1810
S. Malik, K. P. R. Kartha
LETTER
OTr
tritylation reaction was also conducted in CH2Cl2 contain-
ing a small portion of MeOH. Interestingly, the reaction
under these conditions was found to be almost instanta-
neous, and it was judged to be clean by 1H NMR spectros-
copy (entry 10, Table 1). Thus, our contention that if HBr,
produced in situ by the reaction of IBr with MeOH, had
indeed been the main causative agent for the deprotection,
it must be more available for the deprotection reaction in
CH2Cl2 than in MeOH. To further verify this point, when
the trityl ether 3 (56 mg, 0.1 mmol) was treated with a so-
lution of HBr–AcOH reagent (50 mL, 33% w/v) in anhy-
drous CH2Cl2 (1 mL) the deprotection reaction was
complete nearly instantaneously, again giving the desired
alcohol 4 in excellent yield (92%, isolated).17 As O-iso-
propylidene acetals are known to be susceptible to protic
acids, a galactopyranosyl derivative 5, bearing both trityl
and isopropylidene acetal groups, was subjected to the
above deprotection conditions. This reaction allowed
evaluation of the relative advantages of the two methods
in terms of the scope for achieving chemoselectivity. In-
deed, it was found that while the IBr method gave the de-
sired chemoselectivity, resulting in the deprotected
diacetonide 6 (5 min, 95% isolated yield), the same reac-
tion performed in the presence of HBr–AcOH led to the
instantaneous removal of the trityl group along with par-
tial loss18 of the isopropylidene protecting groups
(Scheme 1). The distinct advantage of employing IBr for
the reaction thus became evident.
O
O
OR
O
AcO OR1
AcO
O
O
7 R = Tr
8 R = H
O
B, 5 min,
92%
OR
O
OAc
O
9 R = Me, R1 = Tr
10 R = Me, R1 = H
11 R = SE, R1 = Tr
12 R = SE, R1 = H
A, 5 min
95%
5 R = Tr
6 R = H
A or B,
5 min, 95%
A or B,
5 min, 95%
OR
OR
O
AcO
AcO
OSE
O
OBn
O
BzO
BzO
OAc
A or B,
5 min, 85%
13 R = Tr
14 R = H
BzO
O
BnO
BnO
O
SE = 2-(trimethylsilyl)ethyl
O
AcO
AcO
1 R = Tr
15 R = H
B, 5 min
82%
OSE
OAc
O
OR
O
N
O
O
OR
OH
HN
OH
O
N
O
HO
HN
16 R = Tr
B, 5 min, 95%
17 R = H
18 R = DMTr
B, 1 min, 95%
19 R = DMTr
20 R = H
B, 5 min, 95%
OR
O
O
O
OMe
OMBn
OMe
O
RO
AcO
In addition, treatment of the glycerol derivative 7, bearing
a trityl ether as well as an isopropylidene acetal group,
with IBr in CH2Cl2 led to the chemoselective formation of
1,2-O-isopropylidene glycerol (8; 5 min, 92% isolated). In
contrast, the same reaction in the presence of HBr–AcOH
in CH2Cl2 resulted in the formation of glycerol, confirm-
ing the clear advantage of using IBr for the chemoselec-
tive deprotection of the trityl ether functionality of acid-
sensitive substrates such as 5 and 7.
23 R = Tr
24 R = H
B, 5 min, 85%
O
RO
O
OAc
CO2Me
OC6H4(4-NO2)
21 R = Tr
22 R = H
B, 5 min,
87%
O
AcO
AcHN
AcO
25 R = Tr
26 R = H
B, 5 min, 82%
Scheme 1 Deprotection of trityl ethers using IBr.19 Method A: IBr/
MeCN (1.2 mol equiv), r.t. Method B: IBr (1.2 mol equiv) in CH2Cl2–
The scope of the IBr method was then evaluated by sub- MeOH (9:1), r.t.
jecting various other substrates bearing common protect-
ing groups that are sensitive to different reaction
Acknowledgment
conditions. The results show that functional groups that
are typically susceptible to acidic (Lewis/protic acid; see
9, 11, 13, 21, 23, and 25) or basic (see 1, 9, 11, 13, 21, and
25) conditions are well tolerated. Also, the method is
equally suited for the deprotection of the trityl/dimethoxy-
trityl groups in nucleosides (see 16, 18, and 19). The cur-
rent method is thus superior to literature methods, and its
novelty lies in the fact that it is simple to perform, it re-
quires short time periods, it avoids the formation of by-
products, and is high-yielding.
Satish Malik sincerely thanks the University Grants Commission,
New Delhi for a Senior Research Fellowship. The authors thank
Professor Rob Field, John Innes Centre, Norwich, UK for valuable
help with critical comments on the manuscript.
References and Notes
(1) Iodine and its Interhalogen Compounds: Versatile Reagents
in Carbohydrate Chemistry XXI. For part XX, see:
Kärkkäinen, T. S.; Kartha, K. P. R.; MacMillan, D.; Field,
R. A. Carbohydr. Res. 2008, 343, 1830.
(2) (a) Helferich, B. Adv. Carbohydr. Chem. 1948, 3, 79.
(b) Smith, M.; Rammle, D. H.; Goldberg, I. H.; Khorana,
H. G. J. Am. Chem. Soc. 1969, 84, 430.
(3) (a) Whistler, R. L.; Wolfrom, M. L. Methods in
Carbohydrate Chemistry, Vol. 2; Academic Press: London,
1963, 168. (b) Helferich, B. Adv. Carbohydr. Chem. 1948, 3,
79.
In summary, we have demonstrated that IBr in MeCN and
IBr in CH2Cl2–MeOH are excellent reagent systems for
the deprotection of O-Tr and O-DMTr ethers. These re-
agent systems represent improved, practical alternatives
to many of the reagents that are currently available for the
purpose.19
Synlett 2009, No. 11, 1809–1811 © Thieme Stuttgart · New York