Chair-boat isomerization

Figure 2. The vibrational energy transfer rate, UVA. from reactive states to nonreactive states at energy E is plotted (squares) above the barrier energy of 5500 cm for cyclohexane chair-boat isomerization. Also plotted (circles) is the corresponding transmission coefficient, K(E), calculated with Eq. (9).

Wilson and Chandler calculated the free energy profile for the boat-chair isomerization at each of the CS2 densities. They found that the barrier to chair— boat isomerization was 11 kcal/mol and the reverse process had a barrier of 5 kcal/mol. In particular, they found that these barrier heights were independent of solvent density and did not differ qualitatively from results for gas phase isomerization. 

In simple chemical systems, it is often possible to make a good first guess at the dominant reaction pathway [25-28]. An example of such a reaction is the chair-to-boat isomerization in cyclohexane. In that pathway, a clever combination of two torsion angles provides an excellent reaction coordinate for the isomerization reaction [29,30]. 

This boat-chair difference is not immediately obtainable from experiment, e.g. the high-temperature conformational isomerization—and then quenching—of cyclohexane does not result in a chair — boat interconversion, but rather chair — twist-boat M. Squillacote, R. S. Sheridan, O. L. Chapman and F. A. L. Anet, 7. Am. Chem. Soc., 97, 3244 (1975). 

In general, things are simpler than that, much to our advantage. Within the limits set by the precision of the present estimates, structural features like the chair, boat, or twist-boat conformations of cyclohexane rings, as well as the butane-gawc/ze effects or the cis-tmns isomerism of ethylenic compounds leave no recognizable distinctive trace in zero-point plus heat content energies. Indeed, whatever residual, presently... 

Conformation in such macrocycles is of most interest when there are interactions between the pyridine nitrogens and other components of the macrocyclic ring. This is demonstrated by the difference in conformational preference between the two isomeric pyridinophanes 55 and 56. In the case of the 2,6-disubstituted pyridinophane 55, the attractive interactions between the pyridine nitrogens and the amino protons of the macrocyclic bridge result in the boat-boat conformation shown. For the isomeric case 56, the chair-boat and boat-boat forms have the same stability as shown by variable temperature NMR spectroscopic studies and ab initio calculations <2002J(P2)393>. 

An inseparable mixture of 51 and 54 (3 2 ratio) was methylenated with dimethyltitanocene reagent to furnish enol ethers 52 and 55 in 90% yield (Scheme 3.1.4). Thermal rearrangement of the mixture in a sealed tube produced the desired cyclooctenone 53 and the isomeric 6-5 system 58. The Claisen rearrangement of 52 proceeded with high stereoselectivity. The formation of 58 is a result of the partial isomerization of 52 to 57 followed by an alternative Claisen rearrangement Another product obtained was the enol ether 56, formed by the isomerization of 55. It was too hindered to perform the Claisen rearrangement of 55 and 56. Molecular models indicated that the chairtransition state R should be more favored over the chair-boat transition state [50]. 

General Systems.—Allinger et al. have applied the force-field method to calculations of the energy and conformation of cyclic non-conjugated olefins, including cycloheptene, isomeric cyclo-octeries, cyclo-octadienes, and cyclo-decenes, and cis,cis-cyclodeca-l,6-diene the latter is predicted to exist as a 65 35 chair-boat mixture. Similar calculations have been carried out for various cyclic ketones. Cycloheptanone is expected to exist as a mixture of conformers, whereas cyclo-octanone and cyclononanone should exist as (1) and (2), respectively. The conformation (3 X = Hj) predicted for cyclo-... 

Also, 2,2,3,6-tetra-Me-5-Cl-l,3-dioxan, due to 1,3-diaxial interactions, prefers the 2,5-twist-boat form (76BSF563) the same conformation was reported for the stereoisomeric 2-Ph-4-(2 -furyl)-5-N02-6-Me-l,3-dioxanes and 2,2,6-tri-Me-4-(2 -furyl)-5-N02-l,3-dioxanes (75MI2), for 2-Alk-2,4,4-tri-Me-l,3-dioxane derivatives (78KGS1172) and for the cis isomers of 2-OR-4-Me-l,3-dioxane (R = Et, nPr, /Pr, nBu, n-CsHn) (81DOK116). The corresponding trans isomers adopt the chair conformation with di-eq substitution. The isomeric 2-OR-4,4-di-Me-l,3-dioxanes also prefer the 1,4-twisted-boat conformer (81DOK116). 

