“A Way of Thinking Backwards”: Computing and Method in Synthetic Organic Chemistry

This article addresses the history of how chemists designed syntheses of complex molecules during the mid-to-late twentieth century, and of the relationship between devising, describing, teaching, and computerizing methods of scientific thinking in this domain. It details the development of retrosynthetic analysis, a key method that chemists use to plan organic chemical syntheses, and LHASA (Logic and Heuristics Applied to Synthetic Analysis), a computer program intended to aid chemists in this task. The chemist E. J. Corey developed this method and computer program side-by-side, from the early 1960s through the 1990s. Although the LHASA program never came into widespread use, retrosynthetic analysis became a standard method for teaching and practicing synthetic planning, a subject previously taken as resistant to generalization. This article shows how the efforts of Corey and his collaborators to make synthetic planning tractable to teaching and to computer automation shaped a way of thinking taken up by chemists, unaided by machines. The method of retrosynthetic analysis made chemical thinking (as Corey perceived it) explicit, in accordance with the demands of computing (as Corey and his LHASA collaborators perceived them). This history of automation and method-making in recent chemistry suggests a potentially productive approach to the study of other projects to think on, with, or like machines.