Stereomutation of conformational enantiomers of 9-isopropyl-9- formylfluorene and related acyl derivatives

Article abstract of DOI:10.1021/jo8008897

(Figure Presented) Low-temperature NMR spectra show that the title compound exists as a pair of conformational enantiomers, generated by the restricted rotation about the C9-Prⁱ bond, the corresponding interconversion barrier being 6.9 kcal mol^-1. This interpretation is supported by theoretical (MM and DFT) calculations and by the experimental determination of the analogous barriers occurring in the related MeC=O and Bu^tC=O derivatives.

Full text of DOI:10.1021/jo8008897

CHART 1
Stereomutation of Conformational Enantiomers
of 9-Isopropyl-9-formylfluorene and Related Acyl
Derivatives
Daniele Casarini,*,† Lodovico Lunazzi,‡ and
Andrea Mazzanti*,‡
preparation of drugs acting as calcium antagonists in the case
of cardiovascular activity.4
Department of Chemistry, UniVersity of Basilicata, Via N.
Sauro 85, Potenza 85100, Italy, and Department of Organic
Chemistry “A. Mangini”, UniVersity of Bologna,
Viale Risorgimento 4, Bologna 40136, Italy
As shown in Figure 1, the 13C methyl signal of 1 broadens
on cooling and eventually splits, at -146 °C, into two lines
separated by 3.34 ppm. The rate constants derived from line
shape simulation yield a free energy of activation of 6.9 kcal
mol-1 for the observed dynamic process.5
casarini@unibas.it; mazzand@ms.fci.unibo.it
ReceiVed April 24, 2008
Low-temperature NMR spectra show that the title compound
exists as a pair of conformational enantiomers, generated by
the restricted rotation about the C9-Pri bond, the corre-
sponding interconversion barrier being 6.9 kcal mol-1. This
interpretation is supported by theoretical (MM and DFT)
calculations and by the experimental determination of the
analogous barriers occurring in the related MeCdO and
ButCdO derivatives.
FIGURE 1. Temperature dependence of the 13C methyl signal (150.8
MHz) of 1 in CHF2Cl/CHFCl2 (left). On the right is displayed the
simulation obtained with the rate constants reported.
Also the 13C aromatic signals display the same type of
dynamic behavior on lowering the temperature. In Figure 2,
for instance, the two lines of the two quaternary carbons broaden
and, likewise, split into two pairs of lines at -146 °C.
The barrier derived from this spectrum (6.9 kcal mol-1) is
the same as that obtained by the analysis of the methyl signals,
thus indicating that both spectra are monitoring the same
dynamic process. Analogous spectral features were observed
by means of the 1H spectra, as reported in Figures S-1 and S-2
of the Supporting Information.
These results indicate that the molecule adopts an asymmetric
conformation (C1 point group) having lost the dynamic sym-
metry (Cs) that accounts for the ambient temperature NMR
spectrum.
The measured barrier could arise, in principle, from three
possible situations: (i) if the C9-CHO rotation is faster than
the C9-Pri bond rotation, then the latter motion would be
responsible for the value of the barrier; (ii) if, on the contrary,
the C9-Pri bond rotation is the faster of the two motions, the
measured barrier would be that due to the rotation about the
Restricted rotation processes have been observed in a variety
of fluorenyl derivatives bearing at least one aryl substituent in
position 9.1,2 The large number of reported examples is due to
the fact that the corresponding barriers are relatively high, thus
quite easy to detecte by NMR technique. On the other hand,
the barriers for the analogous processes occurring in the
alkylfluorenyl derivatives are expected to be very low, thus
accounting for the absence of these values in the literature (only
very recently has one such case been detected3). We report here
a study of the dynamics of the rotation process about the
C9-isopropyl bond in the title compound 1 (Chart 1), which
has been selected since it is a key intermediate for the
† University of Basilicata.
‡ University of Bologna.
(1) See: Oki, M. Applications of Dynamic NMR Spectroscopy to Organic
Chemistry; VCH Publisher: Deerfield Beach, FL, 1985211
(2) Nishida, A.; Akagawa, Y.; Shirakawa, S.; Fujisaki, S.; Kajigaeshi, S.
