An efficient synthesis of (E)-α,β-unsaturated ketones and esters with total stereoselectivity by using chromium dichloride

Article abstract of DOI:10.1016/j.tet.2006.01.052

(E)-α,β-Unsaturated ketones 1 or esters 2 can be obtained with complete stereoselectivity by reaction of different 2-chloro-3-hydroxy ketones 3 or esters 4 and CrCl₂. A comparative study of the results of synthesis of ketones 1 with CrCl₂ or samarium is performed. A mechanism to explain both β-elimination reactions has been proposed.

Full text of DOI:10.1016/j.tet.2006.01.052

Tetrahedron 62 (2006) 3292–3300
An efficient synthesis of (E)-a,b-unsaturated ketones and esters
with total stereoselectivity by using chromium dichloride
*
´
Jose M. Concellon, Humberto Rodrıguez-Solla and Carmen Mejica
´
´
´
´ ´ ´ ´ ´ ´
Departamento de Quımica Organica e Inorganica, Facultad de Quımicas, Universidad de Oviedo, Julıan Claverıa, 8, 33071 Oviedo, Spain
Received 21 December 2005; accepted 17 January 2006
Available online 13 February 2006
Abstract—(E)-a,b-Unsaturated ketones 1 or esters 2 can be obtained with complete stereoselectivity by reaction of different 2-chloro-3-
hydroxy ketones 3 or esters 4 and CrCl2. A comparative study of the results of synthesis of ketones 1 with CrCl2 or samarium is performed. A
mechanism to explain both b-elimination reactions has been proposed.
q 2006 Elsevier Ltd. All rights reserved.
1. Introduction
The sum of all theses features would make a general and
highly stereoselective method to prepare a,b-unsaturated
ketones and esters from easily available starting material of
great interest.
The development of methodologies for the formation of
carbon–carbon double bonds could be considered one of the
most important challenges in organic synthesis.1
Recently, we describe the preliminary results of a new
methodology to obtain a,b-unsaturated esters 2 with total
diastereoselectivity by treatment of the easily available
a,b-Unsaturated ketones are one of the most useful starting
materials to prepare different polifunctionalized organic
compounds and have been widely used in organic
synthesis.2 The stereoselective synthesis of a,b-unsaturated
ketones3 has been extensively developed and is generally
achieved by condensation,4 oxidation,5 elimination,6 acyla-
tion7 reactions, and by insertion of carbon monoxide8
among others. However, in most of these syntheses, the
stereoselective control of the carbon–carbon double bond
formation remains unsolved. The poor yields or the difficult
preparation of the starting materials also limit other
methodologies.
a-halo-b-hydroxyesters 4 with chromium dichloride.18
A
CrCl2-promoted sequential condensation–elimination
reaction of various aldehydes with ethyl dibromoacetate to
afford a,b-unsaturated esters in high yield and with total
selectivity has been also published.19 In addition, we have
also reported a synthesis of a,b-unsaturated ketones from
2-chloro-3-hydroxy ketones by using SmI2 or SmI3.20
In the present work, as part of our interest on developing
new selective syntheses of functionalized alkenes, we wish
to extend these previous results and to explore the possible
use of chromium dichloride to carry out other b-elimination
reactions. Concretely, here we report the preparation of
(E)-a,b-unsaturated ketones 1 and esters 2 with total
stereoselectivity promoted by CrCl2.
Respect to a,b-unsaturated esters, its preparation9 is
generally achieved by C]C bond formation by Wittig,10
Horner–Emmons,11 Heck12 or Peterson13 reactions. Another
useful approach employs the Cope rearrangement,14
utilising acetylenic compounds15 or using a-mercaptoesters
derivatives.16 However, most of these methodologies, give a
mixture of diastereoisomers, and poor yields are obtained.
In other cases, poor generality is a major limitation. In
addition, the preparations of a,b-unsaturated esters in which
C]C bond is trisubstituted are scarce.17
2. Results and discussion
2.1. Synthesis of a,b-unsaturated ketones 1
The treatment of a solution of 2-chloro-3-hydroxy ketones 3
in refluxing THF with 3 equiv of CrCl2 during 4 h afforded,
after acid hydrolysis,21 the corresponding a,b-unsaturated
ketones 1 in high yields and with total (E)-selectivity
(Scheme 1 and Table 1).
Keywords: Diastereoisomers; a-b-unsaturated ketones; Ketones; Stereo-
selectivity; a,b-unsaturated esters.
*
Corresponding author. Tel.: C34 985103457; fax: C34 985103446;
e-mail: jmcg@uniovi.es
0040–4020/$ - see front matter q 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.01.052

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J. M. Concellon et al. / Tetrahedron 62 (2006) 3292–3300
3293
R1
similar or slightly higher yields of a,b-unsturated ketones
were obtained by using CrCl2 instead of SmI3 or SmI2, the
stereoselectivity being complete in both cases, the two
proposed methods can be complementary and represent
valuable methods for the preparation a,b-unsaturated
ketones.
O
O
1.THF reflux, 4 h.
2. HCl 1 N
CrCl2
+
R2
OH
R2
R1
Cl
3
1
Scheme 1. Synthesis of (E)-a,b-unsaturated ketones 1.
Table 1. Synthesis of (E)-a,b-unsaturated ketones 1
2.2. Synthesis of a,b-unsaturated esters 2
Entry 1a
R1
R2
Yield
1 (%)b
SmI2
3 (%)c
Our first attempts were carried out using a-chloro-b-
hydroxyesters and a,b-epoxyesters in order to deter-
mine suitable starting materials. Thus, treatment of a
solution of ethyl 2-chloro-3-hydroxy-2-methyldecanoate
4d in THF with CrCl2 at reflux during 4 h afforded
ethyl 2-methyldecan-2-enoate 2d, after hydrolysis, with
total diastereoselectivity (deO98%) and 64% yield.
The same treatment of 2,3-epoxy-2-methyl decanoate
6d, gave 2d with slightly lower diastereoselection (de
95%) and yield (51%). Based on these results,
preparation of a,b-unsaturated esters was performed
from compounds 4. So, the treatment of different
2-halo-3-hydroxyesters 4 with CrCl2 (3 equiv) at room
temperature afforded (E)-a,b-unsaturated esters with
total diastereoselectivity (Scheme 3). Table 2 sum-
marizes the obtained results.
d
CrCl2
1
2
3
4
5
6
7
8
9
10
1a
1b
1c
1d
1e
1f
1g
1h
1i
n-C4H9
n-C7H15
Cyclohexyl
Ph
Ph
Ph
Ph
Ph
Ph
81
84
91
72
85
68
77
71
89
91
96 (72)
98 (91)
67 (72)
73 (80)
82
85
93
80
88
67
64
92
79
61
e
i-Bu
—
e
CH3CH(Ph) Ph
n-C4H9
Ph
n-C4H9
4-MeO-Ph
—
e
n-C4H9
—
82 (70)
65 (58)
n-C4H9
t-Bu
Me
e
—
1j
a Three equivalents of CrCl2 were used in all cases.
b Isolated yield based on the starting a-chloro-b-hydroxy ketones 3.
c Isolated yield based on the starting a-chloroketones 5.
d Isolated yield by using SmI3, in parenthesis.
e This reaction was not performed by using SmI2 or SmI3.
The diastereoisomeric excess was determined on the crude
products by 1H NMR spectroscopy (300 MHz) and GC–MS,
showing the presence of a single stereoisomer. The (E)-
configuration of the C–C double bond in products 1 was
assigned on the basis of 1H NMR coupling constants
observed for the olefinic protons.22 These values are in
agreement with those previously reported (1a–d).20
OH
O
R1
OR3
Hal R2
O
3 CrCl2
THF
4
R1
OR3
R2
O
OR3
R1
2
The starting ketones 3 were easily prepared by reaction of
the corresponding lithium enolates of a-haloketones 5 with
aldehydes at K78 8C20 (Scheme 2 and Table 1).
R2
O
6
Scheme 3. Synthesis of (E)-a,b-unsaturated esters 2.
O
O
R1
1) LDA
R2
R2
OH
Table 2. Synthesis of (E)-a,b-unsaturated esters 2
2) R1CHO
3) H3O+
Cl
Cl
Entry 2a
R1
R2
R3
Hal
Yield
4 (%)b 2 (%)c
5
3
1
2
3
4
5
6
7
8
9
10
2a
2b
2c
2d
2e
2f
2g
2h
2i
n-C7H15
pCl–C6H4
MeCH(Ph)
n-C7H15
Cyclohexyl
Ph
pMeO–C6H4 Me
Ph
Ph
H
H
H
Me
Me
Me
Me
Me
Me
Et
Et
Et
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Br
Br
Cl
87
69
75
93
95
97
91
92
89
84
65
68
52
64
65
60
70
65
90
70
Scheme 2. Preparation of starting compounds 3.
