[2,3]-Wittig rearrangement of methyl β-pyrrolidinyl-γ-allyloxy- (E)-2-butenoate. Expeditious synthesis of 5-alkenyl-4-pyrrolidin-1-yl-5H-furan- 2-ones

Article abstract of DOI:10.1016/j.tetlet.2004.01.013

Dienolates of various γ-allyloxy substituted methyl β-pyrrolidinyl (E)-2-butenoate undergo a [2,3]-Wittig rearrangement to generate various 5-alkenyl-4-pyrrolidin-1-yl-5H-furan-2-one type compounds.

Full text of DOI:10.1016/j.tetlet.2004.01.013

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 1865–1868
[2,3]-Wittig rearrangement of methyl b-pyrrolidinyl-c-allyloxy-
(E)-2-butenoate. Expeditious synthesis of 5-alkenyl-4-pyrrolidin-
1-yl-5H-furan-2-onesq
Yu-Jang Li,a,* Pei-Ting Lee,b Chuen-Mei Yang,b Yuan-Kang Chang,b Ying-Chieh Wengb
and Yi-Hung Liuc
aDepartment of Applied Chemistry, National Chiayi University, Chiayi 600, Taiwan, ROC
bDepartment of Applied Chemistry, Chaoyang University of Technology, Wufeng 413, Taichung county, Taiwan, ROC
cDepartment of Chemistry, National Taiwan University, Taipei 106, Taiwan, ROC
Received 26 November 2003; revised 26 December 2003; accepted 6 January 2004
Abstract—Dienolates of various c-allyloxy substituted methyl b-pyrrolidinyl (E)-2-butenoate undergo a [2,3]-Wittig rearrangement
to generate various 5-alkenyl-4-pyrrolidin-1-yl-5H-furan-2-one type compounds.
Ó 2004 Elsevier Ltd. All rights reserved.
5-Substituted 4-pyrrolidin-1-yl-5H-furan-2-ones 6 are
important synthetic intermediates for natural product
synthesis,1 because they are amenable to chemical
transformations in generating useful a,b-unsaturated
c-lactones and tetronic acids.2;3 It has been shown that
compound 6 could be obtained by the alkylation of
enolates, which are derived from 4-pyrrolidin-1-yl-5H-
furan-2-ones.1c Herein, we would like to report a new
synthetic route for the synthesis of 6 involving the [2,3]-
Wittig rearrangement of c-allyloxy-b-pyrrolidinyl-2-
butenoate dienolates 4 and the subsequent cyclization of
the resulting alkoxides 5.4 This method not only pro-
vides the synthesis of simple C5 allylated products but
also offers the possibility to construct compounds with
more sophisticated C5-substitutions.
When
simple
substituted
compounds
3a–d
(R4 ¼ R5 ¼ H) were treated with 2.5 equiv of LDA at
We commenced the reaction studies with the synthesis of
c-allyloxy substituted compounds 3a–j. Ketoesters 2a–j
were first synthesized by the reaction of various allyl-
oxides with methyl 4-chloroacetoacetate in 68–85%
yields, respectively.5 Subsequent condensation of 2a–j
with pyrrolidine utilizing Dean–Stark apparatus pro-
vided 3a–j in almost quantitative yields (Scheme 1).
Keywords: [2,3]-Wittig rearrangement.
q Supplementary data associated with this article can be found, in the
online version, at doi:10.1016/j.tetlet.2004.01.013
* Corresponding author. Tel.: +886-5-2717899; fax: +886-5-2717901;
e-mail: yjli@mail.ncyu.edu.tw
Scheme 1.
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.01.013

