Reductive metalation of 1,2-diaryl-substituted ethenes: Synthetic applications

Article abstract of DOI:10.1016/j.tet.2005.06.108

Reduction of 1,2-diaryl-substituted ethenes with Na metal in dry THF allowed easy access to a variety of 1,2-diaryl-1,2-disodiumethanes. These diorganometallic intermediates were elaborated into the corresponding 1,2-diarylethanes (aqueous work up), or cycloalkylated with 1,3- dichloropropanes. The last reaction led to a highly diastereoselective synthesis of trans-1,2-diaryl-substituted cyclopentanes.

Full text of DOI:10.1016/j.tet.2005.06.108

Tetrahedron 61 (2005) 8663–8668
Reductive metalation of 1,2-diaryl-substituted ethenes:
synthetic applications
Ugo Azzena, Giovanna Dettori, Caterina Lubinu, Alberto Mannu and Luisa Pisano
*
Dipartimento di Chimica, Universit a` di Sassari, via Vienna 2, I-07100 Sassari, Italy
Received 22 April 2005; revised 10 June 2005; accepted 30 June 2005
Available online 19 July 2005
Abstract—Reduction of 1,2-diaryl-substituted ethenes with Na metal in dry THF allowed easy access to a variety of 1,2-diaryl-1,2-
disodiumethanes. These diorganometallic intermediates were elaborated into the corresponding 1,2-diarylethanes (aqueous work up), or
cycloalkylated with 1,3-dichloropropanes. The last reaction led to a highly diastereoselective synthesis of trans-1,2-diaryl-substituted
cyclopentanes.
q 2005 Elsevier Ltd. All rights reserved.
1
. Introduction
reductive metalation reactions to the regioselective
preparation of substituted aromatic derivatives, we have
previously reported that reduction of several 3,4,5-
trimethoxystilbenes, with Na metal in THF, results in
regioselective cleavage of the methoxy group at the
4-position and, depending upon reaction conditions, to
Reduction of stilbene with alkali metals in aprotic solvents
is a well known reaction, allowing easy access to the
corresponding dianions. Despite the relatively high
stabilities of the resulting diorganometals, this reaction
was investigated mainly from a mechanistic point of view.
1
2
–5
14,15
reduction of the olefinic bond.
Indeed, reaction of these intermediates with alkyl halides,
phosphonates and sulfates, is of limited synthetic useful-
ness, due to the formation of diastereoisomeric mixtures of
As a further useful application to this approach, we
investigated the reductive metalation of several 1,2-
diarylethenes in THF, currently the most commonly used
solvent for this kind of reaction, with the purpose to
apply this procedure to a general synthesis of trans-1,2-
diarylcyclopentanes.
2
–5
alkylated products,
compounds, under Barbier-type conditions, afforded 1,2-
whilst reaction with carbonyl
1
6,17
6
diphenylethane.
At odds with these results, the reaction of 1,2-disodium-1,2-
diphenylethane (1,2-disodiumstilbene) with 1,3-dichloro-
propane or 1,4-dichlorobutane in 1,2-dimethoxyethane
2
. Results and discussion
(
2
DME), afforded good yields of the corresponding trans-1,
-diphenyl cyclopentane or -cyclohexane, respectively,
2
.1. Synthesis of starting materials
3
with very high diastereoselectivity. Surprisingly, the latter
reaction was not synthetically exploited, despite the
potential usefulness of trans-1,2-diaryl-substituted cyclo-
Compounds (E)-1 and (Z)-1, as well as (E)-5, are
commercially available. Other starting materials were
synthesized according to reported procedures,
deprotonation of either diethyl benzylphosphonate, or
diethyl 2-methoxybenzylphosphonate, with NaH in THF,
in the presence of the appropriate aldehyde and a catalytic
amount of 15-crown-5. The corresponding (E)-stilbenes
pentanes as C -symmetric ligands, for employment in
2
18,19
by the
7
–11
catalysis.
Furthermore, it is worth noting that only few reports concern
the reductive metalation of functionalized stilbenes.
1
2,13
2
(
–4, 6 and 7 were recovered in good to satisfactory yields
Scheme 1).
Following on from our interest in the application of
Keywords: Dicarbanions; Stilbenes; Metalation; Reduction;
Cycloalkylation.
