Eliminative Wacker oxidation: An efficient synthesis of α-alkyl vinyl methyl ketones

Article abstract of DOI:10.1055/s-2005-872218

A new facet of Wacker oxidation of substituted 4-pentenals has been reported wherein concomitant elimination takes place during Wacker oxidation to yield α-alkyl vinyl methyl ketones. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2005-872218

PAPER
2939
Eliminative Wacker Oxidation: An Efficient Synthesis of a-Alkyl Vinyl Methyl
Ketones
Synthesis of
a-Alkyl
V
u
inyl Methyl
k
K
etones und G. Kulkarni,* Saryu I. Davawala, Aniruddha K. Doke, Dnyaneshwar D. Gaikwad, Ajit V. Doke
Department of Chemistry, University of Pune, Ganeshkhind, Pune 411 007, India
Fax +91(20)25691728; E-mail: mgkulkarni@chem.unipune.ernet.in
Received 6 April 2005; revised 31 May 2005
zyloxy group leading to the formation of a,b-unsaturated
Abstract: A new facet of Wacker oxidation of substituted 4-pente-
nals has been reported wherein concomitant elimination takes place
during Wacker oxidation to yield a-alkyl vinyl methyl ketones.
methyl ketones (Scheme 1, Table 1).
Wittig olefination of aldehydes and ketones 1a–h, under
the reported conditions,27a,b with ({[(E)-4-benzyloxy)but-
2-enyl]oxy}methyl)triphenylphosphonium chloride (I)27d
afforded the corresponding allyl vinyl ethers 2a–h as an
inseparable mixture of E- and Z-isomers (Scheme 1,
Table 1). Heating allyl vinyl ethers 2a–h in refluxing xy-
Key words: Wacker oxidation, allyl vinyl ether, 4-pentenal, a-
alkyl vinyl methyl ketone, elimination
The palladium(II) chloride catalyzed oxidation of ethyl-
ene to acetaldehyde, often called the Wacker process1–21 is
well established, both as an industrial process and as a re-
action useful in organic synthesis. The importance and
popularity of this reaction in the area of synthetic organic
chemistry is due to the simplicity of operations and the
novel, versatile and useful compounds obtainable by this
process. More than six different types of palladium pro-
moted oxidations have been developed so far.21 Wacker
oxidation tolerates various types of functional groups22–24
such as aldehyde, ketone, ester, and nitrile. Recently,
Takacs25 has extensively reviewed the current chemistry
of Wacker and related alkene oxidation reactions.
O
O
OBn
i)
ii)
R
R1
1a–h
CHO
R
R1
2a–h
CHO
O
CHO
R1
O
iii)
R
R
R
+
R1
R1
OBn
OBn
3a–h
4a
5a–h
BnO
Wacker oxidation of terminal olefins with hydroxy or
alkoxy or silyloxy group in allylic position are reported to
give the normal products namely the a-hydroxy or alkoxy
or silyloxy methyl ketones.3,25 Similarly, terminal olefins
with hydroxy or alkoxy group in homoallylic position are
reported to give the normal products namely the b-hy-
droxy or alkoxy methyl ketones.25 Kang26 has reported
that Wacker oxidation of terminal olefins with allylic ben-
zyl ethers, allylic diols and their acetonides afford a 1:1
mixture of the corresponding methyl ketone and aldehyde
while the cyclic carbonates of allylic diols furnished the
a,b-unsaturated aldehydes through elimination of the a-
oxygen function. Further he has reported that Wacker ox-
idation of allylic diols and their acetonides of the internal
olefins resulted in the corresponding ketone and b-keto
acetonides while the cyclic carbonates of homoallylic di-
ols gave the a,b-unsaturated ketones through the elimina-
tion of a-oxygen function. A concomitant elimination of
the homoallylic alkoxy group leading to the formation of
a,b-unsaturated carbonyl compounds under the Wacker
oxidation conditions has not been documented. We herein
report a novel and different facet of Wacker oxidation in-
volving a concomitant elimination of the homoallylic ben-
OCH2PPh3Cl
I
Scheme 1 Reagents and conditions: i) t-BuO–K+/t-BuOH, 0 °C, I;
ii) xylene, reflux, 6 h; iii) 10 mol% PdCl2, 10 mol% CuCl2, aq THF
(1:9)
Table 1 Substituents R and R1 in Scheme 1
R
R1
Me
H
a
b
c
4-MeC6H4
PhCH2CH2
MeCH2CH2
Me(CH2)6
Me(CH2)8
-H2C
H
d
e
H
H
f
H
H
-H2C
O
g
O
h
H
SYNTHESIS 2005, No. 17, pp 2939–2945
x
x.
x
x
.
