This article presents progress in the computer-aided synthesis of energy-efficient complex column networks based on the automatic temperature collocation algorithm. Three prefractionating complex networks are employed to split several quaternary mixtures into four almost-pure end products. Network solutions for two different mixtures with different difficulties of separation as well as various feed compositions are presented. Twelve network designs, all satisfying stringent product quality requirements, but with different energy demands and capital costs, are laid out in detail. The design computations with the temperature collocation methodology are demonstrated to agree closely with rigorous mass, equilibrium, summation, and heat computations verified with the industrial-standard flow sheet simulator AspenPlus. In fact, detailed design specifications were so accurate that their use to initialize AspenPlus flow sheet simulations leads to convergence in a few iterations to essentially the same end products. The success of the method demonstrates that rigorous solutions to separation problems can be obtained in a fraction of valuable engineering design time by computer methods. The automatic and rigorous flow sheet synthesis is apt to systematically address process design problems such as the synthesis of energy-efficient separation networks, the layout of biorefineries with novel feedstocks, or a sustainable process for reduction of greenhouse gases emissions.