Structural and conformational analysis of 1-oxaspiro[2.5]octane and 1-oxa-2-azaspiro[2.5]octane derivatives by 1H, 13C, and 15N NMR

Article abstract of DOI:10.1002/mrc.3792

A structural and conformational analysis of 1-oxaspiro[2.5]octane and 1-oxa-2-azaspiro[2.5]octane derivatives was performed using ¹H, ¹³C, and ¹⁵N NMR spectroscopy. The relative configuration and preferred conformations we

Full text of DOI:10.1002/mrc.3792

Research Article
Received: 14 October 2011
Revised: 23 December 2011
Accepted: 3 January 2012
Published online in Wiley Online Library: 10 February 2012
(wileyonlinelibrary.com) DOI 10.1002/mrc.3792
Structural and conformational analysis of
1-oxaspiro[2.5]octane and 1-oxa-2-azaspiro
[2.5]octane derivatives by 1H, 13C, and 15N NMR
Rubén Montalvo-Gonzáleza and Armando Ariza-Castolob*
A structural and conformational analysis of 1-oxaspiro[2.5]octane and 1-oxa-2-azaspiro[2.5]octane derivatives was performed
using 1H, 13 C, and 15 N NMR spectroscopy. The relative configuration and preferred conformations were determined by
analyzing the homonuclear coupling constants and chemical shifts of the protons and carbon atoms in the aliphatic rings.
These parameters directly reflected the steric and electronic effects of the substituent bonded to the aliphatic six-membered
ring or to C3 or N2. The parameters also were sensitive to the anisotropic positions of these atoms in the three-atom ring. The
preferred orientation of the exocyclic substituents directed the oxidative attack. Copyright © 2012 John Wiley & Sons, Ltd.
1
Additional NMR data as well as some example of H and 13 C NMR spectra may be found in the online version of this article.
Keywords: 1H, 13C, 15N, NMR; conformation; oxaziridines; oxiranes; spirocyclic
Introduction
Results
Three-membered heterocyclic rings, which can be converted
into
Assignment of the 1H and 13C NMR spectra of the
oxiranes and oxaziridines was conducted based on one- and
two-dimensional NMR experiments. The connectivities were
established by means of homonuclear (1H,1H-COSY) and
heteronuclear (1H,13C-HETCOR) correlation spectroscopy. Addi-
tionally, J-modulated spectra were recorded using the attached
proton test pulse sequence (APT) to distinguish between the
C, CH, CH2, and CH3 groups in compounds 1b–e, 2b–e, 3b–e,
4b–e, 5d, and 5e.
The three-atom ring substituent (R2) effect on the atoms of
the cyclohexenyl moiety of the oxaziridines or oxiranes was
assigned based on the change in the chemical shifts of the
equatorial and axial protons in the compounds derived from
symmetric ketones (1a, 1d, 1e, 2a, 2d, 2e, 3a, 3d, 3e, 4a,
4d, 4e, 5a, 5d, and 5e) or the syn/anti carbons. The magni-
tude of the CH- or N-substituent effects was related to their
orientation (pseudoaxial or pseudoequatorial).
a
large number of functional groups,[1] have been
invaluable intermediates in organic synthesis. They are easily
synthesized from the oxidation of alkenes (oxiranes)[2] or imines
(oxaziridines)[3] with preservation of their configuration, and their
rings are easily broken through addition reactions. Nitrogen
centers functionalized with three different substituents are
usually achiral because of lone-pair inversion; however,
inversion is prevented in oxaziridines at room temperature by
a ≥ 100.32 kJ/mol energy barrier,[4] resulting in a stable configu-
ration at the nitrogen.[5] This property has been advantageous
in the synthesis of chiral oxaziridines. The synthesis of chiral
oxiranes or oxaziridines, followed by ring opening via various
reactions, provides access to many important chiral com-
pounds.[6] In each part of the synthetic process, knowledge of
the configuration and conformational preference of the
spirocyclic oxiranes or oxaziridines is essential.