2
0
0
5
O
BnO
Advanced online publication: 16.09.2005
DOI: 10.1055/s-2005-872218; Art ID: Z07205SS
© Georg Thieme Verlag Stuttgart · New York

2940
M. G. Kulkarni et al.
PAPER
lene effected the Claisen rearrangement and yielded the 4- The above results have revealed a hitherto unknown facet
pentenals 3a–h in almost quantitative yields. When these of Wacker oxidation. The products obtained from this re-
substituted 4-pentenals 3a–h were subjected to Wacker action, namely the a-alkyl vinyl methyl ketones are highly
oxidation conditions, interesting results were obtained. versatile and quite useful synthetic intermediates. Other
The aldehyde 3a on Wacker oxidation under the standard methods28 of preparing such compounds are more cum-
reaction conditions, as reported below, surprisingly fur- bersome. More importantly, this method is complementa-
nished the enone 5a in significant amounts along with the ry to the Baylis–Hilman reaction29 as, in the latter case, a-
normal oxidation product 4a in <5% yield. This was a sig- alkylation is not possible. This eliminative Wacker oxida-
nificant deviation from the normal course of Wacker oxi- tion did not proceed in case of pent-4-enoates like II
dation and efforts were made to optimize the reaction (Figure 1) and 5-benzyloxypent-1-enes such as III, which
conditions to get 5a in major amount or better exclusively. furnished normal Wacker oxidation products only. Also,
In all the substrates studied (Table 2), for the first three pent-4-enal with no substituent a- to the aldehyde like IV
hours, two product spots corresponding to the enone and (R = H) did not exhibit this eliminative Wacker oxidation
ketone along with the substrate spot were seen. After six and gave normal products. In the light of the above results
hours, the enone spot was dominant while traces of the the mechanism and synthetic applications of this reaction
substrate and the ketone were present. In the next two are being investigated.
hours, only enone spot was seen. The enone 5a was ob-
R1
R1
CHO
tained in 75% yield on stirring the reaction mixture for 8
hours, thus resulting in an eliminative Wacker oxidation.
With this serendipitous observation, we subjected the oth-
er 4-pentenals 3b–h to Wacker oxidation under the opti-
mized reaction conditions. The eliminative Wacker
oxidation products were obtained in good yields, while
the normal products, i.e. a-benzyloxymethyl methyl ke-
tones were absent in the reaction mixture.
EtOOC
OBn
OBn
OBn
OBn
III
R1 = Me or H
II
IV
Figure 1 Compounds II–IV
The analytical and spectral data of compounds 2,3 and 5
along with the isolated 4a are given in Table 3.
Table 2 Eliminative Wacker Oxidation: Synthesis of a-Alkyl Vinyl Methyl Ketones
O
CHO
CHO O
OBn
O
R
R
R
R1
R1
R1
R
R1
OBn
No.
1
2
3
5
R
R1
Me
H
Yield (%)
Yield (%)
Yield (%)
a
b
c
4-MeC6H4
PhCH2CH2
MeCH2CH2
Me(CH2)6
Me(CH2)8
-H2C
51a
89
59
69
77
92
94
86
79
76
70
79
64
79
79
H
d
e
H
H
f
H
H
81
70
94
79
94
78
-H2C
O
g
O
h
H
69
71
50
O
BnO
