SRN1 Reactions of 7-Iodobicycloheptane, 1-Iodoadamantane, and Neopentyl Iodide with Carbanions Induced by FeBr2 in DMSO

Article abstract of DOI:10.1021/jo9509566

There was no reaction of 7-iodobicyclo<4.1.0>heptane (7-iodonorcarane, 1 ) exo-endo ratio of ca. 1) with acetophenone enolate ions 2 in DMSO at 25 deg C; however, with the addition of SmI2 or FeBr2 and under the same experimental conditions, the substitut

Full text of DOI:10.1021/jo9509566

J . Org. Chem. 1996, 61, 1645-1649
1645
SRN1 Rea ction s of 7-Iod obicyclo[4.1.0]h ep ta n e, 1-Iod oa d a m a n ta n e,
a n d Neop en tyl Iod id e w ith Ca r ba n ion s In d u ced by F eBr 2 in DMSO
Mo´nica A. Nazareno and Roberto A. Rossi*
Departamento Quı´mica Orga´nica, Facultad de Ciencias Quı´micas, Universidad Nacional de Co´rdoba,
Suc.16, C. C.61, 5016 Co´rdoba, Argentina
Received May 25, 1995X
There was no reaction of 7-iodobicyclo[4.1.0]heptane (7-iodonorcarane, 1) (exo-endo ratio of ca. 1)
with acetophenone enolate ions 2 in DMSO at 25 °C; however, with the addition of SmI2 or FeBr2
and under the same experimental conditions, the substitution product 3 was obtained in 9% and
72% yields, respectively, with an exo-endo ratio of ca. 16 similar to the product ratio from
photostimulated reactions. Thus, it seems that 7-norcaranyl radicals are intermediates of these
reactions. With FeBr2 at 60 °C the yield of 3 was as high as 90%. Reactions of 1 with the enolate
ion of 2-naphthyl methyl ketone 4 induced by FeBr2 gave substitution product 5 in 60% yield (96%
of it the exo isomer). In competition experiments, 4 was 1.7 times more reactive than 2, and the
anion of nitromethane (7) was 6.5 times more reactive than 2 toward 7-norcaranyl radicals. The
reactions of 1-iodoadamantane (9) and neopentyl iodide (11) with carbanion 2 induced by FeBr2
gave the substitution products in 85% and 92% yields, respectively. These observations indicate
that all these reactions induced by FeBr2 occur by the SRN1 mechanism.
Radical nucleophilic substitution, or SRN1, has been
found to be an excellent method for many types of
aromatic and aliphatic substrates with suitable leaving
groups. Even aliphatic substrates without electron-
withdrawing groups, such as cycloalkyl, bicycloalkyl, and
neopentyl halides, react by this mechanism.1 The reac-
tion proceeds by a chain process, and the propagation
steps are shown in eqs 1 and 2. In aliphatic systems that
do not have a π* MO that stabilizes the radical anion
(RX)•-, there is no intermediate (dissociative electron
transfer).2
In aromatic and in aliphatic substrates with electron-
withdrawing groups, SRN1 reactions have also been
initiated by sonication.5 In aromatic systems this has
been initiated by solvated electrons6 or sodium amalgam7
in liquid ammonia, by electrochemically induced reac-
tions,8 or by certain inorganic salts, such as Fe+2 in
aromatic9 or vinylic10 SRN1 reactions. Recently we found
that a solution of SmI2 in THF induced the reaction of
aryl iodides with carbanions in DMSO, so it, too, is a
suitable reagent to initiate these SRN1 reactions.11
All the SRN1 reactions of alkyl halides with nucleophiles
without an electron-withdrawing group, such as cy-
cloalkyl, bicycloalkyl and neopentyl halides, have been
either thermal reactions or reactions under irradiation,
but there are no reports of initiating these reactions by
chemical or other methods. Light is the most common
initiator in SRN1 reactions of these alkyl halides, but
irradiation is effective only in dilute solutions. We are
therefore in search of new procedures for accomplishing
This chain process requires an initiation step. In a few
systems, spontaneous electron transfer (ET) from the
nucleophile to an aromatic substrate has been observed.3
When the ET does not occur spontaneously, it can be
induced by light in aromatic and in aliphatic systems.4
S
RN1 reactions on a synthetic scale, avoiding the disad-
vantages of light initiation.
If reactions induced by inorganic salts were to give the
same selectivity as those induced by photostimulation,
it would seem that the intermediates involved are the
same; in other words, the reactions occur via the same
mechanism.
