Reactions of 1,3-Dihaloadamantanes with Carbanions in DMSO: Ring-Opening Reactions to Bicyclo[3.3.1]nonane Derivatives by the SRN1 Mechanism

Article abstract of DOI:10.1021/jo9620728

The reactions of 1,3-dihaloadamantanes with various carbanionic nucleophiles were studied. Potassium enolates of acetophenone (2) and pinacolone (10b) and the anion of nitromethane (10a) reacted with 1,3-diiodoadamantane (1a) in DMSO under photostimulation by a free radical chain process to form a 1-iodo monosubstitution product as an intermediate, which undergoes concerted fragmentation to form derivatives of 7-methylidenebicyclo[3.3.1]nonene (3 and 11). This reaction does not occur in the dark at 25 °C, and the photostimulated reaction is partially inhibited by p-dinitrobenzene. 1,3-Dibromoadamantane (1b) and 1-bromo-3-chloroadamantane (1c) also reacted under irradiation with 2, although more sluggish than 1a, also giving the 7-methylidenebicyclo-[3.3.1]nonene derivative 3. When a nucleophile was used without acidic hydrogens in the α-position, such as the enolate ion of isobutyrophenone (16), in order to inhibit the ring opening of adamantane, it reacted under irradiation with 1a to give the products adamantane, 1-iodoadamantane, monosubstituted 17, 1-iodo-monosubstituted 19, and disubstituted 20. Their distribution depended on the experimental conditions. In these reactions, 1-iodoadamantane and 19 were intermediates. For reactions involving the radical anion intermediate of the 1-iodo monosubstitution product, the intermolecular ET to the substrate was observed to be much faster than intramolecular ET to the C-I bond.

Full text of DOI:10.1021/jo9620728

4260
J . Org. Chem. 1997, 62, 4260-4265
Rea ction s of 1,3-Dih a loa d a m a n ta n es w ith Ca r ba n ion s in DMSO:
Rin g-Op en in g Rea ction s to Bicyclo[3.3.1]n on a n e Der iva tives by
th e SRN1 Mech a n ism
Andre´s E. Lukach, Ana N. Santiago, and Roberto A. Rossi*
Departamento de Quı´mica Orga´nica, Facultad de Ciencias Quı´micas, Universidad Nacional de Co´rdoba,
A.P. 4, C.C. 61, 5000 Co´rdoba, Argentina
Received November 5, 1996X
The reactions of 1,3-dihaloadamantanes with various carbanionic nucleophiles were studied.
Potassium enolates of acetophenone (2) and pinacolone (10b) and the anion of nitromethane (10a )
reacted with 1,3-diiodoadamantane (1a ) in DMSO under photostimulation by a free radical chain
process to form a 1-iodo monosubstitution product as an intermediate, which undergoes concerted
fragmentation to form derivatives of 7-methylidenebicyclo[3.3.1]nonene (3 and 11). This reaction
does not occur in the dark at 25 °C, and the photostimulated reaction is partially inhibited by
p-dinitrobenzene. 1,3-Dibromoadamantane (1b) and 1-bromo-3-chloroadamantane (1c) also reacted
under irradiation with 2, although more sluggish than 1a , also giving the 7-methylidenebicyclo-
[3.3.1]nonene derivative 3. When a nucleophile was used without acidic hydrogens in the R-position,
such as the enolate ion of isobutyrophenone (16), in order to inhibit the ring opening of adamantane,
it reacted under irradiation with 1a to give the products adamantane, 1-iodoadamantane,
monosubstituted 17, 1-iodo-monosubstituted 19, and disubstituted 20. Their distribution depended
on the experimental conditions. In these reactions, 1-iodoadamantane and 19 were intermediates.
For reactions involving the radical anion intermediate of the 1-iodo monosubstitution product, the
intermolecular ET to the substrate was observed to be much faster than intramolecular ET to the
C-I bond.
Several alkyl halides have been found to react with
nucleophiles by the radical nucleophilic substitution, or
RN1, mechanism.1 The main steps that it involves are
The photostimulated reaction of 1,3-dihaloadaman-
tanes with Ph2P- ions gave mainly the disubstitution
product.7 These substrates with NaMe3Sn in THF give
products that depend on the leaving groups: with iodides
or bromides the reaction proceeds predominantly with
the formation of 1,3-dehydroadamantane, but with chlo-
rides or 1-chloro-3-bromo, the disubstitution product is
formed through the SRN1 mechanism.8
S
shown in eqs 1-3.
Initiation step:
ET
RX + Nu- 8 R• + X- + Nu•
(1)
Propagation steps:
1-Iodoadamantane reacted with carbanionic nucleo-
philes in DMSO under photostimulation9 or was stimu-
lated by FeBr2 by the SRN1 mechanism.10 Taking this
into account as well as the importance in synthesis of
C-C bond formation, we undertook the investigation of
the reactions of 1,3-dihaloadamantanes with carbanions
in DMSO. We also studied the competition between
intra- and intermolecular ET in the intermediate radical
anion.