a The yield is based on recovered (35%) starting material.
Synthesis 2005, No. 17, 2939–2945 © Thieme Stuttgart · New York

PAPER
Synthesis of a-Alkyl Vinyl Methyl Ketones
13C NMR (CDCl3), d
2941
Table 3 Analytical and Spectral Data of Compounds 2,3,5 and 4a Prepared
Producta Bp (°C)/Torr) IR (neat/Nujol) (cm–1) 1H NMR (CDCl3), d, J (Hz)
2a
–
2923, 1650, 1513,
1453, 1278, 1153,
1.91 (s, 3 H, Z-OCH=CCH3), 2.01 (s, 3 H, E-
OCH=CCH3), 2.37 (s, 3 H, ArCH3), 4.03–4.12 (m, 2 H, 69.22, 72.48, 108.35,
14.58, 16.77, 20.63, 67.81,
1113, 1071, 836, 815, CH2OBn), 4.43 (d, J = 4.6, 2 H, OCH2CH=CH), 4.62 109.42, 127.24, 127.83,
738, 698
(s, 2 H, OCH2Ph), 5.74–5.83 (m, 2 H, HC=CH), 6.13
and 6.41 (s, 1 H, E/Z-OCH=C), 7.05–7.38 (m, 9 H,
ArH)
128.32, 128.96, 129.33,
129.71, 129.88, 130.76,
136.23, 136.35, 138.45
2b
–
3061, 2924, 1653,
1603, 1495, 1453,
2.26 (dd, J = 8.1, 16.2, 1 H, PhCH2CHA), 2.41 (dd,
J = 8.1, 16.2, 1 H, PhCH2CHB), 2.54–2.73 (m, 2 H,
26.1, 30.1, 36.2, 37.4, 67.8,
68.8, 72.5, 104.2, 106.7,
126.1, 127.8, 128.4, 128.9,
129.8, 130.1, 131.5, 138.9,
1282, 1098, 1027, 932 PhCH2CH2), 4.13 (d, J = 5.8, 2 H, CH2OBn), 4.19–
4.33 (m, 2 H, CH2CH=CH), 4.36–4.48 (m, 0.5 H, Z-
CH=CHO), 4.57 (s, 2 H, OCH2Ph), 4.81 (dt, J = 13.1, 142.1, 145.1
7.9, 0.5 H, E-CH=CHO), 5.67–5.89 (m, 2 H,
HC=CHCH2OBn), 5.93 (d, J = 7.9, 0.5 H, Z-
OCH=CH), 6.24 (d, J = 13.1, 0.5 H, E-OCH=CH),
7.11–7.38 (m, 10 H, ArH)
2c
2d
2e
2f
–
–
–
–
3029, 2927, 1652,
1495, 1454, 1403,
1092, 1027, 735, 698
0.95–1.02 (t, J = 6.2, 3 H, CH2CH3), 1.32–1.47 (m, 2 H, 13.3, 13.7, 22.9, 23.6, 25.9,
CH3CH2), 1.9–2.2 (m, 2 H, CH3CH2CH2), 4.09 (d,
J = 4.5, 2 H, CH2OBn), 4.48 (d, J = 5.4, 2 H,
OCH2CH=CH), 4.36–4.43 (m, 0.5 H, Z-CH=CHO),
29.9, 66.8, 68.2, 72.1,
104.4, 107.2, 127.7, 128.3,
129.3, 130.2, 131.1, 137.9,
4.53 (s, 2 H, OCH2Ph), 4.76 (dt, J = 12.8, 6.2, 0.5 H, E- 144.1
CH=CHO), 5.71–5.83 (m, 2 H, HC=CHCH2OBn),
5.95 (d, J = 6.2, 0.5 H, Z-OCH=CH), 6.23 (d, J = 12.8,
0.5 H, E-OCH=CH), 7.24–7.36 (m, 5 H, ArH)
3030, 2924, 1653,
1582, 1495, 1455,
0.91 (t, J = 6.1, 3 H, CH2CH3), 1.33 [br s, 10 H,
14.5, 23.1, 24.3, 29.4, 29.6,
CH3(CH2)5], 1.91, 2.08 [m, 2 H, CH3(CH2)5CH2], 4.11 30.2, 31.7, 32.2, 66.2, 67.9,
1402, 1095, 1027, 735, (d, J = 4.6, 2 H, CH2OBn), 4.46, (d, J = 5.1, 2 H,
697
72.7, 105.4, 108.1, 127.6,
128.1, 129.3, 129.8, 130.4,
OCH2CH=CH), 4.35–4.41 (m, 0.5 H, Z-CH=CHO),
4.54 (s, 2 H, OCH2Ph), 4.73 (dt, J = 12.7, 7.3, 0.5 H, E- 137.3, 144.5
CH=CHO), 5.72–5.89 (m, 2 H, HC=CHCH2OBn),
5.95 (d, J = 5.4, 0.5 H, Z-OCH=CH), 6.22 (d, J = 12.7,
0.5 H, E-OCH=CH), 7.18–7.38 (m, 5 H, ArH)
3030, 2924, 1654,
1495, 1456, 1400,
1095, 1026, 735, 698
0.89 (t, J = 6.1, 3 H, CH2CH3), 1.31 [br s, 14 H,
14.1, 22.6, 23.9, 27.7, 28.9,
CH3(CH2)7], 1.93–2.04 [m, 2 H, CH3(CH2)7CH2], 4.12 29.3, 29.5, 29.8, 31.9, 32.6,
(d, J = 4.7, 2 H, CH2OBn), 4.46 (d, J = 5.1, 2 H,
OCH2CH=CH), 4.33–4.41 (m, 0.5 H, Z-CH=CHO),
65.8, 67.5, 72.4, 104.8,
107.9, 127.3, 128.5, 129.4,
4.53 (s, 2 H, OCH2Ph), 4.75 (dt, J = 12.6 6.5, 0.5 H, E- 130.2, 131.3, 137.9, 144.4
