Bifunctional relationship

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... 

In principle, the synthesis of a consonant molecule or a bifunctional relationship within a more complex polyfunctional molecule, does not offer too many difficulties. In fact, all the classical synthetic methods of carbon-carbon bond formation that utilise reactions which are essentially reversible, lead to consonant relationships. For instance, the book by H.O. House "Modem Synthetic Reactions" [22], after dealing, for almost 500 pages, with functional group manipulations, devotes the last 350 pages to carbon-carbon bond formation, all of which lead to consonant relationships. These methods can, actually, be reduced to the following four classical condensations (and their variants) Claisen condensation, aldol condensation, Mannich condensation and Michael addition (Table 2.5). 

The recognition of consonant bifunctional relationships in the target molecule allows their disconnection by a retro-Claisen, a retro-aldol or a retro-Mannich condensation or by retro-Michael addition [equivalent, according to Corey s formalisation, to the application of the corresponding transforms (= operators) to the appropriate retrons]. 

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. 

Although we have already referred to some rearrangements in connection with the synthesis of dissonant bifunctional relationships, in the present Chapter we will consider those rearrangements which affect mainly the molecular skeleton. 

HP-3 FGI, in order to introduce a C=0 group, modify a double bond or to proceed to a "reactivity inversion" operation Umpolung) in dissonant bifunctional relationships (see below iii-a). 

HP-4 EGA, in order to functionalise or create new consonant bifunctional relationships (new dissonances must be avoided) sometimes, introduce a double bond prior to disconnection of bonds (conjugated if a C=0 group is already present). 

MONOFUNCTIONAL, which allow disconnections or FGI of "isolated" functional groups (that is to say, a functional group which does not belong to a bifunctional relationship, from 1,2-D up to 1,6-D). 

In summary, the information given here is obligation for the affected atom of having or not having the indicated characteristics. For instance, all the disconnections of group 2, "MONOFUNCTIONAL", have expressed in some of their atoms the "obligation of not belonging to a bifunctional relationship". 

It is not necessary to emphasise here that the inadequate use of the "control" (see instruction manual. Appendix B-2) for changing the order of disconnections may "spoil" the logic of a retrosynthetic analysis. Thus, giving the highest priority to "FINALS", for example, may destroy all the existing bifunctional relationships which would offer the best solutions. 

CHAOS, of course, also finds and shows (if required) all the bifunctional relationships which are classified as "consonant" and "dissonant". 

Draw the structures of twistane, tropinone, exo-brevicomin, patchouli alcohol, longifolene, sativene, luciduline and porantherine and search bifunctional relationships, rings, synthetically significant rings, bridgeheads, core bonds and strategic bonds of each one of them. 

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