Cationic carbohydroxylation of alkenes and alkynes using the cation pool method

Article abstract of DOI:10.1021/ol049049q

The reactions of an N-acyliminium ion pool with alkenes and alkynes gave γ-amino alcohols and β-amino carbonyl compounds, respectively, after treatment with H₂O/Et₃N. The present reaction serves as an efficient method for cationic carbohydroxylation of alkenes and alkynes. When vinyltrimethylsilane was used as an alkene, the reaction was highly diastereoselective and served as an access to an enantiomerically pure α-silyl-γ-amino alcohol.

Full text of DOI:10.1021/ol049049q

ORGANIC
LETTERS
2004
Vol. 6, No. 16
2709-2711
Cationic Carbohydroxylation of Alkenes
and Alkynes Using the Cation Pool
Method
Seiji Suga,* Yasuhisa Kageyama, Govindarajulu Babu, Kenichiro Itami, and
Jun-ichi Yoshida*
Department of Synthetic Chemistry and Biological Chemistry, Graduate School of
Engineering, Kyoto UniVersity, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan
yoshida@sbchem.kyoto-u.ac.jp
Received May 23, 2004
ABSTRACT
The reactions of an N-acyliminium ion pool with alkenes and alkynes gave γ-amino alcohols and â-amino carbonyl compounds, respectively,
after treatment with H O/Et3N. The present reaction serves as an efficient method for cationic carbohydroxylation of alkenes and alkynes.
2
When vinyltrimethylsilane was used as an alkene, the reaction was highly diastereoselective and served as an access to an enantiomerically
pure r-silyl-γ-amino alcohol.
Carbo-oxylation (carbohydroxylation and carboalkoxylation),
where an organic group and an oxy (hydroxyl or alkoxy)
group add across a carbon-carbon double bond or triple
bond, is an important transformation in organic synthesis.
Several methods involving radical,1 photochemical,2 and
transition metal catalyzed3 reactions have been developed
to do so. 1,3-Dipolar cycloaddition of nitrile oxides4 and
nitrones5 followed by the cleavage of the N-O bond of the
cycloadducts also serves as good and efficient methods for
carbohydroxylation.
by water, also serves as a good and efficient method for
carbohydroxylation (Scheme 1). However, only a few papers
Scheme 1. Cationic Carbohydroxylation
on cationic carbohydroxylation have appeared in the litera-
ture6,7 Stimulated by the straightforwardness of this approach,
we have investigated cationic carbohydroxylation using the
“cation pool” method8 that we have recently developed and
report here our findings.
The addition of a carbocation to a carbon-carbon multiple
bond, followed by the quenching of the resulting carbocation
(1) Wetter, C.; Jantos, K.; Woithe, K.; Studer, A. Org. Lett. 2003, 5,
2899.
(2) Bach, T. Tetrahedron Lett. 1994, 35, 1855.
In the “cation pool” method, carbocations are generated
by low-temperature electrochemical oxidation and accumu-
(3) (a) Nakamura, H.; Sekido, M.; Ito, M.; Yamamoto, Y. J. Am. Chem.
Soc. 1998, 120, 6838. (b) Monteiro, N.; Balme, G. Synlett 1998, 746. (c)
Fu¨rstner, A.; Szillat, H.; Stelzer, F. J. Am. Chem. Soc. 2000, 122, 6785. (d)
Nakamura, I.; Bajracharya, G. B.; Mizushima, Y.; Yamamoto, Y. Angew.
Chem., Int. Ed. 2002, 41, 4328.
(4) (a) Kozikowski, A. P.; Chen, Y.-Y.; Wang, B. C.; Xu, Z.-B.
Tetrahedron 1984, 40, 2345. (b) Kanemasa, S.; Nishiuchi, M.; Kamimura,
A.; Hori, K. J. Am. Chem. Soc. 1994, 116, 2324. (c) Bode, J. W.; Carreira,
E. M. J. Am. Chem. Soc. 2001, 123, 3611 and references therein.
(5) For example, see: (a) Goti, A.; Cacciarini, M.; Cardona, F.; Cordero,
F. M.; Brandi, A. Org. Lett. 2001, 3, 1367. (b) Brandi, A.; Cicchi, S.;
Paschetta, V.; Pardo, D. G.; Cossy, J. Tetrahedron Lett. 2002, 43, 9357
and references therein.
(6) (a) Bott, K. Tetrahedron Lett. 1970, 4301. (b) Bott, K. Angew. Chem.,
Int. Ed. Engl. 1980, 19, 171. For examples of intramolecular carbohy-
droxylation using acyliminium ions, see: Royer, J.; Bonin, M.; Micouin,
L. Chem. ReV. 2004, 104, 2311.
(7) In cationic polymerization, an active polymer end is usually trapped
by the reaction with an alcohol. Therefore, the last step of cationic
polymerization is carboalkoxylation, although transfer reactions also take
place before quenching. For example, see: Cationic Polymerization
Fundamentals and Applications; Faust, R., Schaffer, T. D., Eds.; American
Chemical Society: Washington, DC, 1997.
10.1021/ol049049q CCC: $27.50 © 2004 American Chemical Society
Published on Web 07/14/2004

