Oxovanadium complex-catalyzed aerobic oxidation of propargylic alcohols

Article abstract of DOI:10.1021/jo025918i

A catalytic system consisting of vanadium oxyacetylacetonate [VO(acac)₂] and 3 A molecular sieves (MS3A) in acetonitrile works effectively for the aerobic oxidation of propargylic alcohols [R1CH-(OH)C≡CR²] to the corresponding carbonyl compounds under an atmospheric pressure of molecular oxygen. Although the reactivity of α-acetylenic alkanols (R¹ = alkyl) is lower compared to that of the alcohols of R¹ = aryl, alkenyl, and alkynyl, the use of VO(hfac)₂ as a catalyst and the addition of hexafluoroacetylacetone improve the product yield in these cases. A catalytic cycle involving a vanadium(V) alcoholate species and β-hydrogen elimination from it has been proposed for this oxidation.

Full text of DOI:10.1021/jo025918i

Oxova n a d iu m Com p lex-Ca ta lyzed Aer obic Oxid a tion of
P r op a r gylic Alcoh ols
Yasunari Maeda,† Nobuyuki Kakiuchi,† Satoshi Matsumura,† Takahiro Nishimura,†
Takashi Kawamura,‡ and Sakae Uemura*,†
Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University,
Sakyo-ku, Kyoto 606-8501, J apan, and Department of Chemistry, Faculty of Engineering, Gifu University,
Yanagido, Gifu 501-1193, J apan
uemura@scl.kyoto-u.ac.jp
Received May 8, 2002
A catalytic system consisting of vanadium oxyacetylacetonate [VO(acac)2] and 3 Å molecular sieves
(MS3A) in acetonitrile works effectively for the aerobic oxidation of propargylic alcohols [R1CH-
(OH)CtCR2] to the corresponding carbonyl compounds under an atmospheric pressure of molecular
oxygen. Although the reactivity of R-acetylenic alkanols (R1 ) alkyl) is lower compared to that of
the alcohols of R1 ) aryl, alkenyl, and alkynyl, the use of VO(hfac)2 as a catalyst and the addition
of hexafluoroacetylacetone improve the product yield in these cases. A catalytic cycle involving a
vanadium(V) alcoholate species and â-hydrogen elimination from it has been proposed for this
oxidation.
In tr od u ction
and sustainable chemistry, the use of a cleaner oxidant,
especially molecular oxygen, is particularly attractive and
many methods for the aerobic oxidation of alcohols with
a transition metal catalyst such as Ru,2 Pd,3 Co,4 Cu,5
V,6 Os,7 and Ni8 have been developed. However, some
limitations for the substrate to be oxidized still exist,
because of the instability of the produced carbonyl
compounds in the reaction system, the catalyst deactiva-
tion by the formation of metallic polymer, and the
Transition metal-catalyzed oxidation of alcohols with
various organic and inorganic oxidants has been estab-
lished in recent years.1 Although their methods are
useful, they require stoichiometric oxidants, in which
sometimes toxic wastes are produced. In view of green
† Kyoto University.
‡ Gifu University.
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10.1021/jo025918i CCC: $22.00 © 2002 American Chemical Society
Published on Web 08/23/2002
6718
J . Org. Chem. 2002, 67, 6718-6724

Aerobic Oxidation of Propargylic Alcohols
TABLE 1. Effect of Dr yin g Agen ts
SCHEME 1
formation of stable complexes between metal salts and
some electron donors on the starting alcohols such as
heteroatoms and unsaturated carbon-carbon bonds.
Propargylic alcohols are one type of target substrates for
oxidation, because R,â-acetylenic carbonyl compounds
(ynones) are useful precursors for various heterocycles,
and important frameworks in DNA cleavage agents.9
Although there are some useful oxidation procedures for
these alcohols with stoichiometric oxidants such as MnO2,
chromium salts, a combination of dimethyl sulfoxide and
oxalyl chloride (Swern oxidation), Dess-Martin reagent,
etc.,1,10 the catalytic and aerobic oxidation methods are
quite limited.2i,11
In our recent works on the aerobic oxidation of alcohols
with palladium(II) catalyst,12 the oxidation of propargylic
alcohols failed due to the formation of inactive metallic
palladium, resulting in the formation of unidentified
tarry compounds. To overcome such limitations, we have
continued to search the efficient catalytic system for
aerobic oxidation of such alcohols, and recently found that
some oxovanadium compounds worked as effective cata-
lysts for the aerobic oxidation of propargylic alcohols
under an atmospheric pressure of oxygen (Scheme 1).13,14
We report herein the scope and limitations and some
mechanistic aspects of this catalytic reaction.
drying
agent
conv
of 1a (%)
GLC yield
entry
of 2a (%)a
1b
2b,c
3b,d
4
5
6
MS3A
MS3A
MS3A
MS3A
MS4A
K2CO3
CaSO4
Na2SO4
95
79
48
100
20
0
95
79
48
quant.
18
7
8
6
11
6
8
a
b
Based on alcohol employed. 5 mol % of catalyst and 5 mL of
MeCN. c MS3A (250 mg). MS3A (100 mg).
d
TABLE 2. Oxova n a d iu m Com p lex-Ca ta lyzed Oxid a tion
of 1a to 2a u n d er Molecu la r Oxygen
conv
of 1a (%)
GLC yield
entry
V cat.
of 2a (%)a
1
2
3
4
5
6
7
VO(acac)2
VOCl3
100
100
100
94
99
97
quant.
quant.
quant.
