Symmetrical nitroxide synthesis: Meso versus d,l diastereomer formation

Article abstract of DOI:10.1021/jo981614d

The syntheses of C₂-symmetrical isoindoline nitroxide 2a and meso- isoindoline nitroxide 2b have been achieved by two different routes. The chiral C₂-symmetric nitroxide derives from the addition of a Grignard reagent from the least hindered face opposite the large phenyl group in nitrone intermediate 21, whereas the isoindoline 3b precursor to the meso nitroxide is formed by the addition of a Grignard reagent from the face opposite the large magnesium oxide group of the tight ion pair of iminium 19. The assignment of these structures is confirmed by preparation of several derivatives as well as by X-ray crystallography.

Full text of DOI:10.1021/jo981614d

J . Org. Chem. 1998, 63, 9857-9864
9857
Sym m etr ica l Nitr oxid e Syn th esis: Meso ver su s d ,l Dia ster eom er
F or m a tion
Rebecca Braslau* and Vladimir Chaplinski
Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064
Patricia Goodson
Department of Chemistry, University of Wyoming, Laramie, Wyoming 82071
Received August 7, 1998
The syntheses of C2-symmetrical isoindoline nitroxide 2a and meso-isoindoline nitroxide 2b have
been achieved by two different routes. The chiral C2-symmetric nitroxide derives from the addition
of a Grignard reagent from the least hindered face opposite the large phenyl group in nitrone
intermediate 21, whereas the isoindoline 3b precursor to the meso nitroxide is formed by the addition
of a Grignard reagent from the face opposite the large magnesium oxide group of the tight ion pair
of iminium 19. The assignment of these structures is confirmed by preparation of several derivatives
as well as by X-ray crystallography.
In tr od u ction
a pyrrolidine ring of type 1b,9 a pyrrolidine10 or piperidine
ring11 of type 1c, or are remote to the nitrogen on an
azepine 1d 2b or pyrrolidine ring 1e.12 The technique
The preparation of C2-symmetrical chiral nitroxides
has become a topic of current interest due to the applica-
tion of optically active nitroxides1 to a number of fields,
including asymmetric oxidation,2 stereoselective trapping
of prochiral carbon radicals,3 nitroxide mediated “living”
free radical polymerization,4 and paramagnetic chiral
liquid crystals.5 Reduction of these nitroxides provides
access to the corresponding C2-symmetrical chiral sec-
ondary amines,6 which are of interest in asymmetric
deprotonation, as optically active ligands, and as chiral
auxiliaries. A number of isolable trans C2-symmetric
nitroxides have been prepared in which the asymmetric
substituents are either immediately adjacent to the
nitrogen on a pyrrolidine7 or piperidine ring8 of type 1a ,
(1) Review on the synthesis and applications of optically active
nitroxides: Naik, N.; Braslau, R. Tetrahedron 1998, 54, 667-696.
(2) (a) Ma, Z. K.; Huang, Q. T.; Bobbitt, J . M. J . Org. Chem. 1993,
58, 4837-4843. (b) Rychnovsky, S. D.; McLernon, T. L.; Rajapakse,
H. J . Org. Chem. 1996, 61, 1194-1195.
(3) (a) Braslau, R.; Burrill, L. C.; Mahal, L. K.; Wedeking, T. Angew.
Chem., Int. Ed. Engl. 1997, 36, 237-238. (b) Braslau, R.; Burrill, L.
C.; Chaplinski, V.; Howden, R.; Papa, P. W. Tetrahedron: Asymmetry
1997, 8, 3209-3212.
(4) (a) Puts, R. S.; Sogah D. Y. Macromolecules 1996, 29, 3323-
3325. (b) Hawker has shown by crossover experiments that the
mediating nitroxides undergo facile exchange during these “living”
polymerizations; thus, the simple use of an optically active nitroxide
is not likely to result in optically active polymers: Hawker, C. J . Acc.
Chem. Res. 1997, 30, 373-382.
(5) Tamura, R.; Susuki, S.; Azuma N.; Matsumoto, A.; Toda, F.; Ishii,
Y.; J . Org. Chem. 1995, 60, 6820-6825.
traditionally employed for the preparation of C2-sym-
metrical chiral nitroxides of types 1a -c was originally
developed by Keana13 and relies on the addition of a
Grignard reagent anti to a transannular bulky substitu-
(6) For leading references, see: (a) Woltersdorf, M.; Kranich, R.;
Schmalz, H.-G. Tetrahedron 1997, 53, 7219-7230. (b) Simpkins, N.
Pure Appl. Chem. 1996, 68, 691-694. (c) Chong, J . M.; Clarke, I. S.;
Koch, I.; Olbach, P. C.; Taylor, N. J . Tetrahedron: Asymmetry 1995,
6, 409-418. (d) Shustov, G. V.; Rauk, A. Tetrahedron Lett. 1995, 36,
5449-5452. (e) Kubota, H.; Koga, K. Tetrahedron Lett. 1994, 35, 6689-
6692. (f) Whitesell, J . K. Chem. Rev. 1989, 89, 1581-1590.
(7) (a) Keana, J . F. W.; Cuomo, J .; Lex, L.; Seyedrezai, S. J . Org.
Chem. 1983, 48, 2647-2654. (b) Hankovszky, H. O.; Hideg, K.; Lovas,
M. J .; J erkovich, G.; Rockenbauer, A.; Gyo¨r, M.; Soha´r, P. Can. J .
Chem. 1989, 67, 1392-1400. (c) Benfaremo, N.; Steenbock, M.;
Klapper, M.; Mu¨llen, K.; Enkelmann, V.; Cabrera, K. Liebigs Ann.
Chem. 1996, 1413-1415. (d) Puts and Sogah, ref 4a. (e) Einhorn, J .;
Einhorn, C.; Ratajczak, F.; Gautier-Luneau, I.; Pierre, J .-L. J . Org.
Chem. 1997, 62, 9385-9388.
(9) Rockenbauer, A.; Mercier, A.; LeMoigne, F.; Olive, G.; Tordo, P.
J . Phys. Chem. A 1997, 101, 7965-7970.
(10) (a) Keana, J . F. W.; Prabhu, V. S. J . Org. Chem. 1986, 51, 4300-
4301. (b) Keana, J . F. W.; Seyedrezai, S. E.; Gaughan, G. J . J . Org.
