Synthesis of Halobisnoradamantane Derivatives
J . Org. Chem., Vol. 66, No. 16, 2001 5367
Sch em e 1a
depending on the structure of the substrate, the nature
of the nucleofugal groups, the nucleophile, and the
reaction conditions.1b,7 The first reactive intermediate in
these reactions is a radical-anion which loses a halide
anion to give a haloaryl radical. The coupling reaction of
this radical with the nucleophile forms a new radical
anion, in which the π* MO of the aromatic moiety is the
bridge that mediates the ET to the σ* MO of the
remaining C-X bond. The rate of the intramolecular ET
reaction depends on the energy difference between both
MO’s.8
Also, when an alkyl substrate having two leaving
groups reacts by the SRN1 mechanism, monosubstitution
or disubstitution products are formed. The first reactive
intermediate is a haloalkyl radical, and in the coupling
a
Reagents, conditions, and yields: (a) (1) 10% KOH, MeOH,
(2) concentrated HCl, 2 (98%), 6 (66%); (b) Ac2O, ∆, 88%; (c)
MeONa, MeOH, 85%; (d) IBDA, I2, benzene, hν, 73%; (e) 2-meth-
ylpropene, concentrated H2SO4, CH2Cl2, rt, 59%; (f) H2, 35 atm,
10% Pd/C, Na2CO3, EtOH, 7 days, 1:1 mixture of 7 and 8; (g)
Ph2P-, hν, DMSO, 1.5 h, 70%.
reaction with the nucleophile
a
radical-anion is
formed.1,5b,c,9 In this case, intramolecular ET to the σ*
MO of the C-X bond can take place through the σ bonds
or through space. The rate of intramolecular ET not only
depends on the energy difference between the MO’s but
also on the number of the intervening bonds, on the
distance between the donor and acceptor, and on the
flexibility of the bridge.9-13
Sch em e 2a
To obtain more insight on the effect of the strain in
ET reactions, we decided to study the reactivity of halo-
and dihalobisnoradamantane derivatives toward Ph2P-
ions. To this end, the new iodotricyclo[3.3.0.03,7]octane
derivatives 5, 7, 10, and 17 were prepared. These
compounds together with the known bisethano deriva-
tives 24,14,15 25a ,16 25b,16 and 25c,16 containing the
pentacyclo[6.4.0.0.2,100.3,704,9]dodecane skeleton, are the
subject of the present SRN1 study.
a
Reagents, conditions, and yields: (a) IBDA, I2, benzene, hν,
Resu lts a n d Discu ssion
65%; (b) H2, 1 atm, 10% Pd/C, NaOH, EtOH, 15 h, 70% 10 (14
days 11, not isolated from the solution; (c) (1) 2,2′-dithiobis(pyri-
dine 1-oxide), Bu3P, THF, (2) t-BuSH, hν, 12 (74%) 10, (70%); (d)
(1) 10% KOH, MeOH, (2) concentrated HCl, 72%.
Syn th esis. The synthesis of iodo esters 5 and 7 was
carried out from the known diester 117 by following
standard procedures (Scheme 1). Hydrogenation of 7 at
a pressure of 35 atm, using 10% Pd on charcoal as
catalyst, was shown to be a very slow process, providing
a mixture of starting 7 and tert-butyl ester 8 in a ratio
of about 1:1 after 1 week of reaction. However, pure tert-
butyl ester 8 could be obtained as described later on from
the SRN1 reaction of 7 and diphenylphosphide anion.
The synthesis of iodo compound 10 (Scheme 2) was first
carried out by iododecarboxylation of acid 13.18,19 Unfor-
tunately, it could not be separated (column chromatog-
raphy or distillation) from the iodobenzene formed as a
byproduct in this reaction. Alternatively (Scheme 2), iodo
compound 10 was prepared by decarboxylation of iodo
acid 6 using the Barton procedure.20 Moreover, iodide 10
was obtained in good isolated yield, by controlled hydro-
genation21 at atmospheric pressure of the known diiodide
9.22 Prolonged hydrogenation of diiodide 9 gave the highly
volatile alkane 11, whose volatility precluded isolation
from its methanolic solution.
