Synthesis and stereochemical analysis of some norephedrine-derived isoxazolidines

Article abstract of DOI:10.1002/poc.1454

The diastereoselectivity in the cycloaddition reactions of several mono- and disubstituted alkenes with a (-)norephedrine-derived methylenenitrone has been investigated. The stereochemical analysis of the addition products (i.e., isoxazolidines) has been

Full text of DOI:10.1002/poc.1454

Research Article
Received: 25 June 2008,
Revised: 28 August 2008,
Accepted: 30 August 2008,
Published online in Wiley InterScience: 6 October 2008
(www.interscience.wiley.com) DOI 10.1002/poc.1454
Synthesis and stereochemical analysis of some
norephedrine-derived isoxazolidines
Basem A. Moosaa, Mohamed I. M. Wazeera, Mohammed B. Fettouhia
and Shaikh A. Alia
*
The diastereoselectivity in the cycloaddition reactions of several mono- and disubstituted alkenes with a
(-)norephedrine-derived methylenenitrone has been investigated. The stereochemical analysis of the addition
products (i.e., isoxazolidines) has been carried out by X-ray, NMR, and chemical conversions. The NMR spectra of
the isoxazolidines at low temperatures indicated the presence of either a single or a predominant invertomer. The
stereochemistry of the invertomers and nitrogen inversion barriers are determined using complete line-shape
analysis and their dependence on solvent is discussed. Copyright ß 2008 John Wiley & Sons, Ltd.
Keywords: isoxazoldines; nitrogen inversion; invertomers; inversion barriers; nitrone; cycloaddition reactions; asymmetric
induction; stereochemistry
by Karplus rule, supports the gauche orientation between Ha
and Hb. Since both the faces of the dipole, in the vicinity of N,
INTRODUCTION
1,3-Dipolar cycloaddition reaction of nitrones is the best chemical
template for the construction of isoxazolidine ring; efficient
incorporation of multiple stereocenters makes it an efficient key
step in the synthesis of a great many natural products of
biological interest.[1,2] In recent years, focus has been shifted
towards asymmetric nitrone cycloaddition reactions, the effi-
ciency of which very much depends on the ability of the chiral
auxiliary to effectively transfer chirality to the newly created
stereocenters.[3–8] Even though the nitrone cycloaddition reac-
tions of C,N-disubstituted nitrones have been studied in great
detail,[1,2] the chemistry of chiral (or even achiral) N-substituted
nitrones (i.e., methylenenitrones) has only been investigated to a
limited extent.[9–12] Here we report, for the first time, the
stereochemical features associated with the cycloaddition of a
norephedrine-derived chiral methylenenitrone 2 (Scheme 1) with
several mono- and 1,1-disubstituted alkenes. The study would
reflect the scope and limitations associated with the addition
reactions of this important and readily accessible optically pure
methylenenitrone. The NMR spectroscopy is utilized to examine
the nitrogen inversion process and determine the configuration
of the cycloadducts (isoxazolidines).
have substituents, addition reaction does not offer any clear cut
face selectivity. Sterically favored a-exo (R) or b-exo (R) mode of
attack may happen with equal ease thereby giving the
isoxaolidines 4 and 5 in almost equal yields (Scheme 1).
Since the addition reaction of methyl acrylate (3c) was found to
have a preference to give the isoxazolidine 5c by an a-exo
(CO2Me) mode of approach (Scheme 1), the major adduct in the
addition reaction of methyl methacrylate (6) was similarly
assigned the configuration of 8 obtained by a similar a-exo
(CO2Me) mode of attack (Scheme 2). However, in the absence of
X-ray analysis (owing to difficulty in getting crystalline material),
the configuration of the adduct could not be confirmed.
During the course of the structural investigation of the isomeric
isoxazolidines, it was observed that the isoxazolidines were
present either as a single invertomer or an equilibrating mixture
of two invertomers in a ꢀ80:20 ratio at lower temperatures in
CDCl3. Slow nitrogen inversion in most of the isoxazolidines has
1
been observed to give broadened peaks in H and 13C spectra
recorded at ambient temperature. On lowering the temperature,
the spectral lines became sharper and showed two distinct forms
1
of the compound. Around ꢁ10 8C, the H NMR spectra of these
compounds showed well separated signals for the two
invertomers. Integration of the relevant peaks gives the
population trends in these systems. The 13C chemical shifts
were assigned on the basis of DEPT experiment results, general
chemical shifts arguments and consideration of substituent
effects, and are given in Table 1.
RESULTS AND DISCUSSION
Each nitrone (2)-alkene cycloaddition with 3 (or 6) proceeded
regiospecifically to afford a separable mixture of diastereomeric
isoxazolidines 4 and 5 (or 7 and 8), the compositions of which are
given in Schemes 1 and 2. Since the nitrone is optically pure, the
isoxazolidines differ only in the configuration of the C(5)
*
Correspondence to: S. A. Ali, Chemistry Department, King Fahd University of
Petroleum and Minerals, Dhahran 31261, Saudi Arabia.
E-mail: shaikh@kfupm.edu.sa
substituents. The nitrone
2 is expected to assume the
conformation as depicted in Scheme 1. The planar nitrone
functionality is in Ha-eclipsed conformation[13–15] having Me and
PhCHOH on the a- and b-faces, respectively. The Jab value of
5.5 Hz, corresponding to a torsional angle of 40.58 as determined
a
B. A. Moosa, M. I. M. Wazeer, M. B. Fettouhi, S. A. Ali
Chemistry Department, King Fahd University of Petroleum and Minerals,
Dhahran 31261, Saudi Arabia
J. Phys. Org. Chem. 2009 22 212–220
Copyright ß 2008 John Wiley & Sons, Ltd.

NOREPHEDRINE-DERIVED ISOXAZOLIDINES
¼
¼
The activation parameters DH and DS were calculated from
plots of ln(k/T) versus 1/T. It is well known[16] that NMR band
shape fitting frequently gives rather large but mutually
¼
¼
compensating errors in DH and DS and as such their values
are not reported here. However, band shape fitting is viewed as a
¼
method of getting rather accurate values of DG (probably
within ꢂ 0.3 kJ/mol) in the vicinity of the coalescence tempera-
¼
ture. The DG values calculated at 0 8C are reported in Table 2,
along with the invertomer ratios and DG8 values.
