Synthesis of Unsymmetrical Ketones Using Chelation-Controlled Sequential Substitution of N-Triazinylamide/Weinreb Amide by Organometallic Reagents

N-(2,4-Dimethoxy-1,3,5-triazinyl)amide was found to exhibit similar behavior to N-methoxy-N-methylamide (Weinreb amide) but higher reactivity for nucleophilic substitution by organometallic reagents. Triazinylamide suppresses overaddition, leading to the formation of a tertiary alcohol by the chelating ability of the triazinyl and carbonyl groups. Ureas possessing both triazinylamino and methoxy(methyl)amino groups underwent sequential nucleophilic substitution with different organometallic reagents, which furnished unsymmetrical ketones without any detectable tertiary alcohols.