Several comments are worth of mention: (1) interestingly,
although different mixtures of stereoisomers (ranging from
1:1 to 4:1) of starting materials 3 were used, the
corresponding a,b-unsaturated ketones 1 were obtained
with total (E)-stereoselectivity. (2) The method presents
wide applicability. Both aromatic and aliphatic (linear,
branched or cyclic) (E)-a,b-unsaturated ketones 1 can be
obtained (Table 1). (3) In some cases (1a–d, 1i) the crude
reaction products were obtained with high purity and no
purification by column chromatography was necessary.
Et
n-C6H13 Et
n-C5H11 Et
Me i-Pr
2j
Cyclohexyl
a In all cases de was O98%. It was determinated on crude reaction products
by 1H NMR spectroscopy and GC–MS.
b Isolated yield after column chromatography based on compound 7.
c Isolated yield after column chromatography based on compound 4.
As was previously described,20 the same transformation
(synthesis of (E)-a,b-unsaturated ketones 1 from the same
a-chloro-b-hydroxy ketones 3) can also accomplish by
using SmI3 or SmI2. Results in Table 1 show that, in general,
The starting materials 4 were easily prepared by reaction of
the corresponding lithium enolates of a-haloesters 7
(generated by treatment of a-haloesters with LDA at
K78 8C) with aldehydes at K78 8C (Scheme 4).

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J. M. Concellon et al. / Tetrahedron 62 (2006) 3292–3300
3294
Synthesis of 1 or 2 with total stereoselection from a mixture
of diastereoisomers of 3 or 4 could be also explained taking
into account that after reaction of 3 or 4 with CrCl2, the
stereogenic C–Cl center suffers enolization. Therefore, the
mixture of diastereoisomers 3 or 4 is transformed to a
mixture of enantiomers 8, which eliminates to afford a
single (E)-stereoisomer 1 or 2.
O
OH
O
1) LDA
R2
OR3
R1
OR3
2) R1CHO
3) H3O+
Hal R2
Hal
7
4
Scheme 4. Preparation of starting compounds 4.
a,b-Unsaturated esters 2 were also obtained with total
diastereoselectivity from mixtures of diastereoisomers
(roughly 1:1) of the starting compounds 4. 1H NMR
spectroscopy (300 MHz) and GC–MS of the crude reaction
3. Conclusion
In conclusion, an easy, simple and general method has been
developed to synthesise a,b-unsaturated ketones 1 or esters
2 in high yield and with total (E)-stereoselectity from
readily available 2-halo-3-hydroxy ketones 3 or esters 4 and
being promoted by chromium dichloride.
of products 2, shown the presence of
diastereoisomer.
a single
The E stereochemistry in the C–C double bond of a,b-
unsaturated esters 2 was assigned on the basis of the value of
1H NMR coupling constants between the olefinic protons of
compound 2a–c (Table 2, entries 1–3);23 by NOE experiments
in the case of the trisubstituted compounds 2g, and 2i or by
4. Experimental
1
comparison with the H and 13C NMR spectra of authentic
4.1. General remarks
samples described in the literature (2d–e).24
Reactions which required an inert atmosphere were
conducted under dry nitrogen, and the glassware was oven
dried (120 8C). THF was distilled from sodium/benzophe-
none ketyl immediately prior to use. All reagents were
commercially available 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). 1H NMR spectra were
recorded at 200, 300 or 400 MHz. 13C NMR spectra and
DEPT experiments were determined at 75 or 100 MHz.
Chemical shifts are given in ppm relative to tetramethyl-
silane (TMS), which is used as an internal standard, and
coupling constants J are reported in Hz. The diastereoiso-
This methodology for obtaining a,b-unsaturated esters is
also general: R1, R2 and R3 can be widely varied. R1 can be
aliphatic (linear, branched or cyclic) or aromatic, and
substitution at the C2 position could also be changed using
different esters to prepare the starting compounds 4 (Scheme
4). Interestingly, the diastereoselectivity was unaffected by
changing the carboxyl ester (Table 2, entries 5 and 10) in
opposition to the Wittig olefination reaction.25
2.3. Mechanism
The observed results and the E-configuration of products 1
or 2 can be explained (Scheme 5) assuming the initial
metallation of the C–Cl bond of 3 or 4 by two consecutive
single electron transfers from CrCl2 to afford a chromium
enolate like 8. The CrIII center would be coordinated to the
oxygen atom of the alcohol to produce a six-membered ring.
Tentatively, we assume the involvement of a chair-like
transition state model I, with the R1 group adopting an
equatorial orientation to avoid 1,3-diaxial interactions.
Elimination from I leads to a,b-unsaturated ketones 1 or
esters 2 with total (E)-stereoselectivity.
1
meric excesses were obtained from H NMR analysis and
GC–MS of crude products. GC–MS and HRMS were
measured at 70 eV. Only the most important IR absorptions
(cmK1) and the molecular ions and/or base peaks in MS are
given.
4.2. General procedure for the synthesis of starting
compounds 3
To a K78 8C stirred solution of the a-haloketone
(9.7 mmol) in dry THF (8 mL) was added dropwise lithium
diisopropylamide [prepared from MeLi (6.5 mL of 1.5 M
solution in ether) and diisopropylamine (1.4 mL, 10 mmol)
in THF (50 mL) at 0 8C]. After stirring for 10 min, a solution
of the aldehyde (5 mmol) in dry THF (4.5 mL) was added
dropwise at K78 8C and the mixture was stirred for 2 h.
Then the reaction mixture was quenched with an aqueous
saturated solution of NH4Cl (20 mL). Usual workup
provided the corresponding a-halo-b-hydroxy ketone 3,
which was purified by flash column chromatography on
silica gel (hexane/EtOAc 10:1).
Cl2
Cr
OH
O
HO
R1
O
CrCl2
R1
Y
3 or 4
1 or 2
Y
CrCl2
8
Y = R2, OR3
H
O
R1
O
Y
4.2.1. 2-Chloro-3-hydroxy-1-phenylheptan-1-one (3a).
Data on the 50:50 mixture of diastereoisomers. Yellow
H
CrIII
I
1
oil. H NMR (300 MHz, CDCl3): d 8.11–7.23 (m, 10H),
Chair-like transition state model
5.11 (d, JZ4.3 Hz, 1H), 4.93 (d, JZ7.9 Hz, 1H), 4.22–4.14
(m, 2H), 2.95 (s, 2H), 1.92–1.86 (m, 12H), 0.96–0.89
Scheme 5. Proposed mechanism.

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J. M. Concellon et al. / Tetrahedron 62 (2006) 3292–3300
3295
(m, 6H); 13C NMR (75 MHz, CDCl3): d 194.4 (C), 194.3
(C), 134.5 (2!C), 134.0 (CH), 133.9 (2!CH), 128.9
(4!CH), 128.7 (2!CH), 128.6 (CH), 71.6 (CH), 70.8
(CH), 60.6 (CH), 57.6 (CH), 33.2 (CH2), 32.3 (CH2), 27.6
(CH2), 27.2 (CH2), 22.3 (2!CH2), 13.8 (CH3), 13.7 (CH3);
MS (70 eV, EI) m/z (%) 205 [MKCl]C (3), 154 (12), 123
(25), 105 (100), 78 (14), 77 (44), 51 (12), 41 (19); IR (neat):
(2!CH3), 24.2 (CH3), 23.8 (CH3); RfZ0.37 (hexane/
EtOAc 5:1).
4.2.6. 2-Chloro-3-hydroxy-1,4-diphenylpentan-1-one
(3f). White solid. H NMR (300 MHz, CDCl3): d 8.95–
1
7.31 (m, 10H), 5.03 (s, 1H), 4.31 (dd, JZ8.2, 5.9 Hz, 1H),
3.58 (d, JZ5.9 Hz, 1H), 3.31–3.08 (m, 1H), 1.50 (d, JZ
6.3 Hz, 3H); 13C NMR (100 MHz, CDCl3): d 194.3 (C),
142.7 (C), 133.9 (CH), 133.7 (C), 128.8 (CH), 128.7 (2!
CH), 128.6 (2!CH), 128.1 (2!CH), 127.6 (CH), 127.2
(CH), 75.5 (CH), 60.1 (CH), 43.1 (CH), 17.9 (CH3); RfZ
0.42 (hexane/EtOAc 5:1).
n~Z3476, 3086, 2956, 2870, 1688, 1596, 1448 cmK1
RfZ0.36 (hexane/EtOAc 5:1).
;
4.2.2. 2-Chloro-3-hydroxy-1-phenyldecan-1-one (3b).
Data on the 50:50 mixture of diastereoisomers. Yellow
1
oil. H NMR (300 MHz, CDCl3): d 8.01–7.45 (m, 10H),
4.2.7. 6-Chloro-7-hydroxyundec-5-one (3g). Data on the
60:40 mixture of diastereoisomers. Yellow oil. H NMR
5.09 (d, JZ4.0 Hz, 1H), 4.94 (d, JZ7.7 Hz, 1H), 4.25–4.18
(m, 2H), 3.32 (s, 2H), 2.01–1.15 (m, 24H), 0.89–0.85 (m,
6H); 13C NMR (75 MHz, CDCl3): d 194.4 (C), 194.2 (C),
134.5 (C), 134.2 (C), 133.9 (2!CH), 133.8 (2!CH), 128.8
(4!CH), 128.6 (2!CH), 71.5 (CH), 70.9 (CH), 60.7 (CH),
57.6 (CH), 33.5 (2!CH2), 31.6 (2!CH2), 29.2 (CH2), 29.0
(CH2), 25.4 (CH2), 25.0 (CH2), 22.4 (4!CH2), 13.9 (2!