Both the cis-1,3-dimethylcyclopentane and cis-1,3-dimethyl-
cyclohexane are known[17] to be more stable than their trans
counterparts by an enthalpy difference of 2.3 and 7.1 kJ/mol,
respectively. The slight preference for the cis isomer in
cyclopentane may be attributed to the disposition of the
substituents in the pseudoequatorial orientations. The 2,5-
disubstituted isoxaozolidines, however, have been found to have
a slight preference for the trans-invertomers[18,19]; shortened
bond lengths due to the presence of two heteroatoms are
expected to augment the steric congestion between the cis
substituents. The conformation of 5-membered ring system is
indeed very complex to elucidate with some certainty. The
complexity arises from the fact that changing the size of the
substituent may lead to change in conformation (half chair/
envelope/near planar) and the flap of the envelope. Earlier
works[18,19] on 2,5-disubstituted isoxazolidines revealed the
trans-invertomer as the major isomer. The 2-methyl-, 2-isopropyl-,
and 2-tbutyl-5-tbutyldimethylsiloxymethylisoxazolidines were
found to have the trans- and cis-invertomers in a ratio of
53:47, 55:45, and 63:37, respectively. The compounds studied in
this work are sterically similar to the 2-isopropylisoxazolidines
since they also contain a secondary alkyl substituent at the
2-position (Scheme 1).
To confirm the stereochemistry, adducts 5b and 5c were
subjected to X-ray crystallographic analysis; the ORTEP repres-
entations are shown in Figs 1 and 2. The stereochemistry of the
methyl acrylate adducts 4c and 5c were then correlated to allyl
alcohol adducts 4d and 5d by conversions of the former isomers
to the later by reduction with lithium aluminum hydride. It has
been observed that the minor isomers (4b, 4c) in the addition
reactions of styrene or methyl acrylate always eluted first during
the silica gel chromatography. As a result, in the addition reaction
of 1-hexene, adduct eluted first was given the configuration of 4a.
The X-ray analyses revealed the existence of both the adduts 5b
and 5c in the cis invertomeric form. The chemical shift difference
between the isomers for a particular ring carbon is generally less
Scheme 1.
The nitrogen inversions barriers were determined using NMR
band shape analysis. The proton spectra were used in the
calculation of barriers in all compounds. The complete band
shape analysis yielded the rate constants and the free energy of
activation using Eyring equation. The complete band shape
analysis yielded the rate constants and the free energy of
activation using Eyring equation. Experimental and calculated
spectra for one of the isoxazoli dines (4b) are shown in Figure 3.
Scheme 2.
J. Phys. Org. Chem. 2009 22 212–220
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B. A. MOOSA ET AL.
Table 1. 13C NMR chemical shifts of compounds studied in CDCl3 at ꢁ40 8C
Compound
4a {
Invertomera
C-3
C-4
C-5
CꢁꢁOH
NꢁꢁC
Me
Major (RSR)
Minor (RSS)
Major (RSR)
Minor (RSS)
Major (RSR)
Minor (RSS)
Major (RSR)
Minor (RSS)
(RSR)
Major (RSR)
Minor (RSS)
(RSR)
Major (RSR)
Minor (RSS)
(RSR)
52.32
52.06
53.13
51.87
53.02
52.38
53.90
52.54
51.63
51.78
50.59
53.03
53.64
52.26
52.50
52.08
51.06
33.90
33.81
33.61
34.24
37.48
36.97
36.93
37.51
32.90
32.98
32.18
29.44
30.03
29.26
39.13
39.02
38.10
76.75
77.50
77.48
74.38
77.57
78.95
78.77
78.85
73.38
75.09
76.20
77.47
77.67
78.07
81.11
82.17
81.63
72.59
74.81
72.31
73.96
72.44
75.68
71.98
74.70
72.03
71.68
74.05
71.71
71.61
74.72
71.90
72.06
76.91
65.68
67.26
68.02
65.93
66.31
66.71
68.15
65.99
65.79
66.92
64.46
67.30
67.98
66.09
65.81
66.31
64.06
10.88
7.12
10.75
7.42
10.73
6.44
10.65
7.45
11.07
10.48
5.14
10.36
10.62
7.37
10.80b
10.55c
4.00d
5a {
4b {
5b {
4c
5c {
4d
5d {
7
8 {
Major (RSR)
Minor (RSS)
a Absolute configuration of the chiral centers as defined in Schemes 3 and 4.
b C(5) Me at 22.82 ppm.
c C(5) Me at 24.29 ppm.
d C(5) Me at 22.95 ppm.
than 1 ppm for most carbons and as such the C-13 shifts are not
very sensitive to the difference in the isomeric configurations
(Table 1). This is not surprising in view of the fact that the
five-membered ring does not have the well-defined confor-
mation of six-membered systems. However, one striking
difference in the 13C chemical shift values of CH3C—N was
observed; the signals for the major invertomers appeared at d
10.7 ꢂ 0.2 ppm, while the minor signal appeared at d 6.8 ꢂ 0.9.
The C-3 and C—OH of the major invertomers invariably appeared
downfield and upfield, respectively, in compare to the minor
invertomers (Table 1). The benzylic proton NMR signals for all the
major invertomers appeared downfield than the PhCHO of the
¼
Table 2. Free energy of activation (DG ) for nitrogen inver-
sion, ratio of the invertomers, and standard free energy
change (DG8) for major $ minor isomerization in CDCl3
CDCl3
Invertomer
ratio
¼
DG
DG8
Compound
(kJ/mol)a
(kJ/mol)b
4a
5a
4b
5b
4c
4cc
5c
5cc
4d
5d
7
59.5
59.4
59.4
59.8
—
56.9
58.5
58.5
—
83:17
89:11
88:12
90:10
100:0
83:17
79:21
87:13
100:0
84:16
100:0
63:37
þ3.1
þ4.1
þ3.9
þ4.2
—
þ3.1
þ2.6
þ3.7
—
Figure 1. ORTEP drawing of 5b. The Hydrogen atom of the hydroxyl
group could not be located in difference-Fourier maps most probably due
to disorder
60.3
—
56.5
þ3.2
—
þ1.0
8
a At 0 8C.
b At ꢁ40 8C.
c In CD3OD.