R• + Nu- f (RNu)•-
(2)
(3)
(RNu)•- + RX f RNu + R• + X-
In the initiation step, when there is no spontaneous
ET from the nucleophile to the substrate (eq 1), it can
occur under photostimulation.1 The alkyl radical thus
formed couples with the nucleophile to give a radical
anion (eq 2), which by an intermolecular dissociative ET2
to the substrate yields the substitution product and the
alkyl radical that continue the chain propagation steps
(eq 3).
1-Haloadamantanes as well as other bridgehead ha-
lides react with nucleophiles by ET reactions.1,3 The
reactions of dihalo bridgehead compounds with nucleo-
philes give either the halo monosubstitution or disubsti-
tution product depending on the radical type, the nature
of the nucleofugal group, and the nucleophile.4,5 The
trimethylstannylation of dihalo bridgehead compounds
in THF proceeds by a radical or polar process.6
(3) (a) Smith, G. F.; Kuivila, H. G.; Simon, R.; Sultan, L. J . Am.
Chem. Soc. 1981, 103, 833. (b) Duddeck, H.; Islam, M. R. Chem. Ber.
1984, 117, 565. (c) Palacios, S. M.; Alonso, R. A.; Rossi, R. A.
Tetrahedron 1985, 41, 4147, 2577. (d) Ashby, E. C.; DePriest, R. N.;
Su, W. Y. Organometallics 1984, 3, 1718. (e) Alnajjar, M. S.; Kuivila,
H. G. J . Org. Chem. 1981, 46, 1053. (f) Ashby, E. C.; Sun, X.; Duff, J .
L. J . Org. Chem. 1994, 59, 1270. (g) Adcock, W.; Clark, C. I.; Trout, N.
A. Tetrahedron Lett. 1994, 35, 297. (h) Ahbala, M.; Hapiot, P. K.;
Houmam, A.; J ouini, M.; Pinson, J .; Save´ant, J . M. J . Am. Chem. Soc.
1995, 117, 11488. (i) Adcock, W.; Clark, C. I. J . Org. Chem. 1995, 60,
723.
(4) Palacios, S. M.; Santiago, A. N.; Rossi, R. A. J . Org. Chem. 1984,
49, 4609.
(5) Santiago, A. N.; Iyer, V. S.; Adcock, W.; Rossi, R. A. J . Org. Chem.
1988, 53, 3016.
X Abstract published in Advance ACS Abstracts, May 15, 1997.
(1) For reviews, see: (a) Rossi, R. A.; Pierini, A. B.; Palacios, S. M.
In Advances in Free Radical Chemistry; Tanner, D. D., Ed.; J ai Press:
London, 1990; p 193. Rossi, R. A.; Pierini, A. B.; Palacios, S. M. J .
Chem. Ed. 1989, 66, 720. (b) Rossi, R. A.; Pierini, A. B.; Pen˜e´n˜ory, A.
B. In The Chemistry of Functional Group; Patai, S., Rappoport, Z., Eds.;
Wiley: Chichester, 1995; Suppl. D2, Chapter 24, p 1395.
(2) Save´ant, J . M. Adv. Electron Transfer Chem. 1994, 4, 53 and
references cited therein.
(6) (a) Adcock, W.; Iyer, V. S. J . Org. Chem. 1985, 50, 3706. (b)
Adcock, W.; Gangodawila, H. J . Org. Chem. 1989, 54, 6047.
(7) Lukach, A. E.; Santiago, A. N.; Rossi, R. A. J . Phys. Org. Chem.
1994, 7, 610.
(8) Adcock, W.; Clark, C. I. J . Org. Chem. 1993, 58, 7341.
(9) (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.
(10) Nazareno, M. A.; Rossi, R. A. J . Org. Chem. 1996, 61, 1645.
S0022-3263(96)02072-5 CCC: $14.00 © 1997 American Chemical Society

1,3-Dihaloadamantanes + Carbanions in DMSO
J . Org. Chem., Vol. 62, No. 13, 1997 4261
Ta ble 1. Rea ction s of 1,3-Dih a loa d a m a n ta n es 1 w ith 2 in
DMSO
Sch em e 1
product yields (%)
expt 1, 102
M
2,a
M
conditions
X- b
3c
1
2
3
4
5
6
7
8
9
1a , 3.64
1a , 3.99
1a , 3.99
1a , 0.50
1a , 4.02
1a , 4.00
1a , 4.04
1b, 4.03
1c, 4.00
0.22 dark, 25 °C, 4 h
0.24 hν, 25 °C, 5 min
0.24 hν, 25 °C, 5 mind
0.03 hν, 30 °C, 5 min
0.24 dark, 60 °C, 3 h
0.24 dark, 60 °C, 3 hd
0.24 hν, 60 °C, 3 h
0.24 hν, 60 °C, 3 h
0.24 hν, 60 °C, 3 h
<3
85
25
87
93
73
92
60
26e
80
26
83
88
45
87
50
21
a
0.28 M t-BuOK was added to form the carbanion 2 from
b
acetophenone. Considering two halide ions per molecule (deter-
mined potentiometrically). c Determined by GLC using C24H26 or
Ph3Sb as internal standard. 20 mol % p-DNB was added. e 25%
d
yield of chloride ions and 27% yield of bromide ions.