A
1H NMR structural analysis has been reported for the
Analogs without substituent groups on the six-membered
ring (1a, 2a, 3a, 4a, and 5a) were obtained, and they were
analyzed as racemic mixtures. Oxaziridine 4a and oxirane 1a
displayed a ring inversion frequency that was slower than the
300 MHz NMR time scale, and a pair of conformers was
detected (see the spectra in the supporting material).
spirocyclic oxaziridines with a methylbenzyl group bonded to
the oxaziridine nitrogen.[7] The preferential conformation of
the N-substituent determined the effects of this group on the
5,7 syn-diaxial protons.
Here, we report that the anisotropic positions (axial or
equatorial) of the three-membered ring atoms guided an
oxidant to preferentially attack the double exocyclic bond in
an olefin or imine. The preferential conformation of a six-atom
ring containing a monosubstituted alkyl group and the orienta-
tions of an oxirane or oxaziridine substituent also are described
with consideration for the effects of this group on the chemical
shifts of the six-membered ring atoms. To test this approach,
we synthesized compounds with or without an alkyl group
on the six-membered ring in which either an aromatic or an
alkyl group bonded to one of the atoms of the heterocyclic
ring (Fig. 1).
*
Correspondence to: Armando Ariza-Castolo, Centro de Investigación y de
Estudios Avanzados del IPN, Apartado Postal, 14–740, 07000 México D.F.,
México. E-mail: aariza@cinvestav.mx
a Unidad Académica de Ciencias Químico Biológicas y Farmacéuticas, Universidad
Autónoma de Nayarit, Tepic Nayarit, México
b Centro de Investigación y de Estudios Avanzados del IPN, Apartado postal,
14-740, 07000 México, D.F., México
Magn. Reson. Chem. 2012, 50, 33–39
Copyright © 2012 John Wiley & Sons, Ltd.

R. Montalvo-González and A. Ariza-Castolo
Figure 1. Structure and numbering of oxiranes 1a-1e and oxaziridines 2a-2e, 3a-3e, 4a-4e, 5a, 5d, and 5e.
1
The resonance integrals from the H NMR spectra were used
Discussion
to determine the ratio of isomers produced by oxidant attack
of either of the exocyclic double bond orientations (axial or
equatorial) was 9:1 for aromatic ketimines (oxaziridines 2b–2e
and 3b–3e) and 7 : 1 for aliphatic ketimines (oxaziridines
4a–4e, 5a, 5d, and 5e), which showed an equatorial attack
preference. The ratio for the aromatic exocyclic alkenes
(oxiranes 1a, 1c–1e)[8] was 2.3 : 1, indicating that the axial
attack was favored for the oxidant. The olefin 1b yielded an
oxidation ratio of 6 : 4 (equatorial/axial). The derivatives with
an alkyl group on C6 of the six-atom aliphatic ring (1d, 1e,
2d, 2e, 3d, 3e, 4d, 4e, 5d, and 5e) were present in two
enantiomeric pairs (cis-R and cis-S or trans-R and trans-S).
Derivatives of 3- or 2-methylcyclohexanone (1b, 1c, 2b, 2c, 3b,
3c, 4b, and 4c) were present in four pairs of isomers (namely,
cis-anti, trans-anti, cis-syn, and trans-syn; Fig. 2). The anti : syn
isomeric ratios were 10 : 1 for the 2-methylcyclohexanone
derivatives (1b, 2b, 3b, and 4b) and 10: 9 (anti : syn) for the
3-methylcyclohexanone derivatives (1c, 2c, 3c, and 4c). The
1H NMR spectra showed overlapping resonances for all isomers,
which made complete assignment difficult (see the supporting
material). The assignment of the atoms in the cyclohexenyl
moiety was determined based on the R1 alkyl substituent effects
and the cis/trans and/or syn/anti three-atom heterocyclic substit-
uent (R2) effects. An unequivocal assignment of the 13C NMR
spectra was made after partial chromatographic separation of
isomers 1c, 2b, 3c, and 4c (for instance, see the 13C NMR
spectrum of compound 2b in the supporting material). The
N-aromatic oxaziridines (2a–2e and 3a–3e) were transformed
into the corresponding e-lactams as a thermodynamic isomer.[9]
1H NMR
1
The strategy used for the H NMR spectral assignment included
analysis of the oxiranes and oxaziridines without substituents
on the cyclohexane, followed by spectral analysis of the deriva-
tives that included an alkyl group at C6. The experimental data
were interactively fit to simulated spectra (Fig. 3) using the pro-
gram NUTS or NUMARIT, which yielded the same results.[10]
The data of compounds 1d, 1e, 2d, 2e, 3a, 3d, 3e, 4a, 4d,
4e, 5d, and 5e are provided in Tables 1 and 2. The require-
ment for simulated spectra arose from the complexity of the
results, which included similar chemical shifts and complicated
coupling patterns. The signals of most of the protons revealed
up to five different couplings to other protons. The assignment
was performed with consideration for the chemical shifts, the
multiplicity, and the connectivity.
