Abstract
Various aryl carboxamides with alkoxy substituents at the ortho-position, applicable as direct intermediates toward novel ligands, were synthesised via aminocarbonylation of aryl-iodides (2-iodoanisole, 5-chloro-7-iodo-8-methoxy-quinoline, and 5-chloro-7-iodo-8-benzyloxy-quinoline) in the presence of in situ generated palladium(0) catalysts. Simple primary and secondary amines as well as aminoacid esters were used as N-nucleophiles. The optimization of the reaction conditions allowed the preferential formation of carboxamides or ketocarboxamides by simple or double carbon monoxide insertion, respectively. A strong dependence of the chemoselectivity on carbon monoxide pressure was observed.
ACKNOWLEDGMENT
The authors thank the Hungarian Research Fund (OTKA NI61591), the Portuguese FCT project (PTDC/QUI/66015/2006), and the Joint Project of the European Union–Hungarian National Development Program (GVOP-3.2.1-2004-04-0168/3) for the financial support and Johnson Matthey for the generous gift of palladium(II) acetate. A. F. Peixoto (SFRH/BD/29681/2006) and A. R. Abreu (SFRH/BD/21314/2005) are thankful for their PhD grants.
Notes
a Reaction conditions: 0.025 mmol Pd(OAc)2; 0.05 mmol PPh3, 1 mmol 1; 3 mmol unfunctionalized amine (or 1.1 mmol amino acid methylester hydrochloride), 0.5 ml triethylamine; 10 ml DMF, 50°C.
b Determined by GC-MS.
c Isolated yields are based on the amount of the starting material 1.
d The ketocarboxamide derivative (3e) was isolated and characterized only.
a Reaction conditions: 0.025 mmol Pd(OAc2); 0.05 mmol PPh3; 0.5 mmol substrate; 15 ml DMF; 0.5 ml Et3N; and 1.5 mmol tBuNH2 (or piperidine).
b Determined by GC-MS.
c Isolated yields (in brackets) are based on the amount of the starting material (5 or 8).
d The substrate (4) has been converted to 5-chloro-8-hydroxyquinoline (4′).