metal catalysts such as the Wilkinson’s catalyst.4 More
recently, several other reagents have been utilized for
the direct deprotection of allyl ethers. These include
NBS,5 Cp2Zr,6 SmCl3,7 TiCl3,8 DDQ,9 NaBH4/I2,10 and
CeCl3‚7H2O-NaI.11 Several methodologies demonstrate
that the cleavage of allyl groups can be performed under
palladium-catalyzed reaction conditions.12 All these pal-
ladium-catalyzed methodologies are carried out either
under acidic conditions or in the presence of a reducing
agent such as sodium borohydride. We have been inter-
ested in the deprotection of allyl groups under mildly
basic conditions, since we have utilized this protecting
group for sequence specific incorporation of monomers
in dendrimer synthesis.13 It is also noteworthy that others
have used allyl-protecting groups for functionalized den-
drimer synthesis as well.14
During our dendrimer synthesis based on biaryl
functionalities,15a we noticed that allyl ethers can be
cleaved under Suzuki coupling conditions (Pd(PPh3)4, K3-
PO4, DME, reflux).15b However, this reaction was not
clean enough to be an effective methodology. Therefore,
we optimized the reaction conditions and found that allyl
ethers can be cleaved smoothly using Pd(PPh3)4 (0.05-
1.00 mol %) and K2CO3 (3-6 equiv) in methanol (Table
1). The reagent can be considered as a general deally-
lating agent useful for aryl as well as alkyl allyl ethers,
and the yields range from 82 to 97% as outlined in Table
1.
A Mild Dep r otection Str a tegy for
Allyl-P r otectin g Gr ou p s a n d Its
Im p lica tion s in Sequ en ce Sp ecific
Den d r im er Syn th esis
Dharma Rao Vutukuri, Pandi Bharathi, Zhouying Yu,
Karthik Rajasekaran, My-Huyen Tran, and
S. Thayumanavan*
Department of Chemistry, Tulane University,
New Orleans, Louisiana 70118
thai@tulane.edu
Received September 23, 2002
Abstr a ct: A mild deprotection strategy for allyl ethers
under basic conditions in the presence of a palladium
catalyst is described. Under these conditions, aryl allyl
ethers can be cleaved selectively in the presence of alkyl allyl
ethers. These conditions are also effective in the deprotection
of allyloxycarbonyl groups. The utility of the current meth-
odology in sequence specific dendrimer synthesis is demon-
strated.
Protection and deprotection components of organic
synthesis have been compared to death and taxes in
organic synthesis: they are not desirable; however, they
are unavoidable.1a Although some of the most elegant
syntheses in the literature involve strategies that avoid
the use of protecting groups, protection-deprotection
strategies are ubiquitous in synthesis in general. The
inherent nature of the usage of protection and deprotec-
tion strategies dictates that these reactions must be
performed in the presence of a variety of other functional
groups. This is especially true for the deprotection step,
since it is performed later in the synthesis. Therefore, it
is desirable to develop methodologies that afford high
yielding deprotections under mild reaction conditions.
The allyl group has been frequently used in organic
synthesis as a protecting group for alcohols and amines
due to its stability under basic and acidic conditions.1 In
this paper, we outline a mild deprotection strategy for
allyl ethers. We also show the following: (i) this meth-
odology can be used to deprotect aryl allyl ethers in the
presence of alkyl allyl ethers. (ii) Allyl ethers are cleaved
exclusively in the presence of benzyl ethers. (iii) Ally-
loxycarbonyl groups can also be cleaved in high yields
under these reaction conditions. (iv) This methodology
is useful in the sequence specific incorporation of func-
tionalities in dendrimer synthesis.
At first, we examined the deprotection of 1 with 1 mol
% of Pd(PPh3)4 and 3 equiv of K2CO3 in methanol. After
the mixture was stirred at room temperature for 2 h,
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(12) For methodologies involving Pd(PPh3)4-NaBH4 or LiBH4, see:
(a) Beugelmans, R.; Bourdet, S.; Bigot, A.; Zhu, J . Tetrahedron Lett.
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Choussy, M.; Neuville, L.; Beugelmans, R.; Zhu, J . J . Org. Chem. 1996,
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For palladium-catalyzed allyl cleavage under acidic conditions, see:
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Chem. Soc. 1991, 113, 2092. (f) Nakayama, K.; Uoto, K.; Higashi, K.;
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to react with the Pd-π-allyl species. However, note that this claim is
unsubstantiated at this time.
The removal of an allyl protecting group in classical
syntheses typically involves a two-step sequence, in
which isomerization of the double bond to the corre-
sponding prop-1-enyl ether is followed by either H+- or
Hg2+-catalyzed hydrolysis or oxidative cleavage.2 Isomer-
ization of the allyl to prop-1-enyl group has been achieved
with strong bases such as KOtBu-DMSO3 or transition
(13) Sivanandan, K.; Vutukuri, D.; Thayumanavan, S. Org. Lett.
2002, 4, 3751.
(14) (a) Yamakawa, Y.; Ueda, M.; Nagahata, R.; Takeuchi, K.; Asai,
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J . M.; Chaumette, J .-L.; Sarazin, D.; Parquette, J . R. J . Org. Chem.
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(15) (a) Bharathi, P.; Zhao, H.; Thayumanavan, S. Org. Lett. 2001,
3, 1961. (b) Bharathi, P.; Thayumanavan, S. Unpublished results from
Tulane University.
(1) (a) Kocienski, P. J . In Protecting Groups; Georg Theime Verlag:
Stuttgart and New York, 1994. (b) Greene, T. W.; Wuts, P. G. M.
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10.1021/jo026469p CCC: $25.00 © 2003 American Chemical Society
Published on Web 12/21/2002
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J . Org. Chem. 2003, 68, 1146-1149