Ytterbium(III) triflate-catalyzed selective methanolysis of methoxyacetates: A new deprotective method

Full text of DOI:10.1021/jo960095g

J . Org. Chem. 1996, 61, 4491-4492
4491
Ta ble 1. Yb(III)-Ca ta lyzed Meth a n olysis of Va r iou s
Ester s
Ytter biu m (III) Tr ifla te-Ca ta lyzed Selective
Meth a n olysis of Meth oxya ceta tes: A New
Dep r otective Meth od
Takeshi Hanamoto, Yuichi Sugimoto,
Yasuo Yokoyama, and J unji Inanaga*
Institute for Molecular Science, Myodaiji,
Okazaki 444, J apan, and Institute for Fundamental
Research of Organic Chemistry (IFOC), Kyushu University,
Hakozaki, Fukuoka 812-81, J apan
Received J anuary 17, 1996
The methoxyacetyl (MAc) group was introduced as a
useful protective group for the hydroxy function of
nucleoside derivatives in which the cleavage of a meth-
oxyacetate in methanolic ammonia was reported to pro-
ceed 20 times faster than the corresponding acetate.1
Since then, however, it has not found widespread use in
organic synthesis probably because of the lack of efficient
deprotective methods which would favor use of the
methoxyacetyl group.2 Recently, we introduced the 1-O-
methoxyacetyl sugar as a new glycosyl donor which can
be effectively activated by lanthanide(III) triflate [Ln-
(OTf)3]3,4 through the strong interaction between the Ln
3+ ion and the methoxyacetyl moiety, thus offering a
useful glycosylation method.5-7 This type of activation
prompted us to examine the possibility of the Ln(OTf)3-
catalyzed alcoholysis of methoxyacetates under nonbasic
conditions. In this paper, we report a new method for
the selective deprotection of the methoxyacetyl group in
the presence of other protective groups for the hydroxy
functionality under mild conditions (eq 1).
a
b
Determined by 1H NMR analysis. 1 mol % of the catalyst
was used. c 0.1 mol % of the catalyst was used.
as an economical catalyst and compared the susceptibility
of various acyl derivatives of 1-octanol to methanolysis
(Table 1).
Among the seven esters examined, octyl methoxy-
acetate was cleaved most rapidly. For example, its
methanolysis is more than 300 times faster than that of
the corresponding acetate (Table 1, entries 3 vs 6).
Semiempirical calculations of the related compounds
strongly suggest that the selective activation of the
methoxyacetyl group with a metal ion would be affected
by the formation of the five-membered chelate.6 The
reactions of other esters bearing an ethereal oxygen at
their R carbons such as 2-tetrahydrofuranylacetate (Table
1, entry 4), phenoxyacetate (Table 1, entry 5), and
R-methoxy-R-methylpropionate (Table 1, entry 8) pro-
ceeded rather slowly although the ytterbium-involved
five-membered chelate formation seems to be possible.
The â-methoxypropionate (Table 1, entry 7), which might
produce the six-membered chelate, reacted more slowly
than the acetate (Table 1, entry 6). These results indicate
that not only the chelate formation but also steric factors
influence the rate of the catalytic alcoholysis.
Screening of a series of lanthanide(III) triflates as
catalysts for the methanolysis of benzyl methoxyacetate
has revealed that some heavy-lanthanide(III) triflates
such as Er(OTf)3, Tm(OTf)3, Yb(OTf)3, and Lu(OTf)3 are
superior to light-lanthanide(III) triflates.8 Among the
four heavy-lanthanide(III) triflates, we selected Yb(OTf)3
† To whom correspondence should be addressed at IFOC, Kyushu
University.
(1) Reese, C. B.; Stewart, J . C. M. Tetrahedron Lett. 1968, 4273-
4276.
(2) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic
Synthesis, 2nd ed.; J ohn Wiley and Sons: New York, 1991; pp 10-
142.
