Stereoselective synthesis of tetrasubstituted (Z)-alkenes from aryl alkyl ketones utilizing the Horner-Wadsworth-Emmons reaction

Article abstract of DOI:10.1248/cpb.50.1300

Tetrasubstituted (Z)-alkenes were readily prepared through the Horner-Wadsworth-Emmons reactions of methyl 2-[bis(2,2,2-trifluoroethyl) phosphono]propionate with aryl alkyl ketones by employing Sn(OSO ₂CF₃)₂ and N-ethylpiperidine.

Full text of DOI:10.1248/cpb.50.1300

1300
Notes
Chem. Pharm. Bull. 50(9) 1300—1302 (2002)
Vol. 50, No. 9
Stereoselective Synthesis of Tetrasubstituted (Z)-Alkenes from Aryl Alkyl
Ketones Utilizing the Horner–Wadsworth–Emmons Reaction
Shigeki SANO,* Tomoka TAKEHISA, Shiho OGAWA, Kenji YOKOYAMA, and Yoshimitsu NAGAO
Faculty of Pharmaceutical Sciences, The University of Tokushima; Sho-machi, Tokushima 770–8505, Japan.
Received June 3, 2002; accepted June 27, 2002
Tetrasubstituted (Z)-alkenes were readily prepared through the Horner–Wadsworth–Emmons reactions of
methyl 2-[bis(2,2,2-trifluoroethyl)phosphono]propionate with aryl alkyl ketones by employing Sn(OSO2CF3)2 and
N-ethylpiperidine.
Key words Horner–Wadsworth–Emmons reaction; tetrasubstituted alkene; aryl alkyl ketone; a,b-unsaturated ester; methyl 2-
[bis(2,2,2-trifluoroethyl)phosphono]propionate; Wittig reaction
1
confirmed by H–1H nuclear Overhauser effect (NOE) (400
The Horner–Wadsworth–Emmons (HWE) reaction is the
most popular method of synthesizing a,b-unsaturated esters.1)
MHz, CDCl3) experiments. The E : Z ratios of 4a—c, e—h
1
were determined by utilizing H-NMR analysis (400 MHz,
CDCl3).
We have recently reported a new approach to the stereo-
selective HWE reaction of methyl bis(2,2,2-trifluoroethyl)-
phosphonoacetate (1)2) or ethyl 2-fluoro-2-diethylphospho-
noacetate3) with aryl alkyl ketones by using Sn(OSO2CF3)2
and N-ethylpiperidine.4—8) While a number of methods have
been developed for the stereoselective synthesis of alkenes,
few accounts have appeared in the literature describing the
convenient preparation of tetrasubstituted (Z)-alkenes with
excellent selectivity.9—13) We have already presented a facile
method for obtaining tetrasubstituted (E)-fluoroalkenes.5)
Herein we describe a stereoselective synthesis of tetrasubsti-
tuted (Z)-alkenes based on the HWE reactions of methyl 2-
[bis(2,2,2-trifluoroethyl)phosphono]propionate (2) with aryl
alkyl ketones 3a—h, as shown in Chart 1.
As mentioned above, the HWE reactions of phosphonate 2
with various aryl alkyl ketones 3a, b, e—h under the NaH
conditions gave tetrasubstituted (Z)-alkenes 4a, b, e—h with
moderate selectivity. However, the Z-selectivities of tetrasub-
stituted alkenes under the NaH conditions were better than
the prediction from the viewpoint of the previous results re-
Phosphonate 22,14) was prepared by the methylation of
phosphonate 1 with tert-BuOK and MeI in 53% yield. The
reactions of phosphonate 2 with aryl alkyl ketones 3a—h
using Sn(OSO2CF3)2 and N-ethylpiperidine were examined.
