A novel palladium(0)-catalyzed cyclization to 3,4-disubstituted pyrrolidin-2-ones has been developed. The new approach relies upon the concomitant generation of stabilized acetamide enolate anions and of a ð-allyl-palladium appendage, properly tethered by a nitrogen atom. Reaction conditions have been optimized for the methoxycarbonyl-stabilized model reaction [(Z)-2 f 3] and then applied to other substrates. A broad range of acetamide anion stabilizers was shown to allow the desired intramolecular C-C bond formation (MeO2C, MeCO, NC, (EtO)2PO, PhSO2). The cyclizations gave exclusively 5-exo-trig ring closure, thereby affording ç-lactams. All the cyclizations gave the corresponding 3,4-disubstituted pyrrolidin-2-ones with total diastereoselection. Complete trans preference was unequivocally demonstrated for the model reaction via a NOESY experiment.
A New Palladium-Catalyzed Intramolecular Allylation to Pyrrolidin-2-ones
Giuliano Giambastiani;
1998
Abstract
A novel palladium(0)-catalyzed cyclization to 3,4-disubstituted pyrrolidin-2-ones has been developed. The new approach relies upon the concomitant generation of stabilized acetamide enolate anions and of a ð-allyl-palladium appendage, properly tethered by a nitrogen atom. Reaction conditions have been optimized for the methoxycarbonyl-stabilized model reaction [(Z)-2 f 3] and then applied to other substrates. A broad range of acetamide anion stabilizers was shown to allow the desired intramolecular C-C bond formation (MeO2C, MeCO, NC, (EtO)2PO, PhSO2). The cyclizations gave exclusively 5-exo-trig ring closure, thereby affording ç-lactams. All the cyclizations gave the corresponding 3,4-disubstituted pyrrolidin-2-ones with total diastereoselection. Complete trans preference was unequivocally demonstrated for the model reaction via a NOESY experiment.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