Resu lts a n d Discu ssion
We found that there was no reaction of 1,3-diiodo-
adamantane (1a ) with the enolate ion of acetophenone
(2) at 25 °C in DMSO during 4 h (expt 1, Table 1).
However, there is a very fast reaction with irradiation
for 5 min under the same experimental conditions giving,
through a ring-opening reaction, the monosubstitution
product 3 (80%) after quenching. Although dehalogena-
tion was extensive (85% based on two iodine ions per
molecule of substrate) no disubstitution product was
found (expt 2, Table 1) (eq 4). The photostimulated
lated reaction was carried out under more dilute condi-
tions, and in order to increase the possibility of an
intramolecular ET to give the disubstitution product 6,
only 3 was formed.
These results differ from the results found in the
photostimulated reaction of 1,3-dihaloadamantanes with
Ph2P- ions in liquid ammonia, wherein all the substrates
studied, even 1,3-dichloroadamantane, give mainly the
disubstitution product and small amounts of the mono-
substitution products. The halo monosubstitution prod-
uct was not an intermediate in these reactions to give
the disubstitution product.7
Since neither halo monosubstitution nor disubstitution
products were found, it is suggested that the iodo
monosubstitution product 5 is formed and is deprotonated
under the basic reaction conditions to give the anion 7,
which by a ring-opening reaction renders the product 8
and iodide ions (eq 9). The product 8 is also deprotonated
to give the carbanion 9, and when the reaction is
acidified, it gives the more stable isomer 3 (eq 10). There
reaction was partially inhibited by p-dinitrobenzene (p-
DNB), a well-known inhibitor of SRN1 reactions, giving
26% of product 3 in the same period of time (expt 3, Table
1). The reaction was performed under dilute conditions
in order to see if there was a change in the products, but
only 3 (83%) was obtained again, and no disubstitution
products were found (expt 4, Table 1).
Although there is no reaction at 25 °C during 4 h, at
60 °C in 3 h the reaction of 1a with 2 yields 3 in 88%
yield. This thermal reaction was also partially inhibited
(45% yield of 3) by p-DNB. On the other hand, there is
no increase in the yield under irradiation (expts 5-7,
Table 1).
These results can be explained according to the SRN1
mechanism. The photostimulated or thermal ET from
nucleophile 2 to the substrate 1a gives the radical
intermediate 4 and iodide ion (eq 5). This radical couples
with 2 to give the radical anion intermediate 5•- (eq 6).
This radical anion intermediate which conceivably could
undergo two competing reactions: intermolecular ET
with the substrate 1a to give 4 and 5 (eq 7), or intramo-
lecular ET with the σ* MO of the C-I bond, which by
fragmentation would give a new radical intermediate.
This in turn could couple with 2 leading finally to the
disubstitution product 6 (eq 8) (Scheme 1).
are examples in the literature in which a substituent with
acidic hydrogens, such as OH and SH, is present at C(1)
of 3-bromoadamantane and concerted fragmentation to
7-methylidenebicyclo[3.3.1]nonane derivatives takes place
under basic conditions.11
Since iodide ion is a very good leaving group, we
switched to 1,3-dibromoadamantane (1b) to see if the
ring-opening reaction is slow. In the photostimulated
reaction of 1b with 2 at 60 °C in 3 h, only 3 was found,
together with 60% of bromide ions and 1b (50%) (expt 8,
Table 1). This reaction is slower than the reaction of 1a ,
The fact that no disubstitution product 6 was formed
indicates that intramolecular ET is too slow and does not
compete with intermolecular ET. When the photostimu-
(11) Fischer, W.; Grog, C. A. Helv. Chim. Acta 1978, 1588 and
references cited therein.

4262 J . Org. Chem., Vol. 62, No. 13, 1997
Lukach et al.
Ta ble 2. Rea ction s of 1,3-Dih a loa d a m a n ta n es 1 w ith
10a ,b in DMSO
Ch a r t 1
product
yields (%)
expt 1, 102 M
10,a
M
conditions
X- b
11c
1
2
3
4
5
6
7
8
9
1a , 4.00 10a , 0.24 hν, 40 °C, 1.5 h
1a , 3.97 10a , 0.24 hν, 40 °C, 1.5 hd
1a , 4.00 10a , 0.24 hν, 40 °C, 1.5 he
1a , 3.99 10a , 0.24 hν, 40 °C, 1.5 hf
1a , 3.99 10a , 0.24 dark, 60 °C, 3 hf
1b, 4.00 10a , 0.24 hν, 60 °C, 3 hf
1c, 4.07 10a , 0.20 hν, 60 °C, 3 hf
1a , 3.97 10b, 0.24 hν, 30 °C, 5 min
1a , 3.98 10b, 0.24 hν, 30 °C, 5 mind
75 11a , 67
10 11a , 11
67 11a , 61
83 11a , 55
<5 11a ,
6 and 7, Table 2). All these results indicate that
intermolecular ET to the substrate is much faster than
intramolecular ET to the C-I bond, which would give
the disubstitution product. With nucleophiles 2 and 10a ,
the SOMO value of the radical anion intermediates, such
as 5•- and 12a •-, belongs to the benzoyl and nitro
moieties13 (Chart 1).
