Dissonant

If a chiral aldehyde, e.g., methyl (27 ,4S)-4-formyl-2-methylpentanoate (syn-1) is attacked by an achiral enolate (see Section 1.3.4.3.1.), the induced stereoselectivity is directed by the aldehyde ( inherent aldehyde selectivity ). Predictions of the stereochemical outcome are possible (at least for 1,2- and 1,3-induction) based on the Cram—Felkin Anh model or Cram s cyclic model (see Sections 1.3.4.3.1. and 1.3.4.3.2.). If, however, the enantiomerically pure aldehyde 1 is allowed to react with both enantiomers of the boron enolate l-rerr-butyldimethylsilyloxy-2-dibutylboranyloxy-1-cyclohexyl-2-butene (2), it must be expected that the diastereofacial selec-tivitics of the aldehyde and enolate will be consonant in one of the combinations ( matched pair 29), but will be dissonant in the other combination ( mismatched pair 29). This would lead to different ratios of the adducts 3a/3b and 4a/4b. 

An OECD study identifies several barriers for a new technology to penetrate the market (OECD, 2002). These are lack of awareness, cognitive dissonance, lack of concern for future generations, fear of and resistance to change and, finally, lack of adequate professional advice. Each of these barriers must be countered with special measures if the acceptance for a new technology, in this case hydrogen, is to be increased. 

As a corollary to the cases above, the aldehyde may also contain a proximal center of asymmetry. In these cases the resident chirality in both the enolate and the aldehyde can influence the generation of new asymmetry in either a mutually cooperative (consonant) or an antagonistic (dissonant) fashion. The consonant or dissonant diastere oface selection imparted to both condensation partners has been referred to as double stereodifferentiation (83,109). This issue becomes important in the lasalocid A aldol bond construction illustrated in eq. [93]. This pivotal aldol condensation has been examined in detail... 

The observation that aldehyde diastereoface selection is interrelated with allylborane geometry has important implications for the related aldol processes. The reactions of (-)-180a and (-)-180b with both enantiomers of aldehyde 181 revealed both consonant and dissonant double stereodifferentiation. For the Cram-selective ( )-crotyl... 

Notations 1,2-D, 1,3-C, 1,4-D, etc., refer to the relative position of the two functional groups within the carbon chain. Notice that rings, even if they have no functionality, can be classified as either consonant or dissonant depending upon whether they have an even or an odd number of carbon atoms. Table 2.4 summarises all the possibilities for bifunctional relationships as well as for rings, whether they are carbocycles or heterocycles, and whether they are funtionalised or not. 

TABLE 2.4. Consonant and dissonant linear bifunctional relationships, carbocycles, and heterocycles... 

As we will see later, in contrast to consonant molecules or systems, the synthesis of dissonant molecules is always a more complex problem, that involves a larger number of steps and intermediates and takes place through essentially irreversible processes, which require more critical and sophisticated experimental conditions. 

Alternatively, it is possible to add a functional group (FGA), either to functionalise the carbon skeleton or to create new consonances (dissonances must be always avoided ) which can provide valid bond disconnection mechanisms (HP-4). Of some special interest is the introduction of a double bond (in the a,P-position if a carbonyl group is already present in the target molecule) since it is a typical ambivalent group, of type A, which provides different valid bond disconnection mechanisms, either directly or after substitution by an equivalent synthon, such as a... 

Bifunctional systems In the case of bifunctional systems (or molecules) only two alternatives are possible the bifunctional relationships are either "consonant" or "dissonant" (apart from molecules or systems with functional groups of type A to which we have referred to as "assonant"). In the first case, the synthetic problem will have been solved, in principle, in applying the "heuristic principle" HP-2 that is to say, the molecule will be disconnected according to a retro-Claisen, a retro-aldol or a retro-Mannich condensation, or a retro-Michael addition, proceeding if necessary by a prior adjustment of the heteroatom oxidation level (FGI). 

On the contrary, if a "dissonant" bifunctional relationship is present in the system or molecule under consideration, then the synthetic problem may be much more complex and we will have to resort to some of the methods especially designed for such purposes, which will be discussed in the next Chapter. 

The synthesis of dissonant systems is intrinsically more diffficult than the synthesis of consonant systems and because of this chemists have developed, in the past few years, more and more selective and efficient methods for performing it. Table 5.1 gives a summary of the most important methods developed so far, which have been classified into five main strategies ... 

TABLE 5.1. General strategies for the synthesis of dissonant systems... 

Simple reactivity inversion" implies using an umpoled synthon whose origin has, in principle, nothing in common with the synthon with "unnatural" polarity. An example of this type of reactivity inversion is found in one of the possible synthesis of cw-jasmone (3) in which the nitroethane (4) is used as an equivalent of an "acetyl anion" and reacts with an a,P-unsaturated ketone to give the corresponding 1,4-bifunctional system which can then be transformed by a Nef-type reaction into the dissonant 1,4-dicarbonyl system [5]. An intramolecular aldol condensation finally affords the target molecule (Scheme 5.3). 

Plausible disconnections dissonant three-membered rings... 

In contrast to "illogical disconnections", in "plausible disconnections" a reasonable or, at least, plausible mechanism exists which involves the motion of electron pairs and leads to stable fragments, either ions or molecules. In any case, however, the "principle of maximum simplicity" does not hold here, since one of the resulting fragments is always a dissonant three-membered ring. 

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