Fast Tin-Free Hydrodehalogenation and Reductive Radical Cyclization Reactions: A New Reduction Process

Article abstract of DOI:10.1021/jo035477i

The photostimulated reactions of several aryl and alkyl chlorides and bromides with the monoanion of reduced ethyl benzoate 5H furnish the reduced products in high yields. If the aryl moieties have suitable double bonds, the cyclized reduced products are obtained in high yields. The photostimulated reaction of 1-allyloxy-2-bromobenzene (1a) with 5H affords 3-methyl-2,3-dihydro-benzofuran (2a) in 97% yield. When 1-allyloxy-2-chlorobenzene (1b) is used, the yield of 2a is only 55%, which increases up to 91% when acetone enolate ion is added to the reaction mixture as entrainment reagent. With diallyl-(2-bromophenyl)amine (3a), and 2-allyloxy-1-halonaphthalenes (chloro, 4b, and bromo, 4a) the cyclized reduced products are obtained in yields above 96%. By competition experiments, 5H reacts ca. 5 times faster with 1-naphthyl radicals than benzenethiolate ions do, which is near the diffusion limit rate.

Full text of DOI:10.1021/jo035477i

F a st Tin -F r ee Hyd r od eh a logen a tion a n d Red u ctive Ra d ica l
Cycliza tion Rea ction s: A New Red u ction P r ocess
Santiago E. Vaillard, Al Postigo, and Roberto A. Rossi*
INFIQC, Departamento de Qu´ımica Orga´nica, Facultad de Ciencias Qu´ımicas,
Universidad Nacional de Co´rdoba, 5000 Co´rdoba, Argentina
rossi@dqo.fcq.unc.edu.ar
Received October 8, 2003
The photostimulated reactions of several aryl and alkyl chlorides and bromides with the monoanion
of reduced ethyl benzoate 5H furnish the reduced products in high yields. If the aryl moieties have
suitable double bonds, the cyclized reduced products are obtained in high yields. The photostimulated
reaction of 1-allyloxy-2-bromobenzene (1a ) with 5H affords 3-methyl-2,3-dihydro-benzofuran (2a )
in 97% yield. When 1-allyloxy-2-chlorobenzene (1b) is used, the yield of 2a is only 55%, which
increases up to 91% when acetone enolate ion is added to the reaction mixture as entrainment
reagent. With diallyl-(2-bromophenyl)amine (3a ), and 2-allyloxy-1-halonaphthalenes (chloro, 4b,
and bromo, 4a ) the cyclized reduced products are obtained in yields above 96%. By competition
experiments, 5H reacts ca. 5 times faster with 1-naphthyl radicals than benzenethiolate ions do,
which is near the diffusion limit rate.
In tr od u ction
derived from its cost and difficulty of storage. Further-
more, the radical (TMS)3Si• can react with double bonds
and this may be an inconvenience in reductive radical
cyclization reactions. This reagent is slightly less reactive
than n-Bu3SnH, and many kinetic parameters are known.4
Tin hydrides, mainly tri-n-butylstannane (n-Bu3SnH)
and trimethylstannane (Me3SnH), play a central role in
radical chemistry.1 However, their utility at preparative
levels is usually limited due to their toxicity and difficulty
of elimination from reaction mixtures. Special efforts
have been attempted in order to replace the toxic tin
hydrides, and potential substitute candidates were re-
ported in the last years.2 n-Bu3SnH is a very versatile
reagent, since the abstraction of hydrogen generates the
tin-centered radical Bu3Sn•, which readily reacts in a
selective manner with a wide range of substrates such
as selenides, xanthates, sulfides, and alkyl and aryl
halides.
Special workup procedures and purification protocols,
systems that use tin hydride in catalytic amounts, and
fluorous and polymeric tin hydrides have been developed
with the aim to replace stannanes, but usually traces of
tin remain in the reaction products.1
Tris(trimethylsilyl)silane (TTMSS) is one of the best
options to replace tin hydrides, and reductive cyclization
reactions have been performed with this reagent.3 Al-
though TTMSS is not toxic and can be easily eliminated
from the reaction mixtures, it suffers disadvantages
Germanium hydrides, especially n-Bu3GeH and tri-2-
furylgermane,5 can also be employed for this type of
reaction but are too expensive to have practical applica-
tions. Germanium hydrides are less reactive than tin
hydrides but they react faster with double bonds. Studer
et al.6 have recently described the use of new silylated
cyclohexadienes as powerful and easily available reagents
to perform radical reactions. These compounds are less
reactive than TTMSS but more stable, and they can
easily be handled and eliminated from the reaction
mixtures.
