Stepwise Introduction of π-Electron Cross-Conjugation: A Possible Access to [5]Radialenes?

Article abstract of DOI:10.1021/jo970107d

As starting points to the stepwise access to the corresponding [5]radialene, the unsaturated esters 14a and 18a have been prepared. These compounds have been isolated along with their isomers 14b and 18b, resulting from an intracyclic double-bond migration. Moreover a subsequent base-catalyzed process mediated the total isomerization of these mixtures to the latter more stable compounds 14b and 18b. The energy contents of the various compounds, and the corresponding tri- and tetrasubstituted higher homologues 19 and 20, have been calculated at the ab initio level, using several minimal as well as extended basis sets, and the observed experimental results rationalized.

Full text of DOI:10.1021/jo970107d

J . Org. Chem. 1997, 62, 5339-5343
5339
Step w ise In tr od u ction of π-Electr on Cr oss-Con ju ga tion :
A P ossible Access to [5]Ra d ia len es?
Florence Geneste,† Alec Moradpour,*,† and Georges Dive*,‡
Laboratoire de Physique des Solides (UA2 of CNRS), Universite´ de Paris-Sud, F-91405 Orsay, France,
and Centre d’Inge´nierie des Prote´ines, Institut de Chimie, B-4000 Sart-Tilman, Lie`ge, Belgium
Received J anuary 22, 1997X
As starting points to the stepwise access to the corresponding [5]radialene, the unsaturated esters
14a and 18a have been prepared. These compounds have been isolated along with their isomers
14b and 18b, resulting from an intracyclic double-bond migration. Moreover a subsequent base-
catalyzed process mediated the total isomerization of these mixtures to the latter more stable
compounds 14b and 18b. The energy contents of the various compounds, and the corresponding
tri- and tetrasubstituted higher homologues 19 and 20, have been calculated at the ab initio level,
using several minimal as well as extended basis sets, and the observed experimental results
rationalized.
Ch a r t 1
Radialenes are alicyclic compounds in which all ring
atoms are sp2-hybridized and carry exocyclic double
bonds.1 They are a class of compounds exhibiting very
interesting structural and electronic properties;1 the
cooperative involvement of the latter has also been
considered1,2 in organic conducting, or ferromagnetic,
solid-state.
Two main approaches for the synthesis of these com-
pounds have been studied: (i) the olefin-forming reac-
tions at an already existing cycloalkane ring; (ii) the
metal-induced cyclooligomerization reactions of suitable
[n]cumulenes. While a number of [3]-, [4]-, and [6]radi-
alenes have been obtained, the preparations of [5]radi-
alenes proved to be far more difficult. Thus, besides the
aimed structures in this field, such as 1,3 the number of
isolated [5]radialenes is presently limited to 24 and 3,5
the parent compound 4 (Chart 1) itself being still
unknown.
Clearly, a general and versatile synthetic method is
needed here. We therefore decided to investigate the
possibility to obtain the [5]radialene skeleton, i.e. com-
pound 5. The considered synthesis involved the stepwise
introduction of a suitable substituent containing a double-
bond forming radical Y by a sequence of reactions
involving R-substitutions of the successively formed
exocyclic double bonds (Scheme 1).
Sch em e 1
We wish to report here the experimental as well as the
theoretical results of this study. We find that, as soon
as two radial double-bonds have been formed, i.e. in
compounds 14 and 18, an unexpected rearrangement to
regioisomers 14b and 18b, containing one endocyclic
double-bond, takes place. Our theoretical ab initio
calculations (the results of the semiempirical AM1 ap-
proach were not sufficiently accurate in this case) clearly
† Universite´ de Paris-Sud.
‡ Institut de Chimie.
address this phenomena to the higher stability of the
latter endocyclic regioisomers. The higher homologues
19 and 20 of the series, containing three and four such
double-bonds, also exhibit the same trends, in endocyclic
vs radial exocyclic isomer stability.
X Abstract published in Advance ACS Abstracts, J uly 15, 1997.
