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

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

References

• 1 Rossi R. Bellina F. Raugei E. Synlett  2000,  1749 
• 2 Bellina F. Anselmi C. Rossi R. Tetrahedron Lett.  2002,  43:  2023 
• 3 Bellina F. Anselmi C. Viel S. Mannina L. Rossi R. Tetrahedron  2001,  57:  9997 
• 4 Bellina F. Anselmi C. Rossi R. Tetrahedron Lett.  2001,  42:  3851 
• 5 Ortega MJ. Zubía E. Ocaña JM. Naranjo S. Salvá J. Tetrahedron  2000,  56:  3963 
• 6 Evidente A. Randazzo G. Ballio A. J. Nat. Prod.  1986,  49:  593 
• For reviews on the synthesis of stereodefined 5-ylidene-2(5H)-furanones, see:
• 7a Negishi E.-I. Kotora M. Tetrahedron  1997,  53:  6707 
• 7b Brückner R. Curr. Org. Chem.  2001,  5:  679 
• 7c Brückner R. Chem. Commun.  2001,  141 
• 7d Rossi R. Bellina F. Targets in Heterocyclic Systems: Chemistry and Properties  2002,  5:  169 
• 8 Bellina F. Rossi R. ; Abstracts from Transmediterranean Colloquium on Heterocyclic Chemistry; Bari Italy June 20-24: 2002. 
• 9 Yang X. Shimizu Y. Steiner JR. Clardy J. Tetrahedron Lett.  1993,  34:  761 
• 10 Boukouvalas J. Maltais F. Lachance N. Tetrahedron Lett.  1994,  35:  7897 
• 11 This compound was prepared according to a procedure reported in the literature: Snyder HR. Kuch JA. Johnson JR. J. Am. Chem. Soc.  1938,  60:  105 
• 12 Ngwe H. Nakayama E. Higashi T. Kinoshita H. Inomata K. Chem. Lett.  1995,  713 
• For previous examples of Pd-catalyzed reactions between C_sp ²-hybridized halides and benzylzinc halides, see:
• 15a Negishi E.-i. Tan Z. Liou S.-Y. Liao B. Tetrahedron  2000,  56:  10197 
• 15b Gundersen L.-L. Langli G. Rise F. Tetrahedron Lett.  1995,  36:  1945 
• 15c Gundersen L.-L. Bakkestuen AK. Aasen J. Overas H. Rise F. Tetrahedron  1994,  50:  9743 
• 15d Moriya T. Miyaura N. Suzuki A. Chem. Lett.  1993,  1429 
• 15e Negishi E.-i. King AO. Okukado N. J. Org. Chem.  1977,  42:  1821 
• 17a Chuang C. Gallucci JC. Hart DJ. Hoffmann C. J. Org. Chem.  1988,  53:  3218 
• 17b Labadie JW. Tueting D. Stille JK. J. Org. Chem.  1983,  48:  4634 
• 18 Desponds O. Schlosser M. J. Organomet. Chem.  1991,  409:  93 

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.