Elaboration strategy

From an exhaustive retrosynthetic analysis and from the experimental work performed by Curran [29] [32], it was clear that the synthesis of modhephene required an elaborate strategy. In the first place, the tandem radical cyclisation should be conducted individually rather than just in one step since it allows more flexibility. In the second place, Curran s observation that the precursor of modhephene (54) could be the olefmic exocyclic derivative 55 allows the application of a series of heuristic principles already familiar to us, which greatly simplifies the retrosynthetic analysis and leads to diquinane and, finally, through a second radical retroannulation to the very simple cyclopentanone derivative (Scheme 7.24). 

Scheme 6. Cycloloading and elaboration strategy for benzopyran synthesis according to Nicoloaou et al.

Orlistat (32 tetrahydrolipstatin, Xenical ) is a potent inhibitor of pancreatic lipase [23] which has been launched for the treatment of obesity in 1998. Large amounts of 32 required for clinical development were obtained using a route based on the enantioselective reduction of P-ketoester 29 to provide P-hydroxyester R)-30 followed by diastereoselective elaboration strategies (via (S,S,i )-31, Scheme 6)... 

Pyranone (1) was used to make 4-amino-2,6-diethylpyridine (2) (Scheme 1) <94SC(24)1709), but unlike the dimethyl analogue, diethyl compound (1) required a more elaborate strategy and used tosylisocyanate. The order in which the two oxygen atoms were replaced with nitrogen atoms was important to the practicality of synthesis. 

Characterization of Nanocomposite Microstructure. Mixing clay with a polymer does not necessarily lead to a nanocomposite. Elaboration strategies are aimed at monitoring dispersion of the inorganic compound at the nanometer level, that is down to the elementary clay platelet. Figure 2 provides a schematic illustration of the various microstructures readily achievable, namely a conventional fllled polymer with clay particles in the micrometer range, an... 

An elaborate strategy was needed for the synthesis of a palladium(O) complex with a quinonemethide ligand coordinated by the exocyclic double bond (complex 12 in Scheme 13), which involves aiming at the synthesis of the unstable palladium(n) complex of the zwitterionic form of the molecule 13. This non-observed intermediate spontaneously affords the desired complex. Treatment with dba produces the unstable free quinonemethide, which is a biologically relevant metabolite. The crystal structure of 12 was solved and showed a notably elongated exocyclic double bond (1.437 A) and a displacement of this bond out of the ring plane by 10.78° away from the palladium atom. 

For insoluble potymers, such as PPy an elaborate strategy for film production must be used. The most common is the preparation of the film using the soluble precursor sulfonium polyelectrolyte, with further conversion to PPV. This strategy has the advantage that it permits the use of the casting, doctor-blade, or spin-coating techniques for film deposition, but needs a conversion step, which in most of the cases is based on thermal annealing of the fitoi in a vacuum or inert atmosphere, at temperatures up to 300°C [75] (see also Section 2.2). 

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