Eu(fod)3-catalyzed tandem regiospecific rearrangement of divinyl alkoxyacetates and Diels-Alder reaction

Article abstract of DOI:10.1016/S0040-4039(00)01172-2

Unsymmetrical divinyl alkoxyacetates (such as 7a) undergo a Eu(fod)₃-catalyzed regiospecific allylic rearrangement to form C₅-substituted (E)-2-ethoxy-1,3-dienes at room temperature. When the rearrangement of 7a was carried out in the presence of maleic anhydride, a tandem allylic rearrangement and Diels-Alder reaction occurred to give the adduct 11. Reactions of other dienophiles in this tandem procedure were examined. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)01172-2

Tetrahedron Letters 41 (2000) 7101±7105
Eu(fod)3-catalyzed tandem regiospeci®c rearrangement of
divinyl alkoxyacetates and Diels±Alder reaction
Wei-Min Dai,* Wing Leung Mak and Anxin Wu
Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay,
Kowloon, Hong Kong, China
Received 18 May 2000; revised 21 June 2000; accepted 12 July 2000
Abstract
Unsymmetrical divinyl alkoxyacetates (such as 7a) undergo a Eu(fod)3-catalyzed regiospeci®c allylic
rearrangement to form C5-substituted (E)-2-ethoxy-1,3-dienes at room temperature. When the rearrangement
of 7a was carried out in the presence of maleic anhydride, a tandem allylic rearrangement and Diels±Alder
reaction occurred to give the adduct 11. Reactions of other dienophiles in this tandem procedure were
examined. # 2000 Elsevier Science Ltd. All rights reserved.
Keywords: lanthanides; dienes; rearrangements; Diels±Alder reactions.
The lanthanide complexes Ln(fod)3 and related analogs modi®ed by chiral ligands have been
used as Lewis acid catalysts in organic synthesis.1 The Ln(fod)3 catalysts are ecient for
promoting the cycloaddition of electron-rich dienes with aldehydes.2 Other reactions catalyzed by
Ln(fod)3 include 1,3-dipolar cycloadditions,3a ene reactions,3b radical-mediated allylation,3c and
the ring closure of vinylic epoxy alcohols.3d Recently, Koreeda's group reported that Eu(fod)3
promoted a stereospeci®c rearrangement of allylic methoxyacetates.3e In contrast to Pd(II)
catalysts, Eu(fod)3 is compatible with alkynyl group(s).3e We have successfully applied this
rearrangement to the synthesis of cis-enediynes.4 We report now on a regiospeci®c rearrangement
of unsymmetrical divinyl esters and a tandem allylic rearrangement and Diels±Alder reaction
under Ln(fod)3 catalysis.
We ®rst examined Ln(fod)3 catalysts for the rearrangement of the symmetrical divinyl ester 3
(Scheme 1).5 The (E,E)-divinylcarbinol 2 was prepared according to the literature procedure.6
Addition of BnOCH2CꢀCLi to methyl formate gave the alcohol 1 which was reduced to 2 by
using excess Red-Al7 (0ꢁC, 12 h, 46%). The methoxyacetate 3 was prepared from 2 in 87% yield
under the DCC±DMAP conditions. We used four Ln(fod)3 catalysts (Ln=Pr, Eu, Er, Yb) for
promoting the rearrangement of 3. With 10 mol% of the catalyst, the reaction was completed
* Corresponding author. Fax: +852 2358 7365; e-mail: chdai@ust.hk
0040-4039/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01172-2

7102
Scheme 1.
within 20 h in CHCl3 at room temperature and the diene 4 was isolated in 80±85% yield. Because
the product 4 cannot be separated from 3 on a silica gel TLC plate, the reaction mixture was
checked by 1H NMR spectroscopy and the characteristic signals of 3 were not detected.
We envisaged the unsymmetrical divinyl substrates 7 as the precursors of electron-rich 1,3-
dienes based on the assumption that a regiospeci®c allylic rearrangement is possible. To test this
idea, we synthesized two series of esters 7 (R2=Me and PMB) from a,b-unsaturated aldehydes 5
(Scheme 2). Addition of a-ethoxyvinyllithium prepared from ethyl vinyl ether and t-BuLi8 to 5 at
^78ꢁC gave the alcohols 6. Condensation of 6 with methoxyacetic acid or p-methoxybenzyloxy-
acetic acid under the DCC±DMAP conditions a€orded 7. The PMB ether is cleaved by DDQ
under mild conditions.9 It provides an opportunity to manipulate the PMB-containing ester
group after the rearrangement.
Scheme 2.
Rearrangement of 7 was carried out in CH2Cl2 at room temperature by using 5 mol%
Eu(fod)3. The results are summarized in Table 1. We found that it is necessary to use molecular
sieves to prevent the dienes from hydrolysis by moisture. We isolated the a,b-unsaturated methyl
ketones from the reactions where the molecular sieves were not added. Rearrangement of 7 is
regiospeci®c as only the C5-substituted (E)-1,3-dienes 8 and 9 were formed. The methoxyacetates
are slightly more reactive compared to the p-methoxybenzyloxyacetates. Increase of the catalyst
loading from 5 to 10 mol% reduced the reaction time accordingly (for 8c in Table 1, entry 3).
Overall, the Eu(fod)3-catalyzed rearrangement is general and the 1,3-dienes are formed in good to
excellent yields.