94
VO(OEt)3
VO(tfac)2
VO(hpfdm)2
VO(hfac)2
V2O5
99
97
<1
(9) (a) Adlington, R. M.; Baldwin, J . E.; Pritchard, G. J .; Spencer,
K. C. Tetrahedron Lett. 2000, 41, 575. (b) Basak, A.; Bdour, H. M.;
Shain, J . C.; Mandal, S.; Rudra, K. R.; Nag, S. Bioorg. Med. Chem.
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Mah´ıa, J .; Villalgordo, J . M. Tetrahedron: Asymmetry 2000, 11, 2483.
(d) Wei, H.-X.; Kim, S. H.; Caputo, T. D.; Purkiss, D. W.; Li, G.
Tetrahedron 2000, 56, 2397. (e) Wender, P. A.; Bi, F. C.; Brodney, M.
A.; Gosselin, F. Org. Lett. 2001, 3, 2105. (f) Li, P.; Fong, W. M.; Chao,
L. C. F.; Fung, S. H. C.; Williams, I. D. J . Org. Chem. 2001, 66, 4087
and references therein.
<1
a
Based on alcohol employed.
Resu lts a n d Discu ssion
On the basis of our previous studies, oxidation of
propargylic alcohols (1.0 mmol) under molecular oxygen
was generally carried out in the presence of a catalytic
amount of VO(acac)2 (1 mol %) and MS3A (500 mg) in
acetonitrile (2 mL) under stirring at 80 °C for 3 h (a
standard condition for the oxidation). It was noteworthy
that the product yield was much affected by the amount
of MS3A and the kind of drying agents. When the amount
of MS3A was reduced in the oxidation of 1-phenyl-2-
propyn-1-ol (1a ) with 5 mol % of VO(acac)2 as a catalyst,
the yield of 1-phenyl-2-propyn-1-one (2a) decreased (Table
1, entries 1-3). The use of MS4A instead of MS3A
dramatically diminished the yield of 2a (entry 5: com-
pare to entry 4). Further, the use of other drying agents
such as K2CO3, CaSO4, and Na2SO4 was ineffective for
this oxidation (entries 6-8).15 In other solvents such as
benzonitrile, toluene, THF, and 1,2-dichloroethane, the
yield of 2a decreased. Other oxovanadium compounds
such as VOCl3, VO(OEt)3, VO(tfac)2 (tfac ) 1,1,1-trifluo-
roactylacetonate), VO(hfac)2 (hfac ) hexafluoroacetylac-
etonate), and VO(hpfdm)2 (hpfdm ) 6,6,7,7,8,8,8-hep-
(10) (a) Carreira, E. M.; Bois, J . D. J . Am. Chem. Soc. 1995, 117,
8106. (b) Han, Z.; Shinokubo, H.; Oshima, K. Synlett 2001, 1421. (c)
Luca, L. D.; Giacomelli, G.; Porcheddu, A. J . Org. Chem. 2001, 66, 7907.
(d) Matsuto, J .; Iida, D.; Tatani K.; Mukaiyama, T. Bull. Chem. Soc.
J pn. 2002, 75, 223.
(11) Sakaguchi, S.; Takase, T.; Iwahara, T.; Ishii, Y. Chem. Commun.
1998, 2037.
(12) (a) Nishimura, T.; Onoue, T.; Ohe, K.; Uemura, S. Tetrahedron
Lett. 1998, 39, 6011. (b) Nishimura, T.; Onoue, T.; Ohe, K.; Uemura,
S. J . Org. Chem. 1999, 64, 6750. (c) Nishimura, T.; Kakiuchi, N.; Inoue,
M.; Uemura, S. Chem. Commun. 2000, 1245. (d) Nishimura, T.; Maeda,
Y.; Kakiuchi, N.; Uemura, S. J . Chem. Soc., Perkin Trans. 1 2000, 4301.
(e) Kakiuchi, N.; Nishimura, T.; Inoue, M.; Uemura, S. Bull. Chem.
Soc. J pn. 2001, 74, 165. (f) Kakiuchi, N.; Maeda, Y.; Nishimura, T.;
Uemura, S. J . Org. Chem. 2001, 66, 6620.
(13) Maeda, Y.; Kakiuchi, N.; Matsumura, S.; Nishimura, T.; Ue-
mura, S. Tetrahedron Lett. 2001, 42, 8877.
(14) For recent advances in the aerobic oxidation forming epoxides,
biaryls, and so on catalyzed by oxovanadium complexes, see: (a) Takai,
T.; Yamada, T.; Mukaiyama, T. Chem. Lett. 1990, 1657. (b) Inoki, S.;
Takai, T.; Yamada, T.; Mukaiyama, T. Chem. Lett. 1991, 941. (c)
Mukaiyama, T.; Takai, T. J apanese Patent 03227952; Chem. Abstr.
1992, 116, 20776. (d) Mukaiyama, T.; Takai, T. J apanese Patent
03227951; Chem. Abstr. 1992, 116, 58959. (e) Hirao, T. Chem. Rev.
1997, 97, 2707. (f) Kirihara, M.; Takizawa, S.; Momose, T. J . Chem.
