The first synthesis of spirocyclopentyl derivatives of lupane triterpenoids by radical nitrocyclization of C-2-diallyl substituted betulonates

Article abstract of DOI:10.1016/j.tetlet.2011.11.020

Radical cyclization of the 1,6-hexadiene moiety in 2,2-diallyl substituted methyl or benzyl dihydrobetulonates initiated by Fe(NO₃) ₃·9H₂O in the presence of FeCl₃ or LiCl gave hitherto unknown spirocyclic compo

Full text of DOI:10.1016/j.tetlet.2011.11.020

Tetrahedron Letters 53 (2012) 217–221
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Tetrahedron Letters
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The first synthesis of spirocyclopentyl derivatives of lupane triterpenoids
by radical nitrocyclization of C-2-diallyl substituted betulonates
Anna Yu. Spivak a, , Elvira R. Shakurova a, Darya A. Nedopekina a, Sergey L. Khursan b,
⇑
Michail Yu. Ovchinnikov b, Leonard M. Khalilov a, Victor N. Odinokov a
a Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, 141 Prospekt Oktyabrya, Ufa 450075, Russian Federation
b Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences, 71 Prospekt Oktyabrya, Ufa 450054, Russian Federation
a r t i c l e i n f o
a b s t r a c t
Article history:
Radical cyclization of the 1,6-hexadiene moiety in 2,2-diallyl substituted methyl or benzyl dihydrobetul-
onates initiated by Fe(NO3)3ꢀ9H2O in the presence of FeCl3 or LiCl gave hitherto unknown spirocyclic
compounds in which ring A of the lupane triterpenoid at position C-2 is spiro coupled with a vicinally
substituted nitromethyl- and chloromethylcyclopentane. Based on a quantum-chemical assessment of
the energy characteristics of this reaction, the most probable configurations of the chiral atoms in the spi-
rocyclopentane ring were determined for the major diastereomers isolated in individual form.
Ó 2011 Elsevier Ltd. All rights reserved.
Received 26 September 2011
Revised 24 October 2011
Accepted 4 November 2011
Available online 10 November 2011
Keywords:
Lupane triterpenoids
Betulonic acid
1,6-Hexadienes
Radical cyclization
Spirocycles
Pentacyclic triterpenoids of lupane series constitute an impor-
tant class of bioactive compounds possessing a broad scope of
activity. These compounds are of special interest due to their anti-
tumor and antiviral properties.1 Lupane triterpenoids manifest low
toxicity against animals even in high concentrations, but the rela-
tively weak potential of their biological effect hinders considerably
the use of these compounds in clinical practice. In view of this,
studies on the synthesis of betulin and betulinic acid derivatives
by the modification of functional groups at C-3 and C-28 atoms
have been under way in the past years. These studies resulted in
a group of compounds that had superior antitumor and antiviral
activities in comparison with native compounds.2,3 However, stud-
ies aimed at modifications of ring A in betulinic or betulonic
acids1,3–5 are no less promising. We have recently developed a fac-
ile and efficient method for synthesizing 2,2-diallyl-substituted 3-
ketolupanes 1 and 2 that are of interest as polyfunctional block-
synthons for new derivatives of lupane triperpenoids with modi-
fied ring A.6 These compounds can be converted into potentially
bioactive spirocyclic systems by cyclization of the 1,6-hexadiene
moiety under conditions of radical7,8 or catalytic reactions on
treatment with transition metal complexes,9,10 including olefin
metathesis catalysts.11
In this work, we have studied the radical cyclization of 2,2-dial-
lyl-substituted methyl and benzyl dihydrobetulonates 1 and 2 ini-
tiated by Fe(NO3)3ꢀ9H2O (under its thermal degradation
conditions) in the presence of FeCl3 or LiCl as radical traps. The
reaction performed by short refluxing of the reagents in THF gave
a mixture of diastereomeric compounds 3 and 4, respectively, in
good yields (Scheme 1).12
MALDI TOF mass spectra of a mixture of compounds 3 or 4 con-
tained molecular ion peaks corresponding to their molecular for-
mulas (for compound 3, m/z 654.98 [M+Na]+, 670.96 [M+K]+; for
compound 4, 730.40 [M+Na]+, 746.37 [M+K]+).
