Tris(pentafluorophenyl)borane: a mild and efficient catalyst for the chemoselective tritylation of alcohols

Article abstract of DOI:10.1016/j.tetlet.2007.12.020

An efficient acid-catalyzed protection of alcohols as trityl ethers is described using triphenylmethanol in the presence of tris(pentafluorophenyl)borane (3 mol %) in dichloromethane at room temperature. The chemoselectivity of this protocol is demonstrat

Full text of DOI:10.1016/j.tetlet.2007.12.020

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Tetrahedron Letters 49 (2008) 970–973
Tris(pentafluorophenyl)borane: a mild and efficient catalyst
for the chemoselective tritylation of alcohols
Ch. Raji Reddy *, G. Rajesh, S. V. Balaji, N. Chethan
Organic Division-I, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received 12 October 2007; revised 23 November 2007; accepted 5 December 2007
Available online 8 December 2007
Abstract
An efficient acid-catalyzed protection of alcohols as trityl ethers is described using triphenylmethanol in the presence of tris(penta-
fluorophenyl)borane (3 mol %) in dichloromethane at room temperature. The chemoselectivity of this protocol is demonstrated by
studying the tritylation of a primary alcohol in the presence of a secondary alcohol and also the mildness of this catalyst was studied
with substrates containing acid labile protecting groups.
Ó 2007 Elsevier Ltd. All rights reserved.
Keywords: Tris(pentafluorophenyl)borane; Chemoselective; Tritylation; Alcohol; Lewis acid
The development of efficient and practically useful Lewis
acid catalysts for various organic transformations is of great
importance. Tris(pentafluorophenyl)borane [B(C6F5)3] is
one such Lewis acid catalyst, which is being pursued as a
mild and environmentally benign catalyst for various acid
catalyzed transformations.1–10 It is a non-conventional,
air-stable, water-tolerant, and thermally stable Lewis acid.
Recently, our research group was engaged in exploring
the potential utility of B(C6F5)3 for various organic trans-
formations such as ring-opening of epoxides, and aza-
Ferrier glycosylation,11–13 and also as an efficient activator
for polymethylhydrosiloxane in the reduction of different
functional groups.14,15 In continuation, we report the appli-
cation of B(C6F5)3 in the chemoselective protection of alco-
hols as trityl ethers in a mild acidic medium.
TrATCl5,23 tritylated pyridones,24 BnOTr–DDQ,25 TrOT-
MS–TMSOTf,26 and p-methoxybenzyl trityl ether (p-MBTE)
or prenyl trityl ether (PTE)–DDQ27 are also available.
Most of these tritylating reagents are not available commer-
cially and have to be prepared from trityl chloride. To date,
there are very limited examples known in the literature
describing the protection of alcohols as trityl ethers with tri-
phenylmethanol (as tritylating agent) in the presence of an
acid catalyst.28–31 The reaction conditions employed in
some of these methods involve strong acidic conditions
(H2SO4, FeCl3, etc.). Furthermore, these catalysts were
studied using only a few examples and no systematic study
on chemoselectivity has been carried out. Thus, the devel-
opment of a new Lewis acid for chemoselective protection
of alcohols as trityl ethers under mild reaction conditions
is interesting. Here we disclose our findings wherein
B(C6F5)3 has been identified as a mild and chemoselective
Lewis acid catalyst for the said transformation (Scheme 1).
The triphenylmethyl (trityl) group is a commonly used
protecting group for primary alcohols especially in carbo-
hydrate and nucleoside chemistry.16–18 The introduction
of this group to a hydroxyl functionality is traditionally car-
ried out with trityl chloride in the presence of a base.19–21
Several other reagents such as AgOTf–TrCl,22 TrODT–
B(C6F5)3 (3 mol %)
CH2Cl2, rt, 3-8 h
OH
Ph
OH
R'
R= alkyl, aryl;R'= H, alkyl
Scheme 1. B(C6F5)3-catalyzed tritylation of alcohols.
OTr
+
'
Ph
R
R
R
Ph
*
Corresponding author. Tel.: +91 40 27193128; fax: +91 40 27160512.
E-mail address: rajireddy@iict.res.in (Ch. R. Reddy).
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.12.020

