eroaryl and alkylmethylidene isoindolin-1-ones 20a–h,
structurally related to 13 through an E1cb mechanism
gives rise stereoselectively to the arylideneisoindolin-1-
ones I (R6 ≠ H) (Scheme 1).22
The first facet of the synthesis was the elaboration of the 21a, 22a with moderate to good yields (Table 3). Com-
parent N-acylated isoindolin-1-ones 6–8. We conjectured pounds 20–22 were obtained as mixtures of geometric iso-
that these functionalized isoindolinones would be readily mers with the chromatographically separable Z isomer
obtained by the Parham cyclization protocol23 applied to predominating by a large margin. The stereochemistry of
the dicarbamates 10–12 (Scheme 1). This concept, which the exocyclic double bond was unambiguously assigned
is based upon aromatic lithiation, usually by lithium– from the 1H NMR spectra both by the chemical shift of the
halogen exchange and subsequent reaction with an inter- olefinic proton and by comparison with authentic sam-
nal electrophile, has not yet been applied to the diacyl- ples. In all cases the vinylic proton of the Z isomers ap-
amine functionality.
pears at lower field than the vinylic proton of the
corresponding E isomer.6,13c
Initially, the parent dicarbamates 10–12 were readily ac-
cessible, albeit in moderate yield, by Mitsonobu reaction From a mechanistic point of view one can reasonably as-
involving the suitably substituted benzylic alcohols 14–16 sume that deprotonation of the benzylic position and inter-
with dimethyl iminodicarboxylate 17 (Scheme 2, ception with the appropriate aldehyde allows the
Synthesis 2006, No. 8, 1333–1338 © Thieme Stuttgart · New York

PAPER
Methylidene-1H-isoindolin-1-ones
1335
R1
R1
PPh3 (1.1 equiv)
DEAD (1.1 equiv)
THF, 0 °C then r.t.
O
HN
O
R2
R3
I
R2
R3
I
O
OMe
OMe
OMe
OMe
+
OH
N
R4
R4
O
14–16
17
10–12
for 10 and 11
–90 °C to –70 °C
then H3O+
R1
R1
O
R2
R3
R2
R3
Li
O
n-BuLi (1.1 equiv)
–90 °C
O
OMe
OMe
N
OMe
N
R4
R4
6–8
O
18
for 12
–90 °C to –70 °C
then H3O+
toluene, PTSA
reflux, 3 h
MeO
R1
H
R2 R3
R4
H
HO
OMe
MeO
MeO
14, 10, 6
15, 11, 7
H
H
H
O
OMe
H
OMe OMe
N
16, 12, 8 OMe OMe OMe
H
19
Scheme 2
connection of a transient aryl (or alkyl)methine alkoxide dolin-1-ones 20–22 as the thermodynamically favored Z
appendage (Scheme 3). Intramolecular attack of the re- isomers, either predominantly or exclusively.
sulting oxanion 23 may generate the highly strained isoin-
dolin-1-one derivative 24 accompanied by the release of
To summarize, the goal of our program has been to devel-
op a new general and versatile approach for the synthesis
sodium methoxide which is of sufficient kinetic basicity
of (hetero)aryl- and alkylmethylideneisoindolin-1-ones.
to deprotonate the latent benzylic lactam position. As an-
This new synthetic route offers special advantages includ-
ticipated, E1cb elimination from the resulting carbanionic
ing good stereoselectivity, high efficiency and experimen-
tal simplicity.