Chem. 1983, 48, 2644-2647. (c) Tse-Tang, M. W.; Gaffney, B. J .; Kelly,
R. E. Heterocycles 1981, 15, 965-974. (d) Rotajczak, F. Synthese et
Reactivite de Nitroxydes Chiraux. Ph.D. Thesis, Universite´ J oseph
Fourier, Grenoble, France, 1997.
(11) Einhorn, J .; Einhorn, C.; Ratajczak, F.; Pierre, J .-L. J . Chem.
Soc., Chem. Commun. 1995, 1029-1030.
(12) Keana, J . F. W.; Hideg, K.; Birrell, G. B.; Hankovszky, O. H.;
Ferguson, G. L.; Parvez, M. Can. J . Chem. 1982, 60, 1439-1447.
(8) Einhorn, J .; Einhorn, C.; Ratajczak, F.; Durif, A.; Averbuch, M.-
T.; Pierre, J .-L. Tetrahedron Lett. 1998, 39, 2565-2568.
10.1021/jo981614d CCC: $15.00 © 1998 American Chemical Society
Published on Web 12/04/1998

9858 J . Org. Chem., Vol. 63, No. 26, 1998
Braslau et al.
Sch em e 1
Sch em e 3
Sch em e 4
Sch em e 2
ent in a nitrone intermediate as shown in Scheme 1. This
paper describes several approaches to the formation of
the isoindole-based C2-symmetrical nitroxide 2a ,14 in
which the aromatic ring imposes two sp2 planar carbon
atoms on the pyrrolidine nitroxide ring. Historically,
isoindoline nitroxides derived from phthalimides have
been prepared by the addition of a greater than 4-fold
excess of a single Grignard reagent to an N-alkyl phthal-
imide,15 followed by oxidation (Scheme 2). The approaches
outlined herein allow variation in the substitution around
the nitroxide.
Sch em e 5
Resu lts a n d Discu ssion
N-Benzyl phthalimide was chosen for ease of depro-
tection of the nitrogen in anticipation of eventual nitrox-
ide formation. Experimentation with stepwise addition
of two equiv of methylmagnesium bromide at room
temperature followed by heating at 80 °C for 30 min, and
then introduction of 4 equiv of phenylmagnesium bromide
at 80 °C followed by toluene reflux for 12 h, resulted in
a mixture of biphenyl plus a product resulting from net
addition of two methyl groups and two phenyl groups
(Scheme 3). Purification by flash chromatography pro-
vided the product 3 as a 5:1 mixture of diastereomers in
25% yield. The major component was obtained in purified
form following two recrystallizations, in 17% overall yield.
NMR spectroscopy confirmed that amine 3 was sym-
metrically substituted, but failed to differentiate between
a trans-substituted d,l product 3a and a cis-substituted
meso product 3b. Oxidation with wet 50% m-CPBA over
4 d provided the corresponding nitroxide in 71% yield,
directly, without necessitating a separate step for the
removal of the benzyl protecting group.15a Benzoic acid
is presumed to be the side product formed from the benzyl
residue. Precedence based on work with nitrone inter-
mediates leads one to expect the formation of the trans-
substituted amine 3a and, thus, formation of d,l nitroxide
2a as the major product (Scheme 4).
Coupling of the nitroxide 2 with two different prochiral
radicals,16 4 and 5, surprisingly formed the N-alkoxy
products 6 and 7, respectively, as single diastereomers
(Scheme 5). This could be a result of excellent stereose-
lectivity in the approach of a C2-symmetrical nitroxide
to the prochiral carbon radicals or the reaction of an
achiral meso-nitroxide with the carbon radicals. To
differentiate between these two possibilities (Scheme 6),
(13) Trans addition is only ensured when the steric bulk of Rlarge is
significantly big compared to Rsmall on the nitrone intermediate: Lee,
T. D.; Birrell, G. B.; Keana, J . F. W. J . Am. Chem. Soc. 1978, 100,
1618-1619.
(14) Both the meso and d, l diastereomers of this nitroxide have been
generated as a mixture by cheletropic trapping of nitric oxide in an
ESR tube: Paul, T.; Hassan, M. A.; Korth, H.-G.; Sustmann, R.; Avila,
D. V. J . Org. Chem. 1996, 61, 6835-6848.
(15) (a) Griffiths, P. G.; Moad, G.; Rizzardo, E.; Solomon, D. H. Aust.
J . Chem. 1983, 36, 397-401. (b) Sholle, V. D.; Krinitskaya, L. A.;
Rozantsev, E. G. Bull. Acad. Sci. USSR, Div. Chem. Sci. 1969, 138.
(16) Braslau, R.; Burrill, L. C.; Siano, M.; Naik, N.; Howden, R. K.;
Mahal, L. K. Macromolecules 1997, 30, 6445-6450.

Symmetrical Nitroxide Synthesis
J . Org. Chem., Vol. 63, No. 26, 1998 9859
Sch em e 6
Sch em e 8
Sch em e 7
Sch em e 9
the nitroxide was reduced to the hydroxylamine with
phenyl hydrazine, followed by esterification with optically
1
active (R)-(-)-R-methoxyphenylacetic acid. Both H and
13C NMR spectroscopy indicate formation of a single
product, 8, implying cis substitution of the phenyl groups.
Thus, the correct structure for the major Grignard
addition product is meso-3b rather than the expected d,l-
3a , and that for the nitroxide is meso-2b rather than C2-
symmetric 2a . X-ray crystallography on both the N-ben-
zylated amine and the nitroxide confirm the meso
structure. The X-ray structure for benzylamine 3b shows
the isoindoline ring to be slightly bent, with the nitrogen
atom out of the plane defined by the rest of the isoindoline
ring system. The two methyl groups are in axial-like
positions, with a bond angle of 109.1° from the aromatic
plane. The phenyl groups are situated with a wider angle
from the aromatic plane, of 111.9°. For meso-nitroxide
2b, the isoindole ring is completely planar, as is expected
for the sp2 hybridization at the nitroxide nitrogen atom.
The Grignard addition reaction was then reexamined
to determine if the ratio of d,l versus meso product
formation could be controlled by the order of addition of
the two Grignard reagents (Scheme 7). Thus, 2 equiv of
phenylmagnesium bromide were added to N-benzyl
phthalimide at room temperature over a 5-min period.
