Reactions of 2-Iodo- and 1,2-Dihaloadamantanes with Carbanions in DMSO by the SRN1 Mechanism

Article abstract of DOI:10.1021/jo990156l

The reaction of 2-iodoadamantane (1) with the potassium enolate of acetophenone (2) did not occur in the dark but succeeded under irradiation or in the presence of FeBr₂ to give the substitution product 3 in 62% and 88% yields, respectively. The photostimulated reaction was inhibited by p-dinitrobenzene (p-DNB). There was no reaction of 1 with the anion of nitromethane (4) in the dark or under irradiation. However, 4 reacted with 1 in the presence of acetone enolate ion (entrainment reaction) to yield 88% of the substitution product 2-adamantylnitromethane (5). The photostimulated reaction of 1 with anthrone (6), 2-naphthyl methyl ketone (9), and N-acetylthiomorpholine (11) anions afforded the substitution compounds 7 (37%), 10 (32%), and 12 (20%), respectively. There was no reaction of 1-chloro-2-iodoadamantane (13) with 2 in the dark (2 h), but under irradiation (5 min) it yielded 52% of the monosubstitution product α-(1-chloro-2-adamantyl)-acetophenone (14). Under longer irradiation time (3 h), the same yield of 14 (52%) was obtained but the disubstitution product 15 was formed in 45% yield. Product 15 was also formed in the photostimulated reaction of 14 with 2. 2-Chloro-1-iodoadamantane (18) did not react with 2 in the dark (2 h), but the photostimulated reaction yielded the monosubstitution product α-(2-chloro-1-adamantyl)acetophenone (19) in 53% and 15 in 4% yield. Products 14 and 19 are intermediates in the formation of 15 in these reactions. There was a slow dark reaction of 1,2-diiodoadamantane (20) with 4 in the presence of acetone enolate ion to afford the iodomonosubstitution compound 21 (40%) and the disubstitution product 22 (13%). The photostimulated reaction (25 min) gave 21 (48%) and 22 (41%). On the other hand, after 3 h of irradiation, only traces of 21 could be detected (<5%) and the product distribution consisted mainly of 22. The iodomonosubstitution product 21 is an intermediate in these reactions.

Full text of DOI:10.1021/jo990156l

5826
J . Org. Chem. 1999, 64, 5826-5831
Rea ction s of 2-Iod o- a n d 1,2-Dih a loa d a m a n ta n es w ith Ca r ba n ion s
in DMSO by th e SRN1 Mech a n ism
Andre´s E. Lukach and Roberto A. Rossi*,†
INFIQC, Departamento de Quı´mica Orga´nica, Facultad de Ciencias Qu´ımicas,
Universidad Nacional de Co´rdoba - Ciudad Universitaria, 5000 Co´rdoba, Argentina
Received J anuary 27, 1999
The reaction of 2-iodoadamantane (1) with the potassium enolate of acetophenone (2) did not occur
in the dark but succeeded under irradiation or in the presence of FeBr2 to give the substitution
product 3 in 62% and 88% yields, respectively. The photostimulated reaction was inhibited by
p-dinitrobenzene (p-DNB). There was no reaction of 1 with the anion of nitromethane (4) in the
dark or under irradiation. However, 4 reacted with 1 in the presence of acetone enolate ion
(entrainment reaction) to yield 88% of the substitution product 2-adamantylnitromethane (5). The
photostimulated reaction of 1 with anthrone (6), 2-naphthyl methyl ketone (9), and N-acetylthio-
morpholine (11) anions afforded the substitution compounds 7 (37%), 10 (32%), and 12 (20%),
respectively. There was no reaction of 1-chloro-2-iodoadamantane (13) with 2 in the dark (2 h), but
under irradiation (5 min) it yielded 52% of the monosubstitution product R-(1-chloro-2-adamantyl)-
acetophenone (14). Under longer irradiation time (3 h), the same yield of 14 (52%) was obtained
but the disubstitution product 15 was formed in 45% yield. Product 15 was also formed in the
photostimulated reaction of 14 with 2. 2-Chloro-1-iodoadamantane (18) did not react with 2 in the
dark (2 h), but the photostimulated reaction yielded the monosubstitution product R-(2-chloro-1-
adamantyl)acetophenone (19) in 53% and 15 in 4% yield. Products 14 and 19 are intermediates in
the formation of 15 in these reactions. There was a slow dark reaction of 1,2-diiodoadamantane
(20) with 4 in the presence of acetone enolate ion to afford the iodomonosubstitution compound 21
(40%) and the disubstitution product 22 (13%). The photostimulated reaction (25 min) gave 21
(48%) and 22 (41%). On the other hand, after 3 h of irradiation, only traces of 21 could be detected
(<5%) and the product distribution consisted mainly of 22. The iodomonosubstitution product 21
is an intermediate in these reactions.
Several alkyl halides have been found to react with
mantanes as well as other bridgehead halides react with
Ph2P-,4 Ph2As-,4a and Me3Sn-5 ions. Also, the reaction
of 1-iodoadamantane (1-IAd) with carbanions,6 PhS-,7,8
PhSe-,7 and PhTe- 7 ions has been reported.
The 2-position of the adamantane ring shows a lower
reactivity in polar9 and in free radical10 reactions com-
pared with that at the 1-position. Chloro and bromo
cyclohexanes and derivatives also react under irradiation
with Ph2P- ions by the SRN1 mechanism.11 Recently, it
has been reported that 2-BrAd reacts with Ph2P- ions
under irradiation whereas 2-ClAd does not. The latter
nucleophiles by the radical nucleophilic substitution or
SRN1 mechanism.1 When there is no spontaneous electron
transfer (ET) from the nucleophile to the substrate, the
initiation step can be triggered by photostimulation1 or
by FeBr22 (eq 1). The alkyl radical R‚ thus formed couples
with the nucleophile to yield a radical anion (RNu)‚- (eq
2), which by an intermolecular dissociative ET3 to the
substrate gives the substitution product and the alkyl
radical R‚ that propagates the chain (eq 3).
