Bismuth(III) chloride catalyzed efficient and selective cleavage of trityl ethers

Article abstract of DOI:10.1055/s-2004-825602

A highly selective and efficient protocol has been developed for detritylation using 5 mol% BiCl₃ in acetonitrile. The cleavage proceeds at room temperature in high yields and the conditions are mild enough to tolerate a variety of acid-base sensitive functional groups.

Full text of DOI:10.1055/s-2004-825602

1276
LETTER
Bismuth(III) Chloride Catalyzed Efficient and Selective Cleavage of Trityl
Ethers1
Efficient
a
ndSelec
o
tive Cleavag
w
e
of Trityl Ethers ravaram Sabitha,* E. Venkata Reddy, R. Swapna, N. Mallikarjun Reddy, J. S. Yadav
Organic Division I, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Fax +91(40)27160512; E-mail: sabitha@iict.ap.nic.in
Received 14 October 2003
Initially, trityl ether 1a was subjected to detritylation17
Abstract: A highly selective and efficient protocol has been devel-
oped for detritylation using 5 mol% BiCl3 in acetonitrile. The
cleavage proceeds at room temperature in high yields and the con-
ditions are mild enough to tolerate a variety of acid-base sensitive
functional groups.
with 5 mol% of BiCl3 in acetonitrile at room temperature
to afford 2a in 92% yield within 7 minutes. Encouraged
by this result, several trityl ethers with different protecting
groups were subjected to deprotection using BiCl3 as a
mild Lewis acid (Table 1). Thus, trityl ethers 1c and 1q
containing acid sensitive THP and Boc group respectively
underwent facile cleavage of the trityl ether within 4 min-
utes, retaining the THP and Boc groups. Similarly, trityl
ethers 1e–h having base sensitive Ac, Bz, Ts and Piv
groups underwent smooth and selective deprotection of
the trityl group in 3 minutes to give the corresponding al-
cohols in good yields. In a further study, sugar substrates
possessing glycosidic linkages and O-prenyl, O-allyl, and
Bn groups were also subjected to selective cleavage of tri-
tyl groups in 8–10 minutes to afford the corresponding al-
cohols. The trityl groups of 1d, 1i and 1j were also cleaved
without causing loss of the TBDPS and PMB protecting
groups. Trityl ethers 1k–n having acetonides derived from
secondary alcohols underwent selective deprotection of
the trityl group leaving acetonides intact. Whereas, the
cleavage of acetonides derived from primary alcohols us-
ing BiCl3 is reported.18 The results show that the rate of
detritylation using our conditions is much faster (3–10
min) than those reported in the literature. In addition the
selectivity, for cleavage of trityl ethers in the presence of
a variety of acid/base sensitive groups and substrates such
as carbohydrates, terpenes and amino acids makes this
procedure a valuable alternative to the existing proce-
dures.
Key words: trityl ethers, catalytic, selective, bismuth(III) chloride,
alcohols
The triphenylmethyl (trityl) group is a commonly used
protecting group for primary alcohols in carbohydrate and
nucleoside chemistry due to its ease of installation, re-
moval and stability towards a variety of reagents.2,3 In
general, detritylation is accomplished under strong acidic
conditions such as HCOOH,4 80% CH3COOH,5 mineral
acids,6 CF3COOH,7 or using Lewis acids such as ZnBr2,8
10
AlClEt2,9 Yb(OTf)3 and Ce(OTf)4.11 Other reagents in-
cluding CeCl3/NaI,12 I2/MeOH13 and triethylsilane14 have
also been employed for the removal of trityl group. How-
ever, under protic acid conditions, sensitive substrates fre-
quently undergo acid catalyzed deglycosylations, and
Lewis acid detritylation procedures require either anhy-
drous conditions, use of reagents in stoichiometric quanti-
ties and extended reaction times and heating. Thus there is
still a need to develop a mild and more effective method
to overcome the above drawbacks for trityl deprotection.
Most bismuth compounds are relatively non-toxic, easy to
handle and can tolerate small amounts of moisture. With
increasing environmental concerns and the need for
‘green reagents’, the interest in bismuth and its com-
pounds has increased tremendously in the last decade.15 In
continuation of our studies using BiCl3 for various organic
transformations,16 we report herein a simple, mild and
highly efficient method for the cleavage of trityl ethers us-
ing a catalytic amount of BiCl3 in acetonitrile at room
temperature (Scheme 1).
In conclusion, we have demonstrated that 5 mol% BiCl3
in acetonitrile at room temperature is an effective reagent
system for the detritylation. The high yields, speed, and
chemoselectivity, render this strategy advantageous and it
may find wide application in organic synthesis.
Acknowledgement
EVR, RS and NMKR thank CSIR, New Delhi, for the award of a
fellowship.
References
Scheme 1
(1) IICT Communication No. 031004.
(2) (a) Helferich, B. Adv. Carbohydr. Chem. 1948, 3, 79.
(b) Greene, T. W.; Wuts, P. G. M. Protective Groups in
Organic Synthesis, 2nd ed.; John Wiley and Sons: New
York, 1999, 102. (c) Kocienski, P. J. Protecting Groups;
Thieme: Stuttgart, New York, 1994.
SYNLETT 2004, No. 7, pp 1276–1278
Advanced online publication: 19.05.2004
DOI: 10.1055/s-2004-825602; Art ID: D25403ST
© Georg Thieme Verlag Stuttgart · New York
0
3.
0
6.
2
0
0
4

