Palladium(0)-catalyzed asymmetric cycloaddition of vinyloxiranes with heterocumulenes using chiral phosphine ligands: An effective route to highly enantioselective vinyloxazolidine derivatives

Article abstract of DOI:10.1021/ja964335l

Cycloaddition reaction of 2-vinyloxiranes with carbodiimides using Pd₂(dba)₃·CHCl₃, and TolBINAP as the chiral ligand, in THF at ambient temperature, afforded 4-vinyl-1,3-oxazolidin-2-imines in 70-99% yield and in up to 95

Full text of DOI:10.1021/ja964335l

J. Am. Chem. Soc. 1997, 119, 3709-3715
3709
Palladium(0)-Catalyzed Asymmetric Cycloaddition of
Vinyloxiranes with Heterocumulenes Using Chiral Phosphine
Ligands: An Effective Route to Highly Enantioselective
Vinyloxazolidine Derivatives
Chitchamai Larksarp and Howard Alper*
Contribution from the Department of Chemistry, UniVersity of Ottawa, 10 Marie Curie,
Ottawa, Ontario, Canada K1N 6N5
ReceiVed December 17, 1996X
Abstract: Cycloaddition reaction of 2-vinyloxiranes with carbodiimides using Pd2(dba)3‚CHCl3, and TolBINAP as
the chiral ligand, in THF at ambient temperature, afforded 4-vinyl-1,3-oxazolidin-2-imines in 70-99% yield and in
up to 95% ee. The stereoselectivity is strongly influenced by the structure of the chiral phosphine ligands and
substrates, as well as by the reaction conditions. The enantiodetermination step is assumed to be nucleophilic attack
of a nitrogen nucleophile on a π-allyl palladium intermediate. Reaction of 2-vinyloxiranes with isocyanates using
the same catalyst system afforded 4-vinyl-1,3-oxazolidin-2-ones in high yield but in no greater than 50% ee.
Introduction
One of us reported that the PdCl2(PhCN)2-catalyzed reaction
of the 1,2- or 1,2,3-trisubstituted aziridines with heterocumulenes
proceeds regio- and stereospecifically to give five-membered
heterocycles in high yield6 (eq 1). As a part of our study on
The cycloaddition reaction of oxiranes with heterocumulenes
is an efficient method to prepare five-membered ring hetero-
cycles.1 For instance, 1,3-cycloaddition reactions of isocyanates
with oxiranes have been extensively studied due to the potential
biological activities of 2-oxazolidine derivatives.2-3
Stoichiometric cycloaddition reaction of unsymmetrical epox-
ides with heterocumulenes usually occurs under relatively vig-
orous reaction conditions (reaction temperature of ca. 150 °C
or higher) and with low regioselectivity. Better yields and
regioselectivity can be achieved by introducing catalysts such
as quaternary ammonium salts,4a a lithium halide,4b,c organo-
stibonium,4d,e or organotin compounds,4f,g and transition metal
complexes such as Pd(0) complexes have been shown to be
very effective catalysts.4h
It is well-known that only one of a pair of enantiomers is
usually pharmacologically active while the other could either
be innocuous or damaging to human health. Therefore, the
development of enantioselective approaches to chiral molecules
of biological interest is currently receiving significant attention.5
the ring expansion reaction of three-membered-ring heterocycles
catalyzed by transition metal complexes, we have undertaken
an investigation of the possibility of stereoselective cycloaddition
of vinyloxiranes with heterocumulenes catalyzed by palladium-
(0) complexes modified with chiral ligands.
Methods for the stereoselective or chiral synthesis of 4-vinyl-
1,3-oxazolidin-2-ones have previously been reported. Hayashi
and co-workers7 described the asymmetric cyclization of 2-bu-
tenylenedicarbamate catalyzed by chiral ferrocenylphosphine-
palladium(0) complexes providing 4-vinyl-1,3-oxazolidin-2-ones
in up to 77% ee and in high yield (eq 2). Trost and Sudhakar8
reported the effective stereoselective conversion of vinyloxiranes
to cis-oxazolidin-2-ones catalyzed by Pd2(dba)3‚CHCl3 and
trialkyl phosphite (eq 3), and the stereochemical features were
rationalized on the basis of steric interactions between the R
group on the vinyloxirane and triisopropyl phosphite ligands.
In recent work, Trost and co-workers9 have investigated a series
of 2-(diphenylphosphino)benzoic acid and 2-(diphenylphosphi-
no)aniline based ligands and used them in reactions of urethanes
leading to the formation of oxazolidinones in good to high
enantiomeric excess (eq 4). To our knowledge, there are no
examples of the synthesis of 1,3-oxazolidin-2-imines in high
enantiomeric excess by the cycloaddition of oxiranes to carbo-
diimides.
X Abstract published in AdVance ACS Abstracts, April 1, 1997.
(1) Katritzky, A. R.; Rees, C. W. ComprehensiVe Heterocyclic Chemistry;
Pergamon Press: UK., 1984; Vol. 6, Part 4B.
(2) (a) Katritzky, A. R.; Rees, C. W. ComprehensiVe Heterocyclic
Chemistry; Pergamon Press: U.K., 1984; Vol. 1, Part 1. (b) Shibata, I.;
Toyota, M.; Baba, A.; Matsuda, H. J. Org. Chem. 1990, 55, 2487.
(3) (a) Dyen, M. E.; Swern, D. Chem. ReV. 1967, 67, 197. (b) Murthy,
K. S. K.; Dhar, D. N. J. Heterocyclic Chem. 1984, 21, 1721. (c) Karikomi,
M.; Yamazaki, T.; Toda, T. Chem. Lett. 1993, 1965.
(4) (a) Speranza, G. P.; Pepel,W. J. J. Org. Chem. 1958, 23, 1922. (b)
Herweh, J. E.; Foglia, T. A.; Swern, D. J. Org. Chem. 1968, 33, 4029. (c)
Herweh, J. E.; Kauffman, W. J. Tetrahedron Lett. 1971, 12, 809. (d) Baba,
A.; Fujiwara, M.; Matsuda, H. Tetrahedron Lett. 1986, 27, 77. (e) Fujiwara,
M.; Baba, A.; Matsuda, H. J. Heterocyclic Chem. 1988, 25, 1351. (f) Shibata,
I.; Seki, K.; Matsuda, H. J. Org. Chem. 1986, 2177. (g) Baba, A.; Seki, K.;
Matsuda, H. J. Heterocyclic Chem. 1990, 27, 1925. (h) Trost, B. M.;
Sudhakar, A. R. J. Am. Chem. Soc. 1987, 109, 3792.
