A new reaction system for Horner-Wadsworth-Emmons olefination of optically active 4-hydroxy-2-oxo-alkylphosphonates and 4-hydroxy-1-chloro-2-oxo- alkylphosphonates with aliphatic aldehydes

Article abstract of DOI:10.1055/s-2004-831193

A new and convenient reaction system is described for the synthesis of chiral β′-hydroxy-α,β-unsatuarated ketones based on the Horner-Wadsworth-Emmons olefination of optically active 4-hydroxy-2-oxo- alkylphosphonates and 4-hydroxy-l-chloro-2-oxo-alkylpho

Full text of DOI:10.1055/s-2004-831193

PAPER
2449
A New Reaction System for Horner–Wadsworth–Emmons Olefination of
Optically Active 4-Hydroxy-2-oxo-alkylphosphonates and 4-Hydroxy-1-
chloro-2-oxo-alkylphosphonates with Aliphatic Aldehydes
New
Reaction
Sy
h
stem for Hor
e
ner–Wadsw
n
orth–Emmo
g
ns Olefinatio
f
n
u Xu, Chengye Yuan*
Shanghai Institute of Organic Chemistry, Chinese Academy of Science, 345 Lingling Lu, Shanghai, 200032, P. R. China
Fax +86(21)64166128; E-mail: yuancy@mail.sioc.ac.cn
Received 14 May 2004; revised 24 June 2004
The disadvantages of the above synthetic routes are sig-
nificant, consisting of harsh reaction conditions, expen-
sive reagents, low chemical yields and even low optical
purity.4–9 Development of a new procedure leading to the
preparation of the b¢-hydroxy-a,b-unsaturated ketones (I)
seems necessary. It is reasonable to predict that the Hor-
ner–Wadsworth–Emmons (HWE) reaction will offer bet-
ter results, since this method is usually applied under mild
conditions.
Abstract: A new and convenient reaction system is described for
the synthesis of chiral b¢-hydroxy-a,b-unsatuarated ketones based
on the Horner–Wadsworth–Emmons olefination of optically active
4-hydroxy-2-oxo-alkylphosphonates and 4-hydroxy-1-chloro-2-
oxo-alkylphosphonates with aliphatic aldehydes.
Key words: 2¢-hydroxy-1,2-unsatuarated ketones, Horner–Wad-
sworth–Emmons reaction, 4-hydroxy-2-oxo-alkylphosphonates, 4-
hydroxy-1-chloro-2-oxo- alkylphosphonates
Diethyl 4-hydroxy-2-oxo-4-aryl (or alkyl) butylphospho-
nates and diethyl 4-hydroxy-1-chloro-2-oxo-4-aryl (or
alkyl) butylphosphonates are an important kind of com-
pounds, which could react with aldehydes or ketones to
provide key building blocks of a,b-unsatuarated ketones
through HWE reaction.10 They could also be transformed
into 2-oxo-3-alkenylphosphonates and in the following
reacting with vinyl ethers by hetero-Diels–Alder reactions
leading to 5-substituted 2-phosphoryl-2-cyclohexen-1-
ones.11 Recently, we transformed this kind of compounds
into a new series of tetrahydrofuran units through an in-
tramoleular O–H insertion reaction catalyzed by rhodium
acetate [Rh2(OAc)2].12
b¢-Hydroxy-a,b-unsatuarated ketones (I, Figure 1) are
structure units that are frequently found in the molecule of
natural products, such as pentamycin,1 yashabushitriol,2
3
and 1a, 25-dihydrovitamin D3 etc. For the preparation of
those compounds, several synthetic routes were reported
in the literature including Mukaiyama aldol reaction,4
LnCl3-mediated a¢-alkylations of enone and aldehydes,5
reductive transformation of a,b-epoxy ketones to b-hy-
droxy ketones promoted through a photoinduced electron
transfer process with 1,3-dimethyl-2-phenylbenzimidazo-
line (DMPBI),6 vanadium-catalyzed aldol additions of al-
lenic alcohols and aldehydes,7 boron trifluoride-promoted
reaction of dithio-substituted allylic anions and cyclic
ethers,8 and the reaction of a,b-unsaturated and a-phenyl
acetals with expoxides promoted by lithium-potassium
mixed base LICKOR [butylithium and potassium butox-
ide (so called ‘Schlosser reagent’)].9
Very recently, our group has exploited Candia Antarctic
lipase B (CALB) and crude Candia Rugosa lipase (CRL)
to resolve hydroxyphosphonates and aminophospho-
nates.10a,b,12,13 One of the resulting optically active hy-
droxyphosphonates (II) is a useful intermediate for the
synthesis of tuckolide seco acid (V) that is an inhibitor of
HMGCoA reductase (Scheme 1).14
In this paper, we describe a new and facile reaction system
for the HWE olefination of chiral 4-hydroxy-2-oxo-alkyl-
phosphonates and 4-hydroxy-1-chloro-2-oxo-alkylphos-
phonates with aliphatic aldehydes.
Figure 1
Scheme 1
SYNTHESIS 2004, No. 15, pp 2449–2458
x
x.
x
x
.
2
0
0
4
Advanced online publication: 23.08.2004
DOI: 10.1055/s-2004-831193; Art ID: F06804SS
© Georg Thieme Verlag Stuttgart · New York

2450
C. Xu, C. Yuan
PAPER
Scheme 2
According to our previous papers,10a,b we prepared the op- excess. To our surprise, these optically active substrates
tically active 4-hydroxy-2-oxo-alkylphosphonates (1a–c, gave only low chemical yields and even racemization
2a–c) and 4-hydroxy-1-chloro-2-oxo-alkylphosphonates products in the HWE reaction with aliphatic aldehydes us-
(1d–f, 2d–f) (Scheme 2).
ing a DBU/LiBr system due to long reaction times and
strong alkaline conditions.11 By careful examination of
the reaction conditions, however, we developed a new re-
action system consisting of RCHO/THF/H2O/K2CO3 to
provide olefination products with aliphatic aldehydes
(Scheme 3, Table 1).
In the first part of this paper, we demonstrate that the
HWE reaction of chiral compounds 1a–f and 2a–f ob-
tained from CALB kinetic resolution, underwent normal
olefination with benzaldehyde with good enantiomeric
Scheme 3
Table 1 HWE Reaction of Compounds 1a–f and 2a–f with Aliphatic Aldehydes
Substrate
X
R
R1
3
4
5
6
Yield (%)a ee (%)b
Yield (%)a ee (%)c Yield (%)a ee (%)b
Yield (%)a ee (%)c
a
H
Me
Et
Et
95
96
92
94
95
96
83
81
86
79
85
82
99
95
–
–
–
–
–
–
7
7
7
8
7
7
–
–
–
–
–
–
94
95
–
99
96
–
–
–
–
–
–
–
7
–
–
–
7
7
–
b
H
Et
–
b(1)
b(2)
b(3)
c
H
Et
Me
n-Pr
i-Pr
Et
>99
96
–
H
Et
–
–
–
H
Et
96
–
–
–
H
Vinyl
Me
Et
99
97
84
–
99
99
–
–
d
Cl
Cl
Cl
Cl
Cl
Cl
Et
99
99
97
99
–
e
Et
97
e(1)
e(2)
e(3)
f
Et
Me
n-Pr
i-Pr
Et
>99
97
>99
97
–
–
–
Et
–
–
–
Et
92
92
85
86
95
98
95
98
Vinyl
95
95
a Isolated yields.
b The ee values were determined by chiral HPLC (CHIRALPAK AD, OD, AS n-hexane–i-PrOH = 8:2 to 9:1).
c The E and Z isomers were obtained from the same substrate in one reaction, so the ee values of E and Z isomers were considered to be identical.
Synthesis 2004, No. 15, 2449–2458 © Thieme Stuttgart · New York

PAPER
New Reaction System for Horner–Wadsworth–Emmons Olefination
2451
Based on our experimental data, we found that 4-hydroxy-
2-oxo-alkylphosphonates 1a–c and 2a–c reacted with ali-
phatic aldehydes only to give the respective E isomer,
which was identical to the results of the reaction with ben-
zaldehyde (X = H). However, the reaction time was short-
ened by about 50% and the overall yield was dramatically
increased. We also obtained the same results for the 4-hy-
droxy-1-chloro-2-oxo-alkylphosphonates 1d–f and 2d–f
under analogous reaction conditions. In the latter case a
mixture of E and Z isomers was obtained, which was iden-
tical to the corresponding results of the reaction with ben-
zaldehyde, while the E/Z ratio was greater than 1:10 and
the E isomer could slowly convert into the thermodynam-
ically more favorable Z isomer (X = Cl). The E and Z iso-
Scheme 4
Scheme 5
Table 2 HWE Reaction of Compounds 7a–l with Aliphatic Aldehydes
Substrate
X
Ar
R
8
Yield (%)a
9
ee (%)b
>99
97
Yield (%)a
ee (%)c
a
H
C6H5
Et
94
90
96
94
95
95
93
96
95
94
96
93
86
85
86
83
88
85
–
–
–
–
–
–
–
–
–
–
–
–
4
5
5
8
5
4
–
a(1)
H
C6H5
Me
n-Pr
i-Pr
Et
–
a(2)
H
C6H5
97
–
a(3)
H
C6H5
98
–
b
H
4-EtC6H4
4-MeOC6H4
2-furyl
>99
99
–
c
H
Et
–
d
H
Et
88
–
e
H
2-ClC6H4
2-BrC6H4
4-FC6H4
4-ClC6H4
4-O2NC6H4
C6H5
Et
>99
99
–
f
H
Et
–
g
H
Et
>99
–
d
h
H
Et
–
–
i
H
Et
96
98
–
j
Cl
Cl
Cl
Cl
Cl
Cl
Et
98
98
98
98
>99
97
j(1)
C6H5
Me
n-Pr
i-Pr
Et
98
j(2)
C6H5
98
j(3)
C6H5
98
k
4-MeOC6H4
4-FC6H4
>99
97
l
Et
a Isolated yields.
b The ee values were determined by chiral HPLC (CHIRALPAK AD, OD, AS n-hexane–i-PrOH = 8:2 to 9:1).
c The E and Z isomers were obtained from the same substrates in one reaction, so the ee values of E and Z isomers were considered to be iden-
tical.
d The ee values could not be determined by chiral HPLC.
Synthesis 2004, No. 15, 2449–2458 © Thieme Stuttgart · New York

2452
C. Xu, C. Yuan
PAPER
mers could be determined based on steric effects and 1H
NMR spectra.