X Abstract published in Advance ACS Abstracts, J anuary 1, 1996.
(1) For reviews on SRN1 see: (a) Rossi, R. A., de Rossi R. H. Aromatic
Substitution by the SRN1 Mechanism, ACS Symposium Series 178;
American Chemical Society: Washington D. C., 1983. (b) Bowman,
W. R. Chem. Soc. Rev. 1988, 17, 283. (c) Rossi, R. A., Pierini A. B.,
Palacios, S. M. Advances in Free Radical Chemistry; Tanner, D. D.,
Ed., J AI Press: Greenwich, CT, 1990; p 193. J . Chem. Ed. 1989, 66,
720. (d) Norris, R. K. Comprehensive Organic Synthesis; Trost, B. M.,
Ed.; Pergamon: New York, 1991; Vol. 4, p 451. (e) Rossi, R. A.;
Santiago, A. N. Trends Org. Chem. 1992, 3, 193. (f) Rossi, R. A.; Pierini
A. B.; Pen˜e´n˜ory, A .B. The Chemistry of Functional Groups, Patai, S.;
Rappoport, Z., Eds.,Wiley: Chichester, 1995; Supl. D2, Ch. 24, p 1395.
(2) (a) Save´ant, J . M. J . Am.Chem.Soc. 1992, 114, 10595. (b) Acc.
Chem. Res. 1993, 26, 45. (c) 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, 4653. (d) Save´ant, J . M. Tetrahedron 1994,
50, 10117. (e) Adv. Electron Transfer Chem. 1994, 4, 53, and references
cited therein.
This report describes reactions of 7-iodobicyclo[4.1.0]-
heptane (7-iodonorcarane) with carbanions induced by
(5) (a) Dickens, M. J .; Luche, J . L. Tetrahedron Lett. 1991, 32, 4709.
(b) Manzo, P. G.; Palacios, S. M.; Alonso, R. A. Tetrahedron Lett. 1994,
35, 677.
(6) (a) Kim, J . K; Bunnett, J . F. J . Am. Chem. Soc. 1970, 92, 7464.
(b) Rossi, R. A.; Bunnett, J . F. J . Am. Chem. Soc. 1974, 96, 112.
(7) (a) Austin, E.; Alonso, R. A.; Rossi, R. A. J . Org. Chem. 1991,
56, 4486. (b) Austin, E.; Ferrayoli, C. G.; Alonso, R. A.; Rossi, R. A.
Tetrahedron 1993, 49, 4495.
(3) (a) Kim, J . K.; Bunnett, J . F. J . Am. Chem. Soc. 1970, 92, 7463.
(b) Scamehorn, R. G.; Bunnett, J . F. J . Org. Chem. 1977, 42, 1449. (c)
Bard, R. R.; Bunnett, J . F.; Traber, R. P. J . Org. Chem. 1979, 44, 4918.
(d) Swartz, J . E.; Bunnett, J . F. J . Org. Chem. 1979, 44, 340. (e)
Scamehorn, R. G.; Hardacre, J . M.; Lukanich, J . M.; Sharpe, L. R. J .
Org. Chem. 1984, 49, 4881.
(4) (a) Rossi, R. A.; Bunnett, J . F. J . Org. Chem. 1973, 38, 1407. (b)
Hoz, S.; Bunnett, J . F. J . Am. Chem. Soc. 1977, 99, 4690. (c) Fox, M.
A.; Younathan, J .; Fryxell, G. E. J . Org. Chem. 1983, 48, 3109.
(8) (a) Save´ant, J . M. Acc. Chem. Res. 1980, 13, 323. (b) Save´ant, J .
M. Adv. Phys. Org. Chem. 1990, 26, 1, and references cited therein.
(9) (a) Galli, C.; Bunnett, J . F. J . Org.Chem. 1984, 49, 3041. (b) Galli,
C.; Gentili, P. J . Chem. Soc., Perkin Trans. 2 1993, 1135. (c) van
Leeuwen, M.; McKillop, A. J . Chem. Soc., Perkin Trans. 1 1993, 2433.
(10) (a) Galli, C.; Gentili, P. J . Chem. Soc., Chem. Commun. 1993,
570. (b) Galli, C.; Gentili, P.; Rappoport, Z. J . Org. Chem. 1994, 59,
6786.