Phosphorus reagents constitute an active field of work
since they are nontoxic and inexpensive.7 Much attention
has been centered especially on N-ethylpiperidine hypo-
phosphite and phosphinic acid, but since phosphorus-
centered radicals are less reactive than those derived
from tin and silicon, only halides with weak carbon-
halogen bonds can be employed.
(4) For reviews on rate constant of different silyl radicals, see (a)
Chatgilialoglu, C. Chem. Rev. 1995, 95, 1229-1251. (b) Chatgilialoglu,
C.; Newcomb, M. Adv. Organomet. Chem. 1999, 44, 67-112.
(5) (a) Chatgilialoglu, C.; Ballestri M. Organometallics 1999, 18,
2395-2397. (b) Nakamura, T.; Yorimitsu, H.; Shinokubo, H.; Oshima,
K. Bull. Chem. Soc. J pn. 2001, 74, 747-752
(1) (a) Radicals in Organic Synthesis, Vol. 1 and 2; Renaud, P., Sibi,
M. P., Eds.; Wiley-VCH: Weinheim, Germany, 2001. (b) Giese, B.;
Go¨bel, T.; Dickhaut, G.; Thoma, G.; Kulicke, K. J .; Trach, F. In Organic
Reactions; Paquette, L., Beak, P., Engelbert, C., Curran, D., Czarnik,
A., Scott, E., Hegedus, L., Kelly, R., Overman, L., Roush, W., Smith,
A., White, J ., Eds.; Wiley & Sons: New York, 1996; pp 301-856. (c)
Giese, B. Radicals in Organic Synthesis: Formation of Carbon-Carbon
Bonds; Pergamon: Oxford, U.K., 1986.
(2) For a recent review, see Studer, A.; Amrein, S. Synthesis 2002,
7, 835-849.
(3) Chatgilialoglu, C.; Dickhaut, J .; Giese, B. J . Org. Chem. 1991,
56, 6399-6403.
(6) (a) Studer, A.; Amrein, S. Angew. Chem., Int. Ed. 2000, 39, 3080-
3082. (b) Studer, A.; Amrein, S.; Schlet, F.; Schulte, T.; Walton, J . J .
Am. Chem. Soc. 2003, 125 (19), 5726-5733
(7) (a) Roy, S. C.; Guin, C.; Rana, K. K.; Maiti, G. Tetrahedron 2002,
58, 2435-2439. (b) Gonzalez Martin, C.; Murphy, J .; Smith, C.
Tetrahedron Lett. 2000, 41, 1833-1836. (c) Yorimitsu, H.; Shinokubo,
H.; Oshima, K. Chem. Lett. 2000, 104-106.
10.1021/jo035477i CCC: $27.50 © 2004 American Chemical Society
Published on Web 02/12/2004
J . Org. Chem. 2004, 69, 2037-2041
2037

Vaillard et al.
SCHEME 1
Resu lts a n d Discu ssion
We have recently described the synthesis of substituted
heterocyclic compounds by tandem 5-exo trig ring closure-
S
RN1 reaction with different nucleophiles and adequately
substituted aryl halides.13 To extend the scope of this
methodology, we decided to explore the possibility of
preparing the cyclized reduced products. The fact that
ring closure is a unimolecular process, and therefore does
not depend on the concentration of the reduction reagent,
led us to the reasonable belief that, under controlled
experimental conditions (diluted conditions), the ring
closure-reduction process would be obtained in one-pot
reactions by a tandem cyclization-reduction sequence.
We studied the photoinduced reductive cyclization of
1-allyloxy-2-bromobenzene (1a ) with a mixture of acetone
enolate ions (to initiate the reaction)14 and i-PrO- ions
as hydrogen source. These ions were formed in liquid
ammonia employing 2-propanol and acetone, with t-
BuOK in excess. Upon irradiation, a mixture of 3-methyl-
2,3-dihydrobenzofuran (2a ) and dimer 2b was obtained.
