A general synthesis of (2Z)-terpenoic acids

Article abstract of DOI:10.1016/S0040-4039(00)00457-3

A three-step synthesis of (2Z), (4E)-polyenic acids 6 is described. Condensation of aldehydes 1 with potassium prenal enolate led to dihydropyranols 3 which were oxidized into dihydropyrones 5, precursors of (2Z), (4E)-polyenic acids 6. The procedure was applied to a synthesis of 13- cis-retinoic acids from β-ionylidene acetaldehydes. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)00457-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 3619–3622
A general synthesis of (2Z)-terpenoic acids
Dominique Cahard, Malika Mammeri, Jean-Marie Poirier † and Lucette Duhamel ∗
Université de Rouen, Institut de Recherche en Chimie Organique Fine (IRCOF) associé au CNRS,
F-76821 Mont Saint-Aignan Cedex, France
Received 7 February 2000; accepted 16 March 2000
Abstract
A three-step synthesis of (2Z), (4E)-polyenic acids 6 is described. Condensation of aldehydes 1 with potassium
prenal enolate led to dihydropyranols 3 which were oxidized into dihydropyrones 5, precursors of (2Z), (4E)-
polyenic acids 6. The procedure was applied to a synthesis of 13-cis-retinoic acids from β-ionylidene acetalde-
hydes. © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: enolates; oxidation; stereocontrol; retinoids; terpenes and terpenoids.
We reported that lithium or potassium prenal enolates 2 react with aldehydes 1 yielding to cyclic
adducts 3 by a γ; 1,4-addition and a subsequent intramolecular attack of the alkoxide on the carbonyl
group.1–3 Hydroxydihydropyranes 3 were easily transformed into polyenals 4 with a predominant (2Z)
(kinetic product)4 or (2E) (thermodynamic product)1–3 configuration, according to the experimental con-
ditions. In this note, we report a synthesis of (2Z), (4E)-dienic acids 6 via oxidation of dihydropyranols
3 followed by ring-opening of the resulting dihydropyrones 5 (Scheme 1).
We prepared dihydropyranols 3 by condensation of aldehydes 1 with potassium dienolate 2 easily
obtained by reaction of potassium tert-butoxide with the trimethylsilyl enol ether of prenal.2–5
The oxidation of dihydropyranols 3 was performed using two procedures, either Jones’ reagent6 (CrO3
in acidic medium, method A) or Corey’s reagent7 (PCC, method B).8 Finally, dihydropyrones 5 were
transformed into (2Z), (4E)-dienic acids 6 by means of t-BuOK according to the procedure described
by Cainelli and Cardillo.9,10 Acids 6a–j were isolated as single stereoisomers as evidenced by NMR
analyses. Results are reported in Table 1.
We applied this method to a synthesis of 13-cis-retinoic acids 6k (Scheme 2) used in dermatology and
for the treatment of some cancers.11 As the starting β-ionylidene acetaldehyde 1k was constituted by
(2E) and (2Z) isomers ((2E)/(2Z)=70/30), a mixture of 9-trans, 13-cis- and 9-cis, 13-cis-retinoic acids 6k
was obtained.12,13
∗
†
Corresponding author. Fax: (33) 02 35 52 29 71; e-mail: lucette.duhamel@univ-rouen.fr (L. Duhamel)
Deceased on May 7th, 1997.
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00457-3
tetl 16737

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Scheme 1.
Table 1

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Scheme 2.
In the literature, dihydropyrones 5 are classically obtained by condensation of aldehydes with lithium
or potassium dienolates prepared from senecioic acid and LDA or t-BuOK/nBuLi9,13d–f,14 or from lithium
enolate of methylsenecioate in controlled conditions15 or from the zinc derivative of γ-bromosenecioic
acid.16 In some cases, the desired lactones 5 are contaminated by by-products.
In summary, our three-step procedure to (2Z)-dienic acids 6 presents the advantages to give good
yields, high regio-, and stereoselectivities as well as to use very cheap reagents and mild conditions.
Acknowledgements
We are very grateful to the Ministère de la Recherche et de l’Espace for supporting this research.
References
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