Next, we carefully examined the Yb(OTf)3-catalyzed
methanolysis of dodecanediol monomethoxyacetates hav-
(3) (a) Thom, K. F. U.S. Patent 3615169, 1971; Chem. Abstr. 1972,
76, 5436a. (b) Almasio, M. C.; Arnaud-Neu, F.; Schwing-Weill, M. J .
Helv. Chim. Acta 1983, 66, 1296-1306. (c) Forsberg, J . H.; Spaziano,
V. T.; Balasubramanian, T. M.; Liu, G. K.; Kinsley, S. A.; Duckworth,
C. A.; Poteruca, J . J .; Brown, P. S.; Miller, J . L. J . Org. Chem. 1987,
52, 1017-1021.
(4) We thank the Shin-Etsu Chemical Co., Ltd., and the Central
Glass Co., Ltd., for providing lanthanoid oxides and triflic acid,
respectively, which are starting substrates for Ln(OTf)3.
(5) For the lanthanide(III) triflate-catalyzed glycosylation of 1-O-
methoxyacetyl sugars, see: Inanaga, J .; Yokoyama, Y.; Hanamoto, T.
Tetrahedron Lett. 1993, 34, 2791-2794. See also: Inanaga, J .;
Yokoyama, Y.; Hanamoto, T. J . Chem. Soc., Chem. Commun. 1993,
1090-1091.
(7) For other recent reports concerning Ln(OTf)3-catalyzed reactions,
see: (a) Hosono, S.; Kim, W.; Sasai, H.; Shibasaki, M. J . Org. Chem.
1995, 60, 4-5. (b) Kobayashi, S.; Ishitani, H.; Nagayama, S. Chem.
Lett. 1995, 423-424. (c) Ishihara, K.; Kubota, M.; Kurihara, H.;
Yamamoto, H. J . Am. Chem. Soc. 1995, 117, 4413-4414. (d) Fukuzawa,
S.; Tsuchimoto, T.; Kanai, T. Bull. Chem. Soc. J pn. 1994, 67, 2227-
2232. (e) Kobayashi, S. Synlett. 1994, 689-701. (f) Aspinall, H. C.;
Browning, A. F.; Greeves, N.; Ravenscroft, P. Tetrahedron Lett. 1994,
35, 4639-4640. (g) Matsubara, S.; Yoshioka, M.; Utimoto, K. Chem.
Lett. 1994, 827-830. (h) Chini, M.; Crotti, P.; Favero, L.; Macchia, F.;
Pineschi, M. Tetrahedron Lett. 1994, 35, 433-436. (i) Meguro, M.; Asao,
N.; Yamamoto, Y. J . Chem. Soc., Perkin Trans. 1 1994, 2597-2601.
(8) The reactions were performed using methanol-d4 as a solvent,
and the catalytic activities of 14 Ln(OTf)3 were evaluated from the
NMR yield of the obtained benzyl alcohol: La(OTf)3 (21%), Pr(OTf)3
(62%), Nd(OTf)3 (46%), Sm(OTf)3 (62%), Eu(OTf)3 (53%), Gd(OTf)3
(55%), Tb(OTf)3 (56%), Dy(OTf)3 (58%), Ho(OTf)3 (58%), Er(OTf)3 (94%),
Tm(OTf)3 (90%), Yb(OTf)3 (99%), and Lu(OTf)3 (99%).
(6) For a MNDO-PM3 study on the selective activation of 1-meth-
oxyacetyl sugars by zinc(II) ion, see: Inanaga, J .; Yokoyama, Y.;
Sugimoto, Y.; Hanamoto, T. Mem. Fac. Sci., Kyushu Univ. Ser. C,
Chem. 1993, 19, 29-32.
