Logical disconnection

Among the most logical disconnections of the carbocyclic rings of 272 (or the other precursors shown extending to 278) is that involving the strategic C(4)-C(5), C(6)-0 bond pair in 272 - 278. 

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 ... 

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. 

With the identification of the hemiatninal moiety at the core diazonamide A in 2001 [97], numerous retrosynthetic approaches to the molecule have taken advantage of the logical disconnection at the anomeric carbon to reveal an oxindole... 

The essential features of the strategy which evolved in our original plan that was directed toward the synthesis of 3 are summarized by the logical disconnections depicted in Scheme 3, wherein 26 was envisaged as the key intermediate and primary subgoal of the project. A Wittig construction... 

The second example prepares diketone 140 from alkyl halide 141. The starting material has a cyclopentane unit, which is apparent in 140, but a logical disconnection is between the two carbonyl units, suggesting the donor and acceptor sites shown. The donor site leads to a ketone derived from... 

The readily available 1-propyne reacts with HBr to obtain 29. Disconnection of the bond adjacent to the carbonyl in 27 (the functional group) leads to 30 and 31. Because 30 is the one-carbon fragment, it becomes the acceptor and the synthetic equivalent is iodomethane. This makes 31 the donor, and a reasonable synthetic equivalent is the enolate anion of acetaldehyde, 32 (see Chapter 22, Section 22.9, for alkylation of enolate anions). This leads to the overall synthesis shown, based on the retrosynthesis (see Figure 25.11). The ability to see the relationship between an alkene and an alkyne allowed identification of a logical disconnection and a reasonable synthesis. 

A typical retrosynthesis of a P-hydroxy ketone or P-hydroxy aldehyde involves making a disconnection between the two functional groups, more specifically, between the alpha carbon and the carbon bearing the OH group (the beta carbon). The carbon that now has an OH on it used to be a carbonyl carbon (C=0), which was an electrophilic carbon. Therefore, the other carbon group must have been introduced as a nucleophile this is a logical disconnection since a carbon alpha to a carbonyl can be a nucleophile as an enolate. 

Disconnection of the TM at the newly formed C-C bond gives an illogical synthon (an acyl anion, for which a 1,3-dithiane anion is the synthetic equivalent). An alternate, stepwise approach to the retrosynthesis involves first doing a functional group interconversion, followed by a logical disconnection. Either... 

When disconnection of a C-C bond is completed in a way to obtain synthons with a charge stabilized by the neighboring group, we talk about logical disconnection or disconnection that follows the correct mechanism. As to the electronic properties, synthons resulting from correct disconnection accommodate a stabilized charge, negative or positive, or an electronic sextet in carbene. 

The first retrosynthetic step represents the logical disconnection of the exocyclic C-C bond with the formation of two large synthetic blocks (Scheme 4.23). The... 

The last target molecule is logically disconnected to 2,2-dimethylcyclopentanone and acetylide anions. 

Retrosynthetic analysis of TM 5.13 starts with the logical disconnection of the cyclopropane ring to ethyl diazoacetate as the source of carbene and cyclohexene... 

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