The observed preference of the oxidant for the equatorial
face in the exocyclic ketimine double bond C = N was caused
by the presence of steric restriction over the axial face by the
C5 and C7 axial protons and the preferential orientations of
the aromatic or alkyl N-substituents in the imines (the aromatic
ring was perpendicularly oriented over the plane of the
six-atom aliphatic ring).[8] Among aromatic exocyclic alkenes,
the oxidant showed preference for the axial face because of
the preferential conformation of the aromatic C substituent
(the aromatic ring was in the same plane as the six-atom
aliphatic ring)[8] and to the less energetic transition state.[11]
The equatorial orientation of attack was preferred only in the
Figure 2. Stereoisomers of compounds 1b and 1c. Only one enantiomer is shown, and both are presented as a racemic mixture.
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Copyright © 2012 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2012, 50, 33–39

Structure and conformation of 1-oxa- and 1-oxa-2-aza- spiro[2.5]octane
Figure 3. 1H NMR aliphatic region of oxaziridine 3e. From top to bottom: simulated and experimental spectra with the corresponding assignments.
Table 1. 1H NMR chemical shifts of six member ring region of the oxiranes 1d and 1e and the oxaziridines 2 d, 2e, 3 d, 3e, 4 d, 4e, 5 d, and 5e
4
5
6
7
8
Compound
1 d
eq
ax
eq
ax
1.22
1.3
1.24
1.34
1.44
1.5
1.79
1.45
1.5
eq
—
ax
1.5
eq
ax
eq
ax
1.6
trans
cis
trans
cis
trans
trans
1.46
1.47
1.41
1.45
1.69
1.7
1.84
1.7
1.71
1.58
1.39
1.4
1.99
1.94
1.96
1.93
1.98
1.97
1.84
2.02
2.01
1.58
1.85
1.86
1.75
1.7
1.88
1.74
1.93
1.81
1.92
2.01
1.79
1.96
2.05
1.54
1.83
1.92
1.52
1.63
1.56
1.72
1.51
1.57
1.54
1.57
1.63
1.64
1.83
1.94
0.74
1.29
0.75
1.35
1.01
1.06
1.54
1
1.04
1.64
1.16
1.22
1.23
1.24
1.25
1.23
1.27
1.29
1.41
1.22
1.24
1.85
1.93
1.94
1.98
2.17
2.24
—
1.48
1.04
1.06
1.54
1.14
1.53
1.59
1.18
1.72
1.58
1.14
1.42
1.55
1.32
1.76
1.79
1.41
1.84
1.87
1.85
1.89
1.9
1e*
—
—
2 d
2e
3a
3 d
3e
4a
4 d
4e
5a
5 d
5e
—
—
1.53
—
trans
trans
—
1.54
1.26
1.4
1.72
—
trans
trans
—
1.42
1.44
1.41
1.91
2.01
1.99
trans
trans
1.88
1.94
1.28
1.29
1.61
1.2
1.82
1.9
1.28
1.29
1.74
* The chemical shifts were established from 2D spectra (COSY and HETCOR).