(4) (a) Rossi, R. A.; Palacios, S. M.; Santiago, A. N. J . Org. Chem.
1982, 47, 4654. (b) Bornancini, E. R. N.; Alonso, R. A.; Rossi, R. A. J .
Org. Chem. 1987, 52, 2166. (c) Santiago, A. N.; Morris, D. G.; Rossi,
R. A. J . Chem. Soc., Chem. Commun. 1988, 220. (d) Santiago, A. N.;
Takeuchi, K.; Ohga, Y.; Nishida, M.; Rossi, R. A. J . Org. Chem. 1991,
56, 1581. (e) Santiago, A. N.; Iyer, V. S.; Adcock, W.; Rossi, R. A. J .
Org. Chem. 1988, 53, 3016. (f) Lukach, A. E.; Morris, D. G.; Santiago,
A. N.; Rossi, R. A. J . Org. Chem. 1995, 60, 1000.
(5) (a) Adcock, W.; Hemakanthi, G. J . Org. Chem. 1989, 54, 6040.
(b) Ashby, E. C.; Sun, X.; Duff, J . L. J . Org. Chem. 1994, 59, 1270. (c)
Adcock, W.; Clark, C. I. J . Org. Chem. 1995, 60, 723.
(6) (a) Borosky, G. L.; Pierini, A. B.; Rossi, R. A. J . Org. Chem. 1990,
55, 3705. (b) Rossi, R. A.; Pierini, A. B.; Borosky, G. L. J . Chem. Soc.,
Perkin Trans. 2. 1994, 2577.
(7) Palacios, S. M.; Alonso, R. A.; Rossi, R. A. Tetrahedron 1985,
41, 4147.
(8) Ahbala, M.; Hapiot, P. K.; Houmam, A.; J ouini, M.; Pinson, J .;
Save´ant, J . M. J . Am. Chem. Soc. 1995, 117, 11488.
(9) Bentley, W.; Carter, G.; Robert, K. J . Org. Chem. 1984, 49, 5183.
(10) Tabushi, I.; Aoyama, Y.; Kojo, S.; Hamuro, J .; Yoshida, Z. J .
Am. Chem. Soc. 1972, 94, 1177.
(11) Nazareno, M. A., Palacios, S. M.; Rossi, R. A. J . Phys. Org.
Chem. 1993, 6, 421.
The alkyl halides that react by the SRN1 mechanism
are those that have a relatively low reactivity toward
polar nucleophilic substitution.1 For instance, 1-haloada-
† Fax: 54-51-33-3030. E-mail: rossi@dqo.fcq.unc.edu.ar.
(1) For reviews, see: (a) Rossi, R. A.; Pierini A. B.; Palacios, S. M.
Advances in Free Radical Chemistry; Tanner, D. D., Ed.; J ai Press:
1990; p 193; J . Chem. Ed. 1989, 66, 720. (b) Rossi, R. A.; Pierini A. B.;
Pen˜e´n˜ory, A.B. The Chemistry of Functional Group; Patai S., Rap-
poport, Z., Eds.; Wiley: Chichester, 1995; Supl. D2, Chapter 24,
p 1395.
(2) Nazareno, M. A.; Rossi, R. A. J . Org. Chem. 1996, 61, 1645.
(3) Save´ant, J . M. Adv. Electron-Transfer Chem. 1994, 4, 53, and
references therein.
10.1021/jo990156l CCC: $18.00 © 1999 American Chemical Society
Published on Web 07/23/1999

2-Iodo- and 1,2-Dihaloadamantane-Carbanion Reactions
J . Org. Chem., Vol. 64, No. 16, 1999 5827
reacts, however, with Me3Sn- ions, giving the substitu-
tion product in high yield.12 In competition experiments,
1-BrAd was shown to be 1.4 times more reactive than
2-BrAd toward Ph2P- ions, while 1-ClAd is 12 times more
reactive than 2-ClAd toward Me3Sn- ions.12
When an aromatic substrate bearing two leaving
groups reacts by the SRN1 mechanism, either the mono-
substitution or disubstitution products can be formed,
depending on the structure of the substrate, the nature
of the nucleofugal group, the nucleophile, and the reac-
tion conditions.1b,13 The first reactive intermediate in
these reactions is a haloaryl radical. The coupling reac-
tion 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.14
The photostimulated reaction of dihalobenzenes with
PhS- ions affords the disubstitution product without
the formation of monosubstitution product, unless fluo-
rine is the other leaving group.15 In the reaction of
dihaloarenes with different aromatic sulfanions, disub-
stitution, monosubstitution with retention of one leaving
group, or a mixture of both products has been observed,
depending on the stabilization of the halosubstituted
radical anion.16,17 Kinetics analysis led to the conclusion
that the yield of the monosubstitution product is lower
than that expected. The radical anion of the disubstitu-
tion product can either transfer the odd electron to the
starting dihalide or to the monohalo substitution com-
pound, decreasing its overall yield.17
The reaction of dihalobenzenes with (EtO)2PO- ions
yields the disubstitution product, except when fluorine
is one of the leaving groups or with m-chloroiodoben-
zene.18 The fact that m-chloroiodobenzene affords disub-
stitution with PhS- ions but only monosubstitution with
(EtO)2PO- ions was ascribed to the higher stability (lower
π* MO) of the monosubstituted radical anions.18 Several
examples have been reported on the reaction of diha-
lobenzenes with carbanions as nucleophiles.19
disubstitution products are formed.1,20 The first reactive
intermediate is an haloalkyl radical, and in the coupling
reaction with the nucleophile a new radical anion is
formed. However, in these cases only σ bonds or the space
comprise the bridge between the radical anion formed
and the σ* MO of the C-X bond. The rate of the
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 them, and
on the flexibility of the bridge.21
For example, in the photostimulated reaction of 1,3-
dihaloadamantanes with Ph2P- ions mainly the disub-
stitution product is formed,22 whereas with NaMe3Sn the
product distribution depends on the leaving groups. Thus,
when the halides are iodides or bromides the reaction
proceeds with predominant formation of 1,3-adamantene,
but with the dichlorides, or 1-chloro-3-bromo derivatives,
disubstitution is achieved through the SRN1 mechanism.23
With these nucleophiles the rate of the intramolecular
ET of the radical anion to the σ* MO of the C-X bond is
faster than the intermolecular ET to the substrate.
