TMS Triflate-Catalyzed Cleavage of Prenyl (3-Methylbut-2-enyl) Ester

Article abstract of DOI:10.1021/ol0259692

(Matrix Presented) Prenyl (3-methylbut-2-enyl) ester is catalytically cleaved by TMS triflate affording carboxylic acid and isoprene in high yield under mild conditions with high chemoselectivity without causing epimerization of the neighboring chiral cen

Full text of DOI:10.1021/ol0259692

ORGANIC
LETTERS
2002
Vol. 4, No. 11
1947-1949
TMS Triflate-Catalyzed Cleavage of
Prenyl (3-Methylbut-2-enyl) Ester
Mugio Nishizawa,* Hirofumi Yamamoto, Ken Seo, Hiroshi Imagawa, and
Takumichi Sugihara
Faculty of Pharmaceutical Sciences, Tokushima Bunri UniVersity,
Yamashiro-cho, Tokushima 770-8514, Japan
mugi@ph.bunri-u.ac.jp
Received April 3, 2002
ABSTRACT
Prenyl (3-methylbut-2-enyl) ester is catalytically cleaved by TMS triflate affording carboxylic acid and isoprene in high yield under mild conditions
with high chemoselectivity without causing epimerization of the neighboring chiral center.
In 1994 we reported a novel reductive etherification of silyl
ether using aldehyde and triethylsilane in the presence of a
catalytic amount of trimethylsilyl trifluoromethanesulfonate
(TMSOTf).1 When the procedure was applied to â-hydroxy
ester 1 that has a chiral center on the R carbon, benzyl ether
2 was obtained in quantitative yield without causing epimer-
ization, dehydration, or retro-aldol reaction.2,3 During our
further synthetic study of trehalose dicorynomycolate, we
examined reductive benzylation of prenyl ester alcohol 3 after
silylation and found that the prenyl group was cleaved under
the reaction conditions to give benzyl ether carboxylic acid
4 in quantitative yield.
between silylated prenyl ester 7 and TMS ester 8, and the
equilibrium favors the forward reaction, forming isoprene
(10) (Scheme 1). TMSOTf should be regenerated by the
Scheme 1
Throughout the investigation of simple prenyl ester 5, we
found that neither benzaldehyde nor the reducing agent,
Et3SiH, was required for cleavage of the prenyl ester. Only
a catalytic amount of TMSOTf was required. The reaction
should take place via TMS triflate-catalyzed equilibrium
reaction of TMS ester 8 with TfOH (formed in situ),
establishing the catalytic cycle. When the reaction was carried
(2) Nishizawa, M.; Garc´ıa, D. M.; Minagawa, R.; Noguchi, Y.; Imagawa,
H.; Yamada, H.; Watanabe, R.; Yoo, Y. C.; Azuma, I. Synlett 1996, 452-
454.
(1) Hatakeyama, S.; Mori, H.; Kitano, K.; Yamada, H.; Nishizawa, M.
Tetrahedron Lett. 1994, 35, 4367-4370.
10.1021/ol0259692 CCC: $22.00 © 2002 American Chemical Society
Published on Web 05/03/2002