2.2. Reductive metalation reactions
*
Corresponding author. Tel.: C39 79229549; fax: C39 79229559;
e-mail: ugo@uniss.it
Reductive metalations of stilbenes 1–7 were run in the
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.06.108

8664
U. Azzena et al. / Tetrahedron 61 (2005) 8663–8668
Intermediate, quantitative formation of 1,2-diphenyl-1,2-
disodiumethane resulted by quenching the reduction
mixture with D O (Table 1, entry 2). Under these
2
conditions, quenching the reduction mixture with Cl(CH ) -
2
3
Cl, at K80 8C, allowed the recovery of 1,2-diphenylcyclo-
pentane, 14, as a single diastereoisomer, in 72% yield
(Table 1, entry 3). According to the literature, we assigned a
0
Scheme 1. Synthesis of 1,2-diarylethenes: 2: ArZPh, Ar Z1-naphtyl,
0 0
5%; 3: ArZPh, Ar Z4-pyridyl, 57%; 4: ArZPh, Ar Z2-pyridyl, 61%; 6:
8
2
1
0
0
3 6 4 3 3 6 2
O)C H , 92%; 7: ArZPh, Ar Z3,4,5-(CH O) C H ,
relative trans-configuration to cyclopentane 14.
ArZAr Z2-(CH
0%.
9
The same results were obtained using Li in reductive
metalations of (E)-1 quenched with H O or D O (Table 1,
presence of an excess of the freshly cut metal, in dry THF,
under argon gas. Reaction mixtures were quenched either
with H O, or with D O to provide evidence for the
2
2
entries 4 and 5), whilst quenching the reduction mixture
with Cl(CH Cl led to recover cyclopentane 14 with a
slightly improved yield (Table 1, entry 6).
2
2
)
2 3
intermediate formation of dicarbanions. Cl(CH ) Cl
2
3
quenching was performed by adding 2 equiv of the
electrophile to the reduction mixtures at K80 8C, and
stirring the resulting mixtures for 12 h whilst allowing it to
reach 0 8C, before aqueous work up (Scheme 2).
Reduction of (Z)-1 with Na metal, followed by aqueous
work up, led to the recovery of 1,2-diphenylethane,
although, a relatively longer reaction time (7 h) was
required (Table 1, entry 7). Furthermore, a similar reaction,
quenched after 1 h reaction time, led to recover bibenzyl 8
and (E)-stilbene 1 in 41 and 59% yield, respectively
(
the starting material, in agreement with original
Table 1, entry 8), thus, confirming fast isomerization of
1
,2
observations of Schlenk and Bergmann.
We next, extended our investigation to the reductive
metalation of differently substituted 1,2-diarylethenes 2–7,
to check the applicability of this reaction to the synthesis of
an ecletic array of trans-1,2-diarylcyclopentanes. Attention
was focused on the employment of Na metal as a reducing
agent as it is, by far, the most economical of the alkali
metals. The results are reported in Table 2 (Scheme 2).
0
Scheme 2. Reductive metalation of stilbenes; 1, 8, 14: ArZAr ZPh; 2, 9,
0
0
1
5: ArZPh, Ar Z1-naphtyl, 3, 10, 16: ArZPh, Ar Z4-C
5
H
4
N; 4, 11, 17:
N; 6, 13, 19: ArZ
O) ; 20: ArZ
0
0
ArZPh, Ar Z2-C
Ar Z2-(CH
Ph, Ar Z3,5-(CH
5
H
4
N; 5, 12, 18: ArZAr Z2-C
5
H
4
0
0
3
O)C
6
H
4
; 7: ArZC
6
H
5
, Ar Z3,4,5-(CH
3
3 6 2
C H
0
3
O)
2
C
6
H
3
.
Reduction of naphthyl derivative 2 with an excess of Na
metal in THF at 25 8C, afforded a complex reaction mixture
(not reported in Table 2). A much better result was obtained
performing this reduction at K20 8C, in the presence of
6 equiv of the metal: under these conditions, aqueous work
up afforded 1-(1-naphthyl)-2-phenylethane, 9, in almost
quantitative yield, via quantitative intermediate formation
of the corresponding dianion (Table 2, entries 1 and 2).
We initially investigated the reduction of (E)- and (Z)-
2
stilbene 1 under the above reaction conditions. Indeed,
0
literature data do not agree on the relative reactivities of
1
,2
diastereoisomeric stilbenes towards alkali metals. It was
also necessary to check the stereochemical outcome of the
reaction of the resulting diorganometals with Cl(CH ) Cl in
2
3
THF; several authors reported a solvent effect on the
diastereoselectivities of several alkylation reactions of these
Quenching with Cl(CH ) Cl afforded a single diastereo-
3
isomer of the corresponding 1-(1-naphthyl)-2-phenylcyclo-
pentane, 15, in good yield (Table 2, entry 3).
2
2
,3
intermediates. Selected results are reported in Table 1.
Reduction of (E)-1 with 3 equiv of Na metal during 5 h,
followed by aqueous work up, afforded bibenzyl, 8, as the
only detectable reaction product (Table 1, entry 1).
