Transition states cyclohexane conformations

Other examples of the formation of six-membered rings by means of an intramolecular alkylation of an ester enolate are given in Table 7. Entry 6, i.e., stereoselective transformation of the epoxy ester into the cyclohexane derivative, should be discussed briefly as a representative for the other cases. The probable reason for the unexpectedly high selectivity i.e., the nonappearance of the diastereomer 8, can be demonstrated by the two transition-state-like conformations 9 and 10. 9 displays a very severe 1,3-diaxial interaction in comparison to 10, thus, formation of the diastereomer 7 from conformation 10 is highly favored113. 

A barrier of about 12.8 kcal/mol at —15 °C has been determined for a symmetrical 1,2,3,4,5,6-hexachlorocyclohexane 2) while the highest barrier yet found is) for a substituted cyclohexane which retains a skeleton with six carbon atoms is that of the cis form of 1,2,3,4,5,6-hexamethylcyclohexane 10b. The barrier in this instance is 17.0 kcal/mol at 60 C It appears i 8) that the barrier to ring inversion in as-l,2-di- -butylcyclohexane is 16.3 kcal/mol, a high value that can be explained in terms of the f-butyl groups being eclipsed or nearly eclipsed in the transition state. The conformational processes taking place in this molecule are not thoroughly understood. )... 

On the question of how cyclohexane accommodates a tert-huty group substituent, calculation suggests that torsion about the exocyclic bond relieves strain and the perfectly staggered arrangement is a transition state between conformations skewed by 6-10° in the equatorial and 15-27° in the axial conformation, where parallel 1,3-interactions are no doubt greater. How the ring distorts in these monoalkylcyclo-hexanes has also been studied ... 

The developing interest in conformational analysis in the 1950s diverted attention from the cyclohexane ground state 44 to non-chair conformations, and early work is summarized in sections of books published in 1965, and in greater detail in a review of 1974 The boat conformation 45, except in a few constrained bicyclic compounds, is a transition state between conformations 46, described as twist-boat or twist, so the description non-chair should usually be taken to mean this latter conformation. 

A potential energy diagram for nng inversion m cyclohexane is shown m Figure 3 18 In the first step the chair conformation is converted to a skew boat which then proceeds to the inverted chair m the second step The skew boat conformation is an inter mediate in the process of ring inversion Unlike a transition state an intermediate is not a potential energy maximum but is a local minimum on the potential energy profile... 

According to this concept, the aldol condensation normally occurs through a chairlike transition state. It is further assumed that the stmcture of this transition state is sufficiently similar to that of chair cyclohexane to allow the conformational concepts developed for cyclohexane derivatives to be applied. Thus, in the example above, the reacting aldehyde is shown with R rather than H in the equatorial-like position. The differences in stability of the various transition states, and therefore the product ratios, are governed by the steric interactions between substituents. 

A conformational effect was detected for the H-transfer reactions from cycloalkanes to a series of attacking radicals. The data of Table 6 show that cyclopentane is generally a better H-donor than cyclohexane. The rate ratio is generally largest for the least reactive radicals because the change in hybridization at transition state... 

From the pseudorotating transition state the inversion process proceeds via an intermediate minimum of D2-symmetry (twist-conformation) and across a symmetry-equivalent second pseudorotational transition state to the inverted chair-conformation. The symmetric boat-form of cyclohexane (symmetry C2v) corresponds to a one dimensional partial maximum, i.e. a transition state (imaginary frequency 101.6 cm-1). It links sym-... 

Fig. 16. Three dimensional conformational map of cyclohexane. The representation is analogous to that of Fig. 15 the third (vertical) coordinate is the potential energy. The given calculated potential energy differences (kcal mole-1) of the minima and transition states are drawn to scale. The interconnecting curves are drawn qualitatively they are merely meant to indicate the absence of intermediate further minima and maxima. See ref. 106 for details of analytical representations of conformational maps of cyclohexane...

Fig. 18. Top transition coordinates (with symmetry species) of conformational transition states of cyclohexane (top and side views). Hydrogen displacements are omitted. The displacement amplitudes given are towards the C2v-symmetric boat form, and towards >2-symmetric twist forms (from left), respectively. Inversion of these displacements leads to the chair and an equivalent T>2-form, respectively. Displacements of obscured atoms are given as open arrows, obscured displacements as an additional top. See Fig. 17 for perspective conformational drawings. Bottom pseudorotational normal coordinates (with symmetry species) of the Cs- and C2-symmetric transition states. The phases of the displacement amplitudes are chosen such that a mutual interconversion of both forms results. The two conformations are viewed down the CC-bonds around which the ring torsion angles - 7.3 and - 13.1° are calculated (Fig. 17). The displacement components perpendicular to the drawing plane are comparatively small. - See text for further details.

Alkenyl nitrones, having the alkene connected to the nitrone nitrogen atom, have been used in another approach to intramolecular reactions (231-235). Holmes and co-workers have this method for the synthesis of the alkaloid (—)-indolizidine 209B 137 (210,231). The alkenyl nitrone 134, was obtained from the chiral hydroxylamine 133 and an aldehyde. In the intramolecular 1,3-dipolar cycloaddition, 135 was formed as the only isomer (Scheme 12.45). The diastereofacial selectivity was controlled by the favored conformation of the cyclohexane-like transition state in which the pentyl group was in a pseudoequatorial position, as indicated by 134. Further transformation of 135 led to the desired product 137. 

Special cases of these involving transition states for rotation about single bonds, inversion of pyramidal nitrogen and phosphorus centers and ring inversion in cyclohexane, have been discussed in the previous chapter. The only difference is that these conformational processes are typically well described in terms of a simple motion, e.g., rotation about a single bond, whereas the motion involved in a chemical reaction is likely to be more complex. 

For cyclohexane derivatives to react in this way, the transition-state conformation must have both leaving groups axial ... 

Fig. 5.45 One might have guessed that the chair cyclohexane conformations 1 and I are connected by a boat-shaped intermediate 2. However, this C2v structure shows an imaginary frequency it is a transition state which wants to twist toward 3 (arrows) or 3 (arrows in opposite directions, not shown), which are the actual intermediates (no imaginary frequencies) between 1 and 1. The chair conformation reaches the twist via a half-chair 4...

The gas-phase structure of 1,3,5-trisilacyclohexane was determined by gas electron diffraction (01JMS245) and compared with the results of quantum chemical calculations (98JMS(T)91). The chair conformation, the strongly preferred conformer, is more flattened than cyclohexane due to the intrinsically large Si-C-Si bond angles. By the quantum chemical calculations also the twist and boat conformers were identified to be much less stable than the chair conformation. The chair-to-chair interconversion barrier is 5.5 kcal/mol the transition state was identified as a sofa conformation with an approximately Cs symmetry, similar to the transition state in 173 (cf. Scheme 57). 

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