Anions from dihydro substituted ethyl benzoates and quinoline. New hydrogen donors for tin-free radical chemistry

Article abstract of DOI:10.1016/j.tetlet.2006.02.139

The anions of substituted dihydro ethyl benzoates and quinoline are very good hydrogen donors to radicals in liquid ammonia and DMSO. With 4-substituted dihydro ethyl benzoates the rate of hydrogen transfer decreases and excellent yields of products are obtained by 6-exo ring closure reaction followed by reduction.

Full text of DOI:10.1016/j.tetlet.2006.02.139

Tetrahedron Letters 47 (2006) 3149–3152
Anions from dihydro substituted ethyl benzoates and quinoline.
New hydrogen donors for tin-free radical chemistry
*
´
Javier I. Bardagı, Santiago E. Vaillard and Roberto A. Rossi
Instituto de Investigaciones en Fisicoquı´mica de Co´rdoba (INFIQC), Departamento de Quı´mica Orga´nica,
Facultad de Ciencias Quı´micas, Universidad Nacional de Co´rdoba, Haya de la Torre y Medina Allende, 5000 Co´rdoba, Argentina
Received 2 February 2006; revised 16 February 2006; accepted 23 February 2006
Available online 10 March 2006
Abstract—The anions of substituted dihydro ethyl benzoates and quinoline are very good hydrogen donors to radicals in liquid
ammonia and DMSO. With 4-substituted dihydro ethyl benzoates the rate of hydrogen transfer decreases and excellent yields of
products are obtained by 6-exo ring closure reaction followed by reduction.
ꢀ 2006 Elsevier Ltd. All rights reserved.
-
.
Trialkyltin hydrides, mainly tributyltin hydride, play a
CO2Et
CO2Et
central role in radical chemistry.1 However, tin deriva-
.
ð1Þ
ð2Þ
tives are toxic and difficult to eliminate from reactions
mixtures. Nowadays there is an increasing interest in
the development of new eco-friendly and non-toxic tin
hydride substitutes.2 Among the alternatives available
to perform tin-free radical reactions, most of the atten-
tion has been focused on silicon hydrides, especially
tris-trimethylsilylsilane,3 and has been recently shown
that this reagent behaves as a good hydrogen donor
even in water.4 Other promising reagents, as silylated
cyclohexadienes5 and hypophosphorous acid deriva-
tives,6 have been studied and used in a wide variety of
radical transformations.
+ Ar
+
ArH
H
H
1a
2
CO2Et
.
+ Ar
2 + ArX
+ X
3
tion (Eq. 1) is the rearomatization of 1a to give radical
anion 2. This suggests that anion 1a can be used only
in radical reactions that involve very fast rearrangement
steps. In this work we wish to present our attempts to
diminish the reactivity of this hydrogen donor in order
to get other useful reactive intermediates that can be
used in the slower 6-exo cyclization reaction.
With the notable exception of alcoxides,7 photoinduced
ET from suitable anions has been only scarcely investi-
gated as a source of new reactive intermediates for tin-
free radical reductions. We have recently demonstrated
that the anion of the dihydro ethyl benzoate 1a is an ex-
tremely powerful hydrogen atom donor that can be used
for 5-exo reductive radical cyclization and hydrodehalo-
genation reactions in liquid ammonia.8 This is a chain
reaction, and its mechanism is depicted in Eqs. 1 and 2.
Ethyl benzoate anions 1a–c can be easily prepared in
liquid ammonia by reaction of the corresponding ethyl
esters with Na metal. The amide ions generated in the
formation of 1a–c were neutralized with t-BuOH form-
ing t-BuOꢀ ions (Eq. 3):
The hydrogen transfer step is very fast and is, probably,
near diffusion limit rate. The driving force for this reac-
CO2Et
CO2Et
2 Na
NH3
t-BuOH
+
NH2
1
ð3Þ
Keywords: Reduction; Hydrogen donors; Hydrodehalogenation; 6-exo
Ring closure.
+
H
R
t-BuO
R
1a, R = H
1b, R = Me
1c, R = t-Bu
*
Corresponding author. Tel.: +54 351 4334170; fax: +54 351
4333030; e-mail: rossi@mail.fcq.unc.edu.ar
0040-4039/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.02.139

