Neighboring group effect in Pd-catalyzed carbonylation terminated by lactonization: a need for a protective group and/or DMF.
Synthesis of analogues of antifungal podolactones via Pd-catalyzed processes revealed that tandem 6-exo-alkyne carbopalladation/carbonylative lactonization sequence is strongly solvent-dependent. Contrary to earlier reports, premature esterification was the predominant pathway when the starting enynes derived from (Z)-2-iodohex-2-en-1,4-diol were subjected to Pd-catalyzed carbonylation in MeOH. Apparently, irreversible complexation of Pd by the OH group prevented decarbonylation and hence 6-exo-alkyne carbopalladation. Similarly, the influence of the chelation was also evident when the reaction was applied to the analogous preparation of 3-hydroxymethylbutenolides. The neighboring group effect can be efficiently overcome through using DMF as the solvent in combination with protection of the OH function.
Schiller
Radan
R
Department of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles University, Heyrovského 1203, CZ-500 05 Hradec Králové, Czech Republic.
Pour
Milan
M
Fáková
Helena
H
Kunes
Jirí
J
Císarová
Ivana
I
D000935:Antifungal Agents / Q000138:chemical synthesis; D002384:Catalysis; D004126:Dimethylformamide / Q000737:chemistry*; D007783:Lactones / Q000737:chemistry*; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D010165:Palladium / Q000737:chemistry*
D000935:Antifungal Agents; D007783:Lactones; D010165:Palladium; D004126:Dimethylformamide