I. Kadota et al. / Tetrahedron Letters 50 (2009) 4552–4553
4553
Table 1
alcohols in good yields (entries 1–4). Other primary benzylic pro-
tective groups, such as benzyl, NAP (2-naphthylmethyl), and Tr
(triphenylmethyl) are stable under the reaction conditions (entries
5–7). The reaction proceeded smoothly in the presence of acid-sen-
sitive protective groups such as TBS, TES, and benzylidene acetal
(entries 8–10). The reaction conditions did not affect a Cbz-pro-
tected benzylamino group (entry 11). On the other hand, acyclic
acetal protective groups such as MOM and THP groups were
cleaved under the reaction conditions. Furthermore, the cleavage
of phenolic MPM ether also proceeded cleanly to give the product
in good yield although the reaction was much slower (entry 12).
In conclusion, we have demonstrated a simple and convenient
method for the selective cleavage of primary MPM ethers with
TMSI/Et3N. Various protective groups, including secondary MPM
ethers, can survive under the reaction conditions. We anticipate that
the present method will be useful in natural product synthesis.
Selective cleavage of primary MPM ethersa
Entry
1
Substrate
Product
Yieldb (%)
83
2
3
4
83
96
95
Acknowledgment
This work was financially supported by the Grant-in-Aid for Sci-
entific Research from the Ministry of Education, Culture, Sports,
Science and Technology, Japan.
5
6
7
8
9
87
94
97
90
87
References and notes
1. Wuts, P. G. M.; Greene, T. W. In Protective Groups in Organic Synthesis, 4th ed.;
John Wiley & Sons: New Jersey, 2007; pp 121–130.
2. Kadota, I.; Ueno, H.; Yamamoto, Y. Tetrahedron Lett. 2003, 44, 8935–8938.
3. The reaction conditions were originally developed for the acetal cleavage
giving enol ethers, see: (a) Miller, R. D.; McKean, D. R. Tetrahedron Lett. 1982,
23, 323–326; Also see: (b) Kadota, I.; Sakaihara, T.; Yamamoto, Y. Tetrahedron
Lett. 1996, 37, 3195–3198.
4. For the use of TMSI to cleave a benzyl ether, see: Jung, M. E.; Lyster, M. A. J. Org.
Chem. 1977, 42, 3761–3764.
5. For an example of the deprotection of secondary MPM ethers using TMSI, see:
Gordon, D. M.; Danishefsky, S. J. J. Am. Chem. Soc. 1992, 114, 659–663.
6. Direct conversion of MPM ethers into silyl ethers with R3SiOTf/Et3N has been
reported, see: Oriyama, T.; Yatabe, K.; Kawada, Y.; Koga, G. Synlett 1995, 45–46.
7. The amounts of the reagents used were found to be enough to complete the
reaction although the precise optimization was not performed. The use of large
excess of the reagents did not affect the selectivity.
10
11
92
91
91
8. The work up with MeOH and K2CO3 was carried out for the conversion of the
TMS ether, contained in the reaction mixture, into the primary alcohol.
9. Although further investigation on the amine was not performed, other amines
12c
i
such as Pr2NEt and piperidine are expected to be applicable.
10. The reaction was carried out with 1.2 equiv of TMSI, and quenched after 0.5 h.
The use of an excess amount of TMSI would complete the reaction leading to 6.
See Ref. 5.
a
Reactions were carried out with TMSI (2 equiv) and Et3N (3 equiv) in CH2Cl2 at
0 °C for 1 h. The reaction mixture was then treated with K2CO3 and MeOH.
b
Isolated yield.
11. The reaction of
0.22 mmol) in CH2Cl2 (1.0 mL) at 0 °C were added Et3N (93
and TMSI (63 L, 0.44 mmol). After 1 h, MeOH (2.0 mL) and K2CO3 (150 mg,
4
is representative. To
a
stirring mixture of
4 (82 mg,
c
The reaction was carried out at room temperature for 4 h.
l
L, 0.66 mmol)
l
1.1 mmol) were added, and the stirring was continued for 0.5 h. The reaction
mixture was then diluted with EtOAc, and then washed with water and brine.
The organic layer was dried over Na2SO4 and concentrated. The residue was
purified by column chromatography to give 5 (46 mg, 83%).
various protective groups. The results are summarized in Table 1.11
As expected, the reactions of substrates having secondary MPM
ethers proceeded smoothly to give the corresponding primary
Kadota, Isao