Soc., Perkin Trans. 1 1998, 7. (g) Kirihara, M.; Ichinose, M.; Takizawa,
S.; Momose, T. Chem. Commun. 1998, 1691. (h) Kirihara, M.; Ochiai,
Y.; Arai, N.; Takizawa, S.; Momose, T.; Nemoto, H. Tetrahedron Lett.
1999, 40, 9055. (i) Ishii, Y.; Matsunaka, K.; Sakaguchi, S. J . Am. Chem.
Soc. 2000, 122, 7390. (j) Chu, C.-Y.; Hwang, D.-R.; Wang, S.-K.; Uang,
B.-J . Chem. Commun. 2001, 980. (k) Hirao, T.; Morimoto, C.; Takada,
T.; Sakurai, H. Tetrahedron 2001, 57, 5073. (l) Barhate, N. B.; Chen,
C.-T. Org. Lett. 2002, 4, 2529.
(15) Molecular sieves can work to remove water formed during the
oxidation. Such positive effect has been known. See, for example: (a)
Reference 14b. See also: (b) Kato, K.; Yamada, T.; Takai, T.; Inoki, S.;
Isayama, S. Bull. Chem. Soc. J pn. 1990, 63, 179 and references therein.
J . Org. Chem, Vol. 67, No. 19, 2002 6719

Maeda et al.
TABLE 3. Oxid a tion of P r op a r gylic Alcoh ols u n d er Molecu la r Oxygen
a
b
d
Based on alcohol employed. GLC yield. c 5 mol % of catalyst. For 12 h. e At 60 °C for 36 h.
tafluoro-2,2-dimethyl-3,5-octanedionate), except for V2O5,
could be used as effective catalysts for this oxidation
(Table 2). However, VO(acac)2 was chosen as a suitable
catalyst, considering the ease of handling and low cost.
First, the oxidation of propargylic alcohols having an
arylic, vinylic, or acetylenic substituent at the R-position
was examined. Typical results are listed in Table 3.
Propargylic alcohols having an arylic substituent at the
R-position (1a -g) were converted to the corresponding
carbonyl compounds in high yields (entries 1-7). Simi-
larly, propargylic alcohols having a vinylic substituent
(1h ) and an acetylenic substituent (1i) gave the corre-
sponding carbonyl compounds in good yields (entries 8
and 9).
Next, the alcohols having an alkyl substituent or only
hydrogens at the R-position were examined. The alcohol
having only hydrogens at the R-position (1j) was con-
verted to the corresponding aldehyde (2j) in low yield
(Table 3, entry 10), but when the oxidation was per-
formed with 5 mol % of VO(acac)2, the yield of 2j
improved (entry 11). The alcohols having an alkyl sub-
stituent at the R-position (R-acetylenic alkanols) (1k -q)
gave the corresponding ketones in moderate yields
(entries 12-20) and longer reaction time did not improve
much the product yield.
To obtain a more effective reaction condition of oxova-
nadium complex catalyzed oxidation of R-acetylenic al-
kanols such as 1j-q, the effect of some additives was
6720 J . Org. Chem., Vol. 67, No. 19, 2002

Aerobic Oxidation of Propargylic Alcohols
TABLE 4. Effect of Ad d itives
TABLE 6. VO(a ca c)2-Ca ta lyzed Oxid a tion of Alcoh ols
u n d er Molecu la r Oxygen
conv
of 1m (%)
GLC yield
isolated
yield
R2 of 3 (%) of 4 (%)a
entry
V cat.
additive
of 2m (%)a
conv
entry substrate
R1
1
2
3
VO(acac)2
VO(acac)2
VO(acac)2
V(acac)3
VO(hpfdm)2
VO(hfac)2
VO(hfac)2
68
7
52
5
pyridine
Hacac
1
2c
3
4
5
6
7
8
9
3a
3a
3b
3c
3d
3e
3f
3g
3h
3i
Ph
Ph
Ph
Ph
n-C11H23
n-C10H21
H
H
25
65
50
45
19
15
20
99
91
99
4a , 11b
4a , 62b
4b, 50b
4c, 45
4d , 13
4e, 11
4f, 15
4g, 54
4h , 51d
4i, 60d
56
79
65
65
83
45
70
57
55
71
4b
5b
6b
7b
Me
Ph
H
Me
H
H
H
H
Hhfac
a
b
(E)-PhCHdCH
Based on alcohol employed. For 12 h.
(E)-HCtCC(CH3)dCH
(E)-PhCtCCHdCH
(Z)-PhCtCCHdCH
TABLE 5. VO(h fa c)2-Ca ta lyzed Oxid a tion of
r-Acetylen ic Alk a n ols u n d er Molecu la r Oxygen
10
Based on alcohol employed. GLC yield. c 5 mol % of catalyst
at 50 °C for 14 h. Several unidentified compounds were present.
a
b
d
conv
of 1 (%)
isolated yield
entry
substrate
time (h)
of 2 (%)a
1
2
3
4
5
6
1j
12
3
12
12
12
12
60
49
67
83
77
84
2j, 39
1k
1k
1m
1p
1q
2k , 45
2k , 67
2m , 71b
2p , 50
2q, 57
a
b
Based on alcohol employed. GLC yield.
F IGURE 1. Plots of yield of 2a vs O2 uptake.
