Synthesis of tetrahydropyran/tetrahydrofuran-containing macrolides by palladium-catalyzed alkoxycarbonylative macrolactonizations.
A novel Pd-catalyzed cascade alkoxycarbonylative macrolactonization to construct tetrahydropyran/tetrahydrofuran-containing bridged macrolactones in one step from alkendiols is described. Products with various ring sizes and substituents were obtained. Challenging macrolactones involving tertiary alcohols were synthesized smoothly as well. Mechanistically, experimental evidence to support a trans-oxypalladation step has been provided. The method was applied to the synthesis of potent anticancer compound 9-demethylneopeltolide.
Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, IN 47907 (USA) http://www.chem.purdue.edu/dai/
Yu
Y
Bai
Dexter C
DC
Davis
Mingji
M
Dai
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry; D002384:Catalysis; D005663:Furans / Q000737:chemistry*; D018942:Macrolides / Q000138:chemical synthesis*; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry*; D011714:Pyrans / Q000737:chemistry*
D000970:Antineoplastic Agents; D005663:Furans; D018942:Macrolides; D011714:Pyrans; C018674:tetrahydrofuran; D010165:Palladium
carbonylation; macrolactonization; macrolide; neopeltolide; palladium