The Synthon Approach

A synthon may be defined as— a structural unit that becomes an idealized fragment as a result of disconnection of a carbon-carbon or carbon-heteroatom bond in a retro synthetic step (transform) . 

Therefore, one would broadly imagine that an open-chain structure while undergoing a single-disconnection step would ultimately yield two synthons. Further, an alike disconnection of a bond joining a functional group to a cyclic structure would also give rise to two synthons. 

Interestingly, the synthons being obtained from single bond disconnections could be either ions (cations or anions) or radicals exclusively depending on the fact whether the cleavage encormtered to the bond is heterolytic or homolytic. Invariably, they do not behave 

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ITiis chapter does not introduce new chemical reactions. On the contrary, mainly elementary reactions are employed. The attempt is made here to provide an introduction into the planning of syntheses of simple "target molecules" based upon the synthon approach ofE.J. Corey (1967A, 1971) and the knowledge of the market of "fine chemicals". 

In antithetical analyses of carbon skeletons the synthon approach described in chapter I is used in the reverse order, e.g. 1,3-difunctional target molecules are "transformed" by imaginary retro-aldol type reactions, cyclohexene derivatives by imaginary relro-Diels-Alder reactions. 

The second edition of this extremely successful guidebook for planning organic syntheses is addressed to advanced undergraduate, graduate and research chemists. Retrosynthetic analysis and the synthon approach are presented. This new, extensively revised and enlarged edition takes account of recent developments, such as nanometer-size architecture, while emphasizing the essentials. 

S. Warren, "Designing Organic Syntheses. A Programmed Introduction to the Synthon Approach", John Wiley Sons, Chichester, 1978. 

Try to elaborate "synthesis trees" of most of the exercises found in Warren s book "Designing Organic Syntheses. A Programmed Introduction to the Synthon Approach" (John Wiley Sons, Chichester, 1978) and compare the different synthetic sequences with the solutions proposed therein. 

Section 3.2.1 covers a similar area of synthesis planning as S. Warren s (1978) book Designing Organic Synthesis . This book contains many examples of antitheses of achiral carbo-and heterocyclic compounds that are largely ignored in this chapter (but see sections 2.5,4.6, and 4.7 for heterocycles). Warren s much more elaborate introduction into the "synthon approach to rerro-synthetic analysis is based on E.J. Corey s work (1967A, 1971) and is highly recommended for further study. 

Wang, Y -F, Chen, C -S, Girdaukas, G, Sih, C J 1984, J Am Chem Soc 106, 3695 Warren, S 1978, Designing Organic Synthesis - A Programmed Introduction to the Synthon Approach, Wiley New York London... 

An excellent approach can be found in S. Warren, Designing Organic Syntheses, a Programmed Introduction to the Synthon Approach, Wiley, New York, 1978. 

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.5 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... 

The Synthon Approach as a Pragmatic Tool in Elaborating Viable Synthetic Pathways... 

Finally, it should be noted that in our discussion of synthons we used charged intermediates, carbanions and carbocations. This is not to imply that the synthon approach is limited to heterolytic reactions. Quite the contrary, the ideology of the synthon approach is universal and can be applied to reactions of all possible types. We are about to see this in the next sections. 

Figure 10.12. A comparison of the synthon approach and the chiron approach.

The advantage of using the synthon approach is that it offers a considerable simpHfication in the understanding of crystal structures. For example, the same carboxy dimer motif 1 is present in the structures of benzoic acid, terephthalic acid, isophthahc acid, trimesic acid and adamantane-l,3,5,7-tetracarboxylic acid in zero-, one-, two- and three-dimensional arrangements [9] (see also the article by R. E. Melendez and A. D. Hamilton in this volume). 

S. Warren, Designing Organic Syntheses, The Synthon Approach,... 

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