<5 11a ,
<5 11a ,
86 11b, 80
25 11b, 26
30 11b, 31
86 11b, 81
85 11b, 80
87 11b, 80
10 1a , 3.99 10b, 0.24 dark, 30 °C, 30 min
11 1a , 3.98 10b, 0.24 dark, 60 °C, 30 min
12 1a , 4.00 10b, 0.24 dark, 60 °C, 30 mind
13 1a , 0.50 10b, 0.03 hν, 30 °C, 5 min
In order to facilitate intramolecular ET to the C-I bond
of the radical anion intermediate, formed when the
carbanion couples with the 3-iodo-1-adamantyl radical
(4), we studied the reaction of 1a with pinacolone enolate
ion (10b). In this case, the radical anion intermediate
formed (12b•-) has the antibonding C-I bond lower in
energy than the -COCMe3 moiety and intramolecular
ET is thermodynamically favorable. The photostimu-
lated reaction between 1a and 10b is quite fast. In 5
min at 30 °C it gives an 80% yield of the rearranged
product 11b (eq 11). This photostimulated reaction is
inhibited by p-DNB (26% yield of 11b), and there is a
reaction in the dark at 30 °C (31% yield of 11b) that
increases the yield to 81% at 60 °C. No unrearranged
products were found under more dilute conditions to slow
intermolecular ET (expts 8-13, Table 2).
The photostimulated reaction of 1,3-diiodo-2,2-dimeth-
ylpropane, a neopentyl type of structure with two leaving
groups, with 2 gave the disubstitution product, and no
products derived from the iodo monosubstitution product
were formed.14 These results indicate that the radical
anion intermediate 14 formed in these reactions in the
coupling of 3-iodo-2,2-dimethyl-1-propyl radical (13) with
2 has a very fast intramolecular ET to the C-I bond to
give ultimately the disubstitution product 15 (eqs 12 and
13).
a
0.28 M t-BuOK was added to form the carbanion 10a or 10b
b
from nitromethane or pinacolone, respectively. Considering two
halide ions per molecule (determined potentiometrically). c Deter-
mined by GLC using 4-bromobiphenyl or phenanthrene as internal
standards, respectively. 20 mol % p-DNB was added. e 0.24 M
d
t-BuOK was added to form the carbanion 10a from nitromethane.
f Acetone (0.08 M) and t-BuOK (0.36 M) were added.
in agreement with the higher electron affinity of iodo
compounds compared to the corresponding bromo deriva-
tives.12
The photostimulated reaction of 1-bromo-3-chloro-
adamantane (1c) is even more sluggish;12 thus, in 3 h of
irradiation only a 21% yield of 3 was obtained, with a
27% yield of bromide ions and a 25% yield of chloride
ions. The substrate 1c was recovered in high yield (expt
9, Table 1). These results suggest that the carbanion
intermediates formed in these reactions rearranged very
easily with iodide, bromide, or chloride ions as leaving
groups at the 3-position of the adamantane ring.
We next studied the reaction of substrates 1 with a
more stable and less basic nucleophile such as the
nitromethane anion (10a ) in order to see if the ring-
opening reaction occurs with a more stable carbanion
intermediate. 1-Iodoadamantane did not react with 10a
under irradiation in DMSO. However, the substitution
product 1-adamantylnitromethane was obtained in 87%
yield when the photostimulated reaction was performed
in the presence of good electron donors such as acetone
enolate ions (entrainment reaction).9 However, we found
that 1a reacts under irradiation with 10a , as expected
by the higher electron affinity of 1a compared with
1-iodoadamantane.12 Thus, the photostimulated reaction
of 1a with 10a in 1.5 h at 40 °C gives the rearranged
product 11a (61% yield). This reaction is inhibited by
p-DNB (11% yield), and the yield is not increased with
excess of t-BuOK or with the acetone enolate ion as an
entrainment nucleophile. There was no reaction in the
dark, even at 60 °C in 3 h (expts 1-5, Table 2) (eq 11).