After drying over anhyd Na2SO4, the solvent was removed under re-
duced pressure and the residues were subjected to flash chromatog-
raphy (EtOAc–n-hexane, ca. 1:10). The yields of the products are
listed in Table 1.
Since the results of the HWE reactions with aliphatic al-
dehydes of CALB-catalyzed products 1a–f and 2a–f were
encouragable, it was therefore interesting to examine the
HWE reaction of CRL-catalyzed products (7a–l,
Scheme 4).
(2S,5E)-2-Hydroxyoct-5-en-4-one (3a)
Colorless oil; [a]Na20 = +51.2 (c 1.0, CHCl3).
IR (neat): 3434, 2971, 2935, 1663, 1626, 1375, 1192, 979, 946 cm–1.
1H NMR (300 MHz, CDCl3): d = 6.86 (dt, 1 H, J = 6.3, 16.2 Hz,
COCH=CHCH2), 6.02 (d, 1 H, J = 16.2 Hz, COCH=CHCH2), 4.21–
4.08 (m, 1 H, COCH2CHOH), 3.46 (s, 1 H, OH), 2.69 (dd, 1 H,
J = 3.0, 17.1 Hz, COCH2CHOH), 2.57 (dd, 1 H, J = 8.4, 17.1 Hz,
COCH2CHOH), 2.24–2.15 (m, 2 H, CH=CHCH2CH3), 1.15 (d, 3 H,
J = 7.2 Hz, CH3CHOH), 1.01 (t, 3 H, J = 7.8 Hz, CH=CHCH2CH3).
It is quite exciting that aliphatic aldehydes/THF/K2CO3/
H2O systems performed these experiments successfully
(Scheme 5, Table 2).
The substrates 7a–i, reacted with aliphatic aldehydes, also
provided only the E isomer, as in the case of benzaldehyde
(X = H) while compounds 7j–l also yielded the mixture of
MS (EI, 70 eV): m/z (%) = 143 (M+ + 1, 26), 125 (15), 113 (15), 101
E and Z isomers with the ratio E/Z greater than 1:10. Also (10), 98 (9), 83 (100), 55 (35), 45 (11), 43 (20), 39 (10).
in these cases, the E isomers could be converted slowly
into the corresponding Z isomers. Those two isomers
could be determined based on steric effects and 1H NMR
spectra. These reactions were completed within one hour
and the yields were higher than 90%. Because compounds
7a–l could be partly racemized under basic conditions and
long reaction times (Scheme 6), the ee values of com-
Anal. Calcd for C8H14O2: C, 67.57; H, 9.92. Found: C, 67.43; H,
10.13.
(2R,53E)-2-Hydroxyoct-5-en-4-one (5a)
Colorless oil; [a]Na20 = –50.7 (c 0.7, CHCl3).
IR (neat): 3440, 2971, 2935, 1663, 1626, 1375, 1192, 1054, 979,
946 cm–1.
pounds 8a–l were higher than that of the products ob- 1H NMR (300 MHz, CDCl3): d = 6.86 (dt, 1 H, J = 6.3, 16.5 Hz,
tained from benzaldehyde.10a,b
COCH=CHCH2), 6.02 (d, 1 H, J = 16.5 Hz, COCH=CHCH2), 4.22–
4.09 (m, 1 H, COCH2CHOH), 3.46 (s, 1 H, OH), 2.69 (dd, 1 H,
J = 3.3, 17.1 Hz, COCH2CHOH), 2.57 (dd, 1 H, J = 8.4, 17.1 Hz,
COCH2CHOH), 2.25–2.15 (m, 2 H, CH=CHCH2CH3), 1.15 (d, 3 H,
J = 6.9 Hz, CH3CHOH), 1.01 (t, 3 H, J = 7.5 Hz, CH=CHCH2CH3).
MS (EI, 70 eV): m/z (%) = 143 (M+ + 1, 30), 125 (17), 113 (14), 101
(9), 98 (8), 83 (100), 55 (35), 45 (11), 43 (20), 39 (10).
Anal. Calcd for C8H14O2: C, 67.57; H, 9.92. Found: C, 67.33; H,
10.13.
Scheme 6
(3E,7S)-7-Hydroxynon-3-en-5-one (3b)
Colorless oil; [a]Na20 = +35.3 (c 1.4, CHCl3).
A new facile reaction system for the Horner–Wadsworth–
Emmons olefination was realized by treatment of chiral 4-
hydroxy-2-oxo-alkylphosphonates and 4-hydroxy-1-
chloro-2-oxo-alkylphosphonates with aliphatic alde-
hydes.
IR (neat): 3446, 2969, 2937, 1660, 1625, 1463, 1187, 1114, 977
cm–1.
1H NMR (300 MHz, CDCl3): d = 6.93 (dt, 1 H, J = 6.3, 15.9 Hz,
COCH=CHCH2), 6.10 (d, 1 H, J = 15.9 Hz, COCH=CHCH2), 4.08–
3.95 (m, 1 H, COCH2CHOH), 3.41 (d, 1 H, J = 2.7 Hz, OH), 2.77
(dd, 1 H, J = 3.0, 17.4 Hz, COCH2CHOH), 2.63 (dd, 1 H, J = 9.6,
17.4 Hz, COCH2CHOH), 2.30–2.23 (m, 2 H, CH=CHCH2CH3),
1.59–1.46 (m, 2 H, CH3CH2CHOH), 1.10 (t, 3 H, J = 7.2 Hz,
CH=CHCH2CH3), 0.97 (t, 3 H, J = 7.2 Hz, CH3CH2CHOH).
IR spectra were recorded on a Shimadzu IR-440 spectrometer. EI
mass spectra (MS) were run on a HP-5989A mass spectrometer at
70 eV. 1H NMR spectra were recorded on a Bruker AMX-330 (300
MHz) spectrometer in CDCl3 and chemical shifts were reported in
ppm downfield relative to TMS (internal standard); 31P NMR spec-
tra were taken on the same spectrometer using 80% phosphorus acid
as external standard.
MS (EI, 70 eV): m/z (%) = 156 (M+, 1), 127 (12), 101 (6), 98 (8), 83
(100), 70 (4), 57 (11), 55 (35), 43 (17).
Anal. Calcd for C9H16O2: C, 69.19; H, 10.32. Found: C, 69.36; H,
10.39.
CALB (Novozym 435) was provided from Novo Norvodisk Co.
CRL (901units/mg) was purchased from Sigma Chemical Co.
The chiral liquid chromatography system: Waters 515 HPLC pump;
UV Waters 2487 Dual l Absorbance Detector, 254 nm; Penelson
Network chromatography interface NCI 900, Turbohrom Navigator
data station software; column dimensions: 0.46cm × 25cm; the flow
rate: 0.7mL/min; eluent: hexane–i-PrOH = 9:1 to 8:2 (v/v).
(2E,6S)-6-Hydroxyoct-2-en-4-one [3b(1)]15
Colorless oil; [a]Na20 = +57.2 (c 1.2, CHCl3).
IR (neat): 3448, 2967, 2937, 1664, 1630, 1443, 1378, 1292, 1190,
973 cm–1.
1H NMR (300 MHz, CDCl3): d = 6.97–6.84 (m, 1 H,
COCH=CHCH3), 6.13 (d, 1 H, J = 15.6 Hz, COCH=CHCH3), 4.07–
3.95 (m, 1 H, COCH2CHOH), 3.33 (s, 1 H, OH), 2.76 (dd, 1 H,
J = 2.7, 17.4 Hz, COCH2CHOH), 2.61 (dd, 1 H, J = 9.0, 17.4 Hz,
COCH2CHOH), 1.92 (d, 3 H, J = 7.2 Hz, CH=CHCH3), 1.61–1.43
(m, 2 H, CHCH2CH3), 0.96 (t, 3 H, J = 7.5 Hz, CH3CH2CHOH).
HWE Reaction of Chiral Compounds 1 and 2 with Aliphatic Al-
dehydes; General Procedure
A mixture of substrates (50 mg), THF (1 mL), aliphatic aldehyes
(0.4 mL), H2O (1 mL) and K2CO3 (150 mg) was stirred until the
starting materials disappeared (generally within 1 h) as monitored
by TLC. Then Et2O (5 mL) and a sat. aq solution of NH4Cl (3 mL)
was added, the aqueous layer was extracted with Et2O (3 × 5 mL).
MS (EI, 70 eV): m/z (%) = 124 (M+ – H2O, 2), 113 (10), 87 (5), 84
(9), 69 (100), 57 (9), 43 (16), 41 (49).
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New Reaction System for Horner–Wadsworth–Emmons Olefination
2453
(6E,3S)-3-Hydroxydec-6-en-5-one [3b(2)]
Colorless oil; [a]Na20 = +50.5 (c 0.7, CHCl3).
(3S,6E)-3-Hydroxynona-1,6-dien-5-one (5c)
Colorless oil; [a]Na20 = –25.3 (c 1.1, CHCl3).
IR (neat): 3447, 2964, 2934, 2877, 1663, 1627, 1464, 1380, 1186,
1114, 978 cm–1.
IR (neat): 3443, 2970, 2935, 2879, 1661, 1626, 1423, 1187, 979,
923 cm–1.
1H NMR (300 MHz, CDCl3): d = 6.88 (dt, 1 H, J = 6.9, 16.2 Hz,
COCH=CHCH2), 6.10 (dt, 1 H, J = 1.5, 15.9 Hz, COCH=CHCH2),
4.04–3.95 (m, 1 H, COCH2CHOH), 3.32 (m, 1 H, OH), 2.77 (dd, 1
H, J = 3.0, 17.4 Hz, COCH2CHOH), 2.62 (dd, 1 H, J = 9.6, 17.4 Hz,
COCH2CHOH), 2.26–2.18 (m, 2 H, CH=CHCH2CH2), 1.61–1.43
(m, 4 H, CH=CHCH2CH2CH3, CH3CH2CHOH), 1.00–0.92 (m, 6 H,
CH=CHCH2CH3, CH=CHCH2CH2CH3).
1H NMR (300 MHz, CDCl3): d = 6.94 (dt, 1 H, J = 6.0, 15.9 Hz,
COCH=CHCH2), 6.07 (d, 1 H, J = 15.9 Hz, COCH=CHCH2), 5.95–
8.84 (m, 1 H, CH2=CHCHOH), 5.31 (d, 1 H, J = 17.1 Hz,
CH2=CHCHOH), 5.14 (d, 1 H, J = 10.8 Hz, CH2=CHCHOH),
4.68–4.59 (m, 1 H, COCH2CHOH), 3.40 (s, 1 H, OH), 2.88–2.70
(m, 2 H, COCH2CHOH), 2.32–2.22 (m, 2 H, CH=CHCH2CH3),
1.09 (t, 3 H, J = 7.8 Hz, CH=CHCH2CH3).