1H NMR spectra of cyclization products 3 and 4 contained sig-
nals of CH2NO2 and CH2Cl moieties as broad multiplets that reso-
nate at d 4.30–4.75 and 3.45–3.65, respectively. In the 13C NMR
spectra, these groups manifested themselves as characteristic
methylene signals: d 75.81 and 44.45 for compounds 3; d 75.83,
and 44.46 for compounds 4.
Analysis of NMR spectra of these compounds did not allow us to
determine their stereoisomeric compositions. Major isomers 3a
and 4a were isolated as individual compounds from hardly-
separable diastereomeric mixtures of 3 and 4 using column chro-
matography on silica gel (Fig. 1). The structures of compounds 3a
and 4a were partially confirmed by the analysis of one-dimen-
sional 1H and 13C NMR spectra, two-dimensional homo-(COSY,
NOESY) and heteronuclear experiments (HSQC, HMBC).
The 1H and 13C NMR spectra, with a slight difference in chemical
shifts between compounds 3a and 4a, totally matched their
⇑
Corresponding author. Tel.: +7 347 284 3544; fax: +7 347 284 2750.
E-mail addresses: s.spivak@bashnet.ru (A.Yu. Spivak), chemorg@anrb.ru (S.L.
Khursan).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.11.020

218
A. Yu. Spivak et al. / Tetrahedron Letters 53 (2012) 217–221
NO2
.
Fe(NO3)3 9H2O
CO2R
CO2R
FeCl3, or LiCl
THF, reflux,
63-65% (ref.7)
O
Cl
O
1, 2
3, 4
1, 3 R=Me; 2, 4 R=Bn
Scheme 1. Radical nitrocyclization of dihydrobetulonates 1 and 2.
29
20
spiro compounds. In order to obtain information about the abso-
lute configuration of the chiral carbon atoms of the cyclopentane
ring, we performed a theoretical analysis of the stereochemical fea-
tures of the reaction in question.13
21
30
19
E
NO2
22
18
13
12
26
R
11
D 17
5'
25
5
C
4'
3'
Using 2,2-diallyl substituted cyclohexanone 10 (Fig. 2) as a mod-
el compound whose conformational structure matches the struc-
ture of ring A in the starting lupane terpenoids (1, 2), we studied
the mechanism of radical cyclization that occurs by Scheme 1 (cf.
Ref. 7) by means of DFT and ab initio methods.exo-Cyclization of
1,6-hexadiene moiety in methyl dihydrobetulonate 1 (or model
compound 10) to cyclopentane can result in eight diastereomers:
four pairs of molecules with cis- and trans-arrangement of vicinal
CH2NO2 and CH2Cl groups that differ in arrangement of the latter
with respect to the plane of ring A of the lupane frame (Figs. 1
and 3; only diastereomers 3a–d and 3a0–d0 with an R-configuration
of the spiro atom are shown).
CO2R
16
R
2
14
28
9
15
1
1'
10
8
2'
S
B
A
4
27
7
3
6
Cl
O
3a R=Me
4a R=Bn
23
24
NO2
NO2
NO2
5'
5'
R
5'
S
S
4'
3'
4'
3'
4'
3'
R
R
R
1'
1'
1'
2'
2'
2'
R
S
B
A
R
B
B
A
A
Cl
Cl
Cl
O
O
O
3d
3b
3c
Figure 1. Diastereomeric spiro compounds 3a–d with an R-configuration of the
Calculations of the full energies of optimized structures of all
isomers of model compounds 3a0–d0 (Fig. 3) in B3LYP/6–31G(d)
approximation suggest unambiguously that trans-isomers are
energetically favorable: the energy difference between the least
stable trans-isomer 3b0 and the most stable cis-isomer 3a0 (or reac-
tion products 3b and 3a) amounted to 9 kJ/mol, while the energy
spiro atom.
structure; each spectrum contained a single set of characteristic
signals of the lupane and cyclopentane moieties and those of the
respective substituents. Their 13C NMR spectra showed an upfield
shift of the singlet signal of the quaternary C-2 carbon in ring A
(
D
d 5.7 ppm) in comparison with its positions in the spectra of
NO2
NO2
NO2
NO2
the original esters 1 and 2. The coupling constant of vicinal protons
HC-3 (d 2.7) and HC-4 (d 3.0) observed in 1H NMR spectra, which
amounted to 8 Hz, suggested a mutual cis-orientation of these pro-
tons and hence a cis-arrangement of the CH2NO2 and CH2Cl groups
in the spirocyclopentane moiety. The mutual cis-orientation of
substituents was confirmed by intense cross peaks in the NOESY
spectrum between the protons of CH2Cl (d 3.5) and CH2NO2 (d 4.4).