All results are summarized in Table 1. Treatment of 2 with
phenyl ethyl ketone (3b) at 0 °C produced tetrasubstituted
(Z)-alkene 4b with an E : Z ratio of 6 : 94, and in 38% yield
(Table 1, entry 3). A significant improvement in the yield
(86%) and a similar Z-selectivity (E : Zϭ7 : 93) were found in
the reaction of 2 with 3b under reflux (Table 1, entry 2). In
the HWE reactions of aryl alkyl ketones 3a—c, e, f, the
stereoselectivities were in a range of E : Z ratios of 8 : 92—
3 : 97, as shown in Table 1. No reaction occurred in the case
of ketone 3d bearing a bulky tert-butyl group (Table 1, entry
5). Each reaction of aryl alkyl ketones 3g, h having an elec-
tron-withdrawing nitro group on the aromatic moiety, pro-
ceeded even at 0 °C, but resulted in a lower stereoselectivity
(E : Zϭ25 : 75 or 27 : 73) (Table 1, entries 8 and 9). In the
HWE reactions employing NaH, the E : Z stereoselectivities
of the products were moderate, with ratios of 41 : 59—
11 : 89, as listed in Table 2. It is worth noting that the reac-
tion of ketone 3c bearing a relatively bulky isopropyl group
did not occur under the NaH conditions (Table 2, entry 4),
while it readily proceeded under the Sn(OSO2CF3)2 condi-
tions (Table 1, entry 4). The Sn(OSO2CF3)2-mediated HWE
reactions therefore seem to proceed in a chelation-controlled
manner as we have proposed in a previous report, whereas
the NaH-mediated HWE reactions proceed in a non-chela-
tion-controlled manner.4) The geometry of 4a—c, e—h was
Chart 1
Table 1. Sn(OSO2CF3)2-Mediated Horner–Wadsworth–Emmons Reactions
of 2 with Ketones 3a—ha)
Yield
(%)b)
Alkene
Entry
Ketone
Temp.
(E/Z)c)
1
2
3
4
5
6
7
8
9
3a
3b
3b
3c
3d
3e
3f
Reflux
Reflux
0 °C
Reflux
Reflux
Reflux
Reflux
0 °C
42d)
86
38
4a (8 : 92)
4b (7 : 93)
4b (6 : 94)
4c (4 : 96)
—
4e (4 : 96)
4f (3 : 97)
4g (25 : 75)
4h (27 : 73)
66
e)
—
14d)
49
3g
3h
65
56
0 °C
a) Conditions: CH2Cl2, 20 h, 2/Sn(OSO2CF3)2/N-ethylpiperidine/3 (1.4 : 1.68 : 1.54 : 1).
b) Isolated yields. c) 1H-NMR (400 MHz, CDCl3) analysis. d) Aldol product was
obtained (entry 1: 20%, entry 6: 34%). e) No reaction.
To whom correspondence should be addressed. e-mail: ssano@ph2.tokushima-u.ac.jp
© 2002 Pharmaceutical Society of Japan

September 2002
1301
Table 2. NaH-Mediated Horner–Wadsworth–Emmons Reactions of 2 with
Ketones 3a—ha)
Experimental
All melting points were determined on a Yanaco micro melting point ap-
paratus and are uncorrected. IR spectra were obtained using a Perkin–Elmer
1720 or JASCO FT/IR-420 IR Fourier transform spectrometer. 1H-NMR
(200 and 300 MHz) spectra were recorded on a JEOL JNM-FX 200 or JEOL
JNM-AL300 spectrometer. Chemical shifts are given in d values (ppm)
using tetramethylsilane (TMS) as an internal standard. Electron impact (EI)-
MS spectra were recorded on a JEOL JMS SX-102A spectrometer. Elemen-
tary combustion analyses were performed using a Yanaco CHN CORDER
MT-5. All reactions were monitored by TLC employing 0.25-mm silica gel
plates (Merck 5715; 60 F254). Preparative TLC (PTLC) was performed on
0.5-mm silica gel plates (Merck 5744; 60 F254). Column chromatography
was carried out on silica gel [Katayama Chemical K070; 70—300 mesh,
Kanto Chemical N60 (spherical, neutral); 63—210 mm, Merck 9385; 230—
400 mesh]. The usual workup refers to washing an organic portion with
brine, drying it over anhydrous MgSO4, filtration, and concentration in
vacuo. Tetrahydrofuran (THF) was distilled from sodium benzophenone
ketyl under N2. N-Ethylpiperidine and CH2Cl2 were distilled from CaH2. All
other solvents were distilled prior to use. All reagents were used as pur-
chased.
