Cyclooctanone conformation

Aggarwal and co-workers nsed the same key strategy but with a different Simpkins base (A,A)-41 (Cain et al. 1990) to achieve the rare enantioselective deprotonation of an eight-membered ring ketone (40, Scheme 7.9) at die low temperature of 100°C to ensure the presence of only one cyclooctanone conformer and consequently increase the enantioselectivity of the process (Aggarwal etal. 1999). 

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. 

Mn(II)-catalyzed oxidation of cyclic ketones with lead tetraacetate is zero order in the oxidant. The order of reactivity is cyclohexanone > cyclooctanone > cycloheptanone cyclopentanone. The reactivity has been analysed in terms of the conformation.80... 

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

The BC-3 conformation for cyclooctanone is supported by recent strain energy calculations, which have already been mentioned (Section V). Qualitatively, the BC-3 conformation is also very reasonable, since the non-bonded repulsions between the 3 and 7 methylene groups in the cyclooctane boat-chair conformation are largely removed in the BC-3 form. The 1 position in the boat-chair also has the same kind of advantage that the 3 position has. However, the 3 position is also favored because of the relief of eclipsing strain which occurs in that position, but not in the 1 position (see Table 2 for dihedral angles in the boat-chair). This point will be amplified in the following discussion on methylenecyclooctane. 

Since oxygen is much smaller than a methylene group, the same kind of situation occurs in XVII as was discussed in the previous section. The barrier to methyl rotation in dimethyl ether is 2.7 kcal/mole >, only slightly lower than in propane, where the beirrier is 3.4 kcal/mole. Oxocane should therefore have the BC-1 conformation, as in methylenecyclooctaue rather than the BC-3 and BC-7 conformations. The presence of only a single process in the proton spectrum of XVII is immediately consistent with the BC-1 conformation, but requires rapid pseudorotation between the BC-3 and BC-7 forms at —170 °C if the latter two forms are the correct conformations. The pseudorotation barrier in XVII should be higher than in cyclooctane, and probably comparable to that in cyclooctanone (6.3 kcal/mole). Thus, pseudorotation of the BC-3 form should not be rapid at —170 °C, and further support for this h5q)othesis is provided by 1,3-dioxocane (see below). It is therefore probable that oxocane has the BC-1 conformation. 

Since the interconversions of the conformations of XXIII are very similar to those described in detail for cyclooctanone, no further discussion will be given here. 

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. 

The presence of a heteroatom, a C-C unit, or a carbonyl influences the conformation of medium-size rings, but the changes are often subtle. The calculated low-energy conformation of cyclooctane (174) is compared with those of cii-cyclooctene (175), the ether oxocane (176) and cyclooctanone (177). Although 175 is somewhat flattened, the conformations of the other three eight-membered rings are rather similar. ... 

A comparative calculation study was performed for cyclooctanone (6), octahydroazocine (7), and hexahydroazocin-5-one (8) using MM2 and MNDO. For discussion purposes, the proposed graphical representation of possible conformations by Dunitz and Prelog <60AG896> is used (Figure 1). The most symmetrical heterocycle possesses a crown conformation and there are boat-chair (BC), chair-chair (CC), boat-boat (BB) and other forms. In most cases, the position of the individual ring atoms is not equivalent therefore, additional conformations have to be taken into account. Moreover, twisted forms of the above-mentioned conformations might be more stable than the more noticeable conformations. The calculated heats of formation, AFff, are summarized in Table 1. 

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