CH=CHO), 5.71–5.79 (m, 2 H, HC=CHCH2OBn),
5.94 (d, J = 6.5, 0.5 H, Z-OCH=CH), 6.12 (d, J = 12.6,
0.5 H, E-OCH=CH), 7.21–7.38 (m, 5 H, ArH)
3030, 2924, 1652,
1615, 1455, 1405,
1116, 934, 736, 697
0.81–0.89 (m, 3 H, CHCH3), 1.01–1.42 (m, 3 H,
CH2CH2CHCH3), 1.59 (s, 3 H, CH=CCH3), 1.67 (s, 3H, 30.4, 30.7, 34.1, 36.8, 68.1,
CH=CCH3), 1.71–2.08 (m, 4 H, CH2CH=CMe2 and 70.4, 73.3, 103.3, 106.9,
17.7, 19.1, 19.7, 20.2, 25.5,
CH2CH=CHO), 4.07 (d, J = 4.3, 2 H, CH2OBn), 4.17– 123.6, 127.6, 128.1, 129.4,
4.25 (m, 2 H, OCH2CH=CH), 4.28–4.42 (m, 0.25 H, Z- 130.6, 131.1, 132.3, 137.6,
CH=CHO), 4.52 (s, 2 H, OCH2Ph), 4.74 (dt, J = 12.4, 144.2
7.6, 0.75 H, E-CH=CHO), 5.10 (t, J = 6.7, 1 H,
CH=CMe2), 5.71–5.81 (m, 2 H,
CH2HC=CHCH2OBn), 5.96 (d, J = 7.69, 0.25 H, Z-
CH=CHO), 6.21 (d, J = 12.4, 0.75 H, E-CH=CHO),
7.25–7.41 (m, 5 H, ArH)
2g
–
3030, 2922, 1652,
1582, 1454, 1404,
0.89 (d, J = 6.1, 3 H, CHCH3), 1.01–1.52 (m, 5 H,
CH2CH2CHMeCH2), 1.59 (s, 3 H, CH=CCH3), 1.67 (s, 25.67, 26.13, 27.08, 31.72,
17.57, 19.35, 25.21, 25.44,
1155, 1096, 931, 736, 3 H, CH=CCH3), 1.81–2.12 (m, 4 H, CH2CH=CMe2
36.94, 37.91, 65.66, 68.13,
72.19, 103.89, 106.22,
124.89, 127.59, 127.69,
128.32, 129.23, 130.88,
131.03, 132.28, 137.96,
144.89
698
and CH2CH=CHO), 4.11 (d, J = 4.1, 2 H, CH2OBn),
4.23 (d, J = 4.7, 2 H, OCH2CH=CH), 4.51 (s, 2 H,
OCH2Ph), 4.76 (dt, J = 12.1, 7.6, 1 H, E-CH=CHO),
5.10 (t, J = 6.6, 1 H, CH=CMe2), 5.70–5.81 (m, 2 H,
CH2HC=CHCH2OBn), 6.21 (d, J = 12.1, 1 H, E-
CH=CHO), 7.21–7.38 (m, 5 H, ArH)
Synthesis 2005, No. 17, 2939–2945 © Thieme Stuttgart · New York

2942
M. G. Kulkarni et al.
PAPER
Table 3 Analytical and Spectral Data of Compounds 2,3,5 and 4a Prepared (continued)
Producta Bp (°C)/Torr) IR (neat/Nujol) (cm–1) 1H NMR (CDCl3), d, J (Hz)
13C NMR (CDCl3), d
2h
–
3030, 2929, 1665,
1496, 1454, 1164,
1.36 (s, 3 H, CCH3), 1.56 (s, 3 H, CCH3), 3.81 (d,
J = 4.7, 1 H, OCH), 4.12 (d, J = 6.2, 2 H, CH2OBn),
26.2, 26.6, 64.8, 67.3, 67.7,
72.3, 72.4, 79.3, 83.6, 98.4,
1075, 1024, 862, 800, 4.32 (d, J = 6.3, 2 H, OCH2CH=CH), 4.54, 4.57 (s, 2 H, 101.2, 104.4, 111.2, 127.6,
738, 699
OCH2Ph), 4.61–4.83 (m, 4 H, 2 CH and OCH2Ph),
5.02–5.13, 5.16–5.24 (m, 1 H, E/Z-CH=CHO), 5.66–
5.88 (m, 2 H, Z-HC=CH), 5.91–5.96 (m, 1 H, H-1),
6.14 (d, J = 7.8, 0.5 H, Z-OCH=C), 6.63 (d, J = 15.2,
0.5 H, E-CH=C), 7.12–7.43 (m, 10 H, ArH)
128.2, 129.9, 130.3, 131.5,
137.9, 138.1, 143.7
3a
3b
3c
3d
75–77/0.5
73–76/0.5
65–68/1
2924, 2714, 1723,
1686, 1638, 1561,
Diastereomeric ratio 1:1.3:
1.40 (s, 3 H, CCH3), 2.35, 2.37 (s, 3 H, ArCH3), 3.20– 70.5, 73.2, 118.1, 118.8,
14.6, 17.1, 20.8, 48.9, 54.9,
1100, 1020, 918, 812, 3.35 (m, 1 H, CHCH=CH2), 3.40–3.65 (m, 2 H,
736, 698
127.2, 127.6, 128.3, 129.3,
134.6, 135.2, 135.5, 136.2,
136.6, 136.8, 137.5, 200.7,
CH2OBn), 4.40–4.55 (m, 2 H, OCH2Ph), 4.95–5.10,
5.20–5.40, 5.40–5.70 (m, 3 H, CH=CH2), 7.08–7.22
(m, 4 H, ArH), 7.25–7.42 (m, 5 H, ArH), 9.65, 9.70 (s, 201.4
1 H, CHO)
3027, 2924, 2718,
1721, 1640, 1604,
1495, 1100, 1028, 997, PhCH2CH2), 2.60–2.90 (m, 2 H, CHCHO and
