Regiochemical Control and Suppression of Double Bond Isomerization in the Heck Arylation of 1-(Methoxycarbonyl)-2,5-dihydropyrrole.
Arylation of 1-(methoxycarbonyl)-2,5-dihydropyrrole under standard Heck reaction conditions produces a mixture of compounds. The olefin undergoes two types of palladium-catalyzed reactions: (a) arylation to provide C-3 arylated derivatives and (b) competing double bond isomerization. Addition of silver carbonate and thallium acetate fully suppressed the isomerization, and good yields of C-3 substituted compounds were achieved after arylation with aryl halides. With regard to aryl triflates as arylating agents, addition of lithium chloride was necessary to 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 rendered both regioselective and enantioselective (58% ee) with 1-naphthyl triflate as substrate utilizing a (R)-BINAP/thallium acetate combination. The C-3 arylated enamides were converted further into the corresponding 3-arylpyrrolidines.
Sonesson
Clas
C
Medicinal Chemistry Unit, Department of Pharmacology, Medicinargatan 7, S-413 90 Göteborg, Sweden and Department of Organic Pharmaceutical Chemistry, Uppsala Biomedical Center, Uppsala University, Box 574, S-751 23 Uppsala, Sweden.
Larhed
Mats
M
Nyqvist
Camilla
C
Hallberg
Anders
A