S0022-3263(96)00095-3 CCC: $12.00 © 1996 American Chemical Society

4492 J . Org. Chem., Vol. 61, No. 13, 1996
Notes
Ta ble 2. Yb(III)-Ca ta lyzed Selective Clea va ge of th e
Meth oxya cetyl Gr ou p
aromatic ester were all cleaved cleanly under nonbasic
conditions to give the corresponding alcohols in excellent
yields.
In conclusion, we have developed a new method for the
deprotection of the methoxyacetyl group, in which Yb-
(OTf)3 acted as a Lewis acid catalyst in methanol to
effectively promote the transesterification.9 With the
present new deprotective method, the methoxyacetyl
group should receive further evaluation and should be
more widely used in organic synthesis as a unique acyl-
type protective group which can be selectively removed
under nonbasic conditions. It should also be noted that
the catalyst can be recovered easily and reused without
serious loss of catalytic activity.10
entry
R
temp, °C
time, h
yield,a
%
1
Ac
Ac
Bz
0
25
0
0
0
2
13
3
2
1.5
2
93 (7)
98 (2)
95 (1)
92 (3)
94 (3)
99 (0)
99 (0)
2b
3
4
5
6
7
THP
TBDMS
TBDPS
MEM
0
25
0.5
a
Isolated yield. In parentheses are shown the yields of 1,12-
b
dodecanediol. Ethanol was used instead of methanol.
Exp er im en ta l Section
The following experimental procedures are representative:
Clea va ge of Meth oxya ceta te 1 by Yb(OTf)3 in Meth a n ol.
To a solution of 1,2:3,4-di-O-isopropylidene-6-O-(methoxyacetyl)-
R-D-galactopyranose11 (1, 19.9 mg, 0.051 mmol) in dry methanol
(0.5 mL) was added a solution of Yb(OTf)3 (9.5 mg, 30 mol %) in
dry methanol (1 mL), and the mixture was stirred for 12 min at
25 °C. To the reaction mixture was added a drop of water, and
then the solvent was evaporated under vacuum. Purification
of the crude product by preparative TLC on silica gel afforded
the desired alcohol (13.0 mg, 98%) as a colorless oil.
Ack n ow led gm en t. The present work was partly
supported by a Grant-in-Aid for Scientific Research on
Priority Areas “New Development of Rare Earth Com-
plexes” No. 06241108 from the Ministry of Education,
Science and Culture and also by the J oint Studies
Program (1993-1994) of the Institute for Molecular
Science. We are also grateful to the Asahi Glass
Foundation for financial assistance.
J O960095G
(9) It was also found that Yb(OTf)3 acts as an effective catalyst for
the esterification of methoxyacetic acid with alcohols. For example,
1-octyl methoxyacetate and 1-adamantyl methoxyacetate were pre-
pared in quantitative and 79% yield, respectively, by treating the
corresponding alcohols with methoxyacetic acid (1.1 equiv) and 10 mol
% of the catalyst. Preliminary results were presented at the 65th
meeting of the Chemical Society of J apan, Tokyo, March 1993,
symposium paper II, p 474. For a recent report on the Sc(OTf)3,
catalyzed acylation of alcohols, see ref 7c.
(10) For example, the methanolysis of benzyl methoxyacetate with
the recovered catalyst under the same conditions afforded benzyl
alcohol in 91% isolated yield.
(11) Prepared from 1,2:3,4-di-O-isopropylidene-R-D-galactopyranose
and methoxyacetyl chloride according to the standard esterification
procedure.
F igu r e 1. Yb(OTf)3-catalyzed methanolysis of methoxy-
acetates.
ing different protective groups for the other hydroxy
function (Table 2). As expected, the methoxyacetyl group
was removed selectively in the presence of not only ester
moieties such as acetate and benzoate but also such acid-
labile ethereal protective groups as THP, TBDMS, tert-
butyldiphenylsilyl (TBDPS), and MEM ethers.
As shown in Figure 1, various substrates such as sugar
derivatives (1-3), secondary and tertiary esters, and an