Mild and efficient deprotection of allyl ethers of phenols and hydroxycoumarins using a palladium on charcoal catalyst and ammonium formate

Article abstract of DOI:10.1016/j.tetlet.2006.05.176

An efficient procedure for the cleavage of allyl phenyl ethers and allyl coumarinyl ethers using a catalytic amount of 10% Pd/C in combination with ammonium formate is described. Allyl ethers of phenols are deprotected in preference to those of alcohols and this method is compatible with several reducible functional groups such as CHO, COCH₃, CO₂Et and NHCOCH₃.

Full text of DOI:10.1016/j.tetlet.2006.05.176

Tetrahedron Letters 47 (2006) 5807–5810
Mild and efficient deprotection of allyl ethers of phenols and
hydroxycoumarins using a palladium on charcoal catalyst
and ammonium formate
Nemai C. Ganguly,* Sanjoy Dutta and Mrityunjoy Datta
Department of Chemistry, University of Kalyani, Kalyani 741 235, India
Received 16 March 2006; revised 19 May 2006; accepted 25 May 2006
Available online 23 June 2006
Abstract—An efficient procedure for the cleavage of allyl phenyl ethers and allyl coumarinyl ethers using a catalytic amount of 10%
Pd/C in combination with ammonium formate is described. Allyl ethers of phenols are deprotected in preference to those of alcohols
and this method is compatible with several reducible functional groups such as CHO, COCH3, CO2Et and NHCOCH3.
ꢀ 2006 Elsevier Ltd. All rights reserved.
Ammonium formate has been extensively used1 as a
hydrogen source in the presence of the hydrogen transfer
catalyst, palladium on charcoal, for the reduction of a
host of functionalities, including deprotection of O-benz-
yl ethers, 1,3-dibenzyluracils and deoxygenation of pyr-
idine N-oxides. The use of this reagent system for the
deallylation of allyl ethers of phenols and hydroxy-
coumarins is herein disclosed. Phenolic hydroxyl
groups are ubiquitous in naturally occurring secondary
metabolites of plant and animal origin.2 Unlike alco-
hols, phenols, particularly polyphenols, are acidic in
nature, oxidation-prone, sensitive to radicals and pos-
sess enhanced nucleophilicity. Therefore, protection of
phenolic hydroxyl groups is of importance in multistep
syntheses of biologically important natural products.
The allyl group is a very useful phenol protecting group
because of the stability of allyl ethers under acidic as
well as under basic conditions. Allyl ethers are safety-
catch, or two-stage protecting groups,3 and their depro-
tection involves the two-step process of isomerization of
the stable allyl (prop-2-enyl) ether to a labile prop-1-enyl
ether as a prelude to hydrolytic cleavage.4a–c A second
plausible mechanistic scenario4d–f for deprotection of
aryl allyl ethers with Pd/C or Pd(0) complexes involves
initial oxidative addition of palladium to the allyl ether
to form a p-allyl palladium species. The aryloxy group
in the resulting species is a competent leaving group
and interception by even a weak nucleophile releases
the aryloxy group to furnish the phenol. The known
lability of allyl ethers4g under Suzuki reaction conditions
(Pd(PPh3)4, K3PO4, DME, reflux) and the fact that Pd/
C catalyzes Suzuki reactions also supports this view.