(1) Hopf, H.; Maas, G. Angew. Chem., Int. Ed. Engl. 1992, 31, 931,
and references cited therein.
(2) See for example: (a) Sugimoto, T.; Misaki, Y.; Yoshida, Z. I.;
Yamauchi, J . Mol. Cryst. Liq. Cryst. 1989, 176, 259. (b) Takahashi,
K.; Tarutani, S. Adv. Mat. 1995, 7, 639.
(3) Boese, R.; Bra¨unlich, G.; Gotteland, J .-P.; Hwang, J .-T.; Troll,
C.; Vollhardt, K. P. C. Angew. Chem., Int. Ed. Engl. 1996, 35, 995.
(4) (a) Iyoda, M.; Otani, H.; Oda, M.; Kai, Y.; Baba, Y.; Kasai, N. J .
Chem. Soc., Chem. Commun. 1986, 1794. (b) Iyoda, M.; Mizusuna, A.;
Kurata, H.; Oda, M. J . Chem. Soc., Chem. Commun. 1989, 1690.
(5) Yoshida, Z.; Sugimoto, J . Angew. Chem., Int. Ed. Engl., Adv.
Mater. 1988, 100, 1573.
Exp er im en ta l Section
Gen er a l. NMR spectra were obtained with a Bruker AC
400 MHz spectrometer operating at 100.6 MHz for the 13C
resonance; other details of instrumentation have been reported
recently.6
S0022-3263(97)00107-2 CCC: $14.00 © 1997 American Chemical Society

5340 J . Org. Chem., Vol. 62, No. 16, 1997
Geneste et al.
Compounds 67 and 78 were prepared according to the
literature methods.
chromatography, eluting with dichloromethane. The com-
pound 10 was obtained (the overall yield was not optimized)
as a liquid (0.75 g, 50%) identical to the authentic sample.9
1,3-Cyclop en ta n ed iol Bis(4-m eth ylben zen esu lfon a te)
(15). Into a solution of 1,3-cyclopentanediol (cis + trans,
mainly cis, mixture from Aldrich) (59.49 mmol) in dry pyridine
(60 mL) at 0 °C was added p-toluenesulfonyl chloride (23.3 g,
122 mmol); the mixture was stirred overnight at room tem-
perature under argon. The obtained suspension was poured
into a mixture of ice-water (300 g) containing concentrated
HCl (70 mL), and the resulting solid was filtered and dried;
recrystallization from absolute ethanol yielded 15 (13.9 g, 68%)
as a colorless solid; mp ) 86-87 °C. 1H NMR: (δH, CDCl3)
1.76-1.8 (m, 2H), 1.91-1.95 (m, 2H), 2.08 (m, 2H), 2.41, (s,
6H), 4.92-4.94 (m, 2H), 7.3, (d, J ) 8.2 Hz, 4H), 7.7 (d, J )
8.2 Hz, 4H); 13C NMR: 21.52, 30.71, 40.54, 82.07, 127.59,
129.87, 133.63, 144.85. Anal. Calcd for C19H22O6S2: C, 55.60;
H, 5.40; O, 23.38; S, 15.62. Found: C, 55.51; H, 5.26; O, 23.41;
S, 15.53. Compound 15 is the cis stereoisomer.
Diet h yl 2-(2-Br om ocyclop en t ylid en e)p r op a n ed ioa t e
(11). NBS (2.31 g, 13 mmol) and dibenzoyl peroxide (0.05 g,
0.2 mmol) were added to CCl4 (75 mL) containing 10 (2.94 g,
13 mmol), and the mixture was refluxed for 6 h. The
suspension was cooled to room temperature, and the succin-
imide was filtered off. The filtrate was evaporated, and flash-
chromatography of the residue, eluting with ethyl acetate/
cyclohexane (15:85 v/v), led first to isolation of the corresponding
2,5-substituted dibromo compound (a liquid, 0.75 g, 15%); 13
C
NMR: 13.88, 34.77, 48.01, 61.73, 127.52, 161.25, 163.70) and
then to 11 as a liquid (2.38 g, 60%). 1H NMR: (δH, CDCl3)
1.21-1.34 (m, 6H), 1.81-2.29 (m, 4H), 2.4-2.6 (m, 1H), 2.85-
3.05, (m, 1H), 4.10-4.40 (m, 4H), 5.45-5.55, (m, 1H). 13C
NMR 14.04, 22.38, 30.99, 37.12, 50.55, 61.15, 61.35, 122.83,
163.86, 164.32, 164.78. MS(CI), m/e ) (305, 307) (MH)+.