However, NMR spectroscopy did not allow us to make an
exhaustive conclusion about the stereochemical structure of the
´
´
O
O
O
O
Cl
Cl
Cl
Cl
3a'
3b'
3c'
3d'
Figure 3. Diastereomeric model spiro compounds 3a0–d0 with an R-configuration of
the spiro atom.
Figure 2. Conformational structure of model 2,2-diallyl substituted cyclohexanone 10 and ring A in 2,2-diallyl substituted methyl betulonate 1 (both rings have the ‘twist’
conformation).

A. Yu. Spivak et al. / Tetrahedron Letters 53 (2012) 217–221
NO2
219
NO2
NO2
.
LnFeIII
LnFeII
-
.
Cl
A
NO2
O
Cl
O
O
O
1
5
6
3
Scheme 2. Assumed mechanism of radical nitrocyclization of methyl betulonate 1.
difference between the most stable trans-isomer 3c0 and isomer
3a0 (or reaction products 3c and 3a) is 15 kJ/mol (see Tables 1
and 2 in Supplementary data).
tuted dihydrobetulonates, for example, methyl dihydrobetulonate
1, starts with radical addition of nitrogen dioxide to one of the dou-
ble bonds of the 1,6-diene moiety followed by 5-exo-cyclization of
intermediate 5 to intermediate 6 that contains a cyclopentylmeth-
yl group spiro coupled with ring A of the lupane triterpenoid. Rad-
ical intermediate 6 is trapped by the chlorine atom to give reaction
product 3 (Scheme 2).
When selecting the theoretical method to study the assumed
nitrocyclization mechanism of compound 1, it was taken into ac-
count that the B3LYP hybrid functional overstates the contribution
of the pathway that results in the trans-isomer in radical cycliza-
tion of substituted hexenyl radicals, which occurs in a manner sim-
ilar to the reaction in question.14 It is recommended to use the
HandHLYP (BHLYP) hybrid functional for this purpose and, if pos-
sible, verify the reliability of the calculation results using the com-
However, it follows from our experimental data that cis-isomers
that are less stable thermodynamically are formed in major
amounts. In fact, the yield of cis-isomer 3a amounted to 60% of
the diastereomer mixture 3.12 To explain this apparent contradic-
tion, it was assumed that the selective formation of the cis-isomer,
which is less stable thermodynamically, is determined by the
kinetics and mechanism of the reaction in question. This hypothe-
sis is supported by known facts14 about the preferential formation
of cis-substituted cyclopentanes in the radical cyclization of 1,6-
hexadienes.
According to the hypothetical mechanism suggested for radical
nitrocyclization of 1,6-dienes,7 the reaction of C-2-diallyl substi-
≠
α-TS
...
(3.4)
β
NO2
α
≠
β-TS
(0.0)
1'O
NO2
NO2
.
.
NO2
r (C…N) = 1.978 Å, νimag = 548i см-1
O
O
≠
5'
NO2
6d'
.
(15.2)
NO2
.
O
≠
...
6a'
.
(0.0)
O
NO2
Cl
≠
6c'
(6.2)
O
≠
6b'
(12.3)
...
...
O
NO2
Cl
3d'
...
r (C…C) = 2.203 Å, νimag = 490i см-1
NO2
Cl
NO2
O
3c'
O
O
Cl
3a'
3b'
Figure 4. Radical cyclization mechanism for model compound, 2,2-diallylcyclohexanone 10, as an example. The relative Gibbs energies (kJ/mol) of the transition states
calculated in the BHLYP/cc-pVTZ approximation with nonspecific solvation (tetrahydrofuran) taken into account are shown in parentheses.

