Alkoxydienylstannanes via metalation of α,β-unsaturated and α-phenyl acetals: Preparation and synthetic uses in the Stille cross-coupling reaction

Article abstract of DOI:10.1039/b007500k

Alkoxydienylstannanes via metalation of α,β-unsaturated and α-phenyl acetals were analyzed. Treatment of α,β-unsaturated and α-phenyl acetals with an equimolar mixture of butyllithium and potassium tert-butoxide gave α-metalated 1,3 dienes and vinyl ethers that readily react with chlorotributyltin affording (Z)-functionalized alkoxyvinylstannanes. Stille cross-coupling reaction between these reactants and allyl bromide, iodobenzene, or benzoyl chloride produced derivatives that can be converted into carbonyl compounds according to an umpolung approach.

Full text of DOI:10.1039/b007500k

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Alkoxydienylstannanes via metalation of ꢀ,ꢁ-unsaturated and
ꢀ-phenyl acetals: preparation and synthetic uses in the Stille
cross-coupling reaction
1
Paolo Balma Tivola, Anna Deagostino, Cristina Prandi† and Paolo Venturello*
Dipartimento di Chimica Generale ed Organica Applicata dell’Università di Torino,
Corso Massimo D’Azeglio, 48 - I 10125 Torino, Italy. E-mail: venturello@ch.unito.it
Received (in Cambridge, UK) 15th September 2000, Accepted 22nd December 2000
First published as an Advance Article on the web 24th January 2001
Treatment of α,β-unsaturated (1 and 2) and α-phenyl (3) acetals with an equimolar mixture of butyllithium and
potassium tert-butoxide (Schlosser’s reagent LIC–KOR) gives α-metalated 1,3-dienes and vinyl ethers that readily
react with chlorotributyltin affording (Z)-functionalized alkoxyvinylstannanes 4–6. Stille cross-coupling reaction
between these reactants and allyl bromide, iodobenzene, or benzoyl chloride produces derivatives 7–13 that can be
moreover converted into carbonyl compounds 14–19 according to an umpolung approach.
The palladium(0)-catalysed coupling reaction between an
organotin reagent and an organic electrophile (Stille cross-
coupling reaction)1 is a powerful method for the formation of
carbon–carbon bonds.2 The synthetic utility of the Stille reac-
tion owes a great deal to the mildness of the reaction condi-
tions, which are compatible with many types of functional
groups, and to the ease with which the organostannanes can be
prepared. In particular, alk-1-enylstannanes are prepared via the
hydrostannylation of alk-1-yne precursors in the presence of a
radical initiator such as 2,2-azobis(isobutyronitrile).3 Under
standard experimental conditions the reaction usually affords
the (Z) and (E) isomers as a thermodynamic mixture. Using
this method almost pure (E)-vinyltins can be prepared as the
thermodynamically stable product,4 whereas the (Z)-vinyltin
isomer is more difficult to obtain.5 Careful control of the tem-
perature in the initial step of the reaction is necessary in order
to avoid isomerization to the more stable (E) derivative. New
syntheses have been proposed to prepare (E) isomers, e.g. by
hydrometallation,6 carbometallation7 and stannylmetallation8
of alkynes. Alternative routes to (Z)-vinyltins have been carbo-
metalation9 or stannylmetalation10 of alkynes. Isomerization
is a major limitation. Titanation of alkynyltin acetals has been
used to give the corresponding (Z)-disubstituted vinyltin
derivatives as single geometrical isomers.11 Moreover, stereo-
defined dienyltin derivatives are important intermediates for the
preparation of polyenic building blocks that are of great
importance not only for the synthesis of bioactive com-
pounds,12 but also useful chemicals in the production of
new materials with non-linear optical properties13 or high
conductivity14 and in the perfume industry.15
α-metalated intermediates with chlorotributylstannane in order
to readily prepare dienyltin derivatives useful for Stille cross-
coupling reactions. Experimental procedures are also given for
the conversion of the Stille cross-coupling products into the
corresponding carbonyl compounds. As shown in Scheme 1, in
Scheme 1
Results and discussion
During the past few years we have developed a facile
synthesis of α-functionalized conjugate 1-alkoxy-1,3-dienes16
and β-phenyl enol ethers.17 The method has been set up exploit-
ing the reactivity of α,β-unsaturated and α-phenyl acetals in the
presence of the Schlosser’s mixed superbase LIC–KOR
(LIC = butyllithium and KOR = potassium tert-butoxide).18 In
this paper we provide the details of our work on the reaction of
the presence of LIC–KOR superbase acetals 1–3 underwent
1,4- (1 and 2) or 1,2-elimination (3) reaction, affording unsatur-
ated derivatives. Moreover, working with an excess of the base,
elimination products were further metalated at the α-vinyl site
affording intermediates A and B, which were functionalized
with chlorotributyltin to give dienyl stannanes 4–5 and styrenyl
stannane 6 as pure (Z) isomers. The configuration was deduced
from the Jtrans coupling constant between the α and β protons in
the 1H NMR spectrum of the corresponding derivatives
obtained by quenching the reaction with H2O instead of the
† Permanent address: Dipartimento di Scienze e Tecnologie Avanzate
dell’Università, Corso Borsalino, 54, I 15100 Alessandria, Italy.
