Reactions >> Protecting Groups >> Stability

Allyl ethers

T. W. Green, P. G. M. Wuts, Protective Groups in Organic Synthesis,
Wiley-Interscience, New York, 1999, 67-74, 708-711.

Stability

H₂O:	pH < 1, 100°C	pH = 1, RT	pH = 4, RT	pH = 9, RT	pH = 12, RT	pH > 12, 100°C
Bases:	LDA	NEt₃, Py	t-BuOK	Others:	DCC	SOCl₂
Nucleophiles:	RLi	RMgX	RCuLi	Enolates	NH₃, RNH₂	NaOCH₃
Electrophiles:	RCOCl	RCHO	CH₃I	Others:	:CCl₂	Bu₃SnH
Reduction:	H₂ / Ni	H₂ / Rh	Zn / HCl	Na / NH₃	LiAlH₄	NaBH₄
Oxidation:	KMnO₄	OsO₄	CrO₃ / Py	RCOOOH	I₂, Br₂, Cl₂	MnO₂ / CH₂Cl₂

General

The allyl group is a commonly used protecting group for alcohols, with relative stability towards both acidic and basic conditions that permits orthogonal protection strategies. Isomerization to the more labile enol ether employing KOtBu, with subsequent mild acidic hydrolysis, is one of the most common deprotection methods. However, KOtBu can only be used, when the substrate is not base sensitive.

The properties of the allylic double bond may be exploited to effect a one-step deprotection, by activation of the double bond by a palladium catalyst with subsequent reduction or SET (single electron transfer), or by selective oxidation. Some of these newer methods are highlighted below.

Protection of Hydroxyl Compounds

M. Ishizaki, M. Yamada, S.-I. Watanabe, O. Hoshino, K. Nishitani, M. Hayashida, A. Tanaka, H. Hara, Tetrahedron, 2004, 60, 7973-7981.

Deprotection

A mixture of trihaloboranes triggers a regioselective cleavage of unsymmetrical alkyl ethers to generate alkyl alcohol and alkyl bromide products. This conversion exhibits improved regioselectivity and yield compared with BBr₃ alone.
B. J. P. Atienza, N. Truong, F. J. Williams, Org. Lett., 2018, 20, 6332-6335.

tert-Butyllithium induces a cleavage of allylic ethers to the corresponding alcohols or phenols in excellent yield at low temperatures in n-pentane. The reaction produces 4,4-dimethyl-1-pentene as a coproduct and most likely involves a S_N2' process, in which the organolithium attacks the allyl ether.
W. F. Bailey, M. D. England, M. J. Mealy, C. Thongsornkleeb, L. Teng, Org. Lett., 2000, 2, 489-491.

A new one-pot method is described for the removal of O- and N-allyl protecting groups under oxidative conditions at near neutral pH. The allyl group undergoes hydroxylation and subsequent periodate scission of the vicinal diol. Repetition of this reaction sequence on the enol tautomer of the aldehyde intermediate releases the deprotected functional group.
P. I. Kitov, D. R. Bundle, Org. Lett., 2001, 3, 2835-2838.

Pd(0)-catalyzed deprotection of allyl ethers using barbituric acid derivatives in protic polar solvent such as MeOH and aqueous 1,4-dioxane proceeds at room temperature without affecting a wide variety of functional groups. Control of the reaction temperature allows selective and successive cleavage of allyl, methallyl, and prenyl ethers.
H. Tsukamoto, T. Suzuki, Y. Kondo, Synlett, 2007, 3131-3132.

A mild deprotection strategy for allyl ethers under basic conditions in the presence of a palladium catalyst allows the deprotection of aryl allyl ethers in the presence of alkyl allyl ethers. These conditions are also effective in the deprotection of allyloxycarbonyl groups.
D. R. Vutukuri, P. Bharathi, Z. Yu, K. Rajasekaran, M.-H. Tran, S. Thayumanavan, J. Org. Chem., 2003, 68, 1146-1149.

Deprotection of allyl ethers, amines and esters to liberate hydroxyl, amino and acid groups is achieved under mild conditions. The reagent combination employed for this transformation is polymethylhydrosiloxane (PMHS), ZnCl₂ and Pd(PPh₃)₄.
S. Chandrasekhar, R. Reddy, R. J. Rao, Tetrahedron, 2001, 57, 3435-3438.

A combination of a Ni-H precatalyst and excess Brønsted acid enables a deallylation of O- and N-allyl functional groups. Key steps are a Ni-catalyzed double-bond migration of the O- and N-allyl group followed by Brønsted acid induced O/N-C bond hydrolysis. This deprotection method tolerates a broad range of functional groups.
P. M. Kathe, A. Berkefeld, I. Fleischer, Synlett, 2021, 32, 1629-1632.

Selective cleavage of unsubstituted allyl ethers is provided by SmI₂/H₂O/i-PrNH₂ in very good yields. This method is useful in the deprotection of alcohols and carbohydrates.
A. Dahlen, A. Sundgren, M. Lahmann, S. Oscarson, G. Hilmersson, Org. Lett., 2003, 5, 4085-4088.

Allyl aryl ethers can be easily cleaved by the use of 10% Pd/C under mild and basic conditions. The present reaction would involve a SET process rather than a π-allyl-palladium complex. The scope and limitation of this new deprotective methodology are also described.
M. Ishizaki, M. Yamada, S.-I. Watanabe, O. Hoshino, K. Nishitani, M. Hayashida, A. Tanaka, H. Hara, Tetrahedron, 2004, 60, 7973-7981.

A selective deallylation of o-Allyloxyanisoles by treatment with sec- or tert-butyllithium at low temperature proceeds through a tandem intermolecular carbolithiation-β-elimination process.
R. Sanz, A. Martínez, C. Marcos, F. J. Fañanás, Synlett, 2008, 1957-1960.

Conversion of Allyl Ethers

Claisen Rearrangement

[2,3]-Wittig Rearrangement

B. Schmidt, Eur. J. Org. Chem., 2003, 816-819.

An efficient Z-selective oxidative isomerization process of allyl ethers catalyzed by a cobalt(II) (salen) complex using N-fluoro-2,4,6-trimethylpyridinium trifluoromethanesulfonate (Me₃NFPY•OTf) as an oxidant provides thermodynamically less stable Z-enol ethers in excellent yields with high geometric control. Diallyl ethers can also be isomerized at room temperature.
G. Huang, M. Ke, Y. Tao, F. Chen, J. Org. Chem., 2020, 85, 5321-5329.