Nu cleop h ic Su bstitu tion by th e An ion fr om Dieth yl
(P h en ylt h io)m a lon a t e (7). Gen er a l p r oced u r e. Th e
P r ep a r a tion of Su lfid es 8, 12, a n d 16. Sodium hydride
(0.66 g, 16.5 mmol, 60% dispersion in mineral oil) was
suspended in anhydrous THF (50 mL), or DMF (25 mL) for
12, and diethyl (phenylthio)malonate (7) (4.02 g, 15 mmol) was
added; the suspension was stirred under argon until hydrogen
bubbling ceased. The needed amount of compound which had
to be substituted (12 mmol, for 6 and 11; 6 mmol for 15) was
added, and the mixture was refluxed (THF) for 24 h, or stirred
at room temperature (DMF). The mixture was poured into
water (200 mL) and extracted with dichloromethane (3 × 50
mL). The extracts were dried over MgSO4 and the solvent
evaporated; the compounds were purified by flash-chromatog-
raphy. The following were obtained:
Dieth yl cyclopen tyl(ph en ylth io)pr opan edioate (8): elut-
ed with dichloromethane as a colorless liquid (2.26 g, 56%).
1H NMR: (δH, CDCl3) 1.45 (t, J ) 7 Hz, 6H), 1.75-1.95 (m,
6H), 2.13-2.18 (m, 2H), 2.86, (m, 1H), 4.38 (q, J ) 7 Hz, 2H),
4.39 (q, J ) 7 Hz, 2H), 7.55-7.63 (m, 3H), 7.80-7.82 (m, 2H).
13C NMR: 13.78, 25.76, 28.65, 44.05, 61.49, 68.65 (quaternary
carbon), 128.43, 129.40, 130.77, 136.86, 168.22. MS(CI), m/e
) 337(MH)+.
P r ep a r a tion s of Com p ou n d s 14a ,b a n d 18a ,b by Th er -
m a l Deh yd r osu lfen yla tion . Gen er a l P r oced u r e. The
sulfides 12 (1.97 g, 4 mmol) and 16 (2.4 g, 4 mmol) were
dissolved in anhydrous dichloromethane (40 mL), the solutions
were cooled, with stirring, to -35 °C, and m-chloroperoxyben-
zoic acid (90%, 0.69 g, 4 mmol for 12; 1.38 g, 8 mmol for 16)
was added slowly. The stirring was maintained for an
additional 2 h at the same temperature. The reaction mixture
was heated to room temperature, washed with a saturated
sodium bicarbonate solution (3 × 20 mL), and dried over
MgSO4. The solvent was evaporated, and the sulfoxides 9 and
17 were dissolved, without further purification, in the ap-
propriate solvent for the next thermal dehydrosulfenylation
step. Using toluene first, the mixtures were refluxed 2 h and
evaporated under vacuum, and the residue was purified by
flash-chromatography. The following were obtained:
Tetr a eth yl 2,2′-(1,2-Cyclop en tylid en e)bis(p r op a n ed io-
a te) (14a ) a n d Dieth yl 2-[2-(Dica r beth oxym eth yl)cyclo-
p en t-2-en ylid en e]p r op a n ed ioa te (14b). Elution with ethyl
acetate/cyclohexane (20:80 v/v) afforded the mixture 14a ,b as
a light yellow liquid (0.76 g, 50%). 1H NMR: (δH, CDCl3) 1.15-
1.32 (m), 1.80-1.89 (m), 2.52-2.56 (m), 2.65-2.71 (m), 2.96-
3.02 (m), 3.13-3.15 (m), 4.09-4.30 (m), 4.42 (s), 6.84 (s). Anal.
