Homolytic disconnections

Homolytic disconnections couplings involving electron-transfer... 

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. 

Homolytic disconnections radicals in the synthesis of cyclic systems... 

Curran s retrosynthetic analysis of fused and bridged polycyclic systems through homolytic disconnections... 

As we will see, the general strategy for synthesising this pentagonal polycyclic system requires the homolytic disconnection of two vicinal bonds that are exo to the "central" ring, which remains intact (see Schemes 7.21 and 7.22). In the synthetic direction all the cyclisations must be, according to Baldwin s rules, 5-exo. 

The retro-Diels-Alder step envisages homolytic disconnection of two bonds in the 2,3-position related to the double bond of the cyclohexene ring. Two electrons of each o bond and two electrons from the n bond move to the neighbor o bonds (Scheme 2.5a). Such disconnection corresponds to the pericyclic or concerted character of the Diels-Alder reaction [1, 2]. 

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. 

The elegant formal total synthesis of morphine, accomplished by Parker, shows some similarities to that of Fuchs through analogous disconnections. In both syntheses, the core of the molecule was formed as a result of a tandem process in this case as a result of a radical cascade.79 80 The immediate cyclization precursor 191 was prepared via a Mitsunobu reaction between monoprotected cw-diol 189 (prepared in 8 steps from 2-((3-methoxyphenyl)ethylamine) in 47% overall yield) and phenol 188, followed by cleavage of the silyl ether, Scheme 21. The key step, homolytic cleavage of the Ci2-Br... 

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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