REACTION MECHANISM AND THE STRATEGY OF SYNTHESIS

It has been pointed out already that the early design of synthetic routes for the vast number of simple and complex molecules was a largely intuitive operation. Indeed even the most eminent of synthetic chemists rarely recorded in the literature the thought processes which led to the realisation of the successful synthesis of a complex structure. One notable exception was that of the Robinson tropi-none synthesis.13 In this case the molecule was submitted to an imaginary hydrolysis at the points indicated by the dotted line and resolved into succin-dialdehyde, methylamine and acetone. These reagents were then mixed together 

A review on recent developments classifies these programs into two main categories, the passive programs and the active programs.16 

The major active programs have some similarity between themselves in that most are retrosynthetic and each breaks the target molecule down into synthetic precursor units. These in turn are similarly degraded , via retrosynthetic steps, to readily available starting materials. In achieving these aims two different approaches have been adopted, and useful summaries have been published.19 A third approach has a rather different philosophy since the program operates in a synthetic rather than a retrosynthetic mode. 

In the third approach,22 the programs operate in the synthetic, rather than the retrosynthetic, mode from a database of reaction mechanisms. As such they usefully complement the programs of the previous two groups, offering an answer to the hypothetical question if compound Y is subjected to the reaction conditions Z would X, or some other alternative structure, be formed . 

The principal exponent of the non-computerised approach to retrosynthetic analysis in organic synthesis, and which finds its origin in the early work of E. J. Corey, is S. Warren.5c d A useful shorter account is to be found in the writings of J. Fuhrhop and G. Penzlin.5e The non-computerised retrosynthetic analysis has also been termed the synthon approach, a term which was first introduced and defined by E. J. Corey.15 

---