Calcd for C19H26O8: C, 59.68; H, 6.85; O, 33.47. Found: C,
60.03; H, 6.88; O, 33.75. This mixture was dissolved in ethanol
(20 mL), and KOH (0.1 g) was added. After 3 h stirring at
room temperature, the solution was neutralized to pH 7 with
dilute HCl, more water was added (100 mL), and the mixture
was extracted with CH2Cl2 (3 × 50 mL). The organic extracts
were dried over MgSO4 and evaporated to dryness. The
residue (quantitative yield) corresponded to pure 14b. 1H
NMR: 1.15-1.28 (m, 12H), 2.60-2.70 (m, 2H), 2.90-3.0 (m,
2H), 4.0-4.25, (m, 8H), 4.41 (s, 1H), 6.83, (s, 1H). 13C NMR:
13.88, 14.03, 31.17, 33.51, 54.95, 60.83, 62.01, 116.70, 129.96,
132.35, 156.25, 165.90, 166.29, MS(CI), m/e: 382 (M)+.
Tetr a eth yl 2,2′-(1,3-Cyclop en tylid en e)bis(p r op a n ed io-
a te) (18a ) a n d Dieth yl 2-[3-(Dica r beth oxym eth yl)cyclo-
p en t-2-en ylid en e]p r op a n ed ioa te (18b). Elution with eth-
anol/dichloromethane (3:97 v/v) afforded the mixture 18a ,b as
a light yellow liquid (0.87 g, 57%). 1H NMR: (δH, CDCl3) 1.0-
1.05 (m), 2.41-2.70 (m), 2.90-3.0 (m), 3.20-3.30 (m), 3.95-
4.25, (m), 4.41 (s), 6.83 (s). Anal. Calcd for C19H26O8: C, 59.68;
H, 6.85; O, 33.47. Found: C, 59.88; H, 7.06; O, 33.78. After
the same procedure as for 14a ,b the pure isomer 18b was
quantitatively isolated. 1H NMR: 1.15-1.32 (m, 12H), 2.65-
2.71 (m, 2H), 2.96-3.02 (m, 2H), 4.09-4.20 (m, 8H), 4.42 (s,
1H), 6.84 (s, 1H). 13C NMR: 13.92, 14.08, 31.21, 33.55, 54.99,
60.58, 62.02, 116.7, 130.08, 132.38, 156.24, 165.86, 166.30. The
same thermal dehydrosulfenylation step was also effected
using CH2Cl2 (with the inclusion of succinic anhydride),10 and
THF as solvent, as well as another run with toluene containing
p-toluenesulfonic acid; in every case, the same mixtures of
isomers 14a ,b and 18a ,b were isolated. The compositions of
these 14a /14b and 18a /18b mixtures were estimated, by 1H
NMR, to be, respectively, 40/60 and 55/45.
Dieth yl 2-[2-[(p h en ylth io)d ica r beth oxym eth yl]cyclo-
p en tylid en e]p r op a n ed ioa te (12): eluted with ethyl acetate/
1
cyclohexane (20:80 v/v) as a colorless liquid (2.24 g, 38%). H
NMR: (δH, CDCl3) 1.0-1.22 (m, 12H), 2.0-3.1 (m, 7H), 3.9-
4.2 (m, 8H), 7.12-7.32, (m, 3H), 7.32-7.5 (m, 2H). Anal.
Calcd for C25H32O8S: C, 60.96; H, 6.55; O, 25.98; S, 6.51.
Found: C, 60.76; H, 6.53; O, 25.55; S, 6.40. MS(CI), m/e: 493
(MH)+.
Tet r a et h yl 2,2′-(1,3-cyclop en t a n ed iyl)b is[2-(p h en yl-
th io)p r op a n ed ioa te] (16): eluted with ethyl acetate/cyclo-
hexane (35:65 v/v) as a liquid (2.6 g, 72%). 1H NMR: (δH,
CDCl3) 1.08-1.20 (m, 12H), 1.50-2.12 (m, 6H), 2.51-2.62 (m,
2H), 4.02-4.20 (m, 8H), 7.15-7.36, (m, 6H), 7.50-7.55 (m, 4H).
