A simple and efficient asymmetric synthesis of 3-alkyl-isoindolin-1-ones

Article abstract of DOI:10.1016/S0040-4020(02)00462-3

A simple asymmetric access to 3-alkyl-isoindolin-1-ones was investigated through the diastereoselective alkylation of 2-[(1R)-2-hydroxy-1-phenylethyl]-2,3-dihydro-1H-isoindolin-1-one 5. High diastereoselectivities were observed with LDA or LiHMDS while the isolated yields were modest (about 50%). In contrast the use of NaHMDS gave good isolated yields (up to 85%) but lowered diastereoselectivities. This methodology offers an efficient asymmetric synthesis of 3-alkylated isoindolin-1-ones.

Full text of DOI:10.1016/S0040-4020(02)00462-3

TETRAHEDRON
Pergamon
Tetrahedron 58 !2002) 5103±5108
A simple and ef®cient asymmetric synthesis
of 3-alkyl-isoindolin-1-ones
a
Joelle Perard-Viret, Thierry Prange, Alain Tomas and Jacques Royer
b
b
a,p
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È
a
   Â
Laboratoire de Chimie Therapeutique, Faculte de Pharmacie, UMR 8638 CNRS/Universite Rene Descartes,
4 avenue de l'Observatoire, 75270 Paris Cedex 06, France
  Â
Laboratoire de Cristallographie, Faculte de Pharmacie, UMR 8015 CNRS/Universite Rene Descartes,
b
4 avenue de l'Observatoire, 75006 Paris Cedex, France
Â
Dedicated to the memory of Andre Collet, who introduced me to chirality !J. P.-V.)
Received 5 February 2002; revised 28 March 2002; accepted 26 April 2002
AbstractÐA simple asymmetric access to 3-alkyl-isoindolin-1-ones was investigated through the diastereoselective alkylation of 2-[!1R)-2-
hydroxy-1-phenylethyl]-2,3-dihydro-1H-isoindolin-1-one 5. High diastereoselectivities were observed with LDA or LiHMDS while the
isolated yields were modest !about 50%). In contrast the use of NaHMDS gave good isolated yields !up to 85%) but lowered diastereo-
selectivities. This methodology offers an ef®cient asymmetric synthesis of 3-alkylated isoindolin-1-ones. q 2002 Elsevier Science Ltd. All
rights reserved.
Numerous synthetic and natural products possessing the
3-alkyl-isoindolin-1-one substructure were described. The
compounds isolated from natural sources possess more or
less complex structures1 as for example indolocarbazoles 1
!staurosporine2 and derivatives) or tetrahydro-isoindolo-
benzazepines !lennoxamine !2)).3 On the other hand,
synthetic 3-substituted isoindolin-1-ones were studied as
anxiolytics !pazinaclone !3)),4 5-HT1A antagonists,5 reverse
transcriptase inhibitors,6 or vasodilatators.7 More generally,
the easily metabolised benzylic alcohol can be replaced by
the bioisosteric isoindolinone.8
of N-dimethyl amino isoindolinones. This latter author used
benzotriazole stabilized carbanion as an ef®cient but multi-
step methodology. The carbocationic approach was reported
in some instances11 from which the work developed by Allin
et al.11a,b constitutes the unique asymmetric synthesis of
3-alkyl-isoindolin-1-ones. Modest to good diastereoselec-
tivities were obtained by Allin and co-workers.
We became interested to try and propose a newand asym-
metric approach since we anticipated that an asymmetric
version of the unstabilized carbanion method could be
developed using isoindolidinone bearing a chiral appendage
Several synthetic pathways were known to synthesize
3-alkyl-isoindolin-1-ones.9 Indeed a limited number of
methods towards the preparation of the heterocyclic skele-
ton were reported and only very recent works were devoted
to develop a general synthetic strategy mainly through the
alkylation of isoindolinones at C-3 !Fig. 1).
This alkylation was described using both carbanionic10 and
carbocationic11 strategies. Carbanionic methods may utilise
a stabilizing group,10a that was introduced at the carbon ipso.
Quite recently, the group of A. Couture10b was the ®rst to
propose the substitution of isoindolinones through the
formation of an unstabilized carbanion. This very simple
method was used with success by Guo,10c but was not
found to be generally applicable by Enders10d in the case
Keywords: isoindolin-1-one; alkylation; carbanions; !R)-phenylglycinol;
amide bases.
p
Corresponding author. Tel.: 133-1-537-397-49; fax: 133-1-432-914-03;
e-mail: jacques.royer@pharmacie.univ-paris5.fr
Figure 1.
