dec-3-yne with ButOOH catalyzed by CrO3 produced only dec-
3-yn-2-one.7c Under the same conditions, oct-2-yne 1e afforded
oct-2-yn-4-one 3e with high regioselectivity (run 5). The
terminal alkyne oct-1-yne 1f was oxidized to oct-1-yn-3-one 3f
with high selectivity, although the conversion was moderate
(50%) (run 6). On the other hand, for oct-2-yn-1-al 1g, the
aldehyde moiety was selectively oxidized rather than the prop-
2-ynylic C–H bond, giving oct-2-ynoic acid 6g (run 7).
In conclusion, various alkynes were converted into a,b-
acetylenic carbonyl compounds by aerobic oxidation using
NHPI combined with CoII or CuII complexes. The present
method provides a facile method for preparing conjugated
ynones from alkynes.
conversion, but in the absence of Cu(acac)2 oct-1-yn-2-ol was
converted into the ynone in low yield [eqn. (2)]. This shows that
NHPI (10 mol%)
OH
Additive (0.5 mol%)
2 (1 atm)
O
O
(2)
C6H13
C6H13
MeCN, 70 °C, 3 h
Cu(acac)2 plays an important role in the conversion of ynol into
ynone.
Conventionally, oxidation of alkynes with molecular oxygen
is carried out at higher temperatures, i.e. 110–150 °C. Under
such conditions the reaction results in undesired over-oxidation
products such as oxidatively cleaved carboxylic acids.13 For
instance, the oxidation of dodec-6-yne under 70 atm of air at
110 °C is reported to lead to cleaved products such as hexanoic
acid and pentanoic acid as principal products.
It is noteworthy that the NHPI-catalyzed oxidation of alkynes
with molecular oxygen could be achieved at room temperature,
since undesired side reactions arising from high reaction
temperatures could be suppressed.
The present successful conversion of alkynes into ynones is
believed to result from the fact that the phthalimide N-oxyl
radical (PINO) can be generated from NHPI under the influence
of dioxygen and 1a at room temperature. Thus, EPR analysis of
PINO formed from NHPI under atmospheric dioxygen in the
presence or absence of alkyne 1a at room temperature was
performed. As expected, the EPR signal attributed to PINO was
observed in the presence of 1a after 14 h, but in the absence of
1a no EPR signal was observed. At this stage, we cannot make
an accurate assessment of the interaction between NHPI and the
alkyne 1a. The generation of PINO from NHPI in the presence
of alkyne 1a may be facilitated by the weak coordination of
NHPI, which is a weak acid having pKa = 7.0,14 to the
acelylenic p-bond of the alkyne.
This work was financially supported by the Research for the
Future program JSPS.
Notes and References
† E-mail: ishii@ipcku.kansai-u.ac.jp
‡ Typical procedure for the aerobic oxidation of alkyne: To a solution of
NHPI (0.2 mmol, 10 mol%) and a transion metal complex (0.01 mmol, 0.5
mol%) in MeCN (5 cm3) was added alkyne (2 mmol), then the flask was
flushed with oxygen and equipped with a balloon filled with O2. The
reaction mixture was stirred at 25 °C for 30 h. The solvent was evaporated
under reduced pressure. The products were purified by column chromatog-
raphy on silica gel [hexane–EtOAc (10:1 to 3:1)], and characterised by 1H
and 13C NMR, GC–MS and IR spectroscopy.
1 K. Utimoto, M. Miwa and H. Nozaki, Tetrahedron Lett., 1981, 22,
4277.
2 A. B. Smith, III, P. A. Levenberg and J. Z. Suits, Synthesis, 1986,
184.
3 M. Karpf, J. Huguet and A. S. Dreiding, Helv. Chim. Act., 1986, 65,
13.
4 S. T-K. Tam, R. S. Klein, F. G. de las Heras and J. J. Fox, J. Org. Chem.,
1979, 44, 4854 and references cited therein; C. M. Gupta, G. H. Jones
and J. G. Moffatt, J. Org. Chem., 1976, 41, 3000.
5 N. Sayo, K.-I. Azuma, K. Mikawa and T. Nakai, Tetrahedron Lett.,
1984, 25, 565; K. Midland and N. H. Nguyen, J. Org. Chem., 1981, 46,
4107.
6 (a) M. Yamaguchi, K. Shibata, S. Fujiwara and I. Hirao, Synthesis,
1986, 421; (b) H. C. Brown, U. S. Racherla and S. M. Singh,
Tetrahedron Lett., 1984, 25, 2411; (c) J. F. Normant and M. Bourgan,
Tetrahedron Lett., 1970, 11, 2659; (d) A. G. Davies and R. J.
Puddephatt, Tetrahedron Lett., 1967, 8, 2265.