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J. I. Bardagı´ et al. / Tetrahedron Letters 47 (2006) 3149–3152
The rate constant for the coupling reaction of 1-naph-
thyl radical with PhSꢀ ions in liquid ammonia has been
determined electrochemically (2.0 · 1010 Mꢀ1 sꢀ1).9 If
the amide ions generated in the formation of 1 are neu-
tralized with PhSH, an equimolecular mixture of 1 and
PhSꢀ ions is obtained. When a solution of 1a, PhSꢀ ions
and 1-chloronaphthalene was irradiated for 15 min, a
mixture of naphthalene and the substitution product
1-phenyl-sulfanylnaphthalene10 (4) was obtained (Expt.
1, Table 1). This result indicates that 1a is ca. 5-fold
more reactive than PhSꢀ ions towards 1-naphthyl
radical (Eq. 4):
this anion is ca. 2.8-fold more reactive than PhSꢀ ions
and that its reactivity in the hydrogen transfer step is
between that of anion 1a and 1b:
Br
hν
+ 1a
NH3
H
O
6
ð5Þ
H
O
+
O
7
8
We previously reported8 that anion 1a reacts with
1-allyloxy-2-bromo-benzene (6) to give 3-methyl-di-
hydro benzofurane (7) in 97% and traces of allyloxy-
benzene (8) (Eq. 5).
Cl
hν
+
1
+
PhS
H
NH3
ð4Þ
SPh
Anion 1a reacts with 1-bromo-2-but-3-enyloxy-
benzene12 (9a)13 to afford 4-methyl-chroman14 10
(53%) together with 41% of open chain product14 11
(Eq. 6, Expt. 1, Table 2):
+
4
With the aim of decreasing the hydrogen donor ability
of anion 1a, anions esters 1b,c were studied. In the com-
petition experiment between 1b and PhSꢀ ions towards
1-chloronaphthalene, performed under the same condi-
tions as before, we found that 1b is ca. 2.2-fold more
reactive than PhSꢀ ions and hence approximately half
reactive than 1a (Expt. 2, Table 1). Probably, the dimin-
ished reactivity of 1b is the statistical result of replacing
one of the two active hydrogens of 1a.
X
hν
NH3
+
1
O
H
9a, X = Br
9b, X = Cl
ð6Þ
H
+
O
O
10
11
When the 4-tert-butyl substituted anion 1c was
employed in the competition experiment, the reduction
product naphthalene and substitution product 4 were
obtained and then 1c is ca. 1.4-fold more reactive than
PhSꢀ ions and quarter reactive than 1a (Expt. 3, Table
1). The steric demand of the bulky tert-butyl group in
the para position accounts for the lower reactivity of
anion 1c compared to 1b.
Probably, the slower 6-exo cyclization cannot compete
so efficiently with the hydrogen transfer step as the faster
5-exo cyclization process,15 and then a higher yield of
the open chain product is obtained.
Anion 1c reacts with radical probe 9a to afford cyclized
compound 10 in excellent yield and aryl reduced product
11 (Expt. 3, Table 2). As noted before, the rate of hydro-
gen transfer from 1c is lower than that from 1a and
hence the ring closure of intermediate aryl radical 12
to afford the rearranged radical 12-r can compete effi-
ciently with the direct hydrogen transfer to yield 11
(Scheme 1). Ultimately radical anion 13 propagates the
chain reaction.
When Na metal is added to quinoline in liquid ammonia
and the amide ions neutralized with t-BuOH, a deep
brown solution of dihydroquinoline anion (5) and
t-BuOꢀ ions is obtained. In the competition experiment
of 1-chloronaphthalene with 5 and PhSꢀ ions (Expt. 4,
Table 1) we obtained naphthalene as the main product
together with 4. From this result it can be inferred that
In the same fashion, anion 1a reacts with substrate 14a
(Eq. 7) to give a mixture of cyclized (15) and open chain
(16) products (89% and 11%, respectively, Expt. 2 in
Table 2):
Table 1. Competition experiments of anions 1 and 5 with PhSꢀ ions
towards 1-chloronaphthalene in liquid ammoniaa
Expt.a Competing anion Products (% yield)b
kH/kNu
1
2
3
4c
1a
1b
1c
5
Naphthalene (76), 4 (15) 5.1
Naphthalene (51), 4 (23) 2.2
Naphthalene (33), 4 (24) 1.4
Naphthalene (72), 4 (26) 2.8
X
hν
NH3
+
1a
O
a All reactions were performed twice. The concentration of the
reducing anion and PhSꢀ ions were 0.010 M and of 1-chloronaph-
thalene 0.005 M. All the reactions were irradiated for 15 min using
two water-cooled medium pressure Hg lamps.
14a, X = Br
14b, X = Cl
H
ð7Þ
H
O
+
b Determined by CG analysis by the internal standard method with
authentic samples as references.
O
c The irradiation time was 30 min.
15
16