By GC-MS analysis, an olefinic derivative of 2a was
found in 22% yield, probably arising from disproportion-
ation of the radical intermediate. This olefinic product
could not be isolated from the reaction mixture, due to
the comparable polarity (in radial thin-layer chromatog-
raphy) and similar retention times as observed for 2a .
An excess of i-PrO- ions does not lead to an increase in
the yield of 2a (experiments 1 and 2, Table 1) (eq 4).
SCHEME 2
A NaBH4/10-methyl-9,10-dihydroacridine system has
been used to perform radical cyclizations of suitably
substituted aryl halides.8
Hydrodehalogenation reactions of aryl halides by use
of alkoxide ions with R-hydrogens is a well-established
process, and the kinetics and influence of substituent
groups have been studied.9 The steps of this chain
reaction are shown in Scheme 1.
After electron transfer to ArX and ensuing fragmenta-
tion, an aryl radical is formed (eq 1). The alkoxide ion
transfers the R-hydrogen to the radical Ar• to form the
reduced product ArH, and the radical anion of a carbonyl
compound is generated (eq 2). This can ultimately
propagate the chain reaction (eq 3).
On the other hand, radical ring closure by intramo-
lecular addition of a radical to a double bond is a well-
known process.10 The general reaction pathway is de-
picted in Scheme 2 and involves the generation of the
aromatic radical 1•, followed by cyclization with a teth-
ered double bond in a 5-exo trig fashion to afford the
radical 2•. This radical can be reduced with a hydrogen
donor to obtain a reduced cyclized product (2H)11 or can
be further reacted with different reagents to yield
substituted cyclized compounds (2S).12
Under irradiation, 1a accepts an electron to afford a
radical anion, which fragments to yield radical 1• (Z ) O
in Scheme 2), that cyclizes to radical 2• faster than the
reduction proceeds. Under these reaction conditions,
hydrogen transfer from i-PrO- ions is not fast enough to
compete effectively with disproportionation or dimeriza-
tion of radical 2• (Z ) O in Scheme 2).
When diallyl-(2-bromophenyl)amine (3a ), or 2-allyloxy-
1-bromonaphthalene (4a ) was employed as substrate,
1-allyl-3-methyl-2,3-dihydro-1H-indole (3c) (eq 5) or
In this work we report a new nontoxic and readily
available reactive intermediate that can be used both for
tin-free reductive cyclization of suitably substituted aryl
halides and for hydrodehalogenation of aryl and alkyl
halides.
(12) (a) Patel, V. F.; Pattenden, G.; Russel, J . J . Tetrahedron Lett.
1986, 27, 2303-2306. (b) Meijs, G. F.; Beckwith, A. L. J . J . Am. Chem.
Soc. 1986, 108, 5890-5893. (c) Beckwith, A. L. J .; Meijs, G. F. J . Org.
Chem. 1987, 52, 1922-1930. (d) Togo, H.; Kikuchi, O. Tetrahedron Lett.
1988, 29, 4133-4134. (e) Petrillo, G.; Novi, M.; Garbarino, G.; Filiberti,
M. Tetrahedron Lett. 1988, 29, 4185-4188. (f) Beckwith, A. L. J .;
J ackson, R. A.; Longmore, R. W. Aust. J . Chem. 1992, 45, 857-863.
(g) Amatore, C.; Gareil, M.; Oturan, M. A.; Pinson, J .; Save´ant, J . M.;
Thie´bault, A. J . Org. Chem. 1986, 51, 3757-3761.
(8) Boisvert, G.; Giasson, R. Tetrahedron Lett. 1992, 33, 6587-6590.
(9) (a) Bunnett, J . F. Acc. Chem. Res. 1992, 25, 2-9. (b) Tomaselli,
G. A.; Bunnett, J . F. J . Org. Chem. 1992, 57, 2710-2716. (c) Tomaselli,
G. A.; Ciu, J .; Chen, Q.; Bunnett, J . F. J . Chem. Soc., Perkin Trans. 2.
1992, 9-15. (d) Amatore, C.; Badoz-Lambling, J .; Bonnel-Huyghes, C.;
Pinson, J .; Save´ant, J . M.; Thie´bault, A. J . Am. Chem. Soc. 1982, 104,
1979-1986.