7 (a) W. B. Sheats, L. K. Olli, R. Stout, J. T. Lundzen, R. Justus and
W. G. Nigh, J. Org. Chem., 1979, 44, 4075; (b) J. E. Shaw and J. J.
Sherry, Tetrahedron Lett., 1971, 12, 4379; (c) J. Muzart and O. Piva,
Tetrahedron Lett., 1988, 29, 2321.
8 (a) A. Mckilklop, O. H. Oldenziel, B. P. Swann, E. C. Taylor and R. L.
Robey, J. Am. Chem. Soc., 1973, 95, 1296; (b) M. Schroder and W. P.
Griffith, J. Chem. Soc., Dalton Trans., 1978, 1599; (c) D. G. Lee and
V. S. Chang, J. Org. Chem., 1979, 44, 2726; (d) P. Muller and A. J.
Godoy, Helv. Chem. Acta. 1981, 64, 2531.
Table 2 summarizes the results for the NHPI-catalyzed
oxidation of a variety of alkynes in the presence of Co(acac)2 or
Cu(acac)2 under oxygen atmosphere. The conversions of
substrates were generally high except for terminal alkynes, and
the corresponding a,b-acetylenic carbonyl compounds were
obtained in moderate to good yields. Symmetric alkynes such as
hex-3-yne 1b and dodec-6-yne 1c were oxidized into conju-
gated ynones hex-3-yn-2-one 3b and dodec-6-yn-5-one 3c,
respectively, in good yields, (runs 1–3). Unsymmetrical alkyne,
oct-3-yne 1d gave a 1:1 mixture of the corresponding
conjugated ynones, 3d and 3dA (run 4), although the oxidation of
Table 2 Aerobic oxidation of several alkynes catalyzed by NHPI combined
a
with Co(acac)2 or Cu(acac)2
Conversion Selectivity
(%)
9 (a) R. Curci, M. Fiorentino, C. Fusco, R. Mello, F. P. Ballistreri, S.
Failla and G. A. Tomaselli, Tetrahedron Lett., 1992, 33, 7929; (b) R. W.
Murray and M. Singh, J. Org. Chem., 1993, 58, 5076; (c) S. Sakaguchi,
S. Watase, Y. Katayama, Y. Sakata, Y. Nishiyama and Y. Ishii, J. Org.
Chem., 1994, 59, 5681.
10 (a) S. Sakaguchi, S. Kato, T. Iwahama and Y. Ishii, Bull. Chem. Soc.
Jpn., 1998, 71, 1237; (b) Y. Yoshino, Y. Hayashi, T. Iwahama, S.
Sakaguchi and Y. Ishii, J. Org. Chem., 1997, 62, 6810; (c) Y. Ishii, T.
Iwahama, S. Sakaguchi, K. Nakayama and Y. Nishiyama, J. Org.
Chem., 1996, 61, 4520; (d) T. Iwahama, S. Sakaguchi, Y. Nishiyama
and Y. Ishii, Tetrahedron Lett., 1995, 36, 6923.
Run Substrate
Product
(%)b
1c EtC·CEt 1b
2d,e EtC·CEt 1b
AcC·CEt 3b
AcC·CEt 3b
93
96
81
75
75
70f
3e C5H11C·CC5H11 1c BuC(O)C·CC5H11 3c 89
4c BuC·CEt 1d
PrC(O)C·CEt 3d
BuC·CAc 3dA
BuC(O)C·CMe 3e
92
5e C5H11C·CMe 1e
6c,e C6H13C·CH 1f
94
70
C5H11C(O)C·CH 3f 50
80
74g
7c,e C5H11C·CCHO 1g C5H11C·CCO2H 6g 43
11 D. M. Golden, Annu. Rev. Phys. Chem., 1982, 33, 493.
12 M. A. Umbreit and K. B. Sharpless, J. Am. Chem. Soc., 1977, 99,
5527.
13 P. E. Correa, G. Hardy and D. P. Riley, J. Org. Chem., 1988, 53,
1695.
a Substrate (2 mmol) was allowed to react under O2 atmosphere (1 atm) in
the presence of NHPI (10 mol%) and Cu(acac)2 (0.5 mol%) in MeCN (5
b
cm3) at 50 °C for 6 h. Yields of the products were determined by GC
analysis using an internal standard. Other products were a-alkynyl alcohols
( ~ 5%) and cleaved products such as carboxylic acids ( ~ 3%) except for run
14 D. E. Ames and T. F. Grey, J. Chem. Soc., 1955, 3521.
c
d
e
f
7. 20 h. Co(acac)2 was used instead of Cu(acac)2. 70 °C. A 1:1
regioisomeric mixure was obtained. g Isolated yield.
Received in Cambridge, UK, 29th June 1998; 8/04956D
2038
Chem. Commun., 1998