Conformational preference

Zhang L and J Hermans 1994. 3io-Helix versus a-Helix A Molecular Dynamics Studv of Conformational Preferences of Aib and Alanine. Journal of the American Chemical Society 116 11915-11921. 

We can relate the conformational preference for an equatorial methyl group m methylcyclohexane to the conformation of a noncyclic hydrocarbon we discussed ear her butane The red bonds m the following structural formulas trace paths through four carbons beginning at an equatorial methyl group The zigzag arrangement described by each path mimics the anti conformation of butane... 

Besides the shapes adopted by the rings, considerable attention has been paid to the conformational preferences of substituents, both on carbon and on the heteroatoms (nitrogen and sulfur). The reader is referred to the relevant monograph chapters for details. Noteworthy points are as follows ... 

An appreciable amount of information concerning the conformational preferences of substituted heterocycles has accrued, largely through dipole moment and NMR studies. However, the earliest appreciation of this topic apparently arose out of the extension of studies of restricted rotation in biphenyls to heterocyclic analogues. 

Table 32 Conformational Preference of 2-Substituted Five-membered Heterocycles...

Levitt, M. Conformational preferences of amino acids in globular proteins. Biochemistry 17 4277-4285, 1978. 

From these data, calculate the conformational energy of the hydroxyl group in each solvent. Do you notice any correlation between the observed conformational preference and the properties of the solvent Explain. 

The similarity between the cryptands and the first of these molecules is obvious. Compound 7 7 is a urethane equivalent of [2.2.2]-cryptand. The synthesis of 7 7 was accomplished using a diacyl halide and l,10-diaza-18-crown-6 (shown in Eq. 8.13). Since amidic nitrogen inverts less rapidly than a tertiary amine nitrogen, Vogtle and his coworkers who prepared 7 7, analyzed the proton and carbon magnetic resonance spectra to discern differences in conformational preferences. Compound 7 7 was found to form a lithium perchlorate complex. 

Not all consequences of fluonne mcorporaton m a molecule aid m structure identification Long range coupling and conformational preferences can comph... 

Long-range coupling information can provide msights into conformational preferences [170] and relative transrmssive abilities of intervenmg atoms or moie-... 

A closely related stable cation which also exhibits a strong conformational preference is cyclopropylcarbinyl cation. 

Apply the bent-bond model to the preferred conformations of acetaldehyde and propene. Do bent-bonds maintain or remove eclipsing interactions in the equilibrium structures of the two molecules Formulate a simple rule based on the bent-bond model for predicting conformational preferences in systems containing trigonal atoms. 

Try to explain the conformational preference in terms of steric repulsion. Which ring atom(s) in the higher-energy conformer approach the CH3 group most closely (Make sure that you find all significant nonbonded interactions.) Which of these interactions are absent in the lower-energy conformer Can interactions that appear in both conformers account for the conformational preference ... 

CHa-ring interactions might also be expected to control the conformational preferences of dimethylcylohexanes. It might even be anticipated that the energy differences between a diequatorial conformer and a diaxial conformer will be twice the equatorial-axial energy difference in methylcyclohexane. 

Identify the preferred conformer for each. Are the energy differences in line with your expectations, or are there significant deviations If the latter, what additional nonbonded interactions can explain these deviations Which factor plays the larger role in determining conformational preferences, the additional interactions or CHs-ring interactions ... 

The conformation of alkylcyclohexanes is determined largely by steric repulsion (see Chapter 5, Problems 6 and 7). More polar substituents may show different conformational preferences due to a combination of steric and electronic factors. 

Compare energies for both diaxial and diequatorial chair conformers of trans-2-fluorocyclohexanol (X = OH). Which conformer is preferred Does the preferred conformer minimize steric repulsion Is it reasonable to attribute the conformational preference solely to steric effects Explain. Examine dipole moments for the two conformers. Does the preferred conformer minimize electrostatic repulsion (or maximize electrostatic attraction) Is it reasonable to attribute the conformational preference solely to electrostatic effects Explain. 

Display electrostatic potential maps for both anti and gauche conformers of 1,2-ethanediol. Do you see any examples of destabilizing interactions (between like charges) or stabilizing interactions (between unlike charges) in either conformer Are you able to explain the observed conformational preference ... 

Which isomer, E or Z, has stronger conformational preferences Are these preferences due to resonance effects or might other factors be at work Explain. 