(10) (a) Beckwith, A. L. J .; Gerba, W. B. J . Chem. Soc., Perkin Trans.
2 1975, 593-600. (b) Beckwith, A. L. J . Tetrahedron 1981, 37, 3073-
3099. (c) Beckwith, A. L. J .; Gerba, S. Aust. J . Chem. 1992, 45, 289-
308. (d) Annunziata, A.; Galli, C.; Marinelli, M.; Pau, T. Eur. J . Org.
Chem. 2001, 1323-1329.
(11) Some representative examples can be found in (a) Beckwith,
A. L. J .; Abeywikrema, A. N. Tetrahedron Lett. 1986, 27, 109-112. (b)
Dittami, J . P.; Ramanathan, H. Tetrahedron Lett. 1988, 29, 45-48.
(13) Vaillard, S. E.; Postigo, A.; Rossi, R. A. J . Org. Chem. 2002,
67, 8500-8506.
(14) It is known that acetone enolate anions do not react with
primary alkyl radicals but enable the initiation of the photostimulated
reaction; see (a) Borosky, G. L.; Pierini, A. B.; Rossi, R. A. J . Org. Chem.
1990, 55, 3705-3707. (b) Rossi, R. A.; Pierini, A. B.; Borosky, G. L. J .
Chem. Soc., Perkin Trans. 2. 1994, 2577-2581. (c) Pen˜e´n˜ory, A. B.;
Rossi, R. A. Gazz. Chim. Ital. 1995, 125, 605-609. (d) Lukach, A. E.;
Rossi, R. A. J . Org. Chem. 1999, 64, 5826-5831.
2038 J . Org. Chem., Vol. 69, No. 6, 2004

Hydrodehalogenation and Reductive Radical Cyclization
TABLE 1. P h otostim u la ted Hyd r od eh a logen a tion a n d
Red u ctive Cycliza tion of Or ga n oh a lid es w ith Differ en t
Rea gen tsa
solution of 5H anion is obtained according to the reaction
depicted in eq 7.
expt
substrate
reagentb
X- c
products (% yield)d
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18i
19i,k
20k
1a
1a
1a
1a
1a
1a
1b
1b
3a
3a
3b
4a
4a
4b
6
1-AdBr
1-AdCl
6
6
8
A
90
95
100
100
<3
41
63
96
94
100
68
65
95
93
93
81
52
j
2a (43), 2b (11)
2a (44), 2b (10)
2a (95), 2c (4)
2a (97), 2c (3)
2a (0)
2a (38), 2c (1)
2a (55), 2c (4)
2a (91), 2c (7)
3c (60)
3c (98)
3c (67)
4c (50)
4c (100)
4c (96)
7 (89)
AdH (70)
AdH (50)
7 (78 ( 2), 8 (16 ( 2)
7 (71), 8 (15)
8 (100)
Ae
5H, i-PrO-
B
Bf
Bg
B
-
The NH2 ions generated during the formation of 5H
Bh
were neutralized with i-PrOH, and a mixture of 5H and
i-PrO- ions was obtained. When a solution of 5H, i-PrO-
ions, and 1a is irradiated (366 nm), a clean and quantita-
tive reaction takes place in which 2a was formed in high
yield together with small amounts of the uncyclized
product 2c (eq 8; experiment 3, Table 1).
A
B
Bh
A
B
Bh
B
B
Bh
5H, PhS-
5H, PhS-
5H
j
a
All reactions were performed in liquid ammonia and irradiated
for 2 h with two water-cooled medium-pressure Hg lamps; the
concentration of the substrates was 3.3 × 10-3 M, acetone enolate
ion was 3.3 × 10-3 M; i-PrO- was 6.6 × 10-3 M, and 5H was 6.6
× 10-3 M, unless otherwise indicated. Reduction reagents: A,
b
-
CH3COCH2 and i-PrO- ions; B, 5H and t-BuO- ions. c Deter-
To assess the contribution of 5H in the reduction of
1a , the amide ions formed during the generation of
reducing reagent 5H (eq 7) were neutralized with t-
BuOH, which generates t-BuO- ions that do not bear
R-hydrogens and therefore lack reducing ability. Now 2a
was obtained in high yields (experiment 4, Table 1),
indicating that 5H not only is a very effective hydrogen
donor but also can initiate and propagate the reduction
process.
