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K. Kumamoto et al.
LETTER
(6) Hamann, S. D. Physico-Chemical Effects of Pressure;
Butterworths: London, 1957, 155.
(7) General procedure
methanol in the presence of trimethyl orthoformate under
high-pressure conditions. The results illustrate the poten-
tial utility of this method as an environmentally friendly
process, and further studies of the application of this tech-
nique to other functional-group transformations are now
in progress.
A mixture of ketone and trimethyl orthoformate (2 equiv) in
MeOH was placed in a Teflon reaction vessel (2.0 mL
volume), and the mixture was allowed to react at 0.8 GPa at
the appropriate temperature and for the specified time
(Table 1). After the mixture was cooled and the pressure was
released, the mixture was concentrated in vacuo. The crude
product was purified quickly by column chromatography on
alumina (elution with hexane–Et2O) to afford the pure
product in good to excellent yields.
Acknowledgment
This work was supported in part by a Grant-in-Aid for Scientific
Research from the Ministry of Education, Science, Culture, and
Sports, Japan, as well as a Special Research Grant for Green
Science from Kochi University. K.K. thanks JSPS for a research
fellowship for Young Scientists.
(8) The use of a stoichiometric amount of this reagent resulted
in incomplete conversion.
(9) Firouzabadi, H.; Iranpoor, N.; Karimi, B. Synth. Commun.
1999, 29, 2255; and references cited therein.
(10) Difficulties were encountered only with highly stabilized
ketones such as benzophenone and anthraquinone. See, for
example: (a) Leonard, N. M.; Oswald, M. C.; Freiberg, D.
A.; Nattier, B. A.; Smith, R. C.; Mohan, R. S. J. Org. Chem.
2002, 67, 5202. (b) Thurkauf, A.; Jacobson, A. E.; Rice, K.
C. Synthesis 1988, 233.
(11) The ease of mono-ketalization of these difunctional
substrates can be ascribed to the low electron density at one
of the carbonyl groups.
(12) See for example: Ley, S. V.; Osborn, H. M. I.; Priepke, H.
W. M.; Warriner, S. L. Org. Synth., Coll. Vol. 10; Wiley:
New York, 2004, 523.
(13) Under the normal conditions (1 atm, r.t.) both substrates
were recovered unchanged.
(14) These reactions were best performed in CH2Cl2 using
trimethyl orthoformate (2 equiv) and MeOH (2 equiv).
(15) The acid- or base-catalyzed conjugate addition reaction of
alcohols to enones under high pressure is known:
(a) H2SO4: Scott, J. J.; Brower, K. R. J. Am. Chem. Soc.
1967, 89, 2682. (b) DMAP/LiClO4: Hayashi, Y.;
Nishimura, K. Chem. Lett. 2002, 296. See also: (c) Jenner,
G. Tetrahedron 2002, 58, 4311. (d) Jenner, G. Tetrahedron
Lett. 2001, 42, 4807.
References
(1) (a) High-Pressure Organic Chemistry, Part 29. For Part 28,
see: Matsumoto, K.; Kim, J. C.; Iida, H.; Hamana, H.;
Kumamoto, K.; Kotsuki, H.; Jenner, G. Helv. Chim. Acta
2005, in press. (b) Part 27: Kumamoto, K.; Fukada, I.;
Kotsuki, H. Angew. Chem. Int. Ed. 2004, 43, 2015.
(2) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic
Synthesis; Wiley: New York, 1999.
(3) Reviews: (a) Kotsuki, H.; Kumamoto, K. Yuki Gosei
Kagaku Kyokaishi 2005, in press. (b) Jenner, G.
Tetrahedron 2005, 61, 3621. (c) High Pressure Chemistry;
van Eldik, R.; Klärner, F.-G., Eds.; Wiley-VCH: Weinheim,
2002. (d) Jenner, G. Tetrahedron 2002, 58, 5185.
(e) Klärner, F.-G.; Wurche, F. J. Prakt. Chem. 2000, 342,
609.
(4) For our recent work on a high-pressure-promoted
uncatalyzed reaction, see: Kumamoto, K.; Misawa, Y.;
Tokita, S.; Kubo, Y.; Kotsuki, H. Tetrahedron Lett. 2002,
43, 1035.
(5) Dauben, W. G.; Gerdes, J. M.; Look, G. C. J. Org. Chem.
1986, 51, 4964.
Synlett 2005, No. 14, 2254–2256 © Thieme Stuttgart · New York