lated in the absence of nucleophiles. The “cation pool”
method has been successfully applied to the generation and
reactions of N-acyliminium ions and alkoxycarbenium ions.
We envisioned that the reaction of a “cation pool” with an
alkene or alkyne followed by the trapping of the resulting
carbocation by water would lead to the formation of the
corresponding carbohydroxylation product. The concept
works.
72 h. The stereochemistry was the same as that of the
compound obtained directly from 2 and vinyltrimethylsilane.
The stereochemistry of 3 was determined by X-ray analysis.
As shown in Figure 1, the configuration of the carbon bearing
the hydroxyl group was found to be S.
We chose to study the N-acyliminium ion 2 generated from
1 as shown in Scheme 2 because of the following reasons:
Scheme 2. Formation of N-Acyliminium Ion Pool 2
Figure 1. X-ray structure of 3.
the carbonyl group is expected to interact strongly with the
carbocation generated by the addition to an alkene or alkyne
(vide infra) and stabilize it; without such stabilization, the
second carbocation would decompose before the workup with
water. It is also important to note that the 4-phenyl-2-
oxazolidinone9 group is easily removed after the carbohy-
droxylation. Another important feature of 2 is the possibility
of asymmetric induction.9
Thus, N-acyliminium ion 2 was generated by the anodic
oxidation of silyl-substituted carbamate 1 having a silyl group
as an electroauxiliary,10 which was synthesized from (S)-4-
phenyl-2-oxazolidinone in Bu4NBF4/CH2Cl2 and accumulated
as a solution in the absence of a nucleophile.
Therefore, the present reaction is expected to serve as an
efficient method for the preparation of enantiomerically pure
amino alcohols,11 which are useful intermediates for the
synthesis of various biologically interesting molecules. In
fact, 3 was converted into free amino alcohol 5 as shown in
eq 1.10 Compound 5 is of potential interest from the
viewpoint of its coordination ability to metals because the
hydroxyl group is activated by the interaction of the oxygen
p orbital with the C-Si σ orbital.12
We first examined the reaction with vinyltrimethylsilane.
The reaction took place smoothly at -50 to -25 °C to give
compounds 3 and 4 in 25% and 54% yields, respectively,
after treatment with H2O/Et3N (Scheme 3). Both 3 and 4
The reaction of 2 with an alkyl-substituted olefin also
proceeded smoothly, but products 6 and 7 were obtained as
a mixture of diastereomers (eq 2). The reactions with trans
and cis stilbenes gave carbohydroxylated compound 8 as a
mixture of diastereomers (eqs 3 and 4). The reaction with
vinyl acetate gave the corresponding aldehyde 9 presumably
via the initial carbohydroxylation product (eq 5).
Scheme 3. Reaction of 2 with Vinyltrimethylsilane
Although the detailed mechanism of the present reaction
has not yet been established, the following speculation is
reasonable (Scheme 4).
The initial reaction of 2 with an alkene presumably gives
cycloadduct 10,13 a stabilized form of carbocation 11 (vide
(9) (a) Leroux, M.-L.; Gall, T. L.; Mioskowski, C.; Tetrahedron:
Asymmetry 2001, 12, 1817. (b) Marcantoni, E.; Mecozzi, T.; Petrini, M. J.
Org. Chem. 2002, 67, 2989.
were single stereoisomers. Compound 4 was easily converted
into 3, as a single stereoisomer in quantitative yield, by the
treatment with 1 N NaOH in THF at room temperature for
(10) Yoshida, J.; Nishiwaki, K. J. Chem. Soc., Dalton Trans. 1998, 2589.
(11) For example, see: (a) Yamamoto, Y.; Komatsu, T.; Maruyama, K.
J. Chem. Soc., Chem. Commun. 1985, 814. (b) Barluenga, J.; Fe´rna´ndez-
Mar´ı, F.; Viado, A. L.; Aguilar, E.; Olano, B. J. Org. Chem. 1996, 61,
5659. (c) Toujas, J.-L.; Toupet, L.; Vaultier, M. Tetrahedron 2000, 56, 2665.
(d) Kochi, T.; Tang, T. P.; Ellman, J. A. J. Am. Chem. Soc. 2002, 124,
6518. (e) Co´rdova, A. Synlett 2003, 1651 and references therein.
(12) (a) Yoshida, J.; Maekawa, T.; Murata, T.; Matsunaga, S.; Isoe, S.
J. Am. Chem. Soc. 1990, 112, 1962. See also ref 9.
(8) (a) Yoshida, J.; Suga, S.; Suzuki, S.; Kinomura, N.; Yamamoto, A.;
Fujiwara, K. J. Am. Chem. Soc. 1999, 121, 9546. (b) Suga, S.; Suzuki, S.;
Yamamoto, A.; Yoshida, J. J. Am. Chem. Soc. 2000, 122, 10244. (c) Suga,
S.; Okajima, M.; Yoshida, J. Tetrahedron Lett. 2001, 42, 2173. (d) Suga,
S.; Suzuki, S.; Yoshida, J. J. Am. Chem. Soc. 2002, 124, 30. (e) Yoshida,
J.; Suga, S. Chem. Eur. J. 2002, 8, 2650. (f) Suga, S.; Watanabe, M.;
Yoshida, J. J. Am. Chem. Soc. 2002, 124, 14824. (g) Suga, S.; Nagaki, A.;
Yoshida, J. Chem. Commun. 2003, 354.
(13) Suga, S.; Nagaki, A.; Tsutsui, Y.; Yoshida, J. Org. Lett. 2003, 5,
945.
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Org. Lett., Vol. 6, No. 16, 2004