220
A. Yu. Spivak et al. / Tetrahedron Letters 53 (2012) 217–221
6. Spivak, A. Yu.; Shakurova, E. R.; Nedopekina, D. A.; Khalitova, R. R.; Khalilov, L.
M.; Odinokov, V. N.; Belsky, Y. P.; Ivanova, A. N.; Belska, N. V.; Danilets, M. G.;
Ligatcheva, A. A. Russ. Chem. Bull. Int. Ed. 2011, 60, 694.
posite method. Therefore, the BHLYP functional combined with the
Danning basis set with cc-pVTZ triple splitting was chosen as the
main calculation method.
7. Taniguchi, T.; Ishibashi, H. Org. Lett. 2010, 12, 124.
Calculations of relative Gibbs energies of the b-TS– and
a
-TS–
8. Taniguchi, T.; Goto, N.; Nishibata, A.; Ishibashi, H. Org. Lett. 2010, 12, 112.
9. Yamamoto, Y.; Nakagai, Y.; Ohkoshi, N.; Itoh, K. J. Am. Chem. Soc. 2001, 123,
6372.
10. Okamoto, S.; Livinghouse, T. Organometallics 2000, 19, 1449.
11. Gurjar, M. K.; Ravindranadt, S. V.; Sankar, K.; Karmakar, S.; Cherian, J.;
Chorghade, M. S. Org. Biomol. Chem. 2003, 1, 1366.
transition states for the two pathways of the first cyclization steps
of model compound 10 (Table 3 in Supplementary data) showed
the preferability of nitrogen dioxide reaction with the allyl substi-
tuent in compound 10 having an equatorial configuration (b-orien-
tation of the allyl moiety in 1) to give intermediate 50 (Fig. 4). The
12. Typical procedure: To a solution of 1 (0.10 g, 0.18 mmol) and FeCl3 (0.04 g,
0.27 mmol) or LiCl (0.01 g, 0.27 mmol) in THF (3 ml) was added Fe(NO3)3ꢀ9H2O
(0.09 g, 0.22 mmol), and the mixture was heated at reflux for 3 h. After cooling
to room temperature, the resulting suspension was diluted with EtOAc (5 ml)
and filtered. After removal of solvent under reduced pressure, the residue was
purified by silica gel chromatography (CHCl3) to give 3 (0.07 g, 65%) as a
mixture of diastereomeres. Re-chromatography on SiO2 (hexane:EtOAc, 30?1)
separate of 3a (0.04 g, 60% relative to initial diastereomeric mixture 3. Methyl
3-oxo-3’S-(chloromethyl)-4’R-(nitromethyl)spiro[2(1’)R-cyclopentane]-dihydr
obetulonate (3a): White solid mp = 160–162 °C (EtOH), [a2D0] + 30.30 (c 1.12,
ratio of the rate constants (kb/k = 3, T = 338 K) calculated using the
a
Eyring equation and the relative nonequilibrium Gibbs energy
(
DDG– -b). Hence, based on the data for model compound 10, it
a
can be assumed that the formation of four diastereomers 3a–d
with an R-configuration of the C-2 spiro atom is preferential in
the series of isomeric compounds 3.
CHCl3). IR (m
/cmꢁ1): 1760 (C@O). MS, m/z 654.98 [M+Na]+, 670.96 [M+K]+. Anal.
