The central carbonyl group of diethyl mesoxalate (DEMO) exhibits high electrophilicity that allows it to be attacked by versatile nucleophiles. Even a less nucleophilic acid amide serves as a nucleophile to produce N,O-acetal upon treatment with DEMO in the presence of acetic anhydride. When the obtained N,O-acetal was treated with a base, the elimination of acetic acid generated N-acylimine in situ. N-Acylimine is also highly electrophilic, allowing it to accept the second nucleophilic addition by an amine, resulting in α,α-bis(functionalized) aminals. This protocol facilitates the modification of the two different amino groups by altering nucleophiles, resulting in the production of tetra-functionalized methane derivatives on demand. The ring closure between the amide moiety and the amino group was achieved using the structural features to form a six-membered ring.