Table 1. Reaction of N-Acyliminium Ion 2 and Alkynesa
a The reactions were carried out with 2 (prepared from 0.40 mmol of 1)
and an alkyne (0.36 mmol) at -25 °C for 15 min. Then 7% H2O/Et3N (0.4
mL) was added to the reaction mixture at the same temperature. b Isolated
yields. c Diastereomer ratio was determined by NMR.
supra). In the case of vinyltrimethylsilane, a concerted [4 +
2] cycloaddition mechanism seems to be predominant,13 and
the stereochemistry of the final product should be determined
in this step. In the case of alkyl- and aryl-substituted alkenes,
however, a stepwise mechanism involving a intermediate 11
18, which has a free amino group, was quite unstable, the
amino group was immediately protected as a carbamate to
obtain 19. The removal of the acetal gave 20.
Scheme 5. Removal of the Oxazolidinone Group from 11
Scheme 4. Mechanism of Cationic Carbohydroxylation
Using 2
The present findings offer an example of cationic carbo-
hydroxylation of carbon-carbon multiple bonds using the
“cation pool” method. It is also noteworthy that the reaction
serves as a straightforward access to optically active R-silyl-
γ-amino alcohols from vinylsilane. Further work aimed at
revealing scope and limitations of the present reaction and
its applications to synthesis is currently in progress.
may also play a role, and this leads to lower diastereoselec-
tivity. In the workup process, water attacks the carbon
bearing two oxygen atoms to give carbohydroxylation
products such as 3 (path a). Water may also attack the
benzylic carbon to give byproducts such as 4 (path b).
Another possibility to be considered is the attack of the
carbon bearing R (path c). Clearly more data must be
accumulated before accurate mechanistic conclusions can be
drawn.
Alkynes were also quite effective for the reaction with
N-acyliminium ion 2, and the corresponding ketones 12-
16 were formed in good yields as shown in Table 1. In the
case of disubstituted alkynes, a mixture of two diastereomers
was obtained.
Acknowledgment. This work was partially supported by
the Grant-in-Aid for Scientific Research from the Ministry
of Education, Science, and Culture, Japan and the Project
of Micro Chemical Process for Production and Analysis of
NEDO, Japan.
Supporting Information Available: Experimental pro-
cedures and analytical and spectroscopic data of compounds
and CIF files for the X-ray structural analysis of 3. This
material is available free of charge via the Internet at
http://pubs.acs.org.
Removal of the oxazolidinone group was accomplished
as demonstrated by the following example (Scheme 5).
Protection of the carbonyl group of 16 as an acetal followed
by the reduction with Li/liq NH3 gave 18. Because compound
OL049049Q
Org. Lett., Vol. 6, No. 16, 2004
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