SCHEME 2
investigated with 1m as a substrate. The presence of a
base such as pyridine inhibited the reaction (Table 4,
entry 2). The addition of acetylacetone did not affect the
yield of 2m (entry 3). With use of V(acac)3 as a catalyst,
2m was obtained in good yield (entry 4). VO(hpfdm)2 and
VO(hfac)2 also worked well as a catalyst (entries 5 and
6). Since the addition of hexafluoroacetylacetone in the
system with VO(hfac)2 as a catalyst gave a better yield
of 2m (71% yield, entry 7), this improved catalytic system
was applied to other R-acetylenic alkanols, the results
being listed in Table 5. The improvement of the yield of
the corresponding carbonyl compounds was observed in
the oxidation of alcohols 1k , 1m , and 1q compared with
the results in the case of using VO(acac)2 as a catalyst
(entries 2-4 and 6; compare also with entries 12, 14, and
20 in Table 3).
having alkynic substituents (3g-i) were converted to the
corresponding aldehydes in moderate yields (entries
8-10).
The measurement of O2 uptake during the reaction was
performed with 1a as a substrate to obtain some infor-
mation about the reaction pathway. As a result, it was
observed that a half molar amount of O2 was absorbed
relative to the yield of 2a , showing the stoichiometry of
the oxidation to be that shown in Scheme 2 (Figure 1).
Next, the oxidation of 1a to 2a in the presence or
absence of a radical inhibitor such as 2,6-di-tert-bu-
tylphenol and garvinoxyl (Scheme 3) was examined, the
time profile of the product yield being shown in Figure
2. It was revealed that the addition of the inhibitor did
not affect the reaction rate as well as the product yield,
suggesting that the main reaction course may be an ionic
one.
Next, the oxidation of benzylic, allylic, and aliphatic
alcohols with VO(acac)2 as a catalyst was examined
(Table 6). Benzyl alcohol (3a ) was converted to benzal-
dehyde (4a ) in low yield (entry 1). When the oxidation
was performed with 5 mol % of VO(acac)2, the yield of
4a increased (entry 2). 1-Phenylethyl alcohol (3b) and
diphenylmethanol (3c) were converted to the correspond-
ing ketones in moderate yields (entries 3 and 4). Primary
and secondary aliphatic alcohols (3d and 3e) and cin-
namyl alcohol (3f) gave the corresponding carbonyl
compounds in low yields (entries 5-7). Allylic alcohols
Further, the stoichiometric reaction under a nitrogen
atmosphere was examined. Treatment of 1a (0.1 mmol)
in the presence of VO(acac)2 (0.1 mmol) and MS3A (500
mg) in acetonitrile (20 mL) under N2 at 80 °C did not
give the corresponding carbonyl compound at all even
J . Org. Chem, Vol. 67, No. 19, 2002 6721

Maeda et al.
F IGURE 2. Time profile of the oxidation of 1a in the presence
or absence of garvinoxyl.
F IGURE 3. Plausible reaction pathway.
atm of O2. The spectrum was the same as that of VO-
(acac)2 even measured at 75 °C, showing that the oxida-
tion state of the vanadium did not change even in the
presence of oxygen. When the ESR measurement was
carried out with the sample containing 1a , oxygen,
MS3A, and acetonitrile at room temperature, almost the
same spectrum as above was obtained, but when the
sample was heated to 65 °C, the color of the green
mixture turned yellow to brown and the spectrum due
to VO(acac)2 disappeared completely. This result shows
that a higher vanadium(V) species might be produced
and, for its formation, the presence of both propargylic
alcohol and molecular oxygen is necessary.
On the basis of these results, a plausible reaction
pathway is shown in Figure 3.1a,17 First, a vanadium(IV)
species (A) reacts with both propargylic alcohol and
molecular oxygen to form a vanadium(V) species (B). The
species B further reacts with propargylic alcohol to afford
a vanadium alcoholate (C). Next, the product carbonyl
compound and a dihydroxyvanadium species (D) are
formed via â-hydrogen elimination from species C. The
subsequent dehydration of D by oxidation with oxygen
reproduces species B.
SCHEME 3
after 24 h (Scheme 4). This result suggests that the
presence of oxygen is indispensable for the formation of
an active species for this oxidation.
SCHEME 4
As the electron spin resonance (ESR) study of VO-
(acac)2 has been throughly carried out to disclose the
characteristic spectrum due to vanadium(IV),16 the mea-
surement of the ESR spectrum of a vanadium species in
our reaction system was tried under various conditions
to obtain some information on the reaction pathway.
First, the spectrum of VO(acac)2 was measured in aceto-
nitrile (0.5 M) in the presence or absence of MS3A under
argon at room temperature. Nearly the same spectrum
was obtained in both cases (a(V) ) 10.5 mT, g ) 1.964),
which was in accord with the literature values16a (a(V)
) 10.5 mT, g ) 1.969). The coexistence of suspended
MS3A powder did not induce any abnormal line-width
phenomenon, showing that the vanadium(IV) complex is
not adsorbed on the MS3A powder. These results suggest
that there is no favorable interaction between VO(acac)2
and MS3A. Next, to investigate whether VO(acac)2
changes to a higher valent vanadium species in the
presence of molecular oxygen, its spectrum was measured
in acetonitrile (0.5 M) in the presence of MS3A under 1
Con clu sion
We have disclosed that the oxidation of propargylic
alcohols [R1CH(OH)CtCR2] to the corresponding carbo-
nyl compounds proceeded efficiently with VO(acac)2 as a
catalyst in the presence of MS3A in acetonitrile under
an atmospheric pressure of molecular oxygen. Although
the reactivity of R-acetylenic alkanols (R1 ) alkyl) was
lower compared to that of the alcohols of R1 ) aryl,
alkenyl, and alkynyl, the use of VO(hfac)2 as a catalyst
and the addition of hexafluoroacetylacetone improved the
product yield in these cases.