out in an NMR tube using CDCl3 as solvent, appearance of
a stoichiometric amount of isoprene (10) and carboxylic acid
11 was observed. Therefore, we would like to describe herein
mild and neutral cleavage of the prenyl ester by using a
catalytic amount of TMSOTf under anhydrous conditions.4,5
Cleavage of prenyl ester has been conducted by Pd-catalyzed
hydrolysis,2,6,7 fragmentation using I2,8 heating with sulfated
Table 1. TMSOTf-Catalyzed Cleavage of Prenyl Ester (Yield)
9
SnO2 or K-10 clay,10 and CeCl3‚7H2O-NaI-mediated hy-
drolysis.11 Recently, Sharma and co-workers reported a
similar cleavage of prenyl ethers catalyzed by Yb(OTf)3 and
showed an application for the cleavage of prenyl esters.12
Iodine was also shown to be useful for the cleavage of prenyl
ethers.13
The reaction was carried out simply as follows. A solution
of the prenyl ester (1 mmol) and TMSOTf (0.02-0.03 mmol)
in dichloromethane (3 mL) was stirred at room temperature
for 1 to 5 h. After evaporation of volatile materials under
vacuum, the residue was purified directly by crystallization
or column chromatography on silica gel, providing pure
carboxylic acid in the yield shown in Table 1. As in the case
of 12, the isolated double bond was not affected and the
corresponding carboxylic acid was obtained in nearly
quantitative yield. The isolated triple bond of 14 was
unaffected as well. The conjugated triple bond of 15 and
the conjugated double bonds of 16 or 17 also do not interfere
in the reaction and afford carboxylic acids in 98% and 85%
yield, respectively. The method was particularly useful for
amino acid derivatives. The CBZ-protected prenyl ester of
L-phenylalanine 18 afforded carboxylic acid in 90% yield
without any change in the CBZ group and the optical purity.
The hydroxyl group of 19, pivaloyl group of 20, and acetyl
group of 21 also did not participate in the reaction, affording
the corresponding carboxylic acids in reasonable yields. The
amide moiety of 22 was also stable under the reaction
conditions but required 0.06 equiv of catalyst to complete
the reaction. The FMOC protecting groups of 23 and proline
24 were also entirely inert under the reaction conditions and
afforded FMOC amino acids in 95% and 89% yield,
respectively. The peptide bond and the methyl ester of 25
were also inert, giving the corresponding CBZ-protected
aspartame in 88% yield. On the other hand, BOC-protected
L-phenylalanine 26 did not afford a carboxylic acid, and the
BOC group was cleaved in a stoichiometric amount to the
a TMSOTf (0.06 equiv) was employed. b TMSOTf (0.1 equiv) was
employed, and phenylalanine prenyl ester was formed in ca. 10% yield.
catalyst prior to cleavage of the prenyl group, affording
phenylalanine prenyl ester.
FMOC protected L-tyrosine derivative 27 afforded car-
boxylic acid 28 in only 15% yield, and the major product
was the new amino acid 29 in 70% yield, formed by
incorporating the isoprene unit (Scheme 2).14
Therefore, the present procedure to cleave the prenyl ester
proceeds under very mild conditions and is characteristic in
its high chemoselectivity and operational simplicity without
(3) Watanabe, R.; Yoo, Y. C.; Hata, K.; Mitobe, M.; Koike, Y.;
Nishizawa, M.; Garc´ıa, D. M.; Noguchi, Y.; Imagawa, H.; Yamada, H.;
Azuma, I. Vaccine 1999, 17, 1484-1492.
(4) Kocienski, P. J. Protecting Groups; Thime: Stuttgart, 1994.
(5) Greene, T. W.; Wuts, P. G. M. ProtectiVe Groups in Organic
Synthesis, 3rd ed.; John Wiley and Sons: New York, 1999.
(6) Tsuji, J.; Yamakawa, T. Tetrahedron Lett. 1979, 613-616.
(7) Lemaire-Audoire, S.; Savignac, M.; Blart, E.; Pourcelot, G.; Genet,
J. P.; Bernard, J. M. Tetrahedron Lett. 1994, 35, 8783-8786.
(8) Cossy, J.; Albouy, A.; Scheloske, M.; Pardo, D. G. Tetrahedron Lett.
1994, 35, 1539-1540.
(14) 1H NMR (600 MHz in CDCl3) δ 1.28 (3H, s), 1.28 (3H, s), 1.72
(2H, t, J ) 6.59 Hz), 2.70 (2H, t, J ) 6.59 Hz), 3.01 (1H, dd, J ) 14.01,
6.32 Hz), 3.11 (1H, dd, J ) 14.01, 4.95 Hz), 4.18 (1H, t, J ) 7.14 Hz),
4.32 (1H, dd, J ) 10.71, 7.14 Hz), 4.40 (1H, dd, J ) 10.71, 7.42 Hz), 4.65
(1H, m), 5.33 (1H, d, J ) 7.80 Hz), 6.70 (1H, d, J ) 8.80 Hz), 6.85 (1H,
m), 6.84 (1H, m), 7.27 (2H, t, J ) 7.41 Hz), 7.37 (2H, t, J ) 7.41 Hz),
7.52 (1H, d, J ) 7.41 Hz), 7.55 (1H, d, J ) 7.41 Hz), 7.73 (2H, d, J )
7.41 Hz). 13C NMR (150 MHz, in CDCl3) δ 22.33 t, 26.75 q, 26.81 q,
32.56 t, 36.85 t, 47.02 d, 54.70 d, 67.04 t, 74.17 s, 117.32 d, 119.89 d,
120.98 s, 125.00 d, 126.31 s, 127.00 d, 127.63 d, 128.15 d, 130.23 d, 141.18
s, 143.61 s, 143.68 s, 153.11 s, 155.81 s, 176.03 s. FT-IR ν 3315 (br),
3064, 1718, 1486 cm-1. High-resolution ms m/z 471.2034 (calcd for
(9) Chavan, S. P.; Zubaidha, P. K.; Dantale, S. W.; Keshavaraja, A.;
Ramaswamy, A. V.; Ravindranathan, T. Tetrahedron Lett. 1996, 37, 237-
240.
(10) Gajare, A. S.; Shaikh, N. S.; Bonde, B. K.; Deshpande, V. H. J.
Chem. Soc., Perkin Trans. 1 2000, 639-640.
(11) Yadav, J. S.; Reddy, B. V. S.; Rao, C. V.; Chand, P. K.; Prasad, A.
R. Synlett 2002, 137-139.
(12) Sharma, G. V. M.; Ilangovan, A.; Mahalingam, A. K. J. Org. Chem.
1998, 63, 9103-9104.
(13) Vatele, J. M. Synlett 2001, 1989-1291.
C29H29O5N 471.2046). [R]25 +31.27° (c 1.05, CHCl3).
D
1948
Org. Lett., Vol. 4, No. 11, 2002

though cleavage of the tert-butyl ester has been carried out
by using a stoichiometric amount of TMSOTf/triethyl-
amine,15 we have already found that the present procedure
can be applied to catalytic cleavage of the tert-butyl ester,
and the details will be described elsewhere.
Scheme 2
Acknowledgment. This research was supported by a
Grant-in-Aid for Scientific Research on Priority Areas (A)
Exploitation of Multi-Element Cyclic Molecules from the
the Ministry of Education, Culture, Sports, Science and
Technology, Japan.
OL0259692
causing epimerization of the neighboring chiral center. It is
noteworthy that the process is not a hydrolysis but a novel
catalytic fragmentation under nonaqueous conditions. Al-
(15) Trzeciak, A.; Bannwarth, W. Synthesis 1996, 1433-1434.
Org. Lett., Vol. 4, No. 11, 2002
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