Yield
(%)b)
Alkene
Entry
Ketone
Temp.
(E/Z)c)
1
2
3
4
5
6
7
8
9
3a
3b
3b
3c
3d
3e
3f
Reflux
Reflux
0 °C
Reflux
Reflux
Reflux
Reflux
0 °C
95
70
4a (14 : 86)
4b (12 : 88)
d)
Trace
—
—
—
e)
—
—
e)
90
79
100
73
4e (41 : 59)
4f (11 : 89)
4g (15 : 85)
4h (25 : 75)
3g
3h
0 °C
a) Conditions: THF, 20 h, 2/NaH/3 (1.7 : 1.5 : 1). b) Isolated yields. c) 1H-NMR
(400 MHz, CDCl3) analysis. d) Not determined. e) No reaction.
Methyl 2-[Bis(2,2,2-trifluoroethyl)phosphono]propionate (2) To a so-
lution of tert-BuOK (1.9 g, 17.0 mmol) in THF (20 ml) was slowly added
methyl bis(2,2,2-trifluoroethyl)phosphonoacetate (1) (3.0 ml, 14.2 mmol) at
0 °C under nitrogen. The mixture was stirred at 0 °C for 30 min under nitro-
gen, and methyl iodide (4.42 ml, 70.9 mmol) was slowly added at 0 °C. After
being stirred at room temperature for 14 h under nitrogen, the reaction mix-
ture was treated with an aqueous solution saturated with NH4Cl and then ex-
tracted with AcOEt (50 mlϫ3). The extract was submitted to the usual
workup to give an oily residue, which was purified by column chromatogra-
phy on silica gel [n-hexane/AcOEt (2 : 1)] to afford 2 (2.22 g, 53%) as a col-
orless oil. 1H-NMR (300 MHz, CDCl3) d: 1.52 (3H, dd, 4JH,Pϭ19.3 Hz,
Jϭ7.3 Hz), 3.21 (1H, dq, 2JH,Pϭ22.9 Hz, Jϭ7.3 Hz), 3.78 (3H, s), 4.36—
Chart 2
4.51 (4H, m); IR (neat) 1748, 1421, 1386, 1264, 1173, 1077, 964, 871 cmϪ1
;
Table 3. NaH-Mediated Horner–Wadsworth–Emmons Reactions of 1 with
Ketones 3b, g, ha)
EI-MS calcd for C8H11O5F6P MW 332.0249, found m/z 332.0230 (Mϩ);
Anal. Calcd for C8H11O5F6P: C, 28.93; H, 3.34. Found: C, 28.82; H, 3.31.
Typical Procedure for the HWE Reaction with Sn(OSO2CF3)2 To a
suspension of Sn(OSO2CF3)2 (309 mg, 0.74 mmol) in anhydrous CH2Cl2
(5 ml) was added a solution of phosphonate 2 (206 mg, 0.62 mmol) in anhy-
drous CH2Cl2 (3 ml) and stirred at room temperature for 5 min under argon.
After adding of N-ethylpiperidine (110 ml, 0.68 mmol), the mixture was
stirred at 0 °C for 1 h under argon, and phenyl ethyl ketone (3b) (59 ml,
0.44 mmol) was slowly added to the refluxing solution. After being refluxed
for 20 h under argon, the reaction mixture was poured into H2O (5 ml) and
then extracted with CHCl3 (20 mlϫ3). To the CHCl3 extract was added n-
hexane (120 ml), and the mixture was submitted to filtration through a silica
gel short column [n-hexane/CHCl3 (2 : 1)]. The filtrate was evaporated in
vacuo to afford a crude product 4b (E : Zϭ7 : 93), which was purified by col-
umn chromatography on silica gel [n-hexane/Et2O (25 : 1)] to afford E-4b
(6.3 mg, 7%) and Z-4b (81.1 mg, 79%) as a pale yellow oil and a colorless
oil, respectively.
