GaCl3-catalyzed skeletal rearrangement of α,α, α-trisubstituted aldehydes

Article abstract of DOI:10.1021/ol047640h

(Chemical Equation Presented) GaCl₃ is found to be a superior catalyst for the skeletal rearrangement of α,α,α- trisubstituted aldehydes to ketones. The rearrangement can proceed smoothly in the presence of a catalytic amount of GaCl₃, and even substrates having no heteroatoms α to the carbonyl group or without steric strains can be used. Double activation of a carbonyl group by two molecules of GaCl ₃ was supported on the basis of experimental data and a DFT study.

Full text of DOI:10.1021/ol047640h

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
chatani@chem.eng.osaka-u.ac.jp
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

moves to the aldehyde carbonyl carbon, which is activated
by a strong protic acid to form a protosolvated carboxonium
ion intermediate. A 1,2-hydride shift completes the rear-
rangement. Quite recently, Davies reported on a similar, ring-
by GC (Table 1). It was found that the rearrangement
proceeds in a catalytic manner (20 mol %) to give 2 in 73%
expansion rearrangement of exo-2-norbornanecarbaldehyde
Table 1. Rearrangement of 2,2-Diphenylpropionaldehyde (1)a
7
induced by AlCl
3
. As part of our interest in the unique
8
3
catalytic or stoichiometric activity of GaCl , we found the
GaCl -mediated conversion of adamantane to 1-adamantane-
3
carboxaldehyde under mild reaction conditions (1 atm of CO,
9
at room temperature). The use of methylcyclohexane as the
substrate did not give the expected aldehyde, but cyclohexyl
methyl ketone was formed instead (Scheme 1). Such a
yields (%)
GaCl3
solvent
conditions
2
3
1
00 mol %
methylcyclohexane
methylcyclohexane
ClCH2CH2Cl
rt, 1 h
80 °C, 20 h
80 °C, 1 h
92
73
87
Scheme 1. GaCl
3
-Mediated Carbonylation of
20 mol %
Methylcyclohexanea
20 mol %
9
a
Isolated yield.
yield when the reaction is carried out at 80 °C. Among the
solvents examined, 1,2-dichloroethane was found to be the
solvent of choice (methylcyclohexane 12%, toluene 24%,
THF 0%). Thus, the use of 1,2-dichloroethane gave 2 in 87%
yield along with 3 in 9% at 80 °C for 1 h. We next examined
the effect of Lewis acids other than GaCl
GaCl is the most effective catalyst (AlCl
26%/2%, Sc(OTf) 7%/0%, ineffective; InCl
, PtCl , ZnCl , SnCl ).
3
. It was found that
2/3 ) 66%/8%,
, TiCl
3
3
a
bThe product was isolated as a
Yield based on GaCl
tosylhydrazone.
3
.
ZrCl
HfCl
4
3
3
4
,
4
2
2
2
The relative preference for susceptibility to migration was
next examined (Scheme 3). A phenyl group in 4a migrates
product would be formed by the formylation of methylcy-
clohexane followed by a skeletal rearrangement.
10
This prompted us to examine the latter unique rearrange-
ment. We wish to report here that a common Lewis acid,
Scheme 3. Relative Preference for Susceptibility to Migration
3
such as GaCl , catalyzes the rearrangement of R,R,R-
trisubstituted aldehydes to ketones (Scheme 2). In addition,
3
Scheme 2. GaCl -Catalyzed Rearrangement of Aldehydes
to develop a better understanding of the mechanism of the
rearrangement, theoretical calculations were also done.
The treatment of 2,2-diphenylpropionaldehyde (1, 1 mmol)
3
with 100 mol % of GaCl in methylcyclohexane (3 mL) at
room temperature for 1 h gave 1,2-diphenylpropan-1-one (2)
in 92% isolated yield, and a trace amount of 3 was detected
in preference to a methyl group, even though 4a has two
methyl groups. The product distribution remained unchanged
during the reaction. The more electron-withdrawing a sub-
stituent on an aryl group is, the greater is the preference for
the aryl group migrates compared with a methyl group,
indicating that the migration directs the formation of a stable
cation. The reaction of 7a resulted in a selective ring
expansion to give 9a as a single product. On the other hand,
(
7) Davies, H. M. L.; Dai, X. J. Am. Chem. Soc. 2004, 126, 2692-
2
693.
(
8) Chatani, N.; Inoue, H.; Kotsuma, T.; Murai, S. J. Am. Chem. Soc.
2
002, 124, 10294-10295. Chatani, N.; Oshita, M.; Tobisu, M.; Ishii, Y.;
Murai, S. J. Am. Chem. Soc. 2003, 125, 7812-7813. Oshita, M.; Tobisu,
M.; Yamashita, K.; Chatani, N. J. Am. Chem. Soc., in press.
(
9) Oshita, M.; Chatani, N. Org. Lett. 2004, 6, 4323-4325.
(10) Olah, G. A.; Prakash, G. K. S.; Marinez, E. R. Angew. Chem., Int.
Ed. 2000, 39, 2547-2548.
332
Org. Lett., Vol. 7, No. 2, 2005