Table 2. The 3JH,H and dihedral angle of six member ring part of oxirane 1 d and oxaziridine 5e
1 d (cis)
Dihedral angle (ꢀ)
1 d (trans)
Dihedral angle (ꢀ)
5e (trans)
Dihedral angle (ꢀ)
4ax,5ax
4ax,5 eq
4 eq,5ax
4 eq,5eq
5ax,6ax
5 eq,6ax
6ax,7ax
6ax,7 eq
7ax,8ax
7ax,8 eq
7 eq,8ax
7 eq,8eq
13.0
4.4
3.7
3.4
12.0
3.5
13
3.5
13.8
3.8
3.5
3.4
160
53
56
58
170
56
180
58
166
56
57
58
13.0
4.4
3.7
2.7
11.9
3.5
13.0
3.5
13.0
3.8
4.5
3.4
160
53
56
62
169
56
180
58
160
56
53
58
12.8
4.1
3.8
3.2
12.6
2.9
12
2.8
13.8
3.3
4.7
3.1
158.0
55.0
56.0
59.0
180.0
60.0
170.0
61.0
164.0
59.0
51.0
59.0
Magn. Reson. Chem. 2012, 50, 33–39
Copyright © 2012 John Wiley & Sons, Ltd.
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R. Montalvo-González and A. Ariza-Castolo
proton in the cis isomers of 1d and 1e but the C7 axial protons
were shifted toward higher frequencies by 0.55 Æ 0.05 ppm
relative to the corresponding protons in the trans 1d and 1e
isomers. In the oxiranes, protons bonded to C3 in the
pseudoaxial orientation were shifted toward higher frequencies
by 0.04 Æ 0.01 ppm relative to those in the pseudoequatorial
position.
The coupling constant pattern (Table 2) presented by the
proton base of the methyl group (3JH6ax,H5ax = 12.5 Æ 0.5;
3JH6ax,H5ec = 3.2 Æ 0.3; JH6ax,H7ec = 3.2 Æ 0.3; and JH6ax,H7ax = 12.5
Æ 0.5 Hz) showed that the chair conformation was preferred
based on the dihedral angles.[15] The four bond coupling
constants W (4JH4ec,H8ec) were larger among the oxaziridines
than among the oxiranes, yielding four bond coupling constant
differences between the oxaziridines and oxiranes of Δ4JH4ec,
H8ec = 0.7 Æ 0.1 Hz for the N-aromatic oxaziridines and Δ4JH4ec,
H8ec = 1.4 Æ 0.2 Hz for the N-aliphatic oxaziridines.
3
3
Figure 4. Anisotropic positions of the equatorial/axial protons on C4 or
C8 with respect to the three-atom heterocyclic ring.
oxirane 1b. During axial oxidant attack of the alkene
obtained from 2-methylcyclohexanone (oxirane 1b), large steric
interactions were present in the spirocyclic transition state[12]
because of the position of the methyl bonded to the aliphatic
six-membered ring.
The syn isomers of the 2-methylcyclohexanone derivatives
yielded three-bond coupling constants between the C4 and
Me protons (3JH4,Me = 7.2 Hz), revealing that the methyl group
was axially oriented.[16]
The equatorial protons bonded to the C4 and C8 carbons
of the C2-phenyl oxiranes (1d and 1e) and of the N-Ar
oxaziridines (2d, 2e, 3d, and 3e) exhibited abnormal chemical
shifts. These protons appeared at frequencies lower than
the frequency corresponding to the axial proton (Δd=0.45Æ
0.15).[13] This was caused by the anisotropic positions of the
equatorial C4 and C8 protons relative to the three-membered het-
erocyclic ring (Fig. 4).[13] Oxiranes display a ΔdH for the C4 protons
that is 0.2 ppm larger than the corresponding values of the N-Ar
oxaziridines; however, C8 protons in the N-Ar oxaziridines display
a ΔdH that is 0.55 Æ 0.05 ppm larger than the corresponding
oxirane shift. The ΔdH of the C4 protons of N-propyl (4d and
4e) and N-t-butyl (5d and 5e) oxaziridines are similar to those
of the corresponding protons of the N-Ar oxaziridines (2d, 2e,
3d, and 3e); however, among the C8 protons of the N-aliphatic
oxaziridines, equatorial protons occurred at positions 0.06 Æ 0.01
ppm higher than the axial protons. This was caused by the
presence of strong steric interactions between the N-alkyl group
and the equatorial proton.[14]
The equatorial protons bonded to C5 and C7 of the trans
isomers of the oxiranes (1d and 1e) and N-Ar oxaziridines
(2d, 2e, 3d, and 3e) displayed indistinguishable spectral signa-
tures; however, the axial proton bonded to C7 of these com-
pounds was shifted toward lower frequencies by 0.40 Æ 0.05
ppm relative to the proton bonded to C5. This showed that
the C7 axial proton was shielded by the aromatic C3 (1d and
1e) or N2 (2d, 2e, 3d, and 3e) substituents (Fig. 5). The same
13C NMR
The complete 13C NMR spectral assignments of all isomers of
oxiranes (1a–1e) and oxaziridines (2a–2e, 3a–3e, 4a–4e, 5a,
5d, and 5e) are shown in Table 3. These assignments were
made considering the substituent effects, their positions and
orientations, and the connectivity and abundance of isomers
of all compounds, except for those obtained from the imines
derived from cyclohexanone (1a, 2a, 3a, 4a, and 5a).
