Preparation of (Z)-α-chloro-α,β-unsaturated ketones with total or high diastereoselectivity

Article abstract of DOI:10.1016/S0040-4020(02)00935-3

(Z)-α-Chloroenones are obtained by reaction of α-chloro-β-hydroxyketones with acetic anhydride, pyridine and 4-dimethylaminopyridine with total or high diastereoselectivity and in high yield.

Full text of DOI:10.1016/S0040-4020(02)00935-3

Tetrahedron 58 (2002) 7775–7780
Preparation of (Z)-a-chloro-a,b-unsaturated ketones
with total or high diastereoselectivity
*
Jose M. Concellon and Monica Huerta
´
´
´
´ ´ ´ ´ ´ ´
Departamento de Quımica Organica e Inorganica, Facultad de Quımica, Universidad de Oviedo, Julian Claverıa 8, 33071 Oviedo, Spain
Received 22 May 2002; revised 24 July 2002; accepted 2 August 2002
Abstract—(Z)-a-Chloroenones are obtained by reaction of a-chloro-b-hydroxyketones with acetic anhydride, pyridine and 4-
dimethylaminopyridine with total or high diastereoselectivity and in high yield. q 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
described. This led us to look for a more convenient
preparation of these compounds.
a-Chloroenones are important intermediates in organic
synthesis1 and the development of effective general
methods for the preparation of these compounds is of
significant value. The obtention of a-chloroenones is
generally achieved by C–C double bond formation with
the Wittig reaction,2 by elimination reactions from a,b-
dihaloketones,3 a,a-dihaloketones,4 or a-halo-b-hydroxy-
ketones,5 and by halogenation of a,b-unsaturated ketones.6
2. Results and discussion
The reaction of several a-chloro-b-hydroxyalkanones 1
with acetic anhydride and pyridine in the presence of a
catalytic amount of DMAP at 08C afforded, after hydrolysis,
the corresponding (Z)-a-chloroenones 2 with total or very
high diastereoselectivity and in high yield (Scheme 1 and
Table 1). The three reagents (acetic anhydride, pyridine, and
DMAP) used in this process are necessary to carry out the
transformation, and the elimination reaction does not take
place in the absence of any one of them. So, when
compounds 1 were treated with Ac2O/Py or with Ac2O/
DMAP the O-acetyl ketone 7 was isolated instead of
compound 2.
However, most of these preparations are essentially
restricted to the obtention of cyclic a-chloroenones, and in
some cases among the scarce preparations published of non-
cyclic a-chloroenones, a mixture of different compounds or
diastereoisomers are isolated, whilst in others the a-
chloroenones are obtained in poor yields. Moreover, few
of these methods are inexpensive, convenient, and use
commercial reagents.
The aromatic compounds 1a–c were easily obtained by
reaction of the corresponding potassium enolate of the
In connection with our interest in the synthesis of
functionalized alkenes, in this communication, we describe
a general preparation of (Z)-a-chloro-a,b-unsaturated
ketones from the easily available, a-chloro-b-hydroxyke-
tones, by treatment with the inexpensive reagents, acetic
anhydride, pyridine and 4-dimethylaminopyridine (DMAP).
Previously, a similar preparation had been described by
Narita and co-workers.5 However, this last methodology
uses more expensive reagents (methanesulfonyl chloride,
triethylamine and 1,8-diazabicyclo[5.4.0]undec-7-ene in
CH2Cl2); the (Z)-a-chloroenones are obtained in good
yield, but unpurified, in some cases, with the corresponding
enones and no synthesis of aromatic (Z)-a-chloroenones are
Table 1. Synthesis of (Z)-a-chloroenones
Entry Product
R1
R2
Reaction time Yield
(%)a
deb
(h)
1
2
3
4
5
6
7
8
9
2ac
2a
2b
2c
2d
2e
2f
Ph
C4H9
C4H9
C7H15
Cyclohexyl
CH3CH(Ph)
Ph
4
4
4
18
18
2
2
32
18
90
84
88
87
70
80
82
70
78
76
.98
.98
89
.98
.98
.98
.98
.98
Ph
Ph
Ph
Ph
Ph
Ph
p-Cl–C6H4
2g
2h
C4H9 C4H9
C4H9 Ph
a
b
c
Isolated yield after column chromatography based on the starting
carbonyl compound 1.
de determined by 300 MHz 1H NMR spectroscopy and GC–MS analysis
on the crude product.
This reaction was carried out at room temperature instead of at 08C.
Keywords: a-chloroenones; elimination reactions; diastereoselection.