CH3); MS (70 eV, EI) m/z (%) 247 [MKCl]C (5), 158 (5),
154 (16), 123 (20), 106 (8), 105 (100), 78 (13), 77 (38), 43
(21), 41 (22); IR (neat): n~Z3387, 3063, 2951, 2923, 2855,
1689, 1596, 1581, 1464, 1449 cmK1; RfZ0.45 (hexane/
EtOAc 5:1).
1
(300 MHz, CDCl3): d 4.25 (d, JZ3.4 Hz, 2H), 4.13–4.08
(m, 4H), 2.75–2.66 (m, 4H), 1.65–1.27 (m, 20H), 0.93 (t,
JZ7.2 Hz, 12H); 13C NMR (75 MHz, CDCl3): d 206.3 (C),
205.9 (C), 72.1 (CH), 71.4 (CH), 67.7 (CH), 64.1 (CH), 40.0
(CH2), 39.9 (CH2), 33.5 (2!CH2), 32.6 (2!CH2), 27.5
(CH2), 27.2 (CH2), 25.3 (2!CH2), 22.3 (2!CH2), 22.0
(2!CH3), 13.7 (2!CH3); IR (neat): n~Z3427, 2958, 2932,
2872, 1711, 1466, 1379 cmK1; RfZ0.23 (hexane/EtOAc
10:1).
4.2.8. 2-Chloro-1-hydroxy-1-phenylheptan-3-one (3h).
Data on the 50:50 mixture of diastereoisomers. Yellowish
4.2.3.
2-Chloro-3-cyclohexyl-3-hydroxy-1-phenyl-
1
oil. H NMR (300 MHz, CDCl3): d 7.41–7.32 (m, 10H),
propan-1-one (3c). White solid. 1H NMR (200 MHz,
CDCl3): d 8.00–7.26 (m, 5H), 5.32 (d, JZ2.8 Hz, 1H),
3.89 (ddd, JZ7.9, 4.8, 2.8 Hz, 1H), 3.06 (d, JZ4.8 Hz, 1H),
2.10–2.04 (m, 1H), 1.85–1.53 (m, 5H), 1.48–0.84 (m, 5H);
13C NMR (75 MHz, CDCl3): d 194.5 (C), 134.1 (C), 134.0
(CH), 128.8 (2!CH), 128.7 (2!CH), 75.0 (CH), 59.1
(CH), 40.1 (CH), 28.8 (CH2), 28.5 (CH2), 26.0 (CH2), 25.7
(CH2), 25.5 (CH2); MS (70 eV, EI) m/z (%) 231 [MKCl]C
(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); IR (neat):
n~Z3507, 3058, 2923, 2852, 1683, 1596, 1580, 1448, 1392,
1265, 1208, 1071 cmK1; RfZ0.47 (hexane/EtOAc 5:1).
5.16 (d, JZ5.3 Hz, 1H), 5.01 (d, JZ8.2 Hz, 1H), 4.44 (d,
JZ5.3 Hz, 1H), 4.35 (d, JZ8.2 Hz, 1H), 3.12 (s, 2H), 2.67–
2.30 (m, 4H), 2.30–1.66 (m, 8H), 0.91 (t, JZ6.9 Hz, 3H),
0.86 (t, JZ7.1 Hz, 3H); 13C NMR (75 MHz, CDCl3): d
205.5 (C), 205.2 (C), 139.0 (C), 138.7 (C), 128.4 (CH),
128.3 (2!CH), 128.2 (4!CH), 126.8 (2!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 (neat): n~Z3460, 3088,
3033, 1714, 1604, 1495, 1454, 1380, 1267, 1050 cmK1
;
RfZ0.30 (hexane/EtOAc 5:1).
4.2.9. (R*,R*)-4-Chloro-5-hydroxy-2,2-dimethylnonan-
3-one (3i). Yellow oil. 1H NMR (200 MHz, CDCl3): d
4.38 (d, JZ8.5 Hz, 1H), 4.03 (dt, JZ8.5, 2.3 Hz, 1H), 3.28
(s, 1H), 1.59–1.31 (m, 6H), 1.23 (s, 9H), 0.92 (t, JZ6.8 Hz,
3H); 13C NMR (75 MHz, CDCl3): d 210.6 (C), 72.0 (CH),
55.0 (CH), 44.6 (C), 32.3 (CH2), 27.2 (CH2), 26.2 (3!
CH3), 22.4 (CH2), 13.9 (CH3); IR (neat): n~Z3512, 2986,
2913, 2857, 1715, 1478, 1369, 1096 cmK1; RfZ0.37
(hexane/EtOAc 5:1).
4.2.4. 2-Chloro-3-hydroxy-1,3-diphenylpropan-1-one
(3d). Data on the 65:55 mixture of diastereoisomers.
White solid. 1H NMR (300 MHz, CDCl3): d 8.05–7.28
(m, 20H), 5.37 (d, JZ5.7 Hz, 1H), 5.31 (d, JZ5.7 Hz, 1H),
5.30 (d, JZ8.5 Hz, 1H), 5.20 (d, JZ8.5 Hz, 1H), 3.70 (s,
2H); 13C NMR (75 MHz, CDCl3): d 194.3 (C), 194.0 (C),
139.1 (C), 138.5 (C), 134.5 (2!C), 134.0 (CH), 128.9 (CH),
128.7 (4!CH), 128.1 (2!CH), 128.4 (4!CH), 128.3 (4!
CH), 128.2 (2!CH), 127.1 (CH), 126.7 (CH), 74.5 (CH),
73.2 (CH), 61.3 (CH), 57.4 (CH); IR (neat): n~Z3504, 3087,
4.2.10. 3-Chloro-4-hydroxy-4-(4-methoxyphenyl)butan-
2-one (3j). Orange oil. 1H NMR (300 MHz, CDCl3): d 7.83
(d, JZ6.9 Hz, 2H), 7.01 (d, JZ6.9 Hz, 2H), 5.99 (d, JZ
7.9 Hz, 2H), 3.89 (s, 3H), 3.28 (s, 1H), 1.28 (s, 3H); 13C
NMR (75 MHz, CDCl3): d 195.0 (C), 164.5 (C), 131.9 (2!
CH), 129.6 (C), 114.1 (2!CH), 78.4 (CH), 70.0 (CH), 55.4
(CH3), 22.7 (CH3); RfZ0.44 (hexane/EtOAc 5:1).
3032, 1964, 1903, 1695, 1595, 1580, 1453, 1307, 1062 cmK1
;
RfZ0.34 (hexane/EtOAc 5:1).
4.2.5. 2-Chloro-3-hydroxy-5-methyl-1-phenylhexan-1-
one (3e). Data on the 50:50 mixture of diastereoisomers.
1
Yellow oil. H NMR (300 MHz, CDCl3): d 7.61–7.45 (m,
10H), 7.99 (d, JZ7.9 Hz, 2H), 4.91 (d, JZ7.9 Hz, 2H), 4.29
(s, 2H), 2.14–1.54 (m, 6H), 0.94 (d, JZ6.9 Hz, 6H), 0.89 (d,
JZ6.9 Hz, 6H); 13C NMR (75 MHz, CDCl3): d 197.0 (C),
196.9 (C), 137.1 (2!C), 136.6 (2!CH), 131.5 (4!CH),
131.3 (4!CH), 72.7 (CH), 71.5 (CH), 63.5 (CH), 60.7
(CH), 45.0 (CH2), 44.3 (CH2), 26.8 (CH), 26.2 (CH), 25.8
4.3. General procedure for the synthesis of
(E)-a,b-unsaturated ketones (1) by using CrCl2
To a stirred suspension of CrCl2 (3 equiv) in THF (10 mL)
was added a solution of the corresponding 2-halo-3-hydroxy

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3296
ketone 3 (1 equiv). After stirring at reflux temperature for
4 h, the reaction was quenched with HCl 1 N (5 mL) and
extracted with diethyl ether (3!10 mL). The combined
extracts were washed with water, dried over Na2SO4 and
concentrated under reduced pressure. When it was
necessary, purification by flash chromatography on silica
gel (hexane/EtOAc 10:1) afforded the a,b-unsaturated
ketones 1.
(hexane/EtOAc 10:1). Anal. Calcd for C16H22O: C, 83.43;
H, 9.63. Found: C, 83.65; H, 9.75.