Figure 2. ORTEP drawing of 5c
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NOREPHEDRINE-DERIVED ISOXAZOLIDINES
Table 3. 1H NMR chemical shifts of CH3C–N and PhCHO signals of the compounds studied in CDCl3 at ꢁ40 8C
CH3CꢁꢁN
PhCHO
Isoxazolidine
Majorb d (ppm)
Minorc d (ppm)
Majorb d (ppm)
Minorc d (ppm)
4a
5a
4b
5b
4c
4cc
5c
5cc
4d
5d
7
0.81
0.81
0.85
0.94
0.78
0.77
0.84
0.80
0.85
0.88
0.73
0.80
1.00
Overlapped
1.09
5.26
5.35
5.43
5.43
5.38
5.37
5.45
5.47
5.43
5.42
5.39
5.39
5.14
5.00
5.22
a
1.02
b
—
—
—
b
1.02
0.95
1.01
5.17
5.18
5.17
b
b
—
1.00
—
5.02
b
b
—
0.94
—
5.21
8
a overlapped.
b No minor invertomer.
c In CD3OD.
minor invertomers (Table 3). The methyl protons in CH3C—N of
the major and minor invertomers appeared upfield and down-
field, respectively, in all the compounds studied. Similar trend in
the chemical shift values of PhCHO and CH3C—N protons
(Table 3) and the CH3C—N, C-3, and C—OH carbons (Table 1)
between the major and minor invertomers strongly suggest the
similarity in the configuration among all the major invertomers
(or among all the minor invertomers). As supported by X-ray
analyses, all the dominant or sole nitrogen invertomers are
believed to have the identical configuration of (R), (S), and (R) at
the three chiral centers at benzylic C, exocyclic C attached to
nitrogen, and N, respectively.
X-ray analyses revealed that the proton in exocyclic CH—N is
anti to the nitrogen lone pair as depicted in Scheme 3; the
arrangement will have the lower number of gauche interactions
(two in these cases) around the C—N bond. The protons in the
exocyclic CH—N and PhCHO are not in expected anti
dispositions; the torsional angle between them is found to be
63.38 in 5c as a result of their gauche orientations (Scheme 3 and
Fig. 2). Similar orientation is observed in the ORTEP diagram of 5b
(Fig. 1). Such an orientation will lead to a very low coupling
constant (J ꢃ 1.5 Hz) between these protons as calculated using
Karplus equation. The appearance of PhCHO proton of both the
invertomers as a singlet (i.e., J ꢃ 0 Hz) in the 1H NMR spectrum in
CDCl3 or CD3OD confirmed the gauche orientation between
these protons in solution as well as solid state. Such an
orientation may be helpful in establishing intramolecular H-bond
between the OH and nitrogen lone pair as depicted in Scheme 3.
The question remains: why are the (R),(S),(R)-diastereomers
more stable than their corresponding (R),(S),(R)-invertomers? It
may be the result of an energetically favorable orientation of the
groups around C—N having the larger substituent (PhCHOH) in
gauche orientation with the ring ‘O’ in the major invertomer. The
Newman projections also reveals that the ‘OH’ in the major
invertomers is also capable of forming H-bond with the ring ‘O’,
while this is not possible with the minor form. The special stability
imparted by the (R),(S),(R) arrangement does not mind the
substituent at C-5 to be trans or cis-oriented. Note that while the
2,5 substituents in 4(a-d) remain trans oriented in the major
invertomers, the cis remains the stable form for the correspond-
ing isoxazolidines 5(a-d). The isoxazolidines 4c and 4d remained
exclusively in the (R),(S),(R) configurations; the presence of the
minor invertomers could not be detected. Presumably, the
pseudoaxial orintantion of the CO2Me is better tolerated in
(R),(S),(R) invertomer for its smaller size as
a result of
the sp2-hybridized carbon. It is worth mentioning that the
C(5)—CH2OH in the exclusive invertomer of 4d may gain
additional stability as a result of intramolecular H-bonding with
the nitrogen as depicted in Scheme 3.
The most interesting display of isomeric stability is found with
the isoxazolidines 7 and 8; while the former exists exclusively in
the (R),(S),(R) form, the later remains in the (R),(S),(R) and (R),(S),(S)
forms in a respective ratio of 63:37 (Scheme 4, Table 2). The
C(5)Me carbon of (R),(S),(R)-7, (R),(S),(S)-8, and (R),(S),(R)-8
appeared at d22.82, 22.95, and 24.29 ppm, respectively; the
similarity in the chemical shift values of the former two
invertomers indicates the similar environments of the methyl
group such as its cis orientation with the N(2)substituents. The
extra stability enjoyed by the (R),(S),(R)-7 invertomer could be
attributed to the pseudoequatorial orientation of the bulkier
substituents at C(5) and N(2), while the smaller CO2Me is
pseudoaxially-oriented.
˚
The sum of Van der Waal radii of H,N is known to be 2.75 A, while
˚
the observed distance of 2.44 A in 5c (Fig. 2) suggest the
presence of intramolecular H-bond. A look at the Newman
projections (Scheme 3) revealed that the Me and C-3 are in the
gauche conformations in the major invertomers, while they
remain anti in the minor invertomers. We cannot offer a rationale,
at this stage, for the considerable upfield shift by ꢀ4 ppm for
the methyl carbons in the methyl/C-3 anti-oriented minor
invertomers.
The nitrogen inversion barrier is expected to be high when an
oxygen atom is directly attached to the nitrogen as in
isoxazolidines.[20,21] The inversion barriers hover around 59 kJ/
J. Phys. Org. Chem. 2009 22 212–220
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B. A. MOOSA ET AL.
Scheme 3.
mol for most of the isoxazoldines (Table 2). The similar barriers
were expected since the steric requirements to attain the sp2
hybridized transition state (through which the nitrogen inversion
occurs) remains more or less similar as the substituents in the
immediate vicinity of nitrogen remains the same in all the
isoxazolidines. An increase in the inversion barrier in in
isoxaolidines in CD3OD is attributed to the extra energy required
for breaking of H-bonding prior to inversion.[21] However, the
inversion in the current compounds in CDCl3 also involves the
breaking of the intramolecular H-bonding. As a result the
inversion barrier remains similar in hydrogen bonding
solvent CD3OD and non-protic CDCl3 for the compound 5c
(Table 2).
The solvent effects provided the additional support for the
assigned stereochemistry. In methanol, the intramolecular
H-bonding is disrupted; the steric bulk of the solvation shell of
Scheme 4.
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NOREPHEDRINE-DERIVED ISOXAZOLIDINES
freshly prepared by reaction of Mg with 1,2-dibromoethane. All
reactions were carried out under N2.
