Barriers to pseudorotation

Ab initio molecular orbital calculations (using the Gaussian 80 computer program) on the barrier to pseudorotation (for the furanose ring) of two model compounds, 2-deoxy-/ -D- /) cero-tetrofuranosylamine (781) and 2-deoxy-2-fluoro-)3-D-erythrofuranosylamine (782) were reported. Al-... 

The 13C NMR chemical shifts have been studied over a range of temperatures but showed no evidence of splitting due to individual conformers even at —150 °C. The latter study (77JA2876) suggested a low barrier to pseudorotation of ca. 17 kJ mol-1. 

Dynamic 13C NMR measurements show that azocane exists at -112 °C as a 97 3 mixture of a boat-chair and a crown family conformation (AG° = 5 kJ mol-1, AG+44kJmol-1) (78JOC3021). From the NMR spectrum the barrier to ring inversion in the boat-chair is 31kJmol-1, but the barrier to pseudorotation is apparently too low for measurement. Likely candidates for the crown family and boat-chair conformations of azocane are the chair-chair (420), and the BC-1 (421), BC-3 (422) and BC-7 (423) conformations, respectively, but the precise position of the nitrogen atom is not known experimentally. JV-Methyl-and iV-chloro-azocane also have predominantly boat-chair conformations (75JOC369). 

Trioxocane exists as a 1 1 mixture (i.e, AG° = 0) of a boat-chair and a crown family conformation with an interconversion barrier of 36 kJ mol-1 (72JA1390,1389). The ring inversion barrier in the boat-chair is 28 kJ mol-1 but the barrier to pseudorotation has not been determined. One set of force-field calculations shows that the BC-1, 3, 6 (435) is of... 

Several other sulfur eight-membered heterocycles also exist in boat-chair conformations. 5-Thiacanone (441) has a conformation similar to its oxygen analog (430) and shows barriers to pseudorotation and ring inversion of 28 and 34 kJ mol-1, respectively (80JOC1224). The... 

Corriu and coworkers have found that the barrier to pseudorotation seems to depend on the number of electronegative groups present35. For species with one electronegative substituent, AG >20 kcalmol-1. With two electronegative groups, the barrier decreases to ca 9-12 kcalmol-1, and when three electronegative substituents are present, the pseudorotation barrier has A<7 kcalmol-1. 

In contrast to the findings for the cyclobutanes where the large amplitude motions mainly consist of conversion between rather rigid forms, the cyclopentanes exhibit more complex conformational and dynamic properties. Pseudorotation is a prominent large amplitude motion prevailing not only in cyclopentane but also in other five-membered rings. If the barrier to pseudorotation is high, distinct conformations may exist. In this case, the envelope conformation which has maximum Cs symmetry... 

Barriers to pseudorotation have been determined mainly by various spectroscopic methods239, while electron diffraction has provided important conformational and structural data. 

The title of this paper asks if theories fit the facts. So far it has been argued that for cyclic esters, conformational effects make it exceptionally difficult to control the variables to test any theory but by showing that ligand reorganisation processes in reaction intermediates (as opposed to stable phos-phoranes) are limited then at least some simplification of mechanisms is possible. It is pertinent now to examine the one assumption that was so valuable in explaining the differences in hydrolysis patterns of 5-membered phosphates and phosphonates, viz, the C-P bond provides a barrier to pseudorotation. 

The term pseudorotation was first appUed to cyclopentane like inversion, it has an atomic analogue in 5-coordinate compounds (e.g. PF5). ) The name means false rotation , and it is therefore appropriate for any conformational process which results in a conformation superposable on the original, and which differs from the original in being apparenUy rotated about one or more axes. Pseudorotation, in analogy with real molecular and internal rotations, can be free, as in cyclopentane, or more or less hindered, eis in cycloheptane and higher cycloalkanes. In moderately to severely hindered pseudorotation, it is appropriate to consider distinct stable conformations which are pseudorotation partners, and these cases are often amenable to study by dynamic nmr methods. When the barrier to pseudorotation is very low, or in the limit when pseudorotation is free, it is not really justified to talk about separate stable conformations (e.g. the C2 and Cg forms of cyclopentane), because strictly there is only one conformation, and the pseudorotation is simply a molecular vibration. 

Experimental work, described in Section VII, shows that the barriers to pseudorotation are highly dependent on the nature of the CX2 group, but unfortunately, no strain energy calculations are available on this point. 

In the discussion on 1,1,4,4-tetrafluorocyclooctane the argument was made that substitution of a methylene group in cyclooctane by a difluoro-methylene group increases the barrier to pseudorotation by about 1.2 kcal/ mole, owing to the presence of additional non-bonded repulsions in the transition state for the boat-chair to twist-boat-chair interconversion. Supporting evidence for this view comes from proton nmr studies on 1,1-dimethylcyclooctane (VIII) and on the ethylene ketal (IX) and the ethylene dithioketal (X) of specifically deuterated cyclooctanone. 

Table 9 gives the free energy barriers for conformational interconversions in cyclooctanone. This table also gives the barrier to pseudorotation in... 

The data on barriers to ring inversion in heterocyclic boat-chairs (Table 10) show a trend to lower barriers when the number of hetero-atoms is increased, and in the absence of gew-dimethyl substitution, pseudorotation barriers are also quite low. It is therefore reasonable to expect that the barriers to pseudorotation and inversion in the tetrathiocane boat-chair might be too low for nmr detection, and this would, of course, explain the temperature-independent spectrum. 

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