Reducing properties of 1,2-diaryl-1,2-disodiumethanes

Article abstract of DOI:10.1016/j.tetlet.2005.12.054

1,2-Diphenyl- and 1-phenyl-2-(2-pyridyl)-1,2-disodiumethane efficiently dehalogenate vic-dibromoderivatives, affording the corresponding alkenes. The reaction proceeds rapidly, under mild conditions and is tolerant of a variety of functional groups (alcohol, carboxylic acid, ester and amide). This procedure was successfully extended to similar vic-disubstituted compounds.

Full text of DOI:10.1016/j.tetlet.2005.12.054

Tetrahedron
Letters
Tetrahedron Letters 47 (2006) 1055–1058
Reducing properties of 1,2-diaryl-1,2-disodiumethanes
a,
a
a
a
*
Ugo Azzena, Mario Pittalis, Giovanna Dettori, Simona Madeddu
b
and Emanuela Azara
a
Dipartimento di Chimica, Universit a` di Sassari, via Vienna 2, I-07100 Sassari, Italy
Istituto di Chimica Biomolecolare del C.N.R., Sez. di Sassari, Traversa la Crucca 3, regione Baldinca, I-07040 Sassari, Italy
b
Received 2 November 2005; revised 2 December 2005; accepted 9 December 2005
Available online 27 December 2005
Abstract—1,2-Diphenyl- and 1-phenyl-2-(2-pyridyl)-1,2-disodiumethane efficiently dehalogenate vic-dibromoderivatives, affording
the corresponding alkenes. The reaction proceeds rapidly, under mild conditions and is tolerant of a variety of functional groups
(
ꢀ
alcohol, carboxylic acid, ester and amide). This procedure was successfully extended to similar vic-disubstituted compounds.
2005 Elsevier Ltd. All rights reserved.
1
. Introduction
Na
X
THF
Ar +
R1
Ar
+
R1
Ph
R
Ph
R
Reduction of vic-dihalides to the corresponding alkenes
1
2
Na
X1
2a-i
Scheme 1. 1,2-Diaryl-1,2-disodiumethanes-mediated reductive elimi-
by the action of mono- or polycarbanions is a known
reaction, mainly investigated from a mechanistic point
of view.
1
a, b
3a-i
nations. 1a, Ar = Ph; 1b, Ar = 2-C N; X and/or X = Br, Cl,
OCH ; R, R , see text and Table 1.
5
H
4
1
We recently reported a general procedure allowing the
3
,4
3
1
generation of 1,2-disodium-1,2-diarylethanes, as well
as their easy oxidation to the corresponding stilbenes
3
by reaction with 1,2-dibromoethane, probably occur-
2
temperature and aqueous workup (Scheme 1). Selected
results are reported in Table 1.
ring with contemporary formation of ethene. Due to
the synthetic significance of reductive dehalogenation
5
procedures, we investigated further on this reactivity,
Reaction of an erythro/threo = 9:1 diastereoisomeric
and wish to report some interesting preliminary results.
7
mixture of 1,2-dibromo-1-(4-methoxyphenyl)propane,
2
a, with 1.2 equiv of 1a led, within 10 min at 0 ꢁC, to
the formation of trans-anetole, 3a, inseparable from
trans-stilbene, the product of oxidation of 1a (Table 1,
entry 1).
2
. Results and discussion
Deep red solutions (0.1 M) of 1,2-diaryl-1,2-disodiume-
thanes 1a and 1b were obtained by the reaction of trans-
stilbene or trans-stilbazole, respectively, with an excess
of Na metal in dry THF, under Ar, immediately prior
to use. Solutions of 1 were drained from excess metal,
and reductive eliminations were carried out by adding a
solution of the vic-disubstituted compound 2 to a chilled
solution of 1a or 1b, followed by stirring at the same
More efficiently, dehalogenation of 2a was performed in
the presence of 1.2 equiv of 1b: after aqueous workup
and acid washings (1 N HCl) to separate basic deriva-
tives, trans-anetole 3a was recovered in almost quanti-
tative yield (Table 1, entry 2).
4
,6
8
This procedure was easily extended to the reductive
dehalogenation of dibromocarboxylic acids. Indeed, by
employing an excess of 1a, quantitative dehalogenation
of 10,11-dibromoundecanoic acid, 2b, was obtained
within 10 min at 0 ꢁC (Table 1, entry 3). Application
of this procedure to threo-13,14-dibromodocosanoic
Keywords: Reduction; Elimination; Alkali metals; Dicarbanions.
*
Corresponding author. Tel.: +39 079229549; fax: +39 079229559;
e-mail: ugo@uniss.it
0040-4039/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.12.054