Reductive metalation of pyridyl-substituted derivates 3–5
were run at 0 8C, in the presence of variable amounts
a
Table 1. Reductive metalation of (E)-1 and (Z)-1
b
Entry
Substrate
Metal
t (h)
Quencher
Product
Yield (%)
1
2
3
4
5
6
7
8
(E)-1
(E)-1
(E)-1
(E)-1
(E)-1
(E)-1
(Z)-1
(Z)-1
Na
Na
Na
Li
Li
Li
5
5
5
5
5
5
7
1
H
D
Cl(CH
H
D
Cl(CH
2
2
O
O
8 (H)
8-d (D)
2
14
8 (H)
2
8-d (D)
14
8 (H)
8 (H)
O95
O95
72
c
2
)
3
3
Cl
Cl
2
2
O
O
O95
O95
c
2
)
76
O95
41
Na
Na
H
H
2
2
O
O
d
a
All reductions were run at rt in the presence of 3 equiv of the metal.
1
Yields calculated by H NMR spectroscopy, unless otherwise indicated.
b
c
d
Yields calculated on isolated products.
(
E)-1 (59%) was also recovered.

U. Azzena et al. / Tetrahedron 61 (2005) 8663–8668
Table 2. Reductive metalation of 1,2-diarylethenes 2–7
8665
a
Entry
Substrate
Na (equiv)
T (8C)
t (h)
Quencher
Product
Yield (%)
1
2
3
4
5
6
7
8
9
2
2
2
3
3
3
4
4
4
5
5
5
6
6
6
7
6
6
6
6
6
6
8
8
8
8
8
8
3
3
3
6
K20
K20
K20
0
0
0
0
0
0
0
0
0
0
0
0
20
7
7
7
H
D
Cl(CH
2
O
O
9 (H)
9-d (D)
81
O95
b
2
2
2
2
2
2
)
)
)
)
3
3
3
3
Cl
Cl
Cl
Cl
15
10 (H)
10-d (D)
87
73
88
12
12
12
12
12
12
12
12
12
7
H
D
2
O
O
b
2
2
Cl(CH
16
11 (H)
11-d (D)
64
78
82
H
D
2
O
O
b
2
2
Cl(CH
17
12 (H)
12-d (D)
81
83
90
10
11
12
13
14
15
16
H
D
2
O
O
b
2
2
Cl(CH
18
13 (H)
78
70
80
H
D
2
O
O
b
7
7
7
2
13-d
19
2
(D)
Cl(CH
Cl(CH
2
)
)
3
Cl
Cl
62
59
2
3
20
a
Yields calculated on isolated products, unless otherwise indicated.
1
Yields calculated by H NMR spectroscopy.
b
(
6–8 equiv) of Na metal. Under these conditions, the
quenched with 2 equiv of the electrophile, as described
above. Aqueous work up, followed by acidic hydrolyses,
afforded the corresponding 3,4-diaryl-1-cyclopentanols
(Table 3, Scheme 3).
corresponding heteroaryl-substituted ethanes, 10–12, were
recovered, and intermediate formations of 1,2-disodium
derivatives was evidenced by quenching the reduction
mixtures with D O (Table 2, entries 4 and 5, 7 and 8, 10 and
2
1
1).
Table 3. Synthesis of trans-3,4-diaryl-1-hydroxycyclopentanes
a
Entry
Substrate [ArZ]
1 [Ph]
Product
Yield (%)
Cycloalkylation reactions, performed as described above,
afforded the desired pyridyl-substituted cyclopentanes,
1
2
3
21
22
23
60
35
32
5 [2-C
5
H
6 [2-(CH
4
N]
O)C
16–18, as single diastereoisomers, in good to satisfactory
yields (Table 1, entries 6, 9 and 12).
3
6 4
H ]
a
Yields calculated on isolated products.
Good results were obtained in the reduction of dimethoxy-
substituted stilbene 6 with 3 equiv of Na metal at 0 8C
during 7 h. Under these conditions, aqueous work up
afforded the dihydrostilbene 13 in good yield, with no
1
4
evidence of cleavage of carbon–oxygen bonds (Table 2,
entry 13). Intermediate formation of a diorganometallic
derivative was evidenced, as quenching the reduction
mixture with D O (Table 2, entry 14), whilst cycloalkyl-
2
Scheme 3. Synthesis of trans-3,4-diaryl-1-hydroxycyclopentanes: 1, 21:
ArZPh; 5, 22: ArZ2-C N; 6, 23: ArZ2-(CH O)C ; EOMZ
CH OCH CH
5
H
4
3
6 4
H
ation afforded 1,2-di-(2-methoxy-phenyl)cyclopentane, 19,
as a single diastereoisomer, in 62% yield (Table 2, entry 15).