Can. J. Chem. 1991, 69, 615–619.
(4) Gualtieri, F.; Teodori, E.; Bellucci, C.; Pesce, E.; Piacenza, G. J. Med.
Chem. 1985, 28, 1621–1628.
(5) As often observed in conformational processes, the free energy of
activation was found independent of temperature within the errors, indicating a
negligible value of ∆S*. See, for instance: (a) Lunazzi, L.; Mancinelli, M.;
Mazzanti, A. J. Org. Chem. 2007, 72, 5391–5394, and references quoted therein.
(3) Casarini, D.; Lunazzi, L.; Mazzanti, A. J. Org. Chem. 2008, 73, 2811–
2818.
6382 J. Org. Chem. 2008, 73, 6382–6385
10.1021/jo8008897 CCC: $40.75 2008 American Chemical Society
Published on Web 07/22/2008

SCHEME 1. The Bottom Part Shows the DFT Computed
Enantiomeric Ground State (GS) of 1 and the Top Part the
two Possible Transition States (TS-1 and TS-2) for the
C9-Pri Rotationa
FIGURE 2. Temperature dependence of the 13C signals (150.8 MHz)
of the two aromatic quaternary carbons of 1 in CHF2Cl/CHFCl2 (left).
On the right is displayed the simulation obtained with the rate constants
reported.
a The energies (E) are given in kcal mol-1.
in which the two dihedral angles H-CMe2-C9-CHO and
O-C-C9-CHMe2 are 54° and -14°, respectively (see also
Scheme 1).8 The third minimum (black dot) corresponds to a
diastereomeric structure due to the C9-CHO rotation, in which
the same dihedral angles are 59° and -114°, respectively. This
structure, however, is calculated to have an energy higher by
1.3 kcal mol-1
.
There are two transition states for the C9-Pri bond rotation
(indicated by * and # on the red line), the corresponding
energies being 5.6 and 7.1 kcal mol-1, respectively. The allowed
pathway followed by the C9-Pri bond rotation will be, therefore,
that involving the lowest of the two barriers (5.6 kcal mol-1).
The transition state for the C9-CHO rotation pathway (hollow
circle on the black dotted line) has an energy 2.7 kcal mol-1
higher than that of the ground state, and corresponds to a
dihedral angle O-C-C9-CHMe2 of -54°.
The red and black lines run parallel to the axes, thus indicating
that the two motions are independent,9so that hypothesis iii of
a correlated motion can be discounted. According to these
computations, the barrier for the C9-CHO rotation is much
lower than that for the C9-Pri rotation, and would exchange
two diastereomeric conformers of different energy. Furthermore,
the predicted barrier for the C9-CHO rotation is too low to be
detected in the variable-temperature NMR experiment. These
considerations exclude hypothesis ii, indicating that the mea-
sured value of 6.9 kcal mol-1 corresponds to the C9-Pri
rotation, i.e., to hypothesis i.
FIGURE 3. MMX computed energy (E in kcal mol-1) surface of 1 as
a function of the rotation pathways about the C9-Pri (showing the
two mentioned transition states) and the C9-CHO bonds (red line and
black dotted line, respectively).
C9-CHO bond;6 and (iii) it is also possible that the two
rotations are not independent and, as a result of a correlated
process, the measured barrier would be that due to the two
motions occurring simultaneously.
To identify the geometries of the energy minima and of the
transition states, the three-dimensional energy surface of 1 was
computed (MMX force field7) as a function of the dihedral
angles corresponding to the rotations of the isopropyl and of
the HCO substituents (Figure 3).
Although the lower MMX computed barrier of 5.6 kcal mol-1
is in reasonable agreement with the experiment, it is somewhat
inconsistent that the higher (rather than the lower) computed
barrier is in better agreement with the measured value. For this
(8) The small angle of 14° suggests, however, that the libration about the
plane defined by the dihedral O-C-C9-CHMe2 ) 0 might still take place. If
the C9-Pri bond rotation is fast, this process would create a dynamic plane of
symmetry that would render isochronous the isopropyl methyls and aromatic
signals, in contrast with the experimental observations at-146 °C.
