Addition of Vinylmetallic Reagents to Chiral 2‐Formyltetrahydrofuran

Abstract

Polyketide macrolides, which belong to an interesting family of metabolites, are complex structures with valuable bioactivity. In this work, several procedures for the bond formation between a vinylorganometallic reagent and a chiral formyl-THF compound were examined for the subsequent application to the total synthesis of phormidolides. Model molecules were synthesized to study and optimize the method that

Synthesis of (E)‐4‐Bromo‐3‐methoxybut‐3‐en‐2‐one, the Key Fragment in the Polyhydroxylated Chain Common to Oscillariolide and Phormidolides A–C

“…Several strategies for the synthesis of the macrocyclic core present in phormidolides B and C have been reported as well as a preliminary study to link the macrocyclic core and the polyol by the formation of the allylic alcohol attached to the THF ring but no publications describing the polyol chain synthesis have been reported yet. To deal with this synthesis, we envisage the formation of the polyol chain BMD moiety by the following reaction sequence: a Mukaiyama aldol addition reaction between 2‐bromo‐1‐methoxyvinyl methyl ketone (BMK) ( E )‐ 1 and the corresponding aldehyde, followed by esterification with the appropriate fatty acid and final olefination for the formation of the terminal diene (Figure ).…”

Toward the Synthesis of Phormidolides

“…Having synthesized fragments 5 , 9 , and 4 , the pieces of the synthetic puzzle should be put together. First of all, the union of aldehyde 4 and iodoalkene 9 using the CrCl 2 –NiCl 2 -mediated NHTK coupling (Scheme , a) was attempted. , This methodology allowed the selective formation of the C15–C16 bond in the presence of methyl ketone because of the well-known chemoselectivity of NHTK coupling toward aldehydes, thereby demonstrating the useful orthogonal reactivity of compound 9 . Unfortunately, the reaction between 9 and 4 gave stereoselectively compound 6 possessing the configuration R-C15 with only 18% yield …”

Synthesis of (E)‐4‐Bromo‐3‐methoxybut‐3‐en‐2‐one, the Key Fragment in the Polyhydroxylated Chain Common to Oscillariolide and Phormidolides A–C

“…Several strategies for the synthesis of the macrocyclic core present in Phormidolides B and C have been reported [3], [5] as well as a preliminary study to link the macrocyclic core and the polyol via the formation of the allylic alcohol attached to the THF ring [6] but no publications describing the polyol chain synthesis have been reported yet. To deal with this synthesis, we envisage the formation of the polyol chain BMD moiety by the following reaction sequence: a Mukaiyama aldol addition reaction [7] between 2-bromo-1-methoxyvinyl methyl ketone (BMK) (E)-1 and the corresponding aldehyde, followed by esterification with the appropriate fatty acid and final olefination [8] for the formation of the terminal diene ( Figure 2).…”