Deprotection of benzylic esters catalysed by anhydrous ferric chloride and rhenium carbonyl compounds

Article abstract of DOI:10.1016/S0040-4039(01)02152-9

Anhydrous ferric chloride and [Re(CO)₄Br]₂ are shown to be useful reagents for the catalytic deprotection of benzylic esters. A suitable protecting group is p-MeC₆H₄CH₂ with a working temperature of 5

Full text of DOI:10.1016/S0040-4039(01)02152-9

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 487–488
Deprotection of benzylic esters catalysed by anhydrous ferric
chloride and rhenium carbonyl compounds
a
b
a
b
a,
Timothy J. Davies, Ray V. H. Jones, W. Edward Lindsell, Colin Miln and Peter N. Preston *
a
Department of Chemistry, Heriot-Watt University, Riccarton, Edinburgh, EH14 4AS, UK
b
Syngenta, Earls Road, Grangemouth, Stirlingshire, FK3 8XG, UK
Received 3 October 2001; revised 29 October 2001; accepted 8 November 2001
Abstract—Anhydrous ferric chloride and [Re(CO) Br] are shown to be useful reagents for the catalytic deprotection of benzylic
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esters. A suitable protecting group is p-MeC H CH with a working temperature of 50°C for debenzylation. © 2002 Published
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by Elsevier Science Ltd.
3
5
2–5
Benzyl esters and -ethers are widely used as protecting1
groups for carboxylic acids and alcohols, respectively.
−50 to 40°C ) it should be noted that for ester and
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ether deprotection at least 1 mol equiv. and 8–16 mol
A
common deprotection method is catalytic
equiv. of Lewis acid are required, respectively. There is
a continuing requirement, particularly for industrial-
scale processes, for methods in which the Lewis acid
functions in a catalytic manner. We now illustrate the
hydrogenolysis or transfer hydrogenation but these pro-
cedures can be problematic with certain multifunctional
substrates. Therefore, a variety of alternative strategies
are employed, including the use of Lewis acids, e.g. for
ester deprotection, AlCl for benzyl, p-methoxybenzyl
and benzhydryl; BCl for benzyl, and BF for benzhy-
use of rhenium carbonyl species [Re(CO) X; X=Cl, Br]
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and [Re(CO) Br] in this context, along with a compar-
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3
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ative study with anhydrous ferric chloride. Our interest
in evaluating transition metal organometallics
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dryl. For deprotection of mono- and oligosaccharide
benzyl ethers, anhydrous FeCl has been used. Whilst
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c
7
emanated from a report of their successful application
3
the conditions for such processes are mild (e.g. from
for catalytic mediation of Friedel–Crafts acylation (e.g.
Table 1. Deprotection of benzylic esters by rhenium carbonyl compounds and ferric chloride
Entry
Substrate
Catalysta
Reaction conditions
Yield of carboxylic acid (%)
b
b
1
2
3
4
5
6
7
8
9
ClCH CO CH Ph
[Re(CO) Cl]
Neat/160°C/3 h
Quantitative
Quantitative
Quantitative
Quantitative
Quantitative
2
2
2
5
c
ClCH CO CH Ph
[Re(CO) Br]
Decalin /140°C/25 h
2
2
2
5
b
c
d
ClCH CO CH Ph
[Re(CO) Br]
Mesitylene /130°C/2 h
2
2
2
5
b
c
e
ClCH CO CH C H Me-p
[Re(CO) Br]
Mesitylene /70°C/5 h
2
2
2
6
4
5
f
c
e
ClCH CO CH C H Me-p
[Re(CO) Br]
Mesitylene /50°C/24 h
2
2
2
6
4
4
2
2
2
2
f
f
f
c
d
PhCO CH Ph
[Re(CO) Br]
Mesitylene /90°C/18 h
Quantitative
2
2
4
c
e
3,5-(O N) C H CO CH C H Me-p
[Re(CO) Br]
Mesitylene /90°C/24 h
39
82
2
2
6
4
2
2
6
4
4
c
e
p-HOC H CO CH C H Me-p
[Re(CO) Br]
Mesitylene /90°C/72 h
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2
2
6
4
4
c
3,5-(O N) C H CO CH C H Me-p
FeCl3
FeCl3
Mesitylene /50°C/48 h
Quantitative
Quantitative
2
2
6
4
2
2
6
4
c
1
0
p-HOC H CO CH C H Me-p
Mesitylene /70°C/24 h
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4
2
2
6
4
a
b
c
d
e
f
The catalyst concentration was 1 mol%.
Purchased from Strem chemicals Inc.
The substrate:solvent w/w ratio was ca. 1:2–4.
1
,3,5-Trimethyl-2[(phenyl)methyl]benzene was also isolated, see Ref. 9.
The co-products were mono, bis and tris [p-MeC H CH ]-substituted mesitylenes in ca. 90:8:2 ratio (GC, MS and NMR analyses).
See Ref. 10 for preparative procedure.
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Keywords: debenzylation; protecting groups; carboxylic acids; transition metal catalysts.
*
0
Corresponding author. Tel.: +44 (0)131 451 8035; fax: +44 (0)131 451 3180; e-mail: p.n.preston@hw.ac.uk
040-4039/02/$ - see front matter © 2002 Published by Elsevier Science Ltd.
PII: S0040-4039(01)02152-9