*
Corresponding author. Tel.: þ34-8-510-3457; fax: þ34-8-510-3446;
e-mail: jmcg@sauron.quimica.uniovi.es
0040–4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)00935-3

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J. M. Concellon, M. Huerta / Tetrahedron 58 (2002) 7775–7780
7776
enone 2. The stereochemistry of 2 can be explained by
assuming that the diastereoisomer 7A suffers an anti-
elimination through the transition state (its Newman
projection is shown in Scheme 4) in which Cl and R2
show a cis relationship and, consequently, an anti-
elimination from 7A affords (Z)-a-chloro-a,b-unsaturated
ketones. The other diastereoisomer 7B cannot suffer an anti-
elimination due to the corresponding transition state cannot
be reached by steric hindrance between R1CO and R2
groups, and undergoes an enolization reaction, leading by
protonation, to the diastereoisomer 7A, which by an
elimination affords the a-chloroenone 2.
Scheme 1.
2-chloroacetophenone 3 [generated by treatment of 2-
chloroacetophenone 3 with potassium hexamethyldisilazide
(KMDS) at 2788C] with different aldehydes, at temperature
ranging from 278 to 258C. The obtained epoxyketones 4
were treated with chlorotrimethylsilane (TMSCl) and
dimethylsulphoxide (DMSO), yielding the corresponding
2-chloro-3-hydroxyketones 1a–c7 (Scheme 2). Compounds
1d–f were obtained by reaction of the lithium or potassium
enolate of the 2-chloroacetophenone 3 (generated from 2-
chloroacetophenone 3 and LDA or KHMDS at 2858C) with
the corresponding aldehyde and further hydrolysis at 2858C
(Scheme 2). Compounds 1g and h were prepared by reaction
of the ester 5 with bromochloromethyllithium obtaining the
1-bromo-1-chlorohexan-2-one 6, which was treated with the
corresponding aldehyde in the presence of Zn/CuBr/Et2-
AlCl (Scheme 3).8 It is noteworthy that although the starting
compounds 1 were used as mixtures of diastereoisomers
(roughly 1:1), the corresponding a-chloroenones 2 were
obtained with total stereoselectivity.
To support this mechanism, the geometry of the confor-
mations (shown in Scheme 4) of the diastereoisomers 7A
and 7B (R1¼Ph, R2¼C4H9) were optimized by using the
AM1 semiempirical method.9 The conformation of diaster-
eoisomer 7A is predicted to be 2.7 kcal/mol more stable
than diastereoisomer 7B. According to this result, it can be
expected that the anti-elimination of the acetyl group will
take place, via the conformation of diastereoisomer 7A, thus
producing only the Z alkene, in good agreement with the
experimental evidence. The steric interaction between the
phenyl ring and the butyl group seems to be the responsible
of the destabilization of the conformation of 7B.
3. Conclusion
By using this methodology, it is possible to afford aromatic
and aliphatic chloroenones, in which the double bond C–C
can be connected to aliphatic (linear, branched or cyclic) or
aromatic groups.
In conclusion, we have described a simple, easy, and
convenient preparation of (Z)-a-chloroenones by using
inexpensive commercial reagents.
The diastereoisomeric excess in the formation of the C–C
double bond was determined on the crude reaction products
by H NMR spectroscopy (300 MHz) and GC–MS. The Z
stereochemistry in the C–C double bond of chloroenones 2
was assigned by NOESY experiments (compounds 2b–d
and 2h). In these experiments, a positive NOE was observed
between the olefinic proton and the R1 substituent (Ph in
2b–d and PrnCH2 in 2h) showing a cis relationship between
the chloro atom and the R2.
4. Experimental
4.1. General
1
All reagents were purchased from Aldrich or Merck and
were used without further purification. Silica gel for flash
chromatography was purchased from Merck (230–400
mesh) and compounds were visualized on analytical thin
layer chromatograms (TLC) by UV light (254 nm) and by
cerium molybdate developer.
The transformation of 1 into 2 may be explained taking into
account that reaction of 1 (Scheme 4) with acetic anhydride,
in the presence of DMAP, affords the O-acetyl ketone 7, to
facilitate the elimination reaction. Compound 7 were
isolated and characterized by 13C NMR after treatment of
1 with Ac2O/Py or Ac2O/DMAP. The reaction with pyridine
promotes the elimination reaction affording the a-chloro-
1H NMR and 13C NMR spectra were recorded on a
BRUKER AC-200, AC-300 and on a DPX-300 spec-
trometers. Chemical shifts are given in d (ppm) relative to
TMS as internal standard in the case of 1H NMR spectra and
relative to CDCl3 in the case of 13C NMR spectra.
Scheme 2.

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J. M. Concellon, M. Huerta / Tetrahedron 58 (2002) 7775–7780
7777
Scheme 3.
IR spectra were run in NaCl cells on a UNICAM
MATTSON 3000 FTIR spectrometer. Mass spectra were
recorded on a MD 800 GC 8000 series FISONS Instruments
spectrometer by using EI 70 eV. Only the most important IR
absorptions (in cm21) and the most important peaks in MS
are given.