MS (EI, 70 eV): m/z (%) = 152 (M+ – H2O, 3), 141 (14), 112 (8), 97
MS (EI, 70 eV): m/z (%) = 125 (M+ – C2H5, 7), 98 (16), 97 (7), 83
(100), 70 (9), 55 (62), 43 (17), 41 (26).
(100), 79 (5), 57 (14), 55 (44), 43 (18).
Anal. Calcd for C10H18O2: C, 70.55; H, 10.66. Found: C, 70.53; H,
10.65.
Anal. Calcd for C9H14O2: C, 70.10; H, 9.15%. Found: C, 70.04; H,
9.25.
(3E,7S)-7-Hydroxy-2-methylnon-3-en-5-one [3b(3)]
Colorless oil; [a]Na20 = +46.5 (c 0.8, CHCl3).
(2R,5Z)-5-Chloro-2-hydroxyoct-5-en-4-one (3d)
Colorless oil; [a]Na20 = +42.8 (c 1.0, CHCl3).
IR (neat): 3449, 2966, 2935, 2876, 1686, 1662, 1626, 1466, 1366,
1190, 980 cm–1.
IR (neat): 3429, 2974, 2936, 2881, 1687, 1615, 1376, 1187, 1116,
950, 720 cm–1.
1H NMR (300 MHz, CDCl3): d = 6.84 (dd, 1 H, J = 6.9, 15.9 Hz,
COCH=CHCH), 6.05 (dd, 1 H, J = 1.5, 15.9 Hz, COCH=CHCH),
4.06–3.92 (m, 1 H, COCH2CHOH), 3.29 (m, 1 H, OH), 2.78 (dd, 1
H, J = 2.7, 17.1 Hz, COCH2CHOH), 2.61 (dd, 1 H, J = 9.0, 17.1 Hz,
COCH2CHOH), 2.55–2.43 [m, 1 H, CH=CHCH(CH3)2], 1.62–1.41
1H NMR (300 MHz, CDCl3): d = 6.99 (t, 1 H, J = 7.2 Hz,
COC=CHCH2), 4.38–4.22 (m, 1 H, COCH2CHOH), 3.09 (s, 1 H,
OH), 2.94 (dd, 1 H, J = 3.0, 18.0 Hz, COCH2CHOH), 2.83 (dd, 1 H,
J = 8.7, 18.0 Hz, COCH2CHOH), 2.48–2.38 (m,
2
H,
C=CHCH2CH3), 1.26 (d, 3 H, J = 6.6 Hz, CH3CHOH), 1.14 (t, 3 H,
J = 7.5 Hz, C=CHCH2CH3).
(m,
2 H, CH3CH2CHOH), 1.08 [t, 6 H, J = 6.6 Hz,
CH=CHCH(CH3)2], 1.00 (t, 3 H, J = 7.5 Hz, CH3CH2CHOH).
MS (EI, 70 eV): m/z (%) = 152 (M+ – H2O, 1), 141 (8), 127 (9), 112
MS (EI, 70 eV): m/z (%) = 177 (M+ + 1, 13), 159 (14), 132 (11), 117
(50), 97 (13), 89 (12), 53 (55), 45 (67), 43 (100).
(7), 97 (100), 69 (22), 55 (14), 43 (29), 41 (48).
Anal. Calcd for C8H13ClO2: C, 54.40; H, 7.42%. Found: C, 54.51;
H, 7.40.
Anal. Calcd for C10H18O2: C, 70.55; H, 10.66. Found: C, 70.61; H,
10.71.
(2S,5E)-5-Chloro-2-hydroxyoct-5-en-4-one (4d)
Colorless oil; [a]Na20 = +30.0 (c 0.4, CHCl3).
(3E,7R)-7-Hydroxynon-3-en-5-one (5b)
Colorless oil; [a]Na20 = –35.6 (c 1.0, CHCl3).
IR (neat): 3423, 2974, 2936, 2881, 1687, 1615, 1460, 1187, 1116,
949, 720 cm–1.
IR (neat): 3445, 2969, 2937, 2879, 1659, 1626, 1463, 1188, 1024,
978 cm–1.
1H NMR (300 MHz, CDCl3): d = 6.30 (t, 1 H, J = 7.8 Hz,
COC=CHCH2), 4.30–4.21 (m, 1 H, COCH2CHOH), 2.96 (dd, 1 H,
J = 3.0, 18.6 Hz, COCH2CHOH), 2.82 (dd, 1 H, J = 8.7, 18.3 Hz,
COCH2CHOH), 2.58–2.48 (m, 2 H, C=CHCH2CH3), 1.25 (d, 3 H,
J = 6.9 Hz, CH3CHOH), 1.07 (t, 3 H, J = 7.5 Hz, C=CHCH2CH3).
MS (EI, 70 eV): m/z (%) = 176 (M+, 4), 158 (18), 147 (16), 132 (36),
119 (35), 117 (100), 97 (23), 89 (15), 53 (22), 43 (20).
1H NMR (300 MHz, CDCl3): d = 6.94 (dt, 1 H, J = 6.3, 16.2 Hz,
COCH=CHCH2), 6.10 (d, 1 H, J = 16.5 Hz, COCH=CHCH2), 4.07–
3.96 (m, 1 H, COCH2CHOH), 3.41 (d, 1 H, J = 2.4 Hz, OH), 2.77
(dd, 1 H, J = 3.0, 17.4 Hz, COCH2CHOH), 2.63 (dd, 1 H, J = 9.0,
17.4 Hz, COCH2CHOH), 2.32–2.23 (m, 2 H, CH=CHCH2CH3),
1.59–1.48 (m, 2 H, CH3CH2CHOH), 1.09 (t, 3 H, J = 7.8 Hz,
CH=CHCH2CH3), 0.97 (t, 3 H, J = 7.5 Hz, CH3CH2CHOH).
Anal. Calcd for C8H13ClO2: C, 54.40; H, 7.42%. Found: C, 54.31;
H, 7.29.
MS (EI, 70 eV): m/z (%) = 156 (M+, 1), 127 (18), 101 (8), 98 (9), 83
(100), 70 (7), 57 (11), 55 (27), 43 (13).
Anal. Calcd for C9H16O2: C, 69.19; H, 10.32. Found: C, 69.36; H,
10.39.
(2R,5Z)-5-Chloro-2-hydroxyoct-5-en-4-one (5d)
Colorless oil; [a]Na20 = –42.6 (c 1.0, CHCl3).
IR (neat): 3410, 2972, 2929, 2819, 1687, 1615, 1187, 950, 721 cm–1.
(3R,6E)-3-Hydroxynona-1,6-dien-5-one (3c)
Colorless oil; [a]Na20 = +25.2 (c 1.4, CHCl3).
1H NMR (300 MHz, CDCl3): d = 6.99 (t, 1 H, J = 7.2 Hz,
COC=CHCH2), 4.37–4.21 (m, 1 H, COCH2CHOH), 3.08 (s, 1 H,
OH), 2.95 (dd, 1 H, J = 3.0, 18.0 Hz, COCH2CHOH), 2.84 (dd, 1 H,
IR (neat): 3434, 2970, 2935, 2879, 1661, 1626, 1423, 1186, 978,
923 cm–1.
J = 8.7, 18.0 Hz, COCH2CHOH), 2.48–2.38 (m,
2
H,
1H NMR (300 MHz, CDCl3): d = 6.94 (dt, 1 H, J = 6.3, 15.6 Hz,
COCH=CHCH2), 6.11 (d, 1 H, J = 15.6 Hz, COCH=CHCH2), 5.95–
5.84 (m, 1 H, CH2=CHCHOH), 5.24 (d, 1 H, J = 15.6 Hz,
CH2=CHCHOH), 5.14 (d, 1 H, J = 10.2 Hz, CH2=CHCHOH),
4.67–4.58 (m, 1 H, COCH2CHOH), 3.39 (s, 1 H, OH), 2.86–2.72
(m, 2 H, COCH2CHOH), 2.32–2.22 (m, 2 H, CH=CHCH2CH3),
1.09 (t, 3 H, J = 7.5 Hz, CH=CHCH2CH3).
C=CHCH2CH3), 1.26 (d, 3 H, J = 7.2 Hz, CH3CHOH), 1.13 (t, 3 H,
J = 7.2 Hz, C=CHCH2CH3).
MS (EI, 70 eV): m/z (%) = 176 (M+, 2), 158 (13), 147 (13), 141 (12),
132 (32), 119 (34), 117 (100), 53 (37), 43 (54).
HRMS (EI): m/z [M+] calcd for C8H13ClO2, 176.0604; found,
176.0580.
MS (EI, 70 eV): m/z (%) = 137 (M+ – OH, 7), 126 (15), 111 (10), 99
(16), 98 (22), 83 (100), 71 (42), 57 (71), 55 (60), 43 (66).
(2R,5E)-5-Chloro-2-hydroxyoct-5-en-4-one (6d)
Colorless oil; [a]Na20 = –30.1 (c 0.4, CHCl3).
Anal. Calcd for C9H14O2: C, 70.10; H, 9.15. Found: C, 70.09; H,
9.45.
Synthesis 2004, No. 15, 2449–2458 © Thieme Stuttgart · New York

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C. Xu, C. Yuan
PAPER
IR (neat): 3406, 2972, 2929, 2819, 1687, 1615, 1461, 1120, 950,
721 cm–1.
(m, 3 H, COCH2CHOH,OH), 1.59–1.51 (m, 2 H, CH3CH2CHOH),
1.11 [d, 6 H, J = 6.6 Hz, C=CHC(CH3)2], 0.96 (t, 3 H, J = 6.9 Hz,
CH3CH2CHOH).
MS (EI, 70 eV): m/z (%) = 204 (M+, 2), 175 (14), 146 (48), 131
1H NMR (300 MHz, CDCl3): d = 6.30 (t, 1 H, J = 7.8 Hz,
COC=CHCH2), 4.30–4.22 (m, 1 H, COCH2CHOH), 2.96 (dd, 1 H,
J = 3.3, 18.6 Hz, COCH2CHOH), 2.82 (dd, 1 H, J = 8.7, 18.3 Hz,
COCH2CHOH), 2.58–2.48 (m, 2 H, C=CHCH2CH3), 1.25 (d, 3 H,
J = 7.2 Hz, CH3CHOH), 1.07 (t, 3 H, J = 7.5 Hz, C=CHCH2CH3).