The photostimulated reaction of 1,3-dihaloadaman-
tanes with various carbanions affords products which
depend on the availability of R-hydrogens in the nucleo-
phile. In this case the 1-halo-3-monosubstitution product
formed undergoes deprotonation followed by a concerted
fragmentation to afford 7-methylidenebicyclo[3.3.1]nonene
derivatives.21 With these nucleophiles the rate of the
intramolecular ET of the radical anion to the σ* C-X is
a slow process and does not compete with the intermo-
lecular ET to the substrate.
The reaction of 2-chloro-5-iodo and 2-bromo-5-fluoro
adamantanes (E and Z) with LiMe3Sn gives mainly the
monosubstitution product with retention of chlorine and
fluorine, respectively. The disubstitution product is ob-
tained in high yield when 2-bromo-5-iodoadamantane
was made to react with LiMe3Sn (E and Z).24
The photostimulated reaction of 1,2-dichloroadaman-
tane with Ph2P- ions leads to 1- and 2-adamantyldi-
phenylphosphine in 64% and 15% yields, respectively,
isolated as the oxides. The disubstitution product was
not formed with Ph2P- ions, but when 1,2-dichloroada-
mantane reacts with a nucleophile having less steric
bulk, such as Me3Sn- ions,25 2-chloro-1-trimethylstan-
nyladamantane and the disubstitution product are ob-
tained. The formation of these products has been ratio-
nalized in terms of the different rates of the ET reactions
from the radical anion intermediates.20
When an alkyl substrate with two leaving groups
reacts by the SRN1 mechanism also monosubstitution or
(12) Santiago, A. N.; Stahl, A. E.; Rodriguez, G. L.; Rossi, R. A. J .
Org. Chem. 1997, 62, 4406.
(13) For reviews, see: (a) Rossi R. A.; de Rossi, R. H. Aromatic
Substitution by the SRN1 Mechanism; ACS Monograph 178; Ameri-
can Chemical Society: Washington, D.C., 1983. (b) Rossi, R. A. Acc.
Chem. Res. 1982, 15, 164. (c) Norris, R. K. Compr. Org. Synth. 1991,
4, 451.
(14) (a) Clarke, D. D.; Coulson, C. A. J . Chem. Soc. A 1969, 169. (b)
Dressler, R.; Allan, M.; Haselbach, E. Chimia 1985, 39, 385. (c)
Symons, M. C. R. Acta Chem. Scand. 1997, 51, 127. (d) Pierini, A. B.;
Duca, J . S., J r. J . Chem. Soc., Perkin Trans. 2 1995, 1821. (e) Casado,
J .; Gallardo, I.; Moreno, M. J . Electroanal. Chem. 1987, 219, 197. (f)
Andrieux, C. P.; Save´ant, J . M.; Zann, D. Nouv. J . Chim. 1984, 8, 107.
(15) Bunnett, J . F.; Creary, X. J . Org. Chem. 1974, 39, 3611.
(16) Beugelmans, R.; Bois-Choussy, M. Tetrahedron 1986, 42, 1381.
(17) Amatore, C.; Beugelmans, R.; Bois-Choussy, M.; Combellas, C.;
Thiebault, A. J . Org. Chem. 1989, 54, 5688.
(18) (a) Bunnett, J . F.; Creary, X. J . Org. Chem. 1974, 39, 3612. (b)
Bunnett, J . F.; Traber, R. P. J . Org. Chem. 1978, 43, 1867. (c) Bunnett,
J . F.; Shafer, S. J . J . Org. Chem. 1978, 43, 1873. (d) Bunnett, J . F.;
Shafer, S. J . J . Org. Chem. 1978, 43, 1877. (e) Bard, R. R.; Bunnett, J .
F.; Traber, R. P. J . Org. Chem. 1979, 44, 4918.
Due to the importance of the reaction of carbanions
with 2-adamantyl radical to form a new C-C bond, we
have undertaken the study of the reactions of 2-IAd and
1,2-dihaloadamantanes with these nucleophiles under
SRN1 conditions in order to gain more insight into the
(20) (a) Palacios, S. M.; Santiago, A. N.; Rossi, R. A. J . Org. Chem.
1984, 49, 4609. (b) Santiago, A. N.; Iyer, V. S.; Adcock, W.; Rossi, R.
A. J . Org. Chem. 1988, 53, 3016. (c) Adcock, W.; Iyer, V. S. J . Org.
Chem. 1985, 50, 3706.
(21) Lukach, A. E.; Santiago, A. N.; Rossi, R. A. J . Org. Chem. 1997,
62, 4262.
(22) Lukach, A. E.; Santiago, A. N.; Rossi, R. A. J . Phys. Org. Chem.
1994, 7, 610.