4.5.3. (E)-3-Cyclohexyl-1-phenylpropenone (1c). Yellow
oil. 1H NMR (300 MHz, CDCl3): d 7.93–7.26 (m, 5H), 7.01
(dd, JZ15.4, 6.7 Hz, 1H), 6.82 (dd, JZ15.4, 1.1 Hz, 1H),
2.26–2.22 (m, 1H), 1.85–1.70 (m, 5H), 1.36–1.19 (m, 5H);
13C NMR (75 MHz, CDCl3): d 191.3 (C), 154.9 (CH), 138.0
(C), 132.5 (CH), 128.4 (4!CH), 123.2 (CH), 41.0 (CH),
31.7 (2!CH2), 25.8 (CH2), 25.7 (2!CH2); MS (70 eV, EI)
m/z (%) 214 [M]C (13), 157.2 (7), 120 (9), 115 (9), 105
(100), 91 (9), 79 (12), 77 (60), 67 (14), 55 (21), 51 (20);
HRMS (70 eV) calcd for C15H18O 214.1358, found
214.1368; IR (neat): n~Z3084, 3057, 3025, 2996, 2925,
4.4. General procedure for the synthesis of
(E)-a,b-unsaturated ketones (1) by using Sml2
Over a solution of the starting a-chloro-b-hydroxy ketone 3
(0.4 mmol) in dry THF (2 mL) a solution of samarium
diiodide [prepared from 0.069 g of Sm (0.4 mmol), 5 mL of
dry THF and 0.032 mL of CH2I2] was added dropwise at
K25 8C. The reaction mixture was stirred at the same
temperature over 2 h and then heated at reflux for one
additional hour (the colour changed from yellow to orange).
The reaction mixture was quenched with 5 mL of 0.1 M HCl
and the usual workup gave the crude a,b-unsaturated
ketone. Purification by flash column chromatography over
silica or by distillation afforded the pure compound 1.
2851, 1725, 1665, 1614, 1578, 1446, 1336, 1016, 984 cmK1
;
RfZ0.40 (hexane/EtOAc 10:1). Anal. Calcd for C15H18O:
C, 84.07; H, 8.47. Found: C, 83.67; H, 8.39.
1
4.5.4. (E)-1,3-Diphenylpropenone (1d). White solid. H
NMR (300 MHz, CDCl3): d 8.08–7.28 (m, 12H); 13C NMR
(75 MHz, CDCl3): d 190.3 (C), 144.6 (CH), 137.9 (C), 134.6
(C), 132.6 (CH), 130.4 (CH), 128.8 (2!CH), 128.4 (2!
CH), 128.3 (4!CH), 121.7 (CH); MS (70 eV, EI) m/z (%)
208 [M]C (25), 207 (34), 179 (9), 165 (5), 131 (16), 103
(23), 102 (19), 77 (100), 51 (51), 50 (19). Anal. Calcd for
C15H12O: C, 86.51; H, 5.81. Found: C, 86.62; H, 5.73.
4.5. General procedure for the synthesis of
(E)-a,b-unsaturated ketones (1) by using Sml3
0.4 mmol of the starting ketone were treated with a solution
of 0.4 mmol of samarium triiodide (0.069 g of Sm, 5 mL of
dry THF and 0.150 g of I2) at K25 8C during 2 h and later
heated at reflux by one additional hour. The reaction was
quenched with 5 mL of 0.1 M HCl, extracted with
dichloromethane and concentrated. Purification by flash
column chromatography or by distillation yielded the pure
enone 1.
4.5.5. (E)-5-Methyl-1-phenylhex-2-en-1-one (1e). Yellow
oil. 1H NMR (300 MHz, CDCl3): d 7.96–7.11 (m, 5H), 7.06
(dt, JZ15.1, 7.0 Hz, 1H), 6.88 (d, JZ15.1 Hz, 1H), 2.23 (t,
JZ7.0 Hz, 2H), 2.18–1.80 (m, 1H), 0.98 (d, JZ6.5 Hz,
6H); 13C NMR (75 MHz, CDCl3): d 190.7 (C), 148.8 (CH),
137.9 (C), 132.5 (CH), 128.4 (4!CH), 126.9 (CH), 42.0
(CH2), 27.9 (CH), 22.4 (2!CH3); MS (70 eV, EI) m/z (%)
188 [M]C (5), 158 (120), 77 (30); IR (neat): n~Z3064, 2957,
2870, 1687, 1597, 1449, 1251 cmK1; RfZ0.32 (hexane/
EtOAc 10:1). Anal. Calcd for C13H16O: C, 82.94; H, 8.57.
Found: C, 83.01; H, 8.46.
1
4.5.1. (E)-1-Phenylhept-2-en-1-one (1a). Yellow oil. H
NMR (300 MHz, CDCl3): d 7.93–7.41 (m, 5H), 7.06 (dt,
JZ15.4, 6.8 Hz, 1H), 6.86 (d, JZ15.4 Hz, 1H), 2.29 (q, JZ
6.8 Hz, 2H), 1.70–1.19 (m, 4H), 0.92 (t, JZ7.3 Hz, 3H); 13C
NMR (75 MHz, CDCl3): d 190.8 (C), 150.1 (CH), 137.9
(C), 132.5 (CH), 125.8 (CH), 128.4 (4!CH), 32.4 (CH2),
30.1 (CH2), 22.2 (CH2), 13.7 (CH3); MS (70 eV, EI) m/z (%)
188 [M]C (15), 159 (14), 145 (14), 131 (14), 115 (18), 105
(100), 91 (18), 77 (85), 55 (42), 51 (37), 43 (22), 41 (40); IR
(neat): n~Z3085, 3059, 3028, 2957, 2930, 2871, 1725, 1670,
1620, 1597, 1447, 1344, 1282, 1003 cmK1; RfZ0.34
(hexane/EtOAc 10:1). Anal. Calcd for C13H16O: C, 82.94;
H, 8.57. Found: C, 83.17; H, 8.46.
4.5.6. (E)-1,4-Diphenylpent-2-en-1-one (1f). Yellowish
oil. 1H NMR (300 MHz, CDCl3): d 7.96 (dd, JZ6.9,
1.5 Hz, 2H), 7.58–7.24 (m, 9H), 6.91 (dd, JZ15.5, 1.4 Hz,
1H), 3.79 (quint., JZ7.0 Hz, 1H), 1.57 (d, JZ7.0 Hz, 3H);
13C NMR (75 MHz, CDCl3): d 190.9 (C), 152.9 (CH), 143.3
(C), 137.8 (C), 132.6 (CH), 128.6 (2!CH), 128.4 (4!CH),
127.3 (2!CH), 126.7 (CH), 124.4 (CH), 42.5 (CH), 20.4
(CH3); MS (70 eV, EI) m/z (%) 236 [M]C (19), 221 (8), 131
(27), 105 (100), 77 (46); IR (neat): n~Z3027, 2968, 1669,
1619, 1448, 1290 cmK1; RfZ0.57 (hexane/EtOAc 3:1).
Anal. Calcd for C17H16O: C, 86.40; H, 6.82. Found: C,
86.49; H, 6.73.
4.5.2. (E)-1-Phenyldec-2-en-1-one (1b). Yellow oil. 1H
NMR (300 MHz, CDCl3): d 7.96–7.38 (m, 5H), 7.08 (dt,
JZ15.4, 6.7 Hz, 1H), 6.88 (d, JZ15.4 Hz, 1H), 2.32 (q, JZ
6.7 Hz, 2H), 1.65–1.21 (m, 10H), 0.89 (t, JZ6.8 Hz, 3H);
13C NMR (50 MHz, CDCl3): d 190.7 (C), 150.0 (CH), 137.8
(C), 132.4 (CH), 128.4 (4!CH), 125.6 (CH), 32.7 (CH2),
31.6 (CH2), 29.0 (CH2), 28.9 (CH2), 28.0 (CH2), 22.5 (CH2),
13.9 (CH3); MS (70 eV, EI) m/z (%) 230 [M]C (3), 159 (15),
145 (13), 133 (19), 120 (3), 105 (100), 91 (16), 77 (69), 73
(28), 55 (33), 43 (51), 41 (65); HRMS (70 eV) calcd for
C16H22O 230.1671, found 230.1679; IR (neat): n~Z3059,
2956, 2927, 2855, 1672, 1622, 1463, 1448 cmK1; RfZ0.34
1
4.5.7. (E)-Undec-6-en-5-one (1g). Yellow oil. H NMR
(300 MHz, CDCl3): d 6.80 (dt, JZ14.9, 6.9 Hz, 1H), 6.06
(d, JZ14.9 Hz, 1H), 2.50 (t, JZ7.1 Hz, 2H), 2.19 (q, JZ
7.1 Hz, 2H), 1.59–1.28 (m, 8H), 0.89 (t, JZ7.1 Hz, 6H); 13C
NMR (75 MHz, CDCl3): d 200.9 (C), 147.2 (CH), 130.2
(CH), 39.7 (CH2), 32.0 (CH2), 30.1 (CH2), 26.3 (CH2), 22.3
(CH2), 21.9 (CH2), 13.8 (CH3), 13.7 (CH3); MS (70 eV, EI)
m/z (%) 168 [M]C (!1), 126 (26), 111 (100), 83 (7), 55
(94), 29 (17); IR (neat): n~Z3024, 2961, 2869, 1700, 1676,
1633, 1465, 1261 cmK1; RfZ0.49 (hexane/EtOAc 5:1).