Yield
(%)b)
Alkene
Entry
Ketone
Temp.
(E/Z)c)
1
3b
3g
3h
Reflux
0 °C
0 °C
86
99
99
5b (41 : 59)
5g (35 : 65)
5h (34 : 66)
2d)
3
a) Conditions: THF, 20 h, 1/NaH/3 (1.7 : 1.5 : 1). b) Isolated yields. c) 1H-NMR
(400 MHz, CDCl3) analysis. d) 19 h, ref. 8.
garding the stereoselective synthesis of trisubstituted (Z)-
alkenes.4) In order to compare the stereoselectivity of phos-
phonate 2 with that of phosphonate 1 toward aryl alkyl ke-
tones, the HWE reactions of ketones 3b, g, h with phospho-
nate 1 using NaH were examined. The results showed that
the Z-selectivity of tetrasubstituted alkenes 4b, g, h (E : Zϭ
12 : 88, 15 : 85, or 25 : 75) were superior to that of trisubsti-
tuted alkenes 5b, g, h (E : Zϭ41 : 59, 35 : 65, or 34 : 66), re-
spectively, as shown in Tables 2 and 3. A CH/p attraction
between the a-methyl group of phosphonate 2 and the
phenyl group of ketones 3b, g, h may participate in the tran-
sition state for the formation of pro-(Z)-oxyanion intermedi-
ates.15—17) However, the mechanism governing the stereose-
lective outcome giving tetrasubstituted alkenes 4b, g, h under
NaH conditions is not yet clear. The geometry and the di-
astereomer ratios of 5b, g, h were confirmed on the basis of
Typical Procedure for the HWE Reaction with NaH To a suspension
of NaH (abs. 60% in oil, 22 mg, 0.55 mmol) in anhydrous THF (5 ml) was
added a solution of phosphonate 2 (207 mg, 0.62 mmol) in anhydrous THF
(3 ml) at 0 °C. The mixture was stirred at 0 °C for 1 h under argon, and
phenyl ethyl ketone (3b) (49 ml, 0.37 mmol) was added to the refluxing solu-
tion. After being refluxed for 20 h under argon, 5% HCl (15 ml) was added
and then extracted with Et2O (20 mlϫ3). The extract was submitted to the
usual workup to give a crude product 4b (E : Zϭ12 : 88), which was purified
by column chromatography on silica gel [n-hexane/Et2O (25 : 1)] to afford
E-4b (6.6 mg, 9%) and Z-4b (45.6 mg, 61%) as a pale yellow oil and a color-
less oil, respectively.
Methyl (E)-2-Methyl-3-phenyl-2-butenoate [(E)-4a]: Colorless oil; 1H-
NMR (300 MHz, CDCl3) d: 1.75 (3H, q, Jϭ1.4 Hz), 2.26 (3H, q, Jϭ1.4 Hz),
3.80 (3H, s), 7.12—7.15 (2H, m), 7.27—7.38 (3H, m); IR (neat) 2949, 1716,
1433, 1253, 1133, 1099 cmϪ1; EI-MS calcd for C12H14O2 MW 190.0994,
found m/z 190.1000 (Mϩ).
1H–1H NOE experiments (400 MHz, CDCl3) and H-NMR
(400 MHz, CDCl3) analysis, respectively
In summary, we have demonstrated that the Sn(OSO2CF3)2-
mediated HWE reactions are applicable to the stereoselective
synthesis of tetrasubstituted (Z)-alkenes. Clarification of the
details of the reaction mechanisms of the stereoselective
HWE reactions is currently underway in our laboratory.
1
Methyl (Z)-2-Methyl-3-phenyl-2-butenoate [(Z)-4a]: Colorless oil; 1H-
NMR (300 MHz, CDCl3) d: 2.05 (3H, q, Jϭ0.6 Hz), 2.09 (3H, q, Jϭ0.6 Hz),
3.39 (3H, s), 7.12—7.14 (2H, m), 7.23—7.32 (3H, m); IR (neat) 2947, 1714,
1433, 1316, 1243, 1139 cmϪ1; EI-MS calcd for C12H14O2 MW 190.0994,
found m/z 190.0996 (Mϩ); Anal. Calcd for C12H14O2: C, 75.76; H, 7.42.
