We describe the development of a novel synthesis strategy that uses common reaction conditions to transform a collection of simple building blocks into complex molecules bearing a terminal difluoromethyl group. The core of this approach is the conscious design and synthesis of new difluorinated building blocks which contain inactive and reactive groups on each side of the CF(2) group. The strategy is illustrated by application to the synthesis of CF(2)H-bearing pseudopeptides via Ugi reaction.