Yb(OTf)3/FeCl3 mediated facile conversion of alcohols, ketals and acid sensitive ethers into diphenylmethyl (DPM) ethers

Article abstract of DOI:10.1016/S0040-4039(00)02108-0

10 mol% Yb(OTf)₃ or FeCl₃ have been developed as efficient reagents for the conversion of alcohols into diphenylmethyl (DPM) ethers. Similarly, FeCl₃ has also been advantageously utilised to successfully convert ketals and

Full text of DOI:10.1016/S0040-4039(00)02108-0

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 759–761
Yb(OTf)3/FeCl3 mediated facile conversion of alcohols, ketals
and acid sensitive ethers into diphenylmethyl (DPM) ethers†
G. V. M. Sharma,* T. Rajendra Prasad and A. K. Mahalingam
Discovery Laboratory, Organic Chemistry Division III, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received 11 October 2000; revised 9 November 2000; accepted 15 November 2000
Abstract—10 mol% Yb(OTf)3 or FeCl3 have been developed as efficient reagents for the conversion of alcohols into diphenyl-
methyl (DPM) ethers. Similarly, FeCl3 has also been advantageously utilised to successfully convert ketals and acid sensitive ethers
into DPM ethers. © 2001 Elsevier Science Ltd. All rights reserved.
Selective and efficient protection1 of functional groups
play a prominent role in a multi-step synthesis. The
triphenylmethyl, diphenylmethyl, benzyl and phenyl
groups are frequently used for the protection of alco-
hol, amino and carboxylic acid functional groups. The
diphenylmethyl (DPM) group was found as a part
structure in a few New Chemical Entities (NCEs)2
showing therapeutic activity. Conventionally DPM pro-
tection is carried out by using DPMCl or DPMBr in
the presence of base,3 DPM diazomethane, tri-DPM
phosphate–trifluoroacetic acid4 or diphenylmethanol in
the presence of conc. H2SO4.5 The disadvantages en-
countered with the existing methods include compatibil-
ity towards acid and base sensitive groups. Hence, there
is still a need to identify new reagents and better
methods for the preparation of DPM ethers. In contin-
uation of our interest in the development of new
reagents6 and new methods7–10 for masking and un-
masking functional groups, herein, we describe our
results on the use of diphenylmethanol (A) in the pre-
sence of Yb(OTf)3 or FeCl3 for the conversion of alco-
hols, and FeCl3 mediated one-pot conversion of ketals
and acid sensitive ethers, into DPM ethers (Eq. (1)).
yield in 0.5 h from 1. Having established 10 mol%
Yb(OTf)3 and FeCl3 as efficient reagents for the conver-
sion of alcohols into DPM ethers, the protocol was
extended to a variety of alcohols (Table 1). Unlike the
case of 1, the alcohol group in 2, containing acid
sensitive acetonides, on reaction with FeCl3 gave 2a in
86% yield, while Yb(OTf)3 gave 2a in 92% yield. Like-
wise, the secondary alcohol group in menthol (3) gave
3a in 88 and 86% yields with FeCl3 and Yb(OTf)3,
respectively. Alcohol 4 underwent facile protection with
Yb(OTf)3 to give the DPM ether 4a (80%) in 0.5 h,
which indicates that the acid sensitive acetonide in 4
can withstand the reaction conditions. However, with
FeCl3 compound 4 underwent deprotection and gave a
complex mixture of products.
Selective etherification of symmetrical diol 5 with FeCl3
afforded the mono protected ether 5a (60%) along with
di-ether 5b (20%). Similarly, reaction of the unsymmet-
rical diol in 6 with FeCl3 furnished 6a (60%) and 6b
(20%); however, a better selectivity was observed with
Yb(OTf)3 where 6a was obtained in 78% yield with a
decrease in the formation of di-ether 6b (10%).
Ph CHOH (A)
ROH ꢀꢀꢀꢀꢀꢀꢀꢀꢀ2ꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢁ RODPM
(1)
After establishing Yb(OTf)3 and FeCl3 as two new and
better reagents for the conversion of alcohols into
DPM ethers, FeCl3 has been advantageously utilised
for the one-pot preparation of DPM ethers from ketals
and acid sensitive ethers. Accordingly, TBDPS ether 7
underwent desilylation and protection in 1 h to give 1a
in 81% yield, while the THP ether 8 furnished 1a in
85% yield in 2 h. The acetonide group in ester 9 was
hydrolysed and concomitantly converted into mono-
ether 9a (52%) and di-ether 9b (14%), while the ester
functionality was found to remain intact under the
Yb(OTf) /FeCl (10 mol%), CH Cl
2
3
3
2
Initially, alcohol 1 was subjected to reaction with A and
10 mol% Yb(OTf)3 in CH2Cl2 at room temperature for
0.5 h to give 1a in 87% yield. Similarly, FeCl3 (10
mol%) also induced the formation of ether 1a in 88%
Keywords: Yb(OTf)3; FeCl3; diphenylmethanol; diphenylmethyl
(DPM) ethers.
* Corresponding author. E-mail: esmvee@iict.ap.nic.in
† IICT Communication No. 4657.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)02108-0