DOI: 10.1039/b007500k
J. Chem. Soc., Perkin Trans. 1, 2001, 437–441
This journal is © The Royal Society of Chemistry 2001
437

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electrophile. Moreover, the (Z) configuration was confirmed
through NOE experiments on stannane 6: irradiation of the
olefinic hydrogen gave rise to an Overhauser enhancement of
the signals assigned to the phenyl and methoxy groups.‡
Stannanes 4–6 were coupled with allyl bromide, iodobenzene,
and benzoyl chloride under different experimental conditions
(Scheme 2), yielding derivatives 7–13. The cross-coupling reac-
reactant afforded no Stille product under standard conditions.
In particular, we have used the protocol recently proposed by
Corey, which involves the system Pd(PPh3)4–CuCl–LiCl.21
The synthesis of metallovinyl ethers (metal = Si, Ge, and Sn)
via the transmetalation of lithium derivatives has been previ-
ously reported and the resulting compounds have been used for
the preparation of the corresponding metalloidal ketones.22
However, to our knowledge the present work reports a new
application of α,β-unsaturated and α-phenyl acetals for the
synthesis of dienylstannanes and their use in the Stille cross-
coupling reaction. Moreover a method is described for the
subsequent conversion of the coupling derivatives into car-
bonyl compounds, according to an umpolung procedure.23
Products 7–12 like all enol ethers undergo acidic hydrolysis to
afford enones 14–17 and benzyl ketones 18 and 19. The
hydrolysis was carried out in a dichloromethane suspension
of Amberlyst-1524 (Scheme 3).¶ In particular, enones 14 and
Scheme 3
Scheme 2 Reagents and conditions: a: [(C6H5)3P]4Pd, CHCl3, 60 ЊC;
b: LiCl, [(C6H5)3P]4Pd, CuCl, DMSO, 25 ЊC; c: [(C6H5)3P]4Pd, toluene,
100 ЊC.
15 undergo a double bond shift, in order to extend conju-
gation, while on the other hand ketone 18 retains the terminal
double bond.
tions afforded the stereochemically pure (E) isomers whose
configuration was again deduced on the basis of NOE experi-
ments. In particular, in the case of enol ether 12 irradiation of
the olefinic hydrogen gave rise to an Overhauser enhancement
of the signals assigned to the methoxy and to one of the phenyl
groups.
It is worth pointing out that both allyl bromide and benzoyl
chloride failed to react with metalated intermediates A and B
(Scheme 1). Therefore neither halide can be used as a quenching
electrophile, and the direct functionalisation of the unsaturated
intermediate was thus precluded.§ In the case of iodobenzene,
we took advantage of the co-catalytic effect of copper(), which
was introduced by Liebeskind and Fengl,19 and whose mech-
anistic bases were studied by Farina and Liebeskind,20 since this
Experimental
Reactions were performed in flame-dried glassware under an
argon atmosphere. The temperature of slush liquid nitrogen–
acetone is indicated as Ϫ95 ЊC, that of an ice-bath as 0 ЊC,
and “room temperature” as 25 ЊC. THF was distilled from
benzophenone ketyl, anhydrous DMSO was purchased from
Fluka. BuLi (Aldrich) was used as 1.6 M solution in hexanes.
t-BuOK was sublimed in vacuo (0.1 mmHg). LiCl was dried at
120 ЊC under high vacuum (2 × 10Ϫ3 mm Hg) overnight, CuCl
was dried under high vacuum for 15 h. All other commercially
obtained reagents were used as received. Purification by column
chromatography was performed on Merck silica gel 60 as
stationary phase and Et2O–light petroleum ether (distillation
range 40–60 ЊC) as eluent. 1H and 13C NMR spectra were
recorded at 400 and 100.4 MHz, respectively and were carried
out at the Dipartimento IFM (Università di Torino). Coupling
constants (J) are given in Hz. Mass spectra were obtained on a
mass selective detector HP 5970 B instrument operating at an
ionising voltage of 70 eV connected to a HP 5890 GC, cross
linked methyl silicone capillary column (25 m × 0.2 mm × 0.33
mm film thickness).
‡ The assignment of the stereochemistry is based on the hypothesis
that the mechanism of quenching the reaction with water will give the
same stereochemistry as the stannylation reaction. In any case
the results of NOE experiments on compound 6 seem to validate this
assumption.
§ Experimental results obtained in our laboratory suggest that α-
metalated intermediates A and B do not react by nucleophilic substitu-
tion with electrophiles that contain allylic hydrogens. For example,
when 1-bromohexa-3,5-diene was treated with 1,1-diethoxybut-2-ene in
the presence of the LIC–KOR base, the only isolated products were
hexa-1,3,5-triene and 1-ethoxybuta-1,3-diene. On the other hand, tert-
butyl benzoate was the main isolated product in the reaction between
benzoyl chloride and 1,1-diethoxybut-2-ene under the same experi-
mental conditions.
