Syn-axial interaction

Hall et al.1 s estimated the conformational equilibrium for the structural units in the polymer of 2 using the numerical parameters determined for carbohydrates16. For a frans-l,3-tetrahydropyranoside, conformer 8 is calculated to be more stable than 7 by 9.2 kJmol-1 and would therefore occur almost exclusively (ca. 98%) at equilibrium. For a m-1,3-tetrahydropyranoside unit, the anomeric effect favors con-former 9, but its severe syn-axial interaction between alkoxy and alkyl groups would highly favor 10 (ca. 99%). 

Other studies have also established the preference of the chair conformation with the oxygen in the axial position the rationale for this preference is different from the attractive interaction between the sulfoxide oxygen and the syn-axial hydrogens proposed previously . Rather, a repulsion effect is advocated the equatorial oxygen is squeezed between four vicinal hydrogens, while there are only two corresponding repulsions if it is in the axial position. The correlation between the predicted and observed conformational/orientational preferences in 3,3-dimethylthiane oxide (e.g., equatorial preference in the chair conformation) corroborates this interpretation. The axial preferences of the sulfur-oxygen bond in the thiane oxide is reversed in 3,3-dimethylthiane oxide because of the syn-axial interaction. 4,4-Dimethylthiane oxide, however, maintains a predominance of the axial isomers as deduced from the analysis of NMR data . ... 

It is investigated whether the stereochemical 13C NMR chemical shifts in the resonance peaks can be ascribed to differences in the conformations in the various stereoisomers. The authors follow Boyd and Breitling (A 022) in thair statistical treatment of the PP chain, with the exception that here conformational sequences are not excluded of the type XG/G Y for two adjacent diads unless XG or G Y imply another c (syn-axiall interaction within either diad. Therefore this treatment, which is more rigorous but consistent with Boyd and Breitling s energy calculations, requires statistical weights which are functions of three adjacent torsional angles. 

Thus the conformational free energy of the N-methyl group may be accepted as 2.7kcal mol-1 and the difference from that (1.7 kcal mol 1) in methylcyclohexane is primarily due to the changes in bond lengths, causing an increase in the syn-axial interactions in axial N-methylpiperidine. 

In the conformational equilibrium (Fig. 22) for 5-methyldihydro-l,3,5,-dioxazine (454) the generalized anomeric effect favors the N-Meax conformer 455 and, in addition (relative to jV-Meax piperidine), 455 does not contain the two unfavorable syn-axial interactions involving the axial N-methyl... 

The successive change in position of the N-Mem N-Meeq equilibrium from that in 5-methyldihydro-l,3,5-dioxazine (AG° > 1 kcal mol-1) to 3-methyltetrahydro-l,3-oxazine (AG° 0.10 + 0.05 at — 120°C) to that (AG° —2.7 kcal mol-1) in 1-methylpiperidine results from successive differences of syn-axial interactions involving the axial methyl group and a favoring of the axial methyl conformer by the generalized anomeric effect. 

The composition of the four l,2-dideoxy-3-heptuloses has been determined.32 These compounds are similar to the hexuloses, the hydroxyl group on C-1 having been replaced by a methyl group their composition should be similar to those of the corresponding hexuloses, and, in most cases, this is true. For 1,2-dideoxy-3-/yxo-heptulose, however, and for its lower homolog, 1-deoxytagatose, the a-furanose form (in which 03 and the side chain are cis) is more stable than the / - furanose (with 02 and 03 cis). A study of the conformations can rationalize this observation in the / -furanose, there is a quasi-syn-axial interaction between 0-2 and 04 which is aggravated by the side chain, particularly if bulky. There is a similar effect in the / -pyranose, which also becomes a minor constituent of the equilibrium mixture. 

Usually 2,2-disubstitnted 1,3-dioxanes (for instance, acetonides) are hydrolyzed mote easily than corresponding 1,3-dioxolanes (essentiaOy owing to the strong syn-axial interaction operative in the six-membeied ring [79,98]. 

Methyl carbon shieldings also offer conformational insight in cyclohexanones. In cis-3,5-dimethyl- and 3,3,5-trimethyl-cyclohexanones the equatorial 3-methyl carbon absorbs at ca. 22.3 p.p.m. whereas an equatorial 2-methyl carbon experiences an upfield shift to 14.6 p.p.m. ascribed to a y-interaction between methyl and oxygen. From related compounds these shifts have been estimated as 19.3 and 17.4 p.p.m. respectively. In the former case the upfield shift of 3 p,p.m. is less than the corresponding cyclohexane value on account of the smaller number of syn-axial interactions. In 3-methylcyclohexanone the methyl shielding indicates about 10% axial methyl conformer, corresponding to —AG of ca. 1.3 kcal mol . In cis-2,5-dimethylcyclo-hexanone (67) the observed methyl shieldings of 15.3 and 19.8 p.p.m. are in accord with an equilibrium which contains ca. 80% (67a). 

Chiroptical parameters for esters of L-altruronic acid in various solvents have been shown to reflect the conformational mobility and rotation of the chromophoric group about the C-5-C-6 bond. The conformational equilibria are sensitive to the anomeric configuration, and to the pattern of O-methyla-tion in methylated derivatives. In the permethylated methyl altruronates the a-anomer exists predominantly in the Ci conformation (4) while the j8-anomer prefers the C4 conformation (5), thus reducing the syn-axial interactions involving the glycosidic methoxyl in each case. ... 

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