0040±4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020!02)00462-3

Â
J. Perard-Viret et al. / Tetrahedron58 62002) 5103±5108
5104
Scheme 1.
at nitrogen atom. This was inspired from a methodology we
developed for some years on chiral g-lactam.12 This method
was based on the preparation of the chiral non-racemic
g-lactam 4 in a single step from dimethoxydihydrofuran
and a chiral amine, followed by the asymmetric alkylation
of this chiral lactam !Scheme 1). For this alkylation step, it
was necessary to use a chiral appendage bearing a free
alcohol function able to strongly coordinate the lithium
enolate:12 then the use of !R)-phenylglycinol as the starting
chiral amine was found to be essential in order to get high
diastereomeric excesses.
In our hands, the treatment of a 1/1 mixture of !R)-phenyl-
glycinol and phthalic dialdehyde in isopropanol and in the
presence of HCl gave the isoindolinone 5 in 52% yield after
puri®cation !Scheme 2). Despite the modest yield, we found
this method convenient for our purpose, since it is a very
simple one-step reaction. Indeed, the isoindolinone 5 is a
known product prepared through the condensation of
phenylglycinol and 2-formylbenzoic acid, followed by
reduction !59% overall yield).15
With isoindolinone 5 in hand, we considered its alkylation
through the formation of carbanion. In the ®rst attempt we
chose to use LDA following the procedure described by
Couture.10b The deprotonation was conducted at 2788C,
using 2.2 equiv. of base in THF and the so-formed carb-
anion was trapped with methyl iodide to give the 3-methyl
isoindolinone 6a !Scheme 2) in 40% yield along with the
starting material that was recovered in about 40% yield.
This alkylation was proved to be highly diastereoselective:
compound 6a was isolated as a unique diastereomer. Care-
ful examination of the 1H and 13C NMR spectra of the crude
reaction mixture revealed the presence of less than 5% of
epimeric material. Further studies were undertaken in order
to improve the yield of this very simple process by varying
mainly the nature of the base and the nature of the metal.
Methyl, propyl, allyl and benzyl halides were used in this
study. All the reactions were conducted under the above
This paper will present the asymmetric alkylation of
2-[!1R)-2-hydroxy-1phenylethyl]-2,3-dihydro-1H-isoindol-
1-one 5 through the formation of an unstabilized carbanion.
1. Results and discussion
The preparation of 5 was envisaged through the conden-
sation of the primary amine function of !R)-phenylglycinol
with phthalic dialdehyde following the condensation
method discovered in 1909 by Thiele.13 This method was
widely used for the preparation of isoindolinone skeleton
but claimed to give modest or lowyields with some primary
amines and several modi®cations were proposed giving
improvement in speci®c cases.9,14
Scheme 2.
Table 1. Yield and diastereoselectivity in the alkylation of 5 !THF, 2788C) with different primary alkyl halides !1.2 equiv.) and with different bases
!2.2 equiv.)
Base-.
Electrophile
LDA
LiHMDS
Yielda !%)
NaHMDS
Yielda !%)
KHMDS
Yielda !%)
drb !%)
drb !%)
drb !%)
Yielda
drb
MeI
40
41
±
37
±
95:5
<95:5
±
95:5
±
32
±
39
28
±
95:5
±
.95:5
.95:5
±
71
72
41
80
25
74:26
96:4
50:50
50:50
.95:5
60
63
53
±
53:47
96:4
50:50
±
PrBr
AllBr
BnBr
BnCl
50
66:34
a
Yield of isolated alkylated product.
Diastereoselective ratio for the crude reaction mixture.
b

Â
J. Perard-Viret et al. / Tetrahedron58 62002) 5103±5108
5105
Scheme 3.
conditions. From Table 1 it can be seen that excellent
diastereoselection was obtained with all the alkyl halides
used when the base was LDA or LiHMDS. Unfortunately,
in each case, the yield was always modest and less than
50%. Using a large excess !10 equiv.) of halide did not
give any improvement. Raising the temperature up to rt or
using large excess of base were without effect upon the yield
of the reaction, and about 40% of starting material were
recovered. It must be noticed that, even in this large excess
procedure, no bis-alkylated product was obtained.
derivative 7 !prepared from 5 in 65% yield, Scheme 3).