Found: C, 75.49; H, 7.53.
Methyl (E)-2-Methyl-3-phenyl-2-pentenoate [(E)-4b]: Pale yellow oil;
1H-NMR (300 MHz, CDCl3) d: 0.94 (3H, t, Jϭ7.3 Hz), 1.71 (3H, s), 2.61

1302
Vol. 50, No. 9
MW 190.0994, found m/z 190.0987 (Mϩ); Anal. Calcd for C12H14O2: C,
(2H, q, Jϭ7.3 Hz), 3.80 (3 H, s), 7.09—7.12 (2H, m), 7.28—7.38 (3H, m);
IR (neat) 2922, 2851, 1718, 1684, 1598, 1260, 1098, 1026 cmϪ1; EI-MS
calcd for C13H16O2 MW 204.1150, found m/z 204.1141 (Mϩ).
75.76; H, 7.42. Found: C, 75.47; H, 7.45.
Methyl (Z)-3-Phenyl-2-pentenoate [(Z)-5b]: Colorless oil; H-NMR (200
1
1
Methyl (Z)-2-Methyl-3-phenyl-2-pentenoate [(Z)-4b]: Colorless oil; H-
MHz, CDCl3) d: 1.05 (3H, t, Jϭ7.3 Hz), 2.47 (2H, q, Jϭ7.3 Hz), 3.54 (3H,
s), 5.88 (1H, s), 7.13—7.36 (5H, m); IR (neat) 1730, 1641, 1601, 1493,
1371, 1227, 1165, 1031, 1004, 966, 871 cmϪ1; EI-MS calcd for C12H14O2
MW 190.0994, found m/z 190.1004 (Mϩ).
NMR (300 MHz, CDCl3) d: 0.94 (3H, t, Jϭ7.5 Hz), 2.03 (3H, s), 2.47 (2H,
q, Jϭ7.5 Hz), 3.36 (3 H, s), 7.09—7.12 (2H, m), 7.23—7.31 (3H, m); IR
(neat) 2931, 1716, 1600, 1434, 1305, 1238, 1138 cmϪ1; EI-MS calcd for
C13H16O2 MW 204.1150, found m/z 204.1161 (Mϩ); Anal. Calcd for
C13H16O2: C, 76.44; H, 7.90. Found: C, 76.18; H, 7.95.
Methyl (E)-3-(p-Nitrophenyl)-2-butenoate [(E)-5g]8): Colorless needles
(EtOH): mp 206—208.5 °C; 1H-NMR (200 MHz, CDCl3) d: 2.60 (3H, d,
Jϭ1.0 Hz), 3.79 (3H, s), 6.19 (1H, q, Jϭ1.0 Hz), 7.60—7.64 (2H, m),
8.22—8.26 (2H, m); IR (KBr) 3079, 2958, 1743, 1729, 1515, 1345, 1292,
1147, 1010, 853 cmϪ1; EI-MS calcd for C11H11NO4 MW 221.0688, found
m/z 221.0701 (Mϩ); Anal. Calcd for C11H11NO4: C, 59.73; H, 5.01; N, 6.33.
Found: C, 59.65; H, 5.10; N, 6.23.
Methyl (E)-2,4-Dimethyl-3-phenyl-2-pentenoate [(E)-4c]: Pale yellow
1
oil; H-NMR (300 MHz, CDCl3) d: 0.94 (6H, d, Jϭ6.8 Hz), 1.57 (3H, s),
3.29 (1H, sept, Jϭ6.8 Hz), 3.80 (3 H, s), 7.00—7.02 (2H, m), 7.22—7.37
(3H, m); IR (neat) 2922, 1732, 1646, 1457, 1260, 1024 cmϪ1; EI-MS calcd
for C14H18O2 MW 218.1307, found m/z 218.1340 (Mϩ).