Ch. R. Reddy et al. / Tetrahedron Letters 49 (2008) 970–973
971
Initially, 3-phenyl-1-propanol 1a was treated with tri-
phenylmethanol in the presence of 3 mol % B(C6F5)3 in
dichloromethane at room temperature. The reaction
proceeded smoothly in 3 h and afforded the corresponding
trityl ether 2a in 92% isolated yield (Table 1, entry 1). The
scope of the reaction conditions was then tested for protec-
tion of various other alcohols and the results are summa-
rized in Table 1. The primary alcohols 1b and 1c reacted
well to yield the trityl ethers 2b and 2c in 87 and 93% yields,
respectively (Table 1, entries 2 and 3). The secondary
benzyl alcohols 1d and 1e reacted slowly at room tempera-
ture, however, they reacted under refluxing conditions to
provide the corresponding trityl ethers 2d and 2e in 48
and 56% yields, respectively (Table 1, entries 4 and 5).
Entry 6 (Table 1) demonstrates the chemoselective protec-
tion of a primary benzylic alcohol in the presence of a
phenolic hydroxyl group. Substrates 1g to 1i were selec-
tively converted to the trityl ethers 2g to 2i, without
effecting the acid-labile acetonide, ketal, and benzyl
protecting groups (Table 1, entries 7–9). Similarly, the
reaction succeeded with alcohols 1j and 1k, keeping the
acid-sensitive tert-butylcarbamate (NBoc) protecting group
intact (Table 1, entries 10 and 11).
To check the compatibility and to confirm the mildness
of the reagent system, we studied the protection of 1,3-pro-
panediol monoether substrates 3a to 3h having a free-
hydroxyl group at one end and a hydroxyl-protecting
group at the other end. These substrates underwent trityl-
ation at the free hydroxyl group without affecting the other
protecting groups (Table 2, entries 1–8).
The efficiency of other Lewis acids was also investigated
for this transformation using 3-phenylpropanol as a model
substrate (Table 3). Treatment of 3-phenylpropanol with
triphenylmethanol in the presence of 3 mol % of BF3ÁEt2O
led to a complex mixture (Table 3, entry 1). The other acid
catalysts, ZnCl2, AlCl3, p-TSA, and I2 catalyzed the trityla-
tion (Table 3, entries 2–5). Among these catalysts, B(C6F5)3
was found to be more effective in terms of yield, reaction
profile, and selectivity (Table 3, entry 6).
Table 1
B(C6F5)3-catalyzed tritylation of alcohols
Entry Substrate
Time Product
(h)
Yielda
(%)
Ph
OH
Ph
OTr
1
3
92
87
93
1a
2a
OH
OTr
2b
2
3
3.5
4
1b
OH
OTr
2c
1c
OH
OH
OTr
4
5
8
8
48b
56b
Ph
Ph
Ph
Ph
2d
OTr
1d
1e
2e
OH
OH
6
7
4.5
88
90
OTr
OH
1f
2f
Table 2
Tritylation of alcohols in the presence of other protecting groups
O
O
HO
MeO
TrO
O
O
O
O
Entry Substrate
Time Product
(h)
Yielda
(%)
4
O
MeO
2g
O
1g
HO
OTHP
TrO
OTHP
1
3
90
92
TrO
HO
HO
BnO
3a
4a
4b
O
O
HO
8
3.5
90
HO
OTBDMS
TrO
OTBDMS
2
3.5
3b
BnO
O
O
O
1h
2h
HO
HO
HO
HO
HO
HO
OTBDPS
OMOM
OPMB
OBn
TrO
OTBDPS
OMOM
OPMB
OBn
3
4
5
6
7
8
4
94
85
92
90
93
95
3c
3d
3e
3f
4c
4d
4e
4f
O
O
O
9
4
4
94
87
TrO
3.5
OBn
OBn
TrO
HO
1i
2i
TrO
4
OH
OTr
10
N
N
Boc
Boc
TrO
4
1j
2j
OTr
TrO
OTr
COOMe
COOMe
3.5
HO
TrO
3g
4g
4h
11
3.5
95
NHBoc
1k
NHBoc
2k
OTs
TrO
OTs
4
3h
a
Isolated yields after column chromatography.
Yield from the reaction carried out at reflux.
b
a
Isolated yields after column chromatography.