LETTER
Efficient and Selective Cleavage of Trityl Ethers
1277
Table 1 BiCl3-Catalyzed Selective Cleavage of Trityl Ethers
Entry
a
Substrate
1
Producta
2
Time (min)
7
Yield (%)b
92
b
6
3
90
90
89
93
95
92
88
86
90
90
95
c
d
e
f
R = THP
R = TBDPS
R = Piv
R = Bz
R = THP
R = TBDPS
R = Piv
R = Bz
4
3
3
3
g
h
i
R = Ac
R = Ac
3
R = Ts
R = Ts
3
4
j
4
k
10
l
8
8
90
92
95
m
n
10
o
p
q
5
5
4
92
93
90
a All products were identified by IR, 1H NMR, mass spectral data and known compounds by comparison with authentic samples.
b Isolated yield after column chromatography.
Synlett 2004, No. 7, 1276–1278 © Thieme Stuttgart · New York

1278
G. Sabitha et al.
LETTER
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Spectroscopic data for selected compounds. Compound 1a:
IR (neat): 2941, 1057, 749 cm–1. 1H NMR (200 MHz,
CDCl3): d = 1.92–2.12 (m, 2 H), 2.72 (t, 2 H, J = 10.0 Hz),
3.17 (t, 2 H, J = 5.1 Hz), 7.12–7.35 (m, 15 H), 7.47 (d, 6 H,
J = 8.2 Hz). MS: m/z = 378 [M+]. Compound 2a: IR (neat):
3355, 2943, 1057, 745 cm–1. 1H NMR (300 MHz, CDCl3):
d = 1.92–2.12 (m, 2 H), 2.72 (t, 2 H, J = 5.2 Hz), 3.63 (t, 2
H, J = 9.8 Hz), 7.15–7.25 (m, 5 H). MS: m/z = 136 [M+].
Compound 1d: IR (neat): 2358, 1219, 1109, 773 cm–1. 1H
NMR (200 MHz, CDCl3): d = 1.03 (s, 9 H), 1.38 (s, 2 H),
1.51–1.62 (m, 4 H), 3.02 (t, 2 H, J = 5.9 Hz), 3.62 (t, 3 H,
J = 5.2 Hz), 7.16–7.41 (m, 19 H), 7.39 (d, 6 H, J = 7.9 Hz).
MS: m/z = 585 [M+]. Compound 2d: IR (neat): 3332, 2855,
1104, 1028, 772 cm–1. 1H NMR (300 MHz, CDCl3): d = 1.03
(s, 9 H), 1.39–1.59 (m, 6 H), 3.59 (t, 2 H, J = 6.0 Hz), 3.64
(t, 2 H, J = 6.0 Hz), 7.33–7.38 (m, 2 H), 7.62 (d, 2 H, J = 7.3
Hz). MS: m/z = 342 [M+]. Compound 1e: IR (neat): 2936,
1727, 1156, 1071 cm–1. 1H NMR (200 MHz, CDCl3): d =
1.19 (s, 9 H), 1.46–1.71 (m, 6 H), 3.06 (t, 2 H, J = 5.9 Hz),
4.03 (t, 2 H, J = 5.9 Hz), 7.18–7.33 (m, 9 H), 7.45 (d, 6 H,
J = 8.2 Hz). MS: m/z = 430 [M+]. Compound 2e: IR (neat):
3439, 2938, 1728, 1159, 1057 cm–1. 1H NMR (200 MHz,