Methyl (Z)-3-(p-Nitrophenyl)-2-butenoate [(Z)-5g]8): Colorless needles
(EtOH): mp 117.5—120 °C; 1H-NMR (200 MHz, CDCl3) d: 2.20 (3H, d,
Jϭ1.2 Hz), 3.57 (3H, s), 6.01 (1H, q, Jϭ1.2 Hz), 7.33—7.37 (2H, m),
8.21—8.25 (2H, m); IR (KBr) 2953, 1743, 1728, 1632, 1515, 1345, 1010,
852 cmϪ1; EI-MS calcd for C11H11NO4 MW 221.0688, found m/z 221.0707
(Mϩ); Anal. Calcd for C11H11NO4: C, 59.73; H, 5.01; N, 6.33. Found: C,
59.77; H, 5.09; N, 6.26.
Methyl (Z)-2,4-Dimethyl-3-phenyl-2-pentenoate [(Z)-4c]: Colorless oil;
1H-NMR (300 MHz, CDCl3) d: 0.95 (6H, t, Jϭ6.8 Hz), 2.03 (3H, s), 3.06
(1H, sept, Jϭ6.8 Hz), 3.30 (3 H, s), 7.01—7.04 (2H, m), 7.20—7.30 (3H,
m); IR (neat) 2965, 1716, 1433, 1314, 1241, 1135 cmϪ1; EI-MS calcd for
C14H18O2 MW 218.1307, found m/z 218.1292 (Mϩ); Anal. Calcd for
C14H18O2: C, 77.03; H, 8.31. Found: C, 76.84; H, 8.36.
Methyl (E)-2-Methyl-3-(p-methoxyphenyl)-2-butenoate [(E)-4e]: Color-
less oil; 1H-NMR (300 MHz, CDCl3) d: 1.78 (3H, d, Jϭ1.4 Hz), 2.25 (3H, d,
Jϭ1.4 Hz), 3.79 (3H, s), 3.82 (3H, s), 6.87—6.91 (2H, m), 7.06—7.10 (2H,
m); IR (neat) 2950, 1714, 1608, 1510, 1248, 1132, 1032 cmϪ1; EI-MS calcd
for C13H16O3 MW 220.1100, found m/z 220.1082 (Mϩ).
Methyl (E)-3-(m-Nitrophenyl)-2-pentenoate [(E)-5h]: Colorless plates (n-
1
hexane–Et2O): mp 56—57 °C; H-NMR (300 MHz, CDCl3) d: 1.09 (3H, t,
Jϭ7.5 Hz), 3.14 (2H, q, Jϭ7.5 Hz), 3.78 (3H, s), 6.08 (1H, s), 7.55—7.60
(1H, m), 7.74—7.77 (1H, m), 8.21—8.29 (2H, m); IR (KBr) 1710, 1622,
1529, 1349, 1191, 879 cmϪ1; EI-MS calcd for C12H13NO4 MW 235.0845,
found m/z 235.0835 (Mϩ); Anal. Calcd for C12H13NO4: C, 61.27; H, 5.57; N,
5.59. Found: C, 61.25; H, 5.59; N, 5.98.
Methyl (Z)-2-Methyl-3-(p-methoxyphenyl)-2-butenoate [(Z)-4e]: Color-
less oil; 1H-NMR (300 MHz, CDCl3) d: 2.01 (3H, d, Jϭ0.9 Hz), 2.07 (3H, d,
Jϭ0.9 Hz), 3.44 (3H, s), 3.80 (3H, s), 6.81—6.85 (2H, m), 7.05—7.10 (2H,
m); IR (neat) 2948, 1711, 1608, 1509, 1288, 1247, 1179, 1138, 1032 cmϪ1
;
Methyl (Z)-3-(m-Nitorophenyl)-2-pentenoate [(Z)-5h]: Pale yellow oil;
1H-NMR (300 MHz, CDCl3) d: 1.09 (3H, t, Jϭ7.5 Hz), 2.49 (2H, q, Jϭ
7.5 Hz), 3.56 (3H, s), 5.98 (1H, s), 7.47—7.56 (2H, m), 8.01—8.05 (1H, m),
8.17—8.20 (1H, m); IR (neat) 2971, 1725, 1646, 1530, 1434, 1349, 1233,
1175, 874 cmϪ1; EI-MS calcd for C12H13NO4 MW 235.0845, found m/z
235.0833 (Mϩ); Anal. Calcd for C12H13NO4: C, 61.27; H, 5.57; N, 5.59.