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Anal. Calcd for C11H20O: C, 78.51; H, 11.98. Found: C,
78.73; H, 11.86.
72.4 (CH), 71.7 (CH), 61.9 (CH), 59.4 (CH), 52.9 (CH3),
52.7 (CH3), 31.9 (CH2), 31.5 (CH2), 29.1 (CH2), 28.9 (CH2),
25.7 (CH2), 25.2 (CH2), 24.9 (2!CH2), 24.5 (2!CH2),
22.4 (2!CH2), 13.8 (2!CH3); IR (neat): n~Z3452,
1754 cmK1; RfZ0.30 (hexane/EtOAc 5:1).
1
4.5.8. (E)-1-Phenylhept-1-en-3-one (1h). Yellow oil. H
NMR (200 MHz, CDCl3): d 7.70–7.37 (m, 6H), 6.76 (d, JZ
16.2 Hz, 1H), 2.68 (t, JZ7.4 Hz, 2H), 1.76–1.27 (m, 4H),
0.92 (t, JZ7.2 Hz, 3H); 13C NMR (50 MHz, CDCl3): d
200.6 (C), 142.2 (CH), 134.5 (C), 130.3 (CH), 128.8 (CH),
128.2 (2!CH), 126.2 (2!CH), 40.6 (CH2), 26.4 (CH2),
22.4 (CH2), 13.8 (CH3); MS (70 eV, EI) m/z (%) 188 [M]C
(7), 146 (41), 131 (100), 103 (46), 77 (27), 51 (8); HRMS
(70 eV) calcd for C13H16O 188.1201, found 188.1198; IR
(neat): n~Z3021, 2937, 2865, 1686, 1620, 1500, 1181,
1069 cmK1; RfZ0.47 (hexane/EtOAc 5:1). Anal. Calcd for
C13H16O: C, 82.94; H, 8.57. Found: C, 83.03; H, 8.51.
4.6.2. Methyl 2-chloro-3-(4-chlorophenyl)-3-hydroxy-
propanoate (4b). Data on the 50:50 mixture of diastereo-
1
isomers. Yellow oil. H NMR (300 MHz, CDCl3): d 7.33–
7.26 (m, 8H), 5.07 (d, JZ6.0 Hz, 1H), 4.95 (d, JZ6.0 Hz,
1H), 4.46 (s, 2H), 4.42 (dd, JZ6.0, 1.5 Hz, 1H), 4.33 (dd,
JZ6.0, 1.5 Hz, 1H), 3.76 (s, 3H), 3.65 (s, 3H); 13C NMR
(75 MHz, CDCl3): d 169.0 (C), 168.1 (C), 137.1 (C), 136.7
(C), 134.0 (2!C), 128.3 (CH), 128.2 (2!CH), 128.1 (4!
CH), 127.7 (CH), 74.1 (CH), 73.4 (CH), 62.2 (CH), 58.8
(CH), 53.0 (CH3), 52.8 (CH3); IR (neat): n~Z3468, 1744,
1493, 1285 cmK1; RfZ0.40 (hexane/EtOAc 5:1).
4.5.9. (E)-2,2-Dimethylnon-4-en-3-one (1i). Pale orange
oil. 1H NMR (300 MHz, CDCl3): d 6.94 (dt, JZ15.2,
6.8 Hz, 1H), 6.47 (d, JZ15.2 Hz, 1H), 2.18 (q, JZ7.1 Hz,
2H), 1.47–1.21 (m, 4H), 1.15 (s, 9H), 0.91 (t, JZ7.1 Hz,
3H); 13C NMR (75 MHz, CDCl3): d 204.4 (C), 147.6 (CH),
124.0 (CH), 42.7 (C), 32.1 (CH2), 30.2 (CH2), 26.1 (3!
CH3), 22.2 (CH2), 13.8 (CH3); MS (70 eV, EI) m/z (%) 168
[M]C (5), 111 (100), 83 (8), 57 (30); IR (neat): n~Z2958,
4.6.3. Methyl 2-chloro-3-hydroxy-4-phenylpentanoate
(4c). Data on the 50:50 mixture of diastereoisomers. Yellow
1
oil. H NMR (200 MHz, CDCl3): d 7.50–7.20 (m, 10H),
4.24 (dd, JZ1.4 Hz, 2H), 4.14–4.02 (m, 4H), 3.78 (s, 3H),
3.58 (s, 3H), 2.851 (s, 2H), 1.45 (d, JZ6.9 Hz, 3H), 1.36 (d,
JZ6.9 Hz, 3H); 13C NMR (75 MHz, CDCl3): d 169.1 (C),
169.0 (C), 142.8 (C), 142.3 (C), 128.6 (CH), 128.5 (2!CH),
128.2 (2!CH), 128.0 (2!CH), 127.6 (2!CH), 127.3
(CH), 76.8 (CH), 76.3 (CH), 60.7 (CH), 57.1 (CH), 52.9
(CH3), 52.7 (CH3), 43.0 (CH), 40.9 (CH), 18.0 (CH3), 14.5
2929, 2871, 1705, 1624, 1458, 1364, 1066, 1003, 720 cmK1
;
RfZ0.47 (hexane/EtOAc 10:1). Anal. Calcd for C11H20O:
C, 78.51; H, 11.98. Found: C, 78.75; H, 11.86.
(CH3); IR (neat): n~Z2950, 1717, 1632, 1168, 1039 cmK1
RfZ0.32 (hexane/EtOAc 5:1).
;
4.5.10. (E)-4-(4-Methoxyphenyl)but-3-en-2-one (1j).
1
Yellow oil. H NMR (400 MHz, CDCl3): d 7.92 (d, JZ
11.5 Hz, 1H), 7.43 (d, JZ11.2 Hz, 2H), 6.84 (d, JZ
11.2 Hz, 2H), 6.54 (d, JZ11.5 Hz, 1H), 3.77 (s, 3H), 2.29 (s,
3H); 13C NMR (100 MHz, CDCl3): d 198.6 (C), 161.6 (C),
143.4 (CH), 129.9 (2!CH), 126.9 (C), 124.9 (CH), 114.4
(2!CH), 55.3 (CH3), 27.3 (CH3); MS (70 eV, EI) m/z (%)
176 [M]C (52), 161 (100), 145 (8), 133 (48), 118 (16), 89
(17), 77 (14); IR (neat): n~Z2959, 2918, 2849, 1664, 1602,
1512, 1250 cmK1; RfZ0.48 (hexane/EtOAc 1:1). Anal.
Calcd for C11H12O2: C, 74.98; H, 6.86. Found: C, 75.09; H,
6.77.
4.6.4. Ethyl 2-chloro-3-hydroxy-2-methyldecanoate (4d).
Data on the 60:40 mixture of diastereoisomers. Yellow oil.
1H NMR (300 MHz, CDCl3): d 4.25 (q, JZ7.1 Hz, 2H),
4.24 (q, JZ7.1 Hz, 2H), 3.98 (s, 1H), 3.96 (s, 1H), 2.61 (m,
2H), 1.71 (s, 3H), 1.70 (s, 3H), 1.67–1.27 (m, 30H), 0.86 (t,
JZ7.1 Hz, 3H), 0.79 (t, JZ7.1 Hz, 3H); 13C NMR
(75 MHz, CDCl3): d 170.9 (C), 170.5 (C), 75.9 (CH), 75.6
(CH), 73.6 (C), 71.1 (C), 62.2 (2!CH2), 31.6 (CH2), 31.5
(CH2), 31.0 (4!CH2), 29.2 (4!CH2), 29.1 (CH2), 26.2
(CH2), 22.5 (2!CH3), 22.2 (2!CH3), 13.9 (CH3), 13.8
(CH3); IR (neat): n~Z3425, 1741 cmK1; RfZ0.26 (hexane/
EtOAc 10:1).
4.6. General procedure for the synthesis of starting
compounds 4
To a K78 8C stirred solution of the a-haloester (9.7 mmol)
in dry THF (8 mL) was added dropwise lithium diisopro-
pylamide [prepared from MeLi (6.5 mL of 1.5 M solution in
ether) and diisopropylamine (1.4 mL, 10 mmol) in THF
(50 mL) at 0 8C]. After stirring for 10 min, a solution of the
aldehyde (5 mmol) in dry THF (4.5 mL) was added
dropwise at K78 8C and the mixture was stirred for 2 h.
Then the reaction mixture was quenched with an aqueous
saturated solution of NH4Cl (20 mL). Usual workup
provided the corresponding a-halo-b-hydroxyester 4,
which was purified by flash column chromatography on
silica gel (hexane/EtOAc 10:1).
