Vinyl-allenes as dienes in the Lewis acid-mediated hetero Diels-Alder reaction with aldehydes

Article abstract of DOI:10.1016/S0040-4039(00)01140-0

The Lewis acid-mediated, hetero Diels-Alder reaction of a vinyl-allene system with aldehydes as heterodienophiles has been carried out. In the cases studied, only two cycloadducts have been obtained, which correspond to the endo (major compound) and exo (minor compound) approach of the aldehyde through the less hindered face of the dienic system. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)01140-0

Tetrahedron Letters 41 (2000) 6781±6784
Vinyl-allenes as dienes in the Lewis acid-mediated hetero
Diels±Alder reaction with aldehydes
David Regas, Marõa M. Afonso, Antonio Galindo and J. Antonio Palenzuela*
Â
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Instituto Universitario de Bio-Organica `Antonio Gonzalez', Universidad de La Laguna,
E-38206 La Laguna, Tenerife, Spain
Received 24 May 2000; accepted 5 July 2000
Abstract
The Lewis acid-mediated, hetero Diels±Alder reaction of a vinyl-allene system with aldehydes as
heterodienophiles has been carried out. In the cases studied, only two cycloadducts have been obtained,
which correspond to the endo (major compound) and exo (minor compound) approach of the aldehyde
through the less hindered face of the dienic system. # 2000 Elsevier Science Ltd. All rights reserved.
Keywords: hetero Diels±Alder; vinyl-allenes; aldehydes; cycloaddition; Lewis acid.
Compounds containing the vinyl-allene moiety have been used in several types of pericyclic
reactions, including hydrogen sigmatropic shifts,1 electrocyclization2 and inter-3 and intramolecular4
Diels±Alder reactions. In several instances, the presence of the allene resulted in a facilitated
reaction compared with the non-allenic case.5
Pursuing our interest in the synthetic uses of the hetero Diels±Alder reaction,6 we decided to
try to ®nd general conditions for this reaction with vinyl-allenes as the diene and aldehydes as the
heterodienophile. We have not been able to ®nd examples of this reaction in the literature, and we
feel that it could be of great interest, both theoretically and synthetically, since the allene part of
the molecule can be prepared in enantiomerically pure form.
For non-allenic dienes reacting with aldehydes in the hetero Diels±Alder reaction, some
activation is required, usually through the use of highly oxygenated dienes and high pressures or
Lewis acid catalysis.7 In order to test whether the presence of the allene lowered those requirements,
we started by preparing compounds 4 and 5 (Scheme 1), in which the sole activation is due to the
presence of alkyl groups on the diene.
Compounds 4 and 5 were prepared in good yield by SN20 displacement with EtMgBr/
8
.
CuBr Me2S of the benzoates derived from the propargylic alcohols (2 or 3), obtained by addition
of the lithium acetylide derived from 1-ethynylcyclohexene to the corresponding aldehyde.
* Corresponding author. Tel: +34-922-318443; fax: +34-922-630095; e-mail: jpalenz@ull.es
0040-4039/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01140-0

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Scheme 1.
To test the overall reactivity of these vinyl-allenes, we decided to carry out the Diels±Alder
reaction of 4 and 5 with maleic anhydride, since this reaction has been reported recently with
other vinyl-allenes3 and the published results can be used for comparison. Both compounds 4 and
5 reacted easily at room temperature in toluene, yielding after 24 h only one isomer in greater
than 90% yield. The compound obtained in each reaction was identi®ed as the isomer resulting
from the endo approach of the dienophile through the less hindered face of the diene, i.e. the one
opposite to the substituent on the allene terminus (Scheme 2).
Scheme 2.
These results indicate a high reactivity for 4 and 5 in those pericyclic reactions, since for the
similar reaction reported with other vinyl-allenes,3 the reaction times were much longer, typically
4±7 days, and, in some cases, at a higher temperature.
Encouraged by these results, we submitted compound 4 to the reaction with propion-
aldehyde and boron tri¯uoride etherate, under the same conditions used previously by us in
hetero Diels±Alder reactions with monoactivated dienes.6 A typical experimental procedure is as
follows: the vinyl-allene was added to a mixture of aldehyde (1.5 equiv.) and boron tri¯uoride etherate
(1.1 equiv.) in diethyl ether at 0ꢀC. After stirring for 24 h at room temperature, the reaction was
quenched by addition of triethylamine and ice-water. The crude extract was fractionated ®rst by
column chromatography, and then puri®ed by HPLC in order to isolate and characterize each
compound. Two major compounds were isolated and identi®ed by NMR spectroscopy9 as
cycloadducts (Scheme 3) with regiochemistry consistent with the ethyl group acting as the activating
group on the diene. The relative stereochemistry was established by NOE studies, the major
Scheme 3.

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compound (8) being assigned the cis stereochemistry, consistent with an endo approach of the
heterodienophile to the dienic portion of the molecule. The minor compound (9) was assigned the trans
stereochemistry, which indicated an exo approach of the aldehyde. The con®guration of the exocyclic
double bond in both adducts indicates that the reaction takes place through the less hindered face of
the system, i.e. the one opposite to the methyl group on the allene terminus.
Vinyl-allene 5 also reacted with propionaldehyde to give only two isomers, which were also the
endo and exo adducts. In order to make an initial test of the importance of steric and electronic
factors, 4 and 5 were subjected to the same reaction conditions using isobutyraldehyde and
benzaldehyde as heterodienophiles. The results of those reactions are presented in Table 1.
Table 1
It can be observed that the best yields are obtained with the simpler non-branched propion-
aldehyde, and that the presence of the phenyl group on the vinyl-allene seems to lower the yield of
cycloadducts. It has to be pointed out, however, that in most cases the yield is a€ected during the
puri®cation, since those compounds appear to be quite acid sensitive, especially the major cis
adducts. For that reason, the ratios were estimated on the crude reaction mixtures.
In conclusion, we have prepared a vinyl-allene system highly reactive towards a dienophile such
as maleic anhydride, which also reacts with aldehydes to give hetero Diels±Alder adducts with
high regio- and diastereofacial selectivity and moderate endo/exo selectivity. To our knowledge,
this is the ®rst example of such a reaction, which gives synthetically useful yields of substituted
oxanes.
The feasibility of obtaining the allene moiety in enantiomerically pure form from homochiral
propargyl alcohols allows us to envision the application of this reaction to the enantioselective
synthesis of natural products of interest.

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Acknowledgements
This work was supported by grant PB96-1041 from the DGES (Spain). D.R. gratefully
acknowledges an FPU fellowship from the Spanish MEC.
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1
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