(11) Nazareno, M. A.; Rossi, R. A. Tetrahedron Lett. 1994, 35, 5185.
0022-3263/96/1961-1645$12.00/0 © 1996 American Chemical Society

1646 J . Org. Chem., Vol. 61, No. 5, 1996
Nazareno and Rossi
Ta ble 1. Rea ction of 7-Iod on or ca r a n e (1) w ith
gave low yields of substitution product 5 (6-8%), ca. 90%
of which was exo isomer 5a (eq 4) (Table 1, experiments
9 and 10).
Ca r ba n ion s in DMSO Ca ta lyzed by In or ga n ic Sa ltsa
1,
carbanion, catalysts, temp, products,
exo
expt mmol
mmol
mmol %b
°C
(yield %) isomerc
1d
2
3
4
5
6
7
8
9
1.0
0.5
0.5
0.6
0.6
0.9
0.5
1.0
0.5
0.5
0.5
0.5
0.5
2, 10.0
2, 5.0
2, 5.0
2, 5.0
2, 10
2, 2.6
2, 5.0
2, 10.0
4, 3.0
4, 5.0
4, 3.0
4, 5.0
4, 5.0
-
25
25
25
25
25
60
60
60
25
25
25
25
60
3 (0)
3 (9)
3 (8)
3 (41)
3 (72)
3 (42)
3 (69)
3 (90)
5 (6)
-
80
95
95
97
94
96
93
g
93
96
91
96
SmI2,e 107
SmI2,f 104
FeBr2, 21
FeBr2, 71
FeBr2, 48
FeBr2, 52
FeBr2, 103
SmI2,e 107
SmI2,e 214
FeBr2, 107
FeBr2, 60
FeBr2, 60
(4)
10
5 (8)
Although the yields of substitution products 3 and 5
were low, the fact that almost the same exo/endo product
ratios were observed as in photostimulated reactions
suggests that free 7-norcaranyl radicals are intermedi-
ates in the reactions induced by SmI2.
In the reaction of 1 with 2 at room temperature with
the addition of 21 mol % of FeBr2 (referred to the
substrate concentration), the substitution products 3
were formed in 41% yield. This yield increases to 72%
with 71 mol % of FeBr2; 95-97% of the substitution
product was exo isomer 3a (eq 5) (Table 1, experiments
3 and 4).
11
12
13
5 (38)
5 (54)
5 (60)
a
Reactions carried out in 25 mL of DMSO during 30 min, unless
otherwise stated. Based on substrate 1. c Yield (%) of the total
b
amount of substitution products. Reference 12. e Added as 0.1
d
N solution in THF. f Added as 0.1 N solution in THF with 6% (v/
g
v) of HMPA. Reaction time 15 min. Not quantified.
SmI2 and FeBr2 in DMSO, as well as reactions of
1-iodoadamantane and neopentyl iodide induced by FeBr2
in DMSO.
Resu lts a n d Discu ssion
7-Iod on or ca r a n e (1). The photostimulated reaction
of 7-iodonorcarane (7-iodobicyclo[4.1.0]heptane) 1 (a mix-
ture of exo:endo isomers with a ratio of ca. 1:1) with
carbanions in DMSO gave the expected substitution
products in good yields with a remarkable selectivity,
that is, more than 90% of each substitution product
mixture was the exo isomer, so it was suggested that
7-norcaranyl radicals are intermediates of these reac-
tions.12
When a solution of SmI2 in THF was added to a
solution of 1 with acetophenone enolate ions 2 in DMSO
and reaction was allowed to occur for 30 min at room
temperature, a small amount of the substitution product
R-(7-norcaranyl)acetophenone (3) (9%) was formed, 80%
of it being the isomer exo-3a (eq 3).
These results may indicate that Fe+2 induced the
reaction of 1 with 2 and that 7-norcaranyl radicals are
intermediates of these reactions, with 2 having the same
selectivity as in photostimulated reactions, as well as in
reactions induced with SmI2. The fact that with 21 mol
% of FeBr2 the yield of substitution products 3 was only
41% suggests that there is a chain process, though not a
very efficient one.
The reaction of 1 with 2 in DMSO at 60 °C with 48
mol % of FeBr2 gave 42% of substitution product 3; the
yield increases to 90% when the substrate 1/FeBr2 ratio
is 1, with 93% of the product being isomer 3a .