(9) (a) Grilli, S.; Lunazzi, L.; Mazzanti, A. J. Org. Chem. 2001, 66, 4444–
4446. (b) Grilli, S.; Lunazzi, L.; Mazzanti, A. J. Org. Chem. 2001, 66, 5853–
5858. (c) Jog, P. V.; Brown, R. E.; Bates, D. K. J. Org. Chem. 2003, 68, 8240–
8243. (d) Casarini, D.; Grilli, S.; Lunazzi, L.; Mazzanti, A. J. Org. Chem. 2004,
69, 345–351. (e) Casarini, D.; Lunazzi, L.; Mazzanti, A.; Mercandelli, P.; Sironi,
A. J. Org. Chem. 2004, 69, 3574–3577. (f) Lunazzi, L.; Mazzanti, A.; Minzoni,
M. Tetrahedron 2005, 61, 6782–6790.
Three energy minima (indicated by the full dots) were
localized on the map: two of them (red dots) correspond to a
pair of enantiomers due to the rotation of the isopropyl group,
(6) Even in the hypothesis of a C9-Pri faster than the C9-CHO rotation,
the two methyl groups will be diastereotopic at-146 °C, owing to the molecular
asymmetry (C1 point group, as in Scheme 1) due to the frozen C9-CHO rotation
at that temperature.
(7) MMX force field, PC Model 7.5; Serena Software: Bloomington, IN.
J. Org. Chem. Vol. 73, No. 16, 2008 6383

TABLE 1. Experimental and DFT Computed Barriers (kcal mol-1)
for the C9-PriBond Rotation
compd
exptl
DFT computed
1
2
3
6.9
7.0
7.9
7.8
8.2
8.0
reason we recalculated all the stationary points by making use
of the more reliable DFT approach.10
Indeed DFT calculations confirm that compound 1 does not
exhibit any element of symmetry in its ground state and thus
exists as a pair of conformational enantiomers (Scheme 1,
bottom). The less stable diastereomeric conformer, due to the
C9-CHO rotation mentioned above, is calculated to have an
energy 1.8 kcal mol-1 higher than the ground state (see the
Supporting Information), thus it is not appreciably populated.
The two transition states involved in the isopropyl rotation
are predicted to be 7.8 and 7.0 kcal mol-1 (TS-2 and TS-1,
respectively in Scheme 1) higher than the ground state (GS in
Scheme 1).11The 7.0 kcal mol-1 value, being the lower,
corresponds therefore to the rotation barrier that the isopropyl
group must overcome to interconvert the conformational enan-
tiomers. It is gratifying to observe that the lower DFT barrier
is actually the one closer to the experimental value and, in
addition, that the agreement with the latter (Table 1) is even
better than that obtained by MMX. The DFT computations also
FIGURE 4. DFT computed (left) and X-ray diffraction structure (right)
of compound 3.
case, in fact, these values would have been quite different.15On
the contrary, not only are these barriers are equal, but they are
higher than that of aldehyde 1 only by a relatively small amount.
This means that the greater dimensions of the MeCdO and
ButCdO moieties with respect to HCdO produce only a
moderate increase of the barrier of the C9-Pri bond rotation.16
This can be rationalized by considering that it is the CdO
moiety that is close to the isopropyl group, whereas the Me
and But groups are far away from it (see, for instance, Figure
4).17For this reason their steric effects upon the C9-Pri bond
rotation are, conceivably, not much larger than that due to
HCdO: the difference with respect to the barrier measured in
1 is, in fact, only 1.0 and 1.3 kcal mol-1 for 2 and 3, respectively
(Table 1).
confirm that the C9-CHO bond rotation barrier (3.0 kcal mol-1
)
is too low to be NMR detectable.
To provide experimental support to this interpretation, the
dynamic process was investigated also in the case of derivatives
2 (R ) Me) and 3 (R ) But).