species 2517 followed by decarboxylation delivers the tar-
get NH-free aryl, alkyl and heteroarylmethylideneisoin-
Table 1 Spectroscopic and Physical Data of the Parent Dicarbamates 10–12 and N-Acylisoindolin-1-ones 6–8
Prod- Yield Mp (°C) 1H NMR (CDCl3–TMS)
ucta,b (%)
d (ppm), J (Hz)
13C NMR (CDCl3–TMS)
d (ppm)
10
83
oil
3.80 (s, 6 H, 2 × OCH3), 4.87 (s, 2 H, OCH2), 6.94 (t, J = 7.5, 1 H, 54.2, 54.9, 97.2, 127.8, 128.5, 128.8,
Harom), 7.04 (d, J = 7.7, 1 H, Harom), 7.29 (t, J = 7.5, 1 H, Harom), 139.0, 139.5, 153.9
7.81 (d, J = 7.7, 1 H, Harom
)
11
53
57–59
75–77
3.78 (s, 3 H, OCH3), 3.82 (s, 6 H, 2 × OCH3), 3.84 (s, 3 H, OCH3), 51.9, 53.8, 55.8, 60.8, 89.2, 113.7, 134.6,
5.06 (s, 2 H, CH2), 6.61 (d, J = 8.7, 1 H, Harom), 7.54 (d, J = 8.7, 132.7, 148.5, 153.2, 154.2
1 H, Harom
)
12
6
50
76
44
64
53
3.80 (s, 3 H, OCH3), 3.84 (s, 6 H, 2 × OCH3), 3.85 (s, 3 H, OCH3), 54.3, 55.0, 56.2, 60.8, 60.9, 85.0, 105.5,
3.87 (s, 3 H, OCH3), 4.87 (s, 2 H, CH2), 6.46 (s, 1 H, Harom 134.8, 141.1, 153.1, 154.1
)
136–138 3.93 (s, 3 H, OCH3), 4.78 (s, 2 H, CH2), 7.47 (t, J = 6.1, 2 H, Harom), 49.1, 53.7, 123.2, 125.2, 128.6, 130.9,
7.62 (t, J = 7.4, 1 H, Harom), 7.88 (d, J = 8.3, 1 H, Harom 133.8, 140.8, 152.5, 166.2
)
7
168–170 3.96 (s, 9 H, 3 × OCH3), 4.81 (s, 2 H, CH2), 7.07 (d, J = 8.3, 1 H, 46.9, 53.6, 56.3, 60.4, 113.4, 121.4, 124.1,
Harom), 7.66 (d, J = 8.3, 1 H, Harom 133.1, 143.4, 152.5, 156.5, 165.8
)
8
129–131 3.96 (s, 3 H, OCH3), 3.92 (s, 6 H, 2 × OCH3), 4.07 (s, 3 H, OCH3), 48.5, 53.5, 56.5, 61.5, 62.6, 101.2, 115.7,
4.66 (s, 2 H, CH2), 6.69 (s, 1 H, Harom 138.6, 142.0, 152.4, 152.6, 159.3, 164.1
)
19
76–78
3.66 (s, 3 H, OCH3), 3.86 (s, 3 H, OCH3), 3.90 (s, 9 H, 3 × OCH3), 52.2, 52.4, 56.1, 60.9, 61.8, 109.0, 120.0,
4.24 (d, J = 5.5, 2 H, CH2), 5.47 (br s, 1 H, OH), 6.76 (s, 1 H,
Harom
133.4, 141.6, 152.1, 155.1, 156.5, 157.0,
168.0
)
a Satisfactory microanalyses obtained: C 0.27, H 0.32, N 0.27.
b IR (KBr): nCO two bands 1790–1735 and 1695–1685 cm–1.
Synthesis 2006, No. 8, 1333–1338 © Thieme Stuttgart · New York

1336
M. Lamblin et al.
PAPER
R1
R1
R1
O
O
O
NaH, DMF
R5CH=O (9a–h)
R2
R3
R2
R3
R2
O
O
O
O
N
MeO
N
N
+
R3
OMe
OMe
R4
R4
24
R4
O
R5
R5
23
6–8
R1
1. aq NH4Cl
2. work-up
and separation
R1
O
R1
O
O
N
R2
R3
R2
NH
R3
R2
R3
O
O
E1cb
O
O
N
R4
25
R5
R5
R4
R4
R5
20a–h, 21a, 22a
Z isomer
Scheme 3
alcohol 14–16 (3 mmol), triphenylphosphine (867 mg, 3.3 mmol)
and iminodicarboxylate 17 (400 mg, 3 mmol) in dry THF (50 mL).
The mixture was then stirred at r.t. for an additional 24 h, quenched
with H2O (3 mL) and concentrated under vacuum. The residual oil
was purified by column chromatography (CH2Cl2–Et2O–hexanes,
50:30:20) and finally recrystallized from hexane–toluene (for com-
pounds 11 and 12).
Table 2 Aryl(Alkyl)methylideneisoindolin-1-ones 20–22
Compd R1
R2
H
R3
H
R4
H
R5
20a
20b
20c
20d
20e
20f
H
Ph
H
H
H
H
2-MeOC6H4
H
H
H
H
3,4-(MeO)2C6H3
2,3,4-(MeO)3C6H2
3,4-(OCH2O)C6H3
2-naphthyl
2-thienyl
N-Acylated Isoindolin-1-ones 6–8; General Procedure
A solution of n-BuLi (1.4 mL, 1.6 M in hexanes, 2.2 mmol) was
added dropwise at –90 °C under Ar to a solution of dicarbamate 10–
12 (2 mmol) in dry THF (30 mL). The reaction mixture was stirred
at –90 °C for an additional 5 min, slowly warmed to –70 °C over 15
min and then quenched by addition of a dilute HCl solution in EtOH
(15%, 5 mL). The reaction mixture was warmed to r.t., extracted
with Et2O (3 × 10 mL) and the combined organic extracts were
washed with brine (5 mL) and dried (Na2SO4). After evaporation of
the solvent, the crude residual oil was purified by column chroma-
tography (EtOAc–hexanes, 30:70) to afford the annulated com-
pounds 6–8.