The relative trans-configuration of this compound was
2
2
3
.
Results obtained with stilbenes 1, 5 and 6 are reported in
Table 3: cyclopentanols 21–23 were recovered in 60, 35 and
1
13
confirmed by a comparison of its H and C NMR spectra
8
with literature data.
32% isolated yield, respectively, as single diastereoisomers
(
Table 3, entries 1–3). Besides showing the possibility to
Reductive metalation of 3,4,5-trimethoxystilbene, 7, was
performed under previously optimized reaction conditions
synthesize vic-diarylcyclopentanes functionalized on the
alicyclic moiety, these results support the relative trans
orientation of aryl substituents at C3 and C4; indeed, a
relative cis orientation of these substituents would result in
the presence of a stereocenter at C1, with formation of a
couple of diastereoisomers.
1
6 equiv of Na metal, 20 8C, 7 h); quenching with
4
(
Cl(CH ) Cl afforded, after aqueous work up and flash
2
3
chromatography, 1-(3,5-dimethoxyphenyl)-2-phenylcyclo-
pentane, 20, as a single diastereoisomer, in 59% yield
(
Table 1, entry 16).
To extend the scope of this reductive cycloalkylation, as
well as to confirm the trans stereochemistry of this reaction,
we investigated the reactivity of symmetrically-substituted
3
. Conclusions
The reported synthetic procedure allows for the generation
of several 1,2-disodium-1,2-diarylethanes, bearing an array
of different aromatic rings. Interestingly, this procedure was
successfully applied to ethenes substituted either with
electron-rich or with electron-poor aromatic rings. In both
cases, the corresponding diorganometal derivatives were
generated under particularly mild reaction conditions.
1
dichloropropane, namely 1,3-dichloro-2-ethoxy-
,2-disodium intermediates towards a functionalized 1,3-
2
2
methoxypropane.
Reductive metalations were performed as described above,
and reduction mixtures were chilled to K80 8C and

8666
U. Azzena et al. / Tetrahedron 61 (2005) 8663–8668
Reaction of intermediate diorganometals with 1,3-dichloro-
propanes allowed a simple and highly diastereoselective
approach to the synthesis of several trans-1,2-diaryl-
substituted cyclopentanes. The employment of some of
organic phase was washed with brine (10 mL), dried
(K CO ) and the solvent evaporated.
2
3
D O quenching was performed by slow dropwise addition
2
these derivatives (possessing C -symmetry and/or suitable
2
of 0.75 mL of the electrophile dissolved in dry THF (2 mL),
followed by aqueous work-up as described above.
functional groups) as ligands for transition metals, is under
investigation in our laboratories.
2
3
Quenching with Cl(CH ) Cl was performed by adding the
2
3
appropriate electrophile (2 equiv) to the reduction mixture
chilled to K80 8C. The reaction mixture was allowed to
warm to 0 8C during 12 h, before aqueous work-up as
described above.
4. Experimental
4
.1. General
Quenching with 1,3-dichloro-2-ethoxymethoxypropane was
performed by adding the appropriate electrophile (2 equiv)
to the reduction mixture chilled to K80 8C. The reaction
mixture was allowed to warm to 0 8C during 12 h, before
aqueous work-up as described above. Crude products were
added under Ar to a stirred 0.6 M solution of HCl in MeOH
Boiling and melting points are uncorrected; the air bath
temperature on bulb-to-bulb distillation are given as boiling
points. Starting materials were of the highest commercial
quality and were purified by distillation immediately prior
to use. Na metal (stick) was 99% purity, and Li metal (wire,
diameter 3.2 mm) was 99.9% purity. D O was 99.8%
2
[obtained by adding AcCl (0.5 mL) to MeOH (10 mL)]
chilled to 0 8C. The mixture was stirred at rt for 3 h, until
isotopic purity. THF was distilled from Na/K alloy under N
immediately prior to use. H NMR spectra were recorded at
2
1
complete disappearance of starting material, as determined
by TLC. The mixture was diluted with H O (10 mL), and
1
00 MHz and C NMR spectra were recorded at 75 MHz in
3
3
CDCl3 with SiMe4 as internal standard. Deuterium
2
the MeOH evaporated under reduced pressure. The resulting
mixture was basified (1N NaOH), extracted with Et O (4!
1
incorporation was calculated by monitoring the H NMR
2
spectra of crude reaction mixtures, and by comparing the
integration of the signal corresponding to protons in the
arylmethyl position with that of known signals. Flash
chromatography were performed on Merck silica gel 60
10 mL), and the organic phase dried (K CO ) and
2 3
evaporated.
