Heterolytic disconnections

SYNTHETIC STRUCTURAL ANALYSIS. SIMPLIFICATION. HETEROLYTIC DISCONNECTIONS HEURISTIC PRINCIPLES... 

In contrast with all the heterolytic disconnections considered so far, which have been called "logical" in the sense that they meet all the requirements already mentioned (see Heading 3.5), we will cal "illogical disconnections" those disconnections which, although they do not fulfil some of these requirements, are still useful since they introduce an element of flexibility which is highly desirable in designing complex organic syntheses. 

HP-7 Heterolytic disconnection of the appendages directly attached to sp carbon atoms bearing functional groups of type E and eventually of type A. 

HP-8 Heterolytic disconnection of carbon-carbon bonds of the carbon skeleton at the ipso-, a- or P-position to the functional group. 

Disconnections may involve either the carbon skeleton or functional groups. Normally the first step is to disconnect the sections of a molecule that are held together by functional groups such as esters, amides and acetals, as it is usually easier to find reconnection reactions for these functional groups. Heterolytic disconnections usually provide the most useful approach to synthesis design. 

This is because they divide the molecule into electrophilic and nucleophilic species, which can be more easily converted into the appropriate electrophilic and nucleophilic reagents for reconnection. The most useful heterolytic disconnections are... 

The heterolytic disconnection of the benzyl-vinyl C-C bond is an obvious requisite for the construction of ring B of target compound II, However, this operation cannot be performed directly owing to the great instability of the resulting charged species. Modification of the vinyl carbon /3 to the ketone appears to be, therefore, an indispensible condition before any other transformation can take place. 

Selection of the preferred central C-C bond for disconnection in TM V in Scheme 4.25 depends on the electronic properties of the R and R groups and should result in the most stable synthons. On heterolytic disconnection, the electron pair from the a bond moves to the a-C atom in TM Vd where the carbanion is stabilized by the neighboring electron-withdrawing group. To avoid the formation of an unstable carbocation on the P-C atom, concerted deprotonation of the acid C-H bond in the a-C atom implies participation of the second C=0 group in the 1,5-dicarbonyl unit affording strongly electrophilic enone TM Vc. 

By analogy with the organic bond-forming reactions, it is assumed that bond disconnections take place heterolytically, being classified as "logical disconnections" if the three following criteria are met ... 

In the present chapter, however, because the problem is considered from a retrosynthetic point of view, we will distinguish only between heterolytic and homolytic disconnections -to which we will refer to as "retro-annulations"- and concerted or "pericyclic (or cheletropic) cycloreversions". In the same way that Woodward-Hoffmann rules [2] apply to pericyclic reactions, the Baldwin rules [3] may be said to apply to heterolytic as well as to homolytic "monotopic" annulations (see Table 6.1). Although in the preceding Chapter (see 5.5) we have already described some radical "monotopic" annulations, later on in this Chapter (see 6.1.3) and mainly in Chapter 7 we will refer to some new methods, syntheses and strategies which have been developed recently. 

In the disconnection approach, bonds are usually disconnected by either homolytic or heterolytic fission (Figure 10.11(a) and (b)). However, some bonds may be disconnected by a reverse pericyclic mechanism (Figure 10.11(c)). 

Figure 10.11 (a) Homolytic, (b) heterolytic and (c) pericyclic bond disconnections. Homolytic... 

Chemical bonds can be cleaved heterolytically, homolytically, or through concerted transform (into two neutral, closed-shell fragments). The following discussion will focus on heterolytic and cyclic disconnections. 

Heterolytic retrosynthetic disconnection of a carbon-carbon bond in a molecule breaks the TM into an acceptor synthon, a carbocation, and a donor synthon, a carbanion. In a formal sense, the reverse reaction — the formation of a C-C bond — then involves the union of an electrophilic acceptor synthon and a nucleophilic donor synthon. Tables 1.1 and 1.2 show some important acceptor and donor synthons and their synthetic equivalents. "... 

Interestingly, the synthons being obtained from single bond disconnections could be either ions (cations or anions) or radicals exclusively depending on the fact whether the cleavage encormtered to the bond is heterolytic or homolytic. Invariably, they do not behave... 

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