Diastereomeric ratio 1:2.4:
1.65–2.10 (m, 2 H, CH2CH2Ph), 2.40–2.60 (m, 2 H,
27.8, 27.9, 33.1, 33.3, 44.3,
44.6, 51.8, 52.5, 70.6, 71.2,
72.8, 117.2, 117.4, 125.6,
127.2, 128.1 135.7, 141.2,
922
CHCH=CH2), 3.30–3.40, 3.50–3.60 (m, 2 H,
CH2OBn), 4.42, 4.48 (s, 2 H, OCH2Ph), 5.08–5.18 (m, 202.6, 202.8
2 H, HC=CH2), 5.65–5.85 (m, 1 H, CH=CH2), 7.15–
7.40 (m, 10 H, ArH), 9.64, 9.69 (d, J = 2.67, 1 H, CHO)
3030, 2958, 2718,
1722, 1640, 1496,
Diastereomeric ratio 1:1.5:
0.86–0.92 (m, 3 H, CH2CH3), 1.14–1.67 (br m, 4 H,
14.00, 20.41, 20.76, 28.09,
28.53, 44.79, 44.95, 52.46,
1454, 1099, 1028, 921, CH2CH2), 2.27–2.33 (m, 1 H, CHCH=CH2), 2.60–2.79 53.38, 70.71, 71.52, 72.96,
736
(m, 1 H, CHCHO), 3.36–3.42, 3.43–3.51 (m, 2 H,
CH2OBn), 4.42–4.51 (m, 2 H, OCH2Ph), 5.08–5.15 (m, 127.33, 127.56, 128.22,
2 H, HC=CH2), 5.56–5.81 (m, 1 H, CH=CH2), 7.20–
7.40 (m, 5 H, ArH), 9.57, 9.64 (d, J = 3, 1 H, CHO)
73.04, 117.38, 117.75,
135.97, 136.03, 137.91,
204.11, 204.68
80 – 84/0.5
3030, 2926, 2717,
1724, 1640, 1405,
Diastereomeric ratio 1:2:
0.85–0.89 (m, 3 H, CH2CH3), 1.25 [br s, 10 H, (CH2)5], 27.26, 27.39, 27.51, 27.63,
14.04, 22.57, 26.06, 26.48,
1206, 1099, 1028, 920, 1.42–1.68 (m, 2 H, CH2CHCHO), 2.31–2.47 (m, 1 H, 29.01, 29.45, 29.56, 31.71,
738
CHCH=CH2), 2.60–2.80 (m, 1 H, CHCHO), 3.36–3.42, 44.88, 45.03, 52.75, 53.66,
3.43–3.53 (m, 2 H, CH2OBn), 4.48, 4.51 (s, 2 H, 70.81, 71.61, 73.05, 73.15,
OCH2Ph), 5.08–5.16 (m, 2 H, HC=CH2), 5.58–5.85 (m, 117.48, 117.83, 127.48,
1 H, CH=CH2), 7.20–7.40 (m, 5 H, ArH), 9.57, 9.63 (d, 127.64, 128.29, 136.04,
J = 3, 1 H, CHO)
136.15, 137.90, 204.31,
204.90
3e
86– 89/0.5
3030, 2925, 2715,
1723, 1640, 1456,
Diastereomeric ratio 1:2:
0.89 (t, J = 6.6, 3 H, CH2CH3), 1.25 [br s, 14 H,
14.06, 22.62, 26.07, 26.50,
27.26, 27.63, 29.23, 29.35,
1205, 1100, 1028, 920, (CH2)7], 1.46–1.55 (m, 2 H, CH2CHCHO), 2.32–2.80 29.46, 29.61, 31.83, 44.88,
737
(m, 2 H, CHOCH and CHCH=CH2), 3.37–3.42, 3.43– 45.04, 52.76, 53.67, 70.82,
3.53 (m, 2 H, CH2OBn), 4.46–4.53 (m, 2 H, OCH2Ph), 71.61, 73.06, 73.13, 117.48,
5.10–5.17 (m, 2 H, HC=CH2), 5.57–5.85 (m, 1 H,
CH=CH2), 7.28–7.37 (m, 5 H, ArH), 9.58, 9.65 (d,
J = 3.6, 1 H, CHO)
117.83, 127.55, 127.63,
128.29, 136.05, 136.15,
137.97, 204.29, 204.87
3f
93–96/0.5
3070, 2919, 2719,
1723, 1640, 1453,
1100, 997, 921, 824,
740, 699
Diastereomeric ratio 1:1:
17.5, 19.1 19.9, 20.1, 25.4,
30.4, 30.8, 33.3, 33.7, 45.3,
45.6, 50.5, 51.5, 70.9, 71.3,
71.6, 73.1, 117.5, 124.6,
127.5, 128.2, 131.1, 136.32,
0.90 (t, J = 4.82, 3 H, CHCH3), 1.05–1.55 (m, 5 H,
CH2CHCH2), 1.62 (s, 3 H, C=CCH3), 1.70 (s, 3 H,
C=CCH3), 1.85–2.10 (m, 2 H, CH2CH=CMe2), 2.40–
2.65 (m, 1 H, CHCH=CH2), 2.70–2.85 (m, 1 H,
CHCHO), 3.35–3.55 (m, 2 H, CH2OBn), 4.45, 4.52 (s, 138.1, 203.7, 204.2
2 H, OCH2Ph), 5.00–5.20 (m, 3 H, HC=CH2 and
CH=CMe2), 5.55–5.90 (m, 1 H, CH=CH2), 7.30–7.45
(m, 5 H, ArH), 9.50–9.65 (m, 1 H, CHO)
Synthesis 2005, No. 17, 2939–2945 © Thieme Stuttgart · New York

PAPER
Synthesis of a-Alkyl Vinyl Methyl Ketones
2943