A violet precipitate formed and partially redissolved,
following the completion of the addition of the first
Grignard reagent. The reaction mixture was heated to
80 °C for 30 min, followed by addition of 4 equiv of
methylmagnesium bromide. This mixture was then heated
at toluene reflux for 12 h. Workup provided the meso-
dimethyl-substituted amine 3b in a 1:1 ratio with the
trimethyl-substituted amine 9a . Biphenyl was also pro-
duced. Chromatography provided the products 3b and
9a in 20 and 23% yield, respectively. Use of N-methyl
phthalimide as the starting material (Scheme 8) gave
15% of meso-3b′, the N-methyl analogue of 3b, and 12%
of the triphenyl-substituted amine 9b′. To confirm the
cis stereochemistry, oxidative demethylation17 of N-
methyl 3b′ to form the nitroxide, followed by reduction
with phenyl hydrazine and esterification with optically
active (R)-(-)-R-methoxyphenylacetic acid, gave the same
product 8 as shown in Scheme 6. These experiments
indicate there is an inherent bias for formation of the
meso diastereomer by this synthetic route.
Attention was next focused on the traditional nitrone
route for C2-symmetrical chiral-nitroxide formation
(Scheme 9). Indoline 10 was prepared using the Dele´pine
reaction18 according to the procedure by Meyers.19 At-
tempts to prepare nitrone 11 using urea-hydrogen
peroxide complex with a tungsten catalyst20 gave an
intractable tar. However, stepwise methylation of the
formamidine 12, following the procedures of Rockell21 and
Meyers,19 provided the dimethyl-substituted amine 13 as
an approximately 1:1 mixture of diastereomers in 60%
overall yield. Oxidation unexpectedly produced hydroxy-
nitrone 14. This material was treated with an excess of
phenyl Grignard at toluene reflux for 12 h. After an
aqueous workup, the crude hydroxylamine was submitted
to copper-catalyzed air oxidation to provide the desired
d,l-nitroxide 2a , as a 13:1 diastereomeric mixture with
2b, obtained in 42% overall yield from hydroxynitrone
(18) Dele´pine, M. Compt. Rend. 1895, 120, 501; 1897, 124, 292.
Angyal, S. J . Org. React. 1954, 8, 197.
(19) Meyers, A. I.; Santiago, B. Tetrahedron Lett. 1995, 36, 5877-
5880.
(20) Marcantoni, E.; Petrini, M.; Polimanti, O. Tetrahedron Lett.
1995, 36, 3561-3562.
(21) Beeley, L. J .; Rockell, C. J . M. Tetrahedron Lett. 1990, 31, 417-
420.
(17) Dupeyre, R.-M.; Rassat, A. Tetrahedron Lett. 1975, 1839-1840.

9860 J . Org. Chem., Vol. 63, No. 26, 1998
Braslau et al.
Sch em e 10
isoindole ring is bent, with the two axial methyl groups
occupying an axial-like position. In 3a , one of the bulky
phenyl groups would be required to sit in an axial-like
orientation, destabilizing the C2-symmetrical isomer.
However, submission of a 1.6:1 d,l/meso mixture of 3a /
3b to 2 equiv of phenyl Grignard in refluxing toluene for
15 h, to simulate the reaction conditions, resulted in
recovered starting material in exactly the same ratio of
1.6:1 d,l/meso isomers. This conclusively rules out equili-
bration via an open cation such as 23.
14 following purification by flash chromatography. This
material was clearly different from the meso-2b: the
melting points for 2a and 2b are 139-141 and 105-108
°C, respectively. In addition, in situ reduction of nitrox-
ides 2a and 2b with phenyl hydrazine in separate NMR
tubes give the corresponding hydroxylamines in which
the methyl resonances are observed at δ 1.70 and 1.95
ppm. Confirming the chiral nature of 2a , coupling with
the prochiral 1-phenethyl radical provided the alkoxy-
amine product 15 as a 2.2:1 mixture of diastereomers
(Scheme 10). Interestingly, the room-temperature NMR
spectra of alkoxyamines 6, 7, and 8 derived from meso-
nitroxide 2b show no hint of hindered nitrogen inversion
coupled with slow N-O-bond rotation,22 whereas the
This work establishes a procedure for the regio- and
diastereoselective introduction of differentiated substit-
uents adjacent to the nitrogen of isoindoline nitroxides.
Variation of the substituents, for example, introduction
of long alkyl chains for lipid solubility, holds potential
for application in the preparation of specialized isoindo-
line spin probes with narrow line widths.
Exp er im en ta l Section
Gen er a l. All reactions were run under N2 unless otherwise
noted. Phenyl Grignard was purchased from Aldrich and
methyl Grignard was purchased from Strem as ether solutions.
Solvents were dried as follows: THF and toluene were distilled
under N2 from sodium-benzophenone, and CH2Cl2 was dis-
tilled from calcium hydride. Flash chromatography was per-
formed using Universal Scientific Inc. silica gel 63-200. IR
spectra were recorded in CDCl3 solution. Mass spectra were
obtained at the University of Illinois using Magic Bullet or
fast-atom bombardment (FAB); electrospray mass spectroscopy
(ESMS) was performed at U. C. Santa Cruz using a Quattro
II Triplequadrupole mass spectrometer. Elemental Analysis
was carried out by M-H-W Laboratories, Phoenix, AZ. The
X-ray crystallographic structure was obtained from the facili-
ties at the University of Wyoming. Melting points are uncor-
rected.
1
room-temperature H NMR spectrum of 15 derived from
d,l-nitroxide 2a does show broadened isoindoline methyl
peaks from this phenomenon. An X-ray crystal structure
of 2a confirms the C2 symmetry of the molecule. The
isoindoline ring is clearly planar, with the phenyl groups
splayed across opposite sides of the fused ring system.
The formation of the meso product from the phthal-
imide starting material can be understood by considering
the following mechanistic route depicted in Scheme 11.
Following the addition of the first equivalent of methyl
Grignard, the second equivalent adds to the face opposite
the large alkoxy magnesium salt to give meso-bis-
(alkoxide) intermediate 16. Elimination of OMgBr gives
iminium salt 17 as a tight ion pair. Addition of the first
equivalent of phenyl Grignard occurs from the face
opposite both alkoxy-magnesium bromides, to give in-
termediate 18. Subsequent elimination forms iminium
species 19, again as a tight-ion pair. The second equiva-
lent of phenyl Grignard then adds opposite the complexed
alkoxy-magnesium salt, to give meso-3b. In contrast, the
nitrone route, starting with compound 14, is expected to
react with phenyl Grignard from the face opposite the
alkoxy-magnesium salt to initially give intermediate 20,
which undergoes elimination to produce nitrone 21.
