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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.

Terminal alkyne dicarbonylation can be readily effected under mild conditions b y treating alkynes with carbon monoxide and alcohols or water at 25-80°C in the presence of Pdlp, KI and air, with unprecedented catalytic efficiency. Dicarbonylated products are mainly maleic esters or acids and their ring-chain tautomers. The latter are formed to a large extent at room temperature. Reaction pathways are discussed.Dicarbonylation of alkynes with carbon monoxide has been known for several years,' but even the most recent literature reports methods which are not completely satisfactory particularly from the standpoint of catalytic efficiency. However, alkyl-or aryl-maleic esters and acids are interesting products, which can be used as monomers for polymerization, so an efficient procedure to prepare these compounds is a useful target. We now report such a procedure, which affords high yields of alkyl-or aryl-maleic esters and acids under mild conditions. A preliminary account, limited to prop-2-ynyl alcohol, was published r e c e n t l ~. ~

Estimates of the prevalence of "hardcore" smokers in Ontario varied considerably between the six definitions of the "hardcore" smokers found in the population-based literature. This study underscores the need for consensus on the best definition of "hardcore" smoker.

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