1,2-Diphenylethane, 8, was purified by flash chromato-
graphy (petroleum ether), and characterized by comparison
(
40–63 mm), and TLC analyses on Macherey-Nagel silica
gel pre-coated plastic sheets (0.20 mm). Elemental analyses
were performed by the microanalytical laboratory of the
Dipartimento di Chimica, Universit a` di Sassari.
29 30
with a commercial sample. Compounds 9, 10, 11,
1
graphy (petroleum ether/AcOEt or petroleum ether/AcOEt/
31
32
33
21
8
2, 13, 14, and 19 were purified by flash chromato-
Et N), and characterized by comparison with literature data.
3
1
Deuterated compounds were characterised by H and
13
4
.2. Starting materials
C
NMR spectroscopy: the resonances of arylmethyl CHD
protons appear as unresolved broad triplets shifted 0.02–
0.05 ppm (d) upfield relatively to the corresponding CH2
protons; the resonances of arylmethyl CHD carbions appear
as triplets (JZ18–21 Hz) shifted 0.3–0.5 ppm (d) upfield
Compounds 1 and 5 are commercially available.
Compounds 2, 3, 4, and 7 were synthesized
2
4
25
26
14
1
6
according to a general procedure, by the reaction of
commercially available diethyl benzylphosphonate with
the appropriate arylaldehyde in the presence of 15-crown-5
in dry THF, and characterized according to the
relatively to the corresponding CH carbons.
2
2
7
literature. Compund 6 was similarly obtained by the
Other products were purified and characterized as follows.
2
8
reaction of diethyl 2-methoxybenzylphosphonate with
-methoxybenzaldehyde. Isolated yields are reported in
Scheme 1.
2
4.3.1. trans-1-(1-Naphthyl)-2-phenylcyclopentane (15).
Purified by flash chromatography (petroleum ether/
AcOEtZ9.5:0.5), white solid; mp 74–75 8C (EtOH); R Z
f
4.3. Reductive metalation of 1,2-diarylethenes 1–8, and
reaction with electrophiles. General procedure
0.50 (petroleum ether/AcOEtZ9.5:0.5). Anal. Found: C,
1
20 requires: C, 92.58; H, 7.42%. H
92.30; H, 7.56; C21
H
NMR: d 1.71–1.9 (1H, m, CH), 1.91–2.11 (3H, m, CH),
2.30–2.44 (1H, m, CH), 2.44–2.61 (1H, m, CH), 3.46–3.60
(1H, m, CH), 3.98 (1H, q, JZ8.4 Hz, CH), 6.42–7.11 (1H,
m, ArH), 7.11–7.24 (4H, m, 4!ArH), 7.32–7.50 (4H, m,
4!ArH), 7.64 (1H, d, JZ8.1 Hz, ArH), 7.74–7.83 (1H, m,
ArH), 7.98–8.06 (1H, m, ArH). C NMR: d 24.3, 35.5,
35.6, 47.8, 51.3, 122.7, 123.7, 125.1, 125.4, 125.6, 125.9,
126.3, 127.4, 128.2, 128.7, 132.4, 133.9, 140.6, 144.3.
Two to three pieces of freshly cut metal (3–9 equiv) were
placed under Ar in a 50 mL two-necked flask equipped with
reflux condenser and magnetic stirrer, and suspended in
THF (10 mL) at the reported temperature (Tables). The
appropriate 1,2-diarylethene (5 mmol), dissolved in dry
THF (2 mL), was added dropwise, and each metal piece was
cut into 2–3 smaller pieces with a spatula, and the mixture
was vigorously stirred for the reported time at the reported
temperature (Tables).
1
3
4.3.2. trans-1-(4-Pyridyl)-2-phenylcyclopentane (16).
Purified by flash chromatography (petroleum ether/
Aqueous work-up was performed by slow dropwise addition
of 10 mL of H O (caution!) the cold bath removed, and the
resulting mixture extracted with Et O (3!10 mL). The
2
AcOEtZ1:4), yellow oil; R Z0.53 (petroleum ether/
f
AcOEtZ3:7). Anal. Found: C, 85.76; H, 7.94; N, 6.26
16 17
2
1
C H N requires: C, 86.04; H, 7.69; N, 6.27%. H NMR: d

U. Azzena et al. / Tetrahedron 61 (2005) 8663–8668
8667
1
3
7
2
1
.81–2.04 (4H, m, 2!CH ), 2.19–2.34 (2H, m, CH ), 2.90–
2
CH), 2.14–2.20 (1H, m, CH), 2.17 (1H, br s, OH), 2.30–2.39
(1H, m, CH), 2.50–2.61 (1H, m, CH), 3.60 (1H, dt, JZ11.7,
6.9 Hz, CH), 3.79 (1H, dd, JZ9.6, 6.3, 1.8 Hz, CH), 4.51
(1H, t, JZ3.6 Hz, CHO), 6.97 (1H, dt, JZ7.8, 0.9 Hz,
ArH), 7.02 (1H, dt, JZ7.8, 0.9 Hz, ArH), 7.10 (1H, ddd, JZ
2
.15 (2H, m, CH ), 7.00 (2H, dd, JZ4.5, 1.8 Hz, 2!ArH),
2
.07–7.25 (5H, m, 5!ArH), 8.39 (2H, dd, JZ4.5, 1.8 Hz,
!ArH). C NMR: d 24.5, 34.4, 35.3, 53.2, 53.8, 122.7,
26.2, 127.2, 128.3, 143.3, 149.5, 153.4.