Because of the anionic oxygen bonded to nitrogen, 21 does
not exist as a tight-ion pair, and thus addition of the
second equivalent of phenyl Grignard occurs from the
face opposite the phenyl group, to give intermediate 22,
as normally observed in the Keana method. Although this
is a rationalization of the experimental results, this does
provide a reasonable guide to understanding the observed
stereochemistry with iminium vs nitrone intermediates.
We had also considered thermodynamic equilibration
through a dibenzylic tertiary carbocation, 23, as a
rationale for the formation of predominately meso-iso-
indoline from the phthalimide route (Scheme 12). MM2
molecular mechanics calculations on the N-methyl iso-
indolines give a 0.4 kcal/mol difference in energy for these
two structures, with the meso compound being more
stable. As was seen in the X-ray structure of 3b, the
m eso-2-Ben zyl-1,3-d im et h yl-1,3-d ip h en ylisoin d olin e
(3b). N-Benzyl phthalimide (1.19 g, 5.0 mmol) was dissolved
in 20 mL toluene. A 3.0 M solution of methylmagnesium
bromide (3.33 mL, 10.0 mmol) in diethyl ether was added
dropwise by cannula at room temperature over 5 min. During
the addition, a white precipitate formed and partially redis-
solved. The temperature was raised to 80 °C for 30 min. A 3.0
M solution of phenylmagnesium bromide (6.66 mL, 20.0 mmol)
in diethyl ether was added by cannula over 5 min, and the
resulting clear solution was heated to reflux (bath tempera-
ture: 120 °C). After 12 h, the reaction mixture was cooled,
and 50 mL of concentrated ammonium chloride solution and
50 mL of water were added and stirred until all solids
dissolved. To this was added 20 mL of concentrated sodium
carbonate solution. The organic layer was separated, washed
with 20 mL of brine, dried over magnesium sulfate, and
concentrated in vacuo. Flash chromatography of the residue
(30 mm column, 100:1 hexane/ethyl acetate) was carried out
to separate the product from biphenyl, yielding 480 mg of crude
product as clear brown solid (25% yield). Two recrystallizations
from 3 mL of hexane/ethyl acetate (16:1) gave colorless crystals
of 3b. Alternatively, a single recrystallization from ethanol/
chloroform gave very clean crystals. TLC: 100:1 hexane/ethyl
acetate, molybdenum stain, Rf ) 0.33. Mp: 131 °C. IR
1
(CDCl3): 1214, 1172, 1092 cm-1. H NMR (250 MHz, CDCl3):
δ 7.50-7.38 (m, 4H), 7.30-7.10 (m, 8H), 6.95-6.80 (m, 7H),
3.88 (s, 2H), 1.94 (s, 6H). 13C NMR (APT) (63 MHz, CDCl3): δ
148.5 (s), 148.0 (s), 139.1 (s), 129.0 (d), 127.8 (d), 127.4 (d),
127.2 (d), 127.1 (d), 126.2 (d), 125.9 (d), 122.8 (d), 70.6 (s), 48.0
(t), 23.9 (q). MS (EI): m/e 374 ([M+ - CH3], 100), 312 ([M+
-
Bn], 28), 91 ([Bn+]95). HRMS: exact mass calcd for [M - 15]+
C28H24N 374.1909, found 374.1913.
Oxid a tion of m eso-2-Ben zyl-1,3-d im eth yl-1,3-d ip h en yl-
isoin d olin e (3b ) t o t h e Nit r oxid e: 1,3-Dim et h yl-1,3-
d ip h en ylisoin d olin -2-yloxyl (2b).14 Isoindoline 3b (152 mg,
0.39 mmol) was dissolved in 15 mL of dichloromethane. Wet
(22) Busfield, W. K.; J enkins, I. D.; Thang, S. H.; Moad, G.; Rizzardo,
E.; Solomon, D. H. J . Chem. Soc., Chem. Commun. 1985, 1249-1250.

Symmetrical Nitroxide Synthesis
J . Org. Chem., Vol. 63, No. 26, 1998 9861
Sch em e 11
Sch em e 12
50% m-chloroperbenzoic acid (Aldrich) (470 mg, 1.36 mmol)
was added with stirring at room temperature under a normal
atmosphere. Additional dichloromethane was added over the
course of 4 d to dissolve precipitating solids. The reaction was
monitored by TLC. After 4 d, the slightly yellow reaction
mixture was washed with 35 mL of saturated sodium bicar-
bonate solution, followed by 5 mL of brine, and dried over
magnesium sulfate and the solvent evaporated to provide a
yellow oil. Purification by flash column chromatography (10
mm column, 10:1 hexane/ethyl acetate) afforded 87.7 mg of
2b as a crystalline brown solid (71% yield). Mp: 105-108 °C.
TLC: 10:1 hexane/ethyl acetate, molybdenum stain, Rf ) 0.49.
IR (CDCl3): 1366 (N-O•), 1259 (C-N), 1183 (C-N) cm-1. ESR
(CH2Cl2) triplet, an ) 14.22 G. MS (EI): m/e 314 ([M]+, 39).
HRMS exact mass calcd for [M+] C22H20NO: 314.1545.
Found: 314.1545. 1H NMR (250 MHz, CDCl3) gave a broad,
amorphous spectrum.
to provide a brown oil. The hydroxylamine was purified by
flash column chromatography (10 mm column, 10:1 hexane/
ethyl acetate) to afford 29.6 mg of the hydroxylamine as a
crystalline colorless solid (58% yield). Mp: 114-117 °C. TLC:
10:1 hexane/ethyl acetate, molybdenum stain, Rf ) 0.51. 1H
NMR (250 MHz, CDCl3): δ 7.57 (d, 4H, J ) 7.5 Hz), 7.5-7.1
(m, 8H), 7.05-6.9 (m, 2H), 4.31 (bs, 1H), 1.95 (s, 6H). 13C NMR
(APT) (63 MHz, CDCl3): δ 146.99 (s), 145.03 (s), 127.82 (d),
127.37 (d), 127.10 (d), 126.58 (d), 123.09 (d), 72.18 (s), 21.99
(q).