Unequivocal assignment of all isomer derivatives produced
by oxidation of the imines obtained from 2-methyl- (1b, 2b,
3b, and 4b) or 3-methylcyclohexanone (1c, 2c, 3c, and 4c)
was made using the spectra obtained after partial chromato-
graphic separation.
13C NMR analysis of the substituent effects on the six-
membered ring atoms was performed with consideration for
the chemical shifts of the unsubstituted cyclohexyl com-
pounds (1a, 2a, 3a, 4a, and 5a).
The spiro carbon (C3) signal of the N-aromatic oxaziridines
(2a–2e and 3a–3e) was shifted toward higher frequencies by
4.15 Æ 0.2 ppm relative to the positions of the corresponding
carbons of the N-aliphatic oxaziridines (4a–4e, 5a, 5d,
and 5e). The nitrogen in the heterocyclic three-membered
oxaziridines (2a–5e) shifted the spiro carbon signal by
21.5 Æ 2.0 ppm relative to the positions of the corresponding
carbons (C2) on the oxiranes (1a–1e). Larger shifts were
observed among the aromatic oxaziridines.
Although atoms 1 and 2 of the oxaziridines (O1 and N2) and
oxiranes (O1 and C2) were present at the center of the plane
formed by the six-membered ring, a small increase in the
inductive effect transference of the chemical shift over C3
and C4 (ΔdC3 = 0.6 Æ 0.3 ppm and ΔdC4 = 0.4 Æ 0.14ppm) was
observed for the case in which the oxygen (in the three-atom
ring) was present in the pseudoequatorial position.
The syn/anti orientation of the aromatic substituent of
those compounds obtained from the symmetrically substituted
ketones generated a ΔdC4-C8 of 7.5 Æ 0.2 between C4 and C8
and a ΔdC5-C7 = 1.5 Æ 0.3 between C5 and C7 in the trans
isomer. Larger effects were observed for the aromatic
oxaziridines because of the preferred conformation of the
Figure 5. Preferential orientations of the aryl groups (left) in the oxazir-
idines, and (right) in the oxiranes.