The 13C and variable temperature 1H NMR spectra were
recorded on a JEOL Lambda NMR spectrometer operating at
500.0 MHz. Most of the compounds were studied as 25 mg/cm3
solutions in CDCl3 and CD3OD with TMS as internal standard.
Multiplicities of the carbons were determined using DEPT
experiments. X-ray crystallographic analysis was carried out on
a Bruker-AXS Smart Apex system equipped with graphite-
˚
monochromatized Mo-Ka radiation (l ¼ 0.71073 A). Optical
rotations were measured in a JASCO (P-2000) polarimeter. Mass
spectra were recorded on a GC/MS system (Agilent Technologies,
6890N).
Nitrone 2. Chiral hydroxylamine 1 was prepared from (-)
norephedrine in 38% yield using procedure as described.[22–24]
The compound 1 was not fully characterized in the previous
reports. M.p. 79–80 8C (ether-hexane); [a]23 ꢁ26.3 (c 2.00,
D
methanol). (Found: C, 64.5; H, 7.7; N, 8.3. C9H13NO2 requires C,
64.65; H, 7.84; N, 8.38%.);nmax (KBr) 3480, 3270, 3239, 3081, 3055,
3025, 2974, 2933, 2897, 2877, 2795, 1488, 1442, 1380, 1350, 1314,
1243, 1200, 1140, 1092, 1070, 1049, 1034, 988, 942, 914, 890, 850,
736, and 691 cmꢁ1; dH(CDCl3, þ25 8C): 0.85 (3H, d, J 6.7 Hz), 3.24
(1H, dq, J 2.8, 6.7 Hz), 5.17 (1H, d, J 2.8 Hz), 5.54 (2H, br, NHOH), 7.31
(5H, m); dC(CDCl3, þ25 8C) 10.25, 62.70, 71.93, 125.92 (2C), 127.21,
128.26 (2C), 141.37.
Figure 3. Experimental and calculated band shapes of the 1H Me signals
of 4b in CDCl3 at different temperatures. The temperatures and the
corresponding life times of the minor specie are indicated respectively.
*
Nitrone 2, prepared via condensation of hydroxylamine 1 with
paraformaldehyde, was not isolated (vide infra). But a crude
1H NMR spectrum revealed the following signals attributed to the
nitrone: dH(CDCl3, þ20 8C): 1.36 (3H, d, J 6.8 Hz), 4.10 (1H, m), 5.42
denotes peak from impurities
—
(1H, d, J 5.5 Hz), 6.38 (1H, d, J 7.1 Hz; CH N), 6.54 (1H, d, J 7.1 Hz;
—
the nitrogen lone pair increases in hydrogen-bonding solvents.
This should diminish the preference for the 4-trans- and 5-trans
invertomers in CD3OD since the steric bulk of the salvation lone
pair salvation shell would interfere with the C(5) substituents
(Scheme 3). This is exactly what is observed: the isoxazolidine
trans-4c remained as the sole invertomer in CDCl3 while
in CD3OD the 4-trans/cis ratio becomes 83:17 (Table 2). For the
isoxazolidine 5c the trans/cis ratio of 21:79 in CDCl3 is decreased
to 13:87 in CD3OD.
—
CH N), 7.35 (5H, m). However, the nitrone functionality
—
accounted for only 20% of the product mixture as indicated
by the integration of the olefinic protons of the nitrone
functionalty versus the aromatic protons. The complicated
spectra indicated the involvement of several compounds (e.g.,
2-A, 2-B, etc) under equilibration with nitrone 2 as outlined in
Scheme 1.
Cycloaddition of nitrone 2 with 1-hexene (3a). To a solution of
hydroxylamine 1 (670 mg, 4.0 mmol) in toluene (10 cm3) was
added paraformaldehyde (200 mg, 6.7 mmol) and 1-hexene
(3 cm3). The mixture was stirred using a magnetic stir bar in
the closed vessel under N2 at 105 8C for 12 h. After removal of the
solvent the residual mixture was chromatographed over silica
using ether/hexane mixture as eluant to give pure isomer 4a
followed by a mixture of the adducts 4a and 5a as a colorless
liquid. The combined yield of the cycloadducts was found to be
89%. Spectral analysis adducts revealed the presence of 4a/5a in
a ratio of 50:50, respectively, as determined by integration and
peak heights of C(5)H signals.
Conclusion
(-) Norephedrine is a readily available inexpensive starting
material. The cycloaddition products from the norephedrine-
derived isoxazolidines are readily separable to give optically pure
products. The NMR study has successfully identified the
configuration of the invertomers of the isoxazolidines. Currently
we are working on improving the stereoselctivity of the
cycloadition reactions.
4a: [a]23D -8.5 (c 0.946, methanol); m/z 156 [Mþ-107 (PhCHOH)];
(Found: C, 72.8; H, 9.5; N, 5.2. C16H25NO2 requires C, 72.97; H, 9.57;
N, 5.32%.); nmax (neat) 3517, 3214, 3061, 3027, 2956, 2930, 2859,
1495, 1451, 1379, 1332, 1231, 1198, 1097, 1067, 999, 878, 750, and
702 cmꢁ1; dH(CDCl3, þ20 8C): 0.81 (3H, m), 0.91 (3H, t, J 7.0 Hz)
1.15–2.00 (7H, m), 2.36 (1H, m), 2.50–3.50 (4H, m), 4.13 (1H, m),
5.20 (1H, apparent s), 7.30 (5H, m).
EXPERIMENTAL
General. All m.p.s are uncorrected. I.r. spectra were recorded on a
Perkin Elmer 16F PC FTir spectrometer. Elemental analysis was
carried out on a EuroVector Elemental Analyzer Model EA3000.
Silica gel chromatographic separations were performed with
Silica gel 100 from Fluka Chemie AG (Buchs, Switzerland).
Paraformaldehyde, 1-hexene, styrene, allyl alcohol, methyl
acrylate, methyl methacrylate, (-) norephedrine from Fluka were
used as received. All solvents were of reagent grade. Dichlor-
omethane was passed through alumina before use. MgBr2 was
The 1H NMR spectrum in CDCl3 at ꢁ40 8C revealed the
presence of two invertomers in a 83:17 ratio as determined by
integration of several proton signals.
Major invertomer: dH(CDCl3, ꢁ40 8C): 0.81 (3H, d, J 6.4 Hz), 0.92
(3H, t, J 7.0 Hz) 1.15–1.55 (5H, m), 1.72 (1H, m), 1.93 (1H, m), 2.39
(1H, m), 2.83 (1H, m), 2.90 (1H, m), 3.26 (1H, m), 3.98 (1H, br, OH),
J. Phys. Org. Chem. 2009 22 212–220
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B. A. MOOSA ET AL.