Using LiHMDS as base, compound 7 was alkylated with
propyl iodide to give 8 !85% yield) with only 74:26 dr !the
diastereomeric ratio was lowered to 69:31 by the use of
KHMDS as base).
A 3R con®guration was determined for compound 6b
through an X-ray analysis of suitable crystals. The
ORTEP representation is given in Fig. 2. The same con®gu-
ration was expected for all alkyl compounds 6 obtained
through the deprotonation of 5 by LDA or LiHMDS.
We eventually obtained an improved alkylation yield by
changing the counterion of the base. The use of NaHMDS
gave the alkylation products 6a±d in yields improved up to
80%. Unfortunately, in these cases, the diastereoselectivity
was dramatically lowered, mainly for the more electrophilic
compounds: benzyl and allyl bromides. In order to con®rm
this assumption, we tried an alkylation reaction with benzyl
chloride: if NaHMDS was used as base, the yield was low
!25%) but the diastereoselectivity excellent, while KHMDS
underwent an acceptable 50% yield and a low dr In most
cases deprotonation with KHMDS gave worse diastereo-
selectivity. These different diastereoselectivities observed
through the use of different bases suggested the formation
of a chelated intermediate. The chelation would be better
with lithium than with sodium or potassium.
Furthermore, this was con®rmed for compound 6c,16 since
its hydrogenation !H2, Pd/C in MeOH) gave, in 95% yield,
the propyl derivative identical in all aspects with 6b. The
different experimental results obtained along this work
clearly proved the existence of an intramolecular chelation.
The con®guration of the newly formed chiral centre was
consistent with two possible models for the carbanionic
species depicted in Fig. 3. In model !A), we assumed a
con®gurationally stable anion which is stabilised through
a intramolecular chelation by the alcoholate. The expected
chair like conformation and the retention of con®guration
would lead to the observed 3R con®guration. In the enolate
model !B), an intramolecular chelation is also expected and
the attack of the electrophile from the less sterically
hindered face !anti to the phenyl group) would also provide
the 3R alkylated derivative.
Nevertheless, the results obtained with propyl bromide were
particularly astonishing since they did not followthe same
tendency.
At this stage we have no experimental evidence to support
either model A or B, however further work is underway to
elucidate the most favorable conformation.
An another proof for an intramolecular chelation was given
by the experiments we conducted with the O-tert-butyl
In conclusion we developed a rapid and ef®cient process
for the asymmetric synthesis of 3-alkyl-isoindolinones.
Excellent diastereoselectivities were obtained and render
the process particularly ef®cient despite the modest yield.
Cleavage of the chiral appendage in this 2-hydroxy-1-
phenylethyl isoindolinone series was reported by Fains et
al.15 and by Allin11b to occur in good yield and without loss
of stereochemical integrity.
Figure 2.
Figure 3.

Â
J. Perard-Viret et al. / Tetrahedron58 62002) 5103±5108
5106
2. Experimental
2.2.1. )3R)-Methyl-2-[)1R)-2-hydroxy-1phenylethyl]-2,3-
dihydro-1H-isoindol-1-one )6a). Oil; [a]Dˆ184 !cˆ0.9,
CH2Cl2) !lit.11b 121.3, cˆ2.34, CH2Cl2); !1H NMR d 1.44
!d, Jˆ6.6 Hz, 3H), 4.1 !ddd, Jˆ15.75, 6, 3.6 Hz, 1H), 4.35
!q, Jˆ6.6 Hz), 4.48 !ddd, Jˆ15, 7.5, 6.5 Hz, 1H), 4.78 !dd,
Jˆ8, 3.5 Hz, 1H), 4.90 !t, Jˆ6.9 Hz, 1H !OH)), 7.26±7.35
!m, 6H), 7.45±7.57 !m, 2H), 7.87 !d, Jˆ7.45 Hz, 1H); 13C
NMR d 18.3 !1CH3), 56.9, 62.2 !2CH), 64.5 !1CH2), 121.9,
123.7, 127.2, 127.9, 128.2, 128.8, 131.9 !7CH), 131.9,
137.9, 147.0 !3C), 167.0 !CO); IR !neat) 3387, 1665,
1414, 1071, 697; Found: MH1, 268.1337, C17H18NO2
requires 268.1338.