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T. J. Da6ies et al. / Tetrahedron Letters 43 (2002) 487–488
in 0.05 mol% concentration for the reaction of toluene
and benzoyl chloride).
deprotection of such esters that also contain a benzyl-
protected OH group.
An early experiment in this work (entry 1, Table 1)
showed that benzyl chloroacetate was quantitatively
Acknowledgements
deprotected by treating it with [Re(CO) Cl] (1 mol%),
5
albeit under forcing conditions; the product was poly-
benzyl [C H CH ] which was characterised by spectro-
We thank the EPSRC and Zeneca Agrochemicals (now
Syngenta) for an industrial CASE award (to T.J.D.).
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4
2 n
1
scopic comparison (IR, H NMR) with material
prepared in our laboratory by oligomerization of ben-
8
zyl alcohol in conc. H SO or anhydrous HF. Exten-
2
4
sive
trituration
was
necessary
to
extract
References
oligomer-entrapped chloroacetic acid and an improved
procedure is to use decalin as solvent (entry 2); in this
medium, the suspension of polybenzyl was easily
filtered and the carboxylic acid was isolated quantita-
tively after alkaline extraction.
1. (a) Greene, T. W.; Wuts, P. G. M. Protective Groups in
Organic Synthesis, 3rd ed.; John Wiley: New York, 1999;
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Trans. 1 2000, 2495–2527 and references cited therein.
2
. Tsuji, T.; Kataoka, T.; Yoshioka, M.; Sendo, Y.; Nishi-
tani, Y.; Hirai, S.; Maeda, T.; Nagata, W. Tetrahedron
Lett. 1979, 2793–2796.
Mesitylene was then used as a reactive solvent (cf. Ref.
2
) to divert the incipient benzyl cation believed to be
the source of polybenzyl. The working temperature for
deprotection was not significantly decreased (entry 3),
but p-methylbenzyl chloroacetate was quantitatively
3. Ohtani, M.; Watanabe, F.; Narisida, M. J. Org. Chem.
1984, 49, 5271–5272.
4. Schmidt, U.; Kroner, M.; Griesser, H. Synthesis 1991,
294–300.
9
cleaved by [Re(CO) Br] and [Re(CO) Br] at 70 and
5
4
2
5
0°C, respectively (entries 4 and 5); the latter bromine-
5. Hiskey, R. G.; Smithwick, E. L. J. Am. Chem. Soc. 1967,
89, 437–441.
bridged, binuclear compound dissociates in solution to
create more readily a vacant coordination site which is
believed to be necessary for catalytic activity in Friedel–
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Lett. 1987, 28, 3823–3824; (b) Kartha, K. P. R.; Das-
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7
Crafts reactions. Dimeric [Re(CO) Br] was also used
4
2
to debenzylate benzyl benzoate and related esters
entries 6–8) but a higher temperature was required and
(
the nitro group had a detrimental effect.
7. Kusama, H.; Narasaka, K. Bull. Chem. Soc. Jpn. 1995,
Having established the catalytic utility of [Re(CO) Br]2
68, 2379–2383.
4
we then compared its behaviour with a conventional
Lewis acid, viz. anhydrous ferric chloride. Surprisingly,
in the light of previous accounts (see earlier) it proved
to be an equally effective catalyst (1 mol%) for reac-
tions outlined in entries 1–6 under identical conditions
and more effective for those in entries 7 and 8 [quanti-
tative deprotection at 50°C (48 h) and 70°C (24 h),
respectively (see entries 9 and 10)].
8. Banks, R. E.; Fran c¸ ois, P.-Y.; Preston, P. N. Polymer
1992, 33, 3974–3975.
9. Typical experimental procedure: benzyl chloroacetate
(4.86 g, 26.0 mmol), 1,3,5-trimethylbenzene (10 mL) and
bromopentacarbonylrhenium (1 mol%) were heated
under a nitrogen atmosphere at 130°C for 2 h. The
cooled reaction mixture was extracted with aq. NaHCO
(5×10 mL), the residual organic phase was dried (MgSO
and evaporated to afford 1,3,5-trimethyl-
2[(phenyl)methyl]benzene as an oil { H NMR:
(CDCl ) 2.31 (s, 6H, 2×Me), 2.38 (s, 3H, Me), 4.12 (s,
2H, CH ), 7.00 (s, 2H, Ar-H), 7.10–7.37 (m, 5H, Ar-H)}.
3
)
4
11
1
A brief study of catalytic debenzylation of benzyl
phenyl ether in mesitylene was conducted for compari-
l
3
son. Reaction was complete with anhydrous FeCl (1
2
3
mol%) after 24 h at 50°C but very little reaction
occurred using [Re(CO) Br] under identical conditions.
The combined aqueous extract was acidified with dil. HCl
and extracted with diethyl ether to give chloroacetic acid
in quantitative yield.
4
2
In summary, anhydrous FeCl and [Re(CO) Br] are
10. Abel, E. W.; Hargreaves, G. B.; Wilkinson, G. J. Chem.
Soc. 1958, 3149–3152.
11. Hachiya, I.; Moriwaki, M.; Kobayashi, S. Bull. Chem.
3
4
2
useful reagents for catalytic debenzylation of p-methyl-
benzyl-protected carboxylic acids. Furthermore, the lat-
ter may prove to be valuable for the selective catalytic
Soc. Jpn. 1995, 68, 2053–2060.