(5) (a) Ojima, I. Catalytic Asymmetric Synthesis; VCH Publishers: New
York, 1993. (b) Noyori, R. Asymmetric Catalysis in Organic Synthesis;
John Wiley & Sons: New York, 1993. (c) Noyori, R. Acta Chem. Scand.
1996, 50, 380. (d) Kagan, H. B.; Girard, C; Giullaneux, D.; Rainford, D.;
Samuel, O.; Zhang, S. Y.; Zhao, S. H. Acta Chem. Scand. 1996, 50, 345.
(e) Lautens, M.; Klute, W; Tam, W Chem. ReV. 1996, 96, 49. (f) Berrisford,
D. J.; Bolm, C.; Sharpless, K. B. Angew. Chem., Int. Ed. Engl. 1995, 34,
1059. (g) Blystone, S. L. Chem. ReV. 1989, 89, 1663.
(6) (a) Baeg, J. O.; Bensimon, C.; Alper, H. J. Am. Chem. Soc. 1995,
117, 4700. (b) Baeg, J. O.; Alper, H. J. Org. Chem. 1992, 57, 157.
(7) Hayashi, T.; Yamamoto, A.; Ito, Y. Tetrahedron Lett. 1988, 29, 99.
(8) Trost, B. M.; Sudhakar, A. R. J. Am. Chem. Soc. 1988, 110, 7933.
(9) Trost, B. M.; Van Venkren, D. L. J. Am. Chem. Soc. 1993, 115,
444.
S0002-7863(96)04335-1 CCC: $14.00 © 1997 American Chemical Society

3710 J. Am. Chem. Soc., Vol. 119, No. 16, 1997
Larksarp and Alper
Table 1. Cycloadducts Obtained from the Reaction of
2-Vinyloxiranes (1) and Heterocumulenes 2 or 3 in the Presence of
a
Pd(PPh3)4 and PPh3
isolated yield
compds
R
X
Y
(%)b
4a
4b
4c
4d
5a
5b
5j
H
H
H
CH3
H
H
CH3
O
O
O
O
C6H5N
90
98
95
94
98
96
90
p-ClC6H4N
p-BrC6H4N
p-ClC6H4N
C6H5N
p-ClC6H4N
p-CH3C6H4N
C6H5N
p-ClC6H4N
p-CH3C6H4N
a Reaction conditions: 2-vinyloxirane (1.0 mmol), heterocumulene
(1.0 mmol), Pd(PPh3)4 (0.03 mmol), PPh3 (0.06 mmol), 3 mL of
THF, room temperature, 15 h, N2 atmosphere. b Purified by preparative
TLC.
Scheme 1
We now wish to report a highly enantioselective method for
the synthesis of oxazolidine derivatives in good to excellent
yield, by palladium(0)/2,2′-bis(di-p-tolylphosphino)-1,1′-bi-
naphthyl (TolBINAP)-catalyzed cycloaddition of heterocumu-
lenes with vinyloxiranes.
Results and Discussion
Cycloaddition Reaction of Vinyloxirane with Heterocu-
mulenes. To examine the feasibility of the cycloaddition
pathway for obtaining optically active oxazolidine derivatives
from the reaction of 2-vinyloxiranes with heterocumulenes, we
initially performed this reaction using an achiral-Pd(0) catalyst
such as Pd(PPh3)4. This reaction was successfully carried out
by treatment of the 2-vinyloxirane 1 (R ) H or CH3) with
heterocumulenes 2 or 3 in the presence of Pd(PPh3)4 and
triphenylphosphine in anhydrous THF at room temperature for
15 h. In this manner, the 4-vinyl-1,3-oxazolidin-2-one (4) (X
) O, Y ) NR′) or 4-vinyl-1,3-oxazolidin-2-imine (5) (X ) Y
) NR′′) was formed regioselectively and in 90-98% yield (eq
5 and Table 1). This reaction required 3 mol % of Pd(PPh3)4
nitrogen nucleophile at the C-3 carbon of 6 would generate the
five-membered heterocyclic product (Scheme 1).
A high degree of asymmetric induction could be achieved in
the cycloaddition of vinyloxiranes and heterocumulenes, espe-
cially carbodiimides. Success depends on the choice of the
appropriate combination of metal and chiral ligands as well as
the reaction conditions.5,12 When the cycloaddition of 1 mmol
each of 1a (R ) H) and 3b (X ) Y ) p-ClC6H4N) was
performed in THF at room temperature in the presence of
Pd2(dba)3‚CHCl3 (0.03 mmol) and (S)-TolBINAP13 (0.06 mmol)
for 15 h under an inert atmosphere, N-(p-chlorophenyl)-3-(p-
chlorophenyl)-4-vinyl-1,3-oxazolidin-2-imine (5b) was isolated
in 95% yield and in 94 %ee as determined by chiral HPLC
(Chiracel OD) (eq 6). Other commercially available chiral
ligands such as (-)DIOP14 (94% yield, 20% ee), (-)-MeDU-
PHOS15 (87% yield, 45% ee), (R,R)-NORPHOS,16 (95% yield,
6% ee), and (R)-PROPHOS17 (96% yield, 3% ee) were less
effective in terms of asymmetric induction, whereas (R)-
and 2 equiv of added triphenylphosphine ligand relative to Pd.
Reduced amounts of Pd(PPh3)4 or no additional PPh3, resulted
in lower product yields.10 p-Nitrophenyl isocyanate and bis-
(p-nitrophenyl)carbodiimide failed to give the desired products
presumably because of their poor electrophilicity.
The cycloaddition reaction may proceed via zwitterionic (π-
allyl) palladium intermediates generated by oxidative addition
of vinyloxirane 1 to a palladium(0) species11 followed by reac-
tion with the heterocumulene. Intramolecular attack of the
(11) (a) Hayashi, T.; Yamamoto, A.; Hagihara, T.; Ito, Y. Tetrahedron
Lett. 1986, 27, 191. (b) Hayashi, T.; Yamamoto, A.; Ito, Y. Chem. Lett.
1987, 177. (c) Hayashi, T.; Konishi, M.; Kumada, M. Chem. Soc., Chem.
