Stereochemical factors

In the early days of steroid chemistry, dehydrations were usually carried out under rather drastic conditions, frequently in the presence of strong acids (see, for example, ref. 176, 181, 182). Such conditions have been replaced by milder and more selective methods, except in those instances when either the product is stable e.g. ref. 183, 184) or rearrangement is desired. The importance of stereochemical factors in rearrangements is widely recognized for instance, the Westphalen rearrangement of 5a-alcohols (92) cf. ref. 185,... 

R Jenner, B. Testa, Influence of stereochemical factors on drug disposition. Drug Metab. Rev. 1973, 2, 117-184. 

In contrast, polar and resonance effects must be separated in order to analyze the data for a-substituted arylolefins [ArC(R)=CHR with R H]. Their bromination involves open carbocation intermediates only. Resonance effects cannot be fully developed at the transition states, since the aromatic ring is not in the same plane as that of the developing carbocation, because of steric constraints. Accordingly, application of (33) gives pT < pn. Attenuation of resonance arises mainly from stereochemical factors, at least in the monosubstituted 1,1-diphenylethylene [20] and a-methylstilbene [21] series the pr/pn ratios can be related to the dihedral angle between the substituted phenyl ring and the plane of the ethylenic bond. 

It is not our aim to provide here a comprehensive review of solid-state organic chemistry. We intend rather to dwell on the interplay between stereochemical factors and solid-state effects, using examples from the literature as illustrations. Before this elaboration, however, we provide a brief discussion of some relevant aspects of organic crystal structures and their roles in determining reaction course. 

More recent studies in this field have revealed the importance of the intrinsic acidic sites on the aluminas in directing the course of the dehydration. Recently the consideration of stereochemical factors involved in the dehydration and the use of gas chromatography as an analytical tool has led to a better understanding of this reaction, with a resultant better appreciation of the reaction mechanism. 

In an analysis of stereochemical factors in narcotic analgesics, Portoghese considers that the conformational requirements for most of the 4-phenylpiperidine analgesics appear to be minimal [282]. His argument was based, in part upon (1) the fact that endo and exo isomeric azabicyclo [2,2,1] heptane analogues (LXXXII) of pethidine have similar orders of potency in mice (benzoquinone... 

This behaviour contrasts with the racemization of hyoscyamine to atropine, which also involves an enolate anion derived from an ester system (see Section 10.8). As the term racemization implies, atropine is a 50 50 mixture of the two enantiomers. It shows how the proportion of each epimer formed can be influenced by other stereochemical factors. 

The partially hydrogenated ring of dihydtocorannulene constitutes a 1,3-cyclo-hexadiene ring, a system that has been well-studied with respect to its geometry and the conformational preferences of substituents. However, the curvature of the corannulene surface introduces an additional stereochemical factor that makes the conformational analysis especially interesting. 1,3-Cyclohexadiene (23) and 9,10-dihydrophenanthrene (24) serve as models they are structurally similar systems, and their stereochemistry and conformational preferences are well documented in the literature. In both cases, the reduced ring adopts a nonplanar, semi-chair conformation of symmetry. 

In all these compounds the dihedral dependence of both POCH and POCCH couplings are clearly seen this is of some importance in applications, especially for biological compounds(1969,96)—the only difficulty arises on account of the number of superimposed stereochemical factors as observed in the low temperature data of 182a and b. (1969>173) This means that the ring conformation is the major but not the only important factor. 

The importance of the stereochemistry of the nitrosamine function in the mutagenicity and carcinogenicity of these compounds has not been demonstrated and yet there is considerable indirect evidence that such a stereochemical dependence may be important. It is evident that the metabolism can be related to a stereochemical factor for unsyrametrical nitrosamines. These, of course, give either of two oxygenated metabolites, and there is evidence that only one of these is mutagenic in some cases (23, 24). Thus, the metabolism may be at least regiospecific, if not stereospecific, relative to the nitrosamine function. 

This method has been developed for the research on the stereochemical factors influencing the sence of smell3 5,7) (i.e., the quantitative formulation for Ruzicka s stereochemical theory 6) of olfaction). The comparison of the molecular shape is made by means of molecular model silhouettes within a procedure which consists of ... 

Dihydro-2-methylenefuran and derivatives like (145) exist as such, but their stability is purely kinetic, for a trace of acid immediately allows aromatization into the 2-methylfuran (70TL777, 52JA3193). We have previously mentioned a related methylenefuran (22), that is stabilized by a stereochemical factor and does not isomerize, from which we can conclude that the impetus to aromatization is not great. This fact comes out clearly from the behaviour of 2-hydroxyfuran and 3-hydroxyfuran derivatives which immediately change into lactones or ketones as appropriate and in the absence of any other factor do so completely or almost completely. Several X-ray studies of such compounds are mentioned in Section 3.10.2.4. 

Mechanism. The following types of evidence ere pertinent in selecting on acceptable mechanism for olefin epoxidation by means of peroxy acids (1) the nature of the peroxy acid and the electronic effect of eubBtituents on its reactivity (2) the electronic effect of substituents on the reactivity of the olefin component (3) stereochemical factors affecting the reactivity of the olefin (4) the possibility of acid dialysis (5) solvent effects and (6) neighboring group effects. 

A further stereochemical factor (discussed next) that has bearing on the regiochemistry of some photobrominaiions is the relative difficulty with which equatorial hydrogen atoms on pyranoid rings may be abstracted. In the cases of the tri-0-acylated 1,6-anhydrohexopyranoses, reaction is diverted to 06, because the anhydro bridge holds the pyranoid ring in the iC4 conformation, in which H-l and H-5 are both equatorial. 

The ligands which undergo reaction can be bound to the metal ion in the transition state or in relatively stable, isolable complexes. There is often a geometrical or stereochemical factor in ligand reactions and this factor is manifest in the so-called template reactions. 

During the last years high toxicity was found for a series of bicyclic systems similar to silatranes44, S1) such as phosphatranes, azaadamantanes and trioxabicyclo (2.2.2)octanes (Table 7). This shows that the high toxicity of silatranes1 results to a considerable extent from stereochemical factors. It is connected, first of all, with... 

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