The fact that the reaction of 1 and 2, with FeBr2, gave
substitution products 3a and 3b of which the proportion
of the exo isomer is about 95%, similar to the product
ratio that was found in the photostimulated reaction,
suggests that the reaction of 1 with Fe+2 ions and
carbanion 2 produced σ-type 7-norcaranyl radicals 6a and
6b, which reacted with 2 by the SRN1 mechanism. It is
known that cyclopropyl radicals are σ radicals14 with a
very high rate of interconversion of the exo-endo iso-
mers.15 As explained before,12 6a is more reactive and
reacts with 2 to give high yields of the exo isomer (eq 6).
(3)
The initiation of these reactions by SmI2 was not as
successful as that of reactions of aryl halides with
carbanions in DMSO, where more than 80% yields of
substitution products were obtained.11 It is known that
reactions of SmI2 can be improved by adding HMPA as
cosolvent,13 but in the reaction of 1 with 2 in DMSO with
a solution of SmI2 in THF with 6% of HMPA, 8% yield of
3 was obtained of which ca. 95% was exo isomer 3a , a
ratio similar to that found in photostimulated reactions12
(Table 1, experiments 1 and 2).
The reaction of 1 with the enolate ion of 2-naphthyl
methyl ketone (4) was also induced by FeBr2. Thus, the
reaction at room temperature gave 54% of 5, increasing
slightly at 60 °C (60% yield) (eq 7) (Table 1, experiments
10-12), with more than 90% of the substitution products
being the exo isomer 5a ; similar results were found in
The reactions of 1 with 2-naphthyl methyl ketone
enolate ions 4 with the addition of a solution of SmI2 also
(14) Walborsky, H. M. Tetrahedron 1981, 37, 1625 and references
cited therein.
(15) (a) Kawamura, T.; Tsumura, M.; Yomezawa, T. J . Am. Chem.
Soc. 1977, 99, 8251. (b) J ohnston, L. J .; Ingold, K. U. J . Am. Chem.
Soc. 1986, 108, 2343.
(12) Nazareno, M. A.; Rossi, R. A. Tetrahedron 1994, 50, 9267.
(13) (a) Curran, D. P.; Fevig, T. L.; J asperse, C. P.; Totleben, M. J .
Synlett 1992, 943. (b) Hasegawa, E.; Curran, D. P. Tetrahedron Lett.
1993, 34, 1717.

SRN1 Reactions with Carbanions Induced by FeBr2
the photostimulated reactions.
J . Org. Chem., Vol. 61, No. 5, 1996 1647
Ta ble 2. Com p etition of 2 vs 4 a n d 2 vs 7 Rea ctin g w ith
1 in DMSOa
yield, %
(7)
2,
4 or 7,
FeBr2,
3
5 or 8
rel
expt mmol mmol mmol %b (% exo)c (% exo)c reactivity
The anion of nitromethane (7) did not give substitution
products under irradiation with 1. However, in the
presence of acetophenone enolate ion (2) the photostimu-
lated reaction gave substitution products 8 in 41% yield,
with ca. 90% yield of the substitution products being exo
isomer 8a (eq 8).12 The fact that 7 reacts under irradia-
tion in the presence of 2 but not in its absence to give
substitution products 8a and 8b indicates that 2 facili-
tates initiation of the SRN1 mechanism. The fact that the
8/3 product ratio shows that the 7-norcaranyl radicals
thus formed react faster with 7 than with 2 to give finally
the products observed (vide infra).
1d
2
3
3
4
5
7
4, 3
4, 6
4, 5
4, 3
62
96
102
109
21 (95) 24 (96)
21 (92) 60 (92)
31 (89) 55 (91)
51 (92) 39 (91)
1.2
1.9
1.8
1.8
4
average 1.7 ( 0.23
19 (85) 71 (92) 6.5
5e
5
7, 3
103
a
Reactions carried out in 25 mL of DMSO with 0.572 mmol of
1. Reaction time 30 min at 60 °C, unless otherwise indicated.
Based on the concentration of 1. c Yields based on the total
b
substitution products. Reaction time 40 min, at 30 °C. e 1 mmol
d
of substrate 1.
termination steps. To compare the reactivity of different
carbanions, the relative reactivity was studied by com-
petition experiments with 1. By these competition reac-
tions, the relative rates of the coupling of 7-norcaranyl
radicals toward 2 and 4 were determined.
(8)
When a solution containing carbanions 2 and 4 in
excess is allowed to compete toward 1 in the presence of
FeBr2, the radical 6 is formed and reacts with 2 and 4 to
yield the radical anion intermediates 3•- and 5•- along
the propagation cycle of the SRN1 mechanism (eqs 10a
and 10b).
