An ew,t ransformative methodology for the preparation of diketopyrrolopyrroles from aldehydes,p rimary amines,n itriles,a nd diethyl oxalacetate has been developed. It is nowpossible to prepare diketopyrrolopyrroles bearing an ordered arrangement of three different substituents from abundant and commercially available materials,a llowing the independent regulation of all desired physicochemical properties.F or the first time very electron-rich (carbazol-3-yl, dimethylaminophenyl, pyrrolo[3,2-b]pyrrolyl), and sterically hindered substituents (naphthalen-1-yl, quinolin-4-yl, acridin-9-yl, imidazo[1,5-a]pyridin-1-yl, 2-bromophenyl etc.)c an be appended to the diketopyrrolopyrrole core by condensation of an appropriate nitrile with ap yrrolidin-2-one intermediate. Even greater synthetic possibilities are related to the fact that such demanding substituents as 4-dimethylaminophenyl, indol-3-yl, and 2-methoxyphenyl can be incorporated from aldehyde precursors,b ypassing problems with the nitriles reactivity.