Found: C, 61.25; H, 5.60; N, 5.61.
EI-MS calcd for C13H16O3 MW 220.1100, found m/z 220.1087 (Mϩ); Anal.
Calcd for C13H16O3: C, 70.89; H, 7.32. Found: C, 70.93; H, 7.48.
Methyl (E)-2-Methyl-3-(p-methoxyphenyl)-2-pentenoate [(E)-4f]: Color-
less oil; 1H-NMR (300 MHz, CDCl3) d: 0.93 (3H, t, Jϭ7.5 Hz), 1.73 (3H, s),
2.59 (2H, q, Jϭ7.5 Hz), 3.79 (3H, s), 3.82 (3H, s), 6.87—6.92 (2H, m),
7.02—7.07 (2H, m); IR (neat) 2925, 1716, 1608, 1509, 1246, 1133 cmϪ1
;
EI-MS calcd for C14H18O3 MW 234.1256, found m/z 234.1245 (Mϩ).
Methyl (Z)-2-Methyl-3-(p-methoxyphenyl)-2-pentenoate [(Z)-4f]: Color-
less oil; 1H-NMR (300 MHz, CDCl3) d: 0.93 (3H, t, Jϭ7.5 Hz), 2.02 (3H, s),
2.45 (2H, q, Jϭ7.5 Hz), 3.41 (3H, s), 3.80 (3H, s), 6.81—6.86 (2H, m),
Acknowledgements This work was partially supported by the financial
assistance of the Yamanouchi Award in Synthetic Organic Chemistry, Japan
and the Takeda Science Foundation. The research grant from Faculty of
Pharmaceutical Sciences, The University of Tokushima is also greatly ap-
preciated.
7.02—7.07 (2H, m); IR (neat) 2968, 1713, 1608, 1510, 1248, 1138 cmϪ1
;
EI-MS calcd for C14H18O3 MW 234.1256, found m/z 234.1249 (Mϩ); Anal.
Calcd for C14H18O3: C, 71.77; H, 7.74. Found: C, 71.84; H, 7.92.
Methyl (E)-2-Methyl-3-(p-nitrophenyl)-2-butenoate [(E)-4g]: Colorless
needles (n-hexane–Et2O): mp 70.5—71 °C; H-NMR (300 MHz, CDCl3) d:
1.74 (3H, q, Jϭ1.4 Hz), 2.26 (3H, q, Jϭ1.4 Hz), 3.82 (3H, s), 7.31—7.34
(2H, m), 8.23—8.26 (2H, m); IR (KBr) 2960, 1722, 1594, 1509, 1349, 1301,
1252, 1132, 858 cmϪ1; EI-MS calcd for C12H13NO4 MW 235.0844, found
m/z 235.0857 (Mϩ); Anal. Calcd for C12H13NO4: C, 61.27; H, 5.57; N, 5.95.
Found: C, 61.57; H, 5.67; N, 5.95.
References and Notes
1) Maryanoff B. E., Reitz A. B., Chem. Rev., 89, 863—927 (1989) and
references cited therein.
2) Still W. C., Gennari C., Tetrahedron Lett., 24, 4405—4408 (1983).
3) Machleidt H., Wessendorf R., Justus Liebigs Ann. Chem., 674, 1—10
(1964).
4) Sano S., Yokoyama K., Fukushima M., Yagi T., Nagao Y., Chem. Com-
mun., 1997, 559—560 (1997).
5) Sano S., Ando T., Yokoyama K., Nagao Y., Synlett, 1998, 777—779
(1998).
6) Sano S., Yakugaku Zasshi, 120, 432—444 (2000).
7) Sano S., Yokoyama K., Teranishi R., Shiro M., Nagao Y., Tetrahedron
Lett., 43, 281—284 (2002).