d
mined potentiometrically. Determined by GC analysis by the
internal standard method with authentic samples as references.
e The concentration of i-PrO- ions was 9.9 × 10-3 M. f Dark
g
conditions, 1a was recovered in 97%. To the solution was added
h
20 mol % p-dinitrobenzene; 1a was recovered in 52% yield. With
1.3 × 10-2 M 5H and CH3COCH2- ions. The concentrations were
i
0.010 M for 5H and PhS- ion and 0.0050 M for 6. The reaction
j
k
was performed twice. Not determined. Irradiation time was 15
min.
In dark conditions there is no reaction of 1a with 5H
and t-BuO-, and the photostimulated reaction is inhibited
by p-dinitrobenzene (p-DNB), a well-known inhibitor of
1-methyl-1,2-dihydro-naphtho[2,1-b]furan (4c) (eq 6) was
obtained in moderate yields (experiments 9 and 12, Table
1).
S
RN1 reactions (experiments 5 and 6, Table 1).15 These
results indicate that by irradiation 5H transfers one
electron to 1a to initiate the chain reaction. It is known
that the higher the pKa of the ketones and related
compounds, the higher the electron-donor capability of
its conjugated base and so the higher the probability of
photostimulated electron transfer (ET) reaction.15,16 The
fact that the reaction is inhibited by p-DNB indicates the
presence of radical anions as intermediates.
Under irradiation, 1a accepts an electron to give the
radical anion 1a • -, which fragments to afford the radical
1• (Z ) O in Scheme 2) that mainly cyclizes to afford
radical 2• (Z ) O in Scheme 2) with almost no uncyclized
reduction product (i.e., 2c, eq 8) observed (eq 9). Radical
2• (Z ) O in Scheme 2) reacts fast with 5H to yield 2a
and the radical anion 5• -, whereupon dimerization or
disproportionation reactions do not take place (eq 10).
Radical anion 5• - is able to continue the chain propaga-
tion steps (eq 11). The driving force for the fast hydrogen
transfer reaction from 5H to 2• (eq 10) is the rearoma-
In conclusion, the attempted photoinduced reductive
method with acetone enolate/i-PrO- ions is not effective,
and the target products were obtained in poor yields in
a mixture difficult to separate.
tization of 5H to give radical anion 5• -
.
We found that substitution on aryl iodides by the SRN1
mechanism15 with anions derived from benzoate esters
obtained by reaction of the latter with sodium metal in
liquid ammonia does not occur, and only reduced prod-
ucts are obtained. When sodium metal is added to a liquid
ammonia solution of ethyl benzoate 5, a deep brown
(15) Rossi, R. A.; Pierini, A. B.; Pen˜e´n˜ory, A. B. Chem. Rev. 2003,
103, 71-167.
(16) (a) Bordwell, F. G.; Zhang, X. Acc. Chem. Res. 1993, 26, 510-
517. (b) Bordwell, F. G.; Zhang, X.; Filler, R. J . Org. Chem. 1993, 58,
6067-6071.
J . Org. Chem, Vol. 69, No. 6, 2004 2039

Vaillard et al.
hν
lides and for the hydrodehalogenation of other aryl and
alkyl halides. The competition experiments of PhS- ions
with 1-naphthyl radical indicate that the reduction
process is very effective and probably near diffusion limit
rates.
1a ET8 1a • - f 1• f 2•
(9)
Exp er im en ta l Section
Ma ter ia ls. Acetone, i-PrOH, and t-BuOH were double-
distilled and stored over molecular sieves (4 Å). Ethyl benzoate,
1-bromoadamantane, 1-chloroadamantane, 1-chloronaphtha-
lene, adamantane, naphthalene (7), allyloxybenzene (2d ), and
benzenethiol were commercially available. All solvents were
analytical-grade and were used as received from the supplier.