2.1. General
All solvents were dried by standard methods. Melting points
were determined on a Leica melting point microscope and
are uncorrected. IR spectra were obtained using a Nicolet
205-FT infrared spectrophotometer. Only noteworthy IR
absorptions are listed !cm21). H and 13C NMR spectra !d
1
!ppm), J !Hertz)), solvent CDCl3) were recorded with a
Bruker AC-300 !300 and 75.5 MHz) instrument. Elemen-
tary analyses were performed at the Microanalysis Labora-
tory of the Pierre et Marie Curie University !Paris). Mass
spectra were recorded with a Nermag R10-10C instrument.
HRMS: Micromass LCT !positive Electrospray mode with
internal standard `lock-mass'). Optical rotations were
measured with a Perkin±Elmer 241 polarimeter. Analytical
TLC was carried out using aluminum-backed plates coated
with 0.2 mm silica gel 60 F254, Merck. Preparative ¯ash-
column chromatography was carried out using SDS silica
gel 60 !35±70 mm).
2.2.2. )3R)-Proyl-2-[)1R)-2-hydroxy-1phenylethyl]-2,3-
dihydro-1H-isoindol-1-one )6b). Mp 1438C; [a]Dˆ170
1
!cˆ1.5, CH2Cl2); H NMR d 0.80 !m, 4H), 1.1±1.23 !m,
1H), 1.86±2.05 !m, 2H), 4.1 !ddd, Jˆ3.3, 7.0, 12.2 Hz, 1H),
4.37 !dd, Jˆ3.0, 5.0 Hz, 1H), 4.44 !ddd, Jˆ7.8, 12.4,
7.8 Hz), 4.66 !dd, Jˆ3.3, 8.0 Hz, 1H), 5.00 !t, Jˆ7.4 Hz,
1H !OH)), 7.24±7.36 !m, 6H), 7.45±7.57 !m, 2H), 7.87 !d,
Jˆ7.25 Hz, 1H), 13C NMR d 13.8 !1CH3), 15, 32.2 !2CH2),
60.4, 61.6 !2CH), 64.0 !1CH2), 121.8, 123.5, 127.1, 127.8,
128.0, 128.7, 131.7 !7CH), 132.4, 137.8, 145.3 !3C), 170.1
!CO); IR !nujol) 3300, 1660, 1415, 1076, 701; Anal. calcd
for C19H21NO2: C, 77.26; H, 7.17; N, 4.74. Found: C, 76.7;
H, 7.31; N, 4.49; m/z !CI) 296 [MH1, 100%].
2.1.1. 2-[)1R)-2-Hydroxy-1phenylethyl]-2,3-dihydro-1H-
isoindol-1-one )5). A solution of !R)-phenylglycinol !5 g,
36 mmol) in 150 mL of water and 47.2 mL of HCl 1N was
added dropwise to a solution of 1,2-phthalic dicarboxalde-
hyde !4.8 g, 36 mmol) in 2-propanol !20 mL) at room
temperature. The solution was stirred for 4 h, and then
made alkaline with solid sodium hydrogenocarbonate, and
extracted with dichloromethane. The extracts were
combined, dried over magnesium sulfate and evaporated
under vacuum. The oily residue was puri®ed by precipi-
tation with a mixture of diethyl ether and a small quantity
of dichloromethane, ®ltration gave 1.7 g !18.7%) of a
slightly yellow powder. The ®ltrate was evaporated and
puri®ed by ¯ash column chromatography on SiO2 using
CH2Cl2/MeOH !97.5:2.5) as eluent to afford 3.1 g !34%)
of 5 !total yield 52%).
2.3. X-Ray crystallography
C19H21NO2. Orthorhombic, space group P212121; aˆ9.203
Ê
Ê 3
!1), bˆ11.391 !2), cˆ9.420 !2) A, Vˆ1601.4 !2) A ; Zˆ4;
0.079 mm21; F!000)ˆ632.
Mˆ295.37 g; Dcˆ1.225 g cm23
; absorption coef®cient
The crystal dimensions !0.03 mm£0.10 mm£0.04 mm)
being too small, diffraction data were recorded using the
LURE Synchrotron facility in Orsay !France). Diffraction
Ê
data were collected at wavelenth of 0.964 A using a 345 mm
diameter MAR Research Image Plate system connected to
the W32 beam line; distance crystal-detectorˆ110 mm,
total rotation vˆ3168. A total of 4241 re¯ections with a
processed using the hkl suite of programs.17 This led to 785
independent re¯ections with I.2 s!I), Rsymˆ5.7%. They
were kept in the re®nement calculations.