Allylic carboxylates that are normally unreactive to-
wards mild hydride transfer reagents such as NaBH4
and NaBH4CN are analogously activated towards dis-
placement by initial complex formation with Pd(0)
derivatives and are removed in Àthe presence of weak
nucleophiles, e.g. BH4À, BH3CN .4h
Previously, attempts towards the activation of allyl
ethers under strongly basic conditions using potassium
tert-butoxide5 proved to be too harsh and sluggish. A
more convenient strategy of deallylation is based on
transition metal (Pd, Rd, Ir, Ru) catalyzed isomerization
of the double bond to an enol ether followed by its
hydrolysis to release the phenol. Deallylation protocols
based on the use of a palladium metal catalyst are
well-documented including 10% Pd/C in combination
with p-toluenesulfonic acid,6 10% Pd/C with 10% meth-
anolic KOH,7 electrochemical cleavage employing
PdCl2,8 and Pd(PPh3)4 with reducing agents such as
NaBH4,4d LiBH4,4f Bu3SnH9 and PdCl2/CuCl/O2.10
Recently, several one-step cleavage protocols based on
SmCl3,11 NaI/Me3SiCl,12 NiCl2(dppp)/DIBALH,13
electrochemically generated nickel,14 SmI2/H2O/Et3N15
and CpRuIIIPF6/quinaldic acid16 catalysts have been
described. Surprisingly, the deallylation of allyl ethers
Keywords: Deallylation; Allyl phenyl ether; Allyl coumarinyl ether;
Pd/C and ammonium formate.
*
Corresponding author. Tel.: +91 33 22418066; fax: +91 33
25828282; e-mail: nemai_g@yahoo.co.in
0040-4039/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.05.176

5808
N. C. Ganguly et al. / Tetrahedron Letters 47 (2006) 5807–5810
Table 1. Cleavage of allyl ethers of phenols and hydroxycoumarins
Table 1 (continued)
with 10% Pd/C and HCO2NH4 in methanol
Entry
Substrate
R = allyl
Product
Timea (h)
[Yieldc in (%)]
Entry
Substrate
R = allyl
Product
Timea (h)
[Yieldc in (%)]
OR
OH
OH
OR
11(a)
0.5b [72]
1
(i) 8 [80]
(ii) 0.5b [95]
NO2
11
NH2
11a
1
1a
OH
OH
OR
11a
+
0.5f 11a [5];
11b [70]
2
3
0.5b [98]
11(b)
11
OH
OH
NO2
2
2a
11b
OR
OH
OR
2
2a
9.5 [80]
1d [92]
0.5b [98]
OR
12
3
CH2OC3H7
12a
CH2OR
12
OR
4
5
2
(i) 0.5b [98]
(ii) 0.5e [96]
1.5d [86]
OH
OR
OAc
4
2a
13
14
(i) 8 [90]
(ii) 0.5b [96]
OR
OH
CH2OH
13a
CH2OH
13
OMe
OMe
6 [85]
CHO
5
CHO
5a
RO
HO
O
O
O
O
O
O
(i) 15 [80]
(ii) 1b [98]
OH
OR
14a
14
6
7
(i) 2 [92]
(ii) 0.5b [98]
RO
CO2Et
CO2Et
HO
O
O
6
6a
15
16
1b [95]
OR
OH
15a
15
16
(i) 5 [85]
(ii) 0.5b [98]
I
I
CHO
7
HO
HO
O
O
O
O
CHO
7a
RO
RO
O
O
O
O
1.5b [95]
16a
OH
OR
R
C3H7
8
(i) 5 [90]
(ii) 0.5b [92]
COMe
COMe
17
1b [92]
8
8a
17a
17
18
OR
OH
O
O
O
O
O
O
O
9
(i) 7 [88]
(ii) 1b [90]
18
19
1b [98]
NHCOMe
9
NHCOMe
9a
HO
HO
RO
RO
18a
OR
OH
O
10
8b [85]
1.5b [95]
I
I
10a
10
19
19a

N. C. Ganguly et al. / Tetrahedron Letters 47 (2006) 5807–5810
5809
Table 1 (continued)
ethers bearing reducible or acid-labile functionalities.
Whereas the O-allyl ether of 4-nitrophenol (11) (Table
1, entry 11(a)) underwent concomitant reduction of
the nitro group, selective deallylation without affect-
ing the nitro group could be accomplished using less
(4 mol equiv) ammonium formate (Table 1, entry
11(b)). Sequential removal of the allyl groups of 1,3-
di-O-allyloxybenzene (Table 1, entry 3) was possible at
room temperature. An attempted cleavage of 3-acetoxy-
allyloxybenzene (4) only resulted in facile hydrolysis of
the acetoxy group without affecting the allyl ether moi-
ety. The use of an identical amount of ammonium for-
mate, without Pd/C catalyst, gave the same product 2
in almost identical yield. Simultaneous deallylation
and hydrolysis of the acetoxy group took place upon
prolonged exposure to an excess of the reagents. How-
ever, the more acid-stable anilido function (Table 1,
entry 9) was found to be intact under the deprotection
conditions.