(100), 111 (27), 103 (26), 95 (40), 67 (54), 57 (41), 43 (38).
Anal. Calcd for C10H17ClO2: C, 58.68; H, 8.37. Found: C, 58.59; H,
8.36.
MS (EI, 70 eV): m/z (%) = 177 (M+ + 1, 23), 159 (18), 141 (7), 132
(19), 117 (66), 97 (19), 71 (22), 57 (32), 53 (48), 43 (100).
HRMS (EI): m/z [M+] calcd for C8H13ClO2, 176.0604; found,
176.0586.
(3E,7S)-4-Chloro-7-hydroxynon-3-en-5-one (4e)
Colorless oil; [a]Na20 = +16.0 (c 0.4, CHCl3).
IR (neat): 3446, 2972, 2937, 2881, 1732, 1623, 1463, 979 cm–1.
1H NMR (300 MHz, CDCl3): d = 6.30 (t, 1 H, J = 7.5 Hz,
COC=CHCH2), 4.06–3.98 (m, 1 H, COCH2CHOH), 2.98 (dd, 1 H,
J = 2.7, 18.6 Hz, COCH2CHOH), 2.81 (dd, 1 H, J = 9.0, 18.6 Hz,
COCH2CHOH), 2.59–2.49 (m, 2 H, C=CHCH2CH3), 1.64–1.49 (m,
2 H, CH3CH2CHOH), 1.08 (t, 3 H, J = 7.2 Hz, C=CHCH2CH3),
0.99 (t, 3 H, J = 7.5 Hz, CH3CH2CHOH).
(3Z,7S)-4-Chloro-7-hydroxynon-3-en-5-one (3e)
Colorless oil; [a]Na20 = +29.6 (c 1.0, CHCl3).
IR (neat): 3419, 2973, 2939, 2881, 1733, 1625, 1463, 978, 740 cm–1.
1H NMR (300 MHz, CDCl3): d = 6.99 (t, 1 H, J = 6.9 Hz,
COC=CHCH2), 4.11–4.02 (m, 1 H, COCH2CHOH), 3.02 (s, 1 H,
OH), 2.94 (dd, 1 H, J = 3.0, 17.4 Hz, COCH2CHOH), 2.85 (dd, 1 H,
MS (EI, 70 eV): m/z (%) = 190 (M+, 1), 161 (17), 143 (14), 132 (15),
J = 9.0, 18.0 Hz, COCH2CHOH), 2.48–2.38 (m,
2
H,
119 (33), 117 (100), 97 (15), 89 (15), 57 (24), 43 (13).
C=CHCH2CH3), 1.59–1.51 (m, 2 H, CH3CH2CHOH), 1.13 (t, 3 H,
Anal. Calcd for C9H15ClO2: C, 56.69; H, 7.93. Found: C, 56.70; H,
7.99.
J = 7.8 Hz, C=CHCH2CH3), 0.99 (t,
CH3CH2CHOH).
3 H, J = 7.5 Hz,
MS (EI, 70 eV): m/z (%) = 190 (M+, 7), 172 (11), 143 (40), 132 (50),
117 (53), 97 (82), 83 (100), 76 (21), 55 (49), 43 (14).
(2E,6S)-3-Chloro-6-hydroxyoct-2-en-4-one [4e(1)]
Colorless oil; [a]Na20 = +24.7 (c 0.5, CHCl3).
Anal. Calcd for C9H15ClO2: C, 56.69; H, 7.93. Found: C, 56.99; H,
7.65.
IR (neat): 3427, 2970, 2937, 2881, 1686, 1625, 1379, 1155, 1108,
979 cm–1.
1H NMR (300 MHz, CDCl3): d = 6.41 (q, 1 H, J = 7.8 Hz,
COC=CHCH3), 4.08–3.97 (m, 1 H, COCH2CHOH), 3.02–2.77 (m,
3 H, COCH2CHOH,OH), 2.09 (d, 3 H, J = 7.8 Hz, COC=CHCH3),
1.62–1.39 (m, 2 H, CH3CH2CHOH), 0.99 (t, 3 H, J = 7.2 Hz,
CH3CH2CHOH).
(2Z,6S)-3-Chloro-6-hydroxyoct-2-en-4-one [3e(1)]
Colorless oil; [a]Na20 = +23.5 (c 1.0, CHCl3).
IR (neat): 3427, 2970, 2937, 2881, 1687, 1625, 1379, 1155, 979
cm–1.
1H NMR (300 MHz, CDCl3): d = 7.11 (q, 1 H, J = 6.6 Hz,
COC=CHCH3), 4.14–3.90 (m, 1 H, COCH2CHOH), 3.09–2.78 (m,
3 H, COCH2CHOH,OH), 2.02 (d, 3 H, J = 6.6 Hz, COC=CHCH3),
1.40–1.21 (m, 2 H, CH3CH2CHOH), 0.99 (t, 3 H, J = 7.2 Hz,
CH3CH2CHOH).
MS (EI, 70 eV): m/z (%) = 176 (M+, 1), 158 (11), 147 (28), 118 (20),
103 (100), 83 (12), 75 (22), 57 (45), 43 (45).
Anal. Calcd for C8H13ClO2: C, 54.40; H, 7.52. Found: C, 54.37; H,
7.55.
MS (EI, 70 eV): m/z (%) = 176 (M+, 1), 158 (11), 147 (28), 118 (19),
103 (100), 83 (12), 75 (24), 59 (20), 43 (29).
(3S,6E)-6-Chloro-3-hydroxydec-6-en-5-one [4e(2)]
Colorless oil; [a]Na20 = +16.0 (c 0.6, CHCl3).
Anal. Calcd for C8H13ClO2: C, 54.40; H, 7.52. Found: C, 54.27; H,
7.78.
IR (neat): 3439, 2965, 2935, 2877, 1686, 1616, 1464, 1182, 980
cm–1.
1H NMR (300 MHz, CDCl3): d = 6.30 (t, 1 H, J = 7.5 Hz,
COC=CHCH2CH3), 4.06–4.01 (m, 1 H, COCH2CHOH), 3.01–2.76
(m, 3 H, COCH2CHOH, OH), 2.49 (q, 2 H, J = 7.5 Hz,
C=CHCH2CH2CH3), 1.65–1.26 (m, 4 H, C=CHCH2CH2CH3,
(3S,6Z)-6-Chloro-3-hydroxydec-6-en-5-one [3e(2)]
Colorless oil; [a]Na20 = +33.3 (c 1.0, CHCl3).
IR (neat): 3438, 2965, 2935, 2877, 1686, 1616, 1464, 1182, 980
cm–1.
CH3CH2CHOH), 1.03–0.98 (m,
CH3CH2CHOH).
6
H, C=CHCH2CH2CH3,
1H NMR (300 MHz, CDCl3): d = 7.02 (t, 1 H, J = 7.2 Hz,
COC=CHCH2CH3), 4.04–3.97 (m, 1 H, COCH2CHOH), 3.07 (s, 1
H, OH), 2.92–2.78 (m, 2 H, COCH2CHOH), 2.39 (q, 2 H, J = 7.2
Hz, C=CHCH2CH2CH3), 1.63–1.48 (m, 4 H, C=CHCH2CH2CH3,
CH3CH2CHOH), 0.98 (t, 6 H, J = 7.5 Hz, C=CHCH2CH2CH3,
CH3CH2CHOH).
MS (EI, 70 eV): m/z (%) = 204 (M+, 1), 186 (10), 175 (19), 143 (12),
131 (100), 104 (27), 89 (24), 67 (18), 57 (33), 43 (14).
Anal. Calcd for C10H17ClO2: C, 58.68; H, 8.37%. Found: C, 58.70;
H, 8.41.
MS (EI, 70 eV): m/z (%) = 204 (M+, 1), 186 (10), 175 (18), 143 (13),
131 (100), 104 (28), 89 (26), 67 (20), 57 (45), 43 (19).
(3E,7S)- 4-Chloro-7-hydroxy-2-methylnon-3-en-5-one [4e(3)]
Colorless oil; [a]Na20 = +33.5 (c 0.6, CHCl3).
Anal. Calcd for C10H17ClO2: C, 58.68; H, 8.37. Found: C, 58.76; H,
8.44.
IR (neat): 3442, 2968, 2935, 2876, 1687, 1613, 1466, 1166, 1114,
980 cm–1.
1H NMR (300 MHz, CDCl3): d = 6.06 [d, 1 H, J = 9.9 Hz,
COC=CH(CH3)2], 4.03–3.95 (m, 1 H, COCH2CHOH), 2.97–2.73
(m, 3 H, COCH2CHOH,OH), 1.55–1.47 (m, 2 H, CH3CH2CHOH),
1.06 [d, 6 H, J = 6.6 Hz, C=CHC(CH3)2], 0.96 (t, 3 H, J = 6.9 Hz,
CH3CH2CHOH).
(3Z,7S)-4-Chloro-7-hydroxy-2-methylnon-3-en-5-one [3e(3)]
Colorless oil; [a]Na20 = +29.2 (c 1.0, CHCl3).
IR (neat): 3442, 2968, 2935, 2876, 1687, 1613, 1466, 1386, 1166,
980 cm–1.
1H NMR (300 MHz, CDCl3): d = 6.80 [d, 1 H, J = 9.0 Hz,
COC=CH(CH3)2], 4.06–3.97 (m, 1 H, COCH2CHOH), 3.02–2.77
MS (EI, 70 eV): m/z (%) = 204 (M+, 3), 175 (14), 146 (47), 131
(100), 111 (26), 103 (27), 95 (38), 71 (39), 67 (59), 57 (52), 43 (74).
Synthesis 2004, No. 15, 2449–2458 © Thieme Stuttgart · New York

PAPER
New Reaction System for Horner–Wadsworth–Emmons Olefination
2455
Anal. Calcd for C10H17ClO2: C, 58.68; H, 8.37%. Found: C, 58.42;
H, 8.37.
Anal. Calcd for C9H13ClO2: C, 57.30; H, 6.95. Found: C, 57.45; H,
7.03.
(3Z,7R)-4-Chloro-7-hydroxynon-3-en-5-one (5e)
Colorless oil; [a]Na20 = –29.8 (c 1.0, CHCl3).
IR (neat): 3410, 2967, 2928, 1687, 1465, 1119, 976 cm–1.
(3S,6Z)-6-Chloro-3-hydroxynona-1,6-dien-5-one (5f)
Colorless oil; [a]Na20 = –12.0 (c 1.0, CHCl3).