Table 3 Analytical and Spectral Data of Compounds 2,3,5 and 4a Prepared (continued)
Producta Bp (°C)/Torr) IR (neat/Nujol) (cm–1) 1H NMR (CDCl3), d, J (Hz)
13C NMR (CDCl3), d
3g
94–98/0.5
3068, 2923, 2720,
1723, 1640, 1453,
1098, 996, 920, 826,
738, 698
Diastereomeric ratio 1:1:
0.83–0.87 (m, 3 H, CHCH3), 1.08–1.20 (m, 2 H,
CH2CHCH2), 1.25–1.40 (m, 3 H, CHCH2CH), 1.40–
17.60, 19.23, 19.37, 19.41,
19.47, 23.50, 23.96, 23.97,
25.37, 25.45, 25.68, 32.42,
1.56 (m, 2 H, CH2CHCHO), 1.59 (s, 3 H, HC=CCH3), 34.28, 34.37, 34.75, 34.82,
1.68 (s, 3 H, HC=CCH3), 1.85–2.10 (m, 2 H,
36.55, 36.73, 36.84, 36.98,
44.86, 44.92, 45.01, 45.08,
53.00, 53.04, 53.83, 53.96,
70.80, 70.84, 71.59, 71.64,
73.07, 73.15, 117.50,
CH2CH=CMe2), 2.28–2.42 (m, 1 H, CHCH=CH2),
2.70–2.80 (m, 1 H, CHCHO), 3.35–3.48 (m, 1 H,
CHCH2OBn), 3.50–3.60 (m, 1 H, CHCH2OBn), 4.45
(s, 1 H, OCH2Ph), 4.49 (s, 1 H, OCH2Ph), 5.00–5.20
(m, 3 H, HC=CH2 and CH=CMe2), 5.57–5.84 (m, 1 H, 117.83, 117.87, 124.72,
CH=CH2), 7.20–7.40 (m, 5 H, ArH), 9.56–9.58 (m, 0.5 127.58, 127.63, 128.30,
H, CHO), 9.63–9.65 ((m, 0.5 H, CHO)
131.06, 136.05, 136.10,
136.17, 137.87, 137.96,
204.22, 204.80
3h
4a
–
–
3030, 2929, 2743,
1711, 1639, 1496,
Diastereomeric ratio 1:2:
1.30 (s, 3 H, CCH3), 1.45 (s, 3 H, CCH3), 2.95–3.30 (m, 70.9, 72.1, 72.2, 78.1, 78.3,
26.5, 26.9, 42.1, 42.9, 52.4,
1075, 1026, 920, 862, 1 H, CHCH=CH2), 3.55–3.70 (m, 1 H, CHCHO), 4.10, 78.5, 82.4, 104.3, 111.6,
734, 697
4.25 (d, J = 5.6, 1 H, OCH), 4.30–4.65 (m, 6 H,
117.2, 118.2, 127.6, 127.8,
2 OCH2Ph and 2 OCH), 5.10–5.35 (m, 2 H, HC=CH2), 127.9, 128.4, 135.6, 136.7,
5.75–6.10 (m, 1 H, CH=CH2), 5.90 (d, J = 5.6, 1 H, H- 137.5, 138.2, 200.8, 201.9
1), 7.05–7.45 (m, 10 H, ArH) 9.72, 9.75 (s, 1 H, CHO)
3090, 2925, 2720,
1725, 1714, 1606,
Diastereomeric ratio 1:8:
1.55 (s, 3 H, CCH3), 1.70 (s, 3 H, COCH3), 2.40 (s, 3 H, 69.2, 73.2, 127.1, 127.3,
128.2, 129.2, 129.6, 137.4,
(s, 2 H, OCH2Ph), 7.10–7.50 (m, 9 H, ArH), 9.37, 9.42 137.8, 199.4, 209.6
(s, 1 H, CHO)
14.8, 20.7, 33.1, 53.4, 56.2,
1513, 1020, 825, 737, ArCH3), 3.55–3.90 (m, 3 H, CHCH2OBn), 4.35, 4.48
698
5a
5b
84–87/0.5
82–85/0.5
3106, 2720, 1719,
1676, 1624, 1512,
1.68 (s, 3 H, CCH3), 2.37 (s, 3 H, ArCH3), 2.43 (s, 3 H, 20.6, 21.8, 26.1, 56.7,
COCH3), 5.90 (s, 1 H, C=CHA E to acyl), 6.43 (s, 1 H, 127.1, 128.4, 129.2, 136.6,
1084, 1020, 824, 748, C=CHB Z to acyl), 7.10–7.50 (m, 4 H, ArH), 9.95 (s, 1 137.1, 153.4, 198.4, 199.2
699
H, CHO)
3028, 2723, 1722,
1676, 1627, 1496,
1.85 (dt, J = 6.75, 13.5, 1 H, PhCH2CHA), 2.10–2.40
(m, 1 H, PhCH2CHB), 2.40 (s, 3 H, COCH3), 2.65 (t,
25.1, 29.5, 33.1, 52.3,
125.8, 128.1, 131.4, 140.9,
1075, 1028, 825, 750, J = 7.74, 2 H, CH2Ph), 3.55 (t, J = 6.75, 1 H, CHCHO), 145.5, 198.8, 199.9
700
5.93 (s, 1 H, C=CHA E to acyl), 6.35 (s, 1 H, C=CHB Z
to acyl), 7.10–7.40 (m, 5 H, ArH), 9.65 (s, 1 H, CHO)
5c
58–62/2
72–75/1
2960, 2720, 1725,
1677, 1627, 1461,
0.89 (t, J = 7.5, 3 H, CH2CH3), 1.27–1.37 (m, 2 H,
CH2CH3), 1.44–1.56 (m, 1 H, CH3CH2CHA), 1.84–1.96 52.69, 128.25, 145.88,