1
3
5.1, 2.4, 0.9 Hz, ArH), 7.13 (1H, ddd, JZ5.1, 2.4, 0.9 Hz,
4.3.3. trans-1-(2-Pyridyl)-2-phenylcyclopentane (17).
Purified by flash chromatography (petroleum ether/
ArH), 7.54 (1H, ddd, JZ7.8, 4.2, 1.8 Hz, ArH), 7.52 (1H,
ddd, JZ7.8, 4.2, 1.8 Hz, ArH), 8.57 (1H, ddd, JZ5.1, 1.8,
1
3
AcOEtZ3:2), white solid; mp 41–43 8C (Et O); R Z0.67
0.9 Hz, ArH), 8.60 (1H, ddd, JZ5.1, 1.8, 0.9 Hz, ArH).
NMR: d 41.7, 46.0, 51.8, 54.7, 74.2, 121.1, 121.3, 122.5,
C
2
f
(
petroleum ether/AcOEtZ3:2). Anal. Found: C, 85.81; H,
7
6
.96; N, 6.20 C H N requires: C, 86.04; H, 7.69; N,
122.9, 136.2, 136.8, 149.3, 149.6, 163.4, 165.5.
1
6 17
1
.27%. H NMR: d 1.81–2.19 (4H, m, 2!CH ), 2.20–2.36
2
(
2H, m, CH ), 3.18–3.31 (1H, m, CH), 3.32–3.45 (1H, m,
2
4.3.8. trans-3,4-Di-(2-methoxyphenyl)cyclopentan-1-ol
(23). Purified by flash chromatography (petroleum ether/
CH), 6.91 (1H, dt, JZ7.8, 0.9 Hz, ArH), 7.03 (1H, ddd, JZ
7
7
8
5
1
.2, 4.8, 0.9 Hz, ArH), 7.07–7.16 (3H, m, 3!ArH), 7.16–
.24 (2H, m, 2!ArH), 7.44 (1H, td, JZ7.8, 1.8 Hz, ArH),
AcOEtZ2:3), colourless oil; R Z0.69 (petroleum ether/
f
K1
AcOEtZ2:3). IR (neat) 3230 cm . Anal. Found: C, 76.21;
1
3
1
H, 7.73; C H O requires: C, 76.47; H, 7.45%. H NMR: d
.53–8.56 (1H, m, ArH). C NMR: d 24.7, 34.0, 35.3, 52.8,
5.9, 121.0, 122.8, 125.8, 127.3, 128.2, 135.9, 144.4, 149.4,
63.6.
1
9 22 3
1
.75 (1H, dddd, JZ13.5, 9.6, 4.2, 1.5 Hz, CH), 1.99 (1H,
ddd, JZ13.5, 11.7, 6.6 Hz, CH), 2.05 (1H, br s, OH), 2.24
1H, ddt, JZ13.5, 7.2, 1.5 Hz, CH), 2.73 (1H, ddd, JZ13.5,
.0, 6.6 Hz, CH), 3.55–3.75 (1H, m, CH), 3.68 (3H, s,
OCH ), 3.77 (3H, s, OCH ), 4.00–4.10 (1H, m, CH), 4.50–
(
9
4
.3.4. trans-1,2-Di-(2-pyridyl)cyclopentane (18). Purified
by flash chromatography (petroleum ether/AcOEt/Et NZ
3
ether/AcOEt/Et NZ3:7:1). Anal. Found: C, 80.11; H, 7.41;
3
3
3
:7:1), white solid; mp 76–78 8C; R Z0.60 (petroleum
f
4.56 (1H, m, CHO), 6.74–6.85 (4H, m, 4 !ArH), 7.06–7.13
13
3
(2H, m, 2!ArH), 7.16–7.22 (2H, m, 2!ArH). C NMR: d
41.6, 43.5, 43.5, 55.1, 55.3, 72.3, 110.4, 110.5, 120.3, 120.6,
126.7, 126.7, 127.2, 128.0, 131.5, 131.8, 157.2, 157.6.
