Facile O-deallylation of allyl ethers via SN2′ reaction with tert-butyllithium

Article abstract of DOI:10.1021/ol991342g

(Formula presented) Allylic ethers are converted to the corresponding alcohol or phenol in virtually quantitative yield at temperatures below ambient simply by stirring a hydrocarbon solution of the ether with 1 molar equiv of tert-butyllithium. The reaction, which produces 4,4-dimethyl-1-pentene as a coproduct, most likely involves an S_N2′ attack of the organolithium on the allyl ether.

Full text of DOI:10.1021/ol991342g

ORGANIC
LETTERS
2000
Vol. 2, No. 4
489-491
Facile O-Deallylation of Allyl Ethers via
SN2′ Reaction with tert-Butyllithium
,†
William F. Bailey,* Michael D. England,‡ Michael J. Mealy,†
Charnsak Thongsornkleeb,† and Lisa Teng†
Departments of Chemistry, UniVersity of Connecticut, Storrs, Connecticut 06269-3060,
and Fairfield UniVersity, Fairfield, Connecticut 06430-5195
bailey@uconn.edu
Received December 13, 1999
ABSTRACT
Allylic ethers are converted to the corresponding alcohol or phenol in virtually quantitative yield at temperatures below ambient simply by
stirring a hydrocarbon solution of the ether with 1 molar equiv of tert-butyllithium. The reaction, which produces 4,4-dimethyl-1-pentene as a
coproduct, most likely involves an SN2′ attack of the organolithium on the allyl ether.
The selective metalation resulting from treatment of simple
allyl ethers with an organolithium reagent has been known
for over 25 years.1 As illustrated in Scheme 1, the Z-
electrophiles at low temperature,1 while at higher tempera-
tures [1,2]- and [1,4]-Wittig rearrangements are observed.3
It is significant that in virtually all of these studies a strongly
lithiophilic solvent such as THF was used for the deproton-
ation.1,2
In light of the facility with which allyl ethers are
deprotonated in the presence of an organolithium, we were
intrigued by a 1965 paper by Broaddus reporting the cleavage
of several alkyl allyl ethers upon treatment with n-butyl-
lithium in a hydrocarbon solution at 70 °C to give the lithium
alkoxide and 1-heptene.4 The reaction was formulated
(Scheme 2) as an SN2′ process in which coordination of the
Scheme 1
Scheme 2
configured allyloxy organometallic species produced by
deprotonation at the allylic position2 may be trapped by
† University of Connecticut.
organolithium with the ether oxygen provides a cyclic
transition state for the cleavage.4
‡ Fairfield University.
(1) (a) Evans, D. A.; Andrews, G. C.; Buckwalter, B. J. Am. Chem. Soc.
1974, 96, 5560. (b) Still, W. C.; Macdonald, T. L. J. Am. Chem. Soc. 1974,
96, 5563. (c) Hartmann, J.; Muthukrishnan, R.; Schlosser, M. HelV. Chim.
Acta 1974, 57, 2261. (d) Still, W. C.; Macdonald, T. L. J. Org. Chem.
1976, 41, 3620. (e) Hoppe, D. Angew. Chem., Int. Ed. Engl. 1984, 23, 932
and references therein.
(3) (a) For a review of the literature dealing with Wittig rearrangements,
see: Scho¨llkopf, U. Angew. Chem., Int. Ed. Engl. 1970, 9, 763. (b) For a
discussion of the synthetic utility of the [1,4]-Wittig rearrangement, see:
Schlosser, M.; Strunk, S. Tetrahedron 1989, 45, 2649.
(2) Gschwend, H. W.; Rodriguez, H. R. Org. React. 1979, 1.
(4) Broaddus, C. D. J. Org. Chem. 1965, 30, 4131.
10.1021/ol991342g CCC: $19.00 © 2000 American Chemical Society
Published on Web 01/28/2000

It would appear that solvent has a profound effect on the
outcome of the reaction of an organolithium with an allyl
ether, and this suggests that the state of aggregation of the
organolithium may be the factor responsible for the course
of the reaction. It occurred to us that it might be possible to
test this hypothesis by observing the outcome of the reaction
of an allyl ether with tert-butyllithium (t-BuLi) in various
solvents since it is known that t-BuLi is predominantly
tetrameric in hydrocarbon solution,5 dimeric in diethyl ether,6
and monomeric in THF.7 As demonstrated by the results
presented below, the degree of association of t-BuLi has a
dramatic effect on the course of the reaction of this reagent
with an allyl ether. Herein we report that a variety of allyl
ethers may be deallylated in virtually quantitative yield at
temperatures below ambient simply by stirring a hydrocarbon
solution of the ether with 1 equiv of t-BuLi.
Scheme 3
illustrated in Scheme 3, the course of the reactions is quite
solvent dependent: in THF the principal products arise from
[1,2]- and [1,4]-Wittig rearrangement of the lithiated ether3
and in Et2O the major course of the reaction is cleavage of
the allyl ether, while in a pentane solution the exclusive
Treatment of allyl hexyl ether in THF, Et2O, or n-pentane
solution with 1 equiv of t-BuLi in pentane for 1 h at 0 °C
leads to complete consumption of the ether as adjudged by
GC analysis of the crude reaction mixtures. However, as
Table 1. t-BuLi-Induced Deallylation (Scheme 4)a
a A solution of the allyl ether in dry n-pentane (typically 1 mL per mmol of ether) was cooled to -78 °C, 1.1 equiv of t-BuLi in pentane was added, and
the resulting solution was allowed to warm and stand at room temperature for 1 h before being quenched with 10% aqueous HCl. b Isolated yield of
chromatographically pure product.
490
Org. Lett., Vol. 2, No. 4, 2000

