A facile and stereoselective synthetic method for allylic 1,3-dienyl ethers

Article abstract of DOI:10.1016/j.tetlet.2006.08.100

The 1,4-elimination reaction of 1-allyloxy-4-methoxy-(2Z)-alkenes with n-butyllithium is shown to proceed in a marked preference to the [2,3] Wittig rearrangement to afford the allylic (1Z,3E)-dienyl ethers in high stereoselectivities. The synthetic utili

Full text of DOI:10.1016/j.tetlet.2006.08.100

Tetrahedron Letters 47 (2006) 7533–7535
A facile and stereoselective synthetic method
for allylic 1,3-dienyl ethers
Eiji Tayama,* Sayaka Sugai and Masahiro Hara
Graduate School of Science and Technology, Niigata University, Niigata 950-2181, Japan
Received 28 July 2006; revised 22 August 2006; accepted 24 August 2006
Abstract—The 1,4-elimination reaction of 1-allyloxy-4-methoxy-(2Z)-alkenes with n-butyllithium is shown to proceed in a marked
preference to the [2,3] Wittig rearrangement to afford the allylic (1Z,3E)-dienyl ethers in high stereoselectivities. The synthetic utility
of this method is demonstrated by the Claisen rearrangement of the dienyl ethers thus obtained.
Ó 2006 Elsevier Ltd. All rights reserved.
The Claisen rearrangement is one of the most important
transformations in organic synthesis, since it can readily
create a new C–C bond with a high degree of stereocon-
trol.1 Among several Claisen variants developed so far,
the original Claisen rearrangement of allylic enol (or
dienol) ethers has found relatively limited use due to
the difficulty with the stereoselective preparations of
the substrates thereof. Very recently, we have reported
an efficient and stereoselective synthetic method of 1,3-
dienyl silyl ethers via the 1,4-elimination of 1-siloxy-4-
methoxy-(2Z)-alkenes with n-butyllithium.2–4 With the
method in hand, we have now explored the feasibility
of the similar 1,4-elimination of the 1-allyloxy deriva-
tives, which would afford the corresponding allyl 1,3-
dienyl ethers, useful substrates for the Claisen and tan-
dem Claisen–Cope rearrangement, while the 1-allyloxy
substrates (as bis-allylic ethers) might also undergo the
[2,3] Wittig rearrangement5 (vide infra) which sup-
presses the desired 1,4-elimination. We now wish to
report that a simple treatment of 1-allyloxy-4-meth-
oxy-(2Z)-alkenes (1) with n-butyllithium affords the
allylic 1,3-dienyl ethers (2) in a high (1Z,3E)-stereoselec-
tivity without appreciable occurrence of the [2,3] Wittig
rearrangement concerned.
1-allyloxy-1,3-undecadiene (2a) was obtained in a 77%
yield with a high (1Z,3E)-stereoselectivity.7 The stereo-
chemistry was determined by the 1H NMR assay
(J1H,2H = 6.2 Hz and J3H,4H = 15.2 Hz). Interestingly,
the formation of the a0-[2,3] Wittig product 3a was
almost completely inhibited (5%).8 In contrast, a similar
reaction, when carried out in THF at ꢀ78 °C, provided
the a0-[2,3] Wittig product 3a in a 40% yield (as an
almost single diastereomer) along with a 22% recovery
of 1a.9 Any appreciable amount of the a-1,4-elimination
product 2a was not detected (Scheme 1).
Of mechanistic interest is that the a-1,4-elimination
overwhelmingly prevails the a0-[2,3] Wittig rearrange-
ment in ether (not in THF). This observation strongly
suggests that the 1,4-elimination in ether does not
involve any lithiation process, since the [2,3] Wittig
rearrangement of bis-allylic ethers is known to proceed
via lithiation preferentially on the less substituted allylic
First, we carried out the reaction of 1-allyloxy-4-meth-
oxy-(2Z)-undecene (1a)6 with n-butyllithium (1.5 equiv)
in ether. Fortunately, the 1,4-elimination product,
Scheme 1. a-1,4-Elimination reaction of 1-allyloxy-4-methoxy-(2Z)-
undecene (1a) with n-butyllithium: a The yield was determined by 1H
NMR assay using 1,4-bis(trifluoromethyl)benzene as an internal
standard. b The starting material 1a was recovered in 22%.
Keywords: Allylic 1,3-dienyl ethers; 1,4-Elimination; Wittig rearrange-
ment; Claisen rearrangement; Cope rearrangement.
*
Corresponding author. Tel./fax: +81 25 262 7741; e-mail: tayama@
gs.niigata-u.ac.jp
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.08.100