Exp er im en ta l Section
Gen er a l Meth od s. 1H NMR spectra were obtained in
CDCl3 at 300 or 400 MHz with Me4Si as an internal standard.
13C NMR spectra were obtained at 100 or 75.5 MHz. ESR
spectra were recorded on a J EOL J ES-TE200 spectrometer.
Field sweep was monitored with an Echo Electronics EFM-
1
2000 H NMR gaussmeter. GLC analyses were performed on
(16) (a) Bernal, I.; Rieger, P. H. Inorg. Chem. 1962, 2, 256. (b)
Kivelson, D.; Lee, S.-K. J . Chem. Phys. 1964, 41, 1896. (c) Walker, F.
A.; Carlin, R. L.; Rieger, P. H. J . Chem. Phys. 1966, 45, 4181. (d) Guzy,
C. M.; Raynol, J . B.; Symons, M. C. R. J . Chem. Soc. (A) 1969, 2791.
(17) Itoh, T.; J itsukawa, K.; Kaneda K.; Teratani, S. J . Am. Chem.
Soc. 1979, 101, 159.
6722 J . Org. Chem., Vol. 67, No. 19, 2002

Aerobic Oxidation of Propargylic Alcohols
a Shimadzu GC-14A instrument (25 m × 0.33 mm, 5.0 mm
film thickness, Shimadzu fused silica capillary column HiCap
CBP10-S25-050) with a flame-ionization detector and helium
as carrier gas. Analytical thin-layer chromatography (TLC)
was performed with Merck silica gel 60 F-254 plates. Column
chromatography was performed with Merck silica gel 60.
2H); 13C NMR (75.5 MHz, CDCl3) δ 5.3, 36.1, 71.7, 85.6, 89.0,
122.8, 128.2, 128.2, 131.6.
1-Cycloh exyl-2-p r op yn -1-ol (1n , Ta ble 3, en tr y 17).
1
Yellow oil; H NMR (400 MHz, CDCl3) δ 1.02-1.31 (m, 5H),
1.52-1.88 (m, 6H), 2.24 (br s, OH, 1H), 2.47 (d, J ) 2.2 Hz,
1H), 4.16 (dd, J ) 5.9, 2.2 Hz, 1H); 13C NMR (100 MHz, CDCl3)
δ 25.8, 25.9, 26.3, 28.0, 28.4, 48.7, 66.9, 73.6, 83.9.
Ma ter ia ls. Commercially available organic and inorganic
compounds were used without further purification except for
the solvent, which was distilled by the usual method before
use. VO(tfac)2, VO(hfac)2, and VO(hpfdm)2 were synthesized
by literature methods.18 Commercial MS3A (powder) (Nacalai
Tesque) was activated by calcination just before use. Alcohols
1a , 1h -k , 1m , and 3a -g were commercial products and
purified by normal methods just before use. Alcohols 1b-g,
1l,and 1n -q were prepared from the corresponding aldehydes
and lithium acetylides or alkynylmagnesium bromides, puri-
fied by column chromatography on silica gel (eluent: hexane-
ethyl acetate) and identified by 1H NMR and 13C NMR. All
propargylic alcohols and the corresponding aldehydes and
ketones except for 1q are known compounds. Aldehydes and
ketones 2f, 2i, 2k , and 4a -f are commercial products. Com-
pounds 3h and 3i were prepared by the reported method.19a
Compounds 3h ,19a 3i,19a 4g,19b 4h ,19c and 4i19c were character-
ized by their spectral data. Some selected spectral data of
alcohols and carbonyl compounds are shown below.
1-Cycloh exyl-2-h ep tyn -1-ol (1o, Ta ble 3, en tr y 18).
1
Yellow oil; H NMR (300 MHz, CDCl3) δ 0.91 (t, J ) 4.0 Hz,
3H), 1.02-1.86 (m, 15H), 2.22 (td, J ) 6.6, 1.8 Hz, 2H), 4.13
(dt, J ) 5.9, 1.8 Hz, 1H); 13C NMR (75.5 MHz, CDCl3) δ 13.5,
18.3, 21.8, 25.8, 25.9, 26.4, 28.0, 30.7, 44.2, 67.2, 80.1, 86.0.
1-Cycloh exyl-2-n on yn -1-ol (1p , Ta ble 3, en tr y 19). Yel-
low oil; 1H NMR (300 MHz, CDCl3) δ 0.89 (t, J ) Hz, 3H),
1.02-1.85 (m, 19H), 2.10 (br s, OH, 1H), 2.20 (td, J ) 7.0, 1.1
Hz, 2H), 4.13 (d, J ) 7.7 Hz, 1H); 13C NMR (75.5 MHz, CDCl3)
δ 13.9, 18.6, 22.5, 25.8 26.4, 28.0, 28.4, 28.5, 31.2, 44.2, 67.3,
80.1, 86.1.