13.84, 20.40, 25.42, 30.35,
1103, 1024, 954, 743, (m, 1 H, CH3CH2CHB), 2.39 (s, 3 H, COCH3), 3.51 (t, 198.43, 200.65
699
J = 7.5, 1 H, CHCHO), 5.89 (s, 1 H, C=CHA E to acyl),
6.29 (s, 1 H, C=CHB Z to acyl), 9.61 (s, 1 H, CHO)
5d
3196, 2927, 2719,
1722, 1678, 1626,
1458, 1099, 738, 699
0.87 (t, J = 6.3, 3 H, CH2CH3), 1.26 [br s, 10 H,
(CH2)5], 1.46–1.53 [m, 1 H, CH3(CH2)5CHA], 1.87–
1.95 (m, 1 H, CH3(CH2)5CHB), 2.39 (s, 3 H, COCH3), 52.94, 128.20, 145.94,
3.49 (t, J = 7.5, 1 H, CHCHO), 5.88 (s, 1 H, C=CHA E 198.42, 200.68
to acyl), 6.29 (s, 1 H, C=CHB Z to acyl), 9.61 (s, 1 H,
CHO)
14.00, 22.55, 25.45, 27.23,
28.26, 28.99, 29.38, 31.70,
5e
71–75/0.5
2926, 2717, 1726,
1679, 1626, 1461,
0.89 (t, J = 6.3, 3 H, CH2CH3), 1.26 [br s, 14 H,
(CH2)7], 1.40–1.50 [m, 1 H, CH3(CH2)7CHA], 1.85–
14.00, 22.57, 25.40, 27.19,
28.19, 29.18, 29.30, 29.38,
1229, 1107, 1023, 722, 2.00 [m, 1 H, CH3(CH2)7CHB], 2.40 (s, 3 H, COCH3), 29.41, 31.76, 52.91, 128.23,
659
3.50 (t, J = 7.2, 1 H, CH2CHCHO), 5.90 (s, 1 H,
C=CHA E to acyl), 6.30 (s, 1 H, C=CHB Z to acyl), 9.62
(s, 1 H, CHO)
145.86, 198.37, 200.63
Synthesis 2005, No. 17, 2939–2945 © Thieme Stuttgart · New York

2944
M. G. Kulkarni et al.
PAPER
Table 3 Analytical and Spectral Data of Compounds 2,3,5 and 4a Prepared (continued)
Producta Bp (°C)/Torr) IR (neat/Nujol) (cm–1) 1H NMR (CDCl3), d, J (Hz)
13C NMR (CDCl3), d
5f
–
–
–
2924, 2724, 1724,
1678, 1654, 1454,
1097, 736, 698
0.85 (t, J = 5.12, 3 H, CHCH3), 1.05–1.50 (m, 5 H,
CH2CHCH2), 1.60 (s, 3 H, HC=CCH3), 1.68 (s, 3 H,
HC=CCH3), 1.80–2.05 (m, 2 H, CH2CH=CMe2), 2.40 36.1, 36.7, 37.4, 50.9, 51.2,
(s, 3 H, COCH3), 3.50–3.65 (m, 1 H, CHCHO), 5.00– 124.6, 128.2, 128.5, 131.5,
5.10 (m, 1 H, CH=CMe2) 5.90 (s, 1 H, C=CHA E to
acyl), 6.30 (d, J = 3.84, 1 H, C=CHB Z to acyl), 9.60 (s,
1 H, CHO)
17.8, 19.3, 19.9, 25.4, 25.5,
25.6, 25.8, 30.1, 30.4, 35.3,
146.2, 146.7, 198.6, 200.9
5g
5h
3029, 2924, 2724,
1722, 1678, 1626,
0.87, 0.89 (d, J = 6.6, 3 H, CHCH3), 1.10–1.20 (m, 2 H, 17.61, 19.31, 19.45, 25.43,
CH2CHCH2), 1.20–1.55 (m, 5 H, CHCH2CH2), 1.59 (s, 25.45, 25.48, 25.68, 25.73,
1454, 1098, 1028, 739, 3 H, HC=CCH3), 1.68 (s, 3 H, HC=CCH3), 1.82–2.02 25.90, 32.28, 32.40, 34.38,
699
(m, 2 H, CH2CH=CMe2), 2.40 (s, 3 H, COCH3), 3.45 (t, 34.49, 36.72, 36.88, 53.23,
J = 6, 1 H, CH2CHCHO), 5.00–5.10 (m, 1 H, 124.68, 128.19, 128.24,
CH=CMe2), 5.88 (s, 1 H, C=CHA E to acyl), 6.29 (s, 1 131.16, 145.95, 146.05,
H, C=CHB Z to acyl), 9.60 (s, 1 H, CHO) 198.42, 200.65
2742, 2724, 1714,
1675, 1498, 1074,
1027, 922, 867
1.31 (s, 3 H, CCH3), 1.46 (s, 3 H, CCH3), 2.40 (s, 3 H, 26.8, 27.1, 27.6, 53.1, 72.4,
COCH3), 3.56–3.69 (m, 1 H, CHCHO), 4.24 (d,
J = 5.5, 1 H, OCH), 4.31–4.66 (m, 4 H, OCH2Ph and
78.2, 78.4, 82.4, 104.7,
110.8, 127.2, 127.5, 128.1,
2 × OCH), 5.91 (d, J = 5.6, 1 H, H-1), 6.31 (br s, 2 H, 128.6, 137.6, 146.8, 196.5,
C=CH2), 7.07–7.43 (m, 5 H, ArH), 9.75 (s, 1 H, CHO) 206.1
a The products 2a–h, 3h, 4a, and 5f–h are viscous liquids and 3a–g, 5a–e are colorless thick liquids.
