Synthesis of Unsymmetrical Ketones

1,3-Dimethoxy-1,3-dimethylurea (1) is a carbonyl dication equivalent which is available for synthesis of unsymmetrical ketones. Reich and co-workers have reported synthesis of several unsymmetrical ketones using 1.¹⁾ According to their report, the addition of 1 to solutions of organolithium reagents in THF readily produced the amides (2). The formation of the unsymmetrical ketones (3) from the addition of organolithium reagents to the amide 2 is well precedented. This approach has been used for synthesis of a C1-C21 subunit of the protein phosphatase inhibitor tautomycin by Marshall and co-workers.²⁾