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Synthesis 2007(15): 2249-2272  
DOI: 10.1055/s-2007-983803
PAPER
© Georg Thieme Verlag Stuttgart · New York

Novel Synthesis of Naturally Occurring Pulvinones: A Heck Coupling, Transesterification­, and Dieckmann Condensation Strategy

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

Received 14 May 2007
Publication Date:
26 July 2007 (online)

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Novel Synthesis of Naturally Occurring Pulvinones: A Heck Coupling, Transesterification, and Dieckmann Condensation StrategySynthesis 2009; 2009(09): 1582-1582
DOI: 10.1055/s-0028-1088054

Abstract

Phosphine-free Heck alkenylations of iodoarenes with trifluoroethyl 2-acetoxyacrylate (19) led stereoselectively to trifluo­roethyl (Z)-2-acetoxycinnamates 31-34, 42, 44, and 51. Deacetylation followed by acylation with N,N′-dicyclohexylcarbodiimide activated arylacetic acids yielded the isomerically pure trifluoro­ethyl (Z)-2-(arylacetoxy)cinnamates 38a-o. These were excellent substrates of potassium tert-butoxide mediated Dieckmann condensations, and distinctly superior to fluorine-free analogues, furnishing Z-configured pulvinones 1a-o (1i = aspulvinone A). Cleavage of the aryl ether moieties of pulvinones 1d,e,h,n,o provided aspulvinone E (1r), aspulvinone G (1s), 3′,4,4′-trihydroxypulvinone (1v), and aspulvinones B (1x) and H (1y), respectively. The conversion of the 2,4-diiodophenyl ethers 48 and 49 into the 4-iodo-2-prenylphenyl ethers 46 and 50, respectively, was effected by unprecedented ortho-selective iodine-magnesium exchange reactions followed by prenylation.

Key words

2-(acyloxy)acrylates - β-arylpyruvates - Heck reaction - magnesium-iodine exchange - stereoselective synthesis

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27

We could also esterify trifluoroethyl pyruvate (25) to give trifluoroethyl 2-[(4-methoxyphenyl)acetoxy]acrylate (20), employing the mixed anhydride obtained from (4-meth-oxyphenyl)acetic acid, TFAA (2.0 equiv), and TsOH·H2O (cat., toluene, reflux, 12 h); however, the low yield of 20 (21%) by this route kept us from trying to shortcut our two-step synthesis of trifluoroethyl 2-(arylacetoxy)cinnamates by using the one-step alternative of a Heck coupling between iodoarenes 17 and this reagent.

31

Attempts to arylate ethyl 2-(trimethylsiloxy)acrylate (21), prepared according to: Barton D. H. R., Chern C.-Y., Jaszberenyi J. C.; Tetrahedron; 1995, 51: 1867; with 4-iodoanisole under conditions reasonably effective for ethyl 2-acetoxyacrylate (18, cf. Table [2] , entry 3) failed completely. Therefore, we did not prepare trifluoroethyl 2-(trimethylsiloxy)acrylate (22) as a potential substrate of Heck arylation