When a solution of 1 and the anion 7 was prepared in
DMSO, and FeBr2 was added to initiate reaction, a
precipitate was formed. When the anion of acetophenone
(2) was formed in DMSO, and FeBr2 was added, the color
of the solution changed, probably by interaction of 2 with
FeBr2. A solution of 2 (5 mmol) with an excess of t-BuOK
(6 mmol) and FeBr2 (1.03 mmol) in 25 mL of DMSO at
60 °C was prepared, and then nitromethane (5 mmol) was
added and immediately followed by the addition of 1 (1
mmol) after 30 min. In this case, 8 was formed in 71%
yield, with 92% of it being exo isomer 8a , and 3 was
formed in 19% yield of which 85% was exo isomer 3a (eq
9) (Table 2, experiment 5).
If there is no other competing reaction,16 all the
radicals will give the substitution products 3 and 5, and
it is possible to estimate the relative rates from the
amount of products obtained. The relative reactivities
were calculated as in previous works.17
(9)
These results show that in these experimental condi-
tions, that carbanions 2 and 7 together with FeBr2
remain soluble and able to initiate the SRN1 reaction and
that the 7-norcaranyl radicals thus formed react faster
with 7 than with 2 (see competition experiments).
The fact that in the FeBr2-induced reactions of 1 with
carbanions gave mainly the exo substitution products and
that the relative reactivity of carbanions are similar to
the photostimulated reactions suggests that the FeBr2
associate with enolate ions to produce free 7-norcaranyl
radicals by an electron transfer reaction and probably
rules out a mechanism that involves an organo-Fe bond
as intermediate.9 Although Fe+2 is a modest reductant
(0.1 V in DMSO vs SCE)9b and the redox potential does
not change when the complex with enolate ions is formed,
this complex may facilitate the electron transfer to the
substrate, as was suggested with the aromatic systems.9b
Com p etition Exp er im en ts. The product comparison
from reaction of 1 with carbanions 2 and 4 induced with
FeBr2 shows that 2 is qualitatively more reactive than
4.
In the reaction of 2 and 4 in excess over 1 it was
possible to estimate the relative reactivity, and it was
found that 4 reacts ca. 1.7 faster than 2 (Table 2).
In the competition experiment of 2 and 7 toward 1 it
was found that 7 reacts 6.5 times faster than 2, similarly
to the value reported in the photostimulated reaction
(6.4),12 which suggests the same mechanism reaction in
both systems. In competition experiments of 2 and 7
toward 1-iodoadamantane, it was reported that 7 reacts
3.0 times faster than 2.18
(16) Although there is some reduction of the radicals to the
hydrocarbons, the amount is small and we consider that the reduction
rate of the radicals is similar.
(17) The equation used in the relative reactivity determination of
nucleophiles 2 and 4 in excess vs substrate 1 is:
k4 ln [4]0/[4]t
)
k2
ln [2]0/[2]t
where [4]0 and [2]0 are initial concentrations, and [4]t and [2]t are
concentrations at time t of both nucleophiles. This equation is based
on a first-order reaction of the radicals with both nucleophiles 2 and
4; see Bunnett, J . F. Investigation of Rates and Mechanisms of
Reactions, 3rd ed.; Lewis, E. S., Ed.; Wiley-Interscience: New York,
1974; Part 1, p 159.
(18) (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.
As the SRN1 mechanism is a chain process with
initiation, propagation, and termination steps, overall
reactivity depends on the efficiency of the initiation step,
the individual rates of the propagation steps, and the

1648 J . Org. Chem., Vol. 61, No. 5, 1996
Nazareno and Rossi
Ta ble 3. Rea ction of 1-Iod oa d a m a n ta n e (9) w ith 2 in
Ta ble 4. Rea ction of Neop en tyl Iod id e (11) w ith 2
in DMSOa
a
DMSO Ca ta lyzed by F eBr 2
FeBr2,
mol %b
product 10,
yield (%)
FeBr2,
mol %
temp,
°C
time
(min)
I-,
yield (%)
product 12,
yield (%)
expt
9, mmol
2, mmol
expt
1
2
1
10
5
5
10
5
32
51
0
103
156
79
85
3
35
47
1
-
-
25
25
55
55
25
25
25
25
55
60
240
40
40
20
60
60
60
40
24
c
59
41
c
c
c
c
c
22
7
0.52
0.57
1
2b
3
3
-
45
31
20
74
7
4c
5c
4d
5
-
0.54
22
69
70
100
81
6
a
Reactions carried out in 25 mL of DMSO at 60 °C. Reaction
7e
8
time 30 min. Based on substrate 9. c 1-Bromoadamantane.
