Retrosynthetic transforms

Category Ih cyclizations effect closure of the C2 C3 bond. Scheme 3.1 depicts retrosynthetic transformations corresponding to syntheses in category lb. Included are three variations of the intramolecular aldol condensation and reductive coupling of o,/V-diacylanilines,... 

Several synthetic transformations that are parts of total syntheses of natural products are summarized by retrosynthetic outlines. For each retrosynthetic transform suggest a reagent or short reaction sequence that could accomplish the forward synthetic conversion. The proposed route should be diastereoselective but need not be enantioselective. 

Target molecules which contain a carbon-carbon double bond, in the presence of other functionality or not, may be treated as in a one- or two-group disconnection strategy, as noted above. However, disconnection at the double bond may be a valuable retrosynthetic transform, since the synthons may then be related to reagent equivalents for a Wittig-type (Section 5.2.3, p.495 and Section 5.18) or aldol-type (Section 5.18) synthesis. 

With quinoline [(100), X = H] the first retrosynthetic transform is reduction to 1,2-dihydroquinoline (cf. pyridines above) to facilitate recognition of the derived synthons obtained in the subsequent disconnection. 

But what are we to call the retrosynthetic transformation of 11 into 10 It isn t a disconnection rather an extra carbon atom has been added. So we call this operation a reconnection joining the target molecule back up to something to reveal the precursor. So, consider the synthesis of the m-enone 21, a structure found in insect pheromones, perfumes and flavourings. A Wittig... 

The advantages of Robinson s concept was confirmed in numerous total syntheses of alkaloids. One of the most illustrative examples is served by Stevens synthesis of the tricyclic compound coccinelline 45 (Scheme 3.10), the pheromone of the ladybug (ladybird). As was acknowledged in Stevens review article, in less time than it took to write this paragraph, we had developed on paper an attractive approach that relies on one of the oldest reactions known in alkaloid synthesis, namely the classical Robinson-Schopf condensation . This approach involved the retrosynthetic transformation of 45 into the ketopiper-idine derivative 46, which is amenable to disconnection in accordance with the same logic as used by Robinson in the analysis of tropinone. 

A similar computer-assisted approach was also elaborated envisioning the choice of the Diels-Alder transform as a strategic reaction. The task of the program in this case is to suggest the retrosynthetic transformations of the target structure leading to the creation of the cyclohexene moiety amenable to the retro-Diels-Alder disconnection. The general coiu e of these pursuits is shown in Scheme 3.50. ... 

By applying a RCM retrosynthetic transform directly to cyclopentene 77, the new diene 78 was now identified as a key intermediate for the modified route. We had deliberately left the oxazolidinone ring in place in our retrosynthetic planning, as we believed that it might facilitate the desired ring-closure process as a result of it imparting turn-structure on the diene. Yet again, a Julia-Kocienski methylenation would be used... 

Substitution (SnI or Sn2) is the major reaction of nucleophiles in which one functional group is replaced by another (nucleophilic aliphatic substitution). Nucleophiles can also form a new bond to an acyl carbon (nucleophilic acyl addition). Both of these retrosynthetic transforms are represented by the C-Nuc species, where Nuc = CN , AcQ-, RO , N3-, CO2-, etc. and X = Cl, Br, I, OAc, OSO2R, and so on for Sn2 reactions. In nucleophilic acyl substitutions, the nucleophile is usually a carbon, nitrogen or oxygen species. 

The retrosynthetic transform for syn elimination is that shown for the anti elimination reactions except that the less substituted alkene is the target ... 

Category Ib cyclizations are relatively rare for pyrroles. Three retrosynthetic transformations correspond to indole cyclizations of this type (Scheme 31). 

We call the disconnection of compound 1 into potential precursor building blocks 2 and 3 a retrosynthetic transformation [1]. In this manner, we capture our knowledge about a synthetic reaction that leads from 2 and 3 to compound 1. A retrosynthetic transformation is written in the direction opposite to that of a synthetic transformation. As the overwhelming number of synthetic reactions is based on polar bond-forming events, these feature prominently in delineating retrosynthetic transformations of target structures. 

FGIs (a) and (b) involve retrosynthetic transformation of the hydroxy to carbonyl group the third FGI (c) implies elimination of both OH groups to obtain alkene, the target molecules of the next generation. In the synthetic direction, this means that reduction of the C=0 group(s) or dihydroxylation of the C=C bond is required for rich 1,2-diols. 

Figure 6 Synthetic planning make.s use of retrosynthetic transforms, and may work towards the use of a strategic reaction...

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