4.20 (1H, quint, J 6.3 Hz), 5.26 (1H, d, J 3.0 Hz), 7.35 (5H, m);
dC(CDCl3, ꢁ40 8C) 10.88, 14.26, 22.72, 28.42, 33.90, 35.13, 52.32,
65.68, 72.59, 76.75, 125.96 (2C), 126.73, 127.89 (2C), 140.94.
Minor invertomer: The minor invertomer has the follwing
non-overlapping signals:dH(CDCl3, ꢁ40 8C) 1.00 (3H, d, J 6.5 Hz),
3.05 (1H, m), 3.51 (1H, m), 4.05 (1H, quint, J 6.9 Hz), 5.14 (1H, d, J
5.2 Hz); dC(CDCl3, ꢁ40 8C) 7.12, 14.21, 22.77, 28.24, 33.81, 34.23,
52.06, 67.26, 74.81, 77.50, 125.71 (2C), 126.84, 127.99 (2C), 141.24.
5a: The second fraction was contaminated with a minor amount
4.94%.);nmax (KBr) 3375, 3029, 2980, 2937, 2851, 1603, 1493, 1450,
1381, 1367, 1341, 1327, 1284, 1241, 1204, 1156, 1096, 1043, 1001,
944, 919, 880, 823, 753, and 699 cmꢁ1
.
The 1H NMR spectrum in CDCl3 at ꢁ40 8C revealed the
presence of two invertomers in a 87:13 ratio as determined by
integration of Me doublets.
Major invertomer: dH(CDCl3, ꢁ40 8C) 0.94 (3H, d, J 6.7 Hz), 2.15
(1H, m), 2.74 (2H, m), 3.02 (1H, m), 3.47 (1H, m), 4.49 (1H, s, OH),
5.06 (1H, m), 5.43 (1H, s), 7.35 (10H, m); dC(CDCl3, ꢁ40 8C) 10.65,
36.93, 53.90, 68.15, 71.98, 78.77, 125.99 (2C), 126.69, 126.76 (2C),
127.88, 127.93 (2C), 128.39 (2C), 140.79, 141.44.
1
of 4a. The following signals were attributed to 5a. The H NMR
spectrum in CDCl3 at ꢁ408C revealed the presence of two
invertomers in a 89:11 ratio as determined by integration of
benzylic proton signals. (Found: C, 72.7; H, 9.4; N, 5.2. C16H25NO2
requires C, 72.97; H, 9.57; N, 5.32%.);); m/z 156 [Mþ-107 (PhCHOH)];
nmax (neat) 3424, 3062, 3027, 2958, 2929, 2858, 1494, 1452,1379,
Minor invertomer: The minor invertomer has the following
non-overlapping signals:dH(CDCl3, ꢁ40 8C) 1.02 (3H, d, J 6.5 Hz).
dC(CDCl3, ꢁ40 8C) 7.45, 37.51, 52.54, 65.99, 74.70, 78.85, 125.68 (2C),
125.88, 126.08 (2C), 127.05, 128.09 (2C), 128.52 (2C), 140.79, 141.44.
Cycloaddition of nitrone 2 with methyl acrylate (3c). A mixture of
the hydroxylamine 1 (670 mg, 4.0 mmol) and paraformaldehyde
(200 mg, 6.7 mmol) in chloroform (15 cm3) was stirred using a
magnetic stir bar in a closed vessel under N2 at 65 8C for 2 h.
Methyl acrylate (2 cm3) was then added to the resulting nitrone
solution (at 25 8C) and stirring was continued at 60 8C for 24 h.
After removal of the solvent and excess alkene, the residual
mixture was chromatographed over silica using 9:1 hexane/ether
mixture as eluant to give the minor isomer 4c (417 mg).
Continued elution afforded the pure sample of the major isomer
5c (580 mg). Adducts 4c and 5c were thus formed in a ratio of
42:58, respectively. The 1H NMR analysis of the crude
cycloadducts also supported the ratio obtained from the
chromatographic separation. The combined yield of the
cycloadducts was found to be 94%.
1336, 1197, 1097, 1020, 999, 911, 751, 731, and 702 cmꢁ1
.
Major invertomer: dH(CDCl3, ꢁ40 8C): 0.81 (3H, d, J 6.3 Hz), 0.87
(3H, t, J 6.7 Hz), 1.15–2.00 (7H, m), 2.40 (1H, m), 2.60 (1H, m), 2.91
(1H, m), 3.33 (1H, m), 4.05 (1H, m), 4.22 (1H, br, OH), 5.35 (1H, d, J
2.5 Hz), 7.35 (5H, m); dC(CDCl3, ꢁ40 8C) 10.75, 14.25, 22.82, 28.26,
33.61, 34.56, 53.13, 68.02, 72.31, 77.48, 126.15 (2C), 126.69, 127.87
(2C), 141.22.
Minor invertomer: The minor invertomer has the following
non-overlapping signals: dH(CDCl3, ꢁ40 8C) 5.00 (1H, d, J 5.0 Hz).
dC(CDCl3, ꢁ40 8C) 7.42, 12.54, 22.72, 28.40, 33.83, 34.24, 51.87,
65.93, 73.96, 74.38, 125.63 (2C), 126.95, 128.25 (2C), 141.00.
Cycloaddition of nitrone 2 with styrene (3b). To a solution of the
hydroxylamine 1 (670 mg, 4.0 mmol) in toluene (10 cm3) was
added paraformaldehyde (200 mg, 6.7 mmol) and styrene (3 cm3).
The mixture was stirred using a magnetic stir bar in the closed
vessel under N2 at 90 8C for 6 h. After removal of the solvent and
excess styrene the residual mixture was chromatographed over
silica using 9:1 ether/hexane mixture as eluant to give pure
isomer 4b followed by a mixture of the adducts 4b and 5b.
Continued elution afforded the pure adduct 4b. The combined
yield of the cycloadducts was found to be 89%. Spectral analysis
adducts revealed the presence of 4/5 in a ratio of 40:60,
respectively, as determined by integration of several non-
overlapping signals of the C(5)H and Me doublets.