(19) (a) Komin, A. P.; Wolfe, J . F. J . Org. Chem. 1977, 42, 2481. (b)
Alonso, R. A.; Rossi, R. A. J . Org. Chem. 1980, 45, 4760. (c) Bunnett,
J . F.; Singh, P. J . Org. Chem. 1981, 46, 5022. (d) Carver, D. R.;
Greenwood, T. D.; Hubbard, J . S.; Komin, A. P.; Sachdeva, Y. P.; Wolfe,
J . F. J . Org. Chem. 1983, 48, 1180. (e) Beugelmans, R.; Bois-Choussy,
M. Heterocycles 1987, 26, 1863. (f) Amatore, C.; Combellas, C.; Lebbar,
N. E.; Thie´bault, A.; Verpeaux, J . N. J . Org. Chem. 1995, 60, 18.
(23) Adcock, W.; Clark, C. I J . Org. Chem. 1993, 58, 7341.
(24) Adcock, W.; Clark, C. I.; Trout, N. A. Tetrahedron Lett. 1994,
35, 297.
(25) Estimation of the steric bulk of the trimethyltin group indicates
that it is very similar to that of the chlorine and smaller than bromine
groups. See: Davis, D. D.; Surmatis, A. J .; Robertson, G. L. J .
Organomet. Chem. 1972, 46, C9.

5828 J . Org. Chem., Vol. 64, No. 16, 1999
Ta ble 1. Rea ction s of 2-Iod oa d a m a n ta n e (1) w ith Ca r ba n ion s in DMSO
Lukach and Rossi
carbanion,
mmol
I-,
yield (%)
substitution product,
yield (%)b
AdH,
expt
conditionsa
yield (%)b
1
2
2, 3.0
2, 3.0
2, 3.0
2, 3.0
2, 3.0
2, 3.0
4, 3.0
4, 3.0
4, 3.0
4, 3.0
4, 3.0
4, 10.0
6, 3.0
6, 3.0
6, 3.0
6, 3.0
6, 3.0
9, 3.0
9, 3.0
9, 3.0
11, 6.0
11, 6.0
2, 3.0
dark, 3 h
hν, 2 h
hν, 3 h
hν, 3 h
<3
51
85
69
28
f
<1
<3
30
69
14
91
<5
69
31
77
f
3, <1
3, 48
3, 62
3, 42
3, 15
3, 88
5, -
<5
10
7
<5
f
3
4c
5d
hν, 3 h (p-DNB)
6
FeBr2,e1 h
hν, 3 h
7c
8g
dark, 3 h (-CH2COMe)
hν, 1 h (-CH2COMe)
hν, 3 h (-CH2COMe)
hν, 3 h (-CH2COMe) (p-DNB)
hν, 4 h (-CH2COMe)
Dark, 3 h
5, -
9h
5, 29
5, 68
5, 5
5, 88
7, -
7, 28
7, 11
7, 37
7, <1
10, -
10, 32
10, 10
12, -
12, 20j
f
f
f
10g
11d,h
12i
13
14
15d
16
17
18
19
20d
21
22
23k
<5
hν, 1 h
28
15
35
hν, 1 h (p-DNB)
hν, 3 h
FeBr2,e 1 h
dark, 3 h
hν, 3 h
hν, 3 h (p-DNB)
dark, 3 h
hν, 3 h
hν, 3 h
< 2
55
33
<2
40
<2
20
10
f
a
b
1: 1.0 mmol, t-BuOK: 4.0 mmol in 25 mL of DMSO. Determined by GLC (internal standard method: C24 for 3, phenanthrene for
5, C32 for 7 and 10, naphthalene for AdH). c 3.0 mmol of t-BuOK. p-DNB (20 mol %) was added. e FeBr2: 54 mol %. f Not quantified.
Acetone enolate ion: 2.0 mmol. t-BuOK: 6.0 mmol. Acetone enolate ion: 1.0 mmol. t-BuOK: 5.0 mmol. Acetone enolate ion: 10
mmol. t-BuOK: 22.0 mmol. Isolated yield. 1-Chloroadamantane: 1.0 mmol. t-BuOK: 4.0 mmol.
d
g
h
i
j
k
Ch a r t 1
reactivity of the 2-position. 1,2-Dihaloadamantanes offer
the possibility to study the competition between intra-
and intermolecular ET reactions, as well as the substitu-
tion pattern of the 1- and 2-positions with carbanions.
Resu lts a n d Discu ssion
Rea ction s of 2-Iod oa d a m a n ta n e w ith Ca r ba n -
ion s. There was no reaction of 2-IAd (1) with the enolate
ion of acetophenone (2) in DMSO after 3 h in the dark,
but it reacted under irradiation (3 h) or in the presence
of FeBr2 to give product 3 in 62% and 88% yields,
respectively (eq 4).26
3
2
The photostimulated reaction was inhibited by p-
dinitrobenzene (p-DNB), a good electron acceptor.1 There
was a decrease of the reactivity when the reaction was
performed without excess of t-BuOK (used to form the
carbanion) (Table 1, experiments 1-6). All these results
show that 1 reacts with 2 by the SRN1 mechanism.
There was no reaction under irradiation of 1 with
nitromethane anion (4), but it reacted under photostimu-
lation (3 h) in the presence of acetone enolate anion to
give the product 2-adamantylnitromethane (5) in 68%
yield. No products derived from acetone enolate ion were
found (entrainment reaction). A similar entrainment
reaction was found with 1-IAd and 4.6 This reaction was
partially inhibited by p-DNB, and no reaction of 1 with
4 and acetone enolate ions in the dark was detected.
When the concentration of 4 and that of the acetone
enolate ions were increased and the irradiation time was
prolonged (4 h), the yield of 5 rose to 88% (eq 5) (Table
1, experiments 7-12).