N, 12.23 C H N requires: C, 80.31; H, 7.20; N, 12.49%.
H NMR: d 1.94–2.19 (4H, m, 2!CH ), 2.21–2.36 (2H, m,
1
5 16 2
1
2
CH ), 3.52–3.66 (2H, m, CH), 6.97 (2H, dt, JZ7.8, 0.9 Hz,
2
ArH), 7.02–7.08 (2H, m, ArH), 7.46 (2H, td, JZ7.8, 2.1 Hz,
1
3
ArH), 8.54 (2H, dq, JZ4.8, 0.9 Hz, ArH). C NMR: d 24.9,
3
4.1, 54.4, 121.0, 122.9, 136.0, 149.2, 163.5.
References and notes
4.3.5. trans-1-(3,5-Dimethoxyphenyl)-2-phenylcyclo-
pentane (20). Purified by flash chromatography (petroleum
1. Schlenk, W.; Bergmann, E. Liebigs Ann. Chem. 1928, 463,
1–322. (particularly pages 106–117).
ether/AcOEtZ9:1), colourless oil; R Z0.4 (petroleum
f
ether/AcOEtZ9:1). Anal. Found: C, 80.63; H, 8.03;
2. Wright, G. F. J. Am. Chem. Soc. 1939, 61, 2106–2110.
3. Reesor, J. W. B.; Smith, J. G.; Wright, G. F. J. Org. Chem.
1954, 19, 940–956.
1
C H O requires: C, 80.80; H, 7.87%. H NMR: d 1.77–
1
9 22 2
1
.98 (4H, m, 2!CH ), 2.18–2.31 (2H, m, CH), 2.96–3.14
2
(
2H, m, CH), 3.69 (6H, s, 2!CH ), 6.24 (1H, t, JZ2.1 Hz,
4. Smith, J. G.; Wikman, R. T. J. Organomet. Chem. 1973, 49,
91–101.
3
ArH), 6.27 (2H, d, JZ2.1 Hz, 2!ArH), 7.09–7.17 (3H, m,
1
3
3
3
1
!ArH), 7.18–7.26 (2H, m, 2!ArH). C NMR: d 24.3,
4.9, 35.2, 53.5, 54.0, 54.9, 97.5, 105.4, 125.8, 127.3, 128.1,
44.4, 146.9, 160.4.
5. Smith, J. G.; Oliver, E.; Boettger, T. J. Organometallics 1983,
2, 1577–1582 and references therein.
6. Yus, M.; Mart ´ı nez, P.; Guijarro, D. Tetrahedron 2001, 57,
1
0119–10124.
4.3.6. trans-3,4-Diphenylcyclopentan-1-ol (21). Purified
by flash chromatography (gradient elution, from petroleum
7. Yang, J.-S.; Kondo, K.; Murrakami, Y. Collect. Czech. Chem.
Commun. 2000, 65, 549–554.
ether/AcOEtZ9:1 to petroleum ether/AcOEtZ1:1), white
8. Whitesell, J. K.; Apodaca, R. Tetrahedron Lett. 1997, 38,
2589–2592.
solid; mp 70–72 8C (petroleum ether); R Z0.63 (petroleum
f
K1
ether/AcOEtZ3:7). IR (neat) 3186 cm . Anal. Found: C,
9. Kranenburg, M.; Delis, J. G. P.; Kamer, P. C. J.; van Leeuwen,
P. W. N. M.; Vrieze, K.; Veldman, N.; Spek, A. L.; Goubitz,
K.; Fraanje, J. J. Chem. Soc., Dalton Trans. 1997, 1839–1849.
10. Kanemasa, S.; Yamamoto, H.; Kobayashi, S. Tetrahedron
Lett. 1996, 37, 8505–8506.
1
5.38; H, 7.83; C H O requires: C, 85.66; H, 7.61%. H
8
NMR: d 1.65 (1H, br s, OH), 1.85–1.95 (1H, m, CH), 2.09–
1
7 18
2
.28 (2H, m, 2!CH), 2.70 (1H, ddd, JZ14.1, 9.0, 6.0 Hz,
CH), 3.40–3.66 (1H, dd, JZ20.1, 9.8 Hz, CH), 3.48 (1H, td,
JZ10.8, 7.8 Hz, CH), 4.58–4.63 (1H, m, CHO), 7.08–7.25
11. Fukuda, N.; Mashima, K.; Matsumura, Y.-I.; Takaya, H.
Tetrahedron Lett. 1990, 31, 7185–7188.
12. Platzek, J.; Snatzke, G. Tetrahedron 1987, 43, 4947–4968.
1
10H, m, 10!ArH). C NMR: d 44.9, 44.9, 51.5, 52.6,
3
(
7
2.1, 126.1, 126.1, 127.3, 127.5, 128.2, 128.2, 143.0, 143.7.