Minor isomer 4c: Mp 68–69 8C (ether-pentane); m/z 158
[Mþ-107 (PhCHOH)]; [a]23D ꢁ48.3 (c 0.425, methanol); (Found: C,
63.2; H, 7.1; N, 5.2. C14H19NO4 requires C, 63.38; H, 7.22; N, 5.28%.);
nmax (KBr) 3485 (sharp), 3061, 2986, 2958, 2847, 1746, 1496, 1451,
1430, 1380, 1337, 1286, 1205, 1177, 1086, 1026, 1003, 812, 752,
and 705 cmꢁ1
.
Sharp 1H NMR signals at room temperature indicated the
presence of a single invertomer: dH(CDCl3, þ25 8C): 0.78 (3H, d, J
6.7 Hz), 2.48–2.70 (3H, m), 2.92 (1H, m), 3.32 (1H, m), 3.57 (1H, s,
OH), 3.80 (3H,s), 4.63 (1H, dd, J 3.9, 9.7 Hz), 5.38 (1H, s), 7.33 (5H,
m). The spectrum at ꢁ40 8C remained similar to that at þ25 8C.
dC(CDCl3, ꢁ40 8C) 11.07, 32.90, 51.63, 52.73 (OMe), 65.79, 72.03,
73.38, 125.69 (2C), 126.80, 128.01 (2C), 140.25, 173.87.
Minor isomer 4b: Mp 65–66 8C (ether-pentane); m/z 176
[Mþ-107 (PhCHOH)]; [a]23D þ37.1 (c 0.488, methanol). (Found: C,
76.1; H, 7.5; N, 4.8. C18H21NO2 requires C, 76.30; H, 7.47; N,
4.94%.);nmax (KBr) 3423, 3081, 3055, 3025, 2984, 2948, 2897, 2831,
1595, 1488, 1447, 1437, 1380, 1334, 1299, 1278, 1197, 1105, 1094.
In CD3OD (ꢁ40 8C) the 1H NMR spectrum revealed several
non-overlapping minor signals indicating the major/minor
invertomers of 4c in a ratio of 83:17. The CH3 doublets appeared
at d0.77 (major, d, J ¼ 6.7 Hz) and d1.02 (minor, d, J ¼ 6.1 Hz). The
benzylic proton appeared at d5.38 (major, s) and d5.17 (minor, s).
Major isomer 5c: Mp 60–61 8C (ether-pentane);); m/z 158
[Mþ-107 (PhCHOH)]; [a]23D ꢁ26.4 (c 0.872, methanol); (Found: C,
63.3; H, 7.1; N, 5.2. C14H19NO4 requires C, 63.38; H, 7.22; N, 5.28%.);
nmax (KBr) 3543 (sharp), 3081, 2990, 2942, 2908, 2869, 1754, 1492,
1453, 1434, 1409, 1378, 1349, 1328, 1284, 1262, 1198, 1088, 1061,
1023, 1013, 916, 885, 854, 798, 752, and 696 cmꢁ1
.
The 1H NMR spectrum in CDCl3 at ꢁ40 8C revealed the
presence of two invertomers in a 88:12 ratio as determined by
integration of several proton signals.
Major invertomer: dH(CDCl3, ꢁ40 8C): 0.85 (3H, d, J 6.4 Hz), 2.38
(1H, m), 2.82 (1H, m), 2.96 (2H, m), 3.44 (1H, m), 3.62 (1H, OH), 5.27
(1H, apparent t, J 7.2 Hz), 5.43 (1H, s), 7.35 (10H, m); dC(CDCl3,
ꢁ40 8C) 10.73, 37.48, 53.02, 66.31, 72.44, 77.57, 125.67 (2C), 125.88
(2C), 126.81, 127.48, 127.99 (2C), 128.54(2C), 140.71, 142.57.
Minor invertomer: The minor invertomer has the following
non-overlapping signals:dH(CDCl3, ꢁ40 8C) 1.09 (3H, d, J 6.4 Hz),
3.18 (1H, m), 3.70 (1H, m), 5.07 (1H, apparent t, J 7.2 Hz), 5.22 (1H,
s); dC(CDCl3, ꢁ40 8C) 6.44, 36.97, 52.38, 66.71, 75.68, 78.95, 125.75
(2C), 126.60 (2C), 126.75, 127.00, 128.05 (2C), 128.44 (2C), 140.34,
141.01.
996, 964, 949, 877, 854, 795, 763, and 706 cmꢁ1
.
The 1H NMR spectrum in CDCl3 at ꢁ40 8C revealed the
presence of two invertomers in a 79:21 ratio as determined by
integration of several proton signals.
Major invertomer: dH(CDCl3, ꢁ40 8C): 0.84 (3H, d, J 6.7 Hz), 2.39
(1H, m), 2.66 (1H, m), 2.89 (1H, m), 3.11 (1H, m), 3.31 (1H, m), 3.75
(1H, s, OH), 3.83 (3H, s), 4.64 (1H, dd, J 5.8, 9.2 Hz), 5.45 (1H, s), 7.37
(5H, m); dC(CDCl3, ꢁ40 8C) 10.48, 32.98, 51.78, 52.67 (OMe), 66.92,
71.68, 75.09, 125.84 (2C), 126.70, 127.95 (2C), 141.09, 172.47.
Major isomer 5b: Mp 74–75 8C (ether-pentane); m/z 176
[Mþ-107 (PhCHOH)]; [a]23D ꢁ17.8 (c 0.386, methanol); (Found: C,
76.2; H, 7.3; N, 5.0. C18H21NO2 requires C, 76.30; H, 7.47; N,
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Copyright ß 2008 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2009 22 212–220

NOREPHEDRINE-DERIVED ISOXAZOLIDINES
Minor invertomer: The non-overlapping 1H signals at dH(CDCl3,
ꢁ40 8C) 0.95 (3H, d, J 6.7 Hz), 5.18 (1H, s); dC(CDCl3, ꢁ40 8C) 5.14,
32.18, 50.59, 52.79 (OMe), 64.46, 74.05, 76.20, 125.66 (2C), 127.00,
128.06 (2C), 140.57, 173.33.
In CD3OD (ꢁ40 8C) the 1H NMR spectrum revealed several
non-overlapping minor signals indicating the major/minor
invertomers of 5c in a ratio of 87:13. The CH3 doublets
appeared at d0.80 (major, d, J ¼ 6.7 Hz) and d1.01 (minor, d,
J ¼ 6.1 Hz). The benzyl protons appeared at d5.47 (major, s) and
d5.17 (minor, s).
