Conformational factor

Conformational analysis is the study of how conformational factors affect the structure of a molecule and its physical chemical and biological properties... 

The development of linear ffee-energy relationships in aliphatic molecules is complicated because steric and conformational factors come into pl along with... 

In the case of the 3a-acetoxy-5a,6a-epoxide (33), the electronic and conformational factors are opposed to each other. Thus, the energy of the system is lowered when the axial 3a-acetoxy group is permitted to become... 

The influence of the conformational factors, which play a decisive role in directing oxide fission in the above cases is no longer operative in the case of 3-keto-5a,6a-epoxides and their 3-ethylene ketals. With these substrates the —I effect of the BFs-complexed 3-keto or 3-ketal grouping predominates leading to the fluorohydrins. Thus, treatment of both 5a,6a-oxidopregnane-3,20-dione (35) and its 3,20-bisethylene ketal with BFg-etherate in benzene-ether affords in 45% yield the 6jff-fluoro-5a-hydroxy-derivative (36) and its 3-ethylene ketal, respectively. which are converted into the 6a-fluoro-A -CH3... 

Epoxidation of the A -enol acetate was originally carried out with per-benzoic acid. Monoperphthalic acid has also been used, but is apparently more susceptible to steric and conformational factors. The commercially available peracetic acid is generally most convenient. Based on the expected backside attack, the derived epoxides have the 17a configuration, and hydrolysis always produces the 17a-hydroxy group. 

In contrast to the five-membered ring, conformational factors would be expected to influence the equilibrium between the imine and enamine forms in the case of the six-membered-ring piperideine derivatives (154). 

The high tendency for 1,4-addition can be explained by conformational factors, the cisoid conformer A being favored by the dienone moiety. This orientation now precludes the anion-ized silicate from 1,6-attack, and generates only the five-membered ring35,44. 

Stereochemical constraints in cyclic sulfones and sulfoxides impart increased weight to strain and conformational factors in the generation of carbanions and their stability, causing distinct differences between the behavior of cyclic and open-chain systems233, due primarily to the prevention of extensive rotation about the C —S bond, which is the major way that achiral carbanions racemize. Study of the a-H/D exchange rate fce and the racemization rate ka may provide information concerning the acidity-stereochemical relationships in optically active cyclic sulfone and sulfoxide systems. 

Rearrangement of sulfoxides 38a, b exhibited the interplay of several conformational factors. Both diastereomers afford predominant axial (trans) alcohol, but with opposite absolute configuration. The (R, R)-diastereomer strongly prefers the exo-transition state, whereas the (R, S)-isomer prefers the endo conformation. Hoffmann interprets these results in terms of an approximately 3-fold preference for the exo-transition state but a 6-fold preference for formation of an axial bond, these effects reinforcing each other in one isomer but opposing each other in the second. 

For cyclic ketones conformational factors also come into play in determining enolate composition. 2-Substituted cyclohexanones are kinetically deprotonated at the C(6) methylene group, whereas the more-substituted C(2) enolate is slightly favored... 

Owing to the low barriers to bond formation, reactant conformation often plays a decisive role in the outcome of these reactions. Carbocations, carbene, and radicals frequently undergo very efficient intramolecular reactions that depend on the proximity of the reaction centers. Conversely, because of the short lifetimes of the intermediates, reactions through unfavorable conformations are unusual. Mechanistic analyses and synthetic designs that involve carbocations, carbenes, and radicals must pay particularly close attention to conformational factors. 

Fig. 12.6. Conformational factors affecting syn and anti diastereoselectivity in Sharpless epoxidation. If substituent R4 > H, A1,3 strain favors the syn product. If R4 = H, the preferred transition structure leads to anti product. Reproduced from/. Org. Chem., 67, 1427 (2002), by permission of the American Chemical Society.

Carbocation intermediates are involved and the structure and stereochemistry of the product are determined by the factors that govern substituent migration in the carbocation. Clean, high-yield reactions can be expected only where structural or conformational factors promote a selective rearrangement. Boron trifluoride is frequently used... 

Steric and conformational factors are also important, especially in cyclic systems.233 There is a preference for the migration of the group that is antiperiplanar with respect to the peroxide bond. In relatively rigid systems, this effect can outweigh the normal preference for the migration of the more branched group.234... 

Conformational factors in the photolysis of N-acylimidazoles leading to Norrish type II products or cyclobutanols have been discussed in reference [7]. 7V-Acylimidazoles have been irradiated in tetrahydrofuran using a low-pressure mercury lamp (quartz well,... 

RIES from diazoalkanes is also sensitive to the dihedral angle between the migrating a-H and the C-N bond of the diazo moiety.57 For example, the A values for the pyridine capture of the photolytically generated carbenes from 46 and 47 are in the ratio of 1.7 1. Similarly, the carbene from 46 is more efficiently generated and trapped in methanol, whereas the photolysis of 47 in methanol affords twice as much olefin (by 1,2-H RIES) compared to the photolysis of 46. These phenomena are attributed to conformational factors that favor RIES during the photolysis of 47, with the proximal excited state represented as a pyramidalized 1,3-C-N=N diradical.57... 

The photochemistry of conjugated polyenes has played a central role in the development of modern molecular photochemistry, due in no small part to its ultimate relevance to the electronic excited state properties of vitamins A and D and the visual pigments, as well as to pericyclic reaction theory. The field is enormous, tremendously diverse, and still very active from both experimental and theoretical perspectives. It is also remarkably complex, primarily because file absorption spectra and excited state behavior of polyene systems are strongly dependent on conformation about the formal single bonds in the polyene chain, which has the main effect of turning on or off various pericyclic reactions whose efficiencies are most strongly affected by conformational factors. 

R)-5-C-Cyclohexyl-5-C-phenyl-D-xylose (Methanolysis) Only furanosides formed Pyranosides are excluded by conformational factors since either a cyclohexyl group or at least three oxygenated substituents must be axial 21)... 

All this is true both for low molecular weight compounds and for polymers. However, relevant differences are found not only in specific structural features, but also in the different intent with which the analysis is carried out. In common otganic stereochemistry, attention is essentially on reactivity Many aspects of regio- or stereoselectivity, as weU as reaction rate, can be explained or predicted in terms of conformation. In contrast, in polymers, the focus of interest is almost always on the physical (or mechanical) properties. It should not be forgotten that polymers are principally used as materials (plastics, fibers, elastomers, etc.) and that their properties are sometimes modified during fabrication. The fabri-cation process may induce the formation of particular structures at the molecular and supetmolecular level, which can often be traced back to conformational factors. 

In some cases, well-definable correlations could be demonstrated between the NMR data and the structural parameters of the 1,3-oxazine molecule. The magnitude of the 7-effects on the chemical shifts of 3,4-dihydro-277-1,3-benzoxazines 11 turned out to be influenced significantly by the substituents R attached to the nitrogen atom. A correlation between the Sq values and the steric substituent constants (its ) of the N-substituents proved useful in characterizing the variation of the 7-effects together with the conformational factors <1995STC77>. 

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