¶ Derivative 13 does not hydrolyze under these experimental conditions.
This inertness can probably be ascribed to the presence of the carbonyl
group which destabilizes the cationic intermediate that develops during
the hydrolysis.
438
J. Chem. Soc., Perkin Trans. 1, 2001, 437–441

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General procedure for the synthesis of stannanes (4–6)
diluted with Et2O (15 cm3), and washed with brine (2 × 15 cm3)
and 5% aqueous NH4OH (10 cm3). The combined organic
layers were washed with water (3 × 10 cm3), then dried over
Na2SO4 and concentrated to a residue that was purified as
stated below.
To a cooled (Ϫ95 ЊC) solution of t-BuOK (1.4 g, 12.5 mmol) in
anhydrous THF (10 cm3), acetal (1–3, 5.0 mmol) and BuLi (7.8
cm3, 12.5 mmol) were added dropwise. After a few seconds the
solution turned purple and was stirred for 2 h at Ϫ95 ЊC, then
ClSnBu3 (1.62 g, 5.0 mmol) was added. After 2 h the reaction
was quenched with a THF solution of H2O (10 cm3) and the
colour was discharged. The two phases were separated and the
aqueous one extracted with Et2O (2 × 20 cm3). The combined
organic phases were washed with brine (2 × 15 cm3), dried
(Na2SO4) and concentrated to give crude products that were
purified by chromatography.
(3E)-4-Ethoxyhepta-1,3,6-triene (7). Purification by chroma-
tography (5:95, Et2O–light petroleum ether) gave 7 (0.29 g,
70%) as a yellow oil. δH (400 MHz; CDCl3) 1.29 (t, J = 6.5, 3 H),
3.01 (dt, J = 7.5, 1.5, 2 H), 3.75 (q, J = 6.5, 2 H), 4.81 (dd,
J = 10, 1.5, 1 H), 4.97 (dd, J = 16.5, 1.5, 1 H), 5.04 (dq, J = 10.5,
1.5, 1 H), 5.10 (dq, J = 16.5, 1.5, 1 H), 5.31 (d, J = 10.5, 1 H),
5.80 (m, 1 H), 6.42 (dt, J = 16.5, 10.5, 1 H); δC (100 MHz;
CDCl3) 14.6, 35.6, 62.6, 101.2, 111.4, 116.0, 134.3, 134.5, 157.7;
m/z (EI, 70 eV, rel. int.) 138 (Mϩ, 13), 110 (20), 68 (98), 41 (60),
39 (100) (Found: C, 78.65; H, 10.56. Calc. for C9H14O: C, 78.21;
H, 10.21%).
(Z)-1-(Tri-n-butylstannyl)-1-ethoxybuta-1,3-diene (4). Purifi-
cation by chromatography (2:98, Et2O–light petroleum ether)
gave 4 (1.23 g, 64%) as a yellow oil. δH (400 MHz; CDCl3) 0. 89
(t, J = 7.3, 9 H), 0.92–1.01 (m, 6 H), 1.26–1.29 (t, J = 6.5, 3 H),
1.28–1.32 (sextet, J = 7.3, 6 H), 1.53–1.55 (m, 6 H), 3.77 (q,
J = 6.5, 2 H), 4.81 (dd, J = 10.0, 1.0, 1 H), 4.97 (dd, J = 16.0,
1.0, 1 H), 6.08 (d, J = 10.0, 1 H), 6.22 (dt, J = 16.0, 10.0, 1 H);
δC (100.4 MHz; CDCl3) 10.4, 13.6, 14.5, 28.8, 29.0, 63.0, 110.4,
115.2, 135.6, 174.2; m/z (EI, 70 eV, rel. int.) 386 (Mϩ, 1), 365
(16), 361 (100), 358 (66), 304 (54), 245 (29), 41 (13) (Found: C,
55.64; H 9.56. Calc. for C18H36OSn: C, 55.84; H, 9.37%).
(3E)-4-Ethoxy-2-methylhepta-1,3,6-triene (8). Purification by
chromatography (5:95, Et2O–light petroleum ether) gave 8
(0.30 g, 66%) as a yellow oil. δH (400 MHz; CDCl3) 1.29 (t,
J = 6.5, 3 H), 1.81 (s, 3 H), 3.07 (dt, J = 6.5, 1.5, 2 H), 3.75 (q,
J = 6.5, 2 H), 4.73 (br s, 1 H), 4.81 (br s, 1 H), 5.01 (s, 1 H), 5.04
(dq, J = 10.5, 1.5, 1 H), 5.09 (dq, J = 16.5, 1.5, 1 H), 5.89 (ddt,
J = 16.5, 10.5, 6.5, 1 H); δC (100 MHz; CDCl3) 14.7, 24.7, 30.1,
62.4, 103.4, 111.1, 115.7, 135.6, 141.0, 155.9; m/z (EI, 70 eV, rel.
int.) 152 (Mϩ, 14), 109 (100), 91 (27), 81 (23), 55 (44), 41 (34)
(Found: C, 78.97; H 10.80. Calc. for C10H16O: C, 78.90; H,
10.59%).