13C NMR: 13.87, 28.86, 30.37, 43.23, 61.71, 61.82, 68.20,
128.59, 129.64, 130.32, 137.05, 167.95.
Dieth yl 2-Cyclop en tylid en ep r op a n ed ioa te (10).9 m-
Chloroperoxybenzoic acid (the commercial sample containing
∼10% chlorobenzoic acid) was dissolved in CH2Cl2 and dried
over MgSO4, the solvent was evaporated, and the residue left
under vacuum (0.1 mmHg) overnight) (90%, 1.3 g, 7 mmol)
was added to CH2Cl2 (100 mL) containing sulfide 8 (2.35 g, 7
mmol) at 0 °C. The mixture was stirred an additional 1 h at
0 °C and diluted with more CH2Cl2 (100 mL). The dichlo-
romethane solution was washed three times with saturated
sodium bicarbonate (50 mL) and subsequently dried over
MgSO4. The solvent was evaporated and the corresponding
sulfoxide (2.2 g) dissolved, without further purification, in
toluene (100 mL) and refluxed (∼2 h). The solvent was
evaporated under vacuum and the residue purified by flash-
(6) Gimbert, Y.; Moradpour, A.; Merienne, C. J . Org. Chem. 1990,
55, 5347.
(7) Drahowzal, F.; Klamann, D. Monatsh. 1951, 82, 460.
(8) Huntress, E. H.; Olsen, R. T. J . Am. Chem. Soc. 1948, 70, 2856;
see also: Greengrass, C. W.; Hoople, D. W. T. Tetrahedron Lett. 1981,
22, 1161.
(10) Hermann, J . L.; Berger, M. H.; Schlessinger, R. H. J . Am. Chem.
Soc. 1973, 95, 7923.
(9) Lehnert, W. Tetrahedron 1973, 29, 635.

Stepwise Introduction of π-Electron Cross-Conjugation
J . Org. Chem., Vol. 62, No. 16, 1997 5341
Ta ble 1. AM1 a n d a b In itio Ca lcu la ted En er gy
Sch em e 3
Con ten tsa of Com p ou n d s 14a ,b, 18a ,b, 19a -c, a n d 20a ,b
∆E(∆G) energy (free energy) contentsa
compounds
AM1
MINI 1
6-31G
6-31G*
14a
14b
18a
18b
19a
19b
19c
20a
20b
0
2.88
0
5.23
0
0.49
15.67
0
0.68 (0.93)
0
1.66 (2.17)
0
1.49 (2.02)
0
4.90 (6.98)
1.75 (2.03)
0
4.20 (3.37)
0
3.31 (3.14)
0
-0.73 (0.36)
0
3.67 (6.56)
4.54 (3.88)
0
5.86 (5.43)
0
0.33
a
The energies are expressed in kcal mol-1 by reference (∆E and
∆G ) 0) to the energy-minimized more stable isomers in each
series.
Sch em e 2
Sch em e 4
values of the corresponding analytical second-derivative ma-
trix. It is worth noting that the full geometry optimizations,
found to be highly dependent on the basis set expansions,
aimed primarly to minimize the significant electrostatic repul-
sions involving the ester-group oxygens and resulted in
significant out-of-plane distorted conformations of the latters.