These considerations apply to all cycloalkane derivatives, including steroids. However, the chair form of a ring is inherently more stable than the boat form. Moreover, the fnsed-ring natnre of the system lends it a very considerable rigidity, and cis-trans isomerization wonld necessitate the breaking and formation of covalent bonds. Therefore, steroid snbstitnents maintain their conformation at room temperature, whereas cyclohexane substituents usually do not. Steroids are classified according to their substituents in addition to their occurrence. 

On each carbon, one bond is directed up or down and the other more or less in the plane of the ring. The up or down bonds are called axial and the others equatorial. The axial bonds point alternately up and down. If a molecule were frozen into a chair form, there would be isomerism in monosubstituted cyclohexanes. For example, there would be an equatorial methylcyclohexane and an axial isomer. However, it has never been possible to isolate isomers of this type at room temperature.219 This proves the transient existence of the boat or twist form, since in order for the two types of methylcyclohexane to be non-separable, there must be rapid interconversion of one chair form to another (in which all axial bonds become equatorial and vice versa) and this is possible only through a boat or twist conformation. Conversion of one chair form to another requires an activation energy of about 10 kcal/mol (42 kJ/mol)220 and is very rapid at room temperature.221 However, by... 

In six-membered chelate rings such as those formed by 1,3-propanediamine (tn), at least two conformational energy minima, which correspond to an achiral chair structure (23a) and the chiral skew- or twist-boat forms (25b) and (25c),166-168 occur and both have been observed in crystal structures.169 176 The possible conformational isomerism in tn complexes is therefore even more involved than in en complexes.177 In (OC-6-12)-[CoCl2(tn)2]+ (tratns-[CoCl2(tn)2]+), for example, there are two achiral bis(chair) forms (26a and 26b), two enantiomeric (chair, skew-boat) forms (26c and 26d), one achiral form (26e) and two enantiomeric bis (skew-boat) forms (26f and 26g). Several of these have been isolated in conformationally locked systems.178 180... 

The chair conformer can undergo conformational isomerism to a second chair conformer which is degenerate in energy with the first. Cyclohexane is thus a dynamic molecule which exists largely in one of two chair isomers. These are the lowest energy conformations. Other higher energy conformations of cyclohexane include the boat form, which is 10.1 kcal/mol (42.3 kJ/mol) above the chair form, and the twist boat form, which lies 3.8 kcal/mol (15.9 kJ/mol) above the chair form. 

Generally, when 1,5-dienes are heated, they isomerize in a [3,3]-sigmatropic rearrangement known as a Cope rearrangement17 (not to be confused with the Cope elimination process). The mechanism is a simple six-membered pericyclic process, the chair form being the usual transition state. However, in this case the cyclopropyl moiety forces the geometry of the transition state into boat form 28. 

On the other hand, with heterosubstituted chiral aldehydes, the product distribution for the reaction with methyl ketone enolates is strongly influenced by the nature of the metal, the nature of the heteroatom and its position within the molecule. A chair-like transition state explained the formation of the Felkin adduct, while a boat-like transition state was invoked for the formation of the anti-Felkin adduct. However, this assumption was recently challenged by Roush and coworkers using deuterated pinacolone lithium enolate565. Performing a set of aldolizations with chiral and non chiral aldehydes led these authors to show that the isomeric purity of the enolate correlates almost perfectly with the ratio and pattern of deuterium labeling in the 2,3-an/t-aldol formed consistent with a highly favoured chair-like transition state (Scheme 115). 

The difference of total energies of the two conformations 7 and 8 with symmetry Z)2 and Cu> respectively, for the dibenzotetrathiocine 6 (X = F) was calculated by density functional theory (DFT) to be only 4.6 kj mol 1 in favor of the twist boat 7 <1998CJC1093>. Indeed, 6 (X = F) undergoes a slow conformational isomerization in solution (Section 14.09.3.1) but adopts the chair conformation 8 in crystalline form (cf. Section 14.09.4). 

X-Ray crystallography has confirmed the existence of 1,2,5,6-tetrathiocine 3 as the twisted conformer 4 (see Section 14.09.2) <1996AGE2357>. The fluoro-substituted dibenzo-l,2,5,6-tetrathiocine 6 (X = F) adopts the chair conformation 8 in the crystalline state, while the chloro compound 6 (X = Cl) was found in the twist boat conformation 7 in solid state (see Section 14.09.2) <1998CJC1093>. The calculated difference in the energies of the two conformers 7 and 8 for the fluoro-substituted derivative 6 is very small (<5 kj mol-1), and its slow conformational isomerization in solution was... 

---