1
Methyl (Z)-2-Methyl-3-(p-nitrophenyl)-2-butenoate [(Z)-4g]: Pale yellow
1
oil; H-NMR (300 MHz, CDCl3) d: 2.06 (3H, s), 2.11 (3H, s), 3.44 (3H, s),
7.26—7.29 (2H, m), 8.16—8.19 (2H, m); IR (neat) 2949, 1719, 1596, 1518,
1345, 1245, 1140, 857 cmϪ1; EI-MS calcd for C12H13NO4 MW 235.0844,
found m/z 235.0842 (Mϩ); Anal. Calcd for C12H13NO4: C, 61.27; H, 5.57; N,
5.95. Found: C, 61.42; H, 5.64; N, 5.93.
Methyl (E)-2-Methyl-3-(m-nitrophenyl)-2-pentenoate [(E)-4h]: Pale yel-
low oil; 1H-NMR (300 MHz, CDCl3) d: 0.95 (3H, t, Jϭ7.5 Hz), 1.71 (3H, s),
2.63 (2H, q, Jϭ7.5 Hz), 3.82 (3H, s), 7.44—7.47 (1H, m), 7.54—7.59 (1H,
m), 8.00—8.01 (1H, m), 8.15—8.18 (1H, m); IR (neat) 2969, 1716, 1530,
1349, 1266, 1141, 1100 cmϪ1; EI-MS calcd for C13H15NO4 MW 249.1001,
found m/z 249.0988 (Mϩ).
8) Sano S., Yokoyama K., Shiro M., Nagao Y., Chem. Pharm. Bull., 50,
706—709 (2002).
9) Bestmann H. J., Ermann P., Rüppel H., Sperling W., Liebigs Ann.
Chem., 1986, 479—498 (1986).
10) Shen Y., Qiu W., Tetrahedron Lett., 28, 449—450 (1987).
11) Shen Y., Ni J., J. Fluorine Chem., 89, 141—144 (1998).
12) Shindo M., Sato Y., Shishido K., Tetrahedron Lett., 39, 4857—4860
(1998).
13) Ide M., Nakata M., Synlett, 2001, 1511—1515 (2001).
14) Ciszewski G. M., Jackson J. A., Org. Prep. Proceed. Int., 31, 240—
243 (1999).
15) Nishio M., Hirota M., Tetrahedron, 45, 7201—7245 (1989).
16) Nishio M., Umezawa Y., Hirota M., Takeuchi Y., Tetrahedron, 51,
8665—8701 (1995).
17) Nishio M., Umezawa Y., Hirota M., J. Synth. Org. Chem., Jpn., 55,
2—12 (1997).
Methyl (Z)-2-Methyl-3-(m-nitrophenyl)-2-pentenoate [(Z)-4h]: Pale yel-
low oil; 1H-NMR (300 MHz, CDCl3) d: 0.96 (3H, t, Jϭ7.5 Hz), 2.07 (3H, s),
2.50 (2H, q, Jϭ7.5 Hz), 3.43 (3H, s), 7.41—7.51 (2H, m), 7.97—8.01 (1H,
m), 8.11—8.14 (1H, m); IR (neat) 2972, 1719, 1529, 1433, 1351, 1303,
1238, 1143, 1102 cmϪ1; EI-MS calcd for C13H15NO4 MW 249.1001, found
m/z 249.0991 (Mϩ); Anal. Calcd for C13H15NO4: C, 62.64; H, 6.07; N, 5.62.
Found: C, 63.00; H, 6.17; N, 5.60.
Methyl (E)-3-Phenyl-2-pentenoate [(E)-5b]: Colorless oil; 1H-NMR (200
MHz, CDCl3) d: 1.08 (3H, t, Jϭ7.4 Hz), 3.12 (2H, q, Jϭ7.4 Hz), 3.75 (3H,
s), 6.02 (1H, s), 7.34—7.47 (5H, m); IR (neat) 1718, 1626, 1576, 1495,
1434, 1240, 1040, 1002, 874, 733, 697 cmϪ1; EI-MS calcd for C12H14O2