4.6.5. Ethyl 2-chloro-3-cyclohexyl-3-hydroxy-2-methyl-
propanoate (4e). Data on the 50:50 mixture of diastereo-
1
isomers. White solid. H NMR (300 MHz, CDCl3): d 4.14
(q, JZ7.2 Hz, 4H), 3.84–3.76 (m, 2H), 2.90 (s, 2H), 1.93–
1.09 (m, 22H), 1.88 (s, 6H), 1.21 (t, JZ7.2 Hz, 6H); 13C
NMR (50 MHz, CDCl3): d 170.9 (C), 170.5 (C), 79.3 (CH),
78.7 (CH), 73.6 (C), 71.9 (C), 62.0 (CH2), 61.9 (CH2), 40.7
(CH), 40.3 (CH), 31.0 (CH2), 30.5 (CH2), 30.2 (CH2), 28.4
(CH2), 27.9 (CH2), 26.2 (CH2), 25.9 (CH2), 25.8 (CH2), 25.1
(CH2), 24.9 (CH2), 21.8 (CH3), 21.2 (CH3), 13.6 (CH3), 13.3
(CH3); RfZ0.31 (hexane/EtOAc 10:1).
4.6.6. Ethyl 2-chloro-3-hydroxy-2-methyl-3-phenyl-
propanoate (4f). Pale yellow solid. H NMR (200 MHz,
1
4.6.1. Methyl 2-chloro-3-hydroxydecanoate (4a). Data on
the 50:50 mixture of diastereoisomers. Yellow oil. 1H NMR
(300 MHz, CDCl3): d 4.27 (d, JZ3.9 Hz, 1H), 4.14 (d, JZ
3.9 Hz, 1H), 4.12–3.90 (m, 2H), 3.88–3.75 (m, 2H), 3.73 (s,
3H), 3.71 (s, 3H), 1.66–1.21 (m, 24H), 0.80 (t, JZ6.8 Hz,
6H); 13C NMR (75 MHz, CDCl3): d 169.2 (C), 168.9 (C),
CDCl3): d 7.46–7.34 (m, 5H), 5.22 (s, 1H), 4.29 (q, JZ
7.1 Hz, 2H), 3.22 (s, 1H), 1.66 (s, 3H), 1.32 (t, JZ7.1 Hz,
3H); 13C NMR (75 MHz, CDCl3): d 170.8 (C), 137.4 (C),
128.3 (CH), 128.1 (CH), 127.9 (CH), 127.7 (CH), 127.6
(CH), 77.6 (CH), 69.4 (C), 62.4 (CH2), 21.6 (CH3), 13.8

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3298
(CH3); IR (neat): n~Z2994, 1724, 1454 cmK1; RfZ0.43
(hexane/EtOAc 5:1).
filtration through a pad of Celite provided a,b-unsaturated
esters 2, which were purified by flash column chromato-
graphy on silica gel (hexane/EtOAc 15:1).
4.6.7. Ethyl 2-chloro-3-hydroxy-2-methyl-3-(4-methoxy-
phenyl)propanoate (4g). Data on the 75:25 mixture of
diastereoisomers. Pale orange oil. 1H NMR (300 MHz,
CDCl3): d 7.37–7.28 (m, 4H), 6.89–6.80 (m, 4H), 5.21 (s,
1H), 5.15 (s, 1H), 4.27 (q, JZ7.2 Hz, 2H), 4.26 (q, JZ
7.2 Hz, 2H), 3.78 (s, 3H), 3.73 (s, 3H), 3.29 (m, 2H), 1.64 (s,
3H), 1.57 (s, 3H), 1.31 (t, JZ7.2 Hz, 6H); 13C NMR
(75 MHz, CDCl3): d 170.8 (C), 170.4 (C), 159.4 (C), 159.3
(C), 129.8 (C), 129.4 (2!CH), 129.2 (2!CH), 128.9 (C),
113.1 (2!CH), 112.9 (2!CH), 77.0 (2!CH), 73.5 (C),
69.8 (C), 62.3 (CH2), 62.1 (CH2), 55.0 (2!CH3), 22.6
(CH3), 21.4 (CH3), 13.7 (2!CH3); IR (neat): n~Z3490,
1737 cmK1; RfZ0.33 (hexane/EtOAc 5:1).
4.7.1. (E)-Methyl dec-2-enoate (2a). Yellow oil. 1H NMR
(200 MHz, CDCl3): d 6.96 (dt, JZ15.4, 7.0 Hz, 1H), 5.81
(dt, JZ15.4, 1.3 Hz, 1H), 3.71 (s, 3H), 2.23–2.14 (m, 2H),
1.46–1.26 (m, 10H), 0.87 (t, JZ6.8 Hz, 3H); 13C NMR
(50 MHz, CDCl3): d 167.1 (C), 149.8 (CH), 120.7 (CH),
51.3 (CH3), 32.1 (CH2), 31.6 (CH2), 29.0 (CH2), 28.9 (CH2),
27.9 (CH2), 22.5 (CH2), 14.0 (CH3); MS (70 eV, EI) m/z (%)
184 [M]C (!1), 153 (28), 87 (100); IR (neat): n~Z2928,
1728, 1651 cmK1; HRMS (70 eV) calcd for C11H20O2
184.2753, found 184.1463; RfZ0.50 (hexane/EtOAc 10:1).
Anal. Calcd for C11H20O2: C, 71.70; H, 10.94. Found: C,
71.81; H, 10.85.
4.6.8. Ethyl 2-bromo-3-hydroxy-2-hexyl-3-phenyl-
propanoate (4h). Data on the 50:50 mixture of diastereo-
4.7.2. (E)-Methyl 3-(4-chlorophenyl)prop-2-enoate (2b).
Yellow oil. H NMR (300 MHz, CDCl3): d 7.68 (d, JZ
1
1
isomers. Yellow oil. H NMR (300 MHz, CDCl3): d 7.44–
16.1 Hz, 1H), 7.50–7.48 (AB system, JZ6.5 Hz, 4H), 6.45
(d, JZ16.1 Hz, 1H), 3.85 (s, 3H); 13C NMR (75 MHz,
CDCl3): d 167.1 (C), 143.3 (CH), 136.1 (C), 132.8 (C),
129.1 (2!CH), 129.0 (2!CH), 118.3 (CH), 51.7 (CH3); IR
(neat): n~Z2283, 1728, 1168, 937, 821, 731 cmK1; RfZ0.51
(hexane/EtOAc 3:1). Anal. Calcd for C10H9ClO2: C, 61.08;
H, 4.61. Found: C, 61.28; H, 4.49.
7.33 (m, 10H), 5.09 (s, 2H), 4.25 (q, JZ7.1 Hz, 4H), 3.60 (s,
2H), 2.06–1.76 (m, 4H), 1.56–1.20 (m, 22H), 0.90 (t, JZ
7.1 Hz, 6H); 13C NMR (75 MHz, CDCl3): d 169.7 (C),
169.2 (C), 138.3 (C), 137.8 (C), 127.8 (2!CH), 127.7 (2!
CH), 127.6 (4!CH), 127.1 (2!CH), 78.1 (CH), 77.6 (CH),
75.6 (C), 73.8 (C), 62.0 (CH2), 61.7 (CH2), 37.6 (CH2), 37.0
(CH2), 31.4 (CH2), 31.1 (CH2), 31.0 (CH2), 28.8 (CH2), 28.6
(CH2), 25.8 (CH2), 25.5 (CH2), 22.1 (CH2), 13.6 (CH3), 13.5
(CH3), 13.4 (CH3), 13.3 (CH3); IR (neat): n~Z3503, 2956,
1734, 1717 cmK1; RfZ0.32 (hexane/EtOAc 5:1).
4.7.3. (E)-Methyl 4-phenylpent-2-enoate (2c). Yellow oil.
1H NMR (200 MHz, CDCl3): d 7.50–7.17 (m, 5H), 7.13 (d,
JZ15.6 Hz, 1H), 5.83 (dd, JZ15.6, 1.6 Hz, 1H), 3.78 (s,
3H), 3.67–3.57 (q, JZ7.0 Hz, 1H), 1.44 (d, JZ7.0 Hz, 3H);
13C NMR (75 MHz, CDCl3): d 167.0 (C), 152.8 (CH), 143.1
(C), 129.0 (2!CH), 127.6 (2!CH), 127.2 (CH), 119.5
(CH), 52.8 (CH3), 41.9 (CH), 20.0 (CH3); MS (70 eV, EI) m/
z (%) 190 [M]C (21), 175 (5), 131 (100), 115 (74), 91 (46),
77 (23); RfZ0.53 (hexane/EtOAc 5:1). Anal. Calcd for
C12H14O2: C, 75.76; H, 7.42. Found: C, 75.87; H, 7.31.
4.6.9. Ethyl 2-bromo-3-hydroxy-2-pentyl-3-phenyl-
propanoate (4i). Yellow oil. 1H NMR (300 MHz,
CDCl3): d 7.44–7.36 (m, 5H), 5.12 (s, 1H), 4.30 (q, JZ
7.1 Hz, 2H), 3.39 (s, 1H), 2.06–1.83 (m, 2H), 1.79–1.24 (m,
9H), 0.90 (t, JZ7.1 Hz, 3H); 13C NMR (75 MHz, CDCl3): d
170.1 (C), 137.8 (C), 128.3 (CH), 128.0 (CH), 127.9 (2!