The ground state conformations calculated for these com-
pounds are similar to that of 1: the computed prediction of these
conformers are quite reliable, as shown in the case of 3 where
the X-ray structure was found essentially equal to the computed
one (Figure 4).12
Experimental Section
9-Isopropyl-9H-fluorene-9-carbaldehyde (1).4 See the Sup-
porting Information for the detailed synthetic procedure. 1H NMR
(600 MHz, CD3CN, +25 °C) δ 0.78 (d, J ) 6.8 Hz, 6H), 2.98
(septet, J ) 6.8 Hz, 1H), 7.41 (td, J ) 7.5, 1.2 Hz, 2H), 7.49 (td,
J ) 7.6, 1.1 Hz, 2H), 7.59 (td, J ) 7.5, 1.1 Hz, 2H), 7.87 (dt, J )
7.5, 1.1 Hz, 2H), 9.52 (s, CHO). 13C NMR (150.8 MHz, CD3CN,
+25 °C) δ 18.5 (CH3), 33.9 (CH), 72.6 (Cq), 121.6 (CH), 127.1
(CH), 128.9 (CH), 129.9 (CH), 143.4 (Cq), 143.5 (Cq), 200.7 (CHO).
MS m/z (%) 236 (M•+, 27), 208 (83), 207 (88), 192 (86), 181 (26),
191 (72), 166 (71), 165 (100). HRMS calcd for C17H16O 236.12012,
found 236.1200.
The temperature dependence of the 1H isopropyl methyl
signal13of 2 (Figure S-3 of the Supporting Information) yields
a barrier of 7.9 kcal mol-1 and the 13C isopropyl methyl
signal13of 3 (Figure S-4 of the Supporting Information) yields
a barrier of 8.2 kcal mol-1 (Table 1).
The fact that these two barriers are essentially equal within
the errors ((0.15 kcal mol-1)14rules out the possibility that these
values correspond to the C9-CO bond rotation: if this was the
(15) A few examples: In the case 1-acyl,8-phenylnaphthalene derivatives the
MeCO rotation barrier is 9.5 kcal mol-1 and that of ButCO is 13.2 kcal mol-1
.
Lunazzi, L.; Mazzanti, A.; Mun˜oz` Alvarez, A. J. Org. Chem. 2000, 65, 3200–
3206. In the case of 1,4-diacyl naphthalene derivatives the two barriers are 10.2
and 22.1 kcal mol-1, respectively. Casarini, D.; Lunazzi, L.; Mazzanti, A.; Foresti,
E. J. Org. Chem. 1998, 63, 4991–4995. And in the case of acylmesitylene
derivatives the barriers are 6.1 and 19.2 kcal mol-1, respectively. Casarini, D.;
Lunazzi, L.; Verbeek, R. Tetrahedron 1996, 52, 2471–2480.
(10) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb,
M. A.; Cheeseman, J. R.; Montgomery, J. A., Jr.; Vreven, T.; Kudin, K. N.;
Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci,
B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada,
M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.;
Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian,
H. P.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.;
Stratmann, R. E.; Yazyev, O.; Austin,A. J.; Cammi, R.; Pomelli, C.; Ochterski,
J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.; Dannenberg,
J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.; Farkas, O.;
Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.;
Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.;
Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.;
Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill,
P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Poplez, J. A.
Gaussian 03, Revision D.01; Gaussian, Inc.: Wallingford, CT, 2004.
(11) As shown in Scheme 1, the H-C(Me2)-C9-CHO dihedral angles of
the lower (TS-1) and higher (TS-2) energy transition states are 0° and 121°,
respectively.
(16) Whereas the rotation of the MeCO group in 2 has a quite low DFT
calculated barrier (3.9 kcal mol-1), that for the complete rotation of the ButCO
is computed to be much higher (15.5 kcal mol-1), as expected according to ref
15. The effect of this motion (see also Figure S-5 in the Supporting Information)
is, however, NMR invisible in 3 because, when such a rotation is frozen, the
molecule adopts solely the preferred conformation shown in Figure 4. In this
situation the small amplitude libration of 21° 12about the plane defined by the
dihedral O-C-C9-CHMe2 ) 0 can still take place. This process appears to be
driven by the C9-Pri rotation and when this combined motion is fast, it still
allows the existence of a dynamic plane of symmetry, which keeps isochronous
the isopropyl methyl and aromatic signals of 3. Only when this lower energy
process is also frozen will anisochronous signals be NMR detectable (the DFT
computed barrier for this process is 8.0 kcal mol-1, as in Table 1).