3086, 2956, 2870, 1688, 1596, 1448 cm21. MS m/z 205
[M2Cl]þ (3), 154 (12), 123 (25), 105 (100), 78 (14), 77
(44), 51 (12), 41 (19). Rf¼0.36 (hexane–ethyl acetate¼5:1).
4.2.2. 2-Chloro-3-hydroxy-1-phenyldecan-1-one (1b).
Yield: 85% (obtained as the anti diastereoisomer).10 1H
NMR (300 MHz, CDCl3): d¼8.01–7.45 (m, 5H), 4.94 (d,
1H, J¼7.94 Hz), 4.22 (dt, 1H, J¼7.94, 2.10 Hz), 4.10–3.50
(br s, 1H), 2.02–1.83 (m, 12H), 0.89–0.85 (m, 3H). 13C
NMR (50 MHz, CDCl3): d¼194.2 (C), 134.5 (C), 133.8
(CH), 128.8 (CH), 128.6 (CH), 71.5 (CH), 57.6 (CH), 32.5
(CH2), 31.6 (CH2), 29.2 (CH2), 29.0 (CH2), 25.0 (CH2), 22.4
(CH2), 13.9 (CH3). IR nmax¼3387, 3063, 2951, 2923, 2855,
1689, 1596, 1581, 1464, 1449 cm21. MS m/z 247 [M2Cl]þ
(5), 156 (5), 154 (16), 123 (20), 106 (8), 105 (100), 78 (13),
77 (38), 43 (21), 41 (22). Rf¼0.45 (hexane–ethyl
acetate¼5:1).
4.2. General method for the synthesis of a-chloro-b-
hydroxyketones 1a–c
To a stirred solution of 2-chloroacetophenone 3 (5 mmol) in
dry THF (25 mL), a solution of potassium hexamethyldi-
silazide 0.1 M in toluene (5.5 mmol) was added dropwise, at
2788C. The mixture was stirred at this temperature for
10 min and then a solution of aldehyde (7.5 mmol) in dry
THF (5 mL) was added dropwise. The mixture was stirred
overnight allowing the temperature to rise to room
temperature. The reaction was quenched with saturated
aqueous NH4Cl solution, extracted with CH2Cl2 and
concentrated under reduced pressure, yielding pure a,b-
epoxyketones 4.
4.2.3. 2-Chloro-3-cyclohexyl-3-hydroxy-1-phenylpro-
pan-1-one (1c). Yield: 93% (obtained as the anti diaster-
eoisomer).10 1H NMR (300 MHz, CDCl3): d¼8.00–7.26
(m, 5H), 5.08 (d, 1H, J¼8.46 Hz), 4.07 (ddd, 1H, J¼8.46,
6.16, 4.6 Hz), 2.96 (d, 1H, J¼6.16 Hz), 2.18–1.22 (m,
11H). 13C NMR (50 MHz, CDCl3): d¼194.6 (C), 134.7 (C),
133.8 (CH), 128.9 (CH), 127.8 (CH), 75.1 (CH), 53.8 (CH),
38.5 (CH), 29.9 (CH2), 28.9 (CH2), 26.2 (CH2), 26.1 (CH2),
25.2 (CH2). IR nmax¼3507, 3058, 2923, 2852, 1683, 1596,
1580, 1448, 1392, 1265, 1208, 1071 cm21. MS m/z 231
[M2Cl]þ (9), 156 (7), 154 (20), 147 (19), 123 (9), 105
(100), 83 (12), 82 (13), 78 (25), 77 (72), 73 (28), 55 (41), 51
(20). Rf¼0.47 (hexane–ethyl acetate¼5:1).
Crude epoxyketones 4 (5 mmol) were dissolved in dry
acetonitrile (5 mL) and then trimethylchlorosilane
(15 mmol) and dimethyl sulphoxide (15 mmol) were
added slowly. The reaction was kept at room temperature
by external cooling. After 30 min, the mixture was poured
into water and extracted with diethyl ether. The organic
layer was dried and then evaporated. The residue was
purified by flash column chromatography on silica gel
(eluent: hexane–ethyl acetate¼10:1).
4.3. General method for the synthesis of hydroxyketone
1d
4.2.1. 2-Chloro-3-hydroxy-1-phenylheptan-1-one (1a).