Mp 1158C; [a]Dˆ219 !cˆ0.6, CH2Cl2); 1H NMR d 3.84 !t,
Jˆ6.25 Hz, 1H), 4.12 !d, Jˆ17.1 Hz, 1H), 4.15 !m, 1H),
4.42 !d, 17.1 Hz, 1H), 5.32 !dd, Jˆ8.48, 4.64 Hz, 1H),
7.2±7.5 !m, 8H), 7.8 !d, Jˆ7.4 Hz, 1H); 13C NMR d 48.5
!1CH2), 59.3 !1CH), 63.0 !1CH2), 122.5, 123.6, 127.4,
127.8, 127.9, 128.8, 131.3 !7CH), 132.4, 137.4, 141.4
!3C), 169.7 !CO); IR !nujol) 3440, 1664, 1455, 1213,
1070, 696; Anal. calcd for C16H15NO2: C, 75.87; H, 5.97;
N, 5.53. Found: C, 75.27; H, 5.89; N, 5.27; m/z !CI) 254
[MH1, 100%].
Ê
resolution range 5.2±1.03 A were measured. This set was
The structure was solved by direct methods using SHELXS-
97.18 Re®nement, based on F2, was carried out by full matrix
least squares with SHELXL-9719 software. An ORTEP20
diagram is given in Fig. 2. Non-hydrogen atoms were
re®ned anisotropically. Hydrogen atoms were positioned
geometrically and re®ned riding on their carrier atom with
isotropic thermal displacement parameters ®xed at 1.2 times
those of their parent atoms. Convergence was reached at
Rwˆ0.034 for 785 re¯ections !I.2 s!I), Rw2ˆ0.092 for
all data and Sˆ1.165 for 262 parameters. The residual elec-
tron density in the ®nal difference Fourrer does not show
2.2. General procedure for the alkylation of 5
Isoindolinone 5 !126 mg, 0.5 mmol) was dissolved in anhy-
drous THF !10 mL) under argon, cooled in a dry ice-acetone
bath; then a solution of base !1.1 mmol) was added drop-
wise. After 20 min, the mixture was treated with the appro-
priate alkyl halide !1.2±4 equiv.), stirred for 2 h at 2788C.
The reaction was quenched by 2 mL of saturated aqueous
NH4Cl solution, water was added and the crude product was
extracted with CH2Cl2, dried over magnesium sulfate,
®ltered and evaporated under reduced pressure. The residue
was puri®ed by ¯ash column chromatography on SiO2 using
CH2Cl2/MeOH !97.5:2.5) as eluent.
Ê 23
Ê 23
.
any feature above 0.269 e A and below 20.298 e A
Lists of the fractional atomic coordinates, thermal para-
meters and bond distances and angles have been deposited
with Cambridge Crystallographic Data Centre, UK as
Supporting Information !CCDC reference number 176074).

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J. Perard-Viret et al. / Tetrahedron58 62002) 5103±5108
5107
2.3.1. )3R)-Allyl-2-[)1R)-2-hydroxy-1phenylethyl]-2,3-
dihydro-1H-isoindol-1-one )6c). Mp 122.58C !lit.11b 112±
1148C); [a]Dˆ1111 !cˆ0.5, CH2Cl2) !lit.11b 1152.2,
cˆ2.68, CH2Cl2); 1H NMR d 2.7 !m, 2H), 4.12 !ddd,
Jˆ12.2, 5.9, 3.2 Hz, 1H), 4.37±4.5 !m, 2H), 4.73 !dd,
Jˆ7.7, 3.2 Hz, 1H), 4.9±5.1 !m, 2H), 5.3 !dddd, Jˆ17.0,
10.0, 7.7, 7.7 Hz, 1H), 7.35±7.4 !m, 6H), 7.45±7.6 !m, 2H),
7.87 !d, Jˆ7.1, 1H); 13C NMR d 35.0 !1CH2), 60.6, 62.7
!2CH), 64.6 !1CH2), 119.7, 122.2, 123.8, 127.2, 128.0,
128.3, 128.8, 130.4, 131.8 !8CH, 1CH2), 132.3, 137.8,
144.8 !3C), 170.1 !CO); IR !nujol) 3379, 1647, 1453,
1059, 692; m/z !CI) 294 [MH1, 100%].
Baghi, two undergraduate students who participated in
this work.