ter t-Bu t yl 2-(1,3-Dim et h yl-1,3-d ip h en ylisoin d olin -2-
yloxy)p r op a n oa te (6). Following a modified procedure from
Porter,23 a 2.0 M solution of LDA (135 µL, 0.27 mmol) and 1.0
mL of anhydrous THF were cooled under nitrogen to -78 °C,
and a solution of tert-butyl propionate (29.3 mg, 0.225 mmol)
in 1.0 mL of THF was added dropwise by cannula. The reaction
mixture was kept at this temperature for 1.5 h. In a separate
flask, anhydrous CuCl2 (36.3 mg, 0.27 mmol) and nitroxide
2b (47.2 mg, 0.15 mmol) in 1.0 mL of THF were stirred for 5
min and cooled to -78 °C, and the cold enolate solution was
Red u ction of th e 1,3-Dim eth yl-1,3-d ip h en ylisoin d olin -
2-yloxyl (2b ) t o t h e H yd r oxyla m in e: 2-H yd r oxy-1,3-d i-
m eth yl-1,3-d ip h en ylisoin d olin e. Nitroxide 2b (51.2 mg,
0.163 mmol) was dissolved in 5 mL of dichloromethane, and
phenyl hydrazine (17.6 mg, 0.163 mmol) was added. After 30
min, the almost colorless reaction mixture was concentrated
(23) Porter, N. A.; Su, Q.; Harp, J . J .; Rosenstein, I. J .; McPhail, A.
T. Tetrahedron Lett. 1993, 28, 4457-4460.

9862 J . Org. Chem., Vol. 63, No. 26, 1998
Braslau et al.
added by cannula. After 1 h, the reaction was allowed to warm
to room temperature. The reaction mixture was concentrated,
and the residue was dissolved in the mixture of 5 mL of diethyl
ether, 1.0 mL 10% NH4OH solution, and 2.0 mL of water. The
organic layer was separated and washed with 2 mL of
saturated sodium chloride solution, dried over magnesium
sulfate, and concentrated in vacuo to give crude 6. Purification
by flash column chromatography (10 mm column, 16:1 hexane/
ethyl acetate) afforded 47.6 mg of pure 6 as a colorless oil (72%
yield) and a single diastereomer.
TLC: 16:1 hexane/ethyl acetate, molybdenum stain, Rf )
0.33. IR (CDCl3): 1731 (CdO), 1449, 1373, 1085 cm-1. 1H NMR
(250 MHz, C6D6): δ 8.0-7.7 (m, 4H), 7.4-6.8 (m, 10H), 4.17
(q, 1H, J ) 7.0 Hz), 2.38 (s, 3H), 2.11 (s, 3H), 1.31 (s, 9H),
1.16 (d, 3H, J ) 7.0 Hz). 13C NMR (APT) (63 MHz, CDCl3): δ
172.19 (s), 147.84 (s), 145.84 (s), 145.11 (s), 127.83 (d), 127.68
(d), 127.53 (d), 127.35 (d), 126.82 (d), 126.52 (d), 123.32 (d),
123.19 (d), 80.86 (d), 80.45 (s), 73.22 (s), 73.03 (s), 27.82 (q),
22.68 (q), 18.12 (q). MS (FAB): m/e 444 ([M+ + 1], (100), 314
([nitroxide+], 98). HRMS: mass calcd for [M+ + 1] C29H34NO3
444.2539, found 444.2539.
with 0.5 mL of 1 N hydrochloric acid, followed by 2 × 0.5 mL
of saturated sodium bicarbonate solution and 2 × 0.5 mL of
brine, dried over magnesium sulfate, and concentrated into
an oil. The ester was purified by flash column chromatography
(10 mm column, 10:1 hexane/ethyl acetate) to afford 29.6 mg
of 8 as a colorless oil (75% yield). TLC: 10:1 hexane/ethyl
acetate, molybdenum stain, Rf ) 0.41. IR (CDCl3): 3060, 1766,
1449, 1096 cm-1 1H NMR (250 MHz, CDCl3) δ 7.5-6.9 (m,
.
19H), 4.71 (s, 1H), 3.35 (s, 3H), 1.78 (s, 3H), 1.33 (s, 3H). 13C
NMR (APT) (63 MHz, CDCl3) δ 169.19 (s), 144.81 (s), 144.65
(s), 144.45 (s), 135.95 (s), 128.58 (d), 128.31 (d), 127.54 (d),
127.25 (d), 127.10 (d), 127.00 (d), 126.22 (d), 126.16 (d), 123.64
(d), 81.46 (d), 57.14 (q), 25.17 (q), 24.59 (q). MS (FAB): m/e
464 ([M+ + 1], 24), 121 ([PhCHdOMe]+, 100). HRMS: mass
calcd for [M+ + 1] C31H30NO3 464.2226, found 464.2224.
2-Ben zyl-1,3,3-tr im eth yl-1-p h en ylisoin d olin e (9a ) a s a
1:1 Mixtu r e w ith m eso-2-Ben zyl-1,3-d im eth yl-1,3-d ip h en -
ylisoin d olin e (3b). N-Benzylphthalimide (1.19 g, 5.0 mmol)
was dissolved in 20 mL of toluene. A 3.0 M solution of
phenylmagnesium bromide (3.33 mL, 10.0 mmol) in diethyl
ether was added dropwise by cannula at room temperature
over 5 min. During the addition, a violet precipitate formed,
which partially dissolved again at the end of the addition. The
mixture was heated at 80 °C for 30 min. A 3.0 M solution of
methylmagnesium bromide (6.66 mL, 20.0 mmol) in diethyl
ether was added by cannula over 5 min; the resulting yellow
solution was heated to reflux (bath temperature 120 °C). After
12 h, the mixture was cooled, and 50 mL of concentrated
ammonium chloride solution and 25 mL of water were added
to dissolve all solids. To this was added 20 mL of concentrated
sodium carbonate solution, and the organic layer was washed
with 20 mL of brine, dried over magnesium sulfate, and
concentrated in vacuo. Flash chromatography of the residue
(30 mm column, 100:1 hexane/ethyl acetate) removed biphenyl,
giving 64 mg of pure 2-benzyl-1,3,3-trimethyl-1-phenylisoin-
doline (9a ) as a colorless oil and a mixture of isoindolines 3b
and 9a , which was chromatographed again. This gave 522 mg
of a clean 1:1 isoindolines mixture and 380 mg of a mixture
containing 43% of 3b and 8% of 9a , as determined by 1H NMR
analysis. In summary, the combined yields of isoindolines 3b
and 9a in the reaction were 23 and 20%, respectively.