Yield: 92% (obtained as the anti diastereoisomer).10 1H
NMR (300 MHz, CDCl3): d¼8.1–7.2 (m, 5H), 4.93 (d, 1H,
J¼7.96 Hz), 4.21 (dt, 1H, J¼7.96, 2.32 Hz), 3.75–3.30 (br
s, 1H), 1.92–1.86 (m, 6H), 0.92 (t, 3H, J¼6.92 Hz). 13C
NMR (75 MHz, CDCl3): d¼194.3 (C), 134.5 (C), 133.9
(CH), 128.9 (CH), 128.6 (CH), 71.6 (CH), 57.6 (CH), 32.3
(CH2), 27.2 (CH2), 22.3 (CH2), 13.8 (CH3). IR nmax¼3476,
To a stirred solution of 2-chloroacetophenone 3 (5 mmol) in
dry THF (25 mL), a solution of potassium hexamethyldi-
silazide 0.1 M in toluene (5.5 mmol) was added dropwise, at
2858C. The mixture was stirred at this temperature for
10 min and then a solution of 2-phenylpropanal (7.5 mmol)
Scheme 4.

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J. M. Concellon, M. Huerta / Tetrahedron 58 (2002) 7775–7780
7778
in dry THF (5 mL) was added dropwise. The mixture was
stirred 15 min at the same temperature. The reaction was
quenched with saturated aqueous NH4Cl and usual workup
yielded crude hydroxyketone 1d, which were purified by
flash column chromatography (eluent: hexane–ethyl
acetate¼10:1).
1316, 1227, 1086, 1013 cm21. Rf¼0.33 (hexane–ethyl
acetate¼3:1).
4.5. General method for the synthesis of a-chloro-b-
hydroxyketones 1g–h
To a solution of lithium diisopropylamide in dry THF
[prepared from MeLi (20 mmol of a solution 1.5 M in
diethyl ether) and diisopropylamine (20 mmol) in THF
(40 mL) at 08C] was added very slowly chlorobromo-
methane (20 mmol) in THF (5 mL) at 2958C. After stirring
for 15 min, a solution of ethyl pentanoate 5 (10 mmol) in
THF (5 mL) was added dropwise to the solution of
chlorobromomethyllithium, and the resulting mixture was
stirred for 2.5 h at 295 to 2608C. The reaction was
quenched with HCl 1 M, extracted with ether, washed with
brine, dried (Na2SO4), and concentrated. The residual oil
was purified by silica gel column chromatography (eluent:
ether–hexane¼1:40) if it was necessary, but in general the
obtained 1-bromo-1-chlorohexan-2-one 6 could be used
without further purification.
4.3.1. 2-Chloro-3-hydroxy-1,4-diphenylpentan-1-one
(1d). Yield: 75% (obtained as one diastereoisomer). 1H
NMR (200 MHz, CDCl3): d¼7.58–7.15 (m, 10H), 4.90 (d,
1H, J¼1.54 Hz), 4.23 (dd, 1H, J¼1.54 Hz, J¼9.50 Hz),
3.30–3.25 (br s, 1H), 3.16 (dc, 1H, J¼9.50, 6.92 Hz), 1.48
(d, 3H, J¼6.92 Hz). 13C NMR (75 MHz, CDCl3): d¼193.8
(C), 142.5 (C), 133.6 (CH), 133.5 (C), 128.6 (CH), 128.4
(CH), 128.3 (CH), 127.3 (CH), 126.9 (CH), 75.3 (CH), 60.4
(CH), 42.9 (CH), 17.6 (CH3). IR nmax¼3517, 3060, 2968,
2932, 2875, 1688, 1596, 1580, 1450, 1224, 1013 cm21. MS
m/z 289 [M]þ (10), 235 (7), 187 (12), 186 (100), 155 (7),
102 (27). Rf¼0.33 (hexane–ethyl acetate¼5:1).
4.4. General method for the synthesis of a-chloro-b-
hydroxyketones 1e and 1f
A solution of diethylaluminum chloride (10 mmol) 1.0 M in
hexane was added to a slurry of zinc dust (10 mmol) and a
catalytic amount of copper (I) bromide (0.93 mmol) in THF
(40 mL) with stirring at 208C over 0.5 h. The resulting
mixture was cooled to 258C, and a solution of the 1-bromo-
1-chlorohexan-2-one (10 mmol) and the corresponding
aldehyde (10 mmol) was added slowly over 20 min at
258C. After 2 h at the same temperature, the reaction was
quenched with saturated aqueous NaHCO3, filtered over
celite and extracted with diethyl ether. The ether extracts
were washed with brine, dried (Na2SO4) and concentrated in
vacuo. The obtained oil was purified by flash column
chromatography on silica gel (eluent: hexane–ethyl
acetate¼10:1).