(Z)-1-(Tri-n-butylstannyl)-1-ethoxy-3-methylbuta-1,3-diene
(5). Purification by chromatography (2:98, Et2O–light petrol-
eum ether) gave 5 (1.62 g, 81%) as a yellow oil. δH (400 MHz;
CDCl3) 0.89 (t, J = 7.3, 9 H), 0.92–1.01 (m, 6 H), 1.26–1.29 (t,
J = 6.5, 3 H), 1.28–1.32 (sextet, J = 7.3, 6 H), 1.53–1.55 (m,
6 H), 1.79 (s, 3 H), 3.68 (q, J = 6.5, 2 H), 4.63 (q, J = 1.5, 1 H),
4.71 (q, J = 1.5, 1 H), 5.78 (s, 1 H); δC (100.4 MHz; CDCl3) 11.2,
13.5, 14.6, 26.9, 28.8, 28.9, 63.0, 110.0, 116.2, 143.4, 167.9; m/z
(EI, 70 eV, rel. int.) 313 (Mϩ Ϫ 87, 100), 311 (58), 198 (25), 257
(32) (Found: C, 56.65; H 9.56. Calc. for C19H38OSn: C, 56.88;
H, 9.55%).
(1E)-2-Methoxy-1-phenylpenta-1,4-diene (9). Purification by
chromatography (5:95, Et2O–light petroleum ether) gave 9
(0.45 g, 86%) as a yellow oil. δH (400 MHz; CDCl3) 3.10 (dt,
J = 7.5, 1.5, 2 H), 3.69 (s, 3 H), 5.14–5.19 (m, 2 H), 5.69 (s, 1 H),
5.94–5.98 (ddt, J = 16.5, 10.5, 7.5, 1 H), 7.21 (t, J = 7.2, 1 H),
7.25 (d, J = 7.2, 2 H), 7.31 (t, J = 7.2, 2 H); δC (100 MHz;
CDCl3) 35.5, 54.6, 100.3, 116.0, 125.3, 128.0, 128.4, 134.7,
137.2, 157.2; m/z (EI, 70 eV, rel. int.) 174 (Mϩ, 60), 141 (47), 115
(51), 91 (100), 89 (55), 41 (55) (Found: C, 82.95; H 8.45. Calc.
for C12H14O: C, 82.72; H, 8.10%).
1-(Tri-n-butylstannyl)-1-methoxy-2-phenylethene (6). Purifi-
cation by chromatography (2:98, Et2O–light petroleum ether)
gave 6 (1.94 g, 92%) as a red oil. δH (400 MHz; CDCl3) 0.96 (t,
J = 7.3, 9 H), 0.98–1.03 (m, 6 H), 1.32–1.35 (m, 6 H), 1.35–1.41
(sextet, J = 7.3, 6 H), 3.69 (s, 3 H), 6.5 (s, 1 H), 7.17 (t, J = 7.2,
1 H), 7.25 (t, J = 7.2, 2 H), 7.30 (d, J = 7.2, 2 H); δC (100.4 MHz;
CDCl3) 10.1, 11.1, 27.1, 27.3, 56.5, 114.0, 125.7, 126.8, 128.2,
128.3, 142.0; m/z (EI, 70 eV, rel. int.) 371 (Mϩ Ϫ 51), 365 (51),
151 (98), 91 (12), 41 (100) (Found: C, 59.50; H 8.43. Calc. for
C21H36OSn: C, 59.60; H, 8.57%).
(1E)-1-Ethoxy-1-phenylbuta-1,3-diene (10). Purification by
chromatography (5:95 Et2O–light petroleum ether) gave 10
(0.10 g, 72%) as a yellow oil. δH (400 MHz; CDCl3) 1.37 (t,
J = 7.5, 3 H), 3.92 (q, J = 7.5, 2 H), 4.80 (dd, J = 10.5, 1.5, 1 H),
5.10 (dd, J = 16.5, 1.5, 1 H), 5.60 (d, J = 10.5, 1 H), 6.42 (dt,
J = 16.5, 10.5, 1 H), 7.35 (t, J = 7.5, 1 H), 7.37 (t, J = 7.5, 2 H),
7.41 (d, J = 7.5, 2 H); δC (100 MHz; CDCl3) 14.8, 63.6, 103.4,
112.3, 128.1, 128.6, 129.2, 133.9, 135.2, 158.2; m/z (EI, 70 eV,
rel. int.) 174 (Mϩ, 50), 145 (100), 127 (41), 91 (23), 77 (79), 68
(24) (Found: C, 82.80; H 8.32. Calc. for C12H14O: C, 82.72; H,
8.10%).