Entry
Substrate
Product
Timea (h)
R = allyl
[Yieldc in (%)]
O
O
O
O
20
1.5b [95]
OH
20a
OR
20
a Refers to cleavage reactions conducted at room temperature (25 ꢁC)
using 10% Pd/C (30 mg) and HCO2NH4 (6 mmol) per mmol of
substrate.
b Refers to cleavage time in refluxing methanol using identical amounts
of reagents.
c Refers to yields of chromatographically isolated product character-
ized by comparison with authentic samples (mixed mp, co-TLC,
superimposable IR) and spectral studies (IR, 1H NMR, 13C NMR
and EMS).
d 10% Pd/C (40 mg), HCO2NH4 (10 mmol), in methanol (10 mL)
under reflux.
e HCO2NH4 (6 mmol) was employed only; no Pd/C was used.
f 10% Pd/C (30 mg) and HCO2NH4 (4 mmol) were used per mmol of
11 in methanol under reflux.
The di-O-allyl ether of 4-hydroxybenzyl alcohol (12)
was deallylated to give 4-hydroxy-n-propylbenzyl ether
(12a) demonstrating preferential cleavage of allyl phenyl
ether. Cleavage of the C–O bond of the allyl ether of an
alcoholic hydroxyl group was less straightforward and
the allylic C@C bond was reduced prior to its isomeriza-
tion to the prop-1-enyl ether. However, an ester group, in
contrast to its reduction with SmI2/H2O/Et3N,15
remained unchanged. The method was also compatible
with other reducible groups such as CHO and COCH3.
The iodo group (Table 1, entries 10 and 16) also with-
stood the reaction conditions. Deallylation of 4-allyl-
oxyiodobenzene with electrochemically generated
nickel14 gave the corresponding phenol in low yield
(11%) because of the high reactivity of nickel towards
oxidative addition to the iodo group. It is also significant
that the a,b-unsaturated lactone moiety of allyl coumari-
nyl ethers remained intact during cleavage (Table 1, en-
tries 14–20) in view of the propensity for reduction of
double bonds conjugated to the carbonyl group20 of
a,b-unsaturated aldehydes, ketones and esters22 with
Pd/C and ammonium formate. Attempted cleavage of
8-allyl-7-allyloxy-4-methylcoumarin (17) led to the pref-
erential reduction of the isolated C@C bond of the 8-allyl
group in the presence of the 3,4-double bond of the
coumarin with concomitant deallylation. However,
exposure of 7-methoxycoumarin (21) to the reagent in
refluxing methanol for 2 h in a separate experiment
resulted in the isolation of 7-methoxy-3,4-dihydrocoum-
arin (21a) in a yield of 96% (Scheme 2) demonstrating the
reducibility of the 3,4-double bond of a coumarin moiety
in the absence of a competing faster deally-lation.24
of alcohols has engaged organic chemists more than
their phenolic counterparts. We were interested in the
deprotection of allyl coumarinyl ethers in connection
with our studies on regioselective electrophilic substitu-
tion reactions17 of these ethers. Further synthetic manip-
ulations with hydroxycoumarins necessitated the release
of hydroxycoumarins from O-allyl ethers. To achieve
this aim, 10% Pd/C and ammonium formate seemed to
be appropriate reagents. Ammonium formate is inex-
pensive, readily available, stable and nontoxic. Table 1
summarizes the results of cleavage of allyl ethers of phe-
nols and hydroxycoumarins using a catalytic amount of
10% Pd/C with ammonium formate (Scheme 1).