CDCl3): d = 1.18 (s, 9 H), 1.38–1.72 (m, 6 H), 3.62 (t, 2 H,
J = 6.6 Hz), 4.04 (t, 2 H, J = 6.6 Hz). MS: m/z = 188 [M+].
Compound 1i: IR (neat): 2361, 1219, 1174, 1060, 771 cm– 1.
1H NMR (200 MHz, CDCl3): d = 3.60 (d, 2 H, J = 6.6 Hz),
3.80 (s, 3 H), 3.85 (d, 2 H, J = 6.5 Hz), 4.30 (s, 2 H), 5.60–
5.90 (m, 2 H), 6.76 (d, 2 H, J = 8.2 Hz), 7.15 (d, 2 H, J = 8.1
Hz), 7.30 (m, 9 H), 7.45 (d, 6 H, J = 8.2 Hz). MS: m/z = 450
[M+]. Compound 2i: IR (neat): 3418, 2935, 1514, 1174, 1032
cm–1. 1H NMR (200 MHz, CDCl3): d = 3.80 (s, 3 H), 4.01 (d,
2 H, J = 6.5 Hz), 4.15 (d, 2 H, J = 6.5 Hz), 4.40 (s, 2 H),
5.50–5.90 (m, 2 H), 6.85 (d, 2 H, J = 8.2 Hz), 7.27 (d, 2 H,
J = 8.2 Hz). MS: m/z = 208 [M+]. Compound 1n: IR (neat):
2985, 2935, 1611, 1509, 1216, 1077 cm–1. 1H NMR (200
MHz, CDCl3): d = 1.31 (s, 6 H), 1.45 (s, 3 H), 1.53 (s, 3 H),
3.50–3.63 (m, 2 H), 3.90 (dt, 1 H, J = 6.0 and 2.3 Hz), 4.20–
4.30 (m, 2 H), 4.48–4.58 (m, 2 H), 5.50 (d, 1 H, J = 5.1 Hz),
7.20 (m, 9 H), 7.40 (d, 6 H, J = 7.3 Hz). MS: m/z = 503 [M+].
Compound 2n: IR (neat): 3425, 2980, 2930, 1509, 1077 cm–1.
1H NMR (200 MHz, CDCl3): d = 1.31 (s, 6 H), 1.45 (s, 3 H),
1.53 (s, 3 H), 3.60–3.73 (m, 2 H), 3.80 (dt, 1 H, J = 6.0 and
2.3 Hz), 4.20–4.30 (m, 2 H), 4.48–4.58 (m, 2 H), 5.50 (d, 1
H, J = 5.1 Hz). MS: m/z = 260 [M+].
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(17) General Procedure. Trityl ether (2 mmol) in dry MeCN (2
mL), was treated with a catalytic amount of BiCl3 (5 mol%)
and stirred at r.t. After complete conversion of the reaction
as indicated by TLC, the reaction mixture was filtered
through a small pad of Celite. The filtrate was extracted with
EtOAc, washed with brine and dried over anhyd Na2SO4.
After evaporation, the residue was purified by column
chromatography using silica gel (60–120 mesh; hexane–
EtOAc) to furnish pure alcohol.
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Synlett 2004, No. 7, 1276–1278 © Thieme Stuttgart · New York