General procedure for Stille cross-coupling reaction
Method A (allyl bromide and benzoyl chloride). A flame dried
Schlenk tube was charged with Pd(PPh3)4 (0.035 g, 0.03 mmol,
1% eq.,) in anhydrous CHCl3 (1 cm3), then allyl bromide (0.36
g, 3.0 mmol) and vinyltin compound (3.0 mmol) were added.
The reaction was stirred for 2 h at 60 ЊC, and then was diluted
with CH2Cl2 (5 cm3) and H2O (5 cm3). The organic phase was
washed with brine (2 × 10 cm3), dried over Na2SO4 and concen-
trated to give a residue that was purified as stated below. The
cross-coupling reaction of benzoyl chloride with organotin
reagent 4 was carried out under the same experimental condi-
tions, but using boiling toluene as the reaction solvent.
(1E)-1-Ethoxy-3-methyl-1-phenylbuta-1,3-diene (11). Purifi-
cation by chromatography (5:95, Et2O–light petroleum ether)
gave 11 (0.11 g, 75%) as a yellow oil. δH (400 MHz; CDCl3) 1.26
(t, J = 6.5, 3 H), 1.79 (s, 3 H), 3.68 (q, J = 6.5, 2 H), 4.70 (br s,
2 H), 5.78 (s, 1 H), 7.32 (t, J = 7.5, 1 H), 7.35 (t, J = 7.5, 2 H),
7.40 (d, J = 7.5, 2 H); δC (100 MHz; CDCl3) 14.9, 23.3, 63.6,
105.3, 114.1, 127.89, 129.4, 131.6, 133.7, 133.9, 157.6; m/z (EI,
70 eV, rel. int.) 188 (Mϩ, 34), 145 (35), 105 (32), 77 (100), 51 (56)
(Found: C, 82.96; H 8.62. Calc. for C13H16O: C, 82.94; H,
8.57%).
Method B (iodobenzene). A Schlenk vessel was charged with
LiCl (0.21 g, 5.0 mmol), and flame dried under an inert atmos-
phere. Upon cooling, Pd(PPh3)4 (0.06 g, 0.05 mmol) and CuCl
(0.39 g, 4.0 mmol) were added. DMSO (8.0 cm3) was intro-
duced with stirring, followed by the addition of iodobenzene
(0.16 g, 0.8 mmol,) and a vinyltin compound (1.0 mmol). The
reaction mixture was stirred at 25 ЊC for 2 h. Completion of the
coupling was monitored by GC. The reaction mixture was
1-Methoxy-1,2-diphenylethene (12). Purification by chrom-
atography (5:95, Et2O–light petroleum ether) gave 12 (0.13 g,
78%) as a yellow oil. δH (400 MHz; CDCl3) 3.83 (s, 3 H), 5.85 (s,
1 H), 7.11 (t, J = 7.3, 2 H), 7.26 (t, J = 7.3, 4 H), 7.42 (d, J = 7.3,
4 H); δC (100 MHz; CDCl3) 55.6, 101.6, 125.5, 128.1, 128.3,
128.7, 129.0, 129.4, 136.4, 137.0, 157.33; m/z (EI, 70 eV, rel. int.)
J. Chem. Soc., Perkin Trans. 1, 2001, 437–441
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210 (Mϩ, 100), 167 (75), 165 (88), 105 (74), 91 (87), 77 (50)
(Found: C, 85.76; H 6.75. Calc. for C15H14O: C, 85.68; H,
6.71%).
74% yield) as a yellow oil. νmax(film)/cmϪ1 1718; δH (400 MHz;
CDCl3) 3.20 (dt, J = 7.5, 1.5, 2 H), 3.7 (s, 2 H), 5.12 (dq,
J = 16.0, 1.5, 1 H), 5.18 (dq, J = 10.0, 1.5, 1 H), 5.88 (ddt,
J = 16.0, 10.0, 7.5, 1 H), 7.19 (d, J = 7.5, 2 H), 7.27 (t, J = 7.5, 1
H), 7.34 (t, J = 7.5, 2 H); δC (100 MHz; CDCl3) 46.3, 49.4,
118.9, 126.9, 128.6, 129.3, 130.8, 133.8, 205.9; m/z (EI, 70 eV,
rel. int.) 160 (Mϩ, 5), 119 (24), 91 (99), 65 (40), 41 (81) (Found:
C, 82.55; H 7.56. Calc. for C11H12O: C, 82.46; H, 7.55%).
