REGIOCHEMICAL CONTROL AND SUPPRESSION OF DOUBLE-BOND ISOMERIZATION INTHE HECK ARYLATION OF 1-(METHOXYCARBONYL)-2,5-DIHYDROPYRROLE

Arylation of 1-(methoxycarbonyl)-2,5-dihydropyrrole under standard Hec k reaction conditions produces a mixture of compounds. The olefin unde rgoes two types of palladium-catalyzed reactions: (a) arylation to pro vide C-3 arylated derivatives and (b) competing double bond isomerizat ion. Addition of silver carbonate and thallium acetate fully suppresse d the isomerization, and good yields of C-3 substituted compounds were achieved after arylation with aryl halides. With regard to aryl trifl ates as arylating agents, addition of lithium chloride was necessary t o promote the Heck reaction. This additive excluded the use of silver and thallium salts, but high regioselectivity and good yields could be obtained by employing tri-2-furylphosphine as ligand. Arylation was r endered both regioselective and enantioselective (58% ee) with 1-napht hyl triflate as substrate utilizing a (R)-BINAP/thallium acetate combi nation. The C-3 arylated enamides were converted further into the corr esponding 3-arylpyrrolidines.