1,3-Dim eth yl-2-(1-p h en yleth oxy)-1,3-d ip h en ylisoin d o-
lin e (7). A two-phase mixture of (1-bromoethyl)benzene (41.1
mg, 0.222 mmol) and fuming hydrazine (0.173 mL, 2.22 mmol)
was sonicated for 30 min under nitrogen until a single cloudy
phase was observed. The mixture was diluted with 10 mL of
diethyl ether, and the organic and hydrazine layers were
separated. The hydrazine layer was washed with 5 mL of
diethyl ether. The combined organic phase was washed with
5 mL of 10% aqueous potassium hydroxide followed by 5 mL
of brine, dried over magnesium sulfate, and filtered. Volatiles
were removed in vacuo to give a slightly yellow oil which was
diluted with toluene (0.5 mL) and cooled to -78 °C. In a
separate flask, lead dioxide (42.5 mg, 0.178 mmol), isoindoli-
noxyl 2b (28.0 mg, 0.089 mmol), and toluene (0.5 mL) were
sonicated under nitrogen for 5 min and then cooled to -78
°C. The benzylic hydrazine solution was added by cannula,
and the residues were washed in with an additional 0.5 mL of
toluene. The reaction was allowed to warm to room temper-
ature, diluted with 10 mL of diethyl ether, filtered through
Celite, and washed with 15 mL of diethyl ether. Volatiles were
removed in vacuo to give an orange oil. Purification by flash
column chromatography (10 mm column, 50:1-16:1 hexane/
ethyl acetate) afforded 24.2 mg of impure coupling product 7
as an oil and 10.4 mg of the hydroxyamine (28% yield) as a
slightly yellow oil. Further purification by flash column
chromatography (10 mm column, 5:1 hexane/dichloromethane)
afforded 12.0 mg of slightly impure 7 as a colorless oil (32%
yield) and a single diastereomer. TLC: 32:1 hexane/ethyl
acetate, molybdenum stain, Rf ) 0.30. TLC: 5:1 hexane/
dichloromethane, molybdenum stain, Rf ) 0.34. IR (CDCl3):
2-Ben zyl-1,3,3-t r im et h yl-1-p h en ylisoin d olin e
(9a ).
TLC: 100:1 hexane/ethyl acetate, molybdenum stain, Rf
)
1
0.31. IR (CDCl3): 3026, 1212, 1027 cm-1. H NMR (250 MHz,
CDCl3): δ 7.5-6.8 (m, 14H), 3.82 (dd, 2H), 1.77 (s, 3H), 1.46
(s, 3H), 1.19 (s, 3H). 13C NMR (APT) (63 MHz, CDCl3):
δ
148.26 (s), 147.81 (s), 147.44 (s), 141.96 (s), 128.89 (d), 128.1
(d), 127.77 (d), 127.52 (d), 127.1 (d), 126.98 (d), 126.43 (d),
122.82 (d), 121.3 (d), 71.18 (s), 65.51 (s), 47.4 (t), 30.07 (q),
27.66 (q), 24.94 (q). MS (EI): m/e 327 ([M]+, 4), 313 ([M+
-
14], 37), 250 ([M+ - Ph], 15), 91 ([Bn]+, 100). HRMS: mass
3025, 1449, 1301, 1067 cm-1. H NMR (250 MHz, CDCl3): δ
calcd for [M]+ C24H25N 327.1987, found 327.1986.
1
7.60 (d, 2H, J ) 7.3 Hz), 7.5-6.7 (m, 17H), 4.12 (q, 1H, J )
m eso-1,2,3-Tr im eth yl-1,3-d ip h en ylisoin d olin e (3b′) a n d
1,2-Dim et h yl-1,3,3-t r ip h en ylisoin d olin e (9b′). The N-
methylphthalimide (806 mg, 5.0 mmol) was dissolved in 20
mL of toluene. A 3.0 M solution of methylmagnesium bromide
(3.33 mL, 10.0 mmol) in diethyl ether was added dropwise by
cannula at room temperature over 5 min. During the addition,
a white precipitate formed. The mixture was heated at 80 °C
for 30 min. A 3.0 M solution of phenylmagnesium bromide
(6.66 mL, 20.0 mmol) in diethyl ether was added by cannula
over 5 min, and the resulting clear solution was heated to
reflux (bath temperature 120 °C), becoming yellow and almost
clear after 1 h. After 20 h, the reaction mixture was cooled,
and 25 mL of concentrated ammonium chloride solution and
25 mL of water were added until most of the solids dissolved.
A dark emulsion formed which was filtered through sintered
glass and washed with 20 mL of hexanes. The organic layer
was separated, washed with 20 mL of brine, dried over
magnesium sulfate, and concentrated in vacuo. Four flash
chromatography columns were required to obtain analytical
samples of isoindolines 3b′ and 9b′, in overall yields of 15 and
12%, respectively.
6.5 Hz), 1.99 (s, 3H), 1.86 (s, 3H), 0.84 (d, 3H, J ) 6.5 Hz). 13
C
NMR (APT) (63 MHz, CDCl3): δ 148.29 (s), 147.99 (s), 146.35
(s), 145.87 (s), 143.68 (d), 128.16 (d), 127.8 (d), 127.73 (d), 127.6
(d), 127.53 (d), 126.92 (d), 126.76 (d), 126.49 (d), 126.37 (d),
123.3 (d), 80.85 (d), 73.11 (s), 72.88 (s), 22.75 (q), 22.59 (q),
21.78 (q). MS (FAB): m/e 420 ([M+ + 1], 18), 315 ([nitroxide+
+ 1], 88), 300 ([nitroxide+ - CH2], 100), 104 ([styrene+], 79).
HRMS: mass calcd for [M+ + 1] C30H30NO 420.23274, found
420.2328.