Anthrone anion (6) is a good nucleophile in photo-
stimulated reactions with PhI27 and 1-IAd.6 However, the
photostimulated reaction (1-3 h) of 6 with 1 gave a low
yield of the substitution product 7 (28-37%) along with
almost the same amount of the reduction product ada-
mantane (Table 1, experiments 13-16). The photostimu-
lated reaction of 6 with 1-IAd gave 75% of the substitu-
tion product 8, and the amount of adamantane was low
(Chart 1).6b The reaction of 1 with 6 was not induced by
FeBr2 (Table 1, experiment 17); as observed before with
aromatic substrates, the reaction of highly conjugated
(26) For a preliminary report, see: Lukach, A. E.; Santiago, A. N.;
Szeimies, G.; Rossi, R. A. Anal. Asoc. Quim. Arg. 1998, 86, 281.

2-Iodo- and 1,2-Dihaloadamantane-Carbanion Reactions
J . Org. Chem., Vol. 64, No. 16, 1999 5829
Ta ble 2. Rea ction s of 1,2-Dih a loa d a m a n ta n es w ith Ca r ba n ion s in DMSO
I-,
yield (%)
Cl-,
yield (%)
monosubstitution product,
yield (%)
disubstitution product,
yield (%)
expt
substr
carbanion
conditionsa
dark, 2 h
hν, 5 min
hν, 5 min (p-DNB)
hν, 40 min
hν, 40 min, (p-DNB)
hν, 3 h
hν, 2 h
dark, 2 h
1
2
13
13
13
13
13
13
14
18
18
18
20
20
20
20
20
20
2
2
2
2
2
2
2
2
2
2
4
4
4
4
4
4
<2 (total)
52
<2
14, 52
14, 5
15, -
15, -
15, 10
15, 12
15, 45
15, 23
15, -
15, 4
15, <2
22, 13
22, <2
22, 41
22, 12
22, 68
22, 37
3b
7 (total)
4
90
75
94
12
13
45
e
14, 88
14, 68
14, 52
14, 66
19, -
19, 53
19, 39
21, 40
21, 14
21, 48
21, 68
21, <5
21, 31
5b
6c
7d
8
9
<3 (total)
87
hν, 2 h
23
15
10b
11f
12b,f
13b,f
14f
15f
16
hν, 2 h, (p-DNB)
78
72
16
138
100
164
105
dark, 3 h
dark, 3 h (p-DNB)
hν, 25 min
hν, 25 min (p-DNB)
hν, 3 h
hν, 3 h
a
Carbanions were formed from neutral molecules (2.4 mmol) and t-BuOK (2.8 mmol); substrates (0.40 mmol) in 12.5 mL of DMSO.
b
Substitution products quantified by GLC with internal standard (C24 for 14 and 19, C32 for 15, Ph3Sb for 21 and 22). p-DNB (20 mol
%) was added. c t-BuOK (2.4 mmol). 2 (0.48 mmol) and 14 (0.16 mmol) in 5 mL of DMSO. e Not quantified. f t-BuOK (3.6 mmol) and
d
acetone enolate ion (0.80 mmol).
carbanions is not induced by FeBr2.28 Also, the photo-
Sch em e 1
stimulated reaction of 1 with 2-naphthyl methyl ketone
anion (9) gave a low yield of the substitution product 10
(32%) along with adamantane (20%) (Table 1, experi-
ments 18-20).
The different reactivity pattern of 1 compared to that
of 1-IAd toward 6 may be due to the steric hindrance
encountered in the coupling reaction of 6 with the
2-adamantyl radical. Theoretical calculations show that
the substitution product 7 is less stable than the substi-
tution product with 1-IAd.29 This steric hindrance renders
the coupling process slow, and 2-adamantyl radicals are
therefore reduced to adamantane.
Carbanions such as those derived from acetone6 or
N-acetylmorpholine30 couple rather slowly with 1-ada-
mantyl radicals. However, by changing the carbonyl
group by a thiocarbonyl functionality, an increase in the
reactivity occurs. Thus, 1-IAd reacted under irradiation
or in the presence of FeBr2 with N-acetylthiomorpholine
anion 11 to give 60-65% yield of the substitution
product.30 The photostimulated reaction (3 h) of 1 with
11 gave only 20% yield of product 12 (Chart 1). There
was no reaction in the dark (Table 1, experiments 21-
mental conditions employed. The reaction was almost
22).
completely inhibited by adding p-DNB (Table 2, experi-
ments 1-3) (eq 6).
Rea ction s of 1,2-Dih a loa d a m a n ta n es w ith Ca r -
ba n ion s. When 1,2-dichloroadamantane receives an
electron, the 1-position fragments ca. four times faster
than the 2-position.12 However, in the case of 1-chloro-
2-iodoadamantane (13) the 2-position has a lower LUMO
value (iodide is the best leaving group), and it would
fragment faster than the 1-position, with chlorine as the
substituent.
Under the same experimental conditions but when
irradiation took place for 40 min, the yield of 14 was 88%
No dark reaction of 13 with 2 (2 h) occurred in DMSO,
but in 5 min of irradiation, the monosubstitution product
and 15 was 10%. This reaction was also inhibited by
with retention of chlorine (14) was obtained (52%). No
p-DNB. When the irradiation time was 3 h, the yield of
disubstitution product 15 was found under the experi-
14 was 52%, whereas the yield of 15 increased up to 45%
(Table 2, experiments 4-6). These results indicate that
(27) Borosky, G. L.; Pierini, A. B.; Rossi, R. A. J . Org. Chem. 1992,
this is a stepwise mechanism, as shown in Scheme 1.
Upon irradiation, 2 transfers one electron to 13 to give
the radical 16 (eq 7), which further reacts with 2 to yield
the radical anion intermediate 14-‚ (eq 8). This radical
anion intermediate would have two competing reaction
pathways: intermolecular ET to 13 to afford product 14
and radical 16 that continues the chain reaction (eq 9)
57, 247.
(28) Galli, C.; Gentili, P. J . Chem. Soc. Perkin Trans. 2 1993, 1135.
