New picropodophyllin analogs via palladium-catalyzed allylic alkylation-Hiyama cross-coupling sequences.
Unsaturated malonyl esters underwent Pd-catalyzed intramolecular allylic alkylation to give 4-vinyl-substituted gamma-lactones. In contrast to the formerly studied cyclization of malonamides, this reaction could be achieved only with a substrate incorporating a suitably positioned silicon moiety, which directs the ionization toward the desired eta(3)-allylpalladium complex. The resulting 4-[dimethyl-(2-thienyl)silylvinyl]lactone could be subsequently engaged into Hiyama couplings with various iodoarenes, to give the corresponding 4-(alpha-styryl)-gamma-lactones. The use of a specifically substituted iodoarene generated an advanced tetracyclic lactone intermediate incorporating rings A-D of lignans belonging to the podophyllotoxin family. Subsequent electrophilic aromatic substitution with a variety of electron-rich arenes afforded the target picropodophyllin analogs.
Vitale
Maxime
M
UPMC Univ Paris 06, UMR CNRS 7611 Laboratoire de Chimie Organique, FR2769 Institut de Chimie Moléculaire, case 183, F-75005 Paris, France.
Prestat
Guillaume
G
Lopes
David
D
Madec
David
D
Kammerer
Claire
C
Poli
Giovanni
G
Girnita
Leonard
L
D000478:Alkylation; D000498:Allyl Compounds / Q000737:chemistry*; D001559:Benzhydryl Compounds / Q000737:chemistry; D002384:Catalysis; D003432:Cross-Linking Reagents / Q000737:chemistry*; D003500:Cyclization; D007477:Ions / Q000737:chemistry; D007659:Ketones / Q000737:chemistry; D007783:Lactones / Q000737:chemistry; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010165:Palladium / Q000737:chemistry*; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry
D000498:Allyl Compounds; D001559:Benzhydryl Compounds; D003432:Cross-Linking Reagents; D007477:Ions; D007659:Ketones; D007783:Lactones; C415032:picropodophyllin; D010165:Palladium; D011034:Podophyllotoxin