b
61
92
9
As it has been shown in the relative reactivity of
carbanions toward phenyl radicals19 and 1-adamantyl
radicals,18 the reactivity is higher when the more stable
radical anion intermediate is formed (lower SOMO) in
the coupling of the radical and the carbanion (lower pKa
of the conjugated acid), if the ∆Eπ is similar in this
process. In the competition reaction of 2 and 4, the latter
is sligthly more reactive because the SOMO of the radical
anion intermediate 5•- is lower in energy than the SOMO
a
b
11: 1.13 mmol, 2, 5.0 mmol in ca. 25 mL of DMSO. 17 mol
% of p-DNB, see ref 25. c Not quantified. 21 mol % of p-DNB.
d
e 32 mol % of p-DNB.
increases to 47% yield with an excess of FeBr2 (156 mol
%) (Table 3, experiments 4 and 5).
Neop en tyl Iod id e (11). We have previously reported
photostimulated reactions of neopentyl halides by the
S
RN1 mechanism with different organometallic nucleo-
of the radical anion 3•-
.
philes in liquid ammonia obtaining good yields of the
substitution products.23 In reactions with carbanions we
found only dehalogenation in poor yields without prod-
ucts coming from the radical-nucleophilic coupling in
liquid ammonia.24 However, when the solvent was
changed to DMSO, the photostimulated reaction of neo-
pentyl iodides with carbanions gave the substitution
product in 52-69% yield.25
The fact that 7 is 6.5 times more reactive than 2 agrees
with the pKa of acetophenone (24.7) reported to be higher
than the nitromethane (17.2) in DMSO,20 so that the
coupling process of radicals with nitromethane anions
would give the more stable radical anion intermediates.
Besides, these results suggest that 7-norcaranyl radicals
are slightly more selective than 1-adamantyl radicals
toward carbanions.
The reaction of neopentyl iodide (11) with 2 in DMSO
in 1 h at 25 °C gave 22% of substitution product 12, but
the yield drops to 6% of 12 in 4 h in the presence of 17
mol % of p-DNB,25 but increases to 45% yield at 55 °C.
The reaction at 55 °C was also partially inhibited by
p-DNB (Table 4, experiments 1-4). These results sug-
gest that 11 reacts with 2 in the dark by a thermal SRN1
reaction (eq 12).
1-Iod oa d a m a n ta n e (9). 1-Substituted bridgehead
compounds react slowly by an SN1 mechanism of nucleo-
philic substitution, and the reactivity decreases with
increasing strain in the substrate.21 The reactivity of
bridgehead halides by the SRN1 mechanism depends not
only on the nature of the leaving group (Cl < Br < I),
but also on the strain of the bicyclic moiety22 and on the
presence of substituents.
It has been reported that the photostimulated reaction
of 1-iodoadamantane (9) with 2 in DMSO gives the
substitution product 10 in 65% yield after 240 min of
irradiation.18 The reaction of 9 with 2 and with the
addition of FeBr2 (32 mol % based on 9) rendered the
substitution product 10 in 79% yield, in 30 min of
reaction at 60 °C (eq 11) (Table 3, experiment 1).
The reaction of 11 and 2 at 25 °C and in the presence
of FeBr2 gave 12 in excellent yields. The reaction
catalyzed by FeBr2 was also inhibited by p-DNB (Table
4, experiments 5-7). These results indicate both that
FeBr2 is an efficient reagent for induction of reactions of
11 with carbanions in DMSO and that an SRN1 mecha-
nism is probable in view of the inhibition by p-DNB.
Con clu sion s. FeBr2 has been shown to be an efficient
reagent to induce reactions of 7-iodonorcarane, 1-iodo-
adamantane, and neopentyl iodide with carbanions in
DMSO. No reduction products derived from the ketone
functionality were found. Whereas all these substrates
and probably numerous other alkyl iodides react slowly
with carbanion nucleophiles by polar mechanisms of
nucleophilic substitution, they react easily with by the
(11)
With 51 mol % of FeBr2 the yield of 10 was 85%. In
the same experimental condition, but without adding
FeBr2, the yield of 10 was only 3% (Table 3, experiments
2 and 3). The fact that the yields of 10 are higher than
the equivalents of FeBr2 indicates that there is a chain
propagation step, although the chain is rather short.