Commun. 1984, 107. (d) Fiaud, J-C.; Legros, J.-Y. J. Org. Chem. 1990,
55, 4840. (e) Tsuji, J. Pure Appl. Chem. 1982, 54, 197.
(12) (a) Trost, B. M.; Van Vrenken, D. L. Chem. ReV. 1996, 96, 395.
(b) Trost, B. M.; Bunt, R. Angew. Chem., Int. Ed. Engl. 1996, 35, 99. (c)
Trost, B. M.; Van Vrenken. D. L.; Bingel, C. J. Am. Chem. Soc. 1992,
114, 9327.
(10) Reaction with 1 or 2 mol % Pd(PPh3)4 provided no cycloaddition
reaction and 25% isolated products, respectively. The reaction performed
using 3 mol % Pd(PPh3)4 but without addition of PPh3 afforded 3b in 90%
yield.
(13) (S)-TolBINAP ) (S)-2,2′-bis(di-p-tolylphosphino)-1,1′-binaph-
thyl. See: Takaya, H.; Mashima, K.; Koyano, K.; Yagi, M.; Kumobayashi,
H.; Taketomi, T.; Akutagawa, S.; Noyori, R. J. Org. Chem. 1986, 51,
629.

Cycloaddition of Vinyloxiranes with Heterocumulenes
J. Am. Chem. Soc., Vol. 119, No. 16, 1997 3711
Table 2. Pd-Catalyzed Asymmetric Cycloaddition of
2-Vinyloxirane (1a) and Bis(p-chlorophenyl)carbodiimide (3b)
Using Various Chiral Phosphine Ligands
(Table 3, entries 6 and 7) on the phenyl ring of carbodiimides
proved to be ineffective. The increased steric hindrance resulted
in lower enantioselectivity. A naphthyl substituent on the
nitrogen nucleophile also failed to improve the optical yield of
the product (entry 8). Nevertheless, it must be noted that the
% ee is still high (84-89%). 2-Methyl-2-vinyloxirane (1, R )
CH3) (entries 9-12) reacted at a lower rate and provided
products in somewhat lower % ee (69-91%) compared to that
obtained from 2-vinyloxirane (1, R ) H).
% isolated
ligand
yield of 5ba
% eeb
[R]22D in CHCl3
(S)-TolBINAP
(-)DIOP
(-)Me-DUPHOS
(R,R)-NORPHOS
(R)-PROPHOS
(R)-BINAP
95
94
87
95
96
93
94
20
45
6
3
94
+38.7 (c 5.04)
-7.1 (c 5.14)
-18.2 (c 5.03)
-2.0 (c 5.04)
-0.5 (c 5.04)
-38.7 (c 5.07)
The generally high degree of asymmetric induction found in
the cycloaddition reaction can be explained by the pathway
outlined in Scheme 2. Oxidative addition of a chiral phos-
phine-palladium complex to racemic vinyl oxirane 1 followed
by heterocumulene interception affords the diastereomeric
π-allyl palladium complexes 7 and 8. Intramolecular attack of
the nitrogen nucleophile (X ) Y ) NAr) at the C-3 carbon of
7 and 8 can give the corresponding (S)- and (R)-oxazolidine
derivatives, respectively. The enantiodetermination step in this
asymmetric cycloaddition may involve nucleophilic addition.
The asymmetric cyclization reactions of 2-butenylenedicarbam-
ate in the presence of Pd(0) and chiral phosphine ligands7 are
believed to proceed via similar intermediates, indicating that
the interconversion between π-allyl palladium complexes 7 and
8 occurs via a η3-η1-η3 mechanism19 and is much faster than
attack of the nitrogen nucleophile. Thus, one of the two
intermediate complexes (7 and 8) reacts faster than the other
and consequently gives the major enantiomer. In the case of
using (S)-TolBINAP as the chiral ligand, the intermediate 8
reacts at a greater rate affording the (R)-enantiomer as the major
stereoisomer.
4-Vinyl-1,3-oxazolidin-2-ones 4b,c (Table 3, entries 13 and
14) were obtained from reaction of 1 with isocyanates by
employing a procedure identical to that used for carbodi-
imides. The % ee of these products is appreciately lower than
those derived from carbodiimides, suggesting that TolBINAP
has less influence in the steric interaction in the enantiodeter-
minating step. The results from Table 3 indicates that cycload-
dition reactions of vinyloxiranes and carbodiimides are in-
fluenced not only by the ligands but also by the structure of
the reaction partners. In reactions with 2-vinyloxiranes, car-
bodiimides provide greater steric interaction between the
substituent on the nitrogen nucleophile of 7/8 and the substituent
on the chiral phosphine ligands in comparison with reactions
using isocyanates. Consequently, higher enantiomeric excesses
were realized in using carbodiimides than isocyanates (see
Figure 3).
a Purified by preparative TLC. b Determined by HPLC (Chiracel OD,
15% i-PrOH in hexane).
BINAP18 (93% yield, 94% ee) gave essentially the same yield
and % ee as that obtained by using (S)-TolBINAP but, as
anticipated, for the other enantiomer (Table 2).
The chromatographic separation of racemic 5b, on a chiral
stationary phase using 15% 2-propanol in n-hexane as the mobile
phase produced a chromatogram with two peaks for the two
enantiomers in a 1:1 ratio (Figure 1a). The chromatogram of
5b, obtained by cyclization utilizing Pd/(S)-TolBINAP, showed
a signal due to the predominant enantiomer with retention time
corresponding to that of the first eluted enantiomer (Figure 1b).
N-(p-Chlorophenyl)-3-(p-chlorophenyl)-4-vinyl-1,3-oxazolidin-
2-imine (5b) can be readily obtained in purified form, as
crystalline white needles, by preparative silica gel TLC followed
by preparative HPLC. A single-crystal X-ray diffraction
analysis of 5b revealed it to possess the (R)-configuration (see
Figure 2 for the ORTEP diagram).
A series of other 4-vinyl-1,3-oxazolidines (eq 7) were simi-
larly synthesized, usually in high optical purity, using the
Effect of Temperature on the Enantioselectivity of the
Cycloaddition Reaction. It is known that the reaction tem-
perature can have a pronounced effect on the enantioselectivity
of a reaction.4,20-23 To examine the dependence of the % ee
on temperature, 2-vinyloxirane (1a, R ) H) was reacted with
Pd(0)-TolBINAP catalyst system which was generated in situ
by reaction of 3 mol % of Pd2(dba)3‚CHCl3 with 2 equiv of
bidentate ligand relative to palladium. The reaction mixtures
were stirred under nitrogen at room temperature until the
conversion of the heterocumulenes was complete (monitored
by IR). The results are shown in Table 3.