The ∆G free-energy values (Table 1) were calculated as ∆G(T)
) ∆E + ∆E(T) + P∆V - T∆S(T) (∆E is the usual energy
content and ∆E(T) its thermal dependence, P∆V is negligible,14
and ∆S(T) values were calculated, at 298.15 K, by the usual
statistical mechanic formulas,15a,b by the Gaussian 9416 pro-
gram). The calculations have been effected on the CIP
computers, mainly on a Cray FPS 522 EA and Digital Alpha
8400 8-processor server, using the Gaussian 94 (Rev. B and
D) package.16
Ca lcu la tion s. Full geometry optimizations were performed
for compounds 1, 14a ,b, 18a ,b, 19a -c and 20a ,b (Figures 1
and 2) at the semiempirical AM111 and at ab initio level within
the MINI-1 minimal basis set of Huzinaga,12 as well as the
6-31G double basis set and the 6-31G*13 for compounds 14a ,b
and 18a ,b; the 6-31G* basis set with polarization functions is
known to give excellent results when applied to conjugated
systems. The 6-31G basis set has also been used with
compounds 19a -c. For the higher 67-atom homologues 20a ,b
at such a level of calculation (6-31G), a 421 basis function was
needed; the corresponding calculations are as yet intractable
and were not attempted. The equilibrium structures have first
been investigated by an AM1 conformational analysis around
the rotatable ester single bonds, either by fixed rotors or by
reoptimizations of the other degrees of freedom. The highly
overcrowded esters’ environment resulted usually in a single
minimum located on the maps. Such computed equilibrium
structures are true minima, as shown by the positive eigen-
Resu lts
Syn th esis. The known starting alkene 109 was alter-
natively synthesized from the tosylate 6, by a three-step
(14) Dive, G.; Dehareng, D.; Peeters, D. Int. J . Quant. Chem. 1996,
58, 85.
(15) (a) McQuarrie, D. A. Statistical Thermodynamics; Harper and
Row: New York, 1973. (b) Daudel, R.; Leroy, G.; Peeters, D.; Sana, M.
Quantum Chemistry; Wiley: New York, 1983.
(16) Gaussian 94, Revision D.4, M. J . Frisch, G. W. Trucks, H. B.
Schlegel, P. M. W. Gill, B. G. J ohnson, M. A. Robb, J . R. Cheeseman,
T. Keith, G. A. Petersson, J . A. Montgomery, K. Raghavachari, M. A.
Al-Laham, V. G. Zakrzewski, J . V. Ortiz, J . B. Foresman, J . Cioslowski,
B. B. Stefanov, A. Nanayakkara, M. Challacombe, C. Y. Peng, P.Y.
Ayala, W. Chen, M. W. Wong, J . L. Andres, E. S. Replogle, R. Gomperts,
R. L. Martin, D. J . Fox, J . S. Binkley, D. J . Defrees, J . Baker, J . P.
Stewart, M. Head-Gordon, C. Gonzalez, and J . A. Pople, Gaussian, Inc.
Pittsburgh, PA, 1995.
(11) Dewar, M. J . S.; Zoebisch, E. G; Healy, E. F.; Stewart, J . J . P.
J . Am. Chem. Soc. 1985, 107, 3902.
(12) Tatewaki, H.; Huzinaga, S. J . Comput. Chem. 1980, 1, 205.
(13) Hehre, W. J .; Ditchfield, R.; Pople, J . A. J . Chem. Phys. 1972,
56, 2257.

5342 J . Org. Chem., Vol. 62, No. 16, 1997
Geneste et al.
F igu r e 1. Views of the optimized energy-minimum conformations of the 1,2- and 1,3-disubstituted isomers 14a ,b and 18a ,b,
obtained by the ab initio MINI-1 calculations. The values of the torsion angle C9-C2-C1-C7 remarkably increased as a function
of the calculations accuracies from 42.60° (AM1), 49.04° (MINI-1), 55.33° (6-31G) to 57.95° (6-31G*) for 14a . For 18a the O9-
C6-C7-C1 dihedral angle is found to be -129.09° (AM1), -117.35° (MINI-1), -127.24° (6-31G), -133.37° (6-31G*), and the O10
C8-C7-C1 angle is 29.12° (AM1), 21.51° (MINI-1), 24.96° (6-31G), and 28.38° (6-31G*).
-
procedure (Scheme 2): a nucleophilic substitution reac-
tion involving the malonic phenylthio substituted ester
78 and a subsequent oxidation by m-chloroperbenzoic acid
yielded 9 containing a double-bond forming sulfoxide
group;17 a moderate heating of the latter compound led
to 10. The compound 13, containing the same sulfoxide
group, was then prepared by a similar sequence of
reactions, from the bromo diester 11. However, the
thermal double-bond formation reaction from 13, in
boiling toluene, led to a mixture containing the desired
compound 14a , together with the endocyclic isomer 14b.
