Yb(OTf)3·H2O: A novel reagent for the chemoselective hydrolysis of isopropylidene acetals

Article abstract of DOI:10.1246/cl.2001.430

A facile chemoselective hydrolysis of terminal isopropylidene acetals has been achieved using a catalytic amount of Yb(OTf)₃·H₂O in acetonitrile at ambient temperature.

Full text of DOI:10.1246/cl.2001.430

430
Chemistry Letters 2001
Yb(OTf)3·H2O: A Novel Reagent for the Chemoselective
Hydrolysis of Isopropylidene Acetals
J. S. Yadav,* B. V. Subba Reddy and K. Srinivasa Reddy
Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad 500007, India
(Received December 27, 2000; CL-001167)
A facile chemoselective hydrolysis of terminal isopropyli-
sponding 1,2-diols in high yields. The catalyst Yb(OTf)3·H2O
dene acetals has been achieved using a catalytic amount of
Yb(OTf)3·H2O in acetonitrile at ambient temperature.
selectively deprotected terminal isopropylidene acetals leaving
other functional groups intact. The procedure is highly
chemoselective to deprotect terminal acetals in the presence of
other acid sensitive functional groups. Such selectivity can be
applied in synthetic sequences in which two different types of
acetals must be unmasked at different stages of the synthesis.
The cleavage required relatively longer reaction times with
anhydrous Yb(OTf)3 to afford comparable yields than those
obtained by hydrated ytterbium triflate. The terminal isopropy-
lidene acetals are deprotected in high yields within 2–4 h of
reaction time. The reaction conditions are compatible with var-
ious functional groups like ethers, esters, sulfonates and olefins
present in the molecule. There are many advantages in the use
of Yb(OTf)3·H2O for this cleavage which include the selective
hydrolysis of 5,6-O-isopropylidene acetals in the presence of
other acid sensitive protecting groups such as TBDPS, PMB,
OAc, OBz, O-allyl and MOM ethers. The procedure failed to
differentiate isopropylidene acetals from tetrahydropyranyl and
TBDMS ethers. The cleavage may be effected by the coordina-
tion of Yb(OTf)3 with dioxolane oxygen to form oxonium ion
that is attacked by water to give 1,2-diols.
Performing chemoselective transformations of polyfunc-
tional compounds are a challenging problem in organic synthe-
sis especially in cases where similar structural features limit
reagent choice. Cyclic isopropylidene acetals, known as ace-
tonides, are widely used for the protection of 1,2- and 1,3-diols
in carbohydrate chemistry.1 Subsequently the hydrolysis of ter-
minal isopropylidene acetals in the presence of internal one is
often required in a multi-step synthetic sequence. As a result,
several methods are reported for the hydrolysis of isopropyli-
dene acetals, which include protic acid catalyzed aqueous
hydrolysis2–4 as well as Lewis acid catalyzed5 nonaqueous
hydrolysis. Due to the strong acidity, presence of free protons,
it is necessary to control the reaction pH, temperature and reac-
tion time while performing reactions with protic acids. Other
reagents6 like thiourea and zinc nitrate are also found to effect
this transformation under mild conditions. However, inspite of
their potential utility, these methods often encounter some dis-
advantages including incompatibility with other functional
groups, longer reaction times, unsatisfactory yields and the use
of stoichiometric amount of catalysts. Therefore, the develop-
ment of new reagents that are more efficient and lead to con-
venient procedures and better yields is desirable. The use of
lanthanide triflates as Lewis acids in organic synthesis has
gained more popularity7 due to their high catalytic nature, low
toxicity, ease of handling, water stability, reusability, noncorro-
siveness and greater selectivity. These special properties inher-
ent to lanthanide triflates prompted us to explore these catalysts
for the selective hydrolysis of isopropylidene acetals under mild
conditions.
The cleavage proceeds smoothly in commercial grade ace-
tonitrile containing 1.5% of water that promotes the hydrolysis
of acetals. Further, it should be noted that longer reaction times
(8–12 h) and the use of large quantity of catalyst (30 mol%), the
cleavage of 3,4-O-isopropylidene acetals was also observed.
The results as summarized in Table 1 clearly reveal the scope
and generality of the reaction with respect to various functional-
ized acetals. The catalyst, Yb(OTf)3 was recovered from aque-
ous layer during workup and reused for two times without the
significant loss of activity.
In this report we wish to introduce Yb(OTf)3·H2O as a mild
and versatile catalyst for the selective hydrolysis of terminal
isopropylidene acetals over a wide range of functional groups
(Scheme 1).
In conclusion, we have described a mild and highly effi-
cient procedure using Yb(OTf)3·H2O for the chemoselective
hydrolysis of terminal isopropylidene acetals in presence of a
wide range of functional groups. The method offers several
advantages including compatibility with other functional
groups, high yields of products, catalytic amount of reagent,
greater selectivity, regeneration of the catalyst and experimental
simplicity which makes it a useful and attractive addition to the
existing ones.
The cleavage was effected by catalytic amount of
Yb(OTf)3·H2O in acetonitrile at ambient temperature.8 The reac-
tions proceeded smoothly at room temperature to give the corre-
Copyright © 2001 The Chemical Society of Japan