1-Allyloxy-2-bromobenzene (1a ),13 1-allyloxy-2-chlorobenzene
(1b),13 N,N-diallyl-(2-bromophenyl)amine (3a ),13 N,N-diallyl-
(2-chlorophenyl)amine (3b),13 2-allyloxy-1-bromonaphthalene
(4a ),13 2-allyloxy-1-chloronaphthalene (4b),13 and 1-phenyl-
sulfanylnaphthalene (8)18 were prepared as previously re-
ported. Plates (2-mm silica gel 60 PF254) were used for radial
thin-layer chromatography purification with hexanes-dichlo-
romethane mixtures as eluants.
5
• - + 1a f 5 + 1a • -
(11)
Even aryl chlorides do react with 5H; i.e., when
substrate 1b is brought into reaction, 2a is obtained in
55% yield. When the reaction was performed with acetone
enolate ion as entrainment reagent to facilitate initiation,
high yields of 2a were obtained (experiments 7 and 8,
Table 1).
The photostimulated reactions of substrates 3a , 4a ,
and 4b with 5H yield the cyclized reduced products
almost quantitatively. In these reactions no uncyclized
products were detected (experiments 10, 13, and 14,
Table 1).
Other aryl halides react under irradiation with 5H.
Thus, naphthalene (7) is formed in 89% yield when
1-chloronaphthalene (6) is allowed to react with 5H
(experiment 15, Table 1).
In the photostimulated reaction of 1-bromoadamantane
(1-AdBr) with 5H, adamantane was obtained in good
yield. The yield of adamantane was 50% when 1-AdCl
was the substrate employed (experiments 16 and 17,
Table 1)
The rate constant of the reaction of 1-naphthyl radical
with PhS- ion in liquid ammonia has been determined
electrochemically and a value of 2.0 × 1010 M-1 s-1 has
been reported.17 This prompted us to perform competition
experiments between 5H and PhS- ion to determine the
value of kH for this very reactive intermediate. When a
mixture of 5H, PhS- ions, and 6 is irradiated for 2 h, 7
is obtained as the main product together with 1-phenyl-
sulfanylnaphthalene (8) (eq 12).
P r od u cts. 3-Methyl-2,3-dihydrobenzofuran (2a ),19 1,2-bis-
(dihydrobenzofuran-3-yl)ethane (2b),20 1-allyl-3-methyl-2,3-
dihydro-1H-indole (3c),21 and 1-methyl-1,2-dihydronaphtho-
[2,1-b]furan (4c)22 were purified by radial thin-layer chromatog-
raphy with hexanes-dichloromethane mixtures as eluants.
Spectral data obtained match well with those previously
reported. Adamantane, naphthalene (7), allyloxybenzene (2c),
and 1-phenylsulfanylnaphthalene (8) were identified in the
reaction mixtures by spike experiments with authentic samples.
P h otostim u la ted Rea ction s of 1a , 3a , a n d 4a w ith
Aceton e En ola te An ion a n d i-P r O- Ion s (Exp er im en ts
1, 2, 7, a n d 10). Into a three-necked round-bottomed flask
equipped with a coldfinger condenser charged with ethanol, a
nitrogen inlet, and a magnetic stirrer was condensed 300 mL
of ammonia previously dried with sodium metal under nitro-
gen. Acetone (1.0 mmol), i-PrOH (2.0 mmol), and t-BuOK (3.5
mmol) were added, with 15 min of waiting for acetone enolate
and i-PrO- ion formation. The substrates (1.0 mmol) were
previously dissolved in 1 mL of dried ethyl ether and added
to the ammonia solution. The reaction mixtures were irradi-
ated for 120 min with two medium-pressure mercury lamps
emitting maximally at 366 nm. The reactions were quenched
with ammonium nitrate in excess and then ethyl ether was
added. After evaporation of ammonia, the organic phase was
extracted with water. The aqueous phase was extracted twice
with ethyl ether and reserved for halide titration. The com-
bined organic phases were dried over anhydrous sodium
sulfate and evaporated in a vacuum. The products were
separated by radial thin-layer chromatography. In experiment
2, 3.0 mmol of i-PrOH was used together with 4.5 mmol of
t-BuOK. For quantitative purposes, an adequate internal
standard was added prior to ammonia evaporation.
