Abstract
The aminocarbonylation of 6-iodoquinoline has been investigated in the presence of large series of amine nucleophiles, providing an efficient synthetic route for producing various quinoline-6-carboxamide and quinoline-6-glyoxylamide derivatives. It was shown, after detailed optimization study, that the formation of amides and ketoamides is strongly influenced by the reaction conditions. Performing the reactions at 40 bar of carbon monoxide pressure in the presence of Pd(OAc)2/2 PPh3, the corresponding 2-ketocarboxamides were formed as major products (up to 63%). When the monodentate triphenylphosphine was replaced by the bidentate XantPhos, the quinoline-6-carboxamide derivatives were synthesized almost exclusively under atmospheric conditions (up to 98%). The isolation and characterization of the new carbonylated products of various structures were also accomplished. Furthermore, the structure of three new mono- and double-carbonylated compounds were unambiguously established by using a single-crystal XRD study.
Highlights
The activation of carbon monoxide and its use as a C1 building block in the presence of transition metal complexes is one of the most important stories of homogeneous catalysis
Our study began with the optimization of the aminocarbonylation of 6-iodoquinoline (1) to find the appropriate circumstances for the selective synthesis of the mono- and dicarbonylated derivatives (Table 1)
The quinoline skeleton was functionalized at position 6 via palladiumcatalyzed aminocarbonylation in the presence of amines with various structures, providing several quinoline-6-carboxamides and quinoline-6-glyoxylamides
Summary
The activation of carbon monoxide and its use as a C1 building block in the presence of transition metal complexes is one of the most important stories of homogeneous catalysis. Despite the elevated carbon monoxide pressure that is usually recommended for the production of 2-ketocarboxamides, Han and coworkers described a palladium-catalyzed ligand-free selective double carbonylation method under atmospheric conditions [33]. This special structural motif, known as glyoxamide or glyoxylamide, could be involved in several drug candidates conferring to their skeletons important structural features [34] and, critical pharmacokinetic properties, including metabolic stability in biological medium [35]. Its ability to establish hydrogen bonds and to increase conformational constraints of lead compounds makes it a key component of various new ligand candidates with excellent bioreactivity towards amino acid residues of various receptors and enzymes [31,36,37,38]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