2-Chloroacetophenone 3 (4.5 mmol) was dissolved in 2 mL
of dry THF and added over a solution of lithium
diisopropylamide in THF [prepared from MeLi (5 mmol
of a solution 1.5 M in diethyl ether) and diisopropylamine
(5 mmol) in THF (25 mL) at 08C] at 2908C. After stirring
for 10 min, the corresponding aromatic aldehyde
(6.75 mmol) in THF (4 mL) was added dropwise at the
same temperature and the reaction mixture was stirred for
15 min at the same temperature. Then it was quenched with
saturated aqueous NH4Cl and usual workup yielded crude
hydroxyketones 1e and 1f, which were purified by flash
column
chromatography
(eluent:
hexane–ethyl
acetate¼10:1).
4.4.1. 2-Chloro-3-hydroxy-1,3-diphenylpropan-1-one
(1e). Yield: 80% (obtained as a mixture 3:2 of syn/anti
diastereoisomers).10 1H NMR (300 MHz, CDCl3): d¼8.05–
7.28 (m, 20H), 5.37 (d, 1H, J¼5.78 Hz), 5.31 (d, 1H,
J¼5.78 Hz), 5.30 (d, 1H, J¼8.55 Hz), 5.20 (d, 1H,
J¼8.55 Hz), 3.80–3.60 (br s, 2H). 13C NMR (75 MHz,
CDCl3): d¼194.3 (C), 194.0 (C), 139.1 (C), 138.5 (C),
134.5 (C), 134.0 (CH), 128.9 (CH), 128.7 (CH), 128.6 (CH),
128.3 (CH), 128.2 (CH), 128.1 (CH), 127.1 (CH), 126.7
(CH), 74.5 (CH), 73.2 (CH), 61.3 (CH), 57.4 (CH). IR
nmax¼3504, 3087, 3032, 1964, 1903, 1813, 1695, 1595,
1580, 1453, 1307, 1062 cm21. Rf¼0.34 (hexane–ethyl
acetate¼5:1).
4.5.1. 1-Bromo-1-chlorohexan-2-one. Yield: 92%. 1H
NMR (200 MHz, CDCl3): d¼5.87 (s, 1H), 2.85 (t, 2H,
J¼7.30 Hz), 1.71–1.57 (m, 2H), 1.44–1.57 (m, 2H), 0.87 (t,
3H, J¼6.92 Hz). 13C NMR (50 MHz, CDCl3): d¼197.1 (C),
57.0 (CH), 34.6 (CH2), 25.9 (CH2), 21.9 (CH2), 13.6 (CH3).
4.5.2. 6-Chloro-7-hydoxyundecan-5-one (1g). Yield: 75%
(obtained as a mixture 2:1 of syn/anti diastereoisomers).10
1H NMR (300 MHz, CDCl3): d¼4.25 (d, 1H, J¼3.42 Hz),
4.12–4.08 (m, 3H), 2.75–2.66 (m, 4H), 1.65–1.27 (m,
20H), 0.93 (t, 12H, J¼7.17 Hz). 13C NMR (75 MHz,
CDCl3): d¼206.3 (C), 205.9 (C), 72.1 (CH), 71.4 (CH),
67.7 (CH), 64.1 (CH), 40.0 (CH2), 39.9 (CH2), 33.5 (CH2),
32.6 (CH2), 27.5 (CH2), 27.2 (CH2), 25.3 (CH2), 22.3 (CH2),
22.0 (CH2), 13.8 (CH3), 13.7 (CH3). IR nmax¼3427, 2958,
2932, 2872, 1711, 1466, 1379 cm21. MS m/z 185 [M2Cl]þ
(7), 134 (9), 118 (10), 103 (100), 92 (36), 85 (90), 69 (23),
57 (97), 56 (34), 43 (27), 41 (77). Rf¼0.23 (hexane–ethyl
acetate¼10:1).
4.4.2. 2-Chloro-3-(4-chlorophenyl)-3-hydroxy-1-phenyl-
propan-1-one (1f). Yield: 76% (obtained as a mixture 3:5
of syn/anti diastereoisomers).10 1H NMR (200 MHz,
CDCl3): d¼8.04–7.27 (m, 18H), 5.36 (d, 1H, J¼5.14 Hz),
5.26 (d, 1H, J¼8.44 Hz), 5.24 (d, 1H, J¼5.14 Hz), 5.12 (d,
1H, J¼8.44 Hz), 3.94–3.92 (br s, 1H), 3.90–3.75 (br s,
,1H). 13C NMR (50 MHz, CDCl3): d¼194.2 (C), 194.1
(C), 137.6 (C), 137.1 (C), 134.3 (CH), 134.2 (CH), 134.1
(C), 133.9 (C), 129.0 (CH), 128.8 (CH), 128.7 (CH), 128.6
(CH), 128.4 (CH), 128.3 (CH), 128.2 (CH), 73.7 (CH), 72.5
(CH), 60.8 (CH), 57.2 (CH). IR nmax¼3057, 3081, 3062,
3037, 2936, 2903, 1685, 1596, 1490, 1449, 1400, 1372,
4.5.3. 2-Chloro-1-hydroxy-1-phenylheptan-3-one (1h).