(19) (a) Godleski, S. A. ComprehensiVe Organic Synthesis; Trost, B.
M., Fleming, I., Semmelhack, M. F., Eds.; Pergamon Press: Oxford, U.K.,
1991; Vol. 4, Chapter 3.3, pp 585-662. (b) Trost, B. M.; Hung, M-H. J.
Am. Chem. Soc. 1984, 106, 6837. (c) Trost, B. M.; Bunt, R. C. Angew.
Chem., Int. Ed. Engl. 1996, 35, 99. (d) Dawson, G. J.; Williams, J. M. J.;
Coote, S. J. Tetrahedron Lett. 1995, 36, 461. (e) Auburn, P. R.; Mackenzie,
P. B.; Bosnich, B. J. Am. Chem. Soc. 1985, 107, 2033. (f) Trost, B. M.
Krische, M. J.; Radinov, R.; Zanoni, G. J. Am. Chem. Soc. 1996, 118, 6297.
(g) Trost, B. M.; Murphy, D. J. Organometallics 1985, 4, 1143.
(20) (a) Trost, B. M.; Van Vrenken, D. L. Angew. Chem., Int. Ed. Engl.
1992, 31 328. (b) Trost, B. M.; Organ, M. G. J. Am. Chem. Soc. 1994,
116, 10320. (c) Trost, B. M.; Lee, C. B.; Weiss, J. M. J. Am. Chem. Soc.
1995, 117, 7247. (d) Trost, B. M.; Organ, M. G.; O’Doherty, G. A. J. Am.
Chem. Soc. 1995, 117, 9662.
Attempts to improve the enantioselectivity of this reaction
by introducing an ortho substituent such as a methyl group
(14) (-)DIOP ) (R,R)-2, 3-O-isopropylidene-2,3-dihydroxy-1,4-bis-
(diphenylphosphino)butane. See: Kagan, H. B.; Dang, T.-P. J. Am. Chem.
Soc. 1972, 94, 6429.
(15) (-)MeDUPHOS ) (-)-1,2-bis((2R,5R)-2,5-dimethylphospholano)-
benzene. See: Burk, M. J. J. Am. Chem. Soc. 1991, 113, 8518.
(16) (R,R)-NORPHOS ) (R,R)-5,6-bis(diphenylphosphino)-2-norbornene.
See: Brunner, H.; Pieronczyk, W.; Schˆınhammer, B.; Streng, K.; Bernal,
I.; Korp, J. Chem Ber. 1981, 114, 1137.
(17) (R)-PROPHOS ) (R)-1,2-bis(diphenylphosphino)propane. See:
Fryzuk, M. D.; Bosnich, B. J. Am. Chem. Soc. 1978, 100, 5491.
(18) (R)-BINAP ) (R)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl.
See: Miyashita, A.; Yasuda, A.; Takay, H.; Toriumi, K.; Ito, T.; Souchi,
Y.; Noyori, R. J. Am. Chem. Soc. 1980, 102, 7932.
(21) Buschmann, H.; Scharf, H-D.; Hoffman, N.; Plath, M. W.; Runsink,
J. J. Am. Chem. Soc. 1989, 111, 5367.
(22) Zhu, G.; Terry, M.; Zhang, X. Tetrahedron Lett. 1996, 37,
4475.

3712 J. Am. Chem. Soc., Vol. 119, No. 16, 1997
Larksarp and Alper
Figure 1. Chromatograms showing the resolution of (a) racemic 5b and (b) 94% ee 5b on chiral HPLC (Chiracel OD, 15% i-PrOH in hexane).
Scheme 2
4 summarizes the effect of temperature on the extent of
Figure 2. X-ray structure of (R)-5b obtained from the cycloaddition
asymmetric induction in the cycloaddition reaction.
The cycloaddition of 2-vinyloxirane (1a) with diphenylcar-
bodiimide (3a) or bis(p-chlorophenyl)carbodiimide (3b) showed
reaction of 1a and 3b in the presence of Pd2(dba)3‚CHCl3/(S)-
TolBINAP.
Table 3. Asymmetric Cycloaddition of 2-Vinyloxiranes 1 with
Heterocumulenes 2 or 3 in the Presence of
much the same temperature effects. Performing the reaction at
10 °C resulted in % ee’s essentially identical to those obtained
by reaction at room temperature. However, a slightly lower
selectivity was observed when the reaction was carried out at 5
°C (90% ee). When these cycloaddition reactions were carried
out at 80 or 100 °C a slightly lower degree of asymmetric
induction was observed (90-91% ee). The same pattern was
observed in the case of cycloaddition of p-bromophenyl
isocyanate (2c) with 2-vinyloxirane (1a) (e.g., 49% ee at room
temperature and 41% ee at 80 °C).
Clearly, the reaction temperature does not significantly affect
the enantioselectivity of the reaction. High stereoselectivity is
still maintained at a lower reaction temperature (5-22 °C),
which is in contrast to the results previously reported for the
preparation of vinyloxazolidin-2-one.7 In addition, by perform-
ing the cycloaddition reactions at 10 °C for 24 h, N-p-tolyl-3-
p-tolyl-4-vinyl-1,3-oxazolidin-2-imine (5c) (97% yield, 95% ee)
and N-(p-bromophenyl)-3-(p-bromophenyl)-4-vinyl-1,3-oxazo-
lidin-2-imine (5d) (84% yield, 95% ee) were obtained from the
cycloaddition reactions of 1a with 3c and 3d, respectively.
Therefore, the optimum temperature for achieving the asym-
metric cycloaddition of 2-vinyloxirane with heterocumulenes
in the presence of Pd(0) and chiral phosphine ligands is in the
range between 10 and 22 °C, although excellent results are also
obtained at higher temperatures.
