A novel carbocationic species paired with tetrakis(pentafluorophenyl)borate anion in catalytic aldol reaction

Article abstract of DOI:10.1246/cl.2000.606

The aldol reaction of several aldehydes with silyl enol ethers proceeded smoothly to give the corresponding aldols in good to high yields at -78 °C by using 1.0 mol% of a novel cationic species with tetrakis(pentafluorophenyl)borate anion.

Full text of DOI:10.1246/cl.2000.606

606
Chemistry Letters 2000
A Novel Carbocationic Species Paired with Tetrakis(pentafluorophenyl)borate Anion in
Catalytic Aldol Reaction
Teruaki Mukaiyama, Manabu Yanagisawa, Daisuke Iida, and Iwao Hachiya
Department of Applied Chemistry, Faculty of Science, Science University of Tokyo, Kagurazaka, Shinjuku-ku, Tokyo 162-8601
(Received Febrary 29, 2000; CL-000200)
The aldol reaction of several aldehydes with silyl enol
ethers proceeded smoothly to give the corresponding aldols in
good to high yields at -78 °C by using 1.0 mol% of a novel
cationic species with tetrakis(pentafluorophenyl)borate anion.
The reaction of silyl enol ethers which are stable and
isolable carbon nucleophiles with activated carbonyl com-
pounds is one of the most versatile synthetic tools for the car-
bon-carbon bond formation.1 Although Lewis acids such as
TiCl4, SnCl4, BF3·OEt2, etc. are frequently employed in these
reactions as useful promoters, it is still strongly desired to
explore a new and effective catalyst which accelerates the reac-
tions under essentially neutral conditions.
A typical procedure for the reaction of a silyl enol ether or
a ketene silyl acetal with an aldehyde is as follows: 1 (0.005
mmol) was dissolved in 0.5 mL of dichloromethane, and to the
solution, an aldehyde (0.5 mmol) in 1.0 mL of dichloromethane
and a silyl enol ether or a ketene silyl acetal (0.75 mmol) in 2.0
mL of dichloromethane were added at -78 ˚C. The mixture was
stirred for 30 min, followed by the addition of aqueous sodium
hydrogencarbonate. The aqueous layer was extracted with
ethyl acetate and the organic layer was evaporated. The residue
was dissolved in tetrahydrofuran and 1 M hydrochloric acid
was added to the solution. The mixture was stirred for 15 min
at room temperature and then the reaction mixture was extract-
ed with ethyl acetate. The organic layer was evaporated and the
residue was purified by preparative TLC to give an aldol
adduct. Several examples of the addition reactions are summa-
rized in Table 2.
In almost all cases, the reaction proceeded smoothly to
afford the desired aldol in a high yield. In case of using 3-
phenylpropanal as a carbonyl component, however, the reaction
was slow and the yield decreased even when the reaction was
continued for over 2 h (Entry 17-19). As compared with trityl
salt such as trityl tetrakis(pentafluorophenyl)borate,6 the present
catalyst 1 accelerated this reaction slightly more effectively
(Entry 1 vs 2, Entry 4 vs 5 and Entry 6 vs 7). Thus, it is noted
that 1 has better potential to accelerate the aldol reaction equal-
ly or slightly more effectively compared to that of trityl salts.
The characteristic behavior was further demonstrated when cin-
namaldehyde, an α,β-unsaturated aldehyde, was used (Entry 10
vs 11, Entry 12 vs 13); that is, the Michael adduct was obtained
along with the aldol nearly in the same yields.7 This is a little
different from the general pattern of nucleophilic addition reac-
tion which gives 1,2-adduct exclusively.8
Previously, we had demonstrated that trityl salts such as
triphenylmethyl perchlorate were unique and excellent catalysts
in several synthetic reactions.2 For example, the trityl salts
effectively catalyzed the aldol reaction of silyl enol ethers with
acetals or aldehydes to afford the desired aldols in good to high
yields.3 One of the most characteristic features was that these
reactions were accelerated smoothly by using a catalytic
amount (5−10 mol%) of the trityl salts because of their unique
carbocationic properties. Existence of similar carbocationic
species was proposed in 1970 by W. L. F. Armarego by prepa-
ration of several salts such as 1-oxoisoindolium hexachloroanti-
monate. They proposed that the salts existed as the stable
cationic species in benzene by measuring their NMR, IR and
mass spectroscopies.4 Here, further development of a useful cat-
alyst like trityl salts was tried based on those results, and a novel
carbocationic species 1 having tetrakis(pentafluorophenyl)borate
as a counter anion was found to be an effective catalyst in aldol
reaction. In the present study, methoxy group was introduced
onto the phenyl group located at 3-position because it would
increase the stability of this cationic species. In this communica-
tion, we would like to report the catalytic aldol reaction of several
aldehydes with silyl enol ethers or ketene silyl acetals by utilizing
the novel and stable cationic species 1.5
In the first place, several conditions were screened in order
to optimize the amount of catalyst 1 in the aldol reaction. As
shown in Table 1, only 0.1 mol% of 1 accelerated the reaction
to give the desired aldol in a good yield. Thereafter, 1.0 mol%
of 1 was used in the experiments in order to avoid any errors
caused by the scale effect of the reaction.
Compound 1 was prepared from phthalic anhydride by 4
steps procedure (Scheme 1). Namely, phthalic anhydride was
treated with 4-methoxyphenylmagnesium bromide in tetrahy-
drofuran to give the benzoic acid derivative 6. According to the
procedure reported by Stoll,9 it was transformed to 7 with
intramolecular cyclization followed by a simple amidation of
Copyright © 2000 The Chemical Society of Japan