In calculations of the relative Gibbs energies for transition
–
states 6a0 –d0– (Table 4 in Supplementary data) that lead to model
Calcd for C37H58ClNO5: C, 70.28; H, 9.25; Cl, 5.61; N, 2.22. Found: C, 70.03; H,
9.72; Cl, 5.66; N, 2.52. 1H NMR (400 MHz, CDCl3): d 0.71, 0.95, 0.99, 1.10, 1.12
(all s, 3H each, H(25), H(26), H(27), H(24), H(23)), 0.77, 0.88 (both d, J = 6.0 Hz,
3H each, H(30), H(29)), 1.18 (m, 1H, Ha(15)), 1.19 (m, 1H, Ha(21)), 1.22 (m, 1H,
Ha(12)), 1.24 (m, 1H, Ha(22)), 1.36 (m, 1H, Ha(11)), 1.37 (m, 1H, Ha(16), 1H,
Hb(15); 2H, H(5)), 1.39 (m, 1H, H(18)), 1.43 (m, 2H, H(6)), 1.44 (m, 2H, H(7)),
1.50 (d, 2J = 13.0 Hz, 1H, Ha(1)), 1.51 (m, 1H, Hb(11)), 1.56 (m, 1H, H(9)), 1.60
(m, 1H, Ha(5’)), 1.73 (m, 1H, Hb(12), 1H, Ha(2’)), 1.82 (m, 1H, Hb(20), 1H, Hb(21),
1H, Hb(22)), 2.02 (m, 1H, Hb(2’)), 2.04 (d, 2J = 13.0 Hz, 1H, Hb(1)), 2.24 (m, 1H,
H(19)), 2.25 (m, 1H, Hb(16)), 2.27 (m, 1H, H(13)), 2.43 (dd, 2J = 13.0 Hz,
3J = 8.0 Hz, 1H, Hb(5’)), 2.71 (sext, 3J = 8.0 Hz, 1H, H(3’)), 3.01 (sext, 3J = 8.0 Hz,
1H, H(4’)), 3.53 (dd, 2H, 2J = 14.0 Hz, 3J = 7.0 Hz, CH2Cl), 3.67 (s, 3H, OMe), 4.46,
4.65 (both dd, 2J = 13.0 Hz, 3J = 8.0 Hz, 2H, CH2NO2). 13C NMR (100 MHz,
CDCl3): d 14.53 (C(27)), 14.69 (C(30)), 15.50 (C(26)), 15.75 (C(25)), 20.36 (C(6)),
21.87 (C(11)), 22.56 (C(24)), 22.96 (C(29)), 27.02 (C(12)), 29.58 (C(21)), 29.69
(C(15)), 29.76 (C(20)), 30.25 (C(23)), 32.00 (C(16)), 33.08 (C(7)), 37.28 (C(22)),
37.97 (C(4’)), 38.23 (C(13)), 40.46 (C(2)), 40.48 (C(8)), 42.66 (C(14)), 43.13
(C(3’)), 44.13 (C(19)), 44.45 (CH2Cl), 45.00 (C(5’)), 45.87 (C(4)), 48.10 (C(2’)),
48.36 (C(5)), 48.83 (C(18)), 51.21 (OMe), 51.52 (C(10)), 53.21 (C(9)), 55.93
(C(1)), 56.98 (C(17)), 75.81 (CH2NO2), 176.81 (C(28)), 221.23 (C(3)). Benzyl 3-
oxo-3’S-(chloromethyl)-4’R-(nitromethyl)spiro[2(1’)R-cyclopentane]-dihyd
–
compounds 3a0–d0, the relative energies of transition states 6a0
–
and 6c0 were refined by the G3MP2B3 composite method in
accordance with published recommendations.14 As one can see
–
from Figure 4, transition state 6a0 that leads to isomer 3a0 has
the lowest energy barrier. The DDG–
value was found to be
c–a
8.1 kJ/mol. The reaction rate ratio ka/kc = 15 (T = 338 K) calculated
from this value, that is, the rate constant of cyclization that occurs
toward model compound 3a0 or reaction product 3a is by an order
of magnitude higher than the rate constants for the competing
pathways. Hence, the experimentally observed formation of cis-
isomers 3a and 4a of spirocyclopentane derivatives of betulonates
can be reasonably explained by analyzing data obtained in the
framework of theoretical studies, which eliminate the apparent
contradiction noted above between the isomerism thermodynam-
ics and NMR data for diastereomeric mixtures of compounds 3 or 4.
To conclude, we have synthesized hitherto unknown spirocyclic
derivatives of lupane terpenoids. Theoretical analysis of the reac-
tion mechanism allowed us to establish the most probable struc-
tures of major reaction products 3a and 4a that were isolated in
individual form from diastereomeric mixtures: methyl 3-oxo-3’S-
(chloromethyl)-4’R-(nitromethyl)spiro[2(1’)R-cyclopentane]-dihyd
robetulonate (3a) and benzyl 3-oxo-3’S-(chloromethyl)-4’R-
(nitromethyl)spiro[2(1’)R-cyclopentane]-dihydrobetulonate (4a).
robetulonate (4a): White solid mp = 120–122 °C (EtOH), ½a D20
ꢂ
+ 37.50 (c 0.08,
CHCl3). IR (m
/cmꢁ1): 1725 (C@O). MS, m/z 730.40 [M+Na]+, 746.37 [M+K]+. Anal.
