Correlation between 13C and 17O chemical shifts and torsional strain in spiroacetals

Article abstract of DOI:10.1016/j.tetlet.2006.11.162

The relationship between the ¹³C and ¹⁷O NMR chemical shifts and the dihedral energies (non-bonding interactions) of 1,4-dioxaspiro[4.4]nonane, 1,4-dioxa- and 6,10-dioxaspiro[4.5]decane, 1,4-dioxa- and 6,11-dioxaspiro[4.6]undecane, 1,5-dioxaspiro[5.5]undecane, 1,5-dioxa and 7,12-dioxaspiro[5.6]dodecane and 1,6-dioxaspiro[6.6]tridecane were analyzed. These data showed correlation of the non-bonding interactions with the chemical shift of the spiranic carbon, as well as a linear relationship between ¹³C and ¹⁷O.

Full text of DOI:10.1016/j.tetlet.2006.11.162

Tetrahedron Letters 48 (2007) 795–798
13
17
Correlation between C and O chemical shifts
and torsional strain in spiroacetalsI
Jorge Antonio Guerrero-Alvareza,* and Armando Ariza-Castolob,*
aCentro de Investigaciones Quı´micas de la Universidad Auto´noma del Estado de Morelos,
Av. Universidad No. 1001 Col. Chamilpa, Cuernavaca Morelos 62209, Mexico
bDepartamento de Quı´mica, Cinvestav, Apartado 14-740, 07000 Me´xico, DF, Mexico
Received 24 October 2006; revised 17 November 2006; accepted 28 November 2006
Available online 19 December 2006
Abstract—The relationship between the 13C and 17O NMR chemical shifts and the dihedral energies (non-bonding interactions) of
1,4-dioxaspiro[4.4]nonane, 1,4-dioxa- and 6,10-dioxaspiro[4.5]decane, 1,4-dioxa- and 6,11-dioxaspiro[4.6]undecane, 1,5-dioxa-
spiro[5.5]undecane, 1,5-dioxa and 7,12-dioxaspiro[5.6]dodecane and 1,6-dioxaspiro[6.6]tridecane were analyzed. These data showed
correlation of the non-bonding interactions with the chemical shift of the spiranic carbon, as well as a linear relationship between
13C and 17O.
Ó 2006 Published by Elsevier Ltd.
1. Introduction
quency as the ring size decreases.7 Krivdin determined
that the spiranic systems have a dependence on the
one bond carbon–carbon coupling constant with respect
to annular strength in spiroalkanes.8 Theoretical calcu-
lations revealed that the JC,C value is directly propor-
tional to the steric strain in this type of systems.
The correlation between the chemical shift and the
molecular structure is an essential part of modern chem-
istry. The substituent chemical shift (SCS)1 as well as the
lone-pair are two of the most important effects used in
structure elucidation.2 These effects have been of great
value to explain the change observed in the 13C and
17O chemical shifts of alcohols where it has been applied
to the conformational3 analyses of heterocyclic systems.
Thus it has been concluded that the 15N chemical shift
difference between the axial–equatorial nitrogen substit-
uents can be attributed to steric hindrance in the axial
nitrogen owing to 1,3-syn-diaxial hydrogen interactions.
The structure analyses of spiranic compounds showed
an experimental linear relationship between the 15N
and the 17O chemical shift. The like–unlike4 relative con-
figuration in substituted 1,4-diazaspiro[4.5]decanes was
established by the c-axial, c-equatorial,5 c-heterocycle
and b-heterocycle6 effects.
1
The annular strain of substituted dioxospiro[4.4]nonane,
dioxospiro[4.5]decane, dioxospiro[5.5]undecanes, dioxo-
spiro[4.6]undecanes, dioxospiro[5.6]dodecanes and
dioxospiro[6.6]tridecane is analyzed in this Letter
(Scheme 1). These compounds were prepared by
condensation of cyclic ketones with the corresponding
di-alcohols.9 The 17O and 13C chemical shifts for the
spirane carbon (carbon that is the bridge between two
cyclic systems) showed important effects on the size of
the system due to enhancement of the annular strain.
This effect was analyzed considering the annular energy
parameter due to the torsion angle estimated by mole-
cular mechanics.10
The 17O NMR data for 1,3-dioxane and 1,3-dioxolane
systems have shown that there is a shift to high fre-
2. Results and discussion
Keywords: Dioxaspiro derivatives; Annular strength; 13C and 17O
The data analyses are based on the 13C and 17O chemical
shifts which depend on the size of the spiranic rings. It
was observed that the d13C for the spiranic carbon is
shifted to high frequency when the ring size decreases,
while it seems to be variable for the d17O.
NMR.
q This work is part of the J. A. Guerrero-Alvarez Ph.D. Thesis
Cinvestav 2004.
*
Corresponding authors. Tel.: +52 55 50613727; fax: +52 55 50613389
(A.A.-C.); e-mail: aariza@cinvestav.mx
0040-4039/$ - see front matter Ó 2006 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2006.11.162

