ORGANIC
LETTERS
2
005
Vol. 7, No. 2
31-334
GaCl -Catalyzed Skeletal Rearrangement
3
3
of
r,r,r-Trisubstituted Aldehydes
†
‡
‡
,†
Masayuki Oshita, Takao Okazaki, Kouichi Ohe, and Naoto Chatani*
Department of Applied Chemistry, Faculty of Engineering, Osaka UniVersity,
Suita, Osaka 565-0871, Japan, and Department of Energy and Hydrocarbon
Chemistry, Graduate School of Engineering, Kyoto UniVersity,
Nishikyo-ku, Kyoto 615-8510, Japan
Received November 16, 2004
ABSTRACT
GaCl
3
is found to be a superior catalyst for the skeletal rearrangement of
r
,
r
,
r
-trisubstituted aldehydes to ketones. The rearrangement can
to the carbonyl group or
was supported on the basis of experimental
proceed smoothly in the presence of a catalytic amount of GaCl
without steric strains can be used. Double activation of a carbonyl group by two molecules of GaCl
data and a DFT study.
3
, and even substrates having no heteroatoms
r
3
A skeletal rearrangement is a characteristic feature in
carbocation chemistry. Rearrangement can occur by the 1,2-
R position to the carbonyl group is not always necessary if
the reaction conditions used are harsh. Hopff found that the
1
shift of an alkyl group, an aryl group, or a hydrogen to an
electrophilic carbocation center. A similar rearrangement can
readily occur even on a less electrophilic carbon, such as is
found in aldehydes, ketones, imines, or epoxides, provided
the substrates contain a hydroxyl group or amino group
adjacent to the electrophilic center. Such a system is
rearrangement also proceeds in the presence of AlCl
3
and
4
H SO . Recently, Olah and Prakash reported that strong
2
4
protic acids (H < -11), such as TfOH, anhydrous HF, and
0
trifluoroethanol/BF , mediate the rearrangement of pivalal-
3
5
dehyde to methyl isopropyl ketone, even at 0 °C. They
concluded that the reaction proceeds via a protosolvated
2
6
frequently employed in organic synthesis. In 1926, Danilov
carboxonium ion intermediate on the basis that a large
et al. reported on the rearrangement of pivalaldehyde to
excess of the protic acids is required for the rearrangement
to take place and based on a DFT study. A methyl group
methyl isopropyl ketone in 70% H
2
4
SO at a temperature of
3
130 °C, indicating that the presence of a heteroatom at the
(
3) Danilov, S.; Venus-Danilova, E. Ber. Dtsch. Chem. Ges. 1926, 59,
377-387.
(4) Hopff, H.; Nenizescu, C. D.; Isacescu, D. A.; Cantuiari, I. P. Chem.
†
‡
Osaka University.
Kyoto University.
(
1) ComprehensiVe Organic Synthesis; Trost, B. M., Fleming, I., Eds.;
Ber. 1936, 69, 2244-2251.
Pergamon: Oxford, 1991; Vol. 3, Chapter 3.
(5) Olah, G. A.; Mathew, T.; Marinez, E. R.; Esteves, P. M.; Etzkorn,
M.; Rasul, G.; Prakash, G. K. S. J. Am. Chem. Soc. 2001, 123, 11556-
11561.
(2) For a review, see: Paquette, L. A.; Hofferberth, J. E. Org. React.
2
003, 62, 477-567. For recent papers, see: Ooi, T.; Saito, A.; Maruoka,
K. J. Am. Chem. Soc. 2002, 125, 3220-3221. Suda, K.; Kikkawa, T.;
Nakajima, S.; Takanami, T. J. Am. Chem. Soc. 2004, 126, 9554-9555.
(6) Olah, G. A. Angew. Chem., Int. Ed. Engl. 1993, 32, 767-922. Olah,
G. A.; Klumpp, D. A. Acc. Chem. Res. 2004, 37, 211-220.
1
0.1021/ol047640h CCC: $30.25
© 2005 American Chemical Society
Published on Web 12/22/2004