Isomerization of allyl ethers initiated by lithium diisopropylamide

Article abstract of DOI:10.1021/ol102029u

Lithium diisopropylamide (LDA) promotes virtually quantitative conversion of allylic ethers to (Z)-propenyl ethers. It was discovered that allylic ethers can be isomerized efficiently with very high stereoselectivity to (Z)-propenyl ethers by LDA in THF a

Full text of DOI:10.1021/ol102029u

ORGANIC
LETTERS
2010
Vol. 12, No. 23
5378-5381
Isomerization of Allyl Ethers Initiated by
Lithium Diisopropylamide
Chicheung Su and Paul G. Williard*
Department of Chemistry, Brown UniVersity, ProVidence,
Rhode Island 02912, United States
pgw@brown.edu
Received August 26, 2010
ABSTRACT
Lithium diisopropylamide (LDA) promotes virtually quantitative conversion of allylic ethers to (Z)-propenyl ethers. It was discovered that allylic
ethers can be isomerized efficiently with very high stereoselectivity to (Z)-propenyl ethers by LDA in THF at room temperature. The reaction
time for the conversion increases with more sterically hindered allylic ethers. Different amides were also compared with LDA for their ability
to effect this isomerization.
Vinyl ethers are important synthetic intermediates in numer-
ous reactions such as isoxazoline synthesis,1 cycloaddition,2
Scheme 1. Isomerization of Allyl Ethers Initiated by LDA
and cross aldol reactions.3 Moreover, vinyl ethers can be
easily photopolymerized to produce polymers that are used
as photocurable coatings, inks, and adhesives.4 An efficient
preparation of vinyl ethers is to prepare allyl ethers by
O-alkylating an alcohol with allyl bromide followed by
isomerization.5 Such isomerization reactions have been
studied and are divided into two categories: base-catalyzed6
and transition-metal-catalyzed reactions.7 Ruthenium and
iridium complexes are reported to catalyze allyl ethers
stereoselectively to trans-vinyl ethers.7-9 Although it is
convenient to use transition metal complexes, the methods
suffer from the fact that both ruthenium and iridium are
expensive and are not suitable for large -scale reactions.
While iron and molybdenum complex catalyzed isomeriza-
tion reactions have also been reported, both reactions
produced mixtures of cis and trans isomers.5,10 For the base-
catalyzed reactions, the most widely used method is to treat
the allyl ethers with potassium tert-butoxide (t-BuOK) in
(1) Krompiec, S.; Bujak, P.; Szczepankiewicz, W. Tetrahedron Lett.
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1883.
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Crivello, J. V. Opt. Mater. 2002, 21, 343–347.
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Commun. 1998, 133, 7–1338. (b) Krompiec, S.; Kuznik, N.; Urbala, M.;
Rzepa, J. J. Mol. Catal. A: Chem. 2006, 248, 198–209. (c) Carless, H. A.;
Haywood, D. J. J. Chem. Soc., Chem. Commun. 1980, 980–981
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83, 1773. (c) Taskinen, E.; Laine, M. Struct. Chem. 1997, 8, 367–372.
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1983, 252, 105–112
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10.1021/ol102029u  2010 American Chemical Society
Published on Web 11/01/2010

