Disconnection of Fused-Ring Systems

The formal procedures for analysis of alternative modes of disconnection of fused-ring systems are facilitated by the use of a standard nomenclature for various types of key bonds in such structures. A number of useful terms are illustrated in formulas 111-114, which have been constructed arbitrarily using rings of the most common sizes, 5 and 6. Structures are shown for 

The most generally useful topological criteria for the effective disconnection of a network of fused rings fall into several categories. In the examples which follow most rings are arbitrarily chosen as 5- or 6-membered, and the term ring refers to a primary ring. 

Building-block rings (e.g. benzenoid) which are terminal are not disconnected central benzenoid rings in a polycyclic system may be eligible for disconnection especially if adjacent rings are benzenoid or not readily disconnectible. 

All possible [2+1] disconnections of fused 3-membered rings and [2+2] disconnections of fused 4-membered rings are strategic. 

Fusion bonds are not candidates for strategic one-bond disconnection if such disconnection generates a ring of greater than 7 members. 

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Other procedures for generating chains from polycyclic fused ring systems and for disconnecting fused rings which use simple graph theoretical approaches have been described.35 They make use of the dual of the molecular graph, i.e. the figure... 

Intramolecular cycloadditions are among the most efficient methods for the synthesis of fused bicyclic ring systems [30]. From this perspective, the hetisine skeleton encompasses two key retro-cycloaddition key elements. (1) a bridging pyrrolidine ring accessible via a [3+2] azomethine dipolar cycloaddition and (2) a [2.2.2] bicyclo-octane accessible via a [4+2] Diels-Alder carbocyclic cycloaddition (Chart 1.4). While intramolecular [4+2] Diels—Alder cycloadditions to form [2.2.2] bicycle-octane systems have extensive precedence [3+2], azomethine dipolar cycloadditions to form highly fused aza systems are rare [31-33]. The staging of these two operations in sequence is critical to a unified synthetic plan. As the proposed [3+2] dipolar cycloaddition is expected to be the more challenging of the two transformations, it should be conducted in an early phase in the forward synthetic direction. As a result, a retrosynthetic analysis would entail initial consideration of the [4+2] cycloaddition to arrive at the optimal retrosynthetic C-C bond disconnections for this transformation. 

The method can be illustrated with a simple example let us consider the diagram A which represents a pentacyclic fused system, as well as its dual in the graph theoretical sense. The thick lines are the "core bonds", as they were defined by mle 4. A strategic bond disconnection of the molecule can be effected as follows i) Select the ring which has the largest number of core bonds and at least one noncore bond. Disconnect a noncore bond which is exo to the adjacent ring (A... 

A number of natural sesquiterpenes like hirsutene 90 or corioline 91 have as their common structural unit a system of linearly fused five-membered rings (Scheme 3.21). The standard pathway of the retrosynthetic analysis of this system involves the search for strategic bonds in one of the rings. A, B, or C, disconnection of which would lead to the simplification of the target molecule and eventually to simple cyclopentane derivatives as available starting materials. As a result, diverse synthetic plans were devised and successfully employed in numerous synthetic studies in this field(see also the set of syntheses described in Section 2.23.2). 

As with isolated rings, individual heterorings in fused systems which are synthetic equivalents of acyclic subunits, e.g. lactone, ketal, lactam, and hemiketal, can be disconnected. 

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