796
J. A. Guerrero-Alvarez, A. Ariza-Castolo / Tetrahedron Letters 48 (2007) 795–798
10.0 ppm
O
O
O
O
4.6 ppm
O
O
1,4-dioxaspiro[4.5]decane
1,4-dioxaspiro[4.4]nonane
1,4-dioxaspiro[4.6]undecane
1
2
3
8.7 ppm
10.6 ppm
10.9 ppm
O
O
O
O
O
11.9 ppm
4.3 ppm
O
6,10-dioxaspiro[4.5]decane 1,5-dioxaspiro[5.5]undecane 1,5-dioxaspiro[5.6]dodecane
4
5
6
3.3 ppm
2.5 ppm
3.1 ppm
O
O
O
11.2 ppm
4.5 ppm
O
O
O
6,11-dioxaspiro[4.6]undecane 7,12-dioxaspiro[5.6]dodecane 1,6-dioxaspiro[6.6]tridecane
7
8
9
Scheme 1. Chemical shift effect of spiranic carbon taking compound 5 as reference.
The data in Table 1 show that there are three different
series of dioxaspiro derivatives: the 1,3-dioxolane, 1,3-
dioxane and 1,3-dioxepane, where the chemical shifts
of compounds 2, 5 and 8 are less shifted in carbon, as
well as in oxygen. The chemical shift difference of these
compounds for each series was determined taking as
reference 2, 5 and 8. It can be inferred from these results
that the chemical shift is affected by ring size as
evidenced by the spiranic carbon chemical shift.
dioxane derivatives (4–6) to 1,3-dioxepane derivatives
(7–9) it shifted 3.0 ppm in average. Furthermore, when
the heterocyclic part contracts, as in compounds 2, 5,
8 to 1, 4, 7 it shifted 11 ppm, whereas expansion to 3,
6, 9 shifted the signal to 4.4 ppm, approximately. These
results show a strong tendency of the spiranic carbon
chemical shift on the annular systems. Similar tenden-
cies have been observed in spiroalkanes such as
spiro[4.5]decane,11 where the chemical shift difference
of the spiranic carbon shifted 9.9 ppm with respect to
1,5-dioxaspiro[5.5]undecane 5.
Scheme 1 shows the chemical shift effects due to the sizes
of both rings. This scheme summarizes the chemical
shift effects on the spiranic carbon when the system con-
tracts from 1,3-dioxane derivatives (4–6) to 1,3-di-
oxolane derivatives (1–3) where this carbon is shifted
10.0 ppm. Moreover, when the ring expands from 1,3-
As expected, the chemical shift for the carbon at the
fusion of the two rings was more affected owing to the
annular strain since these compounds have different
cyclic systems. Pitzer12 explained this strain in annular
systems by determining that a small annular system such
as cyclobutane and cyclopentane, has a strong strain
relative to cyclohexane or cycloheptane.
Table 1. 13C and 17O chemical shifts of dioxaspiro derivatives
O
(CH2)n
(CH2)m
In order to determine the effect of annular strain on the
chemical shift, the different energy contributions of these
structures were estimated by means of PM3 semiempir-
ical calculations13 which were used to optimize the
geometry. A linear correlation between the chemical
shift with the energy generated by dihedral angle inter-
actions was found (Fig. 1). The structure analyses of
the optimized geometries showed that the more stable
conformation for five, six and seven member rings, in
spirane derivatives, are the envelope, chair and half
chair, respectively. A linear correlation between the
chemical shift with the energy due to dihedral angle
interactions generated by the MM+14 single point, was
found (Fig. 1).
O
Compound
d13
C
d17
O
2
3
10
20
30
Cspiro
O
1
2
3
4
5
6
7
8
9
63.9
63.8
63.9
37.8 23.3
34.8 23.5 24.6 108.3 54.4
38.4 29.3 22.4 112.9 63.3
118.3 65.3
63.9 29.3 35.2 23.9
58.9 28.9 32.8 22.5 25.9
61.3 29.6 35.2 25.9 21.6 102.0 47.6
61.9 29.6 36.3 20.9 112.0 62.0
61.3 29.7 33.9 23.0 25.6 100.8 53.9
61.8 30.0 37.3 24.2 22.3 105.3 60.4
109.6 51.5
97.7 44.6
n = 0 (1–3), n = 1 (4–6), n = 2 (7–9); m = 0 (1, 4, 7), m = 1 (2, 5, 8),
m = 2 (3, 6, 9).
Note: The d13C and d17O for compounds 1 to 3 are in agreement with
the previous report9a and the 13C for compounds 5 and 6 were reported
in Ref. 9b.
The linear correlation present in plot 1 showed that the
dihedral strain energy is the result of non-bonding inter-
actions10 (interaction energy of the atoms that form the