9-Hexa d ecyn -8-ol (1q, Ta ble 3, en tr y 20). Colorless oil;
1H NMR (300 MHz, CDCl3) δ 0.88 (t, J ) 7.0 Hz, 3H), 0.89 (t,
J ) 7.0 Hz, 3H), 1.29-1.68 (m, 23H), 2.20 (td, J ) 6.8, 1.7 Hz,
2H), 4.35 (t, J ) 6.4 Hz, 1H); 13C NMR (75.5 MHz, CDCl3) δ
14.0, 14.1, 18.8, 22.5, 22.6, 25.2, 28.5, 28.6, 29.2, 31.3, 31.8,
38.2, 62.8, 81.3, 85.6; IR (neat, cm-1) 2932, 2856, 2211, 1709,
1671, 1450, 1243, 1165, 974, 894, 725. Anal. Calcd for
1-(p-Tolyl)-2-p r op yn -1-ol (1b, Ta ble 3, en tr y 2). Yellow
C
16H30O: C, 80.61; H, 12.68. Found C, 80.51; H, 12.40.
1
oil; H NMR (300 MHz, CDCl3) δ 2.34 (s, 3H), 2.62 (dd, J )
Gen er a l P r oced u r e for th e Oxid a tion of P r op a r gylic
2.2 0.5 Hz, 1H), 2.70 (br s, OH, 1H), 5.37 (s, 1H), 7.15 (d, J )
8.2 Hz, 2H), 7.39 (d, J ) 8.2 Hz, 2H); 13C NMR (75.5 MHz,
CDCl3) δ 21.1, 42.1, 74.5, 83.7, 126.5, 129.2, 137.2, 138.2.
Alcoh ols w ith Molecu la r Oxygen . To a solution of VO(acac)2
(2.65 mg, 0.01 mmol) in acetonitrile (1.5 mL) in a 10-mL two-
necked round-bottomed flask was added MS3A (500 mg,
powder). Next, a solution of propargylic alcohol (1 mmol) in
acetonitrile (0.5 mL) was added and the resulting mixture was
stirred. Oxygen gas was then introduced into the flask from
an O2 balloon under atmospheric pressure and then the
mixture was stirred vigorously for 3 h at 80 °C under oxygen.
The mixture was then cooled to room temperature and MS3A
was separated by filtration through a glass filter. The amount
of the product was determined by GLC analysis with bibenzyl
or cyclododecane as an internal standard. For isolation of the
product, the solvent was evaporated and the residue was
purified by column chromatography (Merck silica gel 60;
hexane-ethyl acetate as an eluent).
1-P h en yl-2-p r op yn -1-on e (2a , Ta ble 1 en tr y 1). Yellow
solid, mp 42.5-43.5 °C; 1H NMR (300 MHz, CDCl3) δ 3.45 (s,
1H), 7.49 (t, J ) 7.4 Hz, 2H), 7.63 (t, J ) 7.4 Hz, 1H), 8.16 (d,
J ) 7.4 Hz, 2H); 13C NMR (75.5 MHz, CDCl3) δ 80.1, 80.7,
128.4, 129.4, 134.3, 135.9, 177.1 (CdO).
1-(p-Tolyl)-2-p r op yn -1-on e (2b, Ta ble 3, en tr y 2). Yellow
oil; 1H NMR (300 MHz, CDCl3) δ 2.43 (s, 3H), 3.40 (s, 1H),
7.29 (d, J ) 8.1 Hz, 2H), 8.05 (d, J ) 8.1 Hz, 2H); 13C NMR
(75.5 MHz, CDCl3) δ 21.8, 80.3, 80.4, 129.4, 129.8, 133.9, 145.7,
177.0 (CdO).
1-(2-Ch lor op h en yl)-2-p r op yn -1-ol (1c, Ta ble 3, en tr y 3).
1
Yellow oil; H NMR (300 MHz, CDCl3) δ 2.62 (d, J ) 2.2 Hz,
1H), 3.30 (br s, OH, 1H), 5.79 (d, J ) 2.2 Hz, 1H), 7.19-7.36
(m, 3H), 7.74 (dd, J ) 7.3, 2.1 Hz, 1H); 13C NMR (75.5 MHz,
CDCl3) δ 61.3, 74.6, 82.4, 127.1, 128.1, 129.5, 129.6, 132.5,
137.4.
1-(1-Na p h t h yl)-2-p r op yn -1-ol (1d , Ta b le 3, en t r y 4).
1
White solid, mp 57.7-58.4 °C; H NMR (400 MHz, CDCl3) δ
2.44 (br s, OH, 1H), 2.72 (d, J ) 1.0 Hz, 1H), 6.10 (d, J ) 1.0
Hz, 1H), 7.43-7.56 (m, 3H), 7.82-7.88 (m, 3H), 8.25 (d, J )
8.3 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 62.7, 75.5, 83.2,
123.7, 124.5, 125.1, 125.9, 126.4, 128.7, 129.4, 130.3, 133.9,
134.9.
1-(2-Na p h th yl)-2-p r op yn -1-ol (1e, Ta ble 3, en tr y 5).