1-Bromoadamantane reacts very sluggishly with 2
under irradiation in DMSO.18a The reaction induced with
FeBr2 (103 mol %) gives, however, 35% yield of 10, which
S
RN1 mechanism when induced by FeBr2 in DMSO. Even
1-bromoadamantane, which is almost unreactive with 2
in photostimulated reactions, gave a moderate yield
(47%) of the substitution product when reaction was
induced by FeBr2.
(19) Borosky, G. L.; Pierini, A. B.; Rossi, R. A. J . Org. Chem. 1992,
57, 247.
(20) Bordwell, F. G. Acc. Chem. Res. 1988, 21, 456.
(21) Fort, R. C.; Schleyer, P. v. R. Adv. Alicycl. Chem. 1966, 1, 283.
(22) Pierini, A. B.; Santiago, A. N.; Rossi, R. A. Tetrahedron 1991,
47, 941.
(23) Pierini, A. B., Pen˜e´n˜ory, A. B., Rossi, R. A. J . Org. Chem. 1985,
50, 2739.
(24) Bornancini, E. R. N., Palacios, S. M., Pen˜e´n˜ory, A. B., Rossi,
R. A. J . Phys. Org. Chem. 1989, 2, 255.
(25) Pen˜e´n˜ory, A. B., Rossi, R. A. Gazz. Chim. Ital., in press.

SRN1 Reactions with Carbanions Induced by FeBr2
J . Org. Chem., Vol. 61, No. 5, 1996 1649
potassium tert-butoxide, 5 mmol of 2-naphthyl methyl ketone,
and 0.5 mmol of 7-iodonorcarane (1). To this solution was
added 1.07 mmol of SmI2 (10.7 mL of 0.1 N solution in THF).
The aliquot was transferred by syringe to avoid contact with
air. After 30 min, the reaction was quenched by adding
ammonium nitrate in excess and 100 mL of water and
extracted with three portions of diethyl ether. The ether
extract was washed twice with water, dried, and quantified
by GLC. The reaction products were compared with authentic
samples and were identified as the mixture of R-(7-norcaranyl)
2-naphthyl methyl ketone (5) exo and endo isomers,12 the
overall substitution yield being 8%. These products were
compared with authentic samples.
Da r k Rea ction of Acetop h en on e En ola te Ion (2) w ith
Alk yl Iod id es. The following procedure is representative.
They were carried out in a 100 mL three-necked round-
bottomed flask equipped with a nitrogen inlet and magnetic
stirrer. To 25 mL of dry and degassed DMSO under nitrogen
were added 6 mmol of potassium tert-butoxide and 5 mmol of
acetophenone. The system was enclosed in aluminum foil, and
1.13 mmol of neopentyl iodide was added. The mixture was
stirred and the flask placed in a 55 °C temperature bath. After
40 min, the reaction was quenched by adding ammonium
nitrate in excess and water (100 mL) and extracted with
diethyl ether (three portions of 50 mL). The iodide ions in the
aqueous solution were determined by potentiometric titration.
The ether extract was washed twice with water, and the
substitution product 12 was quantified by GLC. Benzophe-
none was used as internal standard. The reaction yield was
45%, and the product was identified as R-(neopentyl)acetophe-
none25,28 by comparison of the NMR spectra with those of an
authentic sample.
Com p etition Exp er im en ts of Acetop h en on e En ola te
Ion (2) a n d Nitr om eth a n e An ion (5) tow a r d 7-Iod on or -
ca r a n e (1). In order to estimate the relative reactivities of
these nucleophiles, FeBr2-induced reactions were done in 25
mL of DMSO in an inert atmosphere. After the addition of 9
mmol of potassium tert-butoxide and 5 mmol of acetophenone,
0.59 mmol of FeBr2 was added. After a few minutes, enough
for the formation of Fe2+ and nucleophile 2 complex, 3 mmol
of nitromethane were added in order to prepare the nucleophile
7. Finally, 1 mmol of the the substrate 1 was added. After
40 min, the reaction was quenched by excess ammonium
nitrate and 100 mL of water and extracted with three portions
of diethyl ether. The ether extract was washed twice with
water, dried, and quantified by GLC. The products obtained
were compared with authentic samples by GLC and NMR
spectra and identified as R-(7-norcaranyl)nitromethane exo and
endo isomers (8) and R-(7-norcaranyl)acetophenone exo and
endo isomers (3).12
The facts that the yields of the substitution products
with these alkyl iodides are higher than 80-90%, that
reaction times are short, and that the reactions are easily
handled with better yields than the photostimulated
reactions indicate that FeBr2-induced reactions could be
the method of choice to perform nucleophilic substitu-
tions.