1
3. Jeanes, A.; Adams, R. J. Am. Chem. Soc. 1937, 59, 2608–2622.
4.3.7. trans-3,4-Di-(2-pyridyl)cyclopentan-1-ol (22).
Purified by flash chromatography (gradient elution, from
14. Azzena, U.; Dettori, G.; Idini, M. V.; Pisano, L.; Sechi, G.
Tetrahedron 2003, 59, 7961–7966.
petroleum ether/AcOEt/Et NZ5:5:1 to petroleum ether/
15. Azzena, U.; Melloni, G.; Piroddi, A. M.; Azara, E.; Contini, S.;
Fenude, E. J. Org. Chem. 1992, 57, 3101–3106.
16. Yus, M. In Rappoport, Z., Marek, I., Eds.; The Chemistry of
Organolithium Compounds; Wiley: Chichester, 2004; Vol. 1;
Part 2, Chapter 11.
3
AcOEt/Et NZ3:2:1), yellow oil; R Z0.24 (petroleum
3
f
K1
ether/AcOEt/Et NZ3:2:1). IR (neat) 3300 cm . Anal.
3
Found: C, 74.69; H, 6.91; N, 11.45; C H N O requires:
1
5 16 2
1
C, 74.96; H, 6.72; N, 11.66%. H NMR: d 2.02–2.12 (1H, m,

8668
U. Azzena et al. / Tetrahedron 61 (2005) 8663–8668
1
7. For an alternative solvent (dimethyl ether), see: Cohen, T.;
25. Lorance, E. D.; Kramer, W. H.; Gould, I. R. J. Am. Chem. Soc.
2002, 124, 15225–15238.
Kreethadumrongdat, T.; Liu, X.; Kulkarni, V. J. Am. Chem.
Soc. 2001, 123, 3478.
8. Wadsworth, W. S.; Emmons, W. D. J. Am. Chem. Soc. 1961,
26. Chen, C.; Wang, B.; Munoz, B. Synlett 2003, 2404–2406.
27. Wallace, T. W.; Wardell, I.; Li, K.-D.; Leeming, P.; Redhouse,
A. D.; Challand, S. R. J. Chem. Soc., Perkin Trans. 1 1995,
1
83, 1733–1738.
1
9. Baker, R.; Sims, R. J. Synthesis 1981, 117.
0. To the best of our knowledge, there is no report concerning
reduction of (E)- or (Z)-stilbene with alkali metals in THF,
2
293–2308.
2
2
8. Vande Velde, C. M. L.; Blockhuys, F.; Van Alsenoy, C.;
Lenstra, A. T. H.; Geise, H. J. J. Chem. Soc., Perkin Trans. 2
2 2
followed by H O or D O quenching, or alkylation with
2
002, 1345–1351.
dihaloalkanes. However, in a mechanistic study concerning the
reduction of aromatic esters, it was reported that reduction of
2
9. Givens, R. S.; Matuszewski, B.; Neywick, C. V. J. Am. Chem.
Soc. 1974, 96, 5547–5552.
(
(
E)-stilbene, with an excess of Li metal and a catalytic amount
10 mol%) of DBB, under sonication, afforded 1,2-diphenyl-
3
0. Katritzky, A. R.; Shipkova, P. A.; Qi, M.; Nichols, D. A.;
Burton, R. D.; Watson, C. H.; Eyler, J. R.; Tamm, T.;
Karelson, M.; Zerner, M. C. J. Am. Chem. Soc. 1996, 118,
ethane after aqueous work up: Karaman, R.; Fry, J. L.
Tetrahedron Lett. 1989, 30, 4931–4934.
1. L e´ onel, E.; Paugam, J. P.; N e´ d e´ lec, J.-Y.; P e´ richon, J. J. Chem.
Res. (S) 1995, 278–279.
1
1905–11911.
2
3
1. Tilley, J. W.; Zawoiski, S. J. Org. Chem. 1988, 53, 386–390.
2. Vedernikov, A. N.; Pink, M.; Caulton, K. G. J. Org. Chem.
3
2
2. Gu, X. P.; Ikeda, I.; Okahara, M. Bull. Chem. Soc. Jpn. 1987,
2
003, 68, 4806–4814.
3. Tashiro, M.; Yamato, T.; Fukata, G. J. Org. Chem. 1978, 43,
413–1420.
60, 397.
3
2
2
3. Azzena, U.; Cinellu, M. A.; Dettori, G. in progress.
4. Bergbreiter, D. E.; Osburn, P. L.; Wilson, A.; Sink, E. M.
J. Am. Chem. Soc. 2000, 122, 9058–9064.
1