Yield: 61% (obtained as a mixture 1:1 of syn/anti
diastereoisomers).10 1H NMR (200 MHz, CDCl3): d¼7.4–
7.3 (m, 10H), 5.16 (d, 1H, J¼5.38 Hz), 5.01 (d, 1H,
J¼8.22 Hz), 4.44 (d, 1H, J¼5.38 Hz), 4.35 (d, 1H,
J¼8.22 Hz), 3.60–3.35 (br s, 2H), 2.67–2.30 (m, 4H),

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7779
1.66–2.30 (m, 8H), 0.91 (t, 3H, J¼6.92 Hz), 0.86 (t, 3H,
J¼7.18 Hz). 13C NMR (50 MHz, CDCl3): d¼205.5 (C),
205.2 (C), 139.0 (C), 138.7 (C), 128.4 (CH), 128.3 (CH),
128.2 (CH), 126.8 (CH), 126.4 (CH), 74.7 (CH), 73.6 (CH),
67.5 (CH), 63.4 (CH), 40.7 (CH2), 40.1 (CH2), 25.2 (CH2),
25.0 (CH2), 21.8 (CH2), 21.7 (CH2), 13.6 (CH3), 13.5 (CH3).
IR nmax¼3460, 3088, 3064, 3033, 2957, 2872, 1714, 1604,
1495, 1454, 1380, 1267, 1050 cm21. MS m/z 205 [M2Cl]þ
(14), 140 (33), 138 (61), 134 (20), 107 (100), 105 (32), 92
(47), 91 (32), 85 (52), 79 (72), 77 (80), 57 (90), 51 (36), 41
(89). Rf¼0.30 (hexane–ethyl acetate¼5:1).
77 (36), 43 (77). Anal. calcd for C15H17ClO: C, 72.43; H,
6.89. Found: C, 72.32; H, 6.80. Rf¼0.40 (hexane–ethyl
acetate¼10:1).
4.6.4. (Z)-2-Chloro-1,4-diphenylpent-2-en-1-one (2d). 1H
NMR (300 MHz, CDCl3): d¼7.68–7.25 (m, 10H), 6.77 (d,
1H, J¼9.66 Hz), 4.28 (dc, 1H, J¼9.66, 7.11 Hz), 1.50 (d,
3H, J¼7.11 Hz). 13C NMR (75 MHz, CDCl3): d¼190.2 (C),
148.4 (CH), 142.5 (C), 136.5 (C), 132.5 (CH), 131.3 (C),
129.4 (CH), 128.7 (CH), 128.3 (CH), 126.9 (CH), 39.9
(CH), 19.9 (CH3). IR nmax¼3084, 3060, 3027, 2970, 2929,
2872, 1755, 1666, 1598, 1493, 1447, 1241 cm21. MS m/z
270 [M]þ (6), 234 (4), 191, (8), 129 (9), 115 (10), 105 (100),
77 (72), 51 (21). Anal. calcd for C17H15ClO: C, 75.41; H,
5.58. Found: C, 75.29; H, 5.51. Rf¼0.37 (hexane–ethyl
acetate¼10:1).
4.6.5. (Z)-2-Chloro-1,3-diphenylpropen-1-one6 (2e). 1H
NMR (300 MHz, CDCl3): d¼7.86–7.17 (m, 11H). 13C
NMR (75 MHz, CDCl3): d¼191.1 (C), 139.7 (CH), 136.6
(C), 132.6 (C), 132.4 (CH), 130.5 (CH), 130.3 (CH), 130.2
(C), 129.3 (CH), 128.4 (CH), 128.3 (CH). IR nmax¼3059,
3026, 1964, 1908, 1814, 1771, 1730, 1667, 1600, 1491,
1447, 1251 cm21. MS m/z 242 [M]þ (11), 241 (6), 207 (15),
105 (72), 77 (100), 51 (48). Rf¼0.33 (hexane–ethyl
acetate¼10:1).
4.6. General method for the preparation of (Z)-a-chloro-
a,b-unsaturated ketones
To the corresponding a-chloro-b-hydroxyketone 1
(0.4 mmol) were added pyridine (5 mL), acetic anhydride
(5 mL) and 4-dimethylaminopyridine (5 mg) at 08C. After
the time indicated in Table 1, the reaction mixture was
poured into a mixture of water–ice, and then extracted with
diethyl ether. The organic layer was successively washed
with HCl (4£5 mL) and with H2O (4£20 mL), was dried
over anhydrous sodium sulphate and the solvents were
distilled to afford the corresponding a-chloroenones 2
crude, which were purified by column flash chromatography
over silica gel (eluent: hexane–ethyl acetate¼10:1) to
provide pure compounds 2.