J. A. Guerrero-Alvarez, A. Ariza-Castolo / Tetrahedron Letters 48 (2007) 795–798
797
120.0
115.0
110.0
105.0
100.0
95.0
40
39
38
37
36
35
34
33
90.0
15.0
25.0
35.0
45.0
55.0
65.0
32
Dihedral Energy (kJ/mol)
40
50
60
70
Figure 1. Relationship between the dihedral energy and the chemical
shift of the spiranic carbon. d13C = 90.71 + 0.39 (dihedral energy);
r2 = 0.97.
17O
δ
Figure 3. Correlation between 17O and 13C chemical shifts in equiv-
alent positions. d13C = 19.56 + 0.30d17O; r2 = 0.98.
dihedral angles), which is the main contribution of the
observed effects to the chemical shift of the spiranic
carbons in this type of systems.
ever, in the case of 1,6-dioxepanes, the seven member
rings have more flexible conformations.
In addition, the contribution of the Mulliken charge in
¨
In agreement with our previous observations, we found
a linear relationship between 13C and 17O. As expected,
the effect on the oxygen chemical shift was about three
times larger than the carbon effect in the equivalent
position (Fig. 3)
the spiranic carbon was analyzed, even though the
chemical shifts do not depend linearly on this charge.
This analysis is in agreement with previous works15
where the dependence of the chemical shift on the charge
density was determined; in other words, the density of
the charge does not represent the main contribution to
the chemical shift on the spiranic carbons in this type
of systems.
d13C ¼ 19:53 þ 0:3d17O ðr2 ¼ 0:98Þ
3. Conclusions
A similar analysis was made for the variation of the oxy-
gen chemical shift which showed a linear correlation
with the dihedral energy (Fig. 2) when only compounds
1–6 were considered.
The differences observed in the linear correlations with
respect to the chemical shifts of the spiranic carbon
and oxygen are attributed to the fact that the spiranic
carbon is affected by the strain of the two rings that
form the system; whereas the oxygen is present only in
the heterocyclic part.
From these data it can be inferred that the oxygen chem-
ical shift effects are due to the nature of the ring, appar-
ently there is not a general relationship between dihedral
energy and d17O, therefore it is only possible to analyze
it within each series of the three types of derivatives: 1,3-
dioxolane, 1,3-dioxane and 1,3-dioxepane. The nature
of the heterocycle is related to ring strain due to the fact
that it depends on the ring size. This effect is more
important in 1,3-dioxolanes than in 1,3-dioxanes. How-
The positive slopes in the plots of Figures 1–3 are indic-
ative of the chemical shift effect in the spiranic carbon,
as well as in the oxygen. They present similar tendencies
with respect to strain. In general, these analyses show
that any change in the structure affects significantly the
chemical shift. In particular, when the strain in the
spiranic systems increases, the signal for the atom at
the fusion of the two rings shifts to high frequency.
70
65
60
55
50
45
40
Supplementary data
Supplementary data (experimental part, characteriza-
tion and theoretical calculations) associated with this
article can be found, in the online version, at
doi:10.1016/j.tetlet.2006.11.162.
10.0
20.0
30.0
40.0
50.0
60.0
70.0
80.0
Acknowledgements
Dihedral Energy (kJ/mol)
The authors express their gratitude to Dr. Rosa Santi-
llan for her critical reading and CONACYT for the
scholarship of J.A.G.-A.
Figure 2. Relationship between the dihedral energy and the oxygen
chemical shift of compounds 1–6. d17O = 33.88 + 0.45 (dihedral
energy); r2 = 0.93.