Although 14 has the same number of σ-bonds between
the benzoyl radical anion and the C-I bond, the different
rates of the intramolecular ET results can be explained
on account of the rigid structure of the intermediate
radical anions such as 5•- and 12•- in the adamantane
system compared with the flexibility of the structure of
the radical anion intermediate 14 in the neopentyl
system. This radical anion can be a conformer similar
(13) The SOMO values of 5•- (-1.99 eV) and 12a •- (-2.65 eV) belong
to the benzoyl and nitro moieties, respectively, and are lower in energy
than the σ* values of the C-I bonds (2.66 and 2.88 eV, respectively).
On the other hand, the SOMO value of radical anion 12b•- (-1.55 eV)
belongs to the σ* of the C-I bonds, the π* of the carbonyl moiety being
higher in energy. These calculations were carried out with the AM1
method.
There was no photostimulated reaction with substrates
1b,c, even in the presence of acetone enolate ions (expts
(12) The Ep vs SCE in acetonitrile are 1a , -1.80 V; 1b, -2.30 V;
1c, -2.50 V; and 1-iodoadamantane, -2.20 V. Adcock, W.; Clark, C.
I.; Houmam, A.; Krstic, A. R.; Pinson, J .; Save´ant, J . M.; Taylor, D.
K.; Taylor, J . F. J . Am. Chem. Soc. 1994, 116, 4659.
(14) Pen˜e´n˜ory, A. B.; Rossi, R. A. Gazz. Chim. Ital. 1995, 125, 1.

1,3-Dihaloadamantanes + Carbanions in DMSO
J . Org. Chem., Vol. 62, No. 13, 1997 4263
Ta ble 3. Rea ction s of 1-Iod oa d a m a n ta n e w ith
Isobu tyr op h en on e En ola te Ion (16) in DMSOa
Ch a r t 2
product yieldsb (%)
expt
conditions
I-
17a
17b
adamantane
1
2
3
4
hν, 50 °C, 2 h
83
88
25
45
6
6
20
26
35
52
hν, 40 °C, 1.5 hc
dark, 60 °C, 3 h
hν, 60 °C, 3 hd
2
5
e
to the adamantane 14a , or due to the flexibility of this
system, the benzoyl radical anion can be close to the C-I
bond such as in 14b, and from this type of conformer
intramolecular ET is faster than in conformer 14a . It
seems therefore that intramolecular ET occurs through
space and not through bonds because it should also occur
in the adamantane system (Chart 2).
a
1-IAd (0.04 M), isobutyrophenone (0.13 M), acetone (0.05 M),
and t-BuOK (0.18 M). b Adamantane was quantified with camphor
as internal standard and 17 with Ph4Sn; iodide ions determined
potentiometrically. c 18-Crown-6-ether was added (0.18 M). 20
d
mol % p-DNB was added. e Not quantified.
Ta ble 4. Rea ction s of 1a w ith 16 in DMSOa
product yieldsb (%)
These results are in agreement with the γ-radiolysis
of 1-benzoyl-ω-haloalkanes, which form the radical anion
on the benzoyl moiety, and then by a unimolecular ET
reaction to the C-X bond they form the radical. This
ET reaction occurs through a cyclic transition state. With
1-benzoyl-4-iodobutane, a substrate that has the same
amount of C atoms as 14 between the two reacting
centers, the rate of ET is 6.0 × 107 in HMPA at 25 °C.15
The ring-opening reaction of the halo monosubstitution
products formed in all these reactions occurs because of
their acidic hydrogens in the R-position that give carb-
anions under basic reaction conditions. These, then, on
losing the second halide ion in the 3-position of the
adamantane, give the products through ring opening.
We studied the reaction of isobutyrophenone enolate
ion (16), which after coupling with the radicals has no
hydrogens in the R-position, with 1-iodoadamantane and
1a . The photostimulated reaction of 1-iodoadamantane
and 16 is sluggish, giving mainly the reduction product
adamantane (AdH). When the reaction was performed
under the same experimental conditions but in the
presence of acetone enolate ion as an entrainment
nucleophile, the products obtained were adamantane
(35% yield) and the substitution products 17a (6%) and
17b (20%) together with small amounts of unknown
products. When the reaction was performed in the
presence of 18-crown-6 ether, there was a slight increase
in the yield of products (AdH, 52%; 17a , 6%; 17b, 26%)
(expts 1 and 2, Table 3) (eq 14). This reaction did not
expt
conditions
I- c 1-IAd 17a 17b 19 20
1
2
3
4
5
6
7
hν, 25 °C, 5 min
hν, 25 °C, 5 mind
hν, 25 °C, 5 mine
hν, 60 °C, 1.5 hd,f
hν, 60 °C, 3 h
106
125
9
184
180
g
40
42
<1
<1
<2
30
19
28
1
<1
28 <2
24 <1
<1
36
22
17
13
15
3
<1
14
10
2
<1
37
hν, 60 °C, 3 he
dark, 60 °C, 1.5 hd
90
38
a
1a (0.04 M), isobutyrophenone (0.24 M), acetone (0.04 M), and
b
t-BuOK (0.36) M. 1-IAd was quantified with 1-BrAd, and 17, 19,
and 20 with Ph4Sn as internal standard. c Considering two iodide
d
ions per molecule (determined potentiometrically). 18-Crown-6-
ether was added (0.36 M). e 20 mol % p-DNB was added. f Ada-
g
mantane was quantified in 18% yield. Not quantified.
the radical anion of the unsaturated ketone 18, which is
able to propagate the chain process (eq 15). The fact that
the most important substitution product is the one
formed by coupling in the para-position of the benzene
ring suggests that this nucleophile is strongly sterically
hindered.