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Copyright © 2012 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2012, 50, 33–39

Structure and conformation of 1-oxa- and 1-oxa-2-aza- spiro[2.5]octane
Table 3. 13 C Chemical shifts of the spirocyclic region of compounds 1a–5e
Compound
1aa
3
4
5
6
7
8
64.5
35.4
25.43
33.57
32.78
30.59
29.87
33.11
30.73
29.89
30.71
34.52
32.63
27.1
25.17
25.07
32.45
32.66
31.69
30.92
32.07
31.81
30.06
30.99
33.15
32.68
25.87
25.52
24.91
32.36
32.42
31.42
30.75
31.85
31.54
29.89
30.71
33.1
24.69
24
24.7
25.3
28.54
27.91
29.9
trans-antib
cis-antic
cis-synd
trans-syne
cis-antif
trans-antib
cis-synh
trans-syni
transj
60.52
63.36
64.59
64.72
64.76
64.46
64.82
64.35
64.85
64.38
64.95
64.4
37.24
36.61
30.31
29.49
44.14
43.3
36.8
36.44
35.2
34.53
35.71
35.29
35.76
37.62
37.27
31.1
24.98
26.33
24.32
25.53
24.09
23.32
25.2
23.65
33.35
32.41
25.88
25.03
24.69
24.08
24.56
24.32
25.25
22.32
23.39
23.86
23.8
31.52
32.26
24.01
24.93
24.66
23.76
24.33
24.12
25.05
22.03
23.03
23.59
23.46
31.42
32.23
23.62
24.1
1b
20.13
19.53
34.07
34.28
31.63
34.49
31.78
31.97
47.25
47.87
24.06
23.09
23.67
19.5
19.07
33.31
33.78
33.39
33.97
31.04
31.41
46.48
47.11
24.02
22.95
23.42
19.24
18.76
32.89
33.31
32.98
33.5
30.22
29.58
27.98
27.85
35.28
34.66
27.89
27.73
28.38
28.52
29.15
27.8
1c
1 d
cisk
transl
cisc
1e
2a
87.76
89.7
trans-anti
cis-anti
cis-syn
trans-syn
cis-anti
trans-anti
cis-syn
trans-syn
trans
2b
89.26
90.89
90.59
87.86
87.5
87.87
87.5
87.84
87.3
88.06
87.39
88.48
90.47
88.13
91.41
91.2
88.37
88.13
88.41
88.13
88.69
87.92
88.98
88.05
84.25
86.31
85.96
86.9
28.7
30.82
29.27
27.61
29.89
35.2
34.97
27.42
29.15
27.83
n.d.
29.23
27.79
28.67
30.49
29.1
27.47
29.57
34.75
34.46
27.52
29.23
27.55
nd
27.74
26.02
26.18
30.89
29.14
27.27
27.31
36.01
36.14
26.94
27.24
27.42
27.75
29.67
28.21
29.15
28.9
29.82
43.8
43.65
36.29
37.97
34.99
34.72
35.55
35.31
35.55
37.28
36.9
30.88
29.96
43.3
43.11
36.11
37.77
34.77
34.59
34.93
34.5
36.34
38.33
37.68
31.75
31.02
44.93
44.36
36.28
35.57
35.99
35.55
36.54
35.99
38.16
37.75
37.39
38.66
37.83
2c
2 d
2e
cis
trans
cis
3a
3b
trans-anti
cis-anti
cis-syn
trans-syn
cis-anti
trans-anti
cis-syn
trans-syn
trans
3c
3c
3 d
3e
30.94
31.27
45.98
46.76
24.38
22.68
23.15
19.74
19.25
33.81
nd
cis
trans
cis
32.64
25.49
nd
4a
4b
25.3
24.78
25.06
25.1
24.02
25.23
24.07
nd
trans-anti
cis-anti
trans-syn
cis-syn
cis-anti
trans-anti
cis-syn
trans-syn
trans
31.83
32.23
31.2
nd
32.08
nd
86.9
84.6
4c
83.04
84.64
83.04
84.63
84.26
84.63
84.22
85.03
85.87
84.41
86.22
84.45
31.98
nd
33.97
nd
32.16
nd
4 d
4e
33.25
32.97
25.99
25.56
25.3
33.55
33.49
26.17
26.1
31.55
31.88
47.09
47.45
24.43
31.24
31.60-
47.01
47.11
33.21
32.18
25.77
24.67
25.3
33.07
32.36
25.86
24.81
cis
trans
cis
5a
5 d
trans
cis
trans
cis
5e
29.63
adC2 = 65.49; b dC2 = 68.13: c
d
C2 = 67.79; d
d
C2 = 68.00; e
d
C2 = 68.22; f dC2 = 65.73;
bdC2 = 65.31; h
cdC2 = 65.30
d d dC2 = 66.21;
C2 = 65.76; i dC2 = 65.35; j dC2 = 65.94; k C2 = 65.07; l
Magn. Reson. Chem. 2012, 50, 33–39
Copyright © 2012 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/mrc

R. Montalvo-González and A. Ariza-Castolo
aromatic substituent, which generated steric interactions
between the ortho and axial C7 protons. The stronger steric
effects induced by the propyl group in compounds 4a–4e
shifted C8 toward lower frequencies relative to other com-
pounds. The cis isomers of the oxiranes and the oxaziridines