H
H
H
H
H
H
H
H
H
H
H
H
20g
20h
21a
22a
H
H
H
H
H
H
H
H
i-Pr
H
H
OMe
OMe
OMe
H
Ph
OMe
OMe
Ph
Column chromatography of the reaction mixture obtained upon Par-
ham cyclization of 12 delivered 8 (11%) and the primarily annulat-
ed compound 19 which was readily converted into the desired
isoindolin-1-one 8. Thus, compound 19 was refluxed in toluene (20
mL) in the presence of a catalytic amount of PTSA for 3 h. Usual
work-up delivered the N-acylated isoindolin-1-one 8 quantitatively.
Combined crops of 8 were recrystallized from hexane–toluene.
Melting point determinations were carried out on a Reichert–Ther-
1
mopan apparatus and are uncorrected. H and 13C NMR spectra
were measured at 300 MHz and 75 MHz, respectively, on a Bruker
AM 300 spectrometer as solutions in CDCl3 with TMS as internal
standard. Elemental analyses were determined by the CNRS mi-
croanalysis centre. For flash chromatography, silica gel 60 M (230–
400 mesh ASTM) was used. All solvents were dried and distilled
according to standard procedures. Dry glassware for moisture-sen-
sitive reactions was obtained by oven drying and assembly under
Ar. An inert atmosphere was obtained with a stream of Ar and glass-
ware equipped with rubber septa; reagent transfer was performed by
syringe.
Dimethyl iminodicarboxylate 1724 was prepared according to a re-
ported procedure.25 Alcohol 14 is commercially available. The 2-io-
dobenzyl alcohols 1526 and 1627 were synthesized according to the
literature.
Synthesis of (Z)-3-Aryl- and Alkylmethylideneisoindolin-1-ones
20–22; General Procedure
A solution of isoindolin-1-one 6–8 (1 mmol) in dry DMF (10 mL)
was added dropwise to a stirred suspension of NaH (1.1 mmol) in
DMF (40 mL) at 0 °C under Ar. The mixture was stirred at r.t. for
an additional 1 h and a solution of the appropriate aldehyde 9a–h
(1.1 mmol) in DMF (10 mL) was added dropwise. The reaction
mixture was refluxed for 9 h, cooled and quenched with sat. aq
NH4Cl (10 mL). The mixture was diluted with H2O (30 mL), ex-
tracted with Et2O (3 × 30 mL) and the combined organic layers
were dried (Na2SO4). Evaporation of the solvent in vacuo left an
oily residue which was purified by column chromatography (ace-
tone–hexanes, 20:80). The Z-configured stereomers of 20–22 were
invariably eluted first and were finally recrystallized from hexane–
toluene.
Synthesis of Dicarbamates 10–12; General Procedure
DEAD (1.5 mL, 40% in toluene, 3.3 mmol) was added dropwise at
0 °C under Ar to a stirred solution of the suitably substituted benzyl
Synthesis 2006, No. 8, 1333–1338 © Thieme Stuttgart · New York

PAPER
Methylidene-1H-isoindolin-1-ones
1337
Table 3 Spectroscopic and Physical Data of the Aryl(Alkyl)methylideneisoindolin-1-ones 20–22
Prod-
ucta,b
Z/E (%)c Yield
(%)d of
Mp (°C)
1H NMR (CDCl3–TMS)e
d (ppm), J (Hz)
13C NMR (CDCl3–TMS)e
d (ppm)
Z isomer
20a
20b
20c
90:10
90:10
90:10
75
69
73
183–184
(Lit.10b 181–182)
