Rings 6- membered, axial attack

Similarly, ring C is more rigid than ring A. It is also more puckered, being linked by a trans junction to a five-membered ring instead of a six-membered ring The flattening rule then predicts that axial attack will be easier on 1-ketosteroids than on 12-ketosteroids. This is indeed what is observed by Ayres et al. ... 

Intermolecular free radical reactions. Giese notes the diastereoselectivity of reactions of acrylonitrile with cyclic 5- and 6-membered ring radicals can be controlled by adjacent substituents. Thus an axial 3-substituent can favor axial attack, whereas an equatorial 3-substituent favors equatorial attack in the case of 6-membered cyclic radicals. Glucosyl radicals, regardless of the precursor, yield a-substi-tuted products (88 12). 

The previous exercise showed that the ketone in 17 must be more puckered than that in 16 because it is located next to a five-membered ring junction. Hence 16 is more prone to axial attack. 

Epoxide openings are not alone in always giving diaxial products. We can give the general guideline that, for any reaction on a six-membered ring that is not already in the chair conformation, axial attack is preferred. You will see in later chapters that this is true for cyclohexenes, which also have the half-chair conformation described in the next section. Cyclohexanones, on the other hand, already have a chair conformation, and so can be attacked axially or equatorially. 

This result sounds very like the results already noted for six-membered rings and the explanation is similar. Saturated four-membered rings—even the ketones—are slightly puckered to reduce eclipsing interactions between hydrogen atoms on adjacent carbon atoms, and axial attack by the small nucleophile gives the more stable cis product having both substituents equatorial . 

Axial attack is preferred with unsaturated six-membered rings... 

Six-membered rings with two or more trigonal carbon atoms undergo axial attack in order to form chairs rather than boats. The final product may end up with axial or equatorial substitution, but this is not a consideration in the reaction itself... 

Alkylation of cyclic enolates is stereoselective, with reaction taking place on the less hindered face (four- or five-membered rings) or via axial attack (six-membered rings)... 

The effect is most likely more general and not restricted to chair cyclohexane systems. In alloaromadendrene (8), containing a seven-membered ring in a similar conformation, the calculated selectivity for axial attack is again somewhat less than found experimentally the preliminary structure assignment133 of the two diastereomers is confirmed by calculation168. The preference for axial attack in methylenecyclohexane systems is reversed in epoxidation with peracid imides (see Table 5). 

Addition of the tinlithium reagent to the ketone must occur from underneath (axial attack) if formation of the lactone is to succeed and these steps are best seen with conformational drawings. It is necessary to flip the six-membered ring to put the two reactive groups axial before cyclization can occur. 

Cyclohcxyl radicals with //an.s-annulated six-membered rings in y.5-position are expected to show similar selectivitics compared to monocyclic cyclohexyl radicals42. For steroid radicals, a high preference for axial attack is found in hydrogen-abstraction reactions22. 

The reasons for stereochemical perturbation associated with the flexible six-membered ring transition state are discussed in terms of a minimization of steric interactions in axial attack or the adoption of a boat cyclohexane conformation in the transition state. 

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