1
White solid, mp 53.8-54.5 °C; H NMR (400 MHz, CDCl3) δ
2.39 (br s, OH, 1H), 2.71 (d, J ) 2.2 Hz, 1H), 5.61 (d, J ) 2.2
Hz, 1H), 7.47-7.51 (m, 2H), 7.64 (dd, J ) 8.3, 1.5 Hz, 1H),
7.82-7.88 (m, 3H), 7.99, (s, 1H); 13C NMR (100 MHz, CDCl3)
δ 64.5, 75.0, 83.5, 124.3, 125.4, 126.3, 126.3, 127.6, 128.1, 128.2,
128.5, 133.0, 137.2.
1,3-Dip h en yl-2-p r op yn -1-ol (1f, Ta ble 3, en tr y 6). Yellow
oil; 1H NMR (300 MHz, CDCl3) δ 3.10 (br s, OH, 1H), 5.64 (s,
1H), 7.22-7.46 (m, 8H), 7.56-7.59 (m, 2H); 13C NMR (75.5
MHz, CDCl3) δ 64.8, 86.4, 88.8, 122.3, 126.6, 126.7, 128.2,
128.2, 128.5, 131.6, 140.5.
1-P h en yl-2-n on yn -1-ol (1g, Ta ble 3, en tr y 7). Yellow oil;
1H NMR (400 MHz, CDCl3) δ 0.88 (t, J ) 6.8 Hz, 3H), 1.23-
1.40 (m, 6H), 1.50 (quint, J ) 7.8 Hz, 2H), 1.56 (br s, OH, 1H),
2.22 (td, J ) 7.3, 1.9 Hz, 2H), 5.38 (s, 1H), 7.23-7.39 (m, 3H),
7.49 (d, J ) 7.3 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 13.9,
18.7, 22.4, 31.2, 64.4, 64.4, 80.0, 87.2, 126.4, 127.7, 128.1, 141.1.
1-(2-Ch lor op h en yl)-2-p r op yn -1-on e (2c, Ta ble 3, en tr y
3). Pale yellow solid, mp 61.5-62.2 °C; 1H NMR (300 MHz,
CDCl3) δ 3.49 (s, 1H), 7.37-7.52 (m, 3H), 8.10 (ddd, J ) 7.8,
1.6, 0.6 Hz, 1H); 13C NMR (75.5 MHz, CDCl3) δ 81.1, 81.3,
126.7, 131.7, 133.3, 133.8, 133.8, 134.5, 175.8 (CdO).
1-(1-Na p h th yl)-2-p r op yn -1-on e (2d , Ta ble 3, en tr y 4).
1
Yellow solid, mp 59.5-60.5 °C; H NMR (300 MHz, CDCl3) δ
3.44 (s, 3H), 7.56 (m, 2H), 7.67 (t, J ) 7.8 Hz, 1H), 7.89 (d, J
) 7.8 Hz, 1H), 8.08 (d, J ) 7.8 Hz, 1H), 8.60 (d, J ) 7.8 Hz,
1H), 9.20 (d, J ) 7.8 Hz, 1H); 13C NMR (75.5 MHz, CDCl3) δ
79.4 81.6, 124.4, 125.8, 126.9, 128.6, 129.2, 130.6, 131.8, 133.8.
135.5, 135.7, 178.8 (CdO).
4,4-Dim eth yl-1-p h en yl-1-p en tyn -3-ol (1l, Ta ble 3, en tr y
13). Yellow oil; 1H NMR (300 MHz, CDCl3) δ 1.06 (s, 9H), 2.16
(br s, OH, 1H), 4.23 (s, 1H), 7.25-7.31 (m, 3H), 7.39-7.44 (m,
1-(2-Na p h th yl)-2-p r op yn -1-on e (2e, Ta ble 3, en tr y 5).
Yellow solid, mp 102.0-102.9 °C; 1H NMR (300 MHz, CDCl3)
δ 3.50 (s, 1H), 7.56-7.68 (m, 2H), 7.88 (d, J ) 8.6 Hz, 1H),
7.91 (d, J ) 8.6 Hz, 1H), 8.02 (d, J ) 8.6 Hz, 1H), 8.14 (dd, J
) 8.6, 1.7 Hz, 1H), 8.75 (s, 1H); 13C NMR (75.5 MHz, CDCl3)
δ 80.4, 80.7, 123.6, 127.1, 127.9, 128.6, 129.3, 129.9, 132.3,
133.3, 133.7, 136.2, 177.3 (CdO).
(18) (a) Su, C.-C.; Reed, J . W.; Gould, E. S. Inorg. Chem. 1973, 12,
337. (b) Pesiri, D. R.; Morita, D. K.; Walker, T.; Tumas, W. Organo-
metallics 1999, 18, 4916.
(19) (a) Takeuchi, R.; Tanabe, K.; Tanaka, S. J . Org. Chem. 2000,
65, 1558. (b) Muller, B.; Fe´re´zou, J .-P.; Pancrazi, A.; Lallemand, J .-Y.
Bull. Soc. Chim. Fr. 1997, 134, 13. (c) J ohn, J . A.; Tour, J . M.
Tetrahedron 1997, 53, 15515.
J . Org. Chem, Vol. 67, No. 19, 2002 6723

Maeda et al.