We chose O-allyl phenol 1 (entry 1) as the model sub-
strate to optimize the conditions. It was observed that
1 mmol of 1 was cleaved after protracted treatment with
30 mg of Pd/C and 6 mmol of ammonium formate in
methanol at room temperature (8 h) in acceptable yield
(80%). The cleavage was markedly accelerated under
reflux conditions furnishing phenol in an excellent yield
(95%) within 30 min.18 Notably, rigorous exclusion of
water from the ammonium formate and methanol, as
is common in transfer hydrogenations,19,20 is not obvi-
ously essential in this case. Encouraged by the dual
advantages of an improvement in yield and substantial
reduction of reaction time we proceeded to conduct
deprotections of several allyl aryl ethers including resor-
cinols21 which are fairly well-represented in naturally
occurring phenolics. This procedure worked well for
most of the cases studied. The substantial difference in
rates of cleavage at room temperature and under reflux
conditions was found to be quite general. However, the
cleavage at room temperature was more compatible with
In conclusion, a clean, efficient, cleavage of allyl ethers
of phenols and hydroxycoumarins employing a catalytic
MeO
O
O
MeO
O
O
10% Pd/C, HCO2NH4
MeOH, reflux, 2 h
O
10% Pd/C
Ar
ArOH
(70 - 98%)
(6 mol equiv)
HCO2NH4
MeOH, reflux
Ar = aryl, coumarinyl
21
21a (96%)
Scheme 1.
Scheme 2.

5810
N. C. Ganguly et al. / Tetrahedron Letters 47 (2006) 5807–5810
9. Four, P.; Guibe, F. Tetrahedron Lett. 1982, 23, 1825.
10. Mereyala, H. B.; Guntha, S. Tetrahedron Lett. 1993, 34,
6929.
amount of 10% Pd/C in combination with ammonium
formate is reported.
´
11. Espanet, B.; Dunˇach, E.; Perichon, J. Tetrahedron Lett.
1992, 33, 2485.
Acknowledgements
12. Kamal, A.; Laxman, E.; Rao, N. V. Tetrahedron Lett.
1999, 40, 371.
13. Taniguchi, T.; Ogasawara, K. J. Chem. Soc., Chem.
Commun. 1998, 1531.
14. Yasuhara, A.; Kasano, A.; Sakamoto, T. J. Org. Chem.
1999, 64, 4211.
The authors are thankful to DST, India, for support by
way of the DST-FIST programme. We sincerely thank
the reviewer for some helpful suggestions.
15. Dahlen, A.; Sundgren, A.; Lahmann, M.; Oscarson, S.;
Hilmersson, G. Org. Lett. 2003, 5, 4085.
References and notes
16. Tanaka, S.; Saburi, H.; Ishibashi, Y.; Kitimura, M. Org.
Lett. 2004, 6, 1873.
1. For reviews on the use of ammonium formate–Pd/C
reagent system, see: (a) Ram, S.; Ehrenkaufer, R. E.
Synthesis 1988, 91; (b) Ranu, B. C.; Sarkar, A.; Guchhait,
S. K.; Ghosh, K. J. Indian Chem. Soc. 1998, 690.
2. (a) Murray, R. D. H. Nat. Prod. Rep. 1995, 12, 477; (b)
Whiting, D. A. Nat. Prod. Rep. 2001, 18, 583; (c) Wu, Q.;
Fu, D.-X.; Hou, A.-J.; Lei, G.-Q.; Liu, Z.-L.; Chen, J.-K.;
Zhou, T.-S. Chem. Pharm. Bull. 2005, 53, 1065; (d) Murray,
R. D. H. In Progress in the Chemistry of Organic Natural
Products; Springer Wein: New York, 1991; Vol. 58.
17. (a) Ganguly, N. C.; Sukai, A. K.; De, S. Synth. Commun.
2001, 34, 301; (b) Ganguly, N. C.; Datta, M.; De, P.;
Chakravarty, R. Synth. Commun. 2003, 33, 647; (c) Cairns,
N.; Harwood, L. M.; Astles, D. P. Tetrahedron 1992, 48,
7581.