Pd2(dba)3‚CHCl3-TolBINAP as the Catalysta
yield
ee
entry
1
2
ligandb products (%)c (%)d [R]22D in CHCl3
1
2
3
4
5
6
7
8
9
10
11
12
13
14
1a 3a
1a 3b
1a 3c
1a 3d
1a 3e
1a 3f
1a 3f
1a 3g
1b 3a
1b 3b
1b 3c
1b 3e
1a 2b
1a 2c
A
A
A
A
A
A
B
B
B
A
A
A
B
A
5a
5be
5c
5d
5e
5f
98
95
98
84
88
98
98
60
87
98
63
98
94
99
93 +26.2 (c 5.04)
94 +38.7 (c 5.04)
93 +38.5 (c 5.11)
94 +34.5 (c 1.99)
88 +31.7 (c 2.99)
84 +32.8 (c 5.03)
88 -33.5 (c 5.26)
89 -31.4 (c 4.08)
91 -22.1 (c 2.80)
69 +10.4 (c 5.17)
84 +18.1 (c 2.26)
75 +11.6 (c 2.06)
5f
5g
5hf
5i
5jg
5k
4b
4c
43
49
-1.72 (c 4.66)
+1.43 (c 3.49)
a Reaction conditions: 1 (1 mmol); 2 or 3 (1 mmol); Pd2(dba)3‚CHCl3
(0.03 mmol); ligand (0.06 mmol); THF (5 mL); room temperature, 15
h (unless otherwise noted), N2 atmosphere. b A, (S)-TolBINAP; B, (R)-
TolBINAP. c Yield of isolated product after silica gel TLC. d Deter-
mined by HPLC analysis using Chiracel OD, 15% i-PrOH in n-hexane.
e Absolute configuration of major enantiomer is (R)-5b (see Figure 2a).
g
f Reaction time was 17 h. Reaction time was 3 days.
diphenylcarbodiimide (3a) or bis(p-chlorophenyl)carbodiimide
(3b), affording the cycloadducts 5a and 5b, respectively. Table
Conclusion
(23) (a) Ojima, I.; Kogure, T.; Yoda, N. J. Org. Chem. 1980, 45,
4728. (b) Geneˆt, J.-P.; Can˜o de Andrade, M. C.; Retovelomanana-Vidal,
V. Tetrahedron Lett. 1995, 36, 2063. (c) Sinou, D. Tetrahedron Lett. 1981,
2987.
Palladium(0) with TolBINAP as an added chiral ligand is a
useful and effective catalytic system for the enantioselective
synthesis of 4-vinyl-1,3-oxazolidin-2-imines in high enantio-

Cycloaddition of Vinyloxiranes with Heterocumulenes
J. Am. Chem. Soc., Vol. 119, No. 16, 1997 3713
Figure 3. (a) Steric repulsion between the substituent on the nucleophilic nitrogen atom of the diphenylcarbodiimide unit and the p-tolyl portion
of the chiral phosphine ligand. (b) This repulsion has a strong influence on the stereoselectivity compared to that of phenyl isocyanate with the
same chiral phosphine ligands.
Table 4. Effect of Temperature on the Pd-Catalyzed Asymmetric Cycloaddition Reaction of 2-Vinyloxirane (1a) with Diphenylcarbodiimide
(3a) or Bis(p-chlorophenyl)carbodiimide (3b) Affording 5a and 5b, Respectivelya
5a
eec (%)
5b
eec (%)
reaction
temp (°C)
reaction
time (h)
yieldb (%)
[R]22D in CHCl3
yieldb (%)
[R]22D in CHCl3
100
80
1
2
15
24
36
93
95
98
96
98
90
90
93
94
91
+24.8 (c 5.05)
+24.9 (c 5.01)
+26.2 (c 5.04)
+26.8 (c 5.03)
+25.6 (c 5.04)
90
92
95
85
96
90
91
94
94
92
+35.0 (c 5.04)
+35.2 (c 5.10)
+38.7 (c 5.04)
+38.8 (c 5.00)
+ 36.0 (c 5.03)
rtd
10e
5e
a Refer to the Experimental Section for general procedure. b Isolated yield by preparative TLC. c Enantiomeric excess determined by HPLC
using Chiracel OD column. d Approximately 22 °C. e The reaction was performed in a Schlenk tube (N2 atmosphere) inside a cold room.
mmol was used occasionally with the same results)] and 1 mmol of
heterocumulene 2 or 3 were added, and the mixture was stirred under
nitrogen for 15 h at room temperature. The light yellow homogeneous
solution was then concentrated by rotary evaporation, and the resi-
due was purified by silica gel TLC using 1:1 pentane/ether as the
developer. Melting points, IR, NMR, MS, and analytical data for 4
and 5 are as follows (except 4a and 5a, which have previously been
reported).
N-Phenyl-4-vinyl-1,3-oxazolidin-2-one (4a)4e (R ) H, X ) O, Y
) C6H5N): oily liquid; IR (CdO) 1753 cm-1; 1H NMR (CDCl3) 4.15
(dd, 1H, J ) 6.0 and 8.6 Hz), 4.60 (dd, 1H, J ) 8.6 and 8.6 Hz), 4.83
(m, 1H), 5.35 (m, 2H), 5.80 (m, 1H), 7.10-7.50 (m, 5H); 13C NMR
(CDCl3) 59.73, 67.66, 120.84, 121.86, 125.32, 129.43, 135.25, 137.69,
156.22; MS (m/e) 189 [M]+.
meric excess. Furthermore, the stereochemical course of the
cycloaddition with chiral phosphine ligand-Pd(0) complexes
was noticeably influenced by the structure of the heterocumulene
substrates. Up to 95% ee was realized in the asymmetric
syntheses of N-p-tolyl-3-p-tolyl-4-vinyl-1,3-oxazolidin-2-imine
(5c) and N-(p-bromophenyl)-3-(p-bromophenyl)-4-vinyl-1,3-
oxazolidin-2-imine (5d) in excellent yields by a proper choice
of substrates and reaction temperature.
Experimental Section
General Methods. All NMR spectra were recorded in CDCl3 with
TMS as an internal standard on Bruker AMX 500, Varian XL-300,
and Gemini 200 spectrometers. Infrared spectra were recorded on a
Bomem MB 100-C15 Fourier transform spectrometer and are reported
in wavenumbers (cm-1). Mass spectra were obtained on a VG 7070E
spectrometer. A Fisher-Johns apparatus was used for melting point
determinations. Optical rotations were measured on a Perkin-Elmer
polarimeter in a 10 cm cell at 22 °C.
Enantiomeric resolutions were achieved using a Hewlett Packard
HPLC Series II 1090 instrument equipped with an automatic injector
and diode array detector monitoring at 220 nm. A Chiracel OD column
was used with 85:15 n-hexane:2-propanol as the mobile phase at a flow
rate of 1 mL/min (oven temperature 30 °C).