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J. A. Guerrero-Alvarez, A. Ariza-Castolo / Tetrahedron Letters 48 (2007) 795–798
10. (a) Wiberg, K. B. Angew. Chem., Int. Ed. Engl. 1986, 25,
References and notes
312–322; (b) Liebman, J. F.; Greenberg, A. Chem. Rev.
1976, 76, 311–365.
11. (a) Kalinowski, H. O.; Berger, S.; Braun, S. Carbon-13
NMR Spectroscopy; John Wiley: New York, 1984; pp 92–
449; (b) Kutschan, R.; Ernst, L.; Wolf, H. Tetrahedron
1977, 33, 1833–1842.
1. Witanowski, M.; Stefaniak, L.; Webb, G. A. Ann. Rep.
NMR Spectrosc. 1993, 25, 1–480.
2. Alam, T. M. Magn. Reson. Chem. 1998, 36, 132–134.
3. Subramanian, P. K.; ChandraSekara, N.; Ramalingam,
K. J. Org. Chem. 1982, 47, 1933–1935.
12. Eliel, E. L.; Wilen, S. H.; Mander, L. N. Stereochemistry
of Organic Compounds, 1st ed.; John Wiley and Sons: New
York, 1994; pp 665–811.
13. Stewart, J. J. P. J. Comput. Chem. 1989, 10, 209–220.
14. Spregue, J. T.; Tai, J. C.; Allinger, N. L. J. Comput. Chem.
1987, 8, 581–603.
15. Grutzner, J. B. In Recent Advances in Organic NMR
Spectroscopy; Lambert, J. B., Rittner, R., Eds.; Chemical
Shift Theory. Orbital Symmetry and Charge Effects On
Chemical Shift; Norell Press: Landisville, NJ, 1987; pp 17–
42.
4. Seebach, D.; Prelog, V. Angew. Chem., Int. Ed. Engl. 1982,
21, 654–660.
5. Ariza-Castolo, A.; Godoy-Reyes, J. Magn. Reson. Chem.
1999, 37, 219–222.
6. Guerrero-Alvarez, J. A.; Moncayo-Bautista, A.; Ariza-
Castolo, A. Magn. Reson. Chem. 2004, 42, 524–533.
7. Pihlaja, K.; Nummelin, H.; Klika, K.; Czombos, J. Magn.
Reson. Chem. 2001, 39, 657–671.
8. Krivdin, L. B. Magn. Reson. Chem. 2004, 42, 500–511.
9. (a) Taskinen, E. Struct. Chem. 2002, 13, 53–63; (b) Micovic,
V. M.; Stojiljkovic, A. Tetrahedron 1958, 4, 186–1996.