Tandem Claisen Condensation/Transesterification between Arylacetate Enolates and Arylmethylene-Substituted 2,2-Dimethyl-1,3-dioxolan-4-ones: An Improved Synthesis of Z-Configured Pulvinones

Natasza Kaczybura; Reinhard Brückner

doi:10.1055/s-2006-950378

PAPER

Tandem Claisen Condensation/Transesterification between Arylacetate Enolates and Arylmethylene-Substituted 2,2-Dimethyl-1,3-dioxolan-4-ones: An Improved Synthesis of Z-Configured Pulvinones

Natasza Kaczybura, Reinhard Brückner*
Institut für Organische Chemie and Biochemie, Albert-Ludwigs-Universität, Albertstr. 21, 79104 Freiburg, Germany
Fax: +49(761)2036100; e-Mail: reinhard.brueckner@organik.chemie.uni-freiburg.de;

Abstract

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Abstract

Horner-Wadsworth-Emmons (HWE) alkenations of aromatic aldehydes with the novel phosphonate 24b led to E-configured arylmethylene-substituted 2,2-dimethyl-1,3-dioxolan-4-ones 25a-f (79-88% yield). The latter condensed with the lithium enolates of methyl arylacetates lithio-20b-d to give, after acid treatment and crystallization, isomerically pure (Z)-pulvinones 8d-s in 75-91% yield. We also showed that Horner-Wadsworth-Emmons reactions between phosphonate 24b and aliphatic aldehydes lead to E-configured alkylmethylene-substituted 2,2-dimethyl-1,3-dioxolan-4-ones 25g-i (82-96% yield).

Key words

crossed Claisen condensation - Horner-Wadsworth-Emmons alkenation - O-protected α-hydroxyacrylates - α-oxocarboxylates - stereoselective synthesis

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References

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In a related condensation using lithium diisopropylamide/ester 26/dioxolanone 25c, we ascertained that the yield of pulvinone 28 decreased from 60% to 40% upon changing the reactant ratio from 2.5:2.5:1 to 2.5:1.25:1 (Scheme 4). The analogous condensation using lithium diisopropylamide/carboxylic acid 27/dioxolanone 25c (2.2:1.1:1 ratio of the reactants) did not give pulvinone 28 under the conditions otherwise identical to those of Table 5 (Kaczybura, N. Dissertation; Universität Freiburg: Germany, 2005).

Scheme 4

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We could not extend our approach to a synthesis of pulvinic acids 32 and 33. While dioxolanone 31 was accessible by a Horner-Wadsworth-Emmons reaction between phosphonate 24b and α-oxo ester 29 (79% yield), it did not react with the ester enolate 30 by Claisen condensation/transesterification (Scheme 5).

Scheme 5 Reagents and conditions: a) 24b (1.0 equiv), LDA (1.7 equiv), THF, -78 °C, 30 min; 29, 2.5 h; 79% (60:40 mixture of unassigned isomers); (b₁) 30 (2.5 equiv), THF, -78 °C, 2 h, to r.t., 0-2 h; (b₂) evaporation of THF; addition of Et₂O-H₂O (1:1), 60 °C, 1 h.