972
Ch. R. Reddy et al. / Tetrahedron Letters 49 (2008) 970–973
Table 3
3. Chandrasekhar, S.; Babu B. N.; Chandrashekar, G. Review on
tris(pentafluorophenyl)borane. Contribution for Electronic Encyclo-
pedia of Organic Reagents for Organic Synthesis. eEROS, 2005; and
references cited therein.
Tritylation of 3-phenylpropanol in the presence of different acid catalysts
Entry
Acid catalyst (3 mol %)
Time (h)
Yielda (%)
1
2
3
4
5
6
a
BF3ÁEt2O
ZnCl2
AlCl3
p TSA
I2
4
5
4
4
4
3
Complex mixture
4. Ishihara, K.; Yamamoto, H. Eur. J. Org. Chem. 1999, 527–538.
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86
84
88
74
92
B(C6F5)3
Isolated yield.
10. Blackwell, J. M.; Piers, W. E. Org. Lett. 2000, 2, 695–698.
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Deprotection of the trityl group, which is well known
under acidic conditions,16,32–34 was also attempted using
the same catalyst [B(C6F5)3] in methanol, but without suc-
cess even at refluxing temperature.
13. Srihari, P.; Yaragorla, S. R.; Basu, D.; Chandrasekhar, S. Synthesis
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In conclusion, we have demonstrated an extremely facile
and efficient method for protection of alcohols as trityl
ethers in the presence of 3 mol % of tris(pentafluoro-
phenyl)borane. Using this procedure, primary alcohols
were protected as trityl ethers in the presence of secondary
alcohols under mild reaction conditions. The stability of
acid-labile protecting groups is an added advantage of
the method. In addition, the protocol offers the opportu-
nity to install a trityl protecting group in the presence of
base-sensitive functionalities such as esters.
General experimental procedure for the tritylation of alco-
hols: To a mixture of alcohol (1.0 mmol) and triphenyl-
methanol (1.5 mmol) in dichloromethane (5 mL), 3 mol %
of B(C6F5)3 was added and the reaction mixture stirred
for the given time (see Tables 1 and 2). After completion
of the reaction (monitored by TLC), the reaction mixture
was diluted with dichloromethane (5 mL) and washed with
water (1 Â 5 mL) and brine (1 Â 5 mL). The organic layer
was dried over Na2SO4 and evaporated in vacuo. The
crude compound was purified by column chromatography
(hexanes and ethyl acetate) to afford the corresponding
trityl ether.35
Acknowledgments
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29. Salehi, P.; Iranpoor, N.; Behbahani, F. K. Tetrahedron 1998, 54, 943–
948.
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31. Adinolfi, M.; Barone, G.; Iadonisi, A.; Schiattarella, M. Tetrahedron
Lett. 2003, 44, 3733–3735.
G.R. thanks the UGC, S.V.B. and N.C. thank the
CSIR, New Delhi, for financial assistance. The authors
are grateful to Dr. S. Chandrasekhar, Indian Institute of
Chemical Technology, Hyderabad, for his encouragement
and valuable suggestions.
32. Das, B.; Mahendar, G.; Kumar, V. S.; Chowdhury, N. Tetrahedron
Lett. 2004, 45, 6709–6711.
33. Yadav, J. S.; Reddy, B. V. S. Synlett 2000, 1275–1276.
34. Pathak, A. K.; Pathak, V.; Seitz, L. E.; Tiwari, K. N.; Akhtar, M. S.;
Reynolds, R. C. Tetrahedron Lett. 2001, 42, 7755–7757.
35. Spectral data for representative products: (2S,3R,4S,5R)-2,3,4-
Trimethoxy-5-(trityloxymethyl) tetrahydrofuran (2g): 1H NMR
(300 MHz, CDCl3): d 7.49–7.43 (m, 6H), 7.33–7.19 (m, 9H), 5.85 (d,
J = 3.7 Hz, 1H), 4.54 (d, J = 3.7 Hz, 1H), 4.37–4.30 (m, 1H), 3.78 (d,
J = 2.8 Hz, 1H), 3.46–3.40 (m, 1H), 3.32 (s, 3H), 3.29–3.25 (m, 1H),
1.53 (s, 3H), 1.33 (s, 3H); 13C NMR (75 MHz, CDCl3): d 144.1, 128.6,
127.6, 127.1, 111.6, 105.1, 86.5, 84.0, 82.1, 81.8, 79.4, 61.0, 58.1, 27.3;
IR (KBr): m 3418, 1636, 1215, 757 cmÀ1; HRMS-ESI calcd for
Supplementary data
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.
2007.12.020.
References and notes
1. For a review on applications of B(C6F5)3, see: Chen, E. Y.-X.; Marks,
T. J. Chem. Rev. 2000, 100, 1391–1434.
2. Kargbo, R. B. Synlett 2004, 1118–1119.
C
28H30O5Na: 469.1990; found, 469.1992. 2-(2-(Benzyloxy)ethyl)-2-
1
(2-(trityloxy)ethyl)-1,3-dioxolane (2i): H NMR (300 MHz, CDCl3):