The photostimulated reaction of 1a with 16 gave a
mixture of products, and the distribution depends on the
irradiation time. At a short period of time (5 min) and
at 25 °C, the main products obtained are 1-iodoadaman-
tane (40%), the monosubstitution products 17a (19%) and
17b (1%), the iodo monosubstitution product 19 (28%),
and the disubstitution product 20 (<2%) (expt 1, Table
4) (eq 16).
occur in the dark, and the photostimulated reaction is
inhibited by p-DNB, although some dehalogenation is
observed (expts 3 and 4, Table 3).
It is known that when carbanions have hydrogens in
the â-position, the reduction process competes with the
coupling process.16 Carbanion 16 has two methyl groups
in the â-position, which facilitates the reduction process.
The hydrogen abstraction by 1-adamantyl radical gives
All the products found have the adamantane moiety,
and no products through the ring-opening reactions were
observed. The yields are slightly increased in the pres-
ence of 18-crown-6 ether, and the photostimulated reac-
tion is inhibited by p-DNB (expts 1-3, Table 4).
(15) Kimura, N.; Takamuku, S. Bull. Chem. Soc. J pn. 1991, 64,
2433.
(16) Wolfe, J . F.; Moon, M. P.; Sleevi, M. C.; Bunnett, J . F.; Bard,
R. R. J . Org. Chem. 1978, 43, 1019.
When the photostimulated reaction is carried out at
longer irradiation time (1.5 h) and at 60 °C, there is a

4264 J . Org. Chem., Vol. 62, No. 13, 1997
Lukach et al.
methanol gave the pure diiodide: mp 108-109 °C (lit.19 mp
110-111 °C); 13C NMR δ 33.6, 36.6, 44.5, 49.9, 64.3.
3-Bromoadamantanol was obtained from oxidation of 1-bro-
moadamantane and then was halogenated with thionyl chlo-
ride. 1-Bromo-3-chloroadamantane was isolated as a white
solid after chromatography on silica gel (petroleum ether as
eluant) and then sublimation: mp 100-101 °C (lit.20 mp
101.5-103 °C).
In another experiment, 3-bromoadamantanol was halogen-
ated with hydrobromic acid. The 1,3-dibromoadamantane was
isolated as a white solid after chromatography on silica gel
(petroleum ether as eluant) and then sublimation: mp 111-
112 °C (lit.21 mp 112-113 °C).
P h otostim u la ted Rea ction of 1,3-Dih a loa d a m a n ta n e
w ith Acetop h en on e En ola te Ion (2) in DMSO. The
following procedure is representative of all the reactions. Into
a three-necked, 100-mL, round-bottomed flask equipped with
a Liebig-West refrigerant, a nitrogen inlet, and a magnetic
stirrer was added 25 mL of dry DMSO. t-BuOK (7 mmol) was
then added followed by acetophenone (6 mmol) and the
reaction mixture stirred for 10 min. The substrate (1 mmol)
was then added and the mixture irradiated for 5 min. The
reaction was quenched with addition of ammonium nitrate in
excess and 50 mL of water, and then the mixture was extracted
with diethyl ether. The products were quantified by GLC with
the internal standard method. In another experiment the
product was isolated as a white solid after chromatography
on silica gel (petroleum ether-diethyl ether (95-5) as the
eluant).
decrease in the yield of 1-iodoadamantane (<1%) and 19
(<1%) and an increase in the yields of the substitution
products 17a (36%) and 17b (13%) and the disubstitution
product 20 (14%). Similar results were found at a longer
irradiation time (3 h). Under the same experimental
conditions but with the addition of p-DNB, the yield of
1-iodoadamantane was 30%. In dark conditions and at
60 °C, there is a reaction that gives 1-iodoadamantane
(38%) and 19 (37%) (expts 4-7, Table 4).
These results suggest that this is a stepwise reaction,
with 1-iodoadamantane and 19 as intermediates, and the
3-iodoadamantyl radical intermediate (4) can either react
with 16 by hydrogen atom abstraction to give 1-iodo-
adamantane as an intermediate or couple to give the
radical anion 19•- which renders ultimately product 19
by an intermolecular ET. At longer irradiation times and
at an increased temperature, 1-iodoadamantane reacts
with 16 to give adamantane and the monosubstitution
products 17. The iodo monosubstitution product 19 also
reacts with 16 by hydrogen atom abstraction to give 17
or couples to give finally the disubstitution product 20.