(17) This is further confirmed by the unusual high field shift observed for
the acetyl methyl signal of 2 (1.53 ppm) and for the tert-butyl methyl signal of
3 (0.64 ppm). These groups, in fact, experience the well-known effect of the
aromatic ring currents because they lay above the fluorenyl ring; see: Jackman,
L. M.; Sternhell, S. Applications of NMR Spectroscopy in Organic Chemistry,
2nd ed.; Pergamon Press: Oxford, UK, 1969; p 95. Jennings, W. B.; Farrell,
B. M.; Malone, J. F. Acc. Chem. Res. 2001, 34, 885–894. Wu¨thrich, K. Angew.
Chem., Int. Ed. 2003, 42, 3340–3363.
(12) For instance, the O-C-C9-CHMe2 dihedral angle of 3 is 21° in the
computed and 25° in the X-ray structure (Figure 4).
(13) In both 2 and 3 the same barriers were obtained when monitoring the
aromatic signals, as in the case of the aldehyde 1.
(14) Bonini, B. F.; Grossi, L.; Lunazzi, L.; Macciantelli, D. J. Org. Chem.
1986, 51, 517–522.
6384 J. Org. Chem. Vol. 73, No. 16, 2008

1-(9-Isopropyl-9H-fluoren-9-yl)-ethanone (2) and 1-(9-Iso-
propyl-9H-fluoren-9-yl)-2,2-dimethylpropan-1-one (3). A solu-
tion of Me-Li (2 mL, 3 mmol, 1.5 M solution in Et2O) was added
dropwise to a stirred solution of 9-isopropyl-9H-fluorene-9-carbal-
dehyde (0.47 g, 2 mmol in 20 mL of dry THF), kept at -78 °C
under nitrogen. After the addition, the mixture was stirred at -78
°C for about 2 h, then CH3OH (5 mL) was added at -78 °C. The
solution was allowed to warm to room temperature, and quenched
with aqueous NH4Cl. After extraction with Et2O, the organic layer
was dried (Na2SO4) and the solvent was removed at reduced
pressure. The crude was identified by GCMS to contain mainly
the intermediate alcohol. Oxidation was carried on at room
temperature by adding H2SO4 (0.2 mL, 1 N solution) and aliquots
of CrO3 to an acetone solution of the crude alcohol,18following
the reaction by GC-MS. When the alcohol disappeared, acetone
was removed at reduced pressure, than H2O and Et2O were added.
The organic layer was separated and dried (Na2SO4), and the solvent
was removed at reduced pressure. The crude was purified on a silica
gel column (hexanes/acetone 9:1) to obtain a fraction containing
the title compound and 9-isopropyl-9H-fluorene. Analytically pure
samples of 2 were obtained by semipreparative HPLC (C18 column,
250 × 21.2, acetonitrile/H2O 80:20 v/v). The same methodology
was employed in the preparation of 3, using t-Bu-Li (1.5 M in
pentane). Analytically pure samples of 3 were obtained by
semipreparative HPLC (C18 column, 250 × 21.2, acetonitrile/H2O
90:10 v/v). Crystals of 3, suitable for X-ray diffraction, were
obtained by slow evaporation of the acetonitrile from a 1:1 solution
of acetonitrile/H2O.
NMR Spectroscopy. The spectra were recorded at 600 MHz
for 1H and 150.8 MHz for 13C. The assignments of the 13C signals
were obtained by means of the DEPT sequence. The samples for
obtaining the very low temperature spectra were prepared by
connecting to a vacuum line the NMR tubes containing the
compound and a small amount of C6D6 (for locking purposes), and
condensing therein the gaseous CHF2Cl and CHFCl2 (4:1 v/v) under
cooling with liquid nitrogen. The tubes were subsequently sealed
in vacuo and introduced into the precooled probe of the spectrom-
eter. Temperature calibrations were performed before the experi-
ments, using a Cu/Ni thermocouple immersed in a dummy sample
tube filled with isopentane, and under conditions as nearly identical
as possible. The uncertainty in the temperatures was estimated from
the calibration curve to be (2 °C. The line shape simulations were
performed by means of a PC version of the QCPE program DNMR
6 no. 633, Indiana University, Bloomington, IN.