product is 1-hexanol (it should be noted that an equivalent
amount of 4,4-dimethyl-1-pentene is also produced); there
was no evidence of any products arising from deprotonation
of the allyl hexyl ether in the pentane solution. Clearly,
t-BuLi in pentane is an effective reagent for O-deallylation
of allyl hexyl ether and, as demonstrated by the results
summarized in Table 1, this reaction appears to be quite
general.
The allyl unit is widely used as a robust protecting group
for alcohols and phenols, and a variety of methods have been
developed for its removal.8 Most deprotection methods rely
on a two-step process involving isomerization of the allyl
ether to an enol ether and subsequent hydrolysis or oxidation8
although one-pot procedures have been recently developed.9
The facile cleavage of allyl ethers upon treatment with t-BuLi
in hydrocarbon solution (Scheme 4) provides an alternative
Allyl ethers derived from primary, secondary, or tertiary
alcohols (Table 1, entries 1-4) as well as those derived from
a phenol (Table 1, entries 5 and 6) are cleaved cleanly and
in excellent yield. It is significant that the allyl group may
be selectively removed in the presence of a benzyloxy group
(Table 1, entry 6). As might be expected, selective O-
deallylation may be accomplished in the presence of an acetal
(Table 1, entries 7 and 8) or a tert-butyldimethylsilyl
protecting group (Table 1, entry 9).
The O-deallylation reaction outlined above (Scheme 4)
provides a practical, convenient, and highly efficient method
for the removal of an allyl protecting group, providing that
the molecule is otherwise able to tolerate the use of t-BuLi.
The mechanism of the cleavage reaction most likely involves
a formal SN2′ process (Scheme 2) as first suggested by
Broaddus in his pioneering study of the cleavage of alkyl
allyl ethers by n-BuLi in hydrocarbon solution at elevated
temperature.4
Scheme 4
Acknowledgment. This work was supported by Pfizer,
Inc., Groton, CT, and by a NSF Research Experience for
Undergraduates (REU) Program grant. M.D.E. was an REU
participant at UCONN and thanks Pfizer for an Undergradu-
ate Summer Research Fellowship; C.T. thanks Pfizer for
support through the PREPARE program for undergraduates.
We are grateful to Dr. Terry Rathman of FMC, Lithium
Division, for a generous gift of t-BuLi.
and very convenient method for the selective removal of an
allyl protecting group.
The O-deallylation of an allyl ether is easily accomplished
by adding slightly more than 1 molar equiv of t-BuLi in
either pentane or heptane to a cold10 solution of the allyl
ether in dry pentane (ca. 1 mL/mmol of ether), removing
the cooling bath, and allowing the resulting solution to stand
at room temperature for 1 h.11 Addition of aqueous acid
followed by simple extractive workup affords an essentially
pure alcohol in high yield after removal of volatile compo-
nents (including 4,4-dimethyl-1-pentene) by rotary evapora-
tion. Examples representative of the scope of this O-de-
allylation protocol are presented in Table 1.12
Supporting Information Available: Experimental pro-
cedures describing the preparation of previously unreported
compounds and general procedure for deallylation of allyl
ethers. This material is available free of charge via the
Internet at http://pubs.acs.org.
OL991342G
(10) The reaction of t-BuLi with an allyl ether in pentane solution is
typically quite exothermic, and for this reason it is prudent to initiate the
reaction at a low temperature. The reactions summarized in Table 1 were
initiated most conveniently by addition of t-BuLi to a -78 °C solution of
the allyl ether in pentane and removal of the cooling bath. It might be noted
that the reactions may be initiated at higher temperatures (i.e., 0 °C or higher)
if care is taken to control the exotherm.
(11) As suggested by the results summarized in Scheme 3, the deallylation
may also be run at low temperature using diethyl ether as solvent with
only a slight diminution in yield. However, we favor the use of pentane (or
similar hydrocarbon) as solvent due to the fairly rapid reaction of t-BuLi
with diethyl ether at temperatures near ambient.
(12) All but two of the allyl ethers used in this study are known
compounds whose physical and spectroscopic properties are fully in accord
with those reported in the literature. The preparations of 1-allyloxy-4-
(tetrahydropyran-2-yloxy)butane (Table 1, entry 8) and 1-allyloxy-4-(tert-
butyldimethylsilyloxy)butane (Table 1, entry 9) are detailed in the Sup-
porting Information accompanying this Letter.
(5) Brown, T. L. Acc. Chem. Res. 1968, 1, 23.
(6) Bates, T. F.; Clarke, M. T.; Thomas, R. D. J. Am. Chem. Soc. 1988,
110, 5109.
(7) Bauer, W.; Winchester, W. R.; Schleyer, P. v. R. Organometallics
1987, 6, 2371.
(8) (a) Green, T. W.; Wuts, P. G. M. ProtectiVe Groups in Organic
Synthesis, 3rd ed.; Wiley: New York, 1999; pp 67-74. (b) Guibe´, F.
Tetrahedron 1997, 53, 13509; Tetrahedron 1998, 54, 2967.
(9) (a) Takahiko, T.; Ogasawara, K. Angew. Chem., Int. Ed. 1998, 37,
1136. (b) Kamal, A.; Laxman, E.; Rao, N. V. Tetrahedron Lett. 1999, 40,
371. (c) Yasuhara, A.; Kasano, A.; Sakamoto, T. J. Org. Chem. 1999, 64,
4211. (d) Chandrasekhar, S.; Mohanty, P. K.; Ramachander, T. Synlett 1999,
1063.
Org. Lett., Vol. 2, No. 4, 2000
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