Efficient synthesis of ureas by direct palladium-catalyzed oxidative carbonylation of amines.
A general synthesis of symmetrically disubstituted ureas and trisubstituted ureas by direct Pd-catalyzed oxidative carbonylation of primary amines or of a mixture of a primary and a secondary amine, respectively, with unprecedented catalytic efficiencies for this kind of process, is reported. Reactions are carried out at 90-100 degrees C in DME as the solvent in the presence of PdI(2) in conjunction with an excess of KI as the catalytic system and under 20 atm of a 4:1 mixture of CO and air. In some cases, working in the presence of an excess of CO(2) (40 atm) in addition to CO and air (60 atm total) had a beneficial effect on substrate reactivity and product yield. Cyclic five-membered and six-membered ureas were easily formed from primary diamines. The methodology has been successfully applied to the synthesis of pharmacologically active ureas, such as those deriving from alpha-amino esters or urea NPY5RA-972, a potent antagonist of the neuropeptide Y5 receptor.
Gabriele
Bartolo
B
Dipartimento di Scienze Farmaceutiche, Università della Calabria, 87036 Arcavacata di Rende, Cosenza, Italy. b.gabriele@unical.it
Salerno
Giuseppe
G
Mancuso
Raffaella
R
Costa
Mirco
M
D000588:Amines / Q000737:chemistry; D002244:Carbon / Q000378:metabolism*; D002384:Catalysis; D010084:Oxidation-Reduction; D010165:Palladium / Q000737:chemistry*; D014508:Urea / Q000138:chemical synthesis*
D000588:Amines; D010165:Palladium; D002244:Carbon; D014508:Urea