Modified experimental procedures, such as lower elimi-
nation-reaction temperature and/or addition of an acid
to the medium (p-toluenesulfonic acid), invariably led to
a mixture (around 40/60 compositions) of compounds 14a
and 14b. Moreover, a base-catalyzed process, efficiently
isomerized the former mixtures to the pure, undesired,
more stable regioisomer 14b.
This unexpected result prompted us to investigate a
similar double-bond formation process, but in a 1,3
regiochemistry on the cyclopentane ring. Therefore we
synthesized the disubstituted compound 17 (Scheme 3)
from the ditosylate 15. The corresponding disulfoxide 17
led, in boiling toluene, to a 55/45 mixture of the unsatur-
ated compounds 18a and 18b; the latter mixture was also
easily transformed to the pure and more stable isomer
18b.
The knowledge of the respective thermodynamic sta-
bilities of these various regioisomers was needed, in order
to account for these results; we also were anxious to
forsee the behavior of the higher, tri- and tetrasubstituted
homologues of this series, before the corresponding
syntheses were attempted. We therefore computed the
properties of these compounds using the semiempirical
AM1, as well as ab initio methods.
Ca lcu la tion s. We have calculated the relative ener-
gies of the energy-minimized geometries of the various
1,2- and 1,3-disubstituted isomers18 14a ,b and 18a ,b
(Schemes 2 and 3, respectively), using the AM1 and ab
initio methods (Table 1). The same calculations were also
effected for the higher homologues 19 and 20 (Scheme
4), as well as for compound 1 (AM1). The calculated
19
stabilities by the semiempirical AM1 method
were
always in favor of the seemingly more stable radial
double-bond isomers 14a and 18a . But the ab initio
calculations led to values that are in closer agreement
with the experimental results obtained for compounds
14 and 18: the endocyclic isomers 14b and 18b are found
to be more stable than the exocyclic ones 14a and 18a ,
(19) The widely used AM1 method and the corresponding ZDO
approximation probably lead to an underestimation of the important
electrostatic repulsion forces involved in the present highly over-
crowded systems, and these effects are not counterbalanced by the
parametrization of the other terms of the Fock matrix. However, as
calculated by a referee, and we gratefully acknowledge him for this,
the molecular mechanics force field PC model using VESCF charges
correctly find 14b to be more stable that 14a by 7.3 kcal mol-1, and
18b to be more stable by 11 kcal mol-1 (both in ∆H); the twist angle
between the two exocyclic double-bonds of 14a (torsion angle C7-C1-
C2-C9, Figure 1) is about 39° with this approach.
(17) Trost, B. M.; Salzmann, T. N.; Hiroi, K. J . Am. Chem. Soc. 1976,
98, 4887.
(18) The less time-consuming calculations with the methyl esters
were effected for 14, 18, 19, and 20.

Stepwise Introduction of π-Electron Cross-Conjugation
J . Org. Chem., Vol. 62, No. 16, 1997 5343
Comparable, though more attenuated, effects on the
conformation of the central rings, by the moving-in of the
double-bonds, are also observed for 19a ,c and 20a ,b (see
Supporting Information).
Discu ssion
Our present results identify a thermodynamic dead-
lock, with the isolation of the more stable endocyclic
isomers 14b and 18b, in the projected double-bond step-
by-step formation sequence. The calculations allow an
adequate rationalization of these experimental results,
considering the steric effects controlling the relative
stabilities of the various isomers. The driving forces for
these double-bond rearrangements are clearly mediated
by the minimizations of the steric constraints and
simultaneously by the conjugation enhancements within
the carbon-carbon bond π-systems: (i) in the 1,3 regio-
chemistry on the central ring, as in 18a (Figure 1), the
radial double-bonds are hardly conjugated to the ester
groups that are highly distorted out of the alkenes planes,
and conjugation is obtained due to an intracyclic bond
migration toward the formation of 18b; (ii) in the 1,2
regiochemistry, as for 14a , the butadiene fragment built
on the exocyclic double-bonds are significantly twisted
(see the C9-C2-C1-C7 angle for 14a , Figure 1) due to
the constraint of the neighboring ester groups, and the
conjugation within the π-system is obtained by the
intracyclic migration of one double-bond (see the simul-
taneous flattening of the central ring in 14b, Figure 1).