Calcd for C43H62ClNO5: C, 72.90; H, 8.82; Cl, 5.00; N, 1.98. Found: C, 72.52; H,
8.44; Cl, 5.21; N, 1.89. 1H NMR (400 MHz, CDCl3): d 0.73, 0.93, 0.98, 1.09, 1.12
(all s, 3H each, H(25), H(26), H(27), H(24), H(23)), 0.88, 0.90 (both d, J = 6.0 Hz,
3H each, H(30), H(29)), 1.21–2.32 (m, 28H, CH, CH2 in the betulin residue), 2.43
(dd, 2J = 13.0 Hz, 3J = 8.0 Hz, 1H, H(5’)), 2.71 (sext, 3J = 8.0 Hz, 1H, H(3’)), 3.01
(sext, 3J = 8.0 Hz, 1H, H(4’)), 3.52 (dd, 2J = 14.0 Hz, 3J = 7.0 Hz, 2H, CH2Cl), 4.46,
4.64 (both dd, 2J = 13.0 Hz, 3J = 8.0 Hz, 2H, CH2NO2), 5.08–5.17 (m, 2H,
OCH2Ph); 7.32–7.37 (m, 10H, Ph). 13C NMR (100 MHz, CDCl3):
d 14.49
(C(27)), 14.68 (C(30)), 15.37 (C(26)), 15.74 (C(25)), 20.35 (C(6)), 21.86
(C(11)), 22.55 (C(24)), 22.96 (C(29)), 27.04 (C(12)), 28.44 (C(21)), 29.46
(C(15)), 29.76 (C(20)), 30.25 (C(23)), 31.95 (C(16)), 33.07 (C(7)), 36.85
(C(22)), 37.26 (C(4’)), 37.97 (C(13)), 38.17 (C(2)), 40.46 (C(8)), 42.67 (C(14)),
43.13 (C(3’)), 44.13 (C(19)), 44.45 (CH2Cl), 45.00 (C(5’)), 45.86 (C(4)), 48.09
(C(2’)), 48.36 (C(5)), 48.82 (C(18)), 51.51 (C(10)), 53.21 (C(9)), 55.93 (C(1)),
56.95 (C(17)), 65.65 (CH2-Ph), 75.82 (CH2NO2), 128.03, 128.28, 128.47, 136.55
(Ph), 175.95 (C(28)), 221.25 (C(3)).
Acknowledgments
This work was financially supported by the Russian Foundation
for Basic Research (Project No. 10_03_00105), the Division of
Chemistry and Materials Science of the Russian Academy of Sci-
ences (Program ‘Medicinal and Biomolecular Chemistry’), and the
Ministry of Education and Science of the Russian Federation (Fed-
eral Target Program ‘Scientific and Pedagogical Manpower of Inno-
vative Russia’ for 2009–2013, State Contract No. 14.740.11.0014).
13. Conformations of the structures in question were calculated by the B3LYP/6-
31G(d) method.15–17 In the case of the most stable isomers, the structures were
additionally optimized and the vibrational problem was solved in the B3LYP/6-
311G(d,p) approximation.18 Transition states were localized using the B3LYP/
6-311G(d,p), BHandHLYP/cc-pVTZ,19,20 and G3MP2B321 methods. Energy
parameters of the compounds were calculated at 298 K. Nonspecific
solvation by the solvent (tetrahydrofuran) was taken into account in the
framework of the polarized continuum method22 in the BHLYP/cc-pVTZ
approximation. Calculations were performed using Gaussian 09 software,
Revision A.01.23
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2011.11.020.
14. Tripp, J. C.; Schiesser, C. H.; Curran, D. P. J. Am. Chem. Soc. 2005, 127, 5518.
15. Becke, A. D. J. Chem. Phys. 1993, 98, 5648.
16. Lee, C.; Yang, W.; Parr, R. G. Phys. Rev. B. 1988, 37, 785.
17. Hariharan, P. C.; Pople, J. A. Theor. Chem. Acc. 1973, 28, 213.
18. Raghavachari, K.; Binkley, J. S.; Seeger, R.; Pople, J. A. J. Chem. Phys. 1980, 72,
650.
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