On Using Tree Analysis to Quantify the Material, Input Energy, and Cost Throughput Efficiencies of Simple and Complex Synthesis Plans and Networks: Towards a Blueprint for Quantitative Total Synthesis and Green Chemistry

Synthetic plans or networks may be depicted as trees in a graph-theoretical sense. When drawn in a systematic way according to a defined convention key “green” metrics relating to the efficiency of performance of a synthesis to a target molecule may be easily obtained by inspection, that is, by a “connect-the-dots” approach. Example metrics include the cumulative and overall reaction mass efficiency (RME), the overall raw materials cost (RMC), and the fraction of total energy input directed to product (FTE). Throughout this paper kernel metrics are used to determine and compare the intrinsic efficiencies of synthetic plans since these depend directly on the nature of the chemical transformations and not on ancillary variables such as solvent usage, etc. Histograms of these metrics versus reaction stage allow for the easy determination of the mass-, cost-, and input energy-determining steps for a given synthesis plan. Other useful parameters that can be determined from a synthesis tree include the degree o...