Functional group interconversion retrosynthetic analysis

A retrosynthetic analysis of an a,/J-unsaturated aldehyde or ketone involves an initial functional group interconversion into a /1-hydroxycarbonyl compound, followed by a disconnection into the carbocation (12) and the carbanion (13) synthons. The reagent equivalents of these two synthons are the corresponding carbonyl compounds. 

Retrosynthetic analysis involves the disassembly of a TM into available starting materials by sequential disconnections and functional group interconversions. Structural changes in the retrosynthetic direction should lead to substrates that are more readily available than the TM. Synthons are fragments resulting from disconnection of carbon-carbon bonds of the TM. The actual substrates used for the forward synthesis are the synthetic equivalents (SE). Also, reagents derived from inverting the polarity (IP) of synthons may serve as SEs. 

In this final section of the chapter, we will combine the skills from the previous two sections and work on synthesis problems that involve functional group interconversion and C—C bond formation. Recall from Chapter 12 that it is very helpful to approach a synthesis problem work ing forward as well as working backward (retrosynthetic analysis). We will use all of these skills in the following example. 

Two synthons C and D are the result of an alternative disconnection b of the CH2-CH2Ar bond. Finally, retrosynthetic analysis c suggests two functional group interconversions followed by disconnection of the amide N-CO bond, affording synthons E and F. This analysis has been used in the synthesis of the sila-bioisostere of fexofenadine (49), as described in Sect. 10.4.3. 

Abstract Retrosynthetic analysis as an imaginative process is introduced. Disconnection and functional group interconversion are discussed. l-(Pyridine-3-yl) propan-l-ol is selected as an exemplary target molecule for retrosynthetic analysis and its (5 -enantiomer for asymmetric synthesis. Interconversions of oxygen functionalities are overviewed. The acidity of the C-H bond as a key property for C-C disconnections is indicated. Some historical and environmental aspects of organic synthesis are concisely presented. 

Such a systematic review is especially useful since a knowledge of the functional group transformation is essential in retrosynthetic analysis. In the so-called transform -based strategy functional group interchanges (or interconversions FGI) or functional group transpositions (FGT) are applied to simplify a target molecule and one has to look for synthetic reactions which allow these transformations to perform. 

Here it is important to note the principle difference between the retrosynthetic steps in Schemes 1.3 and 1.4. In the first one we anticipate interconversion of the functional group (FGI), in the second one the disconnection of the C-C bond (DIS). They reflect the difference between two basic types of reactions in synthetic organic chemistry the transformation of one functional group and formation of a new C-C bond. By far more synthetically important are C-C bond-forming reactions, which enhance the complexity of the carbon skeleton. A rather sharp difference between these two types of reactions in synthetic organic chemistry is reflected in retrosynthetic analysis. Disconnection of the C-C bond in TM la is presented in some detail (Scheme 1.5). 

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