IR (neat): 3415, 2967, 2929, 2856, 1693, 1465, 1150, 975 cm–1.
1H NMR (300 MHz, CDCl3): d = 6.99 (t, 1 H, J = 6.9 Hz,
COC=CHCH2), 4.08–4.00 (m, 1 H, COCH2CHOH), 3.02 (s, 1 H,
OH), 2.95 (dd, 1 H, J = 3.3, 18.0 Hz, COCH2CHOH), 2.85 (dd, 1 H,
1H NMR (300 MHz, CDCl3): d = 7.00 (t, 1 H, J = 7.2 Hz,
COC=CHCH2), 5.94–5.86 (m, 1 H, CH2=CHCHOH), 5.35 (d, 1 H,
J = 16.8 Hz, CH2=CHCHOH), 5.18 (d, 1 H, J = 13.5 Hz,
CH2=CHCHOH), 4.68–4.65 (m, 1 H, COCH2CHOH), 3.03–2.96
(m, 3 H, COCH2CHOH), 2.50–2.38 (m, 2 H, C=CHCH2CH3), 1.13
(t, 3 H, J = 7.2 Hz, C=CHCH2CH3).
J = 9.0, 18.0 Hz, COCH2CHOH), 2.48–2.35 (m,
2
H,
C=CHCH2CH3), 1.63–1.46 (m, 2 H, CH3CH2CHOH), 1.13 (t, 3 H,
J = 7.5 Hz, C=CHCH2CH3), 0.99 (t,
CH3CH2CHOH).
3 H, J = 7.5 Hz,
MS (EI, 70 eV): m/z (%) = 170 (M+ – H2O, 2), 171 (15), 145 (9),
126 (9), 99 (39), 87 (8), 70 (40), 70 (100), 58 (48), 55 (51), 43 (54).
MS (EI, 70 eV): m/z (%) = 191 (M+ + 1, 65), 173 (79), 161 (20), 143
(17), 132 (15), 117 (100), 99 (21), 71 (23), 57 (64), 53 (45), 43 (57).
HRMS (EI): m/z [M+ – H2O] calcd for C9H11ClO, 170.0498; found,
Anal. Calcd for C9H15ClO2: C, 56.69; H, 7.93. Found: C, 56.87; H,
7.72.
170.0534.
(3S,6E)-6-Chloro-3-hydroxynona-1,6-dien-5-one (6f)
Colorless oil; [a]Na20 = –9.2 (c 0.4, CHCl3).
IR (neat): 3425, 2966, 2928, 2856, 1691, 1465, 1120, 975 cm–1.
(3E,7R)-4-Chloro-7-hydroxynon-3-en-5-one (6e)
Colorless oil; [a]Na20 = –16.0 (c 0.5, CHCl3).
IR (neat): 3418, 2970, 2935, 2880, 1688, 1615, 1153, 1463, 976
cm–1.
1H NMR (300 MHz, CDCl3): d = 6.30 (t, 1 H, J = 7.8 Hz,
COC=CHCH2), 5.96–5.85 (m, 1 H, CH2=CHCHOH), 5.33 (d, 1 H,
J = 16.8 Hz, CH2=CHCHOH), 5.17 (d, 1 H, J = 10.5 Hz,
CH2=CHCHOH), 4.65–4.61 (m, 1 H, COCH2CHOH), 3.05–2.91
(m, 2 H, COCH2CHOH), 2.87 (s, 1 H, OH), 2.59–2.48 (m, 2 H,
C=CHCH2CH3), 1.07 (t, 3 H, J = 7.5 Hz, C=CHCH2CH3).
MS (EI, 70 eV): m/z (%) = 171 (M+ – OH, 3), 145 (11), 132 (7), 117
(10), 99 (42), 85 (12), 70 (100), 57 (69), 55 (55), 43 (70).
HRMS (EI): m/z [M+ – H2O] calcd for C9H11ClO, 170.0498; found,
170.0511.
1H NMR (300 MHz, CDCl3): d = 6.29 (t, 1 H, J = 7.8 Hz,
COC=CHCH2), 4.06–3.98 (m, 1 H, COCH2CHOH), 2.98 (dd, 1 H,
J = 2.7, 18.6 Hz, COCH2CHOH), 2.81 (dd, 1 H, J = 9.0, 18.6 Hz,
COCH2CHOH), 2.59–2.49 (m, 2 H, C=CHCH2CH3), 1.63–1.46 (m,
2 H, CH3CH2CHOH), 1.08 (t, 3 H, J = 7.2 Hz, C=CHCH2CH3),
0.98 (t, 3 H, J = 7.5 Hz, CH3CH2CHOH).
MS (EI, 70 eV): m/z (%) = 190 (M+, 1), 172 (9), 161 (22), 143 (16),
132 (15), 117 (100), 99 (33), 70 (69), 59 (49), 57 (70), 43 (66).
HRMS (EI): m/z [M+] calcd for C9H15ClO2, 190.0706; found,
190.0769.
HWE Reaction of Chiral Compounds 7 with Aliphatic Alde-
hydes; General Procedure
(3R,6Z)-6-Chloro-3-hydroxynona-1,6-dien-5-one (3f)
Colorless oil; [a]Na20 = +11.5 (c 1.0, CHCl3).
The procedures were similar to that used for the aliphatic counter-
parts. The yields of the products were listed in Table 2.
IR (neat): 3447, 2970, 2927, 2800, 1689, 1615, 1463, 1110, 992,
927 cm–1.
(1R,4E)-1-Hydroxy-1-phenylhept-4-en-3-one (8a)
Colorless oil; [a]Na20 = +68.0 (c 0.9, CHCl3).
1H NMR (300 MHz, CDCl3): d = 7.00 (t, 1 H, J = 7.2 Hz,
COC=CHCH2), 5.93–5.86 (m, 1 H, CH2=CHCHOH), 5.35 (d, 1 H,
J = 17.1 Hz, CH2=CHCHOH), 5.18 (d, 1 H, J = 13.5 Hz,
CH2=CHCHOH), 4.69–4.63 (m, 1 H, COCH2CHOH), 3.02–2.95
(m, 3 H, COCH2CHOH), 2.48–2.38 (m, 2 H, C=CHCH2CH3), 1.13
(t, 3 H, J = 7.5 Hz, C=CHCH2CH3).
IR (neat): 3448, 2970, 2936, 1660, 1625, 1455, 1058, 977, 759, 701
cm–1.
1H NMR (300 MHz, CDCl3): d = 7.40–6.96 (m, 5 H, C6H5), 6.91 (dt,
1 H, J = 6.3, 16.2 Hz, COCH=CHCH2), 6.09 (d, 1 H, J = 16.2 Hz,
COCH=CHCH2), 5.22–5.17 (m, 1 H, COCH2CHOH), 3.64 (d, 1 H,
J = 3.0 Hz, OH), 2.95 (d, 2 H, J = 6.0 Hz, COCH2CHOH), 2.28–
2.20 (m, 2 H, CH=CHCH2CH3), 1.07 (t, 3 H, J = 7.5 Hz,
CH=CHCH2CH3).
MS (EI, 70 eV): m/z (%) = 189 (M+ + 1, 3), 171 (15), 159 (9), 132
(28), 117 (56), 97 (24), 70 (40), 57 (98), 55 (69), 53 (88), 43 (100).
Anal. Calcd for C9H13ClO2: C, 57.30; H, 6.95. Found: C, 57.55; H,
7.23.
MS (EI, 70 eV): m/z (%) = 204 (M+, 2), 187 (9), 175 (12), 120 (19),
105 (90), 83 (100), 77 (51), 55 (42), 43 (34).
(3R,6E)-6-Chloro-3-hydroxynona-1,6-dien-5-one (4f)
Colorless oil; [a]Na20 = +9.0 (c 0.3, CHCl3).
HRMS (EI): m/z [M+] calcd for C13H16O2, 204.1150; found,
204.1141.
IR (neat): 3432, 2971, 2927, 2856, 1689, 1614, 1462, 1110, 992
cm–1.
(1R,4E)-1-Hydroxy-1-phenylhex-4-en-3-one [8a(1)]16
Colorless oil; [a]Na20 = +84.5 (c 1.0, CHCl3).
1H NMR (300 MHz, CDCl3): d = 6.30 (t, 1 H, J = 7.8 Hz,
COC=CHCH2), 5.97–5.85 (m, 1 H, CH2=CHCHOH), 5.33 (d, 1 H,
J = 17.1 Hz, CH2=CHCHOH), 5.17 (d, 1 H, J = 10.5 Hz,
CH2=CHCHOH), 4.54–4.52 (m, 1 H, COCH2CHOH), 3.07–2.91
(m, 2 H, COCH2CHOH), 2.87 (s, 1 H, OH), 2.59–2.48 (m, 2 H,
C=CHCH2CH3), 1.10 (t, 3 H, J = 7.8 Hz, C=CHCH2CH3).
MS (EI, 70 eV): m/z (%) = 189 (M+ + 1, 1), 171 (5), 159 (9), 132
(30), 117 (59), 97 (28), 89 (18), 79 (15), 57 (95), 55 (64), 53 (100),
43 (92).
IR (neat): 3449, 3.33, 2973, 1656, 1629, 1442, 1193, 1057, 970,
757, 701 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.39–7.25 (m, 5 H, C6H5), 6.95–
6.83 (m, 1 H, COCH=CHCH3), 6.13 (d, 1 H, J = 15.9 Hz,
COCH=CHCH2), 5.22–5.17 (m, 1 H, COCH2CHOH), 3.64 (d, 1 H,
J = 2.4 Hz, OH), 2.94 (d, 2 H, J = 6.0 Hz, COCH2CHOH), 1.91 (d,
3 H, J = 6.9 Hz, CH=CHCH3).
MS (EI, 70 eV): m/z (%) = 190 (M+, 9), 162 (19), 120 (23), 105 (94),
77 (60), 69 (100), 51 (26), 41 (64), 39 (55).
Synthesis 2004, No. 15, 2449–2458 © Thieme Stuttgart · New York

2456
C. Xu, C. Yuan
PAPER
(1R,1E)-1-Hydroxy-1-phenyloct-4-en-3-one [8a(2)]
Colorless oil; [a]Na20 = +54.1 (c 1.0, CHCl3).
(1R,4E)-1-(2-Furyl)-1-hydroxyhept-4-en-3-one (8d)
Colorless oil; [a]Na20 = +38.9 (c 1.3, CHCl3).