C5 and C7 yielded almost identical chemical shifts. The low-
frequency chemical shifts of C6 (dC = 19.7 Æ 0.4) and C4
(dC = 30.5 Æ 1) in the 2-methylcyclohexanone derivatives
(1b, 2b, 3b, and 4b) of the Z isomer resulted from the
Experimental Section
Synthesis
The synthesis of exocyclic olefin and imine precursors of the
oxiranes (1a–1e) and oxaziridines (2a–4e) has been reported
previously.[8] The synthesis of imines produced the oxaziridines
5a, 5 d, and 5e using TiCl4, as reported by Carlson et al.[21]
The oxiranes 1a–1e and oxaziridines 2a–2e, 3a–3e, 4a–4e,
5a, 5d, and 5e were prepared by mixing 2 molar equivalent
of the m-chloroperbenzoic acid and 1 equivalent of the
corresponding imine or alkene in methylene chloride. The reac-
tions were carried out at 0ꢀC with constant stirring for 1 h. To
the resulting solution was added water in a volume of ten
times the methylene chloride volume, and the solution was
extracted three times with 200 ml CH2Cl2. The portions were
joined and dried over anhydrous MgSO4. The oxaziridines were
purified using a flash chromatography alumina (2a–2e) or silica
gel (3a–3e, 4a–4e, 5a, 5d, and 5e) column and 90% hexane/
10% ethyl acetate as the eluting agent. The oxiranes were
not purified because no side products were obtained. The geo-
metric isomers of 1d and 1e were separated by chromatogra-
phy (silica gel flash column with hexane/ethyl acetate 95 : 5 as
the eluent).
g
axial–ggauche (Δd= 4.5 Æ 0.8) effects of the methyl substituent.
Previous reports have attributed this observation to the
nitrogen lone pair effects on the chemical shift, particularly
with respect to Ca.[17]
15N NMR
The 15 N NMR data for the majority of the isomers are given
in Table 4. Only the derivatives of the methyl group at C3
(2c, 3c, and 4c) yielded two isomers corresponding to the
syn-anti isomers of the trans compounds. The spectra of com-
pounds 3a and 3b were not detected by the INEPT pulse
sequence because it was not possible to estimate JN,H a priori.
The coupling constant was 5.5–6.9, which agreed well with
2
the values reported in the literature for JN,H, in which an alkyl
group was present anti to the lone pair.[18]
The chemical shifts determined here were similar to
those previously reported.[19] The N-C6H5 and N-CH2CH2CH3
derivatives did not display significant differences in the
1H NMR assignments
The chemical shifts and spin–spin coupling constants of the
protons of the cyclohexane rings were determined based on
computer simulations[10] carried out for subsystems of ten nuclei.
The number of spins corresponding to the methyl protons was
reduced by symmetry considerations because the three methyl
protons were chemically and magnetically equivalent. The root
mean square error between the experimental and simulated
spectra was 0.21 Hz. Excellent agreement was observed with
the experimental spectrum when the long-range coupling
chemical shifts of 15 N (ΔdN < 1.4 derivative 2 with 4) and
2/3
the coupling constant
J
(ΔJ < 1.4). The main differences
N-H
were observed for the derivatives containing a C2-CH3 moiety.
Additionally, the syn-anti isomer of compound 2c yielded a
ΔdN of 2.4, similar to that observed for 4c (ΔdN = 2.3), whereas
the difference was only 0.1 ppm for compound 3c. These
observations agreed well with previously reported observa-
tions for spiro[4.5]decanes.[20]
5
constants (4JH,H and JH,H) were taken into account.
