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DOI: 10.1055/s-2002-35994
Synthetic Applications of 3,4-Dihalo-2(5H)-furanones: A Formal Total Synthesis of Nostoclides I and II
Publication History
Publication Date:
06 December 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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References
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.
14The 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.
16It 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.