| The synthesis of ureas from amines has traditionally been accomplished with stoichiometric reactions of phosgene or its derivatives, which are associated with environmental and health issues. Because of the prevalence of urea moieties in molecules of interest for several applications, alternative catalytic routes for the oxidative conversion of amines to ureas using CO or CO2 as the carbonyl source have been developed. W(CO)6-catalyzed oxidative carbonylation of amines to ureas in the presence of CO provides an alternative to stoichiometric reaction of amines with phosgene or its derivatives such as 1,1-carbonyldiimidazole (CDI). Synthesis of the core structure of the HIV protease inhibitors DMP 323 and DMP 450 has been achieved via W(CO)6/I2-catalyzed carbonylation of diamine intermediates. This methodology also has been successfully applied to the carbonylation of amino alcohols to selectively form hydroxyalkyl ureas. Selected examples of 1,2-, 1,3-, 1,4- and 1,5-aminoalcohols were converted to the corresponding ureas in good to excellent yields, with only trace amounts of the cyclic carbamates being present. Other interesting targets such as hydantoins have also been prepared using W(CO)6/I2. Optically pure alpha-amino amides have been shown to produce the corresponding hydantoins in good yields. |