Exp er im en ta l Section
Ma ter ia ls. Potassium tert-butoxide (Fluka) was sublimed
and DMSO (Carlo Erba) distilled under vacuum and stored
over molecular sieves (4 Å). Nitromethane (Aldrich) was
distilled and dried over Na2SO4. Acetophenone (Carlo Erba)
was distilled under vacuum. 2-Naphthyl methyl ketone (Alfa)
was recrystallized from petroleum ether. Commercially avail-
able anhydrous FeBr2 (Strem) was used as received and stored
in a dry-seal desiccator. 1-Iodoadamantane (Aldrich) was
purified by recrystallization from methanol. Samarium diio-
dide (0.1 N solution in THF) was purchased from Aldrich and
stored under nitrogen atmosphere. 1-Bromoadamantane (Al-
drich) and p-DNB (Fluka) were used as received.
Syn th esis of Rea cta n ts. 7-Iodonorcarane was synthesized
as described.26 The crude product was purified by reduced-
presure distillation. The synthesis gave an isomer-products
mixture with an exo-endo ratio of ca. 1. Neopentyl iodide was
synthesized by reaction of the corresponding p-toluene-
sulfonate derivative with KI in DMF27 and purified by distil-
lation. Neopentyl p-toluene sulfonate was prepared from
neopentyl alcohol and p-toluenesulfonyl chloride in pyridine
as solvent. The enolate ions of ketones and nitromethane
anions were prepared by acid-base reaction of potassium tert-
butoxide.
Gen er a l P r oced u r e. F er r ou s Ion -In d u ced Rea ction of
Alk yl Iod id es w ith Acetop h en on e En ola te Ion (2). The
following procedure is representative of these reactions. They
were carried out in a 100 mL three-necked round-bottomed
flask equipped with a nitrogen inlet and magnetic stirrer. To
25 mL of dry and degassed DMSO under nitrogen were added
11 mmol of potassium tert-butoxide, 10 mmol of acetophenone,
and 0.32 mmol of FeBr2. A few minutes later, when the ferrous
ion and enolate anion 2 complex had formed, 1 mmol of
1-iodoadamantane (9) was added. The mixture was stirred
and the flask placed in a 60 °C temperature bath. After 30
min the reaction was quenched by adding ammonium nitrate
in excess and water (100 mL) and extracted with diethyl ether
(three portions of 50 mL). The ether extract was washed twice
with water, and quantified by GLC. 4-Bromobenzophenone
was used as internal standard. The solvent was removed
under reduced pressure. The residue, after column chroma-
tography on silica gel (eluted with petroleum ether:diethyl
ether ) 90:10) gave the substitution product R-(1-adamantyl)-
acetophenone (10), identified by comparison with an authentic
sample.19
Ack n ow led gm en t. This work was supported in part
by Consejo Nacional de Investigaciones Cient´ıficas y
Te´cnicas (CONICET), Consejo de Investigaciones de la
Provincia de Co´rdoba (CONICOR), and Antorchas Foun-
dation, Argentina. M.A.N. acknowledges receipt of a
fellowship from the CONICET. We thank Professor
Bunnett for critical reading of the manuscript.
Sm I2-in d u ced Rea ction of 2-Na p h th yl Meth yl Keton e
En ola te Ion (4) w ith 7-Iod on or ca r a n e (1). The following
procedure is representative. They were carried out in a 100
mL three-necked round-bottomed flask equipped with a ni-
trogen inlet and magnetic stirrer. To 25 mL of dry and
degassed DMSO under nitrogen were added 6 mmol of
J O9509566
(26) Dehmlow, E. V.; Stu¨tten, J . Tetrahedron Lett. 1991, 32, 6105.
(27) Whalon, M.; Bushwelier, H. J . Org. Chem. 1984, 49, 1185.
(28) Mc Millan, D. C.; Balasubramanian, T. R.; Kuivila, H. G. J .
Am. Chem. Soc. 1978, 100, 6407.