Acyla tion of th e Hyd r oxyla m in e of 2b w ith (R)-(-)-R-
Meth oxyp h en yla cetic Acid : 1,3-Dim eth yl-1,3-d ip h en yl-
isoin d olin -2-ol R-Meth oxyp h en yla ceta te (8). (R)-(-)-R-
Methoxyphenylacetic acid (15.6 mg, 0.094 mmol), 4-N,N-
(dimethylamino)pyridine (1.2 mg, 0.0094 mmol), and 1,3-
dicyclohexylcarbodiimide (58.0 mg, 0.107 mmol) were suspended
in 1.5 mL of dichloromethane. A solution of hydroxylamine
derived from 2b (26.8 mg, 0.085 mmol) in 0.5 mL of dichlo-
romethane was added dropwise by cannula. The residues of
the hydroxylamine were washed into the reaction mixture with
2 × 0.5 mL of dichloromethane. After 2 h, the heterogeneous
mixture was filtered, and the cake of dicyclohexylurea was
washed with 3 × 1 mL of hexanes. The filtrate was washed
1,2,3-Tr im eth yl-1,3-diph en ylisoin dolin e (3b′). TLC: 40:1
hexane/ethyl acetate, molybdenum stain, Rf ) 0.35. IR

Symmetrical Nitroxide Synthesis
J . Org. Chem., Vol. 63, No. 26, 1998 9863
1
(CDCl3): 1224, 1066, 1026 cm-1. H NMR (250 MHz, CDCl3):
OH, and 5.0 mg (0.025 mmol) of Cu(OAc)2 to give a pink-red
solution. A stream of air was bubbled through the solution for
30 min. The resulting green solution was concentrated, and
the residue dissolved in the mixture of 10 mL of chloroform, 3
mL of concentrated NaHSO4 solution, and 10 mL of water. The
organic layer was separated, and the aqueous layer was
extracted with 5 mL of chloroform. The combined organic
layers were then washed with 5 mL of saturated sodium
bicarbonate solution, dried over magnesium sulfate, and
concentrated in vacuo to give crude nitroxide 2a . Purification
by flash column chromatography (10 mm column, 10:1 hexane/
ethyl acetate) afforded 66 mg of 13:1 2a /2b as a pale brown
solid (42% yield). mp: 139-141 °C. TLC: 16:1 hexane/ethyl
acetate, molybdenum stain, Rf ) 0.41. IR (CDCl3) 3063, 1369
(N-O‚), 1259 (C-N), 1190 (C-N) cm-1. ESR (CH2Cl2): triplet,
an ) 14.663 G. MS (FAB): m/e 316 ([M+ + 2], 94), 300 (100).
HRMS: mass calcd for [M+ + 2] C22H22NO 316.1701, found
316.1701. 1H NMR (250 MHz, CDCl3) gave a broad, amorphous
spectrum. Addition of phenyl hydrazine formed the corre-
sponding hydroxylamine: δ 1.70 (s, 6H).
δ 7.7-6.9 (m, 14H), 2.25 (s, 3H), 1.87 (s, 6H). 13C NMR (APT)
(63 MHz, CDCl3): δ 147.9 (s), 147.5 (s), 128.0 (d), 127.7 (d),
127.1 (d), 126.6 (d), 122.8 (d), 70.0 (s), 26.6 (q), 23.5 (q). MS
(FAB): m/e 314 ([M+ + 1], 27), 298 ([M+ - CH3], 100), 236
([M+ - Ph], 26). HRMS: mass calcd for [M+ + 1] C23H24
N
314.1909, found 314.1908.
1,2-Dim eth yl-1,3,3-tr iph en ylisoin dolin e (9b′). TLC: 40:1
hexane/ethyl acetate, molybdenum stain, Rf ) 0.38. IR
1
(CDCl3): 3060, 1216, 1028 cm-1. H NMR (250 MHz, CDCl3):
δ 7.7-6.8 (m, 19H), 2.14 (s, 3H), 1.54 (s, 3H). 13C NMR (APT):
(63 MHz, CDCl3): δ 148.9 (s), 147.8 (s), 146.3 (s), 144.7 (s),
143.9 (s), 130.2 (d), 128.3 (d), 128.0 (d), 127.9 (d), 127.6 (d),
127.2 (d), 127.1 (d), 126.9 (d), 126.7 (d), 124.6 (d), 123.0 (d),
78.3 (s), 70.4 (s), 28.8 (q), 21.3 (q). MS (FAB): m/e 376 ([M+
+
1], 18), 360 ([M+ - CH3], 61), 298 ([M+ - Ph], 100). HRMS:
exact mass calcd for [M+ + 1] C28H26N 376.2066, found
376.2058.
Oxid a tive Dem eth yla tion of th e 1,2,3-Tr im eth yl-1,3-
diph en ylisoin dolin e (3b′) to th e Nitr oxide an d th e Am in e:
m eso-1,3-Dim eth yl-1,3-d ip h en ylisoin d olin e 2-Nitr oxid e
(2b) a n d 1,3-Dim eth yl-1,3-d ip h en ylisoin d olin e. To 1,2,3-
trimethyl-1,3-diphenylisoindoline 3b′ (92 mg, 0.27 mmol) and
Na2WO4‚2H2O (4.4 mg, 0.013 mmol) was added 3 mL of
methanol followed by 30% aqueous H2O2 (135 µL, 1.19 mmol),
to give a turbid heterogeneous mixture. After 24 h, 5 mL of
methanol and 10 drops of 30% aqueous H2O2 were added to
the yellow solution. After 12 h, the mixture was concentrated
under reduced pressure, dissolved in 10 mL of dichlo-
romethane, washed with 5 mL of water, dried over magnesium
sulfate, and filtered, and the solvent was evaporated to provide
a yellow oil. Two flash chromatography columns were required
to separate the products: (dichloromethane, then 10:1 dichlo-
romethane/ethyl acetate). This afforded 15 mg of nitroxide 2b
as a crystalline brown solid (18% yield) and 22 mg of the
secondary amine as a colorless oil (28% yield).
Cou p lin g of d ,l-1,3-Dim eth yl-1,3-d ip h en ylisoin d olin e
2-Nitr oxid e (2a ) w ith 1-P h en eth yl Ra d ica l: 1,3-Dim eth yl-
2-(1-p h en yleth oxy)-1,3-d ip h en ylisoin d olin e (15). A two-
phase mixture of (1-bromoethyl)benzene (46.3 mg, 0.250 mmol)
and fuming hydrazine (0.78 mL, 2.50 mmol) was sonicated for
30 min under nitrogen until a single cloudy phase was
observed. The mixture was diluted with 5 mL of 10% aqueous
potassium hydroxide followed by 5 mL of diethyl ether. The
water-hydrazine layer was washed with 5 mL of diethyl ether.