Table 1. LDA-Catalyzed Isomerization of Various Allyl Ethersa
a A solution of diisopropylamine in dry THF was cooled to -78 °C; 1 equiv of n-BuLi in n-pentane was added dropwise; and the resulting solution was
allowed to cool in a -78 °C bath for 5 min before the allyl ether was added drop by drop to the solution. The solution was allowed to warm and stand at
room temperature for the corresponding amount of time before being quenched with saturated ammonium chloride solution.
dimethyl sulfoxide (DMSO) solution. Although the method
achieved varying degrees of success,5,11-13 it is limited by
the fact that heating is usually required for the isomerization
reaction.6a,12,13 Moreover, since the reaction is exothermic,
an increase in temperature will cause the equilibrium to shift
back to the allyl ethers.14 Butyllithium has also been reported
to isomerize allyl ethers,15 but the yields were relatively low
due to the fact that deallylation16 or Wittig rearrangement17
may occur. We report an efficient method of allyl ether
isomerization initiated by LDA (Scheme 1) and a comparison
(11) Endo, K.; Otsu, T. Polymer 1991, 32, 2856–2861
(12) Evans, D. A.; Kvaerno, L.; Dunn, T. B.; Beauchemin, A.; Raymer,
B.; Mulder, J. A.; Olhava, E. J.; Juhl, M.; Kagechika, K.; Favor, D. A.
.
(14) Taskinen, E. J. Chem. Soc., Perkin Trans. 2001, 2, 1824–1834.
(15) Harmata, M.; Lee, D. R.; Barnes, C. L. Org. Lett. 2005, 7, 1881–
1883.
J. Am. Chem. Soc. 2008, 130, 16295–16309
.
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Teng, L. Org. Lett. 2000, 2, 489–491.
(13) Davis, C. E.; Duffy, B. C.; Coates, R. M. J. Org. Chem. 2003, 68,
6935–6943
.
(17) Schollkopf, U. Angew. Chem., Int. Ed. 1970, 9, 763–773.
Org. Lett., Vol. 12, No. 23, 2010
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of a series of t-BuOK-initiated isomerization reactions with
the LDA-initiated isomerization.
Several different amide bases have also been tested for
their ability to effect this isomerization reaction. The allyl
ether derived from cycloheptanol (Scheme 2) was chosen
In 1970, Dimmel and Gharpure reported the use of sodium
amide in dimethoxyethane to isomerize allyl phenyl ether
to (Z)-(prop-1-en-1-yloxy)benzene in 54% yield.18 To the
best of our knowledge, this is the first allyl ether isomer-
ization using an amide base. We report that lithium diiso-
propylamide effects this isomerization in ethereal solvents
like THF and dimethoxyethane readily. Other allyl ethers
have also been investigated, and these results are summarized
in Table 1.
Scheme 2
.
Isomerization of (Allyloxy)cycloheptane Initiated by
Different Amides
as the model substrate for surveying the effectiveness of
different amides because it has no ꢀ branched chain and
because of its relative high boiling point. The results are
summarized in Table 2.
Figure 1. (a) Definition of R and ꢀ positions and R′ group of the
Table 2. Isomerization of (Allyloxy)cycloheptane by Different
Amides
allyl ethers. (b) An example of allyl ether without ꢀ branched chain.
(c) An example of allyl ether with only one ꢀ branched chain. (d)
An example of allyl ether with two ꢀ branched chains.
Branched chains at the ꢀ-position (Figure 1) of the allyl
ethers reduce the speed of isomerization depending on the
extent of substitution and steric bulk of the branched chain.
Allyl ethers with no ꢀ branched chain (Table 1, entries 1-5,
7) isomerize much faster than other allyl ethers with ꢀ
branched chains. Allyl ethers having only one ꢀ branched
chain (Table 1, entries 6, 8) react faster than those with two
ꢀ branched chains (Table 1, entry 10). When ꢀ branched
chains are on both sides of the allyl ether (Table 1, entry
11), the isomerization rate decreases drastically. The results
suggest that steric hindrance in the ꢀ position plays an
important role in the rate of isomerization. Moreover, the
allyl ether derived from borneol (Table 1, entry 9) isomerized
much faster than that derived from isoborneol (Table 1, entry
10) presumably due to the fact that the allyl group from the
former one experiences less steric hindrance than the allyl
group of the latter one.
The isomerization rate slows down when R′ is a methyl
group instead of a proton (Figure 1, 1a). However, the effect
of a γ branched chain (Figure 1, 1a) on reaction rate is small
compared to the effect of a ꢀ branched chain. The isomer-
ization reaction for allyl ether derived from 3,3,5,5-tetram-
ethylcyclohexanol (Table 1, entry 5) was done within 45 min
and was much faster than that of menthol derived allyl ether
(Figure 1, 1c).
a 5 equiv if lithium amide base was used.
Lithium bis(trimethylsilyl)amide (LiHMDS) failed to
initiate the reaction. Neither lithium nor sodium amide
effected this rearrangement. The reaction time for entry 3
was significantly longer than that of entries 1 and 2 probably
because the lithium ion was internally solvated.19
Several experiments using tert-butoxide/DMSO (Scheme
3) have been done, and the results were compared to the
LDA-initiated isomerization (Table 3).
Scheme 3. Allyl Ether Isomerization Catalyzed by tBuOK
We suspect that the yields of the reactions of enol ethers
with lower boiling points appear lower and are correlated
with the boiling points of the enol ethers because some loss
of the lower boiling products was unavoidable upon work
up.
Entries 1-4 in Table 3 highlight that heating (larger than
60 °C) is required for tBuOK-catalyzed reactions. Although
(19) (a) Fraenkel, G.; Chen, X.; Chow, A.; Gallucci, J. C.; Liu, H. J.
Org. Chem. 2005, 70, 9131–9138. (b) Fraenkel, G.; Gallucci, J.; Liu, H.
J. Am. Chem. Soc. 2006, 128, 8211–8216.
(18) Dimmel, D. R.; Gharpure, S. B. J. Am. Chem. Soc. 1971, 93, 3991–
3996.
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Org. Lett., Vol. 12, No. 23, 2010