(2E)-2-Ethoxy-1-phenylpenta-2,4-dien-1-one (13). Purifi-
cation by chromatography (10:90 Et2O–light petroleum ether)
gave 13 (0.41, 86%) as a yellow oil. δH (400 MHz; CDCl3) 1.31
(t, J = 6.4, 3 H), 3.90 (q, J = 6.4, 2 H), 4.92 (dd, J = 10.0, 1.5,
1 H), 5.2 (dd, J = 16.4, 1.5, 1 H), 5.8 (d, J = 10.0, 1 H), 6.64 (dt,
J = 16.4, 10.0, 1 H), 7.40 (t, J = 6.6, 2 H), 7.62 (t, J = 6.6, 1 H),
7.9 (d, J = 6.6, 2 H); δC (100.4 MHz; CDCl3) 14.8, 60.42, 106.8,
116.3, 129.0, 129.71, 134.3, 136.8, 137.0, 156.7, 191.6; m/z (EI,
70 eV, rel. int.) 202 (Mϩ, 20), 182 (10), 105 (100), 77 (53), 55 (37)
(Found: C, 77.75; H 6.86. Calc. for C13H14O2: C, 77.20; H,
6.98%).
2-Phenylacetophenone (19). Purification by chromatography
(10:90, Et2O–light petroleum ether) gave 19 (0.52 g, 88%) as a
yellow oil. νmax(film)/cmϪ1 1685; δH (400 MHz; CDCl3) 4.32 (s,
2 H), 7.25 (m, 3 H), 7.33 (t, J = 7.2, 2 H), 7.46 (t, J = 7.2, 2 H),
7.55 (t, J = 7.2, 1 H), 8.02 (d, J = 7.2, 2 H); δC (100 MHz;
CDCl3) 45.3, 126.7, 128.4, 128.5, 128.6, 129.3, 133.1, 134.4,
136.4, 197.5; m/z (EI, 70 eV, rel. int.) 196 (Mϩ, 1), 105 (100),
91(6), 77 (47), 51 (66) (Found: C, 85.75; H 6.76. Calc. for
C14H12O: C, 85.68; H, 6.16%).
Synthesis of ketones 14–19
To a solution of cross-coupling products (7–12, 3.0 mmol) in
CH2Cl2 (5.0 cm3) Amberlyst-15 (0.03 g) was added. The reac-
tion was monitored by GC. After 1 h at 25 ЊC, the Amberlyst
was filtered off and the organic layer was washed with NaHCO3
5% (2 × 5 cm3), with brine (2 × 5 cm3) and dried over NaSO4.
Evaporation of the solvent gives crude products that were
purified by chromatography. Ketones 14–19 could be obtained
directly in one step, diluting the cross-coupling reaction mixture
with CH2Cl2 and adding Amberlyst (2% by weight) to the
solution.
Acknowledgements
This work was supported by grants from Italian MURST.
We thank Dr Vittorio Farina (Boehringer Ingelheim Pharma-
ceuticals) for useful discussions, and Professor Mariella Mella
(Università di Pavia) for NOE experiments.
References
(2E,5E)-Hepta-2,5-dien-4-one (14). Purification by chroma-
tography (10:90, Et2O–light petroleum ether) gave 14 (0.26 g,
80%) as a yellow oil. νmax(film)/cmϪ1 1668; δH (400 MHz;
CDCl3) 1.87 (dd, J = 7.10, 1.5, 6 H), 6.34 (dq, J = 15.7, 1.5,
2 H), 6.88 (dq, J = 15.7, 6.4, 2 H); δC (100 MHz; CDCl3) 18.2,
129.9, 142.9, 189.2; m/z (EI, 70 eV, rel. int.) 110 (Mϩ, 12), 69
(100), 67 (10), 41 (99), 39 (90) (Found: C, 76.45; H 9.34. Calc.
for C7H10O: C, 76.33; H, 9.15%).
1 J. K. Stille and D. Milstein, J. Am. Chem. Soc., 1978, 100, 3636.
2 For reviews see J. K. Stille, Angew. Chem., Int. Ed Engl., 1986, 25,
508; V. Farina, Pure Appl. Chem., 1996, 68, 73; V. Farina,
V. Krishnamurthy and W. J. Scott, Organic Reactions, 1997, vol. 50,
Wiley, New York, and references therein.
3 J. F. Betzer, F. Delaloge, B. Muller, A. Pancrazi and J. Prunet, J. Org.
Chem., 1997, 62, 7668.
4 E. J. Corey and R. H. Wollenberg, J. Am. Chem. Soc., 1974, 96,
5581; R. F. Cunico and F. J. Clayton, J. Org. Chem., 1976, 41, 1480;
D. Seyferth and S. C. Vick, J. Organomet. Chem., 1978, 144, 1;
T. K. Jones and S. E. Denmark, Helv. Chim. Acta, 1983, 66, 2397;
J. C. Bottaro, R. N. Hanson and D. E. Seitz, J. Org. Chem., 1981, 46,
5221.
5 G. A. Tolstikov, M. S. Miftakhov, N. A. Danilova and Ya. L.
Vel’Der, Synthesis, 1986, 496; F. Lhermitte and B. Carboni, Synlett
1996, 377.
6 M. D. Fryzuk, G. S. Bates and C. Stone, Tetrahedron Lett., 1986, 27,
1537; H. X. Zhang, F. Guibé and G. Balavoine, J. Org. Chem., 1990,
55, 1857; B. L. Groh, Tetrahedron Lett., 1991, 32, 7647; P. J. Fagan,
W. A. Nugent and J. C. Calabrese, J. Am. Chem. Soc., 1994, 116,
1880; S. Kim and K. H. Kim, Tetrahedron Lett., 1995, 36, 3725.