the reaction of 7b resulted in the selective migration of a
phenyl group to give 8b in high yield and the ring-expansion
product 9b was obtained in 9% yield, although the latter
product is derived from a more stable cation. This indicates
that the nature of the reaction is also affected by the ring
size.
a tertiary cation 13. A 1,2-hydride shift leads to the formation
of 14, which then undergoes ligand exchange with 10 to give
11.
Scheme 5. A Possible Mechanism
Surprisingly, when a reaction using a stoichiometric
amount of GaCl
employed, it was curiously found that the amount of GaCl
has a significant effect on the efficiency of the rearrangement
Scheme 4). No reaction took place when 100 mol % of
3
and at lower reaction temperatures was
3
(
3
Scheme 4. Effect of the Amount of GaCl on the Efficiency
of the Rearrangement
To rationalize the experimental results, density functional
theory (DFT) calculations were performed at the B3LYP/
1
3
6
-31G(d) level. Table S1 (see the Supporting Information)
summarizes electronic energies for intermediates and transi-
tion states of the rearrangements.
GaCl
3
was used at room temperature in the reaction of 4a
for 12 h. However, the use of more than 150 mol % of GaCl
3
resulted in a smooth rearrangement to give 5a and 6a in good
yields. A similar drastic effect was also observed for the
11
reactions of 10 and 1. As mentioned above, Olah suggested
that the rearrangement of pivalaldehyde in a large excess of
the strong protic acids proceeds via a protosolvated car-
6
boxonium ion intermediate. Therefore, the results described
in Scheme 4 can possibly indicate that additional molecules
of GaCl
Scheme 5 shows the proposed mechanistic pathway for
the reaction. We propose that two molecules of GaCl are
3
are necessary for the reaction to proceed.
3
operative in the rearrangement based on the results shown
in Scheme 4. The coordination of the carbonyl oxygen to a
dimer of GaCl
carbonyl carbon, where a 1,2-methyl shift takes place to give
, as in 12,12 leads to a highly electrophilic
3
Figure 1. Energy Profile for the Rearrangement Computed by
(
11) In the reaction of 10, the rearrangement product was isolated as a
B3LYP/6-31G(d) Calculations
4
-tosylhydrazone because of the low boiling point of the product 11.
Org. Lett., Vol. 7, No. 2, 2005
333

Figure 1 shows a description of the potential energy
surfaces of the isomerization for the di-GaCl -coordinated
complex. The activation barriers are 19.4 kcal/mol for the
methyl shift (12 f 13) and 19.4 kcal/mol for the hydrides
shift (13 f 14). The activation energy from 12 to 13 is less
Double activation of a carbonyl group by two molecules of
GaCl was supported by a DFT study. Such a unique
characteristic feature of GaCl may continue to have
considerable impact on the development of new transforma-
3
3
3
8
,9,14
tions.
than those in mono-GaCl
mol (Figure 1). This stabilization is caused by more efficient
coordination of the GaCl to a carbon center with developing
positive charge in the transition state. The cationic intermedi-
ate 13 is thermodynamically stabilized with a similar effect,
as shown in Scheme 5.
3
-coordinated complex by 18.6 kcal/
Acknowledgment. This work was supported, in part, by
grants from Ministry of Education, Culture, Sports, Science
and Technology, Japan. M.O. express his special thanks for
the center of excellence (21COE) program “Creation of
Integrated EcoChemistry of Osaka University”.
3
3
In conclusion, we demonstrate here that GaCl is a superior
Supporting Information Available: Experimental pro-
cedures, electronic energies (Table S1) and computed
geometries (Figure S1, Tables S2-15) by DFT calculations.
This material is available free of charge via the Internet at
http://pubs.acs.org.
catalyst for the skeletal rearrangement of R,R,R-trisubstituted
aldehydes. The rearrangement can proceed smoothly in the
presence of a catalytic amount of a weak Lewis acid, such
as GaCl
3
, and even substrates having no heteroatoms R to
the carbonyl group or without steric strains can be used.
OL047640H
(12) For papers on a double activation of aldehydes by bidentate
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1
160. For papers on diprotonated activation, see: Saito, S.; Sato, Y.;
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T.; Ohwada, T.; Shudo, K. J. Am. Chem. Soc. 1997, 119, 6774-6780.
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334
Org. Lett., Vol. 7, No. 2, 2005