18. Representative procedure for the cleavage of allyl aryl
ethers with 10% Pd/C and ammonium formate in methanol:
Ammonium formate (380 mg, 6 mmol) was added to a
solution of the allyl phenyl ether (136 mg, ꢀ1 mmol) in
methanol (8 mL) containing 10% palladium on charcoal
(30 mg) (Aldrich, USA). The reaction mixture was
refluxed for 0.5 h and then allowed to cool. The solution
was filtered through a pad of celite and the residue was
washed with methanol (2 · 2 mL). The filtrate combined
with washings was carefully evaporated under vacuum,
triturated with water (5 mL) and extracted with dichloro-
methane (2 · 5 mL). Removal of the solvent and chroma-
tography over silica gel (60–120 mesh) gave pure crystals
of phenol (90 mg), mp 41–42 ꢁC (lit.23 42 ꢁC).
19. Zacharie, B.; Moreau, N.; Dockendorff, C. J. Org. Chem.
2001, 66, 5264.
´
3. (a) Rudinger, J. Pure Appl. Chem. 1963, 7, 335; (b) Guibe,
F. Tetrahedron 1997, 53, 13509; (c) Schelhaas, M.;
Waldmann, H. Angew. Chem., Int. Ed. 1996, 35, 2056.
4. (a) Cunningham, J.; Gigg, R.; Warren, C. D. Tetrahedron
Lett. 1964, 1191; (b) Greene, T. W.; Wuts, P. G. M.
Protective Groups in Organic Synthesis, 3rd ed.; Wiley:
New York, 1999; (c) Kocienski, P. J. Protecting Groups.
Corrected Edition; Thieme: Stuttgart, 2000; (d) Beugel-
mans, R.; Bourdet, S.; Bigot, A.; Zhu, J. Tetrahedron Lett.
1994, 35, 4349; (e) Beugelmans, R.; Neuville, L.; Bois-
Choussy, M.; Chastanet, J.; Zhu, J. Tetrahedron Lett.
1995, 36, 3129; (f) Bois-Choussy, M.; Neuville, L.;
Beugelmans, R.; Zhu, J. J. Org. Chem. 1996, 61, 9309;
(g) Vutukuri, D. R.; Bharathi, P.; Yu, Z.; Rajasekaran, K.;
Tran, M.-H.; Thayumanavan, S. J. Org. Chem. 2003, 68,
1146; (h) Hutchings, R. O.; Learn, K.; Fulton, R. P.
Tetrahedron Lett. 1980, 21, 27.
20. Ranu, B. C.; Sarkar, A. Tetrahedron Lett. 1994, 35, 8649.
21. Furstner, A.; Seidel, G. J. Org. Chem. 1997, 62, 2332.
¨
22. Ram, S.; Spicer, L. D. Synth. Commun. 1992, 22, 2683.
23. Clarke, H. T. A Handbook of Organic Analysis, 5th ed.;
Arnold: London, 1975.
24. The current deallylation may be an isomerization–hydro-
lysis sequence with ammonium formate acting as a mild
hydrolytic cleaving agent for acid labile enol ethers
generated by isomerization of allyl ethers with Pd/C.
However, insertion of palladium between the C–O bond
by oxidative addition and removal of ArO from
the resulting p-allyl palladium complex by nucleophilic
attack of formate is an equally possible mechanistic
route.
5. Gigg, J.; Gigg, R. J. Chem. Soc. C 1966, 82.
6. Boss, R.; Scheffold, R. Angew. Chem., Int. Ed. Engl. 1976,
15, 558.
7. Ishizaki, M.; Yamada, M.; Watanabe, S.-I.; Hoshino, O.;
Nishitani, K.; Hayashida, M.; Tanaka, A.; Hara, H.
Tetrahedron 2004, 60, 7973.
8. Franco, D.; Panyella, D.; Rocamora, M.; Gomez, M.;
Clinet, J. C.; Muller, G.; Dunach, E. Tetrahedron Lett.
1992, 33, 2485.