In this beautiful synthesis of periplanone B, Still demonstrated a classical aspect and use of total synthesis - the unambiguous establishment of the structure of a natural product. More impressively, he demonstrated the usefulness of the anionic oxy-Cope rearrangement in the construction of ten-membered rings and the feasibility of exploiting conformational preferences of these medium-sized rings to direct the stereochemical course of chemical reactions on such templates. 

Based on the successful series of transformations summarized in Scheme 1, Schreiber and Santini developed an efficient and elegant synthesis of periplanone B (1),8 the potent sex pheromone of the American cockroach, Periplaneta americana. This work constitutes the second total synthesis of periplanone B, and it was reported approximately five years after the landmark periplanone B synthesis by W.C. Still9 (see Chapter 13). As in the first synthesis by Still, Schreiber s approach to periplanone B takes full advantage of the facility with which functionalized 5-cyclodecen-l-one systems can be constructed via anionic oxy-Cope rearrangements of readily available divinylcyclohexanols.5 7 In addition, both syntheses of periplanone B masterfully use the conformational preferences of cyclo-decanoid frameworks to control the stereo- and regiochemical course of reactions carried out on the periphery of such ring systems.10... 

Similar conclusions were reached for sulfoxides 157. Conformation 158 was preferred for (RS/SR)-157 but with some contribution from conformer 159. The (RR/SS) dias-tereomers preferred the reverse conformer 161 was preferred to 160161. An attractive force between Ph/Ar and Ph/R was thought to be the primary factor in determining the conformational preference of sulfoxides 152 and 157. MM2 calculations were carried out on a series of molecules of general structure PhCHR—X—R with X equal to CHOH, C=0, S and S=0151. The main conformers of these molecules have the Ph (or aryl) and R (alkyl) groups gauche. The calculations supported the existence of CH-tr attractive interactions with minor contributions from other effects. 

The conformational preference of the monosulfoxides of 1,2-, 1,3- and 1,4-dithianes (179-181) were determined by NMR experiments which included variable-temperature studies, double irradiation, solvent effects and the influence of lanthanide shift reagents167. For 179 and 181, the axial conformers were the dominant species in CD3OD, but for 180, the equatorial conformer was in excess. 

The conformational preference of 1,3,5-trithiane-l-oxide has been determined in solution and in the solid state168. 13C and dynamic 1H NMR studies indicated that the S=0 bond is equatorial (182) in solution, as did molecular mechanics calculations. Surprisingly, the axial conformation (183) is preferred in the crystalline state. 

Barbarella and coworkers172 have studied the conformational properties of thiolane-1-oxide (187), its mono- and di-methyl derivatives (188-194) and trans-2-thiahydrindane-2-oxide (195) using force-field calculations and 1H, 13C and 17ONMR. They concluded that the overall conformational preference depends on the substituents and their locations... 

The same equatorial preference is also manifested in the 3,3-disubstituted thietane oxides66,194. Thus, the NMR spectra of 5e,f contain two Me singlets at 1.23 and 1.30 ppm and two methylene multiplets at 3.03 and 3.53 ppm (in CDC13). The large difference in the chemical shifts of the axial and equatorial a-methylene hydrogens is characteristic of an axial nonbonded electron pair on sulfur (conformation 5e equation 73). This conformational preference is corroborated by the small differences in the chemical shifts of the two methyl groups, and fits the contention that 1,3-diaxial interactions are responsible for this ultimate result. Certainly, these interactions are greater in the conformer 5f. 

The structures of four-membered rings are of considerable interest, owing in part to the low-frequency ring puckering vibration203. The comparison of the structures and conformational preferences of thietane oxides and dioxides discussed above with those of dithietane oxides and dioxides is therefore appropriate and will follow. 

The conformational preferences of six-membered cyclic sulfoxides are strongly dependent upon the nature of the other ring atoms, especially in 1- and 3-positions322. Indeed, molecular mechanics calculations indicate that most of the energy difference between the... 

The thiophene-2-sulfonyl radicals without substituents at position 3 exhibit rapid rotation about the C—S bond in the ESR time scale, while the 3-bromo-substituted ones demonstrate a marked conformational preference which has been interpreted in terms of a re-type conjugated structure similar to 3 (cf. entries 10 and 11 in Table 2)10. Calculations... 

Spiroketals based upon such structures as l,7-dioxaspiro[5.5]undecane (18), occur frequently in natural products. Accordingly, an extensive amount of literature relates to the isolation and total synthesis of this type of compound. This literature was reviewed104 in 1989. The authors of Ref. 104 listed three factors that influence conformational preferences in these systems. They are (7) steric influences, (2) anomeric and related effects, and (3) intramolecular hydrogen bonding and other chelation effects. 

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