IR (neat): 3449, 3032, 2962, 2933, 1662, 1625, 1454, 1058, 978,
757, 701 cm–1.
IR (neat): 3437, 2970, 2937, 2879, 1663, 1626, 1370, 1147, 1012,
979, 740 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.41–7.26 (m, 5 H, C6H5), 6.86 (dt,
1 H, J = 6.9, 16.2 Hz, COCH=CHCH2), 6.10 (d, 1 H, J = 16.2 Hz,
COCH=CHCH2), 5.20 (d, 1 H, J = 6.3 Hz, COCH2CHOH),
3.65 (s, 1 H, OH), 2.96 (d, 2 H, J = 6.3 Hz, COCH2CHOH),
2.24–2.16 (m, 2 H, CH=CHCH2CH2CH3), 1.55–1.43 (m, 2 H,
1H NMR (300 MHz, CDCl3): d = 7.38–7.37 (m, 1 H, C4H3), 6.97 (dt,
1 H, J = 6.3, 16.8 Hz, COCH=CHCH2), 6.34–6.33 (m, 1 H, C4H3),
6.29–6.27 (m, 1 H, C4H3), 6.12 (d, 1 H, J = 15.9 Hz,
COCH=CHCH2), 5.24–5.19 (m, 1 H, COCH2CHOH), 3.61 (d, 1 H,
J = 4.2 Hz, OH), 3.17 (dd, 1 H, J = 8.4, 17.7 Hz, COCH2CHOH),
3.05 (dd, 1 H, J = 3.3, 17.7 Hz, COCH2CHOH), 2.32–2.22 (m, 2 H,
CH=CHCH2CH3), 1.09 (t, 3 H, J = 7.2 Hz, CH=CHCH2CH3).
CH=CHCH2CH2CH3), 0.93 (t,
CH=CHCH2CH2CH3).
3
H, J = 7.2 Hz,
MS (EI, 70 eV): m/z (%) = 218 (M+, 5), 200 (11), 175 (21), 157 (19),
120 (90), 107 (73), 78 (85), 70 (75), 51 (73), 39 (100).
MS (EI, 70 eV): m/z (%) = 194 (M+, 4), 176 (6), 165 (12), 147 (9),
121 (8), 110 (78), 97 (46), 95 (46), 83 (100), 69 (14), 55 (84), 43
(47).
Anal. Calcd for C14H18O2: C, 77.03; H, 8.31. Found: C, 76.77; H,
8.60,
Anal. Calcd for C11H14O3: C, 68.02; H, 7.27. Found: C, 67.73; H,
7.49.
(1R,43E)-1-Hydroxy-6-methyl-1-phenylhept-4-en-3-one [8a(3)]
Colorless oil; [a]Na20 = +54.9 (c 1.0, CHCl3).
(1R,1E)-1-(2-Chlorophenyl)-1-hydroxyhept-4-en-3-one (8e)
Colorless oil; [a]Na20 = +97.0 (c 1.1, CHCl3).
IR (neat): 3449, 3064, 2966, 2873, 1656, 1624, 1454, 1387, 1364,
1203, 1057, 983, 758, 701 cm–1.
IR (neat): 3443, 2970, 2937, 2880, 1662, 1625, 1440, 1034, 976,
757 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.41–7.26 (m, 5 H, C6H5), 6.82
(dd, 1 H, J = 6.6, 16.2 Hz, COCH=CHCH2), 6.05 (d, 1 H, J = 15.9
Hz, COCH=CHCH), 5.22–5.18 (m, 1 H, COCH2CHOH), 3.65 (d, 1
H, J = 3.0 Hz, OH), 2.97 (d, 2 H, J = 6.3 Hz, COCH2CHOH), 2.49–
2.44 [m, 1 H, CH=CHCH(CH3)2], 1.05 [t, 6 H, J = 6.6 Hz,
CH=CHCH(CH3)2].
1H NMR (300 MHz, CDCl3): d = 7.70–7.64 (m, 1 H, C6H4), 7.35–
7.21 (m, 3 H, C6H4), 6.94 (dt, 1 H, J = 6.3, 16.2 Hz,
COCH=CHCH2), 6.11 (d, 1 H, J = 16.2 Hz, COCH=CHCH2), 5.55–
5.51 (m, 1 H, COCH2CHOH), 3.89 (d, 1 H, J = 3.6 Hz, OH), 3.15
(dd, 1 H, J = 2.1, 17.7 Hz, COCH2CHOH), 2.76 (dd, 1 H, J = 9.3,
17.7 Hz, COCH2CHOH), 2.29–2.24 (m, 2 H, CH=CHCH2CH3),
1.07 (t, 3 H, J = 7.2 Hz, CH=CHCH2CH3).
MS (EI, 70 eV): m/z (%) = 238 (M+, 1), 203 (28), 185 (18), 154 (11),
141 (50), 139 (94), 111 (21), 98 (18), 83 (100), 77 (55), 55 (65), 43
(46).
MS (EI, 70 eV): m/z (%) = 218 (M+, 1), 175 (42), 120 (12), 105 (63),
97 (66), 79 (34), 71 (41), 55 (54), 43 (100).
Anal. Calcd for C14H18O2: C, 77.03; H, 8.31. Found: C, 76.65; H,
8.65.
(1R,4E)-1-(4-Ethylphenyl)-1-hydroxyhept-4-en-3-one (8b)
Colorless oil; [a]Na20 = +84.6 (c 1.1, CHCl3).
Anal. Calcd for C13H15ClO2: C, 65.41; H, 6.33. Found: C, 65.11; H,
6.46.
IR (neat): 3433, 2968, 2936, 2878, 1661, 1626, 1462, 976, 833 cm–1.
(1R,4E)-1-(2-Bromophenyl)-1-hydroxyhept-4-en-3-one (8f)
Colorless oil; [a]Na20 = +105.8 (c 0.9, CHCl3).
1H NMR (300 MHz, CDCl3): d = 7.30 (d, 2 H, J = 8.1 Hz, C6H4),
7.18 (d, 2 H, J = 7.8 Hz, C6H4), 6.91 (dt, 1 H, J = 6.3, 16.2 Hz,
COCH=CHCH2), 6.10 (d, 1 H, J = 16.2 Hz, COCH=CHCH2), 5.20–
5.13 (m, 1 H, COCH2CHOH), 3.59 (d, 1 H, J = 3.0 Hz, OH), 2.96
(t, 2 H, J = 3.9 Hz, COCH2CHOH), 2.64 (q, 2 H, J = 7.5 Hz,
C6H5CH2CH3), 2.27–2.22 (m, 2 H, CH=CHCH2CH3), 1.23 (t, 3 H,
IR (neat): 3446, 2970, 2937, 2879, 1662, 1625, 1467, 1071, 1020,
976, 756 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.65 (d, 1 H, J = 7.2 Hz, C6H4),
7.52 (d, 1 H, J = 7.2 Hz, C6H4), 7.36 (t, 1 H, J = 7.2 Hz, C6H4), 7.14
(t, 1 H, J = 7.5 Hz, C6H4), 6.94 (dt, 1 H, J = 6.3, 16.2 Hz,
COCH=CHCH2), 6.12 (d, 1 H, J = 16.2 Hz, COCH=CHCH2), 5.50–
5.46 (m, 1 H, COCH2CHOH), 3.87 (d, 1 H, J = 3.0 Hz, OH), 3.16
(dd, 1 H, J = 2.7, 17.4 Hz, COCH2CHOH), 2.73 (dd, 1 H, J = 9.3,
17.9 Hz, COCH2CHOH), 2.29–2.22 (m, 2 H, CH=CHCH2CH3),
1.07 (t, 3 H, J = 7.8 Hz, CH=CHCH2CH3).
J = 7.5 Hz, C6H5CH2CH3), 1.07 (t,
CH=CHCH2CH3).
3
H, J = 7.2 Hz,
MS (EI, 70 eV): m/z (%) = 232 (M+, 4), 205 (6), 185 (4), 148 (10),
133 (62), 99 (42), 70 (100), 59 (31), 55 (49), 43 (43).
HRMS (EI): m/z [M+] calcd for C15H20O2, 232.1463; found,
232.1485.
MS (EI, 70 eV): m/z (%) = 283 (M+, 2), 203 (71), 185 (57), 183 (35),
157 (9), 145 (10), 99 (44), 83 (65), 70 (100), 55 (74), 43 (62).
HRMS (EI): m/z [M+] calcd for C13H15BrO2, 282.0255; found,
282.0289.
(1R,4E)-1-Hydroxy-1-(4-methoxyphenyl)hept-4-en-3-one (8c)
Colorless oil; [a]Na20 = +69.1 (c 0.7, CHCl3).
IR (neat): 3453, 2968, 2937, 1662, 1615, 1515, 1249, 1177, 1035,
833 cm–1.
(1R,4E)-1-(4-Fluorophenyl)-1-hydroxyhept-4-en-3-one (8g)
Colorless oil; [a]Na20 = +52.9 (c 0.9, CHCl3).
IR (neat): 3447, 2972, 2938, 1663, 1625, 1511, 1223, 978, 838 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.34 (dd, 2 H, J = 5.4, 9.0 Hz,
C6H4), 7.02 (t, 2 H, J = 6.9 Hz, C6H4), 6.92 (dt, 1 H, J = 6.6, 15.9
Hz, COCH=CHCH2), 6.09 (d, 1 H, J = 15.9 Hz, COCH=CHCH2),
5.18–5.14 (m, 1 H, COCH2CHOH), 3.79 (d, 1 H, J = 3.3 Hz, OH),
2.92 (d, 2 H, J = 6.3 Hz, COCH2CHOH), 2.30–2.20 (m, 2 H,
CH=CHCH2CH3), 1.07 (t, 3 H, J = 7.5 Hz, CH=CHCH2CH3).
1H NMR (300 MHz, CDCl3): d = 7.30 (d, 2 H, J = 6.6 Hz, C6H4),
6.96–6.87 (m, 3 H, C6H4, COCH=CHCH2), 6.10 (d, 1 H, J = 15.9
Hz, COCH=CHCH2), 5.15–5.12 (m, 1 H, COCH2CHOH), 3.80 (s,
3 H, OCH3), 3.58 (d, 1 H, J = 2.7 Hz, OH), 2.94 (t, 2 H, J = 2.1 Hz,
COCH2CHOH), 2.28–2.23 (m, 2 H, CH=CHCH2CH3), 1.07 (t, 3 H,
J = 7.5 Hz, CH=CHCH2CH3).