The combined organic phase was washed with 5 mL of 10%
aqueous potassium hydroxide followed by 5 mL of brine, dried
over magnesium sulfate, and filtered. Volatiles were removed
in vacuo to give a slightly yellow oil which was diluted with
toluene (0.5 mL) and cooled to 0 °C. In a separate flask, lead
dioxide (72.0 mg, 0.300 mmol), d,l-isoindoline nitroxide 2a
(31.4 mg, 0.100 mmol), and toluene (0.5 mL) were sonicated
under nitrogen for 5 min and then cooled to 0 °C. The benzylic
hydrazine solution was added by cannula, and the residues
were washed in with an additional 0.5 mL of toluene. After 5
min, the ice bath was removed, and the reaction was allowed
to warm to room temperature and was stirred overnight. The
reaction mixture was diluted with 5 mL of diethyl ether and
filtered through Celite, the Celite was washed with 7 mL of
diethyl ether, and volatiles were removed in vacuo to give a
pale-yellow oil. Purification by flash column chromatography
(10 mm column, 5:1 hexane/dichloromethane) afforded 34.0 mg
of pure coupling product 15 as a colorless oil (81% yield) and
an inseparable 2.2:1 mixture of diastereomers (as indicated
by integration of the methyl hydrogens at δ 2.16 and 1.73
ppm). TLC: 5:1 hexane/dichloromethane, molybdenum stain,
1,3-Dim eth yl-1,3-d ip h en ylisoin d olin e. TLC: pure ethyl
acetate, molybdenum stain, Rf ) 0.16. IR (CDCl3): 1214, 1172,
1092 cm-1. H NMR (250 MHz, CDCl3): δ 7.7-6.9 (m, 14H),
1
2.45 (br s, 1H), 1.88 (s, 6H).
1-Hyd r oxy-1,3-d im eth yl-1H-isoin d ole 1-oxid e (14). A
mixture of 1,3-dimethyl-1H-isoindoline 13 (420 mg, 2.80 mmol,
mixture of diastereomers) and Na2WO4‚2H2O (46 mg, 0.14
mmol) was suspended in 5 mL of methanol and cooled to 0
°C. Urea-hydrogen peroxide addition complex (530 mg, 5.6
mmol) was added. After 1 h of stirring, more urea-hydrogen
peroxide addition complex (530 mg, 5.6 mmol) was added. After
2 h, the mixture was concentrated under reduced pressure.
Twice the residue was triturated with 20 mL of dichlo-
romethane and filtered to remove the urea. The solvent was
evaporated to provide a pale yellow oil which was purified by
flash column chromatography (30 mm column, 5:1 ethyl
acetate/methanol) to give 170 mg (37% yield) of 14 as a
crystalline brown solid; dec 125-130 °C. TLC: 5:1 ethyl
acetate/methanol, molybdenum stain, Rf ) 0.47. IR (CDCl3):
1
Rf ) 0.28. IR (CDCl3): 3061, 1448, 1370, 1070 cm-1. H NMR
(500 MHz, C6D6, both diastereomers): δ 7.8-6.6 (m, 19H),
4.51-4.44 (q + q, 1H, both diastereomers), 2.16 (s, 3H, minor
diastereomer), 1.73 (s, 3H, major diastereomer), 1.62 (s, 3H,
major diastereomer), 1.57 (s, 3H, minor diastereomer), 1.54
(d, 3H, J ) 6.5 Hz, minor diastereomer), 1.12 (d, 3H, J ) 7.0
Hz, major diastereomer). 13C NMR (APT) (63 MHz, CDCl3,
both diastereomers): δ 148.7 (s), 147.6 (s), 144.0 (s), 143.6 (s),
143.2 (s), 129.9 (d), 129.7 (d), 128.2 (d), 128.1 (d), 128.0 (d),
127.9 (d), 127.73 (d), 127.65 (d), 127.5 (d), 127.4 (d), 127.0 (d),
126.9 (d), 126.82 (d), 126.76 (d), 126.5 (d), 126.3 (d), 123.5 (d),
123.3 (d), 121.6 (d), 81.7 (d), 80.4 (d), 72.5 (s), 72.2 (s), 29.1
(q), 28.3 (q), 22.7 (q), 22.5 (q), 21.1 (q), 20.1 (q). MS (FAB):
m/e 420 ([M+ + 1], 15), 315 ([nitroxide+ + 1], 100), 300
([nitroxide+ - CH2], 77), 104 ([styrene]+, 63). HRMS: mass
calcd for [M+ + 1] C30H30NO 420.2327, found 420.2328.
3072 (broad), 1567 (CdN), 1220 cm-1 1H NMR (250 MHz,
.
CDCl3): δ 7.61 (br s, 1H), 7.5-7.2 (m, 4H), 2.35 (s, 3H), 1.88
(s, 3H). 13C NMR (APT) (63 MHz, CDCl3): δ 141.6 (s), 141.3
(s), 133.3 (s), 129.6 (d), 129.1 (d), 122.1 (d), 119.8 (d), 77.1 (s),
24.5 (q), 9.5 (q). ESMS: m/e 178.10.
d ,l-1,3-Dim eth yl-1,3-d ip h en ylisoin d olin e 2-Nitr oxid e
(2a ).14 1-Hydroxy-1,3-dimethyl-1H-isoindole 1-oxide (14) (88
mg, 0.5 mmol) was suspended in 3 mL of toluene and heated
to 60 °C. To this was added phenylmagnesium bromide, as a
3.0 M solution in diethyl ether (1.00 mL, 3.0 mmol), dropwise
by cannula over 1 min. A small amount of white precipitate
formed, which quickly redissolved. The clear solution was
heated to reflux (bath temperature 120 °C) for 12 h. The
resulting dark-red mixture was cooled, and 10 mL of concen-
trated ammonium chloride solution, 5 mL of water, and 10
mL of diethyl ether were added to get all solids to dissolve.
The organic layer was separated, and the aqueous layer was
extracted with 5 mL of diethyl ether. The combined organic
layers were concentrated, and the residue was treated with a
mixture of 5 mL of methanol, 0.5 mL of concentrated NH4-
Ack n ow led gm en t. We thank the National Science
Foundation (CHE-9527647) for financial support, Pro-
fessor Glenn Millhauser for the ESR spectrum, Marc
Anderson for molecular mechanics calculations, and Dr.
Steven Bottle for constructive discussion. Electrospray

9864 J . Org. Chem., Vol. 63, No. 26, 1998
Braslau et al.
and 3b, details of the X-ray crystal structure data acquisition
and thermal ellipsoid plot of the structure (42 pages). This
material is contained in libraries on microfiche, immediately
follows this article in the microfilm version of the journal, and
can be ordered from the ACS; see any current masthead page
for ordering information.
mass spectra were taken on a MICROMASS Quattro II
Triplequadrupole instrument, the purchase of which
was made possible by a generous gift from the W.M.
Keck Foundation.
Su p p or t in g In for m a t ion Ava ila b le: 1H NMR and 13C
NMR spectra for all new compounds. For compounds 2a , 2b
J O981614D