Table 3. Comparison of tBuOK and LDA-Initiated
Isomerization
Scheme 4. Isomerization of 2a Catalyzed by LDA and tBuOK
the products (see Supporting Information). By comparing
the spectrum of the product from the isomerization of 2a by
LDA with that of pure 2a, we note that one of the two allyl
groups has been selectively isomerized to a propenyl group.
However, the spectrum of the products of tBuOK-catalyzed
isomerization of 2a shows that a mixture of E- and
Z-propenyl ether isomers is formed from the less steric
hindered allyl ether group. Moreover, a significant amount
of the more steric hindered allyl group was isomerized to
propenyl ether before the less hindered allyl group has been
isomerized.
a Ratio ) amount of enol ether/amount of starting allyl ether. b The
end mixture/starting allyl ether is less than 60%.
the isomerization of allyl ethers can be done at 120 °C, the
rate of reaction is far slower than that of LDA-catalyzed
isomerization (Table 3, entries 5 and 6). Besides, for tBuOK-
catalyzed reactions, the mass of the resulting mixtures of
enol and allyl ethers recovered was less than 60% of the
starting allyl ethers. We suggest that this is likely due to the
high temperature of the reaction mixtures allowing the allyl
ethers to volatilize or decompose. Therefore, it is clear that
the LDA-catalyzed isomerization is more effective than that
which utilizes tBuOK.
A comparison of LDA and tBuOK in the isomerization
of 2a was carried out to highlight the advantage of LDA-
catalyzed isomerization over tBuOK (Scheme 4). LDA
regioselectively isomerizes the less steric hindered allyl ether
group to yield Z-propenyl ether completely stereoselectivity
in quantitative yield. However, the tBuOK-catalyzed isomer-
ization of 2a was not as regio- and stereoselective as the
LDA-catalyzed one as shown by the 13C NMR spectrum of
In conclusion, the LDA isomerization reaction outlined
above provides a convenient, inexpensive, and highly ef-
ficient method for the isomerization of allyl ethers to
propenyl ethers. Future work will focus on studying the
kinetics of the reaction with a goal of unveiling a more
detailed mechanism of the complexes involved in this
isomerization reaction.
Acknowledgment. This work was supported through NSF
grant 0718275.
Supporting Information Available: Experimental pro-
cedures, reproductions of NMR, mass spectra, and gas
chromatograms. This material is available free of charge via
the Internet at http://pubs.acs.org.
OL102029U
Org. Lett., Vol. 12, No. 23, 2010
5381