7103
Table 1
Eu(fod)3-Catalyzed regiospeci®c rearrangement of 7a
The dienes 8a±c were reacted with tetracyanoethylene (TCNE) (Table 2). In the absence of
Eu(fod)3, 10b was formed from 8b and TCNE at room temperature for 8 h (51%) as an inseparable
mixture. After a prolonged reaction (24 h), the yield of 10b slightly increased to 55% (entries 2
and 3). In a similar manner, reaction of 8a and 8c with TCNE furnished 10a (50%) and 10c
(60%) as an inseparable mixture, respectively (entries 1 and 5). We found that in the presence of 5
mol% Eu(fod)3, cycloaddition of the diene 8b with TCNE furnished 10b in 58% yield (entry 4).
This result showed that Eu(fod)3 catalyzes the Diels±Alder reaction of 8b with TCNE (entry 4
versus entry 3).10
Table 2
Stepwise versus tandem Diels±Alder reactiona
Next, we used 7a±c in a tandem allylic rearrangement and Diels±Alder reaction (Table 2).11
For example, a mixture of 7a, TCNE, and 5 mol% Eu(fod)3 in CH2Cl2 was stirred for 10 h to
give 10a in 65% yield (entry 1). The reaction time of the tandem procedure is signi®cantly shorter
than the rearrangement of 7a into 8a (Table 1, entry 1) because of the equilibrium between 7a and
8a. In the tandem reaction, the diene 8a formed reacted with the dienophile to give the adduct
10a. Thus, the return path from 8a to 7a was suppressed. Similarly, the cycloadducts 10b and 10c
were formed directly from 7b and 7c with TCNE, respectively. With a large alkyl group in 7c,
steric e€ects came into play to slow down the Diels±Alder reaction. It is evident that the tandem
procedure is better than the stepwise reaction. The overall chemical yield is higher for the tandem
reaction with a slight enhancement in the diastereoselectivity.

7104
We investigated the tandem allylic rearrangement and Diels±Alder reaction of 7a with other
dienophiles (Scheme 3). Treatment of 7a and maleic anhydride with 10 mol% Eu(fod)3 in
re¯uxing CH2Cl2 for 120 h a€orded 11 in 53% yield as a 60:40 inseparable mixture. The
cycloaddition should follow the endo selectivity.10 Yb(fod)3 catalyzed the same tandem reaction
with a similar eciency. The bicyclic compound 12 was obtained from 7a and 1,4-benzoquinone
through the tandem reaction sequence followed by air oxidation (Scheme 3). We found that 12
gradually decomposed at higher temperatures. By limiting the reaction in chlorobenzene at 75ꢁC
for 10 h, 12 was isolated in 37% yield as a 63:37 inseparable mixture. The tandem reaction of 7a
with dimethyl acetylenedicarboxylate also occurred at 60ꢁC in chlorobenzene and 13 was
obtained in 59% yield as a 61:39 inseparable mixture.
Scheme 3.
In summary, we have established the Eu(fod)3-catalyzed regiospeci®c rearrangement of the
unsymmetrical divinyl esters 7 to form the C5-substituted (E)-1,3-dienes 8 and 9 under mild
conditions. This provides an ecient alternative method for the preparation of 2-alkoxy-1,3-
dienes.12 We also developed a tandem allylic rearrangement of the alkoxyacetates 7 and Diels±
Alder reaction of the resultant 1,3-dienes using a single Lewis acid catalyst, Eu(fod)3. Application
of the Ln(fod)3-catalyzed rearrangement of allylic esters in organic synthesis is under way in our
laboratory.
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