Cyclohexanone conformationally fixed

If this interpretation is correct, then in any reaction with asymmetric induction, a search for antiperiplanarity between the incipient bond (Nu-Cl) and an adjacent sigma bond (C2-L) should lead to the most favourable transition states, all other things being equal. Let us apply this rule to the so-called product development control problem. Consider a conformationally fixed cyclohexanone, for example 14. 

Side Note 10.1. Electronic Effects in the Reduction of Conformationally Fixed Cyclohexanones... 

Equatorial, and Axial Addition of Classic Grignard Reagents and Reetz-Grignard Reagents to a Conformationally Fixed Cyclohexanone... 

Figure 9.4 shows stereogenic epoxide formations with S ylides and a ketone. The substrate is a conformationally fixed—because it represents a trans-decalin—cyclohexanone. Both the dimethylsulfoxonium methylide and the dimethylsulfonium methylide convert this cyclohexanone into an epoxide diastereoselectively. As Figure 9.4 shows, the observed diastereoselectivities are complementary. The sulfoxonium methylide attacks the carbonyl carbon equatorially, whereas the attack by the sulfonium ylide takes place axially. 

Fleming and co-workers have examined the Type II photochemistry of some conformationally fixed cyclohexanones. The p-cleavage cyclobutanol formation ratio was higher than was found for acyclic ketones. 

Combined n.m.r., i.r., and u.v. spectroscopic evidence from 2- and 4-methyl-2,3,6-trichloro- and -tribromo-cyclohexanones has shown that the latter have fixed conformations whereas in the former two conformers can exist. In certain solvents one of these is preferred, e.g. triequatorial in MeCN, triaxial in CCl. In a related study of 2,3,6-trichloro-, tribromo-, and mixed trihalogeno-cyclohexanones conformational dependence on solvent was again found. For the 2,3,6-tribromo-cyclohexanone in n-heptane the triaxial conformer is preferred over the triequatorial in the ratio 87 13 in MeCN these proportions are reversed. It was concluded that a 3-halogeno substituent exerts a strong stereoelectronic effect on the conformational behaviour of the 2,3,6-trihalogenocyclohexanones. 

The stereochemistry of enolisation has been mostly examined in cyclic systems where the relative positions of the enolisable hydrogen atoms are fixed. Over the last decade, these studies have benefited from important improvements in the experimental methods, namely mass spectrometry and nmr spectroscopy. Of great interest is the comparison of the relative mobilities of diastereoisomeric axial and equatorial protons from ketones in the cyclohexane series. Indeed, since axial a(C—H) bonds of rigid cyclohexanones are closer than equatorial a(C—H) bonds to the desirable conformation in which the breaking C—H bond is perpendicular to the direction of the C=0 bond, it can be expected that the axial a(C—H) bond-breaking is easier than that of the equatorial one. 

Alkylations of enolates, enamines, and silyl enol ethers of cyclohexanone usually show substantial preference for axial attack. The enamine of 4-f-butylcyclohexanone, which has a fixed conformation because of the i-butyl group, gives 90% axial alkylation and only 10% equatorial alkylation with n-Prl. 

Scheme 5.8 Highly stereoselective hydrogenation to axial alcohols of the cyclohexanones with a fixed conformation.

By examining model compounds with fixed conformations and from earlier work, Corey determined that there were distinct differences in the carbonyl frequencies of cyclohexanones that had a bromine in the a-position, and that depended upon whether the bromine was in an axial or in an equatorial position. Model compound smdies showed that the parent cyclohexanone itself had a carbonyl stretching frequency at 1712cm in carbon tetrachloride, and cyclohexanones that contained an axial bromine in the a position showed their carbonyl absorption at very nearly the same place, about 1712-1716cm . On the other hand, when the bromine was in the equatorial position, the absorption was found about 1728-1730 cm If one had a mixture of conformations with the bromine partly equatorial and partly axial, one could usually more or less resolve these two frequencies. This information could be used to tell in an equilibrium situation whether the bromine was mostly axial or mostly equatorial, and by approximately how much. (The assumption is made here that the inherent intensity of the vibrational band is the same in both the axial and equatorial arrangements. It was later shown that this is not quite true, and the equatorial stretching band has a somewhat... 

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