N-(p-Chlorophenyl)-4-vinyl-1,3-oxazolidin-2-one (4b) (R ) H, X
1
) O, Y ) p-ClC6H4N): mp ) 45-46 °C; IR (CdO) 1754 cm-1; H
NMR (CDCl3) 3.98 (dd, 1H, J ) 6.2 and 8.6 Hz), 4.47 (dd, 1H, J )
8.6 and 8.6 Hz), 4.77 (m, 1H), 5.25 (m, 2H), 5.72 (m, 1H), 7.15-7.40
(m, 4H); 13C NMR (CDCl3) 59.78, 67.70, 121.30, 122.0, 129.67, 129.43,
130.40, 134.87, 136.29, 155.98; MS (m/e) 223 [M]+, 225 [M + 2]+.
Anal. Calcd for C11H10ClNO2: C, 59.07; H, 4.51; N, 6.26. Found: C,
58.93; H, 4.18; N, 6.55.
N-(p-Bromophenyl)-4-vinyl-1,3-oxazolidin-2-one (4c) (R ) H, X
1
) O, Y ) p-BrC6H4N): mp ) 68-69 °C; IR (CdO) 1753 cm-1; H
Vinyloxiranes and isocyanates were purchased from Aldrich and
were used as received. Carbodiimides24 and palladium catalysts25 were
either purchased or prepared according to literature procedures. The
organic solvents were dried and distilled prior to use.
General Procedure for the Palladium-Catalyzed Cycloaddition
Reaction of Vinyloxiranes and Heterocumulenes. A mixture of Pd-
(PPh3 )4 (0.03 mmol), PPh3 (0.06 mmol), and THF (3 mL) was stirred
at room temperature for 30 min. Vinyloxirane 1 [1 mmol (up to 1.5
NMR (CDCl3) 3.99 (dd, 1H, J ) 6.0 and 8.6 Hz), 4.49 (dd, 1H, J )
8.6 and 8.6 Hz), 4.78 (m, 1H), 5.26 (m, 2H), 5.68 (m, 1H), 7.20-7.40
(m, 4H); 13C NMR (CDCl3) 59.74, 67.71, 118.24, 121.38, 123.26,
132.41, 4.20 (dd, 2H, J ) 8.5 and 8.5 Hz), 4.23 (d, 1H, J ) 8.5 Hz),
5.29 (m, 2H), 6.05 (m, 1H), 134.85, 136.79, 155.92; MS (m/e) 267
[M]+, 269 [M + 2]+. Anal. Calcd for C11H10BrNO2: C, 49.28; H,
3.76; N, 5.22. Found: C, 49.25; H, 3.57; N, 5.31.
N-(p-Chlorophenyl)-4-methyl-4-vinyl-1,3-oxazolidin-2-one (4d):
(R ) CH3, X ) Y ) p-ClC6H4N): mp ) 75-76 °C; IR (CdO) 1752
cm-1; 1H NMR (CDCl3) 1.42 (s, 3H), 7.20-7.40 (m, 4H); 7.20-7.40
(m, 4H); 13C NMR (CDCl3) 21.73, 64.18, 74.84, 118.11, 128.57, 129.67,
133.06, 134.66, 139.75, 156.92; MS (m/e) 237 [M]+, 239 [M + 2]+.
(24) Campbell, T. W.; Monagle, J. J.; Foldi, V. J. Am. Chem. Soc. 1962,
84, 3673.
(25) Ukai, T.; Kawazura, H.; Ishii, Y. J. Organomet. Chem. 1974, 65,
253.

3714 J. Am. Chem. Soc., Vol. 119, No. 16, 1997
Larksarp and Alper
Anal. Calcd for C12H12ClNO2: C, 60.64; H, 5.09; N, 5.89. Found:
C, 60.32; H, 4.88; N, 6.01.
MS (m/e) 324 [M]+. Anal. Calcd for C19H20N2O3: C, 70.35; H, 6.21;
N, 8.64. Found: C, 70.67; H, 5.99; N, 8.64.
N-Phenyl-3-phenyl-4-vinyl-1,3-oxazolidin-2-imine (5a)4e (R ) H,
N-o-Tolyl-3-o-tolyl-4-vinyl-1,3-oxazolidin-2-imine (5f) (R ) H, X
) o-CH3C6H5N, Y ) o-CH3C6H5N): mp ) 68-69 °C; IR (CdN)
1688 cm-1; 1H NMR (CDCl3) 2.09 (s, 3H), 2.36 (s, 3H), 4.06 (m, 1H),
4.54 (m, 2H), 5.13 (m, 2H), 5.69 (m, 1H), 6.77-7.27 (m, 8H); 13C
NMR (CDCl3) 18.34, 63.16, 69.65, 121.06, 122.29, 122.71, 125.76,
126.66, 127.65, 129.81, 130.54, 131.16, 134.38, 136.49, 137.08, 146.66,
150.34; MS (m/e) 292 [M]+. Anal. Calcd for C20H22N2O: C, 78.40;
H, 7.24; N, 9.14. Found: C, 78.19; H, 6.84; N, 9.54.
X ) C6H4N, Y ) C6H4N): mp ) 58-59 °C; IR (CdN) 1678 cm-1
;
1H NMR (CDCl3) 4.06 (dd, 1H, J ) 5.9 and 8.2 Hz), 4.45 (dd, 1H, J
) 8.3 and 8.3 Hz), 4.72 (m, 1H), 5.40 (m, 2H), 5.85 (m, 1H), 7.10-
7.75 (m, 10H); 13C NMR (CDCl3) 61.07, 70.02, 120.60, 122.60, 123.22,
124.23, 124.63, 129.36, 129.44, 135.69, 139.39, 148.28, 150.65; MS
(m/e) 264 [M]+.
N-(p-Chlorophenyl)-3-(p-chlorophenyl)-4-vinyl-1,3-oxazolidin-2-
imine (5b) (R ) H, X ) p-ClC6H4N, Y ) p-ClC6H4N): mp ) 95-96
N-r-Naphthyl-3-r-naphthyl-4-vinyl-1,3-oxazolidin-2-imine (5g)
(R ) H, X ) 1-naphthyl, Y ) 1-naphthyl): mp ) 172-173 °C; IR
(CdN) 1676 cm-1; 1H NMR (CDCl3) 4.20 (t, 1H), 4.69 (m, 2H), 5.03
(m, 2H), 5.78 (m, 1H), 7.00-8.60 (m, 14H); 13C NMR (CDCl3) 63.84,
70.08, 121.24, 122.21, 123.25, 123.30, 124.39, 124.56,125.40, 125.63,
126.26, 126.48, 127.51, 128.41, 128.64, 129.33, 134.15, 134.27, 134.78,
144.0, 152.06; MS (m/e) 364 [M]+, 365 [M + 1]+. Anal. Calcd for
C25H20N2O: C, 82.39; H, 5.53; N, 7.69. Found: C, 82.03; H, 5.25; N,
7.80.
