40 J. CHEM. RESEARCH (S), 1999
J. Chem. Research (S),
1999, 40±41$
Cleavage of Protecting Groups Catalysed by
p-Acceptors$
Kiyoshi Tanemura,*a Yoko Nishida,a Tsuneo Suzuki,a
Koko Satsumabayashia and Takaaki Horaguchib
aSchool of Dentistry at Niigata, The Nippon Dental University, Hamaura-cho, Niigata 951-8580, Japan
bDepartment of Chemistry, Faculty of Science, Niigata University, Ikarashi, Nigata 950-2181, Japan
The cleavage of protecting groups is caused by the acidic adducts produced from the methanolysis of acceptors.
We have reported that the deprotection of acetals and
silyl ethers was promoted by several acceptors, such as
2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) in aqueous
MeCN.1 Similarly, the cleavage of acetals and silyl ethers
catalysed by DDQ in aqueous ethyl acetate was reported
by Oku et al. and they pointed out that DDQ acted as a
protic acid and/or a Lewis acid in a wet solvent.2 Iranpoor
et al. have reported the ring opening reaction of epoxides
with alcohols catalysed by DDQ.3 Tetracyanoethylene
(TCNE) was reported to catalyse similar reactions such as
the alcoholysis of epoxides.4 Although many examples of
hydrolyses of protecting groups promoted by acceptors are
known, a mechanism for these reactions is still unclear.
Furthermore, products formed in the reactions of acceptors
with a solvent have barely been studied. In this paper, we
describe the detailed results of deprotection using a variety
of acceptors in MeOH. We also describe the investigation
of the reactions of acceptors with MeOH.
First, we examined the cleavage of dodecyl triethylsilyl
(TES) ether (1a) using 10 mol% of various acceptors at
room temperature. Dry MeOH was used as a solvent in
order to avoid the hydrolysis of acceptors. The results are
summarized in Table 1. The deprotection proceeded more
rapidly using strong acceptors possessing higher reduction
potentials. In the series of quinones examined, the reaction
proceeded most easily with DDQ (entry 1). The reaction
occurred with polyhalogenated quinones (entries 2±5).
p-Benzoquinone which has a low reduction potential did
not catalyse the reaction (entry 6). Amongst the quino-
dimethanes 8±11, the reaction proceeded most rapidly
with 2,3,5,6-tetra¯uoro-7,7,8,8-tetracyanoquinodimethane
(8, TCNQF4). 11,11,12,12-Tetracyano-2,6-naphthoquinodi-
methane (9, TNAP) has less activity than 7,7,8,8-tetracyano-
quinodimethane (10, TCNQ) in spite of its higher reduction
potential compared to that of TCNQ (entries 8 and 9).
Compound 11 required a longer reaction time than TCNQ
(entries 9 and 10). The activity of TCNE is almost compar-
able to that of DDQ and TCNQF4 although the reduction
potential is not so high (entries 1, 7 and 11). In the case
of 2,4,7-trinitro-9-¯uorenylidenemalononitrile (TNFMN,
14) the reaction did not proceed although the reduction
potential is almost the same as that of p-chloranil (entries 4
and 13). The low activity of compounds 9, 11 and 14
could be attributed to the high stability of the acceptors
in MeOH. Deprotection was not catalysed by 2,4,7-trinitro-
9-¯uorenone, 1,2,4,5-tetracyanobenzene, 9,10-dicyanoanthra-
and TCNQF4, was measured in MeOH using a pH meter
under nitrogen. The medium became acidic during the
reactions (For example, the pH after 1 h is 4.08, 4.71, 4.63
and 2.64 for the solution of DDQ, p-chloranil, TCNQ and
TCNQF4, respectively). The reactions of 1a, carried out
in the presence of sulfuric acid under identical conditions
with respect to proton concentration, gave almost the
same results as the acceptor-promoted reactions. Cleavage
of tetrahydropyranyl (THP) ether 1b catalysed by DDQ or
TCNQF4 was quenched by adding 4 equiv. of di-tert-butyl-
pyridine5 (DTBP) although these acceptors reacted with
DTBP slowly to give the corresponding anion radicals
in MeCN when analyzed by UV±VIS spectroscopy. These
facts strongly suggest that the deprotection is promoted by
protons produced in the solvents.
When DDQ was treated with MeOH, 2,3-dichloro-
5-cyano-6-methoxy-p-benzoquinone (18)6 (14%) and 2,3-
dichloro-5,6-dicyanohydroquinone (DDQH2) (20%) were
isolated together with a large amount of recovered DDQ
after 48 h (Scheme 1). Compound 16 could not be isolated
because of the easy elimination of HCN in MeOH solution.
The absorption at 465 nm due to 16 was detected in the
UV±VIS spectra. DDQH2 did not catalyse the deprotection
of 1b and HCN is a very weak acid (pKa 9.2). Therefore,
we deduce that 16 is one of the promotors. Quinone 18
also possessed an activity for the cleavage of 1b, which
was converted into the acidic complex mixture in MeOH
slowly. Since the conversion of p-chloranil in MeOH was
too slow, we could not isolate acidic materials. TCNQ and
TCNQF4 reacted with MeOH slowly to give adducts 21
(96 h, 33%) and 22 (48 h, 94%), respectively (Scheme 2).
During the reactions, we observed the absorptions of the
TCNQ anion radical7 and the TCNQF4 anion radical in
the UV-VIS spectra. Compounds 21 and 22 are suciently
acidic to cause the observed deprotection. Deprotection of
1b catalysed by adduct 22 was quenched by adding 4 equiv.
of DTBP in MeOH.
cene, 1,4-dicyanobenzene and 1,4-dinitrobenzene (Ered
0.66, 0.89, 1.60 and 0.68 V, respectively).
0.43,
Next, we examined the mechanism of the acceptor-
catalysed reactions. The acid concentration of the solution
of representative acceptors, i.e., DDQ, p-chloranil, TCNQ
*To receive any correspondence (e-mail: tanemura@ngt.ndu.ac.jp).
$This is a Short Paper as de®ned in the Instructions for Authors,
Section 5.0 [see J. Chem. Research (S), 1999, Issue 1]; there is there-
fore no corresponding material in J. Chem. Research (M).
Scheme 1