1056
U. Azzena et al. / Tetrahedron Letters 47 (2006) 1055–1058
a
Table 1. 1,2-Diaryl-1,2-disodiumethanes-mediated reductive elimination reactions
b
Entry Dianion (equiv) Substrate (R, R , X, X
1
1
)
Product (R, R
1
)
Yield (%)
c
1
2
3
4
5
6
7
8
9
1
1a (1.2)
1b (1.2)
1a (2.0)
1b (2.0)
1b (2.0)
1a (2.0)
1b (1.1)
1a (1.1)
1b (1.3)
1b (1.1)
2a (4-CH
2a (4-CH
3
OC
OC
6
H
4
, CH
, CH
3
, Br, Br) erythro/threo = 9:1 trans-3a (4-CH
, Br, Br) erythro/threo = 9:1 trans-3a (4-CH
3
OC
OC
6
H
H
4
, CH
, CH
3
)
)
>95
3
6
H
4
3
3
6
4
3
>90
80
>90
>90
70
2b (H, (CH
threo-2c (C
erythro-2c (C
2d (H, (CH
2e (H, (CH
2f (see Scheme 2)
erythro-2g (Ph, Ph, Br, OCH
2h (H, (CH 10CH , Cl, Cl)
2
)
9
COOH, Br, Br)
17, (CH 11COOH, Br, Br)
17, (CH 11COOH, Br, Br)
OH, Br, Br)
OCOCH , Br, Br)
2 9
3b (H, (CH ) COOH)
d
8
H
2
)
3c (C
3c (C
8
8
H
H
17, (CH
17, (CH
2
)
)
11COOH) trans/cis = 65:35
11COOH) trans/cis = >95: <5
d
8
H
2
)
2
2
)
9
3d (H, (CH
3e (H, (CH
2
)
9
OH)
OCOCH
e
2
)
9
3
2
)
9
3
)
82
87
3f (see Scheme 2)
trans-3g (Ph, Ph)
f
3
)
>90
c,f
0
2
)
3
3h (H, (CH
2
)10CH
3
)
>95
a
b
c
d
e
f
All reactions were run at 0 ꢁC during 10 min, unless otherwise indicated.
Yields determined on isolated products, unless otherwise indicated.
1
As determined by H NMR of crude reaction mixture.
As determined by GC–MS of the corresponding methyl esters (see text).
Reaction run at ꢀ80 ꢁC, under inverse addition conditions.
Reaction time = 1 h.
acid,9 threo-2c, afforded the corresponding docos-13-
enoic acid, 3c, as a trans/cis = 65:35 diastereoisomeric
mixture whilst, under identical reaction conditions,
reductive dehalogenation of erythro-13,14-dibromodo-
Br
Br
1a (1 equiv), THF
-80 ºC, 10 min
N
N
9
cosanoic acid, erythro-2c, afforded almost pure trans-
O
O
docos-13-enoic acid, 3c (Table 1, entries 4 and 5). The
ratio between the stereoisomers of 3c was determined
by esterification of crude reaction mixtures with di-
azomethane, followed by GC–MS analysis of the result-
ing products, whilst the stereochemistry of recovered 3c
was assigned by comparison with authentic samples of
2f
3f, 87%
Scheme 2. Reductive dehalogenation of amide 2f.
excess of 1b at 0 ꢁC during 1 h, efficiently afforded
trans-stilbene, 3g (Table 1, entry 9); under similar condi-
tions, reaction of 1,2-dichlorododecane, 2h, with a slight
excess of 1a, allowed the recovery of 1-dodecene, 3h, in
satisfactory yield (Table 1, entry 10).
9
both stereoisomers.
Under similar conditions, 10,11-dibromoundecan-1-ol,
2
d, was efficiently reduced to 10-undecen-1-ol, 3d, by
the reaction with 2 equiv of 1a (Table 1, entry 6).
Finally, we investigated the reductive elimination of
1
-phenyl-1,1-dimethoxy-2-bromoethane, 2i, and found
We next investigated the reaction of 10,11-dibromo-
undecyl acetate, 2e, with dianion 1b. Whilst a reaction
run at 0 ꢁC afforded a complex reaction mixture, a set
of reactions run at ꢀ80 ꢁC in the presence of variable
amounts of 1b (1–2 equiv), led to the recovery of reac-
tion mixtures containing, besides 10-undecenyl acetate,
that its reduction with 1.6 equiv of 1b afforded 1-phen-
yl-1-methoxyethene, 3i, in satisfactory yield (Scheme 3).
From a mechanistic point of view, the described reduc-
tive elimination reaction can be considered to proceed
via a ‘single electron’ reaction pathway, as described
in Eqs. 1–4.
1
3
3
e, variable amounts of starting material and 10-unde-
cen-1-ol, 3d. We rationalized this behavior by assuming
that 1b acts both as a reducing agent, leading to the for-
mation of dehalogenated products, as well as a nucleo-
phile, leading to cleavage of the ester bond and,
eventually, to the formation of alcohol 3d. However,
under inverse addition conditions, that is, by dropwise
adding 1.1 equiv of 1b to a chilled solution of ester 2e,
it was possible to recover the desired unsaturated ester
A first SET from the dianion to the vic-disubstituted
substrate generates two different radical anions (Eq. 1);
the halide-substituted radical anion undergoes an
halide–carbon bond cleavage, thus affording a halide
anion and a radical (Eq. 2); a second SET, from the
1
,2-diaryl radical anion to the radical, afforded the 1,2-
3
e in 82% yield (Table 1, entry 7).10
diarylethene and a b-substituted carbanion (Eq. 3); in
the last step, the b-substituted carbanion is transformed
into the corresponding alkene (Eq. 4).
It is worth noting that a less electrophilic amide did not
1
1
pose similar problems: indeed, addition of amide 2f to
a chilled THF solution of 1.1 equiv of 1a afforded the
desired dehalogenated product, 3f, in satisfactory yield
OCH3
H CO
OCH3
Br
3
1
b (1.6 equiv), THF
(
Table 1, entry 8 and Scheme 2).
0
ºC, 1 h
Our procedure was successfully extended to similar vic-
disubstituted compounds. Indeed, reduction of erythro-
2
i
3i, 70%
1
2
1
-bromo-2-methoxy-1,2-diphenylethane, 2g, with an
Scheme 3. Reductive elimination of 2i.