1
°C; IR (CdN) 1677 cm-1; H NMR (CDCl3) 4.07 (dd, 1H, J ) 6.0
and 8.3 Hz), 4.45 (dd, 1H, J ) 8.3 and 8.3 Hz), 4.75 (m, 1H), 5.35 (m,
2H), 5.81 (m, 1H), 7.00-7.75 (m, 8H); 13C NMR (CDCl3) 61.17, 70.05,
121.22, 123.92, 125.40, 128.19, 129.15, 129.36, 129.92, 134.98, 137.49,
146.28, 150.62; MS (m/e) 332 [M]+, 336 [M + 2]+. Anal. Calcd for
C17H14Cl2N2O: C, 61.28; H, 4.23; N, 8.41. Found: C, 61.43; H, 4.05;
N, 8.38.
N-p-Tolyl-3-p-tolyl-4-methyl-4-vinyl-1,3-oxazolidin-2-imine (5j)
(R ) CH3, X ) p-CH3C6H5N, Y ) p-CH3C6H5N): mp ) 136-137
N-p-Phenyl-3-p-phenyl-4-methyl-4-vinyl-1,3-oxazolidin-2-imine
(5h) (R ) CH3, X ) C6H5N, Y ) C6H5N): mp ) 82-83 °C; IR (CdN)
1
°C; IR (CdN) 1672 cm-1; H NMR (CDCl3) 1.37 (s, 3H), 2.20 (s,
1
1677 cm-1; H NMR (CDCl3) 1.38 (s, 3H), 4.10 (dd 2H, J ) 8.2 and
3H), 2.27 (s, 3H), 4.12 (dd, 2H, J ) 8.2 and 25.1 Hz), 5.17 (m, 2H),
6.00 (m, 1H), 6.80-7.30 (m, 8H); 13C NMR (CDCl3) 20.67, 20.81,
21.05, 64.05, 76.21, 116.86, 123.23, 127.91, 128.94, 129.46, 131.53,
133.77, 136.47, 139.69, 144.59, 152.09; MS (m/e) 306 [M]+. Anal.
Calcd for C20H22N2O: C, 78.40; H, 7.24; N, 9.14. Found: C, 78.13;
H, 7.26; N, 9.12.
25.4 Hz), 5.19 (m, 2H), 6.00 (m, 1H), 6.80-7.40 (m, 10H); 13C NMR
(CDCl3) 20.72, 64.07, 76.24, 116.86, 122.23, 123.43, 126.03, 127.48,
128.37, 128.72, 136.84, 139.64, 147.52, 151.57; MS (m/e) 278 [M]+.
Anal. Calcd for C18H18N2O: C, 77.67; H, 6.52; N, 10.07. Found: C,
77.60; H, 6.25; N, 10.01.
N-(p-Chlorophenyl)-3-(p-chlorophenyl)-4-methyl-4-vinyl-1,3-ox-
azolidin-2-imine (5i) (R ) CH3, X ) p-ClC6H5N, Y ) p-ClC6H5N):
General Procedure for the Asymmetric Palladium-Catalyzed
Cycloaddition Reaction of Vinyloxiranes with Heterocumulenes. A
mixture of Pd2(dba)3‚CHCl3 (0.03 mmol), chiral phosphine ligand (0.06
mmol), and THF was stirred at room temperature for 30 min. Oxirane
(1.0 mmol) and heterocumulene (1.0 mmol) were added, and the mixture
was then stirred under nitrogen atmosphere at either room temperature
or at 10 °C, until the conversion of the heterocumulenes was completed
(as monitored by the shift of the IR-absorption band of the carbodiimide
CdN group at approximately 2100 cm-1 was shifted to the region of
1670 cm-1; the absorption band of the isocyanate unit at about 2200
cm-1 was replaced by one in the region of 1750 cm-1). After the
reaction was complete, the orange brown solution was subjected to
rotary evaporation and the residue was purified by preparative silica
gel TLC. The purified product was rechromatographed on preparative
HPLC to eliminate the rest of the chiral phosphine ligand. The
enantiomeric excess was determined by measuring the area chromato-
gram peaks (obtained from programming an analytical HPLC integra-
tor). Melting points, IR, NMR, MS, and analytical data for 4 and 5
are as follows:
1
mp ) 97-98 °C; IR (CdN) 1675 cm-1; H NMR (CDCl3) 1.39 (s,
3H), 4.14 (dd, 2H, J ) 8.2 and 24.6 Hz), 5.22 (m, 2H), 5.98 (m, 1H),
6.90-7.27 (m, 8H), 13C NMR (CDCl3) 20.50, 64.17, 76.40, 117.5,
124.77, 127.44, 128.39, 128.78, 128.99, 132.02, 135.06, 139.04,
145.70, 151.70; MS (m/e) 346 [M]+, 348 [M + 2]+. Anal. Calcd for
C18H16N2OCl2: C, 62.26; H, 4.64; N, 8.07. Found: C, 62.18; H, 4.40;
N, 7.86.
N-(p-Methoxyphenyl)-3-(p-methoxyphenyl)-4-methyl-4-vinyl-1,3-
oxazolidin-2-imine (5k) (R ) CH3, X ) p-CH3OC6H5N, Y )
1
p-CH3OC6H5N): mp ) 60-61 °C; IR (CdN) 1677 cm-1; H NMR
(CDCl3) 1.34 (s, 3H), 3.68 (s, 3H), 3.72 (s, 3H), 4.12 (dd, 2H, J ) 8.2
and 26 Hz), 5.15 (m, 2H), 5.99 (m, 1H), 6.69-7.23 (m, 8H); 13C NMR
(CDCl3) 20.62, 55.33, 63.85, 75.96, 113.61, 114.07, 116.79, 124.16,
129.23, 129.85, 139.56, 140.77, 152.12, 154.82, 158.21; MS (m/e) 338
[M]+. Anal. Calcd for C20H22N2O3: C, 70.98; H, 6.55; N, 8.28.
