Tris(2,4,6-trimethoxyphenyl)phosphine (TTMPP): A novel catalyst for selective deacetylation

Article abstract of DOI:10.1246/cl.2001.934

Chemo-and stereoselective deacetylation was achieved by the use of a catalytic amount of tris(2,4,6-trimethoxyphenyl)phosphine (TTMPP).

Full text of DOI:10.1246/cl.2001.934

934
Chemistry Letters 2001
Tris(2,4,6-trimethoxyphenyl)phosphine (TTMPP): A Novel Catalyst for Selective Deacetylation
Kazuya Yoshimoto, Hirotoshi Kawabata, Natsuki Nakamichi, and Masahiko Hayashi*
Department of Chemistry, Faculty of Science, Kobe University, Kobe 657-8501
(Received July 6, 2001; CL-010630)
Chemo- and stereoselective deacetylation was achieved by
the use of a catalytic amount of tris(2,4,6-trimethoxyphenyl)-
phosphine (TTMPP).
During the course of our study on the synthesis of carbohy-
drate compounds, we found 3,4,6-tri-O-acetyl-D-glucal (1) was
deacetylated to D-glucal (3) by the aid of 5 mol% of tris(2,4,6-
trimethoxyphenyl)phosphine (TTMPP) (2) in 98% yield (at 22
°C for 5 h in methanol).4 Other phosphine compounds we
examined such as tris(2,6-dimethoxyphenyl)phosphine, tris(4-
methoxyphenyl)phosphine, tri-o-tolylphosphine, triphenylphos-
phine, tri-n-butylphosphine and tri-2-furylphosphine (10 mol%)
in methanol were not effective for deacetylation under the
above conditions (Table 1).5 3,4,6-Tri-O-benzoyl-D-glucal (4)
was also deprotected, though less reactive (entry 8). The pival-
oyl derivative was inert to TTMPP (2) (entry 9). As shown in
Table 2, other acetylated glycopyranosyl and ribofuranosyl
derivatives were also effectively deprotected by the action of 10
mol% of TTMPP (2) in methanol under mild conditions.
The acetyl group is one of the most useful protecting
groups in organic synthesis. Therefore, many protecting and
deprotecting methods have been developed so far.1 Several
reagents have been reported to convert acetylated compounds to
the corresponding hydroxy compounds. Among those, hydroly-
sis and transesterification under basic condition have been often
used. On the other hand, in 1984, Wada and Higashizaki
reported high basicity of tris(2,4,6-trimethoxyphenyl)phosphine
(TTMPP).2 After that Imamoto and his co-workers reported
TTMPP-catalyzed aldol reaction between ketene silyl acetals
and aldehydes.3 Here we would like to report a novel proce-
dure for deacetylation using phosphine-based catalyst.
A variety of acetylated compounds other than carbohy-
drates were converted into the corresponding hydroxy com-
pounds in high yield. Some of the results obtained are summa-
rized in Table 3. High chemoselectivity between benzoyl and
acetyl was observed (eq 1). The discrimination between pival-
Copyright © 2001 The Chemical Society of Japan

Chemistry Letters 2001
935
oyl and acetyl was perfect (eq 2). It should be mentioned that
the acetate of trans-4-tert-butylcyclohexanol was deacetylated
much faster than the corresponding cis-isomer (Scheme 1). In
these reactions, the TTMPP-catalyzed reactions exhibited high-
er selectivity compared with the conventional K2CO3- or
CH3ONa-catalyzed deacetylation reactions.6
Typical procedure is as follows (entry 4 in Table 3); To a
solution of cinnamyl acetate (326 mg, 1.85 mmol) in methanol
(1.5 mL) was added TTMPP (2) (49 mg, 0.092 mmol). The
mixture was stirred at 50 °C for 4.5 h. After confirmation of
the completion of the reaction, the mixture was concentrated
and the resulting residue was chromatographed on silica-gel to
afford cinnamyl alcohol (245 mg, 99%).
The TTMPP catalyst would work as a base in the present
deacetylation reactions. The study on the detailed mechanism
is now in progress in our laboratory.
References and Notes
1
T. W. Greene and P. G. M. Wuts, “Protective Groups in
Organic Synthesis,” 3rd ed., John Wiley & Sons, New
York (1999), pp 150–160 and references cited therein.
M. Wada and S. Higashizaki, J. Chem. Soc., Chem.
Commun., 1984, 482.
S. Matsukawa, N. Okano, and T. Imamoto, Tetrahedron
Lett., 41, 103 (2000).
The use of methanol was essential for deacetylation using
TTMPP system. That is, the deacetylation reaction in
ethanol or isopropyl alcohol did not take place.
2
3
4
5
6
The reactions of 1 with 10 mol% of tris(2,6-dimethoxy-
phenyl)phosphine even at 80 °C for 24 h afforded 3 only in
8% yield. Starting material 1 was recovered in 65% yield.
The yields of competitive reaction in Scheme 1 were esti-
mated by the combined yield of 17 and 19 and the ratio of
17/19 determined by 1H NMR analysis.