(7) For reviews, see: (a) Rossi, R. A.; de Rossi, R. H. Aromatic
Substitution by the SRN1 mechanism; ACS Monograph 178; American
Chemical Society: Washington, DC; 1983. (b) Rossi, R. A. Acc. Chem.
Res. 1982, 15, 164-170. (c) Norris, R. K. In Comprehensive Organic
Synthesis; Trost, B. M., Ed.; Pergamon Press: 1991; Vol. 4, pp 451-
482. (d) Rossi, R. A.; Pierini, A. B.; Santiago, A. N. In Organic
Reactions; Paquette, L. A., Bittman, R., Eds.; J ohn Wiley & Sons: New
York,1999; pp 1-271.
(8) (a) Clarke, D. D.; Coulson, C. A. J . Chem. Soc. A 1969, 169-
172. (b) Dressler, R.; Allan, M.; Haselbach, E. Chimia 1985, 39, 385-
389. (c) Symons, M. C. R. Acta Chem. Scand. 1997, 51, 127-134. (d)
Pierini, A. B.; Duca, J . S., J r. J . Chem. Soc., Perkin Trans. 2 1995,
1821-1828. (e) Casado, J .; Gallardo, I.; Moreno, M. J . Electroanal.
Chem. 1987, 219, 197-208. (f) Andrieux, C. P.; Save´ant, J . M.; Zann,
D. Nouv. J . Chim. 1984, 8, 107-116.
(9) (a) Palacios, S. M.; Santiago, A. N.; Rossi, R. A. J . Org. Chem.
1984, 49, 4609-4613. (b) Lukach, A. E.; Rossi, R. A. J . Org. Chem.
1999, 64, 5826-5831.
(10) Lukach, A. E.; Santiago, A. N.; Rossi, R. A. J . Org. Chem. 1997,
62, 4260-4265.
(11) Lukach, A. E.; Santiago, A. N.; Rossi, R. A. J . Phys. Org. Chem.
1994, 7, 610-614.
(12) Adcock, W.; Clark, C. I. J . Org. Chem. 1993, 58, 7341-7349.
(13) Santiago, A. N.; Stahl, A. E.; Rodr´ıguez, G. L.; Rossi, R. A. J .
Org. Chem. 1997, 62, 4406-4411, and references therein cited.
(14) (a) Branan, B. M.; Paquette, L. A.; Hrovat, D. A.;, Borden, W.
T. J . Am. Chem. Soc. 1992, 114, 774-776. (b) McNeil, D.; Vogt, B. R.;
Sudol, J . J .; Theodoropulos, S.; Hedaya, E. J . Am. Chem. Soc. 1974,
96, 4673-4674.
(18) Moriarty, R. M.; Khosrowshabi, J . S. J . Chem. Soc., Chem.
Commun. 1987, 675-676.
(19) Concepcio´n, J . I.; Francisco, C. G.; Freire, R.; Herna´ndez, R.;
Salazar, J . A.; Sua´rez, E. J . Org. Chem. 1986, 51, 402-404.
(20) (a) Barton, D. H. R.; Crich, D.; Motherwell, W. B. Tetrahedron
1985, 41, 3901-3924. (b) Barton, D. H. R. Tetrahedron 1992, 48, 2529-
2544. (c) Barton, D. H. R.; Samadi, M. Tetrahedron 1992, 48, 7083-
7090. (d) Barton, D. H. R. Pure Appl. Chem. 1994, 66, 1943-1954.
(21) Pinder, A. R. Synthesis 1980, 425-452.
(15) Camps, P.; Font-Bardia, M.; Me´ndez, N.; Pe´rez, F.; Pujol, X.;
Solans, X.; Va´zquez, S.; Vilalta, M. Tetrahedron 1998, 54, 4679-4696.
(16) Camps, P.; Pujol, X.; Rossi, R. A.; Va´zquez, S. Synthesis 1999,
5, 854-858.
(17) Camps, P.; Iglesias, C.; Rodr´ıguez, M. J .; Grancha, M. D.;
Gregori, M. E.; Lozano, R.; Miranda, M. A.; Figueredo, M.; Linares, A.
Chem. Ber. 1988, 121, 647-654.
(22) Camps, P.; Font-Bardia, M.; Pe´rez, F.; Solans, X.; Va´zquez, S.
Angew. Chem., Int. Ed. Engl. 1995, 34, 912-914.