Chemistry Letters 2001
431
References and Notes
1
a) T. W. Greene and P. G. M. Wuts, “Protecting Groups in
Organic Synthesis”, 2nd ed. Wiley, New York, (1991). b)
P. J. Kocienski, “Protecting Groups”, Thieme, Stuttgurt,
New York, (1994).
2
3
a) J. S. Yadav, M. C. Chander, and K. K. Reddy,
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a) M. Sukumar, V. Jacques, Y. Pendri, and J. R. Falck,
Tetrahedron Lett., 27, 2679, (1986). b) K. H. Park, Y. J.
Yoon, and S. G. Lee, Tetrahedron Lett., 35, 9737, (1994).
M. Gerspacher and H. Rapoport, J. Org. Chem., 56, 3700,
(1991)
4
5
a) M. Iwata and H. Ohrui, Bull. Chem. Soc. Jpn., 54, 2837,
(1981). b) K. S. Kim, Y. H. Song, B. H. Lee, and C. S.
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6
a) S. Majumdar and A. Bhattacharjya, J. Org. Chem., 64,
5682, (1999). b) S. Vijayasaradhi, J. Singh, and I. A.
Singh, Synlett, 2000, 110.
7
8
a) S. Kobayashi, Eur. J. Org. Chem., 1999, 15. b) S.
Kobayashi, Synlett, 1994, 689.
General procedure: A mixture of isopropylidene acetal (5
mmol) and Yb(OTf)3.H2O (0.25 mmol) in acetonitrile(15
mL) was stirred at room temperature for an appropriate
time (Table 1). After completion of the reaction as indicat-
ed by TLC, the reaction mixture was diluted with water (10
mL) and extracted twice with ethyl acetate (2 × 20 mL).
The combined organic layers were dried over anhydrous
Na2SO4, concentrated in vacuo and purified by column
chromatography on silica gel (Merck, 100–200 mesh, ethyl
acetate:hexane, 3:7) to afford pure 1,2-diol. Spectroscopic
data for 1f: 1H NMR (CDCl3): δ 1.30 (s, 3H), 1.40 (s, 3H),
1.45 (s, 3H), 1.50 (s, 3H), 3.80 (s, 3H), 3.95 (m, 2H), 4.05
(m, 2H), 4.30 (m, 1H), 4. 50 (dd, 1H, J = 4.0 and 2.0 Hz),
4.55 (2d, 2H, J = 7.8 Hz), 5.85 (d, 1H, J = 4.0 Hz), 6.85 (d,
1
2H, J = 7.8 Hz), 7.25 (d, 2H, J = 7.8 Hz). 2f: H NMR
(CDCl3): δ 1.30 (s, 3H), 1.45 (s, 3H), 3.65 (m, 1H), 3.80 (s,
3H), 3.95 (m, 1H), 4.05 (m, 2H), 4.45 and 4.65 (2d, 2H, J
= 7.8 Hz), 4. 50 (m, 1H), 4.60 (d, 1H, J = 4.0 Hz), 5.90 (d,
1H, J = 4.0 Hz), 6.85 (d, 2H, J = 7.8 Hz), 7.25 (d, 2H, J =
7.8 Hz).
IICT Communication No: 4688
BVS and KSR thank CSIR, New Delhi for the award of
fellowships.