J. I. Bardagı´ et al. / Tetrahedron Letters 47 (2006) 3149–3152
3151
Table 2. Photostimulated reductive radical cyclization and hydrodehalogenation reactions of aryl halides with different reagents and under different
reaction conditionsa,11
Expt.
Substrate
Reagent
Xꢀ (%)b
Product (% yield)c
1
2
3
4d
5
6d
9a
14a
1a
1a
1c
1c
1c
1c
5
100
100
98
54
85
99
85
77
86
79
78
77
8
10 (53), 11 (41)
15 (89), 16 (11)
10 (84), 11 (9)
10 (41), 11 (3)
15 (71), 16 (1)
9a
9b
14a
14b
15 (89), 16 (9)
7
9a
10 (55), 11 (15)
Naphthalene (65)
Phenanthrene (88)
Naphthalene (68)
Naphthalene (61)
Naphthalene (65)
Naphthalene (0)
8e
1-Chloronaphthalene
9-Bromophenanthrene
1-Chloronaphthalene
1-Chloronaphthalene
1-Chloronaphthalene
1-Chloronaphthalene
5
9e
5
10e,f
11e,g
12e,g,h
13e
5
5
5
i
a All reactions were performed in liquid ammonia and irradiated for 2 h using two water-cooled medium pressure Hg lamps. The concentration of the
substrates were 0.0033 M and of the reducing anion 0.0067 M.
b Determined potentiometrically.
c Product yields were determined by CG analysis using authentic samples as references.
d The irradiation time was 3 h and 0.0067 of acetone enolate anion was used as entrainment reagent.
e The solvent was DMSO and the concentration of the substrates was 0.05 M and of 5 0.10 M. The irradiation time was 1 h.
f With 15% of DTBN.
g Dark condition.
h The reaction time was 15 min.
i Reaction with quinoline and t-BuOK in 0.10 M.
CO2Et
1c
TE
-Br
10
9a
+
O
O
12
12-r
Bu-t
1c
13
13
11
+
Scheme 1.
The higher selectivity observed for the reaction of 14a
agrees with the expected higher reactivity in the cycliza-
tion step of the 1-naphthyl radical compared with
phenyl radical.16
Although liquid ammonia is a useful solvent for a wide
variety of SRN1 and related reactions,18 DMSO is easier
to handle than liquid ammonia.
With the aim of exploring the scope of the reduction
reactions, dihydroquinoline was prepared by Birch
reduction of quinoline19 and tested in photostimulated
hydrodehalogenation reactions of aryl halides in
DMSO.
It is known that acetone enolate anion does not react
with primary alkyl radical but initiates effectively SRN
1
reactions (Entrainment Reagent).17,18 On the other hand,
it has been demonstrated that anion 1a does not initiate
efficiently the reduction of 1-allyloxy-2-chlorobenzene in
liquid ammonia.8 The amide ions obtained in the forma-
tion of anion 1c were neutralized with acetone, and mix-
ture of 1c and ꢀCH2COCH3 anions were tested in the
reductive cyclization reaction of chloride substrate 9b.
The reduction process took place with good yield and
high selectivity (Expt. 4, Table 2). Likewise, very good
results were obtained in the reactions of naphthyl deriv-
atives 14a,b (Expts. 5 and 6, Table 2).
Upon treatment of dihydroquinoline with t-BuOK in
DMSO, a dark solution of anion 5 is obtained. Anion
5 reacts with 1-chloronaphthalene and with 9-bromo-
phenanthrene under photostimulation (1 h) to afford
hydrodehalogenation products in high yield (Expts. 8
and 9, Table 2).
The photostimulated reaction of 1-chloronaphthalene
with 5 in DMSO (1 h) is only slightly inhibited in the
presence of 15% DTBN, which is a good radical trap.
A similar result was obtained when the reaction was
performed in the dark for 1 h or 15 min (entries 10–12
in Table 2). On the other hand, only traces of naphth-
alene were obtained in the photoinduced reaction of
Dihydroquinoline anion 5 reacts with substrate 9a in
liquid ammonia to yield cyclized compounds 10 (55%)
and 11 (15%, Expt. 7 in Table 2). The distribution of
cyclized to open chain products agrees with hydrogen
donor ability determined in the competition experiment.

3152
J. I. Bardagı´ et al. / Tetrahedron Letters 47 (2006) 3149–3152
2. Studer, A.; Amrein, S. Synthesis 2002, 7, 835–849.
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results suggest a spontaneous ET from 5 to the aryl
halide to initiate the reaction, and a very effective prop-
agation cycle, probably due to good electron acceptor
ability of the substrate and good electron donor ability
of quinoline radical anion. The basicity of anion 5
precluded its use in the cyclization reactions in DMSO.
However, small amounts of cyclized compounds were
obtained in these reactions.20
4. Postigo, A.; Ferreri, C.; Navacchia, M. L.; Chatgilialoglu,
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In summary, in this work we describe new hydrogen do-
nors derived from 4-substituted ethyl benzoate ester that
can be used for reductive 6-exo cyclization in liquid
ammonia. The ester with a tert-butyl group in the para
position is a quarter reactive than the unsubstituted
compound, which allows its use in slower 6-exo cycliza-
tion reactions with excellent yields. On the other hand,
the anion of dihydroquinoline 5 behaves as powerful
hydrogen donor that gives good results in the cyclization
reaction in liquid ammonia, and also can be used for
hydrodehalogenation reactions of aryl halides in
DMSO.
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This work was supported in part by the Agencia Cordo-
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nia is described in Supplementary data.
ba Ciencia, the Consejo Nacional de Investigaciones
´
´
Cientıficas y Tecnicas (CONICET), SeCyT, Universidad
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Supplementary data
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.
2006.02.139.
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