Stereoelectronic effects of substituents

Similar substituent effects are observed for the anti-MAO activity of / -carbolines and pargyline derivatives (47). In Equation 25, E 6 8 is the sum of values of the 6 and 8 substituents, and o-4b is the o- value of substituents to the 4b position. In Equation 26, E84 corresponds to the para substituent and o-2 to the ortho position of the side chain. The coincidence in the stereoelectronic effects of substituents on the MAO inhibition is surprisingly good for these three classes of inhibitors. On the structural formulas shown above, the arrows indicate positions where the a values are directed, and the shaded circles show sterically limited positions. Thus, the individual correlations are substantiated, and physicochemical significance is proved by similar biological correlations. 

Similarly photocycloaddition of ethylene with chiral 5-alkoxyfuranones 181 proceeds with facial diastereoselection [153], Although selectivity remains low, the reaction has been used for the enantiospecihc synthesis of grandisol because it is easy to separate the initial diastereoisomers [154]. Selectivity is greatly influenced by temperature and by substituents on the ethylenic bond of the furanone ring. It was concluded that steric hindrance of the alkoxy group and stereoelectronic effects of substituents on the conjugated system are responsible for the selectivity observed. It was also proposed that the diastereoselection of the photocycloaddition of ethylene with 181 was dominated by the approach of ethylene to the vibrationally relaxed (71,71 ) excited furanone rather than by the selectivity of the reactions of biradicals. 

Stereoelectronic Effects of Substituents Polyhydroxylated Piperidines and Sugars... 

White, J. M., Stereoelectronic Effects of the Group 4 Metal Substituents in Organic Chemistry, 22, 137. 

Group 4 Metal Substituents, Stereoelectronic Effects of the (White and Clark). .. 22 137... 

Stereoelectronic Effects of the Group 4 Metal Substituents in Organic... 

TABLE 1. Stereoelectronic effect of para-substituents on the ole-fination of acetophenones and benzophenones... 

The dominant contributor to the reactivity of vinylcyclopropanes in any radical reaction is the form (4a), the cyclopropylcarbinyl radical system. The opening of a cyclopropylcarbinyl radical to a butenyl radical is among the fastest radical processes known, with a rate constant of 1.3 x 10 sec". - The various stereoelectronic effects of this rearrangement have been reviewed. The structure of (4a), deduced from its ESR spectrum - and in agreement with calculations (STO-36 basis set), is in the bisected conformation shown, predicted to be 1.4 kcal mol more stable than its perpendicularly oriented counterpart. Above -KX) T only the butenyl radical (4b) can be detected. Substituent efiects do not seem to operate here when the substituents are on the cyclopropane (i.e. product stabilization). The cy-clopropylcaibinyl cation and anion have structures similar to (4a), bisect conformations (5) and (6), respectively. A concise summary of solvolytic and mechanistic data for system (5) has recently appeai Reviews of cyclopropylcarbinyl anions and carbenes are also available. - ... 

The effect of substituents on the stereoselectivity has been studied in the acid-catalyzed hydrolysis of a series of aryloxiranes. Work on the influence of temperature on the steric course of the reaction has demonstrated that the tendency towards retention is explained by the high degree of carbocationic nature in the transition state leading to the cis products, the favorable entropy content of the transition state of cis addition, and the relatively low enthalpy barrier of the benzyl C-0 bond. At the same time, almost complete tram selectivity can be observed in aliphatic and cycloaliphatic oxiranes and ionization of the C-0 bond is associated with high enthalpy values. Attempts have been made to separate the inductive, conformational, and stereoelectronic effects. 3,4-Epoxytetrahydropyran was used to study the inductive effect while the corresponding cis- and trans-methyl derivatives were employed to examine the stereochemical and conformational factors. ... 

Stereoelectronic effects of various remote substituents on the basicity of the carbonyl is yet another intriguing question. Electronic effects of remote substituents have been postulated to be responsible for stereoselective additions to carbonyls in rigid adamantanone systems. If present, such stereoelectronic effects would similarly be expected to bias the energetics and structural features of Lewis acid complexation. 

In the context of the collagen triple helix it can be concluded that the Cf-exo pucker of the proline in Yaa position is favored by stereoelectronic effects of a (4R)-OH substituent which also stabilizes the traus-Xaa-(4R)-Hyp peptide bond, thus preorganizing this residue in a conformation that best befits a triple helix. Conversely, in the Xaa position the Pro residue is preferred in the Cy-endo pucker the related dihedral angles are reported in Table 11.3. 

The observed results agree with the calculated trend. Relative rates of cyclization are in the order 5-exo > 6-endo 6-exo > 1-endo. The relationship holds only for terminal double bonds. An additional alkyl substituent at either end of the double bond reduces the relative reactivity by a steric effect. The underlying conformational and stereoelectronic effects can be modified by both steric and electronic effects of substituents. For example, a 5-methoxycarbonyl substituent promotes the 6-endo mode of cylization by an electronic effect. The reactivity of the (3-carbon is enhanced by the substituent. 

In general, substituent effects on the quinolizidine ring atoms (e.g. (39) and (40)) parallel those in the carbocyclic series <78H(9)507>, with some particular effects due to the nitrogen atom. For instance, the very high-field position of the axial methyl carbon atom of (39) is due to the stereoelectronic effect of the jS-antiperiplanar nitrogen lone pair, and can be used as a criterion to confirm the trans conformation of the ring system. 

Methoxy-l-naphthyl sulfoxide 39b is stable in THF at room temperature however, it undergoes a gradual internal redox reaction in THF at reflux, generating the corresponding phosphine oxide, presumably due to the stereoelectronic effect of the 2-methoxy-l-naphthyl substituent (Scheme 19). 

---