Found: C, 70.75; H, 6.35; N, 7.99.
General Procedure for the Determination of the Effect of
Temperature on the Cycloaddition Reaction. A mixture of Pd2-
(dba)3‚CHCl3 (0.03 mmol), (S)-TolBINAP (0.06 mmol), and 3 mL of
THF was stirred at room temperature for 30 min. 2-Vinyloxirane (1a,
1 mmol) and carbodiimide 3a or 3b (1 mmol) were added, the mixture
was then stirred under nitrogen at a given temperature (see Table 5 for
the reaction time and temperature in each case). The reaction was then
concentrated by rotary evaporation, and the crude product was purified
by silica gel TLC using 1:1 n-pentane/ether as the developer. The
results are summarized in Table 4.
N-p-Tolyl-3-p-tolyl-4-vinyl-1,3-oxazolidin-2-imine (5c) (R ) H,
X ) p-CH3C6H5N, Y ) p-CH3C6H5N): mp ) 102-103 °C; IR (CdN)
1679 cm-1; 1H NMR (CDCl3) 2.21 (s, 3H), 2.24 (s, 3H), 3.99 (dd, 1H,
J ) 6.4 and 8.3 Hz), 4.44 (dd, 1H, J ) 8.3 and 8.3 Hz), 4.68 (m, 1H),
5.26 (m, 2H), 5.74 (m, 1H), 6.85-7.42 (m, 8H); 13C NMR (CDCl3)
21.52, 61.57, 69.89, 120.65, 123.08, 123.73, 129.73, 129.93, 132.19,
134.41, 135.79, 136.62, 145.50, 150.81; MS (m/e) 292 [M]+. Anal.
Calcd for C19H20N2O: C, 78.05; H, 6.89; N, 9.58. Found: C, 77.86;
H, 6.84; N, 9.54.
N-(p-Bromophenyl)-3-(p-bromophenyl)-4-vinyl-1,3-oxazolidin-2-
imine (5d) (R ) H, X ) p-BrC6H5N, Y ) p-BrCH3C6H5N): mp )
Single-Crystal X-ray Diffraction Study Of 5b. Crystals of 5b were
obtained by purification using preparative TLC, preparative HPLC, and
recrystallization from methanol. One of the crystals having proximate
dimension of 0.2, 0.2, and 0.2 mm was mounted on a glass capillary.
All the measurements were made on a Siemens CCD diffractometer
with Mo KR radiation. Cell constants and an orientation matrix for
data collection were obtained from least-squares refinement using the
setting angles of 5734 reflections in the range 3° < 2θ < 57° and
corresponded to a monoclinic cell with dimensions a ) 9.7465(4) Å,
b ) 13.0803(6) Å, c ) 12.8570(6) Å, and â ) 103.015(1)°. For Z )
4 and FW ) 333.21, the calculated density is 1.386 g/cm3. On the
basis of the systematic absences, the space group was determined to
be P21. The data were collected at -100 °C using ω-2θ scan
technique to a maximum 2θ value of 57°.
1
98-99 °C; IR (CdN) 1675 cm-1; H NMR (CDCl3) 4.05 (dd, 1H, J
) 6.3 and 8.0 Hz), 4.49 (dd, 1H, J ) 8.0 and 8.0 Hz), 4.71 (m, 1H),
5.31 (m, 2H), 5.74 (m, 1H), 6.83-7.52 (m, 8 H); 13C NMR (CDCl3)
60.40, 69.36, 115.31, 117.03, 120.53, 123.49, 125.12, 131.39, 131.62,
134.29, 137.27, 145.99, 149.77; MS (m/e) 422 [M]+, 424 [M + 2]+.
Anal. Calcd for C17H14N2OBr: C, 48.37; H, 3.34; N, 6.64. Found:
C, 48.38; H, 3.06; N, 6.59.
N-(p-Methoxyphenyl)-3-(p-methoxyphenyl)-4-vinyl-1,3-oxazoli-
din-2-imine (5e) (R ) H, X ) p-CH3OC6H5N, Y ) p-CH3OC6H5N):
1
mp ) 65-66 °C; IR (CdN) 1678 cm-1; H NMR (CDCl3) 3.67 (s,
3H), 3.69 (s, 3H), 3.97 (dd, 1H, J ) 6.6 and 8.0 Hz), 4.42 (dd, 1H, J
) 8.0 and 8.0 Hz), 4.57 (m, 1H), 5.21 (m, 2H), 5.70 (m, 1H), 6.69-
7.39 (m, 8H); 13C NMR (CDCl3) 55.21, 61.31, 69.09, 113.57, 113.84,
120.03, 123.98, 124.58, 131.40, 134.96, 140.51, 150.46, 154.80, 156.37;
A total of 11377 reflections was collected. The unique set contained
7678 reflections. The data were corrected for Lorentz and polarization

Cycloaddition of Vinyloxiranes with Heterocumulenes
J. Am. Chem. Soc., Vol. 119, No. 16, 1997 3715
effects,26 and an absorption correction was made. The minimum and
maximum transmission factors are 0.542-1.000.
Acknowledgment. We are grateful to the Natural Sciences
and Engineering Research Council of Canada for support of
this research. We thank Dr. C. Bensimon for the X-ray structure
determination.
The structure was solved by direct methods. All the atoms were
refined anisotropically except the hydrogen atoms which were found
by difference Fourier map. The final cycle of full-matrix least-squares
refinement was based on 4430 observed reflections (I > 2.5σ(I)) and
398 variable parameters. Weights based on counting statistics were
used. The maximum and minimum peaks on the final differences
Fourier map corresponded to 0.450 and -0.300 e/a3, respectively.
The absolute structure was determined by refinement of the η
parameter with the Rogers Schemes, giving a value of 1.0177(0.1001),
showing that we have the good hand.
Supporting Information Available: Text giving full details
of the X-ray structure determination of (R)-5b including the
experimental procedure and tables of bond distances and angles
and torsion angles (15 pages). See any current masthead page
for ordering and Internet access instructions.
JA964335L
All the calculations were performed using the NRCVAX crystal-
lographic software package.27
(27) Gabe, E. J.; Lee, A. L.; Lapage, Y. J. Appl. Crystallogr. 1989, 22,
(26) Grant, D. F.; Gabe, E. J. J. Appl. Crystallogr. 1978, 11, 114.
384.