162–163
(Lit.28 163)
163–164
169–170
226–227
3.77 (s, 3 H, OCH3), 3.85 (s, 3 H, OCH3), 6.61 (s,
1 H, Hvinyl), 6.96 (d, J = 8.5, 1 H, Harom), 7.18 (m, 2 H, 117.6, 125.2, 127.5, 127.8,
Harom), 7.50 (t, J = 7.3, 1 H, Harom), 7.65 (t, J = 7.3,
1 H, Harom), 7.75 (d, J = 7.3, 1 H, Harom), 7.98 (d,
J = 7.3, 1 H, Harom), 10.75 (br s, 1 H, NH)
60.6, 60.7, 111.6 117.0,
132.6, 133.3, 133.8, 135.9,
137.2 (C), 137.2 (CH),
153.6, 153.9, 174.2
20d
20e
85:15
90:10
73
70
3.68 (s, 3 H, OCH3), 3.86 (s, 6 H, 2 × OCH3), 6.70 (s, 61.1, 62.2, 111.6, 111.7,
1 H, Hvinyl), 6.85 (s, 2 H, Harom), 7.52 (t, J = 7.3, 1 H, 125.3, 127.9, 133.4, 134.1,
Harom), 7.67 (t, J = 7.3, 1 H, Harom), 7.75 (d, J = 7.3, 1 135.4, 137.0, 137.4, 142.3,
H, Harom), 7.99 (d, J = 7.3, 1 H, Harom), 10.80 (br s, 1 143.9, 158.2, 174.3
H, NH)
6.05 (s, 2 H, CH2), 6.69 (s, 1 H, Hvinyl), 6.95 (d,
111.2, 113.8, 113.9, 125.3,
J = 8.1, 1 H, Harom), 7.11 (dd, J = 1.7, 8.1, 1 H, Harom), 127.8, 129.1, 133.3, 133.9,
7.28 (t, J = 1.7, 1 H, Harom), 7.51 (t, J = 7.3, 1 H,
Harom), 7.67 (d, J = 7.3, 1 H, Harom), 7.73 (d, J = 7.3,
1 H, Harom), 7.99 (d, J = 7.3, 1 H, Harom), 10.68 (br s,
1 H, NH)
136.1, 137.2, 144.1, 151.8,
152.9, 174.1
20f
85:15
70
215–216
6.90 (s, 1 H, Hvinyl), 7.40–7.60 (m, 3 H, Harom), 7.65– 110.0, 125.6, 127.9, 131.4,
8.00 (m, 6 H, Harom), 8.08 (d, J = 7.3, 1 H, Harom), 8.25 131.5, 132.5, 132.6, 132.8,
(s, 1 H, Harom), 10.95 (br s, 1 H, NH)
133.2, 133.4, 137.2, 137.4,
137.5, 138.0, 138.5, 144.0,
174.4
20g
20h
21a
90:10
90:10
100:0
69
75
54
144–146
(Lit.14 144–145)
179–181
(Lit.29 180–181)
209–210
63–164
4.00 (s, 3 H, OCH3), 4.04 (s, 3 H, OCH3), 7.07 (d,
J = 8.3, 1 H, Harom), 7.08 (s, 1 H, Hvinyl), 7.31–7.33
(m, 1 H, Harom), 7.44–7.46 (m, 4 H, Harom), 7.63 (d,
J = 8.3, 1 H, Harom), 7.97 (br s, 1 H, NH)
56.4, 60.1, 110.4, 113.4,
120.0, 127.5, 128.5, 129.2,
122.8, 131.9, 135.8, 144.5,
156.4, 168.3
22a
95:5
71
3.94 (s, 3 H, OCH3), 4.03 (s, 3 H, OCH3), 4.17 (s,
56.4, 61.6, 62.5, 97.8, 104.8,
3 H, OCH3), 6.44 (s, 1 H, Hvinyl), 7.04 (s, 1 H, Harom), 127.5, 128.3, 129.3, 113.6,
7.30 (d, J = 9.0, 1 H, Harom), 7.45–7.47 (m, 4 H,
Harom), 8.21 (br s, 1 H, NH)
132.9, 135.1, 135.6, 142.7,
151.3, 157.9, 167.4
a Satisfactory microanalyses obtained: C 0.25, H 0.30, N 0.21.
b IR (KBr): nNH 3215–3150 cm–1; nCO 1695–1675 cm–1.
c Estimated from 1H NMR spectra.
d Yield of purified product.
e DMSO-d6 as the solvent for 20e.
(3) Achimani, K.; Ashizawa, N.; Kobayashi, F. Jpn Patent JP
03133955, 1991; Chem. Abstr. 1991, 115, 255977.
(4) Laboratori Baldacci S.p.A.; Jpn Patent JP 5946268, 1984;
Chem. Abstr. 1984, 101, 54922.
Acknowledgment
This research was supported by the Centre National de la Recherche
Scientifique and MENESR (grant to M.L.).
(5) Rys, V.; Couture, A.; Deniau, E.; Grandclaudon, P.
Tetrahedron 2003, 59, 6615.
(6) Couture, A.; Deniau, E.; Grandclaudon, P.; Hoarau, C.
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