U. Azzena et al. / Tetrahedron Letters 47 (2006) 1055–1058
1057
X
X _
.
ether/AcOEt), whilst crude products from reactions
run in the presence of 1b were usually >90% pure ( H
NMR and GC–MS).
_
.
.
.
1
_. . Ar
R1
_. . Ar
R1
+
+
Ph
R
Ph
R
X1
X1
ð1Þ
ð2Þ
Although the synthesis of compound 3i was run in the
presence of 1b, the reaction product, which is acid sensi-
tive, was purified by flash chromatography (petroleum
X _
.
_
.
.
.
R1
R1
X
+
ether/AcOEt/Et N).
R
R
3
X1
X1
1
13
All compounds gave analytical and spectral ( H and
C
_
..
.
.
NMR, IR) data in agreement with the assigned struc-
tures and available literature data; the stereochemistry
of starting materials and reaction products was assigned
_. . Ar
R1
Ar
R
R1
+
+
Ph
R
Ph
X1
X1
by comparison with commercially available samples
ð3Þ
ð4Þ
7
(
trans-3a, cis-3c, trans-3g), or with literature data (2a,
9
9
11
12
9
_
_
..
threo-2c, erythro-2c, 2f, erythro-2g, trans-3c ).
.
.
R1
R1
X1
+
R
R
X1
Acknowledgements
We thank the Universit a` di Sassari (Fondo di Ateneo)
for financial support.
In agreement with this hypothesis, with suitable sub-
strates our reductive elimination procedure occurs with
preferential or exclusive formation of trans-alkenes
(
Table 1, entries 1, 2, 4, 5, 8 and 9), as in the case of Na
References and notes
5
k
naphthalenide-promoted reductive debrominations.
1
. (a) Garst, J. F.; Pacifici, J. A.; Singleton, V. D.; Ezzel, M.
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In summary, our results clearly show that 1,2-diaryl-1,2-
disodiumethanes efficiently promote the reductive elimi-
nation of vic-dibromides and related vic-disubstituted
derivatives. Interestingly, our procedure is tolerant of
a variety of functional groups (Table 1, entries 3–8
and Scheme 2). Further work is in progress to extend
the scope of this reaction.
(
2
b) Kofron, W. G.; Hauser, C. R. J. Org. Chem. 1970, 35,
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2
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3
. General experimental procedure
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the reaction of freshly cut Na metal with stilbene or aza-
stilbene, respectively, in dry THF, as reported in Ref. 4.
These solutions were prepared, and drained from excess
metal under an atmosphere of pure argon, immediately
before use. The preparation of starting materials was
realized with standard procedures. THF was distilled
3
4
5
. Azzena, U.; Dettori, G.; Idini, M. V.; Pisano, L.; Sechi, G.
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. For a selection of relevant literature, see: (a) Larock, R. C.
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from Na/K alloy under N immediately prior to use.
2
1
989, pp 133–135; (b) Young, D. W. In Protective Groups
4
. Typical reductive elimination procedure
in Organic Chemistry; McOmie, J. F. W., Ed.; Plenum
Press: London, 1973; Chapter 8, pp 309–320; (c) Bacioc-
chi, E. 1,2-Dehalogenation and Related Reactions. In The
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To 10 mL of 0.1 M solution of 1a or 1b (1 mmol), chilled
at 0 ꢁC, was added a solution of the appropriate vic-disub-
stituted compound 2 (0.8–0.5 mmol) dissolved in 3 mL of
dry THF. After stirring for 10 min (except when other-
wise indicated), the mixture was quenched by slow drop-
wise addition of H O (15 mL), the cold bath removed,
and the resulting mixture extracted with Et O
3 · 10 mL). The organic phase was washed with brine
10 mL) then, in case of reactions with 1b, with 1 N HCl
2
2
8
3–91; (g) Totten, L. A.; Jans, U.; Roberts, A. L. Environ.
(
(
(
Sci. Technol. 2001, 35, 2268–2274; (h) Butcher, T. S.;
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3 · 10 mL), dried (Na SO ) and the solvent evaporated.
2
4
1
998, 54, 1021–1028; (j) Savoia, D.; Tagliavini, E.;
Crude products from reactions run in the presence of 1a
were purified by flash chromatography (petroleum
Trombini, C.; Umani-Ronchi, A. J. Org. Chem. 1982,
47, 876–879; (k) Adam, W.; Arce, J. J. Org. Chem. 1972,

