Reaction antithetic

There is, however, an important class of reactions in which the translation of observations on the products into direct constraints on the structural possibilities is difficult if not impossible In these cases it is essential to consider the application of the reaction to each structural candidate and the relationship of these candidates to their respective products The most common examples of this class are reactions in which a given product or set of products may be obtained from different candidate structures for the unknown Or, stated slightly differently, the class of reactions in which there is more than one way for a given product or set of products to undergo the reverse, or antithetic reaction The following are some simple, but illustrative examples ... 

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. 

Antithetical connections (the reversal of synthetic cleavages) and rearrangements are indicated by a con or rcarr on the double-lined arrow. Here it is always practical to draw right away the reagents instead of synthons. A plausible reaction mechanism may, of course, always be indicated. 

Since (A) does not contain any other functional group in addition to the formyl group, one may predict that suitable reaction conditions could be found for all conversions into (A). Many other alternative target molecules can, of course, be formulated. The reduction of (H), for example, may require introduction of a protecting group, e.g. acetal formation. The industrial synthesis of (A) is based upon the oxidation of (E) since 3-methylbutanol (isoamyl alcohol) is a cheap distillation product from alcoholic fermentation ( fusel oils ). The second step of our simple antithetic analysis — systematic disconnection — will now be exemplified with all target molecules of the scheme above. For the sake of brevity we shall omit the syn-thons and indicate only the reagents and reaction conditions. 

Enantioselective processes involving chiral catalysts or reagents can provide sufficient spatial bias and transition state organization to obviate the need for control by substrate stereochemistry. Since such reactions do not require substrate spatial control, the corresponding transforms are easier to apply antithetically. The stereochemical information in the retron is used to determine which of the enantiomeric catalysts or reagents are appropriate and the transform is finally evaluated for chemical feasibility. Of course, such transforms are powerful because of their predictability and effectiveness in removing stereocenters from a target. 

In the preceding example we did not consider cycloaddition reactions since these would not offer any suitable alternative synthetic pathway. The bicyclic isoquinuclidine derivative given below (G. Biichi, 1963, 1966A) contains only unstrained six-membered rings, and the refro-Diels-Alder transform is obviously the furthest-reaching simplification and the fastest antithetical route to commercial starting materials. Both bridgehead atoms can be introduced in one step. 

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In our new antithetic plan (Scheme 21), Weinreb s oxazolidinone 77 would remain a key synthetic objective. However, the Hoveyda-Grubbs reaction would now be applied to the diene 88. The new route would also block 0(4) of the vinyl aldehyde precursor with a TES ether to prevent hemiacetal formation from occurring. The crucial Vasella... 

In the aldol condensation reported in reaction A in Fig. 7 only one of the four possible stereoisomeric aldehydes undergoes a completely anti stereoselective reaction with the indicated dialkylboron ketone enolate [35]. If the syn aldol is required, the use of the trichloroti-tanium enolate and of the C-3 epimeric aldehyde is necessary. These results show that two stereocenters of the same reagent can constitute a sort of internally matched or mismatched pair, and can operate synergically or antithetically in determining the steric course of a reaction. 

It will be useful to use a few terms coined by Corey and Wipke pS) in the discussion of this work. Since the logic-centred approach of generating a synthetic tree involves analytic processes which depend heavily upon the structural features of reaction products and the consideration of molecular changes in the retro-synthetic sense, the direction of computer analysis is termed antithetic as opposed to the direction of laboratory execution which is termed synthetic . A process in the antithetic direction is called a transform while a process in the synthetic direction is called a reaction . A reac-... 

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