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Y.-J. Li et al. / Tetrahedron Letters 45 (2004) 1865–1868
)78 °C and then warmed to room temperature over a
period of 4 h, a clean conversion of dienolates 4a–d to
compounds 6a–d via [2,3]-Wittig rearrangement were
achieved in moderate to good yields without the com-
plication of [3,3]-sigmatropic rearrangement.6 Mean-
while, product 6c was found to have exclusively
(E)-crotyl substitution (Table 1).
When R4 or R5 mono-substituted compounds 3e–h were
used in the reaction studies, ratios of syn and anti dia-
stereomers were obtained, respectively, as shown in
Table 1.
Rearrangement of 3e and 3f gave both anti-6e and syn-
6e totally in 75% and 78% yields, respectively. The
stereochemistry of the major product anti-6e was
determined by single-crystal X-ray analysis as shown in
Figure 1.7 The outcome of the stereochemistry of the
reactions of 3e and 3f were explained by possible tran-
sition states as shown in Scheme 2. When 3e with a (Z)-
Figure 1. ORTEP drawing of anti-6e.
Table 1. [2,3]-Wittig rearrangement of 3a–ja;b
Scheme 2.
allyloxy substitution was used in the reaction, via 7A as
the preferred transition state, 9C was obtained as the
major product (RZ ¼ n-Pr). On the other hand, when 3f
with (E)-substitution was used in the reaction, since 7A0
suffer less steric interactions between RE group and the
pseudo-equatorial H of the pyrrolidine ring,8 9C0 was
obtained as the major product (RE ¼ n-Pr). Under the
circumstances, though 3e and 3f are different both in
nature by the configuration of the double bond and the
different preference in the reaction transition state, they
reacted to generate anti-6e as the same preferred prod-
1
uct. The H NMR signal of the Ha of endo-vinyl group
of anti-6e at 5.55 ppm, relative to the signal of Ha of exo-
vinyl group of syn-6e at 5.91 ppm, suggested an up-field
shielding of Ha by a neighboring carbonyl group in anti-
6e as shown in Figure 2.
When 3g and 3h were utilized in the reaction studies,
anti-6g was obtained as the major product as shown in
Table 1.9
With tri-substituted compounds 3i and 3j undergoing
[2,3]-Wittig rearrangement, 6i was obtained from the
reaction of 3i as the exclusive product without any [1,2]-
rearrangement product being observed.10 The reaction
of 3j provided anti-6j and syn-6j in 36/64 ratio totally in
84% yields.11
a All the experiments were conducted using THF as solvent.
The chemical yields were indicated after purification by chromato-
graphy.
After having completed the rearrangement studies of
linear allyloxy system 3a–j, endocyclic alkene derived
b Diastereomeric ratios were determined by 1H NMR integration.

Y.-J. Li et al. / Tetrahedron Letters 45 (2004) 1865–1868
1867
using diethyl ether and THF as reaction co-solvent
(ethyl ether/THF, 4/1), excellent diastereoselectivities of
5-(tetrahydro-pyran-2-yl)-5H-furan-2-ones
(syn-13b/
anti-13b) and 5-(tetrahydro-pyran-4-yl)-5H-furan-2-
ones (syn-13c/anti-13c) were obtained in 95/5 and 98/2
ratio, respectively (Scheme 4). The stereochemistry of
major products syn-13b and syn-13c were analyzed by
single crystal X-ray crystallography as shown in Figure
3.14
Transition states 14A and 14B relative to 14C, with less
steric interaction between dihydropyran and pyrro-
lidine-ring moiety, were proposed to account for the
formation of major products syn-13b and syn-13c,
respectively. Excellent diastereoselections of these two
rearrangements of 12b and 12c, relative to the rear-
rangement of 12a, suggest an important involvement of
the lithium–oxygen chelation (Fig. 4).
Figure 2.
allyloxy compounds 12a–c were synthesized in 75–85%
yields according to the precedent procedure and were
utilized in rearrangement studies12 (Scheme 3). Rear-
rangement of 12a under standard procedure, using THF
as solvent, generated 84% yield of syn-13a and anti-13a
in 34/64 ratio.13 When dihydropyran compounds 12b–c
were used, respectively, in the rearrangement studies
Figure 4.
Scheme 3.
In summary, we have shown that [2,3]-Wittig rear-
rangement of the dienolates derived from c-allyoxy-b-
pyrrolidinyl-2-butenoates is applicable to the efficient
synthesis of sophisticated 5-substituted-4-pyrrolidin-1-
yl-5H-furan-2-ones. Further studies on the asymmetric
version of this reaction as well as the synthetic appli-
cations of the methodology are in progress in our lab-
oratory.
Acknowledgements
We thank the National Science Council (NSC-92-2113-
M-415-005) and Sinon Corporation for generous
Scheme 4.
Figure 3. ORTEP drawings of syn-13b and syn-13c.

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I.; Meyer, C.; Cossy, J. Tetrahedron Lett. 2001, 42, 5215–
5218.
financial support. Partial support of the Mass spec-
trometer facility provided by National Chung-Hsing
University and the support of X-ray facility by National
Taiwan University are also acknowledged.
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7. The crystal structure of compound anti-6e has been
deposited at the Cambridge Crystallographic Data Centre
as CCDC 212545.
8. Williard, P. G.; Tata, J. R.; Schlessinger, R. H.; Adams, A.
D.; Iwanowicz, E. J. J. Am. Chem. Soc. 1988, 110, 7901.
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signals with syn-13c and anti-13c.
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