CH), 127.6 (CH), 77.6 (CH), 75.9 (C), 62.5 (CH2), 37.3
(CH2), 31.4 (CH2), 25.5 (CH2), 22.1 (CH2), 13.8 (CH3), 13.7
(CH3); IR (neat): n~Z3503, 2931, 1734, 1455 cmK1; RfZ
0.31 (hexane/EtOAc 5:1).
4.7.4. (E)-Ethyl 2-methyldec-2-enoate (2d). Yellow oil. 1H
NMR (300 MHz, CDCl3): d 6.81–6.72 (m, 1H), 4.20 (q, JZ
7.2 Hz, 2H), 2.21–2.11 (m, 2H), 1.84 (s, 3H), 1.75–1.25 (m,
13H), 0.87 (t, JZ7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3):
d 168.3 (C), 142.4 (CH), 127.5 (C), 60.3 (CH2), 31.7 (CH2),
29.3 (CH2), 29.0 (CH2), 28.6 (CH2), 28.5 (CH2), 22.5 (CH2),
14.2 (CH3), 14.0 (CH3), 12.2 (CH3); MS (70 eV, EI) m/z (%)
212 [M]C (19), 167 (80), 113 (73); IR (neat): n~Z2928,
1728, 1651 cmK1; RfZ0.50 (hexane/EtOAc 10:1). Anal.
Calcd for C13H24O2: C, 73.54; H, 11.39. Found: C, 73.76; H,
11.24.
4.6.10. Isopropyl 2-chloro-3-cyclohexyl-3-hydroxy-2-
methylpropanoate (4j). Data on the 65:55 mixture of
diastereoisomers. Yellow oil. 1H NMR (200 MHz, CDCl3):
d 5.07 (apparent quint., JZ6.1 Hz, 2H), 3.81 (d, JZ4.7 Hz,
1H), 3.75 (d, JZ4.7 Hz, 1H), 2.58 (s, 2H), 1.75 (s, 3H), 1.71
(s, 3H), 1.91–1.18 (m, 22H), 1.30 (d, JZ6.1 Hz, 6H), 1.27
(d, JZ6.1 Hz, 6H); 13C NMR (75 MHz, CDCl3): d 170.4
(C), 170.0 (C), 79.4 (CH), 78.8 (CH), 73.8 (C), 72.2 (C),
69.9 (CH), 69.7 (CH), 40.7 (CH), 40.3 (CH), 31.2 (CH2),
30.8 (CH2), 28.4 (CH2), 26.6 (CH2), 26.3 (2!CH2), 26.0
(2!CH2), 25.9 (2!CH2), 22.4 (2!CH3), 21.9 (CH3), 21.5
(CH3), 21.2 (CH3), 21.1 (CH3); IR (neat): n~Z3499, 1732,
1450, 1376, 1266 cmK1; RfZ0.37 (hexane/EtOAc 5:1).
4.7.5. (E)-Ethyl 3-cyclohexyl-2-methylpropenoate (2e).
1
White solid. H NMR (300 MHz, CDCl3): d 6.57 (d, JZ
9.6 Hz, 1H), 4.17 (q, JZ7.2 Hz, 2H), 2.45–2.25 (m, 1H),
1.82 (s, 3H), 1.83–1.05 (m, 10H), 1.28 (t, JZ7.2 Hz, 3H);
13C NMR (75 MHz, CDCl3): d 168.5 (C), 147.2 (CH), 125.8
(C), 60.3 (CH2), 37.6 (CH), 31.8 (2!CH2), 25.8 (CH2),
25.5 (2!CH2), 14.2 (CH3), 12.3 (CH3); MS (70 eV, EI) m/z
(%) 196 [M]C (30), 151 (34), 123 (10); IR (neat): n~Z2926,
1709, 1649, 1381 cmK1; RfZ0.54 (hexane/EtOAc 10:1).
Anal. Calcd for C12H20O2: C, 73.43; H, 10.27. Found: C,
73.48; H, 10.15.
4.7. General procedure for the synthesis
of a,b-unsaturated esters 2
To a stirred solution of the corresponding b-hydroxyester
a-halogenated 4 (0.4 mmol) in dry THF (5 mL) was added
CrCl2 (0.15 g, 1.2 mmol). After 4 h at reflux the reaction
mixture was quenched with water. Usual workup and

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J. M. Concellon et al. / Tetrahedron 62 (2006) 3292–3300
3299
4.7.6. (E)-Ethyl 2-methyl-3-phenylprop-2-enoate (2f).
Yellow oil. H NMR (300 MHz, CDCl3): d 7.71 (s, 1H),
Acknowledgements
1
´
We thank Ministerio de Educacion y Cultura (CTQ2004-
01191/BQU) for financial support and to Vicente del Amo
for his revision of the English. C.M. thanks Ministerio de
7.69–7.26 (m, 5H), 4.23 (q, JZ7.0 Hz, 2H), 2.14 (s, 3H),
1.30 (t, JZ7.0 Hz, 3H); 13C NMR (75 MHz, CDCl3): d
168.6 (C), 138.6 (CH), 135.9 (C), 129.5 (2!CH), 128.3 (C),
128.1 (3!CH), 60.8 (CH2), 14.2 (CH3), 14.0 (CH3); MS
(70 eV, EI) m/z (%) 190 [M]C (29), 115 (100), 145 (40), 91
(40); IR (neat): n~Z2927, 1708, 1638, 764 cmK1; RfZ0.61
(hexane/EtOAc 3:1). Anal. Calcd for C12H14O2: C, 75.76;
H, 7.42. Found: C, 75.87; H, 7.53.
´
Educacion y Cultura for a predoctoral fellowship. J.M.C.
thanks Carmen Fernandez-Florez for her time.
´
´
References and notes
4.7.7. (E)-Ethyl 2-methyl-3-(4-methoxyphenyl)propeno-
ate (2g). Orange oil. 1H NMR (300 MHz, CDCl3): d 7.60 (s,
1H), 7.37 (d, JZ8.3 Hz, 2H), 6.89 (d, JZ8.3 Hz, 2H), 4.25
(q, JZ7.1 Hz, 2H), 3.80 (s, 3H), 2.12 (s, 3H), 1.33 (t, JZ
7.1 Hz, 3H); 13C NMR (75 MHz, CDCl3): d 168.8 (C),
159.4 (C), 138.2 (CH), 131.2 (2!CH), 128.3 (C), 126.1 (C),
113.6 (2!CH), 60.6 (CH2), 55.0 (CH3), 14.2 (CH3), 13.9
(CH3); MS (70 eV, EI) m/z (%) 220 [M]C (100), 191 (32),
175 (85), 147 (83), 131 (72), 91 (75), 77 (59); IR (neat): n~Z
2975, 1702, 1605 cmK1; RfZ0.43 (hexane/EtOAc 5:1).
Anal. Calcd for C13H16O3: C, 70.89; H, 7.32. Found: C,
71.02; H, 7.25.
1. (a) Patai, S., Ed.; The Chemistry of Alkenes; Interscience:
New York, 1968; Vol. 2. (b) Shen, Y. Acc. Chem. Res. 1998,
31, 584–592.
2. For a review on the synthetic applications of a,b-unsaturated
ketones see: (a) Patai, S.; Rappoport, Z. The Chemistry of
Enones; Wiley: Chichester, 1989; pp 281–312. To see recent
synthetic applications of a,b-unsaturated ketones: (b)
Zhenghong, Z.; Yilong, T.; Lixin, W.; Guofeng, Z.; Qilin,
Z.; Chuchi, T. Synth. Commun. 2004, 1359–1365.
3. For a recent review of the syntheses of a,b-unsaturated ketones
see: (a) Foster, C. E.; Mackie, P. R. In Katritzky, A. R., Taylor,
R. J. K., Eds.; Comprehensive Organic Functional Group
Transformations II; Elsevier Ltd: Oxford, UK, 2005; Vol. 3,
pp 215–266.
4.7.8. (E)-Ethyl 2-hexyl-3-phenylprop-2-enoate (2h).
Yellow oil. H NMR (200 MHz, CDCl3): d 7.67 (s, 1H),
1
4. (a) Mulzer, J.; Sieg, A.; Bru¨cher, C.; Mu¨ller, D.; Martin, H. J.
Synlett 2005, 685–692. (b) Sano, S.; Yokoyama, K.; Shiro, M.;
Nagao, Y. Chem. Pharm. Bull. 2002, 50, 706–709. (c) Snider,
B. B.; Shi, B. Tetrahedron Lett. 2001, 42, 9123–9126. (d) Lee,
H. K.; Kim, E.-K.; Pak, C. S. Tetrahedron Lett. 2002, 43,
9641–9644. (e) Maryanoff, B. E.; Reitz, A. B. Chem. Rev.
1989, 89, 863–927.