(29) The heats of formation (∆H, kcal/mol) are as follows: -7.67
for 7, -10.31 for 8; for the radical anions, -40.86 for 7‚- and -42.52
for 8‚-. The activation energies Ea for the coupling process between
adamantyl radicals and 6 are as follows: 17.1 kcal/mol and 10.82 kcal/
mol for the 2- and 1-adamantyl radicals, respectively. The calculations
were carried out with the AM1 method.
(30) Murgu´ıa, M. C.; Rossi, R. A. Tetrahedron Lett. 1997, 38, 1355.

5830 J . Org. Chem., Vol. 64, No. 16, 1999
Lukach and Rossi
or an intramolecular ET to the C-Cl bond to give radical
17 (eq 10). Radical 17 would give by reaction with 2
ultimately the disubstitution product 15 (eq 11). Since
after a short irradiation time only 14 was obtained, the
intermolecular ET to 2 (eq 9) should be faster than the
intramolecular ET (eq 10).
At longer irradiation times, the disubstitution product
15 is formed, showing that 14 is an intermediate of these
reactions. To ascertain that 14 is an intermediate, the
photostimulated reaction of 14 with 2 was performed. The
disubstitution product 15 was obtained in 23% yield
(Table 2, experiment 7). The outcome of this reaction is
quite surprising, since 1-ClAd does not react with 2 under
irradiation (Table 1, experiment 23).
Product 21 increases the yield to 68%. Under a longer
irradiation time (3 h) almost all the product formed was
the disubstitution product 22 (68%) with mere traces of
21 (<5% yield). In the photostimulated reaction (3 h) of
20 with 4 without acetone enolate ion as the entrainment
reagent, the yields were lower and 21 was formed (31%)
together with 22 (37%) (Table 2, experiments 11-16).
These data are consistent with the SRN1 mechanism.
As 20 has a low reduction potential,34 the dark reaction
occurs by spontaneous ET from the nucleophile and is
inhibited by p-DNB. Since mainly products 21a and 21b
are formed, it appears that 21 are intermediates in the
formation of 22. In the photostimulated reaction there
is an increase in the yield of 22, and in the photostimu-
lated reaction in the presence of p-DNB the yield of 21
increases, which suggests that p-DNB inhibited the
formation of 22, resulting in an overall increase in the
yield of 21.
1-Iodo-2-chloroadamantane (18) does not react with 2
in the dark, but under irradiation (2 h) it affords the
monosubstitution product 19 and small amounts of the
disubstitution product 15 (eq 12). This reaction was
Con clu sion s
Substrate 1 is able to react with carbanions 2 and 4
by the SRN1 mechanism under irradiation, by entrain-
ment with the enolate ion of acetone or by induction with
FeBr2. A decrease in the reactivity of 2-adamantyl
radicals with bulky carbanions (such as 6 and 9) and with
a less reactive nucleophile such as 11 was observed.
The reaction of the chloroiodoadamantanes 13 and 18
with 2 affords the monosubstitution products 14 and 19
as intermediates, the intramolecular ET of the radical
anion intermediates being a slow process. Product 14
with chlorine in the 1-position reacts further to give the
disubstitution product 15, whereas 19 with chlorine in
the 2-position is quite unreactive under these experi-
mental conditions showing that position 1 is more reac-
tive than position 2, as found previously.12
The formation of the monosubstitution compounds 21a
and 21b as intermediates in the reaction of 20 with 4
indicated that the intramolecular ET of the radical anion
intermediates is a slow process. The fact that 21a was
formed as the major monosubstitution product and that
a small amount of 21b was obtained also shows that
when 20 accepts an electron, the 1-position fragments
faster than the 2-position. Monosubstitution products 21
react further to give the disubstitution compound 22.
slightly inhibited by p-DNB (Table 2, experiments 8-10).
There is some decomposition of the products under these
experimental conditions, and there is unbalance between
the halide ion yields and the products obtained.31
These observations show that 18 also reacts with 2 by
the SRN1 mechanism in a fashion similar to that of 14
and in the radical anion formed by the coupling of
2-chloro-1-adamantyl radical with 2 the intermolecular
ET to the substrate is faster than the intramolecular ET
to the σ* MO of the C-Cl bond. Due to their partial
decomposition, these reactions were not studied further.
The reaction of 1,2-diiodoadamantane (20) with 4 and
with acetone enolate ion in the dark gave monosubsti-
tution products with retention of iodine in the 2-position
(21a ) and in the 1-position (21b) in ca. 40% yield32 and
the disubstitution product 22 in 13% yield (eq 13).33
Exp er im en ta l Section
Gen er a l Meth od s. Irradiation was conducted in a reactor
equipped with two 400-W UV lamps emitting maximally at
350 nm (Philips Model HPT, water-refrigerated). Column
chromatography was performed on silica gel (70-270 mesh
ASTM).
Syn th esis of 2-Iod oa d a m a n ta n e. A mixture of 2-ada-
mantanol (1.2 g), sodium iodide (4.9 g), and hydriodic acid
(58%, 13.2 mL) was stirred at 90-100 °C for 48 h. The mixture
was cooled and diluted with 200 mL of water, obtaining a white
solid after filtration. Recrystallization from acetone-water
gave pure 2-iodoadamantane: mp 46-47 °C (lit.35 mp 46-47
°C) (1.4 g, 81% yield).
This dark reaction was inhibited by p-DNB, and these
reactions were light-catalyzed. Thus, the photostimulated
reaction (25 min) gave 21 (48%) and 22 (41%). The
inhibition with p-DNB for 22 decreased the yield to 12%.
Syn th esis of 1,2-Dih a loa d a m a n tes. These compounds
(31) Small amount of unidentified olefins were found.
were obtained from the procedure described in the literature.36
(32) Compound 21a was formed in major proportion, with mere
traces of 21b. These two compounds were quantified together; 21a was
purified and the structure determined.