Calculations. Geometry optimizations were carried out at the
B3LYP/6-31G(d) level by means of the Gaussian 03 series of
programs10(see the Supporting Information). The standard Berny
algorithm in redundant internal coordinates and default criteria of
convergence were employed in all the calculations.19Harmonic
vibrational frequencies were calculated for all the stationary points.
For each optimized ground state the frequency analysis showed
the absence of imaginary frequencies, whereas each transition state
showed a single imaginary frequency. Visual inspection of the
corresponding normal mode was used to confirm that the correct
transition state had been found
Acknowledgment. L.L. and A.M. received financial support
from the University of Bologna (RFO) and from MUR-COFIN
2005, Rome (national project “Stereoselection in Organic
Synthesis”). D.C. received financial support from the University
of Basilicata (RIL-2008).
1
1-(9-Isopropyl-9H-fluoren-9-yl)-ethanone (2). H NMR (600
MHz, CD3CN, +25 °C) δ 0.66 (d, J ) 6.9H, 6H), 1.53 (s, 3H),
3.03 (septet, J ) 6.9 Hz, 1H), 7.37 (td, J ) 7.5, 1.2 Hz, 2H),
7.47-7.50 (m, 4H), 7.89 (m, 2H). 13C NMR (150.8 MHz, CD3CN,
+25 °C) δ 18.9 (CH3), 28.1 (CH3), 34.38 (CH), 74.1 (Cq), 121.6
(CH), 126.5 (CH), 129.0 (CH), 129.7 (CH), 143.5 (Cq), 146.0 (Cq),
208.4 (CO). MS m/z (%) 250 (M•+, 59), 207 (100), 192 (89), 191
(72), 165 (67). HRMS calcd for C18H18O 250.13576, found
250.1357.
1-(9-Isopropyl-9H-fluoren-9-yl)-2,2-dimethylpropan-1-one (3).
1H NMR (600 MHz, CD3CN, +25 °C) δ 0.53 (d, J ) 6.9 Hz, 6H),
0.64 (s, 9H), 3.02 (septet, J ) 6.9 Hz, 1H), 7.36 (td, J ) 7.4, 1.2
Hz, 2H), 7.40 (d, J ) 7.7, 2H), 7.48 (td, J ) 7.4, 1.2 Hz, 2H), 7.87
(d, J ) 7.6, 2H). 13C NMR (150.8 MHz, CD3CN, +25 °C) δ 18.6
(CH3), 28.4 (CH3), 36.0 (CH), 47.6 (Cq), 73.7 (Cq), 121.6 (CH),
126.6 (CH), 128.6 (CH), 129.5 (CH), 144.0 (Cq), 146.0 (Cq), 214.1
(CO). MS m/z (%) 292 (M•+, 4), 208 (21), 207 (100), 192 (65),
191 (28), 165 (29), 85 (31), 57(91). HRMS calcd for C21H24O
292.18272, found 292.1826.
Supporting Information Available: Variable-temperature
NMR spectra of compounds 1-3, MMX computed energy
surface of 3, synthetic procedure and spectroscopic data of 1-3
and their intermediates, X-ray data of compound 3, 1H and 13
C
NMR spectra and HPLC traces of 1-3, and computational data
of 1-3. This material is available free of charge via the Internet
at http://pubs.acs.org.
JO8008897
(19) Thermodynamic corrections were also applied in standard conditions,
using unscaled harmonic frequencies, and the corresponding results are reported
in Tables S1-3 of the Supporting Information. However, these values cannot
be meaningfully compared to the present experimental data because of the
different temperatures, and to relevant errors in the computation of the entropic
factor (see for instance: Ayala, P. Y.; Schlegel, H. B. J. Chem. Phys. 1998, 108,
2314–2325).
(18) Muller, P.; Blanc, J. HelV. Chim. Acta 1979, 62, 1980–1984.
J. Org. Chem. Vol. 73, No. 16, 2008 6385