MS (EI, 70 eV): m/z (%) = 234 (M+, 3), 217 (4), 201 (5), 150 (9),
137 (33), 135 (100), 109 (14), 83 (36), 77 (26), 55 (32), 43 (25).
Anal. Calcd for C14H18O3: C, 71.77; H, 7.74. Found: C, 71.66; H,
7.95.
MS (EI, 70 eV): m/z (%) = 222 (M+, 2), 205 (14), 193 (8), 138 (11),
123 (47), 99 (16), 83 (100), 75 (8), 55 (23), 43 (18).
Synthesis 2004, No. 15, 2449–2458 © Thieme Stuttgart · New York

PAPER
New Reaction System for Horner–Wadsworth–Emmons Olefination
2457
Anal. Calcd for C13H15FO2: C, 70.25; H, 6.80. Found: C, 70.15; H,
7.01.
IR (neat): 3479, 3033, 2963, 2934, 2874, 1687, 1615, 1454, 1180,
760, 700 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.41–7.26 (m, 5 H, C6H5), 6.99 (t,
1 H, J = 6.9 Hz, COC=CHCH3), 5.23 (dd, 1 H, J = 3.6, 8.1 Hz,
COCH2CHOH), 3.34 (s, 1 H, OH), 3.21–3.04 (m, 2 H,
COCH2CHOH), 2.38 (q, 2 H, J = 7.2 Hz, C=CHCH2CH2CH3),
1.59–1.47 (m, 2 H, C=CHCH2CH2CH3), 0.97 (t, 3 H, J = 7.2 Hz,
C=CHCH2CH2CH3).
(1R,4E)-1-(4-Chlorophenyl)-1-hydroxyhept-4-en-3-one (8h)
Colorless oil; [a]Na20 = +60.7 (c 0.8, CHCl3).
IR (neat): 3451, 3062, 2902, 1652, 1608, 1451, 1176, 757, 700 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.38–7.28 (m, 4 H, C6H4), 6.92 (dt,
1 H, J = 6.3, 16.2 Hz, COCH=CHCH2), 6.09 (d, 1 H, J = 16.2 Hz,
COCH=CHCH2), 5.20–5.09 (m, 1 H, COCH2CHOH), 3.74 (s, 1 H,
OH), 2.92 (d, 2 H, J = 6.0 Hz, COCH2CHOH), 2.36–2.21 (m, 2 H,
CH=CHCH2CH3), 1.07 (t, 3 H, J = 7.2 Hz, CH=CHCH2CH3).
MS (EI, 70 eV): m/z (%) = 238 (M+, 2), 209 (11), 191 (5), 165 (6),
154 (24), 141 (50), 139 (100), 111 (25), 83 (71), 77 (49), 55 (54), 43
(36).
MS (EI, 70 eV): m/z (%) = 252 (M+, 5), 235 (7), 217 (4), 131 (19),
105 (100), 79 (36), 77 (36), 51 (10), 43 (9), 39 (11).
Anal. Calcd for C14H17ClO2: C, 66.53; H, 6.78. Found: C, 66.47; H,
7.03.
(1R,4Z)-4-Chloro-1-hydroxy-6-methyl-1-phenylhept-4-en-3-
one [8j(3)]
Anal. Calcd for C13H15ClO2: C, 65.41; H, 6.33. Found: C, 65.33; H,
6.52.
Colorless oil; [a]Na20 = +52.8 (c 0.8, CHCl3).
IR (neat): 3425, 2966, 2874, 1694, 1470, 1363, 1101, 1025, 747,
700 cm–1.
(1R,4E)-1-Hydroxy-1-(4-nitrophenyl)hept-4-en-3-one (8i)
Colorless oil; [a]Na20 = +50.8 (c 1.3, CHCl3).
IR (neat): 3446, 2971, 2938, 1663, 1625, 1521, 1348, 979, 857 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.21 (d, 2 H, J = 7.2 Hz, C6H4),
7.56 (d, 2 H, J = 8.1 Hz, C6H4), 6.95 (dt, 1 H, J = 6.3, 15.9 Hz,
COCH=CHCH2), 6.12 (d, 1 H, J = 15.9 Hz, COCH=CHCH2), 5.32–
5.29 (m, 1 H, COCH2CHOH), 3.96 (d, 1 H, J = 3.0 Hz, OH), 3.01
(dd, 1 H, J = 3.9, 17.7 Hz, COCH2CHOH), 2.93 (dd, 1 H, J = 8.7,
17.7 Hz, COCH2CHOH), 2.304–2.22 (m, 2 H, CH=CHCH2CH3),
1.08 (t, 3 H, J = 7.5 Hz, CH=CHCH2CH3).
1H NMR (300 MHz, CDCl3): d = 7.41–7.26 (m, 5 H, C6H5), 6.78 (d,
1 H, J = 9.0 Hz, COC=CHCH), 5.22 (t, 1 H, J = 4.2 Hz,
COCH2CHOH), 3.37 (d, 1 H, J = 3.0 Hz, OH), 3.22–3.07 (m, 2 H,
COCH2CHOH), 2.97–2.89 [m, 1 H, C=CHCH(CH3)2], 1.08 [d, 6 H,
J = 6.6 Hz, C=CHCH(CH3)2].
MS (EI, 70 eV): m/z (%) = 252 (M+, 7), 209 (15), 173 (7), 131 (21),
105 (100), 98 (27), 83 (42), 79 (50), 71 (69), 43 (66).
Anal. Calcd for C14H17ClO2: C, 66.53; H, 6.78. Found: C, 66.47; H,
7.06.
MS (EI, 70 eV): m/z (%) = 249 (M+, 4), 220 (39), 205 (9), 165 (29),
150 (36), 117 (16), 99 (17), 83 (100), 77 (17), 55 (44), 43 (24).
(1R,4E)-4-Chloro-1-hydroxy-1-phenylhept-4-en-3-one (9j)
Colorless oil; [a]Na20 = +78.0 (c 0.2, CHCl3).
IR (neat): 3449, 2974, 2880, 1686, 1615, 1455, 1110, 761, 701 cm–1.
Anal. Calcd for C13H15NO4: C, 62.64; H, 6.07; N, 5.62. Found: C,
62.34; H, 6.31; N, 5.39.
1H NMR (300 MHz, CDCl3): d = 7.39–7.26 (m, 5 H, C6H5), 6.30 (t,
1 H, J = 7.5 Hz, COC=CHCH2), 5.21 (dd, 1 H, J = 4.2, 9.6 Hz,
COCH2CHOH), 3.24–3.13 (m, 3 H, COCH2CHOH), 2.60–2.49 (m,
2 H, C=CHCH2CH3), 1.07 (t, 3 H, J = 7.5 Hz, C=CHCH2CH3).
MS (EI, 70 eV): m/z (%) = 238 (M+, 6), 203 (4), 132 (11), 117 (11),
105 (100), 79 (42), 77 (39), 53 (17), 43 (12).
(1R,4Z)-4-Chloro-1-hydroxy-1-phenylhept-4-en-3-one (8j)
Colorless oil; [a]Na20 = +43.6 (c 1.0, CHCl3).
IR (neat): 3448, 2974, 2880, 1685, 1616, 1456, 1110, 1059, 761,
700 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.42–7.26 (m, 5 H, C6H5), 6.98 (t,
1 H, J = 7.2 Hz, COC=CHCH2), 5.23 (dd, 1 H, J = 3.9, 8.4 Hz,
COCH2CHOH), 3.35 (s, 1 H, OH), 3.16 (ddd, 2 H, J = 4.2, 8.7, 17.7
Hz, COCH2CHOH), 2.46–2.36 (m, 2 H, C=CHCH2CH3), 1.10 (t, 3
H, J = 7.5 Hz, C=CHCH2CH3).
MS (EI, 70 eV): m/z (%) = 238 (M+, 5), 203 (4), 132 (10), 117 (11),
107 (28), 105 (100), 79 (39), 77 (34), 53 (14), 43 (9).
HRMS (EI): m/z [M+] calcd for C13H15ClO2, 238.0761; found,
238.0790.
(1R,4E)-4-Chloro-1-hydroxy-1-phenylhex-4-en-3-one [9j(1)]
Colorless oil; [a]Na20 = +33.2 (c 0.2, CHCl3).
IR (neat): 3483, 3063, 3033, 2915, 1686, 1624, 1495, 1453, 1293,
1182, 1060, 761, 701 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.41–7.09 (m, 5 H, C6H5), 6.43 (q,
1 H, J = 7.8 Hz, COC=CHCH3), 5.22 (t, 1 H, J = 4.8 Hz,
COCH2CHOH), 3.30–3.12 (m, 3 H, COCH2CHOH), 2.09 (d, 3 H,
J = 7.5 Hz, C=CHCH3).
Anal. Calcd for C13H15ClO2: C, 65.41; H, 6.33. Found: C, 65.14; H,
6.63.
(1R,4Z)-4-Chloro-1-hydroxy-1-phenylhex-4-en-3-one [8j(1)]
Colorless oil; [a]Na20 = +81.9 (c 0.6, CHCl3).
IR (neat): 3483, 3063, 3033, 2914, 1685, 1624, 1495, 1453, 1293,
1182, 1059, 761, 701 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.37–7.25 (m, 5 H, C6H5), 7.07 (q,
1 H, J = 6.9 Hz, COC=CHCH3), 5.20 (dd, 1 H, J = 3.0, 8.1 Hz,
COCH2CHOH), 3.37 (s, 1 H, OH), 3.21–3.04 (m, 2 H,
COCH2CHOH), 2.00 (d, 3 H, J = 6.6 Hz, C=CHCH3).
MS (EI, 70 eV): m/z (%) = 224 (M+, 10), 189 (8), 171 (4), 118 (22),
105 (100), 79 (74), 77 (70), 51 (20), 43 (17), 39 (21).
Anal. Calcd for C12H13ClO2: C, 64.15; H, 5.82. Found: C, 63.94; H,
5.87.
(1R,4E)-4-Chloro-1-hydroxy-1-phenyloct-4-en-3-one [9j(2)]
Colorless oil; [a]Na20 = +15.9 (c 0.2, CHCl3).
MS (EI, 70 eV): m/z (%) = 224 (M+, 5), 189 (5), 131 (4), 118 (13),
105 (100), 79 (52), 77 (48), 51 (16), 43 (19), 39 (21).