1-P h en yl-2-n on yn -1-on e (2g, Ta ble 3, en tr y 7). Yellow
oil; 1H NMR (300 MHz, CDCl3) δ 0.91 (t, J ) 6.8 Hz, 3H), 1.31-
1.35 (m, 4H), 1.43-1.53 (quint, J ) 6.8 Hz, 2H), 1.68 (quint,
J ) 7.5 Hz, 2H), 2.50 (t, J ) 7.2 Hz, 2H), 7.47 (t, J ) 7.3 Hz,
1H), 7.48 (t, J ) 6.9 Hz, 2H), 7.60 (tt, J ) 7.3, 1.3 Hz, 1H),
8.12-8.15 (m, 2H); 13C NMR (75.5 MHz, CDCl3) δ 13.9, 19.1,
22.4, 27.7, 28.5, 31.1, 79.6, 96.8, 128.4, 129.4, 133.8, 136.8,
178.1 (CdO).
(m, 4H), 1.69 (quint, J ) 7.2 Hz, 2H), 2.58 (t, J ) 7.6 Hz, 2H),
3.20 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 13.9, 22.4, 23.5,
31.1, 45.4, 78.2, 81.4, 187.4(CdO).
1-Cycloh exyl-2-p r op yn -1-on e (2n , Ta ble 3, en tr y 17).
1
Yellow oil; H NMR (300 MHz, CDCl3) δ 1.13-1.41 (m, 4H),
1.58-1.98 (m, 6H), 2.36 (tt, J ) 10.8, 3.5 Hz, 1H), 3.18 (s, 1H);
13C NMR (75.5 MHz, CDCl3) δ 25.2, 25.6, 27.8, 52.1, 79.0, 80.7,
190.7 (CdO).
(E)-1-P h en yl-1-p en ten -4-yn -3-on e (2h , Ta ble 3, en tr y 8).
1-Cycloh exyl-2-h ep tyn -1-on e (2o, Ta ble 3, en tr y 18).
Colorless oil; 1H NMR (300 MHz, CDCl3) δ 0.93 (t, J ) 7.2 Hz,
3H), 1.17-1.98 (m, 14H), 2.32-2.40 (m, 3H); 13C NMR (75.5
MHz, CDCl3) δ 13.4, 18.6, 21.9, 25.3, 25.7, 28.2, 29.7, 52.2,
80.1, 95.0, 191.8 (CdO).
1-Cycloh exyl-2-n on yn -1-on e (2p , Ta ble 3, en tr y 19).
Colorless oil; 1H NMR (300 MHz, CDCl3) δ 0.90 (t, J ) 6.9 Hz,
3H), 1.18-1.98 (m, 18H), 2.31-2.44 (m, 3H); 13C NMR (75.5
MHz, CDCl3) δ 14.0, 22.4, 22.4, 25.4, 25.8, 27.7, 28.2, 28.5,
31.2, 52.3, 80.1, 95.0, 191.7 (CdO).
9-Hexa d ecyn -8-on e (2q, Ta ble 3, en tr y 20). Colorless oil;
1H NMR (300 MHz, CDCl3) δ 0.89 (t, J ) 6.8 Hz, 3H), 0.90 (t,
J ) 6.6 Hz, 3H), 1.28-1.68 (m, 18H), 2,36 (t, J ) 7.0 Hz, 2H),
2.52 (t, J ) 7.3 Hz, 2H); 13C NMR (75.5 MHz, CDCl3) δ 14.0,
14.0, 18.9, 22.6, 24.2, 27.7, 28.5, 28.9, 31.2, 31.6, 45.5, 80.9,
94.3, 188.6 (CdO).
1
Yellow solid, mp 51.2-52.2 °C; H NMR (400 MHz, CDCl3) δ
3.32 (s, 1H), 6.81 (d, J ) 16.1 Hz, 1H), 7.42-7.46 (m, 3H),
7.58-7.60 (m, 2H), 7.89 (d, J ) 16.1 Hz, 1H); 13C NMR (100
MHz, CDCl3) δ 79.2, 79.9, 127.9, 128.7, 129.0, 131.3, 133.8,
149.5, 177.4 (CdO).
2-Non yn a l (2j, Ta ble 3, en tr y 10). Yellow oil; 1H NMR
(300 MHz, CDCl3) δ 0.90 (t, J ) 6.8 Hz, 3H), 1.26-1.48 (m,
6H), 1.63 (quint, J ) 7.2 Hz, 2H), 2.41 (t, J ) 7.0 Hz, 2H),
9.18 (s, 1H); 13C NMR (75.5 MHz, CDCl3) δ 13.9, 18.7, 22.4,
27.3, 28.4, 31.2, 72.6. 92.5, 157.9 (CdO).
4,4-Dim eth yl-1-p h en yl-1-p en tyn -3-on e (2l, Ta ble 3, en -
tr y 13). Yellow oil; 1H NMR (300 MHz, CDCl3) δ 1.28 (s, 9H),
7.34-7.47 (m, 3H), 7.56-7.59 (m, 2H); 13C NMR (75.5 MHz,
CDCl3) δ 26.1, 44.8, 85.9, 92.2, 120.1, 128.5, 130.5, 132.9 (Cd
O).
1-Octyn -3-on e (2m , Ta ble 3, en tr y 14). Yellow oil; 1H
NMR (400 MHz, CDCl3) δ 0.90 (t, J ) 6.6 Hz, 3H), 1.31-1.33
J O025918I
6724 J . Org. Chem., Vol. 67, No. 19, 2002