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Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic Chemistry
Volume 39, 2009 - Issue 9
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Original Articles

Synthesis of Ortho-alkoxy-aryl Carboxamides via Palladium-Catalyzed Aminocarbonylation

, , , &
Pages 1534-1548 | Received 08 Aug 2008, Published online: 02 Apr 2009
 

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′).

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