IR (neat): 3480, 3033, 2963, 2934, 2875, 1686, 1615, 1455, 1058,
761, 701 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.39–7.26 (m, 5 H, C6H5), 6.32 (t,
1 H, J = 8.4 Hz, COC=CHCH2), 5.24 (dd, 1 H, J = 3.0, 6.0 Hz,
COCH2CHOH), 3.25 (s, 1 H, OH), 3.18–3.16 (m, 2 H,
COCH2CHOH), 2.52 (q, 2 H, J = 6.9 Hz, C=CHCH2CH2CH3),
Anal. Calcd for C12H13ClO2: C, 64.15; H, 5.82. Found: C, 63.95; H,
6.00.
(1R,4Z)-4-Chloro-1-hydroxy-1-phenyloct-4-en-3-one [8j(2)]
Colorless oil; [a]Na20 = +18.6 (c 0.8, CHCl3).
Synthesis 2004, No. 15, 2449–2458 © Thieme Stuttgart · New York

2458
C. Xu, C. Yuan
PAPER
1.61–1.47 (m, 2 H, C=CHCH2CH2CH3), 0.98 (t, 3 H, J = 7.2 Hz,
C=CHCH2CH2CH3).
MS (EI, 70 eV): m/z (%) = 256 (M+, 3), 221 (17), 149 (13), 125 (49),
123 (100), 117 (16), 97 (61), 77 (19), 53 (21), 43 (23).
MS (EI, 70 eV): m/z (%) = 252 (M+, 7), 217 (7), 131 (16), 105 (100),
79 (51), 77 (45), 51 (11), 43 (8), 39 (9).
Anal. Calcd for C13H14ClFO2: C, 60.83; H, 5.50. Found: C, 60.88;
H, 5.72.
Anal. Calcd for C14H17ClO2: C, 66.53; H, 6.78. Found: C, 66.50; H,
7.03.
(1R,4E)-4-Chloro-1-(4-fluorophenyl)-1-hydroxyhept-4-en-3-
one (9l)
Colorless oil; [a]Na20 = +25.6 (c 0.3, CHCl3).
(1R,4E)-4-Chloro-1-hydroxy-6-methyl-1-phenylhept-4-en-3-
one [9j(3)]
IR (neat): 3425, 2970, 2930, 2881, 1688, 1608, 1512, 1225, 1156,
836 cm–1.
Colorless oil; [a]Na20 = +51.0 (c 0.2, CHCl3).
IR (neat): 3434, 2966, 2874, 1694, 1470, 1363, 1100, 1025, 747,
700 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.37 (dd, 2 H, J = 5.1, 8.1 Hz,
C6H4), 7.06 (t, 2 H, J = 8.7 Hz, C6H4), 6.34 (t, 1 H, J = 7.8 Hz,
COC=CHCH2), 5.19 (t, 1 H, J = 6.0 Hz, COCH2CHOH), 3.24 (s, 1
H, OH), 3.15 (d, 2 H, J = 6.3 Hz, COCH2CHOH), 2.61–2.52 (m, 2
H, C=CHCH2CH3), 1.09 (t, 3 H, J = 7.5 Hz, C=CHCH2CH3).
1H NMR (300 MHz, CDCl3): d = 7.41–7.26 (m, 5 H, C6H5), 6.11 (d,
1
H, J = 10.2 Hz, COC=CHCH), 5.22–5.18 (m, 1 H,
COCH2CHOH), 3.53–3.47 (m, 3 H, COCH2CHOH), 3.18–3.12 [m,
1 H, C=CHCH(CH3)2], 1.09 [d, 6 H, J = 6.9 Hz, C=CHCH(CH3)2].
MS (EI, 70 eV): m/z (%) = 256 (M+, 4), 221 (3), 132 (6), 125 (35),
123 (100), 117 (10), 97 (38), 95 (15), 77 (13), 53 (15), 43 (15).
HRMS (EI): m/z [M+] calcd for C13H14ClFO2, 256.0666; found,
MS (EI, 70 eV): m/z (%) = 252 (M+, 1), 173 (8), 144 (11), 127 (50),
98 (72), 83 (100), 72 (97), 55 (33), 43 (60).
256.0673.
Anal. Calcd for C14H17ClO2: C, 66.53; H, 6.78. Found: C, 66.63; H,
6.97.
Acknowledgment
(1R,4Z)-4-Chloro-1-hydroxy-1-(4-methoxyphenyl)hept-4-en-3-
one (8k)
This project was supported by the National Natural Science Found-
ations of China (Grant No. 20272075 and 20372076).
Colorless oil; [a]Na20 = +21.0 (c 0.8, CHCl3).
IR (neat): 3456, 2971, 1687, 1614, 1515, 1250, 1036, 832 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.31 (d, 2 H, J = 7.5 Hz, C6H4),
6.98 (t, 1 H, J = 7.2 Hz, COC=CHCH2), 6.90 (d, 2 H, J = 6.6 Hz,
C6H4), 5.17 (dd, 1 H, J = 3.6, 8.4 Hz, COCH2CHOH), 3.81 (s, 3 H,
OCH3), 3.35 (s, 1 H, OH), 3.13 (ddd, 2 H, J = 3.9, 8.4, 17.4 Hz,
COCH2CHOH), 2.49–2.38 (m, 2 H, C=CHCH2CH3), 1.10 (t, 3 H,
J = 7.2 Hz, C=CHCH2CH3).
References
(1) Trost, B. M.; Hanson, P. R. Tetrahedron Lett. 1994, 35,
8119.
(2) Matsumoto, K.; Shimagaki, M.; Nakata, T.; Oishi, T.
Tetrahedron Lett. 1993, 34, 4935.
(3) Feldman, K. S.; Simpson, R. E. Tetrahedron Lett. 1989, 30,
6985.
(4) Bercich, M. D.; Cambie, R. C.; Rutledge, P. S. Aust. J.
Chem. 1999, 52, 851.
(5) Hong, B. C.; Chin, S. F. Synth. Commun. 1997, 27, 1191.
(6) (a) Hasegawa, E.; Yoneoka, A.; Suzuki, K.; Kato, T.;
Kitazume, T.; Yanagi, K. Tetrahedron 1999, 55, 12957.
(b) Hasegawa, E.; Chiba, N.; Nakajima, A.; Suzuki, K.;
Yoneoka, A.; Iwaya, K. Synthesis 2001, 1248.
(7) Trost, B. M.; Jonasson, C.; Wuchrer, M. J. Am. Chem. Soc.
2001, 123, 12736.
(8) Fang, J. M.; Chen, M. Y. Tetrahedron Lett. 1988, 29, 5939.
(9) Deagostino, A.; Prandi, C.; Venturello, P. Tetrahedron
1996, 52, 1433.
(10) (a) Zhang, Y. H.; Xu, C. F.; Li, J. F.; Yuan, C. Y.
Tetrahedron: Asymmetry 2003, 14, 63. (b) Xu, C. F.; Yuan,
C. Y. Tetrahedron 2004, 60, 3883. (c) Tsuge, O.;
Kanemasa, S.; Nakagawa, N.; Suga, H. Bull. Chem. Soc.
Jpn. 1987, 60, 4091.
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1989, 62, 860.
(12) Xu, C. F.; Zhang, Y. H.; Yuan, C. Y. Eur. J. Org. Chem.
2004, 2253.
(13) (a) Yuan, C. Y.; Xu, C. F.; Zhang, Y. H. Tetrahedron 2003,
59, 6095. (b) Zhang, Y. H.; Yuan, C. Y.; Li, Z. Y.
Tetrahedron 2002, 58, 2973. (c) Zhang, Y. H.; Li, Z. Y.;
Yuan, C. Y. Tetrahedron Lett. 2002, 43, 3247.
(14) Colle, S.; Taillefumier, C.; Chapleur, Y.; Liebl, R.; Schmidt,
A. Bioorg. Med. Chem. 1999, 7, 1049.
(15) Deagostino, A.; Prandi, C.; Venturello, P. Tetrahedron
1996, 52, 1433.
(16) (a) Hong, B. C.; Chin, S. F. Synth. Commun. 1997, 27, 1191.
(b) Bercich, M. D.; Cambie, R. C.; Rutledge, P. S. Aust. J.
Chem. 1999, 52, 85.
MS (EI, 70 eV): m/z (%) = 268 (M+, 3), 251 (17), 161 (6), 137 (56),
135 (100), 117 (10), 109 (21), 94 (11), 77 (23), 53 (15), 43 (21).
Anal. Calcd for C14H17ClO3: C, 62.58; H, 6.38. Found: C, 62.62; H,
6.68.
(1R,4E)-4-Chloro-1-hydroxy-1-(4-methyoxyphenyl)hept-4-en-
3-one (9k)
Colorless oil; [a]Na20 = +30.8 (c 0.4, CHCl3).
IR (neat): 3493, 2973, 2911, 1685, 1614, 1515, 1250, 1035, 832
cm–1.
1H NMR (300 MHz, CDCl3): d = 7.31 (d, 2 H, J = 7.2 Hz, C6H4),
6.90 (d, 2 H, J = 6.9 Hz, C6H4), 6.30 (t, 1 H, J = 7.2 Hz,
COC=CHCH2), 5.20–5.03 (m, 1 H, COCH2CHOH), 3.82 (s, 3 H,
OCH3), 3.22–3.03 (m, 3 H, COCH2CHOH), 2.59–2.42 (m, 2 H,
C=CHCH2CH3), 1.12 (t, 3 H, J = 7.2 Hz, C=CHCH2CH3).
MS (EI, eV): m/z (%) = 268 (M+, 3), 224 (8), 153 (7), 137 (67), 135
(100), 126 (27), 109 (20), 98 (25), 77 (18), 70 (40), 55 (28), 43 (19).
HRMS (EI): m/z [M+] calcd for C14H17ClO3, 268.0866; found,
268.0904.
(1R,4Z)-4-Chloro-1-(4-fluorophenyl)-1-hydroxyhept-4-en-3-
one (8l)
Colorless oil; [a]Na20 = +31.2 (c 1.0, CHCl3).
IR (neat): 3429, 2972, 2939, 1688, 1608, 1512, 1224, 1156, 837
cm–1.
1H NMR (300 MHz, CDCl3): d = 7.36 (dd, 2 H, J = 5.7, 9.0 Hz,
C6H4), 7.08–6.96 (m, 3 H, C6H4, COC=CHCH2), 5.24–5.20 (m, 1 H,
COCH2CHOH), 3.84 (s, 1 H, OH), 3.21–3.05 (m, 2 H,
COCH2CHOH), 2.42–2.39 (m, 2 H, C=CHCH2CH3), 1.11 (t, 3 H,
J = 7.8 Hz, C=CHCH2CH3).
Synthesis 2004, No. 15, 2449–2458 © Thieme Stuttgart · New York