P h otostim u la ted Rea ction s w ith 5H. Into a three-necked
round-bottomed flask equipped with a coldfinger condenser
charged with ethanol, a nitrogen inlet, and a magnetic stirrer
was condensed 300 mL of ammonia previously dried with
sodium metal under nitrogen. To the ammonia, ethyl benzoate
was added (2.0 mmol) and then sodium metal (4.1 mmol), with
15 min of waiting for 5H formation. i-PrOH (experiment 3) or
t-BuOH (experiments 4, 5, 8, 11, 13, and 14) (2.0 mmol) was
then added. The substrates (1.0 mmol) were dissolved in 1 mL
As product 8 may undergo secondary photolysis to
afford 7, we carried out the irradiation for only 15 min,
but similar yields of 7 and 8 were found. When 8 was
irradiated under the same experimental conditions, 7 was
not formed (experiments 18-20, Table 1). These results
show that 5H is ca. 5-fold more reactive than PhS- ion
toward 1-naphthyl radical, whose coupling reaction has
been reported to be near the diffusion limit rate.
In summary, we report the generation and use of a new
hydrogen-donor reagent derived from nontoxic, reusable,
and inexpensive ethyl benzoate. It can be employed for
reductive cyclization of adequately substituted aryl ha-
(18) Bunnett, J . F.; Creary, X. J . Org. Chem. 1974, 39, 3173-3174.
(19) Boisvert, G.; Giasson, R. Tetrahedron Lett. 1992, 33, 6587-
6590.
(20) Olivero, S.; Dun˜ach, E. Eur. J . Org. Chem. 1999, 64, 1885-
1891.
(21) Zhang, D.; Liebeskind, L. S. J . Org. Chem. 1996, 61, 2594-
2595.
(17) Amatore, C.; Oturan, M.; Pinson, J .; Save´ant, J . M.; Thie´bault,
A. J . Am. Chem. Soc. 1985, 107, 3451-3459.
(22) Abeywickrema, A. N.; Beckwith, A. L. J .; Gerba, S. J . Org.
Chem. 1987, 52, 4072-4078.
2040 J . Org. Chem., Vol. 69, No. 6, 2004

Hydrodehalogenation and Reductive Radical Cyclization
of dried ethyl ether and added to the solution and irradiated
as indicated in Table 1. The workup was similar to previously
indicated. Products 2a , 3c, and 4c were purified as mentioned
above. For quantitative purposes, an adequate internal stan-
dard was added prior to ammonia evaporation.
In experiments 6, 9, 12, and 15, 4.0 mmol of ethyl benzoate,
8.4 mmol of sodium metal, and 4.0 mmol of acetone were used.
Rea ction w ith 5H in th e Da r k . The procedure was similar
to that for the previous reaction, except that the reaction flask
was wrapped with aluminum foil.
In h ibited P h otostim u la ted Rea ction w ith 5H. The
procedure was similar to that for the previous reaction, except
that p-DNB (20 mol %) was added to the solution of nucleophile
prior to substrate addition.
Com p etition Exp er im en t of 5H a n d Ben zen eth iola te
Ion (Exp er im en ts 16 a n d 17). The generation of 5H was
carried out as indicated previously, except that in this case
200 mL of ammonia was used and the amide ions were
neutralized with thiophenol (2.0 mmol) to obtain benzenethi-
olate ions. 1-Chloronaphthalene was dissolved in 1 mL of dried
ethyl ether and added to the ammonia solution of the compet-
ing anions. The reaction was irradiated for the time indicated,
and after quenching with ammonium nitrate in excess, ethyl
ether and suitable internal standards were added and the
extract was analyzed by GC. Naphthalene (7) and 1-phenyl-
sulfanylnaphthalene (8) were identified in the reaction mixture
by use of authentic samples.
Ack n ow led gm en t. This work was supported in part
by the Agencia Co´rdoba Ciencia de la Provincia de
Co´rdoba, the Consejo Nacional de Investigaciones Ci-
ent´ıficas y Te´cnicas (CONICET), SECYT, Universidad
Nacional de Co´rdoba, and FONCYT, Argentina. S.E.V.
gratefully acknowledges receipt of a fellowship from
CONICET.
Su p p or tin g In for m a tion Ava ila ble: General methods
1
and H NMR and 13C NMR spectra of compounds 2a , 3c, and
4c. This material is available free of charge via the Internet
at http://pubs.acs.org.
J O035477I
J . Org. Chem, Vol. 69, No. 6, 2004 2041