Complexity of synthetic reactions. The use of complexity indices to evaluate reactions, transforms and disconnections1Electronic supplementary information (ESI) available: a Prolegomenon to chemical graph theory; Table 13 and Figure 1, summarizing all possible disconnections of azacyclohexane 28. See http://www.rsc.org/suppdata/nj/b2/b210843g/

Complexity and diversity indices based on fundamental mathematical entities (topological invariants) are used to calculate the changes that take place during synthetic reactions, such as the Aldol, Diels–Alder, Wittig, Reppe–Vollhardt, Pauson–Khand and House–Whitesides reactions. Such calculations provide a way to compare the power of various reactions to increase molecular complexity, and they furnish a ‘yardstick’ to gauge the state of the art of synthetic chemistry. Retrosynthetic transforms and disconnections are also evaluated, and in the latter case, topological simplification principles are derived. In this way we may reveal the ‘unseen hand’ of synthesis.