7 F. Bellina, A. Carpita, E. Adorni Fontana and R. Rossi,
Tetrahedron, 1994, 50, 5189.
8 E. Piers, J. M. Chong and H. E. Morton, Tetrahedron, 1989, 45, 363;
P. A. Magriotis, T. J. Doyle and K. D. Kim, Tetrahedron Lett., 1990,
31, 2541; L. Capella, A. Degl’Innocenti, A. Mordini, G. Reginato,
A. Ricci and G. Seconi, Synthesis, 1991, 1201; R. Aksela and A. C.
Oehlschlager, Tetrahedron, 1991, 47, 1163; A. Casarini, B.
Jousseaume, D. Lazzari, E. Porciatti, G. Reginato, A. Ricci and
G. Seconi, Synlett, 1992, 981; A. Barbero, P. Cuadrado, I. Fleming,
A. M. Gonzalez and F. J. Pulido, J. Chem. Soc., Chem. Commun.,
1992, 351; J. Uenishi, R. Kawakama, A. Tanio and S. Wakabayashi,
J. Chem. Soc., Chem. Commun., 1993, 1438; J. A. Cabezas and
A. C. Oehlschlager, Synthesis, 1994, 432; P. Le Menez, V. Fargeas,
I. Berque, J. Poisson, J. Ardisson, J. Y. Lallemand and A. Pancrazi,
J. Org. Chem., 1995, 60, 3592; V. Fargeas, P. Le Mènez, I. Berque,
J. Ardisson and A. Pancrazi, Tetrahedron, 1996, 52, 6613.
9 E. J. Corey and T. M. Eckrick, Tetrahedron Lett., 1984, 25, 2419.
10 P. A. Magriotis, M. E. Scott and K. D. Kim, Tetrahedron Lett., 1991,
32, 6085; O. Z. Pereira and T. H. Chan, J. Org. Chem., 1996, 61,
5406; A. Barbero, P. Cuadrado, I. Fleming, A. M. Gonzales,
F. J. Pulido and R. Rubio, J. Chem. Soc. Perkin Trans 1, 1993, 1657.
11 V. Launay, I. Beaudet and J.-P. Quintard, Synlett, 1997, 821.
12 R. T. Lalonde, C. F. Wong, S. J. Hofstead, C. D. Morris and L. C.
Gardner, J. Chem. Ecol., 1980, 6, 35; K. Mori, “The Synthesis
of Insect Pheromones”, in Total Synthesis of Natural Products,
ed. J. Apsimon, Wiley, New York, 1981, vol. 4, pp. 1–183; K. C.
Nicolau, J. Y. Ramphal, N. A. Petasis and C. N. Serhan, Angew.
(5E)-2-Methylhepta-2,5-dien-4-one (15). Purification by
chromatography (10:90, ethyl ether–light petroleum ether) gave
15 (0.29 g, 78%) as a yellow oil. νmax(film)/cmϪ1 1634; δH (400
MHz; CDCl3) 1.83 (dd, J = 6.5, 1.5, 3 H), 1.86 (br s, 3 H), 2.09
(br s, 3 H), 6.11 (dq, J = 15, 1.5, 1 H), 6.15 (br s, 1 H), 6.78 (dq,
J = 15, 6.5, 2 H); δC (100 MHz; CDCl3) 17.3, 20.6, 27.5, 122.6,
133.3, 141.4, 155.2, 190.1; m/z (EI, 70 eV, rel. int.) 124 (Mϩ, 5),
109 (63), 83 (31), 55 (51), 39 (100) (Found: C, 77.43; H 9.34.
Calc. for C8H12O: C, 77.38; H, 9.74%).
(2E)-1-Phenylbut-2-en-1-one (16). Purification by chromato-
graphy (10:90, Et2O–light petroleum ether) gave 16 (0.32 g,
74%) as a yellow oil. νmax(film)/cmϪ1 1624; δH (400 MHz;
CDCl3) 1.97 (dd, J = 6.5, 1.5, 3 H), 6.92 (dq, J = 15, 1.5, 1 H),
7.04 (dq, J = 15, 6.5, 1 H), 7.45 (t, J = 7.2, 2 H), 7.47 (t, J = 7.2,
1 H), 7.91 (d, J = 7.2, 2 H); δC (100 MHz; CDCl3) 18.4, 127.3,
128.3, 132.4, 137.6, 144.6, 144.87, 190.1; m/z (EI, 70 eV, rel. int.)
146 (Mϩ, 48), 131 (42), 105 (100), 77 (97), 69 (77), 51 (66)
(Found: C, 82.55; H 6.76. Calc. for C10H10O: C, 82.16; H,
6.89%).
