Communication: Liquid crystals with one or more trans-1,3-dioxane building blocks (see Figure) combine high dielectric anisotropy with low birefringence and favorable mesogenic and viscoelastic properties. A new building-block-oriented synthetic strategy is described that offers convenient access to trans-1,3-dioxane-based core structures with various alkyl or alkenyl side chains or with a difluorovinyloxy(methyl) group as a polar end group.