4.6.6. (Z)-2-Chloro-3-(4-chlorophenyl)-1-phenylpropen-
1
1-one12 (2f). H NMR (200 MHz, CDCl3): d¼7.81–7.38
4.6.1. (Z)-2-Chloro-1-phenylhept-2-en-1-one11 (2a). 1H
NMR (300 MHz, CDCl3): d¼7.69–7.46 (m, 5H), 6.66 (t,
1H, J¼7.11 Hz), 2.47 (dt, 2H, J¼7.11, 7.11 Hz), 1.50–1.32
(m, 4H), 0.92 (t, 3H, J¼7.26 Hz). 13C NMR (75 MHz,
CDCl3): d¼190.1 (C), 145.4 (CH), 136.8 (C), 133.0 (C),
132.2 (CH), 129.2 (CH), 128.2 (CH), 29.7 (CH2), 29.4
(CH2), 22.3 (CH2), 13.6 (CH3). IR nmax¼3062, 3028, 2959,
2929, 2861, 1668, 1615, 1598, 1447, 1379, 1317,
1266 cm21. MS m/z 222 [M]þ (5), 179 (12), 157 (9), 129
(15), 115 (29), 105 (100), 77 (89), 51 (33), 41 (21). Rf¼0.40
(hexane–ethyl acetate¼10:1).
4.6.2. (Z)-2-Chloro-1-phenyldec-2-en-1-one (2b). 1H
NMR (300 MHz, CDCl3): d¼7.52–7.37 (m, 5H), 6.66 (t,
1H, J¼7.26 Hz), 2.46 (dt, 2H, J¼7.26, 7.38 Hz), 1.49–1.28
(m, 10H), 0.89 (t, 3H, J¼6.66 Hz). 13C NMR (75 MHz,
CDCl3): d¼190.2 (C), 145.6 (CH), 136.8 (C), 133.0 (C),
132.2 (CH), 129.2 (CH), 128.2 (CH), 31.5 (CH2), 29.8
(CH2), 29.2 (CH2), 28.8 (CH2), 27.6 (CH2), 22.5 (CH2), 13.9
(CH3). IR nmax¼3061, 3027, 2954, 2926, 2856, 1768, 1744,
1667, 1613, 1447, 1370, 1266, 1024 cm21. MS m/z 264
[M]þ (,1%), 167 (11), 145 (11), 115 (21), 105 (100), 77
(72), 55 (9), 51 (16), 43 (26), 41 (29). Anal. calcd for
C16H21ClO: C, 72.57; H, 7.99. Found: C, 72.60; H, 7.91.
Rf¼0.47 (hexane–ethyl acetate¼10:1).
(m, 10H). 13C NMR (50 MHz, CDCl3): d¼190.8 (C), 138.0
(CH), 136.4 (C), 136.2 (C), 132.5 (CH), 131.7 (CH), 131.1
(C), 130.7 (C), 129.4 (CH), 128.7 (CH), 128.4 (CH). IR
nmax¼3062, 3028, 1661, 1605, 1563, 1490, 1447, 1404,
1247, 1204, 1180, 1088, 1013 cm21. MS m/z 276 [M]þ (27),
241 (63), 212 (6), 176 (6), 163 (7), 136 (15), 105 (100), 77
(69), 51 (19). Rf¼0.33 (hexane–ethyl acetate¼10:1).
4.6.7. (Z)-6-Chloroundec-6-en-5-one (2g). 1H NMR
(200 MHz, CDCl3): d¼6.94 (t, 1H, J¼7.18 Hz), 2.73 (t,
2H, J¼7.30 Hz), 2.38 (dt, 2H, J¼7.18, 7.18 Hz), 1.64–1.26
(m, 8H), 0.95–0.88 (m, 6H).13C NMR (50 MHz, CDCl3):
d¼194.5 (C), 140.6 (CH), 133.4 (C), 38.1 (CH2), 29.8
(CH2), 29.1 (CH2), 26.3 (CH2), 22.3 (CH2), 22.2 (CH2), 13.7
(CH3), 13.6 (CH3). IR nmax¼2960, 2872, 1768, 1744, 1696,
1617, 1465, 1403, 1379, 1236, 1160, 1094, 1021 cm21. MS
m/z 202 [M]þ (,1%), 173 (14), 160 (66), 145 (100), 131
(28), 125 (18), 118 (17), 104 (74), 89 (43), 85 (29), 81 (41),
57 (69), 53 (32). Anal. calcd for C11H19ClO: C, 65.17; H,
9.45. Found: C, 65.01; H, 9.51. Rf¼0.33 (hexane–ethyl
acetate¼20:1).