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7, 507–508; (l) Cristol, S. J.; Hause, N. L. J. Am. Chem. 1062. See also: Rankoff, G. Chem. Ber. 1930, 63, 2139–
3
Soc. 1952, 74, 2193–2197.
2142.
6
. Yields of diorganometallics 1 were determined by quench-
ing the reduction mixtures with D O, followed by H
2
NMR analysis of crude reaction mixtures, to determine
the percentage of deuterium incorporation in the aryl-
methyl positions. See Ref. 4.
10. Similar results were obtained employing 1a as a reducing
agent; however, the employment of 1b allowed an easier
purification of reaction products.
11. The trans stereochemistry of amide 2f, was assigned by
comparison with the stereochemistry of the corresponding
N-carboxamide and N-carbonyl chloride, prepared under
similar reaction conditions: Bellucci, G.; Chiappe, C.;
Marioni, F.; Marchetti, F. J. Chem. Soc., Perkin Trans. 2
1992, 637–642, and references cited therein.
12. House, H. O.; Ro, R. S. J. Am. Chem. Soc. 1958, 80, 182–
187.
13. Alternative reductive elimination mechanisms are usually
described as ‘single electron’ or as ‘concerted two elec-
trons’ reaction pathways. For an in-depth comparison of
these mechanisms, see Ref. 5c.
1
7
8
. Fahey, R. C.; Schneider, H.-J. J. Am. Chem. Soc. 1968, 90,
4429–4434.
. The basic fraction contains mainly trans-stilbazole, as well
as a minor amount (10–15%) of 1-phenyl-2-(2-pyridyl)eth-
1
ane (i.e., the product of protonation of 1b); after H NMR
to determine the exact amount of trans-stilbazole, this
mixture can be successfully recycled to a new reductive
dehalogenation reaction.
9
. Maruyama, T. Proc. Imp. Acad. 1934, 10, 467–469;
Chem. Zentralbl. 1935, 106, 2358; Chem. Abs. 1935, 29,