These effects therefore clarify the formation of 14b and
18b that precludes an acceptable synthesis of 14a and
18a . The synthesis of higher homologues, probably
exhibiting the same endocyclic double-bond isomeriza-
tion, as shown by calculations, was presently not at-
tempted.
F igu r e 2. Upper and side views of the optimized conformation
of the compound 1, obtained by AM1 calculations.
though the values of the computed free energy differ-
ences, with the extended basis 6-31G* set, are still small
(≈5 kcal mol -1). For the higher, not synthesized homo-
logues 19 and 20 (Scheme 4), the radial double-bond-
containing isomers 19a and 20a are also found to be less
stable than the corresponding endocyclic isomers 19b,c
and 20b, though by vanishingly small amounts of energy.
The views of the calculated (MINI 1 level) energy-
minimized conformations for compounds 1 (AM1 level),
14a ,b, and 18a ,b are depicted in the Figures 1 and 2.
Similar trends, due to several rather severe overcrowd-
ing problems, are obtained for both the 1,2- and 1,3-
disubstituted compounds 14a and 18a : (i) the steric
hindrance of the two ester groups on the same sp2 carbon
result in important out-of-plane distortions of the latters
as long as the corresponding alkene plane is considered
(Figure 1, see the O9-C6-C7-C1 and O10-C8-C7-C1
dihedral angles for 18a ); this effect is also reflected by
noticeable out-of-plane deformations of the central five-
membered rings mediated by these squeezings of the
radial double-bonds; (ii) additional dramatic distortions,
related to the overcrowding of the esters on two neigh-
boring radial alkenes, are observed for the 1,2-disubsti-
tuted compound 14a ; thus, the butadiene fragment (the
torsion angle C9-C2-C1-C7, Figure 1) is highly twisted
by almost 58°, as found by 6-31G* calculations; this effect
is also illustrated by the nice propeller-like conformation
of the pentafulvalene compound 1 (Figure 2).20 On the
other hand, the intracyclic double-bond migrations lead-
ing to 14b and 18b result in almost complete flattening
of the central rings (Figure 1).
These results emphasize the difficulties related to the
stepwise creation of cross-conjugation on a cyclopentane
ring, as a way to [5]radialenes. Consequently, specific
solutions to such problems will probably be needed for
such a synthetic approach to this family of compounds.
For example, if an alternative pentasubstitution of the
central ring is first carried out, the subsequent forma-
tions of the missing unsaturations, leading to the desired
structure, might be complicated by the formation of
similar undesired endocyclic intermediates.
Ack n ow led gm en t. A.M. gratefully acknowledges
the CNET for financial support of this work, also
supported partly by the Belgian Program on Interuni-
versity Poˆles of Attraction initiated by the Belgian State,
Prime Minister’s Office, Services Fe´de´raux des Affaires
Scientifiques, Techniques et Culturelles (PAI no. 19),
and the Fonds de la Recherche Scientifique Me´dicale
(contract no. 3.4531.92). G.D. is chercheur qualifie´ of
the FNRS, Brussels.
Su p p or tin g In for m a tion Ava ila ble: The views of the ab
initio (MINI 1) computed energy-minimized conformations of
the compounds 19a -c, 20a ,b (3 pages). This material is
contained in libraries on microfiche, immediately follows this
article in microfilm version of the journal, and can be ordered
from the ACS; see any current masthead page for ordering
information.
(20) The synthesis and thermal stability of compound 1 remains an
open question for the moment; see for example: Sauter, H.; Gallen-
kamp, B.; Prinzbach, H. Chem. Ber. 1977, 110, 1382; a theoretical study
of this aspect will be published in a forthcoming article.
J O970107D