(0.80 g, 84%). Spectral analysis revealed the presence of 4d/5d in
a ratio of 50:50.
Cycloaddition of nitrone 2 with allyl alcohol (3d) in the presence
of MgBr2. To a solution of hydroxylamine 1 (167mg, 1.0 mmol) in
dichloromethane (20 cm3), was added paraformaldehyde (34mg,
1.13mmol) and the mixture was stirred in a closed vessel under N2
at 658C for 2 h. Thereafter, the solution was cooled to room
temperature and the volume of the solution was reduced to 5 cm3
by gently blowing N2 at 40 8C. This process is expected to remove
moisture (H2O) by evaporation along with CH2Cl2. Then MgBr2
(184mg, 1.0 mmol) was added to the solution. The resulting
suspension was stirred at 208C for 15min after which allyl alcohol
(3d) (4.0 mmol) was added. The reaction mixture was then stirred
at 658C in the closed vessel under N2 for 48h. After the elapsed
time, the reaction mixture was cooled to room temperature and
was taken up in 10% K2CO3 (20 cm3) and extracted with CH2Cl2
(3ꢄ 20cm3). The combined organic layers were dried (Na2SO4),
concentrated and purified by silica gel chromatography using
98:2dichloromethane/methanol mixture as eluent to give a
non-separable mixture of isomers 4d and 5d as a colorless liquid
(190mg, 80%). The ratio of 4d and 5d was found to be 50:50,
respectively, as determined by 1H NMR spectroscopic analysis (vide
supra). The Lewis acid catalyzed [9–11] cycloaddition thus failed to
improve the diastereselectivity of the addition reaction.
Cycloaddition of nitrone 2 with methyl methacrylate (6). A
mixture of the hydroxylamine 1 (670 mg, 4.0 mmol) and para-
formaldehyde (200 mg, 6.7 mmol) in chloroform (15 cm3) was
stirred using a magnetic stir bar in the closed vessel under N2 at
65 8C in a closed vessel for 2h. Methyl methacrylate (6) (2cm3) was
then added to the resulting nitrone solution (at 25 8C) and stirring
was continued at 60 8C for 24 h. After removal of the solvent and
excess alkene, the residual mixture was chromatographed over
silica using 9:1 hexane/ether mixture as eluant to give the minor
isomer 7 (371mg). Continued elution afforded the pure sample of
the major isomer 8 (690 mg). Adducts 7 and 8 were thus formed in
a ratio of 35:65, respectively. The 1H NMR integration of the benzylic
proton signals (CDCl3, þ25 8C) of the crude cycloadducts at d 5.39
(minor) and 5.26 (major) also supported the ratio obtained from the
chromatographic separation. The combined yield of the cycload-
ducts was found to be 95%.
Lithium aluminium hydride reduction of cycloadducts methyl
acrylate adducts (4c, 5c) to allyl alcohol adducts (4d, 5d). 4d: To a
stirred solution of 4c (120 mg, 0.45 mmol) in ether (15 cm3) was
added lithium aluminium hydride (100 mg, 2.7 mmol) at room
temperature. The reaction was complete in 10 min as indicated
by TLC experiment (silica, ether). To the reaction mixture was
added water (0.1 g), 10% NaOH solution (0.1 g) and water (0.4 g).
The mixture was stirred for 1 h and was then decanted and the
residue washed with CH2Cl2. The organic layer was dried
(Na2SO4), concentrated, and purified by silica gel chromatog-
raphy using a 95:5 CH2Cl2/methanol as the eluant to give 4d as a
colorless liquid (100 mg, 94%), [a]23 ꢁ38.7 (c 1.53, methanol);
D
m/z 130 [Mþ-107 (PhCHOH)]; (Found: C, 65.6; H, 7.8; N,
5.7. C13H19NO3 requires C, 65.80; H, 8.07; N, 5.90%.); nmax. (neat)
3402, 3060, 3027, 2981, 2940, 1494, 1450, 1380, 1334, 1236, 1199,
1097, 1041, 993, 859, 807, 736, and 703 cmꢁ1
.
Sharp 1H NMR signals at room temperature indicated the
presence of a single invertomer. The spectrum at ꢁ40 8C
remained similar to that at þ25 8C.
Single invertomer: dH(CDCl3, ꢁ40 8C) 0.85 (3H, d, J 6.4 Hz), 2.13
(1H, m), 2.30 (1H, m), 2.72 (1H, m), 2.81 (1H, m), 3.22 (1H, m), 3.72
(2H, m), 4.37 (1H, m), 4.75 (1H, broad, OH), 4.89 (1H, broad, OH),
5.43 (1H, s), 7.35 (5H, m). dC (CDCl3, ꢁ40 8C) 10.36, 29.44, 53.03,
63.60, 67.30, 71.71, 77.47, 125.86 (2C), 126.73, 127.94 (2C), 141.40.
5d: Adduct 5c was reduced with LiAlH4 using procedure as
described above to give 5d (95%) as a colorless liquid; [a]23
D
ꢁ18.4 (c 1.58, methanol); m/z 130 [Mþ-107 (PhCHOH)]; (Found: C,
65.5; H, 7.9; N, 5.8. C13H19NO3 requires C, 65.80; H, 8.07; N, 5.90%);
nmax. (neat) 3286, 2982, 2880, 1494, 1451, 1381, 1336, 1198, 1041,
999, 887, 829, 751, and 703 cmꢁ1
.
The 1H NMR spectrum in CDCl3 at ꢁ40 8C revealed the
presence of two invertomers in a 84:16 ratio as determined by
integration of several proton signals.
7: Single invertomer: Mp 78–79 8C (ether-pentane); m/z 172
[Mþ-107 (PhCHOH)]; [a]23D ꢁ70.8 (c 0.267, methanol). (Found: C,
64.3; H, 7.4; N, 4.9. C15H21NO4 requires C, 64.50; H, 7.58; N, 5.01%.);
nmax (KBr) 3502 (very sharp), 3059, 2994, 2955, 2882, 2840, 1738,
1499, 1449, 1409, 1383, 1341, 1279, 1232, 1201, 1126, 1070, 1023,
1002, 971, 933, 906, 848, 818, 752, and 706 cmꢁ1; dH(CDCl3,
þ25 8C): 0.73 (3H, d, J 6.7 Hz), 1.56 (3H, s), 2.13 (1H, ddd, J 2.1, 9.1
12.7 Hz), 2.60 (1H, m), 2.84 (1H, td, J 8.7, 12.6 Hz), 2.91 (1H, dq, J 2.9,
6.6 Hz), 3.29 (1H, dt, J 2.1, 8.7 Hz), 3.58 (1H, s, OH), 3.80 (3H,s), 5.39
(1H, br s), 7.33 (5H, m). Identical 1H NMR spectrum was obtained
at ꢁ40 8C. dC(CDCl3, ꢁ40 8C) 10.80, 22.82, 39.13, 52.50, 52.89
(OMe), 65.81, 71.90, 81.11, 125.70 (2C), 126.73, 127.96 (2C), 140.31,
176.31.