These results indicate that intramolecular ET of the
radical anion intermediates to the C-I bond is much
slower than intermolecular ET, similar to the behavior
of the other carbanions studied here. The iodo mono-
substitution product 19 has no â-hydrogens, and it is
unable to undergo the ring-opening reaction. The ada-
mantyl moiety is maintained in all the products found.
P h otostim u la ted Rea ction of 1,3-Dih a loa d a m a n ta n e
w ith 2 in th e P r esen ce of p-DNB. The procedure was
similar to that for the previous reaction, except that 20 mol %
p-DNB was added to the solution of nucleophile prior to
substrate addition.
Exp er im en ta l Section
r-(7-Me t h ylid e n e b icyclo[3.3.1]n on -2-e n -1-yl)a ce t o-
1
p h en on e, 3: H NMR δ 2.4 (10 H, m), 3.7 (2 H, m), 4.5 (1 H,
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). Gas chromatographic analyses were performed on a
Hewlett-Packard 5890 Series II instrument with a flame-
ionization detector and the data system Hewlett-Packard 3396
Series II, using a HP5 column (5% methyl silicone). Potentio-
metric titration on halide ions was performed in a pH meter
(Seybold Wien), using an Ag/Ag+ electrode and AgNO3 as
standard. HRMS were recorded at the Institute of Advanced
Materials Study, Kyushu University, J apan, and LANAIS,
Buenos Aires, Argentina.
Mater ials. 1-Bromoadamantane, 1-chloroadamantane, thio-
nyl chloride, potassium tert-butoxide, silica gel (Aldrich Chemi-
cal Co.), hydriodic acid (Carlo Erba), phenanthrene, Ph3Sb,
4-bromobiphenyl, p-dinitrobenzene (Fluka), chromic acid, and
C24H26 were commercially available and used as received.
Isobutyrophenone, pinacolone, nitromethane, acetophenone,
and acetone were distilled and dried (molecular sieves, 4 Å).
DMSO (Carlo Erba) was distilled under vacuum and stored
over molecular sieves (4 Å).
m), 4.7 (1 H, m), 5.7 (1 H, m), 7.6 (3 H, m), 8.0 (2 H, m); 13C
NMR δ 28.9, 30.8, 31.0, 35.6, 39.1, 42.6, 47.6, 110.9, 128.3,
128.7, 129.2, 132.7, 132.8, 136.9, 145.2, 196.9; MS (EI+)
51(3.0), 65(2.3), 77(58.1), 78(5.7), 79(4.2), 91(24.9), 92(6.7),
93(2.1), 105(100), 106(11.7), 107(2.9), 119(2.5), 132(7.1), 146(4.4),
197(9.3), 252(1.7); HRMS (EI+) calcd 252.1514, expt 252.1506.
r-( 7 -M e t h y l i d e n e b i c y c l o [ 3 .3 .1 ] n o n -2 -e n -1 -y l ) -
1
n itr om eth a n e, 11a : H NMR δ 2.15 (10 H, m), 4.5 (1 H, m),
4.7 (1 H, m), 4.8 (2 H, m), 5.9 (1 H, m); 13C NMR 28.3, 30.3,
30.9, 33.3, 38.6, 42.7, 82.4, 111.7, 129.1, 136.3, 144.2; HRMS
(EI+) calcd 193.1103, expt 193.1108.
r-(7-Met h ylid en eb icyclo[3.3.1]n on -2-en -1-yl)p in a co-
1
lon e, 11b: H NMR δ 1.12 (9 H, s), 2.00 (10 H, m), 3.1 (2 H,
m), 4.5 (1 H, m), 4.7 (1H, m), 5.4 (1 H, m); 13C NMR δ 26.7,
27.0, 30.9, 31.2, 35.4, 39.2, 42.7, 44.6, 45.1, 110.7, 126.8, 132.6,
145.7, 213.8; MS (EI+) 41(10.7), 57(100), 58(4.9), 59(6.6),
69(6.9), 77(7.1), 79(9.4), 85(23.5), 91(38.8), 105(14.0), 107(6.6),
119(14.8), 132(10.3), 133(5.8), 135(5.7), 146(9.3), 147(9.5),
159(12.1), 177(3.7), 191(3.6), 232(5.3); HRMS (EI+) calcd
232.1827, expt 232.1829.