1-Phenyl-3-methylbut-2-en-1-one (17). Purification by chrom-
atography (10:90 Et2O–light petroleum ether) gave 17 (0.41 g,
86%) as a yellow oil. νmax(film)/cmϪ1 1661; δH (400 MHz;
CDCl3) 2.00 (s, 3 H), 2.20 (s, 3 H), 6.74 (br s, 1 H), 7.43 (t,
J = 7.2, 2 H), 7.51 (t, J = 7.2, 1 H), 7.92 (d, J = 7.2, 2 H); δC (100
MHz; CDCl3) 21.2, 28.0, 121.2, 128.2, 128.5, 132.3, 139.3,
156.74, 191.5; m/z (EI, 70 eV, rel. int.) 160 (Mϩ, 39), 145 (43), 83
(45), 77 (88), 55 (68), 51 (100) (Found: C, 82.55; H 6.76. Calc.
for C11H12O: C, 82.46; H, 7.55%).
1-Phenylpent-4-en-2-one (18). Purification by chromato-
graphy (10:90, Et2O–light petroleum ether) gave 18 (0.35 g,
440
J. Chem. Soc., Perkin Trans. 1, 2001, 437–441

View Article Online
Chem., Int. Ed. Engl., 1991, 30, 1100; V. Launay, I. Beaudet and
J.-P. Quintard, Bull. Soc. Chim. Fr., 1997, 134, 937; B. Dominguez,
B. Iglesia, A. R. de Lera, J. Org. Chem., 1998, 63, 4135; B. H.
Lipshutz, B. Ullman, C. Lindsley, S. Pecchi, D. J. Buzard and
D. Dickson, J. Org. Chem., 1998, 63, 6092.
17 A. Deagostino, M. Mella, C. Prandi and P. Venturello, J. Chem.
Soc., Perkin Trans. 1, 1995, 2757; A. Deagostino, C. Prandi,
P. Venturello, Tetrahedron, 1996, 52, 1433.
18 M. Schlosser, J. Organomet. Chem., 1967, 8, 9. For reviews see:
M. Schlosser, Mod. Synth. Methods, 1992, 6, 227; A. Mordini,
Advances in Carbanion Chemistry, ed. V. Snieckus, JAI Press Inc.,
Greenwich, CT, 1992, vol. 1, pp. 1–45; M. Schlosser, F. Faigl,
L. Franzini, H. Geneste, G. Katsoulos and G. Zhong, Pure Appl.
Chem., 1994, 66, 1439.
19 L. S. Liebeskind and R. W. Fengl, J. Org. Chem., 1990, 55, 5359.
20 V. Farina, S. Kapadia, B. Krishnan, S. Wang and L. S. Liebeskind,
J. Org. Chem., 1994, 59, 5905.
13 D. M. Burland, D. P. Shelton, J. E. Rice, R. D. Miller, C. A. Walsh,
J. Zyss, I. Ledoux, R. M. Corn, D. A. Higgins, W. E. Moerner,
S. M. Silence, L. Dhar, J. A. Rogers, K. A. Nelson, D. R. Kanis,
M. A. Ratner, T. J. Marks, J. L. Brédas, C. Adant, P. Tackx,
A. Persoon and B. M. Pierce, “Optical Nonlinearities in
Chemistry”, Chem. Rev., 1994, 94, 1.
14 D. Baeriswyl, D. K. Campbell, G. C. Clark, G. Harbeke,
P. K. Kahol, H. Kiess, S. Mazumdar, M. Mehring and W. Rehwald,
“Conjugated Conducting Polymers”, ed. H. Kiess, Springer Ser.
Solid-State Sci., 1992, 102.
15 M. Goldbach, E. Jäkel and M. P. Schneider, J. Chem. Soc., Chem.
Commun., 1987, 1434.
16 P. Venturello, J. Chem. Soc., Chem. Commun. 1992, 1032;
P. Balma Tivola, A. Deagostino, C. Fenoglio, M. Mella, C. Prandi
and P. Venturello, Eur. J. Org. Chem., 1999, 2143; S. Aime,
H. Oulyadi, J. Maddaluno and P. Venturello, Org. Lett., 1999, 1,
1631, and references cited therein.
21 X. Han, B. M. Stolz and E. J. Corey, J. Am. Chem. Soc., 1999, 121,
7600.
22 J. A. Soderquist and A. Hassner, J. Am. Chem. Soc., 1980, 102,
1577.
23 J. Hartmann, M. Stähle and M. Schlosser, Synthesis, 1974, 888;
W. C. Still and T. L. Macdonald, J. Am. Chem. Soc., 1974, 96, 5561;
J. E. Baldwin, G. A. Höfle and O. W. Jr. Lever, J. Am. Chem. Soc.,
1974, 96, 7125; C. G. Chavadrian and C. H. Heathcock,
J. Am. Chem. Soc., 1975, 97, 3822.
24 C. Prandi and P. Venturello, J. Org. Chem., 1994, 59, 5458.
J. Chem. Soc., Perkin Trans. 1, 2001, 437–441
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