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G. V. M. Sharma et al. / Tetrahedron Letters 42 (2001) 759–761
reaction conditions. However, the acetonide 10 under-
went facile hydrolysis and resulted in the exclusive
formation of mono protected ether 10a (72%).
DPM ethers in good yields. Thus, the present protocol,
making use of diphenylmethanol instead of its deriva-
tives, in the presence of either Yb(OTf)3 or FeCl3
should be of great use in synthetic chemistry, particu-
larly in carbohydrate chemistry.
Thus, in conclusion, the present protocol demonstrated
that: (a) 10 mol% of Yb(OTf)3 or FeCl3 are efficient
reagents for the conversion of alcohols into DPM
ethers; (b) secondary acetonides in compounds such as
2 and 6 and ester functionality in 9 survive the FeCl3
conditions; (c) Yb(OTf)3 is demonstrated to be the
reagent of choice and has no effect on acetonides; and
(d) FeCl3 has been very advantageously used for the
one-pot conversion of acid sensitive substrates into
Typical experimental procedure: FeCl3 method: A mix-
ture of alcohol/ketal (1 mmol), diphenylmethanol (1
mmol) and FeCl3 (0.1 mmol) in CH2Cl2 (5 mL) was
stirred at room temperature for 0.5–2 h. The reaction
mixture was diluted with CH2Cl2 (25 mL) and washed
with water (2×10 mL), brine (10 mL), dried (Na2SO4),
evaporated and the residue purified by column chro-
Table 1. Yb(OTf)3/FeCl3 mediated conversion of alcohols, ketals and acid sensitive ethers to DPM ethers

G. V. M. Sharma et al. / Tetrahedron Letters 42 (2001) 759–761
761
matography (silica gel, ethyl acetate: pet. ether) to
afford DPM ethers in 52–88% yields.
Acknowledgements
Yb(OTf)3 method: A mixture of alcohol (1 mmol),
diphenylmethanol (1 mmol) and Yb(OTf)3 (0.1 mmol)
in CH2Cl2 (5 mL) was stirred at room temperature for
0.5–1 h. The reaction mixture was filtered, evaporated
and the residue purified by column chromatography
(silica gel, ethyl acetate: pet. ether) to afford DPM
ethers in 78–92% yields.
T. Rajendra Prasad and A. K. Mahalingam are thank-
ful to CSIR, New Delhi (India), for financial support.
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Spectral data for selected compounds: 1H NMR (200
MHz, CDCl3, TMS): 1a: l 1.58–1.83 (m, 4H, H-2, 2%,
3, 3%), 2.62 (t, 2H, J=3.2, 6.9 Hz, H-4,4%), 3.45 (t, 2H,
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