4.6.8. (Z)-2-Chloro-1-phenylhept-1-en-3-one (2h). 1H
NMR (200 MHz, CDCl3): d¼7.88–7.81 (m, 2H), 7.77 (s,
1H), 7.50–7.37 (m, 3H), 2.89 (t, 2H, J¼7.30 Hz), 1.77–
1.62 (m, 2H), 1.50–1.28 (m, 2H), 0.97 (t, 3H, J¼7.17 Hz).
13C NMR (50 MHz, CDCl3): d¼195.6 (C), 134.6 (CH),
132.8 (C), 130.7 (CH), 130.1 (CH), 130.0 (C), 128.4 (CH),
38.3 (CH2), 26.3 (CH2), 22.2 (CH2), 13.8 (CH3). IR
nmax¼3056, 2958, 2932, 2872, 1688, 1597, 1574, 1491,
1400, 1265, 1142, 1008 cm21. MS m/z 222 [M]þ (28), 180
(54), 165 (51), 145 (100), 137 (40), 102 (57), 57 (26). Anal.
calcd for C13H15ClO: C, 70.11; H, 6.79. Found: C, 70.22; H,
6.69. Rf¼0.4 (hexane–ethyl acetate¼20:1).
4.6.3. (Z)-2-Chloro-3-cyclohexyl-1-phenylpropenone
1
(2c). H NMR (300 MHz, CDCl3): d¼7.67–7.41 (m, 5H),
6.50 (d, 1H, J¼9.22 Hz), 2.87–2.68 (m, 1H), 1.84–1.34 (m,
5H), 1.29–1.13 (m, 5H). 13C NMR (75 MHz, CDCl3):
d¼190.4 (C), 149.9 (CH), 136.8 (C), 132.2 (CH), 130.9 (C),
129.3 (CH), 128.2 (CH), 38.9 (CH), 30.9 (CH2), 25.6 (CH2),
25.2 (CH2). IR nmax¼3060, 3023, 2974, 2875, 2840, 1664,
1615, 1578, 1446, 1317, 1261, 1222 cm21. MS m/z 248
[M]þ (100), 213 (37), 191 (25), 183 (27), 167 (34), 105 (74),

´
J. M. Concellon, M. Huerta / Tetrahedron 58 (2002) 7775–7780
7780
5. Narita, S.; Takahashi, A.; Sato, H.; Aoki, T.; Yamada, S.;
Acknowledgements
Shibasaki, M. Tetrahedron Lett. 1992, 33, 4041–4044.
6. Schlama, T.; Gabriel, K.; Gouverneur, V.; Mioskowski, C.
Angew. Chem. Int. Ed. 1997, 36, 2342–2344, Angew. Chem.
1997, 109, 2440–2442.
´
We thank II Plan Regional de Investigacion del Principado
de Asturias (PB-EX01-11) and the Ministerio de Educacion
y Cultura (BQU2001-3807) for financial support and Dr
´
7. Ghelfi, F.; Grandi, R.; Pagnoni, U. M. J. Chem. Res. (S) 1988,
200–201.
´
Francisco J. Gonzalez for the theoretical calculations and
valuable discussions. J. M. C. thanks Carmen Fernandez-
´
8. Takahashi, A.; Shibasaki, M. J. Org. Chem. 1988, 53,
1227–1231.
´
Florez for her time. M. H. thanks the Ministerio de
Educacion, Cultura y Deporte for a predoctoral fellowship.
´
9. The calculations were carried out with the Gaussian 98
program: Frisch, M. J.; Trucks, G. W.; Schegel, H. B.;
Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Zarkzewski,
V. G.; Montgomery, J. A.; Stratmann, R. E.; Burant, J. C.;
Dapprich, S.; Millan, J. M.; Daniels, A. D.; Kudin, K. N.;
Strain, M. C.; Farkas, O.; Tomasi, J.; Barone, V.; Cossi, M.;
Cammi, R.; Mennucci, B.; Pomelli, C.; Adamo, C.; Clifford,
S.; Ochterski, J.; Petersson, G. A.; Ayala, P. Y.; Cui, Q.;
Morokuma, K.; Malick, D. K.; Rabuck, A. D.; Raghavachari,
K.; Foresman, J. B.; Cioslowski, J.; Ortiz, J. V.; Baboul, A. G.;
Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.;
Komaromi, I.; Gomperts, R.; Martin, R. L.; Fox, D. J.;
Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.;
Gonzalez, C.; Challacombe, M.; Gill, P. M. W.; Johnson,
B. G.; Chen, W.; Wong, M. W.; Andres, J. L.; Head-Gordon,
M.; Replogle, E. S.; Pople, J. A. Gaussian 98, revision A.3;
Gaussian, Inc.: Pittsburgh, PA, 1998.
Our thanks to Robin Walker for his revision of the English.
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