Synthon Approaches

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. 

An alternative way to synthesize imidazoles in a more flexible manner is to use a synthon. An example of such a synthon approach, is the synthesis of imidazoles using tosylmethyl isocyanide (TOSMIC). The original procedure using this synthon gave only moderate overall yields of the substituted imidazoles18, mainly due to the poor yield in the first step (figure 7). 

However, recently the yield of the first step of this imidazole synthesis was improved dramatically by replacement of the basic catalyst (tBuOK) by a milder basic catalyst, sodium cyanide19. Due to these milder reaction conditions a greater variety of aldehydes, one of the starting materials for the synthesis of imidazoles, can be used increasing the flexibility of the method20 even more. This synthon approach can also be used to prepare the bioiscsteric substituted thiazole analogs21. 

Other recent improvements of the TOSMIC synthon approach include the use of different precursors for the C5-N1 part of the imidazole ring. For example by the use of silyl imines22. 

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 disconnection or synthon approach now integrated into the text, and the principles of retrosynthetic analysis applied to relevant aliphatic, aromatic, alieyelic and heterocyclic compounds. 

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. 

The aim of this book is to show you how this planning is done to help you learn the disconnection or synthon approach to organic synthesis. This approach is analytical we start with the molecule we want to make the target molecule) and break it down by a series of disconnections into possible starting materials. In the last chapter of the book we shall discuss the synthesis of the natural product a-sinensal (1) and we shall devise a route using five different, easily available starting materials (2-7). 

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