ABSTRACT
The concept of synthesis strategy is the hallmark of organic chemistry. After one has learned about and amassed a library of organic reaction types, one uses this database to develop and invent synthesis plans composed of various combinations of these reactions in some kind of organized sequence to a complex target structure. Though it is an idea that is dif“cult to de“ne and parameterize, it is often best illustrated by examples. This has been the tradition of any type of compilation on organic chemistry. But what are the mechanics of how to come up with a synthesis strategy to a given target molecule? Retrosynthetic analysis provides a path for achieving this. When faced with a dif“cult problem, an effective method of solution is to think and work backward in the reverse sense. This idea, well known in mathematical science as inverse problem solving, provides elegant and beautiful solutions, especially when complementary algebraic and geometric solutions to a problem are found. A good mathematical analogy is factorization of polynomials or factorization of natural numbers into their constituent prime numbers. Retrosynthesis may be thought of in the same way. In effect, retrosynthetic analysis is the solution to the inverse problem of coming up with a route or plan to a target molecule. We may state the problem as follows: “nd a set of building block starting materials that can assemble to form the complex target molecule. When we add green chemistry thinking to this problem, the problem may be posed as follows: “nd an optimal set of building block starting materials that can assemble to form the complex target molecule, where optimal refers to building blocks that are used in their entirety and that are benign.