Chemistry Letters 2000
607
pared when isopropylamine was used instead of methylamine in
step b. The 4-methoxyphenyl moiety was converted to any other
functional groups by using various appropriate Grignard
reagents. Unlike trityl salts having limited substituents, these
results indicated that functionalized carbocationic species are
possibly available.
It is noted that a tetrakis(pentafluorophenyl)borate anion
stabilized novel carbocationic species 1 was synthesized and
only 1.0 mol% of 1 accelerated the reaction of aldehydes with
silyl enol ethers or ketene silyl acetals to give the aldol adducts
in good to high yields. It should also be noted that both aldols
and Michael adducts were obtained in nearly the same yields
when α,β-unsaturated aldehydes were treated with nucleophiles
3, 4 and 5.8 Further study on this topic is now in progress.
References and Notes
1
a) For reviews, see: T.-H. Chan, "Comprehensive Organic
Synthesis," ed. by B. M. Trost and I. Fleming, Pergamon
Press, Oxford (1991), Vol. 2, p. 595; C. Gennari,
"Comprehensive Organic Synthesis," ed. by B. M. Trost
and I. Fleming, Pergamon Press, Oxford (1991), Vol. 2, p.
629. b) For examples, C.-T. Chen, S.-D. Chao, K.-C. Yen,
C.-H. Chen, I.-C. Chou, and S.-W. Hon, J. Am. Chem.
Soc., 119, 11341 (1997), and references cited therein.
T. Mukaiyama, M. Tamura, and S. Kobayashi, Chem. Lett.,
1986, 1817; T. Mukaiyama, Y. Sagawa, and S. Kobayashi,
Chem. Lett., 1986, 1821, and references cited therein.
T. Mukaiyama, S. Kobayashi, and M. Murakami, Chem.
Lett., 1984, 1759; S. Kobayashi, M. Murakami, and T.
Mukaiyama, Chem. Lett., 1985, 1535.
2
3
4
5
W. L. F. Armarego and S. C. Scarma, J. Chem. Soc., C,
1970, 1600.
Crystal data for 1; yellow prismatic crystals, formula:
C40H14BNO2F20, formula weight: 931.34, P1(#2), a =
11.038(2) Å, b = 17.475(3) Å, c = 10.134(1) Å, α =
105.77(1)˚, β = 94.42(1)˚, γ = 82.12(2)˚, V = 1861.7(6) Å3,
Z = 2, Dcalc = 1.661 g cm-3, µ(Cu Kα) = 15.47 cm-1, dif-
fractometer: Rigaku AFC7R, measured reflections: 8137,
unique reflections: 6778, observed reflections: 6397, calcu-
lations: teXsan Crystal Structure Analysis Package
(Molecular Structure Corporation), R(Rw) = 0.072(0.243).
J. C. W. Chien, W.-M. Tsai, and M. D. Rausch, J. Am.
Chem. Soc., 113, 8570 (1991).
Previously, it was shortly described that the addition reac-
tion between silyl enol ethers and α,β-unsaturated aldehy-
des using triphenylmethyl perchlorate as a catalyst gives a
mixture of 1,2 and 1,4 adducts; S. Kobayashi, M.
Murakami, and T. Mukaiyama, Chem. Lett., 1985, 953.
a) M. Yasuda, N. Ohigashi, I. Shibata, and A. Baba, J. Org.
Chem., 64, 2180 (1999), and references cited therein. b) K.
Mikami, M. Terada, and T. Nakai, J. Org. Chem., 56, 5456
(1991).
the caboxyl group, and the resulting lactam 7 was in turn trans-
formed into the corresponding chloride 8 on treatment with
thionyl chloride in dichloromethane. This intermediate was
treated with lithium tetrakis(pentafluorophenyl)borate in boiling
pentane and dichloromethane to form 1.6
6
7
8
9
W. Graf, E. Girod, E. Schmid, and W. G. Stoll, Helv.
Chim. Acta, 42, 1085 (1959); and also see: Ref. 4; and M.
S. Kitching, W. Clegg, M. R. J. Elsegood, R. J. Griffin, and
B. T. Golding, Synlett, 1999, 997.
Several derivatives of 1 were easily prepared by this proto-
col involving the Grignard reaction and simple amidation. For
example, sterically hindered carbocationic species can be pre-