r-(3-Iod oa d a m a n t-1′-yl)isobu tyr op h en on e, 19: 1H NMR
δ 1.25 (6 H, s), 1.85 (8 H, m), 2.52 (6 H, m), 7.40 (5 H, m); 13
C
Syn th esis of 1,3-Dih a loa d a m a n ta n es: Oxid a tion of
1-Ha loa d a m a n ta n e a n d Ha logen a tion of 3-Ha lo-1-a d a -
m a n ta n ol. The procedures were similar regardless of the
starting material used. To a stirred solution of pulverized
1-chloroadamantane (or 1-bromoadamantane) (1.7 g, 10 mmol)
in acetic acid and acetic anhydride (10 mL/10 mL) was added
chromic acid (3 g, 30 mmol) over 60 min, and stirring was
continued at room temperature for 24 h.17 The residue was
dissolved with water and then extracted with diethyl ether
and methylene chloride. The combined organic extract was
washed with a saturated NaHCO3 aqueous solution and dried
with NaSO4 after removal of the solvents; 3-chloro-1-adaman-
tanol was obtained which was then halogenated with hydriodic
acid18 to give 1,3-diiodoadamantane. Recrystallization from
NMR δ 22.5, 32.9, 34.8, 35.7, 43.1, 50.8, 51.6, 51.9, 53.4, 127.2,
128.0, 130.2, 141.8, 211.4; MS (EI+) 43(3.7), 77(21.6), 91(15.2),
105(100), 106(16.3), 107(3.2), 119(5.2), 120(7.2), 121(2.4),
133(3.3), 134(3.5), 175(2.3), 176(4.2), 281(13.8), 283(3.4); HRMS
(FAB+, matrix p-nitrobenzyl alcohol) calcd 409.1029 (M + 1),
expt 409.1038.
r-(Ad a m a n t-1′-yl)isobu tyr op h en on e, 17a : 1H NMR δ
1.25 (6 H, d), 1.65 (6 H, m), 1.75 (6 H, m), 2.00 (3 H, m), 7.35
(3 H, m), 7.50 (2 H, m); 13C NMR δ 22.4, 28.9, 37.0, 37.5, 38.0,
53.7, 127.4, 127.8, 129.9, 142.4, 212.2; MS (EI+) 41(6.4),
43(6.4), 55(11.2), 67(12.7), 77(24.2), 79(30.3), 81(20.1), 93(35.3),
95(15.2), 105(42.1), 121(19.1), 135(100), 136(11.3), 149(2.5),
176(16.4), 177(81.9), 178(11.9), 283(3.4); HRMS (EI+) calcd
282.1984, expt 282.1829.
(17) Schleyer, P. v. R.; Bingham, R. C. J . Org. Chem. 1971, 36, 1198.
(18) Schleyer, P. v. R.; Nicholas, R. D. J . Am. Chem. Soc. 1961, 83,
2700.
(19) Torupka, E. J .; Pincock, R. E. J . Am. Chem. Soc. 1969, 91, 4593.
(20) Perkins, R. R.; Pincock, R. E. Can. J . Chem. 1978, 56, 1269.
(21) Stetter, H. Angew. Chem., Int. Ed. Engl. 1962, 1, 268.

1,3-Dihaloadamantanes + Carbanions in DMSO
J . Org. Chem., Vol. 62, No. 13, 1997 4265
4-(Ad a m a n t-1′-yl)isobu tyr op h en on e, 19b: 1H NMR δ
1.21 (6 H, d, J ) 6.8 Hz), 1.55-2.20 (15 H, m), 3.55 (1 H, sept,
J ) 6.8 Hz), 7.45 (2 H, d, J ) 8.5 Hz), 7.91 (2 H, d, J ) 8.5
Hz); 13C NMR δ 19.2, 28.8, 35.2, 36.7, 42.9, 125.1, 128.3, 133.6,
156.5, 204.1; MS (EI+) 43(16.5), 55(7.0), 67(10.4), 79(24.2),
81(9.6), 91(25.7), 135(13.1), 154(6.7), 169(2.5), 239(100), 283(1.6);
HRMS (FAB+, matrix p-nitrobenzyl alcohol) calcd 283.2061
(M + 1), expt 283.2065.
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) (Argentina),
the Antorchas Foundation, and the Stiftung Volks-
wagenwerk (Germany). A.E.L. gratefully acknowledges
receipt of a fellowship from CONICET.
2-[3-(4-Isob u t yr ylp h e n yl)-1-a d a m a n t yl]-2-m e t h yl-1-
p h en yl-1-p r op a n on e, 20: 1H NMR δ 1.22 (6 H, d, J ) 6.8
Hz), 1.27 (6 H, s), 1.79 (12 H, m), 2.24 (2 H, s), 3.55 (1 H, sept,
J ) 6.8 Hz), 7.44 (7 H, m), 7.91 (2 H, d, J ) 8.5 Hz); 13C NMR
δ 19.2, 22.5, 29.2, 35.2, 35.9, 36.7, 37.5, 38.9, 42.1, 42.9, 53.7,
125.1, 127.3, 127.9, 128.4, 130.1, 133.8, 143.3, 155.9, 204.1,
211.9; MS (EI+) 323(100), 385(67), 428(17); HRMS (EI+) calcd
428.2716, expt 428.2716.
Su p p or tin g In for m a tion Ava ila ble: Spectral data for 3,
11a ,b, 17a ,b, 19, and 20 (9 pages). This material is contained
in libraries on microfiche, immediately follows this article in
the microfilm version of the journal, and can be ordered from
the ACS; see any current masthead page for ordering
information.
J O9620728