Cyclooctane derivatives, conformations

Compound Structure Conformation and positions of substituents ) Dihedral angles Ref. for cyclooctane derivatives (in°)2)... 

In contrast to the parent compound, several cyclooctane derivatives and related compounds have had their structures determined by X-ray diffraction (Table 1). Most of these compounds have boat-chair conformations, but fra s-syM- m s-l,2,5,6-tetrabromocydooctane is a twist chair-chair, and crown conformations are found in octasulfur, the all-cfs tetramer of acetaldehyde, and related compounds. 

The internal angles in all the conformations given in Table 2 are considerably greater than the 111.5° found in cyclohexane. In the crown, chair-chair, twist-chair-chair, boat-chair, and twist-boat-chair, the angles are in the range of 115° to 117°. The experimentally determined internal and dihedral angles for several boat-chair cyclooctane derivatives (Table 1) are very similar to those calculated by Hendrickson and by Bixon and Lifson. 

The nmr spectra of various rather simple cyclooctane derivatives discussed below are only consistent with the boat-chair conformation. Furthermore the structures in the crystalline state are boat-chairs (Table 1), with one exception which can be rationaUzed (see below). The conclusion that cyclooctane exists in solution as the boat-chair therefore appears inescapable. 

Conformational energy barriers have been studied in various cyclooctane derivatives by mechanical relaxation methods. > b The frequency and temperature range of such measurements are very large, but the identities of the processes observed are not as clear as in nmr measurements. With poly(cyclooctyl methacrylate) a process with an activation energy of 10.6 kcal/mole is fovmd, and has been interpreted in terms of a boat-chair... 

In summary, the experimental nmr data presented in this Section stongly support the boat-chair as the lowest energy conformation for simple cyclooctane derivatives. The twist-chair-chair is of next lowest energy and the presence of certain substituents can make this conformation be the dominant one. Boat-boat family conformations are only (if ever) found in very special compounds. 

At one time it was believed that cyclooctane occurs in the extended crown form and the saddle conformation as shown below but on the basis of calculations of minimum energy strain, Hendrickson (1964) and Wiberg (1965) suggested that neither of the above two forms is the correct picture. R. Srinivasav and T. Srikrishnan (Tetrahedron 27, 5, 1009-1012, 1971) showed that the molecule exists as the boat-chair form in a number of crystalline derivatives. 

The conformational properties of such eight-membered ring molecules have been reviewed fairly recently (74MI51900). Cyclooctane is the archetypical molecule in this class, and the heterocyclic analogs, such as the azocanes, oxocanes and thiocanes, as well as carbocyclic derivatives, such as cyclooctanone, all have closely related conformational features and a brief overview of their conformations will now be given. 

Roberts ) originally considered a twist-boat conformation for IV, but the mounting evidence for a boat-chair conformation for cyclooctane and various derivatives, led Roberts and coworkers to suggest boat-chair conformations for IV also. ) Futhermore, the original explanation requires that pseudorotation of the twist-boat via the boat be of lower energy than the pseudorotation via the boat-boat and this is not supported by recent strain energy calculations. 

Another transannular reaction, which likewise proceeds via carbene insertion, is the base-catalyzed decomposition of the tosylhydrazone of cyclooctanone. In general these carbenes react with a- and -C—H bonds to give alkenes and cyclopropanes. However, when the carbene carbon can approach distant C —H bonds, such as in the cyclooctane conformation, then bicyclo[3.3.0]octane derivatives are also formed from transannular insertion.Thus, cyclooctanone- and 5-phenylcyclooctanone tosylhydrazones reacted with sodium methoxide to give a mixture of mono- and bicyclic products 4-6 and 7-10, respectively, in the stated proportions. 

However, the transannular reactions are also highly sensitive toward even minimal conformational changes within the substrate. Thus, attempts to perform analogous cycloisomerizations with ethyl 2-(5-cyclopropylidene-4-methylcyclooctylidene)acetate (the 4 -methyl derivative of compound 22) or l-cyclopropylidene-5-(l-methylethylidene)cyclooctane (a geminal dimethyl derivative of 24) have been unsuccessful. ... 

It is important to note that the symmetry of the boat-chair conformer renders positions 2/8, 3/7, and 4/6 equivalent in a pairwise fashion. In considering substituted cyclooctanes, one can derive a set of A-values that define the preference for substitution at any one site at equatorial versus axial positions with some analogy to the definition accepted in cyclohexane (Figure 1.4) [3]. 

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