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Synthesis 2002(18): 2729-2732
DOI: 10.1055/s-2002-35994
PAPER
© Georg Thieme Verlag Stuttgart · New York

Synthetic Applications of 3,4-Dihalo-2(5H)-furanones: A Formal Total Synthesis­ of Nostoclides I and II

Fabio Bellina*, Renzo Rossi
Dipartimento di Chimica e Chimica Industriale, Università di Pisa, via Risorgimento 35, 56126 Pisa, Italy
Fax: +39(50)918260; e-Mail: bellina@dcci.unipi.it;
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Publikationsverlauf

Received 12 September 2002
Publikationsdatum:
06. Dezember 2002 (online)

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Abstract

3-Benzyl-4-isopropyl-2(5H)-furanone, which is a precursor to two naturally-occurring cytotoxic (Z)-5-ylidene-2(5H)-furanone derivatives, has been conveniently prepared from 3,4-dibromo-2(5H)-furanone by a three-step procedure involving two Pd-catalyzed cross-coupling reactions and a Rh(I)-catalyzed hydrogenation.

Key words

2(5H)-furanones - cross-coupling - regioselectivity - Stille reaction - benzylation

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13

It should be noted that when we attempted to prepare 8a by hydrogenation of 18 in toluene at r.t. in the presence of 10 mol% Pd on BaSO4, the reaction provided significant amounts of a compound which had a MS spectrum corresponding to that of 4-isopropyl-2(5H)-furanone.

14

The catalyst precursor constiting of Pd2(dba)3 (2.5 mol%)/(o-Tol)3P (10 mol%) gave a similar yield, while the use of Pd2(dba)3 (2.5 mol%)/Ph3As (10 mol%) or Pd(PPh3)4 (5 mol%) as catalyst precursors gave less satisfactory results.

16

It should be noted that the crude product, derived from the Pd-catalyzed reaction of 8a with 20, contained compound 14 and significant amounts of 1,2-diphenylethane (22) and a compound which had a MS spectrum in agreement with that of 3,5-dibenzyl-4-isopropyl-2(5H)-furanone.
The use of PdCl2[(o-Tol)3P]2 (5 mol%)/CuI (10 mol%), Pd2(dba)3 (2.5 mol%)/Ph3As (10 mol%)/CuI (10 mol%) or Pd2(dba)3 (2.5 mol%)/t-Bu3P (10 mol%)/CuI (10 mol%) as catalyst precursors in NMP at 85 °C gave less satisfactory results, while employing Pd2(dba)3 (2.5 mol%)/t-Bu3P (10 mol%) as a catalyst precursor in dioxane at reflux and in the presence of 3 equiv of KF no product was obtained.