Dissonant molecules

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. 

The synthetic applications of sigmatropic rearrangements to the synthesis of dissonant molecules (mainly 1,6-D) were extensively studied by Evans [22]. Although such a methodology meets the first two requirements of "logical disconnections", it does not meet the third one since it lacks simplicity. 

Let us suppose a dissonant molecule such as Ej-(C) -E2 (where q is an even... 

In the preceding Chapter we have already referred to some classical synthetic methods which proceed via radicals and which are usually used for the synthesis of dissonant molecules, including some cyclic and polycyclic systems. 

The strategy used in TOSCA is based upon the concept of consonant-dissonant molecules. Consonant molecules are those in which there is an alternative succession of positive and negative charges on the atoms (A B — C - - D—. etc.) and in dissonant molecules this situation do not occur (A... 

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. 

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). 

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. 

As in the case of acyclic compounds, the level of difficulty of the synthesis of a cyclic compound depends upon whether the molecule is a consonant or a dissonant system. However, some additional difficulties may be encountered in molecules with medium-sized rings as well as in polycyclic bridged compounds, which are treated in the next Chapter. On the other hand, as we have seen in Heading 4.3, even simple monofunctionalised cyclic molecules may require a FGA operation before bond disconnection of the cyclic network at the ipso-, a- or 13-positions can be effected. 

In contrast, the so-called bis-nor-Wieland-Miescher ketone (2) is a more complex synthetic problem, since the molecule is a multidissonant system with two dissonant bifunctional group relationships (1,4-D and 1,6-D) and two dissonant cyclopentane rings, besides a 1,5-consonant bifunctional group relationship. Its synthesis was only accomplished 30 years after the synthesis of its consonant homologue [5],... 

We have already referred to the retrosynthetic analysis of dissonant open chain molecules (see Heading 5.5). In this chapter we will deal with Curran s ideas in connection with fused and bridged polycyclic systems present in many natural products. Emphasis on cyclisations leading to 5-membered rings is maintained because ... 

The positive charge (+) is placed at the carbon attached to an E class functional group (e.g., =0, -OH, -Br) and the TM is then analyzed for consonant and dissonant patterns by assigning alternating polarities to the remaining carbons. In a consonant pattern, carbon atoms with the same class of functional groups have matching polarities, whereas in a dissonant pattern, their polarities are unlike. If a consonant pattern is present in a molecule, a simple synthesis may often be achieved. 

Thousands of experiments, run by hundreds of scientists, tell a story that spans billions of years and yet fits onto a single piece of paper, in the form of the periodic table of the elements. This story is painted in the bright colors of the individual elements and the blended shades of complex biochemical molecules. The tape of life unfolds through catastrophic dissonance and resolves with eucatastrophe after inevitable loss. 

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