Conclusions
Spectra
The perpendicular orientations of the N-aryl and N-propyl
groups protected the Re face of the oxidant against attack
in the ketimines, but the preferential coplanar orientations of
the aromatic substituents and the exocyclic alkenes favored
the Re face. The three bonds of the heterocyclic ring (oxiranes
or oxaziridines) generated an unprotected diamagnetic current
over the equatorial protons bonded to C4 and C8. The prefer-
ential conformation of the aryl substituent was one in which
diamagnetic current lines protected the axial proton bonded
to C7.
NMR spectra of compounds 1a–5e were recorded at 18 Æ 1ꢀC
using a Bruker 300 Avance spectrometer equipped with a 5-mm
multinuclear probe. All spectra were obtained using a CDCl3
solution (0.9 mmol of the compound per 0.4 ml solvent). The
chemical shifts were referenced[22] with respect to an internal
(CH3)4Si (d1H = 0, d13C = 0) or neat CH3NO2 (d15N = 0 for Ξ15N =
10.136767 MHz). 1H NMR spectra were recorded at 300 MHz
(spectral width: 6188.1 Hz, acquisition time: 2.648 s, 16 384
data points, equivalent 30o pulse duration, 16 scans, recycle
delay: 1 s). 13C{1H} NMR spectra were recorded at 75.47 MHz
Table 4. 15 N Chemical shifts of compounds 2a–4e
Compound
d
15 N
3JH,H
Compound
d 15
N
3JH,H
Compound
d
15 N
3JH,H
2a
2b
2c
À212.7
À216.9
À212.5
À214.9
À211.9
À211.9
6.2
nd
6.2
6.5
6.6
nd
3a
3b
3c
nd
nd
À218.0
À218.1
À217.4
À217.4
nd
nd
nd
nd
nd
5.9
4a
4b
4c
À211.8
À215.5
À213.6
À215.9
À210.9
À210.8
6.9
nd
5.6
5.5
nd
nd
2 d
2e
3 d
3e
4 d
4e
Nd, not determined.
wileyonlinelibrary.com/journal/mrc
Copyright © 2012 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2012, 50, 33–39

Structure and conformation of 1-oxa- and 1-oxa-2-aza- spiro[2.5]octane
(spectral width: 17 361.1 Hz, 32 768 data points, equivalent 30ꢀ
pulse duration, 256 scans, recycle delay: 0.01 s). Similar conditions
were used for the APT and INEPT spectra. 15N NMR spectra of
compounds 2a–5e were recorded at 30.38 MHz by using INEPT
methods[23] (spectral width: 15151.6 Hz; 16 384 data points, from
1024 to 13 706 scans, depending on the solubility; recycle delay:
[5] (a) W. H. Pirkle, P.L. Rinaldi, J. Org. Chem. 1977, 42, 3217; (b) W.
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251; (c) G. V. Shustov, S. V. Varlamov, I. I. Chervin, A. E. Aliev, R.
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Tetrahedron 2002, 58, 4981.
4 s, the delays were optimized in agreement with JN,H). H–1H
COSY spectra were obtained using the cosy45 pulse sequence[24]
with a 1024 Â 512 data point matrix and a 751.20 Â 751.20 Hz
frequency matrix. The recycle delay was 2 s, and a total of 16
scans were performed. Fourier transformations were carried out
for F1 and F2 using a sine function in the absolute value mode.
13C–1H COSY spectra were obtained with the HETCOR pulse
sequence for the aliphatic region[22] using a 2048 Â 256 data
point matrix and a 6265 Â 751 Hz frequency matrix. The pulse
time intervals 1 and 2 were set to 2 Â 1/4JC,H = 1.85 ms. The
recycle delay was 2 s, and a total of 16 scans were performed.
Fourier transformations were carried out using a square sine
function for F1 and F2 in the absolute value mode. MS studies
of compounds 2a–5e were conducted using a Hewlett–Packard
5890 spectrometer coupled to a gas chromatograph in the EI
mode (at 70 eV). No mass spectra could be obtained for
compounds 1a–1e because of their instability at their respective
boiling temperatures.
3
1
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Magn. Reson. Chem. 2012, 50, 33–39
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