Synthetical reasoning

In the same way that syllogisms and theorems are the essence of analytical reasoning, the "heuristic principles" are the essence of synthetical reasoning. 

Cyclic mew-configurated 1,2-dicarboxylic acid dimethyl esters are excellent substrates for pig liver esterase90. Cyclopropanedicarboxylales have been studied not only for synthetic reasons, but also so that an active-site and/or substrate model of pig liver may be developed13 5. The results obtained, compounds 11-17, are a good demonstration of the scope and limitation of PLE in asymmetric synthesis. Enantiomeric excesses of the monoesters can be determined by conversion into the amides with (S)-l-phenylethylamine and analysis either by GC or H-NMR spectroscopy, whereas the absolute configuration rests on chemical correlation. 

In a few cases pyrolysis and ring contraction occurs under simultaneous loss of carbon-fragments (mostly ethano units because of synthetic reasons). The benzylic side of the disulfone undergoes recombination, whereas the ethano bridge and both the SO2 groups become cleaved and eliminated. 

Obviously, [2,3]-sigmatropic rearrangements of sulfur-containing systems comprise a class of reactions with a considerable constitutional scope. But the configurational consequences of the concerted suprafacial reaction mode are even more exciting, both from a stereochemical point of view and for synthetic reasons. 

Merits of preparation. Selective oxidative transformation of thiols to disulfides is of interest for both biologicaP and synthetic reasons. Most of the existing methods involve the use of metal catalysts or halogenated reagents, which lead to the formation of side-products. 

The impetus for the newer work was the observation that benzyl clavulanate (11c) is a time-dependent inactivator of HLE (ICjq = 5 //M) whereas clavulanic acid (11b) is inactive [211, 212]. This finding led to the hypothesis that, since HLE is an endopeptidase whereas the bacterial serine proteinases are carboxypeptidases, quench(ing) the negative charge that the -lactam antibiotics normally require might yield HLE inhibitors. For synthetic reasons the group at Merck decided to use 7-aminocephalospo-ranic acids (1 Id) for most of their initial SAR studies. In contrast to the result with clavulanic acid, conversion of the cephalosporin 2 -carboxyl group in (1 Id) to an ester (He) was insufificent to transform the compound to an HLE inhibitor. 

There is considerable evidence for this type of reaction in organoarsenic chemistry and, indeed dissociation-equilibrium was believed to be the cause of racemization of arsonium halides which, for synthetic reasons, usually contained at least one alkyl substituent (often" the benzyl group) on the arsenic atom. In 1939, fractional crystallization was achieved of the diastereomers of the diarsonium picrate 3 . The individual diastereo-mers of the salt, racemic (R, R ) and meso (R, S ), were stable in boiling ethanol, a fact that should have dispelled concerns of dissociation equilibria in halide-free arsonium salts. In 1940, the tetrahedral structure of [AsPh4]I was established by X-ray crystallography. ... 

Finite assemblies constructed owing to synthetic reasons have been used to either sequester3 assemblies from solution or develop new solid-state designs. Such assemblies have involved two components, as well as higher-order structures of ID, 2D, and 3D connectivity. 

Whereas the finite assemblies described above have been isolated owing largely to synthetic reasons, the assemblies that follow exhibit a particular function. Examples of such function include host guest behavior, chemical reactivity, and chirality. In doing so, the assembly affects or contributes to a property of a solid (e.g. inclusion, reactivity). Importantly, the functions arise owing to the geometric arrangement of the constituent components within the assemblies. 

The well-known 1,4-cycloadditions to furan have been accorded much attention for both theoretical and synthetic reasons. The archetype, the addition of maleic anhydride, was studied long ago by Woodward and Bauer... 

Methylene-bridged calrx[4]resorcinols (for synthetic reasons derived from 2-aUsylresorcinols) assume a cone conformation at lower temperatures, and AG = 12.0 kcalmoU was found at 298 °C for the cone cone interconversion . This lower value in comparison to those for calixphenols like 2a reflects the fact that no substituents have to pass the annulus during the ring inversion. In addition, the intramolecular hydrogen bonds between exo-OH groups are distinctly weaker than those of the cyclic array of endo-OH groups in 2a as shown by NMR (5 = 6.30 vs. 10.2) and IR (v = 3420 vs. 3140 cm- ). 

Bromine and chlorine substituents have been employed in most syntheses as a compromise of thermal stability and reactivity of the reactants necessary in the pyrolysis procedure as outlined above. Needless to say that these halogen substituents must normally be introduced at those carbon atoms which eventually participate in the new C-C bond. If this is not possible for synthetic reasons, the substitution in other positions can provide an interesting alternative. It has... 

Binaphthol Lewis Acids. In search of Lewis acids which might provide better stereocontrol in these cycloadditions, we turned our attention to l,l -bi-2-naphthol as a potentially useful ligand for the titanium promoter complex. For synthetic reasons, we continued to use benzylic vinyl ethers and silyl vinyl ethers so that these protecting groups could be cleaved to provide the free alcohol later. 

In principle, palladium-catalyzed alkene functionalization can be carried out by employing a series of different nucleophiles. Within the scope of the present chapter, oxygen- and nitrogen-based nucleophiles will be considered, and the discussion will be extended to metals other than palladium where appropriate for synthetic reasons. Addition of heteroatoms to alkenes in the presence of palladium catalysts can proceed through two different fundamental pathways of syn- and anti-nucleopalladation (Figure 16.1) [6]. 

---