Precursors building blocks

A simple, general systematic strategy for the rational design of self-assembled supramolecular species has yet to be developed. However, a promising approach to the formation of novel supramolecular species, by spontaneous self-assembly of precursor building blocks under appropriate conditions, involves the coordination... 

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. 

Ng and co-workers recently prepared semi-flexible dendrons up to the third generation (5,89) using ester terminated quaterthiophene and 3,5-dibromophenol as precursor building blocks, where quaterthiophene moieties were used as branching and peripheral units (Chart 1.81) [517]. Spectroscopic studies revealed that solvent polarity has a strong influence on the absorption and emission spectra of the dendrons. Thus, an increase in the solvent polarity produced a bathochromic shift in the absorption and emission spectra and also a dramatic decrease in the fluorescence quantum yield. 

In general, zeohte crystallization consists of three stages (/) formation of precursors, ie, building blocks that can generate nuclei (2) nucleation and (J) crystal growth. 

The Michael addition reaction has attracted many researchers as a route to convert high melting BMI building blocks into resins with improved processibihty as compared with the BMI precursors. Heat-resistant resin compositions are prepared from BMI and para- or y /i7-aminophenol (38). The idealized stmcture of such a BMI—y -aminophenol adduct follows. 

A rather limited collection of simple precursor molecules is sufficient to provide for the biosynthesis of virtually any cellular constituent, be it protein, nucleic acid, lipid, or polysaccharide. All of these substances are constructed from appropriate building blocks via the pathways of anabolism. In turn, the building blocks (amino acids, nucleotides, sugars, and fatty acids) can be generated from metabolites in the cell. For example, amino acids can be formed by amination of the corresponding a-keto acid carbon skeletons, and pyruvate can be converted to hexoses for polysaccharide biosynthesis. 

The synthetic problem is now reduced to cyclopentanone 16. This substance possesses two stereocenters, one of which is quaternary, and its constitution permits a productive retrosynthetic maneuver. Retrosynthetic disassembly of 16 by cleavage of the indicated bond furnishes compounds 17 and 18 as potential precursors. In the synthetic direction, a diastereoselective alkylation of the thermodynamic (more substituted) enolate derived from 18 with alkyl iodide 17 could afford intermediate 16. While trimethylsilyl enol ether 18 could arise through silylation of the enolate oxygen produced by a Michael addition of a divinyl cuprate reagent to 2-methylcyclopentenone (19), iodide 17 can be traced to the simple and readily available building blocks 7 and 20. The application of this basic plan to a synthesis of racemic estrone [( >1] is described below. 

Compound 16, the projected precursor of 15, could conceivably be assembled from bishomoallylic alcohol 17 via a pathway that features the oxidative functionalization of the A20,21 double bond with participation by the C-17 secondary hydroxyl. Compound 17 is an attractive retrosynthetic precursor for compound 16 because the A20-21 double bond, which could permit the introduction of the adjacent C-20 and C-21 stereocenters in 16, provides a convenient opportunity for significant molecular simplification. Thus, retrosynthetic cleavage of the A20 21 double bond in 17 furnishes compounds 18 and 19 as potential building blocks. The convergent union of the latter two compounds through a Wittig reaction would be expected to afford 17 stereoselectively. 

A retrosynthetic analysis of fragment 152 can be completed through cleavage of the C16-C17 bond in enone 155, the projected precursor of epoxide 152. This retrosynthetic maneuver furnishes intermediates 156 and 157 as potential building blocks. In the forward sense, acylation of a vinyl metal species derived from 156 with Weinreb amide 157 could accomplish the construction of enone 155. Iodide 153, on the other hand, can be traced retrosynthetically to the commercially available, optically active building block methyl (S)-(+)-3-hydroxy-2-methyIpropionate (154). 

A similar Evans asymmetric aldol/reduction sequence could also serve well in a synthesis of fragment 158. Compounds 161 and 162 thus emerge as potential precursors to 158. In theory, building blocks 161 and 162 could be procured in optically active form from commercially available and enantiomerically pure (+)-/ -citro-nellene (163) and D-mannitol (164), respectively (see Scheme 42). 

Pentaphyrin(l.l.l.l.l) is the direct homologous congener of the porphyrin system. Formally, but also synthetically, it can be derived when the porphyrin-forming building blocks are extended by a pyrrole unit and a methine bridge or its precursor. 

Hydroxy-L-prolin is converted into a 2-methoxypyrrolidine. This can be used as a valuable chiral building block to prepare optically active 2-substituted pyrrolidines (2-allyl, 2-cyano, 2-phosphono) with different nucleophiles and employing TiQ as Lewis acid (Eq. 21) [286]. Using these latent A -acylimmonium cations (Eq. 22) [287] (Table 9, No. 31), 2-(pyrimidin-l-yl)-2-amino acids [288], and 5-fluorouracil derivatives [289] have been prepared. For the synthesis of p-lactams a 4-acetoxyazetidinone, prepared by non-Kolbe electrolysis of the corresponding 4-carboxy derivative (Eq. 23) [290], proved to be a valuable intermediate. 0-Benzoylated a-hydroxyacetic acids are decarboxylated in methanol to mixed acylals [291]. By reaction of the intermediate cation, with the carboxylic acid used as precursor, esters are obtained in acetonitrile (Eq. 24) [292] and surprisingly also in methanol as solvent (Table 9, No. 32). Hydroxy compounds are formed by decarboxylation in water or in dimethyl sulfoxide (Table 9, Nos. 34, 35). 

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