Inversion, conformational

Conformational inversion (ring flipping) is rapid in cyclohexane and causes all axial bonds to become equatorial and vice versa As a result a monosubstituted derivative of cyclohexane adopts the chair conforma tion in which the substituent is equatorial (see next section) No bonds are made or broken in this process... 

Substitution on a cyclohexane ring does not greatly affect the rate of conformational inversion but does change the equilibrium distribution between alternative chair forms. All substituents that are axial in one chair conformation become equatorial on ring inversion, and vice versa. For methylcyclohexane, AG for the equilibrium... 

Table 3.5. Half-life for Conformational Inversion of Cyclohesyl Chloride at Various Temperatures"...

The strong preference for a /-butyl group to occupy the equatorial position has made it a useful group for the study of conformationally biased systems. The presence of a /-butyl substituent will ensure that the equilibrium lies heavily to the side having the /-butyl group equatorial but does not stop the process of conformational inversion. It should be emphasized that conformationally biased is not synonymous with conformationally... 

These two energies are, respectively, comparable to the experimental activation energies for conformation inversion of the tub conformer and bond shifting, suggesting that the two planar structures represent the transition states for those processes. 

Since the conformational inversion of 2c-methylcyclohexanone is the key step in this sequence, the corresponding conformationally more stable system, i.e., cw-2-methyl-4-t-butylcyclohexanone (14), should fail to incorporate any deuterium. This was actually shown to be the case. Treatment of this ketone under identical conditions for d exchange did not show any d incorporation. This evidence also rules out the likelihood of any d incorporation via acid- or base-catalyzed enolization. 

Novel cationic methyl and neutral methyl, chloro Pd11 complexes have been synthesized with various functionalized imidazole ligands. For the first time, structurally characterized examples of this type of Pd complex could be obtained. The chelate ligand is shown to adopt a boat conformation. Inversion of the chelate ring was established by NMR spectroscopy. Depending on electronic and steric features of the ligand, the complexes can act as catalysts in the CO/ethylene as well as the Fleck reaction.186... 

For crown ethers in which the H-nmr probes Ha and Hb are diastereotopic in the free crown ether too, the cation exchange process (50) becomes more complicated. For 1 1 complexes the measured free energy of activation also involves conformational inversion components (AG = AG + AG ), whereas exchange between free and complexed crown ether (2 1 ratio of crown ether to salt) only involves the free energy of activation for decomplexation (AG ). Bradshaw et al. (1979b) have recently reported AG -values for cation exchange in RNH3X complexes of crown ethers [257]. The AGf term was estimated to be 0.7, 0.5, and 1.2 kcal mol-1 for compounds [257 n = 1] with... 

Conformational inversion barriers of 5,10-substituted decalins (17) were determined by NMR, and MMI calculations were carried out to see whether the twist-chair (ct) or the boat-boat (bb), correspond to the higher barrier. The ct was found to be higher in cw-decalin (17, R = H), but the introduction of substituents at the ring junction is expected to raise the energy of the bb. The observed AG agreed with the calculated value for ct, which is about 5 kcal/ mol higher than that of bb when R = CH3 or OH (124). 

Five- and six-membered rings formed by coordination of diamines with a metal ion have the stereochemical characteristics of cyclopentane and cyclohexane. The ethylenediamine complexes have puckered rings and the trimethylenediamine complexes have chair conformations. The methylene protons are nonequivalent in these nonplanar conformations, taking on the character of equatorial and axial substituents. They are made equivalent as the result of rapid conformational inversion at room temperature, just as in the alicyclic compounds (Fig. 7.1). This has been observed in nmr studies of planar and octahedral complexes of ethylenediamine-type ligands with a number of metals. 

In another search for an alternative to Potier s modified Polonovski reaction of catharanthine A-oxide (45), it has now been found that anhy-drovinblastine (42) can be generated directly, in 77% yield, from a reaction of catharanthine and vindoline in 0.01 N acid, promoted by ionized ferric salts, followed by reduction with sodium borohydride (Scheme 30) (Wl). Remarkably, the cation radical 106 generated by Fe(III), in accord with other simple amine oxidations by Lindsay Smith and Mead (102), resulted in isoquinuclidine fragmentation and coupling to vindoline at 0°C, without the conformational inversion observed in the modified Polonovski reaction at that temperature (see Scheme 15). Other metal oxidants or ligand-bound Fe(lll) did not promote the coupling reaction. It will be of interest to see if the overwhelming competition of C-5-C-6 bond... 

Carius tube reaction of [Cr(CO)(,] and the appropriate ligand at 140°C for 14 h. The conformational inversion of the five-membered ring has been studied by n.m.r. and some of the complexes have been shown to exhibit marked conformational preferences. ... 

Surface adsorption can also influence observed stereochemistry in a profound way. In enone photocycloadditions on silica gel and on alumina, the reaction which normally occurs from the less hindered alpha face is shifted toward the more hindered beta face, Eq. (9) Adsorption thus apparently disfavors conformational inversion in the intermediate biradical, as is required for formation of trans-fused products. The magnitude of the effect is sufficient to be synthetically useful the above reaction represents a complete reversal of stereochemistry from that observed in methanolic solution... 

Conformational inversions in the field of ketonucleosides were established by n.m.r.-spectral analysis. It has been reported30,32 that the introduction of a carbonyl group at C-4 of the sugar moiety of L-rhamnosyl-purines and -pyrimidines led to ketonucleosides possessing an axially attached nitrogenous base. Such unusual positions of the base have been observed in the case of a glycosyltheophylline,61 and for some derivatives of a rhamnosyl-5-fluorouracil.48... 

H NMR has been used to study the thermodynamics of the conformational inversion of various pyridazino[l,2-a]pyridazines. In the case of l,2,3,4,6,9-hexahydro-7,8-dimethyl-pyridazino[ 1,2-a ]pyridazine-1,4-dione, analysis of the signals from the C-3 and C-6 methylene protons at -60 °C shows that the energy barrier to the conformational inversion must be less than 43.5 kJ mol-1 (66T3477). 

The conformational analysis of saturated multi oxygen and sulfur rings is very well developed. The most recent survey of this area (B-80MI22600) provides an excellent coverage of the topic, updating an important earlier review (B-69MI22600). Within the present chapter, theoretical approaches, ring shapes and structural determinations are covered in Sections 2.26.2.1, 2.26.2.2 and 2.26.2.3. The present section is thus concerned primarily with the conformational preferences of substituents and barriers to conformational inversion. 

Bond lengths, angles, and dihedral angles from MP2/6-31G optimizations are shown in Table 1. Thiepine 1 has a boat conformation, whereas the planar form of thiepine is the transition state for its degenerate conformational inversion. 

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