({[(E)-4-Benzyloxy)but-2-enyl]oxy}methyl)triphenylphospho-
nium Chloride (I)
Wacker Oxidation of 3; General Procedure
In a solution of substituted, functionalized olefin 3a–h (1 equiv), in
aq THF (THF/H2O, 1:9), were suspended PdCl2 (0.1 equiv) and
CuCl2 (0.1 equiv). This mixture was stirred at r.t. under O2 (TLC
control, 6–8 h). The mixture was diluted with H2O and extracted
with Et2O (3 × 20 mL). The combined Et2O layers were washed
with H2O, dried (Na2SO4), concentrated in vacuo and the crude
product was purified by column chromatography using 98:2 hex-
ane–EtOAc as eluent (Table 3).
Dry HCl gas was passed through an ice-cold equimolar mixture of
(E)-4-benzyloxybut-2-en-1-ol (8.9 g, 50 mmol), paraformaldehyde
(1.5 g, 50 mmol) and benzene (5 mL/g of alcohol) at such a rate that
the reaction temperature was maintained between 5–10 °C. The re-
action was generally complete within 6 to 8 hours at the end of
which two phases were formed. The aqueous layer was separated,
the benzene layer was dried (CaCl2) and N2 gas was bubbled
through it to remove dissolved HCl gas. The organic layer was dis-
tilled at atmospheric pressure to remove benzene. The crude
chloromethyl ether obtained was purified by distillation to give
the chloroether, 1-({[(E)-4-(chloromethoxy)but-2-enyl]oxy}meth-
yl)benzene in 85% yield.27c The chloroether (5.65 g, 25 mmol) was
added to a solution of Ph3P (6.65 g, 25 mmol) in anhyd benzene (30
mL) and the mixture was stirred at r.t. for 12 h. The salt separated
as a hygroscopic, white, crystalline solid, was freed from benzene
by decantation and was dried under vacuum. The title compound
Acknowledgment
AKD thanks CSIR, New Delhi and DDG thanks UGC, New Delhi
for fellowships.
References
27d was obtained in 82% yield (10.37g) (on the basis of Ph3P recov-
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Synthesis 2005, No. 17, 2939–2945 © Thieme Stuttgart · New York

PAPER
Synthesis of a-Alkyl Vinyl Methyl Ketones
2945
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(s, 2 H, OCH2Ph), 4.53 (d, J = 6.3 Hz, 2 H, CH2OCH2PPh3),
5.56–5.65 (m, 1 H, CH=CH), 5.76–5.84 (m, 1 H, CH=CH),
5.97 (d, J = 4.2 Hz, 2 H, CH2PPh3), 7.28–7.84 (m, 20 H,
ArH). 13C NMR (22.5 MHz, CDCl3): d = 61.1, 64.1, 64.8,
68.4, 69.1, 71.1, 113.4, 117.2, 125.5, 126.5, 127.1, 128.9,
129.4, 130.2, 132.6, 133.1, 134.1, 137.1. Anal. Calcd for
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(d) Spectral data of the chloromethyl ether: 1H NMR (90
MHz, CDCl3): d = 4.17 (d, J = 5.65 Hz, 2 H, CH2OBn), 4.31
(d, J = 5.65 Hz, 2 H, CH2OCH2Cl), 4.59 (s, 2 H, OCH2Ph),
5.51 (s, 2 H, OCH2Cl), 5.63–6.17 (m, 2 H, CH=CH), 7.43 (s,
5 H, C6H5). 13C NMR (22.5 MHz, CDCl3): d = 70.5, 73.1,
75.9, 86.1, 127.1, 128.9, 129.5, 130.1, 137.1. Anal. Calcd for
C12H15ClO2: C, 63.57; H, 6.67. Found: C, 63.86; H, 6.85.
(e) Spectral data of the phosphonium salt I: 1H NMR (300
MHz, CDCl3): d = 4.09 (d, J = 6.3 Hz, 2 H, CH2OBn), 4.47
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Synthesis 2005, No. 17, 2939–2945 © Thieme Stuttgart · New York