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dihydro-1H-isoindol-1-one )6d). Mp 1678C; [a]Dˆ166
1
!cˆ0.5, CH2Cl2); H NMR d 2.89 !dd, Jˆ13.9, 7.8 Hz, 1
H), 3.36 !dd, Jˆ13.9, 4.4 Hz,1H), 4.1 !ddd, Jˆ12.4, 7.2,
3.4 Hz, 1H), 4.45 !dt, Jˆ12.5, 7.8 Hz, 1H), 4.55 !dd,
Jˆ7.8, 4.4 Hz, 1H), 4.88 !dd, Jˆ7.9, 3.35 Hz, 1H), 5.00
!t, Jˆ7.35 Hz, 1H !OH)), 6.85 !m, 1H), 6.94 !m, 2H),
7.19±7.25 !m, 5H), 7.29±7.36 !m, 3H), 7.42 !m, 2H), 7.80
!m, 1H); 13C NMR d 38.1 !1CH2), 61.8, 63.1 !2CH), 64.6
!1CH2), 122.6, 123.8, 127.1, 127.2, 128.0, 128.3, 128.4,
128.9, 129.4, 121.4 !10CH), 132.1, 135.4, 137.9, 145
!4C), 170 !CO); IR !nujol) 3305, 1656, 1421, 1068, 705;
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100%].
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2.3.3. 2-[)1R)-2-tButoxy-1phenylethyl]-2,3-dihydro-1H-
isoindol-1-one )7). The t-butyl ether 7 was prepared from
5 following the slightly modi®ed method described by
Wright et al.21 110 mL of H2SO4 concentrated was added
to a suspension of magnesium sulfate !830 mg) in dichloro-
methane !6 mL), stirred for 15 min at room temperature
under nitrogen. Then 5 !506 mg, 2 mmol) and anhydrous
tBuOH !950 mL, in 2 mL CH2Cl2) was added. The mixture
was stirred 4 days, quenched by addition of 5% sodium
hydrogen carbonate solution !1.5 mL), extracted twice by
CH2Cl2, dried over MgSO4, ®ltered and evaporated under
vacuum. The residue was puri®ed by ¯ash-column chroma-
tography !eluent ethyl acetate/cyclohexane !1:1) to afford 7
!400 mg) in 65% yield as a pale yellow powder, which was
recrystallized from diisopropyl ether to give clear colorless
crystal.
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È
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Mp 1168C; [a]Dˆ270 !cˆ1.4, CH2Cl2); 1H NMR d 1.22 !s,
9 H), 3.96 !dd, Jˆ5.2, 9.7 Hz, 1H), 4.03 !dd, Jˆ6.2, 9.7 Hz,
1H), 4.18 !d, Jˆ17.2, 1H), 4.58 !d, Jˆ17.2 Hz, 1H), 5.64 !t,
Jˆ5.6 Hz, 1H), 7.22±7.48 !m, 8H), 7.87 !d, Jˆ7.1 Hz, 1H);
13C NMR d 27.3 !1CH3), 48 !1CH2), 54.8 !1CH), 62 !1CH2),
73.3 !1C), 122.5, 123.5, 127.5, 127.6, 127.9, 128.4, 131
!7CH), 132.7, 138.3, 141.7 !3C), 168.4 !CO); IR !nujol)
1682, 1454, 1083, 897; Anal. calcd for C23H21NO2: C,
77.64; H, 7.49; N, 4.53. Found: C, 77.44; H, 7.65; N,
4.40; m/z !CI) 310 [MH1, 100%].
15. Fains, O.; Vernon, J. M. TetrahedronLett. 1997, 38, 8265±
8266.
16. The spectral data for this compound [!3R,10R)-6c] was found
identical from that one described by Allin et al. in Ref. 11b
who assigned a !3S,10R) con®guration. In this Perkin Trans-1
publication, the authors probably inverted the spectral data of
the two epimers obtained after separation !only one epimer is
described).
Acknowledgements
The authors want to thank Professor S. M. Allin for furnish-
ing NMR spectra of 3-allyl-isoindolinone 6c and for stimu-
lating discussions. J. P. and J. R thank V. Jenkin and K.
17. Ottwinosky, Z.; Minor, W. Method inEnzymology ; Carter Jr,

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20. Johnson, C. K. ORTEP: a thermal ellipsoid plotting program;
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structures; University of Gottingen: Germany, 1990.
19. Sheldrick, G. M.; Schneider, T. R. SHELXL: High Resolution
Re®nement. Methods inEnzymology ; Carter Jr, C. W., Sweet,