Ch. R. Reddy et al. / Tetrahedron Letters 49 (2008) 970–973
973
d 7.48–7.38 (m, 8H), 7.34–7.14 (m, 12H), 4.47 (s, 2H), 3.88–3.68 (m,
4H), 3.54 (t, J = 6.7 Hz, 2H), 3.20 (t, J = 6.7 Hz, 2H), 2.03–1.87 (m,
4H); 13C NMR (75 MHz, CDCl3): d 144.5, 138.6, 128.8, 128.5, 127.9,
127.8, 127.6, 127.0, 109.6, 87.0, 76.3, 66.3, 65.3, 60.0, 43.9, 37.9; IR
(KBr): m 2985, 1374, 1242, 1099, 1047 cmÀ1; HRMS-ESI calcd for
33.6, 26.1, 18.5, À5.12; IR (KBr): m 3449, 2928, 1636, 1088, 836,
702 cmÀ1; HRMS-ESI: calcd for C28H36O2NaSi: 455.2376; found,
455.2386. (3-(Methoxymethoxy)propoxy)triphenylmethane (4d): 1H
NMR (300 MHz, CDCl3): d 7.46–7.40 (m, 6H), 7.33–7.18 (m, 9H),
4.57 (s, 2H), 3.67 (t, J = 6.7 Hz, 2H), 3.29 (s, 3H), 3.17 (t, J = 6.7Hz,
2H), 1.96–1.84 (m, 2H); 13C NMR (75 MHz, CDCl3): d 144.5, 128.9,
128.1, 127.9, 127.4, 127.0, 96.6, 86.6, 65.3, 60.7, 55.3, 30.6; IR (KBr): m
3019, 1215, 762, 670 cmÀ1; HRMS-ESI calcd for C24H26O3Na:
385.1774; found, 385.1775. See Supplementary data for spectral data
of all the other new products.
C33H34O4Na: 517.2354; found, 517.2352. tert-Butyldimethyl(3-(tri-
tyloxy)propoxy)-silane (4b): 1H NMR (300 MHz, CDCl3): d 7.42 (d,
J = 6.2 Hz, 6H), 7.24 (m, 9H), 3.70 (t, J = 6.2 Hz, 2H), 3.15 (t,
J = 6.2 Hz, 2H), 1.89–1.61 (m, 2H), 0.92 (s, 9H), 0.06 (s, 6H); 13C
NMR (75 MHz, CDCl3): d 144.6, 128.9, 127.8, 127, 86.6, 60.1, 59.9,