7.41–7.36 (m, 5H), 4.33 (q, JZ7.2 Hz, 2H), 2.54 (t, JZ
7.2 Hz, 3H), 1.60–0.90 (m, 10H), 1.37 (t, JZ6.9 Hz, 3H);
13C NMR (50 MHz, CDCl3): d 168.4 (C), 138.3 (CH), 135.8
(C), 133.9 (C), 129.0 (CH), 128.3 (3!CH), 128.0 (CH),
60.6 (CH2), 31.4 (CH2), 29.3 (CH2), 29.1 (CH2), 27.4 (CH2),
22.5 (CH2), 14.2 (CH3), 13.9 (CH3); MS (70 eV, EI) m/z (%)
260 [M]C (33), 144 (30), 172 (29), 77 (26); IR (neat): n~Z
2957, 2858, 1709, 1630 cmK1; RfZ0.59 (hexane/EtOAc
5:1). Anal. Calcd for C17H24O2: C, 78.42; H, 9.29. Found:
C, 78.60; H, 9.13.
5. (a) Shibuya, M.; Ito, S.; Takahashi, M.; Iwabuchi, Y. Org. Lett.
´
2004, 6, 4303–4306. (b) Jurado-Gonzalez, M.; Sullivan, A. C.;
Wilson, J. R. Tetrahedron Lett. 2004, 45, 4465–4468.
(c) Bora, U.; Chaudhuri, M. K.; Dey, D.; Kalita, D.;
Kharmawphlang, W.; Mandal, G. C. Tetrahedron 2001, 57,
2445–2448. (d) Pelter, A.; Colclough, M. E. Tetrahedron Lett.
1986, 27, 1935–1938.
4.7.9. (E)-Ethyl 2-penthyl-3-phenylprop-2-enoate (2i).
Yellow oil. H NMR (300 MHz, CDCl3): d 7.65 (s, 1H),
1
6. (a) Kim, J. H.; Lim, H. J.; Cheon, S. H. Tetrahedron 2003, 59,
7501–7507. (b) Tachihara, T.; Kitahara, T. Tetrahedron 2003,
59, 1773–1780. (c) Clive, D.; Stephen, P. Chem. Commun.
2002, 1940–1941. (d) Schwarz, I.; Braun, M. Chem. Eur. J.
1999, 5, 2300–2305. (e) Taber, D. F.; Herr, R. J.; Pack, S. K.;
Geremia, J. M. J. Org. Chem. 1996, 61, 2908–2910.
7. (a) Figadere, B.; Franck, X. In Cossy, J., Ed.; Science of
Synthesis; Thieme Chemistry: Paris, France, 2004; Vol. 26; p
401. (b) Hermanson, J. R.; Hershberger, J. W.; Pinhas, A. R.
Organometallics 1995, 14, 5426–5437.
7.37–7.26 (m, 5H), 4.33 (q, JZ7.2 Hz, 2H), 1.72–1.37 (m,
8H), 1.33 (t, JZ7.2 Hz, 3H), 0.91 (t, JZ10.1 Hz, 3H); 13
C
NMR (75 MHz, CDCl3): d 168.4 (C), 138.3 (CH), 135.8
(C), 133.9 (C), 129.1 (2!CH), 128.3 (2!CH), 128.1 (CH),
60.4 (CH2), 31.8 (CH2), 28.9 (CH2), 27.4 (CH2), 22.3 (CH2),
14.2 (CH3), 13.9 (CH3); MS (70 eV, EI) m/z (%) 246 [M]C
(35), 217 (17), 129 (32), 117 (17); IR (neat): n~Z2957, 2930,
1709, 765, 700 cmK1; RfZ0.58 (hexane/EtOAc 5:1). Anal.
Calcd for C16H22O2: C, 78.01; H, 9.00. Found: C, 78.25;
H, 9.05.
8. (a) Xi, Z.; Fan, H.-T.; Mito, S.; Takahashi, T. J. Organomet.
Chem. 2003, 108–112. (b) Deshong, P.; Sidler, D. R.
Tetrahedron Lett. 1987, 28, 2233–2236.
4.7.10. (E)-Isopropyl 3-cyclohexyl-2-methylprop-2-
enoate (2j). Yellowish oil. H NMR (400 MHz, CDCl3): d
9. For a recent synthesis of a,b-unsaturated esters, see: List, B.;
Doehring, A.; Hechavarria Fonseca, M. T.; Wobser, K.; van
Thienen, H.; Rios Torres, R.; Llamas Galilea, P. Adv. Synth.
Catal. 2005, 347, 1558–1560.
1
6.57 (d, JZ9.6 Hz, 1H), 5.06 (apparent quint., JZ6.3 Hz,
1H), 1.84 (s, 3H), 1.68–1.27 (m, 11H), 1.28 (d, JZ6.3 Hz,
6H); 13C NMR (50 MHz, CDCl3): d 168.1 (C), 146.8 (CH),
136.4 (C), 67.5 (CH), 37.7 (CH), 31.9 (2!CH2), 25.8 (2!
CH2), 25.6 (CH2), 21.8 (2!CH3), 12.3 (CH3); MS (70 eV,
EI) m/z (%) 210 [M]C (9), 168 (100), 151 (48), 82 (61), 43
(27); RfZ0.50 (hexane/EtOAc 5:1). Anal. Calcd for
C13H22O2: C, 74.24; H, 10.54. Found: C, 74.33; H, 10.41.
10. For reviews for the synthesis of a,b-unsaturated esters, see: (a)
Franklin, A. S. J. Chem. Soc., Perkin Trans. 1 1998,
2451–2465. (b) Shen, Y. Acc. Chem. Res. 1998, 31, 584–592.
¨
11. (a) Patil, V. J.; Mavers, U. Tetrahedron Lett. 1996, 37,
1281–1284. (b) Suzuki, K.; Matsukura, H.; Matsuo, G.;
Koshino, H.; Nakata, T. Tetrahedron Lett. 2002, 43,

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J. M. Concellon et al. / Tetrahedron 62 (2006) 3292–3300
3300
´ ´ ´
19. Concellon, J. M.; Concellon, C.; Mejica, C. J. Org. Chem.
2005, 70, 6111–6113.
´
20. Concellon, J. M.; Huerta, M. Tetrahedron Lett. 2003, 44,
1931–1934.
8653–8655. (c) Beji, F.; Lebreton, J.; Villieras, J.; Amri, H.
Synth. Commun. 2002, 32, 3273–3278. (d) Huang, Z.; Sun,
R. J. Chin. J. Org. Chem. 2002, 20, 1460–1462.
´
12. (a) Moreno-Man˜as, M.; Perez, M.; Pleixants, R. Tetrahedron
Lett. 1996, 37, 7449–7452. (b) Ando, K. J. Org. Chem. 1997,
62, 1934–1939. (c) Jin, Y. Z.; Yasuda, N.; Inanaga, J. Green
Chem. 2002, 4, 498–500.
21. Hydrolysis with HCl 1 N is essential to reproduce the yields
presented in Table 1. When the reaction mixture was
hydrolysed with 0.1 N HCl or water the isolated yield of 2
dropped in all cases around 20%.
13. (a) Zou, G.; Wang, Z.; Zhu, J.; Tang, J. Chem. Commun. 2003,
´
2438–2439. (b) Salgado, A.; Manmn, E.; Sanchez-Sancho, F.;
22. The coupling constant between the olefinic protons of
compounds 1 ranging JZ15.7–16.3 Hz were in accordance
with the average literature values. Silverstein, R. M.; Bassler,
G. C.; Morrill, T. C. Spectrometric Identification of Organic
Compounds; Wiley: New York, 1991; p 221.
Herradon, B. Heterocycles 2003, 60, 57–71.
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2498–2503. (b) Hayes, B. L.; Adams, T. A.; Pickin, K. A.;
Day, C. S.; Welker, M. E. Organometallics 2000, 19,
2730–2740.
23. The coupling constant between the olefinic protons of
compounds 2a, 2b, and 2c were JZ15.4, 16.1, 15.6 Hz,
respectively, which are in accordance with the average
literature values. Silverstein, R. M.; Bassler, G. C.; Morrill,
T. C. Spectrometric Identification of Organic Compounds;
Wiley: New York, 1991; p 221.
15. (a) Lambert, T. H.; MacMillan, D. W. J. Am. Chem. Soc. 2002,
124, 13646–13647. (b) Liao, B.; Negishi, E. Heterocycles
2000, 52, 1241–1249.
16. (a) Trost, B. M.; Paquette, J. R. J. Org. Chem. 1993, 58,
1579–1681. (b) Tanikaga, R.; Miyashita, K.; Ono, N.; Kaji, A.
Synthesis 1982, 131–132.
´ ´ ´ ´
24. Concellon, J. M.; Perez-Andres, J.; Rodrıguez-Solla, H.
Angew. Chem., Int. Ed. 2000, 39, 2773–2775.
´
17. (a) Castells, J.; Lopez-Calahorra, F.; Yu, Z. Tetrahedron 1994,
50, 13765–13774. (b) Maercker, A.; Van de Flierdt, J.;
Giresser, U. Tetrahedron 2000, 56, 3373–3383.
´ ´ ´
18. Concellon, J. M.; Rodrıguez-Solla, H.; Mejica, C. Tetrahedron
25. One of the great challenges associated with Wittig reaction in
the preparation of a,b-unsaturated esters relates to stereo-
control: Maryanoff, B. E.; Reitz, A. B. Chem. Rev. 1989, 89,
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