7534
E. Tayama et al. / Tetrahedron Letters 47 (2006) 7533–7535
Scheme 2. The E2 elimination mechanism of a-1,4-elimination
reaction.
Scheme 3. Application of allylic 1,3-dienyl ethers for Claisen or
Claisen–Cope tandem rearrangements.
moiety (a0-position at this case) as actually observed in
THF.10 Thus, it appears likely that 1,4-elimination in
ether proceeds via an initial precoordination of the
two alkoxy-oxygens to n-butyllithium followed by a
concerted E2-like mechanism to result in the selective
formation of the (1Z,3E)-dienyl ether as depicted in
Scheme 2. The reaction of 1a carried out in THF might
suppress the precoordination since a stronger coordina-
tion occurs between THF–n-butyllithium than 1a–n-
butyllithium. In this case, the a0-lithiation occurs to
provide the a0-[2,3] Wittig product 3a.
rence of the subsequent Cope rearrangement 4e leading
to 5e. Interestingly, the thermolysis of 2d (refluxing in o-
xylene) afforded the tandem Claisen–Cope13 product 5d
in a 82% yield, whereas the treatment of 2d with
methylaluminium bis(2,6-di-tert-butyl-4-methylphenox-
ide) (MAD) allowed for the isolation of the Claisen
product 4d in a 92% yield.
In summary, we have shown that the 1,4-elimination
reaction of 1-allyloxy-4-methoxy-(2Z)-alkenes with n-
butyllithium is shown to proceed smoothly in ether to
afford various types of allylic 1,3-dienyl ethers in high
(1Z,3E)-stereoselectivities. Thus, this method is widely
applicable for the preparations of different types of the
Claisen and tandem Claisen–Cope substrates.
To define the scope and limitation of the present meth-
od, we prepared a series of 1,4-dialkoxy-(2Z)-alkenes
1b–1f11 and carried out their reactions with n-butyll-
ithium in ether. As shown in Table 1, various types of
allylic 1,3-dienyl ethers 2b–2e were obtained in good
yields with high (1Z,3E)-stereoselectivities. Our method
is also useful for the preparation of benzyl 1,3-dienyl
ether 2f (entry 5).12 In all cases, an appreciable amount
of any Wittig products were not formed.
Acknowledgments
This work was supported by a Grant-in-Aid for the
Scientific Research on Priority Areas ‘Advanced Mole-
cular Transformations of Carbon Resources’ from the
Ministry of Education, Culture, Sports, Science, and
Technology, Japan.
Finally, the Claisen rearrangement of allylic 1,3-dienyl
ethers 2 thus obtained was performed (Scheme 3). The
thermolysis (neat, 100 °C) of 2e gave the (4E,10E)-b,c-
unsaturated aldehyde 4e in a 81% yield without occur-
Supplementary data
Table 1. 1,4-Elimination reaction of various types of 1-alkoxy-4-
methoxy-(2Z)-alkene 1
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.
2006.08.100.
Entry
R1
R2
Yielda
(%)
References and notes
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1
2
3
4
5
(E)-CH2CH@CHCH3
–CH2C(CH3)@CH2
–CH2CH@CH(CH3)2
–CH(n-C5H11)CH@CH2
–CH2Ph
n-C7H15
n-C7H15
n-C4H9
n-C4H9
n-C4H9
b
c
d
e
f
90
74
91
84
84
a Isolated yield.
2. Tayama, E.; Sugai, S. Synlett 2006, 849.

E. Tayama et al. / Tetrahedron Letters 47 (2006) 7533–7535
7535
3. Previously, the 1,4-elimination reactions have reported
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¨