Major invertomer: dH(CDCl3, ꢁ40 8C) 0.88 (3H, d, J 6.7 Hz), 1.85
(1H, m), 2.33 (1H, m), 2.44 (1H, m), 2.87 (1H, m), 3.37 (1H, m), 3.64
(1H, m), 3.81 (1H, m), 4.41 (2H, m, including an OH), 4.87 (1H,
broad s, OH), 5.42 (1H, s), 7.35 (5H, m); dC(CDCl3, ꢁ40 8C) 10.62,
30.03, 53.64, 64.29, 67.98, 71.61, 77.67, 125.99 (2C), 126.71, 127.91
(2C), 141.08.
Minor invertomer: The minor invertomer has the non-
overlapping 1H signals at: dH(CDCl3, ꢁ40 8C) 1.00 (3H, d, J
6.4 Hz), 5.02 (1H, s); dC(CDCl3, ꢁ40 8C) 7.37, 29.26, 52.26, 63.84,
66.09, 74.72, 78.07, 125.67 (2C), 127.13, 128.09 (2C), 140.85.
Cycloaddition of nitrone 2 with allyl alcohol (3d). To a solution of
the hydroxylamine 1 (670 mg, 4.0 mmol) in toluene (10 cm3) was
added paraformaldehyde (200 mg, 6.7 mmol) and allyl alcohol
(3 cm3). The mixture was stirred using a magnetic stir bar in the
closed vessel under N2 at 90 8C for 12 h. After removal of the
solvent the residual mixture was chromatographed over silica
using 98:2 dicholromethane/methanol mixture as eluant to give a
non-separable mixture of adducts 4d and 5d as a colorless liquid
8: Mp 49–50 8C (ether-pentane); m/z 172 [Mþ-107 (PhCHOH)];
[a]23 þ13.5 (c 0.942, methanol); (Found: C, 64.4; H, 7.6; N,
D
4.9. C15H21NO4 requires C, 64.50; H, 7.58; N, 5.01%.); nmax (KBr)
3408, 2999, 2948, 2854, 1741, 1495, 1450, 1383, 1316, 1278, 1203,
1147, 1099, 1064, 1032, 988, 926, 871, 756, and 705 cmꢁ1
.
The 1H NMR spectrum in CDCl3 at ꢁ40 8C revealed the
presence of two invertomers in a 63:37 ratio as determined by
integration of several proton signals.
J. Phys. Org. Chem. 2009 22 212–220
Copyright ß 2008 John Wiley & Sons, Ltd.
www.interscience.wiley.com/journal/poc

B. A. MOOSA ET AL.
Major invertomer: dH(CDCl3, ꢁ40 8C): 0.80 (3H, d, J 6.7 Hz), 1.57
(3H, s), 2.26 (1H, m), 2.71 (1H, m), 2.83–3.25 (2H, m), 3.34 (1H, m),
3.67 (1H, s, OH), 3.84 (3H, s), 5.39 (1H, s), 7.37 (5H, m); dC(CDCl3,
ꢁ40 8C) 10.55, 24.29, 39.02, 52.08, 52.94 (OMe), 66.31, 72.06,
82.17, 125.82 (2C), 126.69, 127.92 (2C), 141.04, 174.73.
Minor invertomer: The invertomer has the following non-
overlapping 1H signals at dH(CDCl3, ꢁ40 8C) 0.94 (3H, d, J 6.7 Hz),
2.11 (1H, m), 1.55 (3H, s), 3.98 (1H, s, OH), 5.21 (1H, s); dC(CDCl3,
ꢁ40 8C) 4.00, 22.95, 38.10, 51.06, 52.90 (OMe), 64.06, 76.91, 81.63,
125.60 (2C), 126.90, 128.04 (2C), 140.64, 176.01.
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Inversion barrier calculations. Simulations of exchange-affected
proton spectra for all compounds were carried out using a
computer program AXEX,[25] corresponding to a two non-
coupled sites exchange with unequal populations. The following
signals were utilized: 4a (or 5a), benzyl protons at d5.26 (major, s)
and d5.14 (minor, s); 5a (or 4a), benzyl protons at d5.35 (major, s)
and d5.00 (minor, s); 4b: (CDCl3), CH3 doublets appeared at d0.85
(major) and d1.09 (minor); 5b: (CDCl3), CH3 doublets appeared at
d0.94 (major) and d1.02 (minor); 4c: (CD3OD), CH3 doublets
appeared at d0.77 (major) and d1.02 (minor); 5c: (CDCl3), benzyl
protons at d5.45 (major, s) and d5.18 (minor, s); 5c: (CD3OD),
methyl doublets at d0.80 (major) and d1.01 (minor); 5d: (CDCl3),
benzyl protons at d5.42 (major, s) and d5.02 (minor, s); 8: (CDCl3),
benzyl protons at d5.39 (major, s) and d5.21 (minor, s).
Experimental and calculated spectra for one of the ioxazolidines
(4b) are shown in Figure 3.
Simulations of exchange affected triplets were carried out by
modifying the two-site exchange program.[26] The first order
coupling to these protons is simply assumed as giving
overlapping two site exchanges with the same population ratio
and equal rates of exchange. Simulations of exchange affected
doublet of doublets were carried out by modifying the two-site
exchange program.[26] The first order coupling to these protons is
simply assumed as giving overlapping two site exchanges with
the same population ratio and equal rates of exchange.
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[23] O. Tamura, K. Gotanda, J. Yoshino, Y. Morita, R. Terashima, M. Kikuchi,
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[26] M. I. M. Wazeer, S. A. Ali, Canad. J. Appl. Spectrosc. 1993, 38, 22–25.
Acknowledgements
The facilities provided by the King Fahd University of Petroleum
and Minerals, Dhahran, are gratefully acknowledged.
www.interscience.wiley.com/journal/poc
Copyright ß 2008 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2009 22 212–220