(33) There was no reaction of 20 with 2 in the dark (3 h), but under
irradiation there was a very fast process (5 min) which gave 15 in low
yield (28%) although iodide ions were quantified to be 162%. The
reaction was inhibited by p-DNB. There were substantial amounts of
several unidentified olefins. These reactions were not studied further.
(34) The LUMO value of 20 is 0.149 eV, compared with 1-IAd (0.446
eV) and 1 (0.523 eV) (AM1 method).
(35) Udding, A. C., Strating, J ., Wynberg, H. Tetrahedron Lett. 1968,
11, 1345.
(36) Abdel-Sayed, A. N., Bauer, L. Tetrahedron 1988, 44, 1873.

2-Iodo- and 1,2-Dihaloadamantane-Carbanion Reactions
J . Org. Chem., Vol. 64, No. 16, 1999 5831
P h otostim u la ted Rea ction of 2-Iod o- a n d 1,2-Dih a -
loa d a m a n ta n es w ith Ca r ba n ion s in DMSO. The procedure
is described in a previous publication.14
r-(2-Ch lor oa d a m a n t-1-yl)a cetop h en on e (19): isolated as
a white solid after radial chromatography on silica gel, eluted
with petroleum ether-diethyl ether (98:02). 1H NMR
(CDCl3): δ 1.36-2.35 (13H, m), 2.81-3.13 (2H, m), 4.70-4.84
(1H, m), 7.38-7.63 (3H, m), 7.88-8.03 (2H, m). 13C NMR
(CDCl3): δ 27.9, 30.5, 36.5, 36.9, 37.1, 37.7, 38.3, 41.7, 47.0,
71.4, 128.0, 128.5, 132.8, 138.3, 199.3. MS (EI+) m/z (%): 290
(5.7), 289 (16.2), 288 (11.3), 253 (13.2), 252(10.3), 251 (4.8),
107 (5.4), 106 (47.2), 105 (100), 104 (41.2), 91 (9.0), 79 (4.8),
78 (8.6), 77 (24.2), 76 (8.5). HRMS: calcd 289.135918, found
289.135024.
1,2-Bis(ben zoylm eth ylen e)a d a m a n ta n e (15): isolated as
an solid after radial chromatography on silica gel, eluted with
petroleum ether-diethyl ether (95:05); mp ) 81-83 °C. 1H
NMR (CDCl3): δ 1.49-1.72 (10H, m), 2.05-2.17 (1H, m), 2.20-
2.31 (2H, m) δ 2.97-3.21 (5H, m), 7.38-7.58 (6H, m), 7.92-
7.97 (4H, m). 13C NMR (CDCl3): δ 35.4, 37.4, 37.6, 41.6, 42.5,
44.0, 46.6, 53.3, 128.1, 128.4, 132.7, 137.4, 200.1. MS (EI+)
m/z (%): 372 (2.7), 254 (12.5), 253 (63.2), 252 (28.4), 251 (11.0),
234 (4.4), 106 (13.8), 105 (100), 104 (73.1), 91 (12.5), 79 (10.9),
78 (7.9), 77 (56.1), 76 (22.2). HRMS: calcd 373.216755, found
373.215966.
Isola tion a n d Id en tifica tion of th e P r od u cts: r-(Ad a -
m a n t-2-yl)a cetop h en on e (3): isolated as a white solid after
radial chromatography on silica gel, eluted with petroleum
ether-diethyl ether (98:02); mp ) 68-70 °C. 1H NMR
(CDCl3): δ 1.66-2.14 (14H, m), 2.36-2.57 (1H, m), 3.09 (2H,
d, J ) 7.7 Hz), 7.38-7.65 (3H, m), 7.92-8.07 (2H, m). 13C NMR
(CDCl3): δ 27.9, 31.9; δ 32.1, 38.3, 39.0, 40.6, 41.9, 128.1, 132.8,
137.6, 200.5. MS (EI+) m/z (%): 255 (43.7), 254 (M+, 44.8),
236 (8.3), 179 (9.0), 149 (9.8), 120 (16.2), 106 (21.4), 105 (100),
91 (11.8), 77 (32.0), 56(9.3). HRMS: calcd 255.174891, found
255.174731.
(Ad a m a n t-2-yl)n itr om eth a n e (5): isolated as an oil after
chromatography on silica gel, eluted with petroleum ether-
diethyl ether (98:02). 1H NMR (CDCl3): δ 1.56-2.05 (14H, m),
2.49-2.64 (1H, m), 4.53 (2H, d, J ) 7.7 Hz). 13C NMR
(CDCl3): δ 27.6, 30.0, 31.6, 37.7, 38.3, 43.5, 79.0. MS (EI+)37
m/z (%): 195 (3), 178 (8), 175 (22), 165 (12), 163 (24), 149 (32),
147 (22), 135 (100), 123 (10), 121 (17), 119 (28), 113 (12), 111
(10), 109 (16), 107 (40), 105 (35), 101 (10).
9-(Ad a m a n t-2-yl)a n th r on e (7): isolated as a white-pink
solid after radial chromatography on silica gel, eluted with
petroleum ether-diethyl ether (98:02); mp ) 186-7 °C. 1H
NMR (CDCl3): δ 1.18-1.44 (3H, m), 1.53-1.82 (9H, m), 2.17-
2.34 (3H, m), 4.24 (1H, d, J ) 10.6 Hz), 7.33-7.53 (6H, m),
8.07-8.20 (2H, m). 13C NMR (CDCl3): δ 27.5, 27.9, 29.8, 32.1,
37.9, 39.0, 45.6, 58.8, 126.8, 127.7, 128.4, 131.1, 133.0, 145.7,
186.5. MS (EI+) m/z (%): 329 (5.5), 328 (M+, 5.8), 196 (5.9),
195 (35.4), 194 (100), 193 (14.8), 166 (6.7), 165 (17.1), 136
(18.4), 135 (32.0), 93 (10.4), 81 (6.1), 67 (12.4). HRMS: calcd
329.190541, found 329.191514.
(Ad a m a n t-2-yl)m eth yl 2-n a p h th yl k eton e (10): isolated
as a white solid after radial chromatography on silica gel,
eluted with petroleum ether-diethyl ether (98:02); mp ) 110-
111 °C. 1H NMR (CDCl3): δ 1.70-2.10 (14H, m), 2.42-2.53
(1H, m), 3.24 (2H, d, J ) 6.9 Hz), 7.49-7.67 (2H, m), 7.82-
8.10 (4H, m), 8.49 (1H, s). 13C NMR (CDCl3): δ 27.9, 31.9, 32.1,
38.2, 39.0, 40.8, 42.0, 124.1, 126.7, 127.7, 128.3, 128.4, 129.57,
129. 61; δ 132.6, 134.9, 135.5, 200.5. HRMS: calcd 305.190541,
found 305.189850.
(Ad a m a n t-2-yl)-N-th ioa cetylm or p h olin e (12): isolated
as a white solid after chromatography on silica gel, eluted with
petroleum ether-diethyl ether (70:30); mp ) 94-96 °C. 1H
NMR (CDCl3): δ 1.47-2.17 (15H, m), 3.05 (2H, d, J ) 6.5 Hz);
δ 3.64-3.84 (6H, m); δ 4.27-4.44 (2H, m). 13C NMR (CDCl3):
δ 27.8, 28.0, 31.8, 38.2, 39.2, 44.7, 46.6, 50.1, 50.5, 66.6, 203.4.
HRMS: calcd 280.173511, found 280,173774.
r-(1-Ch lor oa d a m a n t-2-yl)a cetop h en on e (14): isolated as
a white solid after radial chromatography on silica gel, eluted
with petroleum ether-diethyl ether (98:02); mp ) 80-83 °C.
1H NMR (CDCl3): δ 1.45-2.37 (13H, m), 2.73-2.85 (1H, m),
2.97-3.14 (1H, m), 3.61-3.75 (1H, m), 7.41-7.62 (3H, m),
7.95-8.07 (2H, m). 13C NMR (CDCl3): δ 29.9, 31.4, 31.8, 34.3,
36.2, 37.4, 38.6, 42.5, 47.7, 49.8, 72.7, 128.2, 128.6, 132.9, 137.3,
199.5. MS (EI+) m/z (%): 290 (7.8), 289 (23.7), 288 (14.2), 253
(29.1), 252(28.0), 251 (19.0), 149 (7.0), 106 (42.9), 105 (100),
104 (27.7), 91 (13.8), 79 (13.6), 78 (12.1), 77 (40.2), 76 (10.8).
HRMS: calcd 289.135918, found 289.136247.
(2-Iod oa d a m a n t-1-yl)n itr om eth a n e (21a ): isolated as a
white solid after radial chromatography on silica gel, eluted
with petroleum ether-diethyl ether (99:01) and recrystallized
from petroleum ether; mp ) 123-4 °C. 1H NMR (CDCl3): δ
1.36-2.48 (13H, m), 4.14-4.48 (2H, m), 4.84-4.93 (1H, m).
MS (EI+) m/z (%): 321 (1), 196 (3), 195 (34), 194 (100), 164
(22), 148 (20), 136 (14), 135 (97), 133 (16), 131 (6), 127 (4), 126
(4), 121 (3), 120 (8), 119 (48), 105 (54). 13C NMR (CDCl3): δ
27.7, 28.1, 32.7, 35.7, 37.0, 38.0, 38.4, 38.8, 49.3, 88.5. HRMS:
calcd 321.0226, found 312.0220.
1,2-Bis(n itr om eth yl)adam an tan e (22): isolated as a white
solid after recrystallization from petroleum ether; mp ) 115-6
°C 1H NMR (CDCl3): δ 1.44-1.96 (11H, m), 2.02-2.16 (2H,
m), 2.53-2.68 (1H, m), 4.04-4.33 (2H, m), 4.48-4.88 (2H, m).
MS (EI+) m/z (%): 254 (2), 208 (6), 194 (3), 193 (10), 178 (7),
177 (40), 176 (10), 163 (14), 162 (10), 161 (37), 160 (10), 159
(37), 150 (13), 149 (100), 148 (6), 147 (20), 145 (9), 135 (26),
133 (42), 132 (5), 131 (17), 121 (18), 120 (15), 119 (73), 117
(22), 107 (40), 105 (69). 13C NMR (CDCl3): δ 27.4, 27.6, 30.0,
30.4, 35.4, 36.4, 37.1, 41.1, 43.5, 75.5, 84.0. HRMS: calcd
254.1267, found 254.1259.
Ack n ow led gm en t. This work was supported in part
by the Consejo de Investigaciones de la Provincia de
Co´rdoba (CONICOR), the Consejo Nacional de Investi-
gaciones Cient´ıficas y Te´cnicas (CONICET), SECYT,
and Universidad Nacional de Co´rdoba, Argentina. We
thank Prof. Pelayo Camps of the University of Barce-
lona, Spain, for his help in recording the HRMS in the
Laboratorio de Espectrometr´ıa de Masas, CSIC. A.E.L.
gratefully acknowledges receipt of a fellowship from
CONICET.
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra of compounds 3, 5, 7, 10, 12, 14, 15, 19, 21a , and 22.
This material is available free of charge via the Internet at
http://pubs.acs.org.
(37) The HRMS could not be determined by EI or FAB.
J O990156L